Cardiac Surgery in Adults

Dedication
Contributors
Foreword
Preface
Part I - FUNDAMENTALS
1. History of Cardiac Surgery
2. Surgical Anatomy of the Heart
3. A Synopsis of Cardiac Physiology
4. Pathologic Considerations in the Surgery of Adult Heart Disease
5. Preoperative Evaluation
6. Risk Stratification and Comorbidity
7. Cardiac Anesthesia
8. Cardiac Surgical Pharmacology
9. Extracorporeal Perfusion
10. Intraoperative Protection of Organs: Hypothermia, Cardioplegia, and Cerebroplegia
11. Temporary Mechanical Circulatory Support
12. Early Postoperative Care
13. Complications of Cardiac Surgery
14. Cardiopulmonary Resuscitation
Part II - ISCHEMIC HEART DISEASE
15. Indications for Revascularization
16. Myocardial Revascularization without Thoracotomy
17. Techniques of Myocardial Revascularization
18. First Operation for Myocardial Revascularization
19. Coronary Reoperations
20. Myocardial Revascularization in the Presence of Carotid Arterial Disease
21. Surgery for Acute Myocardial InfarctionCardiogenic Shock
22. Postinfarction Ventricular Septal Defect and Free Wall Rupture
23. Ischemic Mitral Regurgitation
24. Left Ventricular Aneurysm
Part III - SURGERY OF ARRHYTHMIAS
25. Mechanisms of Surgically Treated Arrhythmias and Conduction Disturbances
26. Surgical Treatment of Arrhythmias
27. Practical Considerations in Pacemaker-Defibrillator Surgery
Part IV - VALVULAR HEART DISEASE
28. Pathophysiology of Aortic Valve Disease
29. Mechanical and Bioprosthetic Aortic Valve Replacement
30. Aortic Valvular Allografts and Pulmonary Autografts
31. Complex Operations of the Aortic Root
32. Pathophysiology of Mitral Valve Disease and Operative Indications
33. Mitral Valvuloplasty
34. Mechanical and Bioprosthetic Mitral Valve Replacement
35. Tricuspid Valve Disease
36. Multiple Valve Disease
37. Valvular and Ischemic Heart Disease
Part V - DISEASES OF THE THORACIC AORTA
38. Dissecting Aortic Aneurysm
39. Ascending Aortic Aneurysm
40. Aneurysms of the Aortic Arch
41. Descending and Thoracoabdominal Aortic Aneurysms
42. Traumatic Aorta Rupture
Part VI - OTHER OPERATIONS
43. Blunt and Penetrating Trauma to the Heart and Central Great Vessels
44. Pericardial Diseases
45. Pulmonary Thromboembolism
46. Cardiac Neoplasms
47. Surgery for Adults with Congenital Heart Disease
48. Immunobiology of Heart and Lung Transplantation
49. Heart Transplantation
50. Transplantation of the Heart and Lungs
51. Long-term Mechanical Circulatory Support
52. Cardiomyoplasty
To our patients
Contributors
The numbers in brackets following the contributor name refer to chapter(s) authored or co-authored by
Cary W. Akins, M.D. [20] Robert B. Karp, M.D. [30]

Visiting Surgeon, Massachusetts General Hospital Chief of Cardiac Surgery
Clinical Professor of Surgery, Harvard Medical School Professor of Surgery
Boston, Massachusetts University of Chicago Hospitals
Chicago, Illinois
Mario Albertucci, M.D. [30]
Assistant Professor of Surgery, Section of Cardiac Nicholas T. Kouchoukos, M.D. [39]
Surgery Staff, Missouri Baptist Hospital
University of Chicago Hospital Saint Louis, Missouri
Chicago, Illinois
Hillel Laks, M.D. [47]
Richard P. Anderson, M.D. [46] Professor and Chief, Cardiothoracic Surgery Department
Chief, Cardiothoracic Surgery University of California at Los Angeles Medical Center
Virginia Mason Medical Center Los Angeles, California
Seattle, Washington
Jerrold H. Levy, M.D. [8]
Robert H. Anderson, M.D. [2] Attending Anesthesiologist, Divisions of Cardiothoracic and Critical Care Medicine
Joseph Levy Foundation Professor of Paediatric Cardiac Emory University Hospital
Morphology Professor of Anesthesiology
Royal Brompton National Heart and Lung Institute Emory University School of Medicine
London, England Atlanta, Georgia
Robert C. Ashton, M.D. [21] Steven A. Leyland [5]

Cardiovascular Research Fellow Chief, Cardiac Surgery
Columbia-Presbyterian Medical Center Spartanburg Regional Medical Center
New York, New York Spartanburg, South Carolina
James M. Bailey, M.D. [8] James E. Lowe, M.D. [14, 24]

Attending Anesthesiologist Professor of Surgery and Associate Professor of Pathology
Divisions of Cardiothoracic Anesthesiology and Critical Attending Surgeon, Cardiothoracic Surgery
Care Medicine Duke University Medical Center
Emory University Hospital Durham, North Carolina
Attending Anesthesiologist, Cardiac Surgical Service
Egelston Children's Hospital Bruce W. Lytle, M.D. [19]
Assistant Professor of Anesthesiology and Pediatrics Surgeon, Department of Thoracic and Cardiovascular Surgery
Emory University School of Medicine The Cleveland Clinic Foundation
Atlanta, Georgia Cleveland, Ohio
Hendrick B. Barner, M.D. [17] Joren C. Madsen, M.D. [22]

Professor of Surgery Assistant in Surgery
Washington University School of Medicine Massachusetts General Hospital
Saint Louis, Missouri Assistant Professor of Surgery
Harvard Medical School
William A. Baumgartner, M.D. [49] Boston, Massachusetts
Cardiac Surgeon-in-Charge
The Johns Hopkins Hospital George W. Maier, M.D. [28]
Baltimore, Maryland Associate Director, Heart and Lung Transplant Program
Medical Center of Virginia
Joseph E. Bavaria, M.D. [42] Assistant Professor of Surgery
Assistant Professor of Surgery Cardiac and General Thoracic Surgery
Cardiovascular and Thoracic Surgery Virginia Commonwealth University
University of Pennsylvania Medical Center Richmond, Virginia
Philadelphia, Pennsylvania
Daniel Marelli, M.D. [47]
Hans G. Borst, M.D. [38] Visiting Assistant Professor
Professor Chirurgie University of California at Los Angeles
Cardiovascular and Thoracic Surgery Virginia Commonwealth University
University of Pennsylvania Medical Center Richmond, Virginia
Daniel Marelli, M.D. [47]
Hans G. Borst, M.D. [38] Visiting Assistant Professor
Professor Chirurgie University of California at Los Angeles
Medizinische Hochschule Hannover Los Angeles, California
Hannover, Germany
Dale H. Marsh, M.D. [36]
W. Morris Brown, III, M.D. [18] Surgical Resident
Assistant Professor of Cardiothoracic Surgery The Mayo Clinic
Emory University, School of Medicine Rochester, Minnesota
Atlanta, Georgia
Patrick M. McCarthy, M.D. [11]
Albert T. Cheung, M.D. [7] Director, LVAD and Assist Device Program
Staff, Department of Anesthesia Department of Thoracic and Cardiovascular Surgery
University of Pennsylvania Medical Center The Cleveland Clinic Foundation
Assistant Professor of Surgery, University of Pennsylvania Cleveland, Ohio
Lynn B. McGrath, M.D. [35]
Ray Chu-Jeng Chiu, M.D. [52] Chairman, Department of Surgery
Senior Surgeon and Director, Division of Cardiovascular Deborah Heart and Lung Center
and Thoracic Surgery Browns Mills, New Jersey
The Montreal General Hospital Associate Professor of SurgeryUMDNJ-Robert Wood Johnson Medical School
Professor and Chairman, Division of Cardiovascular and New Brunswick, New Jersey
Thoracic Surgery
McGill University Joseph S. McLaughlin, M.D. [43]
Montreal, Quebec, Canada Professor and Head, Division of Thoracic and Cardiovascular Surgery
University of Maryland, School of Medicine
Lawrence H. Cohn, M.D. [34] Baltimore, Maryland
Chief, Division of Cardiac Surgery
Brigham and Women's Hospital Sanjay M. Mehta, M.D. [13]
Professor of Surgery Research Fellow, Cardiothoracic Surgery
Harvard Medical School The Pennsylvania State University
Boston, Massachusetts The Milton S. Hershey Medical Center
Hershey, Pennsylvania
Joseph S. Coselli, M.D. [41]
Attending Surgeon Michael R. Mill, M.D. [2]
Methodist Hospital Attending Surgeon, Director of Transplantation Services
Professor of Surgery North Carolina Memorial Hospital
Baylor College of Medicine Associate Professor, Cardiothoracic Surgery
Houston, Texas University of North Carolina School of Medicine
Chapel Hill, North Carolina
Delos M. Cosgrove, M.D. [33]
Chairman, Thoracic and Cardiovascular Surgery D. Craig Miller, M.D. [32]
The Cleveland Clinic Foundation Department of Cardiothoracic Surgery
Cleveland, Ohio Falk Cardiovascular Research Center
Stanford University Medical Center
Sergio F. Cossú, M.D. [25] Professor of Cardiovascular Surgery
Fellow, Department of Cardiology Stanford University School of Medicine
Temple University Hospital Stanford, California
John M. Miller, M.D. [25]
James L. Cox, M.D. [26] Director, Electrophysiology Service
Chief, Division of Cardiothoracic Surgery Associate Professor of Medicine
Barnes Hospital Temple University School of Medicine
Evarts A. Graham Professor of Surgery Philadelphia, Pennsylvania
Washington University School of Medicine
Saint Louis, Missouri Derek D. Muehrcke, M.D. [33]
Staff, Smithwick Cardiovascular Group
Willard M. Daggett, Jr., M.D. [22] Jacksonville, Florida
Visiting Surgeon
Massachusetts General Hospital Mehmet C. Oz, M.D. [21]
Professor of Surgery Cardiothoracic Surgeon
Harvard Medical School Assistant Professor of Surgery
Boston, Massachusetts Columbia-Presbyterian Medical Center
New York, New York
Tirone E. David, M.D. [31]
Head, Division of Cardiovascular Surgery Walter E. Pae, Jr. M.D. [13]
The Toronto Hospital Director of Cardiac Transplantation
Professor of Surgery, University of Toronto The Pennsylvania State University
Toronto, Ontario, Canada The Milton S. Hershey Medical Center
Professor of Surgery
Verdi J. DiSesa, M.D. [37] The Pennsylvania State University College of Medicine
Active Staff, Medical College of Pennsylvania Hospital and Hershey, Pennsylvania
Hahnemann University Hospital
Professor of Surgery, University of Toronto The Pennsylvania State University
Toronto, Ontario, Canada The Milton S. Hershey Medical Center
Verdi J. DiSesa, M.D. [37] The Pennsylvania State University College of Medicine
Active Staff, Medical College of Pennsylvania Hospital and Hershey, Pennsylvania
Hahnemann University Hospital
Professor of Medicine and Surgery Harold I. Palevsky, M.D. [45]
Medical College of Pennsylvania and Hahnemann University Director, Pulmonary Vascular Disease Program
School of Medicine Medical Director, Lung Transplant Program
Philadelphia, Pennsylvania Medical Director, Respiratory Care Services
University of Pennsylvania Medical Center
Stephen W. Downing, M.D. [39] Associate Professor of Medicine and Pulmonary Critical Care
Cardiac Surgeon, Moses Cone Health Systems University of Pennsylvania, School of Medicine
Greensboro, North Carolina Philadelphia, Pennsylvania
Davis C. Drinkwater, Jr. M.D. [47] Vivek Rao, M.D. [10]

Associate Professor of Surgery Research Fellow, Division of Cardiovascular Surgery
University of California at Los Angeles The Toronto Hospital
School of Medicine Toronto, Ontario, Canada
Los Angeles, California
Bruce A. Reitz, M.D. [50]
L. Henry Edmunds, Jr., M.D. [5, 9, 23, 42, 44, 45] Professor and Chairman
Julian Johnson Professor of Cardiothoracic Surgery Department of Cardiothoracic Surgery
University of Pennsylvania, School of Medicine Stanford University School of Medicine
Philadelphia, Pennsylvania Stanford, California
M. Arisan Ergin, M.D. [40] Ross M. Reul, M.D. [34]

Active Staff, Professor of Cardiothoracic Surgery Surgical Research Fellow
Mount Sinai Medical Center Brigham and Women's Hospital
New York, New York Boston, Massachusetts
James I. Farm, M.D. [32] Robert C. Robbins, M.D. [50]

Staff, Department of Cardiothoracic Surgery Acting Assistant Professor
Falk Cardiovascular Research Center Stanford University School of Medicine
Stanford University Medical Center Stanford, California
Assistant Professor of Surgery
Stanford University School of Medicine Eric A. Rose, M.D. [21]
Stanford, California Professor of Surgery
Chairman, Department of Surgery
T. Bruce Ferguson, Jr., M.D. [26] Columbia-Presbyterian Medical Center
Heart Care Program New York, New York
Roper CareAlliance, Roper Hospital
Charleston, South Carolina Joseph S. Savino, M.D. [7]
Staff Anesthesiologist, Section of Cardiothoracic Anesthesia
Victor A. Ferraris, M.D. [6] University of Pennsylvania Medical Center
Associate Professor, Department of Surgery Assistant Professor of Anesthesia, University of Pennsylvania
Albany Medical College Philadelphia, Pennsylvania
Albany, New York
Hartzell V. Schaff, M.D. [36]
Michael Fiocco, M.D. [43] Stuart W. Harrington Professor of Surgery
Attending, Division of Thoracic and Cardiovascular Surgery The Mayo Clinic
University of Maryland Hospital Rochester, Minnesota
Assistant Professor of Surgery
University of Maryland Frederick J. Schoen, M.D. [4]
Baltimore, Maryland Professor of Pathology, Harvard Medical School
Vice Chairman, Department of Pathology
Kirk J. Fleischer, M.D. [49] Director, Cardiac Pathology
Cardiac Surgery Research Fellow Brigham and Women's Hospital
The Johns Hopkins Hospital Boston, Massachusetts
Baltimore, Maryland
Hugh C. Smith, M.D. [15]
Oscar H. Frazier, M.D. [51] Consultant, Division of Cardiovascular Disease
Chief, Cardiopulmonary Transplantation The Mayo Clinic
Director, Surgical Research, Cullen Cardiovascular Rochester, Minnesota
Research Laboratories
The Texas Heart Institute Henry M. Spotnitz, M.D. [27]
Houston, Texas Vice Chairman, Department of Surgery
George H. Humphreys, II, Professor of Surgery
Bernard J. Gersh, M.D. [15] College of Physicians and Surgeons of Columbia University
Chief, Division of Cardiology New York, New York
W. Proctor Harvey Teaching Professor of Cardiology
Georgetown University Medical Center Russell F. Stahl, M.D. [12]
Washington, District of Columbia Assistant Professor
University of Massachusetts Medical Center
Donald D. Glower, M.D. [14, 24] Worcester, Massachusetts
Associate Professor of Surgery
W. Proctor Harvey Teaching Professor of Cardiology
Georgetown University Medical Center Russell F. Stahl, M.D. [12]
Washington, District of Columbia Assistant Professor
University of Massachusetts Medical Center
Donald D. Glower, M.D. [14, 24] Worcester, Massachusetts
Associate Professor of Surgery
Assistant Professor Biomedical Engineering Larry W. Stephenson, M.D. [1]
Duke University Medical Center Ford-Webber Professor of Surgery
Durham, North Carolina Chief, Division of Cardiothoracic Surgery
Wayne State
Leonard A. R. Golding, M.D. [11] University School of Medicine
Department of Biomedical Engineering Detroit, Michigan
The Cleveland Clinic Foundation
Cleveland, Ohio Christopher Stone, M.D. [38]
Associate Professor of Medicine
Randall B. Griepp, M.D. [40] Chief, Adult Cardiac Surgery
Professor and Chairman of Cardiothoracic Surgery Medical College of Georgia
Mount Sinai Medical Center Augusta, Georgia
New York, New York
Joseph R. Utley, M.D. [5]
Bartley P. Griffith, M.D. [48] Clinical Professor of Surgery
Chief, Division of Cardiothoracic Surgery Medical University of South Carolina
Presbyterian University Hospital Charleston, South Carolina
The Henry T. Bahnson Professor of Surgery University of South Carolina School of Medicine
University of Pittsburgh Medical School Columbia, South Carolina
Pittsburgh, Pennsylvania
Thomas J. Vander Salm, M.D. [12]
Robert A. Guyton, M.D. [3] Professor and Chairman
Professor of Surgery Thoracic and Cardiac Surgery
Chief, Division of Cardiothoracic Surgery University of Massachusetts Medical Center
Crawford-Long Hospital of Emory University Worcester, Massachusetts
Atlanta, Georgia
Andrew S. Wechsler, M.D. [28]
R. Alan Hall, M.D. [46] Co-Director, MCV Heart Center
Staff, Virginia Mason Medical Center Adult Cardiac Surgery
Seattle, Washington Professor and Chairman, Department of Surgery
Virginia Commonwealth University
Graeme L. Hammond, M.D. [44] Richmond, Virginia
Professor Surgery
Yale University School of Medicine Richard D. Weisel, M.D. [10]
New Haven, Connecticut Cardiovascular Surgeon, Associate Director
Centre for Cardiovascular Research
Alden H. Harken, M.D. [44] The Toronto Hospital
Professor and Chairman, Department of Surgery Professor of Surgery, Director, Surgical Research
University of Colorado Faculty of Medicine
Staff Surgeon, Cardiovascular Surgery University of Toronto
University of Colorado Health Sciences Center Toronto, Ontario, Canada
Staff Surgeon, Veterans Administration Hospital
Denver, Colorado Benson R. Wilcox, M.D. [2]
Steven C. Hendrickson, M.D. [14] University of North Carolina School of Medicine
Resident in Thoracic Surgery Chief, Division of Cardiothoracic Surgery
Duke University Hospital North Carolina Memorial Hospital
Durham, North Carolina Chapel Hill, North Carolina
Carl C. Hug, Jr., M.D. [8] James T. Willerson, M.D. [16]

Director, Cardiac Anesthesiology Medical Director, Texas Heart Institute
The Emory Clinic Chief of Adult Cardiology, St. Luke's Episcopal Hospital
Professor of Anesthesiology and Pharmacology Edward Randall III Professor of Medicine
Deputy Chairman for Research, Department of Chairman, Department of Internal Medicine
Anesthesiology The University of Texas-Houston Medical School
Emory University School of Medicine Houston, Texas
Atlanta, Georgia
David D. Yuh, M.D. [50]
Neil B. Ingels, Jr., Ph.D. [32] Postdoctoral Fellow in Cardiothoracic Surgery
Chairman, Department of Cardiovascular Physiology and Stanford University Medical Center
Biophysics Stanford, California
Research Institute of Palo Alto Medical Foundation
Consulting Professor of Cardiothoracic Surgery
Stanford University School of Medicine
Stanford, California
W. R. Eric Jamieson, M.D. [29]

University Heart Centre
Saint Paul's Hospital
Stanford University School of Medicine
Stanford, California
W. R. Eric Jamieson, M.D. [29]

University Heart Centre
Saint Paul's Hospital
University of British Columbia
Vancouver, British Columbia, Canada
Ellis L. Jones, M.D. [18]

Professor of Cardiothoracic Surgery
Emory University School of Medicine
Atlanta, Georgia
Mark E. Josephson, M.D. [25]

Director, Harvard-Thorndike Electrophysiology Institute and
Arrhythmia Services
Beth Israel Hospital
Professor of Medicine, Harvard Medical School
Boston, Massachusetts
The impact of this new book can quickly be inferred be looking at the authors of the
individual chapters. All are experienced practitioners of cardiac surgery or a related
discipline, and all are scholars vitally concerned with the generation of new and useful
information. This value is amplified many times over by the unique and outstanding
characteristics of the editor. Dr. Edmunds has not been a passive editor. Rather, his
knowledge, experience, and scholarly influence are evident in the organization of the
book and in the content of each chapter. This ubiquitous influence essentially
guarantees the reader that the time he or she spends with this book will generate a
bountiful reward in the form of new knowledge, new techniques, and new
understandings.
I do not wish to delay the reader's plunging into this valuable text with a long and boring
foreword. However, I must confess that I have favored, in books of this type, a focused
authorship involving only a few people. Close collaboration between the numerous
contributors and editor in this book is a step toward the concept that I favor. Yet, I realize
that others may fairly say that books generated by only a few authors would be better
with more authors, each addressing a smaller subject. We must confess that we don't
really know the relative merits of few or numerous authors or how well this book
synthesizes the two concepts.
All that we know is that it is a superb text. Is anything else important?
John W. Kirklin
The purpose of this book is to provide an authoritative, scholarly, and comprehensive
text of contemporary cardiac surgery in adult patients. The book is designed to
complement, rather than duplicate, available cardiology texts and to provide in-depth
information regarding the selection, management, and outcomes of patients for whom
surgery is a therapeutic option. The text emphasizes pathophysiology, preoperative and
intraoperative decision making, operative technics and management, postoperative
care, and short and long-term results. Difficult and controversial issues are reviewed
and squarely addressed with both rationale and data to support recommendations and
practices. Ample but selected references document each chapter and guide further
reading. New chapters, not found in standard texts, address such subjects as
preoperative evaluation, cardiac physiology applied to clinical cardiac surgery, risk
stratification, cardiac resuscitation, trauma, surgery for acute myocardial infarction,
reoperative revascularization, ischemic mitral insufficiency, the pathophysiology of
single and multiple valvular heart disease, and immunobiology of heart and lung
transplantation. The book provides the busy cardiac surgeon, cardiologist, and cardiac
anesthesiologist with comprehensive reviews of current surgical practice by recognized
experts.
This book reflects the explosive growth of adult cardiac surgery and cardiology during
the past four decades. In the beginning the same surgeons operated on both children
and adults, but in the 1970s pediatric and adult cardiac surgery began separate as
increasingly complex congenital and acquired heart diseases were addressed. While
sharing a common technology with pediatric surgery, rapid advances in the diagnosis
and treatment of acquired heart disease vastly expanded the population of treatable
patients and the menu of operative options. In the United States alone over one half
million patients currently have surgery for acquired heart disease each year, and this
number is expected to grow, since nearly one in four American adults has some form of
heart disease. Cardiac surgeons have kept pace; this book records their progress.
The editor thanks Ms. Mary Wittrock for her invaluable contributions, not only to the
assembly of this book, but for help with thousands of patients and projects for more than
two decades. Thanks also go to Ms. Myra Monahan, who patiently and exactly typed
and corrected edited manuscripts after they arrived, and to Mr. Ralph Curcio and Mr.
Joe Anello, who translated the disks into Microsoft Word. Messrs. Marty Wonsiewicz,
Rick Ruzycka, and Peter Boyle of McGraw-Hill merit my appreciation particularly for
accelerating production of this volume. I also thank my wife Martha Mel for, among other
things, her patience and encouragement during this period. Lastly, the editor thanks the
contributors, who took time from incredibly busy lives to set down their expert
knowledge for the benefit of colleagues, students, and, most importantly, patients. This
book is their book; at best an editor is a coach, and coaches don't score runs or
touchdowns.
[ Table of Contents ]
Chapter 1
HEART WOUNDS
OPERATIVE MANAGEMENT OF PULMONARY EMBOLI
SURGERY OF THE PERICARDIUM
CATHETERIZATION OF THE RIGHT HEART
HEART VALVE SURGERY BEFORE THE ERA OF CARDIOPULMONARY BYPASS
CONGENITAL CARDIAC SURGERY: PRE-HEART-LUNG MACHINE ERA
THE DEVELOPMENT OF CARDIOPULMONARY BYPASS
EXTRACORPOREAL LIFE SUPPORT
MYOCARDIAL PROTECTION
EVOLUTION OF CONGENITAL CARDIAC SURGERY DURING THE ERA OF CARDIOPULMONARY BYPASS
VALVULAR SURGERY: CARDIOPULMONARY BYPASS ERA
CORONARY ARTERY SURGERY
DYSRHYTHMIA SURGERY
PACEMAKERS
HEART, HEART-LUNG, AND LUNG TRANSPLANTATION
HEART ASSIST AND ARTIFICIAL HEARTS
THORACIC AORTA SURGERY
Chapter 2
OVERVIEW
Location of the Heart Relative to Surrounding Structures
The Pericardium and Its Reflections
Mediastinal Nerves and Their Relationships to the Heart
SURGICAL INCISIONS
Median Sternotomy
Bilateral Transverse Thoracosternotomy (Clam Shell Incision)
Anterolateral Thoracotomy
Posterolateral Thoracotomy
RELATIONSHIP OF THE CARDIAC CHAMBERS AND GREAT ARTERIES
CARDIAC CHAMBERS AND VALVES
Morphology of the Right Atrium and Tricuspid Valve
Appendage, vestibule, and venous component
Sinus node
Atrial septum
Atrioventricular septum and node: Triangle of Koch
Tricuspid valve
Morphology of the Left Atrium and Mitral Valve
Appendage, vestibule, and venous component
Mitral valve
Morphology of the Right Ventricle and Pulmonary Valve
Inlet and apical trabecular portions
Outlet portion and pulmonary valve
Supraventricular crest and pulmonary infundibulum
Morphology of the Left Ventricle and Aortic Valve
Inlet and apical trabecular portions
Outlet portion
Aortic valve
THE CORONARY ARTERIES
Main Stem of the Left Coronary Artery
Left Anterior Descending Artery
Circumflex Artery
Right Coronary Artery
THE CORONARY VEINS
Coronary Sinus and Its Tributaries
Anterior Right Ventricular Veins
Thebesian Veins
Chapter 3
SPECIAL ELECTRICAL AND MEMBRANE PROPERTIES OF CARDIAC CELLS
The Cell Membrane or Sarcolemma
Basic composition of the sarcolemma: The phospholipid bilayer
Sarcolemmal channels: Voltage-gated and ligand-gated
Energy-dependent ion pumps and ion exchange
T-Tubules and the Sarcoplasmic Reticulum
T-tubules
Subsarcolemmal cisternae
The sarcotubular network
Electrical Activation of the Heart
The negative resting membrane potential
Depolarization of the sarcolemma: The action potential
Spontaneous depolarization: Pacemaker activity
Propagation of action potential
Arrhythmias
Regulation of Cellular Function by Sarcolemma Receptor Proteins
Parasympathetic regulation
Adrenergic stimulation and blockade
Adenosine
Cardiac glycosides
Calcium-channel blockers
CONTRACTION OF CARDIAC MUSCLE
The Contractile Element (Sarcomere)
Excitation-Contraction Coupling
Regulation of the Strength of Contraction by Initial
Sarcomere Length
THE PUMP
Mechanics
The Frank-Starling relationship
Preload and diastolic distensibility (or compliance)
Afterload and aortic impedance
Pressure-volume loops
Clinical indices of contractility
Myocardial wall tension
Energetics
Chemical fuels
Determinants of oxygen consumption
CORONARY BLOOD FLOW
Normal Coronary Blood Flow
Control of Coronary Blood Flow
Coronary Artery Stenosis
Endothelial Dysfunction
The Sequelae of Myocardial Hypoperfusion: Infarction, Myocardial Stunning, Myocardial Hibernation
HEART FAILURE
Systolic and Diastolic Heart Failure
Early Systemic and Cardiac Sequelae of Heart Failure
The Late Sequelae of Congestive Heart Failure: The Vicious Cycle of Left Ventricular Remodeling and Dilatation
Chapter 4
GENERAL CONSIDERATIONS
Myocardial Hypertrophy
Atherosclerosis
Ischemic Myocardial Injury
Progression of damage
Effects of reperfusion
Biomaterial-Tissue Interactions
Blood-surface interaction
Tissue-surface interaction
Vascular graft healing
Infection
ISCHEMIC HEART DISEASE
Pathogenesis
Role of fixed coronary obstructions
Role of acute plaque change
Pathology of Coronary and Myocardial Interventions
Thrombolysis
Angioplasty, atherectomy and stents
Coronary artery bypass graft surgery
Transmyocardial laser revascularization
Myocardial Infarction and Its Complications
VALVULAR HEART DISEASE
Structure-Function Correlations in Normal Valves
Mitral valve
Aortic valve
Valve histology
Etiology and Pathologic Anatomy
Degenerative calcific aortic valve stenosis
Mitral annular calcification
Myxomatous degeneration of the mitral valve (mitral valve prolapse)
Rheumatic heart disease
Infective endocarditis
Valve Reconstruction
Mitral valve repair
Catheter balloon valvuloplasty
Surgical and laser debridement
Valve Replacement
Valve types and prognostic considerations
Valve-related complications
Valvular allografts/homografts
Pulmonary valvular autografts
New developments
MYOCARDIAL DISEASE
Cardiomyopathy
Dilated cardiomyopathy
Hypertrophic cardiomyopathy
Restrictive cardiomyopathy
Cardiac Transplantation
Early ischemic injury
Rejection
Infection
Graft vasculopathy (graft coronary disease or graft coronary arteriosclerosis)
Posttransplant lymphoproliferative disorders
CARDIAC ASSIST AND MECHANICAL REPLACEMENT
Cardiac Assist Devices and Total Artificial Heart
Skeletal Muscle Augmentation of Cardiac Function
NEOPLASTIC HEART DISEASE
Myxoma
Other Cardiac Tumors and Tumor-Like Conditions
Chapter 5
BASIC PREOPERATIVE EVALUATION
History
Present illness
Past history
Review of systems
Family history
Social history
Physical Examination
Vital signs
Head, eyes, ears, nose, and throat
Chest
Abdomen
Pelvic and rectum
Neurologic
Extremities
Skin
Blood Examination
Complete blood count
Electrolyte survey
Creatinine
Other blood measurements
Urinalysis
Chest X-Ray
Electrocardiogram
Cardiac Catheterization
Coronary arteriography
Selective angiography
Left ventriculogram
Right-sided heart catheterization
Aortogram
EMERGENCY AND URGENT OPERATION
FURTHER PREOPERATIVE EVALUATION
Cardiovascular Disease
Myocardial enzyme testing
Transthoracic echocardiography (TTE)
Transesophageal echocardiography (TEE)
Exercise testing
Thallium-201 and sestamibi myocardial imaging
Positron-emission tomography
Computed tomographic scans
Magnetic resonance imaging
Peripheral arterial studies
Duplex scans
Pulmonary Disease
Bedside spirometry
Pulse oximetry
Arterial blood gases
Ventilation-perfusion scanning
Smoking
Renal Disease
Serum creatinine
Creatinine clearance
Renal insufficiency
Prostatic hypertrophy
Neurologic Disease
Carotid arterial duplex scan
Brain CT or MRI scans
Gastrointestinal disease
Blood Disease
Endocrine Disease
Chapter 6
HISTORICAL PERSPECTIVES AND THE PURPOSE OF RISK STRATIFICATION
DEFINITIONS OF RISK STRATIFICATION AND COMORBIDITY
Arranging Patients According to Severity of Illness
Outcomes and Risk Stratification
Measures of Comorbidity
GOALS OF RISK STRATIFICATION
Improving the Quality of Care
Efficacy Studies versus Effectiveness Studies
Other Goals of Risk Stratification (Cost of Containment and Altering Physician Practices)
TOOLS OF RISK STRATIFICATION
Databases
Analytic Tools of Risk Stratification
Regression analysis
Statistics of Survival
Bayesian Analysis: Models Based on Experience
TOTAL QUALITY MANAGEMENT (TQM) AND RISK ANALYSIS
RISKS OF OPERATION FOR ISCHEMIA HEART DISEASE
Risk Factors for Mortality
Risk Factors for Outcomes Other than Mortality
RISKS OF OPERATION FOR VALVULAR HEART DISEASE
Risk Factors for Mortality and Morbidity
AORTIC SURGERY
Morbidity and Mortality Risks
OTHER CONSIDERATIONS AND CONCLUSIONS
Validity and Reliability of Risk-Stratification Methods
Risk Stratification to Measure the Effectiveness of Care
Ethical Implications of Risk Stratification: The Dilemma of Managed Care
The Costs of Gathering Data
WHAT DOES THE FUTURE HOLD?
New Risk Stratification Methods: Neural Networks
Information Management: Electronic Medical Records
CONCLUSIONS
Florence Nightingale , 1863
Chapter 7
PREOPERATIVE EVALUATION
MONITORING PHYSIOLOGICAL FUNCTIONS DURING ANESTHESIA
Measurement of Blood Pressure
Electrocardiogram (ECG)
Capnography
Pulse Oximetry
Measurement of Temperature
Measurement of Cardiac Output, Central Venous and Pulmonary Artery Pressures
Transesophageal Echocardiography
Anesthetic Gas Monitors
Measurement of Electrolyte Concentration
Monitoring the Nervous System
ANESTHESIA
Anesthetics and Neuromuscular Blockers
Inhaled anesthetics
Sedative hypnotics
Narcotic anesthetics
Neuromuscular blocking drugs
Local anesthetics
Special Anesthetic Techniques
Emergency airway management
Single lung ventilation
Regional anesthesia and analgesia
Controlling lumbar cerebral spinal fluid pressure
THE CONDUCT OF ANESTHESIA, SURGERY, NURSING, AND PERFUSION
ANESTHESIA IN THE IMMEDIATE POSTOPERATIVE PERIOD
Chapter 8
ANTIDYSRHYTHMICS
Class I Agents
Class Ia
Class Ib
Class Ic
Class II Agents
Class III Agents
Class IV Agents
Other Drugs
INOTROPIC AGENTS
VASOPRESSORS
VASODILATORS
Stimulation of Adenylate Cyclase (Cyclic AMP)
Nitrates and Stimulation of Guanylyl Cyclase (Cyclic GMP)
Dihydropyridine Calcium Channel Blockers
Phosphodiesterase Inhibitors
Angiotensin Convecting Enzyme (ACE) Inhibitors
ANTICOAGULANTS
Heparin
Warfarin (Coumadin)
Platelet Inhibitors
Fibrinolytics
PROCOAGULANTS
Heparin Reversal
Cardiovascular Manifestations of Protamine Reactions
Alternatives to Protamine
Recombinant Platelet Factor 4
Heparinase
Heparin Binding Filters
Pharmacologic Approaches to Decrease Bleeding Following CPB
Desmopressin acetate
Aprotinin
The lysine analog antifibrinolytic agents
Blood Products
BETA-ADRENERGIC RECEPTOR BLOCKERS
Clinical Indications
Angina pectoris
Acute myocardial infarction
Supraventricular tachycardias and ventricular dysrhythmias
Hypertension
Pheochromocytoma
Acute dissecting aneurysm
Other indications
Side Effects and Toxicity
Drug Interactions
DRUGS FOR AIRWAY MANAGEMENT
Airway Obstruction
Aspiration
Endotracheal Intubation
Normalizing Pulmonary Function During Intermittent Positive Pressure Ventilation
Restoration of Spontaneous Ventilation and Airway Protective Mechanisms
DIURETICS
Osmotic Diuretics
High Ceiling (Loop) Diuretics
Benzothiazides
Carbonic Anhydrase Inhibitors
Potassium-Sparing Diuretics
Other Measures to Enhance Urine Output and Mobilization of Edema Fluid
Chapter 9
COMPONENTS OF EXTRACORPOREAL
PERFUSION SYSTEMS
Venous Cannulae
Venous Reservoir
Oxygenator
Heat Exchanger
Pumps
Filters
Arterial Cannulas
Cardiotomy Suction System
Left Ventricular Venting System
Cardioplegia
Cell Saver
Perfusionist
MANAGEMENT OF CARDIOPULMONARY BYPASS
Assembly of Heart-Lung Machine
Priming
Anticoagulation
Protamine
Flow Rates and Pressures
Safety Monitors
Temperature
Deep Hypothermia and Circulatory Arrest
Retrograde cerebral perfusion
Dialysis and Ultrafiltration
Emergency Cardiopulmonary Bypass
Blood Conservation
OTHER APPLICATIONS OF EXTRACORPOREAL PERFUSION
Extracorporeal Life Support (ECLS)
Left Ventricular Assistance
PATHOLOGIC PHYSIOLOGY OF CARDIOPULMONARY BYPASS
Hemodynamics
Activation of Blood Constitutents
Adsorbed plasma proteins
Activation of blood elements
Consequences of Blood Activation During CPB
Bleeding
Emboli and thrombi
Vasoactive substances and hormones
Fluid balance
Organ dysfunction
OTHER COMPLICATIONS OF CPB
Massive Air Embolism
Arterial Catheters
Venous Cannulas
Pericardial Tamponade
Postpericardiotomy Syndrome
CONTROL OF THE COMPLICATIONS OF CPB
Substitutes for Heparin
Surface-bound heparin
Recombinant desulfatohirudin
Low-molecular-weight heparin
Factor Xa inhibitors
Platelet Anesthesia
Aprotinin
Other Protease Inhibitors
Chapter 10
INTRAOPERATIVE CARDIAC PHYSIOLOGY
Myocardial Oxygen Consumption
Aerobic versus Anaerobic Metabolism
Stunned Myocardium
Reperfusion Injury
PERIOPERATIVE ASSESSMENT OF MYOCARDIAL FUNCTION AND METABOLISM
Measurements of Systolic Function
Measurements of Diastolic Function
Measurements of Metabolism
Measurements of Cardioplegic Distribution
Clinical Outcome Measures
PRINCIPLES OF CARDIOPLEGIA
CONTEMPORARY RESULTS WITH HYPOTHERMIC FIBRILLATORY ARREST
BLOOD VERSUS CRYSTALLOID
THE OPTIMAL TEMPERATURE FOR CARDIOPLEGIA
ROUTE OF CARDIOPLEGIC DELIVERY
Antegrade
Retrograde
Combined Antegrade Retrograde Delivery
SUBSTRATE-ENHANCED CARDIOPLEGIA
Glucose-Insulin-Potassium
Glutamate-Aspartate for Urgent Surgery
Calcium-Channel Blockers
Antioxidants
Nitric Oxide
Ischemic Preconditioning
Aprikalim
Coenzyme Q10
Summary of Cardioplegic Additives
SYSTEMIC TEMPERATURE MANAGEMENT
pH-Stat versus Alpha-Stat Blood Gas Management
CEREBRAL PROTECTION
Profound Hypothermia
Low-Flow Cardiopulmonary Bypass
Cerebroplegia
Retrograde Cerebral Perfusion
MANAGEMENT OF THE DISEASED AORTA
SUMMARY
Chapter 11
COUNTERPULSATION
Historical Notes
Physiology
Indications
Techniques of Insertion
Complications
Results
DIRECT CIRCULATORY SUPPORT
Continuous Flow Pumps
Pumps
Extracorporeal membrane oxygenation (ECMO)
Left, right, and biventricular assist devices
Complications
Results
Hemopump
Temporary Pulsatile Pumps
Abiomed BVS 5000
Thoratec ventricular assist device
MECHANICAL VENTRICULAR COMPRESSION
Chapter 12
OVERVIEW OF MAJOR DERANGEMENTS
INFLAMMATORY RESPONSE OF CARDIOPULMONARY BYPASS
COMPLICATIONS: ANTICIPATION AND TREATMENT
HEART
Minimal Requirements
Determinants of Cardiac Output
Perioperative Causes of Left Ventricular Dysfunction
Thyroid hormone
Pericardial tamponade
Support of Cardiac Performance
Pharmacologic support
Mechanical circulatory support
BLEEDING
Causes
Predisposition to bleeding
Mechanical, anatomic, or surgical causes
Bleeding diathesis
Diagnosis
Treatment
Intraoperative technique: Prevention
Intraoperative: Pharmacologic manipulation
Reinfusion of shed blood
Volume replacement
Blood factor replacement
Other methods of controlling bleeding
Reexploration for Bleeding
LUNG
Initial Assessment
Pulmonary Dysfunction
Pulmonary effects of cardiopulmonary bypass
Phrenic palsy
Other causes
Ventilation
Initial management: Ventilator settings
Maintenance
Ventilator weaning
Weaning criteria
Postextubation support
Reintubation
Complications
Long-Term Ventilator Support
Causes of failure to wean from mechanical ventilation
Weaning after prolonged mechanical ventilation
Weaning techniques
Tracheostomy
General care
KIDNEY
Adequacy of Postoperative Renal Function
Criteria for Postoperative Renal Dysfunction
Causes of Postoperative Renal Dysfunction
Temporary Renal Support
Pharmacologic support
Dialysis and ultrafiltration
Renal Failure: Prognosis
NERVOUS SYSTEM
Central Neurologic Complications
Neuropsychologic Complications
Peripheral Deficits
GASTROINTESTINAL SYSTEM
PROPHYLACTIC ANTIBIOTICS
Chapter 13
ANESTHESIA AND MONITORING
Timing Invasive Monitoring
Airway
Anesthetic Agents
Allergic Reactions
Monitors
Arterial catheters
Central venous catheters
Pulmonary arterial monitoring
NONSPECIFIC COMPLICATIONS
Thoracostomy Tubes
Temporary Epicardial Pacemaker Leads
Great Vessel and Thoracic Duct Injuries
Vena cava and left innominate vein
Pulmonary vessels
Aortic false and mycotic aneurysms
Aortic dissection
Atherosclerotic aortic emboli
Thoracic duct
Cardiopulmonary Bypass
Pulmonary Embolism
Wounds
Sternal wires
Sterile wound dehiscence
Superficial wound infection
Deep wound infection
COMPLICATIONS SPECIFIC TO ORGAN SYSTEM
Heart and Pericardium
Supraventicular Arrhythmias
Ventricular arrhythmias
Conduction disturbances
Perioperative myocardial infarction
Early and late pericardial tamponade
Constrictive pericarditis
Postcardiotomy syndrome
Chest, Lung and Airway
Pneumothorax
Hemothorax
Late airway injuries
Pneumonia
Phrenic nerve injury
Chronic ventilatory dependence
Adult Respiratory Distress Syndrome (ARDS)
Kidney
Acute renal failure
Complications associated with chronic renal failure
Peripheral Vascular Complications
Gastrointestinal Tract
Gastrointestinal bleeding
Perforated ulcer
Biliary complications
Pancreatitis/hyperamylasemia
Ischemic colitis
Diverticulitis
Liver
Blood
Nervous System
Central nervous system
Peripheral nerve injuries
Neuropsychologic changes
Chapter 14
BACKGROUND
HISTORY OF CARDIAC RESUSCITATION
CARDIOPULMONARY RESUSCITATION (CPR)
Airway
BLS airway management
Advanced airway management
Breathing
Closed Chest Massage
Technique
Hemodynamics
Assessment of ongoing cardiac massage
Complications of closed chest massage
CARDIAC ARREST
Ventricular Fibrillation/Ventricular Tachycardia
Treatment
Prognosis
Asystole
Treatment
Prognosis
Electromechanical Dissociation/Pulseless Electrical Activity Treatment
DEFIBRILLATION
Energy Requirements
Transthoracic Impedance
Defibrillation Threshold
Special Situations
New Techniques of Defibrillation
Precordial Thump
PHYSIOLOGY OF CLOSED CHEST CARDIAC MASSAGE
Mechanism of Blood Flow
ALTERNATIVE TECHNIQUES AND MECHANICAL ADJUNCTS TO CPR
Simultaneous Compression/Ventilation
Interposed Abdominal Compression (IAC) CPR
High-Impulse CPR
Pneumatic Antishock Garment/Abdominal Binder
Pneumatic Vest
Active Compression Decompression (ACD)
Intraaortic Balloon Pump (IABP)
Direct Mechanical Ventricular Actuation (DMVA)
OPEN CARDIAC MASSAGE (OCM)
Technique
Hemodynamics
Results of OCM
Complications
Role of OCM in Cardiac Resuscitation
PHARMACOLOGY OF RESUSCITATION
Route of Administration
Resuscitation Medications
Supplemental oxygen
Intravenous fluids
Alpha-adrenergic agonists
Antiarrhythmics
Other agents
CEREBRAL PROTECTION/RESUSCITATION
Postresuscitation Cerebral Care
OUTCOME
In-Hospital Cardiac Arrest
Predictors for in-hospital cardiac resuscitation
Out-of-Hospital Cardiac Arrest
Predictors for out-of-hospital cardiac resuscitation
Chapter 15
CHRONIC STABLE ANGINA
CABG Surgery versus Medical Therapy
Survival
Other benefits
PTCA versus Medical Therapy
PTCA versus CABG Surgery
Single-vessel disease
Indications for coronary revascularization in patients with single-vessel disease
Multivessel disease
Results
Left ventricular dysfunction
Current indications for PTCA and CABG in patients with multivessel disease
ACUTE CORONARY SYNDROMES
CABG versus Medical Therapy
Revascularization for Unstable Angina
PTCA for Acute Myocardial Infarction
INDICATIONS FOR REVASCULARIZATION
Chapter 16
THROMBOLYSIS FOR ACUTE MYOCARDIAL INFARCTION
Background
Thrombolytic Agents
Streptokinase
Tissue Plasminogen Activator (Activase)
Anisoylated Plasminogen Streptokinase Activator
Complex (Eminase)
Urokinase
Prognostic Criteria
Indications for thrombolysis
Contraindications
Choice of thrombolytic agent
Thrombolysis with Other Treatment Strategies
Early invasive vs early conservative strategies: TIMI IIIB
Angioplasty and Thrombolytic Therapy
Gender
Cost
PERCUTANEOUS TRANSLUMINAL CORONARY
ANGIOPLASTY
Indications for PTCA
Contraindications
Surgical Backup for PTCA
Single-Vessel Coronary Artery Disease
Angioplasty vs Surgery
Complications of Angioplasty
Abrupt vessel closure
Restenosis
MECHANISMS OF RESTENOSIS
PREVENTION OF RESTENOSIS
Arterial Remodeling
Lipid-lowering agents
Platelet inhibitors
ALTERNATIVE APPROACHES TO CONVENTIONAL
BALLOON ANGIOPLASTY
Stents
Palmaz-Schatz stent
Gianturco-Roubin stent
Directional Coronary Atherectomy
Rotablator
THE FUTURE IN ALTERNATIVE CORONARY
INTERVENTIONS
Chapter 17
VEIN GRAFTS
Sources of Vein
Harvesting Techniques
Histology of Harvested Vein
The vein wall
Endothelium
Reactivity to chemical agonists
Distal Anastomosis
Arteriotomy site
Arteriotomy incision
End-to-side anastomosis
Order of preference for distals
Y anastomosis
Vein-patch angioplasty
Side-to-side anastomoses
Y grafts
Proximal Anastomosis
Selection of aortic sites
Timing proximal anastomosis
Proximal anastomotic technique
Solutions to problems
Single versus Multiple Touchdowns (Sequential Grafts) versus Y Grafts
Advantages
Disadvantages
Patency rates
Occlusion of Vein Grafts
Early graft closure (1 month)
Graft failure from 1 to 12 months
Graft behavior from 1 to 5 years
Graft failure beyond five years
Graft atherosclerosis
PEDICLED ARTERIAL GRAFTS
Internal (Mammary-Thoracic) Artery (ITA)
Harvesting techniques
Histology
Response to agonists
Flow Capacity
Distal Anastomosis
Coronary vessels
Technique
Side-to-side anastomosis
Indications and contraindications
Y Grafts
T grafts
Angioplastic Anastomosis
Composite Graft with Vein
Conduit Failure
Conduit patency
Technical errors
OTHER PEDICLED ARTERIAL CONDUITS
Gastroepiploic
Harvest technique
Routes to the pericardium
Histology and response to agonists
Patency rates
FREE ARTERIAL GRAFTS
Internal Thoracic Artery
Storage after harvest
Technique of proximal anastomosis
Chapter 18
INDICATIONS FOR OPERATION
Preinfarction Ischemia
Acute Myocardial Infarction
Postthrombolytic operative intervention
Effect of age
PREOPERATIVE DATA GATHERING
History and Physical Examination
Risk Factors/Risk Stratification
Medications
Laboratory Investigations
Other Tests
Blood Bank Protocols
Preoperative Viability Testing
Myocardial bridging
Right ventricular infarction
Coexisting conditions
Determination of graftable vessels
CHOICE OF CONDUIT
In Situ Arterial Grafts
Internal mammary preparation
Other Arterial Grafts
Internal mammary artery free graft
Right internal mammary artery graft
Gastroepiploic artery graft
Inferior epigastric artery graft
Radial artery graft
Saphenous Vein Grafts
Greater saphenous vein
Lesser saphenous vein
Other Grafts
Endarterectomy
Intraoperative Angioplasty and Laser
General Strategy for Graft Usage
CONDUCT OF THE PROCEDURE
Before Cardiopulmonary Bypass
Antibiotics
Carotid endarterectomy
Epivascular echocardiography
Cardioplegia
Distal Anastomoses
Weaning from Cardiopulmonary Bypass
Choice of inotropes
Failure to wean
Secondary cardioplegia
Mechanical ventricular assist
Open chest
Special Circumstances
Preoperative stroke
Preoperative gastrointestinal hemorrhage
Cryoglobulins
Religious objection to blood transfusion
Heparin-induced thrombocytopenia and thrombosis
Postoperative Bleeding
Rational Use of Blood Products
POSTOPERATIVE HEMODYNAMIC MEASUREMENTS
POSTOPERATIVE RESPIRATORY MANAGEMENT
Anesthetic Management
POSTOPERATIVE ICU CARE
Chapter 19
PATHOLOGY
Mural thrombus
Intimal fibroplasia
Vein graft atherosclerosis
Incidence of stenosis
INDICATIONS FOR REOPERATION
Does Reoperation Prolong Survival?
Interventional Cardiology
Summary of Current Indications
TECHNICAL ASPECTS OF CORONARY REOPERATIONS
Preoperative Assessment
Median Sternotomy, Conduit Preparation, and Cannulation
Cardioplegia
Pericardial Dissection
Stenotic Vein Grafts
Arterial Grafts
Arterial Graft Replacement of a Vein Graft
Alternative Arterial Grafts
Proximal Anastomoses
ALTERNATIVE APPROACHES TO CORONARY REOPERATIONS
Management of the Bad Aorta during Reoperation
Management without cardiopulmonary bypass
Deep hypothermia and circulatory arrest
Reoperations via Left Thoracotomy
Minimally Invasive Reoperation
RESULTS OF CORONARY REOPERATIONS
LATE RESULTS
MULTIPLE CORONARY REOPERATIONS
CONCLUSION
Chapter 20
PERIOPERATIVE STROKE
Incidence of Perioperative Stroke
Causes of Perioperative Stroke
Relationship of Carotid Stenosis to Perioperative Stroke
Mechanism of Perioperative Stroke with Carotid Stenosis
Relationship of Uncorrected Carotid Stenosis to Late Stroke
CAROTID STENOSIS IN CORONARY ARTERY BYPASS PATIENTS
Incidence of Carotid Stenosis in Coronary Artery Bypass Patients
Diagnosis of Carotid Artery Disease
Physical examination
Noninvasive testing
Indications for noninvasive testing
Direct carotid angiography
Magnetic resonance angiography
Definition of Severe Carotid Stenosis
EFFICACY OF CAROTID ENDARTERECTOMY AS A TREATMENT FOR CAROTID STENOSIS
Carotid Endarterectomy for Symptomatic Carotid Stenosis
Carotid Endarterectomy for Asymptomatic Carotid Stenosis
MYOCARDIAL ISCHEMIC EVENTS IN PATIENTS WITH CAROTID ARTERY DISEASE
Incidence of Coronary Artery Disease in Carotid Endarterectomy Patients
Risk of Myocardial Ischemic Events
Short-term risks
Long-term risks
TIMING OF CAROTID AND CORONARY SURGERY
Staged Carotid and Coronary Operations
Concomitant Carotid and Coronary Operations
OPERATIVE TECHNIQUES FOR CONCOMITANT CAROTID AND CORONARY OPERATIONS
Standard Approach
Alternate Approaches
HIGHLIGHTS OF POSTOPERATIVE MANAGEMENT
RESULTS OF STAGED AND CONCOMITANT CAROTID AND CORONARY ARTERY OPERATIONS
Early Results
Staged carotid and coronary operations
Concomitant carotid and coronary operations
Late Results
SUMMARY
Chapter 21
PATHOGENESIS OF ACUTE OCCLUSION
CARDIOGENIC SHOCK
Definition
Prevalence
Infarct Size Relationship to Shock
MEDICAL MANAGEMENT MYOCARDIAL INFARCTION
Medical Treatment of Cardiogenic Shock
STATES OF IMPAIRED MYOCARDIUM
Hibernating Myocardium
Stunned Myocardium
Diagnosis of Viable Myocardium
Treatment of Stunned Myocardium
Summary
RATIONALE FOR AGGRESSIVE MANAGEMENT OF MYOCARDIAL INFARCTION
REPERFUSION
Methods of Reperfusion
Role of thrombolytic therapy
Role of PTCA
Stents and atherectomy
Role of coronary artery bypass grafting (CABG)
USE OF THE INTRAAORTIC BALLOON PUMP
ROLE OF CIRCULATORY ASSIST
Weaning of Circulatory Support
Ethical Considerations
SURGICAL MANAGEMENT
Columbia-Presbyterian Approach
Operative Techniques for Acute Myocardial Infarction
Preoperative
Anesthesia
Bleeding
Choice of conduits
Intraoperative considerations
Postoperative care
CONCLUSION
Chapter 22
DEFINITIONS
POSTINFARCTION VENTRICULAR SEPTAL DEFECT
History
Incidence
Pathogenesis
Pathophysiology
Diagnosis
Natural History
Management
Preoperative Therapy
Operative Techniques
General techniques
Apical septal rupture
Anterior septal rupture
Posterior septal rupture
Endocardial patch repair with infarct exclusion
Other techniques
Percutaneous closure
Simultaneous Myocardial Revascularization
Management of Bleeding
Highlights of Postoperative Care
Operative Mortality
Long-Term Results
Recurrent Ventricular Septal Defects
Chronic Ventircular Septal Defects
POSTINFARCTION VENTRICULAR FREE WALL RUPTURE
History
Incidence
Pathogenesis and Pathophysiology
Diagnosis
Natural History
Preoperative Management
Subacute rupture of the free wall
False aneurysm of the left ventricle
Results
Subacute rupture of the free wall
False aneurysm of the left ventricle
Chapter 23
PREVALENCE
PATHOLOGY
PATHOPHYSIOLOGY
NATURAL HISTORY
CLINICAL PRESENTATIONS
Acute Postinfarction Mitral Regurgitation
Pathophysiology
Clinical presentation
Diagnostic studies
Medical management
Definitive therapy
Operation
Results
Episodic Ischemic Mitral Regurgitation
Chronic Ischemic Mitral Regurgitation
Pathophysiology
Diagnostic studies
Indications for surgery
Operation
Results
CONCLUSIONS
Chapter 24
DEFINITION
HISTORY
INCIDENCE
ETIOLOGY
PATHOPHYSIOLOGY
Early Expansion Phase
Late Remodeling Phase
NATURAL HISTORY
CLINICAL PRESENTATION
DIAGNOSIS
PREPARATION FOR OPERATION
OPERATIVE TECHNIQUES
General
Plication
Linear Closure
Circular Patch
Endoventricular Patch
Coronary Revascularization
Mitral Regurgitation
Ventricular False Aneurysm
Ventricular Rupture
EARLY RESULTS
Hospital Mortality
In-Hospital Complications
Left Ventricular Function
LATE RESULTS
Survival
Symptomatic Improvement
Chapter 25
ABNORMALITIES OF CARDIAC IMPULSE FORMATION AND CONDUCTION
Physiology and Anatomy of the Cardiac Conduction System
Cellular physiology
Conduction system anatomy
Bradyarrhythmias
Abnormal impulse formation
Abnormal impulse transmission
Tachyarrhythmias
Automaticity
Reentry
Triggered activity
Common types of clinical arrhythmias
DIAGNOSIS OF CARDIAC ARRHYTHMIAS
Clinical symptoms
Noninvasive Methods
The resting electrocardiogram
Ambulatory electrocardiogram (also known as Holter monitoring)
Event monitors (EM)
Exercise (stress) testing
Signal-averaged ECG (SAECG)
Invasive Methods
Electrophysiologic (EP) study
Endocardial mapping
THERAPEUTIC CHOICES FOR CARDIAC ARRHYTHMIAS
Pharmacologic
Historical overview
Bradyarrhythmias
Tachyarrhythmias
Pacemakers
Background and indications
Types and modes of pacing
Catheter ablation
Historical overview
Techniques
Implantable Defibrillators
Historical overview
Features
Problems associated with ICD therapy
Results
Surgery
Historical overview
Wolff-Parkinson-White syndrome and concealed bypass tracts
AV nodal reentry
Atrial fibrillation (AF)
Postinfarction uniform sustained VT
Ventricular fibrillation (and rapid polymorphic VT)
ARRHYTHMIAS RESULTING FROM CARDIAC SURGICAL PROCEDURES
Bradyarrhythmias and Conduction Disturbances
Sinus node injury
Damage to AV conduction
Bundle branch block
Supraventricular Tachyarrhythmias
Postoperative atrial fibrillation
Atrial flutter and intraatrial reentrant tachycardia
Accelerated junctional rhythm/junctional tachycardia
Ventricular Tachyarrhythmias
Uniform sustained ventricular tachycardia
Ventricular fibrillation
CONCLUSIONS
Chapter 26
Cardiac Anatomy
Embryology of conduction tissues
Embryology of the atrioventricular (AV) groove
Embryology of the atrial septum and ventricular septum
Anatomy of the Mature Conduction System
Anatomic Principles Pertaining to Ablative Therapies for Supraventricular Arrhythmias
The horizontal plane
The atrial septum
The vertical plane
The posterior septal space
Other conditions
Anatomic Principles Pertaining to Ablative Therapies for Ventricular Arrhythmias
Nonischemic ventricular tachycardias
Ischemic ventricular tachycardias
INTRACARDIAC AND EPICARDIAL MAPPING OF ARRHYTHMIAS
Epicardial Intraoperative Mapping Techniques
Ventricular Arrhythmias
THERAPY FOR SUPRAVENTRICULAR ARRHYTHMIAS
AV Reentrant Tachycardia
Left free-wall accessory pathways
Posterior septal accessory pathways
Right free-wall accessory pathways
Anterior septal accessory pathways
Results
Surgical intervention following failed RF ablation
AV Nodal Reentrant Tachycardia
Cryosurgical modification of the AV node
Surgical dissection
Automatic Atrial Tachycardia: Surgical Ablation
Atrial Flutter
Atrial Fibrillation
Previous surgical therapies for atrial fibrillation
The Maze procedure
Results of technical modifications to the Maze procedure
Current results with the Maze III procedure
Modifications of the Maze procedure and rheumatic mitral valve disease
The left atrial isolation procedure
ABLATIVE THERAPY FOR NONISCHEMIC AND ISCHEMIC VENTRICULAR TACHYCARDIA
Nonischemic Ventricular Tachycardia
Surgical techniques
Ischemic Ventricular Tachycardia
Direct Surgery: Indications
Surgical Techniques
Surgical Results Pre-ICD
Surgical Results Post-ICD
Role of ICD in Direct Surgical Candidates with Ventricular Tachycardia
ICD Therapy in Ischemic Ventricular Tachycardia
VT Surgery versus ICD Therapy versus Catheter Ablation
Cost Issues: VT Surgery versus ICD Therapy
Chapter 27
PACEMAKERS
History
International Pacemaker Code
Anatomic Factors
Physiology
Cellular electrophysiology
AV block
Sinus node dysfunction
Dual-chamber pacing and AV synchrony
Rate response to increased metabolic demand
Clinical Considerations
Indications for pacemaker insertion
Choice of pacing technique
Technical Considerations
Temporary pacing
Polarity and rate in temporary pacing
Permanent Pacing
Device description
Dual chamber pacing algorithm
Epicardial/endocardial leads
Unipolar/bipolar
Lead fixation
Technique of Pacemaker Insertion
Equipment/environment
Anesthesiology
Monitoring
Antibiotic prophylaxis
Pacing-systems analyzer
Cables
Fluoroscopy
Venous access
Pacemaker insertion
Pacemaker generator replacement
Wound care
Length of Stay After Pacemaker Implantation
Ambulatory surgery
Pacemaker-dependent patients
Results
Mortality
Complications
Postoperative testing/follow-up
Pacemaker Programming
Computer Support
Innovations and Special Problems
Atrial fibrillation/mode switching in dual-chamber pacing
Pacemaker-mediated tachycardia in dual-chamber pacing
Evaluation/identification of pacemakers before general surgery
Electrocautery
Magnet mode
Steroid-eluting leads
Adults with congenital heart disease
Pacing in infants and children
Dementia
AV-node ablation
Transplant recipients
Implantable cardiac defibrillator (ICD) recipients
Long Q-T syndrome
Idiopathic hypertrophic subaortic stenosis (IHSS)
Environmental Issues
Electromagnetic interference
Chapter 28
EMBRYOLOGIC DEVELOPMENT
ANATOMY
BIOMECHANICAL PROPERTIES
Mechanics of Movement
Opening
Closing
Rheology
AORTIC STENOSIS
Rheology
Hemodynamics
Calculation of Valve Area
The Gorlin formula
The continuity equation
Ventricular Adaptations
Molecular effects
Diastolic function
Systolic function
Coronary blood flow
Mechanisms of Symptoms and Signs
Indications for Operation
AORTIC REGURGITATION
Indications for Surgery
CONCLUSION
Chapter 29
MORPHOLOGY
Aortic Stenosis
Aortic Regurgitation
Combined Aortic Stenosis/Regurgitation
CLINICAL FEATURES AND DIAGNOSIS
Aortic Stenosis
Aortic Stenosis/Regurgitation
PATHOPHYSIOLOGY
Aortic Stenosis
NATURAL HISTORY
Aortic Stenosis
INDICATIONS FOR AORTIC VALVE REPLACEMENT
Aortic Stenosis
Combined Aortic Stenosis/Regurgitation
TECHNIQUE OF OPERATION
Choice of Operation and Replacement Device
Perioperative Preparation
Anaesthetic Considerations
Myocardial Protection Techniques
Postoperative Care
Aortic Valve Replacement
Aortotomy
Operation
Mechanical prosthesis
Stented bioprosthesis
Stentless bioprosthesis
Allograft aortic valve
Replacement of the Aortic Valve and Ascending Aorta
Prosthetic valve cylinder
Allograft aortic valve cylinder
Pulmonary autograft cylinder
Replacement Ascending Aorta with and Preservation of Aortic Valve
Reoperative Replacement of the Prosthetic Aortic Valve
Reoperative Replacement of the Ascending Aortic Graft and Prosthetic Valve
Aortic Valve Replacement with Myocardial Revascularization
Predictors of Operative Risk
Special Surgical Considerations
Aortic root enlargement
Aortic root reduction
Reparative aortic valve surgery
Percutaneous balloon aortic valvuloplasty
Functional mitral incompetence with aortic valve disease
Calcified porcelain ascending aorta
Conduction defects
Right coronary artery injury
Aortic Valve Replacement Devices
Mechanical prostheses
Stented bioprostheses
Stentless bioprostheses
Hemodynamic characteristics
Technical considerations
CHOICE OF PROSTHESES: ADVANTAGES AND DISADVANTAGES
Mechanical Prostheses
Xenograft Bioprostheses
Allografts
Autografts
Chapter 30
CELLULAR AND IMMUNOLOGIC CHARACTERISTICS OF ALLOGRAFTS
MECHANICAL CHARACTERISTICS OF ALLOGRAFTS
ALLOGRAFT PROCUREMENT AND PRESERVATION TECHNIQUES
TECHNICAL CONSIDERATIONS
TECHNIQUES OF ALLOGRAFT AORTIC VALVE REPLACEMENT
Indications and Contraindications
Preoperative Evaluation
Cannulation
Myocardial protection
Aortotomy
Excision of the native valve, debridement of the annulus, and sizing
Trimming of the allograft
Free-Hand 120-Degree-Rotation Two-Suture-Line Technique
Free-Hand Intact Noncoronary Sinus Two-Suture-Line Technique
Aortic Root Replacement Technique
Aortic Root Inclusion Technique (Miniroot)
Assessment of Competence of the Allograft Valve Replacement
AORTIC ROOT REPLACEMENT WITH PULMONARY AUTOGRAFTS
Indications
Contraindications
Operative Procedure
Cannulation and myocardial protection
Aortotomy, excision of the native aortic valve and preparation of the aortic root
Harvesting the pulmonary valve
Allograft root implantation
Reconstruction of right ventricular outflow tract
Deairing, weaning from cardiopulmonary bypass, and testing the valve replacement
ALLOGRAFT AND AUTOGRAFT RESULTS
Early and Long-Term Survival
Allograft Valve Failure
Contemporary Era
Valve-Related Complications
CONCLUSION
Chapter 31
AORTIC VALVE REPLACEMENT IN PATIENTS WITH A SMALL AORTIC ANNULUS
Aortic Valve Replacement with Stentless Biological Valves
Implantation of a Prosthetic Valve in a Supraannular Position
Path Enlargement of the Aortic Annulus along the Noncoronary Aortic Sinus
Patch Enlargement of the Aortic Annulus along the Interventricular Septum
Clinical Results
ENDOCARDITIS OF THE AORTIC VALVE
Pathogenesis
Clinical Presentation and Diagnosis
Treatment
Surgery for Infective Endocarditis of the Aortic Valve
Clinical Results
Operative Technique
Reimplantation of the aortic valve
Remodeling the aortic root with angioplasty
Clinical Results
MYECTOMY FOR HYPERTROPHIC CARDIOMYOPATHY
Septal Myectomy
Clinical Results
AORTIC VALVE REPLACEMENT WITH STENTLESS PORCINE AORTIC VALVE
Operative Technique
Clinical Results
I do not use systemic hypothermia unless circulatory arrest is necessary.
Chapter 32
THE NORMAL MITRAL VALVE
Anatomy
Annular Size, Shape, and Dynamics
Dynamic Leaflet Motion
Chordae Tendineae and Papillary Muscles
MITRAL STENOSIS
Etiology
Hemodynamics
Ventricular Adaptation
Atrial Adaptation
Pulmonary Changes
Symptoms
Diagnostic Evaluation
Chest radiography
Electrocardiography
Echocardiography
Cardiac catheterization
Medical Therapy
Indications for Surgery and Postoperative Outcome
Summary
MITRAL REGURGITATION
Etiology
Myxomatous degeneration
Rheumatic disease
Papillary muscle dysfunction
Mitral annular calcification
Hemodynamics
Atrial Adaptation
Pulmonary Changes
Symptoms
Chest radiography
Electrocardiography
Echocardiography
Magnetic resonance imaging
Medical Therapy
Predictors of Postoperative Outcome
Postoperative Changes in Left Ventricular Function
Summary
Chapter 33
HISTORICAL PERSPECTIVE
PATHOPHYSIOLOGY OF MITRAL VALVE DISEASE
Left Ventricular Volume Overload
Reduced Cardiac Output
Left Atrial Enlargement
Atrial Arrhythmias
Left Atrial Thrombus
Pulmonary Congestion
Pulmonary Hypertension
Natural History
SURGICAL ANATOMY OF THE MITRAL VALVE
Leaflets
Annulus
Chordae Tendineae
Papillary Muscles
Left Ventricle
DYNAMICS OF THE NORMAL MITRAL VALVE
INDICATIONS AND CONTRAINDICATIONS TO MITRAL VALVE REPAIR
Mitral Insufficiency
Mitral Stenosis
PREOPERATIVE EVALUATION OF MITRAL VALVE DISEASE
Clinical findings
Echocardiographic assessment
Mitral Stenosis
Clinical findings
Echocardiography
PREOPERATIVE PREPARATION
OPERATION
Anesthetic and Monitoring
Methods to Expose the Mitral Valve
Alternative Methods to Expose the Mitral Valve
ASSESSMENT OF THE MITRAL VALVE FOR REPAIR
TYPES OF MITRAL VALVE DISEASE
Degenerative Mitral Valve Disease
Chordal shortening
Chordal transfer
Chordal replacement
Annuloplasty
Rheumatic Valvulitis
Ischemic Mitral Insufficiency
Bacterial Endocarditis
Frequency of Mitral Valve Repair
COMPLEX PROBLEMS IN MITRAL VALVE REPAIR
Commissural Prolapse
Left Ventricular Outflow Tract Obstruction and Systolic Anterior Motion (SAM)
Deficient Leaflet Tissue
Calcified Mitral Annulus
ASSESSMENT AFTER REPAIR BEFORE CLOSURE OF THE ATRIUM
HIGHLIGHTS OF POSTOPERATIVE CARE, SPECIAL CONSIDERATIONS, OR CONCERNS
RESULTS
Hospital Mortality
Long-Term Results
Chapter 34
INDICATIONS FOR MITRAL VALVE REPLACEMENT
Mitral Stenosis
CHOICE OF VALVE TYPE
Indications for Bioprosthetic Valves
Indications for Mechanical Valves
HEMODYNAMICS OF PROSTHETIC MITRAL VALVES
HEMODYNAMICS OF BIOPROSTHETIC VALVES
Anesthetic Preparation and Management of Cardiopulmonary Bypass for Mitral Valve Replacement
Exposure of the Mitral Valve
Intracardiac Technique
Weaning off Cardiopulmonary Bypass
Postoperative Care
RESULTS
Early Results
Late Results
Functional improvement
Survival
Late Morbidity
Thromboembolism
Anticoagulant hemorrhage
Structural valve degeneration
Perivalvular leak
Endocarditis
CONCLUSIONS
Chapter 35
PATHOPHYSIOLOGY
DIAGNOSIS
SURGICAL DECISION MAKING
Tricuspid Valve Reconstruction
Tricuspid Valve Annuloplasty Repair
Bicuspidization repair
DeVega repair
Carpentier repair
Intraoperative assessment of tricuspid valve repair
Tricuspid Valve Replacement
Interventions for Endocarditis
POSTOPERATIVE SURGICAL HEART BLOCK
RESULTS: DEBORAH HEART AND LUNG CENTER DATA
Patient Population and Procedures
Comparison of tricuspid repair versus replacement groups
Mortality
Hospital death
Late death
Morbidity
Early events
Late events
Reoperation
Tricuspid Valve Excision
CONCLUSION
Chapter 36
PATHOPHYSIOLOGY OF MULTIPLE VALVE DISEASE
Primary Aortic Valve Disease with Secondary Mitral Regurgitation
Tricuspid Valve Regurgitation Secondary to Other Valvular Disease
VALVE SELECTION FOR MULTIPLE VALVE REPLACEMENT
SURGICAL METHODS
Aortic and Mitral Valve Replacement
Cannulation
Cardioplegia
Procedure
Aortic Valve Replacement and Mitral Valve Repair
Mitral Valve Replacement and Tricuspid Valve Replacement or Repair
Procedure
Tricuspid Valve Replacement and Pulmonary Valvotomy for Carcinoid Heart Disease
Triple Valve Replacement
RHEUMATIC HEART DISEASE AFFECTING MULTIPLE VALVES
Introduction
Rheumatic Mitral Stenosis with Rheumatic Aortic Regurgitation
Diagnosis, signs, and symptoms
Pathophysiology of mitral stenosis with aortic regurgitation
Operative decision making
Rheumatic Mitral Stenosis with Rheumatic Aortic Stenosis
Pathophysiology of combined mitral and aortic stenosis
Rheumatic Mitral Regurgitation with Rheumatic Aortic Regurgitation
Pathophysiology of mitral regurgitation with aortic regurgitation
MYXOMATOUS AND PROLAPSING VALVE DISEASE AFFECTING MULTIPLE VALVES
Introduction
Diagnosis, Signs, and Symptoms
Operative Decision Making
Myxomatous Mitral Regurgitation with Tricuspid
Regurgitation
SENILE CALCIFIC AORTIC VALVE DISEASE WITH MULTIPLE VALVE INVOLVEMENT
Patterns of Multiple Valve Involvement with Calcific Aortic Stenosis
Calcific aortic stenosis with infective endocarditis of the mitral valve
Calcific aortic stenosis with functional mitral valve disease
Calcific aortic stenosis with calcification of the mitral valve
Diagnosis, Signs, and Symptoms of Aortic Stenosis and Mitral Regurgitation
Physical findings
Electrocardiography
Echocardiography
INFECTIVE ENDOCARDITIS AFFECTING MULTIPLE VALVES
Introduction
Aortic Regurgitant Jet Lesion of the Mitral Valve
Prosthetic Valve Endocarditis
Tricuspid Valve with Left-Sided Valve Replacement
Results
CARCINOID HEART DISEASE AFFECTING MULTIPLE VALVES
Introduction
Signs and Symptoms/Diagnosis
Echocardiography
Invasive Studies
Pathophysiology
Timing of operation
Tricuspid valve operation
Pulmonary valve options
RARE CAUSES OF MULTIPLE VALVE DISEASE
Chapter 37
AORTIC STENOSIS AND CORONARY ARTERY DISEASE
Clinical Presentation
Pathophysiology
Operative Management
Results
AORTIC REGURGITATION AND CORONARY ARTERY DISEASE
Pathophysiology
Results
MITRAL REGURGITATION AND CORONARY ARTERY DISEASE
Pathophysiology
Results
MITRAL STENOSIS AND CORONARY ARTERY DISEASE
Pathophysiology
Results
AORTIC STENOSIS, MITRAL REGURGITATION, AND CORONARY ARTERY DISEASE
Pathophysiology
Results
AORTIC AND MITRAL REGURGITATION AND CORONARY ARTERY DISEASE
Pathophysiology
Results
SUMMARY
Chapter 38
HISTORY
DEFINITION
CLASSIFICATION
INCIDENCE
ETIOLOGY
HISTOLOGY AND STRUCTURE
ACUTE AORTIC DISSECTION
Physical findings
Diagnostic studies
Blood tests
Initial Management
Pharmacologic therapy
Diagnostic Imaging
Aortography
CT scanning
Magnetic resonance imaging (MRI)
Echocardiography
Intravascular ultrasound
B-mode ultrasound
Diagnostic Strategy
Natural History
Indications and Selection of Operation
Proximal aorta and arch dissection
Distal aortic dissection
CHRONIC AORTIC DISSECTION
OPERATION
General Considerations
Anesthesia and Monitoring
Hemostasis
Extracorporeal Circulation and Cardioplegia
Cerebral Protection
Deep hypothermic circulatory arrest
Retrograde cerebroplegia
Two-stage cooling
Operative Techniques for Proximal Dissections
Exposure
Replacement of the aortic root and ascending aorta
Acute dissection involving the aortic arch
Chronic aortic arch dissection
Operative Techniques for Distal Dissections
General considerations
Distal arch and descending thoracic aorta
Thoracoabdominal dissection
Malperfusion of Aortic Branches
Incidence
Pathogenesis
Operative strategies
Operations
RESULTS
Acute Proximal and Arch Dissection
Acute Distal Dissection
Chronic Dissection
FOLLOW-UP CARE
Long-term Medical Management
Re-operation
LATE RESULTS
Chapter 39
HISTORY
Early Descriptions
Early Surgical Treatment
Evolution of Modern Surgical Techniques
RISK FACTORS AND INCIDENCE
ETIOLOGY AND PATHOPHYSIOLOGY
Annuloaortic Ectasia and Cystic Medial Degeneration
The Marfan Syndrome
Atherosclerosis
Aneurysms Associated with Aortic Dissection
Aneurysms Associated with Aortic Valve Disease
Infection
Bacterial
Syphilitic
Arteritis
Ehlers-Danlos Syndrome
Trauma
Pseudoaneurysms
NATURAL HISTORY
Cystic Medial Degeneration and Atherosclerosis
Marfan Syndrome
Syphilitic Aneurysms
Symptoms and Signs
DIAGNOSTIC STUDIES
Electrocardiogram
Chest Radiography
Echocardiography
Aortography
Computed Tomography
Magnetic Resonance Imaging
Coronary Angiography
Symptoms
Progressive Enlargement of the Aorta
Size of the Aneurysm
GENERAL
MARFAN SYNDROME
Coexisting Aortic Valve Disease with Ascending Aortic Enlargement
New or Persistent Aneurysms of the Sinus of Valsalva
Pseudoaneurysms
CHOICE OF PROCEDURE
Ascending Aortic Aneurysm with or without Valvular Disease
Annuloaortic Ectasia
Composite graft
Aortic allograft
Pulmonary autografts
Alternative procedures
Management of associated conditions
General
Monitoring and anesthesia
Incisions
Perfusion
Myocardial protection
Choice of graft and graft preparation
Specific Operative Techniques
Replacement of the ascending aorta
Chapter 40
ETIOLOGY OF ARCH ANEURYSMS
NATURAL HISTORY AND INDICATIONS FOR OPERATION
Risk of Rupture
Operative Risk
APPROACH TO THE PATIENT
Assessment of Cardiac Status and Management of Coronary Artery Disease
Assessment of Cerebral Vessels and Prevention of Stroke
Assessment of Cannulation Sites
STRATEGIES FOR CEREBRAL PROTECTION
Hypothermic Circulatory Arrest (HCA): Historical and Theoretical Considerations
Clinical Implementation of HCA
Selective Cerebral Perfusion (SCP): Historical and Theoretical Considerations
Clinical Implementation of SCP
Retrograde Cerebral Perfusion (RCP): Historical and Theoretical Considerations
Clinical Implementation of RCP
ANESTHESIA AND MONITORING PERFUSION
Incision
Cooling and Rewarming
Graft and Suture Materials
Myocardial Protection
Prevention of Paraplegia
Control of Hemorrhage
Use of Glues
Treatment of Infected Grafts and Mycotic Aneurysms
REPRESENTATIVE PROCEDURES
A Bentall Procedure, with Replacement of the Underside of the Aortic Arch
A Descending Thoracic Aortic Aneurysm Involving the Distal Aortic Arch
RESULTS
LONG-TERM FOLLOW-UP
Chapter 41
ETIOLOGY AND PATHOGENESIS
NATURAL HISTORY
DIAGNOSTIC EVALUATION
Ultrasonography
Computed Tomography
Aortography
PREOPERATIVE ASSESSMENT AND PREPARATION
Heart
Kidney
Lung
OPERATIVE TREATMENT
Classification of Thoracoabdominal Aneurysms
Incisions
Exposure
Repair
Closure
PARAPLEGIA AND SPINAL CORD PROTECTION STRATEGIES
Incidence
Vascular Anatomy of the Spinal Cord
Pathophysiology of Aortic Cross-Clamping
Pathophysiology of Spinal Cord Ischemia
Protection Strategies
RESULTS OF TREATMENT
Chapter 42
INCIDENCE
PATHOLOGY
Acute Ruptured Aorta
Chronic Traumatic Aortic Aneurysm
PATHOGENESIS
NATURAL HISTORY
Acute Aortic Rupture
DIAGNOSTIC STUDIES
Plain Chest X-ray
Aortography
Computerized Axial Tomography
Echocardiographic features of traumatic aortic rupture
MANAGEMENT PLAN
Initial Management
Preoperative Imaging
Timing of Operation
OPERATION
Preparations
Incision
Management of Lower Body Circulation
Simple aortic cross-clamping
Lower body perfusion systems
Management of the Ruptured Aorta
Special Problems
Previous left thoracotomy
Extension of tear into the left subclavian artery
Non-isthmic Lacerations
Associated injuries
POSTOPERATIVE CARE
COMPLICATIONS
RESULTS
CHRONIC TRAUMATIC AORTIC ANEURYSM
Operation
Results
Chapter 43
BLUNT TRAUMA TO THE HEART
Demographics
Mechanics of Injury
Myocardial Contusion
Diagnostic studies
Clinical management
Myocardial Laceration
Diagnosis
Treatment
Ventricular Aneurysm
Septal Defects
Valvular and Valvular Apparatus Injury
Aortic valve injury
Mitral valve injury
Tricuspid valve injury
Pericardial Injury
Coronary Artery Injury
PENETRATING INJURY OF THE HEART
Incidence and Demographics
Mechanics of Injury
Presentation and Pathophysiology
Diagnosis
Subxiphoid pericardial window
Management of Penetrating Wounds
The lifeless patient
The patient with signs of life
Incision decision
Operating room care
Conduct of operation
Cardiopulmonary bypass
Foreign bodies
The stunned heart
Postoperative Evaluation
CENTRAL VASCULAR INJURY
Mechanics of Injury
Anatomy
Management and Strategy
Incision Decision
Exposure of Specific Vessels
Technique of Repair
Ca . 1000 B.C.
Chapter 44
ANATOMY
Ultrastructure
PATHOPHYSIOLOGY OF PERICARDIAL COMPRESSION
Pulsus Paradoxus
Pericardial Effusion without Tamponade
Constrictive Pericarditis
PERICARDIAL CONSTRICTION VERSUS RESTRICTIVE CARDIOMYOPATHY
PERICARDIAL DEFECTS AND CYSTS
Congenital Defects
Pericardial Cysts
PERICARDITIS
Infectious Pericardial Disease
Viral and Idiopathic Pericarditis
Uremic Pericarditis
Drug-Induced Pericarditis
Radiation Pericarditis
Post-Myocardial Infarction and Cardiac Surgery
CHRONIC CONSTRICTIVE PERICARDITIS
MALIGNANT PERICARDIAL DISEASE
OPERATIONS
Postoperative Pericardial Tamponade
Pericardiocentesis
Percardial Window
Pericardial Stripping
Chapter 45
DEEP VENOUS THROMBOSIS (DVT)
Pathology
Pathogenesis
Risk Factors for DVT
Diagnosis
Prophylaxis
PULMONARY EMBOLISM
Pathology and Pathogenesis
Natural History
ACUTE PULMONARY EMBOLISM
Diagnosis
Management of Major Pulmonary Embolism
Management of Massive Pulmonary Embolism
Emergency Pulmonary Thromboembolectomy
Postoperative Care
Results
CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION
Pathogenesis and Pathology
Diagnosis
Medical Management
Natural History
Pulmonary Thrombendarterectomy
Indications
Operation
Postoperative care
Complications
Results
Late follow-up
Chapter 46
HISTORICAL BACKGROUND
CLASSIFICATION
PRIMARY BENIGN TUMORS
Myxoma
Incidence
Pathology
Presentation
Clinical examination
Surgical management
Results
Nonmyxomatous Benign Cardiac Tumors
Lipoma
Lipomatous hypertrophy of the interatrial septum
Papillary fibroblastoma of heart valves
Rhabdomyoma
Fibroma
Mesothelioma of the A-V node
Pheochromocytoma
Hemangioma
Teratoma
PRIMARY MALIGNANT TUMORS
Angiosarcoma
Rhabdomyosarcoma
Other Sarcomas
HEART TRANSPLANTATION
SECONDARY METASTATIC TUMORS
RIGHT ATRIAL EXTENSION OF SUBDIAPHRAGMATIC TUMORS
Chapter 47
MANAGEMENT CONSIDERATIONS
Preoperative Considerations
Perioperative Management
Postoperative Care
Long-Term Follow-Up
Pregnancy
SPECIFIC CONGENITAL MALFORMATIONS
Atrial Septal Defects
Ventricular Septal Defects
Patent Ductus Arteriosus
Aortic Coarctation
Tetralogy of Fallot
Pulmonary Atresia with Ventricular Septal Defect
Transposition of the Great Arteries
Single-Ventricle and Tricuspid Atresia: The Glenn Operation and Modified Fontan
The Glenn shunt
The modified Fontan procedure
Late reoperations after the Fontan procedure
Ebstein's Anomaly
Tricuspid valve replacement
Transplantation
Heart and heart-lung transplantation
Chapter 48
THE MAJOR HISTOCOMPATIBILITY COMPLEX
ANTIGEN PROCESSING
ALLORESPONSE
T-CELL LYMPHOCYTE MATURATION AND ALLOACTIVATION
REJECTION OF HEART AND LUNGS
Hyperacute Rejection
Acute Rejection
Chronic Rejection of the Heart
Chronic Rejection of Lung Allografts
NEW IMMUNOSUPPRESSIVE DRUGS
Corticosteroids
Cytokine Synthesis Inhibitors
Inhibitors of DNA Synthesis
Inhibition of T- and B-Cell Maturation
Receptor Antagonists and Monoclonal Antibodies
TOLERANCE
MICROCHIMERISM AND SOLID ORGAN
TRANSPLANTATION
XENOTRANSPLANTATION
Xenograft Hyperacute Rejection
Acute Vascular Xenograft Reaction
Cell-Mediated Xenograft Rejection
Chapter 49
HISTORY OF HEART TRANSPLANTATION
ECONOMICS OF HEART TRANSPLANTATION
THE CARDIAC TRANSPLANT RECIPIENT
Recipient Selection
Etiology of end-stage cardiac failure
Evaluation of the potential cardiac recipient
Indications for cardiac transplantation
Contraindications for cardiac transplantation
Management of the Potential Cardiac Recipient
Tailored medical therapy for end-stage cardiac failure
Pharmacologic bridge to transplantation
Mechanical bridge to transplantation
High-risk revascularization procedures
Life-threatening ventricular arrhythmias
Recipient Prioritization for Transplantation
THE CARDIAC DONOR
Donor Availability
Allocation of Donor Organs
Brain Death
Donor Selection
Management of the Cardiac Donor
Donor Heart Procurement
Organ Preservation
Donor-Recipient Matching
OPERATIVE TECHNIQUES IN HEART TRANSPLANTATION
Orthotopic Heart Transplantation
Anesthetic management
Operative preparation of the recipient
Implantation
Alternative techniques for orthotopic heart transplantation
Recipients with congenital anomalies
Heterotopic Heart Transplantation
Donor allograft preparation
Implantation
Domino Donor Procedure
POSTOPERATIVE MANAGEMENT
Intensive Care Unit
Isolation and monitoring
Hemodynamic management
Respiratory management
Renal function
Nutrition and activity
Intermediate Care Unit and Convalescent Ward
Outpatient Follow-up
IMMUNOSUPPRESSIVE THERAPY
Pharmacologic Immunosuppressive Strategies
Individual Immunosuppressive Agents
Corticosteroids
Azathioprine
Cyclosporine
Polyclonal antibodies
OKT3
Investigational agents
Nonpharmacologic Immunosuppressive Strategies
Total lymphoid irradiation (TLI)
Photopheresis
Apheresis
ACUTE REJECTION
Diagnosis of Acute Rejection
Chapter 50
INDICATIONS FOR HEART-LUNG TRANSPLANTATION
Recipient Selection Criteria
Clinical and Laboratory Criteria for Listing
RECIPIENT MANAGEMENT AFTER LISTING
ORGAN PROCUREMENT AND PRESERVATION
Donor Selection
Donor Management
Donor Operation
Organ Preservation and Transport
RECIPIENT OPERATION
EARLY POSTOPERATIVE MANAGEMENT
Heart-Lung Graft Physiology
The Early Postoperative Period
Immunosuppression
Patient Follow-up
POSTOPERATIVE COMPLICATIONS
Acute Rejection
Chronic Rejection
Infection
Neoplasm
Airway Complications
Hemorrhage
THE DOMINO PROCEDURE
RESULTS OF HEART-LUNG TRANSPLANTATION
CONCLUSION
Chapter 51
DESCRIPTION OF AVAILABLE LONG-TERM CIRCULATORY SUPPORT SYSTEMS
Thoratec VAS
Novacor LVAS
HeartMate LVAS
Implantable pneumatic LVAS
Vented electric LVAS
PATIENT SELECTION
INSERTION OF DEVICE
Thoratec
Novacor
HeartMate
WEANING FROM CARDIOPULMONARY BYPASS
POSTOPERATIVE CARE
COMPLICATIONS
Bleeding
Right Ventricular Failure
Infection
Thromboembolic Complications
End-organ Failure
RESULTS
Thoratec
Novacor
HeartMate
PERMANENT LVAS
THE FUTURE OF MECHANICAL CIRCULATORY SUPPORT
Chapter 52
HISTORICAL DEVELOPMENT
BIOLOGIC BASIS OF SKELETAL MUSCLE-POWERED CARDIAC ASSIST
Skeletal Muscle Transformation
Conformational Changes in Skeletal Muscle Geometry and Fiber Length
Skeletal Muscle Power Output and Blood Flow
Selection of Skeletal Muscle for Cardiac Assist
CARDIOMYOSTIMULATORS
EXPERIMENTAL STUDIES
Methods to Couple Transformed Skeletal Muscle to the Circulation
Dynamic Cardiomyoplasty: Experimental Studies and Mechanisms of Action
CLINICAL EXPERIENCE
Postoperative Management
Results
CONCLUSIONS AND FUTURE PERSPECTIVES
HEART WOUNDS
Dr. Ludwig Rehn, of Frankfurt, Germany, is generally credited with performing the first
successful heart operation. * According to Rehn's case report: [1 ]
On August 31, 1896, a 22-year-old gardener was dismissed from the military service
because of fast and irregular heart action. On September 7, 1896, he was stabbed in
his heart and collapsed. After three hours of unconsciousness, he moved 300 feet and
collapsed again. The police found him pale, covered with cold sweat and extremely
short of breath. He could barely give his name. The pulse was irregular and intermittent.
His clothes were soaked with blood. The wound was not bleeding and was located over
the fourth left intercostal space three fingers from the sternal edge. Percussion of the
heart demonstrated widening to the right. Heart and lung sounds were clear.
September 9Worsening status. Pulse weaker, increasing cardiac dullness on

percussion, respiration 76, further deterioration during the day, diagnostic tap reveals
dark blood. Patient appears moribund. Diagnosis: increasing hemothorax. I decided to
operate entering the chest through the left fourth intercostal space, there is massive
blood in the pleural cavity. The mammary artery is not injured. There is continuous
bleeding from a hole in the pericardium. This opening is enlarged. The heart is
exposed. Old blood and clots are emptied. There is a 1.5 cm gaping right ventricular
wound. Bleeding is controlled with finger pressure. . . .
I decided to suture the heart wound. I used a small intestinal needle and silk suture. The
suture was tied in diastole. Bleeding diminished remarkably with the third suture, all
bleeding was controlled. The pulse improved. The pleural cavity was irrigated. Pleura
and pericardium were drained with iodoform gauze. The incision was approximated,
heart rate and respiratory rate decreased and pulse improved postoperatively.
September 10Temp = 38.7°C. Pleural gauze strip is removed and bloody fluid emptied.
There is a fine rub audible. The patient is nauseated.
September 15Irregular pulse worsening after camphor injections. Morphine helps.

Oxygen therapy is initiated.
September 19Temp = 39.7°C. Pleural tube obstructed by pus. Pleural cavity drained via
incision in the back. Lung remains collapsed. The pericardial edges are adhesed.
Today the patient is cured. He looks very good. His heart action is regular. I have not
allowed him to work physically hard. This proves the feasibility of cardiac suture repair
without a doubt! I hope this will lead to more investigation regarding surgery of the
heart. This may save many lives.
Certainly, stab wounds of the heart were common prior to 1896, but what held surgeons
back? Perhaps it was the belief, held by authorities since antiquity, that cardiac wounds
could not be healed. Aristotle wrote, The heart alone of all the viscera cannot withstand
injury. This is expected because when the main source of strength (the heart) is
destroyed, no strength can be brought to the other organs which depend on it. [2 ]
Fabricius summed up the feeling about heart injuries prior to the last century: If the heart
is wounded the fear is desperate. It is, therefore, unnecessary to attempt treatment. [3 ]
During the latter half of the nineteenth century, however, interest in the possibility of
repairing cardiac wounds arose. George Fischer published a monograph in 1868 that
documented a 10 percent recovery rate in 452 patients with heart wounds. [4 ] This
report indicated that heart wounds did not necessarily result in certain death.
Investigators began to explore the possibility of surgical intervention in heart wounds. In
1882, Block reported creating stab wounds in rabbits and then repairing them. He
suggested attempts in patients. [5 ]
In 1894 Del Vecchio created and repaired heart wounds in dogs and confirmed Block's
earlier work. [6 ] However, Block's work did not lead directly to clinical application. In
fact, Riedingen in 1888 stated, The suggestion to suture a wound of the heart, although
made in seriousness, scarcely deserves mention. [7 ] Stephen Paget stated in his 1896
textbook, Surgery of the Chest : Surgery of the heart has probably reached the limits
set by nature to all surgery: no new method and no new discovery can overcome the
natural difficulties that attend a wound of the heart. It is true that heart suture has been
vaguely proposed as a possible procedure and that it has been done in animals, but I
cannot find that it has ever been attempted in practice. [8 ] Comments by prominent
surgeons such as Riedingen and Paget only served to impede the beginnings of
cardiac surgery. Although denied by some scholars, [9 ] , [10 ] Billroth allegedly
commented on Block's repair of rabbit heart wounds, A surgeon who tries to suture
heart wounds deserves to lose the esteem of his colleagues. [11 ] , [12 ]
Ten years after Rehn's initial repair, he had accumulated a series of 124 cases with a
mortality of only 60 percentquite a feat at that time. [13 ] Dr. Luther Hill was the first
American to report the successful repair of a cardiac wound. [14 ] This was in a
13-year-old boy who was a victim of multiple stab wounds. When the country doctor
arrived, the boy was in profound shock. The doctor remembered that Dr. Luther Hill had
spoken on the subject of repair of cardiac wounds at a local medical society meeting in
Montgomery, Alabama. With the consent of the boy's parents, Dr. Hill was sent for. He
arrived with his brother, who was also a physician. The surgery took place on the
patient's kitchen table in a run-down shack. Lighting was provided by two kerosene
lamps. Luther Hill's brother administered chloroform anesthesia. The boy was suffering
from cardiac tamponade as a result of a stab wound to the left ventricle. The stab wound
to the ventricle was repaired with two catgut sutures. Although the early postoperative
course was stormy, the boy made a complete recovery. Hill went on to report this case
in 1902. That paper also tabulated 37 other cases of heart suture.
The next major milestone in cardiac surgery for trauma occurred during World War II
when Dwight Harken, then a U.S. Army surgeon, removed 134 missiles from the
mediastinum, including 55 from the pericardium and 13 from cardiac chambers, without
a death. [15 ] It is hard to imagine this type of elective (and semielective) surgery taking
place without sophisticated indwelling pulmonary artery catheters, blood banks, and
electronic monitoring equipment. Rapid blood infusion consisted of pumping air into
glass bottles of blood.
OPERATIVE MANAGEMENT OF PULMONARY EMBOLI
Frederic Trendelenburg was first to attempt a pulmonary embolectomy. [16 ] In his

classic paper that appeared in 1908, he states:
The clinical picture is characteristic: rapid collapse, frequently accompanied by substernal

pain which often causes the patient to suddenly scream wildly, then turn pale and
sometime with cyanotic facial skin color, distention of the jugular and subcutaneous veins
of the upper thorax, cold sweat, peripheral vasoconstriction, shallow and irregular pulse,
rapid and labored breathing, dilated pupils, diminished level of consciousness, then
unconsciousness and death after some agonal respiration. . . . But in my experience,
most patients live for at least 15 minutes. Only 2 out of 9 patients died within 2 minutes.
The other 7 lived for 10 minutes to even one hour.
. . . Regarding surgical technique, I reported my animal studies in 1907: following rapid

exposure of the heart, I quickly incised the conus pulmonalis, inserted a cannula,
advanced it into the pulmonary artery and removed emboli using suction. This was
occasionally successful, but in general not safe enough and too traumatic. Further
experimentation revealed that a direct incision in the artery with removal of the emboli
using forceps (those designed for removal of polyps) was much easier.
He then describes some animal experimentation and techniques for exposure. Next, he
describes his first attempt in a human at pulmonary embolectomy. That operation
became famous and is known as the Trendelenburg operation :
The woman was 70 years old and deaf. She had suffered a femoral neck fracture 6 days
before. One half hour after her linen had been changed, she collapsed and became
massively diaphoretic and moaned fearfully. After three minutes, her level of
consciousness was remarkedly disturbed. Her pupils were dilated, her eyes widely open,
her face ashen, lips and tongue slightly cyanotic, jugular veins distended. Her breathing
was labored. She had lost the pulses and her heart tones were not audible. This was
unchanged at the beginning of the operation, 18 minutes following the first symptoms. The
patient responded to the skin incision and some breaths of chloroform were given. Small
vessels were barely bleeding. The blood appeared dark. The pulmonary artery and the
aorta were tense without evidence of pulsation. I cannot report about the heart action, but
it must have been beating. There remained good spontaneous respirations after the chest
was opened. I did not observe the heart.
This is a situation similar to the animal experiment of pulmonary artery compression. Lack
of pulses is not a contraindication to surgical intervention. Recovery is possible as long as
respirations are present. This patient, if not already dead at the beginning of the operation,
died during the procedure.
This case shows that in the hospital setting there is enough time to intervene surgically,
as long as the instruments are readily available. In this case I had been called into the
hospital from my home 8 minutes away. It took only 5 minutes to expose the pulmonary
artery, although entry was difficult due to dense pleural adhesions.
Trendelenburg goes on to say, In contrast to the failure in my patient, I wish to present a

successful animal experiment.
Trendelenburg subsequently reported two more cases, both fatal. [17 ] The first of those
two patients died 15 hours postoperatively of cardiac failure, the second 37 hours
postoperatively. Kirschner, Trendelenburg's student, reported the first patient who fully
recovered after undergoing pulmonary embolectomy in 1924. [18 ] In 1937, John
Gibbon estimated that 9 of 142 patients who had undergone the Trendelenburg
procedure worldwide left the hospital alive. [19 ] These dismal results were an impetus
for Gibbon to start work on a pump oxygenator that could maintain the circulation during
pulmonary embolectomy. Sharp in 1962 was first to perform pulmonary embolectomy
using cardiopulmonary bypass. [20 ]
SURGERY OF THE PERICARDIUM
Morgagni reported seven cases of constrictive pericarditis in 1761 and described the
dangers of cardiac compression by stating that the heart was so constricted and
confined that it could not receive a proper quantity of blood to pass through it. [21 ] Pick
presented a paper in 1896 in which he described the course of chronic pericarditis
under the guise of cirrhosis of the liver. [22 ] Weill in 1895 and Delorme in 1898
proposed excision of the thickened fibrous pericardium in constrictive pericarditis. [23 ]
, [24 ] Pericardial resection was introduced independently by Rehn [25 ] and
Sauerbruch. [26 ] Since Rehn's report, there have been few advances in the surgical
treatment of constrictive pericarditis. Some operations are now performed with the aid
of cardiopulmonary bypass. In certain situations, radical pericardiectomy that removes
most of the pericardium posterior to the phrenic nerves is done.
CATHETERIZATION OF THE RIGHT SIDE OF THE HEART
Although cardiac catheterization is not considered heart surgery, it is an invasive

procedure and may replace many heart operations. Catheter operations include the
Rashkind balloon septotomy for transposition of the great arteries, percutaneous
balloon dilation of coronary arteries, laser resection of arterial lesions, stent
placements, closure of atrial septal defects, closure of patent ductus, and dilation of
stenotic heart valves with balloon catheters.
Warner Forssmann is credited with the first heart catheterization. He performed the
procedure on himself and reported it in Kleinische Wochenschrift. [27 ] In 1956,
Forssmann shared the Nobel Prize in Physiology or Medicine with Andre F. Cournand
and Dickenson W. Richards, Jr. His 1929 paper starts:
Sudden episodes of cardiac arrest, as during a systolic vascular collapse, heart disease,
or due to an anesthetic complication, often make a pharmacologic intervention necessary.
Often an intercardiac injection remains the only life-saving measure. But this is always
risky as demonstrated by cases of injury to coronary arteries, which end up in death from
pericardial tamponade. An inadvertent pleural puncture can also lead to death from
pneumothorax. These are reasons why one often hesitates to use intercardiac injections.
Often, time is wasted with other measures. This is why I kept looking for different, safer
access to the cardiac chambers: the catheterization of the right heart via the venous
system.
He goes on to say, I confirmed these facts by studies on a cadaver, catheterizing any

vein near the elbow, the catheter would pass easily into the right ventricle. . . .
After these successful preliminary studies, I attempted the first experiment on a living
human, performing the experiment on myself. In a preliminary experiment, I had asked a
colleague to puncture my right brachial vein with a large-bore needle. Then I advanced a
well-lubricated No. 4 ureteral catheter through the cannula into the vein. The catheter was
easily passed to 35 cm, but we aborted the experiment which my colleague considered
too risky. I felt perfectly well during the experiment. One week later I tried it again without
assistance this time. I proceeded with vena puncture in my left antebrachial vein and
introduced the catheter to its full length of 65 cm. I only perceived some sensation of
warmth similar to the sensation during intravenous ejection of calcium chloride. There was
no pain. When I pushed on the catheter, I felt a warm sensation behind the clavicle and
near the sternomastoid. There was also a minor stimulus to cough, probably due to
irritation of a vagus branch.
I checked the catheter position radiologically, after having climbed stairs from the OR to
the radiology department. A nurse was holding a mirror in front of the x-ray screen for me
to observe the catheter advance in position. The length of the catheter did not allow further
advancement than into the right atrium. I paid particular attention to the possible effects on
the cardiac conduction system, but I could not detect any effect.
In this report by Forssmann, a photograph of the x-ray taken of Forssmann with the
catheter in his heart is presented. Forssmann, in that same report, goes on to present
the first clinical application of the central venous catheter for a patient in shock with
generalized peritonitis. Forssmann concludes his paper by stating, I also want to
mention that this method allows new options for metabolic studies and studies about
cardiac physiology. I am currently in the process of investigating these possibilities.
In a 1951 lecture, Forssmann discussed the tremendous resistance he faced during his
initial experiments. [28 ] Such methods are good for a circus, but not for a respected
hospital, was the answer to his request to pursue physiologic studies using cardiac
catheterization. His progressive ideas pushed him into the position of an outsider with
ideas too crazy to give him a clinical position. Klein applied cardiac catheterization for
cardiac output determinations using the Fick method a half year after Forssmann's first
report. [29 ] In 1930 Forssmann described his experiments with catheter cardiac
angiography. [30 ] Further use of this new methodology had to wait until Cournand's
work in the 1940s.
HEART VALVE SURGERY BEFORE THE ERA OF
CARDIOPULMONARY BYPASS
The first clinical attempt to open a stenotic valve was carried out by Theodore Tuffier on
July 13, 1912. [31 ] Alexis Carrel was present at the operation. [32 ] Tuffier attempted to
invaginate the ascending aortic wall with his finger to reach the stenotic aortic valve. He
was able to dilate the valve and supposedly push the invaginated aortic wall through it.
The 26-year-old patient recovered and returned to his home in Belgium. One must be
skeptical as to what was accomplished. Russell Brock attempted to dilate calcified
aortic valves in humans in the late 1940s by passing an instrument through the valve
from the innominate or another artery. [33 ] His results were poor, and he abandoned
the approach. During the next several years, Brock [34 ] and Bailey et al. [35 ] used
different dilators and various approaches to dilate stenotic aortic valves in patients.
Mortality for these procedures that were often done with mitral commissurotomy was
high.
Harvey Cushing attempted to create mitral stenosis in dogs but was not successful. [36 ]
He encouraged Eliott Cutler, a young surgeon working with him, to continue. In
collaboration with a Boston cardiologist, Samuel Levine, Cutler worked 2 years on a
mitral valvulotomy procedure in the laboratory. [37 ] Their first patient was a desperately
ill 12-year-old girl who was confined to bed for 6 months before operation. She
underwent successful valvulotomy on May 20, 1923, using a special knife called a
valvulatome. Unfortunately, most of Cutler's subsequent patients died, and he soon
gave up the operation. In 1925 Mr. Suttar, an English surgeon, successfully performed a
mitral valvulotomy using his finger to fracture the commissures in a young female who
had been bedridden for 6 months. [38 ] His case was successful, but he did not do
more operations.
In 1961 Dr. Dwight Harken wrote Henry Suttar a letter and asked him why he did not
continue with his mitral valvuloplasty. His reply [39 ] :
Dear Dr. Harken:
Thank you so much for your very kind letter. I did not repeat the operation because I could
not get another case. Although my patient made an uninterrupted recovery, the physicians
declared that it was all nonsense and in fact the operation was unjustifiable. In fact, it is of
no use to be ahead of one's time. . . .
With very kind regards.
Sincerely yours,
Henry Suttar
In Charles Bailey's 1949 paper entitled The Surgical Treatment of Mitral Stenosis, he
states, After 1929 no more surgical attempts [on mitral stenosis] were made until 1945.
Dr. Dwight Harken, Dr. Horace Smithy, and the author recently made operative attempts
to improve mitral stenosis. Our clinical experience with the surgery of the mitral valves
has been 5 cases to date. During the past 8 years, the author and his associates have
performed operations on the mitral valves of 60 mongrel dogs. [40 ] Bailey goes on to
state several conclusions from their animal research. He then describes the 5 cases,
summarized below.
Case 1 was a 37-year-old man operated upon November 14, 1945. The patient bled to
death on the operating table when a tear in the distended and friable atrial appendage
could not be controlled.
Case 2 was a 29-year-old female operated upon June 12, 1946. The valve was forcibly
dilated digitally and appeared to tear open at both commissures. The patient's condition
improved for the first 30 hours after the surgery, but then suddenly deteriorated and she
died 48 hours after the surgery. At autopsy, the tears in the commissures were not in the
normal marginal valve tissue. The tears had become agglutinated with fibrin. It was felt that
the orifice had actually decreased in size, and was responsible for the death.
Case 3 was a 38-year-old male operated upon March 22, 1948. The commissurotomy was
performed. The patient's condition remained excellent throughout the operation. Because
of the bitter experience with the previous patient, this patient was anticoagulated. The
second postoperative day, the patient hemorrhaged into the left pleural cavity requiring
repeated thoracentesis. The patient probably died from a hemothorax possibly with other
complicating factors as described in the case report.
Case 4 was a 32-year-old male who underwent surgery June 10, 1948. The patient
arrested after the thoracotomy was performed, but before an attempt at mitral
commissurotomy was made. The patient could not be resuscitated and died in the
operating room.
Case 5 was a 24-year-old woman who underwent surgery the same day as Case 4 but at
a different hospital. She underwent a successful commissurotomy. She was
asymptomatic and felt better than she had been for years.
Bailey's home base, Hahnemann Hospital, refused to allow him to attempt any more
mitral commissurotomies after two deaths. He became known as the butcher of
Hahnemann Hospital. [39 ] However, his cardiologist, Dr. Durant, continued to support
him. On June 10, 1948, Bailey scheduled cases 4 and 5 (above). The patient operated
on at Philadelphia General Hospital in the morning died (case 4). The surgical team
regrouped and rushed to Episcopal Hospital, where the second operation was started
promptly before the bad morning news was known and before the hospital
administration forbade the procedure. The surgery was completed, and 1 week later
Bailey brought the patient by train 1000 miles to Chicago, where he presented the
woman to the American College of Chest Physicians. [41 ] A few days after Bailey's
success, on June 16 in Boston, Dr. Dwight Harken successfully performed his first
valvulotomy for mitral stenosis. Three months later, Russell Brock in England did his first
successful clinical case. He did not report this, however, until 1950, when he described
success with six patients. [42 ]
The first successful pulmonary valvulotomy was performed by Thomas Holmes Sellers
on December 4, 1947. A systemic pulmonary shunt was planned on the left side, but the
attempt was abandoned in this patient with severe tetralogy of Fallot and advanced
bilateral pulmonary tuberculosis. [43 ] The pericardium was opened. Dr. Sellers could
feel the stenotic valve each time it pushed through the pulmonary trunk during ventricular
systole. Sellers used a tenotomy knife, which he passed through the right ventricle to
perform the valvulotomy. The patient made a good recovery and was markedly
improved.
Russell Brock also attempted pulmonary valvulotomies in a number of patients during
the same period using various techniques. Brock's first three patients died, but he
eventually developed a successful procedure similar to Sellers'. [44 ]
In the early 1950s, Charles Hufnagel, in Washington, D.C., and J. M. Campbell, in

Oklahoma, independently developed and implanted artificial valves in the descending
aorta of dogs. The valves consisted of a mobile ball inside a Lucite case. [45 ] , [46 ]
After presenting this first model of a mechanical prosthesis at the American College of
Surgeons meeting in 1949, Hufnagel applied this concept clinically for the treatment of
aortic valvular insufficiency. In his first clinical paper published in Surgery in 1954, [47 ]
Hufnagel reported a series of 23 patients starting September 1952 who had this
operation for aortic insufficiency. There were 4 deaths among the first 10 patients and 2
deaths among the next 13. Hufnagel's caged ball valve, which used multiple-point
fixation rings to secure the apparatus to the aorta, was the only surgical treatment for
aortic valvular incompetence until the advent of cardiopulmonary bypass and heart
valves that could be sewn into the aortic annulus position.
The first surgical treatment of multiple valvular disease was by Trace et al. [48 ] After
closed mitral commissurotomy on May 2, 1952 in a 24-year-old woman, the surgeon
noted that the right auricular appendage was gravely distended and pointed directly
toward the left. Its pulsation was noticed and it was quite blue-purple in color. The
purse-string was being placed around the appendage in order to explore it when the
patient's heart became arrhythmic. It was deemed advisable to terminate the surgical
procedure at this point. The patient did poorly postoperatively. In the 2 weeks after the
first operation, a tricuspid commissurotomy was performed. The patient made a good
recovery and at 1-year follow-up remained improved.
Combined mitral and tricuspid commissurotomy was performed by Brofman in 1953.

[49 ] Likoff et al. [50 ] reported a series of 74 patients who had combined aortic and
mitral valve commissurotomies in 1955 with up to a 2-year follow-up. C. Walton Lillehei
was the first to report repair of multiple valvular lesions using cardiopulmonary bypass.
On May 23, 1956, he successfully performed an open mitral commissurotomy and
aortic valvuloplasty in a 52-year-old man with mitral stenosis and combined aortic
stenosis and incompetence. [51 ] Borman performed a quadruple valve
commissurotomy in October 1973 in a 12-year-old Israeli girl with stenosis of all four
valves. [52 ]
CONGENITAL CARDIAC SURGERY: PRE-HEART-LUNG MACHINE
ERA
Congenital cardiac surgery began when John Streider at the Massachusetts General
Hospital first successfully interrupted a ductus on March 6, 1937. The patient was septic
and died on the fourth postoperative day. At autopsy, vegetations filled the pulmonary
artery down to the valve. [53 ] On August 16, 1938, Robert Gross, at Boston Children's
Hospital, operated on a 7½-year-old girl with dyspnea after moderate exercise. [54 ] Dr.
Gross described the ductus as 7 to 8 mm in diameter and 5 to 6 mm in length. A No. 8
braided silk tie was placed around the ductus with an aneurysm needle, and the vessel
was occluded temporarily for a 3-minute observation. During this time, blood pressure
rose from 100/35 to 125/90. According to Dr. Gross, Since there was no
embarrassment of the circulation, it was decided to ligate the ductus permanently. The
patient made an uneventful recovery (Fig. 1-1) .
When Dr. Gross proposed surgical closure of the ductus to his chief, Dr. William E.
Ladd, the response was, Don't do it. Nevertheless, the procedure was performed while
Dr. Ladd was out of town. [55 ] When he returned and learned of his subordinate's
disobedience, he fired Dr. Gross. News of the operation, however, spread rapidly.
Modifications of the ductus operation soon followed. In 1944 Dr. Gross reported a
technique for successfully dividing the ductus.
The next major congenital lesion to be overcome was coarctation of the aorta. Dr.
Clarence Crafoord, in Stockholm, Sweden, successfully resected a coarctation of the
aorta in a 12-year-old boy on October 19, 1944. [56 ] Twelve days later he successfully
resected the coarctation of a 27-year-old patient. Dr. Gross, in Boston, who had been
working on a coarctation model in the laboratory, first operated on a 5-year-old boy with
this condition on June 28, 1945. [57 ] After he excised the coarctation and rejoined the
aorta, the patient's heart suddenly stopped. The patient died in the operating room. One
week later, however, Dr. Gross operated on a second patient, a 12-year-old girl. This
patient's operation was successful (Fig. 1-2) . Dr. Gross had been unaware of Dr.
Crafoord's successful surgery several months previously, probably because of World
War II.
In 1945 Dr. Gross reported the first successful case of surgical relief for tracheal
obstruction from a vascular ring. [58 ] The operation was performed on June 9, 1945 on
a 1-year-old boy who had had numerous admissions for severe cough and chest
wheezing. Immediately after one admission, the patient became quite cyanotic and
collapsed for a few hours. He was placed in an oxygen tent and intramuscular penicillin
was started. . . . He was diagnosed as having a vascular ring. After successful surgical
interruption on June 9, the patient made a fairly uneventful recovery. In the 5 years that
followed Gross's first successful operation, he reported 40 more cases. [59 ]
The famous Blalock-Taussig operation also was reported in 1945. The first patient was
a 15-month-old girl with a clinical diagnosis of tetralogy of Fallot with a severe
pulmonary stenosis. [60 ] At age 8 months the baby had her first cyanotic spell, which
occurred after eating. Dr. Helen Taussig, the cardiologist, followed the child for 3
months, and during that time, cyanosis increased and she failed to gain weight. She
was readmitted and during the next 6 weeks refused most of her feedings, lost weight,
and weighed only 4 kg at operation. The operation was performed by Dr. Alfred Blalock
at Johns Hopkins University on November 29, 1944. The left subclavian artery was
anastomosed to the left pulmonary artery in an end-to-side fashion (Fig. 1-3) . The
operation required slightly less than an hour and a half, and the pulmonary artery was
occluded for approximately 30 minutes. The postoperative course was described as
stormy; she was discharged at approximately 2 months. Two additional successful
cases were done within 3 months of their first patient.
Thus, within a 7-year period, three congenital cardiovascular defects, patent ductus
arteriosus, coarctation of the aorta, and vascular ring, were attacked surgically and
treated successfully. However, the introduction of the Blalock-Taussig shunt was
probably the most powerful stimulus to the development of cardiac surgery because this
operation palliated a complex intracardiac lesion and focused attention on the
pathophysiology of cardiac disease.
Anomalous coronary artery in which the left coronary artery communicates with the
pulmonary artery was the next surgical conquest. The surgery was performed on July 22,
1946 and was reported by Gunnar Biorck and Clarence Crafoord. [61 ] The patient was
a 15-year-old boy who was unable to do gymnastics or play football because of
dyspnea shortly after beginning exercise. At operation, the ductus arteriosus was found
to be a cord, but there was a thrill over the pericardium. When the pericardium was
opened, the anomalous coronary artery was identified and doubly ligated. The patient
made an uneventful recovery.
Muller [62 ] reported successful surgical treatment of transposition of the pulmonary

veins in 1951, but the operation addressed a partial form of the anomaly. Later in the
1950s, Gott, Varko, Lillehei, and Cooley reported successful operative variations for
anomalous pulmonary veins.
Another of Gross's pioneering surgical procedures was the surgical closure of an

aortopulmonary window in a 4-year-old girl who had dyspnea with slight exertion and a
cardiac murmur that was consistent with a patent ductus. [63 ] Operation was carried
out on May 22, 1948. The great vessels lay immediately contiguous to one another, and
there was fear of entering the thin-walled communication between them and creating
uncontrollable bleeding. After dissecting the posterior aspect of the vessels, a similar
plane was developed between the vessels above the shunt. Finally, an aneurysm needle
was passed completely around the shunt, although there was little room between and
behind the vessels to permit this. [11 ] A piece of linen tape 1 cm wide was drawn
around the vessel so that it encircled the shunt. At this point, arterial blood began to
escape from the depths of the wound so that it was evident that the thin posterior wall of
the shunt had been slightly torn. Believing that the one hope of controlling the situation
might be to quickly tie the tape that had been placed previously, this was now rapidly
and tightly drawn down. Fortunately, all bleeding stopped. All the thrill in the pulmonary
artery disappeared. The chest was closed, and the patient made a satisfactory
convalescence.
Gross went on to state in the discussion, After successfully treating the child, it is felt that
the fortunate outcome had been attended by a high degree of luck and that simple
ligature might lead to disaster if attempted in all cases of aortopulmonary artery
fenestration. As far as is known, this is the first instance of successful surgical
correction of this congenital abnormality. Others were soon to follow using various
techniques to interrupt the aortopulmonary window. Cooley et al. [64 ] were the first to
report on the use of cardiopulmonary bypass to repair this defect. The use of
cardiopulmonary bypass converted a difficult and hazardous procedure into a relatively
straightforward one.
The cavopulmonary anastomosis has had several variations by different designers.

Carlon et al. [65 ] are credited with first proposing the anastomosis in 1951. Glenn [66 ]
reported the first successful clinical application in the United States in 1958 for what has
been termed the Glenn shunt. Similar work was done in Russia during the 1950s by
several investigators. On January 3, 1957, Galankin [67 ] performed a cavopulmonary
anastomosis in a 16-year-old patient with tetralogy of Fallot. The patient made a good
recovery with significant improvement in exercise tolerance and cyanosis.
THE DEVELOPMENT OF CARDIOPULMONARY BYPASS
The development of the heart-lung machine made repair of intracardiac lesions

possible. Lillehei wrote, A physician at the bedside of a child dying of an intracardiac
malformation as recently as 1952 could only pray for a recovery! Today with the
heart-lung machine, correction is routine. [68 ] To bypass the heart, one needs a basic
understanding of physiology of the circulation, a method of preventing the blood from
clotting, a pump to pump blood, and finally, a method to ventilate the blood.
During the last century, physiologists were interested in isolated organ perfusion and
therefore needed a method to oxygenate blood. Von Frey and Gruber [69 ] described a
blood pump in 1885 in which gas exchange occurred as blood flowed into a thin film
over the inner surface of a slanted rotating cylinder. In 1895 Jacobi passed blood
through an excised animal's lung that was aerated by artificial respiration. [70 ] In 1926,
Professors S. S. Brukhonenko and S. Tchetchuline [71 ] in Russia designed a machine
that used an excised lung from a donor animal as an oxygenator and two mechanically
actuated blood pumps. Their machine was used initially to perfuse isolated organs but
later was used to perfuse entire animals.
Alexis Carrel, a Nobel laureate, and Charles Lindbergh, the famous aviator, developed
a device that successfully perfused the thyroid gland of a cat for 18 days, beginning
April 5, 1935. [72 ] A picture of the two investigators with their perfusion apparatus
appeared on the July 1, 1935 cover of Time Magazine . [73 ] At the end of that time,
much of the tissue was partially preserved, and pieces grew epithelial cells in tissue
culture. According to Edwards and Edwards, [72 ] many other organs were perfused
over the next few years by Carrel and Lindbergh. Hearts were kept beating for several
days. Although perfused organs survived surprisingly well, all showed progressive
degenerative changes in a few days. Edema fluid filled tissue spaces, arteries became
calcified, and connective tissue cells outgrew the more specialized cells.
One of the key requirements of the heart-lung machine was anticoagulation. Heparin
was discovered by a medical student, Jay McLean, working in the laboratory of Dr.
William Howell, a physiologist at Johns Hopkins. [74 ] In 1915 Howell gave McLean the
task of studying a crude brain extract known to be a powerful thromboplastin. Howell
believed that the thromboplastic activity was caused by cephalin contained in the
extract. McLean's job was to fractionate the extract and purify the cephalin. McLean also
studied extracts prepared from heart and liver. McLean discovered that a substance in
the extract was retarding coagulation. McLean wrote [75 ] :
I went one morning to the door of Dr. Howell's office, and standing there (he was seated at
his desk), I said, Dr. Howell, I have discovered antithrombin. He smiled and said,
Antithrombin is a protein and you are working with phospholipids. Are you sure that salt is
not contaminating your substance?. . . I told him that I was not sure of that, but it was a
powerful anticoagulant. He was most skeptical, so I had the diener, John Schweinhand,
bleed a cat. Into a small beaker full of its blood, I stirred all of the proven batch of
heparphosphotides, and placed this on Dr. Howell's laboratory table and asked him to tell
when it clotted. It never did.
McLean described his finding in February 1916 at a medical society meeting in

Philadelphia and later reported it in an article entitled, The Thromboplastic Action of
Cephalin. [75 ] , [76 ] Howell and Holt [77 ] reported their work on heparin in 1918. In the
1920s, animal experiments confirmed that heparin was an effective anticoagulant. [78 ]
John Gibbon probably contributed more to the success of the development of the
heart-lung machine than anyone else. His interest began one night in 1931 in Boston
during an all-night vigil by the side of a patient with a massive embolus. . . [79 ] :
My job that night was to take the patient's blood pressure and pulse every 15 minutes and
plot it on a chart. During the 17 hours by the patient's side, the thought constantly
recurred that the patient's hazardous condition could be improved if some of the blue blood
in the patient's distended veins could be continuously withdrawn into an apparatus where
the blood could pick up oxygen and discharge carbon dioxide and then pump this blood
into the patient's arteries. At 8 a.m. the patient's blood pressure could not be measured.
Dr. Edward Churchill; the chief of surgery, immediately opened the chest through an
anterior left thoracotomy, then occluded both the pulmonary artery and the aorta as they
exited from the heart. He opened the pulmonary artery and removed massive blood clots.
The patient did not survive.
In 1937, Gibbon reported the first successful demonstration that life could be
maintained by an artificial heart and lung and that the native heart and lungs could
resume function. Unfortunately, only three animals recovered adequate
cardiorespiratory function after total pulmonary artery occlusion and bypass, and even
they died a few hours later. [80 ] Gibbon's work was interrupted by World War II;
afterwards, he resumed his work at the Thomas Jefferson Medical College in
Philadelphia. Meanwhile, other groups, including Clarence Crafoord in Stockholm,
Sweden, J. Jongbloed at the University of Utrecht in Holland, Clarence Dennis at the
University of Minnesota, Mario Dogliotti and coworkers at the University of Turino in
Italy, and Forrest Dodrill at Harper Hospital in Detroit, also worked on a heart-lung
machine. [81 ]
Clarence Dennis's first clinical attempt at open heart surgery was in a 6-year-old girl
with end-stage cardiac disease. [82 ] Her heart was already massive, and her only hope
was surgical closure of an atrial septal defect. At operation on April 5, 1951, her
circulation was supported by a heart-lung machine that Dennis and coworkers had
developed. [83 ] The atrial septal defect was very difficult to close. Although the
heart-lung machine functioned well, the patient did not survive, probably because of a
combination of blood loss and surgically induced tricuspid stenosis.
In August of 1951, Mario Digliotti used his heart-lung machine to support the circulation
in a 49-year-old patient during resection of a large mediastinal tumor. [84 ] During the
operation, the patient developed hypotension and cyanosis. He was placed on partial
bypass at 1 liter/min. Although the mass was resected successfully, the Italian machine
was never used for open heart surgery in humans.
Forrest Dodrill and colleagues used the mechanical blood pump they developed with
General Motors on a 41-year-old man. [85 ] The machine was used to substitute for the
left ventricle for 50 minutes while a surgical procedure was carried out on the mitral
valve. Although Dodrill's report lacks details of the procedure and omits important
hemodynamic information, it nevertheless represents a landmark in the field of
cardiothoracic surgery. This, the first clinically successful total left-sided heart bypass,
was done July 3, 1952 and followed from Dodrill's experimental work with a mechanical
pump for univentricular, biventricular, or cardiopulmonary bypass. Although Dodrill et al.
had used their pump with an oxygenator for total heart bypass in animals, [86 ] they felt
that left-sided heart bypass was the most practical method for their first clinical case
because it was not associated with a profound hypotensive reflex that occurred in other
forms of bypass. When their patient was interviewed at age 68, he recalled seeing dogs
romping on the roof of a nearby building from his hospital room in 1952. Later he
learned that they had been used in the final test of the Dodrill-General Motors
mechanical heart machine.
Later, on October 21, 1952, Dodrill et al. used their machine in a 16-year-old boy with
congenital pulmonary stenosis to perform a pulmonary valvuloplasty under direct vision;
this was the first successful right-sided heart bypass. [87 ]
Hypothermia was another method to stop and open the heart. In 1950, Bigelow et al. [88
] reported on 20 dogs that had been cooled to 20°C, with 15 minutes of circulatory
arrest; 11 animals also had a cardiotomy. Only 6 animals survived after rewarming.
Bigelow and colleagues continued to study hypothermia [89 ] , [90 ] and hibernation and
learned that a groundhog could be cooled to a body temperature of 5°C and be revived.
This temperature allowed circulatory arrest and cardiotomy for 2 hours without ill effects.
[91 ]
In 1953, F. J. Lewis and M. Taufic reported on 26 dogs that had surgically induced atrial
septal defects which they attempted to close using a hypothermia technique. In this
paper, the authors also reported a 5-year-old girl who had closure of her atrial septal
defect on September 2, 1952 using a hypothermic technique. [92 ]
She was anesthetized with pentothal sodium and curare and the trachea was intubated.
She was then wrapped in refrigerated blankets until after a period of two hours and ten
minutes her rectal temperature had fallen to 28o. At this point the chest was entered
through the bed of the right fifth rib. The cardiac inflow was occluded for a total of five and
one-half minutes and during this time the septal defect measuring 2 cm in diameter was
closed under direct vision. The patient was rewarmed by placing her in hot water kept at
45°C and after 35 minutes her rectal temperature had risen to 36°C at which time she was
removed from the bath. Recovery from the anesthesia was prompt and her subsequent
postoperative convalescence was uneventful.
The Louis-Taufic article describes the first successful repair of an atrial septal defect
with surface cooling under direct vision. Shortly after, Swan et al. [93 ] reported
successful results in 13 clinical cases using a similar technique. However, use of
systemic hypothermia for open intracardiac surgery was relatively short-lived. After the
heart-lung machine was introduced clinically, it appeared that deep hypothermia was
obsolete. However, during the 1960s it became apparent that operative results in
infants under 1 year of age using cardiopulmonary bypass were poor. In 1967, Hikasa
et al., [94 ] from Kyoto, Japan, published an article that reintroduced profound
hypothermia for cardiac surgery in infants and used the heart-lung machine for
rewarming. Their technique involved surface cooling to 20°C, cardiac surgery during
circulatory arrest for 15 to 75 minutes, and rewarming with cardiopulmonary bypass. At
the same time, other groups reported using profound hypothermia with circulatory arrest
in infants with the heart-lung machine for cooling and rewarming. [95 ] [98 ] Results were
much improved, and subsequently the technique also was applied for resection of aortic
arch aneurysms.
After World War II, John Gibbon resumed his research. He eventually met Thomas
Watson, chairman of the board of the International Business Machines (IBM)
Corporation. Watson was fascinated by Gibbon's research and promised help. Soon
afterward, six IBM engineers arrived and built a machine that was similar to Gibbon's
earlier machine, which contained a rotating vertical cylinder oxygenator and a modified
DeBakey rotary pump (Fig. 1-4) . Gibbon successfully used this new machine for
intercardiac surgery on small dogs and had several long-term survivors, but the blood
oxygenator was too small for patients. Eventually, the team developed a larger
oxygenator that the IBM engineers incorporated into a new machine. [99 ]
In 1949, Gibbon's early mortality in dogs was 80 percent, but it gradually improved. [81 ]
The first patient was a 15-month-old girl with severe congestive heart failure. The
preoperative diagnosis was atrial septal defect, but at operation, none was found. She
died, and a huge patent ductus was found at autopsy. The second patient was an
18-year-old girl with congestive heart failure also due to an atrial septal defect. This
defect was closed successfully on May 6, 1953 with the Gibbon-IBM heart-lung
machine. The patient recovered, and several months later the defect was confirmed
closed at cardiac catheterization. [100 ] Unfortunately, Gibbon's next two patients did
not survive intracardiac procedures when the heart-lung machine was used. These
failures distressed Dr. Gibbon, who declared a 1-year moratorium for the heart-lung
machine until more work could be done to solve the problems causing the deaths.
During this period, C. Walton Lillehei and colleagues at the University of Minnesota
studied a technique called controlled cross-circulation . With this technique the
circulation of one dog was temporarily used to support that of a second dog while the
second dog's heart was temporarily stopped and opened. After a simulated repair in
the second dog, the animals were disconnected and allowed to recover. Lillehei
remarked [68 ] :
Clinical cross-circulation for intracardiac surgery was an immense departure from the
established surgical practice. This thought of taking a normal human to the operating room
to serve as a donor circulation (with potential risk, however small) even temporarily was
considered by critics at that time to be unacceptable, even immoral as one prominent
surgeon was heard to say. Some others, skilled in the art of criticism were quick to point
out that this proposed operation was the first in all of surgical history to have the potential
(even the probability in their judgment) for a 200 percent mortality.
However the continued lack of any success in the other centers around the world that
were working actively on heart-lung bypass made the decision to go ahead inevitable. I
felt the technique was ready to use in man; however even in such a progressive and
pioneering medical school as Minnesota University, there was opposition to the idea.
Dr. Owen Wangenstein, Chairman of the Department of Surgery, was a tremendous
help. He was well aware of these experiments and whole-heartedly supported them.
Where there seemed a possibility that the first clinical operation might be canceled the
night before because of this opposition, I left a note for Dr. Wagenstein asking, Is our
case still on in the morning? His answer, Dear Walt-By all means, go ahead.
Lillehei et al. [101 ] used their technique at the University of Minnesota to correct a
ventricular septal defect in a 12-month-old infant on March 26, 1954 (Fig. 1-5) . The
patient had been hospitalized 10 months for uncontrollable heart failure and
pneumonitis. At operation, a 2-cm membranous ventricular septal defect (VSD) was
closed with suture. The patient made an uneventful recovery until death on the eleventh
postoperative day from a rapidly progressing tracheal bronchitis. At autopsy, the VSD
was closed, and the respiratory infection was confirmed as the cause of death. Two
weeks later the second and third patients had VSDs closed by the same technique 3
days apart. Both remained long-term survivors with normal hemodynamics confirmed by
cardiac catheterization.
In 1955 Lillehei et al. [102 ] published a report of 32 patients that included repairs of
ventricular septal defects, tetralogy of Fallot, and atrioventricularis communis defects.
By July of 1955, the blood pump used for systemic cross-circulation by Lillehei et al.
was coupled with a bubble oxygenator developed by Drs. DeWall and Lillehei, and
cross-circulation was abandoned after use in 45 patients during 1954 and 1955.
Although its clinical use was short-lived, cross-circulation was an important stepping
stone in the development of cardiac surgery. [68 ]
Meanwhile, at the Mayo Clinic only 90 miles away, John W. Kirklin and colleagues
launched their open heart program on March 5, 1955. [103 ] They used a heart-lung
machine based on the Gibbon-IBM machine, but with their own modifications. Dr. Kirklin
wrote [104 ] :
In 1951, now on the surgical staff of the Mayo Clinic I did a closed pulmonary valvulotomy
on a 30-year-old man with pulmonary stenosis and intact ventricular septum. He had
massive ventricular hypertrophy and died about two days after the operation. At autopsy it
was apparent that the pulmonary valve was open, but also that the subvalvular muscle
hypertrophy was enormous. The patient could not survive without relief of the muscular
obstruction. Dr. Earl Wood, a great physiologist and my co-worker and I went back to his
office after we viewed that autopsy and decided that we would either have to be content
with cardiac surgery as a rather minor specialty, limited to passing instruments into the
heart or we would need a heart-lung machine. In earlier times, Earl Wood had worked with
Maurice Vissher at the University of Minnesota and had extensive experience with the
Starling heart-lung preparation. It's the oxygenator that is the problem, said Earl Wood.
We investigated and visited the groups working intensively with the mechanical pump
oxygenators. We visited Dr. Gibbon in his laboratories in Philadelphia, and Dr. Forrest
Dodrill in Detroit, among others. The Gibbon pump oxygenator had been developed
and made by the International Business Machine Corporation and looked quite a bit like
a computer. Dr. Dodrill's heart-lung machine had been developed and built for him by
General Motors and it looked a great deal like a car engine. We came home, reflected
and decided to try to persuade the Mayo Clinic to let us build a pump oxygenator similar
to the Gibbon machine, but somewhat different. We already had had about a year's
experience in the animal laboratory with David Donald using a simple pump and bubble
oxygenator when we set about very early in 1953, the laborious task of building a
Mayo-Gibbon pump oxygenator and continuing the laboratory research.
Most people were very discouraged with the laboratory progress. The American Heart
Association and the National Institutes of Health had stopped funding any projects for
the study of heart-lung machines, because it was felt that the problem was
physiologically insurmountable. David Donald and I undertook a series of laboratory
experiments lasting about a year and a half during which time the engineering shops at
the Mayo Clinic constructed a pump oxygenator based on the Gibbon model. [105 ]
Of course a number of visitors came our way and some of them came to the laboratory
to see what we were doing. [104 ] One of those visitors was Ake Senning (from
Stockholm, Sweden). I still remember one day when he was there and one of the
connectors came loose and we ruined his beautiful suit as well as the ceiling of the
laboratory by spraying blood all around the room.
The electrifying day came in the spring of 1954 when the newspapers carried an
account of Walt Lillehei's successful open heart operation on a small child. Of course, I
was terribly envious and yet I was terribly admiring at the same moment. That
admiration increased exponentially when a short time later, a few of my colleagues and I
visited Minneapolis and observed one of what was now a series of successful open
heart operations with control cross-circulation. Walt then took us on rounds and it was
absolutely exciting to see small children recovering from these miraculous operations,
however it was also for a time, a difficult period for me. Some of my colleagues at the
Mayo Clinic, and some of my influential ones, indicated to me that we had wasted much
time and money. After all, this young fellow in Minneapolis was successful with a very
simple apparatus and did not even require an oxygenator. Visitors coming from
Minneapolis to Rochester asked, What are you working on these days? When I said we
were working with an integrated pump oxygenator, most said, Oh, yes, but I understand
even Gibbon has given that up. As the months went by and my anxiety grew and I
worried that we too might not make the effort a successful one. My apprehension was
heightened early in 1955 when Time Magazine published an interview with Dick Varco
who described all too accurately the damaging effects of artificial oxygenators and why
they were impractical and dangerous.
However in the winter of 1954 and 1955 we had 9 surviving dogs out of 10
cardiopulmonary bypass runs. With my wonderful colleague and pediatric cardiologist,
Jim DuShane, we had earlier selected 8 patients for intracardiac repair. Two had to be
put off because two babies with very serious congenital heart disease came along and
we decided to fit them into the schedule. We had determined to do all 8 patients even if
the first 7 died. All of this was planned with the knowledge and approval of the
governance of the Mayo Clinic. Our plan was then to return to the laboratory and spend
the next 6 to 12 months solving the problems that had arisen in the first planned clinical
trial of a pump oxygenator. Gibbon, of course, had done a successful case in 1953, but
it was an isolated case and the next four patients died. In the deepest recesses of my
heart, I felt that those four patients died in part because of the lack of appreciation of
some of the technical aspects of the cardiac surgery.
We did our first open heart operation on a Tuesday in March 1955. That evening I had a
telephone call from Dick Varco in Minneapolis who indicated that Sir Russell Brock was
visiting their cardiac surgical program at the University of Minnesota at that time. Walt
Lillehei and Dick Varco indicated to Sir Russell that we had done the operation earlier
that day and they called to see if he could come to Rochester the next day to see the
patient of which I said Certainly. I was afraid that they would ask if we planned to do
another case, and they did. I replied, Yes, and we will be doing another case on
Thursday. They asked if Sir Russell could watch the operation. Well, as you can
imagine, I had enough on my mind without having a world-famous surgeon sitting in the
gallery watching this young guy try to work his way through his second open heart
operation. However, we acceded to Sir Russell's coming and I am happy to say he was
a marvelous guest during the second operation, and the patient did well as had the first
one.
Four of our first 8 patients survived, but the press of the clinical work prevented our ever
being able to return to the laboratory with the force that we had planned. By now, Walt
Lillehei and I were on parallel, but intertwined paths. I witnessed an earlier parallel
pathway existing between Dwight Harken and Charles Bailey in the first days of closed
mitral valve surgery. I felt, and I hope you will forgive me, that their interactions were in
some ways demeaning to themselves and to the scientific progress of cardiac surgery. I
am extremely grateful to Walt Lillehei and am very proud for the two of us, that during
that 12 to 18 months when we were the only surgeons in the world performing open
intracardiac operations with cardiopulmonary bypass and surely in intense competition
with each other, we shared our gains and losses with each other. We continued to
communicate and we argued privately in nightclubs and on airplanes rather than publicly
over our differences. Walt was more cheerful and more optimistic than I when we
discussed problems. I remember saying to him one day, Walt, I am so discouraged with
complete atrial ventricular canal. Oh, sure, he said, that is a tough lesion, but we will
learn to do well with it.
By the end of 1956, many university groups around the world had launched into open
heart programs. Currently, it is estimated that more than 500,000 cardiac operations
are performed each year worldwide with the use of the heart-lung machine. In most
cases, the operative mortality is quite low, approaching 1 percent for some operations.
Little thought is given to the courageous pioneers in the 1950s whose monumental
contributions made all this possible.
EXTRACORPOREAL LIFE SUPPORT
Extracorporeal life support is an extension of cardiopulmonary bypass.

Cardiopulmonary bypass initially was limited to no more than 6 hours. The development
of membrane oxygenators in the 1960s permitted longer support. Donald Hill and
colleagues, in 1972, treated a 24-year-old man who developed shock lung after blunt
trauma. [106 ] The patient was supported for 75 hours using a heart-lung machine with a
membrane oxygenator, cannulated via the femoral vein and artery. The patient was
weaned and recovered. Hill's second patient was supported for 5 days and recovered.
This led to a randomized trial supported by the National Institutes of Health to determine
the efficacy of this therapy for adults with respiratory failure. The study was conducted
from 1972 to 1975 and showed no significant difference in survival between patients
managed by extracorporeal life support (9.5 percent) and those who received
conventional ventilatory therapy (8.3 percent). [107 ] Because of these results, most U.S.
centers abandoned efforts to support adult patients using extracorporeal life support
(ECLS), also known as extracorporeal membrane oxygenation (ECMO).
One participant in the adult trial decided to study neonates. The usual causes of
neonatal respiratory failure have in common abnormal postnatal blood shunts known as
persistent fetal circulation (PFC). [108 ] [111 ] This is a temporary, reversible
phenomenon. In 1976, Bartlett and colleagues, at the University of Michigan, were the
first to successfully treat a neonate using extracorporeal life support. Since that time,
two prospective studies have shown the efficacy of ECLS for management of neonatal
respiratory failure. [112 ] , [113 ] More than 8000 neonatal patients have been treated
using ECLS worldwide with a survival rate of 82 percent (ELSO registry data).
Alexis Carrel reported in 1914 that The arresting of the circulation of the heart has
already been performed in many ways by various experimenters. We ourselves have
used all known methods of stopping the circulation through the heart. [114 ] He also
referred to work of Borrel and others, who had experimented with different forms of
myocardial preservation. Carrel goes on to state, When the above-mentioned
precautions were taken, it was possible to clamp the pedicle of the heart (aorta and
pulmonary artery) for two and a half or three minutes without any subsequent trouble. As
soon as the clamp was removed, the heart resumed its pulsations, and after a very short
time, the pulsations were again normal. In an earlier article, in 1910, Alexis Carrel
discussed performing a coronary anastomosis in a dog and describes development of
ventricular fibrillation before the anastomosis could be completed. [115 ]
Melrose et al. [116 ] in 1955 presented the first experimental study describing induced
arrest by potassium-based cardioplegia. Blood cardioplegia was used to preserve
myocardial energy stores at the onset of cardiac ischemia. These authors state, Ringer
drew attention in 1883 to the effect of the differentiations on the heartbeat and Hooker,
in 1929 suggested that potassium inhibition induced by an excess of potassium
chloride could be used to stop the heart when its beat was disorganized by ventricular
fibrillation. Melrose goes on to state that . . .they have succeeded in evolving a reliable
method of stopping and restarting the heart at both normal and reduced body
temperatures. Unfortunately, the Melrose solution proved to be toxic to the myocardium,
and as a result, cardioplegia was not used widely for several years.
Gay and Ebert [117 ] and Tyres et al. [118 ] demonstrated that cardioplegia with lower
potassium concentrations was safe. Studies by Kirsch et al., [119 ] Bretschneider et al.,
[120 ] and Hearse et al. [121 ] demonstrated the effectiveness of cardioplegia with other
constituents and renewed interest in this technique. Gay and Ebert in 1973
demonstrated a significant reduction in myocardial oxygen consumption during
potassium-induced arrest when compared with that of the fibrillating heart. [117 ] They
also showed that the problems in the use of the Melrose solution in the early days of
cardiac surgery probably were due to its hyperosmolar properties and perhaps not to
the high potassium concentration. Ebert later wrote, Much of the credit for the
enthusiasm to reinvestigate the use of potassium and cardioplegia clearly belongs to
Bill Gay. Bill talked about the fact that potassium arrested cell membrane metabolism
from some work he had done in the individual cell physiology department at Duke
University. When he went back and looked at the formula for Melrose solution, it was
clear that there were other elements of abnormality that could have accounted for some
of the injury. Initial requests for funding were rejected, so the initial studies were
financed by departmental funds. [122 ]
In a 1978 publication by Follette et al., [123 ] the technique of blood cardioplegia was
reintroduced. In experimental and clinical studies, these authors demonstrated that
hypothermic, intermittent blood cardioplegia provided better myocardial protection than
normothermic, continuous coronary perfusion and/or hypothermic, intermittent blood
perfusion without cardioplegia solution. The composition of the best cardioplegia
solution remains controversial, and new formulations, methods of delivery, and
recommended temperature continue to evolve.
EVOLUTION OF CONGENITAL CARDIAC SURGERY DURING THE
ERA OF CARDIOPULMONARY BYPASS
With the advent of cardiopulmonary bypass using either the cross-circulation technique
of Lillehei et al. or the version of the mechanical heart-lung machine developed by
Kirklin et al., the two groups led the development of intracardiac repairs for many of the
commonly occurring congenital heart defects. Because of the morbidity associated with
the heart-lung machine, palliative operations also were developed to improve circulatory
physiology without directly addressing the anatomic pathology. These palliative
operations included the Blalock-Taussig subclavian-pulmonary arterial shunt [60 ] with
modifications by Potts et al. [124 ] and Waterston et al., [125 ] the Blalock-Hanlon
operation to create an atrial septal defect, [126 ] and the Galankin-Glenn superior vena
cava-right pulmonary arterial shunt. [66 ]
As the safety of cardiopulmonary bypass steadily improved, surgeons addressed more

and more complex abnormalities of the heart in younger and younger patients. Some of
the milestones in the development of operations to correct congenital heart defects
using cardiopulmonary bypass appear in Table 1-1 . These advances coincided with
simultaneous advances in the surgery of adult heart disease, and the same surgeons
operated on both children and adults. In the 1970s, although dependent on the same
technology and basic knowledge, pediatric and adult cardiac surgery began to
separate. Operations for more complex congenital lesions in younger and younger
patients required new techniques, and likewise the advent of direct operations for
ischemic heart disease required new technology and methods to deal with damaged
ventricles and acute complications of ischemia. With the exception of sporadic patients
who reached adult life with uncorrected or partially corrected congenital heart defects,
cardiac surgery in the adult represents the surgery of acquired heart disease.
Nevertheless, a close connection continues because the advances in one subspecialty
usually are applicable in the other, and this kinship and interdependence probably will
remain for the foreseeable future.
VALVULAR SURGERY: CARDIOPULMONARY BYPASS ERA
Cardiac valve repair or replacement under direct vision awaited the development of the
heart-lung machine. The first successful aortic valve replacement in the subcoronary
position was performed by Dr. Dwight Harken and colleagues. [145 ] A caged ball valve
was used. Many of the techniques described in Harken's 1960 report are similar to
those used today for aortic valve replacement (Fig. 1-6A,B) .
That same year, Starr and Edwards [146 ] successfully replaced the mitral valve using a
caged ball valve of their own design. Starr later wrote [147 ] :
In 1958, Lowell Edwards presented himself in my office with a proposal to develop an

implantable artificial heart. I learned that he was a retired engineer with considerable
financial resources. His visit was fortuitous, because just about that time, I had become
interested in valvular prostheses. The few Bahnson leaflets that we had inserted seemed
unsatisfactory. . . . Edwards agreed to begin the project by working on one valve at a time.
. . . The obvious direction then was towards the ball valve prosthesis. I drew out for
Edwards the general configuration of the Hufnagel valve. He then drew out for me how he
thought that particular valve could be adapted for intracardiac use using an open cage. The
first animal to have this implant survived for more than a year, but all other subsequent
animals died of thrombosis. . . . . The big breakthrough came at the end of 1958 when we
developed the Silastic shield for the ball valve, which allowed an 80 percent long-term
survival. I remember very well the day I thought of the idea of the Silastic shield. It was a
beautiful spring afternoon. I was bounding up the steps of the Basic Science Building with
my mind wandering aimlessly when it suddenly struck me that a Silastic shield over the
area where thrombus formed on the valve would give us a chance to have long-term
survivors.
This takes me up to the summer of 1960. Our animal work was well known to the chief of
cardiology, Dr. Herbert Griswold. It was Dr. Griswold who insisted that we perform the first
clinical implant after I took him to the animal laboratory and he saw a kennel full of active
dogs that had mitral valve replacements. Dr. Dunphy, the chairman of the department of
surgery at that time was extremely supportive and urged us to go ahead.
The first operation was done in September of 1960 on a young girl in her mid-twenties. The
patient was in pulmonary edema in an oxygen tent prior to operation. On the evening of the
day of surgery, I returned to the hospital to see her and found her to be hemodynamically
stable, and in excellent condition and wide awake.
By 1967, nearly 2000 Starr-Edwards valves had been implanted, and the caged ball
valve prosthesis was established as the standard against which all other mechanical
prostheses would be compared.
In 1964, Starr and associates reported 13 patients who had undergone multiple valve
replacement. [148 ] One patient had the aortic, mitral, and tricuspid valves replaced on
February 21, 1963. Cartwright et al., however, on November 1, 1961, were first to
successfully replace both the aortic and mitral valves with ball-valve prostheses that they
had developed. [149 ] Knott-Craig et al., [150 ] from the Mayo Clinic, successfully
replaced all four heart valves in a patient with carcinoid involvement.
In 1961, Andrew Morrow and Edwin Brockenbrough [151 ] reported the treatment for
idiopathic hypertrophic subaortic stenosis by resecting a portion of the thickened
ventricular septum. They referred to this as subaortic ventriculomyotomy. They gave
credit to William Cleland and H. H. Bentall in London, who had encountered this
condition unexpectedly at operation and resected a small portion of the ventricular
mass. The patient improved, but no postoperative hemodynamic studies had been
reported. The subaortic ventriculomyolotomy became the standard surgical treatment
for this cardiac anomaly, although in some patients systolic anterior motion (SAM) of the
anterior leaflet of the mitral valve necessitates mitral valve replacement with a
low-profile mechanical valve.
An aortic homograft valve was used clinically for the first time by Heimbecker and
associates in Toronto for replacement of the mitral valve in one patient and an aortic
valve in another. [152 ] Survival was short, 1 day in one patient and 1 month in the other.
Donald Ross reported on the first successful aortic valve placement with an aortic valve
homograft. [153 ] He used a technique of subcoronary implantation developed in the
laboratory by C arlos D uran and Alfred Gunning in Oxford.
The technique of aortic valve replacement with a pulmonary autograft initially described
by Ross in 1967 is advocated for younger patients who require aortic valve replacement
by some groups. [154 ] , [155 ] An aortic or pulmonary valve homograft is used to
replace the pulmonary valve that has been transferred to the aortic position.
Other autogenous materials that have been used to manufacture valve prostheses
include pericardium, fasciae latae, and dura mater. In the 1960s, Binet et al. [156 ]
began to develop and test tissue valves. In 1964, Duran and Gunning in England
replaced an aortic valve in a patient using a xenograft porcine aortic valve. Early results
with formaldehyde-fixed xenografts were good, [156 ] but in a few years these valves
began to fail because of tissue degeneration and calcification. [157 ] Carpentier and
associates revitalized interest in xenograft valves by fixating porcine valves with
gluteraldehyde. Carpentier also mounted his valves on a stent, to produce a
bioprosthesis. Carpentier-Edwards porcine valves and Hancock and Angell-Shiley
bioprostheses became popular and were implanted in large numbers of patients. [158 ]
, [159 ]
Carpentier later wrote, In 1964 as a young resident in thoracic surgery, I was asked by
J. P. Binet, chief of the service, to collect homograft valves from cadavers. Studies of
the anatomy of the valves in various animal species showed that the valves from the
pigs were the closest to those of humans. [160 ] Carpentier described the first
successful xenograft valve replacement in 1965, followed by 12 other operations, but
within 5 years all the heterograft valves had to be replaced. Carpentier goes on to state:
The use of formalin proposed by O'Brien did not significantly improve the results. I began
mounting the valves on a stent in 1966, which permitted the use of heterograft valves in the
mitral position. It became obvious that the future of tissue valves would depend upon the
development of methods of preparation capable of preventing inflammatory cell reaction,
and penetration into the tissue. My background in chemistry is obviously insufficient. I
decided to abandon surgery for two days a week to follow the teaching program in
chemistry at the Faculty of Sciences and prepare a Ph.D. It is certainly not easy to
become a student in chemistry when you are 35 and an associate professor of surgery.
I began to investigate numerous cross-linking inducing factors and found that

gluteraldehyde was able to almost eliminate inflammatory reaction. . . .My wife, Sophie,
was a tremendous help all those years. [Early clinical failures in the 1970s are described.]
I was almost ready to abandon twice. The last time, the patient, a 39-year-old business
man, developed a diastolic murmur and I told him he would have to have a re-operation and
have a mechanical valve implanted. He protested that he wanted to have another
bioprosthesis. The patient then explained the reason for his decision. I know three other
patients with which I remain in close contact with mechanical valves. One died in 6
months, the second had a transient cerebral attack and the third is still doing well, but
cannot sleep with his wife because of the noise of the valve. So please give me another
bioprosthesis. Which I did.
With the development of cardiopulmonary bypass, valves could be approached under

direct vision, and for the first time mitral insufficiency could be attacked. Techniques for
mitral annuloplasty were described by Wooler et al., [161 ] Reed et al., [162 ] and Kaye
et al. [163 ] The next step forward was development of annuloplasty rings by Carpentier
and Duran. In the 1970s, few groups were involved in valve repairs. Slowly, techniques
evolved, were tested clinically, and were followed over the years. Carpentier led the
field. He established the importance of careful analysis of valve pathology, described in
detail several techniques of valve repair, and reported good results after early and late
follow-up. [164 ]
From 1966 to 1968, a small epidemic of infective endocarditis in Detroit among heroin
addicts broke out. Patients were dying of intractable gram-negative endocarditis, often
due to Pseudomonas aeruginosa . Long-term antibiotic administration in combination
with tricuspid valve replacement was 100 percent fatal. These results prompted Agustin
Arbulu and colleagues to remove the tricuspid valve without replacing it in seven dogs in
1969. Six survived with satisfactory hemodynamic performance. Starting in 1970,
Arbulu operated on 55 patients; in 53, the tricuspid valve was removed without
replacing it, and in 2, he also removed the pulmonic valve without replacement. [165 ] ,
[166 ] At 25 years, the actuarial survival is 61 percent.
CORONARY ARTERY SURGERY
Alexis Carrel remarked in 1910 [115 ] :
I attempted to perform an indirect anastomosis between descending aorta and the left
coronary artery. It was for many reasons a difficult operation. On account of the
continuous motion of the heart, it was not easy to dissect and to suture the artery. In one
case, I implanted one end of a long carotid artery, preserved in a cold storage on the
descending aorta. The other end was passed through the pericardium and anastomosed to
the pericardial end of the coronary near the pulmonary artery. Unfortunately, the operation
was too slow. Three minutes after the interruption of the circulation fibrillary contractions
appeared, but the anastomosis took five minutes. By massage of the heart, the dog was
kept alive, but he died less than two hours afterwards. It shows that the anastomosis must
be done in less than three minutes.
Not much happened after that until 1930, when Claude Beck, a Cleveland surgeon,
developed methods to indirectly revascularize the hearts of animals by attaching
adjacent tissues in hopes of forming collateral blood flow to ischemic myocardium. [167
] These tissues included pericardium, pericardial fat, pectoralis muscle, and omentum.
Postmortem examination showed that anastomotic vessels did develop between these
tissues and the myocardium. In the first patient, Beck roughened the outer surface of the
heart with a burr and then sutured a pedicle graft of pectoralis muscle to the left
ventricular wall. [168 ] The patient made an uneventful recovery and was angina-free
after the operation. Beck subsequently performed this operation with modifications on
16 patients. [169 ]
Arthur Vineberg, a Canadian surgeon, in 1946 reported implanting the internal

mammary artery through a tunnel in the myocardium. [170 ] He showed in animals that
communications developed between the internal mammary and the coronary arteries.
Contemporary surgeons, however, remained skeptical, but Mason Sones validated
Vineberg's concept by demonstrating communications between the graft in the
myocardium and the coronary system by angiography in two patients operated on 5 and
6 years earlier. In the middle 1960s the Vineberg operation with many variations was
performed at many institutions in the United States and Canada. [171 ] At the same
time, other surgeons performed coronary arterial endarterectomies. Longmire et al.
[172 ] were the first to report endarterectomy of the coronary arteries for the treatment of
ischemic coronary disease. In 1958 they reported five patients, with four hospital
survivors. Although the operation was used subsequently by other groups, mortality was
high, and the procedure was abandoned as an isolated operation.
Selective coronary angiography was developed by Sones and Shirey, at the Cleveland
Clinic, and reported in their 1962 classic paper, Cine Coronary Arteriography. [173 ]
They used a catheter to directly inject contrast material into the coronary artery ostia.
This technique gave a major impetus to direct revascularization of obstructed coronary
arteries.
W. Dudley Johnson, one of the pioneers in the development of coronary artery surgery,
wrote, From 1962 to 1967, several sporadic instances of coronary grafting have
subsequently been reported. All were isolated cases and, for uncertain reasons, were
not reproduced. None had an impact on the development of coronary surgery. [174 ] An
example of Dr. Johnson's comment involved a case of autogenous saphenous vein
bypass grafting performed on November 23, 1964 in a 42-year-old man who was
scheduled to have endarterectomy of his left coronary. [175 ] Since the lesion involved
the entire bifurcation, endarterectomy with venous patch graft was abandoned as too
hazardous. The anterior descending coronary artery was softer distal to the bifurcation.
An autogenous saphenous vein graft was therefore placed from the aorta to the left
anterior descending. This was probably the first clinical case of successful coronary
artery bypass surgery using saphenous vein. The authors, Garrett, Dennis, and
DeBakey, however, did not report this case until 1973. The patient was alive at that
time, and angiograms showed the vein graft to be patent.
Shumaker [176 ] credits Longmire with the first internal mammary to coronary artery
anastomosis. It was almost surely Longmire, long-time chairman at U.C.L.A. and his
associate, Jack Cannon, who first performed an anastomosis between the internal
mammary artery and a coronary branch, probably in early 1958. Longmire wrote:
At that time we were doing the coronary thromboendarterectomy procedure, we also, I

think, performed a couple of the earliest internal mammarycoronary anastomoses. . . . We
were forced into it when the coronary artery we were endarterectomizing disintegrated, and
in desperation we anastomosed the internal mammary artery to the distal end of the right
coronary arteryand later decided it was a good operation.
The reference that Shumacker gives for this quotation from longtime is a personal
communication to Shumacker in 1990, thirty-two years after the fact!
As early as 1952, Vladimir Demikhov, the renowned Soviet surgeon, was

anastomosing the internal mammary artery to the left coronary artery in dogs. [177 ] In
1967, at the height of the Cold War, a Soviet surgeon, V. I. Kolessov, from Leningrad,
reported his experience in an American surgical journal with mammary arterycoronary
artery anastomoses for treatment of angina pectoris in six patients. [178 ] Operations
were performed through a left thoracotomy without extracorporeal circulation or
cineangiography. Donald Effler, then chief of cardiac surgery at the Cleveland Clinic,
commented on Kolessov's paper and recommended that preoperative cineangiography
be performed.
The following year, Green et al. [179 ] and Bailey and Hirose [180 ] separately published
reports in which the internal mammary artery was used for coronary artery bypass in
patients. Bailey and Hirose carried out the anastomosis on the beating heart and
advocated using 2× power Loupes for magnification. Green et al. advocated using
cardiopulmonary bypass, fibrillating the vented heart, cross-clamping the aorta, and
washing all blood from the coronary system while performing the anastomosis. Frank
Spencer later wrote [181 ] :
My own contributions (F.C.S.) to coronary bypass were principally experimental studies

that led to the internal mammary technique at the University of Kentucky between 1962
and 1966. Coronary revascularization was a major project in our experimental laboratory.
The satisfactory long-term patency of anastomoses of the internal mammary to the
anterior descending coronary artery was demonstrated in a group of animals and reported
in 1964.
At New York University in 1966, George Green was one of our first thoracic residents.
After reading our experimental paper, he became interested in a microvascular approach
with the internal mammary artery. I thought the artery was probably too small in man, but
fortunately, encouraged Dr. Green to proceed first experimentally, then clinically with David
Tice in 1968. This launched our clinical use of coronary bypass at NYU.
As experienced by others, initial reactions were those of skepticism and intense criticism.
A small contribution of mine unwittingly arose after Dr. Green left NYU. One of the
hospitals at which Dr. Green worked wished to severely restrict his operative privileges in
this area. Through a combination of efforts, I was successful in getting the decision
postponed for a few months. Dr. Green's excellent results soon spoke for themselves and
required no further help from me.
Rene Favalaro from the Cleveland Clinic used saphenous vein for bypassing coronary
obstructions. [182 ] Favalaro's 1968 article focused on 15 patients, who were part of a
larger series of 180 patients who had undergone the Vineberg procedure. In these 15
patients with occlusion of the proximal right coronary artery, an interpositional graft of
saphenous vein also was placed between the ascending aorta and the right coronary
artery distal to the blockage. The right coronary was divided, and the vein graft was
anastomosed end-to-end. Favalaro states that this procedure was done because of the
unfavorable results with pericardial patch reconstruction of the coronary artery. In an
addendum to that paper, 55 cases were added, 52 for segmental occlusion of the right
coronary and 3 others for circumflex disease.
The contributions by Favalaro, Kolessov, Green et al., and Bailey and Hirose were all
important, but arguably the official start date of coronary bypass surgery as we know it
today happened in 1969 when W. Dudley Johnson and colleagues from Milwaukee
reported their series of 301 patients who had undergone various operations for
coronary disease since February of 1967. [183 ] In that report, the authors presented
their results with direct coronary surgery during a 19-month period (Fig. 1-7) . They
state:
After two initial and successful patch grafts, the vein bypass technique has been used
exclusively. Early results were so encouraging that last summer the vein graft technique
was expanded and used to all major branches. Vein grafts to the left side of the arteries
run from the aorta over the pulmonary artery and down to the appropriate coronary vessel.
Right-sided grafts run along the atrio-ventricular groove and also attach directly to the
aorta. There is almost no limit of potential (coronary) arteries to use. Veins can be sutured
to the distal anterior descending or even to posterior marginal branches. Double vein grafts
are now used in over 40 percent of patients and can be used to any combination of
arteries. . . . This direct approach to coronary flow immediately improves heart function,
alleviates most clinical symptoms. Dyskinetic, akinetic or frankly failing myocardium in no
way contraindicates surgery. . . . Angina is almost always absent following surgery. We
have not yet been able to define a degree of failure so severe that this alone
contraindicates the direct attack on coronary reconstruction.
Our experience indicates that five factors are important to direct surgery. One: Do not limit
grafts to proximal portions of large arteries. . . . Two: Do not work with diseased arteries.
Vein grafts can be made as long as necessary and should be inserted into distal normal
arteries. Three: Always do end-to-side anastomosis. . . . Four: Always work on dry, quiet
field. Consistently successful fine vessel anastomoses cannot be done on a moving,
bloody target. . . . Five: Do not allow the hematocrit to fall below 35.
In discussing Dr. Johnson's presentation, Dr. Frank Spencer commented, [183 ] I would
like to congratulate Dr. Johnson very heartily. We may have heard a milestone in
cardiac surgery today. Because for years, pathologists, cardiologists, and many
surgeons have repeatedly stated that the pattern of coronary artery disease is so
extensive that direct anastomosis can be done in only 5 to 7 percent of patients. If the
exciting data by Dr. Johnson remain valid and the grafts remain patent over a long
period of time, a total revision of thinking will be required regarding the feasibility of
direct arterial surgery for coronary artery disease.
The direct anastomosis between the internal mammary artery and the coronary artery
was not initially as popular as the vein graft technique; however, due to the persistence
of Drs. Green, Loop, Grondin, and others, internal mammary artery grafts eventually
became the conduit of choice when their superior long-term patency became known.
[184 ]
Denton Cooley and colleagues made two important contributions to the surgery for
ischemic heart disease. [185 ] In 1957, with the use of cardiopulmonary bypass, they
were the first to repair a ruptured interventricular septum following acute myocardial
infarction. The patient initially did well but died 6 weeks after operation of complications.
Cooley et al. also were the first to report the resection of a left ventricular aneurysm with
the use of cardiopulmonary bypass. [186 ]
Beck [187 ] in 1944 was the first to successfully excise a left ventricular aneurysm, and
Bailey et al. [188 ] in 1951 had five survivors of six attempts with a clamp and oversew
technique. In 1959, Boris Petrovsky, [189 ] a prominent Soviet cardiac surgeon,
reported using diaphragmatic pedicle flaps in humans to treat left ventricular aneurysm.
He sutured the muscle grafts directly to the pericardial surface of the scarred left
ventricle. This was done under sufficient tension to flatten the aneurysm. About 30
percent of these patients experienced relief of chest pain and dyspnea. Operative
mortality was approximately 20 percent. Petrovsky later abandoned this procedure.[189
] [193 ]
DYSRHYTHMIA SURGERY
Sealy and colleagues at Duke University developed the first successful surgical
treatment for cardiac arrhythmias. [194 ] , [195 ] A 32-year-old fisherman was referred
for symptomatic episodes of atrial tachycardia that caused congestive heart failure. On
May 2, 1968, after epicardial mapping, a 5-to-6-cm cut was made extending from the
base of the right atrial appendage to the right border of the right atrium during
cardiopulmonary bypass. The incision transsected the conduction pathway between the
atrium and ventricle. Subsequent epicardial mapping indicated eradication of the
pathway. Six weeks after operation heart size had decreased and lung fields had
cleared. The patient eventually returned to work.
A year earlier, Dr. Dwight McGoon at the Mayo Clinic closed an atrial septal defect in a
patient who also had the Wolf-Parkinson-White syndrome (WPW). [195 ] At operation,
Dr. Birchell mapped the epicardium of the heart and localized the accessory pathway to
the right atrioventricular groove. Lidocaine was injected into the site, and the delta wave
immediately disappeared. Unfortunately, conduction across the pathway reappeared a
few hours later. This was probably the first attempt to treat the WPW syndrome
surgically. As a result of knowledge gained from the surgical treatment for WPW
syndrome, over 95 percent of all refractory clinical cases are treated successfully by
nonsurgical means. [195 ]
Guiraudon et al., [196 ] from Paris, France, reported their results with an encircling
endomyocardial ventriculotomy for the treatment of malignant ventricular arrhythmias.
The following year, in 1979, Josephson et al. [197 ] described a more specific
procedure for treatment of malignant ventricular arrhythmias. After endocardial
mapping, the endocardial source of the arrhythmia was excised. Although the
Guiraudon technique usually isolated the source of the arrhythmia, the incision also
devascularized healthy myocardium and was associated with high mortality.
Endocardial resection was safer and more efficacious, and became the basis of all
approaches for the treatment of ischemic ventricular tachycardia. [195 ]
Ross et al., [198 ] in Sydney, Australia, and Cox et al., [199 ] in St. Louis, Missouri, used
cryosurgical treatment of atrial ventricular node reentry tachycardia. Subsequently, Cox,
after years of laboratory research, developed the maze operation for atrial fibrillation.
[200 ]
Stimulated by the death of a close personal friend from ventricular arrhythmias, Dr.
Mirowski developed a prototype defibrillator over a 3-month period in 1969. In 1980,
Mirowski et al. described three successful cases using their implantable myocardial
stimulator at Johns Hopkins. [201 ]
PACEMAKERS
Lidwill and Booth in Australia supposedly revived a stillborn infant with electrical pacing
in the 1920s. [202 ] Hyman temporarily paced the heart using two needle electrodes
that were passed through the ribs and an electrical device of his own design. In the early
1950s, Bigelow and colleagues reported controlling the heart rate in dogs using
external pacemakers. [88 ]
Paul Zoll is given credit for ushering in the clinical era of pacemaking. In 1952, he
reported on two patients suffering from recurring prolonged ventricular standstill whom
he treated with an external pacemaker. [203 ] The first patient was a 75-year-old man
with complete heart block who had been revived with 34 intracardiac injections of
epinephrine over a 4-hour period. Zoll applied electric shocks 2 ms in duration that were
transmitted through the chest wall at frequencies from 25 to 60 per minute and
increased the intensity of the shock until ventricular responses were observed.
After 25 minutes of intermittent stimulation, however, the spontaneous ventricular

electrocardiographic complexes became smaller, more irregular and fewer. The
peripheral pulsations and electrocardiographic deflections following the electrical
stimulation disappeared. Another intercardiac injection of epinephrine was followed by
ventricular flutter, then fibrillation, then the patient died. Many subsequent patients,
however, recovered.
The next step came when Lillehei and associates reported a series of patients who had
external pacing after open heart surgery during the 1950s. [204 ] The field of open heart
surgery gave a major impetus to the development of pacemakers. This is so because
there was a high incidence of heart block following many intracardiac repairs. The major
difference between Zoll's pacing and that of Lillehei et al. was that Zoll used external
electrodes placed on the chest wall, whereas Lillehei et al. attached electrodes directly
to the heart at operation. Lillehei et al. used a relatively small external pacemaker to
stimulate the heart and much less electric current. This form of heart pacing was better
tolerated by the patient and was a more efficient way to stimulate the heart. The survival
rate of Lillehei's patients with surgically induced heart block was significantly improved.
During this period, progress was made toward a totally implantable pacemaker.
Elmquist and Senning [205 ] developed a pacer battery that was small enough for an
epigastric pocket with electrodes connected to the heart. They implanted the unit in a
patient with atrioventricular block in 1958. Just before implantation, the patient had 20 to
30 cardiac arrests a day. To avoid publicity, the implantation was done in the evening
when the operating rooms were empty. According to Dr. Senning, the first pacemaker
that was implanted functioned only 8 hours; the second pacemaker implanted in the
same patient had better success. The patient survived more than 25 years and had at
least five additional pacemakers. Chardack, Gage, and Greatbatch are perhaps better
known for their development of the totally implantable pacemaker. [206 ] In 1961 they
reported a series of 15 patients who had pacemakers implanted that they had
developed. Other completely implantable units were developed by Zoll and colleagues
in 1961 and by Kantrowitz and associates in 1962. The technique for inserting
permanent transvenous bipolar pacemaker electrodes was developed in 1962 by
Parsonnet et al. [207 ] in the United States and Ekstrom et al. [208 ] in Sweden.
Early implantable pacemakers were fixed-rate, asynchronous devices that delivered an

impulse independent of the underlying cardiac rhythm. During the past 35 years,
enormous progress has been made in the field of pacing technology. The number of
individuals with artificial pacemakers is unknown; however, estimates indicate that
approximately 500,000 Americans are living with a pacemaker and that each year
another 100,000 or more patients require permanent pacemakers in the United States.
HEART, HEART-LUNG, AND LUNG TRANSPLANTATION
Alexis Carrel and Charles Guthrie reported transplantation of the heart and lungs while
at the University of Chicago in 1905. [209 ] The heart of a small dog was transplanted
into the neck of a larger one by anastomosing the caudad ends of the jugular vein and
carotid artery to the aorta and pulmonary artery. The animal was not anticoagulated, and
the experiment ended about 2 hours after circulation was established because of blood
clot in the cavities of the transplanted heart. Carrel also reported in 1906 that he had
transplanted the heart and lungs of a 1-week-old cat into the neck of a larger cat. [210 ]
The coronary circulation was immediately reestablished, and the auricles began to
beat. The lungs became red and after a few minutes effective pulsation of the ventricles
appeared. Carrel stated that a phlegmon of the neck terminated this observation 2 days
later.
Vladimir Demikhov, the great Soviet investigator, described more than 20 different
techniques for heart transplantation in 1950. [211 ] He also published various
techniques for heart and lung transplantation. He was even able to perform an
orthotopic heart transplant in a dog before the heart-lung machine was developed. This
was accomplished by placing the donor heart above the dog's own heart, and then with
a series of tubes and connections, he rerouted the blood from one heart to the other
until he had the donor heart functioning in the appropriate position and the other heart
removed. One of his dogs climbed the steps of the Kremlin on the sixth postoperative
day but died shortly afterwards of rejection.
Richard Lower and Norman Shumway established the technique for heart
transplantation as it is performed today. [212 ] Preservation of the cuff of recipient left
and right atria with part of the atrial septum was described earlier by Brock [213 ] in
England and Demikhov [177 ] in the Soviet Union, but it became popular only after
Shumway and Lower reported it in their 1960 paper. Shumway stated [214 ] :
In 1958 when I started work at Stanford, the idea [cardiac transplantation] grew out of our
local cooling experiments, since we had one hour of aortic cross-clamping during
cardiopulmonary bypass. Accordingly we decided to remove the heart at the atrial level
and then to suture it back into position. After several of these experiments, we found it
would be easier to remove the heart of another dog and to do the actual allotransplant.
Something like 20 to 30 experiments were performed before we had a survivor. All of this
was done before chemical immune suppression was available.
The first attempt at a human heart transplantation was made by Hardy et al. [215 ] at the
University of Mississippi. Since no human donor organ was available at the time, a
large chimpanzee's heart was used; however, it was unable to support the circulation.
The first human-to-human heart transplant occurred December 3, 1967, at the Groote
Schuur Hospital in Capetown, South Africa. [216 ] The surgical team, headed by
Christiaan Barnard, transplanted the heart of a donor who had been certified dead after
the electrocardiogram showed no activity for 5 minutes into a 54-year-old man whose
heart was irreparably damaged by repeated myocardial infarctions. The second human
heart transplant using a human donor was performed on a child 3 days after the first on
December 6, 1967, by Adrian Kantrowitz in Brooklyn, New York. Dr. Kantrowitz's patient
died of a bleeding complication within the first 24 hours. [217 ] Barnard's patient, Lewis
Washkansky, died on the eighteenth postoperative day. At autopsy, the heart appeared
normal, and there was no evidence of chronic liver congestion, but bilateral pneumonia,
possibly due to severe myloid depression from immunosuppression, was present. [218
]
On January 2, 1968, Barnard performed a second heart transplant on Phillip Blaiberg,

12 days after Washkansky's death. [219 ] Blaiberg was discharged from the hospital
and became a celebrity during the several months he lived after the transplant.
Blaiberg's procedure indicated that a heart transplant was an option for humans
suffering from end-stage heart disease. Within a year of Barnard's first heart transplant,
99 heart transplants had been performed by cardiac surgeons around the world.
However, by the end of 1968, most groups abandoned heart transplantation because of
the extremely high mortality related to rejection. Shumway and Lower, and a few others,
persevered both clinically and in the laboratory. Their efforts in the discovery of better
drugs for immunosuppression eventually established heart transplantation as we know it
today.
A clinical trial of heart-lung transplantation was commenced at Stanford University in

1981 by Reitz et al. [220 ] Their first patient was treated with a combination of
cyclosporine and azothioprine. The patient was discharged from the hospital in good
condition and was well more than 5 years after the transplant. Reitz's clinical success
was based on earlier experiments with primates using allografts. [221 ] , [222 ] These
primate recipients survived for more than 140 days when cyclosporine A was used for
immune suppression (Fig. 1-8) . Several of these animals lived for more than 5 years
after allotransplantation. [223 ]
The current success with heart, heart-lung, and lung transplantation is in part related to
the discovery of cyclosporine by workers at the Sandoz Laboratory in Basel,
Switzerland, in 1970. In December of 1980, cyclosporine was introduced at Stanford for
cardiac transplantation. The incidence of rejection was not reduced, nor was the
incidence of infection. However, these two major complications of cardiac
transplantation were less severe when cyclosporine was used. Availability of
cyclosporine stimulated many new programs across the United States in the
mid-1980s.
Andre Juvenelle showed that animals could survive autologous lung transplantation for
many years. [224 ] Lung transplantation from dog to dog was fatal when attempted in the
early 1950s. [225 ] Some animals, however, survived with an autotransplant up to 29
days before succumbing to rejection. [226 ] The first human lung transplant was
performed by Hardy et al. [227 ] at the University of Mississippi on June 11, 1964. A
pneumonectomy for carcinoma with pleural adhesions had to be performed first. The
patient died on the seventeenth postoperative day. In 1971, a Belgian surgeon, Fritz
Derom, achieved a 10-month survival in a patient with pulmonary silicosis. [228 ]
Much of the credit, however, for the success of lung transplantation belongs to the
Toronto group whose efforts were headed by Joel Cooper. Their successes were
based on laboratory experimentation and the discovery of cyclosporine. After losing an
early patient to bronchial anastomotic dehiscence in 1978, the group substituted
cyclosporine for cortisone and wrapped the bronchial suture line with a pedicle of
omentum. They also developed a comprehensive preoperative preparation program
that increased the strength and nutritional status of the recipients. In 1986, Cooper and
associates presented their first two successful patients, who had returned to normal
activities and were alive 14 and 26 months after operation. [229 ] This success was the
culmination of more than 40 previous attempts throughout the world made after Derom's
case.
HEART ASSIST AND ARTIFICIAL HEARTS
The concept of intraaortic counterpulsation was first described by Harken [230 ] in 1958
and reported by Clauss et al. [231 ] in 1961. This idea proposed removal of blood via
the femoral artery during systole and rapid reinfusion of the same blood during diastole
to increase coronary perfusion. Technical difficulties and complications secondary to
hemolysis delayed clinical use until 1962, when Moulopoulos and coworkers introduced
a balloon catheter placed in the thoracic aorta. [232 ] In 1963, Kantrowitz and
associates reported the first use of the intraaortic balloon pump in three patients. [233 ]
All were in cardiogenic shock but improved during balloon pumping. One survived to
leave the hospital.
Akutsu and Kolff reported the development and first application of a totally artificial heart
in an animal model at the Cleveland Clinic in 1957. [234 ] The authors implanted a
totally artificial heart in a living dog that survived for 90 minutes with the mechanical
heart.
In 1963, Liotta and colleagues reported a 42-year-old man who had a stenotic aortic
valve replaced but suffered a cardiac arrest the following morning. [235 ] The patient
was resuscitated but developed severe ventricular failure. An artificial intrathoracic
circulatory pump was implanted. The patient's pulmonary edema cleared, but he died 4
days later with the pump working continuously. In 1966, the same group used a newer
intrathoracic pump to support another patient who could not be weaned from
cardiopulmonary bypass. This pump maintained the circulation. The patient eventually
died before the pump could be removed. [176 ] Later that year, the same group used a
left ventricular assist device in a woman who could not be weaned from
cardiopulmonary bypass after double valve replacement. [176 ] After 10 days of
circulatory assistance, the patient was weaned successfully from the device and
recovered. This woman was probably the first patient to be weaned from an assist
device and to leave the hospital.
The first human application of a totally artificial heart was by Denton Cooley and
colleagues as a bridge to transplantation. [236 ] They implanted a totally artificial heart
in a patient who could not be weaned from cardiopulmonary bypass. After 64 hours of
artificial heart support, heart transplantation was performed, but the patient died of
Pseudomonas pneumonia 32 hours after transplantation. The first two patients
successfully bridged to transplantation were reported at almost the same time and in
the same location by different groups. On September 5, 1984, in San Francisco, [237 ]
Donald Hill implanted a Pierce-Donachy left ventricular assist device in a patient in
cardiogenic shock. The patient was transplanted successfully 2 days later and was later
discharged. The assist device used by Hill was developed at Pennsylvania State
University by Pierce and Donachy. Phillip Oyer and associates at Stanford University
placed an electrically driven Novacor left ventricular assist device in a patient in
cardiogenic shock on September 7, 1984. [238 ] The patient was transplanted
successfully and survived beyond 3 years. The device used by the Stanford group was
developed by Peer Portner.
The first implantation of a permanent totally artificial heart (Jarvik-7) was performed by
DeVries and colleagues at the University of Utah in 1982. [239 ] By 1985, they had
implanted the Jarvik in four patients, and one survived for 620 days after implantation
(Fig. 1-9) . This initial clinical experience was heavily based on the work of Kolff and
associates.
The effort to use autologous skeletal muscle to assist the failing circulation began in
1959 when Adrian Kantrowitz wrapped diaphragm around the canine aorta to produce
diastolic counterpulsation. [240 ] The problem of muscle fatigue was solved in 1969
when Salmons and Vrbova [241 ] discovered that fast-twitch fibers found in skeletal
muscle could be transformed into slow-twitch fatigue-resistant fibers by chronic
electrical stimulation of the motor nerve. The observation led Stephenson and
colleagues to develop an electrical conditioning protocol for fiber transformation of large
canine muscles [242 ] , [243 ] and Chiu and associates [244 ] to develop the concept of
burst stimulation to increase the force of muscle contraction. These advances prompted
several surgeons to wrap latissimus dorsi muscle around ventricles of failing hearts and
stimulate the muscle to contract during systole. Alain Carpentier in 1985 first performed
this procedure in a patient. [245 ] Subsequently, more than 600 patients worldwide have
had this procedure, known as cardiomyoplasty (see Chap. 52). An alternative method
to harness skeletal muscle power to the circulation is to wrap a muscle around a
pericardial or endothelial cell-lined pouch attached to the thoracic aorta. Canine studies
have demonstrated that these skeletal muscle ventricles continue to function for over 2.5
years. [246 ]
THORACIC AORTA SURGERY
Alexis Carrel was responsible for one of the great surgical advances of the twentieth
century: techniques for suturing and transplanting blood vessels. [247 ] Although Carrel
initially developed his methods of blood vessel anastomosis in Lyon, France, his work
with Charles Guthrie in Chicago led to many major advances in vascular, cardiac, and
transplantation surgery. In a short period of time, these investigators perfected
techniques for blood vessel anastomoses and transposition of arterial and venous
segments using both fresh and frozen grafts. After leaving Chicago, Carrel continued to
expand his work on blood vessels and organ transplantation and in 1912 received the
Nobel Prize. Interestingly, Carrel's work did not receive immediate clinical application.
Rudolph Matas pioneered clinical vascular surgery. Matas's work took place before
drugs were available to prevent blood clotting, before antibiotics, and without reliable
blood vessel substitutes. [248 ] Matas performed 620 vascular operations between
1888 and 1940. Only 101 of these were attempts to repair arteries; most involved
ligation. Matas developed three variations of his well-known endoaneurysmorrhaphy
procedure. The most advanced was to reconstruct the wall of the blood vessel from
within while using a rubber tube as a stent.
Vascular surgery advanced tentatively during World War II as traumatic injuries to major
blood vessels were repaired in a few soldiers with results significantly better than with
the standard treatment of ligation. [249 ] The successful treatment of coarctation of the
aorta by Crafoord and Gross added a major boost to the reconstructive surgery of
arteries.
Shumacker reported the excision of a small descending thoracic aortic aneurysm with
reanastomosis of the aorta in 1948. [250 ] Swann et al. [251 ] repaired a complex
aneurysmal coarctation and used aortic homograft for reconstruction in 1950. Gross
[252 ] reported a series of similar cases using homograft replacement. In 1951, DuBost
et al. [253 ] from Paris resected an intraabdominal aortic aneurysm with homograft
replacement.
In 1953, Henry Bahnson [254 ] from Johns Hopkins successfully resected six saccular
aneurysms of the aorta in eight patients. In the same year, DeBakey and Cooley [255 ]
reported a 46-year-old man who had resection of a huge aneurysm of the descending
thoracic aorta that measured approximately 20 cm in length and in greatest diameter.
The aneurysm was resected and replaced with an aortic homograft approximately 15
cm in length. Lam and Aram [256 ] also used an aortic homograft to bypass a
descending thoracic aneurysm, which was then ligated.
During the Korean War, the arterial homograft and autogenous vein graft were used to
reconstruct battlefield arterial injuries and reduce the overall amputation rate from 49.6
percent in World War II [249 ] to 11.1 percent. [257 ] Although the vein autograft remains
the first-choice peripheral vascular conduit today, the arterial homograft was
superseded by the development of synthetic vascular grafts by Arthur Voorhees at
Columbia University in 1952. Voorhees and colleagues developed Vinyon-N cloth tubes
to substitute for diseased arterial segments, [258 ] but because of kinking, these
smooth-lined tubes could not be used across joints. Development of the crimped graft
by Edwards and Tate [259 ] and the introduction of Dacron by DeBakey [260 ] were
important milestones. DeBakey's account of his discovery of Dacron reflects the
resourcefulness and innovation of these pioneering surgeons. [260 ]
We were greatly impressed with the report of Voorhees on the use of a

fabric woven of Vinyon-N. On my first trip to obtain some of these fabrics
from a department store here, I found that they only had some sheets of
Dacron. I purchased several yards and cut them in different sizes to make
tubes by sewing on my wife's sewing machine. I had been taught by my
mother as a boy to sew and I became an expert not only in the use of the
sewing machine, but also on the other aspects of sewing. These tubes
proved highly successful in animals, and although we later obtained sheets
of Orlon, Teflon, nylon and Ivalon, none of these were as good as the original
Dacron fabric. It was rather interesting and an example of serendipity that
the first material we obtained (Dacron), the only one available at the store at
the time, proved later to be the best. One of these Dacron grafts that I had
fabricated as a bifurcation graft was used to replace an aneurysm of the
abdominal aorta in September, 1954.
Another advance in aortic surgery appeared in 1955 when DeBakey et al.

[251 ] reported six cases of aortic dissection treated by aggressive surgery.
This paper included a description of pathologic and hemodynamic factors
associated with the dissections and led to a more logical approach to
treatment of these lesions. Because mortality of operation for acute
dissections remained high, Myron Wheat, Jr., introduced medical therapy
for the disease. [262 ]
During the late 1950s, the Houston group led by Michael DeBakey
systematically developed operations for resection and graft replacement of
the ascending aorta [263 ] and descending and thoracoabdominal aorta.
[264 ] Cardiopulmonary bypass was used for ascending aortic resections.
The high risk of paraplegia highlighted a major complication of
thoracoabdominal aortic resections. The aortic arch, however, remained
beyond the surgeon's knife until 1967, when the Houston group successfully
excised an arch aneurysm and replaced the diseased aorta with a
reconstituted aortic arch homograft [265 ] (Fig. 1-10) .
In 1968, Bentall and De Bono [266 ] introduced replacement of the

ascending aorta and aortic valve with reanastomoses of the coronary ostia
to the replacement graft. They described the composite-graft technique for
replacement of the ascending aorta with reimplantation of the coronary
arteries into the composite Dacron graft containing the prosthetic aortic
valve. As previously mentioned, Cooley and DeBakey were first to replace
the supracoronary ascending aorta in 1956. In 1963 Starr et al. [267 ]
reported replacing the supracoronary ascending aorta and also the aortic
valve at the same sitting. The technique of fashioning buttons of aortic tissue
adjacent to the coronary ostia and then incorporating these buttons into the
aortic graft along with the aortic valve replacement was described by Wheat
et al. [268 ] in 1964. Bentall and De Bono incorporated the aortic prosthesis
into the tube graft and used the Wheat technique for implanting the coronary
arteries into the composite graft.
The history of adult cardiac surgery continues and will continue indefinitely
as long as acquired heart disease shortens lives. In the early days after the
introduction of cardiopulmonary bypass, the pace of advance was torrid but,
in a way, narrowly focused. Now hundreds of thousands of clinicians,
scientists, and engineers are involved in a broad and deep effort to develop
new and safer operations and procedures, new valves, new
revascularization techniques, new biomaterials, new heart substitutes, new
life-support systems, and new methods to control cardiac arrhythmias and
ventricular remodeling after injury. This research and development are
supported by a vigorous infrastructure of basic science in biology and
medicine, chemistry and pharmacology, engineering and computer
technology. The history of cardiac surgery is only a prelude; the moving
finger writes and having writ moves on to a bright, exciting future.
OVERVIEW
Location of the Heart Relative to Surrounding Structures
The overall shape of the heart is that of a three-sided pyramid located in the middle
mediastinum (Fig. 2-1) . When viewed from its apex, the three sides of the ventricular
mass are appreciated readily (Fig. 2-2) . Two of the edges are named: The acute
margin lies inferiorly and describes a sharp angle between the sternocostal and
diaphragmatic surfaces. The obtuse margin lies superiorly, and is much more diffuse.
The posterior margin is unnamed, but is also diffuse in its transition.
One-third of the cardiac mass lies to the right of the midline, and two-thirds to the left.
The long axis of the heart is oriented from the left upper gastrium to the right shoulder.
The short axis, which corresponds to the plane of the atrioventricular groove, is oblique
and is oriented closer to the vertical than the horizontal plane (Fig. 2-1) .
Anteriorly, the heart is covered by the sternum and the costal cartilages of the third,
fourth, and fifth ribs. The lungs contact the lateral surfaces of the heart, whereas,
posteriorly, the heart abuts onto the pulmonary hila. The right lung overlies the right
surface of the heart and reaches to the midline. In contrast, the left lung retracts from the
midline in the area of the cardiac notch. The heart has an extensive diaphragmatic
surface inferiorly. Posteriorly, the heart lies on the esophagus and the tracheal
bifurcation, and bronchi that extend into the lung. The sternum lies anteriorly and
provides rigid protection to the heart during blunt trauma and is aided by the cushioning
effects of the lungs.
The Pericardium and Its Reflections
The heart lies within the pericardium, which is attached to the walls of the great vessels
and to the diaphragm. The pericardium can be visualized best as a bag into which the
heart has been placed apex first. The inner layer, in direct contact with the heart, is the
visceral epicardium, which encases the heart and extends several centimeters back
onto the walls of the great vessels. The outer layer forms the parietal pericardium, which
lines the inner surface of the tough fibrous pericardial sack. A thin film of lubricating fluid
lies within the pericardial cavity between the two serous layers. Two identifiable
recesses lie within the pericardium and are lined by the serous layer. The first is the
transverse sinus, which is delineated anteriorly by the posterior surface of the aorta and
pulmonary trunk and posteriorly by the anterior surface of the interatrial groove. The
second is the oblique sinus, a cul-de-sac located behind the left atrium, delineated by
serous pericardial reflections from the pulmonary veins and the inferior caval vein.
Mediastinal Nerves and Their Relationships to the Heart
The vagus and phrenic nerves descend through the mediastinum in close relationship to
the heart (Fig. 2-3) . They enter through the thoracic inlet, with the phrenic nerve located
anteriorly on the surface of the anterior scalene muscle and lying just posterior to the
internal thoracic artery (internal mammary artery) at the thoracic inlet. In this position, it
is vulnerable to injury during dissection and preparation of the internal thoracic artery for
use in coronary arterial bypass grafting. On the right side, the phrenic nerve courses on
the lateral surface of the superior caval vein, again in harm's way during dissection for
venous cannulation for cardiopulmonary bypass. The nerve then descends anterior to
the pulmonary hilum before reflecting onto the right diaphragm, where it branches to
provide its innervation. In the presence of a left-sided superior caval vein, the left
phrenic nerve is directly applied to its lateral surface. The nerve passes anterior to the
pulmonary hilum and eventually branches on the surface of the diaphragm. The vagus
nerves enter the thorax posterior to the phrenic nerves and course along the carotid
arteries. On the right side, the vagus gives off the recurrent laryngeal nerve that passes
around the right subclavian artery before ascending out of the thoracic cavity. The right
vagus nerve continues posterior to the pulmonary hilum, gives off branches of the right
pulmonary plexus, and exits the thorax along the esophagus. On the left, the vagus nerve
crosses the aortic arch, where it gives off the recurrent laryngeal branch. The recurrent
nerve passes around the arterial ligament before ascending in the tracheoesophageal
groove. The vagus nerve continues posterior to the pulmonary hilum, gives rise to the
left pulmonary plexus, and then continues inferiorly out of the thorax along the
esophagus. A delicate nerve trunk known as the subclavian loop carries fibers from the
stellate ganglion to the eye and head. This branch is located adjacent to the subclavian
arteries bilaterally. Excessive dissection of the subclavian artery during shunt
procedures may injure these nerve roots and cause Horner's syndrome.
SURGICAL INCISIONS
Median Sternotomy
The most common approach for operations on the heart and aortic arch is the median
sternotomy. The skin incision is made from the jugular notch to just below the xiphoid
process. The subcutaneous tissues and presternal fascia are incised to expose the
periostium of the sternum. The sternum is divided longitudinally in the midline. After
placement of a sternal spreader, the thymic fat pad is divided up to the level of the
brachiocephalic vein. An avascular midline plane is identified easily, but is crossed by a
few thymic veins that are divided between fine silk ties or hemoclips. Either the left or
right, or occasionally both, lobes of the thymus gland often are removed in infants and
young children to improve exposure and to minimize compression on extracardiac
conduits. If a portion of the thymus gland is removed, excessive traction may result in
injury to the phrenic nerve. The pericardium is opened anteriorly to expose the heart.
Through this incision, operations within any chamber of the heart or on the surface of the
heart, and operations involving the proximal aorta, pulmonary trunk, and their primary
branches can be performed. Extension of the superior extent of the incision into the
neck along the anterior border of the right sternocleidomastoid muscle provides further
exposure of the aortic arch and its branches for procedures involving these structures.
Exposure of the proximal descending thoracic aorta is facilitated by a perpendicular
extension of the incision through the third intercostal space.
Bilateral Transverse Thoracosternotomy (Clam Shell Incision)
The bilateral transverse thoracosternotomy (clam shell incision) is an alternative incision

for exposure of the pleural spaces and heart. This incision may be made through either
the fourth or fifth intercostal space, depending on the intended procedure. After
identifying the appropriate interspace, a bilateral submammary incision is made. The
incision is extended down through the pectoralis major muscles to enter the
hemithoraces through the appropriate intercostal space. The right and left internal
thoracic arteries are dissected and ligated proximally and distally prior to transverse
division of the sternum. Electrocautery dissection of the pleural reflections behind the
sternum allows full exposure to both hemithoraces and the entire mediastinum. Bilateral
chest spreaders are placed to maintain exposure. Morse retractors are particularly
suitable with this incision. The pericardium may be opened anteriorly to allow access to
the heart for intracardiac procedures. When required, standard cannulation for
cardiopulmonary bypass is achieved easily. This incision is popular for bilateral
sequential double lung transplants because of enhanced exposure of the apical pleural
spaces. When made in the fourth intercostal space, the incision is useful for access to
the ascending, arch, and descending thoracic aorta.
Anterolateral Thoracotomy
The right side of the heart can be exposed through a right anterolateral thoracotomy.
The patient is positioned supine, with the right chest elevated to approximately 30
degrees by a roll beneath the shoulder. An anterolateral thoracotomy incision can be
made that can be extended across the midline by transversely dividing the sternum if
necessary. With the lung retracted posteriorly, the pericardium can be opened just
anterior to the right phrenic nerve and pulmonary hilum to expose the right and left atria.
The incision provides access to both the tricuspid and mitral valves and the right
coronary artery. Cannulation may be performed in the ascending aorta and the superior
and inferior caval veins. Aortic cross-clamping, administration of cardioplegia, and
deairing of the heart after cardiotomy are difficult through this approach. This incision is
particularly useful, nonetheless, for performance of the Blalock-Hanlon atrial septectomy
or for valvar replacement after a previous procedure through a median sternotomy. A
left anterolateral thoracotomy performed in a similar fashion to that on the right side may
be used for isolated bypass grafting of the circumflex coronary artery, or for left-sided
exposure of the mitral valve.
Posterolateral Thoracotomy
A left posterolateral thoracotomy is used for procedures involving the distal aortic arch
and descending thoracic aorta. With left thoracotomy, cannulation for cardiopulmonary
bypass must be done through the femoral vessels.
RELATIONSHIP OF THE CARDIAC CHAMBERS AND GREAT
ARTERIES
The surgical anatomy of the heart is best understood when the position of the cardiac
chambers and great vessels is known in relation to the cardiac silhouette. The
atrioventricular junction is oriented obliquely, lying much closer to the vertical than the
horizontal plane. This plane can be viewed from its atrial aspect (Fig. 2-4) if the atrial
mass and great arteries are removed by a parallel cut just above the junction. The
tricuspid and pulmonary valves are widely separated by the inner curvature of the heart
lined by the transverse sinus. Conversely, the mitral and aortic valves lie adjacent to one
another, with fibrous continuity of their leaflets. The aortic valve occupies a central
position, wedged between the tricuspid and pulmonary valves. Indeed, there is fibrous
continuity between the leaflets of the aortic and tricuspid valves through the central
fibrous body. With careful study of this short axis, several basic rules of cardiac anatomy
become apparent. First, the atrial chambers lie to the right of their corresponding
ventricles. Second, the right atrium and ventricle lie anterior to their left-sided
counterparts. The septal structures between them are obliquely oriented. Third, by virtue
of its wedged position, the aortic valve is directly related to all of the cardiac chambers.
Several other significant features of cardiac anatomy can be learned from the short axis
section. The position of the aortic valve minimizes the area of septum where the mitral
and tricuspid valves attach opposite each other. Because the tricuspid valve is attached
to the septum further toward the ventricular apex than the mitral valve, a part of the
septum is interposed between the right atrium and the left ventricle to produce the
muscular atrioventricular septum. The central fibrous body, where the leaflets of the
aortic, mitral, and tricuspid valves all converge, lies cephalad and anterior to the
muscular atrioventricular septum. The central fibrous body is the main component of the
fibrous skeleton of the heart and is made up, in part, by the right fibrous trigone, a
thickening of the right side of the area of fibrous continuity between the aortic and mitral
valves, and in part by the membranous septum, the fibrous partition between the left
ventricular outflow tract and the right heart chambers (Fig. 2-5) . The membranous
septum itself is divided into two parts by the septal leaflet of the tricuspid valve, which is
directly attached across it (Fig. 2-6) . Thus, the membranous septum has an
atrioventricular component between the right atrium and left ventricle, as well as an
interventricular component. Removal of the noncoronary leaflet of the aortic valve
demonstrates the significance of the wedged position of the left ventricular outflow tract
in relation to the other cardiac chambers. The subaortic region separates the mitral
orifice from the ventricular septum; this separation influences the position of the
atrioventricular conduction tissues and the position of the leaflets and tension apparatus
of the mitral valve (Fig. 2-7) .
CARDIAC CHAMBERS AND VALVES
Morphology of the Right Atrium and Tricuspid Valve
APPENDAGE, VESTIBULE, AND VENOUS COMPONENT
The right atrium has three basic parts: the appendage, the vestibule, and the venous
component (Fig. 2-8) . Externally, the right atrium is divided into the appendage and the
venous component, which receives the systemic venous return. The junction of the
appendage and the venous component is identified by a prominent groove, the terminal
groove. This corresponds internally to the location of the terminal crest. The right atrial
appendage has the shape of a blunt triangle, with a wide junction to the venous
component across the terminal groove. The appendage also has an extensive junction
with the vestibule of the right atrium; the latter structure is the smooth-walled atrial
myocardium that inserts into the leaflets of the tricuspid valve. The most characteristic
and constant feature of the morphology of the right atrium is that the pectinate muscles
within the appendage extend around the entire parietal margin of the atrioventricular
junction (Fig. 2-9) . These muscles originate as parallel fibers that course at right angles
from the terminal crest. The venous component of the right atrium extends between the
terminal groove and the interatrial groove. It receives the superior and inferior caval
veins and the coronary sinus.
SINUS NODE
The sinus node lies at the anterior and superior extent of the terminal groove, where the
atrial appendage and the superior caval vein are juxtaposed. The node is a
spindle-shaped structure that usually lies to the right or lateral to the superior cavoatrial
junction (Fig. 2-10) . In approximately 10 percent of cases, the node is draped across
the cavoatrial junction in horseshoe fashion. [1 ]
The blood supply to the sinus node is from a prominent nodal artery that is a branch of
the right coronary artery in approximately 55 percent of individuals, and a branch of the
circumflex artery in the remainder. Regardless of its artery of origin, the nodal artery
usually courses along the anterior interatrial groove toward the superior cavoatrial
junction, frequently within the atrial myocardium. At the cavoatrial junction, its course
becomes variable and may circle either anteriorly or posteriorly, or rarely both anteriorly
and posteriorly, around the cavoatrial junction to enter the node. Uncommonly, the artery
arises more distally from the right coronary artery and courses laterally across the atrial
appendage. This places it at risk of injury during a standard right atriotomy. The artery
also may arise distally from the circumflex artery to cross the dome of the left atrium,
where it is at risk of injury when utilizing a superior approach to the mitral valve. Incisions
in either the right or left atrial chambers always should be made with this anatomic
variability in mind. In our experience, these vessels can be identified by careful gross
inspection and should prompt appropriate modification of surgical incisions.
ATRIAL SEPTUM
The most common incision into the right atrium is made into the atrial appendage
parallel and anterior to the terminal groove. Opening the atrium through this incision
confirms that the terminal groove is the external marking of the prominent terminal crest.
Anteriorly and superiorly, the crest curves in front of the orifice of the superior caval vein
to become continuous with the so-called septum secundum, which, in reality, is the
superior rim of the oval fossa. When the right atrium is inspected through this incision,
there appears to be an extensive septal surface between the tricuspid valve and the
orifices of the caval veins. This septal surface includes the opening of the oval fossa
and the orifice of the coronary sinus. The apparent extent of the septum is spurious, as
the true septum between the atrial chambers is virtually confined to the oval fossa (Fig.
2-11) . [2 ] , [3 ] The superior rim of the fossa, although often referred to as the septum
secundum, is an extensive infolding between the venous component of the right atrium
and the right pulmonary veins. The inferior rim is directly continuous with the so-called
sinus septum that separates the orifices of the inferior caval vein and the coronary sinus
(Fig. 2-12) .
The region around the coronary sinus is where the right atrial wall overlies the
atrioventricular muscular septum. Removing the floor of the coronary sinus reveals the
anterior extension of the atrioventricular groove in this region. Only a small part of the
anterior rim of the oval fossa is a septal structure. The majority is made up of anterior
atrial wall overlying the aortic root. Thus, dissection outside the limited margins of the
oval fossa will penetrate the heart to the outside, rather than provide access to the left
atrium via the septum.
ATRIOVENTRICULAR SEPTUM AND NODE: TRIANGLE OF KOCH
In addition to the sinus node, another major area of surgical significance is occupied by
the atrioventricular node. This structure lies within the triangle of Koch, which is
demarcated by the tendon of Todaro, the septal leaflet of the tricuspid valve, and the
orifice of the coronary sinus (Fig. 2-13) . The tendon of Todaro is a fibrous structure
formed by the junction of the eustachian valve and the thebesian valve (the valves of the
inferior caval vein and coronary sinus, respectively). The entire atrial component of the
atrioventricular conduction tissues is contained within the triangle of Koch, which must
be avoided to prevent surgical damage to atrioventricular conduction. The
atrioventricular bundle (of His) penetrates directly at the apex of the triangle of Koch
before it continues to branch on the crest of the ventricular septum (Fig. 2-14) . The key
to avoiding atrial arrhythmias is careful preservation of the sinus and atrioventricular
nodes and their blood supply. No advantage is gained in attempting to preserve
nonexistent tracts of specialized atrial conduction tissue, although it makes sense to
avoid prominent muscle bundles where parallel orientation of atrial myocardial fibers
favors preferential conduction (Fig. 2-15) .
TRICUSPID VALVE
The vestibule of the right atrium converges into the tricuspid valve. The three leaflets
reflect their anatomic location, being septal, anterosuperior, and inferior (or mural). The
leaflets join together over three prominent zones of apposition; the peripheral ends of
these zones usually are described as commissures. The leaflets are tethered at the
commissures by fan-shaped cords arising from prominent papillary muscles. The
antero-septal commissure is supported by the medial papillary muscle. The major
leaflets of the valve extend from this position in anterosuperior and septal directions.
The third leaflet is less well defined. The antero-inferior commissure is usually
supported by the prominent anterior papillary muscle. Often, however, it is not possible
to identify a specific inferior papillary muscle supporting the infero-septal commissure.
Thus, the inferior leaflet may seem duplicated. There is no well-formed collagenous
annulus for the tricuspid valve. Instead, the atrioventricular groove more or less folds
directly into the tricuspid valvar leaflets at the vestibule, and the atrial and ventricular
myocardial masses are separated almost exclusively by the fibro-fatty tissue of the
groove. The entire parietal attachment of the tricuspid valve usually is encircled by the
right coronary artery running within the atrioventricular groove.
Morphology of the Left Atrium and Mitral Valve
APPENDAGE, VESTIBULE, AND VENOUS COMPONENT
Like the right atrium, the left atrium has three basic components: the appendage,
vestibule, and venous component (Fig. 2-16) . Unlike the right atrium, the venous
component is considerably larger than the appendage and has a narrow junction with it
that is not marked by a terminal groove or crest. There also is an important difference
between the relationship of the appendage and vestibule between the left and right
atria. As shown, the pectinate muscles within the right atrial appendage extend all
around the parietal margin of the vestibule. In contrast, the left atrial appendage has a
limited junction with the vestibule, and the pectinate muscles are located almost
exclusively within the appendage (Fig. 2-8) . The larger part of the vestibule that
supports and inserts directly into the mural leaflet of the mitral valve is directly
continuous with the smooth atrial wall of the pulmonary venous component.
Because the left atrium is posterior and tethered by the four pulmonary veins, the
chamber is relatively inaccessible. Several approaches are used by surgeons to gain
access. The most common is an incision just to the right of and parallel to the interatrial
groove, anterior to the right pulmonary veins. This incision can be carried beneath both
the superior and inferior caval veins parallel to the interatrial groove, to provide wide
access to the left atrium. A second approach is through the dome of the left atrium. If the
aorta is pulled anteriorly and to the left, an extensive trough may be seen between the
right and left atrial appendages. An incision through this trough, between the pulmonary
veins of the upper lobes, provides direct access to the left atrium. When this incision is
made, it is important to remember the location of the sinus node artery, which may
course along the roof of the left atrium if it arises from the circumflex artery. The left
atrium also can be reached via a right atrial incision and an opening in the atrial
septum.
When the interior of the left atrium is visualized, the small size of the mouth of the left
atrial appendage is apparent. It lies to the left of the mitral orifice as viewed by the
surgeon. The majority of the pulmonary venous atrium usually is located inferiorly away
from the operative field. The vestibule of the mitral orifice dominates the operative view.
The septal surface is located anteriorly, with the true septum relatively inferior (Fig.
2-17) .
MITRAL VALVE
The mitral valve is supported by two prominent papillary muscles located in anterolateral
and posteromedial positions. The two leaflets of the mitral valve have markedly different
appearances (Fig. 2-18) . The aortic (or anterior) leaflet is short, relatively square, and
guards approximately one-third of the circumference of the valvar orifice. This leaflet is
in fibrous continuity with the aortic valve and, because of this, is best referred to as the
aortic leaflet, since it is neither strictly anterior nor superior in position. The other leaflet
is much shallower but guards approximately two-thirds of the circumference of the mitral
orifice. As it is connected to the parietal part of the atrioventricular junction, it is most
accurately termed the mural leaflet, but is often termed the posterior leaflet. It is divided
into a number of subunits that fold against the aortic leaflet when the valve is closed.
Although generally there are three, there may be as many as five or six scallops in the
mural leaflet.
Unlike the tricuspid valve, the mitral valve leaflets are supported by a rather dense
collagenous annulus, although it may take the form of a sheet rather than a cord. This
annulus usually extends parietally from the fibrous trigones, the greatly thickened areas
at either end of the area of fibrous continuity between the leaflets of the aortic and mitral
valves (Fig. 2-6) . The area of the valvar orifice related to the right fibrous trigone and
central fibrous body is most vulnerable with respect to the atrioventricular node and
penetrating bundle (Fig. 2-7) . The mid-portion of the aortic leaflet of the mitral valve is
related to the commissure between the noncoronary and left coronary cusps of the
aortic valve. An incision through the atrial wall in this area may be extended into the
subaortic outflow tract, and may be useful for enlarging the aortic annulus during
replacement of the aortic valve (Fig. 2-19) . The circumflex coronary artery is adjacent to
the left half of the mural leaflet, whereas the coronary sinus is adjacent to the right half of
the mural leaflet (Fig. 2-20) . These structures can be damaged during excessive
dissection, or by excessively deep placement of sutures during replacement or repair of
the mitral valve. When the circumflex artery is dominant, the entire attachment of the
mural leaflet may be intimately related to this artery (Fig. 2-21) .
Morphology of the Right Ventricle and Pulmonary Valve
INLET AND APICAL TRABECULAR PORTIONS
The morphology of both the right and left ventricles can be understood best by
subdividing the ventricles into three anatomically distinct components: the inlet, apical
trabecular, and outlet portions. [2 ] This classification is more helpful than the traditional
division of the right ventricle into the sinus and conus parts. The inlet portion of the right
ventricle surrounds the tricuspid valve and its tension apparatus. A distinguishing
feature of the tricuspid valve is the direct attachment of its septal leaflet. The apical
trabecular portion of the right ventricle extends out to the apex. Here, the wall of the
ventricle is quite thin and vulnerable to perforation by cardiac catheters and pacemaker
electrodes.
OUTLET PORTION AND PULMONARY VALVE
The outlet portion of the right ventricle consists of the infundibulum, a circumferential
muscular structure that supports the leaflets of the pulmonary valve. Because of the
semilunar shape of the pulmonary valvar leaflets, this valve does not have an annulus in
the traditional sense of a ring-like attachment. The leaflets have semilunar attachments
that cross the musculo-arterial junction in a corresponding semi-lunar fashion (Fig. 2-22)
. Therefore, instead of a single annulus, three rings can be distinguished anatomically in
relation to the pulmonary valve. Superiorly, the sinotubular ridge of the pulmonary trunk
marks the level of peripheral apposition of the leaflets (the commissures). A second ring
exists at the ventriculo-arterial junction. A third ring can be constructed by joining
together the basal attachments of the three leaflets to the infundibular muscle. None of
these rings, however, corresponds to the attachments of the leaflets, which must be
semilunar to permit the valve to competently open and close. In fact, these semilunar
attachments, which mark the hemodynamic ventriculo-arterial junction, extend from the
first ring, across the second, down to the third, and back in each cusp (Fig. 2-23) .
SUPRAVENTRICULAR CREST AND PULMONARY INFUNDIBULUM
A distinguishing feature of the right ventricle is a prominent muscular shelf, the

supraventricular crest, which separates the tricuspid and pulmonary valves (Fig. 2-24) .
In reality, this muscular ridge is the posterior part of the subpulmonary muscular
infundibulum that supports the leaflets of the pulmonary valve. In other words, it is part of
the inner curve of the heart. Incisions through the supraventricular crest run into the
transverse septum and may jeopardize the right coronary artery. Although this area is
often considered the outlet component of the interventricular septum, in fact the entire
subpulmonary infundibulum, including the ventriculoinfundibular fold, can be removed
without entering the left ventricular cavity. This is possible because the leaflets of the
pulmonary and aortic valves are supported on separate sleeves of right and left
ventricular outlet muscle. There is an extensive external tissue plane between the walls
of the aorta and the pulmonary trunk (Fig. 2-25) , and the leaflets of the pulmonary and
aortic valves have markedly different levels of attachments within their respective
ventricles. This feature enables enucleation of the pulmonary valve, including its basal
attachments within the infundibulum, during the Ross procedure without creating a
ventricular septal defect. When the infundibulum is removed from the right ventricle, the
insertion of the supraventricular crest between the limbs of the septomarginal
trabeculation is visible (Fig. 2-26) . This trabeculation is a prominent muscle column that
divides superiorly into anterior and posterior limbs. The anterior limb runs superiorly into
the infundibulum and supports the leaflets of the pulmonary valve. The posterior limb
extends backwards beneath the ventricular septum and runs into the inlet portion of the
ventricle. The medial papillary muscle arises from this posterior limb. The body of the
septomarginal trabeculation runs to the apex of the ventricle, where it divides into
smaller trabeculations. Two of these trabeculations may be particularly prominent. One
becomes the anterior papillary muscle and the other crosses the ventricular cavity as
the moderator band (Fig. 2-27) .
Morphology of the Left Ventricle and Aortic Valve
INLET AND APICAL TRABECULAR PORTIONS
The left ventricle can be subdivided into three components, as was the right ventricle.
The inlet component surrounds, and is limited by, the mitral valve and its tension
apparatus. The two papillary muscles occupy anterolateral and posteromedial positions
and are positioned rather close to each other. The leaflets of the mitral valve have no
direct septal attachments because the deep posterior diverticulum of the left ventricular
outflow tract displaces the aortic leaflet away from the inlet septum. The apical
trabecular component of the left ventricle extends to the apex, where the myocardium is
surprisingly thin. The trabeculations of the left ventricle are quite fine compared with
those of the right ventricle (Fig. 2-28) . This characteristic is useful for defining
ventricular morphology on diagnostic ventriculograms.
OUTLET PORTION
The outlet component supports the aortic valve and consists of both muscular and
fibrous portions. This is in contrast to the infundibulum of the right ventricle, which is
composed entirely of muscle. The septal portion of the left ventricular outflow tract,
although primarily muscular, also includes the membranous portion of the ventricular
septum. The posterior quadrant of the outflow tract consists of an extensive fibrous
curtain that extends from the fibrous skeleton of the heart across the aortic leaflet of the
mitral valve, and supports the leaflets of the aortic valve in the area of aortomitral
continuity (Fig. 2-5) . The lateral quadrant of the outflow tract is again muscular and
consists of the lateral margin of the inner curvature of the heart, delineated externally by
the transverse sinus. The left bundle of the cardiac conduction system enters the left
ventricular outflow tract posterior to the membranous septum and immediately beneath
the commissure between the right and non-coronary leaflets of the aortic valve. After
traveling a short distance down the septum, the left bundle divides into anterior, septal,
and posterior divisions.
AORTIC VALVE
The aortic valve is a semilunar valve, morphologically quite similar to the pulmonary
valve. Likewise, it does not have a discrete annulus. Because of its central location, the
aortic valve is related to each of the cardiac chambers and valves (Fig. 2-4) . A
thorough knowledge of these relationships is essential to understanding aortic valve
pathology and many congenital cardiac malformations. The aortic valve consists
primarily of three semilunar leaflets. As with the pulmonary valve, attachments of the
leaflets extend across the ventriculo-arterial junction in a curvilinear fashion. Each
leaflet, therefore, has attachments to the aorta and within the left ventricle (Fig. 2-29) .
Behind each leaflet, the aortic wall bulges outward to form the sinuses of Valsalva. The
leaflets themselves meet centrally along a line of coaptation, at the center of which is a
thickened nodule, the nodule of Arantius. Peripherally, adjacent to the commissures, the
line of coaptation is thinner and normally may contain small perforations. During systole,
the leaflets are thrust upward and away from the center of the aortic lumen, whereas,
during diastole, they fall passively into the center of the aorta. With normal valvar
morphology, all three leaflets meet along lines of coaptation and support the column of
blood within the aorta to prevent regurgitation into the ventricle. Two of the three aortic
sinuses give rise to coronary arteries, from which arise their designations as right, left,
and non-coronary sinuses.
By sequentially following the line of attachment of each leaflet, the relationship of the
aortic valve to its surrounding structures can be clearly understood. Beginning
posteriorly, the commissure between the non-coronary and left coronary leaflets is
positioned along the area of aorto-mitral valvar continuity. The fibrous sub-aortic curtain
is beneath this commissure (Fig. 2-29) . To the right of this commissure, the
non-coronary leaflet is attached above the posterior diverticulum of the left ventricular
outflow tract. Here the valve is related to the right atrial wall. As the attachment of the
non-coronary leaflet ascends from its nadir toward the commissure between the
non-coronary and right coronary leaflets, the line of attachment is directly above the
portion of the atrial septum containing the atrioventricular node. The commissure
between the non-coronary and right coronary leaflets is located directly above the
penetrating atrioventricular bundle and the membranous ventricular septum (Fig. 2-30) .
The attachment of the right coronary leaflet then descends across the central fibrous
body before ascending to the commissure between the right and left coronary leaflets.
Immediately beneath this commissure, the uppermost part of the subaortic outflow tract
is formed by the wall of the aorta. An incision through this area passes into the space
between the facing surfaces of the aorta and pulmonary trunk (Fig. 2-30) . As the facing
left and right leaflets descend from this commissure, they are attached to the outlet
muscular component of the left ventricle. Only a small part of this area in the normal
heart is a true outlet septum, since both pulmonary and aortic valves are supported on
their own sleeves of myocardium. Thus, although the outlet components of the right and
left ventricle face each other, an incision below the aortic valve enters low into the
infundibulum of the right ventricle. As the lateral part of the left coronary leaflet descends
from the facing commissure to the base of the sinus, it becomes the only part of the
aortic valve that is not intimately related to another cardiac chamber.
The anatomy of the aortic valve and its relationship to surrounding structures is
important to successful replacement of the aortic valve, particularly when elargement of
the aortic root is required. The Konno-Rastan aortoventriculoplasty involves opening
and enlarging the anterior portion of the sub-aortic region. [4 ] , [5 ] The incisions for this
procedure begin with an anterior longitudinal aortotomy that extends through the
commissure between the right and left coronary leaflets. Anteriorly, the incision is
extended across the base of the infundibulum. The differential level of attachment of the
aortic and pulmonary valve leaflets permits this incision without damage to the
pulmonary valve (Fig. 2-31) . Posteriorly, the incision extends through the most medial
portion of the supraventricular crest into the left ventricular outflow tract. By closing the
resulting ventricular septal defect with a patch, the aortic outflow tract is widened to
allow implantation of a larger valvar prosthesis. A second patch is used to close the
defect in the right ventricular outflow tract.
Alternative methods to enlarge the aortic outflow tract involve incisions in the region of
aortomitral continuity. In the Manouguian procedure (Fig. 2-19) , a curvilinear aortotomy
is extended posteriorly through the commissure between the left and non-coronary
leaflets down to, and occasionally into, the aortic leaflet of the mitral valve. [6 ] A patch is
used to augment the incision posteriorly. When the posterior diverticulum of the outflow
tract is fully developed, this incision can be made without entering other cardiac
chambers, although not uncommonly the roof of the left atrium is opened. The Nicks
procedure for enlargement of the aortic root involves an aortotomy that passes through
the middle of the non-coronary leaflet into the fibrous sub-aortic curtain and may be
extended into the aortic leaflet of the mitral valve. [7 ] This incision also may open the
roof of the left atrium. When these techniques are used, any resultant defect in the left
atrium must be closed carefully.
As discussed previously, the differential level of attachment of aortic and pulmonary

valves, as well as the muscular nature of their support, allows the pulmonary valve to be
harvested and used as a replacement for the aortic valve in the Ross procedure. [8 ] , [9
] This procedure can be combined with the incisions of the Konno-Rastan
aortoventriculoplasty to repair left ventricular outflow tract obstructions in young children
with a viable autograft that has potential for growth and avoids the need for
anticoagulation.
Accurate understanding of left ventricular outflow tract anatomy is also important in the
treatment of aortic valvar endocarditis. [10 ] , [11 ] Because of the central position of the
aortic valve relative to the other valves and cardiac chambers (Fig. 2-4) , abscess
formation can produce fistulas between the aorta and any of the four chambers of the
heart. Patients may, therefore, present with findings of left heart failure, left-to-right
shunting, and/or complete heart block in addition to the usual signs of sepsis and
systemic embolization.
THE CORONARY ARTERIES [12 ][14 ]
The right and left coronary arteries originate behind their respective aortic valvar leaflets
(Fig. 2-26) . The orifices usually are located in the upper third of the sinuses of Valsalva,
although individual hearts may vary markedly. Because of the oblique plane of the aortic
valve, the orifice of the left coronary artery is superior and posterior to that of the right
coronary artery. The coronary arterial tree is divided into three segments; two (the left
anterior descending artery and the circumflex artery) arise from a common stem. The
third segment is the right coronary artery. The dominance of the coronary circulation
(right vs. left) usually refers to the artery from which the posterior descending artery
originates, not the absolute mass of myocardium perfused by the left or right coronary
artery. Right dominance occurs in 8590 percent of normal individuals. Left dominance
occurs slightly more frequently in males than females.
Main Stem of the Left Coronary Artery
The main stem of the left coronary artery courses from the left sinus of Valsalva
anteriorly, inferiorly, and to the left between the pulmonary trunk and the left atrial
appendage (Fig. 2-32) . Typically it is 1020 millimeters in length but can extend to a
length of 40 millimeters. The left main stem can be absent, with separate orifices in the
sinus of Valsalva for its two primary branches (1 percent of patients). The main stem
divides into two major arteries of nearly equal diameter: the left anterior descending
artery and the circumflex artery.
Left Anterior Descending Artery
The left anterior descending (or interventricular) coronary artery continues directly from
the bifurcation of the left main stem, coursing anteriorly and inferiorly in the anterior
interventricular groove to the apex of the heart (Fig. 2-33) . Its branches include the
diagonals, the septal perforators, and the right ventricular branches. The diagonals,
which may be two to six in number, course along the anterolateral wall of the left
ventricle and supply this portion of the myocardium. The first diagonal generally is the
largest and may arise from the bifurcation of the left main stem (formerly known as the
intermediate artery). The septal perforators branch perpendicularly into the ventricular
septum. Typically there are three to five septal perforators; the initial one is the largest
and commonly originates just beyond the take-off of the first diagonal. This
perpendicular orientation is a useful marker for identification of the left anterior
descending artery on coronary angiograms. The septal perforators supply blood to the
anterior two-thirds of the ventricular septum. Right ventricular branches, which may not
always be present, supply blood to the anterior surface of the right ventricle. In
approximately 4 percent of hearts, the left anterior descending artery bifurcates
proximally and continues as two parallel vessels of approximately equal size down the
anterior interventricular groove. Occasionally, the artery wraps around the apex of the
left ventricle to feed the distal portion of the posterior interventricular groove. Rarely, it
extends along the entire length of the posterior groove to replace the posterior
descending artery.
Circumflex Artery
The left circumflex coronary artery arises from the left main coronary artery roughly at a
right angle to the anterior interventricular branch. It courses along the left atrioventricular
groove and, in 8595 percent of patients, terminates near the obtuse margin of the left
ventricle (Fig. 2-34) . In 1015 percent of patients, it continues around the atrioventricular
groove to the crux of the heart to give rise to the posterior descending artery (left
dominance, Fig. 2-21 ). The primary branches of the left circumflex coronary artery are
the obtuse marginals. They supply blood to the lateral aspect of the left ventricular
myocardium, including the posteromedial papillary muscle. Additional branches supply
blood to the left atrium and, in 4050 percent of hearts, the sinus node. When the
circumflex coronary artery supplies the posterior descending artery, it also supplies the
atrioventricular node.
Right Coronary Artery
The right coronary artery courses from the aorta anteriorly and laterally before
descending in the right atrioventricular groove and curving posteriorly at the acute
margin of the right ventricle (Fig. 2-35) . In 8590 percent of hearts, the right coronary
artery crosses the crux, where it makes a characteristic U-turn before bifurcating into the
posterior descending artery and the right posterolateral artery. In 5060 percent of
hearts, the artery to the sinus node arises from the proximal portion of the right coronary
artery. The blood supply to the atrioventricular node (in patients with right dominant
circulation) arises from the mid-portion of the U-shaped segment. The posterior
descending artery runs along the posterior interventricular groove, extending for a
variable distance toward the apex of the heart. It gives off perpendicular branches, the
posterior septal perforators, that course anteriorly in the ventricular septum. Typically,
these perforators supply the posterior one-third of the ventricular septal myocardium.
The right posterolateral artery gives rise to a variable number of branches that supply
the posterior surface of the left ventricle. The circulation of the posteoinferior portion of
the left ventricular myocardium is quite variable. It may consist of branches of the right
coronary artery, the circumflex artery, or both. The acute marginal arteries branch from
the right coronary artery along the acute margin of the heart, before its bifurcation at the
crux. These marginals supply the anterior free wall of the right ventricle. In 1020 percent
of hearts, one of these acute marginal arteries courses across the diaphragmatic
surface of the right ventricle to reach the distal ventricular septum. The right coronary
artery supplies important collaterals to the left anterior descending artery through its
septal perforators. In addition, its infundibular (or conus) branch, which arises from the
proximal portion of the right coronary artery, courses anteriorly over the base of the
ventricular infundibulum and may serve as a collateral to the anterior descending artery.
Kugel's artery is an anastomotic vessel between the proximal right coronary and the
circumflex coronary artery that can also provide a branch that runs through the base of
the atrial septum to the crux of the heart, where it supplies collateral circulation to the
atrioventricular node. [15 ]
THE CORONARY VEINS [14 ]
A complex network of veins drains the coronary circulation. An extensive degree of

collateralization amongst these veins and the coronary arteries, and the paucity of
valves within coronary veins, enables the use of retrograde coronary sinus cardioplegia
for intraoperative myocardial protection. The venous circulation can be divided into
three systems: the coronary sinus and its tributaries, the anterior right ventricular veins,
and the thebesian veins.
Coronary Sinus and Its Tributaries
The coronary sinus predominantly drains the left ventricle and receives approximately
85 percent of coronary venous blood. It lies within the posterior atrioventricular groove
and empties into the right atrium at the lateral border of the triangle of Koch (Fig. 2-36) .
The orifice of the coronary sinus is guarded by the crescent-shaped thebesian valve.
The named tributaries of the coronary sinus include the anterior interventricular vein,
which courses parallel to the left anterior descending coronary artery. Adjacent to the
bifurcation of the left main stem, the anterior interventricular vein courses leftward in the
atrioventricular groove, where it is referred to as the great cardiac vein. It receives blood
from the marginal and posterior left ventricular branches before becoming the coronary
sinus at the origin of the oblique vein (of Marshall) at the posterior margin of the left
atrium. The posterior interventricular vein, or middle cardiac vein, arises at the apex,
courses parallel to the posterior descending coronary artery, and extends proximally to
the crux. Here, this vein drains either directly into the right atrium or into the coronary
sinus just prior to its orifice. The small cardiac vein runs posteriorly through the right
atrioventricular groove.
Anterior Right Ventricular Veins
The anterior right ventricular veins travel across the right ventricular surface to the right
atrioventricular groove, where they either enter directly into the right atrium or coalesce
to form the small cardiac vein. As indicated, this vein travels down the right
atrioventricular groove, around the acute margin, and enters into the right atrium directly
or joins the coronary sinus just proximal to its orifice.
Thebesian Veins
The thebesian veins are small venous tributaries that drain directly into the cardiac
chambers. They exist primarily in the right atrium and right ventricle.
SPECIAL ELECTRICAL AND MEMBRANE PROPERTIES OF
CARDIAC CELLS
The Cell Membrane or Sarcolemma
The cardiac cell is surrounded by a membrane ( plasmalemma or sarcolemma ) with

unique properties. These properties allow the origination and then the conduction of an
electrical signal through the heart leading to near-synchronous depolarization of atrial
myocytes and, with an appropriate delay, near-synchronous depolarization of ventricular
myocytes. The sarcolemma further possesses properties that lead to the initiation of the
excitation-contraction coupling process. Finally, the sarcolemma allows regulation of
excitation, contraction, and intracellular metabolism in response to neuronal and
chemical stimulation. Each of these functions will be considered, with emphasis on
those features of the cardiac sarcolemma that differ from the plasmalemma of other
cells.
BASIC COMPOSITION OF THE SARCOLEMMA: THE PHOSPHOLIPID BILAYER
A phospholipid bilayer provides a barrier between the extracellular compartment and

the intracellular compartment, or cytosol. This membrane, only two molecules thick,
consists of phospholipids and cholesterol aligned so that the lipid, or hydrophobic,
portion of the molecule is on the inside of the membrane and the hydrophilic portion of
the molecule is on the outside (Fig. 3-1) . The phospholipid bilayer provides a fluid
barrier , like a film of oil on the surface of water, that is particularly impermeable to
diffusion of ions. Small, lipid-soluble molecules such as oxygen and carbon dioxide
diffuse easily through the membrane. The water molecule, although insoluble in the
membrane, is small enough that it diffuses easily through the membrane (or through
pores in the membrane). Other, slightly larger molecules (sodium, chloride, potassium,
calcium) cannot easily diffuse through the lipid bilayer and require specialized
mechanisms for transport. [1 ] [4 ]
The specialized systems within the sarcolemma for ion transport consist of
membrane-spanning proteins that float in and penetrate the lipid bilayer (with a helical
hydrophobic segment spanning the membrane and hydrophilic segments on the inner
and outer surfaces of the membrane). These proteins, many of which have now been
isolated and sequenced, are associated with three different types of ion transport: (1)
diffusion through transmembrane channels that can be opened or closed (gated) in
response to electrical or chemical (ligand) stimuli, (2) exchange of one ion for another
with binding of these ions to portions of the transmembrane protein for exchange in
response to an electrochemical gradient, and (3) active (energy-dependent) transport of
ions against an electrochemical gradient.
In addition to the proteins that facilitate ion movement, other proteins float in the
sarcolemma and serve as receptors for neuronal or chemical control of cellular
processes. Familiar examples of this type of protein are beta-adrenergic receptors and
muscarinic acetylcholine receptors.
SARCOLEMMAL CHANNELS: VOLTAGE-GATED AND LIGAND-GATED
The protein components of many different ion channels have remarkably similar amino
acid sequences, indicating a common evolutionary heritage. Most of the voltage-gated
channels consist of tetrameters of four-ion-channel subunits that surround the
water-filled pore through which ions cross the membrane. Each subunit has six
membrane-spanning alpha helices. A schematic diagram of an ion channel is shown in
Figure 3-2 . Each channel contains a selectivity filter (which selectively and powerfully
prefers particular ions for passage based on pore size and electric charge) and an
activation gate that is regulated by conformational changes induced by either a
voltage-sensitive or a ligand-binding region of the protein. Many channels also have an
inactivation gate , which is again voltage- or ligand-controlled. The function of this gate
will be considered in the following discussion of sodium channels. [2 ] , [3 ] , [5 ]
Voltage-gated sodium channels
The voltage-gated sodium channel is prominent in most electrically excitable muscle

and nerve cells. As will be discussed below, the energy-dependent sodium-potassium
pump leads to a large concentration gradient of sodium from outside the cell to inside
(142 to 10 meq/liter). In addition, potassium permeability leads to a resting electrical
membrane potential of -70 to -90 mV. There is, therefore, both a powerful concentration
gradient and a strong electrical force favoring flow of Na + from the outside of the cell to
the inside (by convention, the flow of a positive ion from outside to inside is termed an
inward current ). As depolarization begins, the activation gate of the sodium channel
opens as the resting potential rises to between -70 and -50 mV. As the activation gate
opens, a flood of Na + ions rushes inward, leading to rapid membrane depolarization.
The inactivation gate of the sodium channel begins to close at about the same voltage,
but with a built-in time delay such that the sodium channel is open for a few
milliseconds. (Because these channels open and close so quickly, they have been
called fast channels .) The sodium channel remains closed by the inactivation gate until
the resting negative membrane potential is restored (in cardiac cells this repolarization
is delayed by the plateau of the action potential). [6 ] [8 ]
Voltage-gated calcium channels
There are two important populations of calcium channels. The T (transient) channels
open as the membrane potential rises to -60 to -50 mV and then close (with an
inactivation gate) quickly. These T-calcium channels are important in early
depolarization (especially in atrial pacemaker cells), but they contribute little to the
sustained depolarization of the plateau of the action potential and have much less
activity in the ventricles.
A second major calcium channel is especially important in cardiac muscle because it

leads to an inward (depolarizing) current that is slowly inactivated. These slow channels
, voltage-activated calcium channels, cause a sustained depolarization of the
membrane (the plateau of the action potential) that allows the sustained contraction of
cardiac muscle needed for ejection of blood. These more common calcium channels,
the L (long-lasting) channels , open at a less negative potential (-30 to -20 mV) and are
inactivated slowly, contributing an inward calcium current (Figure 3-3) that sustains the
action potential and provides a pulse of cytosolic calcium that is the trigger for the
initiation of the excitation-contraction sequence. The activity of this channel is altered by
catecholamine stimulation. Beta-receptor stimulation activates a G-protein, which in turn
stimulates a cyclic AMP-dependent protein kinase to phosphorylate a portion of this
L-calcium channel. Conformational changes occur that enhance the flow of calcium ions,
leading to an increase in the strength of sarcomere contraction. These effects are
attenuated by other inhibitory G-proteins that are activated by stimulation of
acetylcholine and adenosine receptors. The sarcolemmal L-calcium channels are
voltage-gated, but by the receptor system they are prominently regulated by the
neurohumoral control system. [9 ] , [10 ]
Potassium channels
Cardiac cells contain a variety of potassium channels, both voltage-regulated and

ligand-gated. Three of these voltage-regulated potassium channels are important in
repolarization of the cell membrane. [11 ] , [12 ]
The potassium channel primarily responsible for the bulk of the potassium permeability
of the sarcolemma is that channel associated with the first potassium current , or i Kl .
This channel is open at negative membrane potentials and tends to close (in fact, it
tends to favor inward K + flow) at positive membrane potentials. With time, the channel
reopens, powerfully favoring repolarization at the end of the plateau of the action
potential.
A second potassium channel is closed at negative membrane potentials. As the

sarcolemma depolarizes, this channel opens in a delayed manner, leading to an
outward current at the end of the plateau of the action potential that helps repolarize the
membrane. This current is called i K , or the delayed rectifier current . This channel is
highly regulated, with increased current caused by cyclic AMP, protein kinase C, and
protein kinase A. [13 ]
A third voltage-regulated potassium channel opens briefly with depolarization, allowing

a transient outward current i to that contributes to very early repolarization of the action
potential (helping create the hyperpolarized spike of the Purkinji fiber action potential).
Several ligand-gated potassium channels have been identified. Acetylcholine- and

adenosine-activated potassium channels are time-independent and lead to
hyperpolarization in pacemaker and nodal cells, delaying spontaneous depolarization.
A calcium-activated potassium channel opens in the presence of high levels of cytosolic
calcium and probably enhances the delayed rectifier current, leading to early
termination of the action potential. An ATP-regulated potassium channel is closed in the
metabolically normal myocyte but is opened in the metabolically starved myocyte,
tending to retard depolarization and contraction.
ENERGY-DEPENDENT ION PUMPS AND ION EXCHANGE
Sodium-potassium-ATP-dependent pump
The sodium-potassium pump utilizes the energy obtained from the hydrolysis of ATP to
move three na + ions out of the cell and two k + ions into the cell. In the process, the
Na-K-ATPase converts ATP to ADP and inorganic phosphate. It should be noted that
the movement of both Na + and K + are against a concentration gradient. Because
there is a net outward current (three Na + ions for two K + ions), the pump is
electrogenic and contributes about 10 mV to the resting membrane potential. The
activity of the pump is strongly stimulated by attachment of Na + to the binding site on
the inside of the membrane (activity increase is approximately proportional to the third
power of the cytosolic sodium concentration). [1 ] The Na-K-ATPase has a very high
affinity for ATP so that the pump continues to function even if ATP levels are moderately
reduced. There is, however, a second regulatory ATP-binding site on the sodium pump
(which accelerates the turnover of pump ions when ATP is bound) with a lower affinity
for ATP. Because of this regulatory site, modest reductions in ATP levels will decrease
the activity of the pump. [3 ] , [14 ]
ATP-dependent calcium pump
A second energy-dependent pump is important in regulating the calcium level of the

cytosol. This pump functions by binding ATP and calcium, hydrolyzing the ATP, and
utilizing the consequent energy to transport calcium out of the cell. This represents a net
outward current, but the magnitude of this current is quite small because the bulk of
calcium transferred out of the cell occurs with sodium-calcium exchange (described
below). The C-terminal portion of the protein that makes up the sarcolemmal calcium
pump inhibits the pump by interacting with the ATP and calcium-binding sites of the
protein. A cytosolic protein, calmodulin, can complex with calcium and bind to this
C-terminal domain, facilitating the action of the pump. The pump is therefore stimulated
by increased calcium levels within the cytosol. [3 ] , [15 ] , [16 ]
Sodium-calcium exchange
Yet another complex protein bridges the sarcolemma and facilitates an exchange of
sodium ions for calcium ions. The energy used for this exchange comes from the
concentration gradient and the electrical gradient that tend to force sodium ions into the
cell. Three sodium ions are exchanged for one calcium ion, leading to a net single
positive charge transported into the cell with each exchange. The exchange is therefore
electrogenic and may contribute a few millivolts to the resting membrane potential. The
exchange system is sensitive to the concentration of calcium on both sides of the
membrane to the concentration of sodium on both sides of the membrane, and to the
membrane potential. Indeed, when the membrane is depolarized, the pump may be
temporarily reversed, pumping small amounts of calcium into the cell. If external sodium
concentrations fall, the driving force for removal of calcium from the cell is decreased,
leading to an increase in cytosolic calcium (and a consequent increase in contraction).
This explains an observation made some years ago that hyponatremia can lead to an
increase in cardiac contractility. The sodium-calcium exchange mechanism has a
maximum exchange rate that is some 30 times higher than the sarcolemmal
ATP-dependent calcium pump described above and is likely the primary mechanism for
removal of excess cytosolic calcium. [10 ]
T-Tubules and the Sarcoplasmic Reticulum

T-TUBULES
A system of transverse tubules (or T-tubules ) extends the sarcolemma into the interior
of the cardiac cell. These tubules are generally perpendicular to the sarcomere at the
level of the Z lines. The T-tubules also may run longitudinally along the sarcomere. By
extending the extracellular space into the cell, the electrical excitation of the
sarcolemma can be brought very close to the contractile proteins, enabling more rapid
contraction and relaxation of these contractile elements than would be the case if
diffusion of a transmitting chemical were the method for delivery of the contraction
signal into the center of the cell. The transverse tubules contain the calcium channels
described above, which are in close relationship to the foot proteins of the
subsarcolemmal cisternae.
SUBSARCOLEMMAL CISTERNAE
The bulk of the sarcoplasmal reticulum in the cardiac cell contains only small amounts of
RNA and is not concerned with protein synthesis. Its primary function is
excitation-contraction coupling by sudden release of calcium to stimulate the contraction
proteins and then rapid removal of the same calcium to allow relaxation of the
contractile elements. The subsarcolemmal cisternae and the sarcotubular network are
the two portions of the sarcoplasmic reticulum concerned with this process. The
subsarcolemmal cisternae are beneath the sarcolemma and surround the T-tubules.
Specialized bulky proteins are found in the membrane of the sarcoplasmic reticulum,
with a large protein component extending into the gap between the subsarcolemmal
cisternae and the sarcolemma or the T-tubule. These foot proteins respond to the
release of calcium by the sarcolemma (or T-tubule) by rapid opening of a calcium
channel (actually a part of the foot protein) that allows release of a much larger quantity
of calcium from the subsarcolemmal cisternae. This is calcium-triggered calcium
release, with calcium transported across the sarcolemma leading to calcium release
from the subsarcolemmal cisternae. The magnitude of release from the
subsarcolemmal cisternae appears to be related to the magnitude of the trigger. The
calcium channels appear then to close (perhaps in response to the high concentrations
of cytosolic calcium), and calcium uptake can occur by the energy-dependent calcium
pump of the sarcoplasmic reticulum, which is located primarily in the sarcotubular
network . [2 ] , [3 ] , [16 ]
THE SARCOTUBULAR NETWORK
The portion of the smooth sarcoplasmic reticulum that is responsible for the uptake of
calcium from the cytosol is called the sarcotubular network . This network of tubules
surrounds the contractile elements of the sarcomere, while the T-tubules and the
sarcolemma cisternae are at the level of the Z line. Calcium uptake is accomplished by
large numbers of ATP-dependent calcium pumps. A large number of these pumps is
necessary because calcium ion movement through the pumps is much slower than it is
through calcium channels. Calcium concentration in the extracellular fluid or in the
sarcoplasmic reticulum is in the millimolar range, whereas cytosolic calcium
concentration is about 0.2 µ M . This huge downhill gradient has been estimated to lead
to a calcium-channel flow of 3 million ions per second through a single channel. The
calcium pump, on the other hand, has been estimated to pump 30 ions per second. It
has been estimated that each cardiac cell contains approximately 3000 sarcolemmal
calcium channels, 12,000 sarcoplasmic reticulum calcium release channels, and 150
million sarcoplasmic reticulum calcium pump sites. The pumps appear to work
throughout the cardiac cycle, but their ability to remove calcium is obviously
overwhelmed during the short period of time that the calcium channels are opened by
depolarization. [3 ]
Regulation of calcium transport by the cardiac sarcoplasmic reticulum occurs primarily

at the site of the calcium pump. The sarcolemmal calcium pump has a C-terminal
portion that inhibits the ATPase- and calcium-binding sites of that protein, as described
earlier. This C-terminal portion is not present on the sarcoplasmic reticulum calcium
pump, but instead, a protein called phospholamban in the cytosol has an amino acid
sequence very similar to the C-terminal portion of the sarcolemmal calcium pump.
Phospholamban inhibits the basal rate of calcium transport by the cardiac sarcoplasmic
reticulum calcium pump. This inhibition can be reversed when phospholamban is
phosphorylated by a cyclic AMP-dependent or a calcium, calmodulin-dependent protein
kinase. This effect appears to be a very important mechanism by which beta-adrenergic
stimulation regulates the heart, since increased levels of cytosolic cyclic AMP are a
consequence of activation of the beta-catecholamine receptor. As phospholamban is
phosphorylated, there is accelerated calcium turnover and increased sensitivity of the
calcium pump that facilitates uptake of calcium from the cytosol and relaxation of the
heart when the heart comes under the influence of beta-adrenergic agonists. It should
be noted that phosphorylation of phospholamban does not affect the sarcolemmal
calcium pump, thereby tending to favor retention of calcium within the cell (increasing
the calcium content of the sarcoplasmic reticulum at the expense of calcium removed
from the cell through the sarcolemma). This might lead to an increased pulse of calcium
within the cell favoring increased contractility. [10 ] , [16 ]
Electrical Activation of the Heart
THE NEGATIVE RESTING MEMBRANE POTENTIAL
The cardiac cell, in its polarized (diastolic) state, has a resting electrical potential
across the cell membrane that is determined primarily by the concentration gradient of
potassium across the membrane (developed by the sodium-potassium pump
described earlier). Because the sarcolemma prevents the diffusion of large anions
(e.g., proteins and organic phosphates) and is relatively permeable to potassium ions
(because most potassium channels are open in the polarized state), potassium ions
flow across the membrane in response to the concentration gradient, leading to an
outward flow of positive ions until a Donnan equilibrium is established such that the
electronegativity of the cell interior retards potassium ion efflux to the same degree that
the concentration gradient favors K [1 ] efflux. For potassium ions, this electronegativity
is quantified by the Nernst equation: E m = 61.5 log(K o /K i ). With approximate K ion
activity inside (K i ) and outside (K o ) of 100 and 4 m M respectively (activity is different
from concentration because of interaction with water and other ions), the resting
electrical membrane potential of cardiac cells is predicted to be -86 mV, very close to
measured values. Because the diastolic permeability of potassium is 100 times the
permeability of sodium and other ions, potassium gradients determine the resting
membrane potential. [1 ] , [2 ]
DEPOLARIZATION OF THE SARCOLEMMA: THE ACTION POTENTIAL

A typical ventricular action potential is depicted in Figure 3-3 . The membrane is
depolarized by an electric current traveling longitudinally along the membrane from
another cell (the signal originates in a pacemaker area, as will be discussed). As the
membrane potential rises to approximately -60 mV, the fast sodium channel opens.
This channel remains open for only a few milliseconds before the inactivation gate of the
sodium channel closes. This causes the rapid spike of the action potential (phase 0) as
the cell is completely depolarized and in fact becomes slightly positive. A transient
potassium current ( i to ) causes a very early repolarization (phase 1 of the action
potential), but this channel closes quickly. The plateau of the action potential (phase 2)
is sustained at a slightly positive level by an inward-flowing calcium current, first from the
transient channel and second through the long-lasting channel. The plateau is also
sustained by a decrease in the outward potassium current ( i Kl ). With time, the
long-lasting calcium channel begins to close, and repolarizing potassium current ( i K ,
the delayed rectifier current) leads to the beginning of repolarization of the membrane
(phase 4). As repolarization progresses, the stronger first potassium current ( i Kl )
dominates, leading to full repolarization of the membrane to the resting negative
potential. During the bulk of the depolarized interval (phase 4), the first potassium
current predominates.
Because the sodium channels cannot respond to a second wave of depolarization until
the inactivation gates are reopened, the membrane is refractory to the propagation of a
second impulse during this time interval, termed the absolute refractory period (see Fig.
3-2 ). As the membrane is repolarized and some of the sodium channels have been
reactivated, a short interval exists during which only very powerful impulses can be
propagated, the relative refractory period . A drug that speeds up the kinetics of the
inactivation gate will shorten both the absolute and the relative refractory periods. [1 ] [3
] , [17 ] [19 ]
SPONTANEOUS DEPOLARIZATION: PACEMAKER ACTIVITY
The heart rate, in most circumstances, is determined by the rate of spontaneous

depolarization of pacemaker cells in the sinoatrial (SA) node. Different regions of the
heart contain different concentrations of the various ion channels. The pacemaker cells
in the SA node appear to be somewhat leaky to sodium ions and do not contain
normally functioning sodium channels. The resting membrane potential in these cells,
because of increased permeability to sodium ions, is -70 to -60 mV. Spontaneous
depolarization occurs because of the sodium current (funny current, or i f ), as depicted
in Figure 3-4 . This sodium current and a long-lasting calcium current predominate over
potassium currents, leading to a gradual rise in the membrane potential to
approximately -50 mV. At this level the transient calcium channel is opened, leading to
an action potential that rises more slowly than the action potential described earlier
(because these calcium channels open much more slowly than the fast sodium
channels). The action potential generally does not become positive, and repolarization
begins without a sustained plateau because of decay at the calcium current and a
prominent delayed rectifier potassium current. Note that in the SA node the delayed
rectifier potassium current predominates over the first potassium current. [19 ] [21 ]
PROPAGATION OF ACTION POTENTIAL
Each myocyte is electrically connected to the next myocyte by an intercalated disk at the
end of the cell. These disks contain gap junctions that allow free flow of charged
molecules from one cell to the next. These channels in the intercalated disks are
composed of a protein called connexon . Permeability through the cardiac gap junction
is increased by both ATP- and cyclic AMP-dependent kinases. This allows the gap
junctions to close if ATP levels fall (which is essential in limiting cell death when one
region of the heart is damaged) and permits conduction to increase when cyclic AMP
increases in response to adrenergic stimulation.
After spontaneous depolarization occurs in the pacemaker cells of the atrioventricular

(AV) node, the action potential is conducted throughout the heart. This conduction is
facilitated by special conduction pathways. These cells are, in general, large cells that
lead to rapid conduction of the action potential. Three internodal paths exist through the
atrium between the SA node and the AV node. After traversing the AV node, the action
potential is propagated rapidly through the bundle of His and into the Perkinji fibers
located on the endocardium of the left and right ventricles. The rapid conduction through
the atrium causes contraction of most of the atrial muscle synchronously (within 60 to
90 ms). Similarly, the rapid conduction of the signal throughout the ventricle leads to
synchronous contraction of the bulk of the ventricular myocardium (within 60 ms). The
delay in the propagation of the action potential through the AV node (a delay 120 to 140
ms) leads to sequential contraction of the atrium followed by the ventricle. This allows
the atrium to pump a pulse of blood into the ventricle just prior to ventricular contraction.
Slow conduction in the AV node is related to a relatively higher internal resistance
because of a small number of gap junctions between cells and to slowly rising action
potentials. In parts of the AV node, functional fast sodium channels are absent and
depolarization depends on the slow calcium channels. [2 ] , [3 ]
ARRHYTHMIAS
Aberrant pacemaker foci
One innocuous type of abnormal cardiac rhythm that frequently occurs is the origin of
extracardiac beats from abnormal aberrant pacemaker foci. Spontaneously
depolarizing areas occur in the heart in the SA node, the AV node, and the His-Purkinji
system. Ordinarily, the SA node depolarizes spontaneously the most quickly such that
the cardiac beat originates from the SA node. If the SA node is damaged or slowed by
vagal or drug stimulation, pacemakers in the AV node or the His-Perkinji system may
take over. Occasionally, aberrant foci in the heart depolarize spontaneously, leading to
the insertion of aberrant beats from either the atrium or the ventricle. These beats
ordinarily do not interfere with the normal depolarization of the heart and have very little
tendency to degenerate into disorganized electrical activity. Therefore, these beats are
generally not clinically threatening.
Reentry arrhythmias, unidirectional block
A second type of cardiac rhythm is perhaps the most common dangerous cardiac
rhythm. This consists of reentry arrhythmias . This type of rhythm is caused by
propagation of an action potential through the heart in a circus movement. In ordinary
circumstances, the action potential depolarizes the entire atrium or the entire ventricle in
a short enough time that all the muscle is refractory to further stimulation at the same
time. If a portion of the myocardium has repolarized before the propagation of the action
potential throughout the atrium or ventricle is completed, then that action potential can
continue its propagation into his repolarized muscle. Such an event generally requires
either dramatic slowing of conduction of the action potential, a long conduction pathway,
or a shortened refractory period (Fig. 3-5) . All these situations occur clinically. Ischemia
leads to slowing of the sodium-potassium pump (by the ATP-dependent regulation
system described above), which leads to a decreased resting membrane potential and
slowing of the propagation of the action potential. Hyperkalemia similarly leads to an
increase in the extracellular potassium level, a decrease in the resting membrane
potential, and a slowing of the propagation of the action potential. Progressive atrial
dilatation as occurs with mitral valve disease leads to a long conduction pathway
around the atrium, which can lead to the development of a reentry or circus movement in
the atrium. Adrenergic stimulation leads to a shortened refractory period (by
mechanisms described below), which increases the likelihood of a reentry arrhythmia. It
should be noted that most reentry circuits require unidirectional propagation of the
action potential along the reentry pathway. The conditions for unidirectional propagation
are often created by ischemia or by myocardial damage. [3 ]
A special type of reentry arrhythmia occurs in the Wolff-Parkinson-White (WPW)

syndrome in which an accessory pathway electrically connects the atrium and the
ventricle. This accessory pathway can complete a circular electrical pathway between
the atrium and the ventricle that meets the conditions described in the preceding
paragraph for a reentry arrhythmia: conduction is unidirectional across the AV node
(because of the special properties of the AV node), and conduction is delayed. The
aberrant pathway allows retrograde conduction from the ventricle back to the atrium,
completing the circle necessary for the reentry circuit. We have therefore a circular
pathway with unidirectional, delayed conduction. The accessory pathway of the WPW
syndrome is dangerous in another way. Because it does not have the inherent delay
and refractory period of the AV node, rapid atrial tachycardias can be conducted in a
1:1 manner across the accessory pathway, leading to ventricular rates as fast as 300
beats per minute, a potentially lethal situation in a patient with atrial fibrillation and an
accessory pathway.
Afterpotentials or parasystole
Most ventricular tachyarrhythmias are reentry arrhythmias. The primary exception to this
is parasystole, or afterpotentials. Normally, ventricular action potentials have a flat
phase 4 during diastole without spontaneous depolarization. If, however, there are
elevated levels of cytosolic calcium, there may be a transient diastolic inward
(depolarizing) current related probably to sodium-calcium exchange. Afterpotentials are
thought to underlie the development of ventricular automaticity during digitalis toxicity.
The afterdepolarizations associated with digitalis toxicity appear to be delayed
afterdepolarizations. Another type of afterdepolarization is an early afterdepolarization
that occurs before the end of complete repolarization. This early afterdepolarization
appears to be the mechanism for the ventricular tachycardia called torsades de pointes
in which varying QRS complexes appear. A prolongation of the QT interval and the
varying QRS complexes in torsades de pointes indicate a heterogeneity of the action
potential duration within the ventricle predisposing to degeneration into ventricular
fibrillation. [18 ]
Antiarrhythmic agents, proarrhmthmia
Antiarrhythmic agents generally act on the two major factors causing arrhythmias,
automaticity and reentry. Four classes of antiarrhythmic agents are usually identified.
Class I agents are sodium-channel blockers . Class IA agents (quinidine,

procainamide) inhibit the opening of sodium channels, leading to a slowing of
conduction in the heart. They have additional effects, perhaps on the inactivation gate of
the sodium channel, that prolong the action potential and thereby increase the refractory
period. Class IB agents such as lidocaine and diphenylhydantoin moderately inhibit
sodium channels and may shorten the refractory interval. These agents are particularly
effective in inhibiting opening of sodium channels in relatively depolarized cells so that
they are especially effective in decreasing spontaneous depolarization (or automaticity)
and are useful when the myocardium is ischemic with partially depolarized myocytes.
Class IC agents markedly inhibit sodium-channel opening with a mild prolongation of
refractoriness. These agents delay conduction and prevent automaticity.
Class II antiarrhythmic drugs are drugs that cause beta-adrenergic blockade . These
drugs inhibit adrenergic stimulation of calcium-channel opening by competitively
inhibiting the effect of beta-adrenergic agonists, which are discussed below.
Class III antiarrhythmic agents prolong the cardiac action potential . This appears to be
primarily an effect on the repolarizing potassium current, leading to an increased
refractory period. Examples of these drugs are amiodarone, bretillium, and sotalol.
Class IV agents are calcium-channel blockers . These drugs are especially important
in decreasing the rate of conduction through the AV node. As discussed above, some
cells in the AV node have a paucity of sodium channels and depend on calcium
channels for depolarization.
Many antiarrhythmic drugs have a proarrhythmic effect. As discussed above, many

drugs, particularly the class IA and IC drugs, lead to a decrease in conduction velocity.
As illustrated in Figure 3-5 , a decrease in conduction velocity increases the likelihood
of a reentry arrhythmia. If the refractory period is concomitantly prolonged (as is the
case with class IA drugs), then the tendency toward more rapid conduction may be
counterbalanced by a longer refractory period, and reentry arrhythmias may not occur. If,
on the other hand, as is the case with class IC drugs, the conduction velocity is slowed
and the refractory period is not sufficiently prolonged, reentry arrhythmias become more
likely. Class IC drugs have been shown to have a great clinical risk in prolonged
prophylactic use, presumably because of their proarrhythmic effect. [22 ]
Regulation of Cellular Function by Sarcolemmal Receptor Proteins
PARASYMPATHETIC REGULATION
The parasympathetic nervous system is particularly important in control of the

pacemaker cells of the SA node. Release of acetylcholine by the nerve endings of the
parasympathetic system stimulate muscarinic receptors in the heart. These activated
receptors in turn produce an intracellular stimulatory G-protein that opens
acetylcholine-gated potassium channels. An increased outward (repolarizing) flow of
potassium leads to hyperpolarization of the SA node cells. Stimulation of the muscarinic
receptors also inhibits the formation of cyclic AMP. Decreased cyclic AMP inhibits the
opening of calcium channels. A decreased inward flow of calcium combined with an
increased outward flow of potassium leads to a slowing (sometimes dramatic) of the
spontaneous depolarization of the SA nodal cells (see Figure 3-4 ). A similar effect in
the AV node leads to slowing of conduction through the AV node by the
hyperpolarization of cells and inhibition of the slow calcium channel. [2 ]
ADRENERGIC STIMULATION AND BLOCKADE
Among the most important sarcolemmal receptor proteins are the beta-adrenergic
receptors. There are two types of beta-adrenergic receptors, the beta1-adrenergic
receptors, which predominate in the heart, and the beta 2 -adrenergic receptors, which
tend to be present in the lungs and the liver. In the human, approximately 15 percent of
the beta receptors in the ventricles are beta 2 receptors, but a larger portion of beta 2
receptors are present in the atrium. Cardioselective beta blockers (metoprolol, atenolol,
acebutolol) act predominantly on the heart because they are bound more tightly to beta1
receptors than to beta 2 receptors. The number of receptors per unit area of the
sarcolemma is not fixed but can increase or decrease in various circumstances. These
changes are called upregulation or downregulation of receptor density. In addition to
changes in receptor density, the receptors can be desensitized or internalized by
chemical changes such that although the receptors are still present, they are not
available for signal transmission. [23 ]
The beta-adrenergic receptor couples with adenylcyclase, another sarcolemmal protein.

As diagramed in Figure 3-6 , when the receptor site is occupied by a catecholamine
(the best fit is isoproterenol, followed by epinephrine and then norepinephrine), a
stimulatory G-protein is formed that combines with GTP. This activated G-proteinGTP
complex then promotes the activity of adenylcyclase, leading to the formation of cyclic
AMP from ATP. Cyclic AMP classically has been described as the second messenger
of the beta-adrenergic receptor system, but one probably should consider the
stimulatory G-protein to be the second messenger and cyclic AMP to be the third
messenger. The stimulatory G-protein directly stimulates calcium-channel opening. The
third messenger, increased cyclic AMP, also actively promotes calcium-channel
opening. As described earlier in the discussion of the sarcoplasmic reticulum calcium
pumps, cyclic AMP and increased cytosolic calcium lead to phospholamban activation,
which leads to increased calcium uptake by the sarcoplasmic reticulum.
The increased tendency for calcium channels to open leads to a number of

electrophysiologic effects. There is an accelerated discharge rate of the SA node and
other spontaneously depolarizing areas of the heart. There is accelerated conduction
through the AV node (an area of the heart in which depolarization is particularly
dependent on calcium channels). The increased cytosolic levels of calcium lead to a
positive inotropic effect (by mechanisms to be discussed subsequently). The
phospholamban-stimulated increased activity of the sarcoplasmic reticulum calcium
pump results in a more rapid removal of calcium from the cytoplasm at the termination
of systole, leading to a more rapid relaxation of the cell. Therefore, beta-adrenergic
stimulation leads to a positive inotropic effect, a positive lusitropic (relaxation) effect, a
positive chronotropic effect, and a positive dromotropic (conduction) effect. These
effects are mediated by a series of messengers, the stimulatory G-protein, cyclic AMP,
phospholamban, and increased cytosolic calcium levels. [24 ] , [25 ]
Also shown in Figure 3-6 are two negative feedback systems that contribute to the
diminished response (tachyphylaxis) observed when beta-agonist stimulation is
repetitive or persistent. Increased cyclic AMP leads to increased phosphorylation of
beta receptors, which in turn leads to internalization of the receptor (or desensitization).
Increased levels of cyclic AMP lead to increased activity of phosphodiesterase, the
enzyme that degrades cyclic AMP.
A new class of inotropic drugs, phosphodiestrase inhibitors (amrinone, milrinone),

inhibit the breakdown of cyclic AMP and thereby increase its level in the cytosol.
Because of the site of action of the phosphodiestrase inhibitors, their effect is generally
additive to the effect of beta agonists. Also, since they do not cause the production of
the stimulatory G-protein depicted in Figure 3-6 , they have a lesser effect on
calcium-channel activation and therefore have less of the troublesome positive
chronotropic and dromotropic effects of beta-adrenergic stimulation. [25 ] , [26 ]
Cyclic AMP appears to play a central role in the regulation of the cardiac cell. Cytosolic
levels of cyclic AMP are increased by receptors other than beta receptors (histamine,
dopamine, glucagon) and are decreased by inhibitory G-proteins produced by
stimulation of acetylcholine and adenosine receptors.
Beta-blocking drugs compete with beta agonists for binding sites on the
beta-adrenergic receptor, thereby preventing activation of the receptor. They cause,
therefore, by the scheme shown in Figure 3-6 , a negative chronotropic effect, a
negative inotropic effect, and negative lusitropic effect. These drugs are particularly
useful in pathologic conditions in which excessive adrenergic stimulation might cause
ischemia by an undesirable increase in oxygen consumption. By decreasing cyclic
AMP levels (and by other mechanisms), beta blockers lead to resensitization of beta
receptors in the sarcolemma. If beta-receptor drugs are therefore suddenly stopped,
this resensitization has led to an increased density of active beta receptors on the cell
membrane. This may cause a temporarily enhanced (and potentially dangerous)
sensitivity to adrenergic stimulation.
ADENOSINE
Adenosine is an especially useful drug in treating rapid superventricular tachycardias.

Adenosine receptors lead to formation of an inhibitory G-protein that results in inhibition
of the slow calcium channel and opening of an adenosine-activated potassium channel.
This leads to hyperpolarization in pacemaker cells, slowing spontaneous depolarization
and depressed depolarization in nodal cells (remember that calcium channels are
generally responsible for depolarization in these cells rather than sodium channels). The
end result is delayed conduction through the AV node and a slowed ventricular
response to atrial tachycardia. [2 ] , [27 ]
CARDIAC GLYCOSIDES
Cardiac glycosides (oubain, digitoxin, digoxin) act not through a separate receptor
protein but by binding to and inhibiting the protein comprising the ATP-dependent
sodium-potassium pump. This leads to a slightly increased intracellular concentration of
sodium. By the mechanism discussed earlier when considering the sodium-calcium
exchange system, the driving force for calcium removal from the cell (the sodium
gradient across the sarcolemma) is decreased, and the increased intracellular sodium
concentration leads to less calcium binding to the intracellular portion of the
sodium-calcium exchange protein. These two effects decrease the extrusion of calcium
from the cell, which in turn leads to an increased strength of myocardial contraction, as
will be discussed later. Because the sodium-potassium pump may be stimulated by
increased extracellular levels of potassium, hyperkalemia tends to reverse the effects of
digitalis toxicity, while hypokalemia tends to amplify these effects. [2 ] , [3 ] , [24 ]
CALCIUM-CHANNEL BLOCKERS
Calcium-channel blockers bind to the membrane-spanning protein of the L-type calcium

channel. There are three chief categories of these drugs resembling nifedipine,
verapamil, and diltiazem. Each category appears to bind in a different site on the
calcium-channel protein, leading to different effects on these voltage-gated and
time-dependent channels. Diltiazem and verapamil are particularly useful in slowing AV
conduction (thereby decreasing the ventricular response to atrial tachycardias) because
AV nodal depolarization depends primarily on a calcium current in the general absence
of functional sodium channels. [2 ]
CONTRACTION OF CARDIAC MUSCLE
The Contractile Element (Sarcomere)
The myocyte is made up of myofibrils surrounded by sarcoplasmic reticulum (for

calcium release and uptake, as described earlier) and mitochondria (for generation of
ATP, the energy source for contraction). Each myofibril is made up of a number of
sarcomeres longitudinally connected by dense attachments between sarcomeres at the
Z band (the insertion site of the actin filament). A portion of a sarcomere is depicted in
Figure 3-7 . Each sarcomere contains thick myosin filaments (a longitudinal helix of
myosin molecules). Each myosin molecule has a head that when energized by
hydrolysis of ATP (by an ATPase that is part of the myosin molecule) stands out at right
angles to the myosin molecule like a cocked oar (see Fig. 3-7A ). Each myosin filament
is surrounded by six actin filaments (light chains). There are a number of active sites on
the actin filaments that can interact with the myosin heads. In the resting state these
active sites on the actin filaments are covered by another protein, tropomyosin. The
tropomyosin covering of the actin active sites is altered by yet another protein, troponin.
When calcium combines with one of the protein subunits of troponin, the tropomyosin
molecule is altered such that the actin active sites become available to the myosin
head. Calcium therefore leads by this mechanism to uncovering of the actin active sites,
which then interact with the cocked oars of the myosin heads. The energy stored in the
myosin heads is utilized in a conformational change that pushes the actin filament
longitudinally along the myosin filament. Each oar stroke leads to a movement of 5 to 10
nm. At the end of the stroke an uncoupling of the myosin head from the actin site occurs,
and the myosin head is then reenergized and moved back into a cocked position by
hydrolysis of another molecule of ATP (see ( Fig. 3-7B ). The myosin heads then act in a
wavelike fashion sweeping the actin filaments along, moving the Z lines closer together.
When calcium is rapidly removed from the cell at the termination of the action potential
(by the huge number of ATP-dependent calcium pumps in the sarcotubular system
described earlier), a conformational change again occurs between troponin and
tropomyosin leading to recovering of the actin active sites with disengagement of the
actin filament from the myosin filament and relaxation of the sarcomere. The removal of
calcium from the cytosol is an energy-dependent process. Relaxation therefore requires
energy. [4 ] , [28 ] [30 ]
Excitation-Contraction Coupling
The basic elements of the excitation-contraction coupling sequence were described

earlier in descriptions of calcium channels and calcium pumps, but a synthesis of this
sequence is appropriate at this point. Depolarization of the sarcolemmal membrane
(and the T-tubule extensions of this membrane into the middle of the myocyte) leads to
influx, through the sarcolemmal calcium channels, of calcium ions into the cell. This influx
occurs in close proximity to the foot protein. These foot proteins are a portion of the
calcium channels of the subsarcolemmal cisternae in which a large quantity of
intracellular calcium is concentrated. These channels open, and calcium floods from the
subsarcolemmal cisternae into the cytosol surrounding the contraction elements. This
calcium channel subsequently closes (in about 200 ms), and the huge number of
ATP-dependent calcium pumps in the sarcotubular system rapidly remove the calcium
from the cytosol. As described in the preceding section, this pulse of increased
cytosolic calcium ions leads to an actin-myosin interaction that converts chemical
energy into mechanical movement. Energy is expended as the myosin heads are
reenergized after each oarlike movement, and energy is expended in the removal of
calcium from the cytosol back into the sarcotubular system. [10 ] , [18 ] , [29 ]
The strength of the myocardial contraction appears to be mediated primarily by the

degree of uncovering of the actin active sites as tropomyosin is pulled away from the
active sites by the combination of troponin and calcium. The magnitude of this effect
depends on the affinity of troponin for calcium and the availability of calcium ions (i.e.,
the magnitude of the systolic pulse of calcium). The magnitude of the initial calcium ion
influx through the sarcolemmal calcium channels is altered by cyclic AMP levels, by
stimulatory G-proteins from beta-adrenergic receptors, and by inhibitory G-proteins
from adenosine and acetylcholine receptors. This change in the magnitude of the
calcium trigger leads to a change of the magnitude of the cytosolic calcium pulse. The
rate of uptake of calcium from the cytosol (and thereby the duration of the calcium
pump) is altered by cyclic AMP, as depicted in Figure 3-6 . In addition to this
mechanism, cyclic AMP can lead to phosphorylation of a portion of the troponin
molecule in a manner that allows more rapid release of calcium from troponin, thereby
increasing the rate of relaxation of the actin-myosin complex. [10 ] , [29 ]
In addition to regulation of the strength of contraction by the primary mechanism of

cytosolic calcium levels, the rate at which the myosin heads are reenergized can alter
the speed and strength of the contraction. The rate of this reaction can be altered by
phosphorylation of the myosin molecule during beta-adrenergic stimulation leading to
an increased rate of the myosin ATPase reaction. Changes in the rate of cross-bridge
cycling also may be caused by alterations in the myosin heavy chains that are a
consequence of the synthesis of various isoforms of myosin (regulated by gene
expression). [3 ] , [18 ]
Regulation of the Strength of Contraction by Initial Sarcomere Length
In the heart, as in skeletal muscle, a relationship exists between resting sarcomere

length and the strength of contraction. In skeletal muscle this relationship is bell-shaped,
with maximum contraction at a sarcomere length of 2.2 µm. It has been proposed that at
a greater sarcomere length force declines because there is a decreased overlap of
actin and myosin and thereby a decreased availability of cross-bridging sites. In the
heart, a decrease in contractility related to decreased overlap of the filaments does not
seem to occur, since the resting length of the cardiac sarcomere rarely exceeds 2.2 to
2.4 µm. As the heart attempts to dilate beyond this state, a stiff parallel elastic element
prevents dilatation. Even if dilatation does occur, there appears to be primarily slippage
of fibers or myofibers rather than stretching of sarcomeres. [2 ]
The increase in contractility that is associated with stretching of the myocardium

appears to be related to an increased sensitivity of the contractile elements to cytosolic
calcium. A calcium pulse that will cause approximately 50 percent maximal tension if the
initial sarcomere length is 1.95 µm will lead to more than 75 percent maximal tension if
the initial sarcomere length is 2.4 µm. [2 ] This poorly understood but dramatically
increased sensitivity to calcium as length is increased is an important part of the
ascending limb of the Starling curve observed in the intact ventricle.
THE PUMP
Mechanics
The heart is a pump whose primary purpose is the conversion of chemical to

mechanical energy to the end that blood flow can distribute oxygen and nutrients and
retrieve carbon dioxide and waste products. In the preceding sections an understanding
of the conversion of ATP (the final packaging of stored chemical energy) to mechanical
energy in the form of sarcomere contraction has been developed. The method by which
the sarcomere contraction is synchronized, electrical activation of the heart, also has
been considered. In this section we will attempt to describe the function of the heart as
an organ, a syncytium of myocytes made up of sarcomeres that contract in near
synchrony to deliver external work by ejection of a volume of blood from the ventricular
cavity against an aortic or pulmonary artery pressure. This discussion will center on the
left ventricle.
THE FRANK-STARLING RELATIONSHIP
Two renowned physiologists almost a century ago developed the concept that within
physiologic limits, the heart will function as a sump pump. That is, the greater the heart
is filled during diastole, the greater the quantity of blood that will be pumped out of the
heart in systole. Under normal circumstances, the heart pumps all the blood that comes
back to it without excessive elevation of venous pressures. This relationship is depicted
in Figure 3-8 for the left ventricle. In the normal heart, as ventricular filling is increased,
the strength of ventricular contraction increases as sarcomeres are stretched (related
by unknown mechanisms to increased sensitivity to cytosolic calcium, as described
earlier). In addition, stretching of the right atrium leads to perhaps a 20 percent increase
in heart rate, which contributes to the heart's ability to pump more blood.
Also depicted in Figure 3-8 are two other states, the condition of normal adrenergic
stimulation and the condition of maximal adrenergic stimulation. With sympathetic
stimulation, the heart contracts more forcefully with every beat (inotropic effect). Equally
important, however, are the other effects (chronotropic, dromotropic, and lusitropic) of
sympathetic stimulation. The heart rate increases dramatically. Conduction velocity
increases, and the action potential is shortened, leading to a shortening of systole. An
increased rate of relaxation allows a relatively greater time for the heart to fill. This is
particularly important with tachycardia. If the length of systole remains at 300 ms as the
heart rate is increased (as it tends to do if the heart rate is increased by pacing), then
when the heart rate reaches 120 beats per minute with a cardiac cycle duration of 500
ms, the time available for the heart to relax and fill is shortened to only 200 ms. This will
begin to lead to a dynamic diastolic failure of the heart with backing up of blood in the
systemic and pulmonary veins. With electrical stimulation, the optimal heart rate for
maximal cardiac output is between 100 and 150 beats per minute. With sympathetic
stimulation, positive dromotropic and lusitropic effects lead to a dramatic shortening of
systole relative to diastole. Because of these effects, the optimal heart rate for maximal
cardiac output during sympathetic stimulation is approximately 200 beats per minute (a
cardiac cycle length of only 300 ms). [1 ]
PRELOAD AND DIASTOLIC DISTENSIBILITY (OR COMPLIANCE)
The preload of the left ventricle describes the intracavitary pressure and volume
immediately prior to contraction. From the clinician's point of view, preload traditionally
has been considered to be the filling pressure. Since the physiologist is more
concerned with the degree of stretch of the sarcomere, preload to the physiologist
generally means the initial volume of the ventricle. The relationship between the
end-diastolic pressure and the end-diastolic volume is complex. Several different
diastolic pressure-volume relationships are shown in Figure 3-9 . The compliance or
distensibility of the ventricle is defined as the change in volume divided by the change
in pressure. The stiffness of the ventricle is the reciprocal of compliance, the change in
pressure divided by the change in volume.
A number of factors affect the diastolic pressure-volume relationship. A fibrotic heart, a

hypertrophied heart, or an aging heart becomes increasingly stiff (see Fig. 3-9C,E ). In
the case of fibrosis, this is related to the development of a collagen network. In the case
of hypertrophy, this is related to increased stiffness of the noncontractile components of
the heart and also likely related to impaired relaxation of the heart. Relaxation, as
described earlier, is an active, energy-requiring process. This process is accelerated
by catecholamine stimulation but is impaired by ischemia, hypothyroidism, and chronic
congestive heart failure. Examination of the curves in Figure 3-9 allows one to
appreciate the potential importance of these static and dynamic diastolic distensibility
changes in pathologic cardiac conditions. [31 ] , [32 ]
AFTERLOAD AND AORTIC IMPEDANCE
The afterload of an isolated muscle is the tension against which it contracts. When
considering the heart as an organ, the afterload of the left ventricle is generally
considered to be the pressure developed during ventricular systole, which in turn is
determined by the aortic pressure against which it must eject. The greater the afterload,
the more mechanical energy that must be imparted to the ejected blood to bring it from
atrial pressure to aortic pressure. In addition to the potential energy imparted to the
ejected blood by a change in pressure, an additional kinetic energy is generated by the
contracting left ventricle. This additional energy is utilized to overcome the compliance
of the distensible aorta and systemic arterial system (this system becomes increasingly
stiff with aging and atherosclerosis) and to cause the actual flow of blood into the
arterial system (the energy necessary for this flow is ordinarily small unless there is
some obstruction to flow such as aortic stenosis). If one considers only the energy used
to change the pressure of blood, one relates afterload to resistance (resistance equals
change in pressure divided by cardiac output). If one wishes to more accurately
describe the forces resisting ejection of blood from the ventricle, then one must
consider compliance, kinetic energy, and potential energy and one must speak of aortic
impedance rather than resistance. This distinction becomes important if there is an
impediment to aortic flow or if the compliance of the aortic/arterial system is altered by
disease processes.
PRESSURE-VOLUME LOOPS
An understanding of the mechanics of normal and abnormal ventricular contraction is

facilitated by graphic depiction of ventricular volume and pressure during the cardiac
cycle. This depiction, called a pressure-volume loop , is shown for a normal heart in
Figure 3-9A . The diastolic component of this pressure-volume loop is determined by
the diastolic pressure-volume relationship discussed earlier. The shape of the
pressure-volume loop during systole is determined by the contractility of the heart and
the afterload against which the ventricle is ejecting. As systole begins, pressure in the
heart builds up during the period of isovolumic contraction. When the pressure in the
ventricle exceeds the pressure in the aortic valve, the period of ejection occurs. As
pressure in the ventricle falls at the end of systole, closure of the aortic valve terminates
the period of ejection, and ventricular volume again remains constant during a period of
isovolumic relaxation. When the pressure within the ventricle falls below the pressure in
the atrium, the mitral valve opens and the ventricle fills (period of filling). [33 ]
As the end-diastolic pressure-volume relationship has been used to describe the filling
or compliance properties of the ventricle, the end-systolic pressure-volume relationship
can be used to describe the contraction property of the ventricle termed contractility .
Contractility refers to the strength of the ventricular contraction. Unfortunately,
contractility is influenced by so many different factors that quantification has been very
difficult. One might compare the attempt to quantify the contractility of the heart to an
attempt to quantify the vitality of a society. One can often easily say that contractility or
vitality has improved or has diminished, but quantification in reproducible terms is elu
sive. Various indices of contractility will be discussed later. One such index is the slope
of the end-systolic pressure-volume relationship shown as a solid line in Figure 3-9 .
Pressure-volume loops can be used to analyze various physiologic and

pathophysiologic situations. Figure 3-9B demonstrates the effect of an increase in
afterload. This moves the pressure-volume loop slightly upward and to the right. Stroke
volume can be maintained with a minimal rise in end-diastolic pressure with no
requirement for a change in contractility. Note, however, that because the
pressure-volume loop is shifted to the right, the ejection fraction is slightly decreased if
stroke volume remains constant. Figure 3-9C shows the effect of a decrease in
ventricular compliance. If systolic function is maintained, stroke volume can be
maintained without ventricular distension but at the price of an increased end-diastolic
pressure. Note that ejection fraction in this circumstance has not changed, indicating
that ejection fraction generally reflects contractility or systolic function rather than
diastolic function. Figure 3-9D demonstrates the effect of adrenergic stimulation
(presuming stroke volume is held constant). A positive inotropic effect combines with
the positive lusitropic effect of adrenergic stimulation to lead to a decrease in
end-diastolic pressure, a shift of the pressure-volume loop to the left, and an increase in
the ejection fraction. Figure 3-9E represents the hypertrophied heart with decreased
diastolic compliance and increased systolic contractility. In this instance, a constant
stroke volume leads to an increase in end-diastolic filling pressure with a shift of the
pressure-volume loop to the left and a consequent decrease in ejection fraction. Note
that the ability of the hypertrophied heart to increase stroke volume is severely limited
because of decreased diastolic compliance. Figure 3-9F represents an ischemic heart
with decreased diastolic compliance and decreased contractility. This leads to an acute
shift in the pressure-volume loop to the right if stroke volume is to be maintained and a
consequent acute decrease in ejection fraction and increase in filling pressure.
CLINICAL INDICES OF CONTRACTILITY
For decades clinicians have attempted to assess contractility with an index that was
independent of heart rate, preload, and afterload. Contractility, however, is clearly not
independent of heart rate, afterload, or preload, and this attempt is futile. A number of
indices have been described, however, that allow the clinician to determine, in general,
whether contractility has increased or decreased in clinical situations. One measure of
contractility is represented by the family of Starling curves depicted in Figure 3-8 . If one
can determine, for example, that at a constant heart rate, aortic pressure, and cardiac
output the left ventricular preload is higher at time B than it is at time A , then one might
conclude that contractility is diminished at time B relative to time A . However, this
conclusion makes the somewhat tenuous assumption that the diastolic pressure-volume
relationship of the heart has not changed between time A and time B .
Ejection fraction is a second clinical index of contractility that is used commonly. Again,
ejection fraction gives one a general idea of contractility, but as can be seen by
examination of the pressure-volume loops in Figure 3-9 , ejection fraction is easily
changed by preload and afterload alterations without requiring any change in
contractility.
The end-systolic pressure-volume relationship can be defined clinically by inscribing a

family of pressure-volume loops obtainable by temporary occlusion of the inferior vena
cava while simultaneously measuring ventricular volume and instantaneous pressures.
The end-systolic pressure-volume points from these loops inscribe a line that is
generally linear. The slope of this line (called E max ) is an index that is relatively (but not
completely) independent of instantaneous preload and afterload. [34 ]
A final index of contractility that is perhaps best in terms of independence from other
parameters is the preload recruitable stroke work relationship. If one plots end-diastolic
volume on the abscissa and stroke work on the ordinate from a family of
pressure-volume loops (obtained again by inferior vena cava occlusion), one obtains a
quite linear relationship, the slope of which appears to be related to contractility in a
manner that is independent (within physiologic ranges) of preload and afterload. Stroke
work in this situation can be determined by integration of the area of the
pressure-volume loops. [35 ]
MYOCARDIAL WALL TENSION
As changes in left ventricular geometry are considered, one must remember that the left
ventricle is a pressurized, irregularly shaped chamber. The circumferential stress or
tension in the wall of this chamber is determined by the pressure within the chamber
and the geometry of the ventricle. A rough approximation, which is useful for considering
the effects of ventricular dilatation on wall tension, is an approximation that considers
the ventricle to be a cylinder. In this circumstance, the wall tension is proportional to the
pressure times the radius of the cylinder, a relationship known as the law of LaPlace .
Because the cylinder is thick-walled, increasing wall thickness leads to decreased
tension because a greater number of muscle fibers reduces the tension on each fiber.
Tension, therefore, is proportional to pressure times radius divided by wall thickness.
This concept has several important implications.
If systolic pressure within the ventricle is chronically increased (as it is in aortic

stenosis), then compensatory hypertrophy or thickening of the ventricular wall can bring
systolic wall tension back close to normal. The price that is paid for this return of systolic
wall tension to normal is that end-diastolic pressures must be higher (with increased
wall thickness and constant chamber radius) in order to achieve the same diastolic wall
tension (and thereby end-diastolic sarcomere length). This is the geometric explanation
for the shift in the diastolic pressure-volume curve observed in Figure 3-9E in the
hypertrophied heart.
In the heart that has failure of systolic function, compensation can occur with progressive
ventricular dilatation. This allows wall tension (and diastolic sarcomere stretching) to be
elevated at nearly normal end-diastolic pressures (because of the increased diastolic
diameter of the heart). Once again, there is a price to be paid. As the heart contracts, it
dilates throughout the cardiac cycle (at end-systole as well as at end-diastole) (see Fig.
3-9G ). This dilatation means that wall tension at end-systole is also increased,
requiring excessive energy utilization from this dilated, failing heart, as will be discussed
in the following section.
Energetics
CHEMICAL FUELS
The major fuels that serve as an energy supply for the myocardium are carbohydrates
(glucose and lactate) and nonesterified free fatty acids. Under ordinary conditions, when
oxygen is present, these fuels are all broken down to acetyl coenzyme A, which enters
the tricarboxylic acid cycle (Krebs cycle) in the mitochondria to form ATP. The heart is
quite flexible in the aerobic state in its use of fuels. In the fasting state when free fatty
acid levels are high, lipids may account for 70 percent of the fuel utilized by the heart.
On the other hand, after a high-carbohydrate meal or glucose feeding, blood glucose
and insulin levels are high and free fatty acids are low. Glucose will then become the
major fuel of the heart, accounting for close to 100 percent of metabolism. During acute
exercise, lactate levels rise. These elevated lactate levels inhibit the uptake of free fatty
acids. Carbohydrates (mostly lactate) then can account for up to 70 percent of the
cardiac fuel use. [36 ]
In hypoxic or relatively anaerobic conditions, glycolysis is stimulated (with concomitant

increased uptake of glucose from the blood and breakdown of glycogen in the myocyte
to glucose). This anaerobic glycolosis can produce 2 moles of ATP from every mole of
glucose metabolized. By-products of this system of ATP production are lactate or
hydrogen ions, which, combined with decreased cytosolic ATP levels, lead to a rapid
diminution in contractility and a decreased rate of relaxation of the affected sarcomeres.
There is a dramatic difference in the quantity of ATP produced by oxidative metabolism
of 1 mole glucose compared with anaerobic glycolosis of glucose (36 moles versus 2
moles of ATP).
Most of the ATP utilized by the heart (60 to 70 percent) is expended in the cyclic
contraction of the muscle. An additional 10 to 15 percent of the ATP is required for
maintaining the concentration gradients across the cell membrane (primarily through the
sodium-potassium pump). A small portion is wasted in so-called futile cycles such as
the constant uptake and release of calcium by mitochondria, the breakdown and
regeneration of glycogen, and the synthesis of triglycerides. In all these situations a
great portion of the actual energy liberated by ATP hydrolysis is converted into heat.
Only about 20 to 25 percent of the chemical energy of ATP is actually converted into
mechanical work.
ATP is compartmentalized in the cell in the mitochondrial and cytosolic compartments.

ATP molecules generated within the mitochondria cannot cross the mitochondrial
membrane into the cytosol. A mitochondrial creatine kinase isoenzyme is situated
within the mitochondrial membrane such that ATP inside the mitochondria can lead to
generation of creatine phosphate that freely traverses the outer mitochondrial
membrane into the cytosol. In the cytosol, creatine phosphate reacts with ADP to form
ATP (this reaction favors the formation of ATP by a factor of some 50:1). This rapid
formation of ATP from creatine phosphate explains the observation that when the cell
becomes acutely hypoxic, creatine phosphate levels fall rapidly to near 0 while ATP
levels fall much more slowly. A specific cardiac isoenzyme of creatine kinase is
released into the circulating blood with myocyte necrosis and is a marker for myocardial
cell death. [2 ]
With ischemia, ATP breaks down to ADP and subsequently to AMP, adenosine, and
inosine. Adenosine is particularly important because diffusion to local coronary vessels
can lead to coronary vasodilatation, which may increase local coronary flow and reverse
the hypoxic state. Adenosine, inosine, and hypoxanthine are lost from the ischemic
myocardium. If an aerobic state is restored, ATP levels can be partially restored by
salvage pathways leading to regeneration of adenosine nucleotides from inosine,
hypoxanthine, or inosine monophosphate. These salvage pathways operate fairly
quickly. The de novo synthesis of ATP also operates in the postischemic recovery
period, but this de novo synthesis takes hours or even days. Considerable controversy
has existed concerning the ATP levels that are found in irreversibly damaged cells.
Because very low ATP values have been found in cells that subsequently recovered, it is
now thought that very low ATP levels are not necessarily a cause of cellular necrosis, but
cells dying of ischemia always contain very low levels of ATP.
DETERMINANTS OF OXYGEN CONSUMPTION
As discussed above, the bulk of the energy utilized by the contracting heart is expended
in the contractile cycle. The remainder of the energy is expended in cellular
homeostasis. Changes in the rate of oxygen consumption of the heart are directly
related to changes in the contraction cycle. Energy utilization by the heart can be
increased by an increase in the work demand placed on the heart (i.e., the energy that
the heart must impart to the blood as it passes through the left ventricle) or by a
decrease in the efficiency with which the heart converts chemical energy to mechanical
energy. Since the minute work of the heart is the heart rate times the stroke volume
times developed pressure, the energy imparted by the heart to the blood is linearly
related to each of these three factors. A rise in heart rate, a rise in stroke volume, and a
rise in aortic pressure all lead to a rise in oxygen consumption. There is a great
difference, however, in the change in cardiac efficiency as heart rate, stroke volume, or
aortic pressure is altered.
The primary energy sink in the heart in the contraction process is the development of
tension with each cardiac cycle. This tension is forced to alter series elastic elements
and parallel elastic elements and to rearrange the geometry of the ventricle with each
cardiac cycle before ejection even occurs. Indeed, during the period of isovolumic
contraction, energy is expended by the heart without the delivery of any potential energy
to the blood. [37 ]
If one were to attempt to achieve a similar increase in the potential energy delivered to
the blood by increasing heart rate, stroke volume, or blood pressure, one would find that
this increase in energy could be achieved with the greatest efficiency (and lowest
energy cost to the heart) by an increase in stroke volume. This is so because the
wasteful development of tension in the heart is not greatly increased when this method
of increasing work output is utilized. This is particularly true because end-systolic
volume remains small so that end-systolic wall tension (by the law of LaPlace,
described above) generally does not change. If the minute work of the heart is
increased by increasing aortic pressure, then the wall tension of the heart during systole
is increased not only because the pressure has increased but also because the radius
of the heart at end-systole and throughout systole has increased (see Fig. 3-9B ). An
equally inefficient way to increase the minute work of the heart is by increasing heart
rate, because then the wasteful development of tension must be repeated more times
per minute.
Because heart rate and aortic pressure figure so much more prominently in the
determination of myocardial oxygen consumption than the stroke volume, two clinical
indices based on heart rate and aortic pressure have been developed for estimation of
myocardial oxygen consumption. These are the double product (the heart rate times the
blood pressure) and the tension-time index (the average ejection pressure of the left
ventricle multiplied by the duration of ejection). Both these indices correlate well with
cardiac oxygen consumption, but neither takes into account the effect of ventricular
dilatation or altered contractility. It is obviously from this discussion that the efficiency of
the heart can be improved phamacologically by a reduction in heart rate and a
decrease in mean systemic arterial pressure (vasodilation).
Dilatation of the heart during heart failure is an energetic disaster. Because of the law of
LaPlace, for any developed pressure, the wall tension is much greater in a dilated heart
than in a small heart. Because the inefficiencies of cardiac contraction are associated
with the development of tension in the myocardium, these inefficiencies are greatly
exaggerated in the dilated heart. In physiologic exercise, contractility increases (by
beta-adrenergic stimulation, by the contractility increase caused by an increase in heart
rate, and by the contractility increase caused by mild stretching of the sarcomere). This
contractility increase often actually decreases the end-systolic volume of the heart (see
Fig. 3-9D ) such that a greatly increased cardiac work can be performed with a
relatively small increase in myocardial oxygen consumption. In the failing heart, an
increase in work output generally cannot be achieved by increased contractility and can
be accomplished only by an increase in end-systolic volume and an increase in heart
rate. This leads to an exaggerated increase in oxygen utilization by the dilated heart.
CORONARY BLOOD FLOW
Normal Coronary Blood Flow
Resting coronary blood flow is slightly less than 1 mL/g of heart muscle per minute. This
blood flow is delivered to the heart through large epicardial conductance vessels and
then into the myocardium by penetrating arteries leading to a plexus of capillaries. The
bulk of the resistance to coronary flow is in the penetrating arteries (20 to 120 µm in
size), which are called the resistance arteries . Because the heart is metabolically very
active, there is a high density of capillaries such that there is approximately one
capillary for every myocyte, with an intercapillary distance at rest of approximately 17
µm. When there is an increased myocardial oxygen demand (e.g., with exercise),
myocardial blood flow can increase to three or four times normal. This is accomplished
by vasodilation of the resistance vessels and by recruitment of additional capillaries
(many of which are closed in the resting state). This recruitment is also important in
decreasing the intercapillary distance and thereby decreasing the distance that oxygen
and nutrients must diffuse through the myocardium.
In addition to the resistance of the small arteries and arterioles, compressive force in
the left ventricle impedes nutrient coronary blood flow during systole. With contraction of
the left ventricle, the compressive forces in the inner wall of the left ventricle may equal
or exceed intracavitary pressures, effectively preventing nutrient coronary flow during
systole in most of the left ventricular wall, particularly the subendocardium. Nutrient
coronary flow occurs primarily in diastole when the heart is relaxed and these
compressive forces are not present. Because of the gradient of these compressive
forces from epicardium to endocardium, the capillary density in the left ventricle is
greatest in the subendocardium to counterbalance the described gradient in
compressive forces. High-fidelity measurements of coronary flow in the left ventricle
have revealed a phasic flow, with minimal flow during systole and rapid flow during
diastole. [38 ]
Nutrient coronary flow is ordinarily closely matched to the metabolic needs of the heart,
since approximately 70 percent of the oxygen available in coronary arterial blood is
extracted. This delicate balance requires a precise system for regulation of local
coronary blood flow.
Control of Coronary Blood Flow
Local coronary blood flow is controlled by a balance of vasodilatory and vasoconstrictor

mechanisms. The three components of this delicate system are (1) the metabolic
vasodilatory system, (2) the neurogenic control system, and (3) the vascular
endothelium. [39 ]
The metabolic vasodilatory system causes local vasodilation of resistance vessels

whenever local nutrient blood flow is insufficient to meet metabolic demand. The primary
mediator of this effect appears to be adenosine, which is generated within the myocyte,
is freely diffusible across the cell membrane, and acts directly on the smooth muscle
cells in the arterioles to cause relaxation.
The sympathetic nervous system acts through alpha receptors (which cause
vasoconstriction) and beta receptors (which cause vasodilation). There appears to be
direct innervation of the large conductance vessels and lesser direct innervation of the
smaller resistance vessels (although sympathetic receptors on the smooth muscle cells
of the resistance vessels certainly can respond to humoral catecholamines). Alpha
receptors predominate over beta receptors such that when norephinephrine is released
from the sympathetic nerve endings, vasoconstriction ordinarily occurs. A second
substance, neuropeptide-y , appears to be stored with and released with
norepinephrine and may have a role in coronary vasoconstriction.
The endothelium plays a very important role in the regulation of local coronary blood
flow. This is accomplished by a balance between endothelial-derived relaxing factor
(EDRF, identified as nitric oxide, which is synthesized from L -arginine in the
endothelium) and endothelial-derived constricting factor (endothelin, a recently isolated
peptide). Nitric oxide generation from the endothelium is stimulated by a number of
factors, including adenosine, acetylcholine, and sheer stress from increased
intraluminal blood flow. This nitric oxide leads to powerful vasodilation of the resistance
vessels. Release of acetylcholine by the parasympathetic nervous system appears to
act by way of the endothelial-derived relaxing factor system. If the endothelium is intact,
acetylcholine causes vasodilation through generation of nitric oxide. If the endothelium
is not functionally intact, acetylcholine causes vasoconstriction by direct stimulation of
the vascular smooth muscle to contract.
Under ordinary circumstances, the metabolic vasodilatory system is by far the most
powerful force acting on the resistance vessels. During sympathetic stimulation, for
example, the increased metabolic activity caused by sympathetic stimulation leads to
vasodilation of the coronary arterioles through the metabolic system despite a direct
vasoconstrictor effect of norepinephrine release. [40 ] [42 ]
Coronary Artery Stenosis
Atherosclerotic coronary artery disease is the most common cause of death in the
United States, accounting for approximately 33 percent of all mortality. Atherosclerotic
disease primarily affects the large conductance vessels of the heart. The hemodynamic
effect that a coronary stenosis has on blood flow may be considered in terms of
Poiseuille's law , which describes the resistance to laminar flow of a viscous fluid
through a cylindrical tube. Resistance is inversely proportional to the fourth power of
the radius and directly proportional to the length of the narrowing . Generally,
conductance vessels are sufficiently large that a 50 percent reduction in the diameter of
the vessel has minimal hemodynamic effect. A 60 percent reduction in the diameter of
the vessel offers only a small resistance. As the stenosis progresses beyond 60
percent, however, the effects are dramatic. By Poiseuille's law, a 1-cm-long 80 percent
stenosis has a resistance that is 16 times as high as the resistance of a 1-cm-long 60
percent stenosis. Similarly, if this progresses to a 90 percent stenosis, the resistance is
256 times as great as the resistance of a 60 percent stenosis. [43 ]
These considerations are especially important when one understands that

atherosclerosis may leave partially intact the ability of the conductance vessel to
constrict (indeed, the endothelium is often destroyed or damaged and the
vasoconstricting mechanisms are often relatively unopposed by the EDRF mechanism).
Suppose an epicardial vessel has an atherosclerotic lesion leading to an 80 percent
reduction in the lumen diameter of that vessel. If the individual should attempt to
exercise or should become excited, sympathetic stimulation could lead to
vasoconstriction of that epicardial vessel such that the residual lumen is further
narrowed to a 90 percent obstruction. This would lead to a 16-fold increase in
resistance. [44 ]
Another important concept is the idea of coronary blood flow reserve. Coronary reserve
may be defined as the capacity of the myocardium to increase nutrient flow in response
to demand. Ordinarily, coronary reserve is such that flow may be increased to three to
four times resting levels. As proximal atherosclerotic disease progresses, coronary
reserve remains essentially normal until the proximal stenosis exceeds 60 percent.
Between 60 and 90 percent stenosis, coronary reserve progressively decreases as the
capacity of the resistance vessels to dilate (reduce distal resistance) is used up as the
proximal resistance increases (in series with and therefore additive with the distal
resistance). As the proximal narrowing approaches 90 percent, the ability of the
resistance vessels to dilate is essentially fully utilized, further dilatation is not possible,
and coronary reserve becomes zero. In this condition, a stimulus that increases
myocardial oxygen demand (such a tachycardia or hypertension) cannot be met with an
increase in nutrient blood flow, and myocardial ischemia results. [39 ]
In the human, coronary arterial vessels are end vessels with little collateral flow between
major branches except in pathologic situations. With sudden coronary occlusion in the
human heart there usually is very modest collateral flow through very small vessels (20 to
200 µgmm in size). Unfortunately, this flow is generally not sufficient to maintain cellular
viability in the collateralized region. Collateral flow gradually begins to increase over the
next 8 to 24 hours, doubling by about the third day after total occlusion. Collateral flow
development appears to be nearly complete after 1 month, restoring normal or nearly
normal resting flow to the surviving myocardium in the ischemic region. Previous
ischemic events or gradually developing stenoses can lead to larger preexisting
collaterals in the human heart. The presence of these preexisting collaterals has been
shown to be important in the prevention of ischemic damage if coronary occlusion
should occur. [45 ]
The development of collateralized regions in the human heart leads to some unusual
pathophysiologic possibilities. Presuming that the collateralized region is distal to a
totally occluded conductance vessel, flow into the collateralized region depends on a
second, nearby conductance vessel. If this second conductance vessel develops a
flow-limiting stenosis and there is a sudden sustained increase in myocardial oxygen
demand, then the resistance vessels related to that second conductance vessel will
dilate, causing an increased pressure gradient across the secondary proximal stenosis,
decreased pressure in the collateral vessels, and consequent ischemia of the
collateralized region. This can cause angina pectoris or even infarction at a distance
(narrowing of the stenotic left anterior descending artery by this mechanism could cause
infarction of a collateralized region on the inferior surface of the heart).
The subendocardium of the heart is particularly susceptible to reduced pressure in the

distal coronary artery (caused by proximal stenosis or occlusion). This is related to the
compressive effects of ventricular contraction on subendocardial vasculature and to the
fact that endocardial wall tension is higher than epicardial wall tension, leading therefore
to increased local oxygen utilization in subendocardial muscle. In addition, if the heart
begins to fail acutely and end-diastolic pressure is elevated to 25, 30, or 35 mmHg,
then there is diastolic as well as systolic compression of endocardial vasculature.
Studies have shown that flow to the subepicardium of the heart is effectively
autoregulated as long as the pressure in the distal coronary artery is above
approximately 40 mmHg. Flow to the subendocardium, however, is effectively
autoregulated only down to a mean distal coronary artery pressure of approximately 60
to 70 mmHg. Below this level, local coronary reserve in the subendocardium is
exhausted, and local blood flow decreases linearly with decreases in distal coronary
artery pressure. These effects generally lead to more extensive subendocardial
ischemia and infarction than subepicardial ischemia in the face of severe coronary
stenosis or coronary occlusion. Subendocardial perfusion problems are obviously
increased by situations such as chronic hypertension and aortic stenosis that lead to an
increased wall thickness and increased systolic and diastolic wall tension. Aortic
regurgitation particularly threatens the subendocardium because diastolic systemic
arterial pressures are reduced at the same time that intraventricular systolic and
diastolic pressures are elevated. [38 ] , [46 ]
Endothelial Dysfunction
The endothelium of the coronary vascular system is becoming increasingly recognized

as an important participant in normal and pathophysiologic states of coronary blood
flow. As was described earlier, the endothelium causes local dilation of coronary
vasculature by elaboration of nitric oxide (endothelial-derived relaxing factor, EDRF)
that generally overwhelms the action of endothelin (endothelial-derived constricting
factor). In some pathologic states the ability of the endothelium to generate nitric oxide
is impaired, and vasoconstriction may predominate. Temporary myocardial ischemia is
one situation in which EDRF production may be impaired, leading to a vicious cycle in
which the vasodilatory reserve of the resistance vessels is reduced with consequent
progressive ischemia. The EDRF system also seems to be impaired in some coronary
surgical situations, particularly when crystalloid cardioplegia is utilized for myocardial
protection. This withdrawal of endothelial-stimulated vasodilation could lead to
postoperative infarction of a poorly revascularized area even if that same area had not
been ischemic preoperatively. [47 ] [49 ]
Besides its vasodilatory effects, the endothelium is important in preventing platelet

activation and aggregation and leukocyte adhesion and migration. In the normal
situation, the negatively charged surface of the endothelium tends to repel leukocytes
and platelets. If damage occurs, the damaged endothelium (or in some cases the
denuded collagen layers or atherosclerotic layers of the coronary artery) leads to
leukocyte adhesion, activation, and migration and platelet adhesion and activation.
Damaged endothelium elaborates adhesion molecules that tend to facilitate such
adhesion and activation. The bulk of transmural myocardial infarction appears to be
related to coronary artery occlusion, which is usually a thrombic effect. The absence of
normal endothelial function in atherosclerotic regions of coronary arteries appears to be
an important mediator of this thrombosis. [48 ]
The Sequelae of Myocardial Hypoperfusion: Infarction, Myocardial Stunning,

Myocardial Hibernation
If local coronary blood flow is acutely reduced to less than 20 percent of resting levels, a
portion of the myocardium in the affected region will die. Cardiac muscle requires
approximately 1.3 mL of oxygen per 100 g of muscle per minute for cellular survival (in
comparison with approximately 8 mL of oxygen per 100 g per minute normally delivered
to the contracting left ventricle). As oxygen delivery is reduced, contraction decreases
dramatically (within 8 to 10 heartbeats). If the reduction in regional myocardial blood
flow is moderate and persistent, regional contraction is prominently diminished, but the
metabolic processes of the heart remain intact. This condition can lead to a chronic
hypocontractile state known as hibernation . Hibernation appears to be associated with
a decrease in the magnitude of the pulse of calcium involved in the
excitation-contraction process such that inadequate calcium levels are developed within
the cytosol during each heartbeat for effective contraction to occur. With reperfusion,
hibernating myocardium can very quickly resume normal and effective contraction. [50 ]
[52 ]
If the extent of reduction in coronary blood flow is more severe, mild to moderate
abnormalities in cellular homeostasis occur. There is reduction in cellular levels of ATP
leading to a loss of adenine nucleotides from the cell. If this reduction in coronary flow is
sustained, progressive loss of adenine nucleotides and elevation of intracellular and
intramitochondrial calcium lead to cellular death and subsequent necrosis. If the
myocyte is reperfused prior to irreversible damage to subcellular organelles, the
myocyte may slowly recover. A period of days is necessary for full recovery of myocyte
ATP levels because adenine nucleotides must be resynthesized. During this time,
contractile processes are impaired. This impairment seems to be related to damage to
the contractile proteins such that their responsiveness to cytosolic levels of calcium is
diminished. The magnitude of the cytosolic pulse of calcium with each heartbeat
appears to be nearly normal, but the magnitude of the consequent contraction is greatly
reduced. Over a period of 1 to 2 weeks, the contractile proteins gradually recover. This
gradually recovering myocardium is called stunned myocardium . [51 ] , [53 ]
Reperfusion of myocardium that has been damaged by ischemia may lead to

progression of cellular damage and necrosis rather than immediate recovery of all
those cells which are not irretrievably damaged. This reperfusion injury is multifactorial.
Damaged endothelium in the reperfused region can cause adhesion and activation of
leukocytes and platelets as described above. Oxygen free radicals can be released,
causing further damage to subcellular organelles. Membrane leakage often leads to
elevation of intracellular calcium levels with uptake of calcium into the mitochondria and
subsequent formation of insoluble calcium phosphate crystals. Temporary derangement
of the ATP-dependent sodium-potassium pump can lead to loss of cell volume
regulation with consequent leakage of water into the cell, explosive cell swelling, and
rupture of the cell membrane. Techniques have been developed for modification of
reperfusion injury to the end that the adverse sequelae of reperfusion can be minimized
and that the maximum number of myocytes may be salvaged. As might be suspected
from the preceding discussion, these techniques have included leukocyte depletion,
free-radical scavenging, reperfusion with solutions low in calcium content, and
reperfusion with hyperosmolar solutions. [54 ] , [55 ]
The metabolic changes that occur with ischemia represent a complex system of
adaptive mechanisms that allow the myocyte to survive despite a temporary reduction in
oxygen delivery. These adaptive mechanisms may be triggered by a very brief coronary
occlusion (as short as 5 minutes) such that the negative sequelae of a subsequent
prolonged coronary occlusion are greatly minimized. This phenomenon has been called
ischemic preconditioning. A coronary occlusion that might cause as much as 40
percent myocyte death in a region subjected to prolonged ischemia might cause only
10 percent myocyte death if the prolonged period of ischemia is preceded by a
5-minute interval of coronary occlusion. The mechanisms of this intrinsic protective
system are currently a topic of intense investigation. [54 ] , [56 ] , [57 ]
HEART FAILURE
Systolic and Diastolic Heart Failure
The term heart failure means that the capacity of the heart to pump is impaired such
that the heart is unable, with acceptable filling (venous) pressures, to deliver to the body
adequate blood to meet the needs of other body organs (at rest or during mild to
moderate exercise). Heart failure may be primarily systolic failure , such that an
impairment of contraction leads to low cardiac output and an excessive filling pressure
(see Fig. 3-9 ). The early stages of a large acute myocardial infarction represent an
example of systolic heart failure. Diastolic pressure-volume curves are not greatly
changed, but the systolic ability of the heart to pump blood may be inadequate to meet
even resting needs (particularly if there is systolic bulging of a large infarction). [58 ] , [59
]
Diastolic failure may occur without an impairment of systolic contractility if the heart
becomes stiff and an excessive shift in the diastolic pressure-volume curve occurs (see
Fig. 3-9 ). The most common cause of this situation is chronic hypertension with
consequent left ventricular hypertrophy and diastolic stiffness (related both to myocyte
hypertrophy and to increased fibrosis of the ventricle). [60 ] , [61 ]
The most common form of heart failure is mixed systolic and diastolic failure . This is
the case in chronic cardiac decompensation, in which systolic function has been
impaired (often by multiple myocardial infarctions) and diastolic stiffness has increased
because of proliferation of interstitial cells and collagen leading to a fibrotic heart (see
Fig. 3-9G ).
Early Systemic and Cardiac Sequelae of Heart Failure
When cardiac function acutely deteriorates, cardiac output is diminished and

neurohumoral reflexes attempt to restore both cardiac output and blood pressure. The
sympathetic nervous system increases adrenergic stimulation of both the heart and the
peripheral vasculature leading to systemic vasoconstriction and increased cardiac
contractility. The renin-angiotensin system responds to decreased cardiac output with
increased production of angiotensin II. This causes vasoconstriction and helps in renal
retention of salt and water, leading to rapid volume expansion. Aldosterone output is
increased, again helping conserve sodium. These early sequelae of heart failure lead to
an expansion of blood volume, shifting the pressure-volume loop as in Fig. 3-9F and
leading to a restoration of cardiac output and blood pressure despite diminished
contractility.
Acute alterations in cardiac geometry may occur early after a large myocardial
infarction with thinning of the left ventricular wall in the region of the infarct as well as
expansion of overall left ventricular cavity size. This is particularly true if the infarct is
apical because of geometric considerations related to the thinness of the left ventricular
wall in the region of the apex (related to the short radius of curvature of the left
ventricular apex). As volume expansion occurs, production of a cardiac peptide, atrial
naturetic peptide, is increased, which tends to prevent excessive sodium retention and
inhibit activation of the renin-angiotensin and aldosterone systems. [62 ] [67 ]
The Late Sequelae of Congestive Heart Failure: The Vicious Cycle of Left
Ventricular Remodeling and Dilatation
As heart failure progresses, the kidney tends to continue to retain sodium and become
hyporesponsive to atrial naturetic peptide. The response of the heart to sympathetic
stimulation is diminished with desensitization of beta-adrenergic receptors as a
consequence of sustained stimulation. Concentrations of norepinephrine in sympathetic
nerve endings are depleted. Circulating catecholamine levels are elevated, but these
increased circulating levels are of little benefit because of desensitization of receptors.
[23 ] , [64 ]
The heart appears to respond to systolic hypofunction by progressive dilatation. This

leads to preservation of stroke volume at the expense of ejection fraction (see Fig. 3-9G
). This progressive dilatation is accompanied, at least in the early phases, by
hypertrophy of the myocytes as well as by lengthening of the myocytes as sarcomeres
are added. In addition, there is significant slippage of myofibrils leading to dilatation
without an increase in the number of myocytes. Angiotensin and aldosterone both
appear to stimulate collagen formulation and proliferation of fibroblasts in the heart,
leading to an increase in the ratio of interstitial tissue to myocardial tissue in the
noninfarcted regions of the heart. The progressive dilatation of the heart leads to an
increase in the wall tension necessary to generate systolic intracavitary pressures (by
the law of LaPlace). The progressive fibrosis of the heart caused by left ventricular
remodeling leads to increased diastolic stiffness and an inability to increase contractility
in response to increased filling pressure. Fibrosis and increased ventricular size
predispose to reentry ventricular arrhythmias, which are a common cause of death in
the late stages of heart failure. These rapidly deteriorating clinical cycles explain the
observation that once the diagnosis of heart failure was made in one clinical study, the
5-year survival rate was only 25 percent in men and 38 percent in women. [66 ] , [68 ]
[72 ]
Therapeutic intervention in the vicious cycles of left ventricular remodeling, dilatation,

and progressive heart failure has achieved some success. Fig. 3-9 H depicts the
improvement that afterload reduction can achieve in the remodeled, dilated heart as left
ventricular end-diastolic pressure is reduced and both systolic and diastolic ventricular
volumes are reduced. This leads to a prominent reduction in wall tension throughout the
cardiac cycle and thereby a dramatic reduction in myocardial energy demands.
Angiotensin-converting enzyme inhibitors have shown particular clinical benefit in terms
of survival and in terms of prevention of left ventricular dilatation and remodeling. These
drugs lead to afterload reduction and decrease angiotensin II levels, diminishing the
direct effect of angiotensin II in promoting fibrosis in the remodeling heart. Treatment of
chronic heart failure with beta blockade often leads to a temporary increase in
symptoms followed by a sustained and long-term improvement in cardiovascular
function. This appears to be related to a reversal, at least in part, of the desensitization
of adrenergic receptors. A third therapy that offers some prospect for benefit is
treatment with drugs that antagonize aldosterone, which may inhibit the tendency of
aldosterone to cause left ventricular dilatation, remodeling, and fibrosis. [31 ] , [67 ] , [73
] [75 ]
Progress in the treatment of chronic congestive heart failure is a dramatic example of

successful therapy based on an understanding of pathophysiology, which in turn is
made possible by increasingly accurate concepts of normal cardiac physiology.
Myocardial Hypertrophy
Cardiac hypertrophy is the compensatory response of the myocardium to increased

work (Fig. 40-1) . [1 ] Myocardial hyperfunction induces an increase in the overall mass
and size of the heart that reflects increased size of myocytes through addition of
contractile elements (sarcomeres) and mitochondria. Cardiac myocyte diameters,
normally approximately 15 µm, can increase to 25 µm or more in hypertrophy. Since
cardiac myocytes are terminally differentiated cells that cannot divide, augmentation of
myocyte number (hyperplasia) does not occur in the adult heart. Since the vasculature
does not proliferate commensurate with increased cardiac mass, hypertrophied
myocardium is usually relatively deficient in blood vessels. Moreover, myocardial fibrous
tissue may be increased.
Pressure overloaded ventricles (e.g., resulting from hypertension or aortic stenosis)

develop concentric hypertrophy with an increased ventricular mass and ratio of wall
thickness to cavity radius, without appreciable dilatation. In contrast, volume overloaded
ventricles (e.g., resulting from chronic aortic or mitral regurgitation) develop hypertrophy
with chamber dilatation in which both ventricular radius and wall mass are increased.
However, in volume hypertrophy, dilation masks the degree of hypertrophy, and wall
thickness frequently is near normal. Concentric hypertrophy is accomplished
predominantly by augmentation of cell width (parallel addition of sarcomeres); in
contrast, dilatation stimulates augmentation of both cell width and length (parallel and
series addition of sarcomeres). However, hypertrophy (with or without chamber
dilatation), decreases myocardial compliance, may hinder diastolic filling, and often is
associated with depressed myocardial contractility. Thus, the mechanical changes
described previously initially enhance function and are thereby adaptive but may
ultimately become deleterious. In situations where there is obvious death of myocytes
(e.g., myocardial infarction), the remaining, non-infarcted regions of myocardium not
only hypertrophy (called compensatory hypertrophy) but also may be overwhelmed by
mechanical disadvantage. In contrast, the chamber wall is affected globally by the
increased chamber pressure of hypertension, the increased pressure or volume work
load of valvular heart disease, and in dilated cardiomyopathy.
In hypertrophied hearts molecular changes that initially mediate enhanced function may
subsequently contribute to the development of heart failure. [1 ] [3 ] Hemodynamic
overload alters myocardial gene expression, leading to re-expression of a pattern of
protein synthesis that has features that occur during both mitosis of other types of cells
capable of normal proliferation and fetal cardiac development. Proteins comprising
contractile elements and those involved in excitation-contraction coupling and energy
utilization are altered quantitatively or through production of different isoforms; such
variant proteins may be less functional than the normal. Hypertrophied and/or failing
myocardium may have additional abnormalities that include reduced adrenergic drive,
decreased calcium availability, impaired mitochondrial function, and microcirculatory
spasm. Nevertheless, neither the mechanisms by which mechanical load induces
cardiac cellular hypertrophy nor those that mediate the progression from hypertrophy to
cardiac failure are understood in detail. [4 ]
In sum, cardiac hypertrophy comprises a tenuous balance between adaptive

characteristics (including new sarco-meres) and potentially deleterious structural,
functional, and biochemical/molecular alterations (including enlarged muscle mass with
enhanced metabolic requirements, synthesis of abnormal proteins, decreased
capillary/myocyte ratio, fibrosis, microvascular spasm, and impaired contractile
mechanisms). Thus, cardiac hypertrophy can evolve to cardiac failure. In addition, left
ventricular hypertrophy is an independent risk factor for cardiac mortality and morbidity,
especially for sudden death. [5 ]
Left ventricular hypertrophy induced by systemic hypertension is reversible in many

cases. [6 ] However, it is uncertain to what extent hypertrophy owing to other stimuli is
capable of resolution. Indeed, the hemodynamic adjustment that occurs following
cardiac valve surgery is not always accompanied by reversal of the myocardial changes
secondary to the valvular disorder, and progressive cardiac failure may ensue despite
valve replacement or repair (Fig. 4-2) . Even in well-compensated ventricles
postoperatively, regression of hypertrophy often is incomplete, and some degree of
hypertrophy may persist for decades. In addition, the increased cardiac muscle mass in
many patients requiring cardiac surgery, with its attendant global ischemia, renders
intraoperative myocardial preservation difficult to achieve and the heart thereby
particularly susceptible to ischemic damage.
Atherosclerosis
Atherosclerosis is a chronic, progressive, multifocal disease of the vessel wall intima

whose characteristic lesion is the atheroma or plaque. [7 ] The key processes, intimal
thickening (mediated predominantly by smooth muscle cell proliferation), and lipid
accumulation (mediated primarily by monocyte phagocytosis), primarily affect the large
elastic arteries and large and medium-sized muscular arteries of the systemic
circulation, particularly at points of branches, sharp curvatures, and bifurcations.
Importantly, and not entirely understood, coronary atherosclerosis generally is limited to
the epicardial vessels and does not involve their intramural branches. Moreover, venous
bypass grafts interposed within branches of the arterial system also can develop intimal
thickening and ultimately atherosclerotic obstructions, yet, for inexplicable reasons,
some arteries are consistently spared (such as the internal thoracic [mammary] artery).
Although isolated plaques in the aorta are virtually always eccentric in location (that is,
involving only a portion of the arterial circumference), atheromas in the coronary arteries
may be either concentric (2530 percent) or eccentric (7075 percent). The plaque-free
segment may comprise a substantial fraction of the vessel wall. With early lesions, the
arterial lumen remains circular in cross section and often is essentially the same size as
originally, despite plaque formation, in a process often called vascular remodeling. [8 ]
High-grade but slowly developing occlusions probably stimulate collateral vessels over
time that may protect against distal myocardial ischemia and infarction.
The contemporary understanding of the pathogenesis of atherosclerosis envisions an

initial interaction of the cells of the blood vessel wall (especially smooth muscle cells
and endothelial cells, circulating blood cells (platelets and monocytes) and plasma
lipoproteins (Fig. 4-3) . [7 ] [9 ] , [11 ] In the most recently modified response-to-injury
hypothesis, the initiating event is a subtle, non-denuding injury to endothelial cells (owing
to the effects of chronic hypercholesterolemia, homocystinemia, chemicals in cigarette
smoke, viruses, localized hemodynamic forces, systemic hypertension, hyperglycemia
or the local effects of cytokines). [10 ] The endothelial cell injury (termed endothelial
dysfunction) is characterized by altered metabolism (e.g., depressed production of
vasorelaxants such as nitric oxide [NO]), alteration or loss of the selective permeability
barrier with entry of plasma lipoproteins into the vessel wall, induction of a thrombogenic
surface on endothelial cells (largely by endothelial cell membrane expression of tissue
factor), and/or adherence of inflammatory cells or platelets, mediated by injury-induced
surface expression of molecules that increase endothelial cell-monocyte adhesion. [10 ]
[12 ]
A complex series of events ensues, including (1) adherence of blood monocytes to

endothelial cells and their emigration into the subendothelial space; (2) transformation
of blood monocytes into tissue macrophages; (3) smooth muscle cell migration from the
media into the intima; (4) smooth muscle cell proliferation within the intima; (5) secretion
of large amounts of collagen and other extracellular matrix components by intimal
smooth muscle cells; (6) lipid accumulation, both intracellularly (primarily in
macrophages, but also in smooth muscle cells [ultimately producing foam cells]) and
extracellularly; (7) oxidative modification of lipoproteins that generate potent biological
stimuli (neoantigens, chemoattractants, cytotoxins) within the vessel wall; (8) cell death
with release of intracellular lipids (mostly cholesterol esters), and often; (9) calcification;
and (10) a chronic inflammatory reaction (that includes lymphocyte/macrophage
infiltration, and neovascularization). [8 ] , [10 ]
In essence, atherosclerosis is an inflammatory-and-healing response of the arterial wall

to various stimuli, an initially protective and adaptive response that in excess becomes
a disease process. This paradigm acknowledges the multifactorial nature of
atherosclerosis, involving well-defined and multiple risk factors and mediators, with
pathogenetic similarities to and interactions of the cellular and molecular mechanisms
with those of thrombosis, chronic inflammation and wound healing, and with an
unpredictable natural history. [13 ]
Atherosclerotic plaques have three major components [7 ] , [9 ] [15 ] : (1) cells, including
vascular smooth muscle cells and blood-derived monocytes/macrophages; (2)
connective tissue fibers (e.g., collagen) and amorphous extracellular matrix, both
predominantly synthesized by smooth muscle cells; and (3) lipids imbibed from blood,
largely low density lipoprotein (LDL) cholesterol and its esters. In the early stages,
lesions remain covered by endothelial cells. Mature atheromatous plaque is composed
of a core (containing lipid and cholesterol crystals, macrophages, foam cells, necrotic
cell debris, and plasma proteins and degenerating blood elements), separated from the
lumen by a layer of fibrous tissue (fibrous cap). To a great extent, the integrity of the
fibrous cap determines plaque stability. [8 ] , [16 ] , [17 ] The composition of atheromas
can vary considerably, among individuals, among arteries in the same individual, or
among regions of one artery.
The clinical effects of advanced atherosclerotic plaques in most medium-sized arteries,

including the coronary arteries, are either owing to their encroachment of the lumen,
leading to progressive stenosis, or acute plaque disruption with thrombosis (Fig. 4-4) .
[7 ] , [12 ] [18 ] In contrast, in larger vessels such as the aorta, ulcerated atheromatous
plaques can (1) release atheroemboli from soft plaques; (2) become covered with mural
thrombus that may dislodge to yield peripheral thromboemboli; or (3) impinge on the
media with resultant tissue atrophy or destruction that may cause vascular dilation,
aneurysm formation, and potential rupture.
The natural history of atheromatous plaque and the efficacy and safety of interventional
therapies likely depend on relative plaque composition and the spatial distribution of the
constituents. [7 ] , [12 ] [20 ] The distinction between soft atheromas, consisting primarily
of necrotic debris and therefore potentially moldable, versus hard, fibrocalcific, rigid
plaques may be important clinically, because plaque mechanical properties can
determine the propensity to complications as well as influence the success rate of
interventions such as balloon angioplasty. [7 ] [12 ] [20 ] An individual plaque region can
be characterized as soft or hard by intravascular ultrasound, [21 ] and calcification,
portending hard plaque, can be detected noninvasively by electron beam computed
tomography. [22 ] However, despite group epidemiological correlations of outcome with
luminal stenosis and plaque calcium, neither predict plaque rupture or subsequent
thrombosis in an individual patient.
Cardiac ischemia is typified by an imbalance between the supply and demand of tissue
for blood. [1 ] , [23 ] It is caused most commonly either by decreased perfusion (e.g.,
vascular obstruction or narrowing caused by atherosclerosis, thrombosis, embolism, or
spasm), global hypotension (such as occurs in shock or during cardiopulmonary
bypass), or vascular compression; or by increased cardiac demand for blood (such as
occurs in exercise, tachycardia, hyperthyroidism, or ventricular hypertrophy/or
dilatation). Its consequences depend on severity and duration, and on the pre-existing
adaptive and nutritional/metabolic state of the affected cells and tissues. Ischemic injury
is potentiated by anemia, hypoxemia, or cardiac failure and protracted onset may
permit development of collaterals and metabolic adjustments. Moreover, as discussed
above, hypertrophy increases vulnerability to myocardial ischemic injury through the
combined effects of increased numbers of cells requiring perfusion, coupled with
relatively decreased vascularity.
PROGRESSION OF DAMAGE
Intracellular changes following the onset of myocardial ischemia are sequential,

complex, and difficult to recognize early (Table 4-1) . [24 ] , [25 ] Cardiac myocyte
ischemia induces anaerobic glycolysis within seconds, leading to both inadequate
production of high-energy phosphates (e.g., creatine phosphate and ATP) and the
accumulation of potentially noxious breakdown products (e.g., lactic acid), thereby
causing intracellular acidosis. Myocardial function is exquisitely sensitive to these
cellular biochemical consequences of severe ischemia and rapidly becomes deranged;
a striking contractility defect is evident within 60 seconds. Within a few minutes,
characteristic ultrastructural changes develop, including glycogen depletion, and cell
and mitochondrial swelling.
Nevertheless, these early changes are sublethal and cell death is not immediate.
Ischemic changes in an individual cell are potentially reversible if the duration of
ischemic injury is short and perfusion is restored prior to the onset of irreversible
lesions. [1 ] , [25 ] Irreversible (lethal) injury of cardiac myocytes (associated with
structural defects in the sarcolemmal membrane) is evident at least focally only after
2040 minutes of severe ischemia (when regional blood flow is 10 percent of normal or
less). When ischemic injury is of sufficient severity and duration, groups of involved cells
die, and myocardial infarction results.
Within the region made vulnerable by loss of perfusion (so-called area at risk), not all
cells are equally injured. [1 ] , [24 ] , [25 ] A gradient of ischemia exists across the
myocardium; the most affected regions are the subendocardium and papillary muscles.
Thus, following the abrupt occlusion of a coronary artery by thrombus, the most severely
ischemic myocytes (and the first to become necrotic) are in the center of the perfusion
defect, near the endocardium. However, the myocytes immediately beneath the
endocardium (to a depth of approximately 100 µm) usually are effectively perfused by
the well-oxygenated blood in the left ventricular chamber. As uninterrupted ischemia
progresses, there is a wave-front of cell death (called coagulation necrosis) outward
from the mid-subendocardial region toward and eventually encompassing the lateral
borders and less ischemic subepicardial and peripheral regions. [24 ] , [25 ] The final
transmural extent of an infarct is generally established within 612 hours. At autopsy, the
presence of a necrotic region may be indicated as a staining defect with triphenyl
tetrazolium chloride (TTC), a dye that turns myocardium a brick-red color on reaction
with intact myocardial dehydrogenases (indicating viability), as early as 23 hours
following onset of infarction. [26 ]
During cardiopulmonary bypass or organ procurement for transplantation, susceptibility

to ischemic injury is global. [23 ] [25 ] Existing hypertrophy and coronary obstructions
tend to enhance injury, whereas decreased tissue temperature and cardioplegic arrest
slow chemical reactions and thereby protect myocytes from progressive ischemic
damage. Moreover, when the heart's chambers are not filled with oxygenated blood
(such as in donor heart transport for transplantation), the immediately subendocardial
myocytes, normally perfused from the lumen and protected from acute ischemic injury,
are also vulnerable to ischemic injury. [27 ]
Myocardial ischemia also contributes to the induction of arrhythmias. [24 ] , [25 ] Sudden
death usually is caused by ventricular tachycardia/fibrillation caused by myocardial
irritability induced by ischemia or infarction. This conclusion derives from autopsy
studies of sudden death victims and clinical studies of resuscitated survivors that show
that only a minority develops acute myocardial infarction. [28 ] , [29 ] Thus, ischemia
caused by severe chronic coronary arterial stenosis, and in many cases, acute plaque
change with less than occlusive thrombus, and possibly emboli, presumably leads
directly to lethal arrhythmias.
The histologic changes of myocardial necrosis that occurred less than approximately 6
hours prior to death generally are not visible. [1 ] , [23 ] Inflammatory exudation, initially
with polymorphonuclear leukocytes, begins following approximately 612 hours and the
stereotyped sequence of tissue changes ensues. The inflammatory reaction that
eventuates in necrotic tissue removal by macrophages (in days) is followed by a
fibroblastic reparative response accompanied by neovascularization (granulation
tissue) beginning (1 week or more subsequent to tissue injury) at the margins of
preserved tissue. Overall, the repair sequence following an infarct is similar to that
which follows tissue injury of diverse causes and at various non-cardiac anatomic sites.
Since cardiac muscle cells are incapable of regeneration, the infarcted tissue ultimately
is replaced by scar; maturation usually is complete in approximately 6 weeks. Healing
of myocardial ischemic injury may be slowed by anti-inflammatory agents administered
following myocardial infarction or as a component of immunosuppressive therapy
following transplantation. [27 ] , [30 ] Resolution may also be slowed in otherwise
debilitated or malnourished patients. Sublethal but chronic ischemic injury may be
revealed by myocyte vacuolization, usually most prevalent in the subendocardium.
EFFECTS OF REPERFUSION
The progression of myocardial ischemic injury can be modified by restoration of blood

flow to jeopardized myocardium (reperfusion). [1 ] , [23 ] [25 ] Reperfusion salvages
reversibly injured myocytes; reperfusion occurring early before the onset of irreversibility
(less than 20 minutes in the most severely ischemic regions and less than a few hours
overall), may substantially limit infarct size or prevent cell death altogether. In contrast,
later reperfusion does not prevent infarction entirely, but myocytes that are only
reversibly injured at the time of reflow may be salvaged. The potential for recovery
decreases with increasing severity and duration of ischemia (Fig. 4-5) . Nevertheless,
late reperfusion, following the interval at which myocyte salvage continues to be
possible, may also lead to functional benefits, by mechanisms that are yet poorly
understood. [23 ] , [31 ] , [32 ]
The morphologic effects of reperfusion of ischemic myocardium are summarized in

Figure 4-6 . Hemorrhage may be seen grossly and microscopically (see Fig. 4-6A , Fig.
4-6B , and Fig. 4-6C ). Moreover, reperfusion has structural and biochemical effects on
cells that were already lethally injured at the time of reflow, including marked cell
swelling, massive cellular Ca 2+ entry from the plasma, and myocyte contraction bands
(representing coalescence of multiple hypercontracted sarcomeres, often with
calcification visible by light microscopy or transmission electron microscopy) (see Fig.
4-6B ). [1 ] , [23 ] , [25 ] , [33 ] Areas of necrosis with contraction bands (often called
contraction band necrosis) frequently are seen in hearts of patients with infarcts treated
early with thrombolytic therapy, and in those following cardiac surgery. In widespread
and severe cases of such damage, the left ventricular myocardium may undergo a
massive tetanic contraction to a small, hard mass that comprises the stone heart
syndrome. [34 ]
Restoration of systemic pressure to an artery supplying an intact and patent

microvasculature generally will restore adequate blood flow. However, since
microvascular damage accompanies severe, prolonged ischemia, achievement of
arterial pressure to an artery supplying a damaged capillary bed may have additional
effects that are deleterious: (1) hemorrhage, owing to vascular wall incompetence; or (2)
impaired local return of myocardial blood flow (no-reflow), owing to occlusion of
capillaries by extravascular compression, cardiac rigor, endothelial swelling, or platelet
or inflammatory cell aggregates. [25 ]
Moreover, there is evidence that the process of reperfusion may damage some of the
myocytes that were not already dead at the time at which reflow occurred, often called
reperfusion injury (a term that is frequently, and undesirably, used to describe the
constellation of morphologic changes described in the preceding that occur on
reperfusion of ischemic myocardium). [23 ] , [35 ] Reperfusion injury is mediated
primarily by toxic oxygen species (such as free radicals) that are overproduced by
myocytes or polymorphonuclear leukocytes upon restoration of oxygen supply to the
tissues. Complement activation also may contribute. Consequently, injury may be
ameliorated by free radical scavengers such as superoxide dismutase and catalase,
inhibitors of polymorphonuclear leukocyte endothelial cell adhesion, or drugs that
regulate complement. [35 ] [38 ]
Although reperfusion of reversibly salvaged myocytes usually prevents their subsequent

necrosis, metabolic and functional recovery are not instantaneous, and contractile
dysfunction may continue for hours to several days following brief periods of ischemia.
[1 ] , [23 ] [25 ] The prolonged biochemical and functional abnormalities of reversibly
injured cells comprise a state of post-ischemic myocardial dysfunction, often called
myocardial stunning, which may have important clinical implications. [39 ] , [40 ] For
example, persistent but ultimately recoverable contractile abnormalities are
encountered after thrombolysis or cardiopulmonary bypass. [41 ] , [42 ] It is difficult to
quantitate the impact of stunning on the function of reperfused hearts containing areas
of necrosis. However, potentially recoverable but stunned myocardium may contribute to
reversible cardiac failure in humans with acute infarction (with or without thrombolysis),
postoperatively, or subsequent to cardiac arrest, thereby providing the pathophysiologic
rationale for the use of cardiac assist devices in some instances. [43 ] [45 ] Regrettably,
histological markers for stunned myocardium are not available.
Hibernating is a term used to describe viable regions of myocardium with impaired

function in the setting of chronically reduced coronary blood flow. [46 ] [48 ] Contractile
function of hibernating myocardium should improve if blood flow returns toward normal
or if oxygen demand is reduced. Myocardial hibernation is characterized by: (1)
persistent wall motion abnormality (diagnosed by ventriculography or
echocardiography); (2) low myocardial blood flow (reflected by a defect in perfusion by
thallium scanning or positron-emission tomography [PET]); (3) evidence of viability of at
least some of the affected areas (demonstrated by PET or stimulation of contraction by
inotropic agents); and (4) functional improvement following return of normal coronary
blood flow. Indeed, correction of this abnormality is likely responsible for the reversal of
long-standing defects in ventricular wall motion that may be observed following coronary
bypass graft surgery or angioplasty. [48 ]
Interestingly, adaptation to short-term transient ischemia may induce tolerance against

subsequent, more severe ischemic insults (ischemic preconditioning). [25 ] , [49 ] , [50 ]
Typically, a short (5-min) period of cardiac ischemia followed by reperfusion is capable
only a short time later of protecting the affected myocardium against injury from a much
longer period of subsequent ischemia. The mechanism of this protection is uncertain,
but stimulation of adenosine receptors when adenosine is released during ischemia
and enhanced expression of heat-shock proteins, which makes the heart more resistant
to prolonged ischemia, have been suggested. [51 ] , [52 ]
Biomaterial-Tissue Interactions
Biomaterials are synthetic or modified biological materials that are used in implanted or
extracorporeal medical devices that augment or replace body structures and functions.
[23 ] , [53 ] , [54 ] Examples of biomaterials include polymers, metals, ceramics,
carbons, processed collagen, and chemically treated animal or human tissues, the latter
exemplified by glutaraldehyde-preserved heart valves, pericardium, and blood vessels.
Comprising effects of both the implant on the host tissues and the host on the implant,
biomaterial-tissue interactions are important in mediating complications and device
failure (Fig. 4-7) . [23 ] , [54 ] , [55 ] Major morphologic effects of biomaterials on tissues
are illustrated in Figure 4-8 . Complications of cardiovascular medical devices,
irrespective of anatomic site of implantation, can be grouped into six major categories:
(1) thrombosis and thromboembolism; (2) device-associated infection; (3) exuberant or
defective healing; (4) degeneration, fracture, or other biomaterials failure; (5) adverse
local tissue interaction, such as toxicity or traumatic hemolysis; and (6) adverse effects
distant from the intended site of the device, such as biomaterials migration or systemic
hypersensitivity. [23 ]
No synthetic or modified biological surface is as thromboresistant as the normal,

unperturbed endothelium. Like a blood vessel denuded of endothelium, foreign
materials on contact with blood spontaneously and rapidly (seconds) absorb a film of
plasma components, primarily protein, followed by platelet adhesion. [23 ] , [56 ] If
conditions of relatively static flow are present, macroscopic thrombus can ensue.
BLOOD-SURFACE INTERACTION
Thromboembolic complications of cardiovascular devices cause significant mortality

and morbidity. [23 ] , [54 ] , [56 ] , [57 ] Thrombotic deposits can impede the function of a
prosthetic heart valve, vascular graft or blood pump, or cause distal emboli. As in the
cardiovascular system in general, surface thrombogenicity, hypercoagulability, and
locally static blood flow (Virchow's triad), present individually or in combination,
determine the relative propensity toward thrombus formation and location of thrombotic
deposits with specific devices. Considerable evidence implicates a primary role for
blood platelets in the thrombogenic response to artificial surfaces (see Fig. 4-8A ).
However, the clinical approach to control thrombosis in cardiovascular devices is the
use of systemic anticoagulants, particularly coumadin (warfarin), which inhibits thrombin
formation but does not inhibit platelet-mediated thrombosis. The specific physical and
chemical characteristics of materials that regulate the outcomes of blood-surface
interaction are incompletely understood. [57 ]
Coagulation proteins, complement products, other proteins and platelets also are
activated, damaged, and consumed by blood-material interactions. [56 ] , [57 ] For
example, blood contact with the large areas of synthetic surfaces during the
extracorporeal perfusion of cardiopulmonary bypass (CPB), may have at least four
consequences: (1) activation and resultant dysfunction of platelets; (2) progressive
denaturation of plasma proteins and lipoproteins; (3) activation of coagulation proteins,
the fibrinolytic system and, through interaction with inflammatory pathways, production of
various bioactive molecules, including bradykinin, a potent vasodilator; and (4)
activation of complement through the alternative pathway, with production of C3a and
C5a, inducing polymorphonuclear leukocyte stasis in the pulmonary circulation with the
occasional sequelae of acute pulmonary hypertension and inflammatory lung injury.
Hemolysis (damage to red blood cells) in implants and extracorporeal circulatory

systems results from both blood-surface interactions and turbulence. [23 ] , [57 ]
Erythrocytes have reduced survival following cardiopulmonary bypass. Also, with earlier
model heart valve prostheses, renal tubular hemosiderosis or cholelithiasis occurred in
many patients, indicative of chronic hemolysis. With contemporary valves, hemolysis
generally is modest and well compensated, but may be accentuated with valve
dysfunction.
TISSUE-SURFACE INTERACTION
Synthetic biomaterials typically are not immunogenic, but they elicit a foreign body
reaction, a special form of nonimmune inflammatory response with an infiltrate
predominantly composed of macrophages. [23 ] , [58 ] Although immunological
reactions have been proposed rarely for synthetic biomaterial-tissue interactions, they
are theoretically possible with tissue-derived biomaterials, and antibodies can be
elicited by implantation of some materials in finely pulverized form. [59 ] , [60 ]
Nevertheless, clinical cardiovascular device failure owing to immunological reactivity is
rare. For most biomaterials implanted into solid tissue, encapsulation by a relatively thin
fibrous tissue capsule (composed of collagen and fibroblasts) resembling a scar
ultimately occurs, often with a fine capillary network at its junction with normal tissue
(see Fig. 4-8B ). [23 ] , [58 ] An ongoing inflammatory infiltrate consisting of
monocytes/macrophages and multinucleated foreign body giant cells in the vicinity of a
foreign body generally suggests persistent tissue irritation (see Fig. 4-8C ).
VASCULAR GRAFT HEALING
The healing of fabric prostheses or components within the cardiovascular system can
yield exuberant fibrous tissue at the anastomosis as an overactive but physiologic
repair response (Fig. 4-9) . [7 ] , [23 ] Synthetic and biological vascular grafts often fail
because of generalized or anastomotic narrowing mediated by connective tissue
proliferation in the intima, and heart valve prostheses can have excessive pannus that
occludes the orifice (see Fig. 4-28B ). Intimal hyperplasia results primarily from smooth
muscle cell migration, proliferation, and extracellular matrix elaboration following and
possibly mediated by acute or ongoing endothelial cell injury. [7 ] , [23 ] , [61 ]
Contributing factors include (1) surface thrombogenesis; (2) delayed or incomplete
endothelialization of the fabric; (3) disturbed flow across the anastomosis; and (4)
mechanical factors at the junction of implant and host tissues.
Tissue lining a vascular graft or coating a heart valve sewing cuff has two major
sources: overgrowth from the host vessel across anastomotic sites, and tissue ingrowth
through fabric interstices. [23 ] A potential third mechanism, deposition of functional
endothelial cell from the circulating blood, is non-existent or ineffective. In a graft with
interstices large enough to permit ingrowth of fibrovascular elements, endothelial cells
can arise from capillaries extending from outside to inside the graft and migrate to the
luminal surface at a large distance from the anastomosis. However, since most clinical
vascular grafts are impervious, in order to obviate hemorrhage, existing grafts (and
other fabrics used as cardiovascular implants) heal primarily by ingrowth of endothelium
and smooth muscle cells from the cut edges of the adjacent artery or other tissue.
Humans have a limited ability to spontaneously endothelialize cardiovascular

prostheses, and full endothelialization of clinical grafts (yielding an intact neointima)
usually does not occur. [23 ] Luminal coverage develops relatively slowly and
incompletely. For uncertain reasons, endothelial cell coverage generally is restricted to
a zone near an anastomosis, typically 1015 mm, thereby allowing healing of
intracardiac fabric patches and prosthetic valve sewing rings, but not long vascular
grafts. Thus, except adjacent to an anastomosis, a compacted platelet-fibrin aggregate
(pseudointima) comprises the inner lining of clinical fabric grafts, even after long-term
implantation. Because firm adherence of such linings to the underlying graft may be
impossible, dislodgement of the lining and formation of a flap-valve can occur and
cause acute obstruction. [62 ] Since therapeutic endothelial seeding of vascular grafts
has yielded only modest benefit, attempts to seed genetically modified endothelial cells
and block smooth muscle cell proliferation are ongoing. [63 ] , [64 ]
INFECTION
Infection, occurring in as many as 510 percent of patients with implanted prosthetic

devices, is a frequent source of morbidity and mortality. [23 ] , [54 ] , [65 ] Because
medical devices usually are coated with platelet-fibrin thrombus and are remote from
capillary vessels, associated infections often are difficult to treat with antibiotics and are
resistant to host defenses. Consequently, such infections generally persist until the
devices are removed.
Early implant infections (less than approximately 12 months postoperatively) most likely
result from intraoperative contamination or early postoperative wound infection,
whereas late infections generally occur by a hematogenous route, and can be initiated
by bacteremia induced by therapeutic dental or genitourinary procedures. [23 ] , [65 ]
Antibiotics given prophylactically at device implantation and shortly before subsequent
diagnostic and therapeutic procedures may protect against implant infection. Infections
associated with foreign bodies are characterized microbiologically by a high
prevalence of coagulase-negative staphylococci, including Staphylococcus
epidermidis , an organism with low virulence, and an infrequent cause of
non-prosthesis-associated deep infections, as well as other more virulent
staphylococci, especially S. aureus , and less virulent strains of streptococci. [66 ]
The presence of a foreign body potentiates infection in several ways. [23 ]

Micro-organisms may inadvertently be introduced by device contamination, provided
access to deeper tissue by damage to natural barriers against infection during
implantation or subsequent device function, and permitted to survive adjacent to the
implant. Moreover, through damaged vasculature, an implanted foreign body could limit
phagocyte migration into infected tissue or interfere with inflammatory cell phagocytic
mechanisms, by release of soluble implant components or surface-mediated
interactions.
Despite the large numbers of implants used clinically over an extended duration,
neoplasms occurring at the site of implanted cardiovascular and other medical devices
are exceedingly rare. [23 ] , [67 ] , [68 ]
ISCHEMIC HEART DISEASE
The dominant influence in the causation of the ischemic heart disease syndromes is
diminished coronary perfusion relative to myocardial demand, owing largely to a
complex dynamic interaction among fixed atherosclerotic narrowing of the epicardial
coronary arteries, intraluminal thrombosis overlying a ruptured or fissured
atherosclerotic plaque, platelet aggregation, and vasospasm. [1 ] , [8 ] , [23 ] , [69 ]
Increased myocardial demand or reduced oxygen carrying capacity of the blood may be
contributory.
Pathogenesis
ROLE OF FIXED CORONARY OBSTRUCTIONS
Under normal conditions, coronary arterial flow provides adequate myocardial perfusion
at rest, and compensatory vasodilation provides flow reserve that is generally more than
sufficient to accommodate the increased myocardial metabolic demands during
vigorous exertion. When the luminal cross-sectional area is decreased by 75 percent or
more, coronary blood flow generally becomes limited with exertion. With 90 percent or
greater reduction, coronary flow may be inadequate at rest. Over 90 percent of patients
with ischemic heart disease have advanced stenosing coronary atherosclerosis (fixed
obstructions). [8 ] Among these, most have one or more lesions causing at least 75
percent reduction of the cross-sectional area in one or more of the major epicardial
arteries. Thus, the clinical effects of advanced atherosclerotic plaques in most
medium-sized arteries, including the coronary arteries, are in part owing to their
encroachment on the lumen, leading to stenosis.
However, the onset and prognosis of ischemic heart disease and other complications
of atherosclerosis are not well predicted by the arteriographically determined extent and
severity of fixed anatomic disease. [7 ] , [13 ] , [16 ] [20 ] , [23 ] , [69 ] [75 ] Considerable
evidence exists that dynamic vascular changes are largely responsible for the
conversion of chronic stable angina or an asymptomatic state to acute ischemic heart
disease (unstable angina, myocardial infarction, or sudden coronary death). Acute
coronary occlusion can be caused by vasospasm, intravascular plugging by blood
constituents, disruption of or hemorrhage into plaque, platelet aggregation, thrombosis,
embolization, or a combination of these events.
ROLE OF ACUTE PLAQUE CHANGE
The acute coronary syndromesunstable angina, acute myocardial infarction, and

sudden ischemic deathusually are precipitated by atherosclerotic plaque disruption with
hemorrhage, fissuring, and/or ulceration. [8 ] , [18 ] , [19 ] , [69 ] , [71 ] , [72 ]
Angiographically, disrupted plaque appears substantially different from that of chronic
stable disease. Microscopically, injury spans a broad morphologic range, from minimal
surface erosions, to lacerations that extend deep within the plaque. Regardless of the
extent of injury, however, the result is flow disruption and exposure of the luminal blood
to a thrombogenic surface (collagen or necrotic debris), thereby setting the stage for
mural or total thrombosis (Fig. 4-10) .
Pathologic and clinical studies also show that plaques that undergo abrupt disruption
leading to acute ischemic heart disease often are those that previously produced only
mild to moderate luminal stenosis. [69 ] , [71 ] [73 ] In one study, 70 percent of the
vessels with thrombi over plaque tears and deeper intimal injury had pre-existing
stenosis of <60 percent in diameter (or <85 percent in luminal area), correlating with the
observation that, following thrombolytic therapy for acute myocardial infarction, the
underlying lesion often has <75 percent diameter stenosis (or <95 percent in luminal
area). [73 ] Plaque fissures without substantial thrombosis also are found in occasional
patients without acute coronary syndromes. In a group of patients who died of
non-cardiac disease, plaque fissures without thrombosis were found in 9 percent of
patients without hypertension or diabetes and 17 percent of those with these
atheroma-related diseases. [73 ]
Potential outcomes for unstable lesions include healing at the site of plaque erosion,
atheroembolization, nonocclusive thrombosis, thromboembolization, organization of
mural thrombus (plaque progression), acute thrombotic occlusion, and organization of
the occlusive mass, with varying degrees of recanalization. Among these outcomes, the
most common fate is plaque progression, owing either to resealing of the plaque fissure
or to organization of a nonocclusive mural thrombus. Indeed, asymptomatic plaque
rupture and its subsequent healing is likely an important mechanism of stenosis
progression.
The events that trigger abrupt changes in plaque configuration and superimposed
thrombosis are poorly understood. [13 ] , [18 ] [20 ] , [71 ] [75 ] Influences both extrinsic
and intrinsic to the plaque likely are important. Surface erosions, fissures, and ruptures
are more likely to involve soft and eccentric plaques than hard and concentric lesions,
those that contain large areas of foam cells, and fibrous caps that are thin or contain
clusters of inflammatory cells that can produce tissue metalloproteinases that degrade
collagen. Fissures and ruptures most frequently occur at the junction of the fibrous cap
with the adjacent normal arterial wall (plaque-free segment), a location associated with
high circumferential stress. [16 ] , [17 ] Vasospasm, tachycardia, hypercholesterolemia,
or intraplaque hemorrhage are likely contributors, as are stresses produced by
abnormal blood flow and/or coronary intramural pressure or tone in areas of stenosis.
Interestingly, there is a pronounced circadian periodicity for the time of onset of acute
myocardial infarction and other acute coronary syndromes, with a peak incidence
between 911 a.m., concurrent with a surge in blood pressure and immediately following
heightened platelet reactivity. [74 ] , [75 ]
Pathology of Coronary and Myocardial Interventions
THROMBOLYSIS
Revascularization by thrombolysis in early acute myocardial infarction limits infarct size

and enhances function and survival. [1 ] , [23 ] , [25 ] , [76 ] [78 ] The pathologic basis of
thrombolytic therapy is as follows: (1) Untreated thrombotic occlusion of a coronary
artery usually causes transmural infarction; (2) the extent of necrosis during an evolving
myocardial infarction progresses as a wavefront and becomes complete only 6 hours or
more following coronary occlusion (see Fig. 4-5 ); (3) both early- and long-term mortality
following acute myocardial infarction correlate strongly with the amount of residual
functioning myocardium; and (4) early reperfusion prevents necrosis of some
jeopardized myocardium. The benefit of thrombolytic therapy depends on and is
assessed by the amount of myocardium salvaged, recovery of left ventricular function,
and resultant reduction in mortality. These important clinical endpoints largely are
determined by the time interval between onset of symptoms and a successful
intervention, adequacy of early coronary reflow, and the degree of residual stenosis of
the infarct vessel.
Recanalization rates vary from 6090 percent; the best efficacy relates to the earliest
time of infusion of thrombolytic agents (streptokinase, urokinase, or tissue-derived
plasminogen activator). [76 ] [78 ] Most studies conclude that the critical time for
substantial myocardial salvage is approximately within 4 hours for intracoronary and 3
hours for intravenous administration but studies also suggest that at least some benefit
can occur following later reperfusion, usually within 12 hours of symptoms. Moreover,
spontaneous recanalization, presumably owing to inherent thrombolysis, can be
beneficial to left ventricular function, and has been well-documented within 24 hours of
infarct initiation. However, spontaneous thrombolysis with reperfusion probably occurs
in fewer than 10 percent of patients within the critical 34 hours after symptom onset.
Successful thrombolytic therapy re-establishes antegrade flow in the infarct-related

coronary artery but does not reverse factors responsible for initiating the original
thrombosis, such as advanced atherosclerotic plaque, intimal rupture, enhanced platelet
adhesiveness, or coronary spasm. High-grade residual stenosis is likely to be
associated with recurrent ischemic events, as evidenced by post-infarction angina or
recurrent infarction. Thus, balloon angioplasty or surgical revascularization during infarct
evolution constitutes a more effective management of the underlying disease process
than thrombolysis alone. The most common complications of streptokinase or
tPA-mediated reperfusion are myocardial and systemic hemorrhage and so-called
reperfusion arrhythmias. [76 ] [78 ]
ANGIOPLASTY, ATHERECTOMY, AND STENTS
Percutaneous transluminal coronary angioplasty (PTCA) is used widely in patients with

stable angina, unstable angina, or acute myocardial infarction. [7 ] , [18 ] , [23 ] , [79 ] In
PTCA, the progressive and substantial expansile force induced by balloons inflated at
812 atm of pressure causes the essentially non-distensible plaque to split at its weakest
point, a site not necessarily most severely involved with atherosclerosis. [7 ] , [18 ] , [23 ]
, [81 ] , [82 ] The split extends at least to the intimal-medial border and often into the
media, with consequent circumferential and longitudinal dissection of the media (Fig.
4-11) . [1 ] , [8 ] , [18 ] , [23 ] , [80 ] Dissimilar plaques respond differently to balloon
dilation, and the composition and configuration of the original atherosclerotic lesion play
a key role in the outcome of angioplasty. [18 ] , [81 ] Immediate success probably is
enhanced in dilated arteries having eccentric plaques with large lipid-rich necrotic cores
and/or calcification, in contrast to concentric fibrotic lesions. For eccentric atheromas,
balloon-induced splits most commonly involve the junction between the plaque and the
disease-free portion of the arterial wall. Structural/stress analysis based on
intravascular ultrasound imaging prior to balloon angioplasty can predict the location of
plaque fracture that accompanies angioplasty. [82 ] Acute dissection may contribute to
the propensity for acute closure that occurs in up to 5 percent of patients. For example,
a dissection that involves a considerable portion of the circumference can generate a
flap that may impinge on the lumen. Alternatively, a dissection that involves a substantial
proximal-to-distal segment of the vessel, which traverses a large plaque-free wall
segment, can induce compression of the vessel at a point of minimal disease. [23 ]
Thus, the key vascular consequences of angioplasty are plaque fracture, medial
dissection, and stretching of the media beyond the dissection. These, in turn, are
accompanied by local flow abnormalities and generation of new, thrombogenic
blood-contacting surfaces. This supports the concept that an atherosclerotic plaque
following angioplasty has many features of a spontaneously disrupted plaque, namely
those associated with the acute coronary syndromes. [23 ] The immediate
post-angioplasty healing process in either arteries or bypass grafts is not well
understood, but dissolution of soft atheromatous material, retraction of the split plaque,
thrombus formation, and intimal healing with re-endothelialization likely occur.
The long-term success of angioplasty is limited by the development of progressive,

proliferative restenosis over a period of months to years (Fig. 4-12) . [23 ] , [79 ] , [80 ] ,
[83 ] [86 ] Clinically significant restenosis occurs in approximately 3040 percent of
patients following coronary balloon angioplasty, most frequently within the first 46
months. Restenosis probably represents a fundamental vascular healing response that
achieves clinical significance only in some patients.
The factors causing restenosis are complex. [79 ] , [84 ] , [86 ] Although vessel wall
recoil and organization of thrombus likely contribute, the major process leading to
restenosis is excessive medial and plaque smooth muscle proliferation as an
exaggerated response to angioplasty-induced injury. Medial smooth muscle cells
migrate to the intima where, along with existing plaque smooth muscle cells, they
proliferate and secrete abundant extracellular matrix, consisting predominantly of
collagen and glycosaminoglycans. Early lesions have a loose myxoid matrix in which
numerous stellate smooth muscle cells are haphazardly arranged. Over weeks to
months, the extracellular matrix becomes more densely collagenous, and the neointima
becomes less cellular, with scattered spindle-shaped cells in a more laminar
arrangement. The restenosis process has mechanistic similarities to both
atherosclerosis and vascular graft healing previously described (see the preceding). [23
] Moreover, following prominent thrombus formation, or in a hyperlipidemic patient, the
site of healing also may contain foam cells and cholesterol crystals, resembling a
mature fibrofatty atheroma. There is considerable interest in locally delivered
pharmacologic and molecular therapies to mitigate restenosis; regrettably, success is
limited. [87 ] [90 ]
The general goals with the newer techniques of plaque ablation and stent devices are to
enhance the acute success rate and lumen size, decrease disease complications,
reduce late proliferative stenosis, extend the range of treatable lesions, and increase
cost-effectiveness. In general, the largest acute luminal diameter safely possible
provides better tolerance of subsequent intimal hyperplasia before hemodynamically
significant renarrowing results at the treatment site. [83 ] , [91 ]
The morphology of arterial vessel healing after transluminal procedures that remove
obstructive tissue by excision, such as directional or rotational atherectomy, is similar to
that following angioplasty. [80 ] , [92 ] , [93 ] However, atherectomy techniques may
permit a larger acute lumen than angioplasty, with potential benefit. [94 ] Moreover,
beyond therapeutic objectives, directional atherectomy obtains human restenosis tissue
for tissue culture, and molecular or other studies, and aids in evaluating differences in
the pathobiology of restenosis following various pharmacological or mechanical
therapies or plaque ablation procedures.
Recent studies suggest that as an adjunct to interventional procedures that manipulate
plaque, metallic balloon-expandable and self-expanding intravascular stents may
reverse the untoward effects of PTCA. Such devices could provide a larger and more
regular lumen initially acting as a scaffold to support the intimal dissections that occur in
PTCA, mechanically prevent vascular spasm, and increase blood flow, all of which
could minimize thrombus formation, and reduce the impact of postangioplasty
restenosis. [95 ] [97 ] Stent wires initially are covered with a variable platelet-fibrin
coating, and may eventually become covered by neointima (Fig. 4-13) . [98 ] [100 ]
Nevertheless, the neointima may thicken, and proliferative restenosis currently is not
prevented by stenting. Important questions remain relative to determinants of healing
and the potential for late complications of endovascular stents, such as migration,
perforation, or infection.
CORONARY ARTERY BYPASS GRAFT SURGERY
Now widely done, coronary artery bypass graft surgery is widely acknowledged to
improve survival in patients with significant left main coronary artery disease, improve
survival in patients with three-vessel disease and reduced ventricular function, and
prolong and improve the quality of life in patients with left main equivalent disease
(proximal left anterior descending and proximal left circumflex), but not protect from the
risk of subsequent myocardial infarction. [101 ] Moreover, graft patency deteriorates
with time and accelerated changes of atherosclerosis develop in bypassed vessels. [23
] , [102 ]
Early cardiac failure with low output or arrhythmias following uncomplicated coronary
artery bypass surgery occurs infrequently; the causes are unclear in many cases. Many
such patients have no detectable myocardial necrosis, either clinically or at autopsy. In
others, the extent of necrosis noted at autopsy seems insufficient to account for the
profound ventricular dysfunction encountered clinically; possible explanations include (1)
evolving myocardial necrosis either undetectable clinically or too recent to detect at
autopsy; (2) postischemic dysfunction of viable myocardium, for which no morphologic
markers of the dysfunctional state are known; or (3) a metabolic cause, such as
hypokalemia, for which there is no morphologic counterpart. Thus, although established
myocardial necrosis causes cardiac dysfunction in many patients with postoperative
failure; it may not be the predominant lesion or the cause of death. However, when such
necrosis is detected at autopsy, it may indicate that a potentially larger volume of
adjacent myocardium was biochemically and functionally (but not morphologically)
deranged. [23 ]
Early thrombotic occlusion occurs in approximately 15 percent of grafts, and the

clinical and autopsy incidences of early graft occlusion are not widely different. [23 ] ,
[102 ] Factors in the acute occlusion of aortocoronary bypass grafts (with or without
superimposed thrombus) include anastomotic compression by atherosclerosis,
suboptimal insertion site, poor distal run-off, graft or native vessel mural dissection at
the anastomotic site, and distortion of a graft that is too short or too long for the
intended bypass. In some cases, thrombosis occurring early postoperatively involves
only the distal portion of the graft, suggesting that early graft thrombosis is most
frequently initiated at the distal anastomosis. Inadequate distal run-off from extremely
small distal native coronaries, frequently further compromised by partial atherosclerotic
occlusions, comprises the major cause of early graft thrombosis.
Graft thromboses account for only a minority of early cardiac deaths; most patients who
die early have patent grafts. Moreover, graft occlusions frequently do not account for
early postoperative myocardial necrosis, which occurs most often in regions perfused
by patent grafts. Perioperative infarction usually is caused by either hypotensive
episodes during anesthesia induction or inadequate intraoperative regional
preservation owing to severe obstruction of the feeding artery and poor collaterals.
Such necrosis usually predominates in the subendocardium and often has the
morphology of necrosis with contraction bands. As in cardiac surgery in general,
perioperative myocardial infarction is more likely to occur in patients with cardiomegaly
than in those with normal-sized hearts.
In contrast, both progression of obstructive atherosclerosis in non-bypassed coronary

artery segments and graft obstruction are major factors in late symptom recurrence .
[23 ] , [101 ] , [102 ] As in the coronary arteries, atherosclerosis in aortocoronary bypass
grafts can cause myocardial ischemia through progressive luminal stenosis or plaque
rupture with secondary thrombotic obstruction. The potential for disruption and
embolization of atherosclerotic lesions in vein grafts exceeds that for native coronary
atherosclerotic lesions. Plaques in grafts generally involve dilated segments, often have
poorly developed fibrous caps, have large necrotic cores, and develop secondary
dystrophic calcific deposits that may be adjacent to the lumen rather than deep to the
surface as in typical native arterial atherosclerosis (Fig. 4-14) . Finally, because of the
large size of the affected graft relative to the coronary artery to which it is anastomosed,
atheroembolization is likely to be widespread or occlusive, often with catastrophic
results; balloon angioplasty or intraoperative manipulation of grafts may stimulate
atheroembolism. [103 ]
The long-term patency of saphenous vein grafts is 60 percent or less at 10 years, owing
to pathologic changes, including thrombosis (early), intimal thickening (several months
to several years postoperatively), and graft atherosclerosis (years). [23 ] , [101 ] , [102 ] ,
[104 ] , [105 ] These may be associated with superimposed plaque rupture, thrombi, or
aneurysms (usually more than 23 years postoperatively).
In contrast, the internal mammary (internal thoracic) artery has a greater than 90 percent
patency rate at 10 years (Fig. 4-15) . [23 ] , [101 ] , [102 ] , [106 ] Multiple factors likely
contribute to the remarkably higher long-term patency of IMA grafts compared to vein
grafts. [23 ] , [101 ] , [102 ] Free saphenous vein grafts, during autotransplantation,
sustain not only disruption of their vasa vasora but also endothelial damage, medial
ischemia, and acutely increased internal pressure. In contrast, the internal mammary
artery generally has minimal pre-existing atherosclerosis, requires minimal surgical
manipulation, maintains its nutrient blood supply, is accustomed to arterial pressures,
needs no proximal anastomosis, and has an artery-to-artery distal anastomosis. The
sizes of graft and recipient vessel are comparable with the internal mammary artery but
disparate (graft substantially larger) with saphenous vein. As another distinguishing
feature, the IMA is an elastic artery, whereas coronary arteries are muscular.
TRANSMYOCARDIAL LASER REVASCULARIZATION
Transmyocardial laser revascularization is being tested in selected patients with chronic

obstructive coronary artery disease that is refractory to conventional revascularization
techniques and to maximal medical therapy. Performed on a beating heart through a left
thoracotomy, the operation employs a high-energy laser to bore transmural channels (1
mm in diameter) into the left ventricle. The rationale for this procedure is the hypothesis
that blood will flow directly from the left ventricular chamber into the channels and then
into the intramyocardial vascular plexus, thereby restoring perfusion to potentially viable
myocardium and improving ventricular function. Although experimental and clinical
reports suggest benefit, the morphological basis for success is yet uncertain. [107 ]
[111 ] Our examinations of hearts from patients who have died at various post-mortem
intervals fail to reveal patent channels (Fig. 4-16) . [112 ]
Myocardial Infarction and Its Complications
Although an electrocardiogram cannot reliably distinguish transmural from

subendocardial infarcts, patients who develop Q-waves usually have transmural infarcts
and those with subendocardial infarcts usually do not (Q-wave and non-Q-wave infarcts,
respectively). [78 ] The two types of myocardial infarction have differing morphology and
clinical significance. In the more common transmural infarct, ischemic necrosis involves
at least one-half and usually the full or nearly full thickness of the ventricular wall in the
distribution of a single coronary artery. [1 ] It usually is associated with chronic coronary
atherosclerosis, and with acute plaque rupture and superimposed thrombosis. In
contrast, a subendocardial (nontransmural) infarct constitutes an area of ischemic
necrosis limited to the inner one-third or at most one-half of the ventricular wall. It often
extends laterally beyond the perfusion territory of a single coronary artery and can be
multifocal. It is commonly associated with diffuse stenosing coronary atherosclerosis
without acute plaque rupture or superimposed thrombosis, in the setting of episodic
hypotension, global ischemia, or hypoxemia. However, a subendocardial infarct also
can result from a coronary thrombus that is nonocclusive or becomes lysed before
myocardial necrosis becomes transmural.
Important and frequent complications of myocardial infarction include ventricular

dysfunction, cardiogenic shock, arrhythmias, infarct rupture, infarct extension and
expansion, papillary muscle dysfunction, right ventricular involvement, ventricular
aneurysm, pericarditis, and systemic arterial embolism. [1 ] , [78 ] Of the many patients
who have conduction disturbances or myocardial irritability following myocardial
infarction, histologic evidence of direct conduction system involvement is present only in
a minority. Heart block following myocardial infarction usually is transient, and owing to
efflux of extracellular necrotic debris and electrolytes, from a nearby infarct, that gain
entry to venules and lymphatics that drain directly through the AV node and AV (His)
bundle. Nevertheless, conduction block in the proximal atrioventricular conduction
system may necessitate pacemaker implantation. In contrast, tachyarrhythmias usually
originate in areas of severely ischemic or necrotic myocardium.
Myocardial infarcts produce functional abnormalities approximately proportional to their

size. [78 ] Cardiogenic shock occurs in 1015 percent of patients following myocardial
infarction and is generally indicative of a large infarct (often >40 percent of the left
ventricle). The previously high mortality of cardiogenic shock has been alleviated
somewhat in recent years by the use of intra-aortic balloon pumps (IAPB) and
ventricular assist devices.
Frequently catastrophic, cardiac rupture syndromes include three entities: (1) rupture of
the ventricular free wall (most commonly), usually with hemopericardium and cardiac
tamponade; (2) rupture of the ventricular septum (less commonly), leading to an
acquired ventricular septal defect with a left-to-right shunt; and (3) papillary muscle
rupture (least commonly), resulting in the acute onset of severe mitral or, very rarely,
tricuspid regurgitation. Cardiac rupture is the cause of death noted at autopsy in 810
percent of patients with fatal acute transmural myocardial infarcts. Ruptures tend to
occur relatively early following infarction, with a mean interval of approximately 45 days,
and a range of 110 days. Even though they can be associated with large or small
infarcts, all free wall and septal ruptures involve transmural infarcts. [113 ] Although the
lateral wall is the least common site for left ventricular infarction, it is the most common
site for postinfarction free-wall rupture. Acute free-wall ruptures usually are rapidly fatal,
but repair may be possible in some cases. [114 ]
A strategically located pericardial adhesion that arrests the rapidly moving blood front
and aborts a rupture may result in the formation of a false aneurysm (that is, a contained
rupture with a hematoma communicating with the ventricular cavity). [115 ] False
aneurysms contain no myocardial elements in their walls, and consist only of epicardium
and adherent parietal pericardium. Many are filled with mural thrombus. Half of
postinfarction false aneurysms ultimately rupture.
Acute ventricular septal defect complicates only 12 percent of infarcts. Grossly,

infarct-related septal defects are of two types: (1) single or multiple, sharply localized,
jagged, linear passageways that connect the ventricular chambers (simple type); and
(2) defects that tunnel serpiginously through the septum to a somewhat distant opening
on the right side (complex type). [116 ] In simple lesions, neither gross hemorrhage nor
peripheral laceration usually is present. In complex lesions, the tract may extend into
regions remote from the site of the infarct. Complex ruptures most frequently involve the
inferoseptal wall, especially basally. Without surgery, the prognosis following
infarct-related septal rupture is poor; 50 percent of patients die within the first week (half
of these within 24 hours), and only 1520 percent survive beyond 2 months.
Mitral regurgitation secondary to myocardial infarction reflects loss of the structural or

functional integrity of the mitral valve apparatus, usually at the level of the papillary
muscle-left ventricular wall. Since chordae tendineae arise from the heads of the
papillary muscles and provide continuity with each of the valve leaflets, interference with
the structure or function of either papillary muscle can result in dysfunction of both mitral
valve leaflets. Papillary muscles are perfused with blood that has traversed the entire
transmural extent of the myocardium, and thus are particularly vulnerable to ischemic
injury. Since the collateral circulation of the posterior myocardium is not as extensive as
it is in the anterolateral segments, the posterior medial papillary muscle is susceptible
to widespread necrosis and rupture. [117 ] Papillary muscle ruptures can occur with
either subendocardial or transmural infarcts. They also can occur later than other rupture
syndromes (i.e., as late as 1 month), since healing in this area can be particularly
retarded because of the limited vasculature and resultant inaccessibility of inflammatory
cells.
Other mechanisms can produce mitral regurgitation in the setting of chronic rather than
acute ischemic heart disease. A papillary muscle can fail to tighten the chordae during
systole, thereby allowing the mitral leaflets to prolapse into the left atrium. Additionally, a
previously infarcted papillary muscle that ultimately undergoes fibrosis and shortening
can fix the chordae deeply within the ventricle, maintaining an opened valve orifice.
Moreover, left ventricular failure can cause ventricular dilation with distortion and
malalignment of the papillary muscle axes. Left ventricular failure with subsequent
dilation can produce mild stretching of the mitral annulus and contribute to valvular
incompetence.
Isolated right ventricular infarction is rare. In contrast, involvement of the right ventricular
myocardium by extension of an inferoseptal infarct occurs in approximately 10 percent
of transmural infarcts and can have important functional consequences. [118 ] , [119 ]
These include right ventricular failure with or without tricuspid regurgitation and
arrhythmias, among others.
Following myocardial infarction, ventricular function and prognosis are influenced by

changes in left ventricular size, shape, and thickness, involving both the infarcted and
the noninfarcted segments of the ventricle. [78 ] The composite process, called
ventricular remodeling, occurs by a combination of changes in left ventricular dimension
(dilation) and regional compensatory hypertrophy of residual non-infarcted myocardium
(determined by the metabolic state of the adjacent and remote myocardium). [120 ] ,
[121 ] The extent of architectural reorganization is determined by the patency of the
infarct-related artery, ventricular loading conditions, size and distensibility of the infarct,
and activation of tissue hormonal systems. Ventricular remodeling likely begins at the
time of acute infarction and probably continues for months to years, until either a stable
hemodynamic state is achieved or progressively severe cardiac decompensation
occurs.
Intuitively, compensatory hypertrophy of noninfarcted myocardium should be

hemodynamically beneficial. However, late decreases in ventricular performance with
depression of regional and global contractile function may reflect degenerative changes
in viable myocardium, as may occur in other states of hypertrophy in which pathologic
changes follow those that are initially physiologic.
Congestive heart failure secondary to the myocardial consequences of coronary artery

disease, often referred to as ischemic cardiomyopathy, may occur when the overall
function of non-scarred myocardium can no longer maintain an adequate cardiac
output. Moreover, the vulnerability of regions of hyperfunctioning but failing residual
myocardium to additional ischemic episodes may be increased. [122 ]
Infarct extension is characterized by new necrosis in the same distribution as the

existing recent infarct, but following its completion. [123 ] , [124 ] In contrast, infarct
expansion is defined as disproportionate thinning and dilation of the infarcted region.
[124 ] , [125 ] Infarct expansion increases the size of the infarcted segment by a
combination of (1) slippage between muscle bundles, reducing the number of myocytes
across the infarct wall; (2) disruption of the normal myocardial cells; and (3) tissue loss
within the necrotic zone.
Expansion can be detected by two-dimensional echocardiography in up to 30 percent

of transmural infarcts. More than 25 percent of hearts with infarcts studied at autopsy
have marked expansion of the infarcted zone, frequently with superimposed mural
thrombus. Patients with infarct expansion have increased morbidity and mortality.
Regional dilation contributes to a significant increase in ventricular volume, thereby
increasing the wall stress and workload of noninfarcted myocardium. Moreover, a
combination of local myocardial contractility abnormality (causing stasis), endocardial
damage (causing thrombogenicity), and systemic hypercoagulability can potentiate
intracardiac mural thrombosis.
Ventricular aneurysms may develop in areas of infarct expansion. They most commonly
result from a large transmural infarct that heals as a large area of thin scar tissue that
paradoxically bulges during ventricular systole. [126 ] In contrast to false aneurysms, true
ventricular aneurysms rarely rupture. Markedly hypertrophied myocardial remnants often
are present in aneurysm walls. In addition, foci of mummified myocardium (necrotic but
inadequately healed) may be present, indicating incomplete healing of an infarct.
Although 50 percent of patients with chronic fibrous aneurysms have mural thrombus
contained within the ventricle, systemic embolization occurs only rarely. Aneurysm
formation historically was considered to be caused by stretching of maturing scars, but
recent evidence suggests that early expansion of myocardial infarcts provides the
substrate for scar thinning and late aneurysm formation. [23 ] Interestingly, some
pharmacologic approaches to limiting infarct size, such as steroids and other
anti-inflammatory agents, could exacerbate infarct expansion and aneurysm formation.
[30 ] , [78 ] Whether the hemorrhage that frequently accompanies reperfusion facilitates
or hinders infarct healing is yet unsettled. [33 ]
The specific anticipated complications and prognosis of myocardial infarction depend

on myocardial infarct size, site, and transmurality. [78 ] Large infarcts have a higher
probability of cardiogenic shock, arrhythmias, and late congestive heart failure. Patients
with anterior infarcts are at greatest risk for regional dilatation and mural thrombi and
have a substantially worse clinical course than those with inferior infarcts. In contrast,
posterior infarcts are more likely to have serious conduction blocks and right ventricular
involvement. Although the relative prognosis of patients with subendocardial versus
transmural infarcts is controversial, mechanical complications clearly are more frequent
and significant in patients with transmural lesions.
VALVULAR HEART DISEASE
Normal valve function requires integrity and coordinated interactions among all
components in the system. For the mitral valve, these elements comprise the so-called
mitral apparatus: including leaflets, annulus, chordae tendineae (tendinous cords),
papillary muscles, and the atrial and ventricular myocardium. For the aortic valve, they
comprise the cusps and their supporting structures in the aortic root.
Structure-Function Correlations in Normal Valves
The anatomy of the mitral and aortic valves is illustrated in Figure 4-17 .
MITRAL VALVE (see Figure 4-17A )
Of the two leaflets of the mitral valve, the anterior (also called septal, or aortic) leaflet is
roughly triangular and deep, with the base inserting on one-third of the annulus. The
posterior (also called mural, or ventricular) leaflet, although less deep, is attached to
about two-thirds of the annulus, and typically has a scalloped appearance. The mitral
leaflets have a combined area approximately twice that of the annulus; they meet during
systole with apposition to approximately 50 percent of the depth of the posterior leaflet
and 30 percent that of the anterior leaflet. Each leaflet receives chordae tendineae from
both the anterior and posterior papillary muscles.
The mitral valve orifice is D-shaped, with the flat anteromedial portion comprising the
attachment of the anterior mitral leaflet in the subaortic region. This part of the annulus is
fibrous and non-contractile; the remainder is muscular, and contracts during systole,
thereby reducing the area of the orifice, but asymmetrically. The edges of the mitral
leaflets are held in or below the plane of the orifice by the submitral components of the
mitral apparatus. The orifice of the tricuspid valve is larger and less distinct than that of
the mitral; its three leaflets (anterior, posterior, and septal) are larger and thinner than
those of the mitral valve. The mitral and tricuspid valves comprise the atrioventricular
valves.
AORTIC VALVE (see Figure 4-17B )
The functional elements of the aortic valve are cusps, annular fibrous tissue, and aortic
root, including the dilated pockets of aortic root behind the valve cusps called the
sinuses of Valsalva, from which the right and left coronary arteries arise from individual
orifices. At the midpoint of the free edge of each cusp is a fibrous nodule (nodule of
Arantius). A thin, crescent-shaped portion of the cusp on either side of the nodule,
termed the lunula, defines the surface of apposition of the cusps when the valve is
closed (approximately 40 percent of the cuspal area). Fenestrations (holes) near the
free edges and within the lunula commonly occur as a developmental or degenerative
abnormality. They generally are small (less than 2 mm diameter) and have no functional
significance, since the lunular tissue does not contribute to separating aortic from
ventricular blood during diastole. In contrast, fenestrations below the lunula are not only
associated with functional incompetence but also suggest previous or active infection.
The pulmonic valve cusps and surrounding tissues have architectural similarity to but
are lighter than that of the corresponding aortic components, and lack coronary arterial
origins. The aortic and pulmonic valves are called the semilunar or arterial valves.
VALVE HISTOLOGY (see Figure 4-17C )
All cardiac valves essentially have the same microscopically inhomogeneous

architecture. [23 ] The prototypical aortic valve cusps have four well-defined tissue
layers, observable histologically: (1) the thin ventricular layer (or ventricularis), facing the
left ventricular chamber, is comprised predominantly of collagenous fibers with radially
aligned elastic fibers; (2) the centrally located spongy layer (or spongiosa), is
composed of loosely arranged collagen and abundant proteoglycans; (3) the thick
fibrous layer (or fibrosa), is composed predominantly of circumferentially aligned,
densely packed collagen fibers, largely arranged parallel to the cuspal free edge; and
(4) the thin aortic layer (or aorticus) consists of a few collagen fibers along the aortic
surface of the cusps. The fibrosa provides structural integrity and mechanical stability.
The spongiosa, in contrast, has negligible structural strength, but appears to lubricate
relative movement between the two fibrous layers and absorb shock during closure. The
rich elastin of the ventricularis enables the cusps to have minimal surface area when the
valve is open but stretch during diastolic back pressure to form a large coaptation area.
Endothelial cells line the surfaces of the valves, and the predominant deep cells are
fibroblasts. Normal human aortic and pulmonary valve cusps are nearly avascular; they
are sufficiently thin to be perfused from the surrounding blood. In contrast, the mitral and
tricuspid leaflets contain a few capillaries in their most basal thirds.
The orientation of architectural elements is nonrandom in the plane of the cusp, yielding
unequal mechanical properties of the valve cusps in different directions (anisotropic
behavior). Consequently, although the pressure differential across the closed aortic
valve during the diastolic phase induces a large load on the cusps, the geometry of the
whole valve and the fibrous network within the cusps effectively transfers the resultant
stresses to the annulus and aortic wall. With specializations that include crimp of
collagen fibers along their length and bundles of collagen in the fibrous layer, oriented
largely toward commissures and that produce grossly visible corrugations, cusps are
extremely soft and pliable when unloaded, but taut and stiff during the closed phase.
This minimizes sagging of the cusp centers, preserving maximum coaptation, and
prevents regurgitation. For the mitral valve, the subvalvular apparatus (including
tendinous cords and papillary muscles) serves a similar function.
During valve closure, cusps and leaflets do not touch along only their free edges like
closing double doors. Rather, adjacent cusps coapt with relatively large areas of
surface-to-surface contact. This involves the lunular surfaces of semilunar valve cusps
and roughly the apical third of atrioventricular valve leaflets. Thus, normal cusp and
leaflet areas are substantially greater than that needed to close the valve orifice.
Etiology and Pathologic Anatomy
Cardiac valve operations usually are undertaken for dysfunction caused by calcification,
fibrosis, fusion retraction, perforation, dilatation, or congenital malformations. [1 ]
Valvular stenosis almost always both is caused by a primary cuspal abnormality and is
a chronic process (except for massive vegetations). Valvular insufficiency may result
from either intrinsic disease of the valve cusps or damage to or distortion of the
supporting structures (e.g., the aorta, mitral annulus, chordae tendineae, papillary
muscles, and ventricular free wall) without primary cuspal pathology. Both stenosis and
insufficiency can coexist in a single valve, usually with one process predominating.
Regurgitation may appear either acutely, as with rupture of cords, or chronically, as with
leaflet scarring and retraction. The most commonly encountered etiology-specific
morphologies of valvular heart disease are illustrated in Figure 4-18 and Figure 4-19 .
Changing disease patterns and an aging United States population have altered the
relative frequency of the major causes of valve disease during the past quarter century.
[1 ] , [127 ] , [128 ] Degenerative (senile) calcific aortic valve disease is the most
common cause of aortic stenosis; calcification of congenitally bicuspid aortic valves
comprises the second most common cause. Postinflammatory (rheumatic) disease has
continued to decline as a cause of aortic valve dysfunction. Indeed, the leading cause of
chronic aortic insufficiency is aortic root dilatation, causing stretching and outward
bowing of the commissures and a lack of cuspal coaptation. Over the age of 40, aortic
root dilatation appears owing to age-related aortic degeneration or, less commonly,
aortitis; under 40 years, root dilatation occurs most frequently in association with
Marfan's syndrome, other connective tissue disorders or operated congenital heart
disease. Moreover, whereas post-rheumatic deformity remains the leading cause of
mitral stenosis, the incidence of postinflammatory mitral valve disease continues to
decline; at most institutions, myxomatous (floppy) mitral valve disease is the most
common cause of pure mitral valve regurgitation and indeed, a major indication for
mitral valve replacement or repair.
The term functional regurgitation is used in the setting of valves that are neither
damaged nor appreciably distorted (dynamic valvular incompetence secondary to
altered ventricular configuration and related structures). [1 ] , [23 ] The implication is that
downstream hemodynamic adjustment would restore valve competence. Conversely,
mitral valve function may be normal despite abnormal anatomic features. This occurs
both because the combined areas of the normal mitral leaflets are considerably larger
than the area of the valve orifice and, to some extent, because the functions of the
various components of the mitral apparatus are partially redundant.
DEGENERATIVE CALCIFIC AORTIC VALVE STENOSIS
The most frequent valvular abnormality requiring surgery, acquired aortic stenosis (AS)
usually is the consequence of calcification of aortic valves with previously normal
anatomy in aged individuals or calcification induced by wear and tear of congenitally
bicuspid valves (see Fig. 4-18 ). [1 ] , [23 ] , [127 ] Stenotic, previously normal valves
(with three cusps) come to clinical attention primarily in the eighth to ninth decades of
life. Pre-existing bicuspid valves with superimposed age-related degenerative
calcification generally become symptomatic earlier (usually sixth to seventh decades).
Nonrheumatic, calcific aortic stenosis (involving valves with either two or three cusps) is
characterized by heaped-up, calcified masses initiated in the cuspal fibrosa at the
points of maximal cusp flexion (the margins of attachment); they ultimately ulcerate and
protrude distally into the sinuses of Valsalva, inhibiting cuspal opening. Distinct from the
cellular proliferation and lipid deposition that typify atherosclerosis, the dystrophic
calcification process does not involve the free cuspal edges and largely preserves the
microscopic layered architecture. Aortic valve sclerosis comprises an earlier,
hemodynamically less significant, stage of the calcification process. In contrast to
rheumatic aortic stenosis, appreciable commissural fusion is absent and the mitral
valve generally is free of rheumatic changes.
Aortic valves are congenitally bicuspid in approximately 12 percent of the population.

Most frequently, the two cusps are of unequal size, with the larger (conjoined) cusp
having a midline raphe, representing an incomplete separation or congenital fusion of
two cusps. Less frequently, the cusps are of equal size, and a raphal ridge may or may
not be identifiable. When a raphe is present, the most commonly fused cusps are the
right and left, accounting for about 75 percent of cases. Neither stenotic nor
symptomatic at birth or throughout early life, bicuspid valves are predisposed to
accelerated calcification, especially along the raphe. Less often, they may become
incompetent, be complicated by infective endocarditis, or be associated with acute
aortic dissection.
Aortic stenosis leads to a gradually increasing pressure gradient across the valve,
which may reach 75100 mg Hg in severe cases, with a left ventricular pressure of 200
mg Hg or more; cardiac output is maintained by the development of concentric
(pressure overload) left ventricular hypertrophy. The onset of symptoms (particularly
angina, syncope, or heart failure) in aortic stenosis heralds the exhaustion of
compensatory cardiac hyperfunction, and therefore carries a poor prognosis if not
treated by aortic valve replacement (>50 percent mortality within 3 years). [129 ] If
cardiac output is low, as may occur in heart failure or in the elderly, then neither the
gradient nor the resultant murmur may appear significant. In this setting, critical aortic
stenosis can be overlooked clinically.
MITRAL ANNULAR CALCIFICATION
Degenerative calcific deposits also can develop in the ring (annulus) of the mitral valve
of elderly individuals, especially women, and may accompany mitral valve myxomatous
degeneration (see the following). Although generally asymptomatic, the calcific nodules
may lead to regurgitation by interference with systolic contraction of the mitral valve ring
or, very rarely, stenosis by impairing opening of the mitral leaflets. Occasionally, the
calcium deposits may penetrate sufficiently deeply to impinge on the atrioventricular
conduction system and produce arrhythmias (and rarely sudden death). Patients with
mitral annular calcification have an increased risk of stroke, and the calcific nodules can
be the nidus for thrombotic deposits or infective endocarditis. [130 ]
When valvular calcific deposits extend as nodules below the leaflets, leaflets can
become immobilized, producing either stenosis or regurgitation. As a general rule, for
both aortic and mitral valves, the more heavily calcified a valve becomes, the less likely
it is to become infected.
MYXOMATOUS DEGENERATION OF THE MITRAL VALVE (MITRAL VALVE

PROLAPSE)
Myxomatous mitral valve disease is the most frequent cause of chronic, pure, isolated
mitral regurgitation. [1 ] , [128 ] Usually, one or both mitral leaflets are enlarged,
redundant or floppy and prolapse, or balloon back into the left atrium, during ventricular
systole (see Fig. 4-19C ). The three essential anatomic changes in mitral valve prolapse
are (1) interchordal ballooning (hooding) of the mitral leaflets or portions thereof (most
frequently the posterior half of both leaflets), with or without elongated, thinned, or
ruptured cords; (2) rubbery diffuse leaflet thickening that hinders adequate coaptation
and interdigitation of leaflet tissue during valve closure; and (3) substantial annular
dilation, with diameters and circumferences usually exceeding 3.5 and 11.0 cm,
respectively (see Fig. 4-19D ). [131 ] Pathological mitral annular enlargement is usually
confined to the posterior leaflet, since the anterior leaflet is firmly anchored by the
fibrous tissue at the aortic valve end and is far less distensible. Histologically, the
essential change is attenuation or focal disruption of the fibrous layer of the valve, on
which the structural integrity of the leaflet depends. This is accompanied by focal or
diffuse thickening of the spongy layer. Deposited amorphous extracellular matrix gives
the tissue an edematous, blue appearance on routine hematoxylin and eosin staining,
an appearance called myxomatous by pathologists. Concomitant involvement of the
tricuspid valve is present in 2040 percent of cases, and the aortic and pulmonic valves
also may be affected. Myxomatous tricuspid valve may be associated with pulmonary
disease.
Secondary changes may occur, including: (1) focal pad-like fibrous thickening along
both surfaces of the valve leaflets; (2) linear thickening of the subjacent mural
endocardium of the left ventricle as a consequence of friction-induced injury by cordal
hamstringing of the prolapsing leaflets; (3) thrombi on the atrial surfaces of the leaflets,
particularly in the recesses behind the ballooned leaflet segments; (4) calcification
along the base of the posterior mitral leaflet; and (5) chordal thickening and fusion
(resembling post-rheumatic disease). In a presently largely unidentifiable subgroup of
affected individuals, mitral valve prolapse is associated with infective endocarditis,
stroke or other manifestation of thromboembolism, progressive congestive heart failure,
or sudden death. The pathogenesis is uncertain, but this valvular abnormality is one
common feature of Marfan's syndrome and occasionally occurs with other hereditary
disorders of connective tissues, suggesting an analogous but localized connective
tissue defect.
Distinction should be made between the clinical diagnosis of mitral valve prolapse in
young people and the pathologic diagnosis of a myxomatous (or floppy) mitral valve in
mature individuals. The former generally is associated with a competent and minimally
distorted valve and occurs in women about 1.5 times as frequently as in men. The latter,
in contrast, usually is severely regurgitant and structurally deformed and affects men
more often than women. More important, probably 95 percent of young people with
clinically detected mitral valve prolapse will never develop severely distorted and
incompetent mitral valves as they grow older.
RHEUMATIC HEART DISEASE
Rheumatic fever is an acute, often recurrent, inflammatory disease that generally follows
a pharyngeal (but not skin) infection with group A beta-hemolytic streptococci,
principally in children. [132 ] In the past several decades, rheumatic fever and rheumatic
heart disease have declined markedly but not disappeared in the United States and
other developed countries. Evidence strongly suggests that rheumatic fever is the result
of an immune response to streptococcal antigens, inciting either a cross reaction to
tissue antigens, or a streptococcal-induced autoimmune reaction to normal tissue
antigens. [133 ] The cardiac surgical implications of rheumatic fever primarily relate to
chronic rheumatic heart disease, characterized principally by chronic, progressive,
deforming valvular disease (particularly mitral stenosis), that produces permanent
dysfunction and severe, sometimes fatal, cardiac failure decades later.
Chronic rheumatic heart disease most frequently affects the mitral and to a lesser extent
the aortic and/or the tricuspid valves. Chronic rheumatic valve disease is characterized
by fibrous or fibrocalcific distortion of leaflets or cusps, valve commissures, and
chordae tendineae, with or without annular or papillary muscle deformities (see Figure
4-19A and Figure 4-19B) . Stenosis results from leaflet and chordal fibrous thickening
and from commissural and chordal fusion, with or without secondary calcification.
Regurgitation entails other mechanisms, including scarring-induced retraction of
chordae and leaflets and, less commonly, fusion of a commissure in an opened
position. Only very rarely does chordal rupture involve a rheumatic valve. Combinations
of lesions may yield valves that are both stenotic and regurgitant. Although considered
the pathognomonic inflammatory myocardial lesions in acute rheumatic fever, Aschoff
nodules are found infrequently in myocardium sampled very late at autopsy or at valve
replacement surgery, most likely reflecting the extended interval from acute disease to
critical functional impairment. [134 ]
INFECTIVE ENDOCARDITIS
Infective endocarditis is characterized by colonization or invasion of the heart valves,

mural endocardium, aorta, aneurysmal sacs, or other blood vessels by a microbiologic
agent, leading to the formation of friable vegetations laden with organisms. Virtually any
type of microbiologic agent can cause infective endocarditis, but most cases are
bacterial (i.e., bacterial endocarditis).
The clinical classification into acute and subacute forms is based on the range of
severity of the disease and its tempo, on the virulence of the infecting microorganism,
and on the presence of underlying cardiac disease. Acute endocarditis is a destructive
infection, often involving a previously normal heart valve, with a highly virulent organism,
that leads to death within days to weeks in over 50 percent of patients. In contrast, in
subacute endocarditis, organisms of low virulence cause infection on previously
deformed valves; the infection pursues a protracted course of weeks to months and
may be undetected and untreated.
Vegetations in both clinical variants are composed of fibrin, inflammatory cells, and
organisms. Staphylococcus aureus is the leading cause of acute endocarditis and
produces necrotizing, ulcerative, invasive, and highly destructive valvular infections.
Cardiac abnormalities, such as rheumatic heart disease, congenital heart disease
(particularly anomalies that have small shunts or tight stenoses creating high-velocity jet
streams), myxomatous mitral valve, only mildly calcified bicuspid aortic valve, and
artificial valves and their sewing rings predispose to the subacute form, usually caused
by Streptococcus viridans . In intravenous drug abusers, left-sided lesions
predominate, but right-sided valves are commonly affected; the usual organism is S.
aureus . [135 ] In about 520 percent of all cases of endocarditis, no organism can be
isolated from the blood (culture-negative endocarditis), often because of prior antibiotic
therapy.
The complications of endocarditis include valvular insufficiency (or rarely stenosis), ring
(annular) abscess, suppurative pericarditis, and embolization. With appropriate
antibiotic therapy, vegetations may undergo progressive sterilization, organization,
fibrosis, and occasionally calcification. Regurgitation generally occurs on the basis of
cusp or leaflet perforation, chordal rupture, or fistula formation (from a ring abscess into
an adjacent cardiac chamber or great vessel). Ring abscesses tend to be associated
with virulent organisms, are technically difficult to deal with surgically, and are
associated with a relatively high mortality rate.
Valve Reconstruction
Reconstructive procedures to eliminate mitral insufficiency of various etiologies and to
minimize the severity of rheumatic mitral stenosis are now highly effective and
commonplace, accounting presently for over 70 percent of mitral valve operations. [136
] , [137 ] Reconstructive therapy of selected patients with aortic insufficiency and aortic
dilatation may also be done [138 ] , [139 ] but repair of aortic stenosis has been notably
less successful. [138 ] [141 ] The major advantages of repair over replacement relate to
the elimination of both prosthesis-related complications and the need for chronic
anticoagulation. Other reported advantages include a lower hospital mortality, better
long-term function and a lower rate of postoperative endocarditis. Figure 4-20 illustrates
the pathologic anatomy of various mitral valve reconstruction procedures.
MITRAL VALVE REPAIR (see Figure 4-20 )
The hemodynamic disturbances in most forms of mitral valve disease are the result of
multiple structural deformities at different levels within the complex mitral apparatus.
Identification of each component of the anatomic lesion and an underlying
understanding of normal valve anatomy and function is essential to adequate valve
reconstruction. [23 ] , [136 ] , [137 ]
In general, reconstructive techniques are more easily applied to mitral valves with
nonrheumatic disease than those affected by rheumatic disease. [136 ] , [137 ] The
fibrosis and shortening of both chordae and leaflets that causes mitral stenosis and is
the result of an advanced rheumatic process that makes gaining adequate mobility and
adequate leaflet area difficult. Commissurotomy commonly is employed in the operative
repair of a stenotic mitral valve. In mitral stenosis, leaflet calcification, subvalvar
(predominantly chordal) fibrotic changes, and significant regurgitation owing to scar
retraction are major factors that inhibit reconstructive surgical repair, and thereby
necessitate valve replacement. Since the annular portions of the leaflet are normally
devoid of chordal support, splitting to 23 mm from the annulus may avoid the potential
complication of a new or residual regurgitant jet. Anterior leaflet mobility often is
sufficient to allow an acceptable mitral opening despite posterior leaflet immobility, and
pliable leaflets can partially compensate for a rigid subvalvar apparatus. Five factors
compromise the late functional results of mitral commissurotomy: (1) left ventricular
dysfunction; (2) pulmonary venous hypertension and right-sided cardiac factors,
including right ventricular failure, tricuspid regurgitation, or a combination of these; (3)
systemic embolization; (4) other co-existent cardiac disorders, such as coronary artery
or aortic valve diseases; (5) residual or progressive mitral valve disease. Late
deterioration following mitral commissurotomy may be owing to restenosis of the valve,
residual (unrelieved) stenosis, or regurgitation induced at operation.
The structural defects in mitral regurgitation include: (1) dilatation of the mitral annulus;
(2) elongation or rupture of chordae tendineae, permitting leaflet prolapse into the
atrium; (3) redundancy and deformity of leaflets; (4) leaflet perforations or defects; (5)
restricted leaflet motion as a result of commissural fusion in an opened position, and
leaflet retraction, chordal shortening or thickening or both. [23 ] Necrosis solely of a
papillary muscle following an acute myocardial infarction generally does not induce
insufficiency. More frequently, mitral regurgitation results from the underlying necrotic
and nonfunctional free wall segment or distortion of the papillary muscle geometry by
ventricular dilatation, where lateral movement of the papillary muscles alters the axis of
their tension on the cords.
Leaflet abnormalities in mitral regurgitation include retraction, redundancy or
perforation. The posterior leaflet is more delicate and has a shorter
annulus-to-free-edge dimension than the anterior. It is therefore more prone to
postinflammatory fibrous retraction. Following resection of excess anterior or posterior
leaflet tissue, as in floppy valves, annuloplasty with or without a prosthetic ring generally
is used to reduce the annulus dimension to correspond to the amount of leaflet tissue
available. Tissue substitutes such as glutaraldehyde-pretreated xenograft or autologous
pericardium can be used to repair or enlarge leaflets. A smooth white leaflet perforation
with raised borders suggests prior healed infection, whereas irregular pink-tan borders
or vegetations signal an active infection. Retracted or elongated chordae, respectively,
reduce or enhance leaflet mobility. Ruptured or elongated chordae may be treated by
shortening procedures or replacement with pericardial tissue or thick suture.
CATHETER BALLOON VALVULOPLASTY
Percutaneous transluminal balloon dilatation of stenotic valves has been used

successfully to relieve congenital and acquired stenoses of native pulmonary, aortic,
and mitral valves, and stenotic right-sided porcine bioprosthetic valves. [142 ] Mitral
valvuloplasty yields favorable results in elderly patients with mitral stenosis complicated
by pulmonary hypertension, a difficult group of patients to manage surgically. For
acquired calcific aortic stenosis, individual functional responses to balloon dilatation
vary considerably and data suggest a modest incremental benefit, high early mortality,
and high restenosis rate. [143 ] Some patients have dramatic improvement in valvular
and ventricular function, whereas others show little change. The major reported
complications of balloon valvuloplasty include cerebrovascular accident secondary to
embolism or massive regurgitation owing to valve trauma, cardiac perforation with
tamponade, and with mitral valvuloplasty, creation of an atrial septal defect owing to
septal dilatation. [142 ] , [143 ]
Improvement following catheter balloon valvuloplasty of aortic stenosis derives from

commissural separation, fracture of calcific deposits, and displacing and stretching of
the valve cusps. [142 ] , [143 ] Fractured calcific nodules can themselves prove
dangerous (Fig. 4-21) . [144 ] In pediatric cases in which the cusps are generally
pliable, cuspal stretching, tearing, or avulsion may also occur. In the relief of mitral
stenosis, balloon valvuloplasty largely involves commissural separation; thus, this
procedure is unlikely to provide significant alteration in the subvalvular pathology of the
chordae and papillary muscles of patients with rheumatic mitral stenosis. Commissural
splitting generally is successful only in valves with little or no commissural calcification.
Thus, balloon valvuloplasty has been far more applicable in third world countries in
which rheumatic mitral stenosis is commonly severe but noncalcific at a young age,
rather than in the United States, in which the disease is usually only severe and calcific
in middle-aged or elderly adults.
SURGICAL AND LASER DEBRIDEMENT
Since valvular aortic stenosis in most patients over 60 years of age is characterized by
calcific deposits superimposed upon a valve largely free of either congenital or
rheumatic deformities, such valves are stenotic simply because the leaflets are
immobilized by extensive deposits of calcium. However, because the calcific deposits
arise deep in the valve fibrous layer (see Fig. 4-18D and E ), their removal by sharp
dissection or ultrasonic debridement generally requires dissection that removes this
layer and may cause damage to the spongiosa layer, resulting in severe compromise of
cuspal mechanical integrity. [140 ] , [141 ] In some cases, the vegetations of infective
endocarditis may be surgically debrided.
Valve Replacement
Severe symptomatic valvular heart disease other than pure mitral stenosis of
incompetence is most frequently treated by excision of the diseased valve(s) and
replacement by a functional substitute. [145 ] Five factors principally determine the
results of valve replacement in an individual patient: (1) technical aspects of the
procedure; (2) intraoperative myocardial ischemic injury; (3) irreversible and chronic
structural alterations in the heart and lungs secondary to the valvular abnormality; (4)
coexistent obstructive coronary artery disease; and (5) valve prosthesis reliability and
host-tissue interactions. [23 ]
VALVE TYPES AND PROGNOSTIC CONSIDERATIONS
Cardiac valvular substitutes are of two generic types, mechanical and biological tissue (
Fig. 4-22 and Table 4-2 ). [146 ] [150 ] Prostheses function passively, responding to
pressure and flow changes within the heart. Mechanical valves are usually composed of
non-physiologic biomaterials that employ a rigid, mobile occluder (pyrolytic carbon disk)
in a metallic cage (cobalt-chrome or titanium alloy [Bjork-Shiley, Hall-Medtronic, or
OmniScience valves]) or two carbon hemidisks in a carbon housing (St. Jude Medical,
Edwards-Duromedics, or CarboMedics CPHV prostheses). Pyrolytic carbon has high
strength and fatigue and wear resistance, with exceptional biocompatibility, including
thromboresistence. [151 ] In contrast, tissue valves are, to a large extent, anatomically
similar to natural valves. The major advantages of tissue valves compared to
mechanical prostheses are their pseudo-anatomic central flow and relative
nonthrombogenicity, usually not requiring anticoagulant therapy. [147 ] , [149 ]
Approximately two-thirds of all valves implanted in the present era are mechanical
(mostly bileaflet tilting disk); nearly one-third are bioprosthetic (mostly xenografts
fabricated from porcine aortic valve, which have been preserved in a dilute
glutaraldehyde solution), and a small percentage are cryopreserved allografts (Fig.
4-23) . [150 ]
It is well accepted (but not proven) that in both animals and patients, valve replacement
that preserves chordae and papillary muscles is associated with better postoperative
left ventricular function when compared with replacement surgery that destroys the
subvalvular apparatus, especially in patients with mitral regurgitation and impaired left
ventricular performance. [152 ] , [153 ] Analogously, this may be the reason why
ventricular function is better preserved after mitral valve repair than after valve
replacement. With modern substitute valves, especially bileaflet tilting disk valves that
offer protection of the poppets from interference, a major drawback to prosthetic leaflet
retention has been obviated.
Early mortality after cardiac valve replacement now is generally in the range of 35
percent, with the majority of deaths owing to hemorrhage, pulmonary failure, low cardiac
output, and sudden death (with or without myocardial necrosis or documented
arrhythmias). Early prosthetic valve-associated complications are unusual. [154 ]
Potential complications related to valve insertion include hemorrhagic disruption and
dissection of the atrioventricular groove, perforation, or entrapment of the left circumflex
coronary artery by a suture, and pseudoaneurysm or rupture of the left ventricular free
wall. An additional advantage of resecting only the anterior leaflet and leaving the
posterior leaflet intact is that postoperative rupture of the left ventricular free wall has
nearly disappeared as a complication of mitral valve replacement.
Improvement in late outcome derives from earlier referral of patients for valve
replacement, decreased intraoperative myocardial damage, and improved cardiac
valve prostheses. Following valve replacement with currently used devices, the
probability of 5-year survival is about 80 percent and of 10-year survival about 70
percent, dependent on overall functional state, preoperative left ventricular function, left
ventricular and left atrial size, and extent and severity of coronary artery disease. [145 ] ,
[148 ] , [155 ]
VALVE-RELATED COMPLICATIONS
Prosthetic valve-associated pathology is common beyond the early postoperative

period. The few randomized studies available show that with contemporary mechanical
prosthetic and bioprosthetic valves, approximately 60 percent or more patients have an
important device-related complication within 10 years postoperatively. [148 ] , [155 ] ,
[156 ] However, as discussed in the following, thrombotic and thromboembolic
problems that frequently complicate mechanical valves tend to occur earlier than the
structural failures that complicate tissue valve prostheses. [157 ] Valve-related
complications frequently necessitate reoperation, now accounting for approximately
515 percent of all valve procedures, and they may cause death. Late death following
valve replacement results predominantly from either cardiovascular pathology not
related to the substitute valve or prosthesis-associated complications. [23 ] , [145 ] ,
[154 ] Moreover, late death is caused by a device-related complication in 2561 percent
of patients. [23 ] , [154 ] , [158 ] As might be expected, autopsy studies generally reveal
a higher rate of valve-related pathology than clinical investigations. One-fifth or more of
valve recipients will ultimately die suddenly; in a recent autopsy study of a highly
selected referral population, 40 percent of valve recipients who died suddenly had a
valve-related cause. [159 ]
Four categories of valve-related complications are most important: thromboembolism

and related problems, infection, structural dysfunction (i.e., failure or degeneration of the
biomaterials comprising a prosthesis), and nonstructural dysfunction (i.e.,
miscellaneous complications and modes of failure not encompassed in the previous
groups) ( Table 4-2 ). [23 ] , [145 ] , [150 ] , [154 ] [169 ] The clinicomorphologic features
of these problems have been widely described in the literature. [165 ] [169 ] The relative
performance and risk of complications of various types of widely used substitute heart
valve types is summarized in Table 4-3 .The risk of some valve-related complications
(particularly thromboembolism) is potentiated by preoperative functional impairment.
Thromboembolic complications are the major cause of mortality and morbidity after
cardiac valve replacement with mechanical valves, and patients with them require
chronic therapeutic anticoagulation with warfarin derivatives. [23 ] , [146 ] , [148 ] , [149 ]
, [155 ] [157 ] , [170 ] Thrombotic deposits can immobilize the occluder or shed emboli
(Fig. 4-24) . Tissue valves are less thrombogenic than mechanical valves. Most patients
with bioprostheses and other tissue valves are not maintained on long-term
anticoagulation, unless they have atrial fibrillation or another specific indication.
Nevertheless, the rate of thromboembolism in patients with mechanical valves on
anticoagulation is not widely different from that in patients with bioprosthetic valves
without anticoagulation (24 percent per year). [148 ] , [149 ] Chronic oral anticoagulation
also induces a risk of hemorrhage. [146 ] , [148 ] , [149 ] , [169 ] , [171 ] A recent study
suggested that the optimal intensity of anticoagulation in patients with mechanical heart
valves (balancing both thromboembolism and bleeding) both at approximately 2 percent
per year was best achieved with a target INR (international normalized ratio) of 3.04.0.
[172 ]
As in the cardiovascular system in general, Virchow's triad of factors promoting

thrombosis (surface thrombogenicity, hypercoagulability, and locally static blood flow)
largely predicts the relative propensity toward and locations of thrombotic deposits. [23 ]
, [56 ] , [167 ] For example, with caged-ball prostheses, thrombi form distal to the
poppet at the cage apex. Moreover, tilting disk prostheses are particularly susceptible
to total thrombotic occlusion or emboli from small thrombi, both generally initiated in a
stagnation zone in the minor orifice of the outflow region of the prosthesis. In contrast,
late thrombosis of a bioprosthetic valve is unusual and, in most such cases, large
thrombotic deposits are usually present in one or more of the prosthetic sinuses of
Valsalva. [23 ] , [56 ] , [167 ] Usually, no causal underlying cuspal pathology can be
demonstrated by routine microscopic studies. Noninvasive visualization of prosthetic
valve thrombi is aided by transesophageal endocardiography. [173 ]
As with other devices in which nonphysiologic artificial surfaces are exposed to blood at
high fluid shear stresses, platelet deposition dominates initial blood-surface interaction
and prosthetic valve thromboembolism correlates strongly with altered platelet function.
[23 ] , [56 ] , [174 ] Nevertheless, although platelet-suppressive drugs largely normalize
indices of platelet formation and partially reduce the frequency of thromboembolic
complications in patients with mechanical prosthetic valves, antiplatelet therapy alone
does not adequately prevent thromboembolism. [175 ] The friability and thus
susceptibility to embolization of thrombi that form on bioprosthetic or mechanical valves
is prolonged, because lack of adjacent vascular tissue retards their histologic
organization. [23 ] For similar reasons, the age of such thrombi is difficult to determine
microscopically. Moreover, in selected circumstances, thrombolytic therapy may be a
practical nonsurgical option. [176 ] Some valve thromboemboli, especially early
postoperatively, are thought to be initiated at the valve sewing cuff.
High-intensity transcranial Doppler signals are reported to occur in many patients with
heart valve prostheses. Although presumed by several authors to represent subclinical
emboli, the origin and clinical significance of these signals is uncertain. [177 ] , [178 ]
Illustrated in Figure 4-25 , prosthetic valve infective endocarditis occurs in 36 percent of

recipients of substitute valves. [23 ] , [148 ] , [149 ] , [179 ] Infection is generally
categorized into early (less than 60 days postoperative) and late. [180 ] , [181 ] The
microbial etiology of early prosthetic valve endocarditisis dominated by staphylococcal
species, S. epidermidis and S. aureus , even though prophylactic regimens used today
are targeted against these microorganisms. The clinical course of early prosthetic valve
endocarditis tends to be frequently fulminant, with rapid deterioration of the
hemodynamic status due to valvular or annular destruction or persistent bacteremia.
[180 ] In late endocarditis, a probable source of infection can be found in 2580 percent
of patients, the most frequent causes being dental procedures, urological infections and
interventions, and indwelling catheters. [181 ] The most common organisms are S.
epidermidis, S. aureus, Streptococcus viridans , and enterococci. Surgical
reintervention usually is indicated by large highly mobile vegetations or if there are
cerebral thromboembolic episodes. Transesophageal echocardiography enhances
diagnosis of prosthetic valve endocarditis and its intracardiac complications. [182 ] The
rates of infection of bioprostheses and mechanical valves are similar, but previous
endocarditis markedly increases the risk.
Virtually all infections associated with mechanical prosthetic valves and some with
bioprosthetic valves are localized to the prosthesis-tissue junction at the sewing ring,
and accompanied tissue destruction around the prosthesis (see Fig. 4-25A ). [23 ] ,
[166 ] , [167 ] , [183 ] , [184 ] This comprises a ring abscess, with potential valve
dehiscence, paraprosthetic leaks, fistula formation, or heart block caused by conduction
system damage. In addition, bioprosthetic valve infections may involve, and indeed are
occasionally limited to, the cuspal tissue, sometimes causing secondary cuspal tearing
or perforation with valve incompetence or obstruction (see Fig. 4-25B ). [23 ] , [161 ] ,
[162 ] , [167 ] , [168 ] Cases without annular involvement have a better prognosis than
those associated with infected annular margins of resection. Additional complications
of prosthetic valve endocarditis include embolization of vegetations and congestive
heart failure secondary to obstruction or regurgitation.
Prosthetic valve dysfunction owing to materials degradation can necessitate

reoperation or cause prosthesis-associated death (see Fig. 4-26 ). [23 ] , [147 ] , [150 ]
, [155 ] [169 ] Durability considerations vary widely for mechanical valves and
bioprostheses, for specific types of each, for different models of a particular prosthesis
(utilizing different materials or having different design features), and even for the same
model prosthesis placed in the aortic rather than the mitral site. [23 ] , [167 ] , [168 ]
Fractures of metallic or carbon valve components occur rarely. [23 ] , [151 ] , [185 ] Of
approximately 86,000 Bjork-Shiley 60- and 70-degree Convexo-Concave heart valves
implanted, a cluster of over 500 cases has been reported in which the welded outlet
strut fractured because of metal fatigue, leading to disk escape (see Figure 4-26A ).
[23 ] , [146 ] , [148 ] , [149 ] , [160 ] [167 ] , [169 ] Although complete strut fracture is
usually fatal, elective removal of structurally intact prostheses is not recommended.
However, a new cineangiographic imaging technique may facilitate detection of single
leg strut fractures at a presymptomatic stage, thereby allowing consideration of elective
valve removal. [186 ] , [187 ] In contrast, fractures of carbon components (disks or
housing) are unusual in single bileaflet tilting disk valves. [23 ] , [151 ] , [160 ] , [167 ] ,
[188 ] However, a group of 37 fractures of an estimated 20,000 Edwards-Duramedics
bileaflet-tilting valves has occurred, possibly a combined result of carbon coating
defects and cavitation bubbles impacting on the carbon surfaces during function. [189 ] ,
[190 ]
Structural dysfunction of tissue valves is the major cause of failure of the most widely
used bioprostheses (flexible-stent-mounted, glutaraldehyde-preserved porcine aortic
valves [Hancock and Carpentier-Edwards types]) (see Figs. 4-26B and 4-26C ). [23 ] ,
[147 ] [149 ] , [157 ] , [160 ] [164 ] , [167 ] , [168 ] , [192 ] Within 15 years following
implantation, 3050 percent of porcine aortic valves implanted as either mitral or aortic
valve replacements require replacement because of primary tissue failure. [23 ] , [147 ]
[149 ] , [161 ] , [167 ] , [193 ] Cuspal mineralization is the major responsible pathologic
process. [23 ] , [147 ] , [167 ] , [191 ] , [192 ] Regurgitation through secondary tears is
the most frequent failure mode. Pure stenosis owing to calcific cuspal stiffening and
noncalcific cuspal tears or perforations (reflecting direct mechanical destruction of
collagen) occur less frequently. [191 ] Calcific deposits are usually localized to cuspal
tissue (intrinsic calcification), but calcific deposits extrinsic to the cusps may occur in
thrombi or endocarditic vegetations. [23 ] , [161 ] , [162 ] , [191 ] [195 ] Calcification is
markedly accelerated in younger patients with children and adolescents having an
especially accelerated course. [23 ] , [147 ] , [192 ] , [193 ]
Bovine pericardial valves suffer primarily design-related tearing, with calcification

frequent but less limiting (see Fig. 4-26D ). [23 ] , [161 ] , [196 ] , [197 ] Abrasion of the
pericardial tissue is an important contributing factor. [198 ] Bioprosthetic valve failure
generally causes slowly progressive symptomatic deterioration, permitting reoperation.
In contrast, mechanical valve failure is often catastrophic and may be life-threatening.
The morphology and determinants of calcification of bioprosthetic valve tissue have

been widely studied in experimental models. [23 ] , [161 ] , [192 ] The process is
initiated primarily within residual membranes and organelles of connective tissue cells
that are devitalized by glutaraldehyde pretreatment procedures. [23 ] , [192 ] , [199 ] ,
[200 ] The dystrophic calcification mechanism involves reaction of calcium-containing
extracellular fluid with membrane-associated phosphorus. Subsequently, calcification of
collagen occurs. The determinants of calcification include recipient metabolic factors
(young age potentiates), valve factors (glutaraldehyde fixation enhances), and
mechanical stress (accelerates). Since the endothelium of contemporary tissue heart
valves is lost and their cells are nonviable, valve function resides in the integrity of the
collagenous skeleton. However, without viable intravalvular fibroblasts, there is no way
to repair or replenish collagen fibers that are damaged by normal wear-and-tear. An
additional problem is that valve preservation causes the collagen to be mechanically
locked so that normal cyclical cuspal deformation is inhibited, inducing abnormal
stresses. Moreover, residual nonviable connective tissue cells serve no apparent
beneficial role and, indeed, can be deleterious (e.g., causing calcification and
potentially an immune response).
Commissural region dehiscence of the aortic wall tissue from the inside of the stent of
porcine bioprosthetic valve in the mitral position causing mitral insufficiency has recently
been described. Primarily reported for Carpentier-Edwards bioprostheses, this
complication has also been noted in Hancock porcine valves of several models (Fig.
4-27) . [201 ] , [202 ]
Paravalvular defects may be clinically inconsequential or they may aggravate hemolysis

or cause heart failure through regurgitation. Early paravalvular leak usually is the result
of either suture knot failure, inadequate suture placement, or separation of sutures from
a pathologic annulus in endocarditis with ring abscess, myxomatous valvular
degeneration (floppy mitral valve), or calcified valvular annulus (calcific aortic stenosis
or mitral annular calcification). Small and difficult to locate by surgical or pathological
examination, late small paravalvular leaks usually are caused by anomalous tissue
retraction from the sewing ring between sutures during healing (Fig. 4-28A) .
Hemolysis owing to turbulent flow and blood-material surface interactions is an

ever-present risk. It was more common with earlier-model heart valve prostheses and
resulted in renal tubular hemosiderosis or cholelithiasis in many patients. Although
severe hemolytic anemia is unusual with contemporary valves, paravalvular leaks or
dysfunction owing to materials degeneration may induce clinically important hemolysis.
Extrinsic factors can mediate late prosthetic valve stenosis or regurgitation, including a
large mitral annular calcific nodule, septal hypertrophy, exuberant overgrowth of fibrous
tissue (Fig. 4-28B) , interference by retained valve remnants (such as a retained
posterior mitral leaflet or components of submitral apparatus) (Fig. 4-28C) or unraveled,
long or looped sutures or knots ( Fig. 4-28D , Fig. 4-28E , and Fig. 4-28F ). For
bioprosthetic valves, cuspal motion can be restricted by sutures looped around stents,
and suture ends cut too long may erode into or perforate a bioprosthetic valve cusp.
VALVULAR ALLOGRAFTS/HOMOGRAFTS
Aortic or pulmonic valves (with or without associated vascular conduits) transplanted

from one individual to another have exceptionally good hemodynamic profiles, a low
incidence of thromboembolic complications without chronic anticoagulation, and a low
reinfection rate following valve replacement for endocarditis. [203 ] , [204 ] Early valvular
allografts sterilized and/or preserved with chemicals (using propriolactone or ethylene
oxide) or irradiation suffered a high rate of leaflet calcification and rupture yielding
failure rates of near 50 percent at 1012 years and 5090 percent at 1520 years. [205 ]
Pathologic examination of such valves revealed variable host fibrous tissue overgrowth,
and marked structural changes, including loss of architectural elements and cellularity,
fibrosis, calcification, and often cuspal ruptures. [206 ] , [207 ]
Subsequent technical developments have led to cryopreserved allografts, in which

freezing is performed with protection from crystallization by dimethyl-sulfoxide; storage
until valve use is carried out at -196°C in liquid nitrogen. Contemporary allograft valves
yield freedom from degeneration and/or replacement times equal to or better than those
of conventional porcine bioprosthetic valves (approximately 5090 percent valve survival
at 1015 years compared with 4060 percent for bioprostheses). [202 ] [204 ]
Some studies suggest that a fraction of viable cells may remain at the time of
implantation of grafts cryopreserved using current technology. [208 ] However, unknown
are the extent of residual cells and their functional activity on the one hand, and whether
allograft cell viability at implantation is an important determinant of long-term durability
on the other. While cellular preservation can be postulated to enhance both
thromboresistance and durability, the presence of viable cells could have deleterious
consequences, through potentiating immunological reactivity. [209 ]
We recently studied 33 explanted left- and right-sided cryopreserved human allograft

heart valves/conduits in place several hours to 9 years. [209 ] Cryopreserved human
allograft heart valves/conduits implanted >1 day had progressively severe loss of
normal structural demarcations. Long-term explants were generally devoid of both
surface endothelium and deep connective tissue cells and had hyalinized collagen,
laminated elastin, and minimal inflammatory cellularity (Fig. 4-29) . Our studies and
others demonstrate that cryopreserved allograft heart valves/conduits are
morphologically non-viable, their structural basis for function seems primarily related to
the largely preserved collagen. They are unlikely to have the capacity to grow, remodel,
or exhibit active metabolic functions and their degeneration generally is not secondary
to immunologic responses.
PULMONARY VALVULAR AUTOGRAFTS
Often called the Ross operation in recognition of its originator, pulmonary autograft
replacement of the aortic valve is technically difficult but avoids anticoagulation, carries
a low risk of thromboembolism, is purported to permit growth of the autograft
proportional to the somatic growth of a child or young adult, and has excellent
hemodynamic performance. [210 ] [212 ] The risk of late valve failure requiring
reoperation for either the autograft valve or the homograft right ventricular outflow tract
reconstruction is low. Ross and associates have reported freedom from autograft
replacement of 85 percent at 20 years and a freedom from all valve-related events of 70
percent at 20 years. With the more recently used implantation of the autograft as a root
replacement and the cryopreserved pulmonary homograft for right ventricular outflow
tract reconstruction, actuarial freedom from reoperation (autograft or homograft) was 89
percent ± 3 percent at 5 years, and 92 percent ± 3 percent for the autograft alone. [212 ]
Late autograft valve failure was most frequently due to aortic annulus dilatation and less
frequently to degeneration. Autograft dysfunction can be corrected by autograft repair in
patients with central insufficiency and aortic annular dilatation. The long-term structure of
valvular autografts has not yet been reported.
NEW DEVELOPMENTS
Methods are being actively sought and studied to prevent calcification in bioprosthetic
valves. [161 ] [167 ] [192 ] [213 ] [216 ] Other approaches to provide improved valves
include modifications of bioprosthetic valve stent design and tissue mounting
techniques to reduce cuspal stresses, tissue treatments alternative to glutaraldehyde to
enhance durability and post-implantation biocompatibility, non-stented porcine valves,
minimally cross-linked autologous pericardial valves, flexible trileaflet polymeric
(polyurethane) prostheses, and mechanical and tissue valves with novel design features
to improve hemodynamics, enhance durability, and reduce thromboembolism. [216 ]
MYOCARDIAL DISEASE
Two broad categories of myocardial disease are distinguished: cardiomyopathy (CM),

defined as heart muscle disease of unknown cause, generally referred to as primary or
idiopathic cardiomyopathy; and specific cardiomyopathy, formerly called specific heart
muscle disease, defined as heart muscle disease of known cause or associated with
disorders of other systems. [217 ] , [218 ] Myocardial dysfunction also frequently occurs
as a complication of ischemic, valvular, hypertensive (systemic and pulmonary), and
congenital heart disease and some pericardial disease, through hypertrophy and
subsequent degenerative changes and/or ischemic damage. [1 ] Impairment of
ventricular performance in the setting of coronary atherosclerosis often is called
ischemic cardiomyopathy.
There are three functional/pathophysiologic/anatomic patternsdilated, hypertrophic or

restrictive. [1 ] For each, the cause may be known or unknown. The cause of a specific
cardiomyopathy is usually revealed by light and/or electron microscopic examination,
whereas the morphology is non-specifically abnormal in idiopathic cardiomyopathy.
Moreover, in idiopathic dilated cardiomyopathy, the severity of the morphologic
changes does not necessarily correlate with the severity of dysfunction or the patient's
prognosis.
Endomyocardial biopsy has been used widely in the diagnosis and management of
patients with myocardial disease and in the ongoing surveillance of cardiac transplant
recipients. [219 ] The bioptome, inserted into the right internal jugular or femoral vein
and advanced under fluoroscopic or echocardiographic guidance through the tricuspid
valve, obtains 1- to 3-mm fragments of endomyocardium, most frequently derived from
the apical half of the right side of the ventricular septum. Interpretation of right-sided
biopsy specimens assumes that this location produces representative pathology. Since
most myocardial diseases affect both ventricles, correlation between right- and
left-sided findings generally is good.
Cardiomyopathy
DILATED CARDIOMYOPATHY
Idiopathic dilated cardiomyopathy is characterized by biventricular hypertrophy and

four-chamber dilatation of unknown cause and by subsequent cardiac failure. [1 ] , [23 ] ,
[217 ] , [218 ] Genetic influences have been documented increasingly, and dilated
cardiomyopathy has a familial occurrence in approximately 25 percent of cases, with
autosomal dominant, autosomal recessive, and X-linked inheritance variably proposed
for particular kindreds. [220 ] A history of chronic alcoholism can be elicited in 20
percent of patients, and biopsy-proved myocarditis precedes the development of
cardiomyopathy in 510 percent. Pregnancy-associated nutritional deficiency or
immunological reaction is another possible contributory factor.
The primary functional abnormality in dilated cardiomyopathy is impairment of left

ventricular systolic function, as measured by the ejection fraction (<25 percent in
end-stage, normal approximately 5065 percent). Pathologic findings include
cardiomegaly with heart weight two to three times normal and four-chamber dilatation.
Cardiac mural thrombi, a potential source of thromboemboli, are sometimes present
and may occur in any chamber. The histologic changes comprise myocyte hypertrophy
and interstitial and endocardial fibrosis of variable degree, but they do not reflect an
etiologic agent.
A recently described variant is arrhythmogenic right ventricular cardiomyopathy or

arrhythmogenic right ventricular dysplasia, characterized by a focally to generally, but
severely, thinned right ventricular wall, with extensive fatty infiltration, loss of myocytes,
myocyte hypertrophy and interstitial fibrosis, with or without inflammation. [221 ] , [222 ]
Sometimes familial, this disorder is most commonly associated with right-sided and
sometimes left-sided heart failure and various rhythm disturbances, particularly
ventricular tachycardia and sudden death. [223 ]
HYPERTROPHIC CARDIOMYOPATHY
Hypertrophic cardiomyopathy is characterized by a heavy muscular hypercontracting

heart, in striking contrast to the flabby, hypocontracting heart of dilated cardiomyopathy.
It represents a diastolic, rather than systolic, disorder.
The essential anatomic feature of hypertrophic cardiomyopathy is massive myocardial

hypertrophy without dilatation. [1 ] , [23 ] , [217 ] , [224 ] , [225 ] The classic pattern is
characterized by disproportionate thickening of the ventricular septum relative to the
free wall of the left ventricle (ratio >1.5), frequently termed asymmetric septal
hypertrophy, and usually localized to the subaortic region. When the basal septum is
markedly thickened at the level of the mitral valve, the outflow of the left ventricle may be
narrowed during systole. Endocardial thickening in the left ventricular outflow tract and
thickening of the anterior mitral leaflet result from contact between the two during
ventricular systole (observed by echocardiography as systolic anterior motion of the
mitral valve), correlating with systolic left ventricular outflow tract obstruction. Nonclassic
cases also exist. In about 10 percent of cases, left ventricular hypertrophy is symmetric,
and in other cases disproportionate hypertrophy involves the midventricular or apical
septum, extends onto the left ventricular free wall anteriorly or inferiorly, or causes right
ventricular outflow tract obstruction.
The most important microscopic features in hypertrophic cardiomyopathy include: (1)

haphazard disarray of myocytes and contractile elements within cells (myofiber
disarray) typically involving 1050 percent of the septum; (2) extreme myocyte
hypertrophy, with transverse myocyte diameters frequently more than 40 µm (normal
approximately 1520 µm); and (3) interstitial and replacement fibrosis. [1 ] , [218 ]
Nevertheless, despite these distinctive structural abnormalities, the diagnosis of
hypertrophic cardiomyopathy cannot be made on endomyocardial biopsy. Hypertensive
heart disease coupled with age-related sub-aortic septal hypertrophy, amyloidosis, and
occasionally, valvular or congenital sub-valvular aortic stenosis, various storage
diseases, and mitochondrial cardiomyopathy can also mimic hypertrophic
cardiomyopathy.
Hypertrophic cardiomyopathy has an extremely variable course, with potential

complications including atrial fibrillation with mural thrombus formation, embolization
from the mural thrombi, infective endocarditis of the mitral valve, intractable cardiac
failure, and sudden death. [1 ] , [218 ] , [225 ] Sudden death occurs in approximately 23
percent of adults and 46 percent of children per year and is the most common cause of
death. It is particularly likely in young males with familial hypertrophic cardiomyopathy or
with a family history of sudden death. In hypertrophic cardiomyopathy, cardiac failure is
owing to reduced stroke volume that results from decreased diastolic filling of the
massively hypertrophied left ventricle. Although symptoms are not owing solely to
thickening of the ventricular septum, some patients benefit from thinning of the septum
by surgical myotomy/myectomy. End-stage heart failure can be accompanied by
dilatation, for which cardiac transplantation may be recommended.
Hypertrophic cardiomyopathy has a genetic basis in many cases. [226 ] [228 ] In

approximately half or more of patients the disease is familial, and the pattern of
transmission is autosomal dominant with variable expression; remaining cases appear
to be sporadic. In several kindreds with hypertrophic cardiomyopathy, various missense
mutations have been identified in the genes for either isoforms of the heavy chain of
cardiac myosin (the principal contractile protein in the thick filaments of muscle
sarcomeres, located on chromosome 14), or other contractile proteins. [226 ] [228 ] The
mechanism by which defective sarcomeric proteins produce the phenotype of
hypertrophic cardiomyopathy is uncertain. Interestingly, the different responsible gene
mutations carry vastly differing prognoses and certain genetic defects indicate a
relatively high likelihood of sudden death. [228 ]
RESTRICTIVE CARDIOMYOPATHY
Restrictive cardiomyopathy is characterized by impeded diastolic relaxation and left

ventricular filling. Left ventricular contractile (systolic) function is often unaffected.
Morphologically, the ventricles are of approximately normal size or slightly enlarged, but
the cavities are not dilated (unless valvular regurgitation coexists), and the myocardium
is firm. Biatrial dilatation commonly is observed. Any disorder that interferes with
ventricular filling can cause restrictive cardiomyopathy (including eosinophilic
endomyocardial disease, amyloidosis, or postirradiation fibrosis), or mimic it
(constrictive pericarditis or hypertrophic cardiomyopathy). Distinct morphologic patterns
indicative of specific heart muscle disease may be revealed by light or electron
microscopy of endomyocardial biopsy specimens, including amyloid deposition, or
products of an inborn error of metabolism. [1 ] , [219 ]
Cardiac transplantation provides long-term survival and rehabilitation to many

individuals with end-stage cardiac failure. [229 ] Overall predicted 1-year survival is
presently approximately 80 percent and 5-year survival is about 60 percent. [230 ] The
most common indications for cardiac transplantation, accounting for 90 percent of the
patients, are idiopathic cardiomyopathy and end-stage ischemic heart disease; other
recipients have congenital, other myocardial, or valvular heart disease. [23 ] , [229 ] ,
[231 ]
Explanted hearts typically have the expected pathologic features of the underlying
diseases. However, previously undiagnosed conditions and unexpected findings may
be encountered. Most frequent is eosinophilic or hypersensitivity myocarditis, seen in
approximately 20 percent of explants and characterized by a focal or diffuse mixed
inflammatory infiltrate, rich in eosinophils, and generally associated with minimal
associated myocyte necrosis. [232 ] , [233 ] In virtually all cases, the myocarditis
represents hypersensitivity to one or more of the many drugs taken by transplant
candidates, including dobutamine, and is unrelated to but superimposed on the original
disease necessitating transplantation. [233 ] It is important to recognize that several
diseases responsible for the original cardiac failure can recur in and cause dysfunction
of the allograft. These include amyloidosis, sarcoidosis, giant-cell myocarditis, acute
rheumatic carditis, and Chagas' disease. [231 ] , [234 ]
Recipients of heart transplants undergo surveillance endomyocardial biopsies

according to an institution-specific schedule, that typically evolves from weekly during
the early postoperative period, to twice weekly until 36 months, and then approximately
two to four times annually following 1 year, or at any time when there is a change in
clinical state. [231 ] , [234 ] Histologic findings of rejection frequently precede clinical
signs and symptoms of acute rejection. Optimal biopsy interpretation requires at least
four pieces of myocardial tissue; reviews of technical details and artifacts are available.
[23 ] , [231 ] , [234 ] , [235 ]
The major sources of mortality and morbidity following cardiac transplantation are
perioperative ischemic injury, infection, allograft rejection, lymphoproliferative disease,
and obstructive graft vasculopathy. [23 ] , [27 ] , [230 ] , [231 ] , [234 ] , [235 ] Cardiac
pathologists play an important role in the management of cardiac transplant recipients
through the evaluation of endomyocardial biopsies for rejection and other pathological
findings, and the effective communication of results to the clinical team.
Although there is considerable interest in xenotransplantation, especially using

miniature swine as organ donors, a discussion of relevant pathology is beyond the
scope of this chapter. [236 ]
EARLY ISCHEMIC INJURY
Ischemic injury can originate in the obligatory ischemia that accompanies procurement
and implantation of the donor heart. Several time intervals are potentially important: (1)
the donor interval between brain death and heart removal, perhaps partially related to
terminal administration of pressor agents; (2) the interval of warm ischemia between
donor cardiectomy to cold storage during transportation from donor to recipient; (3) the
interval during cold transport; and (4) during warming, trimming, and reimplantation, or
some combination of these. As in other situations of transient myocardial ischemia,
either frank necrosis or prolonged ischemic dysfunction of viable myocardium or both
may be present. Massive myocardial injury can cause potentially fatal low cardiac output
in the perioperative period. [27 ] Donor cardiac hypertrophy and/or pre-existing
coronary obstructions may contribute to inadequate preservation.
Perioperative myocardial ischemic injury as diagnosed by conventional histologic

criteria is prevalent in endomyocardial biopsies early after heart transplantation at some
institutions. [27 ] , [231 ] , [234 ] , [237 ] The histologic progression of healing of
myocardial necroses in transplanted hearts, as noted on subsequent endomyocardial
biopsies, is prolonged and the cellular infiltrate may be distorted owing to the
anti-inflammatory effects of immunosuppressive therapy ( Figs. 4-30 and 4-31 ).
Therefore, the repair phase of perioperative myocardial necrosis frequently confounds
the diagnosis of rejection in the first postoperative month, and in some cases, for as
long as 6 weeks. [27 ] In contrast, ischemic necrosis noted following 36 months
postoperatively is usually secondary to occlusive graft vasculopathy (see the following).
It remains to be determined whether and to what degree early ischemic injury has a late
impact on allograft dysfunction, possibly through loss of myocytes, accumulation of
fibrosis, potentiation of rejection, or stimulation or graft vasculopathy (through
associated vascular ischemic damage).
REJECTION
Improved current clinical immunosuppressive regimens in heart transplant patients have

substantially decreased the incidence of serious rejection episodes. [229 ]
Nonetheless, rejection phenomena still cause cardiac failure or serious arrhythmias in
some patients. Hyperacute rejection occurs rarely, most often when a major blood
group incompatibility exists between donor and recipient, and acute rejection is unusual
earlier than 24 weeks postoperatively. [234 ] Acute rejection episodes occur largely but
not exclusively in the first several months after transplantation. However, since rejection
can occur years postoperatively, many transplant centers continue late surveillance
biopsies at widely spaced intervals. [238 ]
The histological features of acute rejection are an inflammatory cell infiltrate, with or
without damage to cardiac myocytes; in late stages, vascular injury may become
prominent (Fig. 4-32) . [23 ] , [230 ] , [233 ] , [234 ] In general increasing numerical
grades of rejection represent escalating severity of the rejection response, as
manifested by the number and intensity of inflammatory cells, inflammatory foci, and
amount of myocyte and ultimately vascular damage. The histologic diagnosis and
grading of acute rejection on serial endomyocardial biopsies, based on the
morphologic features originally described by Billingham, is used to guide the
immunosuppressive therapy of heart transplant recipients. [23 ] , [231 ] , [234 ] , [239 ] ,
[240 ] Effective communication of results is facilitated through consistent reporting of
histologic results by the pathologist to the clinical team, which itself has calibrated usual
clinical responses to the specific morphology. Grading schemes facilitate
communication between pathologists and clinicians; the essential logic of a grading
scheme is summarized in Table 4-4 .
The International Society for Heart and Lung Transplantation working formulation,
illustrated in Figure 4-33 , is most widely accepted and used. [231 ] , [234 ] , [239 ] ,
[240 ] In this grading system, Grade O represents no evidence of rejection or healed
rejection. Mild rejection (ISHLT grades 1A and 1B) is characterized by a focal or
diffuse, respectively, mild perivascular (or interstitial) lymphocytic infiltrate without
myocyte damage. Lymphocytic inflammatory infiltrates with associated myocyte
encroachment or damage, generally called moderate rejection, either can be limited to
a single focus (ISHLT grade 2), present in a multifocal pattern (ISHLT grade 3A), or
distributed diffusely (ISHLT grade 3B). In severe rejection (ISHLT grade 4), myocyte
necrosis is more evident, and there is often patchy interstitial hemorrhage owing to
vascular damage, and vasculitis (usually arteriolitis) may be prominent. The increased
inflammatory infiltrate often also includes neutrophils or eosinophils (presumably in
response to myocyte necrosis or vascular damage).
Immunosuppressive protocols and the threshold for treatment of histological rejection

vary greatly among heart transplant centers; in particular, the clinical significance of mild
to low moderate rejection is controversial. [231 ] , [241 ] ISHLT grades 1A, 1B, and 2
have been shown to resolve without specific change in management in over 80 percent
of cases and, therefore, these levels of rejection remain untreated in many (but not all)
heart transplant centers. [241 ] Progression of lower rejection grades to advanced
rejection on subsequent biopsies becomes less likely with increasing postoperative
interval, and is especially unusual beyond 2 years (Fig. 4-34) . [234 ] , [241 ] To what
extent lower grades of untreated rejection may contribute to long-term functional
deterioration or chronic graft vasculopathy remains an important unanswered question.
Other important findings in surveillance endomyocardial biopsies that must be

distinguished from rejection, but probably have no independent clinical significance,
include lymphoid infiltrates either confined to the endocardium or extending into the
underlying myocardium and often accompanied by myocyte damage (Quilty A or B
lesions, respectively), and healing previous biopsy sites. [23 ] , [230 ] , [233 ] , [234 ]
Lymphoproliferative disorders (see the following) may also be seen in biopsies.
INFECTION
The immunosuppressive therapy required in all heart transplant recipients confers an

increased risk of infection with bacterial, fungal, viral, and protozoan pathogens. Such
infections occasionally involve the heart. In particular, the cellular infiltrate associated
with postoperative viral or parasitic infections (e.g., CMV [cytomegalic virus] or
toxoplasmosis), occasionally can be difficult to distinguish from that of rejection. Both
can produce multifocal lymphocytic infiltrates with occasional myocyte necrosis.
GRAFT VASCULOPATHY (GRAFT CORONARY DISEASE OR GRAFT

CORONARY ARTERIOSCLEROSIS)
Graft vasculopathy is the major limitation to long-term graft and recipient survival
following heart transplantation. [23 ] , [229 ] [231 ] , [235 ] , [242 ] [244 ] It represents a
diffuse, concentric, or eccentric, proliferative intimal lesion in the coronary arteries of
cardiac allografts that can cause distal ischemic injury (Fig. 4-35) . Its pathogenesis
remains uncertain. By 5 years following transplantation, up to 50 percent of recipients
have angiographically evident disease. [245 ] Graft vasculopathy may become
significant at any time during the posttransplant course and can progress at variable
rates. Nearly half of our posttransplant deaths owing to graft coronary disease at the
Brigham and Women's Hospital have occurred within 612 months postoperatively. [246
]
Coronary arterial occlusive disease in allografts can lead to myocardial infarction,

arrhythmias, congestive heart failure, or sudden death. [23 ] , [229 ] [231 ] , [235 ] , [242 ]
[244 ] , [246 ] , [247 ] The myocardial pathology resulting from the perfusion defects, and
which may be noted on endomyocardial biopsy, includes subendocardial myocyte
vacuolization, indicative of sublethal ischemic injury, and myocardial coagulation
necrosis, indicative of infarction (Fig. 4-36) . [242 ] , [246 ] , [247 ]
Early diagnosis of graft vasculopathy is limited by the lack of clinical symptoms of

ischemia in the denervated allograft, by the insensitivity of coronary angiography which
frequently underestimates the extent and severity of this diffuse disease, and by the
exclusive or predominant involvement of small intramyocardial vessels in some cases
(which does not occur in typical atherosclerosis). Since the denervated transplanted
heart has no afferent sensory nerves, myocardial ischemia usually does not elicit chest
pain, and ischemic damage can be clinically silent until far advanced.
Intravascular ultrasound is becoming an important, albeit invasive, means of diagnosis,

and correlates between anatomy and prognosis are under evaluation. [248 ] , [249 ]
Paradoxical vasoconstriction induced by acetylcholine, suggesting defective
endothelium-mediated vasodilation, may reveal early graft vasculopathy in some cases
and also predict which patients eventually will develop occlusions. [250 ] , [251 ]
Although graft vasculopathy has been called accelerated atherosclerosis, the

morphology of the obstructive lesion of graft vasculopathy is distinctive in comparison to
typical atherosclerosis (unless patients are hyperlipidemic or hypertensive) (Table 4-5) .
[23 ] , [234 ] , [242 ] [244 ] , [252 ] [254 ] Histologically, the vessels involved have
occlusions characterized by marked cellular intimal proliferation with deposition of
collagen, ground substance, and lipid. Lymphocytic cellular infiltration varies from
almost none to quite prominent, yet lymphocytes often are noted in a subendothelial
location in close approximation to the overlying endothelial cells. The internal elastic
lamina often is almost completely intact, with only focal fragmentation. Diffuse
obliteration of intramyocardial vessels often is present. The recipient's vasculature
elsewhere is spared. Although the precise mechanisms of graft vasculopathy are not
definitely established, proliferative vascular changes are probably the result of repetitive
or continuous immunological damage to the intima followed by intimal proliferation of
smooth muscle cells. As previously discussed, whether and to what extent either
perioperative graft ischemia or low grades of rejection, cyclosporine, or CMV play a
role in the the evolution of graft vasculopathy is uncertain. [242 ] [244 ] , [255 ] , [256 ]
There is no apparent difference in the frequency with which graft vasculopathy develops
in patients who were transplanted for end-stage coronary artery disease and those
operated for idiopathic cardiomyopathy. Although not usually amenable to angioplasty,
endarterectomy, or coronary artery bypass grafting because of their diffuse distribution,
stenoses may be alleviated by these procedures in occasional cases. For most cases,
however, retransplantation is the only effective therapy.
POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDERS
Lymphoproliferative disorders are a well-recognized complication of high-intensity

long-term immunosuppressive therapy. Solid organ transplant recipients, including
those with cardiac allografts, are at particular risk. Approximately 2 percent develop
lymphoproliferative disorders. [257 ]
Posttransplant lymphoproliferative disorders present as either an infectious

mononucleosis-like illness or with localized solid tumor masses, especially in extranodal
sites (e.g., heart, lungs, gastrointestinal tract). [23 ] , [231 ] , [234 ] , [235 ] Most
posttransplant lymphoproliferative disorders derive from the B-lymphocyte lineage.
There is strong evidence that the lesions progress from benign polyclonal B-cell
hyperplasia to malignant lymphoma in a short period of time, in association with the
appearance of cytogenetic abnormalities. [258 ] Epstein-Barr virus has been implicated
as the causal agent. Interestingly, early lesions may respond to reduction in
immunosuppression. However, although feasible in recipients of renal allografts,
modification of therapy is difficult in heart, heart-lung, or liver recipients in which
inadequately treated graft rejection is fatal. The mortality of posttransplant
lymphoproliferative disorders exceeds 80 percent.
CARDIAC ASSIST AND MECHANICAL REPLACEMENT
Continuing and increasing discrepancy between the number of available donor hearts
and the number of patients who might benefit from cardiac transplantation has
prompted efforts in the development of mechanical assist devices, and cardiomyoplasty
techniques. [259 ] These areas are briefly reviewed in the following, from the
perspective of cardiac pathology.
Cardiac Assist Devices and Total Artificial Heart
Mechanical cardiac assist devices and artificial hearts have been used primarily in two
settings: for ventricular augmentation sufficient to permit a patient to survive
postcardiotomy or postinfarction cardiogenic shock while ventricular recovery is
occurring; and as a bridge to transplantation, when ventricular recovery is not expected
and the goal is hemodynamic support until a suitable donor organ is located. [23 ] , [44 ]
, [260 ] In a small number of cases, ventricular assist devices and artificial hearts have
also been used clinically with the intent of providing long-term cardiac support. [261 ]
With either a left or right ventricular assist device, the inflow to the device is connected
by means of a cannula to the atrium or ventricle of the natural heart, and the outflow is
connected via a cannula to the appropriate great artery. [262 ] , [263 ] Bilateral support
can be provided by two separate pumps. In contrast, an artificial heart is composed of
two chambers that replace both excised ventricles of the natural heart, analogous to an
orthotopic cardiac transplant. Current pumps have valves (mechanical or bioprosthetic),
fabric (primarily Dacron) conduits, and a flexible, polyurethane, blood-containing
chamber positioned within a rigid housing. Most available pulsatile assist and
replacement pumps are activated by rapidly delivered air pulses transmitted through
tubes from an external pneumatic unit that result in high-velocity ejection of blood from
the chamber. Heart rate, percent systole, dp/dt, and driving pressures are regulated by
the pneumatic activator. Temporary pumps may be positioned internally or externally,
the latter adjacent to the patient, with the blood conduits passing percutaneously through
the body wall. Internally placed pumps would have pneumatic tubes passing through the
chest wall. Electrically powered, nonpulsatile centrifugal pumps, which move blood by
means of rotating impellers, also are used as externally situated temporary assist
pumps. Although some of these pumps can be used with peripheral access to the
circulation (for example, femoral artery and vein), the present discussion primarily
relates to implanted pumps with intrathoracic access to the cardiovascular system.
First used successfully by DeBakey in 1963, pneumatic ventricular assist pumps have
provided temporary (days) circulatory support for patients with profound ventricular
failure after open-heart operations. [44 ] When used as a left ventricular pump, the unit
fills from the left atrium or left ventricle and ejects into the aorta; when used for right
ventricular support, the pump fills from the right atrium or ventricle and discharges into
the pulmonary artery.
The heart can be replaced by two pneumatically powered polyurethane sac-type blood
pumps, implanted intrathoracically, that provide both systemic and pulmonary
circulations. [260 ] Tilting-disk-type prosthetic inflow and outflow valves provide
unidirectional blood flow in the two ventricles. The Jarvik-7 heart has served as a
long-term mechanical cardiac replacement in several individuals since 1982; this and
several other types of replacement devices have also been used as a bridge to
transplantation. [260 ] , [261 ] Compact, totally implantable electrical motor-driven
ventricular assist pumps and artificial hearts are being developed for long-term support
of the systemic circulation in patients with irreparably damaged ventricles. A recent
report describes 217 patients in which a total artificial heart was used clinically; survival
was 56 percent with average duration of support 26 days (maximum 795 days). [261 ]
The major observed complications of both cardiac assist and replacement with
mechanical devices have been thrombus, thromboembolism, and infection (Fig. 4-37) .
[23 ] , [260 ] [266 ] Thrombi form primarily in association with crevices and voids,
especially in areas of disturbed blood flow such as near connections of conduits and
other components to each other and to the natural heart. Although emboli have been
less frequent with short-term devices (711 percent of the 217 patients mentioned
previously), thromboembolism has occurred in most patients having long-term
implantation of the Jarvik-7 artificial heart for temporary or permanent support.
Infectious complications have been a major limiting factor in the prolonged use of
mechanical hearts, affecting many of the long-term recipients of the Jarvik-7 artificial
heart and those with long-term ventricular assist devices. [260 ] [262 ] , [264 ] [266 ]
Infection usually is within the device but may also be associated with percutaneous
pneumatic drive lines, sometimes spreading to the mediastinum. Susceptibility to
infection is not only potentiated by the usual prosthesis-associated factors, but also by
the multisystem organ damage from the underlying disease, the periprosthetic culture
medium provided by postoperative hemorrhage, and by prolonged percutaneous
cannulas. Device failure can also occur because of fracture of a mechanical prosthetic
valve (this application provides a particularly severe test of prosthetic valve durability) or
rupture of the synthetic diaphragm. Hemolysis generally is associated with an excessive
pump pressure pulse rate (high dp/dt). Pannus formation can occlude conduits,
especially at anastomoses.
Complications of the various forms of cardiac assist devices in potential transplant

recipients do not differ widely from those encountered in the use of permanent artificial
hearts or in the use of temporary assist devices in other patients. [260 ] , [261 ]
However, contraindications to transplantation such as infection or critical
thromboembolism can develop during mechanical assist in candidates.
Nonthrombogenic blood-contacting surfaces are essential for a clinically useful

temporary or permanent cardiac assist device or artificial heart. [23 ] , [44 ] The most
fruitful approaches to design of the blood-material interface of the moving blood pump
bladder have included smooth or textured (fibrillar) elastomeric polyurethane surfaces.
Smooth surfaces are designed to repel thrombosis, whereas the textured surfaces
accumulate a limited platelet/fibrin pseudointimal membrane. Although each type of
surface has been associated with heavy mineralization in long-term investigational
devices implanted into calves or sheep, macroscopic mineralization has not been noted
following cardiac assist device or artificial heart implantation in humans.
Skeletal Muscle Augmentation of Cardiac Function
Autologous skeletal muscle has been used to provide active cardiac assist in the form
of both cardiomyoplasty and skeletal muscle ventricles. [267 ] [269 ] Chronic
low-frequency electrical stimulation of skeletal muscle results in the acquisition by that
muscle of fatigue-resistant properties and in accompanying structural and biochemical
changes, including increases in capillary density, activity of oxidative enzymes, and
mitochondrial volume. Another approach is to use skeletal muscle to power a
mechanical circulatory assist device. Relevant pathology in these applications has not
yet been reported in detail.
NEOPLASTIC HEART DISEASE
Although metastatic tumors to the heart occur in about 5 percent of patients dying of
cancer, primary tumors of the heart are unusual. [1 ] , [23 ] , [270 ] [272 ] Those most
common, in descending order of frequency, are: myxomas, fibromas, lipomas, papillary
fibroelastomas, and rhabdomyomas, all benign and accounting collectively for 8090
percent of primary tumors of the heart. The remaining 1020 percent are usually
malignant tumors, including angiosarcomas and other sarcomas.
Myxoma
Myxomas are the most common primary tumor of the heart in adults. [1 ] ; [23 ] , [270 ]
[273 ] They may arise in any of the four chambers or, rarely, on the heart valves. About
90 percent are atrial myxomas, with a left-to-right ratio of approximately 4:1. Those in
the left atrium usually arise along the septum in the region of the fossa ovalis. The
tumors almost always are single, although multiple tumors occur simultaneously in rare
instances. A familial syndrome (Carney's syndrome or syndrome myxoma) includes
cardiac myxomas, cutaneous myxomas, and pigmented adrenal cortical lesions.
Myxomas range from small (<1 cm) to large (up to 10 cm) and form sessile or
pedunculated masses that vary from globular and hard lesions mottled with hemorrhage
to soft, translucent, papillary, or villous lesions having a myxoid and friable appearance
(Fig. 4-38) . [270 ] [273 ] The pedunculated form frequently is sufficiently mobile to move
into or sometimes through the ipsilateral atrioventricular valve annulus during ventricular
diastole, thereby causing intermittent and often position-dependent obstruction.
Sometimes, such mobility exerts a wrecking ball effect, causing damage and secondary
fibrotic thickening to the valve leaflets.
Histologically, myxomas are composed of stellate or globular cells, often in formed

structures that variably resemble poorly formed glands or vessels, endothelial cells,
macrophages, mature or immature smooth muscle cells, and a variety of intermediate
forms embedded within an abundant acid mucopolysaccharide matrix and covered by
endothelium. Although it has long been questioned whether cardiac myxomas are
hamartomas or organized thrombi, the weight of evidence is on the side of benign
neoplasia. All the cell types present are thought to derive from differentiation of primitive
multipotential mesenchymal cells.
The major clinical manifestations are owing to either valvular obstruction, embolization,
or a syndrome of constitutional symptoms, such as fever and malaise, likely owing to the
elaboration by some myxomas of the cytokine interleukin-6, a major mediator of the
acute phase response of the systemic inflammatory reaction. Sometimes,
fragmentation with systemic embolization calls attention to these lesions.
Echocardiography provides a means to identify the masses noninvasively. Surgical
removal usually is curative. Rarely, the neoplasm recurs months to years later, usually
only if the stalk is incompletely removed at the time of surgical resection.
Other Cardiac Tumors and Tumor-Like Conditions
Lipomas are localized, poorly encapsulated, not necessarily neoplastic, masses, that
may occur in the subendocardium, subpericardium, or within the myocardium. Many are
asymptomatic. They can create ball-valve obstructions as with myxomas, or produce
arrhythmias, most often with lesions in the left ventricle, right atrium, or atrial septum.
Adipose depositions in the atrial septum are called lipomatous hypertrophy.
Papillary fibroelastomas are usually solitary incidental masses, and are generally
located on the valves, particularly the ventricular surfaces of semilunar valves and the
atrial surfaces of atrioventricular valves. They constitute a distinctive pompom-like
cluster of hairlike projections up to 1 cm or more in length, and covering up to several
centimeters in diameter of the endocardial surface (Fig. 4-39) . [274 ] Histologically,
they are composed of a dense core of irregular elastic fibers, coated with myxoid
connective tissue, and lined by endothelium. They may contain focal platelet-fibrin
thrombus and serve as a source for embolization. Although classified with neoplasms,
fibroelastomas may represent organized thrombi, similar to the much smaller, usually
trivial, whisker-like Lambl's excrescences that are frequently found on the aortic valves
of older individuals.
Rhabdomyomas, included for completeness, comprise the most frequent primary tumor
of the heart in infants and children. [272 ] They consist of gray-white myocardial masses
up to several centimeters in diameter that are located on either the left or right side of
the heart, and may protrude into the ventricular or atrial chambers. Histologically, they
consist of a mixed population of cells, the most characteristic of which are large,
myofibril-containing rounded or polygonal cells containing numerous glycogen-laden
vacuoles. These, in turn, are separated by strands of cytoplasm running from the plasma
membrane to the more or less centrally located nucleus, forming so-called spider cells.
Many cardiac rhabdomyomas occur in patients with tuberous sclerosis.
Cardiac angiosarcomas and other sarcomas are not distinctive from their counterparts
in other locations. They tend to involve the right side of the heart, especially the right
atrioventricular groove (or sulcus) (Fig. 4-40) .
Recently described, and of importance only insofar as they need to be distinguished

from primary cardiac tumors or metastatic carcinoma, are peculiar microscopic-sized
cellular cardiac lesions that have been noted incidentally as part of endomyocardial
biopsy or surgically removed tissue specimens or at cardiac surgery, free-floating or
loosely attached to a valvular or endocardial mass. [271 ] , [275 ] , [276 ] Termed
mesothelial/monocytic incidental cardiac excrescences (MICE), they appear
histologically largely as clusters and ribbons of mesothelial cells and entrapped
erythrocytes and leukocytes, embedded within a fibrin mesh. Some represent reactive
mesothelial and/or monocytic (histiocytic) hyperplasia, whereas others are now
considered to be artefacts formed by compaction of mesothelial strips (likely from the
pericardium) or other tissue debris and fibrin, which are transported via catheters or
around an operative site on a cardiotomy suction tip.
BASIC PREOPERATIVE EVALUATION
The basic evaluation is required for every patient who undergoes open heart surgery. In
emergency situations, this information may not be available or obtainable if lifesaving
emergency surgery is the only chance for survival. In other patients, the presence of
comorbid conditions or the severity of heart disease requires additional information to
assess both the potential benefits and risks of operation. The basic evaluation includes
history, physical examination, blood testing, urinalysis, chest x-ray, electrocardiogram,
and almost always cardiac catheterization (Table 5-1) . Each of these components of
the basic evaluation should be performed with the planned surgical procedure in mind.
For example, if coronary artery bypass grafting is planned, the history should indicate
prior phlebitis or vein stripping; if a mitral prosthesis must be replaced, a previous deep
postoperative sternotomy wound infection is relevant.
For some patients, an appropiate indication for operation and information from the
basic evaluation are all that are needed to prescribe and carry out the procedure. These
are nearly always patients for whom the operation has a low risk of mortality and
morbidity. For others, much more information is needed, the decision to recommend
operation is more complex and difficult, the operation and postoperative course are
likely to be more costly, the benefits may be less dramatic, and the risk is higher. These
patients are addressed at the end of this chapter.
History
The history is an important source of information that usually establishes the indications
for operation and the need for studies beyond the basic evaluation. The reason for
having an operation should be elicited from the patient's point of view. What symptom,
threat, or restriction does the patient expect the operation to remove? What quality of
lifestyle does the patient expect after surgery? In addition to information regarding the
severity of heart dysfunction, the history provides an inventory of comorbid diseases
and compromised organ and system functions. In elderly patients, heart disease is
seldom the only disease. A thorough history sometimes provides clues to occult
disease not previously known (e.g., emphysema, alcoholic liver disease, diabetes, renal
insufficiency, arrhythmias, etc.) or reveals long-forgotten events, such as a serious
automobile accident, in a patient with a mass lesion over the aortic isthmus. During the
history, the patient should be assessed carefully to determine motivation and ability to
care for basic needs. [2 ]
PRESENT ILLNESS
The principal symptoms of cardiac disease are chest pain or discomfort, dyspnea,
fatique, peripheral edema, and syncope. Symptoms and prior manifestations of the
patient's cardiac disease should be described in terms of chronicity and severity.
Episodic aspects of the disease, such as pulmonary congestion, recent chest
discomfort, syncope, palpitations, hemoptysis, or infection, should be described in
terms of frequency, duration, and severity. Severity of symptoms is described and
assessed by a standard classification of severity such as the New York Heart
Association functional classification of heart failure [3 ] (Table 5-2) or the Canadian
Heart Association classification for severity of angina pectoris [4 ] (Table 5-3) . The
surgeon should particularly note combinations of symptoms, such as episodic chest
pain (angina) and shortness of breath (heart failure), that may be manifestions of one
disease process (ischemia) or two (ischemia and valve disease or severe left
ventricular dysfunction).
PAST HISTORY
Allergies
All allergies should be reviewed carefully and recorded prominently in the hospital chart
and, when appropiate, on the order sheet. Antibiotic allergies influence choices of
prophylactic and therapeutic antibiotics. Heparin-induced thrombocytopenia occurs in 2
to 5 percent of patients exposed to the drug, and the catastrophic form of the disease,
heparin-induced thrombocytopenia and thrombosis, occurs in 0.1 to 0.2 percent. [5 ] , [6
] Fish allergy or use of protamine insulin may indicate a predisposition to a protamine
reaction. [7 ] Prior cardiac surgery may immunize a patient to bovine thrombin (fibrin
glue) [8 ] or aprotinin [9 ] ; a second exposure may cause a severe bleeding disorder
from factor V deficiency (bovine thrombin) or an anaphylactic reaction (aprotinin).
Medications
Medication intolerance may be due to allergy or to side effects. Although allergy is

uncommon (see above), undesirable side effects of various cardiovascular drugs are
extremely common. In addition, combinations of drugs may produce serious cumulative
or adverse effects (e.g., aspirin plus Coumadin). The history should include not only the
drugs that the patient is taking but also drugs taken in the past that caused unpleasant
side effects. No one can remember all drugs or combination drug side effects, but each
physician should be aware of adverse effects of drugs that he or she frequently
prescribes. A history that reveals an adverse reaction to a drug commonly used by the
surgeon may save the patient discomfort postoperatively. Standard pharmacologic
texts, the package inserts of specific drugs, and the Physician's Desk Reference are
ready sources of information regarding adverse effects of medications.
Prior hospitalization and illnesses
It is particularly important to record prior procedures, operations, treatments, or

radiation involving the thorax or cardiovascular system. Previous radiation for breast
cancer may affect a decision to use the ipsilateral internal mammary artery for
myocardial revascularization. Diabetes may preclude using both mammary arteries for
conduits. Prior gastric resection may render the gastroepiploic artery unavailable for
coronary arterial bypass. Steroid dependency for arthritis may predispose to infection.
Multiple hospitalizations related to any organ system may be an indication for further
investigation. The operating surgeon is in the best position to evaluate the relevance or
prior operations and illness on the design of the proposed operation (i.e., are
modifications needed?) and on reducing the risk of postoperative complications.
REVIEW OF SYSTEMS
General function
The level of intelligence and general ability of the patient to care for himself or herself
independently bear on the decision to operate and on expected benefits of operation.
Elderly, frail, and forgetful patients must be interrogated carefully and respectfully. The
ability to live alone and care for basic needs independently are good indications of an
elderly patient's strength, motivation, and mental state. Elderly patients who require
nursing home care or who cannot be trusted at home alone are poor candidates for
operation. Patients with substance abuse problems, neglected dental care, or poor
hygiene are not good candidates for prosthetic heart valves or other procedures that
require careful regulation of postoperative medications, infection prophylaxis, or
immunosuppression therapy.
The ambulatory status of the patient is extremely important not only for rapid recovery
from operation but also for long-term care and quality of life. To a large extent, recovery
from open heart surgery is based on postoperative walking as an economic and
effective means to progressively increase exercise tolerance and to prevent
complications such as pneumonia and decubitus ulcers. In nonambulatory or morbidly
obese patients, operation is associated with a higher risk of morbidity and increased
length of stay. [10 ] , [11 ] Patients should be questioned about their motivation and
determination to ambulate quickly postoperatively.
Eyes
Amaurosis fugax (transient losses of vision) indicates the probable presence of carotid
arterial disease of atheroemboli from the aorta and should prompt further investigation
by appropriate ultrasonic studies.
Ears, nose, and throat
Occasionally, the pain of angina pectoris is manifest in the throat or ear. Symptoms of
cough, purulent sputum production, or hemoptysis raise the suspicion of upper airway
bronchitis, infection, or malignancy that needs further evaluation, especially in smokers
and abusers of alcohol. A history of difficult endotracheal tube intubation is noteworthy.
False teeth, dental caps, and a history of painful teeth or dental abscesses are relevant
to anesthesia and to value surgery.
Pulmonary
Cough, shortness of breath, sputum production, hemoptysis, unexplained weight loss,

chest pain, wheezing, and episodes of infection require further evaluation for primary
pulmonary disease. A history of smoking, particularly a long, heavy one, is relevant to
the possibility of chronic obstructive pulmonary disease that may exacerbate symptoms
of congestive heart failure. The surgeon should carefully evaluate the possibility that the
patient may require long-term postoperative intubation and respiratory support because
of age, frailty, and intrinsic lung disease. Spirometry, pulse oximetry, and arterial blood
gases may provide further information relevant to this risk.
Cardiovascular
Most of this history is recorded in the present illness. However, a history of

hypertension, childhood murmurs, rheumatic fever, syncopal episodes, chest radiation,
traumatic myocardial contusion, viral myocarditis, and so on may not be directly related
to the patient's present complaint but may be relevant to intraoperative and
postoperative assessment and management.
A detailed history of aortic and/or peripheral vascular disease is important as an

indication of diffuse atherosclerotic vascular disease and as a potential for
complications of vessel cannulation. Patients should be queried for symptoms of
aneurysm and peripheral vascular ischemia. Occasional patients are referred for
myocardial revascularization when coronary arterial disease is first discovered after an
abdominal aortic aneurysm or peripheral vascular disease becomes symptomatic.
Gastrointestinal
Recent change in chronic gastrointestinal (GI) symptoms or recent onset of new

symptoms may be an indication for detailed GI evaluation. The patient should be
questioned regarding symptoms of or factors predisposing to liver disease. A history of
hepatitis requires further evaluation to determine activity and degree of functional
impairment. A history of pancreatitis or liver disease may predispose postoperative
dysfunction of these organs. A history of GI bleeding from either the upper or lower
intestitinal tract may be a determining factor in the choice of a tissue or mechanical
cardiac valve prosthesis.
Genitourinary
Loss of a kidney, chronic renal disease, or prior treatment for renal insufficiency
generally requires further evaluation and estimation of renal functional reserve if
laboratory tests are elevated and a complicated operation is planned. Previous urinary
tract surgery and symptoms of recurrent urinary tract infection or prostatism may impair
insertion of a Foley catheter and predispose to systemic infection. Preoperative
evaluation of symptomatic patients by a urologist is often advisable.
Neurologic
A history of stroke, transient ischemic attack, headache, visual disturbance, or change

in mental status or personality should be noted and may require further evaluation.
Patients with a history of stroke or transient ischemic attack (TIA) are at great risk of
intraoperatiave and postoperative stroke, particularly if carotid artery bruits are also
present. [12 ] , [13 ]
The patient's functional capacity and strength and the effect of neurologic abnormalities
should be described. Elderly patients who are drowsy and sleep a great deal, who are
difficult to arouse, who are forgetful or cannot be left alone comfortably, and who are
nonambulatory or marginally ambulatory are poor candidates for cardiac surgical
procedures. Furthermore, these patients rarely initiate consideration of cardiac surgery;
more often the possibility of operation is raised by loving family members or
overzealous physicians.
Musculoskeletal
Abnormalities of joint function and muscle strength and function should be described.
The possibility that shoulder or neck pain may be muscular or skeletal in origin should
be considered carefully. Early symptoms of arthritis and musculoskeletal injury or
disease occasionally are interpreted as angina. Musculoskeletal dysfunction may be the
main determinant of the patient's ability to rehabilitate postoperatively.
Hematologic
Any history of a bleeding abnormality or unusual susceptibility to infection should be

recorded and evaluated by relevant blood screening tests. A history of easy bruising,
joint hematoma, or excessive bleeding from prior dental work or surgical procedures in
an indication for further hematologic evaluation and consultation. Anemia may unmask
coronary artery disease by triggering angina. A history of a transfusion reaction and the
patient's attitude or religious beliefs relevant to blood transfusion should be solicited.
Immunosuppressed patients require full evaluation of their defenses against infection.
Endocrine
Diabetes is commonly associated with ischemic heart disease, and insulin-dependent

diabetes over many years may be associated with moderate or severe renal and
peripheral vascular disease. In addition, a severe diabetic may have retinopathy and
peripheral neuropathy that will not be helped by cardiac surgery. Non-insulin-dependent
diabetes does not add to operative risks.
Rare patients may present with hypothyroidism or hyperthyroidism. Hypothyroid patients

recover from anesthesia slowly, and hyperthyroid patients may have angina or more
frequent angina because of their hypermetabolic state. When suspected, blood
triiodothroidine should be measured.
FAMILY HISTORY
The family history of heart disease is usually recorded in the medical evaluation and is
relevant primarily to the etiology of the heart disease and the risk of heart disease in
individual family members but does not often influence the indications for or conduct of
operation. However, the presence of an extensive family history of atherosclerotic
disease, including coronary, cerebrovascular, and peripheral vascular disease, may
affect the patient's motivation for surgical therapy.
SOCIAL HISTORY
History of tobacco, alcohol, or substance abuse should be recorded in terms of

duration, frequency, and amount. The patient's history of work and activities may give an
indication of the need for and ability to rehabilitate the patient postoperatively. The
social history is often very relevant to patient care during the first few weeks after
hospital discharge and the need for a rehabilitation or convalescent facility.
If the patient is admitted directly to the surgical service, the surgeon is responsible for a
complete and thorough physical examination. This examination is often done by a
general internist or cardiologist. However, the wise surgeon, who is most aware of
abnormalities or conditions that adversely affect surgical outcome, selectively checks
for specific findings relevant to the planned operation. The surgeon is responsible for
preoperative orders (Table 5-T4) .
Before elective cardiac surgery, correctable abnormalities such as infection, rhythm

disturbances, fluid overload, hypertension, electrolyte or sugar imbalances, and so on
are resolved. The surgeon must be sure that the patient is indeed ready for operation
and that the correctable but unresolved abnormalities that may lead to postoperative
complications are addressed. An example is treating acute or chronic bronchitis before
an elective operation.
VITAL SIGNS
These are checked for temperature elevation, arrhythmias, tachypnea, and hypo-or
hypertension.
HEAD, EYES, NOSE, AND THROAT
Sunken eyes in an elderly patient who is sedentary and frail are a poor prognostic sign;
these patients have often lost interest in life. Carious teeth should be removed or
repaired before aortic or valve surgery and, if severe, before any cardiovascular
surgery. Carotid bruits require noninvasive preoperative testing to estimate the severity
of stenoses and risk of stroke [12 ] , [14 ] ; in selected patients, further testing and the
possibility a combined carotid/cardiac procedure may be indicated (see Chap. 20).
Funduscopic observation of cholesterol or atherosclerotic emboli may be a
contraindication to operation. [15 ]
CHEST
Cardiac rhythm and murmurs should be confirmed to be sure that the findings are
consistent with other data from the cardiac workup. Physical evidence of pulmonary
rales, pleural effusions, or areas of absent or poor breath sounds prompt careful
examination of the chest x-ray. The site of the planned incision should be inspected for
skin lesions. A murmur of mild aortic regurgitation may complicate administration of
antegrade cardioplegia.
ABDOMEN
The abdomen is palpated for evidence of liver, spleen, other organ enlargement,
abnormal masses, and abdominal aortic aneurysms. The presence of ascites and
areas of point tenderness may prompt further testing. Bruits over the abdomen may be
an indication of diffuse vascular disease.
PELVIS AND RECTUM
The pelvic and rectal examinations usually are not done in patients with cardiac
disease, especially if coronary artery disease is suspected. These examinations are
done by general internists or other specialists after the cardiac condition is corrected,
unless performed previously within a few months.
NEUROLOGIC
Signs of motor and sensory deficit and evidence of peripheral neuropathy should be
documented thoroughly. The patient should be examined for signs of stroke, dementia,
Alzheimer's disease, and deterioration of mental function. [13 ] The preoperative
examination provides an extremely important baseline for postoperative evaluations of
possible new central or peripheral neurologic lesions.
EXTREMITIES
A chart or diagram showing the strength of brachial, radial, femoral, popliteal, dorsalis
pedis, and posterior tibial pulses should be recorded in the hospital chart. Diminished
pulses or bruits indicative of aortoiliac-femoral occlusive disease are specifically noted.
Feet should be inspected for signs of ischemia that may impair postoperative lower leg
healing. Patients with lower extremity occlusive disease may require balloon pump
insertion into the ascending aorta to avoid ischemic leg complications. [16 ] Occlusive
disease is also associated with a greater incidence of stroke and leg wound
complications. [17 ] , [18 ]
Superficial leg and arm veins should be examined to determine suitability for coronary
artery bypass grafting. Venous conduit may be absent due to amputation or prior
excision. Varicosities, venous stasis changes, palpable thrombosis of veins, and prior
operations or injuries in the region of the superficial veins may render veins unsuitable
for bypass grafting. Unavailability of the greater saphenous, lesser saphenous,
cephalic, or basilic vein should be described and prompts further studies to locate a
suitable conduit (Fig. 5-1) .
Evidence of cholesterol or atheromatous embolization to the skin or the blue toe

syndrome is indicative of generalized atheromata and greater risk of intra- and
postoperative stroke, renal insufficiency, and extremity necrosis. [15 ] Because cardiac
surgery and cardiopulmonary bypass greatly increase the risk of embolization in these
patients, and because preventive measures are not available, operation may be
contraindicated. [15 ]
SKIN
The patient should be inspected for bruising, petechiae, ecchymoses, rashs, pimples,
boils, factitial lesions, spider hemangiomas, liver palms, or any sign of systemic or skin
disease. Skin lesions or infection, particularly if near the proposed incision, may require
further diagnosis and therapy before operation.
Blood Examination
COMPLETE BLOOD COUNT
Measurement of blood hemoglobin or hematocrit, white blood cell count, and platelet
count is routine for every preoperative patient. Anemia (hematocrit < 35 percent) is
associated with greater need for blood transfusion and postoperative morbidity. [19 ]
Leukocytosis (white cell count > 10,000 per cubic millimeter) requires further evaluation
for sources of infection or inflammation. A platelet count below 100,000 per cubic
microliter is a clue for heparin-induced thrombocytopenia and/or thrombosis and
requires further evaluation of possible IgG antibodies against platelets in the presence
of heparin. [6 ]
ELECTROLYTE SURVEY
Hypokalemia is the most common preoperative electrolyte abnormality and is found

most often in hypertensive patients who are taking diuretics. Unsuspected
hyperkalemia, hyponatremia, or hypernatremia necessitates explanation and further
evaluation. High bicarbonate concentrations may be associated with respiratory
acidosis (co 2 retention) due to chronic obstructive lung disease.
CREATININE
Elevated preoperative creatinine is a strong predictor of postoperative renal failure and

other postoperative complications. [20 ] [22 ] The normal creatinine level is less than 1.5
mg/dL (133 µmol/liter) and is in the upper range for more aged patients because of a
reduced number of nephrons. Blood urea nitrogen ranges between 10 and 20 mg/dL
(3.6 and 7.1 mmol/liter). Unexpected values above the normal range may require further
evaluation.
OTHER BLOOD MEASUREMENTS
Other blood chemical studies, such as glucose and bilirubin, may be included in the
hospital blood chemistry panel that is measured automatically with blood electrolytes,
creatinine, and urea nitrogen at low cost. Values outside the normal range may or may
not trigger concern. Before cardiac surgery, both the prothrombin time and partial
thromboplastin time should be measured with a platelet count and careful history of
bleeding problems to rule out the possibility of an occult bleeding disorder. Routine
preoperative bleeding times are not recommended. [23 ]
All patients should have blood typing with a sample available in the blood bank before
operation.
Urinalysis
Urinalysis is a cost-effective method to detect occult urinary tract and renal disease.
Glucosuria, proteinuria, hematuria, and pyuria may require further preoperative
evaluation and treatment. A Gram stain of urine bacteria may provide enough
information for antibiotic prophylaxis to avoid delay of operation if the patient is not
febrile, but the urine also should be cultured.
Chest X-Ray
The basic examination includes posteroanterior and lateral views. Pulmonary

mediastinal and spinal abnormalities unrelated to the patient's cardiac disease and not
known before may require further evaluation before operation (Fig. 5-2) . Cardiac
abnormalities observed on chest x-ray should be consistent with other information
obtained by physical examination, electrocardiogram, and cardiac catheterization. The
chest x-ray often provides additional information relevant to operation. In patients who
require reoperation, the proximity of the aorta or right ventricle to the underside of the
sternum on the lateral view may prompt a decision to cannulate groin vessels before
sternotomy or to expose the heart through a right thoracotomy. An ascending aortic
aneurysm abutting the sternum or a mycotic or pseudoaneurysm is often an indication
for presternotomy groin cannulation. Evidence of calcification of the ascending aorta,
aortic valve, or mitral valve should be noted and may alter operative decisions. If the
right phrenic nerve is paretic or paralyzed, the surgeon may be deterred from using the
left internal mammary artery and risking injury to the left phrenic nerve.
Electrocardiogram
The electrocardiogram (ECG) is most helpful in determining abnormalities of heart

rhythm, conduction, and rate, recent or remote myocardial infarction, and left or right
ventricular hypertrophy. Preoperative control of heart rate is particularly important, and
medications, with the exception of amiodarone, are continued until induction of
anesthesia to prevent breakthrough of the arrhythmia for which the drug or drugs were
prescribed. A series of ECGs is especially helpful for distinguishing recent changes
from more remote disease. Tachycardia should be controlled preoperatively by
medication or cardioversion. Bradyarrhythmias may require adjustment of medication
or even pacing preoperatively. Evidence of ischemia or infarction requires enzyme
testing to estimate the possibility and timing of a recent infarction.
Cardiac catheterization within at least 6 months in stable patients and preferably closer
to the time of operation is required for the vast majority of adult patients who have open
heart surgery. Currently, no other diagnostic test provides details of the anatomy and
pathology of the coronary vasculature. Coronary arteriography provides the roadmap
that guides all revascularization operations and is usually indicated in patients with
acute life-threatening complications of myocardial infarction (e.g., postinfarction
ventricular septal defect, postinfarction mitral regurgitation). Cardiac catheterization
provides chamber pressures and estimates of cardiac output and pulmonary and
systemic arterial resistances. In selected patients with congenital, valvular, or aortic
disease who are under 40 years of age, cardiac catheterization may be omitted in favor
of echocardiography; however, this practice is the exception and not the rule.
The surgeon's preoperative evaluation of cardiac catheterization data is critical. The

pathologic anatomy of the coronary arteries must be memorized. The presence or
absent of valve disease must be noted; significant mitral regurgitation from ischemia
may need treatment; even mild aortic insufficiency may preclude or compromise
antegrade cardioplegia. Chamber pressures and the causes of elevated chamber
pressures must be well understood. If left ventricular end-diastolic pressures are very
high in a patient with low cardiac output and severe aortic stenosis, relief of stenosis
immediately improves ventricular function. If left ventricular end-diastolic pressures are
elevated from severe myocardial disease that is not likely to be reversed by
revascularization, little or no benefit can be expected. A decision to repair tricuspid
regurgitation may rest on the expected immediate relief of pulmonary hypertension from
left-sided valvular or ischemic disease.
The arterial-venous oxygen saturation difference is a more reliable index of cardiac

function at the time of blood sampling than estimates made by the Fick equation or by
thermodilution. Oxygen saturation is easily measured precisely, and catheters can be
placed in the pulmonary and systemic arteries reliably. The Fick equation requires
measurement or estimates of oxygen comsumption for a specified time period; this
measurement is usually estimated from tables rather than measured.
CORONARY ARTERIOGRAPHY
Although other tests may raise the suspicion or make the diagnosis of coronary arterial
disease, coronary angiography is essential to indicate the location and severity and
anatomy of both obstructed and nonobstructed vessels. Coronary angiograms are
evaluated for the presence of significant obstruction in both native and previous vein or
arterial grafts, areas suitable for bypass grafting, and the existence of bypassable
vessels in areas of jeopardized myocardium. Vulnerable myocardium without target
vessels suggests the presence of bypassable vessels not visible on the angiogram due
to total occlusion and poor collateral flow. In reoperative patients, coronary angiograms
indicate the location of previous pedicled mammary arterial grafts, the degree of
stenosis in partially occluded vein grafts at risk of perioperative embolization, and the
approximate location of target vessels that may be difficult to find because of an
intramyocardial location or pericardial adhesions and epicardial fibrosis.
SELECTIVE ANGIOGRAPHY
If questions arise concerning the availability of internal mammary, gastroepiploic, or

inferior epigastric arteries for myocardial revascularization, selective angiograms may
be obtained during cardiac catheterization. [24 ] Alternatively, the mammary, radial, and
inferior epigastric arteries can be evaluated by duplex scanning. A reduced brachial
blood pressure may be indicative of subclavian artery stenosis.
LEFT VENTRICULOGRAM
A left ventriculogram is indicated in most patients who have cardiac catheterization but
is often omitted in patients with severe left ventricular dysfunction or with moderately
severe or severe renal disease. Contraction abnormalities on the ventriculogram may
represent scar or infarcted, stunned, or hibernating myocardium. Low ejection fraction
with a history of multiple myocardial infarctions, long-standing mitral insufficiency, or
congestive cardiomyopathy is indicative of severe left ventricular function and possibly
much greater operative risk. Low ejection fraction with aortic valve disease, particularly
aortic stenosis, is not associated with increased operative risk in our experience. In
patients with low ejection fraction and coronary artery disease, the outcome of bypass
grafting may be excellent if sizable portions of the noncontracting myocardium are
viable but stunned or hibernating. Operation carries a low risk in patients with angina
and minimal or no heart failure and left ventricular end-diastolic pressures less than 20
mmHg. Patients with low ejection fraction who have a much greater risk and lesser
benefit from coronary arterial bypass grafting are those with some or all of the following
characteristics: long history of symptomatic heart failure; failure symptoms are
predominant over anginal symptoms; significant cardiac chamber enlargement by
ventriculogram, chest x-ray, or echocardiogram; and ECG evidence of old myocardial
infarction.
RIGHT-SIDED HEART CATHETERIZATION

Right-sided heart catheterization is usually not performed in patients with coronary
artery disease with good or excellent left ventricular function. The examination is
important in patients with chronic mitral valve disease, congenital heart disease,
tricuspid valve disease, pulmonary vascular disease, or severe left ventricular
dysfunction.
AORTOGRAM
The size of the ascending aorta should be observed carefully in whatever projections it
is viewed, including coronary artery injections, left ventriculogram, or aortogram. If the
ascending aorta appears to be greatly enlarged, a computed tomographic (CT) scan
may be necessary to determine the need for aortic replacement. Mobile atheromata
may be visible on the aortogram but are more likely found by echocardiography. Aortic,
valvular, coronary artery, and other sites of cardiac calcification should be noted. Aortic
atherosclerosis is a major risk factor for perioperative stroke. [12 ] , [25 ] Extensive or
near-total calcification of the ascending aorta may preclude aortic cross-clamping or
proximal anastomoses of vein grafts and necessiate more complicated surgery or
contraindicate operation entirely.
EMERGENCY AND URGENT OPERATION
The basic evaluation may be incomplete in unstable patients who require operation
quickly. The most extreme example is a patient who is brought to the hospital by
ambulance after an acute coronary event. If the patient is intubated and no family is
present, very little history is available. Hemodynamic instability may preempt evaluation
of organ systems other than the heart. Immediate operation before cardiac
catheterization is rarely indicated in these patients. The cause and reversibility of the
cardiovascular disease must be known with reasonable certainty before operation. The
best approach is to stabilize the circulation by drugs and/or temporary mechanical
circulatory assistance until sufficient information can be obtained.
Patients scheduled for interventional cardiologic procedures should have the basic
evaluation, including blood group typing, before the procedure. Between 2 and 7
percent of patients undergoing percutaneous transluminal coronary angioplasty (PTCA)
develop abrupt closure of a coronary artery. [26 ] , [27 ] Although occasional patients
with unstable angina or myocardial infarction undergo catheter thrombolytic therapy or
angioplasty before the basic evaluation is completed, as much information as possible
regarding function of other organ systems, prior operations, allergies, and medications
should be obtained before and during the PTCA procedure.
If the circulation cannot be stabilized in the catheterization laboratory, and if rational

indications for operation exist, the surgeon may be forced to obtain as much useful
information as possible on the way to the operating room with an unstable patient.
Aside from concerns regarding the reversibility of the cardiac dysfunction and ischemic
damage to other organ systems, the surgeon must ascertain that venous or arterial
conduit is available. In the absence of data from the basic evaluation, the risk of death
and/or intra- and postoperative complications increases markedly.
Preoperative evaluation of a patient who is already hospitalized on the cardiac surgical

service should not be overlooked when an early return to the operating room is needed.
Updated hematocrit, white cell and platelet counts, coagulation tests, an ECG, and
chest x-ray are desirable for operative management and postoperative comparisons. It
also may be necessary to send another sample of blood to the blood bank for
crossmatching.
FURTHER PREOPERATIVE EVALUATION
The results of the basic evaluation indicate areas that require further evaluation. To
control costs and to protect the patient, further studies must be selected carefully for
relevance to indications and timing of operation and for preventing and controlling
intraoperative and postoperative complications. In this section we present additional
studies that are often helpful in achieving these goals.
Cardiovascular Disease
MYOCARDIAL ENZYME TESTING
Creatine phosphokinase and the MB isoenzyme should be measured to rule an acute

myocardial infarction in or out in patients with a history of recent chest pain lasting over
15 minutes and/or ECG evidence of myocardial infarction. Creatine kinase is normally
under 90 units/liter, and the MB fraction, which is specific for cardiac muscle, should be
less than 6 percent. Absence of enzyme elevation does not completely rule out recent
infarction because of clearance; therefore, serial ECGs should be obtained if suspicion
of an acute infarction is high.
TRANSTHORACIC ECHOCARDIOGRAPHY (TTE)
Transthoracic two-dimensional echocardiography and color-flow Doppler mapping

image ventricular dimensions and chamber sizes; segmental wall motion and thickness;
presence of mural thrombus, pericardial constriction, or effusion; some segments of the
aorta; septal defects; and valvular anatomy and function. The specific reason for
obtaining a two-dimensional echocardiogram before operation varies with the patient.
In adults with ischemic heart disease, ejection fraction, left ventricular chamber size,
specific wall motion abnormalities (relevant to stenotic or obstructed coronary arteries),
and the presence and degree of mitral regurgitation are common indications for a
preoperative echocardiogram. After recent myocardial infarction, an echocardiogram
may detect a ventricular mural thrombus (Fig. 5-3) . Because mural thrombus is a risk
factor for perioperative stroke, we obtain an echocardiogram on patients with recent
myocardial infarction whenever possible. [28 ]
Transthoracic echocardiography may provide important information regarding left

ventricular function in patients with valve disease or ischemic damage. Patients with
severely impaired left ventricular function may not be improved by revascularization if
large areas of scar are present and heart failure is the predominant ischemic symptom.
Depressed left ventricular function is not a contraindication to operation in patients with
aortic stenosis but may be in patients with moderate or severe mitral regurgitation. TTE
is useful for detecting vegetations and abscesses in patients with infective endocarditis.
TRANSESOPHAGEAL ECHOCARDIOGRAPHY (TEE)
Transesophageal echocardiography (TEE) is indicated preoperatively for patients in

whom the TTE examination is incomplete or not satisfactory for a variety of reasons.
TEE requires sedation or light general anesthesia, whereas TTE can be done in any
cooperative patient.
TEE is now an essential intraoperative monitor for patients who have valvular and aortic
surgery, for all patients with poor right or left ventricular function, for unexpected patients
who develop poor cardiac function following cardiopulmonary bypass, and for locating
positions of intraaortic devices. The method is also standard for evaluating repaired
mitral and tricuspid valves (see Chap. 33). In unstable patients with suspected aortic
dissection, traumatic rupture of the aorta, or massive pulmonary embolism, TEE may be
used for preoperative diagnosis in the operating room (see Chaps. 38, 42, and 45).
TEE requires a skilled operator to obtain and interpret images.
Intraoperative direct echocardiography, wherein the echo probe is encased in a sterile

sleeve and manipulated by the surgeon, is used to detect the presence and severity of
aortic atheroma in patients with suspicious aortograms or TEE images [29 ] , [30 ] (Fig.
5-4) or in patients who develop aortic atheroemboli during cardiac catheterization. [31 ]
[33 ]
EXERCISE TESTING
Exercise testing is used to determine the severity and significance of coronary artery
disease and to determine which patients will benefit from myocardial revascularization.
[34 ] [39 ] Many patients have exercise testing before referral for operation. Thus the
exercise test is important for determining the indication for operation but is not
otherwise important in preoperative evaluation.
THALLIUM-201 AND SESTAMIBI MYOCARDIAL IMAGING
Radionuclide myocardial imaging is a sensitive and reliable means to visualize acute

myocardial infarction. In patients with chronic myocardial ischemic disease,
radionuclide imaging is combined with exercise, dipyridamole, or adenosine to
demonstrate areas of myocardium that cannot increase coronary blood flow in
response to demand or vasodilatation. [40 ] [42 ] These studies are usually done before
operation is prescribed to relate areas of viable myocardium to stenotic or obstructed
vessels that can be revascularized. Radionuclide studies also may be done in patients
with poor left ventricular function in an attempt to differentiate viable myocardium from
scar.
POSITRON-EMISSION TOMOGRAPHY
Positron-emission tomographic (PET) scanning is advocated for predicting wall motion

recovery after revascularization in patients with coronary disease and poor left
ventricular function. [43 ] [47 ] The method differentiates stunned and hibernating
myocardium from scarred myocardium in patients who have both anginal pain and
symptoms of heart failure. The method may extend surgical revascularization to
subgroups of patients who otherwise would not be considered candidates for surgery
because of high risk. The method is helpful but not infallible because scans must be
interpreted. PET scanning is expensive and not widely available; therefore, the utility of
the method in most practices is low.
COMPUTED TOMOGRAPHIC SCANS

Computed tomographic (CT) scans are particularly useful for evaluation of the thoracic
aorta if abnormalities, dissection, or enlargement is suggested by the basic evaluation,
chest x-ray, cardiac catheterization, or echocardiogram. Saccular aneurysms and the
relationship of abnormal aortic segments to surrounding structures are well delineated
by CT scans. CT scans are also indicated for mass lesions, such as primary or
secondary tumors, that involve the heart, pericardium, lungs, or pleura. An abdominal
CT examination may be ordered to rule out an abdominal aortic aneurysm in an obese
patient.
Rapid CT scans are rarely prescribed for preoperative patients but can provide
high-resolution images of left ventricular masses, chamber size, abnormal masses, and
wall thickness changes during the cardiac cycle. These scans are helpful in selected
patients with repaired or unrepaired complex congenital heart lesions, in the location of
abscesses, and in defining the anatomy of the great vessels. Rapid CT scans are also
used to assess right ventricular volume and function.
MAGNETIC RESONANCE IMAGING
Magnetic resonance imaging (MRI) also is used selectively for the preoperative
evaluation of cardiac surgical patients. MRI requires a cooperative patient, does not
expose the patient to radiation, detects blood flow, and provides high-resolution images
in coronal, sagittal, and transverse views. In general, MRI provides similar morphologic
information as rapid CT but also can determine whether or not an aneurysm is leaking
or a previous vein graft is patent. MRI also can provide sophisticated information about
segmental wall motion and ventricular remodeling. The expense, availability, and
additional information provided by MRI restrict its use to a few highly selected patients
with atypical cardiovascular problems.
PERIPHERAL ARTERIAL STUDIES
Peripheral noninvasive arterial studies (Doppler pulses, segmental pressure

measurements, etc.) should be performed in patients with severe arterial occlusive
disease by history and physical examination to determine the preferred site for
harvesting venous conduit. In patients with peripheral vascular disease, a vein is
removed from the leg with the least occlusive desease, as determined by the
ankle-brachial index. Thigh veins may be preferable in patients with bilateral peripheral
vascular disease. Aortoiliac occlusive disease often prevents passage of an intraaortic
ballon or perfusion catheter from the groin.
DUPLEX SCANS
The combination of ultrasound and color-flow Doppler velocity mapping is commonly

termed duplex scanning . Vein mapping by duplex scanning is useful to locate suitable
conduit or to select the site for harvesting conduit. The study is particularly helpful in
minimizing dissection in very obese patients, patients who have had multiple vascular
procedures, and patients with a history of deep venous phlebitis. If greater saphenous
veins have been stripped or removed previously or are varicose or phlebitic, we
determine the size and location of the lesser saphenous vein by duplex scanning (see
Fig. 5-1 ), although scans may underestimate vein size. Vein mapping is also
recommended in patients who have arterial occlusive disease and an ankle-brachial
index less than 0.6 to minimize dissection necessary to harvest the vein. In some
patients, mapping arm veins by duplex scanning is helpful.
Pulmonary Disease
In patients needing elective operations, any new pulmonary symptom or abnormality on

chest x-ray requires further investigation to determine etiology. This may require
treatment of pneumonia, pleurocentesis, or a full workup for a mass lesion. A decision
to treat the pulmonary disease before or after operation first requires thorough
knowledge of both the cardiac and pulmonary diseases, the urgency of one or the other,
and the impact of the first treatment on the deferred disease.
The most common reason for delaying operation for pulmonary reasons is the need to
treat productive cough with or without wheezing. Usually this is due to acute or chronic
bronchitis that may be exacerbated by smoking. If pneumonia is ruled out by physical
examination and chest x-ray, broad-spectrum antibiotics will control productive cough in
most patients. Sputum Gram stain and/or culture may guide prescription of more
specific antibiotics in patients with poor pulmonary function. Bronchodilators may be
necessary preoperatively to relieve bronchoconstriction and wheezing; steroids are
needed occasionally. The hospital is a smoke-free environment, and smoking is
prohibited during hospitalization.
Dyspnea during rest or moderate exercise may be due to heart disease, pulmonary
disease, or both. Further evaluation to determine the severity of lung disease in usually
indicated, but extensive tests in preoperative patients are rarely indicated. Bedside
spirometry, pulse oximetry, and/or measurement of arterial blood gases may be all that
is needed for even high-risk cardiac patients. The absence of dyspnea with moderate
exercise and a normal basic evaluation is adequate evidence of satisfactory lung
function for operation.
BEDSIDE SPIROMETRY
Bedside spirometry measures vital capacity (VC), inspiratory and expiratory volumes,
total lung capacity, and simple dynamic measurements such as forced expiratory
volumes (FEV) versus time (Fig. 5-5) . The patient's measurements are compared with
predicted meaurements based on the patient's age, sex, and size. Spirometry reliably
detects severe restrictive lung disease and also chronic obstructive pulmonary disease
(COPD) (see Fig. 5-5 ). Normally, the FEV 1 (FEV in 1 second) is 80 percent of
predicted; values below 50 percent usually require further evaluation that includes
laboratory pulmonary function tests, ventilation-perfusion scans, and pulmonary
consultation. Bedside testing may underestimate the patient's best FEV 1 or VC.
PULSE OXIMETRY
Pulse oximetry is a cost-effective method to determine arterial oxygen saturation at the

bedside. Because of the prevalence of COPD in adult patients with coronary arterial or
aortic disease, pulse oximetry is often used as a screening test for the need for further
evaluation of advanced pulmonary disease.
ARTERIAL BLOOD GASES
Arterial blood gases are usually the next step if the basic evaluation and bedside
spiromety indicate intrinsic lung disease. Chronic obstructive pulmonary disease
(COPD) is common in adult patients who need cardiac surgery; blood gases are helpful
in estimating the severity of COPD and/or the need for preoperative bronchodilator and
nonsmoking therapy. Dyspneic patients with severe COPD may have nearly normal
arterial blood oxygen saturations and low-normal arterial Pco 2 because of
hyperventilation; laboratory pulmonary function tests are needed to help estimate the
severity of the COPD. In other patients with severe bronchitis and COPD, the resting
arterial Pco 2 is increased and the arterial Po 2 is reduced; a resting arterial Pco 2
above 50 mmHg or room air arterial Po 2 of less than 70 mmHg indicates very severe
bronchitic COPD. Severe COPD is a risk factor for morbidity [11 ] , [47 ] , [48 ] and
mortality [47 ] , [48 ] and raises the question of whether the benefit of the operation
justifies the risk.
Occasional patients may have hypoxia and increased intrapulmonary shunting from
reversible causes such as atelectasis, bronchospasm, or pleural effusions.
VENTILATION-PERFUSION SCANNING
Ventilation-perfusion scanning is useful in preoperative evaluation for cardiac surgery

only if pulmonary emboli are suspected. Ventilation-perfusion scans and other special
pulmonary tests may be part of an extensive pulmonary workup for intrinsic pulmonary
disease.
SMOKING
In our experience, current smoking is not a risk factor for mortality or morbidity following
coronary artery bypass grafting. [49 ] Smokers have greater red cell volume and
hematocrit and are less likely to require transfusion postoperatively. [33 ] , [49 ] , [50 ]
Others find that current smoking is a risk factor for stroke, sternal wound complications,
and pulmonary complications. [12 ] , [48 ] , [51 ] [53 ] Stopping smoking for less than 6
weeks preoperatively does not diminish the incidence or severity of pulmonary
complications. [54 ] , [55 ] Educational materials that advocate cessation of smoking
are part of our preoperative preparation, but patients are not required to stop smoking
prior to operation. Coronary artery bypass grafting is a potent incentive to stop
smoking; up to 80 percent of patients stop smoking long term after myocardial
revascularization. [56 ] , [57 ]
Renal Disease
SERUM CREATININE
If the patient's serum creatinine is less than 1.5 mg/dL and urinalysis is normal, no
further renal evaluation is needed. Patients with successful, functioning renal transplants
are not at higher risk for cardiac surgery. Nonsteroidal anti-inflammatory drugs or
angiotensin-converting enzyme (ACE) inhibitors should be stopped for 48 hours in
diabetics and patients with serum creatinine levels greater than 1.5 mg/dL if the patient
is stable. ACE inhibitors may predispose to hyperkalemic renal failure.
CREATININE CLEARANCE
If creatinine is greater then 1.7 mg/dL, a creatinine clearance is helpful if the patient's
stability permits. Normal values range between 90 and 130 mL/min. Below-normal
creatinine clearance and serum creatinine levels greater than 1.7 mg/dL are relevant to
medication doses and may prompt increased hydration, low-dose dopamine, and
stopping nephrotoxic medications before operation. Renal ultrasound is a good method
to determine the presence of solitary kidney, cystic renal disease, or urinary obstruction
above the bladder.
RENAL INSUFFICIENCY
Selected patients with chronic renal insufficiency and even dialysis dependency may
undergo cardiac surgery [58 ] but at higher risk of mortality [47 ] , [48 ] and morbidity. [11
] , [47 ] During cardiopulmonary bypass, both fluids and solutes can be removed by
dialysis to maintain normal electrolyte concentrations [59 ] (see Chap. 9).
PROSTATIC HYPERTROPHY
A history of prostatism, nocturia, or pyuria prompts measurement of residual urine. If

obstructive uropathy is present, urine culture, antibiotic therapy, and catheter drainage
of the bladder for 48 to 72 hours preoperatively may be advisable.
Neurologic Disease
CAROTID ARTERIAL DUPLEX SCAN
Patients with history of stroke or transient ischemic attacks and/or carotid bruits are at
greater risk of stroke. [14 ] If the urgency of the patient's cardiac conditions allows, we
perform carotid artery duplex scanning preoperatively in such patients. Cerebrovascular
disease or carotid stenosis of greater than 80 percent is correlated with postoperative
stroke [18 ] , [60 ] , [61 ] and may prompt consideration of a combined operation on both
the carotid artery and heart (see Chap. 20). A cerebral angiogram may be required in
selected patients to further evaluate the carotid lesion. Preoperative cerebrovascular
disease increases postoperative morbidity [11 ] , [47 ] and mortality. [48 ] We do not
recommend an electroencephalogram as part of the preoperative evaluation.
BRAIN CT OR MRI SCANS
Preoperative evaluation of the brain in patients with stroke, transient ischemic attack, or
change in mental capacity or status may be important for comparison with
postoperative studies if a neurologic event accompanies operation. MRI is useful when
multiple small strokes or strokes in the posterior cerebral circulation are suspected.
Preoperative MRI studies of patients having coronary artery bypass grafting show that
58 to 93 percent of patients have preoperative abnormalities. [62 ] [64 ]
GASTROINTESTINAL DISEASE
Patients with anemia or a history of heartburn, epigastric pain, dysphagia, or ulcer
disease may require further evaluation prior to operation. In anemic patients scheduled
for elective surgery, stool is examined for occult blood. If stool contains blood, a
bleeding source within the upper gastrointestinal (GI) tract is sought and controlled
before exposing the patient to heparin and cardiopulmonary bypass, but it is usually not
necessary to perform exhaustive studies of the lower GI tract before operation.
Esophagogastroduodenoscopy (EGD) is recommended to locate and sometimes treat
an upper GI bleeding source. If the EGD is normal and liver function tests are normal,
proceeding with operation is usually safe.
The presence of liver disease may be suggested by the history or dark urine and
acholic stools. If hepatosplenomegaly, ascites, jaundice, spider hemangiomas, or
palmar erythema is present, liver function is evaluated by blood tests.
Hyperbilirubinemia, hypertransaminasemia, high serum alkaline phosphatase, and
hypoproteinemia are indications for further evaluation of liver function before operation.
Hyperbilirubinemia is indicative of hepatic disease, biliary disease, hemolysis, or a

genetic defect in bilirubin metabolism. Further investigations including imaging studies
are necessary to determine whether hepatobiliary disease is the cause. High alkaline
phosphatase and glutamyl transpeptidase levels are also indications for imaging
studies of the liver and biliary tree for evidence of mass and/or obstructive lesions. In the
absence of anticoagulant therapy preoperatively, hypoprothrombinemia is usually
indicative of hepatic dysfunction.
Significant liver disease greatly increases operative risk, and often the benefits of
operation are meager. Nonoperative forms of therapy should be considered seriously if
the hepatic dysfunction is independent of cardiac disease. Although the operative risk
of valve surgery is greater in patients with associated congestive hepatomegaly, early
relief of hepatic congestion usually reverses liver dysfunction and provides excellent
long-term benefits.
Blood Disease
Platelet count, prothrombin time, and partial thromboplastin time are recommended
preoperatively as part of the basic evaluation. If the history, physical examination, or
abnormal basic laboratory studies suggest possible coagulation deficiency, more
specific analysis of soluble blood coagulation proteins is recommended to determine
the cause and also treatment.
Temporary coagulation abnormalities are common in cardiac surgical patients who

receive heparin, aspirin, or thrombolytic therapy preoperatively. We do not consider
these abnormalities a contraindication to operation. Sustained prior heparin
administration may produce heparin resistance (inability to adequately prolong the
activated clotting time) at the time of operation. [65 ] Heparin resistance is due to a
relative deficiency of antithrombin, the essential cofactor of heparin, and is treated by
infusion of fresh-frozen plasma. Aspirin inhibits all platelets at the time of administration
but does not affect new platelets that are constantly being added to blood. Aprotinin is
effective in patients who have received prior aspirin, [66 ] and if postoperative bleeding
occurs, platelet transfusions are given. Similarly, preoperative fibinolytic drugs may
partially deplete plasma fibrinogen, but this can be replaced by fresh-frozen plasma.
Endocrine Disease
DIABETES
Diabetes is common in adult patients requiring cardiac operations and is usually

discovered from the patient's history. Occasionally, hyperglycemia is found by urinalysis
or blood chemistry without a prior history, and control is necessary with insulin or oral
hypoglycemics before operation.
Diabetics undergoing cardiopulmonary bypass usually require larger amounts of insulin

than during other types of surgery. [67 ] Blood sugars are monitored during and early
after operation by finger stick and daily chemistry until the patient is eating normally.
Insulin-dependent diabetics who have taken protamine insulin preparations are more
prone to protamine reactions. [68 ] , [69 ]
Internal mammary grafts in insulin-dependent diabetics are associated with an

increased incidence of sternal wound complications and phrenic nerve dysfunction. [70 ]
[72 ] Other morbidity associated with insulin-dependent diabetes includes longer
hospital stay, mortality, renal failure, wound complications, infection, and stroke. [12 ] ,
[33 ] , [53 ] , [73 ] , [76 ] Unfortunately, no preoperative intervention lowers the risk of
complications in diabetics.
THYROID
Treatment of myxedema may be delayed until after coronary artery bypass grafting in
patients with coronary disease. [77 ] Hyperthyroidism should be controlled before
cardiac surgery.
HYPERPARATHYROIDISM
Patients with unstable angina and hypercalcemia due to hyperparathyroidism may be

managed medically until after coronary artery bypass grafting.
Nutritional Status
Routine nutritional assessment is of no value in guiding preoperative management. [78 ]

In very aged patients, cachexia (body weight below the tenth percentile) is a risk factor
for mortality. [79 ]
OBESITY
Extreme obesity is easily determined subjectively, but the degree can be quantitated by
the body mass index. [80 ] Various studies show that obesity is a risk factor for sternal
and leg wound infection, postoperative arrhythmias, myocardial infarction,
postoperative bleeding, and length of hospital stay [33 ] [53 ] [81 ] [86 ] but not mortality.
Although weight loss is encouraged and recommended for all obese patients, extreme
obesity is rarely a reason for delaying operation. Preoperative weight loss may improve
symptoms of angina and heart failure as part of medical therapy but is not effective
once surgery is indicated.
Infection
SURVEILLANCE CULTURES
Although others recommend surveillance nasal cultures to reduce the risk of

postoperative infection by prophylactic antibiotics, [87 ] we do not recommend
screening patients to determine their carrier state. Prophylactic antibiotics may
enhance colonization of more pathogenic organisms and require costly repeated
cultures and assessment. Prolonged preoperative stay is associated with an increased
risk of infectious complications. [88 ]
LATENT INFECTION
Latent infections that are asymptomatic or produce low-grade, chronic inflammation

should be treated with specific antibiotics preoperatively to prevent bacteremia.
Examples include chronic bronchitis with sputum production, prostatitis, pyelonephritis,
pyuria, and skin infections, including cellulitis, boils, and eczema. Cultures and, if time is
a factor, Gram stains should be obtained to identify specific organisms and guide
antibiotic therapy. In the absence of pus, treating skin lesions rarely decreases the
infectious risk of operation. Psoriasis and other noninfectious skin diseases do not
require culture or antibiotics.
Carious, infected teeth should be treated or extracted prior to elective valve operations,
but this is usually not necessary before coronary arterial surgery. Preoperative dental
work is usually not possible or advisable in unstable patients; broad-spectrum
antibiotics are used to reduce the possibility of septicemia in these individuals.
ENDOCARDITIS
Occasionally, endocarditis is insidious and may present with nonspecific symptoms in

afebrile patients. Valve dehiscence within the first year after operation is frequently due
to infection with Staphylococcus epidermidis or low-grade nosocomial organisms. The
surgeon should seek evidence of endocarditis by history and physical examination,
including search for microembolic manifestations of endocarditis in nails, skin, eye
grounds, and urinalysis. Suspicion of endocarditis is an indication for echocardiography
and blood cultures.
Medication Management
POTASSIUM
Patients with low serum potassium levels are susceptible to premature ventricular
contractions, ventricular fibrillation, and ventricular tachycardia. If a patient's
preoperative serum potassium level is less than 3.5 meq/liter, parenteral potassium
supplements are given preoperatively. Oral potassium supplements are used for serum
potassium levels between 3.5 and 4.0 meq/liter. Our goal is a serum potassium level
above 4.0 meq/liter before beginning operation.
ANTIARRHYTHMICS
Prophylactic digoxin is generally not indicated but may be started for heart failure or
supraventricular arrhythmias or in patients with recent myocardial infarction or in those
who require valve surgery. [89 ]
Beta-blocking agents, calcium-channel blockers, and other antiarrhythmics, except

amiodarone, are continued up to operation. Prophylactic digoxin, calcium-channel
blockers, and amiodarone do not reduce the incidence of postoperative atrial
fibrillation; however, in patients with adequate left ventricular function, some reports
indicate that prophylactic beta blockade reduces postoperative atrial fibrillation. [90 ]
STEROIDS AND VITAMIN A
Steroids are not discontinued before operation in patients who receive these drugs
long-term. Indeed, these patients receive supplemental intravenous steroids during
operation and for the first day or two afterwards. Chronic steroid therapy is a risk factor
for wound complications. [75 ] Vitamin A, 50,000 units per day, may be given prior to
operation to block the effect of steroids on wound healing.
HISTORICAL PERSPECTIVES AND THE PURPOSE OF RISK
STRATIFICATION
Risk stratification had its beginnings in the examination of standards of care as early as
the mid-1800s. One of the earliest advocates of analyzing outcome data was Florence
Nightingale, who was troubled by observations that hospitalized patients died at higher
rates than those treated out of hospital. [1 ] She also noted that there was a vast
difference in mortality rates among different hospitals, with London hospitals having
mortality rates as high as 90 percent while smaller rural hospitals had mortality rates of
12 to 15 percent. Nightingale noted that raw mortality rates were not an accurate
reflection of outcome, since some patients were sicker when they presented to the
hospital and therefore would be expected to have a higher mortality. She was able to
carry her observations to the next level by suggesting simple measures such as
improved sanitation, less crowding, and location of hospitals distant from crowded
urban areas that would ultimately result in dramatic improvement in patient outcomes.
This is arguably one of the earliest examples of total quality management (see below)
as a means of improving patient outcomes.
Ernest Amory Codman, a Boston surgeon, was one of the most outspoken early
advocates of outcome analysis and scrutiny of results. Codman was a classmate of
Harvey Cushing and apparently became interested in the issues of outcome analysis
after a friendly bet with Cushing about who had the lowest complication rate with the
delivery of anesthesia. In the early 1900s, the medical students were responsible for
administering anesthesia. Since vomiting and aspiration were common upon induction
of anesthesia, many operations were over before they started. Cushing and Codman
compared their results and kept records concerning the conduct of anesthesia while
they were medical students. This effort not only represented the first intraoperative
patient records but also served as a foundation for Codman's later interest in (almost
passion for) documentation of outcomes. Codman actually paid a publisher to
disseminate the results obtained in his privately owned Boston hospital. [2 ] Codman
was perhaps the first advocate of searching for a cause of all complications. He linked
specific outcomes with specific interventions (or errors). He felt that most bad outcomes
were ultimately the result of errors or omissions on the part of the physician.
Both Codman and Nightingale viewed outcome analysis as an intermediate step

toward improvement of patient care. It is not enough to know the rates of a given
outcome. That is only the first step. Outcome analysis only becomes meaningful when it
can help to improve patient care. While it is axiomatic that any valid comparison of
quality of care or patient outcome must account for the severity of illness, this is only the
initial step toward improving patient outcome.
Unfortunately, some agencies (both governmental and private) are willing to use
outcome measures, with or without risk adjustment, punitively to control medical
practice and costs. However, such efforts may influence patient care adversely, since
physicians or hospitals may be less willing to accept difficult cases. The institution of the
New York State Department of Health Cardiac Surgery Reporting System (CSRS),
which generated the first physician-specific mortality report published in the lay press,
may have discouraged operative treatment of high-risk patients. [3 ] It was widely
reported that the risk-adjusted mortality rate for patients undergoing coronary artery
bypass grafting (CABG) in New York declined after institution of CSRS. [4 ] The
inference was that the lower mortality rate was a product of improved surgical results
and was possibly facilitated by the CSRS reporting system. [5 ] However, alternative
explanations also were proposed. [6 ] [8 ] Some providers (either surgeons or
hospitals) may have deliberately refused to operate on high-risk patients or fraudulently
altered preoperative risk factors. Some high-risk patients may have been referred out of
New York State. [7 ] At least one New York hospital admitted rejecting 23 high-risk
patients specifically to improve reported CABG outcomes. [8 ] This behavior fails to
grasp the purpose of risk adjustment or expresses a basic distrust in the adequacy of
risk-adjustment methodology. The prudent surgeon serves all patients best by
knowledge of outcome analysis and risk adjustment and with this information can
improve patient care and counter efforts to affect medical practice adversely.
DEFINITIONS OF RISK STRATIFICATION AND COMORBIDITY
Arranging Patients According to Severity of Illness
Risk stratification is defined as the ability to predict outcomes for a given intervention
by arranging patients according to severity of illness. The usefulness of any
risk-stratification system arises from how the system links severity of illness to a
specific outcome.
There have been numerous attempts to describe severity of illness by means of a score
or number. Table 6-1 lists some of the severity measures commonly used for risk
assessment of cardiac surgical patients. All these severity measures share two
common features. First, all are linked to a specific outcome or clinical state. Second, all
measures view a period of hospitalization as the episode of illness. In Table 6-1 ,
clinical measures (e.g., risk of death, clinical or hemodynamic instability, treatment
difficulty, etc.) define severity of illness. Two of the severity measures shown in Table
6-1 (Variation of Medis Groups used in the Pennsylvania Cardiac Surgery Reporting
System and the Canadian Provincial Adult Cardiac Care Network of Ontario) also
define severity based on resource use (e.g., hospital length of stay, cost, etc.). [10 ] , [19
] Of the nine systems to measure severity of illness listed in Table 6-1 , only one, the
APACHE III system, computes a risk score independent of patient diagnosis. [9 ] All the
others are diagnosis-specific systems for computing severity scores.
Each of the risk-stratification measures shown in Table 6-1 has been tested against a
validation set of patients and found to be adequate to measure the risk of operative
mortality or other outcome. However, assessment of the validity and performance of
various risk-adjustment methods entails more than simple cross-validation. No severity
score accurately describes patient risks for death, complications, or increased
resource use. Iezzoni [22 ] has prepared an excellent review of the subtleties of
evaluating performance of risk-adjustment methods.
Outcomes and Risk Stratification
There are at least four outcomes of interest to surgeons dealing with cardiac patients:
mortality, morbidity, resource utilization, and patient satisfaction. Which patient
characteristics constitute important risk factors may depend largely on the outcome of
interest. Operative mortality is an easily defined, readily measured outcome, and its
value to patients is undeniable. Most studies, especially earlier ones, focused on
mortality as an outcome. However, in many instances, other outcomes such as resource
utilization or quality of life may be more relevant. Outcome measures other than
operative mortality are particularly important for deciding how to spend health care
dollars wisely.
The clinical variables associated with increased resource utilization after operation may
differ from those associated with increased mortality risk. There is evidence to suggest
that the risk factors associated with in-hospital death are likely to reflect concurrent
disease-specific variables, while factors associated with increased resource utilization
reflect serious comorbid illness. [23 ] , [24 ] For example, mortality risk after CABG is
associated with disease-specific factors such as ventricular ejection fraction, recent
myocardial infarction, and hemodynamic instability at the time of operation, whereas
risk factors for increased resource utilization (as measured by length of stay) include
comorbid illnesses such as peripheral vascular disease, renal dysfunction,
hypertension, and chronic lung disease. It is not surprising that comorbid conditions are
important predictors of hospitalization charges, since they often require prolonged
hospitalization not only for treatment of the primary surgical illness but also for treatment
of complicating comorbid conditions.
Measures of Comorbidity
Comorbidities are coexisting diagnoses that are unrelated to the principal surgical
diagnosis but that have an impact on the outcome of operation. Clearly, physicians or
hospitals that care for patients with a higher prevalence of serious comorbid conditions
are at significant disadvantage in unadjusted comparisons. The prevalence of comorbid
illness in patients with cardiac disease has been well demonstrated. In one series of
patients with myocardial infarction, 26 percent also had diabetes, 30 percent had
arthritis, 6 percent had chronic lung problems, and 12 percent had gastrointestinal
disorders. [25 ]
Several attempts at measuring comorbidity have been made. Table 6-2 compares five
commonly used comorbidity measures: the Charlson index, the RAND Corporation
index, the Greenfield index, the Goldman index, and the APACHE III scoring system. [25
] [31 ] There are many limitations of comorbidity indices, and they have not been applied
widely in studies of efficacy or medical effectiveness. Perhaps the most serious
drawback of comorbidity scoring systems is the imprecision of databases used to form
the indices. Most of the data used to construct the indices come from two sources: (1)
administrative databases in the form of computerized discharge abstract data and (2)
out-of-hospital follow-up reports. Discharge abstracts include clinical diagnoses that are
often assigned by nonphysicians who were not involved in the care of the patient.
Comprehensive entry of correct diagnoses is not a high priority for most clinicians, and
problems with discharge coding have been identified by Iezzoni et al. [32 ] Likewise, the
accuracy of out-of-hospital follow-up studies is hard to validate and may contain
significant inaccuracies. Nevertheless, analyses that compare physician or hospital
outcomes and do not provide adequate adjustment for patient comorbidity discriminate
against providers or hospitals that treat disproportionate numbers of elderly patients
with multiple comorbid conditions. [33 ] For example, Goldman et al. [29 ] reported that
preexisting heart conditions and other comorbid diseases were important predictors of
postoperative cardiac complications for patients undergoing noncardiac procedures.
Although less well studied, comorbid conditions are also likely to influence outcomes in
patients undergoing cardiac procedures.
GOALS OF RISK STRATIFICATION
There are multiple areas where the tools of risk stratification can be used to judge
effectiveness of care and to aid providers in quality improvement, including the
following: (1) cost containment, (2) patient education, (3) effectiveness-of-care studies,
and (4) improving provider practices. Table 6-3 provides an idealized list of some of the
potentially beneficial uses and goals of risk stratification.
Improving the Quality of Care
The ultimate goal of risk stratification is to account for differences in patient risk factors
so that patient outcomes can be used as an indicator of quality of care. A major
problem arises because uniform definitions of quality of care are not available. This is
particularly true of cardiovascular disease. For example, there are substantial
geographic differences in the rates at which patients with cardiovascular diseases
undergo diagnostic procedures, but there is little evidence that these variations relate to
survival. [33 ] [37 ] In one study, coronary angiography was performed in 45 percent of
patients in Texas after acute myocardial infarction compared with 30 percent of patients
in New York State ( p < 0.001 for comparison between states). [34 ] The rate of
coronary revascularization was similar in the two populations, and survival was not
related to type of treatment or diagnostic procedures. These regional variations suggest
that a rigorous definition of the correct treatment of acute myocardial infarction is
elusive and that any definition of quality of care is imperfect. Similar imperfections exist
for nearly all outcomes in patients with cardiothoracic disorders. Risk-adjustment
methodologies can isolate patient risk factors that are associated with poor outcome.
Much more work is required to define optimal outcomes and treatment standards,
particularly in areas of rapid technologic and therapeutic innovation.
Efficacy Studies versus Effectiveness Studies
There have been many efficacy studies relating to cardiothoracic surgery. These
studies attempt to relate one procedure or device to patient outcome. Typical examples
of efficacy studies include randomized, prospective clinical trials comparing the use of a
procedure or device in a well-defined, fairly uniform population compared with a control
population.
Efficacy studies are different from effectiveness studies. The latter deal with random
populations and attempt to determine the best treatment option in a random population
that more typically represents clinical practice. An example of an effectiveness study is
a retrospective study of outcome in a whole population treated with a given procedure
or device. Risk stratification is capable of isolating potential causes of poor outcome
and in reducing biases inherent in population-based, retrospective studies.
One strategy for using risk stratification to improve patient care is to isolate high-risk
subsets from population-based, retrospective studies and then to test different
interventions in these high-risk subsets using prospective efficacy trials. For example,
two population-based studies on postoperative blood transfusion revealed that the
following factors were significantly associated with excessive blood transfusion (more
than 4 units of blood products after CABG): (1) template bleeding time, (2) red blood
cell volume, (3) cardiopulmonary bypass time, and (4) patient age. [38 ] Based on these
retrospective studies, it was postulated that methods to reduce blood transfusion after
CABG would most likely benefit patients with prolonged bleeding time and low red
blood cell volume. A prospective, stratified clinical trial was then performed to test this
hypothesis in patients undergoing CABG using two blood-conservation techniques:
platelet-rich plasma saving and whole blood sequestration. The results showed that
both blood-conservation interventions only benefited the high-risk subset of patients as
defined by risk stratification. [39 ] Other strategies that use risk-adjustment methods to
improve quality of care also have been developed.
Other Goals of Risk Stratification (Cost Containment and Altering Physician

Practices)
Financial factors are a major force behind health care reform. America's health care
costs amount to 15 percent of the gross national product, and this figure is rising at a
rate of 6 percent annually. Institutions that pay for health care are demanding change,
and these demands are fueled by studies that suggest that 20 to 30 percent of care is
inappropriate. [40 ] Charges of inappropriate care stem largely from the observation
that there are wide regional variations in the use of expensive procedures. [41 ] , [42 ]
Health care costs are now considered as important as clinical outcomes. Relman [43 ]
suggests that concerns about clinical outcomes and costs will be used by patients,
payers, and providers as a basis for distribution of future funding. Failure to account for
patient risks will bias clinical outcomes and thus distort allocation of health care funds.
Therefore, risk adjustment is an essential element of outcome management.
TOOLS OF RISK STRATIFICATION
Databases
Perhaps the most important ingredient of any risk-stratification endeavor is a database

that represents the study group of interest. The need for accuracy of data elements in
any database cannot be overemphasized. [44 ] [46 ] Factors such as source of data,
outcome of interest, methods used for data collection, standardized definitions of the
data elements, data reliability checking, and the time frame of data collection are
essential features of all databases. [45 ] , [46 ] An evaluation of the quality of the
database is an essential first step in risk stratification.
Data obtained from claims databases are criticized because of clinical inaccuracies
and the likelihood that complications are overestimated for billing purposes. [47 ]
Furthermore, claims data underestimate the effects of comorbid illness in CABG
patients and have major deficiencies in such important prognostic variables as left
ventricular function and number of diseased vessels. [48 ] The Duke Databank for
Cardiovascular Disease found major discrepancies between clinical and claims
databases, and found that claims data failed to identify more than half of patients with
important comorbid conditions such as congestive heart failure, cerebrovascular
disease, and angina. [49 ] The Health Care Financing Administration (HCFA) uses
claims data to evaluate mortality rates in hospitals treating Medicare patients. After
initially disastrous efforts to adjust risk from claims data, [50 ] , [51 ] new algorithms
were developed. Despite these advances, HCFA has delayed release of the most
recent (1993) Medicare hospital mortality report because of database concerns and
fears of unfair evaluation of inner-city public facilities. [52 ]
Analytic Tools of Risk Stratification
Development of significant risk factors that are predictive of outcomes of interest

requires analytic statistics. Outcome analysis relies on statistical techniques that can
evaluate large populations with multiple variables in an interdependent manner, i.e.,
multivariate analyses. Some basic knowledge of analytic statistics provides a
foundation for assessment of risk-adjustment methods and critical interpretation of
results. This knowledge and physician acceptance of risk-adjusted outcome analysis
can lead to improved patient care.
REGRESSION ANALYSIS
Elementary statistics is the starting point for understanding multivariate statistical

methods. Several basic, readable statistical texts are available for health care
professionals. [53 ] [56 ] These texts cover basic terminology, simple parametric
(normally distributed) univariate statistics, linear regression, analysis of variance,
nonparametric (not normally distributed) statistical techniques, and ultimately
multivariate statistical methods.
Regression analysis is a statistical technique that is commonly used to describe how

one variable (the dependent or outcome variable) depends on or varies with a set of
independent (or predictor) variables. The dependent variable can be either continuous
(e.g., hospital cost or length of stay) or discrete (e.g., mortality). Discrete outcome
variables can be either dichotomous (two discrete values such as alive or dead) or
nominal (multiple discrete values such as improved, unimproved, or worse). The
relationship between the outcome variable and a set of descriptor variables can be
linear or any nonlinear mathematical relationship. Glantz and Slinker [57 ] provide a
primer on regression analysis that is geared to the biomedical sciences.
Regression analysis determines the relationship (also termed constructing a model )

that describes how an outcome variable depends on a set of independent predictor
variables. In simple terms, multivariate regression analysis is model building . The
resulting model is useful only if it accurately predicts outcomes for patients by
determining significant risk factors associated with the outcome of interest. When the
outcome variable is a continuous variable such as hospital cost, linear multivariate
regression is often used to construct the model. A multivariate linear regression model
contains a set of independent variables that are linearly related to and can be used to
predict an outcome variable. These significant independent variables are termed risk
factors , and knowledge of these risk factors permits separation of patients according
to their degree of risk, i.e., risk stratification.
Statistical terminology used to describe variables and distribution patterns of variables

is particularly important in understanding statistical modeling. Statistical variance R 2 is
an important concept. R 2 summarizes the performance of a statistical model and
indicates the fraction of all variables affecting the dependent variable explained by the
statistical model. Most investigators report R 2 as a performance measure of
risk-adjustment models. [58 ] For example, the APACHE III risk-adjustment scoring
system described in Table 6-1 can be used to predict intensive care unit (ICU) length of
stay. When this is done, the model is associated with an R 2 value of 0.15. [27 ] , [58 ]
This implies that 15 percent of the variability in ICU length of stay is explained by
variables encompassed in the APACHE III score and that 85 percent of the variability is
not explained by this model. This R 2 value does not rate the APACHE III scoring
system very highly for predicting ICU length of stay. APACHE III was developed to
predict in-hospital mortality, not hospital costs or length of stay. [27 ] The system uses
patient data obtained within 24 hours of admission and excludes important events that
occur after admission in the prediction of length of stay [59 ] ; hence it is not surprising
that APACHE III is a poor predictor of resource utilization.
Shwartz and Ash [60 ] give an excellent review of evaluating the performance of
risk-adjustment methods using R 2 as a measure of model performance. An R 2 value
of 0.15 for the APACHE III model is not as horrible as it sounds. Hartz et al. [61 ] point
out that no large multivariate regression model can completely account for all the
variability of any complex outcome. These authors constructed a so-called perfect
model of simulated mortality data for CABG and found that this model accounted for
only 31 percent of the variation in mortality rate. The APACHE III value for R 2 looks
somewhat better when judged by these standards. Ideally, refinement in any regression
model is an ongoing process aimed at maximizing the value of R 2 .
Logistic regression is the nonlinear method used most widely to model dichotomous
outcomes of discrete variables (e.g., mortality). Logistic regression uses the
mathematical fact that the expression e x /1 + e x assumes values between 0 and 1 for
all positive values of x . The value x in the expression can be a linear sum of a set of
predictor variables (either continuous or discrete), and the value of e x /1 + e x is the
outcome probability between 0 (survival) and 1 (death) for any set of predictor variables.
Computer iteration techniques are used to produce a model of independent variables
that best predicts the occurrence of a dichotomous outcome variable. The significant
independent variables identified by the logistic regression model are risk factors that
can be used to stratifiy patients for their risk of experiencing the dichotomous outcome
(e.g., survival or death).
Table 6-4 shows a 2 × 2 table generated from a hypothetical logistic regression model
used to predict dichotomous outcomes, and Table 6-5 describes the statistical terms of
interest that can be derived from the predicted and observed outcomes. Figure 6-1 is a
receiver operator characteristic (ROC) curve derived from a plot of the sensitivity versus
1 minus the specificity (same as a plot of the true-positive rate versus the false-positive
rate). The ROC curve in Figure 6-1 is produced by assuming a particular cutpoint for a
predicted probability of one outcome (e.g., death).
The performance of logistic regression models can be assessed in several ways.

However, there is less agreement about performance measurements of these models
that predict binary outcomes than about R 2 for multivariate linear regression models.
The c statistic is one commonly used parameter to evaluate performance of logistic
regression models [62 ] and is equal to the area under the ROC curve (e.g., Figure 6-1
). Figure 6-1 is from the work of Knaus et al., [63 ] who developed the APACHE III
scoring system for prediction of in-hospital death from variables on admission to the
ICU. These authors reported a c statistic (area under the ROC curve) of 0.90 for
predicting death in 17,440 patients from 40 hospitals used to develop the model. This
statistic suggests good performance of their logistic regression model. [29 ] , [63 ] An
excellent critique of the various methods used to assess performance of regression
models of dichotomous outcomes is given by Ash and Shwartz. [64 ]
Statistics of Survival
When the outcome of interest is a time-dependent variable (e.g., hospital length of stay
or survival after valve implantation), regression modeling is more complex but still
manageable. Regression models for time-dependent outcome variables are used
extensively to study survival following heart valve implantation, and hence this type of
regression is termed survival regression . These models can be developed using
computer iteration methods. Several excellent texts are available that cover the gamut
of technical information from the relatively simple [65 ] , [66 ] to the complex. [67 ] [69 ]
One model that has been used extensively in the biomedical sciences is the Cox
proportional hazards regression model. [67 ] In some regression models, such as
logistic regression, the dependent or outcome variable is known with precision. With
time-dependent outcome variables, the possibility exists that only a portion of the
survival time is observed for some patients. Thus the data available for analysis consist
of some outcomes that are incomplete or censored. Some regression models, such as
logistic regression, do not adapt easily to censored data. Cox's model overcomes
these technical problems by assuming that the independent variables are related to
survival time by a multiplicative effect on the hazard functionthus proportional hazards
model . The hazard function is defined as the slope of the survival curve (or the
time-decay curve) for a series of time-dependent observations. In the Cox model, one
assumes that the hazard functions are proportional, and hence it is not necessary to
know the underlying hazard function to determine the relative importance of independent
variables that contribute to the overall survival curve. Table 6-6 shows an example of the
use of Cox regression to evaluate the independent variables that are predictive of
hospital length of stay (a time-dependent outcome variable) for patients undergoing
CABG. [24 ] For the purposes of this analysis, hospital deaths are considered censored
observations. The independent variables shown in Table 6-6 are considered risk
factors for increased length of stay and can be used to stratify patients into groups with
varying risk of prolonged hospitalization.
Measures of the performance for Cox regression models are less well developed than
those for logistic regression or for multivariate linear regression. Simple methods of
checking the predictive value of Cox models are usually reported in the medical
literature. One of the most commonly used methods is called cross-validation . This
consists of using Cox regression to determine significant independent variables
predictive of outcome in a training set of data (e.g., Table 6-6 ). The significant
variables and their coefficients from the Cox model are then used to compute values of
the outcome variables in a different data set (called the validation set ). The agreement
between predicted values and observed values in the validation set is used as an index
of the performance of the Cox model. Figure 6-2 shows a cross-validation set of data
used to check the results of the Cox regression described in Table 6-6 . This figure
shows fair validation of the Cox model using a relatively small data set (1200 patients
operated on during 1994 at a single institution).
Bayesian Analysis: Models Based on Experience
Thomas Bayes was a nonconformist minister and mathematician who described the
probability of an event using knowledge of prior probabilities that the same event had
already occurred. [70 ] Using the bayesian approach, three sets of probabilities are
defined: (1) the probability of an event before the presence of a new finding is revealed
( prior probability ), (2) the probability that an event is observed given that an
independent variable is positive ( conditional probability ), and (3) the probability of an
event occurring after the presence of a new finding is revealed ( posterior probability ).
The mathematical relationship between the three probabilities is Bayes' theorem. The
prior and posterior probabilities are defined with respect to a given set of independent
variables. In the sequential process common to all bayesian analyses, the posterior
probabilities for one finding become the prior probabilities for the next, and a
mathematical combination of prior and conditional probabilities produces posterior
probabilities. Bayes' theorem can be expressed in terms of the nomenclature of Table
6-5 as P Bayes = sensitivity × prior probability/ (sensitivity × prior probability) +
[false-positive rate × (1 - prior probability)] where P Bayes is defined as the probability of
a given outcome if prior probabilities are known. The principles of bayesian statistics
have been used widely in decision analysis [71 ] and also can be used to generate
multivariate regression models based on historical data about independent variables.
[12 ] , [72 ] [74 ] Bayesian multivariate regression models are generated using
computer-based iterative techniques [12 ] , [74 ] and have been used to develop the
risk-stratification analysis for the Society of Thoracic Surgeons National Database. [12 ]
, [13 ] Evaluation of the performance of the bayesian statistical regression models is
usually done by cross-validation studies similar to those used to validate the Cox
survival regression model. Performance of bayesian models also can be expressed in
terms of ROC curves and the c statistic as for logistic regression models. [75 ] Marshall
et al. [75 ] have shown that bayesian models of risk adjustment give comparable results
and similar ROC curves to conventional models generated from logistic regression
analysis.
TOTAL QUALITY MANAGEMENT (TQM) AND RISK ANALYSIS
Total quality management (TQM), developed for industry by W. Edwards Deming, [76 ]
is a system of management and efficiency based on quality. Using this approach, health
care is viewed as a process requiring raw materials (e.g., sick patients), manufacturing
steps (e.g., delivery of care to the sick), and finished products (e.g., outcomes of care).
Managerial interventions are important at each step of the process to ensure a
high-quality product. Table 6-7 outlines the key features of TQM.
Berwick et al. [77 ] describe the experiences of the National Demonstration Project on
Quality Improvement in Health Care in applying principles of TQM to solve a broad
spectrum of health care problems. Twenty-one health care organizations throughout the
United States participated in an experiment in the application of TQM to health care.
Each organization selected a problem at their institution and, with the aid of an industrial
consultant, applied the principles of TQM to solve the problem. Each institution involved
in the project reported that the initiation of TQM practices was far more valuable than
the actual solution of a particular problem. In the jargon of TQM, implementation and
understanding of TQM principles at every level within an institution produced significant
improvement in customer-supplier throughput, i.e., improvement in patient care.
An important component of the TQM process is the use and availability of statistical
methods to provide the necessary information to managers and workers who must
make decisions about the health care process. [78 ] [80 ] While the statistical methods
of TQM have a slightly different focus than those outlined above for risk adjustment, the
goal is the same, i.e., improving the quality of health care.
Table 6-8 provides an outline of the sequential steps involved in solving a problem using
TQM. Risk stratification plays an important role in the TQM process. One of the most
important applications of risk stratification in TQM occurs in the project when definition
of the problems that affect quality is considered. Usually a problem is identified from
critical observationse.g., excessive blood transfusion after operation results in
increased morbidity, including disease transmission and increased infection risk, as
well as increased cost. Tools such as flow diagrams that document all the steps in the
process (e.g., steps involved in the blood transfusion process after CABG) are helpful in
this phase of the analysis.
A logical starting point for efforts to improve quality of the blood transfusion process is
to focus on a high-risk subset of patients who consume a disproportionate amount of
resources. An Italian economist, Pareto, observed that only a few factors account for the
majority of outcomes of a complex process. In the jargon of TQM, this has been termed
the Pareto principle . A graphic method that identifies the spectrum of outcomes in a
process is termed a Pareto diagram . The Pareto diagram is an example of a graphic
method of risk identification. Figure 6-3 is an example of a Pareto diagram for blood
products transfusion at Albany Medical Center Hospital during 1994. The data are
arranged in histogram format, and the population distribution of patients receiving
transfusion is plotted simultaneously. By looking at the diagram, a subset of patients
who consume more than a certain threshold of blood products can be identified. For
example, 20 percent of patients consume 80 percent of the blood products transfused.
Therefore, substantial savings in cost and morbidity will result by decreasing blood
transfusions in this group of high-end users. The next step is to devise and test
strategies to decrease blood products consumption in the high-risk subset. Some of the
risk-stratification analytic tools discussed previously can be equally useful in the TQM
process. For example, linear regression analysis can identify which of several factors
are most important in predicting improved blood transfusion profiles after CABG, or
Cox analysis can identify risk factors for increased hospital length of stay in patients at
high risk for excessive blood transfusion. Other tools of TQM, such as data-sampling
strategies and use of control charts, also play important roles in the process.
The study reported by de Leval et al. [81 ] is an example of a TQM project in clinical
cardiothoracic surgery. In this study, surgeons identified an increase in the mortality rate
of infants undergoing total repair of dextrotransposition of the great vessels. Using the
principles of TQM, they identified risk factors for poor outcome and separated the
sources of variation in mortality rate into random (common cause) or nonrandom
(special cause) variation. By identifying and altering nonrandom (presumably
surgeon-related and process of care-related) causes of increased mortality, they
improved results.
RISKS OF OPERATION FOR ISCHEMIC HEART DISEASE
Risk Factors for Mortality
By far the bulk of available experience with risk stratification in cardiothoracic surgery
deals with risk factors associated with operative mortality, particularly in patients
undergoing coronary revascularization. Most of the risk-stratification analyses shown in
Table 6-1 have been used to evaluate life or death outcomes in surgical patients with
ischemic heart disease, in part because mortality is such an easy endpoint to measure
and track. As mentioned previously, each of the risk-stratification systems shown in
Table 6-1 , with the exception of the APACHE III system, computes a risk score based
on risk factors that depend on patient diagnosis. For the diagnosis of ischemic heart
disease, Table 6-9 shows the significant risk factors found to be important for each of
the risk-stratification systems. The definition of operative mortality varies among the
different systems (either 30-day mortality or in-hospital mortality), but the risk factors
identified by each of the stratification schemes in Table 6-9 show more similarities than
differences between each of the models. Each of the models has been validated using
separate data sets; hence there is some justification in using any of the
risk-stratification methods both in preoperative assessment of patients undergoing
CABG and in making postoperative comparisons among providers (either physicians
or hospitals). At present it is not possible to recommend one risk-stratification method
over another. There are many critical features of any risk-adjustment outcome program
that must be considered when determining quality of the risk-stratification method or
when comparing one with another. Daley [45 ] provides a summary of the key features
that are necessary to validate any risk-adjustment model. She makes the point that no
clear-cut evidence exists that differences in risk-adjusted mortalities across providers
reflect differences in the process and structure of care. [45 ] , [82 ] This issue needs
further study.
Controversy exists as to whether changes in risk-adjusted mortality over time reflect

changes in care or if these changes are due to other factors not related to individual
providers. [3 ] [7 ] One set of innovative studies to address this issue has been carried
out by the Northern New England Cardiovascular Disease Study Group. [20 ] , [83 ] [85 ]
These investigators used a risk-adjustment scheme ( Tables 6-1 and 6-9 ) to predict
mortality in patients undergoing CABG at five different institutions. After risk
stratification, significant variability was found among the different institutions and
providers. Statistical methods suggested that the variation in mortality rate was
nonrandom (i.e., special variability in the TQM vernacular). To study this variability, they
visited each institution and reviewed the processes involved in performing CABG.
Surgical technique, communication among providers, leadership, decision making,
training levels, and environment were assessed at each institution. Significant variation
among many of the processes was observed, and attempts to correct deficiencies were
undertaken at each institution. Subsequent publications from these authors will help
answer questions regarding the ability of risk-stratification models to account for
differences in patient care among institutions and providers. These efforts are an
example of using the principles of risk stratification and TQM to improve quality of care.
Until more of this sort of information is available, it is irresponsible to make major health
care decisions based on differences in risk-adjusted mortality among providers.
There are literally hundreds of patient variables other than those shown in Table 6-9 that
have been proposed as factors for operative mortality following coronary
revascularization. Such variables as serum blood urea nitrogen (BUN) level, [86 ] serum
albumin level, [87 ] cachexia, [88 ] oxygen delivery, [89 ] HIV status, [90 ] pulmonary
function, case volume, [91 ] and resident involvement in the operation [92 ] , [93 ] fit this
description. On the surface, the clinical relevance of these variables may seem
undeniable in published reports, but very few of these putative risk factors have been
tested with the rigor of the variables shown in Table 6-9 . The regression diagnostics
(e.g., ROC curves and cross-validation studies) performed on the models included in
Table 6-9 suggest that the models are good at predicting outcomes but not perfect. In
statistical terms, only part of the variability in operative mortality is explained by the risk
factors included in regression models. Hence it is possible that new putative risk factors
may improve the validity and precision of the models.
New regression models must be scrutinized and tested using cross-validation methods
and other regression diagnostics before acceptance. It is uncertain whether inclusion of
additional risk factors will improve the quality and predictive ability of regression models
significantly. For example, the STS risk-stratification model described in Tables 6-1 and
6-9 includes many predictor variables, while the Ontario risk-adjustment scheme
includes only six predictor variables. Yet the regression diagnostics for these two
models are similar and suggest that both models have equal precision and predictive
capabilities. Further work is needed to explain the differences in risk factors between
various risk-stratification models and to determine which models are best for studies of
quality improvement.
Risk Factors for Outcomes Other than Mortality
Patients with nonfatal outcomes following operations for ischemic heart disease make
up more than 95 percent of the pool of patients undergoing operation. Of approximately
300,000 patients having CABG yearly, between 50 and 75 percent have an
uncomplicated postoperative course. The complications occurring in surviving patients
range from serious organ system dysfunction to minor limitation or dissatisfaction with
lifestyle but account for a significant fraction of the costs. I estimate that as much as 40
percent of the yearly hospital costs for CABG are consumed by 10 to 15 percent of the
patients who have serious complications after operation. [24 ] This is an example of the
Pareto principle and suggests that reducing morbidity can reduce costs significantly.
A great deal of information is available on nonfatal complications after operation for

ischemic heart disease. Several large databases identify risk factors for both nonfatal
morbidity and increased resource utilization. Table 6-10 is a summary of some of the
risk factors identified by available risk-stratification models using either serious
postoperative morbidity or increased length of stay as a measure of undesirable
outcome.
Occasionally, studies suggest that a specific patient variable is not a risk factor for a
particular patient outcome. Care must be exercised in interpreting negative results.
Many putative risk factors labeled as no different from control in studies using
inadequate samples have not received a fair test. For example, Burns et al. [95 ]
studied preoperative template bleeding times in 43 patients undergoing elective
CABG. They found no increased postoperative blood loss in patients with prolonged
bleeding times and concluded that the test was not predictive. [96 ] However, their study
reports five patients whose bleeding times were prolonged greater than 8 minutes. In
this small sample size, there was a trend toward more units of blood transfused, but
differences between high and low bleeding time groups were not significant at the = 5
percent level ( p = 0.06). Using the authors' data, the error for this negative observation
calculates to less than 0.5. This means that there is a 50 percent chance that the
negative finding is really a false-negative result because of the small sample size and
wide variation in the bleeding time values. Similarly, Freiman et al., [97 ] after reviewing
the medical literature over a 10-year period, found that 50 of 71 negative randomized
controlled trials could have missed a 50 percent therapeutic improvement from an
intervention because sample sizes were too small. They concluded that many therapies
discarded as ineffective after inconclusive negative trials may in fact have a clinically
important effect.
Other post-CABG outcomes, such as patient satisfaction and sense of well-being, have
been less well studied. The increasing importance of patient-reported outcomes reflects
the increasing prevalence of chronic disease in our aging population. The goal of
therapeutic interventions is often to relieve symptoms and improve quality of life rather
than to cure a disease and prolong survival. This is especially important in selecting
elderly patients for operation. One report from the United Kingdom suggests that as
many as one-third of patients over age 70 do not have improvement in their disability
and overall sense of well-being after a cardiac operation. [98 ] Risk-stratification
methods may improve selection of elderly patients for myocardial revascularization
based on quality-of-life considerations.
Surprisingly little published information is available regarding long-term functional status

or patient satisfaction following CABG. One comparative study found no difference
between patients older than 65 years and those younger than age 65 with regard to
quality-of-life outcomes (symptoms, cardiac functional class, activities of daily living,
and emotional and social functioning). [99 ] This study also found a direct relationship
between clinical severity and quality-of-life indicators, since patients with fewer
comorbid conditions and better preoperative functional status had better quality-of-life
indicators 6 months after operation. These findings suggest that the risks of patient
dissatisfaction after CABG depend on preoperative comorbid factors as well as
operative indications and technical problems. At present, no risk-stratification scheme
identifies patients who are likely to report dissatisfaction with operative intervention
following CABG.
Despite considerable research, there are several difficulties with measurements of

patient-reported outcomes. One problem is that patient-reported outcomes may be
dependent on the type of patient who is reporting them and not on the type of care
received. For example, younger Caucasian patients with better educations and higher
incomes are more likely to downgrade ratings of physician care. [100 ] At least two
patient satisfaction measures, the Short-Form Health Survey, or SF-36, [101 ] and the
San José Medical Group's Patient Satisfaction Measure, [102 ] have been used to
monitor patient satisfaction over time. Unfortunately, the quality of data does not allow
comparisons among providers because of low response rates, inadequate sampling,
infrequent use, and unavailability of satisfactory benchmarks. Nonetheless, available
evidence indicates that patient-reported outcomes can be measured reliably [103 ] ,
[104 ] and that patient satisfaction data can significantly improve physician practices.
[105 ] Managed care organizations and hospitals probably will use patient-reported
outcome measures to make comparisons between institutions and individual providers.
Risk-adjustment methods for patient-reported outcomes are required to provide valid
comparisons.
RISKS OF OPERATION FOR VALVULAR HEART DISEASE
Risk Factors for Mortality and Morbidity
Evaluating risks of operation for valvular heart disease is a complex process because
of the variety of valves available and the multiple number of valve-related events that
must be considered. Fatal and nonfatal events related to implanted prosthetic heart
valves occur early and late after operation, and for this reason, it is essential to include
both short- and long-term follow-up. Recognizing these complexities, a joint committee
of two thoracic surgical societies developed guidelines (STS/AATS guidelines) for
defining and reporting morbidity and mortality after cardiac valvular operations. [106 ]
These guidelines facilitated comparisons of risks, operative results, and valve-related
outcomes for a broad spectrum of valve types. Table 6-11 represents a summary of risk
factors identified from a review of the current literature for operative mortality and
valve-related morbidity. Only studies that used multivariate analyses and the STS/AATS
guidelines were tabulated to provided a synopsis of important risk factors associated
with poor outcome. No reference identifies all risk factors, and the relative importance
of each factor to overall outcome cannot be inferred from this list. Nevertheless, Table
6-11 shows that preoperative functional status (as reflected by New York Heart
Association functional classification) and left ventricular function are the most frequently
cited risk factors for both early and late mortality following cardiac valvular procedures.
The table also identifies many other risk factors that are cited less frequently, perhaps
because of small numbers, different valves, or different patients.
Valve-related postoperative morbidity has been studied extensively. Many studies have
compared mechanical valves and bioprostheses, but few substantive differences
between these two types of valves have been reported. This statement is true for the
rate of thromboembolism, development of prosthetic valve endocarditis, and freedom
from all valve-related complications. [163 ] [166 ] There are obvious differences
between bioprosthetic and mechanical valves in the rates of structural valve
degeneration and anticoagulation-related hemorrhage, but the overall rate of serious
valve-related complications (including reoperative mortality, serious hemorrhage or
thrombosis, valve-related late mortality, and valve-related reoperation) is similar for both
types of prostheses. [163 ] [166 ] This statement is true because there is obvious bias in
the selection of a prosthesis for a given patient. Elderly patients are more likely to
receive bioprosthetic valves and younger patients mechanical prostheses. Because of
these biases and different patient populations, risk factors for development of serious
postoperative morbidity or mortality are very dependent on the type of prosthesis used
and patient subsets. Therefore, it is not possible, despite large amounts of data, to
make sweeping generalizations regarding risk identification in patients who have
cardiac valvular procedures.
There is surprisingly little information concerning resource utilization by patients

undergoing valvular heart operations, and what there is conflicts. Olsson et al. [167 ]
studied the duration of ventilatory support, ICU stay, and hospital stay in octogenarians
undergoing aortic valve replacement (AVR). These authors found no difference in
resource utilization between octogenarians and younger patients. In contrast, other
investigators found that age and severity of illness are significant multivariate risk
factors for increased hospital costs in patients undergoing AVR [168 ] , [169 ] and that
age, left ventricular dysfunction, and comorbid illness are risk factors for resource
utilization in reoperative AVR. [135 ]
Several studies have noted that certain patient variables are not risk factors for a
particular valve procedure. A study by Scott et al. [113 ] evaluated risk factors for
mortality in patients undergoing AVR in conjunction with CABG. They found that
concomitant CABG was not an independent risk factor for operative mortality. Other
more recent studies have found that the extent of coronary artery involvement, [108 ] ,
[109 ] including left main coronary artery disease, [170 ] is a significant multivariate risk
factor for AVR. The extent of concomitant coronary artery disease undoubtedly
influences decisions to perform CABG; thus there is obvious bias in the selection of
patients who receive CABG in conjunction with AVR. The negative result that CABG is
not an independent risk factor for mortality after AVR must be interpreted with caution
because of selection bias.
AORTIC SURGERY
Morbidity and Mortality Risks
Operations for disease of the aorta (either aneurysms or dissections) are associated
with significant mortality and morbidity. Risk factors associated with operative mortality
depend on the site of operative repair (ascending, descending arch or combination of
sites), preoperative indications (either aneurysm disease or dissection), and comorbid
or preexisting conditions (e.g., rupture, concomitant coronary artery disease, or
preoperative stroke). Table 6-12 outlines some of the risk factors identified in recent
studies. Studies were included in Table 6-12 if they used multivariate techniques and
presented results of a broad-based surgical experience.
The in-hospital operative mortality risk for elective ascending aortic aneurysm repair (or
replacement) is between 5 and 10 percent [171 ] , [172 ] but is much higher for
emergency repairs, which usually concern acute dissection. [183 ] , [184 ] This
difference has led investigators to develop a rational plan for decisions about operative
timing and risk-benefit relationships. [185 ] Unfortunately, there is little objective
evidence on which to base these decisions, and only rough guidelines are available.
For example, the risk of rupture of ascending thoracic aneurysms is believed to be
greater in patients with symptoms, saccular aneurysms, Marfan's syndrome, and
aneurysmal diameter greater than 6 cm. [185 ] However, because of the relatively slow
growth rate of ascending thoracic aneurysms, a conservative, nonoperative approach
with careful follow-up by CT scan every 3 to 6 months also seems rational. Available
information about risk factors for rupture or aneurysm progression is inadequate to
guide decisions for operation and to assess the risk-benefit relationship of operation at
this time.
Opinion favors emergency surgery for essentially all patients with acute ascending
dissections. Risk factors associated with this intervention are indicated in Table 6-12 .
Medical management is usually the initial preferred treatment for patients with acute
descending dissections. However, when medical therapy fails, death usually follows.
[186 ] In a large cooperative study from Duke and Stanford, multivariate risks of early
mortality for both medical and surgical patients with acute descending dissections were
found to be age, cardiac status, dissection-related complications, and whether or not
aortic rupture had occurred. [187 ] In hopes of avoiding rupture during medical
management for descending dissections, several centers suggested earlier surgery for
some patients. [188 ] Clear indications for emergency operation included impending
rupture, major end-organ ischemia, and progression of the dissection during optimal
medical therapy (e.g., recurrent pain). In patients without these complications, no data
defined a subpopulation that might benefit from early surgery. Yet with the advent of
transesophageal echocardiography, a European Cooperative Study Group on
Echocardiography suggested that fluid extravasation around the aorta and an open
false lumen with a high communication were signs of impending rupture. [183 ]
Eventually, risk analysis may identify high-risk subsets of patients with descending
dissection who might benefit from early operation.
The risk of paraplegia is also a critical variable in the decision to operate on aneurysms
or dissections of the descending thoracic aorta. Risk factors for spinal cord injury
include type of aortic disease, [189 ] [191 ] extent of aortic involvement, [192 ] presence
of aortic dissection, [178 ] duration of aortic clamping, [190 ] , [192 ] and periods of
intraoperative hypotension. [192 ] , [193 ] Since many risks of spinal cord ischemia from
aortic surgery are known, patients can be stratified for the risk of paraplegia, and
interventions to minimize spinal cord injury can be tested. Such interventions as distal
aortic perfusion, [194 ] reimplantation of critical intercostal arteries, [195 ] various drug
therapies, [196 ] [198 ] and hypothermia with circulatory arrest [199 ] may be tested
using risk-stratification methods to assign patients to treatment groups. However,
Kouchoukos and Rokkas [200 ] point out that controlled assessment of a very large
number of risk-stratified patients is necessary because the risk of paraplegia is small (3
to 25 percent depending on risk category) and the variability within each risk group is
great. At present, only studies pooling the experience of several institutions would be
capable of addressing issues regarding spinal cord protection. No such studies have
been performed to date.
OTHER CONSIDERATIONS AND CONCLUSIONS
Validity and Reliability of Risk-Stratification Methods
There is little or no consensus about how to assess the validity of risk-adjustment

methods. As pointed out by Daley, [82 ] the concept of validity is something that
everyone understands but is without definition. The concept of validity is made up of
many parts, including five listed by Daley: (1) face validityWill the user accept the risk
model as valid? (2) content validityDoes the model include risk factors that should be
included based on known risks? (3) construct validityHow well does the model compare
with other measures of the same outcome? (4) predictive validityHow well does the
model predict outcome in patients who were not used to construct the model? and (5)
attributional validityDoes the model measure effectiveness of care rather than patient
variability? Of these components, face and content validity are arguably the most
important. Clinicians can readily accept results of risk stratification if the model uses
familiar variables and includes risk factors that the clinician recognizes as important
outcome determinants. All the risk models shown in Fig. 6-1 satisfy some or all of these
criteria of validity. No objective measure defines validity, but most clinicians agree that
risk models are relevant to clinical practice and contain features that one would expect
to be predictive of CABG morbidity and mortality.
The issue of reliability of a risk-stratification model is more easily quantitated than

validity. Reliability of a risk-adjustment method refers to the statistical term precision or
the ability to repeat observations using similar input variables and statistical techniques
with similar outcomes. There are literally hundreds of sources of variability in any
risk-stratification model. Some of these include errors in data input, inconsistencies in
coding diagnosis or use of therapeutic interventions, data fragility (final model may be
very dependent on a few influential outliers), and the type of rater (physician, nurse, or
coding technician), to name a few. [201 ] The most common measure of reliability is
Cohen's kappa, which measures the level of agreement between two or more
observations compared with agreement due to chance alone. [202 ] Kappa is defined
as K = P o - P o /1 - P c where P c is the fraction representing the agreement that would
have occurred by chance, and P o is the observed agreement between two observers. If
two observers agree 70 percent of the time on an observation where agreement by
chance alone would occur 54 percent of the time (i.e., P o = 0.7 and P c = 0.54), then
kappa = 0.35. Landis and Koch [203 ] have offered a performance estimate of kappa
as follows: kappa = 0 to 0.2, slight agreement; kappa = 0.2 to 0.4, fair agreement;
kappa = 0.4 to 0.6, good agreement; kappa = 0.6 to 0.8, substantial agreement; kappa
= 0.8 to 1.0, near-perfect agreement. Other methods of quantitating the agreement
between two models include weighted kappa, interclass correlation coefficient, the tau
statistic, and the gamma statistic. These methods are discussed in the work of Hughes
and Ash, [201 ] and all offer an objective means to assess the reliability of a
risk-adjustment model.
Surprisingly little work has been done in assessing the reliability and validity of
risk-adjustment methods used with large cardiac surgical databases. It is absolutely
essential that validity and reliability be tested in these models for clinicians to feel
comfortable with comparisons generated by risk-stratification models and for
policymakers (either government or managed-care organizations) to feel confident in
making decisions based on risk-adjusted outcomes.
Risk Stratification to Measure the Effectiveness of Care
The biggest single shortcoming of risk-adjustment methodology is a lack of proven

effectiveness in delineating quality of care. Although it may seem obvious that
differences in risk-adjusted outcomes reflect differences in quality of care, this
connection is far from proven. The little information available on this subject is
inconsistent. Hartz et al. [204 ] compared hospital mortality rates for patients undergoing
CABG. They found that differences in hospital mortality rates correlated with differences
in quality of care between hospitals. Hannan et al. [11 ] attempted to evaluate quality of
care in outlier hospitals in the New York State risk-adjusted mortality cohort. They
concluded, as did Hartz et al., that risk-adjusted mortality rates for CABG reflected
quality of care. The measures of quality used in these studies were somewhat arbitrary
and did not include a complete array of factors that might be expected to influence
outcomes after CABG. In TQM jargon, the entire clinical process of surgical intervention
for coronary revascularization was not assessed. Other studies have not found a
correlation between global hospital mortality rates and indicators of quality of care. [205
] , [206 ] Indeed, one study suggested that nearly all the variation in mortality among
hospitals reflects variation in patient characteristics rather than hospital characteristics.
[207 ] Two ongoing quality-improvement studies use risk-adjusted outcome
measurements to assess and influence the clinical process of surgery for treatment of
coronary artery disease: the Northern New England Cardiovascular Disease Study [20 ]
, [83 ] [85 ] and the Veteran's Administration Cardiac Surgery Risk Assessment
Program. [14 ] [16 ] Future reports from these and other groups will better define what
risk-adjusted outcome data really measure and, in particular, what these outcome
measures mean about quality of care and cost-effectiveness of providers. Until such
time as these results become available, risk-adjusted data must be used with caution.
At present, it is not justified to equate risk-adjusted outcome measurements with
provider quality. [208 ] , [209 ]
Ethical Implications of Risk Stratification: The Dilemma of Managed Care
New proposals for health care reform mandate reports on quality of care. [210 ] While
these reports sound appealing, many problems arise, and some pose ethical
dilemmas. [211 ] [214 ] By general agreement, quality indicators must be risk-adjusted
to allow fair comparisons among providers. However, risk adjustment in this setting is
extremely difficult, may be misleading, and what is worse, may not reflect quality of care
at all. Release of risk-adjusted data may alienate providers and reduce care for the
sickest patients. As discussed earlier, this unethical result may have happened already
in New York State [6 ] [8 ] , [215 ] and in other regions where risk-adjusted mortality and
cost data have been released to the public.
At the same time, physicians are rewarded by hospitals and managed-care

organizations for limiting costs. Some inducements and incentives threaten our
professionalism. [216 ] This may seem like a strong statement, but consider some of
the policies advocated by insurers and organizational administrators: Physicians are
advised to recruit younger patients and discourage Medicare-aged patients away from
the managed-care practice, not disclose costly services not covered by the
managed-care plan, and use accounting services to track and limit frequency of office
visits. [217 ] [220 ] Strategies are needed that allow physicians to care for patients
properly and to benefit from risk-adjusted outcome measurements.
A major concern of the current move toward market-oriented health-care delivery is that
health plans will only enlist the best health risk participantsa practice termed cream
skimming by van de Ven et al. [221 ] The effect of cream skimming will certainly widen
the gap between impoverished, underserved patients and affluent patients. To address
these concerns, plans have been proposed to reward health plans for serving people
with disabilities and residents of low-income areas. [222 ] [225 ] Some form of risk
adjustment to allocate payments to providers based on overall health risk and expected
needs is at the heart of these plans. Use of risk stratification in this setting is new and
unproved but offers promise.
The Costs of Gathering Data
Collecting risk-adjusted data adds to the administrative costs of the health-care system.
It is estimated that 20 percent of health-care costs are spent on administration. [226 ] ,
[227 ] The logistic costs of implementing a risk-adjustment system are substantial.
Additional costs are incurred in implementing quality measures that are suggested by
risk-stratification methodology. A disturbing notion is that costs of quality care may
outweigh the payers' willingness to pay and that quality improvement may cost rather
than save money. Ultimately, improved quality will be cost-efficient, but startup costs are
daunting, and several organizations have already expressed concerns about the logistic
costs of data gathering and risk adjustment. [228 ] [230 ] It is imperative that cost
savings realized by improved quality be factored into the total costs of gathering
risk-adjusted data.
WHAT DOES THE FUTURE HOLD?
New Risk-Stratification Methods: Neural Networks
The goal of risk adjustment is to determine the contribution of patient-related risk factors
to the outcome of interest. This allows patient outcomes to be used as an indicator of
the care rendered by providers and by hospitals. This chapter has outlined some of the
risk-adjustment methods commonly used for this purpose. Inevitably, refinements and
newer techniques will improve methods of risk adjustment.
One of the most promising new risk-adjustment methods is the use of neural networks
(also termed artificial intelligence ) to develop prediction models based on patient risk
factors. [231 ] [233 ] A weakness of multivariate regression techniques is that some
variables occur too seldom to be used in multivariate regression models but
nevertheless contribute significantly to outcome. Neural networks and cluster analysis
overcome this deficiency. [231 ] Both techniques use computer iteration to detect
patterns of variables associated with outcome and are far less affected by
low-frequency variables. These methods may find more than one solution to the best
prediction of outcome and may identify a combination of variables that reflect a unique
clinical situation. Neural network modeling has been used to predict length of stay in the
ICU after cardiac surgery [232 ] and to predict valve-related complications following
valve implantation. [233 ] , [234 ] Preliminary evidence suggests that the performance of
neural network models may be superior to that of multivariate regression models since
the c statistic for neural network models approaches 95 percent in ideal situations. [231
]
Information Management: Electronic Medical Records
Accurate patient data are essential to apply the principles of risk stratification and
quality improvement outlined in this chapter. The quality and accuracy of administrative
(or claims) databases have been questioned. [32 ] , [47 ] [52 ] , [237 ] Therefore,
risk-adjustment methodology has placed greater reliance on data extracted from the
medical record. The American College of Surgeons was among the earliest advocates
of medical records for quality review. [236 ] In the 1960s, Weed [235 ] , [238 ]
advocated standardization and computerization of medical records. Little substantive
progress was made in computerization of records until the need arose for risk
adjustment and outcome assessment. Now, more and more pilot studies are being
undertaken to computerize and standardize the medical record in a variety of clinical
situations. [239 ] [242 ] Iezzoni [243 ] has pointed out difficulties with computerized
medical records and observed that they may not adequately reflect the importance of
chronic disability and decreased functional status. Nevertheless, efforts to computerize
medical records will expand. Useful applications of electronic medical records for
cardiothoracic surgeons include monitoring patient outcomes, [239 ] supporting clinical
decision making with real-time third-party analysis of the medical record, [240 ] , [241 ]
and real-time tracking of resource utilization. [242 ]
CONCLUSIONS
Risk stratification and outcome analysis are here to stay. The methods of risk analysis
are straightforward but are early in their development. The goal of risk adjustment in
analysis of outcomes is to credit the contribution of patient-related risk factors so that
patient outcomes can be used as an indicator of the quality of care. Refinements in
risk-adjustment methods and increasing use of these techniques will occur at all levels
of health-care delivery. Although cardiothoracic surgery is at the forefront of this
movement, more work remains in educating surgeons and others in the use and
application of this technology. The ultimate goal is to improve patient outcome and to
maintain high professional quality.
The preoperative visit by the anesthesiologist is aimed at formulation of an anesthetic

plan based on the patient's surgical illness, scheduled operation, and concomitant
medical problems. The anesthesiologist is responsible for informing the patient of the
conduct of the planned anesthetic and associated risks and obtaining consent for the
anesthesia and related procedures. The medical history is elicited by questioning the
patient and reviewing the medical records. The nature and severity of the surgical
illness and related cardiovascular and pulmonary disease often dictate the choice of
anesthetic drugs and monitors and predict the subsequent course of events. All
anesthetic drugs have a direct effect on cardiac function, vascular tone, or the
autonomic nervous system. The anesthesiologist must know the status of the
cardiovascular system, related morbidity, and concurrent medications to safely design
the anesthetic for a patient undergoing heart surgery.
The exchange of information between patient and physician is often a balance between
providing sufficient insight regarding possible complications and producing harmful
anxiety. An outline of upcoming events accompanied by an informative discussion of
risks and options usually leads to informed consent. Laboratory tests are ordered to
complement findings of the medical history and physical examination. Routine
preoperative tests for patients scheduled for a cardiac operation include a complete
blood and platelet count, electrolyte battery, determination of glucose, serum creatinine,
and blood urea nitrogen levels, prothrombin time and partial thromboplastin time, chest
radiograph, electrocardiogram (ECG), and urine analysis.
The American Society of Anesthesiologists (ASA) developed a physical status

classification to provide a general measure of the patient's severity of illness [1 ] (Table
7-1) , but this classification is not a dependable method of risk stratification for cardiac
surgical patients because it does not consider the operative procedure and expected
outcome. The patient with unstable angina and uncompensated heart failure may be
considered an ASA physical status 4E independent of whether he or she is scheduled
to undergo coronary revascularization or open reduction and internal fixation of a
fractured hip.
Concurrent medical illness often defines an acceptable range for monitored parameters
that are controlled during cardiac surgery, contributes to postoperative morbidity, or
influences the response to a specific drug. Acceptable intraoperative blood pressure is
defined by the range of blood pressure before surgery. A severely hypertensive patient
may significantly hypoperfuse vital organs if the blood pressure during surgery is
maintained within a normal range rather than within the patient's usual range. A previous
stroke with apparent recovery may become manifest after general anesthesia without
evidence of a new neurologic injury. Chronic obstructive pulmonary disease (COPD)
and its response to bronchodilators permit guided management of perioperative
bronchospasm and inadequate respiration. Prior surgical and anesthetic procedures
are investigated by reviewing medical records. A history of a difficult intubation or
adverse response to a specific drug is highly relevant to the anesthesia plan.
Concurrent medications usually are continued until operation, although the dose may be
altered or a shorter-acting preparation substituted. Oral medications are administered
according to schedule on the day of surgery with a small sip of water. Intravenous
heparin given for unstable angina pectoris is not discontinued before surgical incision.
For patients scheduled for late afternoon surgery and not receiving maintenance
intravenous fluids, preoperative diuretics may be withheld to avoid dehydration. The
physical examination includes measurement of vital signs and height and weight and a
comprehensive assessment of the heart, lungs, peripheral vasculature, nervous system,
and airway. Samsoon's modification of the Mallampati classification to predict a difficult
airway is based on the ability to view intraoral structures by an examiner as follows [2 ] ,
[3 ] :
Class 1: Soft palate, tonsillar fauces, tonsillar pillars, and uvula
Class 2: Soft palate, tonsillar fauces, and uvula
Class 3: Soft palate and base of uvula
Class 4: Soft palate not visualized
Before the patient enters the operating room, the anesthesiologist formulates a plan to
control the circulatory response to anesthesia, secure the airway, and maintain body
homeostasis. Emergency operation frequently is incompatible with leisurely preparation
but is dictated by a sense of urgency. In such a situation, rarely is there no opportunity to
provide reassurance or to meticulously prepare for anesthesia and operation.
MONITORING PHYSIOLOGICAL FUNCTIONS DURING
ANESTHESIA
Extensive physiologic monitoring is employed during cardiac operations because

virtually every major physiologic system required for life is modified. The reasons for
physiologic monitoring are (1) to ensure patient safety in the absence of protective
reflexes made ineffective by anesthetic drugs, (2) to enable pharmacologic and
mechanical control of physiologic functions, and (3) to diagnose acute emergencies that
require immediate treatment. For example, morbidity as a consequence of breathing
circuit disconnects, loss of oxygen from the hospital's central supply, or unrecognized
esophageal or main-stem intubations can be prevented by capnography, pulse
oximetry, airway pressure monitors, oxygen analyzers, and a stethoscope.
The senses of touch, hearing, and sight are the basic monitors. Electronic monitors are
vigilance aids that supplement the anesthesiologist's perceptions. In setting up a
monitoring system, it is important to establish the sensitivity and specificity for detecting
physiologic changes and disease. Sensitivity is a measure of the ability of a monitor to
detect change in whatever is measured ( measurand ). Specificity is the degree that a
change in the measurand is peculiar to a singular condition or disease. Sensitivity and
specificity of a monitor depend on sensor calibration, accuracy, and precision. A sensor
is an instrument that detects change in the measurand and provides a corresponding
output signal.
Calibration is the relationship between the measurand and the output signal such that
the magnitude of the output signal reflects the magnitude of the parameter being
measured. Pressure transducers, light detectors, flowmeters, thermistors, and gas
analyzers are examples of commonly used sensors in the operating room. The ideal
sensor is accurate during static and dynamic conditions, precise, reliable, safe,
practical, and inexpensive. Accuracy is defined by how well the output signal agrees
with the true value or a calibration quality standard. Precision is a measure of
repeatability. A sensor is precise if it provides little variability between repeated
measures. A pulse oximeter is an accurate monitor of percent oxyhemoglobin because
it agrees with in vitro measures. Thermodilution is an imprecise method of determining
cardiac output because successive measurements vary by 20 percent or more. All
monitors are properly calibrated prior to clinical use, and specifications for accuracy
and precision must be established to maximize sensitivity and specificity for detecting
physiologic perturbations.
The selection of monitors is dictated by the utility of the generated data, expense, and
risk. Routine or essential monitors that have been deemed cost-effective with low
risk-benefit ratios include pulse oximetry, noninvasive blood pressure, capnography,
temperature, ECG, precordial or esophageal stethoscope, and oxygen analyzers.
These have been defined by the American Society of Anesthesiologists (House of
Delegates, 1989) as essential monitors to be used in all surgical patients requiring
anesthesia unless there are contraindications (e.g., esophageal stethoscope during
esophageal surgery) or they are not applicable (e.g., inspired oxygen concentration
during a regional anesthetic). Essential monitors are the standard of care in anesthesia
because of their small risk and potential for lifesaving information (Table 7-2) . Other
noninvasive and invasive monitors are used only with clear indication.
The growth in monitoring technology and sophistication is paralleled by an equal growth

in cost. The balance between cost and enhancement of patient safety must be
considered when additional monitoring is selected. It is difficult to justify a monitor that
provides data that do not influence medical or surgical management. Appropriately
selected monitors are cost-effective for patients, physicians, hospitals, and insurance
companies. Improved safety decreases patient morbidity and mortality, decreases
direct costs of health care providers, and reduces legal costs, insurance premiums, and
possibly the risk of early retirement by physicians. However, monitors do not interpret
data and must themselves be monitored by a human being.
Measurement of Blood Pressure
Blood pressure changes abruptly during anesthesia and surgery and is the most
commonly measured index of cardiovascular stability in the perioperative period.
Anesthetics and surgery cause changes in blood pressure that may be great enough to
cause harm unless anticipated and treated. A change in blood pressure alters perfusion
pressure but may not change organ blood flow. Most vital organs have autoregulation of
blood flow in response to changes in mean arterial blood pressure, permitting a
constant blood flow over a range of perfusion pressure. [4 ] In hypertensive patients, the
boundaries for autoregulation are shifted so that significant decreases in organ
perfusion may occur with blood pressures in the normal range. Both the type and dose
of anesthetic medications affect the relationship between vital organ perfusion and
blood pressure. Volatile anesthetics are potent vasodilators that tend to disrupt
autoregulation in a dose-dependent manner to render blood flow more linearly
dependent on blood pressure (Fig. 7-1) .
Although noninvasive blood pressure monitoring suffices for most patients during
routine noncardiac surgery, direct measure of arterial blood pressure with an indwelling
catheter is necessary for cardiac surgery to detect changes rapidly, to measure
nonpulsatile blood pressure during cardiopulmonary bypass, and to facilitate blood
sampling for laboratory analysis. The measuring system includes an intraarterial
catheter and low-compliance saline-filled tubing connected to a transducer with a
pressure-sensing diaphragm. The transducer has a strain gauge that converts the
mechanical energy (displacement of the diaphragm by a change in pressure) into an
electric signal that is typically displayed as a pressure waveform with numeric outputs
for systolic, diastolic, and mean pressures. The mean blood pressure is determined by
calculating the area under several pulse waveforms and averaging over time. This
represents a more accurate measure of mean arterial blood pressure than weighted
averages of systolic and diastolic pressures.
The transducer requires a zero reference at the level of the right atrium. Any movement
of the patient or the transducer that changes the vertical distance between the
transducer and the right atrium affects the value of the blood pressure measured. If the
transducer is lowered, the pressure diaphragm senses arterial blood pressure plus
hydrostatic pressure generated from the vertical column of fluid contained in the tubing
and displays a falsely high blood pressure. A transducer elevated above the zero
reference level decreases the displayed blood pressure. A 1-cm column of water
(blood) exerts a hydrostatic pressure equal to 0.74 mmHg. Small changes in patient or
transducer position have a relatively insignificant effect on arterial blood pressure
measurements but have a more important effect on lower amplitude pressure
measurements, such as central venous, pulmonary artery, and pulmonary artery
occlusion pressures.
The intraarterial cannula, tubing, and transducer assembly are prepared prior to surgery
and flushed with heparinized saline. All air bubbles must be cleared from the system to
prevent damping and arterial air embolism. The radial artery is the most common site
for the insertion of an intraarterial catheter. Twenty-gauge catheters are preferred
because larger catheters are more likely to cause thrombosis. Thrombosis of the radial
artery does not produce ischemia of the hand and fingers in the presence of intact ulnar
blood flow and a patent palmar arch. The Allen's test was designed to assess ulnar and
palmar arch blood flow during abrupt occlusion of the radial artery, but its value to
predict morbidity with radial artery cannulation is equivocal. [5 ] Other sites selected for
the insertion of an intraarterial catheter include the brachial, axillary, and femoral
arteries.
The contour of the arterial pressure waveform is different in central and peripheral
arteries. The propagating pressure waveform loses energy and momentum with a
corresponding delay in transmission, loss of high-frequency components such as
anacrotic and dicrotic notches, lower systolic and pulse pressures, and decreased
mean pressure. [6 ] The changes in the pulse waveform can be attributed to damping,
blood viscosity, vessel diameter, vessel elastance, and the effects of reflectance of the
incident arterial waveform by the artery-arteriolar junction. [7 ] , [8 ] The effect of the
reflectance waves on the incident pulse waveform is an increase in the high-frequency
components of the pressure waveform. The pressure waveform measured at a given
site represents a summation of the incident waveform and reflected waves from prior
heartbeats. The closer the site of blood pressure measurement is to the site of
reflectance, the more important are the high-frequency components of the reflected
waves. The blood pressure waveform measured in the ascending aorta is minimally
affected by reflected waves in contrast to the measurement of blood pressure in the
dorsalis pedis or radial artery. Vasodilators decrease terminal impedance at the
artery-arteriolar junction and decrease the resonant frequency of the arterial waveform.
The contour of the pressure waveform is affected by the physical construction of the
monitoring system. A hyperresonant response to a change in pressure, or ringing ,
occurs when the frequency response of the monitoring system (extension tubing,
catheter, stopcocks) is close to the frequency of the pressure waveform. [6 ] The natural
or resonant frequency fn of a monitoring system is defined by
where
C = compliance of the measuring system
L = length of the tubing
D = diameter of the catheter extension tubing
P = density of the solution
To prevent ringing, the natural frequency of the monitoring system fn must be greater
than the frequencies of the pulse waveform. Any process that decreases fn , such as
narrow, long, compliant tubing, may cause ringing. [9 ] Ringing increases the value of
the systolic blood pressure and decreases the value of the diastolic blood pressure but
generally does not affect the value of the mean arterial pressure.
Damping is the tendency of the measuring system through frictional losses to blunt the
peaks and troughs in a signal. [10 ] Kinks in the pressure tubing or catheter, stopcocks,
and air bubbles contribute to damping. Overdamped systems underestimate systolic
blood pressure and overestimate diastolic blood pressure. When long lengths of tubing
are necessary (e.g., extension pressure tubing from a femoral arterial cannula),
deliberate damping may improve the fidelity of the arterial waveform.
Testing a measuring system for ringing and damping ensures that an arterial contour is
faithfully reproduced. A simple test is the brief flush of a high-pressure heparinized
saline-filled catheter-extension assembly. Flush and release should produce a rapid
return of the pressure waveform to baseline with minimal oscillations. A gradual return to
baseline and loss of higher-frequency components of the waveform suggest
overdamping. A rapid return to baseline followed by sustained oscillations suggests
ringing.
Electrocardiogram (ECG)
The intraoperative ECG monitor has evolved from the fading ball oscilloscope to a
sophisticated microprocessor analog display. ECG signals are digitally filtered to
eliminate electrical artifact produced by high-frequency (60-Hz) electrical power lines,
electrocautery, patient movement, and baseline drift. The bandwidth filter modes are
diagnostic, monitor, and filter. The diagnostic mode has the widest bandwidths
(least-filtered signal) and is preferred for detecting ST-segment changes caused by
myocardial ischemia. Monitor and filter modes have progressively narrower bandwidths
that effectively eliminate high-frequency interference and baseline drift but decrease the
sensitivity of detecting ST-segment changes and decrease the specificity of
ST-segment change to diagnose myocardial ischemia. Abnormal ST-segment
depression (> 1 mV) can occur from excessive low frequency filtering and result in the
misdiagnosis of myocardial ischemia. Filter modes are useful for detecting P waves
and changes in cardiac rhythm in the presence of high-frequency interference.
The ECG is the most sensitive and practical monitor for the detection and diagnosis of
disorders of cardiac rhythm and conduction and myocardial ischemia and infarction.
Continuous monitoring of leads II and precordial lead V5 is common (Fig. 7-2) .
Together, these leads detect greater than 90 percent of ischemic episodes in patients
with coronary artery disease who have noncardiac surgery. [11 ] The ECG leads
selected for monitoring of myocardial ischemia can be guided by preoperative testing.
The sensitivity of the ECG is enhanced if myocardial ischemia is manifested by a
known pattern of ECG changes in an individual patient. Myocardium at risk, identified
by exercise testing or coronary angiograms, can be monitored by selecting the lead
with the appropriate vector. A reversible perfusion defect of the inferior wall of the left
ventricle during an exercise thallium reperfusion scan may encourage the
anesthesiologist to specifically monitor myocardial ischemia by using leads II, III, and
AVF.
Diagnostic criteria for myocardial ischemia based on the ECG are (1) acute
ST-segment depression greater than 0.1 mV 60 s beyond the J point lasting for greater
than 1 min or (2) acute ST-segment elevation greater than 0.2 mV 60 s beyond the J
point lasting for greater than 1 min [12 ] (see Figure 7-3 ). The normal ST segment
curves smoothly into the T wave. Flat ST segments that form an acute angle with the T
wave or downsloping ST segments are worrisome for subendocardial ischemia.
ST-segment elevation occurs with transmural myocardial injury but also may occur after
direct-current (dc) cardioversion and in normal adults. The lack of specificity of ST-T
wave changes for myocardial ischemia is a major limitation of intraoperative ECG
monitoring. Pericarditis, myocarditis, mitral valve prolapse, stroke, and digitalis therapy
may produce changes in the ST segment that mimic myocardial ischemia.
Digital signal processing handles much larger quantities of information compared to the
unaided eye and may increase the ability to detect ischemic episodes. ST-segment
position analyzers automatically measure the displacement of the ST segment from a
predetermined reference and may enhance the ability to quantify changes in
ST-segment position. Appropriate application requires accurate identification of the
various loci in the P-QRS-T wave complex. The operator defines the baseline and the J
point of a reference QRS complex by movement of a cursor. New QRS-T wave
complexes are superimposed onto a predefined mean reference complex. Vertical
ST-segment displacement is measured in millivolts and displayed graphically in 1-mV
increments (see Figure 7-3 ). Because the accuracy of automated ST-segment
monitoring is vulnerable to baseline drift and dependent on the appropriate
identification of the PR and ST segments, the diagnosis of myocardial ischemia is
always verified by inspecting the actual ECG tracing.
Disturbances of rhythm and conduction are common during anesthesia and especially
during cardiac surgery. Instrumentation of the heart, hypothermia, electrolyte
abnormalities, myocardial reperfusion, myocardial ischemia, and mechanical factors
such as surgical manipulation of the heart affect the normal propagation of the cardiac
action potential. Heart rate is measured by averaging several RR intervals of the ECG;
this method is unreliable for patients in atrial fibrillation. The ECG may not sense the R
wave of the selected lead if the electrical vector of the heart is isoelectric. A prominent T
wave or pacemaker spike may be miscounted as an R wave by the ECG and
artifactually double the rate. Usually, heart rate is best monitored by selecting the lead
with an upright R wave and adjusting the sensitivity.
The QT interval can only be measured on hard copy. A normal QT interval is less than
half the RR interval, but the QT interval must be corrected for heart rates greater than 90
or less than 65 beats per minute. A prolonged QT interval increases the risk of reentrant
ventricular tachydysrhythmias and may occur from hypokalemia, hypothermia, and toxic
drug effect (quinidine or procainamide). The electrically dormant heart during aortic
cross-clamping and perfusion with cold cardioplegia is monitored by the ECG.
Hypothermia decreases action potential conduction velocity and potassium decreases
the transcell membrane potassium concentration gradient to prevent depolarization of
cardiac muscle. During cardiopulmonary bypass and aortic cross-clamping, the loss
and persistent absence of electromechanical activity suggest that myocardial oxygen
consumption is maintained at a minimum.
Monitoring the ECG is most valuable when it begins before induction of general
anesthesia. A hard copy of the pertinent leads permits comparison should a change be
detected. An abnormal or marginal finding is less worrisome if it was present in the
preoperative ECG and remains unchanged during the perioperative period. However,
new-onset ST-T wave changes or disturbances in rhythm and conduction suggest an
ongoing active process that usually requires immediate attention.
Capnography
Capnometry is the measure of carbon dioxide (CO2) concentration in a gas. The

capnogram is the continuous graphic display of airway carbon dioxide partial pressure
(Figure 7-4) . Changes in its contour reflect disorders of ventilation, carbon dioxide
production, or carbon dioxide transport to the lungs. The capnogram is the single most
effective monitor for detecting esophageal intubation, apnea, breathing circuit
disconnects, accidental extubation of the trachea, and airway obstruction. Tracheal
intubation is verified by detection of physiologic carbon dioxide concentrations in the
exhaled gas. A steep increase in the phase 3 slope in the exhaled CO2 concentration
suggests partial airway obstruction, either mechanical (tube kinking) or physiologic
(bronchospasm). A progressive decrease in exhaled carbon dioxide concentration
occurs with decreased CO2 production (hypothermia), increased minute ventilation,
increase in physiologic dead space ventilation (e.g., pulmonary embolus), or low
cardiac output. A progressive increase in exhaled carbon dioxide concentration occurs
with hypoventilation or increased CO2 production (malignant hyperthermia). The contour
of the capnogram is also affected by the expiratory flow rate, distribution of pulmonary
blood flow, distribution of ventilation, and the use of sidestream or mainstream carbon
dioxide analyzers. Despite the interplay of mechanical and physiologic factors that
affect the shape of the capnogram, any abrupt change in contour always signifies an
acute change in the patient's cardiovascular, pulmonary, or metabolic state.
Pulse Oximetry
Pulse oximeters were universally adopted into the practice of anesthesia almost
immediately after their introduction despite lack of data demonstrating improved
outcome with their use. Oxyhemoglobin saturation and arterial oxygen tension are
measured routinely during cardiac surgery by intermittent arterial blood sampling.
Arterial blood gas analysis does not replace the pulse oximeter, which continuously
measures arterial hemoglobin saturation and pulse rate. The pulse oximeter detects
decreasing percentages of oxyhemoglobin before changes in the color of the patient's
skin or blood are evident. [13 ] The pulse oximeter is reusable, inexpensive, and
noninvasive and provides continuous on-line data. Its major limitations include electrical
interference, motion artifact, high failure rate during periods of low flow or inadequate
perfusion, and the need for pulsatile flow for proper operation. [14 ]
Pulse oximetry measures the percent oxyhemoglobin in arterial blood by

transillumination and detection of differences in the optical absorption properties of oxy-
and deoxyhemoglobin. Transmission oximetry at wavelengths of 660 and 940 nm and
photoplethysmography and rapid signal processing permit reliable and rapid
determination of the relative proportion of oxy- and deoxyhemoglobin. Oxyhemoglobin
has a higher optical absorption in the infrared spectrum (940 nm), whereas reduced
hemoglobin absorbs more light in the red band (660 nm). The ratio R of light
absorbence at the two wavelengths is a function of the relative proportions of the two
forms of hemoglobin. Photoplethysmography permits the measure of arterial
hemoglobin saturation by isolating the pulsatile component of the absorbed signal. The
peaks and troughs in the blood volume of the finger or ear being transilluminated
produce a corresponding pulsatile effect on light absorption, rendering the calculated
oxyhemoglobin saturation independent of nonpulsatile venous blood and soft tissue.
Calculation of arterial hemoglobin saturation is based on calibration algorithms derived
from healthy volunteers. The R values were determined by in vitro measures of
oxyhemoglobin saturation and are less accurate at oxyhemoglobin saturations below 70
percent. Motion artifact produces a high absorption of light at both wavelengths and an
R value of approximately 1 that corresponds to an oxyhemoglobin saturation of
approximately 85 percent.
The pulse oximeter is unable to distinguish other hemoglobin species that absorb light
at the emitted wavelengths. Methemoglobin (ferric instead of ferrous hemoglobin) has
similar absorption at both 660 and 940 nm with an R value of 1 and a corresponding
displayed saturation of 85 percent regardless of the true value. Carbon monoxide
poisoning produces carboxyhemoglobin that has significant absorption at 660 nm and
is erroneously interpreted by the pulse oximeter as oxyhemoglobin.
Measurement of Temperature
Profound changes in body temperature during cardiac surgery are common and
frequently deliberate and significantly affect vital organ function (Fig. 7-5) . Anesthetized
patients are poikilothermic. Intrinsic temperature regulation normally controlled by the
hypothalamus fails during general anesthesia. Hypothermia occurs by passive and
active heat loss. Passive mechanisms of cooling include radiation, evaporation,
convection, and conduction. Active cooling usually occurs with extracorporeal circulation
and with the use of cold or iced solutions poured into the chest cavity. Deliberate
hypothermia during cardiac surgery is designed to arrest and cool the heart and
decrease systemic oxygen consumption. Hyperthermia may result from preexisting
fever, bacteremia, malignant hyperthermia, or overzealous rewarming during
cardiopulmonary bypass.
Malignant hyperthermia is a rare inherited disorder of muscle and is potentially fatal. [15
] It is an autosomal dominant trait with variable penetrance that is almost always
quiescent until the patient is exposed to a triggering agent, such as volatile anesthetics
or succinylcholine. Malignant hyperthermia is associated with derangements in calcium
metabolism. Ineffective uptake of calcium by sarcoplasmic reticulum and abnormal
release of calcium from intracellular storage sites occurs with massive skeletal muscle
depolarization in response to triggering agents. Clinical manifestations of malignant
hyperthermia include increased production of carbon dioxide, tachycardia, and
increased cardiac output, followed by fever, metabolic and respiratory acidosis,
hyperkalemia, cellular hypoxia, rhabdomyolysis, myoglobinuria, renal failure, and
cardiovascular collapse. Serum creatine kinase is increased and may be of diagnostic
value. The fever may reach 43°C but may be masked by deliberate hypothermia during
cardiopulmonary bypass. Despite increased awareness, improved monitors, and the
advent of established treatment algorithms with dantrolene, mortality rates are still as
high as 10 percent. Treatment is aimed at discontinuing the trigger agent and
controlling body temperature through active cooling. Oxygen, hyperventilation, and
correction of metabolic acidosis and electrolyte abnormalities are the cornerstone of
therapy.
Dantrolene blocks calcium release and is administered at a dose of 2 mg/kg

intravenously every 5 minutes for a total dose of 10 mg/kg. [16 ] Intravenous dantrolene
is generally continued at 12-hour intervals for a minimum of 24 hours because episodes
of malignant hyperthermia may recur even after the trigger agent has been
discontinued. The incidence of malignant hyperthermia is approximately 1 in 62,000
anesthetics. Patients with a history of prior malignant hyperthermia crises and those
with most types of muscular dystrophies are at increased risk. Not all episodes of
malignant hyperthermia lead to progressive metabolic and cardiovascular collapse.
Unexplained fever after an anesthetic or in the recovery room may identify a patient at
increased risk. Testing by in vitro skeletal muscle responses to halothane and/or
caffeine is recommended for the preoperative diagnosis of patients suspected to be at
increased risk. High-risk patients can be anesthetized safely by using anesthetic drugs
such as narcotics, barbiturates, nitrous oxide, local anesthetics, and nondepolarizing
muscle relaxants that are not believed to trigger malignant hyperthermia.
Hypothermia after cardiopulmonary bypass is the result of ineffective rewarming, cold

operating rooms, cold wet surgical drapes, a large surgical incision, and the
administration of cold intravenous fluids. Hypothermia exacerbates dysrhythmias and
coagulopathy, potentiates the effects of anesthetic drugs and neuromuscular blockers,
increases vascular resistance, decreases the availability of oxygen, and contributes to
postoperative shivering. The elderly are especially susceptible because of limited
compensatory reserve.
Temperature is typically monitored from several sites during cardiac surgery. Blood
temperature is measured from the tip of the pulmonary artery catheter and within the
cardiopulmonary bypass circuit (typically venous and arterial lines). Blood temperature
is the first to change in response to deliberate hypothermia or active rewarming during
cardiopulmonary bypass. Nasopharyngeal and tympanic temperatures reflect the
temperature of the brain and closely track blood temperature because these sites are
highly perfused. Rectal and bladder temperatures provide a measure of core
temperature only at equilibrium. Esophageal temperature often underestimates core
temperature because of the cooling effects of ventilation in the adjacent trachea. Axillary
and inguinal temperature measurements are impractical.
The degree and site of temperature change are important indicators of an intact
circulatory system. Persistent temperature discrepancy between two sites may be a
subtle sign of ineffective perfusion. Rewarming during cardiopulmonary bypass is
normally associated with an increase in nasopharyngeal or tympanic temperature
accompanied by a more gradual increase in temperature in organs with low perfusion
(e.g., rectum) or peripheral temperature. A persistently cold nasopharynx with a normal
rate of increase in rectal temperature may be due to a malpositioned temperature
probe or an early sign of aortic dissection and hypoperfusion of the head.
Measurement of Cardiac Output and Central Venous and Pulmonary Artery

Pressures
Cannulation of the central venous circulation permits central administration of drugs,

passage of catheters and pacing electrodes into the heart, rapid administration of fluids
through short, large-bore cannulas, and the measure of central venous pressure. The
most commonly used site for central venous access is the internal jugular vein because
of easy, reliable insertion, easy access from the head of the table, decreased risk of
pneumothorax, and decreased risk of catheter kinking during sternal retraction. The
subclavian vein is the preferred site for the insertion of a central venous catheter for
long-term intravenous total parenteral nutrition because of a decreased risk of
blood-borne infection.[17 ] The most important complication of internal jugular vein
cannulation is inadvertent puncture or cannulation of the carotid or subclavian artery. To
avoid significant injury to the carotid artery, cannulation of the central venous circulation
is confirmed by transducing the pressure waveform prior to the insertion of a large-bore
catheter. Ultrasound-guided cannulation of the internal jugular vein renders the
procedure less dependent on anatomic landmarks and is associated with a decrease
in the number of unsuccessful cannulation attempts [18 ] (Fig. 7-6) .
Central venous pressure (CVP) is an index of right ventricular preload. The pulsatile a, c
, and v pulse waveforms are a function of uninterrupted return of venous blood to the
right atrium, right atrial contraction and right atrial size and compliance, intrathoracic
pressure, and mechanical properties of the tricuspid valve and right ventricle. The
normal CVP is 6 to 10 mmHg and is measured at end-exhalation. A decrease in CVP
suggests hypovolemia or vasodilation. An increased CVP with normal cardiac function
occurs with hypervolemia, vasoconstriction, and increased intrathoracic pressure. CVP
is increased by positive pressure ventilation and positive end-expiratory pressure.
Systemic hypotension accompanied by an increased CVP suggests cardiac
dysfunction. The most common disorder that produces venous hypertension is left-sided
heart failure, although acute left ventricular dysfunction may cause an increase in left
atrial and pulmonary artery occlusion pressure without significant change in CVP.
Pulmonary artery catheters are inserted via the central venous circulation through the
right side of the heart with the catheter tip positioned just downstream to the pulmonic
valve. The pulmonary artery catheter measures pulmonary artery pressure, pulmonary
artery occlusion pressure, cardiac output, and mixed venous oxygen saturation and
permits calculation of the derived values of systemic and pulmonary vascular
resistance. The pulmonary artery occlusion pressure is an index of left ventricular
preload in the absence of mitral stenosis. However, the use of a pressure measurement
to estimate preload is limited because of variability in left ventricular size and
compliance. The hemodynamic parameters derived from the pulmonary artery catheter
may be used to detect myocardial ischemia if ischemia produces ventricular
dysfunction that is associated with a decrease in cardiac output, increase in left
ventricular end-diastolic pressure, or pulmonary hypertension (Fig. 7-7) . However,
hemodynamic parameters derived from the pulmonary artery catheter are not as
sensitive or as specific for detecting myocardial ischemia as the ECG. [19 ] Pulmonary
artery occlusion pressure is affected by volume status, myocardial compliance, mode of
ventilation, and ventricular afterload.
Complications associated with the insertion of a pulmonary artery catheter include

dislodgment of pacemaker wires or right atrial or ventricular clot or tumor, atrial and
ventricular arrhythmias, pulmonary infarction, pulmonary artery rupture, catheter
entrapment, and heart block. The incidence of right bundle branch block (RBBB) is
approximately 3 percent and may cause complete heart block in patients with a
preexisting left bundle branch block (LBBB). [20 ] A mechanism to treat complete heart
block (e.g., external pacer) should be available for these patients. The passage of the
pulmonary artery catheter can be delayed until after sternotomy for most patients when
heart block can be treated with epicardial pacing wires. Chronic indwelling pulmonary
artery catheters are associated with a progressive thrombocytopenia. [21 ]
Heparin-bonded catheters decrease the incidence of thrombus formation, [22 ] but
high-dose aprotinin may increase the risk of early thrombus formation. [23 ]
Multiport pulmonary artery catheters equipped with a tip thermistor permit the measure
of pulmonary blood flow or cardiac output by thermodilution. Thermodilution cardiac
output is an indicator-dilution technique. The indicator, a known volume of cold saline, is
injected rapidly into the right atrium. Cardiac output is calculated from the rate of change
in blood temperature in the pulmonary artery over time using the Stewart Hamilton
equation [24 ] , [25 ] :
where CO = cardiac output

V = volume of injectate
B 0 = blood temperature at time = 0
I = injectate temperature at time = 0
B t = blood temperature at time = t
K 1 = density factor
K 2 = computation factor
Thermodilution measures the degree of mixing that occurs between the cold injectate
and blood. More mixing implies increased flow. Complete mixing of 10 ml of cold
injectate with a circulating blood volume of several liters produces no detectable
decrease in temperature at the catheter tip. Poor mixing, suggestive of slow, sluggish
flow, produces a large decrease in temperature as the injectate bolus passes the
thermistor in the pulmonary artery. The derived value for cardiac output is inversely
proportional to the area under the thermodilution curve. Rapid infusion of cold
intravenous fluids at the time of measurement may falsely increase the derived cardiac
output. Thermodilution measures right-sided cardiac output, which does not equal
left-sided cardiac output in patients with intracardiac shunts.
Cardiac output may be monitored continuously using a specialized pulmonary artery

catheter. The continuous cardiac output catheter intermittently heats blood adjacent to a
proximal portion of the catheter and senses changes in blood temperature at the
catheter tip using a fast-response thermistor. The method requires no manual injections,
and values are acquired, averaged, and updated automatically every several minutes.
Disadvantages include increased cost and a cardiac output display that is not
instantaneous but is an average value over the prior 2 to 10 minutes. This interval is
often too long to monitor the dynamic changes that occur during a cardiac operation.
Other methods of measuring cardiac output that do not depend on an indwelling
pulmonary artery catheter include transthoracic bio-impedance, echocardiography, and
analysis of the aortic pressure pulse contour. These have been cumbersome,
impractical, or unreliable for routine use. [26 ]
Mixed venous oxygen saturation (Svo2) can be measured intermittently by manual blood
sampling from the pulmonary artery or continuously using a modified pulmonary artery
catheter equipped with an oximeter. The Svo2 provides a continuous monitor of
cardiovascular well-being. Assuming normal oxygen consumption, a normal Svo2
generally denotes adequate oxygen delivery but does not provide information about the
adequacy of perfusion to specific organs. A normal Svo2 may not reflect adequate
tissue perfusion in patients with intracardiac shunts, sepsis, or liver failure. A decrease
in Svo2 is rarely caused by an increase in oxygen consumption during cardiac surgery
but is more likely a sign of decreasing systemic oxygen delivery due to decreased
cardiac output, anemia, or hypoxia.
Svo2 provides an alternative method to calculate cardiac output if oxygen consumption
is assumed to be constant. By the Fick equation, cardiac output is equal to the rate of
systemic oxygen consumption divided by the arterial-venous oxygen content difference.
where Vo 2 = oxygen consumption

CO = cardiac output
Cao 2 = oxygen content in arterial blood
Cvo 2 = oxygen content in mixed venous blood
Although routine use of a pulmonary artery catheter for monitoring patients during
cardiac operation is debated, it does provide clinical information that is used to direct
therapy in high-risk patients (Fig. 7-8) . Hypotension associated with normal or
increased cardiac output with a normal pulmonary artery occlusion pressure is likely
caused by vasodilation and is effectively treated by a vasoconstrictor such as
phenylephrine or norepinephrine. Hypotension associated with a low cardiac output and
a low pulmonary artery occlusion pressure indicates hypovolemia and is treated with
volume expansion (Fig. 7-9) . Hypotension associated with a low cardiac output and
increased pulmonary artery and pulmonary artery occlusion pressure indicates cardiac
dysfunction and may require treatment with an inotropic or anti-ischemic medication. An
insidious decrease in Svo2 may be an early warning of impending circulatory
insufficiency due to a decrease in arterial oxygen tension, ventricular dysfunction,
bleeding, or tamponade. Svo2 pulmonary artery catheters serve as vigilant monitors,
especially in the intensive care unit, where early deterioration in cardiac function can be
detected and treated before an adverse event occurs.
Transesophageal echocardiography (TEE) is an essential diagnostic and monitoring

tool for cardiac surgery. The cardiac anesthesiologist with TEE training is a
diagnostician who understands the utility and limitations of TEE in the interpretation of
functional and anatomic data, operation of echocardiography equipment, insertion of
the probe, and generation of suitable images and Doppler measurements. The cardiac
anesthesiologist-echocardiographer also understands the effects of surgery and
anesthetic drugs on ventricular wall motion, ventricular chamber size, fractional area
change, loading conditions, and regurgitant fractions and includes this information in the
interpretation of images. [27 ] More often than not, the cardiac anesthesiologist's
interpretation of echo images directly influences intraoperative surgical and medical
mangement. [28 ]
TEE is indicated in many patients who have cardiac surgery and should be available to
all. Indications for intraoperative TEE vary, but the procedure is recommended for all
valvular and aortic surgery, intracardiac masses and shunts, for all patients with poor left
or right ventricular function, and for the emergency evaluation of intraoperative
hypotension or heart failure. [29 ] TEE can establish the intraoperative diagnosis of a
ruptured aorta, identify the location and extent of aortic dissections and the position of
wires, catheters, and balloons within the aorta, confirm or establish the diagnosis of
massive pulmonary embolism, verify the presence of pericardial fluid or cardiac
tamponade, and detect and grade atheroma of the thoracic aorta and potential embolic
debris (Table 7-3) .
The intraoperative TEE study is a systemic and comprehensive examination of the

heart and adjacent structures using two-dimensional and Doppler echocardiography
and is performed for defined indications (Table 7-4) . The lubricated probe is inserted
into the distal esophagus after induction of general anesthesia and tracheal intubation.
The acoustically favorable window of the heart through the esophagus produces
high-resolution images of cardiac anatomy and function without disturbing the
operation. Although confinement within the esophagus restricts the number of image
planes obtained by probe manipulation, these limitations are partially overcome by
multiplane rotational probes. [30 ] , [31 ] Bacteremia from TEE probe insertion is
uncommon, and antibiotic prophylaxis is not recommended routinely but may be
advisable in patients at risk for endocarditis who need prolonged procedures with
intraoperative TEE. [32 ] , [33 ]
The TEE machine and gain settings are calibrated, and this is followed by systematic
examination of cardiac structures and flow velocity measurements. A predefined
examination sequence avoids omissions and facilitates detection of occult disease.
After this overview, a targeted or focused evaluation tailored to the patient's disease
and planned operation is done. For example, a patient scheduled for coronary artery
bypass grafting and mitral valve surgery undergoes meticulous scrutiny of left ventricular
wall motion and provocative testing of mitral valve competence. Once completed, a
succinct, detailed summation of observations is conveyed to attending physicians. The
examination is repeated after separation from cardiopulmonary bypass. The findings of
intraoperative TEE are recorded in the medical record, stored on hard copy (typically
½-in VHS tape), and archived for later retrieval.
TEE assessment of ventricular wall motion during cardiac surgery permits quantitative
evaluation of global and regional ventricular function. [34 ] , [35 ] Regional left ventricular
(LV) contractile properties provide a more sensitive and quantitative indicator of
myocardial ischemia than electrocardiographic ST-segment changes. Abrupt
decreases in coronary blood flow produce almost immediate decreases in contractile
function of the affected myocardium. [36 ] Segmental ventricular wall motion
abnormalities are assessed by measuring changes in wall thickening and endocardial
excursion. Wall thickness is measured from the epicardium to endocardium using the
leading-edge to leading-edge method. Changes in wall thickness from diastole to
systole are measures of regional myocardial function. Endocardial excursion describes
displacement or movement of an endocardial edge toward the centroid of the LV.
Because of rotation and translational movements of the heart during the cardiac cycle,
the LV centroid is not stationary and renders measurement of endocardial excursion
dependent on off-line determinations of the internal LV center of mass (centroid). Global
LV function is typically dependent on two-dimensional area measurements, such as
fractional area change (FAC).
where
LVEDA = left ventricular end-diastolic area
LVESA = left ventricular end-systolic area
Fractional area change is based on only a single cross section of the LV and may not
correspond to ventricular ejection fraction measured using volumetric techniques in
patients with ventricular asymmetry or aneurysm. Three-dimensional LV geometry and
anatomy of cardiac structures can be produced by combining multiple cross-sectional
images. Automatic detection of integrated backscatter and improvements in transducer
technology provide continuous, real-time, graphic displays of fractional area change
(Fig. 7-10) .
Most echocardiography machines are equipped with cine loop storage and retrieval
systems that permit side-by-side comparisons of real-time images acquired at different
times. Similar to comparisons of intraoperative ECG recordings, new regional wall
motion abnormalities are most significant.
TEE assessment of valvular heart disease tries to determine valvular anatomic

abnormalities and grade the severity of valve dysfunction. Preoperative cardiac
catheterization and often chest wall echocardiograms do not provide sufficient data and
image resolution to determine the mechanism of valve pathology. TEE provides a
detailed assessment of valvular morphology and semiquantitative grades of valvular
stenosis and insufficiency. Grading mitral stenosis and regurgitation is based on
Doppler blood flow velocity measurements. [37 ] , [38 ] Mitral valve area and transmitral
valve pressure gradients are calculated from the transvalvular blood flow velocity profile
using Doppler echocardiography. The peak and mean transvalvular pressure gradients
are calculated using a modified Bernoulli equation. The rate of deceleration of diastolic
blood flow velocity through the mitral valve is a function of left atrial emptying and the
instantaneous transvalvular pressure gradient over time. Normal transmitral valve blood
flow velocity decays rapidly during diastole because left atrial pressure decreases
rapidly after mitral valve opening. Impedance to left atrial emptying in patients with mitral
stenosis produces an increased transvalvular pressure gradient throughout diastole and
causes a more gradual decay in transvalvular blood flow velocity. The method of the
pressure half-time is a Doppler technique designed to calculate functional mitral valve
area from the rate of decay of diastolic transmitral valve blood flow velocity. Pressure
half-time P t1/2 is the interval required for the peak transmitral valve diastolic pressure
gradient to decrease by 50 percent, which is equivalent to a 70 percent decrease in
peak transmitral valve inflow velocity. Mitral valve area is calculated by the following
equation:
In patients with atrial fibrillation, estimation of mitral valve area customarily is taken from
Doppler measurements obtained over several cardiac cycles. Transvalvular blood flow
velocity profile and pressure half-time depend on the geometry of the mitral valve orifice,
left atrial and ventricular compliance, peak transvalvular pressure gradient, heart rate,
and the presence of aortic regurgitation. [39 ]
TEE is more sensitive than transthoracic echocardiography for detecting mitral

regurgitation. [40 ] However, color-flow Doppler velocity mapping permits only
semiquantitative estimates of the actual regurgitant fraction. A color-flow Doppler jet
represents a contour of blood velocity that is selected by settings of the
echocardiography machine. Hence the size and shape of the jet are variable and
depend on both machine and settings. Maximum regurgitant jet area is the most
commonly used semiquantitative index of the severity of regurgitation. However,
maximum jet area does not relate to regurgitant fraction for eccentric jets because
eccentric jets that impinge on the atrial wall produce smaller color Doppler areas than
central jets with similar regurgitant volumes (Coanda effect). [41 ] [43 ] Maximum jet
areas greater than 8 to 10 cm2 are associated with severe mitral regurgitation with
regurgitant fractions greater than 40 percent. [43 ] Systolic reversal of pulmonary vein
blood flow velocity measured by pulse-wave Doppler echocardiography is also a
sensitive and specific marker for severe mitral regurgitation.
Aortic stenosis is caused by primary calcification, rheumatic heart disease, or

secondary calcification of a congenitally abnormal valve. Commissure fusion is variable
and may render a previously normal aortic valve echocardiographically
indistinguishable from a congenital bicuspid valve with secondary calcification. Severe
aortic valve deformity does not necessarily mean functional aortic stenosis. Valve
deformity that does not limit orifice size is not an indication for valve surgery, although
the risk of infective endocarditis is increased. TEE methods of grading the severity of
aortic stenosis are based on assessment of aortic valve cusp separation, cusp mobility,
measurement of the mean and peak transaortic valve pressure gradients, and aortic
valve area. [44 ] Estimates of transvalvular pressure gradients are based on
transvalvular blood flow velocities measured by continuous-wave Doppler aligned
through the flow-limiting orifice and application of the modified Bernoulli equation. An
estimate of aortic valve area is made by manual planimetry of the aortic valve opening
using the basal short-axis view. This en fosse still image is used to manually trace the
aortic valve orifice during systole. A large left ventricle to aortic pressure gradient with
near-normal excursion of aortic valve cusps raises suspicion that an obstruction to left
ventricular ejection may not be at the aortic valve but may be due to a subaortic
membrane or dynamic left ventricular outflow obstruction.
Grading aortic regurgitation by color-flow Doppler echocardiography is not based on

the size of the regurgitant jet. The width of the regurgitant jet relative to the width of the
left ventricular outflow tract is a more reliable index of the severity of aortic regurgitation.
An aortic regurgitant jet that fills more than 0.6 of the left ventricular outflow tract is
severe aortic regurgitation. A thin jet emanating from a small regurgitant orifice in the
left ventricular outflow tract is graded mild aortic regurgitation even though the jet may
extend deep into the left ventricular cavity. [45 ]
The intraoperative echographer describes the functional anatomy of the diseased valve
to the cardiac surgeon. By identifying elements involved and the mechanism and locus
of regurgitation, surgical repair can be planned prior to starting cardiopulmonary
bypass. Functional abnormalies of the mitral valve may not be obvious during inspection
in a flaccid, arrested heart. Anatomic assessment of the aortic valve defines the
integrity of cusps, aortic root, and ascending aorta. Congenitally bicuspid aortic valves
are identified most easily during systole. A prominent raphe in the conjoined cusp may
be misdiagnosed as fusion of two otherwise normal cusps. The size of the aortic
annulus, the diameter of the root at the sinuses of Valsalva, and the diameter of the
sinotubular junction are pertinent measurements for surgical planning. The growing use
of autografts adds the need to size the pulmonic artery and valve for appropriate
matching. TEE and color-flow Doppler velocity mapping are essential for evaluation of
aortic allografts and autografts, repaired mitral, aortic, and tricuspid valves, and
iatrogenic, acquired, or congenital intracardiac defects.
TEE is also valuable in the post-cardiopulmonary bypass period. Real-time assessment

of valvular reconstructive procedures immediately after separation from
cardiopulmonary bypass is valuable in determining valvular morphology and function,
technical deficiencies, residual intracavity air, and quantitative measures of ventricular
performance and permits immediate correction or replacement of inadequate valves.
TEE increases the safety and quality of complex and reconstructive procedures and
procedures in high-risk patients with poor ventricular function and aids in the
management of intraoperative complications. TEE is not indicated in patients with
normal ventricular function who otherwise require straightforward operations.
Contraindications for TEE include esophageal cancer, strictures, webs, or other

abnormalities that may impede the safe passage of a nonoptically guided gastroscope.
Oropharyngeal injury is uncommon but potentially dangerous if it occurs. [46 ] The most
important risk of TEE is not physical injury from probe insertion and manipulation but
rather misinterpretation of TEE-acquired data leading to mismanagement.
Anesthetic Gas Monitors
Inhaled volatile anesthetics are different from other parenteral medications in that the
dose of the drug administered is dictated by its concentration in the blood rather than by
a set standard. The concentration of an anesthetic in the exhaled gas at end-exhalation
reflects the alveolar gas concentration that is in direct equilibrium with the blood.
Monitoring the concentration of anesthetic in the end-tidal gas mixture adds precision to
the administration of inhaled anesthetics, ensures that a therapeutic concentration is
present, and guards against inadvertent overdose.
The concentration of anesthetic gases is measured clinically by mass spectroscopy. A

gas sample retrieved from the breathing circuit is analyzed off-line by measuring the
dispersion of the ionized sample as it is accelerated and deflected by a magnetic field.
The site of impact on a collecting plate is specific for a gas species and the number of
impacts represents the relative concentration of the gas species in the sample. The
end-tidal concentration is determined by gating the measure of the anesthetic gas to the
carbon dioxide expirogram (capnogram). Other methods of measuring anesthetic and
respiratory gases include infrared spectroscopy, Raman spectroscopy, electrochemical
and polarographic sensors, and piezoelectric absorption. [47 ]
Measurement of Electrolyte Concentration
Electrolyte abnormalities most commonly occur prior to stopping cardiopulmonary

bypass and are monitored intermittently using routine laboratory tests that are promptly
reported to the operating room. The capability to detect and correct electrolyte
disturbances is an important aspect of intraoperative care. [48 ]
Abnormalities in sodium and water homeostasis are caused primarily by hemodilution
with solutions used to prime the cardiopulmonary bypass circuit. Nonosmotic secretion
of arginine vasopressin provoked by surgical stress, pain, hypotension, or nonpulsatile
perfusion contributes to the development of hyponatremia by stimulating renal retention
of free water. A 2-to-5-meq/liter decrease in the plasma sodium concentration is
expected after beginning cardiopulmonary bypass and does not normally require
treatment. Hyperglycemia or excessive mannitol administration causes
pseudohyponatremia by artificially decreasing the plasma sodium concentration.
Hypernatremia is usually caused by excessive diuresis without free water repletion or by
the administration of hypertonic sodium bicarbonate solutions that have a sodium
concentration of 1000 meq/liter.
Hyperkalemia is common because high-potassium cardioplegic solutions are

distributed into the systemic circulation. Hyperkalemia during cardiac surgery also may
be caused by hemolysis, acidosis, massive depolarization of muscle, and tissue cell
death. Increasing serum potassium concentration is manifested by peaked T waves, a
widened QRS complex, disappearance of the P wave, heart block, and conduction
abnormalities that may be life-threatening. Very high concentrations of potassium used
to provide cardioplegia inhibit spontaneous depolarization and produce asystole.
Patients with diabetes mellitus are at increased risk for hyperkalemia because cellular
uptake of potassium is mediated by insulin. Impaired renal excretion of potassium
enhances hyperkalemia in patients with renal insufficiency. The initial treatment of
hyperkalemia is aimed at redistributing extracellular potassium into cells, but the
elimination of potassium from the body requires excretion by the kidneys or
gastrointestinal tract. Insulin and glucose administration rapidly and effectively decrease
the extracellular concentration of potassium by redistributing the ion into cells. Alkalosis,
hyperventilation, and beta-adrenergic agonists also favor redistribution of potassium
into cells, but the response is less predictable. Calcium carbonate and calcium chloride
antagonize the effects of hyperkalemia at the cell membrane. A typical intravenous dose
of glucose and insulin for the acute treatment of hyperkalemia is 1 g glucose per
kilogram and 1 unit of regular insulin per 4 g of glucose administered.
Hypokalemia is also common during cardiac surgery and may be caused by

hemodilution with nonpotassium priming solutions, diuresis, or increased sympathetic
tone during nonpulsatile perfusion. [48 ] Intraoperative hypokalemia is exacerbated by
preoperative potassium depletion due to chronic diuretic therapy. Beta2-adrenergic
agonists acutely decrease the plasma potassium concentration by directly stimulating
cellular uptake of potassium. Hypokalemia predisposes to atrial arrhythmias, ventricular
ectopy, digitalis toxicity, and prolonged response to neuromuscular blocking drugs but
is not a risk factor during general anesthesia if it is recognized and treated.
Hypokalemia is treated by slow administration of KCl in increments of 10 meq, with
potassium concentrations measured between doses.
Hypocalcemia decreases myocardial contractility and peripheral vascular tone and is

associated with tachycardia. [49 ] , [50 ] Hypocalcemia produces prolongation of the QT
interval and T-wave inversions, but significant arrhythmias due to disturbances in
ionized calcium concentration are not common. Hypocalcemia occurs soon after the
onset of cardiopulmonary bypass but may recover to preoperative levels prior to ending
of extracorporeal perfusion. Increasing serum concentrations of parathyroid hormone
during cardiopulmonary bypass may, in part, explain the gradual increase in ionized
calcium concentration to pre-cardiopulmonary bypass levels. [50 ] The etiology of
cardiopulmonary bypassinduced hypocalcemia is probably multifactorial, but
hemodilution and decreased metabolism of citrate after rapid blood transfusion are
contributing factors. Hypocalcemia and its consequences on the circulation are
corrected effectively by the administration of calcium chloride. [30 ] The routine
administration of calcium salts without prior measurement of ionized calcium
concentration poses the risk of hypercalcemia. Excessive calcium administration may
increase the risk of postoperative pancreatitis and myocardial reperfusion injury. [52 ]
Magnesium deficiency is common in cardiac surgical patients, and acute magnesium

supplementation decreases the incidence of postoperative cardiac dysrhythmias and
overall morbidity after cardiac operations. [53 ] , [54 ] However, measuring total plasma
magnesium concentration has questionable clinical significance because the value
primarily reflects the concentration of protein-bound magnesium and not physiologically
active, ionized magnesium. [55 ]
Monitoring the Nervous System
Anesthetics produce characteristic changes in the electrical activity of the brain. The
cellular mechanism of general anesthetics is controversial, but unconsciousness and
general anesthesia are not achieved by producing energy failure in the brain. The
central nervous system cellular concentrations of ATP, ADP, phosphocreatine, glucose,
and glycogen are increased, and lactate concentrations are decreased during general
anesthesia. Most general anesthetics, and especially the extensively studied
barbiturates, decrease cerebral metabolic rate and oxygen consumption. [56 ] Despite
the potential protective effects of anesthetics, neurologic complications are common
after cardiac operations, with the incidence of stroke estimated to be between 3 and 19
percent. [57 ] , [58 ] Neurologic deficits elicited by neuropsychological testing are more
common and have been detected in up to 70 percent of patients after cardiac
operations. [59 ] Neurophysiologic monitoring techniques permit assessment of nervous
system function during and early after operation because clinical evaluation is not
possible. Techniques to monitor neurophysiologic function during general anesthesia
include electroencephalography (EEG) and somatosensory evoked potentials (SSEP).
The EEG is a recording of the spontaneous electrical activity of the cerebral cortex and
is defined by frequency, amplitude, and spatial distribution. [60 ] The amplitude of
electrical activity decreases by more than 80 percent when the recording electrode is
displaced only 2 cm from the site of maximum amplitude. This necessitates multiple
electrodes and channel recordings to obtain a spatial representation of the EEG rhythm.
[61 ] A change in EEG amplitude or frequency may be produced by cerebral ischemia
(EEG slowing), anesthetics, or hypothermia. Barbiturates produce a flat EEG, whereas
enflurane may cause seizurelike activity. EEG burst suppression is not uncommon after
induction of general anesthesia but does not exclude an impending neurologic
catastrophe if induced by changes in cerebral blood flow. While continuous EEG
monitoring may detect cerebral ischemia during carotid operations, its application
during cardiac operations is problematic because the decrease in EEG frequency and
amplitude due to anesthesia and hypothermia during operation cannot be distinguished
from changes caused by cerebral ischemia. [62 ] , [63 ] Electrical artifacts from the
heart-lung machine also severely interfere with the ability to continuously monitor the
EEG during operation. Intraoperative monitoring of SSEP to detect cerebral ischemia
overcomes some of the problems inherent to EEG monitoring because the temperature
dependency of SSEP is well established. [64 ] Embolic stroke and brachial plexus injury
[65 ] , [66 ] can be detected using intraoperative SSEP monitoring, but the utility,
sensitivity, and specificity of this technique for detecting, preventing, and guiding
treatment of neurologic complications remain to be established [65 ] , [66 ] (Fig. 7-11) .
Alternatively, intraoperative TEE and transcranial Doppler (TCD) ultrasonography may

be used to detect arterial embolic events (Fig. 7-12) . The embolic burden to the
cerebral circulation measured by quantitative TCD correlates with the incidence of
intraoperative surgical manipulation and postoperative neurologic deficits. [67 ]
Intraoperative TEE can be applied to detect right-to-left intracardiac shunting through an
atrial septal defect, [68 ] , [69 ] intracardiac masses, [70 ] , [71 ] or residual air within the
cardiac chambers. [72 ] Routine epiaortic ultrasonography to assess the degree of
aortic atherosclerosis and guide the insertion of the aortic cannula and application of
the aortic cross-clamp may decrease the risk of embolic stroke, but outcome data to
suggest efficacy is sparse. [73 ]
ANESTHESIA
Anesthetic techniques presently employed for patients undergoing cardiac operations

have been selected after extensive testing and clinical experience. Techniques in
clinical practice have minimal organ toxicity, predictable cardiovascular and physiologic
effects, well-established pharmacokinetic behavior, and excellent safety profiles. No
benchmark anesthetic technique has been defined for all patients undergoing cardiac
operations. [74 ] [77 ] Combining drugs that selectively provide hypnosis, amnesia,
analgesia, and muscle relaxation permits control of the anesthetic state and minimizes
side effects of a single anesthetic drug used in high concentrations. Achieving the
desired anesthetic state while preserving or improving vital organ function during
operation requires an understanding of the physiologic actions of anesthetics,
individually and in combination, in patients with a wide range of medical conditions.
Anesthesia drug management is dictated, in part, by the underlying cardiovascular

disorder. Coronary artery disease renders the ventricle susceptible to myocardial
ischemia, and management strategy is designed to support coronary perfusion
pressure while decreasing myocardial oxygen demands. Tachycardia, hypertension,
and increased inotropic state caused by nociception during operation are prevented by
anticipating the inciting events and providing effective anesthesia. In contrast, patients
with heart failure due to valvular disease, dilated cardiomyopathy, or cardiac
tamponade may be dependent on underlying sympathetic tone to support the
circulation. In these patients, the anesthetist must be prepared to pharmacologically
replace endogenous catecholamines as the patient is anesthetized.
Anesthetic-induced hemodynamic perturbations must be considered when assessing

valve function intraoperatively using TEE (Fig. 7-13) . Patients with regurgitant valve
lesions frequently exhibit acute hemodynamic improvement during anesthesia because
systemic oxygen demand and ventricular afterload decrease with anesthetic agents.
Potent volatile anesthetics produce varying degrees of dose-dependent vasodilation
and afterload reduction: isoflurane > enflurane > halothane. Assessment of mitral
regurgitant grade during general anesthesia is not necessarily predictive of regurgitant
grade in the awake state and may lead to mismanagement. [78 ] , [79 ] Provocative
pharmacologic testing may be required to mimic circulatory conditions in the awake,
exercising patient. Stress-testing the mitral valve may be achieved with incremental
doses of phenylephrine to increase the transmitral systolic pressure gradient; however,
the determinants of regurgitant volume are many, and it is unlikely that phenylephrine
reliably reproduces the cardiovascular conditions that occur when a patient is
exercising.
In contrast, maintenance of cardiovascular stability during general anesthesia for

patients with aortic stenosis is based on avoiding systemic vasodilation and
tachycardia and preserving sinus rhythm. Systemic vasodilation provides no significant
decrease in left ventricular afterload because of the stenotic aortic valve. Tachycardia is
poorly tolerated due to shortened systole and diastole and decreased filling of the
noncompliant left ventricle. Nonsynchronous atrial contraction, a common occurrence
during induction of general anesthesia, may produce significant hypotension and rapid
deterioration in stroke volume. Narcotic-based anesthetics possess many desired
hemodynamic attributes for patients with aortic stenosis. Synthetic narcotics are potent
vagotonic drugs that decrease heart rate with minimal vasodilating effects and provide
profound analgesia.
Anesthetics and Neuromuscular Blockers
INHALED ANESTHETICS
Inhaled anesthetics alone produce all the conditions necessary for operation. [80 ] All
inhaled anesthetics cause circulatory depression at concentrations necessary to
produce general anesthesia. Especially in patients with cardiovascular disease, when
ventilation is controlled, circulatory actions of the inhaled anesthetics usually limit the
anesthetic dose that can be tolerated. For this reason, inhaled anesthetics are usually
combined with other anesthetics to produce general anesthesia for cardiac operations.
The decrease in blood pressure caused by volatile anesthetics is a direct result of

vasodilation and depression of myocardial contractility and an indirect result of
attenuation of sympathetic nervous system activity. The decrease in blood pressure is
so predictable that it is often used as a sign for assessing the depth of anesthesia.
Overdose with inhaled anesthetics is manifested by hypotension, arrhythmias, and
bradycardia that, if unrecognized, may lead to circulatory shock.
The inhaled anesthetics decrease myocardial contractility based on both experimental

and clinical studies [81 ] [83 ] (Fig. 7-14) . Inhalation anesthetics produce a
dose-dependent decrease in mean maximal velocity of circumferential shortening,
mean maximal developed force, and dP/dt . [84 ] [86 ] The effects of each individual
inhaled anesthetic on cardiovascular function depend on selective dose-dependent
effects of the drug on myocyte contraction and relaxation, vascular smooth muscle tone,
and sympathetic nervous system reflexes, as well as the underlying disease state,
intravascular volume status, surgical stimulation, temperature, mode of ventilation, and
acid-base status. The decrease in blood pressure in response to 1.0 minimum alveolar
concentration (MAC) of halothane is primarily the result of decreased cardiac output
caused by direct myocardial depression. Despite a decrease in myocardial
contractility, cardiac output is generally unchanged at 1.0 MAC of isoflurane because of
direct arterial vasodilation and preservation of baroceptor reflexes with a resulting
decrease in ventricular afterload and increase in heart rate and stroke volume [87 ]
(Figure 7-15) . Halothane, enflurane, isoflurane, desflurane, and sevoflurane decrease
global left ventricular systolic function at any given left ventricular loading condition or at
any given degree of underlying sympathetic tone (Figure 7-16) . Experimental studies
suggest that these agents cause minimal changes in left ventricular diastolic
compliance but impair left ventricular diastolic relaxation in a dose-dependent manner.
[88 ] These agents have minimal direct effects on left ventricular preload, but rather left
and right ventricular end-diastolic pressures may increase during anesthesia because
of impaired diastolic filling and decreased cardiac output. Halothane and enflurane are
the most potent direct myocardial depressants, followed by isoflurane, desflurane,
sevoflurane, and nitrous oxide.
Patients in shock or with profound ventricular dysfunction may not tolerate the
cardiovascular depressant effects of inhaled anesthetics given in concentrations that
are needed to produce anesthesia. Volatile anesthetics have a proportionally greater
negative inotropic effect on diseased myocardium compared with normal myocardium.
[65 ] In contrast, sympathetic nervous system activation due to nociception may mask
clinical signs of circulatory depression caused by inhaled anesthetics.
Cardiodepressants and adrenergic antagonists potentiate the cardiovascular
depressant actions of inhaled anesthetics.
The administration of inhaled anesthetics in patients with preexisting cardiovascular

diseases has potential advantages. The myocardial depressant and arterial
vasodilating actions of anesthetics benefit patients with coronary insufficiency if
perfusion pressure is maintained. The negative inotropic properties of inhalation
anesthetics decrease myocardial oxygen demand and may create a more favorable
myocardial oxygen balance. The vasodilating and antihypertensive actions of
anesthetics effectively control an increase in blood pressure in response to surgical
pain, but anesthetic-induced hypotension may reduce coronary perfusion pressure and
coronary blood flow.
Enflurane is a mild coronary vasodilator, and halothane has little effect on coronary
vascular tone. Regional wall motion abnormalities and ECG evidence of myocardial
ischemia associated with enflurane or halothane are due to decreases in coronary
perfusion pressure rather than to a redistribution of myocardial blood flow. [89 ] , [90 ]
Isoflurane causes endothelium-dependent inhibition of the contractile response of
canine coronary arteries. [91 ] The direct coronary artery vasodilating action of
isoflurane may increase coronary blood flow but also may increase the risk of
myocardial ischemia in patients with steal-prone coronary anatomy by attenuating
autoregulation of coronary blood flow. Coronary anatomy associated with
isoflurane-induced coronary steal is a total occlusion of a major coronary branch and a
hemodynamically significant (greater than 50 percent) stenosis in the artery that
supplies the collateral-dependent myocardium. The proposed mechanism is
vasodilation and a decrease in coronary perfusion pressure downstream to the 50
percent stenosis that decreases blood flow through the high-resistance, less-responsive
collateral network. [92 ] However, there is no convincing clinical evidence that isoflurane
should be avoided in patients with coronary artery disease any more than other
nonselective coronary vasodilators (e.g., nitroprusside). [93 ] The increase in heart rate
and sympathetic tone associated with isoflurane and desflurane increases oxygen
demand by producing tachycardia and may cause myocardial ischemia in susceptible
patients. This is more important than the theoretical risk of coronary steal. [94 ] [96 ]
Halothane sensitizes the myocardium to epinephrine-induced ventricular dysrhythmias

and may be problematic in patients at risk for ventricular tachycardia, especially if
sympathomimetics are given concurrently. The subcutaneous dose of epinephrine
required to cause ventricular premature contractions during anesthesia with isoflurane,
enflurane, or desflurane is approximately fourfold greater than the dose required during
halothane anesthesia. [97 ] , [98 ] The susceptibility to catecholamine-induced
dysrhythmias is exacerbated by hypercarbia.
Junctional rhythms are observed often with all inhaled anesthetics but most commonly
with enflurane. The loss of atrial augmentation of ventricular preload with a junctional
rhythm contributes to a decrease in blood pressure during inhalation anesthesia.
Junctional rhythms are frequently problematic in patients with aortic stenosis and left
ventricular hypertrophy who have poor ventricular diastolic compliance. Junctional
rhythms can be treated with transesophageal, transvenous, or direct atrial pacing,
decreasing the dose of inhalation anesthetic, or administering an anticholinergic drug
such as glycopyrrolate or atropine.
Regional blood flow to other vital organs may be modified by inhaled anesthetics
because of their effects on metabolic demands and autoregulation. The normal
circulatory response to hypotension and low cardiac output is redistribution of blood
flow to vital organs (brain, heart, kidneys) and a decrease in blood flow to skin, muscle,
and the gastrointestinal system. Volatile inhalation anesthetics impair this protective
response and compromise vital organ perfusion if administered in high doses during
periods of circulatory shock.
Nitrous oxide (N2O) is also an inhaled anesthetic but not potent enough to be used
alone for general anesthesia. It is often used with other anesthetics because it
decreases the MAC of halothane and isoflurane. N2O is rarely used during cardiac
operations because it diffuses into and expands the volume of gas-containing cavities
and may increase the size of arterial gas emboli.
Halothane administration has been attributed to rare cases of acute postoperative

hepatic necrosis. [99 ] Although the epidemiologic evidence implicating halothane as
the cause of this syndrome remains controversial, the incidence of this idiosyncratic
reaction is estimated in the range of 1 in 10,000 to 1 in 35,000 halothane anesthetics.
Repeated exposures to halothane, reduced splanchnic blood flow, obesity, hypoxemia,
enhanced reductive metabolism of the drug, increased levels of hepatic enzymes
induced by chronic drug use, malnutrition, and underlying liver disease appear to be risk
factors for postoperative hepatitis. The perceived risk of halothane-induced hepatitis
has favored increased use of newer anesthetic agents such as enflurane, isoflurane,
and desflurane. These newer agents undergo minimal hepatic metabolism, do not
decrease hepatic blood flow, and have not been implicated in anesthetic-induced liver
dysfunction.
In general, carefully conducted clinical trials suggest that any inhaled anesthetic can be
administered safely to patients with cardiovascular disease when the hemodynamic
condition of the patient is closely monitored and controlled. [76 ] , [98 ]
SEDATIVE-HYPNOTICS
Sedative-hypnotics are a broad class of anesthetic drugs that includes the barbiturates,
benzodiazepines, etomidate, propofol, and ketamine. They are used for preoperative
sedation, producing immediate loss of consciousness during intravenous induction of
general anesthesia, supplementing the actions of the inhaled anesthetics, and to
provide sedation in the immediate postoperative period. The circulatory effects of
individual agents are an important consideration for patients with cardiovascular
disease. The sedative-hypnotics have direct effects on cardiac contractility and vascular
tone in addition to indirect effects from affecting autonomic tone.
The barbiturates, such as thiopental or methohexital, are negative inotropic agents.

They produce dose-dependent decreases in ventricular dP/dt and the force-velocity
relationship of ventricular muscle. [100 ] Induction of general anesthesia with a
barbiturate is associated with a decrease in blood pressure and cardiac output. In
comparison with barbiturates, propofol appears to cause less myocardial depression.
[101 ] , [102 ] The decrease in arterial pressure after propofol administration is
attributed primarily to arterial and venous dilatation. [103 ] , [104 ] Propofol is well suited
for continuous intravenous infusion for sedation because it has a short duration of action
and can be titrated to effect. [77 ]
Etomidate and ketamine are administrated for rapid induction of general anesthesia in
patients with preexisting hemodynamic compromise because they generally cause little
or no change in circulatory parameters. [105 ] These agents are useful for unstable
patients undergoing emergency operation, reexploration for bleeding, or cardioversion.
Etomidate has virtually no effect on myocardial contractility even in diseased ventricular
muscle. [106 ] , [107 ] However, etomidate inhibits adrenal synthesis of cortisol by
blocking 11--hydroxylase and therefore is limited to short-term use as an intravenous
anesthetic induction agent. Ketamine often increases heart rate and blood pressure
after anesthetic induction because it has sympathomimetic properties. [108 ] The direct
negative inotropic and vasodilating effects of ketamine can be unmasked when it is
administered to critically ill patients with catecholamine depletion. [109 ] Ketamine is
not used routinely because it may cause postoperative delirium, especially if it is
administered in the absence of other sedative-hypnotics.
Centrally acting alpha2-adrenergic agonists such as clonidine possess sedative and

analgesic actions but do not produce anesthesia. Preoperative administration of
clonidine to cardiac surgical patients decreases narcotic requirements and improves
hemodynamic stability during operation. [110 ] Alpha2 agonists are potent
sympatholytic agents and also may be effective at attenuating sympathetically mediated
myocardial ischemia. [111 ] Dexmedetomidine, a highly selective intravenous
alpha2-adrenergic agonist, is being investigated as an anesthetic adjunct for cardiac
and major abdominal operations. [112 ]
NARCOTIC ANESTHETICS
Narcotics remain an important adjunct for cardiac anesthesia. Their analgesic actions
are mediated by direct activation of opioid receptors in the central nervous system,
spinal cord, and periphery. The three types of opioid receptors most studied are the mu,
delta, and kappa receptors. Mu receptors are densely concentrated in the neocortex,
brainstem, and regions of the central nervous system associated with nociception and
sensorimotor integration. [113 ] Two different mu receptor subtypes produce analgesia
and respiratory depression, leading to the possible development of selective agonist or
antagonist compounds. [114 ]
Narcotic-based anesthetics offer the advantages of profound analgesia, attenuation of

sympathetically mediated cardiovascular reflexes in response to pain, and virtually no
direct effects on myocardial contractility or vasomotor tone. Narcotics may be
administered intravenously, intrathecally, or into the lumbar or thoracic epidural space.
Even though narcotics have little direct action on the cardiovascular system, they may
cause profound hemodynamic changes indirectly by attenuating sympathetic nervous
system tone. Narcotics decrease serum catecholamine levels and may produce
cardiovascular depression indirectly, especially in a patient who is critically ill and
dependent on endogenous catecholamines (e.g., hypovolemia, cardiac tamponade).
Morphine sulfate also may decrease blood pressure by provoking the release of
histamine.
Problems encountered with narcotic-based anesthetics include difficulty estimating the

dose required because of patient variability, predicting the duration of postoperative
narcotic-induced respiratory depression, and ensuring hypnosis during operation.
Rapid administration of narcotics is also associated with muscle rigidity that may
impede the ability to ventilate the patient immediately after the induction of general
anesthesia. [115 ] The rigidity usually affects the thoracic and abdominal musculature
and is commonly observed with doses of narcotic used in cardiac anesthesia.
Myoclonic activity often associated with muscle rigidity can easily be mistaken for grand
mal seizures. There is no evidence that opioids induce seizures when there is adequate
oxygenation and ventilation. [116 ] Opioid-induced muscle rigidity is immediately
reversed by the administration of neuromuscular blockers.
The nonselective opioid antagonist naloxone reverses narcotic-induced respiratory

depression. When indicated, narcotic antagonists must be titrated carefully to effect.
Sudden reversal of opioid-mediated analgesia may produce systemic and pulmonary
hypertension and tachycardia and is potentially life-threatening for patients with
coronary artery disease. [117 ] The reversing effect of naloxone on narcotic-induced
respiratory depression is significantly shorter than the respiratory depressant effects of
most opioids, except for ultra-short-acting synthetic narcotics (e.g., alfentanil,
remifentanil). A patient who receives a single intravenous dose of naloxone is
susceptible to renarcotization after initial, effective reversal of respiratory depression.
For this reason, the initial bolus dose of naloxone is typically followed by an
intramuscular injection or intravenous infusion, and patients are monitored closely.
Longer-acting opioid antagonists include nalmefene, which has an elimination half-life
of 8.5 hours, in contrast with the t 1/2B of 1.5 hours for naloxone. [118 ] Mixed opioid
agonists-antagonists (e.g., nalbuphine) may decrease the risk of hypertension,
tachycardia, and dysrhythmias but do not reverse respiratory depression as reliably on
naloxone. [119 ]
Opioid tolerance is a decrease in response (both analgesia and respiratory

depression) to a narcotic due to prior exposure. Tachyphylaxis is the rapid
development of drug tolerance. Drug dependence is a patient condition or disorder that
occurs as a consequence of sustained exposure to a drug such that withdrawal or
antagonism of the drug prohibits normal function. [114 ] Perioperative exposure to
morphine and synthetic narcotics is unlikely to produce the down regulation and
desensitization of opioid receptors believed necessary for narcotic dependence. [120 ]
Acute tolerance to fentanyl in humans is likely to occur only after prolonged infusion and
to a lesser extent in the perioperative period. Cardiac surgical patients receiving
narcotic infusions in the intensive care unit develop tolerance and require increasing
doses to sustain the desired effect. [121 ]
The newer synthetic narcotics such as fentanyl, sufentanil, and alfentanil overcome
some of the problems of morphine-based anesthetics because of increased lipid
solubility, more rapid onset of action, increased anesthetic potency, absence of
histamine release, and independence of renal function for drug clearance. Development
of short-acting narcotic anesthetics also may improve the ability to control anesthetic
depth without prolonging recovery time. Ultra-short-acting narcotics (e.g., remifentanil)
may have a unique niche in cardiac anesthesia because their effect is terminated
immediately on stopping the drug infusion due to rapid in vivo ester hydrolysis. [122 ]
Other side effects of narcotics include pruritus, nausea, constipation, and urinary
retention.
NEUROMUSCULAR BLOCKING DRUGS
Neuromuscular blocking drugs are administered to facilitate intubation of the trachea,

prevent patient movement during operation, improve surgical exposure of the operating
field, and attenuate metabolic demands caused by shivering during hypothermia.
Except for succinylcholine, the neuromuscular blocking drugs used in clinical practice
are all nondepolarizing, competitive antagonists of acetylcholine at the nicotinic
acetylcholine receptor at the motor end plate. Succinylcholine acts by preventing
coordinated muscular contraction by depolarizing the motor end plate.
Muscle relaxants are chosen based on the desired speed of onset, duration of action,
route of elimination, spectrum of cardiovascular side effects, and cost (Table 7-5) . The
newer neuromuscular blocking drugs such as vecuronium, atracurium, doxacurium, and
rocuronium have virtually no cardiovascular side effects and are not dependent on renal
function for elimination. Metocurine and gallamine are completely dependent on renal
function for elimination. Succinylcholine has the most rapid onset of action (90 s) but
produces unpredictable changes in heart rate, increases serum potassium
concentration by approximately 0.5 meq/liter, may cause life-threatening hyperkalemia
in patients with denervation, burn, or compression injuries, and can trigger malignant
hyperthermia in susceptible individuals. Pancuronium increases blood pressure and
heart rate by blocking muscarinic acetylcholine receptors in the sinoatrial node,
increases sympathetic activity via antimuscarinic actions, and inhibits reuptake of
catecholamines. The neuromuscular blockers d -tubocurarine, metocurine, mivacurium,
and atracurium may decrease blood pressure and increase heart rate indirectly by
mediating release of histamine. The cardiovascular effects of these neuromuscular
blockers may be attenuated by pretreatment with H1 and H2 receptor antagonists.
Long-term administration of vecuronium is associated with development of myopathy in
patients on glucocorticoid therapy. [123 ]
Discontinuing general anesthesia or sedation before complete recovery from

neuromuscular blockade is very distressing for a patient because the awake, alert, and
paralyzed patient has no means to communicate discomfort. Discontinuing mechanical
ventilatory support in patients with residual neuromuscular blockade may cause acute or
delayed respiratory failure. Even mild residual neuromuscular blockade contributes to
pulmonary insufficiency by compromising mechanics of breathing and decreasing
negative inspiratory force, vital capacity, tidal volume, and the ability to generate an
effective cough. Muscle fatigue may produce airway obstruction by decreasing muscle
tone in the oropharynx. Recovery from nondepolarizing neuromuscular blockade may be
hastened by administering an acetylcholine- esterase inhibitor, such as neostigmine or
edrophonium, that prevents degradation of acetylcholine at the neuromuscular junction
and thereby increases the concentration of the neurotransmitter at the motor end plate.
The undesirable systemic effects of acetylcholine-esterase inhibitors are
bronchospasm, bradycardia, and hypersalivation, which can be minimized by
simultaneous administration of anticholinergic agents; atropine or glycopyrrolate.
Reliable reversal of neuromuscular blockade with cholinesterase inhibitors is usually
achieved only after muscle strength has recovered spontaneously to approximately 25
percent of baseline levels. Recovery of neuromuscular function is measured by a
train-of-four twitch monitor applied to the ulnar nerve.
LOCAL ANESTHETICS
Local anesthetic drugs block the propagation of action potentials in electrically excitable
tissue. Local anesthetics can be delivered by topical application to mucosa, infiltration
into tissues, injection into the region of a peripheral nerve, infusion into the epidural
space, or injection intrathecally into cerebral spinal fluid. Regional nerve blocks can be
used to supplement a general anesthetic or to provide postoperative analgesia.
Inadvertent intravascular injection of a local anesthetic or drug overdose may cause
seizures and cardiac dysrhythmias. Epidural or spinal local anesthetic nerve blocks
decrease blood pressure and heart rate by blocking the sympathetic ganglia. Regional
nerve blocks provide profound analgesia with minimal sedation or respiratory
depression. Local anesthetic drugs are chosen according to onset and duration of
action.
Special Anesthetic Techniques
EMERGENCY AIRWAY MANAGEMENT
Establishing a patent and secure airway is essential for the conduct of general
anesthesia and is the first step in emergency life support for cardiovascular
resuscitation. Tracheal intubation for airway protection and mechanical ventilation can
be challenging in a patient with cardiovascular disease. Anesthesia is often necessary
to facilitate tracheal intubation; however, the effects of general anesthetics on
respiratory and circulatory function typically produce respiratory depression and may
cause apnea, instability of the patient's airway, aspiration pneumonitis, hypoxia,
hypercarbia, and cardiovascular collapse. Inadequate anesthesia during tracheal
intubation may provoke myocardial ischemia or tachyarrhythmias in susceptible
patients. The American Society of Anesthesiologists has established practice
guidelines for the emergency management of the difficult airway.[124 ] The patient with
the difficult airway (e.g., Mallampati class 4) often can be intubated in a sedated state
using fiberoptic bronchoscopy. This technique requires time and special equipment.
The risk of hypertension, tachycardia, and discomfort during awake tracheal intubation
can be offset partially by topical anesthesia and intravenous sedation. Other techniques
include mask ventilation, laryngeal mask ventilation, esophageal-tracheal combitube
ventilation, blind oral or nasal intubation, direct laryngoscopy, rigid ventilating
bronchoscopy, light wand intubation, retrograde intubation, transtracheal jet ventilation,
cricothyroidotomy, and tracheostomy.
SINGLE-LUNG VENTILATION
Single-lung ventilation, or the ability to collapse one lung and selectively ventilate the
contralateral lung, is necessary for operative exposure when the heart or great vessels
are approached through a lateral thoracotomy incision. Adequate surgical exposure
with minithoracotomy for coronary revascularization without cardiopulmonary bypass
requires deflation of the left lung. Single-lung ventilation is also used for management of
patients undergoing thoracoscopic procedures, lung transplantation, thoracic aortic
operations, mitral valve surgery through a right thoracotomy, closure of large
bronchopleural fistulas, or life-threatening hemoptysis. Single-lung ventilation may be
achieved using double-lumen endobronchial tubes (Fig. 7-17) or bronchial blockers
(Fig. 7-18) . Bronchial blockers incorporated into modified endotracheal tubes are also
available. The routine use of fiberoptic bronchoscopy has decreased the complication
rates and eliminated uncertainty regarding positioning of these devices in the airway.
Hypoxemia caused by transpulmonary shunt through the nonventilated lung during
single-lung ventilation often requires modification of the anesthetic technique to
preserve hypoxic pulmonary vasoconstriction.
REGIONAL ANESTHESIA AND ANALGESIA
Epidural or intrathecal administration of local anesthetics and narcotics can provide

profound postoperative analgesia after thoracic and major abdominal operations
without the sedation or respiratory depression associated with parenteral narcotic
analgesia. Patient-controlled epidural analgesia using infusion pumps can be triggered
by patient demand with a predetermined maximum lock-out dose to prevent narcotic
abuse and overdose. Patient-controlled epidural analgesia is an effective method to
titrate the dose of narcotics based on clinical need. Although epidural analgesia has
been employed successfully during open heart surgery, it is rarely used because of the
risk of epidural hematoma in the completely anticoagulated patient. [125 ] , [126 ] Use
of a single intrathecal dose of narcotic for postoperative analgesia after cardiac
operations has been studied and eventually may provide improved postoperative
analgesia compared with parenteral narcotic administration. [127 ] [129 ]
Thoracic epidural anesthesia has been employed successfully for treatment of

refractory angina. [130 ] , [131 ] Selective anesthesia of T1 to T5 thoracic dermatomes
with epidural local anesthetic inhibits sympathetic innervation of the heart and regional
vasculature. Thoracic epidural anesthesia decreases left ventricular contractility and
heart rate while prolonging phase IV of the cardiac action potential. [132 ] The decrease
in myocardial oxygen consumption, reduced arrhythmogenicity, and increase in
diameter of the stenotic coronary arteries are the proposed mechanisms for the
abolition of chest pain in unstable angina patients who receive thoracic epidural local
anesthetic. [133 ] [137 ] With exercise testing, these patients have a smaller ischemic
burden (less ST-segment depression) for a given workload with epidural anesthesia
compared with control exercise without epidural anesthesia. Treatment of myocardial
ischemia with an infusion of local anesthetics or opioids into the epidural space is not
without risk in patients who are likely to receive anticoagulants and/or thrombolytics and
who may have significant preexisting left ventricular dysfunction.
CONTROLLING LUMBAR CEREBRAL SPINAL FLUID PRESSURE
Several experimental studies suggest that spinal fluid drainage may improve neurologic
outcome from spinal cord ischemia during thoracoabdominal aortic operations. [137 ]
[140 ] Although the clinical efficacy of lumbar cerebral spinal fluid (CSF) drainage
remains controversial, the technique is routine at some institutions. [141 ] , [142 ] CSF
drainage and a decrease in the lumbar CSF pressure can be achieved by aseptically
inserting a subarachnoid catheter through a Tuohy needle positioned in a lower lumbar
vertebral interspace. The catheter is typically inserted after induction of general
anesthesia with the patient in a lateral decubitus position. Injury to a nerve root may
occur because the symptoms of pain and paresthesia when impinging a nerve with a
needle cannot be elicited in the anesthetized patient. CSF is passively drained to
reduce lumbar CSF pressure to approximately 10 to 15 mmHg or equal to central
venous pressure. Reducing CSF pressure further may cause an abducens nerve palsy
and postoperative diplopia. The catheter may be secured and used for several days
after operation for pain relief. Careful attention to disconnecting the continuous fluid
flush mechanism of the pressure-measuring system decreases the risk of infusing fluids
or drugs into the intrathecal space.
THE CONDUCT OF ANESTHESIA, SURGERY, NURSING, AND
PERFUSION
Cardiac surgery is conducted in an interdisciplinary environment between surgeon,

anesthesiologist, perfusionist, and nursing staff. The operating room requires a
minimum of 800 ft2 to comfortably accommodate the patient, health care providers,
standard operating room equipment, cell saver, heart-lung machine, and assist devices,
if needed. [143 ]
The anesthetic begins before the patient arrives in the operating room. Patients are
premedicated with a sedative-hypnotic (e.g., scopolamine, benzodiazepine) and
analgesic (e.g., morphine) unless the associated mild degree of respiratory depression
is unwarranted. The patient's identification and scheduled procedure are verified
immediately on arrival to the operating room. The patient is escorted into the operating
room and placed onto the operating table, and routine noninvasive monitors are
applied. The physical condition of the patient is assessed clinically, and medical events
that occurred over the previous 12 to 24 hours are reviewed. For elective surgery, the
patient should have fasted for a minimum of 6 hours prior to induction of general
anesthesia. Prophylactic antibiotics are administered after insertion of an intravenous
catheter. A catheter is inserted in the radial artery. A blood sample is acquired for
laboratory analysis, and a blood type and crossmatch are requested should transfusion
become necessary. A central venous catheter is always indicated, although in some
patients it can be inserted after the induction of general anesthesia. A pulmonary artery
catheter is commonly used to provide measures of cardiac output and estimate
ventricular filling pressures. [144 ] Large-bore intravenous catheters are inserted for
patients who undergo reoperation because of the possibility of rapid blood loss during
sternotomy. The immediate availability of typed and crossmatched blood is verified
before skin incision. Patients undergoing reoperations are more likely to have a
positive antibody screen that delays the availability of blood products. External
defibrillation pads are always applied to patients undergoing reoperation because
access to the heart with internal paddles is not available until adhesions are lysed.
The anesthesia record begins in the preinduction period, documents significant events
of surgery, and becomes part of the patient's medical record. Prior to induction of
general anesthesia, a baseline set of hemodynamic measurements is obtained and
recorded. These measures often guide the choice of anesthetic drugs and technique,
provide a baseline for comparison later, and confirm hemodynamic data acquired
during cardiac catheterization. Automated record keepers eventually may relieve the
anesthetist of recording data.
Induction of general anesthesia is achieved by inhalation of volatile potent anesthetics,

the intravenous administration of sedative-hypnotics, or both. Inhalation inductions
permit maintenance of spontaneous ventilation and a controlled titration of anesthetic
dose but prolong the excitatory phase of anesthesia when the patient is prone to cough,
move, develop laryngospasm, or vomit and aspirate. Inhalation inductions are not used
commonly in adults unless tracheal intubation is expected to be technically difficult.
Intravenous induction produces rapid apnea that requires immediate ventilatory support.
Administration of neuromuscular blocking drugs produces profound muscle paralysis
and facilitates laryngoscopy and tracheal intubation. Vasoactive drugs are titrated, if
necessary, to counteract the cardiovascular effects of anesthetics. Laryngoscopy is
extremely stimulating (painful) and, if the patient is inadequately anesthetized, causes
severe hypertension and tachycardia and stimulates vasovagal reflexes. The inability to
ventilate or intubate the trachea in a patient after the induction of general anesthesia is
a medical crisis and may require such emergency airway management techniques as
transtracheal jet ventilation, cricothyroidotomy, or tracheostomy. Patients with a history
of a technically difficult tracheal intubation, poor dentition, large tongue, limited mouth
opening, inability to sublux the mandible, or a recessed chin are at increased risk of
airway complications, and it may be prudent to secure the airway while they are still
awake. Successful intubation of the trachea is verified by the appearance of a carbon
dioxide expirogram on capnography. Most adult patients can be intubated with an
8.0-mm-internal-diameter polyvinyl chloride endotracheal tube that accommodates an
adult flexible bronchoscope. The tip of the tracheal tube is secured above the carina by
documenting breath sounds bilaterally. The patient is positioned prior to surgical
preparation and draping. Regions susceptible to pressure injuries are protected and
padded as required.
Maintenance of general anesthesia is achieved by continuous or intermittent

administration of anesthetic drugs titrated to effect while monitoring the conduct of
operation and vital physiologic functions. Short-acting vasoactive agents with rapid
onset of action are usually preferred for controlling the circulation because conditions
constantly change. The cardiovascular actions of inhaled anesthetics are often utilized
for short-term blood pressure control because effective concentrations can be reached
quickly and monitored in real time by expired gases. Direct-acting vasodilators may be
required for blood pressure control if the patient cannot tolerate myocardial depressant
effects of an inhaled anesthetic. Vasopressors and inotropic agents sometimes are
required to support the circulation in response to anesthetic-induced vasodilation and
cardiac depression. Utilizing nitroglycerin to modify venous capacitance permits
buffering acute changes in intravascular volume. Heart rate can be controlled by
short-acting cardioselective beta-adrenergic agonists and antagonists, vagolytic
agents, or chronotropic drugs or, alternatively, by direct cardiac pacing (see Chap. 8).
Preoperative alpha2-adrenergic agonists can attenuate sympathetically mediated
hemodynamic fluctuations. The urgency to control hemodynamic parameters with
pharmacologic therapy must be tempered by recognizing the risk of drug overdose from
overzealous treatment. Intraoperative events associated with acute increases in
anesthetic requirements are sternotomy, chest wall retraction, manipulations and
cannulation of the aorta, rewarming during cardiopulmonary bypass, and sternal wiring.
Intraoperative awareness from insufficient anesthesia may occur during cardiac
surgery, especially if the anesthetist places a greater emphasis on avoiding
cardiovascular actions of anesthetic agents than on providing sufficient anesthesia.
Initiation of cardiopulmonary bypass acutely changes circulating drug concentrations.

The addition of 2 liters of pump prime has a negligible effect on plasma concentrations
of lipophilic drugs with a large volume of distribution but significantly decreases the
concentration of drugs distributed primarily in the intravascular space. Despite
measurable decreases in blood anesthetic concentrations during cardiopulmonary
bypass, the anesthetic level may not change because systemic hypothermia decreases
anesthetic requirements, potentiates the effects of neuromuscular blocking drugs, and
increases the solubility of volatile anesthetics in blood. Rewarming returns anesthetic
requirements to baseline levels and predisposes to inadequate anesthesia if
therapeutic drug concentrations are not maintained. The judicious use of
sedative-hypnotics, analgesics, and amnestic agents during rewarming decreases the
incidence of recall but does not guarantee unconsciousness. Volatile inhalation
anesthetics can be given during cardiopulmonary bypass by adding them to the
oxygen-rich gas mixture ventilating the pump oxygenator. This use of volatile anesthetics
requires an effective scavenging system to prevent accumulation of anesthetic gases in
ambient air.
Separation from cardiopulmonary bypass requires effective communication among

members of the intraoperative team. Similar to an airline pilot preparing to land, the
cardiac anesthesiologist has a checklist that ensures that all systems are in working
order (Table 7-6) and prepared for any crisis.
ANESTHESIA IN THE IMMEDIATE POSTOPERATIVE PERIOD
Continuous monitoring of physiologic functions during transport to the postoperative

intensive care unit is paramount because of the possibility of hemodynamic instability.
Cardiac output, blood pressure, and vascular tone decrease acutely in the immediate
postoperative period because surgical stimulation no longer increases sympathetic
tone. Vasodilation also occurs from increases in cutaneous blood flow during active
rewarming. Reducing positive pressure ventilatory support during weaning from
mechanical ventilation may alter hemodynamic function by increasing venous return and
decreasing pulmonary vascular resistance. Sedative-hypnotic or analgesic drugs
administered in the immediate postoperative period contribute to changes in the
circulatory state.
Anesthesia is required in the early postoperative period because of mechanical

ventilatory support, hypothermia, and the possibility of hypertension and tachycardia
from pain and tracheal intubation if abrupt emergence occurs. Several hours may be
needed to achieve criteria for tracheal extubation (e.g., minimal bleeding,
cardiovascular stability, systemic rewarming). Arrival in the intensive care unit triggers a
battery of laboratory tests designed to assess rapid changes in vital organ function and
prompt corrective therapy. These tests include a chest radiograph, complete blood and
platelet count, chemistry battery with blood urea nitrogen and serum creatinine, serum
glucose, ECG, prothrombin time and partial thromboplastin time, and arterial blood
gases.
Understanding and effective management of the anesthetic state in the immediate

postoperative period is important for patient comfort and safety. Rewarming of a
hypothermic patient, correction of a coagulopathy, recovery from neuromuscular
blockade, and elimination of anesthetic drugs that obtund mental status usually
necessitate several hours of mechanical ventilatory support beyond the operating room.
Preemptive patient management during operation and in the early postoperative period
can decrease intensive care unit and hospital length of stay after cardiac surgery. [145 ]
Traditionally, high-dose narcotic anesthesia provided profound analgesia, sympathetic
blockade, and a gradual emergence that was managed over a time course of 8 to 12
hours. With high-dose narcotic anesthesia, patient recovery often was determined by
the duration of anesthetic given in the operating room. The time required for recovery
from general anesthesia may be decreased by short-acting sedative-hypnotics or
analgesics administered by infusion that continues into the postoperative period and
permits recovery according to the patient's condition rather than the anesthetic.
Implementation of protocol-based care plans, designed to expedite patient recovery
after cardiac operations, requires a coordinated effort and mutual understanding
between the anesthesiologist, surgeon, and critical care team.
Hemodynamic management of cardiac surgical patients is integrated with anesthetic

management. The ability to control the circulation during anesthesia is essential for safe
conduct of cardiac operations. The challenge to maintain control of the cardiovascular
system during the course of a typical operation is complicated by actions of the
anesthetic drugs on the circulation, autonomic nervous system reflexes, variability in
individual responses to vasoactive drug therapy, continuous fluctuations in the intensity
of painful stimuli, rapid intravascular volume shifts, the patient's underlying medical
condition, and the urgency of operation.
ANTIDYSRHYTHMICS
Dysrhythmias are common in the cardiac surgical patient. A stable cardiac rhythm
requires depolarization and repolarization in a spatially and temporally coordinated
manner, and dysrhythmias occur when this coordination is disturbed. The mechanisms
for dysrhythmias can be divided into abnormal impulse initiation, abnormal impulse
conduction, or combinations of both. [9 ] , [10 ] Abnormal impulse initiation occurs as a
result of increased automaticity (spontaneous depolarization of tissue that does not
normally have pacemaking activity) or as a result of triggered activity from abnormal
after depolarizations during phase 3 or 4 of the action potential. Abnormal conduction
often involves re-entry phenomena, with recurrent depolarization around a circuit owing
to unilateral conduction block in ischemic or damaged myocardium and retrograde
activation via an alternate pathway through normal tissue. In this simplistic view, it is
logical that dysrhythmias could be suppressed by slowing the conduction velocity of
ectopic foci, allowing normal pacemaker cells to control heart rate by prolonging the
action potential duration (and hence refractory period) to block conduction into a limb of
a re-entry circuit, or by overdrive suppression with higher extrinsic heart rates.
Antidysrhythmic agents often are classified by a scheme originally proposed by

Vaughan Williams and subsequently modified, [11 ] , [12 ] and although alternative
schemes have been proposed and may be more logical, [13 ] we will organize our
discussion using the Vaughan Williams system of four major drug categories. In this
scheme, Class I agents are those with local anesthetic properties that block na +
channels, Class II drugs are beta-blocking agents, Class III drugs prolong action
potential duration, and Class IV are calcium entry blockers.
Class I Agents
Although each of the Class I agents blocks na + channels, they may be subclassified on
the basis of electrophysiological differences. These differences can be explained, to
some extent, by consideration of the kinetics of the interaction of the drug and the na +
channel. [14 ] , [15 ] Class I drugs bind most avidly to open (phase 0 of the action
potentialsee (Fig. 8-1) or inactivated (phase 2) na + channels. Dissociation from the
channel occurs during the resting (phase 4) state. If the time constant for dissociation is
long in comparison to the diastolic interval (corresponding to phase 4), drug will
accumulate in the channel to reach a steady-state, slowing conduction in normal tissue.
This occurs with Class Ia (procainamide, quinidine, disopyramide) and Class Ic
(encainide, flecainide, lorcainide, propafenone) drugs. In contrast, for the Class Ib drugs
(lidocaine, tocainide, mexilitine), the time constant for dissociation from the na +
channel is short, drug does not accumulate in the channel, and conduction velocity is
minimally affected. However, in ischemic tissue the depolarized state is more
persistent, leading to greater accumulation of agent in the na + channel, and slowing
conduction in the damaged myocardium.
CLASS Ia
Procainamide probably is the Class Ia drug most commonly used in the perioperative
period. Procainamide has a variety of electrophysiological effects. [16 ] As noted
earlier, conduction velocity in atrial, His-Purkinje, and ventricular tissue is decreased as
a result of na + channel blockade. Action potential duration and effective refractory
period are also increased. However, procainamide also has mild vagolytic
(anticholinergic) effects that may lead to a decreased AV nodal refractory period and an
increased ventricular response in supraventricular tachycardia. Despite these effects,
procainamide remains an effective treatment of supraventricular tachycardia, especially
if other drugs are given that reduce AV nodal conduction.
The primary intraoperative use of procainamide is intravenous therapy for ventricular

arrhythmias after failure of lidocaine. Administration may be limited by side effects of
hypotension and decreased cardiac output. [17 ] , [18 ] The loading dose is 2030
mg/min, up to 17 mg/kg, although lower total doses are more commonly employed, and
should be followed by an intravenous infusion of 2080 µg/kg/min. Since it prolongs
action potential duration, a potential overdose often is heralded by widening of the QRS
complex. The elimination of procainamide involves hepatic metabolism, acetylation to a
metabolite with antiarrhythmic and toxic side effects, and renal elimination of this
metabolite. Thus the infusion rate for patients with significant hepatic or renal disease
should be at the lower end of this range. Oral procainamide also may be used in the
perioperative period. The usual dose is 50 mg/kg/day and a sustained release form is
available so that dosing every 34 hours can be avoided. The side effects of oral
procainamide include GI symptoms, CNS complaints (headache, insomnia), and a
lupus-like syndrome with rash, agranulocytosis, myalgesia, pleuritis, pericarditis, and
fever. [19 ]
Quinidine is another Class Ia agent often encountered in the perioperative period. It is

seldom administered by the intravenous route because of decreased cardiac
contractility and hypotension. [10 ] , [16 ] The direct electrophysiological effects are
similar to procainamide; however, its indirect anticholinergic effects are more
pronounced. This vagolytic property may increase conduction through the AV node and
increase the rate of ventricular response in atrial fibrillation or flutter. Usually it should be
given in conjunction with digoxin or a beta-blocking agent when used for the treatment of
atrial fibrillation or flutter. [20 ] It is also effective in the treatment of ventricular
arrhythmias. The usual oral dose for an adult is 300600 mg every 68 hours. Side effects
include tinnitus, headache, visual disturbances, and GI symptoms. The cardiac
depressant effect is heralded by widening of the QRS complex. It should be noted also
that quinidine is highly protein bound and may increase free digoxin levels and effects
by competing for protein binding sites. [10 ]
Less commonly encountered Class Ia antiarrhythmics are disopyramide and

diphenylhydantoin. [21 ] The electrophysiological effects of disopyramide are very
similar to procainamide and quinidine and its usefulness is limited by negative inotropic
effects. Diphenylhydantoin has electro-physiological effects that resemble both Class Ia
and Class Ib drugs. Its primary use is the treatment of dysrhythmics caused by digitalis
toxicity. [10 ] , [15 ]
CLASS Ib
Class Ib drugs include what is probably the most widely administered dysrhythmic
agent, lidocaine. Lidocaine is a na + channel blocker that has little effect on conduction
velocity in normal tissue but slows conduction in ischemic myocardium. [14 ] , [15 ] Other
electrophysiological effects include a decrease in action potential duration but a small
increase in the ratio of effective refractory period to action potential duration. The exact
role of these electrophysiological effects on dysrhythmia suppression is unclear.
Lidocaine has no significant effect on atrial tissue and is indicated for the treatment of
ventricular dysrhythmia. [22 ] One of the major advantages of lidocaine is its
pharmacokinetics. [23 ] , [24 ] After an initial bolus dose of 11.5 mg/kg, plasma levels
decrease rapidly because of redistribution to muscle, fat, and other tissues. Effective
plasma concentrations are maintained only by following the bolus dose with an infusion
of 2050 µg/kg/min. Elimination occurs via hepatic metabolism to active metabolites that
are cleared by the kidney. Consequently, the dose should be reduced by approximately
50 percent in patients with liver or kidney disease. The primary toxic effects are
associated with the CNS, and a lidocaine overdose may cause drowsiness, depressed
level of consciousness, or seizures in very high doses. Negative inotropic or
hypotensive effects are less pronounced than with most other anti-dysrhythmics.
The other Class Ib drugs likely to be encountered in the perioperative period are
tocainide and mexiletine. Their electrophysiological effects are very similar to lidocaine.
These drugs are available for oral administration only. [15 ]
CLASS Ic
The final category of na + channel-blocking drugs, the Class Ic agents, include

flecainide, encainide, and propafenone. These drugs markedly decrease conduction
velocity. [10 ] , [15 ] They were developed, in large part, for the suppression of ventricular
dysrhythmia. However, enthusiasm for flecainide and encainide waned since the
Cardiac Arrhythmia Suppression Trial (CAST) study. [25 ] , [26 ] This multi-center trial of
encainide, flecainide, and moricizine found that although ventricular arrhythmias were
suppressed, the incidence of sudden death was greater with encainide and flecainide
than placebo. Propafenone is available for oral use. The usual adult dose is 150300 mg
every 8 hours. It has beta-blocking (with resultant negative inotropic effects) as well as
na + channel-blocking activity; lengthens the PR, QRS, and QT duration; and may be
used to treat both atrial and ventricular dysrhythmia. [15 ]
Class II Agents
Beta-receptor blocking agents are another important group of antidysrhythmics

(denoted Class II in the Vaughan Williams scheme). However, because of their use as
anti-hypertensive as well as antidysrhythmic agents, they are discussed elsewhere in
this chapter.
Class III Agents
Bretylium, amiodarone, and sotalol are Class III agents in the Vaughan Williams
scheme. These drugs have a number of complex ion channel-blocking effects, but
possibly the most important activity is k + channel blockade. [27 ] Since the flux of k +
out of the myocyte is responsible for repolarization, an important electrophysiological
effect of Class III drugs is prolongation of the action potential. [28 ] Amiodarone also has
na + and ca 2+ channel-blocking activity, whereas sotalol has beta-blocking activity. [29 ]
Bretylium is the Class III agent that has the longest history of use in the United States. Its
primary use and efficacy are for treatment of ventricular tachycardia or fibrillation that is
refractory to lidocaine or countershock. [30 ] [32 ] It is not effective in the treatment of
atrial arrhythmias. Usually it is administered as an intravenous bolus of 510 mg/kg with
an infusion of 12 mg/min. Its use may be limited by hemodynamic effects. Initially it
induces norepinephrine release from adrenergic nerve terminals, and then subsequently
prevents norepinephrine release. This leads to a transient increase in heart rate and
blood pressure with the initial dose followed by decreases in heart rate, systemic
vascular resistance, and blood pressure that may be quite pronounced. [18 ] , [32 ]
Sotalol is a nonselective beta-blocking agent that also has k + channel-blocking activity.

[33 ] It is available for intravenous and oral administration and has an approved
indication for the treatment of life-threatening ventricular arrhythmias, although it is also
effective against atrial arrhythmias. It is not a first-line therapy and should be reserved
for dysrhythmias refractory to other therapy. In patients with significant ventricular
impairment, the beta-blocking effects may lead to heart failure. [34 ] , [35 ]
Amiodarone, which has become available for routine intravenous use in the United
States recently, has been described as the most effective, most toxic, and most studied
antidysrhythmic agent available. [29 ] As noted in the preceding, it has a variety of ion
channel-blocking activities. [10 ] , [29 ] , [36 ] The resultant electrophysiological effects
are complex, and there also are differences in the acute and chronic effects. Acutely
(after intravenous administration), there is little change in heart rate or a mild
tachycardia, little change in QRS duration or QT interval, and an increase in AV nodal
refractory period. After chronic use, there may be significant bradycardia and increases
in action potential duration in AV nodal and ventricular tissue, with increased QRS
duration and QT interval.
The primary indication for amiodarone is ventricular tachycardia or fibrillation refractory

to other therapy. It is the most efficacious agent for reducing ventricular arrhythmias and
suppresses the incidence of post-myocardial infarction sudden death. [37 ] Also, it is
effective, in doses lower than those used for ventricular dysrhythmia, for the treatment of
atrial dysrhythmia, and is effective in converting atrial fibrillation to sinus rhythm. [38 ] ,
[39 ]
Amiodarone can be administered by both the oral and intravenous routes. The
pharmacokinetics of amiodarone are unusual and are characterized by a huge
distribution volume (60 L/kg), a very long duration of action, and an active metabolite.
[40 ] Because of these distinctive pharmacokinetic properties, steady-state plasma
levels are achieved slowly. Oral administration for a typical adult consists of a loading
regimen of 801600 mg/day (in two or three doses) for 10 days, then 600800 mg/d for
46 weeks, and then maintenance doses of 200600 mg/d. For intravenous loading
75150 mg may be given over 10 min for acute therapy in an adult followed first by a
secondary loading infusion of 3060 mg/h for 6 hours and then the maintenance infusion
of 1530 mg/h. Sometimes much larger doses are needed.
There are numerous adverse reactions to amiodarone. The most serious is pulmonary
toxicity, which may progress from dyspnea and cough to a fibrosing alveolitis with
hypoxia. [41 ] Thyroid abnormalities also are common. [42 ] Amiodarone's structure is
similar to thyroxine (T4) and triodothyronine (T3). It suppresses the conversion of T4 to
T3 and some of its electrophysiological effects may be caused by altered thyroid
function.
Amiodarone originally was used as an antianginal agent because of its vasodilating
effects, including coronary vasodilation. [43 ] , [44 ] It decreases beta-receptor density,
apparently via an antithyroid action. [45 ] Cardiac output usually is maintained after
administration, but hypotension can occur with intravenous therapy.
Class IV Agents
Another prominent category of antidysrhythmics, calcium entry blockers (Class IV in the

Vaughan Williams scheme), are discussed elsewhere in this chapter, but their roles as
antiarrhythmics, especially verapamil and diltiazem, are considered here. In sinoatrial
and atrioventricular nodal tissue, ca 2+ channels contribute significantly to phase 0
depolarization and the AV nodal refractory period is prolonged by ca 2+ entry blockade.
[46 ] , [47 ] This explains the effectiveness of verapamil and diltiazem in the treatment of
supraventricular arrhythmias. Also it is clear why these drugs are negative inotropes.
Both verapamil and diltiazem are effective in slowing the ventricular response to atrial
fibrillation, flutter, or paroxysmal supraventricular tachycardia and in converting these
dysrhythmias to a sinus rhythm. [48 ] [50 ] Verapamil can be used both orally or
intravenously. The intravenous dose is 0.070.15 mg/kg with the dose repeated in 30
min if there is an inadequate response. It has greater negative inotrope effects than
diltiazem and, for this reason, the recent introduction of intravenous diltiazem has led to
its supplanting, to some degree, verapamil in the acute treatment of supraventricular
arrhythmias. The intravenous dose of diltiazem is 0.25 mg/kg with a second dose of
0.35 mg/kg if the response is inadequate after 15 min. The loading dose should be
followed by an infusion of 515 mg/h.
Other Drugs
One of the difficulties of the Vaughan Williams classification of antidysrhythmics is that

not all drugs can be incorporated into this scheme. Three examples are digoxin,
adenosine, and magnesium, each of which has important uses in the perioperative
period.
Digoxin inhibits na + /k + -ATPase, leading to decreased intracellular k + , a less

negative resting membrane potential, increased slope of phase 4 depolarization, and
decreased conduction velocity. These direct effects, however, usually are dominated by
indirect effects, including inhibition of reflex responses to congestive heart failure and a
vagotonic effect. [10 ] , [51 ] The net effect is greatest at the AV node, where conduction
is slowed and refractory period is increased. This explains the effectiveness of digoxin
in slowing the ventricular response to atrial fibrillation. The major disadvantages of
digoxin are the relatively slow onset of action and numerous side effects. These latter
include GI and CNS complaints, but of greatest concern is eliciting other dysrhythmias,
specifically nonparoxysmal junctional tachycardia, ventricular ectopy, and excessive
block atrioventricular junctional with a ventricular escape rhythm.
Adenosine is an endogenous nucleoside that has an electrophysiological effect very

similar to acetylcholine. Adenosine decreases AV node conductivity, and its primary
antidysrhythmic effect is to break AV nodal reentrant tachycardia. [52 ] An intravenous
dose of 100200 mcg/kg is the treatment of choice for paroxysmal supraventricular
tachycardia. Adverse effects, such as bronchospasm, are short-lived because its
plasma half-life is so short (12 seconds). This short half-life makes it ideal for the
treatment of reentry dysrhythmia where transient interruption can eliminate the
dysrhythmia.
Finally, no discussion of antiarrhythmics is complete without mentioning the importance

of appropriate acid-base and electrolyte balance. It should be clear that
electrophysiological effects reflect membrane potential. Electrolyte imbalance can
perturb the membrane potential, leading to dysrhythmia generation, as can altered
acid-base status, via effects on k + concentrations and sympathetic tone. Therapy for
dysrhythmia should include correction of acid-base and electrolyte imbalance.
Magnesium supplementation should be considered. [65 ] Magnesium deficiency is
common in the perioperative period and magnesium administration has been shown to
decrease the incidence of post-operative dysrhythmia. [66 ]
It is difficult to rationally summarize the actions of antidysrhythmic drugs, primarily

because of the complexity of their electrophysiological effects and the fact that often it is
difficult to see how the particular electrophysiological property translates into an
observed clinical effect. The Vaughan Williams classification scheme provides a
framework for discussion but is less useful for clinical decision making. In acute
management, the selection of specific drugs often is not based so much on the
specificity of their electrophysiological effects (since multiple drugs can accomplish the
same desired electrophysiological effects) as it is on their suitability for intravenous
administration, pharmacokinetics, and effects on ventricular function. The latter two
characteristics warrant special emphasis.
Drugs that have short effective half-lives after bolus administration, such as adenosine,
esmolol, or lidocaine, are preferable in the acute management of dysrhythmia, since the
undesirable consequences of their administration, particularly adverse hemodynamic
effects, are short-lived. Since many surgical patients with dysrhythmias have depressed
myocardial function, it is rational to select drugs for first-line acute therapy that have
minimal negative inotrope effects. The first step in clinical management is to determine
whether the patient is hemodynamically stable. If not, then electrical cardioversion is
almost always indicated. If the patient is hemodynamically stable then intravenous drug
therapy is appropriate.
Selection of a specific drug depends on the source of the dysrhythmia. If it is

supraventricular the priority is to slow the ventricular response. For paroxysmal
supraventricular tachycardia the treatment of choice either is adenosine, a drug with a
very short half-life, or cardioversion. For atrial fibrillation or flutter in a patient with
preserved ventricular function, esmolol is often useful. Although digitalization is
important for long-term heart rate control, its onset of action is slow. This agent also has
a short half-life. If there are concerns about ventricular function, diltiazem is useful since
it has less negative inotropic effects than many antiarrhythmics and has a relatively short
duration of action. In some cases it is difficult to determine whether the arrhythmia is
ventricular or supraventricular. In this situation, procainamide may be a good choice for
intravenous therapy since it is effective against both ventricular and supraventricular
arrhythmias. For ventricular arrhythmias, lidocaine remains the first treatment of choice
because of its relatively benign hemodynamic effects and its rapid clearance from
blood by redistribution. Amiodarone has been used in Europe as an agent for
supraventricular tachycardia.
INOTROPIC AGENTS
Biventricular function is commonly depressed with a nadir at approximately 4 hours after

cardiac surgery. [55 ] [57 ] The etiology is multifactorial: pre-existing disease,
incomplete correction of the cardiac pathology, myocardial edema, post-ischemic
dysfunction, reperfusion injury, cytokine release and generation of nitric oxide; the
dysfunction is usually reversible. Although cardiac output can be altered by exploiting
the Starling curve with higher preload, often the ventricular function curve is flattened,
and it is necessary to utilize inotropic agents.
The interaction of the proteins actin and myosin, in which chemical energy (in the form of
ATP) is converted into mechanical energy, provides the molecular basis for cardiac
contractility. In the relaxed state (diastole) the interaction of actin and myosin is inhibited
by tropomyosin, a protein associated with the actin-myosin complex. With the onset of
systole, ca 2+ enters the myocyte (during phase 1 of the action potential). This
extracellular influx of ca 2+ triggers the release of much larger amounts of ca 2+ from
internal stores in the sarcoplasmic reticulum. The binding of ca 2+ to the C subunit of the
protein troponin interrupts the inhibition of the actin-myosin interaction by tropomyosin,
facilitating hydrolysis of ATP and generation of mechanical force. With repolarization of
the myocyte and completion of systole, ca 2+ is actively taken up into the sarcoplasmic
reticulum to allow tropomyosin to inhibit the interaction of actin and myosin and relax the
myocyte. Thus, inotropic action is mediated by intracellular ca 2+ . [58 ] Although
experimental drugs currently under investigation increase the sensitivity of the
contractile apparatus to ca 2+ , [59 ] positive inotropic agents available for clinical use
achieve increased contractility by increasing free ca 2+ concentrations in the
sarcoplasma.
The first drug to consider is ca 2+ itself. The administration of ca 2+ prior to separation

form cardiopulmonary bypass is common practice. However, the inotropic effects are
very dependent on the plasma ca 2+ concentration. Calcium plays important roles in
cellular function, and the intracellular ca 2+ concentration is highly regulated by
membrane ion channels and intracellular organelles. [46 ] If the extracellular ca 2+
concentration is normal, administration of ca 2+ has little effect on the intracellular level
and does little to increase the inotropic state. On the other hand, if ionized plasma
calcium is low, exogenous calcium administration may increase contractility. [60 ] It
should be realized also that even with normal plasma ca 2+ concentrations,
administration of ca 2+ may increase vascular tone, leading to increased blood
pressure but no change in cardiac output. This increased afterload may be the basis of
the observation that ca 2+ administration can blunt the response to epinephrine. [61 ]
Routine use of ca 2+ at the end of bypass should be tempered by the realization that ca
2+
may have little effect on contractile function, although it may increase systemic
vascular resistance, which in itself may be important. If there is evidence of myocardial
ischemia, ca 2+ administration may be deleterious since it may exacerbate both
coronary spasm and the pathways leading to cellular injury. [62 ] , [63 ]
Digoxin is not very effective as acute therapy for low cardiac output syndrome in the
perioperative period; nevertheless, it serves to illustrate the role of intracellular ca 2+ .
Digoxin functions by inhibiting the Na-K-ATPase, which is responsible for the exchange
of intracellular na + with extracellular k + . [3 ] , [4 ] It is responsible for maintaining
intracellular/extracellular k + and na + gradients. When Na-K-ATPase is inhibited,
intracellular na + levels increase. Increased intracellular na + increases the chemical
potential for driving the ca 2+ /na + exchanger, an ion exchange mechanism in which
intracellular na + is removed from the cell in exchange for ca 2+ . The net effect is an
increase in intracellular ca 2+ and enhancement of inotropy.
The beta-adrenergic agonists are the most commonly used positive inotropic agents by
far. The beta-1 receptor is part of a complex that is composed of the receptor on the
outer surface of the cell membrane, coupled with membrane-spanning G-proteins (so
named because they bind GTP). The G-proteins stimulate adenylate cyclase on the
inner surface of the membrane, to catalyze formation of cyclic adenosine
monophosphate (cyclic AMP). The inotropic state is modulated by cyclic AMP via its
catalysis of phosphorylation reactions by protein kinase A. These phosphorylation
reactions open ca 2+ channels on the cell membrane and lead to greater release and
uptake of ca 2+ from the sarcoplasmic reticulum. [3 ] , [4 ]
The large number of drugs that stimulate beta-1 receptors and have a positive inotropic
effect include epinephrine, norepinephrine, dopamine, isoproterenol, and dobutamine.
These are the most commonly used catecholamines in the perioperative period.
Although there are differences in binding at the beta-1 receptor, the relative effects of
the various catecholamines on alpha and beta-2-adrenergic receptors are more
important. In general, alpha stimulation of peripheral vasculature receptors causes
vasoconstriction, whereas beta-2 stimulation leads to vasodilation. (See the discussion
elsewhere in this chapter.) For some time beta-2 and alpha receptors were thought to
be only in peripheral vessels and a few other organs, but not in the myocardium.
However, recent investigation has shown that alpha receptors are in the myocardium
and mediate a positive inotropic effect. [5 ] , [6 ] The mechanism for this positive
inotropic effect probably is stimulation of phospholipase C to hydrolyse phosphotidyl
inositol to diacylglycerol and inositol triphosphate compounds that increase ca 2+
release from the sarcoplasmic reticulum and increase myofilament sensitivity to ca 2+ . It
is possible also that alpha-adrenergic agents increase intracellular ca 2+ by prolonging
the duration of the action potential by inhibiting outward k + currents during
repolarization or by activating the Na + /H + exchange mechanism to increase
intracellular pH and myofilament sensitivity to ca 2+ . Because the exact mechanism is
uncertain, the exact contribution of alpha-adrenergic stimulation to the inotropic state is
unclear; however, it is apparent that onset of the effect is slower than that of beta-1
stimulation.
In addition to alpha receptors, beta-2 receptors are present in the myocardium. [64 ]
The fraction of beta-2 receptors (compared to beta-1 receptors) is increased in chronic
heart failure and thus may explain the efficacy of drugs with beta-2 activity for this
condition. This phenomenon is part of a general observation that beta-1 receptors are
down-regulated (decreased in receptor density) and desensitized (uncoupling of effect
from receptor binding) in chronic heart failure. [65 ] Interestingly, as demonstrated in a
dog model, this same phenomenon occurs with cardiopulmonary bypass. [66 ] Thus, for
chronic heart failure a newer class of drugs, the phosphodiesterase inhibitors, may be
beneficial. These drugs, typified by the agents available in the United Statesamrinone
and milrinoneincrease cyclic AMP levels independently of the beta receptor by
selectively inhibiting phosphodiesterase III, the myocardial enzyme responsible for the
breakdown of cyclic AMP. [3 ] , [4 ]
In clinical use, selection of a particular inotropic agent usually is based more on side
effects than on inotropic properties. Of the commonly used catecholamines,
norepinephrine has alpha and beta-1 but little beta-2 activity and is both an inotrope and
a vasopressor. Epinephrine and dopamine are mixed agonists with alpha, beta-1, and
beta-2 activity, and at lower doses are primarily inotropes and not vasopressors;
however, at higher doses vasopressor effects become more pronounced. This is
especially true for dopamine, the synthetic precursor for norepinephrine in the
sympathetic nerve terminal, which achieves vasopressor effects at higher doses by
stimulating release of norepinephrine. [67 ] Dobutamine is a more selective beta-1
agonist, in contrast to isoproterenol, which is a mixed beta-1 and -2 agonist. Drug
selection depends on the particular hemodynamic problem at hand. For example,
depressed myocardial function in the presence of profound vasodilation may require a
drug with both positive inotropic and vasopressor effects (e.g., norepinephrine),
whereas a patient who is vasoconstricted may benefit from another choice. The initial
selection of an inotropic agent is rationally based in the preceding considerations but
careful monitoring of the response is necessary and may indicate the addition of or the
substitution of another agent to achieve optimal hemodynamic effects.
Clinical experience indicates that phosphodiesterase inhibitors can be very effective

when catecholamines do not produce an adequate cardiac output. [68 ] [70 ] There are
few differences in the hemodynamic effects of the two cyclic AMP-specific (Type III)
agents, amrinone and milrinone. Both agents increase contractility with little effect on
heart rate and both produce significant venodilation and arteriodilation. Maintenance of
an adequate preload is important for inotropic effectiveness and for minimizing
systemic hypotension. [71 ] Milrinone is often preferred to amrinone because of lower
cost and less pronounced thrombocytopenia with prolonged administrations. [72 ] If
amrinone is used, the bolus dose recommended in the product insert, 0.75 mg/mL, is
inadequate to maintain therapeutic plasma levels, and a loading dose of 1.52.0 mg/mL
should be used. [73 ] For both drugs, the loading dose is administered over 510 min to
ameliorate systemic hypotension. Although both drugs have long half-lives, plasma
levels drop quickly after a loading dose as a result of redistribution; therefore, the
loading dose should be followed immediately by a continuous infusion. [73 ] , [74 ]
Because of long plasma half-lives, infusion rates are relatively difficult to titrate
according to effect.
Despite common use after cardiac surgery, there are few comparative studies of
inotropic agents in the perioperative period. In 1978, Steen et al. reported the
hemodynamic effects of epinephrine, dobutamine, and epinephrine immediately after
separation from cardiopulmonary bypass. [75 ] The largest mean increase in cardiac
index was achieved with dopamine at 15 mcg/kg/min. However, the only epinephrine
dose studied was 0.04 mcg/kg/min, which is a very small dose. In a later comparison of
dopamine and dobutamine, Salomon, Plachetka, and Copeland concluded that
dobutamine produced more consistent increases in cardiac index, although the
hemodynamic differences were small and all patients had good cardiac indices at the
onset of the study. [76 ] Fowler et al. also found insignificant differences in the
hemodynamic effects of dobutamine and dopamine, although they reported that
coronary blood flow increased more in proportion to myocardial oxygen consumption
with dobutamine. [77 ] Although neither of these groups reported significant increases in
heart rate for either dopamine or dobutamine, clinical experience shows otherwise, as
is documented by a study by Sethna et al., who found that the increase in cardiac index
with dobutamine is simply owing to increased heart rate, without change in myocardial
oxygen balance. [78 ] In a more recent study, Butterworth et al. showed that epinephrine,
which is much cheaper, effectively increases stroke volume without increasing heart
rate as much as dobutamine. [79 ]
VASOPRESSORS
Catecholamines also are administered routinely for the treatment of vasodilation. The
catecholamines most often given to cardiac surgical patients to increase systemic
vascular resistance and blood pressure include phenylephrine, dopamine, and
norepinephrine, [80 ] Alpha-1 adrenergic receptor stimulation produces
vasoconstriction. As noted earlier, stimulation of these receptors activates membrane
phospholipase-C, which in turn hydrolyzes phosphatidylinositol 4,5 diphosphate. [7 ]
This leads to the subsequent generation of two second messengers, including
diacylglycerol and inositol triphosphate. Both of these second messengers increase
cytosolic ca 2+ by different mechanisms, which include facilitating release of calcium
from the sarcoplasmic reticulum, direct effects on calcium flux from extracellular to
intracellular sites, and potentially increasing calcium sensitivity of contractile proteins in
vascular smooth muscle.
Vasodilation following cardiopulmonary bypass, or during anaphylactic or septic shock,

is produced by multiple vasoactive mediators that affect both vascular endothelium and
vascular smooth muscle. Mediator-induced vasodilation often is poorly responsive to
catecholamines, [81 ] but norepinephrine in high doses and infusion rates usually raises
systemic blood pressure. Many clinicians are concerned about renal, hepatic, and
mesenteric function during norepinephrine administration. However, in septic patients
norepinephrine-induced increases in blood pressure can improve renal perfusion and
function, [82 ] [85 ] and may improve mesenteric perfusion as well. [86 ] Given the
hemodynamic similarities between septic patients and some patients at the end of
cardiopulmonary bypass, these observations also may pertain to the cardiac surgical
patient; however, no confirmatory study has been done.
VASODILATORS
Different pharmacologic approaches are available to produce vasodilation, including:

(1) blockade of alpha-1 adrenergic receptors, ganglionic transmission, and calcium
channel receptors; (2) stimulation of central alpha-2 adrenergic receptors or vascular
guanylate cyclase and adenylate cyclase; and (3) inhibition of phosphodiesterase
enzymes and inhibition of angiotensin-converting enzymes [87 ] (Table 8-1) . Adenosine
in low concentrations also is a potent vasodilator with a short half-life, but the drug
primarily is used to inhibit atrioventricular conduction (see antidysrhythmics). Losartan,
a novel angiotensin II antagonist (AII), has just been released for treatment of
hypertension but is not available for intravenous use.
Stimulation of Adenylate Cyclase (Cyclic AMP)
Prostacyclin, prostaglandin E1, and isoproterenol increase cyclic nucleotide formation

[adenosine-3,5-monophosphate (cyclic AMP)] in vascular smooth muscle and produce
calcium movement out of the muscle. Phosphodiesterase inhibition of the breakdown of
cyclic AMP increases it. [87 ] Increasing cyclic AMP in vascular smooth muscle
facilitates calcium uptake by intracellular storage sites and decreases calcium available
for contraction. The net effect of increasing calcium uptake is to produce vascular
smooth muscle relaxation and vasodilation. However, phosphodiesterase inhibitors and
most catecholamines with beta-2 adrenergic activity (i.e., isoproterenol) have positive
inotropic and other side effects that include tachycardia, glycogenolysis, and kaluresis.
[87 ] Prostaglandins (prostacyclin and prostaglandin E1) are potent inhibitors of platelet
aggregation and activation. Catecholamines with beta-2 adrenergic activity,
phosphodiesterase inhibitors, and prostaglandin E1 and prostacyclin also have been
used to vasodilate the pulmonary circulation in patients with pulmonary hypertension
and right ventricular failure. [87 ] Recently, prostacyclin (Glaxo-Wellcome) was approved
by the FDA for administration in patients with primary pulmonary hypertension.
Nitrates and Stimulation of Guanylyl Cyclase (Cyclic GMP)
The vascular endothelium modulates vascular relaxation by releasing both nitric oxide
and prostacyclin. [88 ] [90 ] Inflammatory mediators can also stimulate vascular
endothelium to release excessive amounts of endothelium-derived relaxing factor
(EDRF or nitric oxide), which activates guanylyl cyclase to generate cyclic GMP. [89 ] ,
[90 ] Nitrates and nitroprusside, however, generate nitric oxide directly independent of
vascular endothelium. [89 ] , [90 ] The active form of any nitrovasodilator is nitric oxide
(NO) in which the nitrogen is in a +2 oxidation state. Any nitrovasodilator must be first
converted to nitric oxide to be active. In nitroprusside, nitrogen is in a +3 oxidation state
and the nitric oxide molecule is bound to the charged iron molecule in an unstable
manner; thus nitroprusside readily donates nitric oxide. In nitroglycerin, nitrogen
molecules exist in a +5 oxidation state; thus these molecules require significant
transformation before conversion to an active molecule. As compared to nitroprusside,
nitroglycerin is a relatively select coronary vasodilator and does not produce coronary
steal because small intracoronary resistance vessels (less than 100 µm) lack the
required transformation pathway to convert nitroglycerin to nitric oxide. [89 ] , [90 ]
Chronic nitrate therapy can produce tolerance through different mechanisms as shown
in Table 8-2 . [89 ] , [91 ] [93 ] Nitroprusside and nitroglycerin produce venodilation,
which may contribute to excessive hypotension. [88 ] Intravenous volume administration
often is required with nitroprusside to correct a relative intravascular hypovolemia.
Dihydropyridine Calcium Channel Blockers
Dihydropyridine calcium channel blockers are direct arterial vasodilators. [88 ] , [94 ]
Nifedipine was the first dihydropyridine calcium channel blocker, and the newer second
generation water-soluble agents that are available in intravenous form include
isradipine and nicardipine. Isradipine and nicardipine produce arterial vasodilation
without any effects on venous capacitance beds, atrioventricular nodal conduction, or
ventricular function (i.e., contractility). [95 ] [100 ] Nicardipine is the first intravenous drug
of this class available in the United States and offers a novel and important therapeutic
option for perioperative hypertension following cardiac surgery. Because currently
available intravenous calcium channel blockers have longer half-lives than
nitrovasodilators, rapid loading infusion rates or bolus loading doses are needed to
attain therapeutic levels. Bolus nicardipine also can be used to treat acute hypertension
during the perioperative period (i.e., intubation, extubation, cardiopulmonary
bypass-induced hypertension, aortic cross-clamping). However, slower elimination of
nicardipine makes it more difficult to titrate than nitroprusside, and more prolonged
vasodilation may be undesirable when hypotension-inducing factors disappear (e.g.,
recovery from hypothermia) or other vasodilating factors arise (e.g., hypothermia).
Phosphodiesterase Inhibitors
The phosphodiesterase inhibitors currently available for use produce both positive
inotropic effects and vasodilation. [101 ] When administered to patients with ventricular
dysfunction, they increase cardiac output and decrease pulmonary artery pressure,
systemic vascular resistance, and pulmonary vascular resistance. Because the
mechanism of vasodilation is unique, phosphodiesterase inhibitors are especially
useful for patients with acute pulmonary vasoconstriction and right ventricular
dysfunction. Multiple drugs are currently under investigation. The bipyridines (amrinone
and milrinone), the imidazolones (enoximone), and the methylxanthines (aminophylline)
are the ones most widely available. Papaverine, a benzylisoquinolinium derivative
isolated from opium, is a nonspecific phosphodiesterase inhibitor and vasodilator used
to dilate the internal mammary artery. [87 ]
Angiotensin Converting Enzyme (ACE) Inhibitors
Angiotensin converting enzyme (ACE) inhibitors have growing indications for the
management of heart failure and more patients now receive these drugs. ACE
inhibitors prevent the conversion of angiotensin I to angiotensin II by inhibiting kininase,
an enzyme in the pulmonary and systemic vascular endothelium. This enzyme also
metabolizes bradykinin, a potent endogenous vasodilator and agonist for release of
EDRF. Although little data regarding preoperative management of patients receiving
these drugs are available, our clinical practice is to withhold them on the day of surgery
because of their potential to produce excessive vasodilation during CPB. However,
Tuman was unable to find any difference in blood pressure during CPB in patients who
were or were not receiving ACE inhibitors; but contact activation during CPB generates
bradykinin, [101 ] and the vasoconstrictor requirements were increased after bypass in
his study.
ANTICOAGULANTS
Heparin
Heparin is the only available intravenous anticoagulant available in the United States
(103). Because arterial thrombosis is the basis of myocardial infarction and most
anginal states, increasing numbers of hospitalized patients awaiting myocardial
revascularization are receiving heparin. Heparin infusions should be continued until
reliable revascularization is accomplished (i.e., 1224 hours after PTCA, up to CPB for
CABG). [104 ] Plasma antithrombin (AT) levels decrease in patients who receive
preoperative heparin, and thus may alter heparin dose response relationships. [105 ] ,
[106 ] There are now purified concentrates of AT (Thromdate®) that are available for
patients with altered heparin dose responses or with known AT deficiency states. These
concentrates are heat treated to remove potential viral contaminants. Heparin also
binds to a number of blood and endothelial proteins that may influence dose responses
and affect its ability to act as an anticoagulant (Table 8-3) .
Heparin can produce platelet dysfunction following continuous administration or after

high bolus doses administered during cardiac surgery. [107 ] In patients who have
received heparin or heparin infusions before operation, a preoperative platelet count is
mandatory to detect heparin-induced thrombocytopenia, which may develop 57 days
after heparin exposure [108 ] (see Chap.9).
Warfarin (Coumadin)
Warfarin is a potent anticoagulant that is used in cardiac surgical patients with prior
valvular replacement or atrial fibrillation. Although many clinicians believe that warfarin
anticoagulation predisposes patients to postoperative bleeding, there are no
substantial data to support this belief. In fact, Dietrich reports less thrombin activation
and less perturbation of the clotting cascade in patients who are receiving warfarin
derivatives. [109 ] , [110 ] Because heparin therapy does not completely suppress
thrombin generation during CPB, preoperative use of warfarin may reduce the potential
for postoperative coagulopathy. [111 ] , [112 ]
Platelet Inhibitors
Aspirin is an irreversible, partial platelet inhibitor used in patients with unstable angina.
[113 ] The drug inhibits platelet cyclooxygenase and thromboxane A2 as well as
prostacyclin production. Patients undergoing revascularization procedures commonly
have received a daily dose of aspirin preoperatively. Although aspirin increases
postoperative mediastinal drainage, its role in increasing the need for donor blood
products is uncertain. [114 ]
Patients undergoing cardiac surgery also receive other platelet inhibitors. Ticlopidine is
a novel drug that interferes with the ability of platelets to aggregate by inhibiting IIb/IIIa
receptors that are involved in binding of fibrin/fibrinogen. Rheopro is a monoclonal
antibody that directly binds to the IIb/IIIa receptor of platelets and has been approved for
clinical use in high-risk angioplasty patients. Patients who receive this drug and who
require cardiac surgery are at risk for platelet dysfunction. Other antiplatelet drugs for
angioplasty patients are in clinical trials.
Fibrinolytics
Patients with impending infarction may receive fibrinolytic drugs including tissue
plasminogen activator (TPA), streptokinase, or urokinase before operation. These
drugs inactivate fibrinogen and other adhesive proteins, and have the potential to affect
platelets as well. [115 ] [116 ] Patients receiving these drugs within 24 hours of surgery
should be considered to be at a high risk for coagulopathy, and fibrinogen levels should
be measured.
PROCOAGULANTS
Heparin Reversal
Unfractionated heparin sulfate, the mainstay therapy for anticoagulation, is reversed by

protamine, the only currently available neutralizing agent. Protamine is a basic
polypeptide isolated from salmon sperm, where it functions as a histone to provide
structural integrity to DNA. Protamine reverses heparin, an acidic glycosaminoglycan,
by a nonspecific acid-base interaction (polyanionic-polycationic interaction). A
spectrum of adverse reactions to protamine has been reported that ranges from
minimal cardiovascular effects with rapid administration to life-threatening
cardiovascular collapse following even small doses. Although multiple immunologic and
non-immunologic mechanisms have been reported for the pathophysiology of
protamine reactions in humans, animal, and in-vitro models, the life-threatening
cardiopulmonary collapse following protamine administration in humans appears to
represent true anaphylaxis or allergy, mediated by immunospecific antibodies. [81 ]
Allergic mechanisms (i.e., immunospecific antibodies against protamine) are the only
logical explanation for the unpredictable cardiovascular effects that occur. [81 ] Although
protamine reactions have been classified according to systemic or pulmonary vascular
effects, this does not elucidate the underlying pathophysiologic mechanisms. [117 ]
The incidence of reported protamine reactions depends on the high-risk patient groups
studied. Stewart first reported a 27 percent incidence of reactions following cardiac
catheterization in insulins dependent diabetics who received neutral protamine
Hagedorn (NPH) insulin preparations, [118 ] but subsequent studies in cardiac surgical
patients found a low incidence. [119 ] , [120 ] Levy studied approximately 4,700 patients
undergoing cardiac surgery with cardiopulmonary bypass and reported that the
incidence of life-threatening reactions ranges from 0.6 to 2 percent in NPH
insulin-dependent diabetics as compared to 0.06 percent in
non-NPH-insulin-dependent diabetics. [119 ] , [120 ]
Cardiovascular Manifestations of Protamine Reactions
The spectrum of cardiovascular manifestations of protamine reactions in humans range

from systemic vasodilation with increases in cardiac output, to acute pulmonary
vasoconstriction and right ventricular dysfunction. [119 ] , [128 ] Morel demonstrated
increased levels of C5a and thromboxane in three patients who had acute pulmonary
vasoconstriction and suggested that complement activation and release of
thromboxane was responsible. [128 ] In patients previously exposed to protamine, IgG
antibodies may be responsible for complement activation. [81 ] Lowenstein reported
that five patients developed pulmonary hypertension and systemic hypotension after
protamine administration, and four had mitral valve disease and increased pulmonary
artery pressures. [126 ] Patients with otherwise normal pulmonary artery pressures who
develop acute pulmonary hypertension may not tolerate the increase in right ventricular
afterload as well as patients with prior valvular heart disease and chronically elevated
pulmonary artery pressures.
Although endothelial activation mediated by anaphylaxis appears to cause excessive

vasodilation in protamine reactions, [81 ] therapy is based on catecholamines with
alpha-adrenergic effects, epinephrine, and norepinephrine. In patients who develop
acute pulmonary hypertension and right heart failure, therapy attempts to reduce
pulmonary artery pressure and maintain systemic pressure and right ventricular
contractility. [81 ] Vasodilators such as nitroglycerin and cyclic AMP-specific
phosphodiesterase inhibitors (i.e., amrinone, milrinone, enoximone) may be useful. As
a third-line therapy, alprostadil (PGE 1 ) can be used but often infusion of a
catecholamine with alpha-agonist properties (e.g., norepinephrine) through a left atrial
catheter is needed. [81 ] Lock also reported that heparin could reverse
protamine-induced pulmonary hypertension by decreasing heparin-protamine
complexes and stopping thromboxane release from macrophages, but this has not
been confirmed. [129 ] Pulmonary hypertension and systemic hypotension routinely
occur in most animal models when protamine or any other polycation is given by rapid
injection. [130 ] [134 ]
Alternatives to Protamine
Although alternatives to protamine are under development (Table 8-4) , none are
clinically available if a patient develops a reaction or is allergic. [81 ] Although reports
suggest methylene blue is effective, recent data indicate otherwise. [135 ] , [136 ]
Polybrene (hexadimethrine), a polybasic inorganic amine used in the 1960s, is no
longer available for clinical use. [137 ] Two important potential pharmacologic agents
are under development. Recombinant platelet factor 4, a peptide normally found in
platelets, directly combines with heparin. Heparinase, an enzyme produced by certain
bacteria, degrades heparin into biologically inert fragments. Heparin reversal filters also
have been reported and are briefly described in the following.
Recombinant Platelet Factor 4
Platelet factor 4 (PF4) is a basic polypeptide that has a molecular weight of

approximately 7,800 daltons. [130 ] , [131 ] , [138 ] , [139 ] The protein is stored in
platelet dense granules and has some complex biological effects, but PF4's apparent
major role is to neutralize vascular heparans following endothelial injury. A recombinant
form of PF4 (rPF4) has been synthesized and studied in vitro, in animals, and in
humans as a reversal agent. Levy studied the ability of rPF4 to neutralize heparinized
blood from cardiopulmonary bypass circuits that contained heparin concentrations
ranging from 2.7 to 4.1 U/mL. [138 ] An rPF4 reversal ratio of 3.0: 1 (rPF4: heparin) was
the minimum dose required to neutralize heparin. Recombinant PF4 does not interfere
with viscoelastic measurements of coagulation or differences in clot lysis, as
determined by thromboelastography. [138 ]
Dehmer reported human studies of rPF4 to reverse heparin following cardiac

catheterization using doses of 0.5, 1.0, 2.5, or 5.0 mg/kg rPF4 administered over 3 min.
[139 ] Recombinant PF4 doses of 2.5 or 5.0 mg/kg were required to decrease the ACT
to <200 seconds within 5 min of administration. Activated partial thromboplastin times
(aPTT) returned to baseline values within 5 min in 11 of 12 patients. Arterial blood
pressure and pulmonary artery pressure did not change from baseline after rPF4.
Immuno-specific antibodies as detected by enzyme-linked immunosorbent assays to
rPF4 were not found at 7 days. Of all the pharmacologic alternatives for heparin
reversal, rPF4 appears to be a most promising agent.
Heparinase
Heparinase is isolated from Flavobacterium heparinum , bacteria that produce an

enzyme that metabolizes heparin-like carbohydrates. [140 ] [145 ] Hutt and Kingdon first
proposed heparinase to neutralize heparin in in-vitro samples taken for coagulation
studies. [142 ] Heparinase was successfully used for in-vitro studies and currently is in
phase 1 and 2 studies. [140 ] [144 ] Michelsen determined the concentration-response
relationship between heparinase and heparin neutralization in blood immediately after
cardiopulmonary bypass for clinical heart surgery. [134 ] Heparinase at concentrations
>0.054 IU/mL successfully decreased heparin concentrations of 3.3 ± 0.3 (mean ±
SEM) U/mL, and maximally reduced the ACT, but neutralization took 5 min as
compared to an ionic neutralizing agent that produces immediate reversal. [134 ]
In canine studies, heparinase neutralized heparin as effectively as did protamine within

5 to 10 min. In this animal model, heparinase at all doses did not alter hemodynamics.
[134 ] However, protamine caused severe systemic hypotension and pulmonary
hypertension. Heparinase at doses of 0.625 IU/kg to 2.5 IU/kg antagonized heparin
doses of either 100 or 300 U/kg in rabbits and returned the ACT to baseline. [134 ] The
half-life of heparinase is very short (2.2 ±pm 0.2 min). Additional studies must evaluate
its effectiveness and potential side-effects. [144 ]
Heparin-Binding Filters
Heparin-binding filters are based on the concept of placing a highly basic molecule,
either hexadimethrine, polylysine, or protamine, on a matrix that is separated by a
membrane. [145 ] [146 ] After cardiopulmonary bypass (CPB), a two-stage venous
cannula is placed into the right atrium. Blood passes over the filter that binds and
decreases circulating heparin. Additional human studies will demonstrate the safety and
efficacy of the method.
Pharmacologic Approaches to Decrease Bleeding Following CPB
Bleeding following cardiopulmonary bypass (CPB) results from multiple defects in

coagulation proteins, platelet function, and activation of the fibrinolytic cascade.
Pharmacologic approaches to reduce bleeding and transfusion requirements are
based on either preventing or reversing defects produced by CPB. [147 ] [149 ]
Because clinical coagulation requires appropriate platelet-fibrinogen interactions, the
goal is to preserve normal coagulation but avoid hypercoagulability. Different
pharmacologic agents have been reported to decrease perioperative bleeding,
especially following cardiac surgery. In addition, the protease inhibitor, aprotinin, or the
lysine analogs, epsilon aminocaproic acid or tranexamic acid, are used to inhibit
fibrinolysis. Because platelet function also plays an important role in perioperative
hemostasis, desmopressin is reviewed in the following. Although erythropoietin can
increase red blood cell production, the time required precludes routine use for most
cardiac surgical procedures.
DESMOPRESSIN ACETATE
Desmopressin acetate (1-deamino-8-D-arginine vasopressin-DDAVP) is a synthetic

analogue of vasopressin that increases plasma levels of factor VIII 2- to 20-fold, and
also stimulates vascular endothelium to release the larger multimers of von Willebrand
factor (vWF). [150 ] Von Willebrand factor mediates platelet adherence to vascular
subendothelium by functioning as a bridge between platelet glycoprotein 1b receptors
and subendothelial vascular basement membrane proteins. [151 ]
Desmopressin first was reported to decrease 24-hour mediastinal drainage (1317 +

486 mL, mean ± standard deviation) compared to placebo (2210 ± 1415 mL). [152 ]
Czer administered desmopressin to patients bleeding more than 100 mL/h at least 2
hours after CPB and treated control patients by transfusion. [153 ] Patients who
received desmopressin required fewer blood products, including platelets, but the study
was not randomized or blinded. In 1988, Rocha reported a randomized, double-blinded
trial of desmopressin in 100 patients who had atrial septal defect repair or valvular
replacement. There was no significant difference in overall blood loss between the
desmopressin and placebo groups (131 vs 193 mL). [154 ] Hackman reported a
double-blind, randomized study comparing the effects of desmopressin or placebo on
blood loss in patients undergoing primary coronary artery bypass grafting and/or
valvular replacement. [155 ] There was no difference between groups in blood-product
transfusion rates or blood loss within the first 24 hours after operation. Mongan reported
that patients with a thromboelastogram taken after protamine administration and who
have a maximal amplitude less than 50 mm benefit from desmopressin. [156 ] In this
study, patients with reduced platelet function bled significantly more than those with near
normal TEG. DDAVP was administered to patients with abnormal platelet function
(TEG < 50 mm) with a reduction in chest tube output similar to those with normal platelet
function. Studies have not shown an advantage for combining DDAVP with a lysine
analog fibrinolytic inhibitor (tranexamic acid). [157 ] Currently it is unclear which patients
may benefit from desmopressin. [158 ] , [159 ]
APROTININ
Aprotinin (Trasylol) is a polypeptide serine protease inhibitor isolated from bovine lung
that inhibits multiple proteases including trypsin, chymotrypsin, plasmin, tissue
plasminogen activator, serum urokinase plasminogen activator, and both tissue and
plasma kallikreins. [160 ] Aprotinin was used clinically first in the treatment of acute
pancreatitis; in the 1960s its ability to diminish the adverse effects of cardiopulmonary
bypass on bleeding was studied. [160 ] Early reports used aprotinin to treat bleeding
following cardiopulmonary bypass and reported low-dose administration with variable
results.
In the 1980s a prophylactic high-dose technique was first studied. [161 ] Van Oeveren
reported a 47 percent reduction in chest-tube drainage in patients receiving aprotinin
during coronary bypass surgery. [161 ] Bidstrup and Royston also reported three
different groups of patients who received aprotinin, including 22 patients who had
reoperative cardiac surgery using bubble oxygenators. [162 ] The original design of this
study was to develop a pharmacologic approach to inhibit inflammatory responses to
cardiopulmonary bypass by maintaining effective levels of a protease inhibitor of
contact activation. They administered aprotinin at a loading dose of 2 million units
following intubation and maintained therapeutic levels with a continuous infusion of
500,000 U/h and a pump-prime dose equal to the loading dose of 2 million units. The
investigators reported significant reductions in chest-tube drainage from aprotinin
patients with mean values of 286 mL as compared to controls who lost 1,509 mL. [162 ]
In a subsequent study of 80 patients undergoing primary coronary bypass grafting by
the same investigators, patients who received aprotinin bled 46 percent less than
controls, and received fewer units of packed red blood cells (13 units vs 75 units,
aprotinin group vs placebo). A platelet-preserving effect of aprotinin was suggested
because patients who received aprotinin had shorter bleeding times as compared to
placebo-treated patients. [163 ] These findings led to multiple studies throughout the
world to test the theory that aprotinin reduces bleeding and transfusion requirements.
Multiple studies have all confirmed decreased chest-tube drainage and the need for
allogeneic blood in patients who receive aprotinin at high doses based on the
Hammersmith or high dose regimen. [164 ] [168 ] Aprotinin also reduced blood loss
4975 percent and allogeneic transfusion requirements from 4977 percent in three
studies of patients who received aspirin. [169 ] [172 ]
In 171 redo coronary artery surgery patients, Cosgrove reported a reduction in

postoperative chest-tube drainage for both full-dose and half-dose aprotinin as
compared to placebo-treated patients. [173 ] Havel reported decreased chest-tube
drainage and transfusion requirements in 20 heart-transplant patients after 2,000,000 U
administered after intubation and 2,000,000 U added to the CPB circuit; 70 percent of
aprotinin-treated patients did not receive allogeneic blood compared to 30 percent of
controls. [174 ]
Aprotinin inhibits plasmin formation and activity and kallikrein. By inhibiting plasmin, the
active proteolytic enzyme of the fibrinolytic system, aprotinin inhibits fibrinolysis. In
addition, by partially inhibiting kallikrein, which helps to amplify and accelerate contact
activation of factor XII (Hageman factor) to XIIa, activation of the intrinsic pathway of
coagulation is inhibited or attenuated. Despite the use of heparin, contact activation and
coagulation changes that occur during extracorporeal circulation lead to thrombin
formation. Thrombin is the most important amplification agent for a wide range of
coagulation factors and is a powerful platelet activator. By inhibiting kallikrein, aprotinin
may decrease thrombin formation and protect platelets from activation. Because
kallikrein also activates fibrinolysis, by inhibiting kallikrein aprotinin inhibits fibrinolysis
independently of its ability to inhibit plasmin. Although Van Oevren postulates that
aprotinin inhibits plasmin-related degradation of the platelet glycoprotein Ib receptor,
the precise mechanism by which aprotinin reduces blood loss and transfusion
requirements is not clear. Aprotinin preserves platelet function [175 ] and may preserve
platelet glycoprotein IIb/IIIa receptors. [176 ] Multiple mechanisms appear to be
responsible for aprotinin's efficacy.
Dosing strategies
Different dosing regimens have been studied. The pharmacokinetics of aprotinin have
been recently well described; the elimination half-life is approximately 5 hours. [177 ]
Recent studies in repeat cardiac surgical patients using one-half of the full
Hammersmith dose indicate reduced bleeding and transfusion requirements. Van
Oeveren found similar results in patients treated with either low-dose or high-dose
aprotinin. [175 ] Mohr reported similar results in patients undergoing primary CABG
surgery. [178 ] Schonberger reported that a single dose of aprotinin (2 million units
added to the CPB prime) in primary CABG patients also was effective; however,
primary CABG patients are not at high risk for bleeding complications. [179 ] , [180 ]
In a study of 171 patients undergoing repeat CABG surgery, Cosgrove found that
low-dose aprotinin (half Hammersmith dose) was as effective as high-dose aprotinin
(Hammersmith dose) in decreasing blood loss and blood transfusion requirements.
[173 ] Levy reported four different treatment groups in 287 patients undergoing repeat
myocardial revascularization that included high-dose aprotinin, consisting of 2,000,000
KIU aprotinin loading dose, 2,000,000 KIU added to the CPB circuit prime, and a
continuous infusion of 500,000 KIU during surgery; low-dose aprotinin consisting of
1,000,000 KIU aprotinin loading dose, 1,000,000 KIU added to the CPB circuit prime,
and a continuous infusion of 250,000 KIU/h during surgery; pump-prime aprotinin only,
consisting of 2,000,000 KIU aprotinin added to CPB circuit prime; and placebo. [181 ]
The number of units of allogeneic packed red blood cells was significantly less in the
aprotinin-treated patients compared to placebo (high dose 1.6 units, low dose 1.6 units,
pump prime only 2.5 units, placebo 3.4 units). There were even greater reductions in
total blood-product exposure in high-dose and half-dose groups compared to placebo
or pump prime. There were no differences in treatment groups for the incidence of
perioperative myocardial infarction. [181 ]
Effects of aprotinin on ACT
The celite activated ACT is significantly prolonged by aprotinin. [182 ] DeSmet

suggested a heparin-sparing effect of aprotinin based on the ACT prolongation.
Unfortunately, the ACT can be prolonged without inhibiting thrombin as reported in
patients with factor XII deficiency. [182 ] Wang reported that kaolin-activated ACT is
less affected by aprotinin. [183 ] Kaolin absorbs aprotinin and minimizes its effects on
the ACT. ACTs greater than 750 seconds during cardiopulmonary bypass are
recommended for celite ACTs. [84 ] , [160 ] Although kaolin activated ACTs are
preferred for anticoagulation management, the ACT is a complex test that is affected by
different factors independent of anticoagulation. Most clinical studies evaluating
aprotinin use heparin-protamine titrations to maintain anticoagulation. Additional doses
of 100 U/kg heparin every hour in a fixed dosing scheme after the initial loading dose of
heparin is an alternative. Heparin doses should not be reduced in the presence of
aprotinin.
Adverse effects of aprotinin
Based on the large number of patients that have received aprotinin, only a few adverse
effects are reported. However, Cosgrove found a trend towards a higher incidence of
myocardial infarction and postoperative increases in serum creatinine levels in
aprotinin-treated patients. Further studies to evaluate these procoagulant trends do not
support these findings. [173 ] Studies by Bidstrup, Havel, and Lemmer find no
statistically significant differences in postoperative graft patency. [167 ] , [169 ] , [174 ]
Bidstrup reported no differences in vein graft patency 7 to 12 days postoperatively by
magnetic resonance imaging in 90 patients who had primary CABG surgery. [169 ]
There were no differences between treatment or control groups and 46 evaluated IMA
grafts were patent. Using ultra-fast computed tomography, Lemmer reported vein and
IMA graft patency 7 to 60 days after primary CABG surgery in 151 patients and repeat
CABG surgery in 65 patients and found no statistically significant differences between
groups, although there was trend toward lower vein and IMA graft patency rate in
aprotinin patients. [167 ] There were no significant differences in perioperative
myocardial infarction. Levy reported a randomized prospective study of repeat CABG
patients to evaluate perioperative myocardial infarction in full-dose, half-dose, and
pump-prime-only aprotinin-treated patients. [177 ] The rate of myocardial infarction was
not statistically different in high-dose, low-dose, pump-prime-only, and placebo groups.
The incidence of stroke was statistically lower in the aprotinin-treated patients
compared to placebo. A large body of literature currently supports the claim that
aprotinin does not independently increase the risk for graft thrombosis or perioperative
myocardial infarction.
Renal effects
Aprotinin is metabolized by the proximal tubules of the kidney, and has the potential to
produce renal dysfunction during prolonged used. Increased urine output, osmolar
clearance, and fractional sodium excretion are reported in aprotinin-treated patients.
[165 ] However, creatinine concentrations, electrolytes, and creatinine clearances are
not altered. In a review of recent U.S. studies, Lemmer reports no differences in renal
function in aprotinin- versus placebo-treated patients. [185 ] In patients undergoing
hypothermic arrest, creatinine increases greater than 1.5 times preoperative values
were reported [186 ] and compared to historical controls. The patients who received
aprotinin also received significantly lower doses of heparin compared to their historical
controls (unpublished data).
Allergic reactions
Because aprotinin is a bovine protein, it causes anaphylactic reactions in approximately

0.5 percent of patients. [81 ] , [187 ] These reactions will probably become more
common with prior exposure. From pooled European data, the incidence of
hypersensitivity reactions ranges from 0.3 to 0.6 percent in patients. [187 ] Protamine, a
polypeptide with a similar molecular weight, produces anaphylactic reactions in 0.62
percent of high-risk, previously sensitized patients. [119 ] , [120 ] Therefore, the
incidence of anaphylaxis to aprotinin may be similar upon re-exposure. Because
antibody titers fall with time, a longer time interval from previous exposure lessens the
risk. All patients to receive aprotinin should receive a small intravenous test dose at
least 10 minutes before the loading dose. In addition, in patients who undergo repeat
exposure, the initial dose should be delayed until cardiopulmonary bypass can be
instituted if cardiovascular collapse occurs (i.e., with aortic or femoral artery exposure).
The risk:benefit ratio for aprotinin in repeat exposure situations should be weighed
carefully. The efficacy of pretreatment with steroids and histamine blockers in
preventing complications is not proven.
THE LYSINE ANALOG ANTIFIBRINOLYTIC AGENTS
Other drugs inhibit the conversion of plasminogen to plasmin and interfere with lysis of
fibrinogen and fibrin. The amino carboxylic acid analogues of lysine bind to
plasminogen and plasmin and occupy the binding site for fibrinogen and fibrin. [188 ] ,
[189 ] Both epsilon-aminocaproic acid (EACA, Amicar) and trans- p
aminomethylcyclohexane-carboxylic acid (tranexamic acid) are used to decrease
fibrinolysis during cardiac surgery. Because of their similarity to lysine, EACA and
tranexamic acid attach to lysine binding sites on plasminogen and plasmin to inhibit
binding to fibrinogen and fibrin. Because plasmin and plasminogen cannot bind to fibrin
and fibrinogen, fibrinolysis is inhibited. Tranexamic acid is six to ten times more potent
than epsilon-aminocaproic acid, probably because of subtle differences in the
molecular structure, which mimics lysine. [188 ] , [189 ]
Fibrinolysis occurs routinely during CPB.[(190) ] Early studies from the 1960s and
1970s reported the use of antifibrinolytic agents but lacked controls, were often
retrospective, and were not blinded. Since cardiopulmonary bypass equipment,
anticoagulation practices and monitoring, and other factors may have affected these
results, only recent studies are reviewed.
In 1988 Vander Salm administered either EACA or placebo to primary CABG patients
before protamine administration and reported less chest tube drainage in
EACA-treated patients in the first 12 postoperative hours (273 vs 332 mL). Data
regarding blood-product transfusions were not reported. [191 ] In a randomized, blinded
study of 350 patients undergoing routine CABG, Del Rossi examined a 5-g loading
dose of EACA at the time of skin incision followed by a 1-g/h infusion during the next 68
hours, and reported decreased chest tube drainage in the EACA vs. placebo group
(617 vs 883 mL) and a reduction in transfusion of packed red blood cells (2.8 vs 4.2
mean units transfused). [192 ] There were no differences between groups in myocardial
infarction, cerebrovascular accidents, and graft failures, but the overall complication rate
was very low.
Horrow subsequently reported several studies of tranexamic acid for primary CABG
surgery. [193 ] [195 ] In one study, 12-hour chest-tube drainage was 496 mL in the
tranexamic acid group compared to 750 mL in the placebo group, but there were no
differences in transfusions. [193 ] A subsequent study found no increased benefit with
the combination of DDAVP and tranexamic acid. [194 ] Dosing studies in 148 patients
(2.5 to 40 mg/kg and one-tenth the loading dose hourly for 12 h) showed no further
decrease in bleeding with larger doses when the drug was given at skin incision. [195 ]
Even higher doses of tranexamic acid have been reported. Rousou described 415
consecutive patients who had primary CABG surgery and received a 2-g bolus of
transexamic acid before initiation of CPB and subsequently 8 g by infusion during
bypass. [196 ] Chest-tube drainage decreased from 1,114 mL to 803 mL in treated
patients. Small but statistically significant differences in the need for allogeneic red
blood cells (1.70.69 U/patient), fresh frozen plasma (0.230.024 U/patient), and platelets
(1.060.3 U/patient) were also observed. There were no differences in postoperative
complications, but all data were collected retrospectively and the study was not blinded.
Adverse effect of lysine analog antifibrinolytic drugs
Reports on therapy with lysine-analog antifibrinolytic drugs during cardiac surgery do

not indicate differences in the incidence of thrombotic complications, but the design of
these studies was not prospective and was not consistent with phase 3 studies
sponsored by the FDA (Food and Drug Administration). The incidence of perioperative
myocardial infarction and stroke as reported is not different in treatment groups as
compared to controls. However, because the incidence of these complications in
routine CABG surgery is low, and only small numbers of patients were studied,
thepossibility of thrombotic complications is not excluded. Prospective studies to
evaluate safety issues, including the risk of perioperative myocardial infarction, graft
patency, and renal dysfunction, are needed. Tranexamic acid is approved for use in the
United States to prevent bleeding in patients with hereditary angioedema undergoing
teeth extraction, but has no FDA indication for use in cardiac surgical patients.
Blood Products
Blood products are widely administered in cardiac surgery; this places a major demand
on blood banking facilities. Once given empirically, blood products are now given for
specific indications (Table 8-5) . In addition to costs, blood products carry significant
risks. Although the risk of viral transmission is low, immunosuppressive effects,
transfusion-related acute lung injury, and costs are disadvantages of allogenic blood
products. Each institution should develop its own algorithm for blood products in cardiac
surgical patients.
BETA-ADRENERGIC RECEPTOR BLOCKERS
Beta-adrenergic receptor blockers are competitive inhibitors; hence, the intensity of

blockade is dependent on both the dose of the blocker and receptor concentrations of
catecholamines, primarily epinephrine and norepinephrine. This competitive interaction
between beta-blocking agents and catecholamines can be demonstrated in normal
human volunteers and in isolated tissues. [198 ] The presence of disease and other
drugs modify responses to beta-blocking agents observed in patients, but the
underlying competitive interaction is still operative. Successful utilization of
beta-adrenergic receptor blockers requires titrating the dose to a desired effect.
Excessive inhibition can be overcome by (1) administering a catecholamine to compete
at the blocked receptors and/or (2) administering other drugs to reduce unopposed,
counterbalancing autonomic mechanisms. An example of the latter remedy is
propranolol-induced bradycardia, which produces unopposed vagal cholinergic
dominance on cardiac nodal tissue. Atropine relieves the excessive bradycardia by
blocking cholinergic receptors in the sinus and atrioventricular (AV) nodes.
Knowledge of the type, location, and action of beta receptors is fundamental to

understanding and predicting effects of beta-adrenergic receptor blocking drugs (Table
8-6) . [199 ] The net effect of stimulating beta receptors depends on several variables.
For example, in the heart, increased automaticity and conduction velocity in nodal and
conduction tissues is opposed by stimulating cholinergic receptors usually by vagal
acetylcholine. Therefore, beta1 blockade decreases heart rate as the vagal actions are
unopposed. If both beta1 and cholinergic receptors are blocked completely, the intrinsic
heart rate dominates (normally greater than 100 bpm). The increase in automaticity
usually is not apparent in the normal heart because the rate of spontaneous
depolarization in myofibrils is lower than in nodal and conducting tissues. When these
are diseased, increased automaticity in myocardial muscle cells becomes apparent
with beta1 receptor stimulation, and beta-blocking agents are needed as
antidysrhythmics (see the preceding). Increased automaticity can also occur in
myocardial ischemia by interrupting normal conduction pathways that usually produce
coordinated myofibril depolarization at a rate faster than spontaneous depolarization of
individual myofibrils. As is evident in Table 8-6 , many actions of beta receptor
stimulation are opposed by stimulation of alpha-adrenergic or cholinergic receptors in
the same tissues. With cholinergic receptors, opposing effects are usually produced by
acetylcholine spontaneously released from cholinergic nerves or released by giving a
cholinomimetic drug. With adrenergic receptors, norepinephrine and epinephrine are
released from sympathetic nerve terminals and from the adrenal medulla.
Administration of sympathomimetic drugs with varying preferences for different
adrenergic receptors can modify responses to beta receptor stimulation and blockade.
Beta-adrenergic receptor antagonists (blockers) include many drugs (Table 8-7) that
are typically classified by their relative selectivity for beta1 and beta 2 receptors (i.e.,
cardioselective and nonselective); the presence or absence of agonistic activity;
membrane-stabilizing properties, alpha-receptor blocking efficacy, and various
pharmacokinetic features (e.g., lipid solubility, oral bioavailability, elimination half-time).
[200 ] The practitioner must realize that the selectivity of individual drugs for beta1 and2
receptors is relative, not absolute. Although the risk of inducing bronchospasm with a
beta1 (cardioselective) adrenergic blocker (e.g., metoprolol) may be relatively less than
with a nonselective blocker (e.g., propranolol), the risk is still present. With respect to
alpha-adrenergic receptor blocking properties, only labetalol has that action and is used
primarily for hypertension. Membrane-stabilizing effects of beta-adrenergic blockers
generally occur at much higher doses than those given clinically; therefore, other drugs
are usually chosen to produce membrane stabilization (e.g., local anesthetics,
antidysrhythmics). The reader is referred to pharmacology textbooks and drug
compendia for pharmacokinetic details.
Clinical Indications
The list of clinical indications and uses of beta-adrenergic receptor blockers is long
(Table 8-8) . [200 ] In some of these clinical uses, the mechanisms principally
responsible for the desired effects appear obvious and logical but are, in fact, not
always proven. In some instances, there are actions that appear to oppose the
desirable ones. In the end, the success of therapy has to be judged in terms of the
balance of beneficial and undesirable effects. Some considerations in the use of
beta-adrenergic receptor blockers for specific diseases treated by cardiac surgery are
discussed in the following.
ANGINA PECTORIS
The primary goal of beta-blocking agent therapy is to reduce cardiac responses to

sympathetic nervous system activation by exertion, emotion, and other types of stress.
Limiting or preventing sympathetically induced increases in heart rate, contractility, and
systolic blood pressure minimizes increases in myocardial oxygen demand. Doses
required to achieve these goals often reduce resting heart rate. This effect may slightly
increase ventricular end-systolic volume and myocardial oxygen demand, but this
concern is not a clinically important problem. Also, nonselective beta-blocking agents
risk coronary vasospasm owing to unopposed alpha-adrenergic receptor responses,
but this too is not a clinically important problem, possibly because of routine use of
coronary vasodilators (e.g., nitroglycerin). Side-effects of antianginal therapy with
beta-blocking agents are considered in the following, but the most common complaints
from chronic ingestion are mental depression, fatigue, limited work capacity, and
impotence.
ACUTE MYOCARDIAL INFARCTION
Clinical trials of intravenous beta-adrenergic blockers in the early phases of acute

myocardial infarction suggest that mortality decreases 10 percent. Following
myocardial infarction, chronic oral beta-blocking agents reduce the incidence of
recurrent myocardial infarction. The major risk of beta-blocking agents after acute
myocardial infarction is congestive heart failure, since the heart may be dependent on
sympathetic tone to maintain cardiac output.
SUPRAVENTRICULAR TACHYCARDIAS AND VENTRICULAR DYSRHYTHMIAS
Adrenergic beta-blocking agents are Class II antidysrhythmics that primarily block

cardiac responses to catecholamines. Beta-blocking agents decrease spontaneous
depolarization in the sinus and atrioventricular (AV) nodes, decrease automaticity in
Purkinje fibers, increase AV nodal refractoriness, increase the threshold for fibrillation
(but not for depolarization), and decrease ventricular slow responses that are
dependent on catecholamines. There is evidence that beta-blocking agents also
decrease intramyocardial conduction in ischemic tissue and reduce the risks of
dysrhythmias, to the extent that they decrease myocardial ischemia. Beta-adrenergic
blockers are not particularly effective in controlling dysrhythmias that are not induced or
maintained by catecholamines. Membrane stabilizing effects of beta-adrenergic
blockers occur at doses much higher than those tolerated by patients.
HYPERTENSION
Our understanding of the mechanisms for the antihypertensive effects of

beta-adrenergic receptor blockers is incomplete, yet it is clear that these effects are
caused by beta blockade. During the early phases of therapy there is a decrease in
cardiac output, a rise in systemic vascular resistance (SVR), and relatively little change
in mean arterial blood pressure. Within hours to days SVR normalizes and blood
pressure declines. In addition, the release of renin from the juxtaglomerular apparatus in
the kidney is inhibited (beta 1 blockade). Presumably, beta-blocking agents with
intrinsic agonistic activity reduce systemic vascular resistance below pretreatment
levels, presumably by activating beta 2 receptors in vascular smooth muscle. In addition,
labetalol has the ability to block alpha-adrenergic receptors on vascular smooth muscle.
Most often beta-adrenergic receptor blockers are used with other drugs in the treatment
of chronic hypertension. When combined with a vasodilator, beta-blocking agents limit
reflex tachycardia. When propranolol is combined with intravenous nitroprusside, the
beta-blocking agent prevents reflex release of renin and reflex tachycardia induced by
the vasodilator.
PHEOCHROMOCYTOMA
The presence of catecholamine-secreting cells is tantamount to continuous or

intermittent infusion of a varying mixture of norepinephrine and epinephrine. It is
absolutely essential that virtually complete alpha-adrenergic receptor blockade be
established before beta receptor blocker is given to prevent hypertensive episodes
owing to unopposed alpha-adrenergic receptor activity in vascular smooth muscle. [201
]
ACUTE DISSECTING AORTIC ANEURYSM
The primary goal in the management of these patients is to reduce stress on the
dissected aortic wall by reducing systolic acceleration of blood flow. Beta receptor
blockers reduce cardiac inotropy and acceleration of blood during ventricular ejection.
Beta-blocking agents also limit reflex sympathetic responses to vasodilating drugs used
to lower systemic arterial pressure.
OTHER INDICATIONS
Other clinical applications of beta-adrenergic receptor blockers listed in Table 8-8 are
based largely on symptomatic treatment or empiric trials of beta-adrenergic receptor
blocking therapy.
Side Effects and Toxicity
The most obvious and immediate evidence of a toxic overdose of a beta-adrenergic

receptor blocker is hypotension, bradycardia, decreased AV conduction, and a
widened QRS complex on the electrocardiogram. Treatment is aimed at blocking
cholinergic receptor responses to vagal nerve activity (e.g., atropine) and administering
a sympathomimetic to compete with the beta-blocking agents at adrenergic receptors.
Bronchospasm is uncommon in the absence of preexisiting pulmonary disease, and
hypoglycemia is rare.
Side effects of chronic beta-adrenergic receptor blockade include mental depression,

physical fatigue, altered sleep patterns, excessive bradycardia, exacerbation of
congestive heart failure, increased symptoms of peripheral vascular disease,
exacerbation of bronchospasm in patients with pulmonary disease, masking
hypoglycemic episodes in diabetics, delayed recovery from hypoglycemia, sexual
dysfunction, and gastrointestinal symptoms that include indigestion, constipation, and
diarrhea.
Drug Interactions
Pharmacokinetic drug interactions include reduced gastrointestinal absorption of the

beta-blocking agent (aluminum-containing antacids, cholestyramine), increased
biotransformation (phenytoin, phenobarbital, rifamtin, smoking), and increased
bioavailability caused by decreased biotransformation (e.g., cimetidine, hydralazine).
Pharmacodynamic interactions include an additive effect with calcium channel blockers
to decrease intracardiac conduction and reduced antihypertensive effect of
beta-blocking agents when administered with some nonsteroidal antiinflammatory
drugs.
DRUGS FOR AIRWAY MANAGEMENT
The human airway extends from the external nares and lips to the alveolar capillary
membrane. Airway management in the perioperative period is a primary responsibility
of the anesthesiologist, but the surgeon becomes involved in the anesthesiologist's
absence or in difficult situations. Airway management involves instrumentation and
mechanics (not discussed here) and employs drugs to facilitate manipulation and
instrumentation of the airway and to overcome pathophysiologic problems that
contribute to airway obstruction. Most drugs used for airway management are taken
from drug classes that have other important therapeutic applications (e.g.,
sympathomimetics).
There are five major challenges encountered in airway management. Each is described
succinctly in the following to facilitate understanding of the role drugs have in airway
management. Details of pharmacology such as doses, side-effects, and toxicity are left
to standard textbooks of pharmacology and drug compendia. The five challenges are:
(1) overcoming airway obstruction; (2) preventing pulmonary aspiration; (3) performing
endotracheal intubation; (4) normalizing pulmonary function during intermittent positive
pressure ventilation (IPPV); and (5) restoring spontaneous ventilation and airway
protective reflexes.
Airway Obstruction
Obstruction to gas flow can occur from a foreign object (including food) or from
pathophysiologic processes involving airway structures (e.g., trauma, edema). [128 ] In
the anesthetized or comatose patient, loss of muscle tone can allow the tongue or
epiglottis to collapse and cause obstruction. The first therapeutic measure involves
manipulation of the head and jaw, insertion of an artificial nasal or oral airway device,
and evacuation of obstructing objects and substances (e.g., blood, secretions, food
particles). Except for drugs used to facilitate endotracheal intubation (see the following),
the only drug useful for improving gas flow through a narrowed airway is a mixture of
helium and oxygen (Heliox). This mixture reduces viscosity and resistance to gas flow.
Aspiration
The upper airway (above the larynx/epiglottis) is a shared atrium leading to the lungs
(gas exchange) and gastrointestinal tract (fluids and nutrition). Passive regurgitation or
active vomiting that accumulate gastric contents in the pharynx places the patient at risk
of pulmonary aspiration. This risk is greatly increased when airway reflexes (glottic
closure, coughing) and voluntary avoidance maneuvers are suppressed (e.g.,
anesthesia, coma). Particulate matter obstructs the tracheal bronchial tree and acidic
fluid (pH < 2.5) injures lung parenchyma. The resulting pneumonitis causes significant
morbidity (e.g., ARDS [acute respiratory distress syndrome]) and mortality.
Preoperative restriction of fluids and food (i.e., NPO status) does not guarantee
absence of aspiration. Similarly, advance placement of a naso/orogastric tube may
reduce intragastric pressure but does not guarantee complete removal of gastric
contents. Nevertheless, both NPO orders and insertion of a naso/orogastric tube under
some circumstances are worthwhile measures to reduce the risks of pulmonary
aspiration. In some circumstances, the deliberate induction of vomiting in a conscious
patient may be indicated, but this is rarely done in cardiac patients and almost never
involves an emetic drug. More often, antiemetic drugs are employed to reduce the risks
of vomiting during airway manipulation and induction of anesthesia.
The most widely used measure to minimize the risks of pulmonary aspiration in the
anesthetized or comatose patient is endotracheal intubation. Drugs to reduce the risks
of pulmonary aspiration focus on decreasing the quantity and acidity of gastric contents
and on facilitating endotracheal intubation (see the following). Nonparticulate antacids
(e.g., sodium citrate-Bicitra) are used to neutralize gastric acidity. Drugs that reduce
gastric acid production include H 2 -receptor blockers (e.g., cimetidine-Tagamet,
ranitidine-Zantac) and omeprazole (Prilosec). Metochlopramide (Reglan) enhances
gastric emptying and increases gastroesophageal sphincter tone.
Antiemetic drugs are used more commonly in the postoperative period and include
several different drug classes: anticholinergic (scopolamine), antihistamines
(hydroxyzine-Vistaril, promethazine-Pherergan), antidopaminergics
(droperidol-Inapsine, prochlorperazine-Compazine), and antiserotoninergics
(ondansetron Zofran). The intravenous hypnotic-anesthetic, propofol, has significant
antiemetic effect.
Endotracheal Intubation
Drugs are employed for three purposes to facilitate endotracheal intubation: (1) to
improve visualization of the larynx during laryngoscopy; (2) to prevent closure of the
larynx; and (3) to facilitate manipulation of the head and jaw. [202 ]
Improved visualization of the larynx includes decreasing salivation and tracheal

bronchial secretions by an anticholinergic drug (e.g., scopolamine), reducing mucosal
swelling by a topical vasoconstrictor (e.g., phenylephrine), and minimizing traumatic
bleeding caused by mucosal erosion (e.g., phenylephrine). Steroids may have some
delayed benefit in minimizing acute inflammatory responses in the airway, but are not
indicated just prior to intubation.
Reflex responses to airway manipulation, laryngoscopy, and endotracheal intubation

can be suppressed by several different methods, alone or in combination. Topical
anesthesia (e.g., 2 or 4% lidocaine spray) anesthetizes the mucosal surfaces of the
nose, oral cavity, pharynx, and epiglottis. Atomized inhaled local anesthetics
anesthetize mucosa below the vocal cords. The subglottic mucosa can be anesthetized
topically by injecting local anesthetic through the cricothyroid membrane into the
tracheal lumen (transtracheal block). A bilateral superior laryngeal nerve block
eliminates sensory input from mechanical contact or irritation of the larynx above the
vocal cords. It must be remembered that mucosal anesthetics obtund airway reflexes,
compromise reflex protective mechanisms, and increase the risk of aspiration.
Intravenous systemic drugs can obtund the cough reflex. Intravenous lidocaine (12
mg/kg) transiently obtunds the cough reflex without significantly affecting spontaneous
ventilation. The risks of stimulating the central nervous system and seizure-like activity
can be reduced by prior small doses of an intravenous barbiturate or benzodiazepine.
Intravenous opioids suppress cough reflexes, but the doses required impair
spontaneous ventilation to the point of apnea. A combination of an intravenous opioid
with a major tranquilizer (e.g., neuroleptanalgesia) allows tolerance of an endotracheal
tube with less opioid and less embarrassment of spontaneous ventilation. Small doses
of opioids also obtund airway reflexes during intravenous (e.g., thiopental) or inhaled
(e.g., isoflurane) general anesthesia. Opioids not only obtund the cough reflex that
closes the larynx, but also limit the autonomic sympathetic response (hypertension,
tachycardia) to endotracheal intubation.
Skeletal muscle relaxants are most commonly used with a general anesthetic to
facilitate manipulation of the head and jaw and to prevent reflex closure of the larynx.
Since the patient is apneic, two procedures commonly are used to maintain
oxygenation. Pure oxygen by mask while the patient is still awake eliminates nitrogen
from the lungs; then, in rapid sequence, an intravenous anesthetic (e.g., thiopental) is
followed immediately by a rapid-acting neuromuscular blocker (e.g., succinylcholine).
As soon as the maximum effect of the muscle relaxant is apparent (3090 s)
laryngoscopy is performed, an endotracheal tube is inserted, the tracheal tube cuff is
inflated, and the position of the tube in the trachea is verified. Alternatively, when the risk
of pulmonary aspiration is minimal (presumed empty stomach), the patient is
anesthetized and paralyzed while ventilation is supported by intermittent positive
pressure delivered by face mask. At the appropriate time, laryngoscopy is performed
and the endotracheal tube is inserted.
Normalizing Pulmonary Function During Intermittent Positive Pressure

Ventilation
Once an endotracheal tube is in place, general anesthesia and partial muscular

paralysis are maintained for the operation (see Chap. 7). Postoperatively, general
anesthesia and partial muscular paralysis may be continued if prolonged positive
ventilation is anticipated. Alternatively, if the patient is not extubated promptly, low
doses of hypnotics and opioids are given to suppress the stimulus of the endotracheal
tube until spontaneous ventilation recovers and tracheal extubation is imminent (203).
Three other problems are encountered in intubated patients supported by mechanical

ventilators: (1) poor ventilatory compliance; (2) bronchoconstriction; and (3) impaired
gas exchange. Poor ventilatory compliance can reflect limited compliance of the chest
wall and diaphragm and/or limited compliance of the lungs per se. Deepening general
anesthesia and a skeletal muscle relaxant can reduce intercostal and diaphragmatic
muscle tone, but do not improve chest cavity compliance that is impaired by disease
(e.g., scoliosis, emphysema).
Poor lung compliance may reflect pulmonary interstitial edema, consolidation, bronchial
obstruction (e.g., mucous plugs), bronchoconstriction, or compression of the lung (e.g.,
pneumothorax, hemothorax, tumor mass). Treatment of these conditions involves drug
therapy for heart failure or infection and procedures such as bronchoscopy,
thoracentesis, etc.
Bronchoconstriction may exist chronically (e.g., asthma, reactive airways disease), and
this may be exacerbated by the presence of an endotracheal tube. Tracheal bronchial
secretions collect in the airway in the presence of an endotracheal tube that reduces
cough effectiveness in clearing the airway. Occasionally bronchoconstriction is induced
by an endotracheal tube or other object in an otherwise normal patient. Drug treatment
is focused on reducing bronchial smooth muscle tone (beta-2 sympathomimetic,
anticholinergic), minimizing tracheal bronchial secretions, and decreasing sensory input
from the tracheal bronchial tree (e.g., topical anesthetic, deeper general anesthesia,
intravenous lidocaine or an opioid). Acute treatment of bronchoconstriction may involve
any combination of the following: (1) aerosolized beta-2 sympathomimetic and/or
anticholinergic; (2) systemic intravenous administration of a beta-2 sympathomimetic, a
phosphodiesterase inhibitor (e.g., aminophylline), and/or an anticholinergic; (3)
intravenous steroids. The latter are indicated in severe bronchoconstriction, especially
in the asthmatic patient who benefitted previously. With 100 percent oxygen, blood
oxygenation usually is satisfactory, but the progressive development of hypercarbia and
air trapping reduces ventilatory compliance and increases intrathoracic pressure that
reduces venous return and cardiac output.
Impaired alveolar capillary gas exchange may result from alveolar pulmonary edema
(treated by diuretics, inotropes, and vasodilators), decreased pulmonary perfusion
(treated by inotropes and vasodilators), and lung consolidation (antibiotic therapy for
infection).
Restoration of Spontaneous Ventilation and Airway Protective Mechanisms
The anesthesiologist tailors the anesthetic plan according to postoperative

expectations. In a relatively healthy patient who will be extubated in the operating room,
the goal is to have the patient breathing spontaneously with intact airway reflexes and
arousable to command immediately after operation. The challenge is to maintain
satisfactory general anesthesia during the surgery but to have the patient recover from
anesthetic drugs, including hypnotics and opioids, immediately afterwards. If this is not
possible, the patient is transferred to the PACU (post-anesthesia care unit) to allow
additional time for eliminating drugs that depress spontaneous ventilation and cough
reflexes. Another option is to administer an opioid antagonist (e.g., naloxone) and/or
benzodiazepine antagonist (e.g., flumazenil); however, this approach risks sudden
awakening, anxiety, pain, uncontrolled autonomic sympathetic activity, and recurrent
ventilatory depression because of mismatching antagonists and residual anesthetic
drugs. On the other hand, neuromuscular blockers routinely are antagonized by an
anti-cholinesterase (e.g., neostigmine) in combination with an anticholinergic (e.g.,
atropine) to limit the cholinergic side-effects of the anticholinesterase.
When the postoperative plan calls for maintenance of mechanical ventilation for some
time, tolerance of the endotracheal tube is facilitated by residual anesthetic drugs
supplemented by intravenous hypnotics (e.g., propofol) and opioids (e.g., fentanyl,
morphine) in low doses. The goals are to prevent pain, limit reflex responses to the
endotracheal tube, and allow variable degrees of spontaneous ventilation
supplemented by intermittent positive pressure ventilation. When ready for extubation,
these sedative and analgesic drugs are reduced in dosage or discontinued to allow
satisfactory blood oxygenation and carbon dioxide removal, easy arousal of the patient,
and partial restoration of airway reflexes.
DIURETICS
Diuretics are drugs that act directly on the kidneys to increase urine volume and to
produce a net loss of solute (principally sodium and other electrolytes) and water. [204 ]
Currently available diuretics have a number of uses in medicine (e.g., treatment of
hypertension, glaucoma, increased intracranial pressure) that are not discussed here.
The principal indications for intravenous diuretics in the perioperative period are: (1) to
increase urine flow in oliguria; (2) to reduce intravascular volume in patients at risk of
acute heart failure from excessive fluid administration; and (3) to mobilize edema.
Renal function depends on adequate renal perfusion to maintain the integrity of renal
cells and to provide hydrostatic pressure for glomerular filtration. There are no drugs
that act directly on the renal glomerulus to affect the glomerular filtration rate (GFR). In
an average-size normal adult human, GFR averages 125 mL/min and urine production
approximates 1 mL/min. In other words, 99 percent of the glomerular filtrate is
reabsorbed. Diuretics act on specific renal tubal segments to alter reabsorption of
water and electrolytes, principally sodium.
There are two basic mechanisms behind renal tubular reabsorption of sodium. (1)
Sodium is extruded from the tubular cell into peritubular fluid primarily by active transport
of the sodium ion by the Na-K-ATPase pump and by the bicarbonate reabsorption
mechanism (see the following). This extrusion of sodium creates an electrochemical
gradient causing diffusion of sodium from the tubular lumen into the tubular cell. (2)
Sodium also moves from the glomerular filtrate into the peritubular fluid by several
different mechanisms. The most important quantitatively is the sodium electrochemical
gradient created by active extrusion of sodium from the tubular cell into peritubular fluid.
Sodium also is coupled with organic solutes and phosphate ions, exchanged for
hydrogen ions diffusing from the tubular cell into the tubular lumen, and coupled to the
transfer of a chloride ion or a combination of a potassium and two chloride ions
(Na-K-Cl cotransport) from tubular fluid into the tubular cell. Diuretics are classified by
their principal site of action in the nephron and by the primary mechanism of their
naturetic effect (Table 8-9) .
Osmotic Diuretics
Mannitol is the principal example of this type of diuretic, which is used for two primary
indications: (1) prophylaxis and early treatment of acute renal failure characterized by a
decrease in GFR leading to a decreased urine volume and an increase in the
concentration of toxic substances in the renal tubular fluid; and (2) to enhance other
diuretics by retaining water and solutes in the tubular lumen.
Normally, 80 percent of the glomerular filtrate is reabsorbed isosmotically in the

proximal tubule. By an osmotic effect, mannitol limits reabsorption of water and dilutes
proximal tubular fluid. This reduces the electrochemical gradient for sodium and limits
its reabsorption so that more reaches the distal nephron. Mannitol produces a
prostaglandin-mediated increase in renal blood flow that partially washes out medullary
hypertonicity that is essential for the counter current mechanism promoting reabsorption
of water in the late distal tubule and collecting system under the influence of antidiuretic
hormone. The principal toxicity of mannitol is acute expansion of extracellular fluid
volume in patients with compromised cardiac function. The drug also reduces chloride
and accompanying sodium ion diffusion from the tubular fluid through the pericellular
pathway (in between tubular cells) into the peritubular fluid.
High Ceiling (Loop) Diuretics
Furosemide (Lasix), bumetanide (Bumex), and ethacrynic acid (Edecrin) are three
chemically dissimilar compounds that have the same primary diuretic mechanism of
action. They act on the tubular epithelial cell in the thick ascending limb of Henle's loop
to inhibit the Na-K-2Cl cotransport mechanism. Their peak diuretic effect is far greater
than other diuretics currently available. Administered intravenously, these drugs have a
rapid onset and relatively short duration of action, owing to both pharmacokinetics and
compensatory mechanisms. These three diuretics increase renal blood flow without
increasing GFR and redistribute blood flow from the medulla to the cortex and within the
renal cortex. These changes in renal blood flow also are short-lived and reflect the
reduced extracellular fluid volume that results from diuresis. Carbonic anhydrase
inhibition by furosemide and bumetanide and actions on the proximal tubule and on
sites distal to the ascending limb remain controversial. All three of the loop diuretics
increase release of renin and prostaglandin; indomethacin blunts this release as well as
the augmentation of renal blood flow and natruresis. The drugs also produce an acute
increase in venous capacitance for a brief time after the first intravenous dose that is
blocked by indomethacin.
Potassium, magnesium, and calcium excretion are increased in proportion to the

increase in sodium excretion. In addition, there is augmentation of titratable acid and
ammonia excretion by the distal tubal leading to metabolic alkalosis, which also is
produced by contraction of the extracellular volume. Hyperuricemia can occur but is of
little physiological significance usually. The nephrotoxicity of cephaloridine, and possibly
other cephalorsporins, is increased. A rare but serious side-effect of the loop diuretics
is deafness, which may reflect electrolyte changes in the endolymph.
Because of their high degree of efficacy, prompt onset, and relatively short duration of
action, high ceiling or loop diuretics are favored for intravenous administration in the
perioperative period to treat the three principal problems cited above. Dosage
requirements vary considerably among patients. Some require only 35 mg furosemide
IV to produce a good diuresis; others may need only the less potent benzothiazides.
Benzothiazides
Hydrochlorothiazide (HCTZ) is the prototype of more than a dozen currently available

diuretics in this class. Although the drugs differ in potency, all act by the same
mechanism and have the same maximum efficacy. All are actively secreted into the
tubular lumen by tubular cells and act in the early distal tubule to decrease the
electroneutral Na-Cl co-transport reabsorption of sodium. Their moderate efficacy
probably is because more than 90 percent of filtered sodium is reabsorbed before
reaching the distal tubule. Efficacy is enhanced by simultaneous administration of an
osmotic diuretic such as mannitol. Benziothiazides increase urine volume and excretion
of sodium, chloride, and potassium. Reduced reabsorption of potassium reflects
diminished reabsorption time from the higher rate of urine flow through the distal tubule.
This class of diuretics produces the least disturbance of extracellular fluid composition.
Principal side-effects include hyperuricemia, decreased calcium excretion, and
enhanced magnesium loss. Hyperglycemia can occur as a result of multiple variables.
With prolonged use and contraction of extracellular fluid volume, urine formation
decreases. Also, these agents have a direct effect on renal vasculature to decrease
GFR.
Carbonic Anhydrase Inhibitors
Acetazolamide (Diamox) is the only diuretic of this class available for intravenous
administration. Its clinical use is primarily directed to alkalinization of urine in the
presence of a metabolic alkalosis that develops commonly from prolonged diuretic
therapy. Acetazolamine acts in the proximal convoluted tubule to inhibit carbonic
anhydrase in the brush border of the tubular epithelium to reduce destruction of
bicarbonate ion (i.e., prevents conversion to co 2 ). Tubular cellular carbonic anhydrase
is also inhibited so that conversion of co 2 to carbonic acid is reduced markedly and
fewer hydrogen ions are available for the Na-H exchange mechanism. Reabsorption of
both sodium and bicarbonate in the proximal tubule is diminished, but more than half of
the bicarbonate is reabsorbed in more distal segments of the nephron, to reduce the
overall efficacy of the drug.
Potassium-Sparing Diuretics
Spironolactone (Aldactone) is a competitive antagonist of aldosterone. Spironolactone

binds to the cytoplasmic aldosterone receptor and prevents conformational change to
the active state. The drug aborts the synthesis of active transport proteins in the late
distal tubal and collecting system where the reabsorption of sodium and secretion of
potassium are reduced.
Triamterene (Dyrenium) and amiloride (Midamar) are potassium-sparing diuretics.

They have a moderate naturetic effect that leads to an increased excretion of sodium
and chloride with little change or a slight increase in potassium excretion when the latter
is low. When potassium secretion is high, the drugs produce a sharp reduction in
electrogenic entry of sodium ions into distal tubular cells and thereby reduce the
electrical potential that drives potassium secretion.
Both types of potassium-sparing diuretics are used primarily in combination with other
diuretics to reduce potassium loss. The principal side effect is hyperkalemia. It is
appropriate to limit intake of potassium when using this type of diuretic. It is also
appropriate to use this type of diuretic cautiously in patients taking ACE (angiotensin
conversion enzyme) inhibitors that decrease aldosterone formation and consequently
increase serum potassium concentrations.
Other Measures to Enhance Urine Output and Mobilization of Edema Fluid
Infusion of albumin (525% solutions) or other plasma volume expanders (e.g.,

hetastarch) is often employed to draw water and electrolytes (i.e., edema fluid)
osmotically from tissues into the circulation for delivery to the kidneys for excretion. With
a reduced circulating blood volume, this is a logical way to increase circulating blood
volume and renal perfusion. Because the osmotic effect of albumin and plasma
expanders is transient because of their diffusion into tissues, the diuretic effect is
limited and water tends to remain in the interstitial space. The same limitation applies to
osmotic diuretics such as mannitol, which also diffuse through the capillary membrane.
Dopamine (Intropin) is a catecholamine that has the unique ability to interact with
vascular D1-dopaminergic receptors in coronary, mesenteric, and renal vascular beds.
By activating adenyl cyclase and raising intracellular concentrations of cyclic-AMP,
D1-receptor stimulation leads to vasodilation. Infusion of low doses of dopamine (13
µg/kg-1/min-1) causes an increase in glomerular filtration rate, renal blood flow, and na
+
excretion. As a catecholamine and a precursor in the metabolic synthesis of
norepinephrine and epinephrine, dopamine has inotropic and chronotropic effects on
the heart. The inotropic effect is mediated by beta1-adrenergic receptors and usually
requires infusion rates higher than those able to produce enhanced renal perfusion and
diuresis. Infusion rates greater than 810 µg/kg -1/min-1 lead to vasoconstriction
produced by dopamine activation of alpha1-adrenergic receptors in vascular smooth
muscle.
COMPONENTS OF EXTRACORPOREAL PERFUSION SYSTEMS
The heart-lung machine is the most option-laden model of extracorporeal perfusion

systems (Table 9-1) . The basic components are one or more venous cannulas, a
venous reservoir, an oxygenator/heat exchanger, a pump, an arterial line filter, and an
arterial cannula (see Table 9-1 ). The machine is built from biocompatible materials that,
by definition, are nontoxic, nonimmunogenic, nonallergic, and nonmutagenic. These
biocompatible materials, or biomaterials , also must be suited for machining and
fabrication. Examples include polycarbonate, polyvinylchloride, Teflon, polyethylene,
stainless steel, titanium, silicone rubber, and polyurethanes. Blood flow paths are
designed to minimize turbulence, cavitation, stagnant areas, and changes in flow
velocity and to minimize the volume of perfusate required for priming. Multiple access
ports are needed in the basic system to connect subsystems, obtain blood samples,
and add perfusate and drugs.
For most applications, subsystems supplement the basic heart-lung machine. A

cardiotomy suction system (see Table 9-1 ) aspirates blood from open cardiac
chambers and the surgical field. This blood is filtered and debubbled and added directly
to the perfusate. Diluted field blood is retrieved by a separate cell saver system that
filters and concentrates red cells before returning them to the perfusate. A cardioplegic
delivery system consists of a separate pump, reservoir, and heat exchanger and is
designed to provide potassium-enriched blood or crystalloid solution directly into the
coronary circulation. Current heart-lung machines and subsystems have an open
architecture with lengths of tubing connecting separated components. The open
architecture permits the perfusionist to visually monitor the system and to correct
problems but exposes blood to large areas of synthetic materials, multiple air-entry
sites, and potential contamination.
Venous Cannulas
Through one or more venous cannulas, deoxygenated blood drains by gravity into the
extracorporeal circuit or pump-oxygenator system. The number of venous cannulas
depends on the type of cardiac surgical procedure and, to some extent, on the
surgeon's preference. When one cannula is used, it is usually placed in the right atrium
through the right atrial appendage. When two cannulas are used, the cannulas are
passed through purse-string sutures in the right atrium into the superior and inferior
venae cavae. If a left superior vena cava drains into the coronary sinus, a third venous
cannula can be inserted into the sinus from the right atrium. A single cavoatrial cannula
or a two-stage cannula (Fig. 9-1) is used by many surgeons for operations involving the
aortic valve, left ventricular outflow tract, ascending aorta, and coronary arterial bypass
procedures. Two venous catheters with snares tightened around both cavae are
necessary for work within the right atrium or right ventricle. In certain operations, either
cava may be cannulated directly.
Venous cannulas also can be inserted into either cava or the right atrium from the
femoral, iliac, or jugular vein. Flow is limited through a peripheral venous cannula if the
cannula tip is greater than one-half the diameter of the great vein [7 ] ; therefore, longer
catheters that reach the right atrium are preferred. These peripheral catheters are
inserted percutaneously or directly over a wire guide and advanced into the right atrium.
[7 ] Insertion may be monitored by fluoroscopy or echocardiography, but monitoring is
usually unnecessary. Peripheral cannulation is used for some reoperations, in
occasional emergencies, when long-term circulatory or ventilatory support is needed,
and for thorascopic myocardial revascularization. [7 ]
The size of the venous cannulas is determined by the number used, the size of the
patient, and the anticipated flow rate. [8 ] During perfusion, central venous pressure
must be kept between 5 and 15 mmHg. Negative pressure causes collapse of
thin-walled great veins around the cannula and obstructs flow. [7 ] In most extracorporeal
perfusion systems, systemic venous blood drains by gravity into the venous reservoir
that is placed 25 to 30 inches below the plane of the systemic great veins.
Venous Reservoir
The venous reservoir is a compressible polyvinyl bag with up to 3 liters of capacity.

Hard-shell reservoirs are also manufactured but add an air-blood interface to the
system. [9 ] A venous reservoir is used with membrane oxygenator perfusion systems
and is placed upstream to the pump. The outlet port is located at the bottom of the
reservoir and designed to allow high-flow perfusion at low reservoir volumes. The
venous reservoir is incorporated into the oxygen-blood mixing chamber in bubble
oxygenators. [9 ]
Oxygenator
There are two types of oxygenators, membrane and bubble . [8 ] A polypropylene

microporous membrane or, less commonly, a silicone rubber membrane separates
blood and gas compartments in a membrane oxygenator. Oxygen is driven by the high
differential pressure between the two compartments (approximately 640 mmHg) and
diffuses into blood across nonporous membranes or through 1-µm micropores (Fig.
9-2A) . Although plasma surface tension seals micropores and prevents gas emboli, the
holes greatly reduce the diffusion barrier and increase the efficiency of the membrane
for oxygen transfer. Because oxygen diffuses poorly in plasma, blood must be spread
thinly over a relatively large surface area (2.0 to 5.4 m 2 ) to achieve complete
hemoglobin saturation. Areas of turbulence and secondary flow enhance the diffusion of
oxygen within blood and therefore improve oxyhemoglobin saturation. [10 ] Carbon
dioxide is highly diffusible in plasma and easily exits the blood compartment despite
small differential pressures between venous co 2 and the co 2 concentration in the gas
compartment. Oxygen content of the gas compartment is regulated by a blender that
mixes oxygen and air to produce any desired oxygen concentration. To some extent co
2 exchange is influenced by the rate of gas flow, which raises or lowers partial co 2 in
the gaseous washout. The thin blood path and large blood-membrane surface area
produce relatively high resistance to flow; therefore, a separate venous reservoir is
needed, and the arterial pump is placed upstream to the oxygenator in most membrane
oxygenator perfusion systems. [9 ] A heat exchanger is built into the unit. Current
membrane oxygenators are disposable, single-use units.
Three different designs are used to bring red cells near the membrane surface within
the blood compartment. The most popular design is the hollow fiber membrane
oxygenator, which contains sheaves of microporous polypropylene hollow fibers (120 to
200 µm in diameter) connected to inlet and outlet manifolds within a cylindrical housing.
[11 ] Usually oxygen is passed inside the fibers, and blood passes between and over
individual fibers (Fig. 9-3) . Blood also can circulate through the fibers with gas outside;
however, because secondary flows and turbulence are greater with blood outside,
oxygenation is also more efficient. [8 ]
Microporous membranes are also used as flat sheets. Multiple parallel spacers
between membranes separate blood flow and gas flow into parallel, thin columns
analogous to hollow fibers. Blood and gas compartments alternate within the stack;
manifolds direct blood or gas into the appropriate compartment.
In the spiral coil oxygenator, which is largely used for prolonged perfusions for
respiratory or circulatory support, an envelope of silicone rubber membrane is wound
around a central spool. Oxygen enters the envelope, and blood passes between the
windings. The blood flow path is irregular and produces secondary flows and
turbulence.
In bubble oxygenators, venous blood drains directly into a chamber into which oxygen is
infused through a diffusion plate (sparger). The sparger produces thousands of small
oxygen bubbles within blood. Commercial oxygenator diffusion plates produce bubbles
(approximately 36 µm) that efficiently remove carbon dioxide and fully oxygenate blood.
Gas exchange occurs across a thin film at the blood-gas interface around each bubble
(see Fig. 9-2B ). Carbon dioxide diffuses into the bubble, and oxygen diffuses outward
into blood. Since oxygen diffuses slowly in plasma, many small bubbles improve oxygen
exchange by effectively increasing the surface area of the gas-blood interface. [12 ]
Carbon dioxide diffuses 25 times more rapidly than oxygen in plasma; its removal is
facilitated by larger bubbles, which accommodate more co 2 and are easier to remove
from blood. Carbon dioxide escapes into the gas phase when bubbles and blood are
separated by settling, filtration, and defoaming surfactants in the arterial reservoir.
Contemporary bubble oxygenators incorporate a reservoir and heat exchanger within
the same unit and are placed upstream to the arterial pump.
Commercial bubble oxygenators are highly efficient and add 350 to 400 mL oxygen to
blood and remove 300 to 330 mL co 2 at flow rates from 1 to 7 liters/min. [8 ] , [11 ]
Priming volumes are less than 500 mL. Modern membrane oxygenators are equally
efficient and add up to 470 mL of O 2 and remove up to 350 mL of co 2 at 1 to 7
liters/min flow. [8 ] , [11 ] Priming volumes range from 220 to 560 mL, but pressure
differences across membrane oxygenators approximate 12 to 15 mmHg per liter of
blood flow. Specifications for both types of oxygenator approach those of the
mammalian lung at resting cardiac outputs. However, during exercise, the human lung
transfers up to 2 liters of O 2 and 1.6 liters of co 2 at flows reaching 15 liters/min with
pressure differences of only 2 mmHg per liter of flow. [13 ] The priming volume of the
human lung is approximately 140 mL, but the surface area of the blood-gas interface is
nearly 90 m 2 . Surface areas of membrane oxygenators are around 2.2 m 2 .
Both membrane and bubble oxygenators activate blood proteins and cells and produce
microemboli. Bubble oxygenators are efficient gas exchangers and less expensive than
membrane oxygenators, but blood trauma is progressive, since each new bubble
presents a new foreign surface to which blood elements react. [14 ] , [15 ] The blood
contact surfaces of membrane oxygenators are constant and quickly become coated
with a layer of plasma proteins that reduce activation of some blood elements. Most of
the blood injury occurs within the first few minutes in membrane oxygenators; therefore,
these devices, which are just as efficient for gas transfer, cause less blood trauma with
perfusions that last more than 2 or 3 hours. [16 ] [18 ]
Heat Exchanger
Heat exchangers are necessary to control body temperature during cardiopulmonary

bypass. Body temperature controls metabolism and often is manipulated during
operation for a variety of reasons. Because the brain is most vulnerable to ischemia,
nasopharyngeal temperature (the probe is placed close to the base of the brain) is
measured in addition to rectal or bladder temperature during hypothermic CPB.
Water circulates within the heat exchanger between 1 and 2°C and 42°C. Temperatures
above 42°C risk denaturing blood proteins. Cooling is more rapid than rewarming
because greater temperature differences can be maintained between blood leaving
and entering the patient. In adults, nasopharyngeal temperatures decrease at a rate of
0.7 to 1.5°C/min between 30 and 37°C and more slowly at lower temperatures. [16 ]
During rewarming, temperature increases at the rate of 0.2 to 0.5°C/min. Caloric
exchange is most rapid at the beginning of cooling or rewarming but may not be
reflected immediately by temperature changes because of heat redistribution within the
body.
Dalton's and Boyle's laws mandate that gases are more soluble in cold plasma.
Therefore, perfusion of very cold blood into warm patients must be avoided to prevent
microbubble formation within the patient. Rapid cooling during induction of hypothermia
poses the greatest danger. Rapid warming may produce visible microbubbles within
the circuit, but these will dissolve after reaching the cold patient. For safety reasons,
temperature differences between perfusate and patients greater than 12 to 14°C are
avoided.
Pumps
Pumps propel blood, and three different types, centrifugal, impeller, and roller, are used
commonly during clinical cardiopulmonary bypass (CPB) for heart surgery. Valved
pumps are rarely used for clinical CPB but are often used in circulatory assist devices.
The roller pump consists of two rollers, 180 degrees apart, that rotate through a
half-circular metal raceway (Fig. 9-4A) . Polyvinyl, silicone rubber, or latex rubber tubing
between ¼ and &frac58; in (ID) is placed between the rollers and raceway so that the
rollers barely occlude the tubing at 180 mmHg backpressure. [9 ] As one roller begins to
compress the tubing, the opposite roller releases so that blood within the tubing is
continuously propelled in one direction. Roller pumps are reliable, safe, and easy to
operate, maintain forward flow regardless of outflow line pressure, and have very low
operating costs. Pump output is proportional to the rotational speed of the rollers and
the diameter of the compressible tubing. In practice, rate of blood flow is calculated or
read from a chart that correlates roller speed, tubing diameter, and blood flow. Roller
pumps produce a sinewave pressure curve of low amplitude.
Centrifugal and impeller pumps consist of a rapidly rotating impeller (either concentric
cones or blades) within a blood compartment (see Fig. 9-4 B ). Rotating blades push
the blood forward in the impeller pump; concentric cones rotating at high speed within
the compartment move blood by centrifugal force in the centrifugal pump. The
centrifugal pump is safe, reliable, disposable, and simple to operate; however, flow
varies as a function of outflow line pressure and must be monitored by an
electromagnetic flowmeter. Both impeller and centrifugal pumps can produce negative
pressure when inflow is impeded. Centrifugal pumps have several advantages over the
roller and impeller pumps in that they do not produce high backpressures when tubing is
temporarily obstructed or kinked, do not produce spallated emboli from compression of
tubing, and cannot pump large gas emboli. Centrifugal and impeller pumps produce
continuous, nonpulsatile blood flow.
Any of the three pumps may be used to pump oxygenated blood to the patient. A
venous reservoir is used upstream with all pumps to prevent negative pressure within
the venous line. A roller pump is used to produce negative pressures to operate the
cardiotomy suction system or actively vent the left side of the heart. A third pump, usually
of the roller type, is also used to deliver cardioplegic solution or to perfuse the coronary
arteries directly during open operations involving the aortic root.
Filters
Blood filters are designed to trap particulate and gaseous emboli. [17 ] Arterial line
filters are required for bubble oxygenator perfusion systems and are used routinely with
membrane oxygenator systems. [18 ] Two types of filters are in general use. Screen
filters are made of nylon or polyester with pore sizes between 20 and 43 µm. Surface
areas vary between 600 and 890 cm 2 . Flow rates up to 7 liters/min produce pressure
differences across 40-µm pore filters below 30 mmHg and higher pressures with
smaller pores. A bypass shunt around the filter is usually used in case the filter must be
removed during perfusion. Most filters require 200 mL of perfusate to prime; trapped air
is removed through an air vent. Depth or packed filters contain packed fibers or foam
that does not have uniform spaces between solid material. The Dacron wool filter is an
example of this type and is an equal alternative to screen filters with similar
hemodynamics. [9 ] Screen filters are also included in cardiotomy and cell saver suction
systems, gas flow lines, and temporary filters used during prebypass circuit priming.
Arterial Cannulas
The arterial cannula is usually placed in the ascending aorta just proximal to the
innominate artery, but it can be placed anywhere in the arterial system that is large
enough to accommodate the necessary flow. Alternative cannulation sites include the
femoral, iliac, and axillary arteries and the descending thoracic or abdominal aorta.
Femoral arterial cannulation is often used in patients with dissecting aortic aneurysms,
in patients who require reoperation, whenever CPB may be needed before the
mediastinum can be dissected safely, and in emergencies when rapid cannulation of
the femoral artery and vein is necessary to establish circulation with partial CPB.
Percutaneous arterial (and venous) cannulas that are passed through tiny skin incisions
into a peripheral artery over a guidewire are also available for thorascopic myocardial
revascularization and special situations.
The size of the arterial cannula varies with the size of the patient and the anticipated
blood flow rate through the heart-lung machine. [19 ] The pressure difference across the
cannula is directly proportional to blood flow rate and inversely proportional to the
internal diameter of the cannula. [20 ] High flow through narrow cannulas produces
unacceptable pressure differences (>100 mmHg), turbulence, and cavitation that are
destructive to blood elements and dangerous for connections. To reduce pressure
differences at high flow rates, only the tip that is inserted into the vessel is reduced to a
diameter less than that of the connecting tubing. Internal diameters of commercially
available arterial cannulas vary between 6 and 24 French.
Cardiotomy Suction System
This system is necessary to return blood spilled into the operative field from opened
cardiac chambers directly into the perfusion circuit. The system avoids potentially
tremendous blood losses that might otherwise occur but, beyond filtering and
defoaming, does not process blood. Aspirated blood, therefore, contains enzymes
activated by blood contact with the wound and is not the same as the perfusate with
which it will be mixed. [21 ] The suction system is a major cause of hemolysis, [9 ] is
very destructive of all blood elements, [22 ] and if not used, may actually decrease
postoperative blood loss. [23 ] During operation, the cardiotomy sucker system
aspirates both tissue debris and large volumes of air that must be removed by the filter
in the cardiotomy suction reservoir.
The cardiotomy suction system usually consists of two sucker tips, connecting tubing,
one or two roller pumps, and a combined blood filter and hard-shell reservoir unit (Fig.
9-5) . A vacuum system can be used instead of roller pumps to provide negative
pressure for the system, and the degree of blood destruction can be reduced by
systems that control the amount of suction. [9 ] A filter in the cardiotomy suction system
reservoir is mandatory to remove particulate and gaseous emboli. [17 ]
Left Ventricular Venting System
Decompression of the flaccid, noncontracting heart prevents ventricular distension and

nonischemic myocardial creep. [24 ] Ventricular distension significantly reduces
myocardial contractility, [24 ] may reduce subendocardial coronary blood flow, [9 ] and
sometimes produces acute lung damage from increased pulmonary venous pressures.
Left ventricular venting also facilitates exposure of the aortic valve and root. Bronchial
arterial blood and blood flowing through the pulmonary artery from the coronary sinus
and right atrium are the primary sources of blood reaching the left heart during CPB.
The left ventricle can be decompressed in several ways. The ventricle is most
commonly vented by a catheter inserted through the junction of the right superior
pulmonary vein and left atrium. Less conveniently, a catheter can be inserted through the
left atrial appendage or superior wall of the left atrium behind the aorta. If the left atrial
approach is used, the catheter is usually advanced across the mitral valve into the left
ventricle. The left ventricle also may be vented directly through a catheter inserted into
the left ventricular apex. Lastly, a pulmonary arterial catheter may be used. Since
pulmonary veins do not have valves, a suction catheter inserted into the main pulmonary
artery decompresses the left atrium and ventricle and prevents myocardial distension.
Vented blood may be drained directly into the venous reservoir of the perfusion system
by gravity. More commonly, a roller pump is used to aspirate blood into the cardiotomy
reservoir. One-way valves in the system prevent accidental air entry into the heart;
however, once the left side of the heart is opened, all air must be carefully removed
before cardiac contractions begin.
Separate catheters are not necessary for venting the right ventricle. If the right atrium is
not open, the cavoatrial catheter adequately decompresses the right atrium and
ventricle. Separate caval catheters without caval snares reroute most of the returning
venous blood into the perfusion system, but in some individuals, caval snares must be
added to reduce pulmonary arterial blood flow and ensure against right ventricular
distension. If caval snares are used, coronary sinus blood, which is minimal during
aortic cross-clamping but which may be substantial during antegrade cardioplegia,
reaches the right atrium. This blood enters the low-pressure pulmonary vasculature and
reaches the left side of the heart but seldom causes right ventricular distension.
Cardioplegia
Various methods and solutions are employed to protect the myocardium during cardiac
operations. These are reviewed in Chapter 10. Methods vary to some extent by type of
cardiac operation and to a greater extent by surgeon preference. The most popular
method uses cold, potassium-enriched blood or crystalloid (4 to 12°C) infused
antegrade through the aortic root or retrograde through the coronary sinus. [25 ] More
recently, continuous, warm, potassium-enriched blood perfusion has been
recommended for myocardial revascularization in some centers. [26 ] , [27 ] If the aortic
root is opened, cardioplegia may be delivered directly into the coronary arteries by
handheld catheters.
Cardioplegic solutions are given through a special perfusion system that uses a roller
pump, reservoir, separate heat exchanger, and optionally, a leukocyte filter. The solution
is mixed on-line by adding preselected volumes of crystalloid cardioplegia and
perfusate using a double-channel roller pump (see Chap. 10). Temperature, pressure,
and flow rate of the cardioplegic solution are monitored closely. Many surgeons also
monitor myocardial temperature with a thermistor inserted directly into the heart.
Cell Saver
Only blood that is fully anticoagulated should pass through the heart-lung machine.
Clotting within the perfusion circuit is a major disaster and results in abrupt termination
of bypass with possible death of the patient. Large numbers of red cells may be lost if
unheparinized field blood or pericardial blood diluted by topical cooling solutions is not
retrieved by a cell saver system. Such a system usually consists of one or two suckers
powered by the wall vacuum system (Fig. 9-6) . As blood enters the sucker tip, heparin
is immediately added; blood then passes through a 20-µm filter to a reservoir where the
cells are washed and concentrated using a centrifuge. [28 ] The wash, which includes
plasma constituents and heparin, is discarded, but concentrated red blood cells are
placed into plastic bags for reinfusion as needed.
Perfusionist
Alert, attentive, well-trained perfusionists are required to assemble and operate the
heart-lung machine. Current standards encourage assignment of two perfusionists to
each patient, but often only one is present. Perfusionists are responsible for the safe,
smooth, and continuous operation of the machine and operate under the direct control
of the operating surgeon. In many cardiac operations, the surgeon alters temperature,
flow rate, and volume in the system to improve operative exposure and in all cases
bears the ultimate responsibility for the outcome of the operation. Ideally, the primary
perfusionist is in frequent contact with the operating surgeon; however, many surgeons
prefer to delegate this responsibility to the anesthesiologist.
The perfusionist receives specific instructions regarding flow rates, temperature levels,
and differential allocation of perfusate between patient and machine. The perfusionist is
responsible for monitoring pressures within the system, maintaining adequate oxygen
and carbon dioxide transfer, avoiding air intake or obstructions to flow, and maintaining
adequate perfusion and metabolism of all organs and tissues.
Schools for training cardiopulmonary perfusionists are accredited by the Council for
Allied Health Education and Accreditation (CAHEA), which is the sole accrediting body
recognized by the Department of Education of the United States government. [29 ]
Courses of instruction include didactic material and hands-on training and usually last 1
to 2 years. Matriculating students are examined by the American Board of
Cardiovascular Perfusion and, if successful, receive a certificate.
MANAGEMENT OF CARDIOPULMONARY BYPASS
Assembly of Heart-Lung Machine
The heart-lung machine is partially assembled 30 to 60 minutes before bypass is

scheduled to begin. For most cardiac surgery, the basic perfusion system and
cardioplegia, cardiotomy suction, left ventricular venting, and cell saver subsystems are
used. Partial assembly of the various components of the system requires approximately
20 minutes for bubble oxygenator systems and 30 minutes for membrane oxygenator
systems. The wheeled chassis of the basic machine contains roller pumps, space for a
centrifugal pump, and poles and clamps for the other components of the system. Usually
the perfusionist assembles the machine and primes the circuit before handing up a
sterile tubing pack containing the surgical ends of the venous, arterial, cardiotomy
sucker, vent, and cardioplegic delivery lines. The system is primed with crystalloid and
recirculated for several minutes through a sterile 0.2-to-0.5-µm filter to remove all air
bubbles and particulate emboli from the system and priming perfusate. The filter is
discarded before perfusion begins. During recirculation, the system is inspected
thoroughly, and all monitoring devices are tested.
Priming
About 2 liters of priming solution are required to prime the system for adults. The
priming solution usually consists of balanced salt solution; sometimes 500 mL of a
starch solution are added. Because of expense, albumin and plasma are rarely used.
Unless the adult patient is anemic, blood is not added to the system. Once CPB starts,
the patient's hematocrit is kept in the range of 20 to 25 percent. Some surgeons accept
lower hematocrits during perfusions at low temperatures. [30 ] If the hematocrit drops
below a predetermined concentration, homologous blood or packed cells are added to
the system. During perfusion, additional perfusate may be required to operate the
system safely. The type of perfusate added is determined by the hemoglobin
concentration.
Reducing hematocrit during cardiopulmonary bypass has a number of advantages.

First, less blood is required for operation, and the risk of serum hepatitis and viral-borne
pathogens is proportionately reduced. Second, trauma to blood cells and blood
proteins is reduced, since less blood is in the circuit. Less plasma hemoglobin is
produced. Hemodilution also increases urine flow and clearance of sodium, potassium,
and creatinine. The incidence of oliguria and acute tubular necrosis is less with
hemodilution. [31 ] Since blood is less viscous, flow characteristics are improved
through partially obstructed vessels and through smaller arterioles and capillaries,
especially during hypothermia. Hemodilution, however, does reduce intravascular
osmotic pressure and therefore increases interstitial edema. However, this
disadvantage does not offset the multiple advantages of hemodilution and blood
conservation techniques.
Anticoagulation
Heparin is absolutely required for CPB but is not an ideal anticoagulant. Directly and
indirectly, the drug contributes to operative and postoperative bleeding. The desire to
minimize blood loss and to avoid transfusion of homologous blood products has raised
questions regarding the amount of heparin needed for open heart surgery. [32 ] , [33 ]
Both the initial dose and the maintenance concentration of heparin are unsettled, but no
one recommends operation without heparin. CPB and the surgical wound produce a
powerful thrombotic stimulus that must be inhibited to prevent clots within the perfusion
system.
Heparin acts near the end of the coagulation cascade and during CPB does not
suppress production of a number of powerful serine proteases as the enzymatic
waterfall is accelerated and amplified until blocked by heparin and its essential
cofactor, antithrombin (AT). [34 ] Even though clotting does not occur, these proteases
circulate and stimulate other plasma protein systems and blood cells. Heparin prevents
clotting by activating the natural plasma protein, antithrombin (AT). AT is a large (58,000
daltons), abundant (140 µg/mL) [34 ] plasma protease inhibitor that inhibits many
proteases, including factor XIIa, kallikrein, activated complement, plasmin, and
coagulation factors IXa, Xa, XIa and thrombin. [34 ] [37 ] In general, the specificity of a
protease inhibitor for a particular protease is determined by the concentrations of the
two enzymes and the rate of association. From these data, the half-time of the inhibition
reaction can be calculated, and the fastest inhibition reaction determines the specificity
of the inhibitor for a particular protease. [38 ]
The rate of association of antithrombin for thrombin is 7200; this rate is much higher
than for other proteases. Thus thrombin is the primary target protease for antithrombin
because it has the highest rate constant and lowest inhibition half-time. Heparin
accelerates the action of AT approximately 1000-fold to achieve a second-order rate
constant for thrombin of 3.7 × 107 m-1 s-1. [39 ] Heparin acts only as a catalyst and
does not become part of the thrombin-AT complex. After the reaction, heparin is
released to catalyze another coupling, and the thrombin-AT complex is excreted through
liver and kidney. [38 ] Compared with thrombin-AT, inhibition of factor Xa is slower and
incomplete; inhibition of factor IXa is much less. [34 ]
The surgical wound and CPB produce a powerful thrombotic stimulus, and despite
activated clotting times over 400 s, thrombin is progressively formed during CPB in
every patient. [40 ] , [41 ] Open heart surgery overwhelms the ability of AT-heparin to
prevent thrombin production and circulation. F1.2, a marker of the conversion of
prothrombin to thrombin, and fibrinopeptide A (FPA), a fragment produced by
conversion of fibrinogen to fibrin, increase progressively during CPB. Standard doses
of heparin (300 to 400 units/kg) fail to completely suppress thrombin formation; as a
result, thrombin, which is a powerful protease with many different targets, circulates.
Heparin has some additional drawbacks. Standard heparin preparations vary in

anticoagulant effectiveness, and the anticoagulant effect is influenced by concentrations
of plasma antithrombin. [42 ] Heparin resistance results if plasma concentrations of AT
are low; such patients, who undergo cardiopulmonary bypass, need immediate
transfusion of fresh frozen plasma to supplement AT concentrations to increase
activated clotting times to a safe level (>400 s) before starting CPB. Approximately 0.2
to 0.4 percent of the population have congenital AT deficiency, [42 ] and newborns have
approximately half of adult concentrations. [34 ] Heparin resistance due to AT deficiency
is also encountered in premature and cyanotic infants, patients with advanced liver or
renal disease, [34 ] cachexic patients, women taking estrogens, and patients who have
had recent heparin infusions. [43 ] , [44 ]
Heparin also increases the sensitivity of platelets to various agonists [45 ] , [46 ] and
slightly increases bleeding times. [47 ] AT-heparin does not inhibit thrombin bound to
fibrin [48 ] and cannot prevent thrombin activation of platelets and fibrinogen conversion
within clots. [48 ] Heparin also contributes to the activation of neutrophils [49 ] and when
complexed with protamine is a major stimulus to complement activation. [50 ]
Heparin-induced thrombocytopenia (HIT) (platelet count < 50,000/µL) occurs in
approximately 2 to 3 percent of patients. [51 ] [53 ] On rare occasions (0.01 to 0.02
percent), heparin-induced thrombocytopenia and thrombosis (HITT) is a catastrophic
problem. [54 ] Thus heparin is not an ideal anticoagulant.
Heparin monitoring is essential during CPB to ensure that clotting does not occur, but
neither heparin nor thrombin concentrations can be measured directly in the operating
room. [55 ] The activated clotting time is the most common and simplest method used
to measure the degree of heparin anticoagulation, but this test may not be as accurate
as direct titration measurements using specially designed kits. [55 ] , [56 ] Although
heparin titration improves control of heparin dosage, the method remains an
approximation of the true hepa rin concentration as measured by a chromogenic assay
of factor Xa inhibition. Sensitivity to heparin and metabolism of heparin vary among
patients, [37 ] , [57 ] and sensitivity to the drug is decreased by prior heparin
administration before operation. [43 ] , [44 ] , [58 ] For these reasons, titration of the
amount of heparin needed to achieve a target activated clotted time (>400 s) is
recommended before CPB by some clinicians to avoid unusually prolonged activated
clotting times that may occur if a standard dose of 300 to 400 units/kg is given routinely.
[37 ]
Whether the dose of heparin is determined by pre-CPB titration or given as a fixed

dose, the activated clotting time is measured afterwards. CPB does not begin until the
activated clotting time is greater than 400 s. [59 ] It must be acknowledged that the
threshold activated clotting time of 400 s is arbitrary, since no one knows the minimum
heparin and maximum thrombin concentrations that can be circulated safely during
open heart surgery. Safety dictates an excess of heparin because too little in the
presence of too much thrombin may be catastrophic. Additional heparin is given if
needed; occasionally, fresh frozen plasma must be given to correct antithrombin
deficiency ( heparin resistance ). Activated clotting time is rechecked every 30 minutes
during bypass, and supplemental heparin is added to maintain the activated clotting
time over 400 s. If aprotinin is used and activated clotting times are measured in celite
test tubes, the combination artifactually delays clot formation and prolongs the activated
clotting time. [60 ] In this circumstance, CPB must be delayed until activated clotting
times reach 750 s. Aprotinin does not affect clotting times in kaolin test tubes [60 ] or in
heparin titration measurements. [61 ]
Protamine
After cardiopulmonary bypass has stopped and the venous cannulas are removed,
protamine (1 mg for each 100 units of heparin) is given to neutralize heparin. The
positively charged protamine molecule binds negatively charged heparin to form a
complex that no longer catalyzes antithrombin but does activate complement. [50 ] In
approximately 50 percent of patients, protamine causes transient hypotension and
reduced cardiac output. [62 ] Activated complement causes vasodilation, cardiac
dysfunction, and an increase in capillary permeability but also stimulates mast cells and
basophils to release histamine. This reaction usually responds to calcium and nearly
always is transient.
In rare instances, protamine may cause anaphylactic reactions in certain diabetics, in

patients with fish allergies, or in patients with a previous exposure to protamine.
Preexisting IgE or IgG antibodies to protamine can be demonstrated in many of these
patients. [63 ] In even rarer instances, administration of protamine causes synthesis and
release of thromboxane A2 from platelets. [64 ] This produces severe pulmonary
vasoconstriction and severely reduces left ventricular loading and cardiac output.
Immediate reheparinization and reinstitution of CPB may be required. It is not known
whether a second dose of protamine is safe, but in my experience it was once.
Following CPB, usual practice is to give 1 mg protamine for every 100 units of heparin
injected before and during CPB. Alternatively, a protamine response test may be done
to calculate the amount of protamine needed to neutralize the circulating heparin
concentration. [33 ] Sometimes, after initial protamine, residual heparin may continue to
inhibit clot formation even though the activated clotting time returns to normal values
(<120 s). [33 ] Clinically, if wound bleeding continues or clotting is poor, an additional
small dose of protamine (25 to 50 mg) often is given empirically to neutralize residual
heparin. In excessive doses protamine is a weak anticoagulant, and patients who
require considerably more than 1 mg protamine for each 100 units of heparin for full
neutralization may become anticoagulated with protamine if a protamine response test
is not done. [33 ] Calculation of individual heparin doses for CPB and use of the
protamine response test do reduce postoperative bleeding due to mismatch of the two
drugs. [33 ]
Heparin rebound describes an apparent anticoagulation effect with increased partial

thromboplastin times that occurs 1 to 3 hours after apparent full neutralization of heparin
with protamine following cardiac surgery. [65 ] Heparin is initially cleared from the
circulation rapidly due to binding by endothelial cells and macrophages and then more
slowly by renal clearance. [66 ] The half-life of the drug varies considerably among
individuals, and hypothermia decreases the rate of heparin clearance. As heparin
concentrations fall, endothelial cells release bound heparin that has not been
neutralized. Since protamine is a small molecule, it may be cleared from the circulation
before all the bound heparin is released. The problem is no longer important clinically. If
heparin rebound is suspected, a small additional dose of protamine, which can be
given without fear of an anticoagulant effect, [67 ] is all that is needed.
Platelet factor 4 (PF4) is a protein stored in platelet alpha granules that binds with high
affinity to heparin. [68 ] , [69 ] In contrast to the ionic bond between positively charged
protamine and negatively charged heparin, PF4 binds and neutralizes heparin using a
specific binding site at the C-terminus of PF4. [68 ] , [69 ] PF4-heparin complex is
cleared by liver and kidney. Recombinant PF4 (rPF4) has the same amino acid
composition and terminal sequence as native PF4 except for a unique methionine link.
[69 ] , [70 ] This protein neutralizes heparin after CPB in baboons without side effects
[71 ] and is currently in clinical trials as an alternative to protamine.
Flow Rates and Pressures
Since oxygen is not stored within the body, flow rates and perfusate oxygen-carrying
capacity must meet the metabolic requirements of all tissues and organs continuously.
Oxygen consumption at normothermia is 80 to 125 mL/min per m 2 and is similar to that
in the anesthetized adult not on bypass. [72 ] , [73 ] At 37°C, flow rates of 2.2 liters/min
per m 2 are adequate to meet metabolic requirements and to avoid metabolic acidosis
during cardiopulmonary bypass in anesthetized adults. [73 ] Generally, normothermic
flow rates of 2.5 liters/min per m 2 are used to ensure perfusion of the microcirculation
and to add a margin of safety. [74 ] Hypothermia reduces metabolic requirements and
therefore permits flow rates less than 2.2 liters/min per m 2 .
Blood pressure during normothermic cardiopulmonary bypass is generally kept in the

range of 50 to 70 mmHg (mean). In patients with known carotid arterial disease,
perfusion pressure is often increased by 10 to 15 mmHg, and the
electroencephalogram (EEG) is monitored in the operating room. An increase in
neurologic problems correlates with mean blood pressures less than 45 mmHg. [75 ]
With moderate hypothermia, blood pressures above 35 mmHg are considered safe for
patients without cerebrovascular disease. During CPB, blood pressure is controlled by
flow rate (which can be increased above 2.2 liters/min per m 2 ), intravascular volume,
and infusion of peripheral vasodilators (e.g., trimethaphan, nitroglycerin, or
nitroprusside) or vasoconstrictors (e.g., methoxamine, phenylephrine, or
norepinephrine). A deeper level of anesthesia also helps to reduce blood pressure.
Safety Monitors
A number of safety monitors are available for extracorporeal perfusion systems, but
none replaces the complete attention of alert perfusionists. Patient monitors are
presented in Chapter 7. The perfusionist continuously monitors perfusion flow rate
(using an electromagnetic flowmeter), venous return and reservoir volume, arterial line
blood oxygen saturation, arterial line pressure, and nasopharyngeal and rectal or
bladder temperatures. Temperatures of both inflow and outflow blood in the perfusion
circuit and temperature of cardioplegic solutions are monitored routinely. Measurement
of venous blood oxygen saturation is optional. During cardioplegia, the perfusionist
monitors rate of cardioplegia flow and perfusion pressure and often follows myocardial
temperature. Perfusionists report obstructions of cardiotomy suction and vent catheters.
Optional safety devices include an electronic level-sensing device on the venous (or
arterial) reservoir upstream to the pump to detect dangerously low levels of perfusate
within the system. Some perfusionists also measure oxygen saturation in the arterial
line. An arterial line ultrasound bubble detector is another optional safety feature.
Temperature
Metabolic activity, and thus oxygen consumption, decreases with decreasing body
temperature (Fig. 9-7) . Oxygen consumption decreases by 50 percent for every 10°C
decrease in body temperature. [72 ] There are advantages and disadvantages of
moderate hypothermia during cardiopulmonary bypass. [74 ] Since hypothermia
reduces oxygen requirements, flow rates can be reduced without production of lactate
or metabolic acidosis. [73 ] Below 28°C, flow rates of 1.6 liters/min per m 2 are safe for
as long as 2 hours. [72 ] Reduced body temperature enhances the safe duration of
cardiac ischemia after infusions of cold cardioplegia by reducing the temperature
difference between the heart and body. Moderate hypothermia adds safety to the
perfusion, since more time is available for repairs if perfusion must be interrupted
because of accidents in the surgical field or failure of the perfusion apparatus. The extra
time required to rewarm is the major disadvantage of hypothermia. Hypothermia also
alters the reactivity of some blood elements, particularly platelets, and affects the
metabolism of heparin.
Various organs and tissues within the body cool and rewarm at different rates. In
general, the rate of cooling or rewarming is proportional to the blood flow per unit of
tissue mass. [72 ] , [76 ] Thus small organs with large proportionate blood flows cool and
rewarm rapidly (e.g., kidney, adrenal, heart); large tissue masses, such as skeletal
muscle or fat, cool and rewarm slowly. Because of its sensitivity to ischemic injury, brain
temperature, as estimated by nasopharyngeal temperature, must be monitored closely.
Brain blood flow at 80 to 90 mL per 100 g is intermediate between that of heart and
nonworking skeletal muscle. [76 ]
Recent practice tends to carry out some relatively short operations at normothermia or
only modest hypothermia (e.g., 32 to 34°C). [77 ] , [78 ] Normothermic CPB is reported
to reduce systemic vascular resistance and blood loss during the early postoperative
period, [78 ] but the practice also decreases cerebral venous oxygen saturation,
particularly during the early period of perfusion. [74 ] Improved cardioplegic techniques
that better maintain protective low cardiac temperatures or provide continuous
perfusion of the coronary vasculature at 37°C during aortic cross-clamping are essential
features of normothermic CPB.
Deep Hypothermia and Circulatory Arrest
Deep hypothermia is a clinical term used for nasopharyngeal temperatures below

20°C. The techniques of deep hypothermia and low perfusion flow (0.5 liter/min per m 2
) or circulatory arrest are used when blood flow to the brain must be interrupted
temporarily (e.g., aneurysms involving the aortic arch, pulmonary thromboembolectomy,
or during repair of certain complex congenital heart lesions).
Cooling is achieved by perfusion in combination with a hypothermia blanket beneath the

patient and ice packing around the head if the period of circulatory arrest is expected to
exceed 20 minutes. [79 ] Both nasopharyngeal and rectal or bladder temperatures are
monitored; occasionally, esophageal temperature is also observed. During cooling,
temperature differences between patient and perfusate are limited to 10 to 14°C to
avoid microembolism when cold blood enters the warm patient. Infants cool and rewarm
rapidly as compared with adults, and caloric exchange is proportional to body mass,
rate of perfusion flow, and temperature differences between perfusate and patient. [72 ]
It is essential to cool long enough to reduce temperatures of the brain to desired levels
(see Fig. 9-7) ; for adults, at least 30 minutes of cooling before reducing or stopping
flow are recommended. Surface hypothermia without extracorporeal perfusion is no
longer used because of the danger of arrhythmias at temperatures below 32°C and the
threat of ventricular fibrillation at temperatures below 30°C.
Perfusion cooling requires special considerations. Cooling increases blood viscosity,

but hemodilution reduces viscosity and facilitates uniform distribution of blood flow even
at low temperature. [76 ] Cooling also shifts the oxygen-hemoglobin saturation curve to
the left; this impairs release of oxygen from hemoglobin at low oxygen tensions. At very
low temperatures, cell metabolism depends primarily on dissolved oxygen, which is
increased in cold plasma. Below 18°C, plasma oxygen tensions must decrease to very
low partial pressures for hemoglobin to release bound oxygen. Lastly, hyperglycemia
appears to be detrimental to the brain at low temperature and is associated with
increased postoperative evidence of brain ischemia. [80 ]
Temperature also affects acid-base balance, and management of both pH and co 2 is

of special concern during deep hypothermia. [81 ] Two commonly used management
protocols are termed pH-stat and alpha-stat . The advantages and drawbacks of each
protocol are not settled, and the subject is under active investigation. [82 ] [84 ] If
measurements of blood co 2 below 37°C are corrected for temperature (pH-stat
protocol), co 2 must be added to blood to maintain pH at 7.4 at the low temperature.
This protocol produces an excess of hydrogen ions in the perfusate but may increase
cerebral blood flow during cooling and rewarming and hasten recovery of anaerobic
metabolism. [83 ] However, the effect on cerebral vascular autoregulation and sensitivity
to co 2 remains controversial. [79 ] , [84 ] The alternative alpha-stat protocol is easier
and does not correct blood measurements made at 37°C for the lower temperature; this
produces a relative alkalosis and a low paco 2 . By not correcting for temperature, the
buffering capacity of an important blood buffer, the alpha-imidazole group of histidine, is
maximized, [79 ] and the function of other important enzymes, including lactate
dehydrogenase and phosphofructokinase, is maintained. [85 ] It is not yet clear which
protocol is associated with the greater number of postoperative neurologic problems.
[79 ] , [86 ]
The safe duration of circulatory arrest below 20°C is not precisely known. The brain is
susceptible to ischemic (metabolic) injury, emboli, and perhaps a poorly understood
cold injury that occurs sporadically at temperatures below 12°C. [87 ] Experimental
evidence clearly shows that 90 minutes of circulatory arrest at 18°C are associated with
a high incidence of neurologic injury and prolonged abnormalities of cerebral blood flow
and oxygen metabolism, [82 ] , [88 ] but neurologic injuries and abnormalities of
cerebral metabolism occur during deep hypothermia even if blood flow is not
interrupted. [89 ] Quantitative electroencephalography is recommended as a method for
monitoring the state of brain metabolism during periods of circulatory arrest. [88 ]
Circulatory arrest is usually not initiated until the nasopharyngeal temperature is below
18°C; for longer anticipated periods of arrest, cooling is continued to 13 to 15°C. [79 ]
At these temperatures circulation has been stopped for up to 2 hours without neurologic
problems. [79 ] , [90 ] However, the incidence of stoke in adults and developmental
abnormalities in infants correlates with longer arrest times. [79 ] , [86 ] , [90 ] A history of
cerebrovascular disease, age, and prolonged duration of CPB also increase the
likelihood of postoperative neurologic problems.
RETROGRADE CEREBRAL PERFUSION
Retrograde cerebral perfusion (see Chap. 10) combined with deep hypothermia is an
alternative method to protect the brain during circulatory arrest. [91 ] [93 ] The superior
vena cava is perfused with cold blood (12 to 15°C) at 20 to 30 mmHg [94 ] , [95 ] (Fig.
9-8) . Blood exits the head via the carotid arteries, and provision must be made to
decompress the aortic arch to avoid backpressure if the ostia of the cerebral vessels
are not exposed. Flow rates range from 250 to 800 mL/min, but only a small portion
perfuses the brain. [95 ] , [96 ] Retrograde cerebroplegia has been used safely for up to
2 hours, [95 ] , [96 ] but shorter perfusions are recommended until more is known
regarding the distribution of blood flow within the brain and safety of the technique. The
method can maintain cerebral oxygen saturation, as monitored by cutaneous oximetry,
within 10 percent of the normal range. [96 ] The method is associated with a reduced
incidence of postoperative neurologic injuries. [95 ] , [96 ]
The entire body also can be perfused retrograde using separate superior and inferior
caval catheters. Perfusion pressures are maintained below 30 mmHg; blood
temperature is 13 to 15°C; flow rates vary between 150 and 250 mL/min per m 2 . This
technique, which has not achieved widespread application, has been used during
arterial circulatory arrest for operations on the aortic arch and descending thoracic
aorta. [97 ]
Dialysis and Ultrafiltration
Hemodialysis and/or ultrafiltration is easily accomplished during CPB by connecting a

hollow fiber exchange unit to the extracorporeal perfusion circuit. [98 ] These units are
often connected to the arterial line of the perfusion system downstream to the pump.
Processed blood is returned to the cardiotomy suction reservoir. Alternatively, blood
may be taken from the venous line or any reservoir in the system and pumped through
the dialysis or filtration unit. The dialysate is pumped countercurrent through the unit by a
separate pump or pulled through the filtration unit by vacuum. Additional heparin is not
required, but because heparin may be removed, activated clotting times should be
monitored carefully.
Filtration units remove plasma water and low-molecular-weight solutes. [98 ] Negative
pressure is applied on one side of a porous membrane to draw fluid off; no dialysate is
used. Blood flows on the other side of the membrane. Rate of fluid exchange is
proportional to the pressure difference across the membrane, pore size (10 to 35 Å),
thickness of the membrane, rate of blood flow, and colloid osmotic pressure in the
blood compartment. [98 ] Low temperature decreases the rate of filtration. Pore size
determines the molecular weight of solutes that are removed. Ultrafiltration units can
remove very large amounts of plasma water (e.g., 15 liters) during CPB and are
sometimes used after CPB to raise the hemoglobin concentration. Unlike the cell saver,
ultrafiltration removes water but does not remove most plasma proteins.
Dialysis units perfuse the nonblood side of a semipermeable membrane with a liquid
dialysate. The dialysate is pumped countercurrent through the unit by a separate pump
or pulled through the unit by vacuum. Solute concentrations in the dialysate control
removal of specific substances from the blood. Pore sizes in the membrane are slightly
larger (50 Å) than in ultrfiltration units. [98 ] Dialysis units are able to remove excess
potassium, urea, other metabolic wastes, and plasma water and are usually used in
patients who are dialysis-dependent. [99 ]
Emergency Cardiopulmonary Bypass
In emergency situations within or outside the operating room, partial cardiopulmonary

bypass is rapidly initiated by cannulation of the femoral artery and vein. For best results
outside the operating room, a resuscitation team should be organized and trained and
necessary equipment and supplies should be preassembled. [100 ] The method of
cannulation primarily depends on whether or not the circulation has arrested, availability
of personnel and equipment, and other circumstances. If a circulation is present,
femoral and venous cannulas are inserted percutaneously over guidewires. A cutdown
is used to insert catheters under direct vision if the vessels are not easily entered.
Heparin must be given (300 units/kg) before cannulas are inserted. Perfusion flow rates
are usually limited by the volume of systemic venous blood returning to the heart-lung
machine. [7 ] If a femoral or jugular venous catheter is advanced into the right atrium, full
flow rates of 2.2 liters/min per m 2 can be achieved.
If cardiac arrest or ventricular fibrillation occurs during operation before the chest is
opened, full bypass can be initiated by either accelerating the operation or by rapid
cannulation of the femoral vessels. Rapid cannulation of the aorta and right atrium is
fastest for patients who have not had a previous operation; groin cannulation is perhaps
most expedient for reoperations. If massive bleeding occurs during the initial dissection,
administration of heparin, cannulation of the aorta or femoral artery, and aspiration of
shed blood by the cardiotomy suction system permit partial perfusion until the site of
hemorrhage is controlled.
Blood Conservation
Current practice stresses the need for blood conservation and transfusion avoidance,
and 40 to 65 percent of open cardiac operations can be performed without the use of
homologous blood and blood derivatives. [101 ] [103 ] Furthermore, many patients can
tolerate postoperative anemias as low as 9 g of hemoglobin without difficulty and can
replenish their own red cells within 1 month with added iron. Erythropoetin is an
expensive but effective method to accelerate replenishment of the red cell mass in
postoperative patients who wish to avoid transfusion. [104 ]
Improved blood screening tests have greatly reduced the risk of blood-borne pathogens
from homologous donors. [105 ] , [106 ] The risk of transmitting HIV by transfusion is
estimated to be between 1 in 450,000 and 1 in 660,000. [105 ] , [107 ] The risk of
posttransfusion hepatitis C is approximately 3 cases per 10,000 transfusions. [106 ]
Nevertheless, the fear of transfusion-related HIV infection remains in the minds of many
patients despite the low risk. Furthermore, there is evidence that homologous blood
transfusion increases the risk of postoperative bacterial infections. [103 ] Nonlethal
morbidity of blood transfusions, such as fever and allergic and delayed hemolytic
reactions, and costs [108 ] are also incentives for limiting homologous blood
transfusions.
To reduce the risk of blood-borne pathogens, some patients donate 1 or 2 units of their
own blood before scheduled operations. This practice reliably reduces the chances of
acquiring a blood-borne pathogen, but only a small percentage of adult patients who
have open heart surgery actually donate. [108 ] , [109 ] Emergency operation, age,
anemia, type of heart disease, symptoms, and logistic problems are some of the
reasons autologous donation is not more common. Moreover, preoperative autologous
blood donation is not cost-effective for the small decrease in risk of blood-borne
pathogens. [108 ]
Autologous blood can be protected from exposure to the heart-lung machine by

removing 1 or 2 units of heparinized blood shortly before or at the time of starting CPB.
[101 ] Alternatively, plasmapheresis can be done in the operating room to preserve
platelets and soluble clotting factors without reducing the circulating red cell mass. [102
] The sequestered blood or plasma is reinfused after CPB ends. In most reports this
practice reduces postoperative blood loss. [101 ] [103 ] , [110 ]
Meticulous surgical hemostasis is the cornerstone of any blood conservation program;
careful hemostasis before heparin and CPB is as important as hemostasis after
administration of protamine. During operation, all shed blood, except that adsorbed on
sponges and drapes, is recovered by either cardiotomy suction or the cell saver
system. Even heavily soaked sponges can be wrung out into a basin and aspirated into
the cell saver system. Cell-saving devices scavenge shed, nonheparinized blood from
the surgical field. This blood is washed and centrifuged to prepare packed cells; no
other blood constituents are saved by the method. Blood lost from chest tubes after
operation may be reinfused directly after filtration [111 ] , [112 ] or as washed packed
cells if the collection and processing are done aseptically. Filtered blood directly infused
from chest tubes has few coagulation factors, has high concentrations of fibrinopeptide
A, and probably should be washed and returned as packed cells. [113 ]
Plasmin inhibitors: tranexamic acid, epsilon-aminocaproic acid, and aprotinin reduce

postoperative blood loss and transfusion requirements by 40 to 50 percent in first-time
and reoperative patients and in patients who have ingested aspirin. [114 ] [119 ]
Aprotinin also attenuates the expected increase in postoperative bleeding times [114 ]
and appears to have a platelet-sparing effect. [120 ] These drugs must be given before
skin incision and, in the case of the aminocarbocyclic acids, must be continued up to 10
hours after operation to be maximally effective. [117 ] , [118 ] , [120 ] Indications,
contraindications, pharmacology, dose schedules, and results with these antifibrinolytic
drugs are presented fully in Chapter 8.
Newer attempts to reduce bleeding associated with CPB involve pharmacologic

preservation of platelets [54 ] , [121 ] [123 ] and strategies to more carefully monitor
heparin dosage [37 ] , [56 ] (see Anticoagulation, p. 264). Rerouting all wound blood into
the cell saver system, [124 ] topical aprotinin, [125 ] and biologic glues and sealants
[126 ] are other investigative strategies to conserve blood during CPB.
OTHER APPLICATIONS OF EXTRACORPOREAL PERFUSION
This technology is sometimes called extracorporeal membrane oxygenation (ECMO),

particularly when used to provide circulatory assistance after open heart surgery, but the
preferred term is extracorporeal life support (ECLS). The concept is to provide
circulatory and/or respiratory support using a basic extracorporeal perfusion system
over a period of days or a few weeks until the native heart or lungs recover. [127 ] [130 ]
The basic extracorporeal circuit for ECLS consists of a venous cannula, reservoir,
centrifugal or servo-controlled roller pump, membrane oxygenator, heat exchanger, and
either an arterial or second venous cannula. [131 ] A bridge is necessary between the
inflow and outflow perfusion lines to permit recirculation of minimally anticoagulated
blood during weaning tests. Either a spiral coil or hollow fiber (blood outside)
oxygenator is used. A heat exchanger is needed to maintain body temperature at 37°C.
An ultrafiltration or dialysis unit can be included in the circuit if necessary. Heparin is
given as an initial bolus (approximately 100 units/kg) and then as a constant infusion to
maintain activated clotting times between 180 and 200 s. Activated clotting times are
measured every 30 minutes. Patients usually need transfusions of packed cells to
maintain hematocrits around 45 percent and platelets and fresh frozen plasma
periodically to replace clotting factors and to control bleeding from cannulation sites and
wounds.
For respiratory support in a variety of clinical problems including acquired respiratory

distress syndrome (ARDS) and lung transplantation, [132 ] venovenous perfusion is
usually preferred [130 ] (Fig. 9-9) . Venous blood is withdrawn from a jugular, iliac, or
femoral venous catheter and returned to a different large vein. Flow rates are enhanced
if the large-bore inflow catheter is advanced over a wire into the right atrium. [7 ] In
neonates a single double-lumen venous catheter can be used for venovenous perfusion.
The extracorporeal circuit removes co 2 and adds oxygen to blood that is mixed with
hypercarbic, desaturated venous blood returning from peripheral tissues. No circulatory
support is provided. This technique provides excellent respiratory assistance, allows the
native lungs to be rested (i.e., ventilated at an F IO 2 of 0.5 and inspiratory pressures of
less than 40 mmHg), and simplifies cannulation. [129 ] , [131 ]
Venoarterial perfusion provides circulatory and respiratory support and often is used
after open cardiac surgery in patients who fail to be weaned from cardiopulmonary
bypass, who have biventricular failure, and who are believed to have reversible cardiac
dysfunction. In these patients CPB is essentially continued until the native heart
recovers, but the perfusion circuitry is altered to permit temporary closure of the chest
and transfer out of the operating room. Only one venous cannula is needed; one right
atrial cannula can be retained, or a peripheral cannula can be inserted over a guidewire
into the right atrium from a femoral or iliac vein. Usually the aortic cannula is shifted to a
femoral artery to more easily monitor bleeding. Wound bleeding is controlled by surgical
means. The native heart continues to beat.
When used to provide intermediate-term circulatory and respiratory support in patients

who do not have a fresh sternotomy, a single venous cannula is inserted percutaneously
or by cutdown into a large peripheral vein and advanced over a wire into the right
atrium. The femoral or iliac artery is also cannulated, but provision must be made to
supply both the proximal and distal artery to prevent ischemia of the leg. In neonates,
children, and a few adults the arterial catheter has been inserted into a carotid artery
with ligation of the distal vessel. This technique has been surprisingly free of neurologic
injury, but experience in adults is still relatively sparse. [133 ]
Bleeding is the major complication of ECLS [128 ] and is sometimes difficult to control
because of the need for heparin. Antifibrinolytic drugs, platelets, and fresh frozen
plasma and return to the operating room for surgical hemostasis are the principal
remedies.
ECLS reduces right ventricular preload and afterload but increases left ventricular
afterload and wall stresses in dysfunctional hearts [134 ] (Fig. 9-10) . This drawback can
be offset partially by insertion of the intraaortic balloon pump. [135 ] If the native heart is
unable to eject during ECLS, the prognosis is poor.
In selected adults, survival of ECLS for ARDS is approximately 50 percent. In neonates

with respiratory insufficiency, survival rate is 80 to 90 percent. [136 ] When used for
circulatory support following open heart surgery, survival rate in infants and children is
35 to 45 percent [137 ] ; adult survival rates are slightly lower. [130 ] , [132 ]
Left Ventricular Assistance
The most common indication for temporary left ventricular assistance is failure to wean
from CPB after heart surgery. [138 ] Other indications include bridging to transplantation
and treatment of cardiogenic shock after acute myocardial infarction or other causes of
acute cardiac decompensation. The method complements and to some extent
competes with long-term ECLS but has the advantage that an oxygenator is not
required and trauma to blood elements is much less. Left ventricular circulatory
assistance using components of the heart-lung machine also competes with newer
devices that are described in Chapter 11.
The basic circuit consists of an inflow cannula inserted into the left atrium or ventricle, a
venous reservoir, a centrifugal pump, and an arterial cannula. A heat exchanger is
usually not needed, although perfusion lines are wrapped with silver foil to decrease
heat loss. Flow is monitored by an electromagnetic flowmeter and is strongly influenced
by the position of the catheter in the left side of the heart, left-sided heart loading by the
right ventricle, and left-sided heart blood volume. The position of the left atrial catheter is
critical for maintenance of flows of 2 to 4.5 liters/min. Volume and flows are adjusted to
maintain ejection by the native heart to prevent intracardiac clot formation. Activated
clotting times are maintained between 140 and 180 s with an infusion of heparin.
When a patient cannot be weaned from CPB, temporary left ventricular assistance is
most easily implemented by inserting a wire-wrapped catheter directly into the left
atrium through either the left atrial appendage or the junction of the right superior
pulmonary vein and left atrium. This catheter is connected directly to a centrifugal pump
that is connected to either the existing arterial cannula in the ascending aorta or to a
new catheter inserted percutaneously or under direct vision into the femoral or iliac
artery. The venous reservoir is connected by a T-connector upstream to the pump.
Perfusate is added to the reservoir, which is clamped closed except when solution is
added.
In contrast to ECLS, left ventricular assistance reduces left ventricular volumes of

dilated, poorly contracting hearts at both end-diastole and end-systole [139 ] (Fig. 9-11)
. In some instances temporary left ventricular assistance actually improves myocardial
contractility in postischemic hearts. [139 ] In effect, temporary left ventricular assistance
rests the contracting, ejecting, injured heart and perhaps enhances prospects for
recovery by reversing myocardial creep.
Temporary left ventricular assistance can be used without thoracotomy. A catheter is

introduced into the jugular or femoral vein and is passed across the interatrial septum
into the left atrium using fluoroscopy and/or echocardiography. [140 ] Left atrial blood is
pumped into an arterial catheter inserted into either a femoral or iliac artery.
Other applications of extracorporeal technology are used to assist various operative

procedures. Left ventricular assistance is used frequently to preserve blood flow to the
lower body during resection of descending thoracic aneurysms. The inflow catheter is
usually inserted into the left atrial appendage or left atrium through a pulmonary vein but
can be inserted directly into the left ventricular apex or into the ascending aorta. A
modification of this technique, used by me, consists of venoarterial bypass without an
oxygenator. A catheter is inserted into the femoral or iliac vein and passed into the right
atrium. Partially saturated blood is perfused by the centrifugal pump directly into the
femoral or iliac artery; after returning to the right atrium, this blood mixes with venous
blood from the upper body that contains more oxygen and less carbon dioxide. These
methods prevent ischemia of the lower body, require activated clotting times between
160 and 180 s, and minimize trauma to blood elements.
PATHOLOGIC PHYSIOLOGY OF CARDIOPULMONARY BYPASS
Hemodynamics
During CPB blood is circulated without a pulse by a mechanical pump that is

independent of physiologic controls. Many physiologic reflexes are set aside or
modified by changes in temperature, acid-base balance, hemodilution, heart rate and
volume, and vasomotor tone caused by production and release of a host of vasoactive
substances. Intravascular pressures, particularly venous pressures, stray outside normal
ranges. Plasma colloid osmotic pressure is reduced, capillary permeability increases,
and massive fluid retention occurs.
Clearly, nonpulsatile flow is abnormal; however, nonpulsatile extracorporeal perfusion is

technically easier than pulsatile perfusion. No conclusive data indicate that nonpulsatile
blood flow is detrimental for short-term perfusions lasting several hours at
recommended flow rates. [141 ] , [142 ] Roller and centrifugal pumps, which are simple,
inexpensive, and reliable, deliver a shallow sinewave pulse that is essentially
nonpulsatile. During CPB, pulseless and nonpulsatile blood flows at 37°C have
inconsequential differences in distribution within the body. [143 ] Pulseless blood flow
provided by a mechanical heart does not adversely affect the physiology of calves
perfused for 9 to 34 days. [144 ] On the other hand, various experimental studies
suggest that at low blood flow rates, pulsatile blood flow improves tissue perfusion and
capillary blood flow over that produced by nonpulsatile flow. [141 ] At present, possible
benefits of pulsatile blood flow during short-term CPB or ECLS do not justify the
additional hardware and expense required to produce a pulse in vivo.
CPB increases blood flow to the stomach, intestines, and adrenal glands, [145 ] but
pulsatility does not affect the distribution of blood flow. [143 ] Deep hypothermic
perfusion does not prevent the increase in stomach, intestinal, and adrenal blood flow
but does cause a decrease in brain and renal blood flow. [77 ]
CPB decreases systemic vascular resistance, but there is considerable variability

among patients. Deep hypothermia also reduces systemic vascular resistance. [146 ]
Activation of Blood Constituents
During open cardiac surgery, blood, which normally glides over endothelial cells,
encounters the plastic and metal surfaces of the heart-lung machine and the wound.
This contact activates plasma enzyme systems and blood cells, dilutes and denatures
plasma proteins, and introduces contaminants and foreign materials into the perfusate.
A host of vasoactive substances [147 ] that affect capillary permeability [148 ] and
vasomotor tone is generated. The perfusate becomes an angry, enzymatic stew that
causes massive fluid retention and intercompartmental fluid shifts, [149 ] multiple organ
dysfunction, [150 ] [152 ] showers of emboli, [153 ] and unique bleeding complications.
[67 ] Temporary dysfunction of nearly every organ ensues. A massive defense
reaction-aptly termed the whole-body inflammatory response -is initiated. [154 ]
ADSORBED PLASMA PROTEINS
When heparinized blood touches a nonendothelial cell surface, plasma proteins are
instantly adsorbed onto the surface to produce a protein layer 100 to 200 Å thick [155 ]
(Fig. 9-12) . The final thickness of the protein layer varies with the biomaterial and the
conditions and duration of exposure. Chemical and physical characteristics of the
surface influence the amounts and distribution of surface-adsorbed proteins, but so far
no physical or chemical attribute or attributes predict the molecular topography of the
protein mosaic. [156 ] , [157 ] The amounts of adsorbed proteins are not proportional to
bulk plasma concentrations. Hydrophobic surfaces adsorb more fibrinogen than
hydrophilic materials. [157 ] Adsorbed surface proteins are both reactive and mobile
[158 ] and differ from those in the bulk layer and from plasma. Surface proteins change
over time and respond to their environment. Adsorbed fibrinogen rapidly undergoes
conformational changes, loses its ability to recognize fibrinogen antibody, [159 ] is
partially displaced by an activated form of high-molecular-weight kininogen, [160 ] and
no longer binds platelets. [159 ] , [161 ] Other plasma proteins are also adsorbed.
Albumin, factor XII, prekallikrein, high-molecular-weight kininogen, von Willebrand
factor, fibronectin, thrombospondin, hemoglobin, and immunoglobulins all adsorb onto
the surface in various amounts that differ between surfaces. [162 ] A dynamic
equilibrium between circulating and adsorbed surface proteins is quickly established for
each synthetic material. Over time, adsorbed proteins desorb or are degraded and
replaced by new proteins. [162 ]
All nonendothelial cell surfaces produce a thrombotic stimulus, but the intensity of the
stimulus varies among surfaces. Rough surfaces are more thrombogenic than smooth,
[163 ] and some materials are more thromboresistant and bind fewer cells than others.
[164 ] However, we do not know the surface protein mosaic that confers
thromboresistance [158 ] and cannot predict the thrombogenicity of any biomaterial in
advance of testing. [40 ] Beyond the need for smoothness and chemical inertness, the
physical and chemical characteristics of surfaces that reduce the thrombotic stimulus
are not defined. Heparin coatings change the composition and perhaps the reactivity of
surface proteins but continue to produce a thrombotic stimulus. [165 ] , [166 ] In contrast
to all known biomaterials, endothelial cells are not covered by a protein layer, selectively
attract plasma proteins by expressing specific receptors, produce both anti- and
procoagulants, and remain in direct contact with flowing blood. Only endothelial cells are
able to maintain the fluidity of blood and the integrity of the vascular system
simultaneously.
ACTIVATION OF BLOOD ELEMENTS
CPB activates at least five plasma protein systems and five blood cells during perfusion
of heparinized blood. The vasoactive substances, enzymes, and microemboli produced
by activation of these protein systems and cells mediate much of the morbidity
associated with CPB.
Contact system
The contact system consists of four primary plasma proteins: factors XII and XI,
prekallikrein, and high-molecular-weight kininogen (HK). [167 ] When blood contacts a
negatively charged surface, factor XII cleaves into factor XIIa and factor XIIf.
Prekallikrein and HK must be present. Factor XIIa cleaves prekallikrein to produce
kallikrein. Kallikrein greatly accelerates cleavage of factor XII in a feedback loop and
thus amplifies activation of the contact system. Surface-adsorbed proteins provide
sufficient negative charges to activate factor XII. The activated forms of factor XII directly
initiate activation of the intrinsic coagulation pathway, complement, and neutrophils.
Intrinsic coagulation pathway
In the presence of HK, factor XIIa also activates factor XI, the fourth protein of the
contact system. Activation of factor XI to factor XIa initiates the intrinsic coagulation
pathway that proceeds through factor IX to activate factor X (Figure 9-13) . Factor Xa
converts prothrombin to thrombin. Thrombin catalyzes the conversion of fibrinogen to
fibrin. This pathway provides a major coagulation stimulus during all applications of
extracorporeal perfusion technology.
Extrinsic coagulation pathway
Open cardiac surgery produces a large wound that directly stimulates thrombin
formation by the extrinsic coagulation pathway. Most tissues, although not pericardial
cells, [21 ] express tissue factor. [168 ] Tissue factor is an integral membrane
glycoprotein that is present and constitutively expressed on most nonvascular cells and
can be induced by various agonists in endothelial cells and monocytes. In the wound,
tissue factor, which does not circulate, is expressed by epicardium, vascular adventitia,
and monocytes. Tissue factor rapidly binds to factors VII and VIIa to initiate the extrinsic
pathway that proceeds to activate factor X [169 ] (see Figure 9-13 ). The activated form
of factor X, factor Xa, is produced by both the intrinsic and extrinsic coagulation
pathways and is the gateway protein of the common coagulation pathway. Although
there is overlap of the two pathways, [169 ] the intrinsic pathway is not particularly
involved in wound hemostasis.
Complement
The fourth plasma protein system activated during extracorporeal perfusion is the
complement system. [170 ] Like the coagulation system, two separate pathways
activate the gateway complement protein C3 to form C3a and C3b. Factor XIIa,
produced by the contact system, activates C1 of the classic pathway. The alternative
system, thought to be the principal complement activation pathway during CPB, [170 ] is
activated by generation of 3b by the classic pathway or by hydrolysis of a third bond of
C3 [171 ] to produce C3bBb. C3bBb, the C3 convertase produced by the alternative
pathway, cleaves C3 to produce more C3bBb and also activates C5 to C5a and C5b.
C5a directly activates neutrophils, and C5b initiates formation of the membrane attack
complex that is capable of producing cell lysis and death.
Complement is also activated by the classic pathway [49 ] that involves C1, C2, and C4
and in sequential steps forms C4b2a. C4b2a is the C3 convertase of the classic
pathway and cleaves C3 to form C3a and C3b. [171 ] C4b2a, with the help of C3b, also
activates C5 to form C5a and C5b. The classic pathway proceeds in sequential steps,
but the alternative pathway contains a feedback loop (C3bBb) that serves to amplify
complement activation. Both the alternative and classic pathways are activated during
CPB, but amplification of the alternative system predominates.
C3a and the terminal attack complex, C5b-9, increase progressively during CPB. [170 ]
, [172 ] Protamine also activates complement. [50 ] Many factors, including steroids,
[173 ] type of oxygenator, [174 ] , [175 ] biomaterials within oxygenators, [176 ] , [177 ]
inhibitors, [178 ] [180 ] and surface-bound heparin, [172 ] , [181 ] , [182 ] alter the
amounts of C3a and membrane attack complex produced during CPB. Plasma heparin
actually inhibits C3 convertase and complement activation by a mechanism that is
independent of antithrombin. [183 ]
C3a, C5a, and C4a are anaphylatoxins that contribute to the inflammatory response by
increasing capillary permeability, [184 ] altering vasomotor tone, impairing cardiac
function, [185 ] and activating neutrophils (C5a) [186 ] and mast cells. [187 ] However,
recent studies indicate that the membrane attack complex (C5b-9) is also responsible
for neutrophil activation and some aspects of platelet activation and that inhibition of
C5b-9 prevents up regulation of neutrophil CD11b receptors, expression of platelet
GMP-140 receptors, and formation of platelet-neutrophil and platelet-monocyte
conjugates. [188 ] The membrane attack complex also directly causes cell lysis and can
cause vesiculation of platelet and endothelial cell membranes. [189 ] , [190 ]
Fibrinolysis
The fifth plasma protein system activated during CPB is the fibrinolytic system. [191 ]
During CPB, endothelial cells, stimulated by thrombin, [192 ] produce tissue
plasminogen activator (t-PA), [193 ] which cleaves plasminogen to plasmin. t-PA
primarily activates plasminogen adsorbed onto fibrin. Fibrinolysis, as demonstrated by
detection of plasma d-dimer, [193 ] progressively increases during CPB and primarily
occurs in blood aspirated from the wound by the cardiotomy suction system. [124 ]
Platelets
Open heart surgery activates platelets and causes a decrease in platelet numbers and
function and an increase in postoperative bleeding times. The magnitude of
thrombocytopenia and platelet dysfunction appears to vary among perfusion systems
and patients [15 ] , [194 ] but is a major cause of postoperative bleeding.
Platelets are activated during open heart surgery, and aside from the wound, heparin is
the initial platelet agonist. Heparin increases the sensitivity of platelets to soluble
agonists [195 ] and modestly increases bleeding times. [196 ] After CPB starts,
generation of thrombin probably activates platelets and causes some circulating
discoid platelets to develop pseudopods, express glycoprotein IIb/IIIa receptor
complexes, aggregate, adhere to surface-adsorbed fibrinogen, and release granule
contents. [15 ] , [194 ] As CPB continues, activated complement (C5b-9), [188 ]
thrombin, [197 ] plasmin, [196 ] hypothermia, [198 ] platelet-activating factor (PAF),
cathepsin G, serotonin, epinephrine, and other agonists also activate platelets and
contribute to their loss and dysfunction.
During CPB, platelets adhere to binding sites located on surface-adsorbed fibrinogen

[199 ] and form aggregates. [200 ] Platelets also express GMP-140 (P-selectin)
receptors and, using this receptor, [201 ] form aggregates with circulating monocytes
and, to a lesser extent, neutrophils. [202 ] Both surface adhesion of platelets and platelet
aggregation primarily involve the glycoprotein IIb/IIIa receptor complex (fibrinogen
receptor) [203 ] , [204 ] and do not involve the glycoprotein Ib receptor, which is more
important for hemostasis in the wound. Surface density of platelet glycoprotein Ib
receptors, however, decreases during CPB, [205 ] possibly because low circulating
concentrations of plasmin cause reversible internalization of the receptors. [206 ] , [207 ]
Platelet adhesion occurs almost instantly, [203 ] but the density of platelet accumulation
varies with the chemical and physical attributes of the surface. [208 ] Surface-bound
heparin surfaces appear to decrease platelet adhesion. [166 ] , [209 ] Rough surfaces
accumulate more platelets than smooth surfaces. [163 ] As perfusion continues, some
adherent platelets detach, leaving behind fragments of platelet membrane. [210 ]
Platelet membrane fragments also detach and circulate. [199 ] , [210 ] Platelet
adhesion, platelet aggregation, and blood dilution are the major causes of
thrombocytopenia during CPB.
A small percentage of platelets, both attached and circulating, release granule contents.
Alpha granules contain several coagulation and chemotactic proteins; a soluble form of
the adhesion receptor, GMP-140 [211 ] ; and factors that increase capillary permeability
and smooth muscle cell proliferation. Dense granules contain ADP and ATP, calcium,
and serotonin. Lysosomes contain potent acid hydrolases and neutral proteases.
Activated platelets also synthesize and release thromboxane A2, and a potent
vasoconstrictor and powerful platelet agonist. [212 ] Thromboxane A2 has a critical role
in platelet hemostasis and a half-life in plasma of approximately 30 s. Release of
thromboxane A2, lysosomes, and other granular contents contributes to the systemic
inflammatory response.
At the end of CPB, the circulating platelet population is a heterogeneous mixture that
probably varies among patients and perfusion systems. Hemodilution, adhesion,
aggregation, release, and destruction reduce platelet numbers by 30 to 50 percent. [15 ]
, [194 ] Some platelets are intact and discoid; others show pseudopod formation. [194 ]
Some larger platelets recently arrived from the bone marrow are present. Partially and
completely degranulated platelets are also present, as are platelet membrane
fragments and resealed platelets. The majority of the reduced numbers of platelets
appear morphologically normal. [194 ]
The functional state of the circulating intact platelet during and early after CPB is
reduced, but it is not clear whether this functional defect is intrinsic or extrinsic to the
platelet or both. Circulating platelets still express glycoprotein IIb/IIIa and glycoprotein Ib
receptors when measured by flow cytometry. [47 ] , [188 ] Heparin increases bleeding
times modestly, [47 ] , [196 ] but bleeding times, which correlate with platelet function,
remain prolonged for several hours after protamine is given. Plasmin protects platelet
glycoprotein Ib receptors during CPB [206 ] , [207 ] but may impair platelet glycoprotein
Ib-von Willebrand factor interaction afterwards. [213 ] The membrane attack complex
increases platelet GMP-140 expression and formation of platelet-neutrophil and
platelet-monocyte conjugates. [188 ] Analysis of shed blood from bleeding time wounds
shows reduced platelet sensitivity to agonists and reduced concentrations of plasma
thromboxane B2. [47 ] The relative contributions of extrinsic platelet inhibition and
intrinsic change of circulating platelets during CPB are under active investigation.
Reversal of extrinsic platelet inhibitory factors, such as plasmin, [114 ] and the addition
of new platelets to the circulation [214 ] tend to speed restoration of normal platelet
function, [215 ] but protection of platelets from activation and development of intrinsic
defects during the period of CPB [122 ] also may be necessary to restore bleeding
times to normal at the time protamine is given. However, at the present time, the end
result of clinical CPB is an increase in bleeding time [15 ] , [67 ] that requires 4 to 12
hours to return to the normal range.
Neutrophils
During CPB, leukocyte counts decrease in response to dilution and then increase
moderately after operation. [216 ] , [217 ] Only a few neutrophils attach to synthetic
surfaces and platelets. [202 ] , [218 ] Several agonists activate circulating neutrophils
during CPB: C5a, [186 ] , [188 ] C5b-9, [188 ] kallikrein, [219 ] factor XIIa, [220 ]
interleukin-1, [221 ] and less strongly, neutrophil-activating peptide 2 (NAP-2) from
platelets are all neutrophil agonists. The MAC-1 receptor (CD11b/CD18) is a cell
adhesive protein that is up regulated during CPB [222 ] , [223 ] and is particularly
involved in neutrophil chemotactic responses and intravascular locomotion. [224 ] [226 ]
MAC-1 receptors also bind various coagulation proteins and may have a role in
thrombogenesis. [222 ] During CPB, neutrophils generate leukotriene B4, a potent
chemotactic and aggregating product of arachidonic metabolism. [224 ]
Neutrophils release a variety of enzymes and cytotoxic substances, including elastase,

myeloperoxidase, several lysosomal enzymes, cytotoxic neutral proteases, and reactive
chemicals that include hydroxyl radicals, hydrogen peroxide, and hypobromous and
hypochlorous acids. [216 ] , [224 ] [227 ] [229 ] , [230 ] Although recent studies fail to
show a correlation between neutrophil elastase release and postoperative pulmonary
dysfunction, [231 ] , [232 ] CPB induces activated neutrophils to accumulate in the lungs,
where they increase capillary permeability and interstitial edema. [150 ] , [227 ]
Activation of neutrophils during CPB results in the release of multiple vasoactive and
cytotoxic substances and cellular agonists (e.g., platelet-activating factor, cathepsin G)
and therefore has a central role in the inflammatory response associated with CPB.
[231 ]
Monocytes
Monocytes are also activated during CPB, but the speed of activation is much slower
than the rapid responses of other blood elements. C3b may be a mechanism by which
monocytes are activated, [233 ] but it is likely that other agonists including contact with
biomaterials, [234 ] C5b-9, [188 ] and endotoxin contribute. Monocytes form conjugates
with platelets via the GMP-140 receptor, [201 ] adhere to foreign surfaces, [235 ] and
express tissue factor and monocyte chemotactic activating factor. [21 ] , [235 ]
Monocytes also produce and release cytokines during and after extracorporeal
perfusion. Interleukin 8 (IL-8) and to a lesser degree IL-6 increase during CPB [217 ] ,
[236 ] and afterwards. IL-1, Il-2, and IL-4 usually increase after bypass. [217 ] , [231 ] ,
[237 ] Changes in plasma concentrations of tumor necrosis factor (TNF) are not
conclusive; it does not change or increases slightly late in the process. [217 ] , [231 ] ,
[238 ] Monocytes express tissue factor and up regulate MAC-1 receptors during
simulated extracorporeal perfusion of human blood [235 ] and during clinical open
cardiac surgery. [21 ] , [202 ]
Endothelial cells
Endothelial cells are the fourth blood cell activated by CPB. Although these cells do not
circulate, endothelial cells are in constant contact with blood and cover a surface area
estimated to be between 1000 and 5000 m 2 in an adult. [239 ] Endothelial cells
maintain the fluidity of blood, influence vascular tone, and maintain the integrity of the
vascular system by active metabolic processes. [239 ] Endothelial cells produce
prostacyclin; heparan sulfate; thrombomodulin and protease nexin 1, both of which
remove thrombin; protein S, which accelerates the natural anticoagulant protein C;
tissue factor pathway inhibitor, which regulates the extrinsic coagulation pathway; and
tissue plasminogen activator (t-PA). Endothelial cells produce vasoactive substances,
such as nitric oxide (endothelial cellderived relaxing factor), PGI2, endothelin-1, [147 ] ,
[240 ] and platelet-activating factor (PAF), and inactivate others, such as histamine,
norepinephrine, and bradykinin. [239 ] During CPB, endothelial cells produce t-PA,
probably in response to thrombin. [192 ] Plasminogen activator inhibitor increases only
slightly. Prostacyclin concentrations increase rapidly at the beginning of CPB and then
begin to decrease. [212 ] Endothelin-1 peaks several hours after CPB ends. [241 ]
Lymphocytes
CPB decreases the total number of lymphocytes and specific subsets of lymphocytes.
The mechanism is not clear, but the effect is to weaken the immune response. CPB
decreases the ability of monocytes to present antigen and to synthesize IL-1 [242 ] and
decreases B-lymphocytes, natural killer cells, T-helper cells, and T-suppressor
lymphocytes for 3 to 7 days. [243 ] Responses to various agonists and mitogens are
depressed. [242 ] IL-2 and -interferon production by T-lymphocytes is reduced, [242 ] ,
[244 ] as is CD4+ and IL-2 receptor expression. [245 ] Delayed hypersensitivity
responses to antigen panels are attenuated in the majority of patients after CPB. [245 ]
Changes in lymphocytes, cytokines, complement proteins, and immunoglobulins and
reduced white cell phagocytosis after CPB increase the susceptibility of postoperative
patients to infection.
Consequences of Blood Activation During CPB
BLEEDING
Nonsurgical bleeding complications associated with CPB are related to heparin,

platelets , and fibrinolysis . Deficiency of soluble coagulation factors is a rare cause of
bleeding during and after open heart surgery, and if normal concentrations are present
before operation, dilution and slight consumption of factor V during CPB do not
decrease concentrations to levels that interfere with clotting. [246 ] Bleeding due to
reduced plasma coagulation proteins is most likely seen in patients with congenital or
acquired coagulation protein deficiencies, uremia, or severe cachexia and in infants or
children with deep cyanosis, polycythemia, and reduced plasma volumes.
Several CPB-related bleeding problems are related to heparin. These include

antithrombin (AT) deficiency, heparin resistance, and heparin rebound, which were
discussed earlier (p. 264), and heparin-induced thrombocytopenia (HIT).
Heparin-induced thrombocytopenia (HIT) occurs in 2 to 5 percent of patients who

receive heparin, and heparin-induced thrombocytopenia and thrombosis (HITT) occur in
0.1 to 0.2 percent. [52 ] , [53 ] HIT causes bleeding, but HITT causes thrombosis that is
often catastrophic. Since these diseases are different manifestations of the same
mechanism, both are discussed here. In susceptible patients, exposure to heparin
induces formation of IgG antibodies against heparin. Heparin binds with platelet factor 4
(PF4), but in patients with heparin-induced IgG antibodies, the heparin-IgG complex
binds to PF4 and the platelet Fc receptor on the platelet surface. [247 ] PF4 is the
recently discovered, long-sought cofactor that is essential for binding and activation of
the platelet. Bound complex stimulates platelet aggregation and sometimes release to
produce a pronounced decrease in the number of circulating platelets. [248 ] HIT is
defined as a 40 to 50 percent decrease in platelet count in the absence of another
reason. [249 ] Continued or subsequent exposure to heparin produces
thrombocytopenia with platelet counts below 50,000 per microliter, usually 5 to 10 days
after the exposure. [250 ] Treatment of HIT requires stopping heparin, including heparin
flushes and locks, and giving platelet transfusions to prevent internal bleeding. Platelet
counts return to the normal range in about 5 days. [249 ] , [250 ] In the absence of
bleeding, platelet transfusions are given for platelet counts below 30,000 per microliter;
if bleeding occurs, platelet transfusions are needed for control.
Laboratory tests for HIT and HITT measure platelet aggregation and/or serotonin
release when the patient's plasma is added with heparin to normal platelets. [248 ] ,
[250 ] , [251 ] However, before a patient receives heparin, laboratory tests are negative
and therefore do not predict which patients will develop heparin-induced IgG antibodies.
The IgG antibodies often disappear within 10 days, [250 ] but reexposure can trigger
reformation of heparin-induced antibodies in as little as a few hours. Because cardiac
patients are universally exposed to heparin before cardiac surgery, an argument can be
made to test every patient for heparin-induced antibodies before operation.
Unfortunately, at the present time the test is not widely available, and preoperative
testing is not standard practice. [250 ]
Two clues may alert clinicians to the possibility of HIT or HITT. A fall in platelet count to
less than 50 percent of preheparin counts and any past or present history of a venous or
arterial thromboembolic complication associated with heparin are warning signs. [249 ]
, [250 ]
Management of patients with evidential or suspected HIT follows one of two strategies,
but experience is anecdotal and is not standardized. [252 ] Low-molecular-weight
heparins are less likely than standard heparin to induce heparin antibodies, but they do
not completely remove the risk. [52 ] Heparinoids are least likely to produce HIT or HITT.
[253 ] , [254 ] Another anticoagulant, such as recombinant hirudin, [255 ] may be used in
lieu of heparin. The defibrinogenating venom ancrod has been used for deep vein
thrombosis and for anticoagulation after CPB in a patient with HITT. [257 ] Following
CPB, there is no reversing antidote for either recombinant hirudin or ancrod, and the
very low concentrations of fibrinogen after ancrod render the patient susceptible to
internal as well as external bleeding. The second strategy involves platelet anesthesia
during the period of CPB. Iloprost, an analogue of prostacyclin, has been used
successfully in a series of patients [54 ] but must be given with large doses of
phenylephrine because of profound vasodilatation. Aggressive plasmapheresis with
partial inhibition of platelets with aspirin also has been used successfully. [258 ]
Any evidence of venous or arterial thrombosis with or without organ or limb ischemia in
association with platelet counts below 40 to 50 percent of preoperative counts raises
the possibility of HITT. [249 ] , [250 ] All heparin must be stopped immediately with the
suspicion of HITT; more heparin to prevent further thrombosis only aggravates the
disease. Laboratory tests should confirm the presence of IgG antibodies, but results
provide only retrospective confirmation. HITT often involves small and medium-sized
arteries that are occluded with platelet aggregates and fibrin with relatively few red cells
(white clot) [259 ] and are difficult to reopen. Thrombolytic therapy is seldom successful
and may be contraindicated in thrombocytopenic patients with fresh surgical wounds.
Surgical or catheter embolectomy may be helpful in some patients but is often
unsuccessful. Once HITT occurs, treatment is prevention of more platelet aggregates
and management of the ischemic damage produced by the disease.
The deficiency in platelet numbers and function after CPB is a major cause of
postoperative bleeding. Thrombocytopenia is due to dilution, platelet adhesion to circuit
surfaces, aggregation, and activation and removal of damaged platelets by the
reticuloendothelial system. At the end of CPB, platelet counts are usually above
100,000 platelets per microliter but are 30 to 50 percent lower than preoperative values.
[15 ] , [194 ] Bleeding times are approximately double prebypass values. Over the next
few hours, platelet counts do not change consistently, but bleeding times shorten
progressively and return to normal within 4 to 12 hours; platelet counts reach the normal
range in 3 to 7 days.
During CPB, endothelial cells produce tissue-type plasminogen activator (t-PA), which
primarily converts fibrin-bound plasminogen to plasmin. [193 ] Although most plasmin is
bound, small amounts of unbound plasmin circulate. Lysis of bound fibrin tends to
increase bleeding. The success of the antifibrinolytic agents aprotinin and
aminocarbocyclic acid in reducing postoperative blood losses strongly suggests that
fibrinolysis contributes to bleeding. Fibrinolytic activity is very high in blood aspirated
from the wound. [260 ] To be effective, antifibrinolytic agents must be given at the
beginning of surgery to prevent binding of plasminogen to fibrin and inhibition of
fibrinolysis in the surgical wound. [261 ]
EMBOLI AND THROMBI
CPB produces a variety of large and small emboli that can be reduced but not totally
prevented by filtration [262 ] (Table 9-2) . A depth filter or a 40-µm (pore size) arterial
line screen filter removes macroemboli (>100 µm); screen filters with smaller pore sizes
increase the pressure difference across the filter and interfere with pump flow. During
CPB, arterioles, precapillaries, and capillaries are bombarded with microemboli (<40
µm), but cell death is diffusely distributed and involves relatively few cells in any one
location. For the most part, microembolization during CPB is not detected but can be
documented by special studies. [263 ] [265 ]
The majority of particulate emboli are aspirated from the wound by cardiotomy suckers
and include fibrin, fat, calcium, cellular debris, talc, suture material, and other foreign
materials. [262 ] In addition, aspiration of large quantities of air produces
nitrogen-containing microbubbles. Nitrogen is poorly soluble in plasma; therefore, these
microbubbles are more dangerous than those of oxygen or carbon dioxide. All blood
aspirated from the surgical field must be filtered and allowed to settle to enhance
removal of microbubbles.
Blood activation and trauma produce fibrin emboli, macroaggregates of denatured

proteins and lipoproteins, fat globules, and platelet and leukocyte aggregates. [262 ] ,
[263 ] The amount is directly proportional to the duration of CPB. Bubble oxygenators
produce microbubbles of oxygen. [263 ] Foreign material also may enter the perfusion
system. Homologous blood contains platelet and leukocyte aggregates, fibrin, lipid
precipitates, and red cell debris and should be filtered before it is added to the
perfusate. [262 ] Crystalloid solutions may contain inorganic debris, and dust may
remain on the inside of commercially produced tubing. Roller pumps cause spallation of
bits of the compressed tubing. [262 ] Arterial line filters remove most but not all emboli
over 40 µm.
Thrombosis during CPB can occur if the heparin dose is inadequate. There is no
rationale for giving inadequate doses of heparin (activated clotting times less than 400
s) to reduce bleeding. Such practice risks microscopic fibrin emboli and catastrophic
thrombosis and is more likely to increase bleeding than to decrease it.
Massive air embolism from a perfusion accident is rare. More commonly air remains in
the left side of the heart or aortic root after the aortic clamp is removed and the heart
begins to beat. Transesophageal echocardiography is helpful in ensuring removal of all
air prior to releasing the aortic clamp.
The surgical procedure is the most important source of macroemboli and microemboli
that produce lasting damage to the central nervous system. [265 ] [267 ] In an autopsy
study Blauth et al. [268 ] found that atherosclerotic emboli are present in 16.3 percent of
patients after CPB. Cannulation and manipulation of the ascending aorta, particularly in
patients with soft atheromatous material in the aorta, are a major source of
atheromatous macroemboli. [266 ] , [268 ] Routine intraoperative echocardiographic
examination of the ascending aorta before cannulation decreases the incidence of
perioperative embolic stroke. [269 ] Microemboli also are produced during cardiac
surgery and cause postoperative neuropsychologic deficits in proportion to the numbers
of emboli. [266 ] , [267 ] Surgical steps, particularly aortic cannulation and manipulation
of either the heart or the aorta, correlate with the highest production of microemboli.
[266 ]
VASOACTIVE SUBSTANCES AND HORMONES
The combined stresses of anesthesia, surgery, anticoagulation, hypothermia, and CPB

trigger a hormonal stress response and a massive defense reaction compounded by
hemodilution and nonpulsatile flow that is largely independent of physiologic controls.
Dilution of blood at the beginning of CPB reduces initial concentrations of cortisol [269 ]
and 3,5,3-triiodothyronine (T3), [270 ] [272 ] but plasma levels of cortisol increase during
perfusion, continue to increase after CPB, and remain elevated postoperatively for
more than 48 hours. [269 ] , [273 ] In contrast, total T3 and free T3 remain well below the
normal range for at least 24 hours after CPB. [270 ] , [272 ] Epinephrine and
norepinephrine increase progressively three- to fourfold during perfusion, but dopamine
concentrations remain relatively unchanged. [147 ] Blood glucose concentrations
increase in response to the increased concentrations of the stress hormones. Pituitary
responses are generally depressed during CPB and immediately thereafter. [272 ] ,
[274 ] , [275 ] , [274 ] , [275 ] Other hormones involved in the stress reaction,
vasopressin, angiotensin II, renin, and atrial natriuretic factor, generally increase or are
not changed appreciably. [147 ] , [274 ]
The defense reaction produced by activation of at least five plasma protein systems
and most blood cells produces a host of vasoactive substances that mediate a
whole-body inflammatory response that is unique to open heart surgery. [147 ] , [229 ] ,
[231 ] , [236 ] , [276 ] Vasoactive substances are defined as chemicals or proteins that
alter the contractile state of cardiac myocytes, vascular smooth muscle, or endothelial
cells. Table 9-3 presents a list of known vasoactive hormones and substances that are
altered by CPB. [147 ] , [217 ] , [236 ] , [277 ] These substances affect myocardial
contractile force, blood volume, distribution of blood flow, vascular resistance, blood
pressure, fluid balance, and capillary permeability. Plasma proteases, platelets,
neutrophils, monocytes, mast cells, and endothelial cells are the sources of most of the
autocoids, eiconsanoids, cytokines, and cytotoxic substances that produce the
inflammatory response. Although many of these vasoactive substances circulate and
can be detected in the perfusate, chemotactic substances [224 ] , [278 ] and expression
of surface membrane receptors [199 ] , [201 ] also target specific blood cells to specific
organs (e.g., lung) or the wound. When added to the stresses of anesthesia and
surgery, CPB turns homeostasis into physiologic and biochemical chaos.
The diversity and complexity of the CPB-initiated defense reaction are in the process of
description and understanding, [147 ] , [231 ] and efforts to control various subsystems
of this massive reaction are only beginning. At present, the tolerance and success of
CPB rest on marginal control of physiologic and biochemical stresses by natural
protease inhibitors and clearance mechanisms that evolution has provided. Because
interrelationships of participating mediators and target cells are only partially
understood, the significance and importance of specific alterations are primarily of
investigational rather than clinical interest. The clinician is concerned with the
consequences, not the details, of the biochemical and physiologic chaos. These
problems are presented below, but it is worth remembering that the problems are
mediated primarily by the host of altered vasoactive substances and myriad of emboli
produced by the heart-lung machine.
Triiodothyroidinine
Changes in the concentrations of the thyroid hormones during and after open heart
surgery are consistent with the euthyroid sick syndrome [270 ] , [279 ] and raise the
question of possible benefits of thyroid supplements. The biochemistry and
pharmacology of the thyroid hormones are exceedingly complex and incompletely
understood, but T3 acutely enhances sarcoplasmic reticulum ca 2+ - AT Pase activity
and may improve myocardial diastolic relaxation and protect myocardium from
excessive calcium uptake during reperfusion after ischemia. [280 ] , [281 ] Studies have
shown that T3 improves recovery of left ventricular function after ischemia in porcine
hearts [282 ] and after cardioplegia and transplantation in patients, [283 ] , [284 ] as well
as in patients with chronic congestive heart failure. [279 ] The mechanism of action of
the hormone in postcardioplegic hearts and the need for supplements in postoperative
patients remain under active investigation.
Endotoxins
Endotoxins are structural fragments of bacteria that trigger the body's defense reaction.
Lipopolysaccharides derived from the walls of gram-negative bacteria are particularly
powerful agonists for complement, neutrophils, and monocytes. Endotoxins have been
detected during CPB [285 ] [288 ] and after aortic cross-clamping. [289 ] [290 ] Sources
of endotoxins include infusion solutions, [285 ] bypass tubing, [285 ] [288 ] and the
gastrointestinal tract. [287 ] Aside from contaminants, congestion of the gastrointestinal
tract during CPB due to a relative increase in blood flow [76 ] and/or loss of pulsatile
perfusion [291 ] and depressed Kupffer cell function are believed the major causes of
endotoxemia. Endotoxins are potent agonists of blood elements, but with modern
methods of providing pyrogen-free supplies and managing CPB, their importance as a
cause of postoperative morbidity is not clearly established. [287 ] , [288 ]
FLUID BALANCE
CPB causes massive fluid retention and intercompartmental fluid shifts. Intermittent or
sustained increases in systemic venous pressure raise capillary filtration pressure.
Hemodilution dilutes plasma protein concentrations and decreases colloid osmotic
pressure. Capillary permeability increases [148 ] due to circulating vasoactive
substances [147 ] that cause endothelial cells to contract and widen intercellular
junctions. The coefficient for Starling's law of fluid exchange across capillaries
increases, [148 ] enabling water, electrolytes, and small molecules to pour into the
extracellular compartment. The interstitial compartment may increase 18 to 33 percent,
[149 ] but CPB does not alter intracellular fluid balance. As compared with
normothermic perfusions, hypothermia tends to reduce fluid accumulation.
The increase in interstitial fluid is restrained by increases in interstitial fluid pressure

and slight dilution of interstitial proteins. Interstitial fluid pressure is influenced by the
rapidity of lymph flow and by the compliance of the interstitial space, [292 ] which varies
for different organs and tissues.
ORGAN DYSFUNCTION
Heart
It is difficult to separate cardiac dysfunction due to CPB from that due to operative
manipulations, the disease being treated, early consequences of surgery on ventricular
mechanics, and myocardial ischemia and reperfusion changes. CPB produces
endothelin-1, which constricts coronary arteries, and C3a, a negative inotrope [185 ]
and powerful agonist for neutrophils. Myocardial stunning is inevitable during aortic
cross-clamping. [292 ] During reperfusion following aortic cross-clamping, neutrophils
are activated and adhere to endothelial cells and cardiac myocytes via MAC-1
(CD11b/CD18) adhesion receptors. [294 ] , [295 ] Activated intracardiac neutrophils
release free oxygen radicals and other cytotoxins [296 ] [298 ] during and after aortic
cross-clamping. Monoclonal antibodies against the MAC-1 receptor attenuate
neutrophil adhesion, edema, and myocardial diastolic dysfunction. [295 ] Both
myocardial edema and distension of the flaccid cardioplegic heart [24 ] reduce
contractility. When the heart contracts poorly, the high afterload produced by CPB
during the weaning process increases wall stress and myocardial oxygen consumption.
[134 ] Although the final performance of the heart depends on many variables, aortic
cross-clamping and activation of complement and neutrophils by CPB contribute to
cardiac dysfunction early after operation.
Lung
CPB temporarily impairs lung function. Activation of complement and neutrophils

causes sequestration of neutrophils in the pulmonary microvasculature [170 ] , [299 ]
[301 ] and release of peroxidation products, particularly after release of the aortic
cross-clamp. [299 ] Activated neutrophils produce perivascular edema [300 ] and
increase pulmonary capillary permeability and interstitial edema. Although there is
direct evidence of pulmonary neutrophil sequestration and activation, [170 ] , [299 ]
postoperative pulmonary dysfunction does not correlate with neutrophil elastase
release, [217 ] nor is it reduced by leukocyte filtration. [302 ]
CPB changes the composition of alveolar surfactant [303 ] and reduces its ability to
maintain alveolar stability. Atelectasis develops and continues to be a problem during
the first 48 hours after CPB ends. Functional residual volume and pulmonary
compliance decrease. [304 ] The work of breathing increases. The physiologic shunt
and alveolar arterial oxygen difference increase. In occasional patients blood
extravasates into alveoli to produce the acute respiratory distress syndrome. Incisional
pain, reduced compliance, increased atelectasis, increased work of breathing,
increased shunting, and interstitial edema contribute to postoperative pulmonary
dysfunction.
Central nervous system
CPB is associated with a significant incidence of stroke and other neurologic problems.
The incidence of stroke ranges between 1 and 5 percent [305 ] and is higher in older
patients, those with symptomatic carotid arterial disease, [265 ] or those with severe
atherosclerotic disease of the ascending aorta. [264 ] , [268 ] The majority of strokes
are embolic and related to cannulation, surgical manipulations, and CPB. [265 ] There
is little evidence that lack of pulse pressure affects postoperative neurologic function.
[306 ]
Careful neuropsychologic tests demonstrate subtle neurologic injuries in up to 50

percent of patients. [265 ] , [307 ] , [308 ] In some patients, deficits are temporary, but in
as many as one-third of these patients, neuropsychologic deficits are still present at 1
year. [308 ] Microemboli are the most likely cause of these subtle deficits.
Deep hypothermia and circulatory arrest are associated with a significant number of
postoperative neurologic injuries. [89 ] The major causes of injury are ischemia and
emboli, but excessive cooling below train temperatures of 10 to 12°C also may cause
postoperative neurologic dysfunction. [79 ] , [87 ]
Kidney
Prolonged CPB, hemodilution, circulating hormones, low perfusion pressure, diuretics,

hypothermia, aprotinin, [309 ] microemboli, and hemolysis all affect renal function.
Temporary renal dysfunction as assessed by urine protein analysis occurs in every
patient. [310 ] Preoperative renal status and periods of low cardiac output that CPB are
the most important predictors of postoperative renal insufficiency. [151 ] Reduced renal
perfusion pressure stimulates renin release and angiotensin II production, which
decrease renal blood flow. Increased aldosterone and vasopressin raise sodium and
water resorption. When plasma binding proteins become saturated from excessive
hemolysis, hemoglobin precipitates in renal tubules. Kidneys have high blood flow and
are bombarded with microemboli. Without hemodilution, renal blood and plasma flow,
creatinine clearance, free water clearance, and urine volume decrease. [311 ]
Hemodilution attenuates most of the detrimental effects of CPB on renal function.

Hemodilution improves outer cortical and total renal blood flow; increases creatinine,
electrolyte, and water clearance; and increases glomerular filtration and urine volume.
[311 ] After CPB, renal function, which is so important for restoration of fluid balance,
largely reflects preoperative renal function, postoperative cardiac output, any toxic drugs
given, microemboli, and any ischemia injuries incurred during CPB.
Gastrointestinal organs
The liver, pancreas, and intestinal tract are subjected to vasoactive substances and
microemboli, but few clinical manifestations result. Some liver enzymes increase slightly
early after CPB, and mild jaundice appears in 10 to 20 percent of patients. [312 ] The
connection between CPB and occasional patients who develop severe jaundice and
hepatic failure is unclear. Clinical appearance of jaundice increases the risk of death,
[313 ] and fulminant hepatic failure is uniformly fatal. [314 ] Up to 27 percent of patients
develop a slight increase in blood amylase and approximately 8 percent have clinical
symptoms and signs, but less than 1 percent of patients develop necrotizing
pancreatitis. [315 ] Postoperative gastritis, ulcers, and occasional lower gastrointestinal
(GI) bleeding are consequences of stress and preexisting factors but are not directly
related to CPB. Duodenal or gastric bleeding is by far the most common postoperative
GI complication [313 ] and not infrequently requires endoscopic and occasionally
operative intervention. Rare patients may develop a vasculitis of mesenteric vessels
that produces severe and often fatal intestinal ischemia postoperatively. This
catastrophic complication usually occurs in octogenarians and near-octogenarians and
is heralded by abdominal pain, loss of peristalsis, a sharp leukocytosis, and
angiographic evidence of severe ischemia. If suspected and diagnosed early,
intramesenteric arterial infusion of papaverine may alleviate the spasm and save the
bowel; laparotomy and bowel resection are usually futile. This uncommon problem may
be a late manifestation of a CPB injury. [315 ]
OTHER COMPLICATIONS OF CPB
Massive Air Embolism
Massive air embolism occurs in 0.1 to 0.2 percent of perfused patients, and
approximately half these patients suffer permanent neurologic damage or death. [316 ] ,
[317 ] The open architecture of extracorporeal perfusion systems offers numerous entry
portals for large amounts of air. When recognized at operation, retrograde cerebral
perfusion with hypothermia and venting of the aortic arch may preempt permanent injury.
[316 ] Prompt institution of hyperbaric compression also may alleviate some of the
permanent sequelae of massive air embolism.
Arterial Catheters
Postoperative bleeding is the most common complication of aortic cannulation.

Occasionally, an atherosclerotic plaque may be dislodged during cannulation, but the
cannulation procedure itself is associated with significant production and dissemination
of macro- and microembolic material. [266 ] , [268 ] Aortic dissection is a rare
complication of aortic cannulation and is more common after cannulation of the femoral
artery. [318 ] Dissection can be detected immediately after starting extracorporeal
perfusion by transesophageal echocardiography. Insertion of femoral or iliac catheters
over guidewires reduces the possibility of dissection or rupture of the vessel. Femoral
arterial cannulation also may produce postoperative ischemic complications of the
ipsilateral leg and is associated with occasional groin wound infections.
Venous Cannulas
If air enters the venous cannula from a loose connection or from a leak around the
cannula at its site of insertion during CPB, obstruction to venous return may occur from
air lock. Tubing kinks, forgotten clamps, and obstruction of the intake port of the cannula
against the wall of the vein are other causes of obstruction to venous return. Tears in the
thin-walled right atrium or cavae occasionally occur and sometimes are difficult to
repair. Cannulas in the superior vena cava may partially obstruct venous return before
and after bypass and decrease cardiac filling and output.
This complication may occur with or without surgical closure of the pericardium.
Accumulation of blood around atria and ventricles compromises ventricular filling and
contractility and can occur even in the presence of patent mediastinal chest tubes.
Reduced cardiac output, increased right atrial pressure (relative to left atrial pressure),
blood pressure variation with respiration (pulsus paradoxicus), widening of the
mediastinum, and a sudden decrease in mediastinal chest tube drainage raise the
possibility of pericardial tamponade in the early postoperative period (see also Chap.
44).
Postpericardiotomy Syndrome
This syndrome is characterized by one or more of the following signs or symptoms:
malaise, fever, pericardial effusion, leukocytosis, pleuritic chest pain over the left chest,
electrocardiographic abnormalities, and pericardial friction rub. This syndrome typically
appears 1 to 2 weeks after cardiac surgery, may last 3 to 5 weeks, and is usually
self-limited. Most patients respond to nonsteroidal anti-inflammatory compounds, but in
more severe cases, steroids may be required. The etiology of the postpericardiotomy
syndrome is not clear, but it has been associated with increased viral antibody titers in
some patients, particularly children. [319 ]
CONTROL OF THE COMPLICATIONS OF CPB
Substitutes for Heparin
The inadequacies of standard heparin for CPB have stimulated attempts to develop
alternatives. These alternatives include binding heparin onto surfaces of the perfusion
circuit, using recombinant desulfatohirudin (r-hirudin), using low-molecular-weight
heparin, or adding factor Xa inhibitors with heparin.
SURFACE-BOUND HEPARIN
Heparin can be attached to certain plastic materials by ionic or covalent bonds.

Ionic-bound heparin leaches into the circulation [320 ] ; covalent bonds prevent leaching.
The commercially available Carmeda (Medtronic, Inc.) heparinized surface covalently
binds partially degraded heparin attached to spacer arms (100 Å) to laminated
biomaterial surfaces. [321 ] The competing Duraflo II heparin coating (Baxter Health
Care, Inc.) ionically binds standard heparin using a proprietary process that retards
heparin leaching. [320 ] Surface-bound heparin reduces platelet adhesion. [209 ] , [322 ]
When heparin-coated circuits are used without systemic heparin for up to 7 days in
animal perfusions, macroscopic clotting does not occur, and plasma fibrinogen
concentrations are not reduced. [323 ]
Surface-bound heparin reduces complement and granulocyte activation [172 ] , [181 ] ,

[182 ] , [327 ] , [328 ] , [330 ] , [331 ] and reduces circulating cytokines IL-6 and IL-8.
[332 ] In one study this reduction in markers of the inflammatory response correlated
with decreased clinical signs of inflammation. [331 ] Heparin-coated perfusion circuits
attenuate activation of platelets in some studies [165 ] , [166 ] , [209 ] but not others.
[321 ] , [325 ] , [330 ]
Heparin-coated circuits do not reduce thrombin formation or activity, [165 ] , [166 ] and
F1.2 formation is significantly higher at the end of bypass in patients perfused with
coated circuits and reduced doses of systemic heparin even though macroscopic
clotting does not occur [330 ] (Fig. 9-14) . When these circuits are used for life support
without systemic heparin, the incidence of visible thrombus within the ventricle or pump
head is 27 percent. [331 ]
In first-time revascularization patients, both Carmeda- and Duraflo II-coated systems

have been used with reduced doses of systemic heparin (usually 150 units/kg) and
activated clotting times around 280 s. [181 ] , [320 ] , [324 ] , [325 ] , [329 ] , [330 ] , [332
] Authors reported 4.5 to 24 percent reductions in postoperative blood loss [324 ] , [325
] , [329 ] , [330 ] , [332 ] , and small [329 ] or insignificant [324 ] , [325 ] , [330 ] , [332 ]
decreases in transfusion requirements. However, in a recent clinical study involving use
of surface-bound heparin circuits and half-dose systemic heparin in conjunction with a
comprehensive program of blood conservation that included aspiration of all wound and
pericardial blood into the cell saver system (instead of the cardiotomy suction system),
significant reductions in blood loss, transfusion requirements, length of ventilatory
support, intensive care, hospital stay, and perioperative myocardial infarction were
found. [333 ] Blood aspirated from the pericardium contains large amounts of thrombin
[21 ] and plasmin, [124 ] and exclusion of this blood from the perfusate decreases
postoperative blood loss [23 ] and probably is as important as using the coated circuits.
The clinical benefits of the comprehensive program and lack of complications are only
partially related to the heparin-coated circuitry and reduced systemic heparin
concentrations; exclusion of wound thrombin and plasmin from the perfusate is equally
important.
Clinical experience with reduced systemic heparin indicates that higher doses of
thrombin can be circulated safely in first-time revascularization patients during CPB
[330 ] and that this practice may have clinical benefits. [327 ] , [333 ] The agonist effects
of reduced concentrations of heparin on blood elements may be attenuated, [196 ] and
higher concentrations of circulating thrombin may decrease bleeding, especially if
wound blood is excluded and fibrinolysis is inhibited after CPB ends. [333 ]
Unfortunately, it is not possible to monitor circulating thrombin in the operating room in
real time, and it is not known what concentration of thrombin causes clot formation
within the CPB circuit. For these reasons, successful use of heparin-coated perfusion
circuitry and reduced systemic heparin require strict adherence to protocols designed
to avoid stagnation [329 ] and to reduce the addition of thrombin to the perfusate. [333 ]
The safety margins of these methods are not known; the evidence is empirical and
specific for first-time myocardial revascularization operations; extrapolation of this
experience to different patients and different protocols may or may not be safe.
RECOMBINANT DESULFATOHIRUDIN
Recombinant desulfatohirudin (r-hirudin) is a small, tight-binding, specific thrombin

inhibitor that directly inhibits soluble thrombin and thrombin bound to fibrin in clots.[48 ]
The second-order rate constant for native hirudin is 3.25 × 10 [7 ] mol/liter per s, [334 ]
which is similar to AT-heparin (3.7 × 10 [7 ] mol/liter per s). [335 ] However, during in
vitro simulated extracorporeal perfusion, r-hirudin is not as effective as standard heparin
in attenuating the expected increase in F1.2 or FPA. [336 ] These results may be due to
the fact that heparin partially inhibits factor Xa in addition to thrombin. R-Hirudin has
been used successfully during clinical CPB in a woman with heparin-induced
thrombocytopenia and thrombosis. [255 ] At the present time, there is no antidote,
analogous to protamine, for r-hirudin.
LOW-MOLECULAR-WEIGHT HEPARIN
Low-molecular-weight (LMW) heparins are fractions of standard heparin (MW 4000 to

6500) that inhibit thrombin and factor Xa by catalyzing antithrombin. [337 ] , [338 ] For
the same degree of thrombin inhibition, low-molecular-weight heparins are two to four
times more avid factor Xa inhibitors than standard heparin. [337 ] LMW heparins have a
longer half-life in plasma and offer many advantages for in-hospital heparinization (e.g.,
deep vein thrombosis). [52 ] , [338 ] LMW heparin has been used successfully for CPB,
[339 ] [341 ] but clots have been observed. [339 ] , [340 ] Protamine only partially
reverses factor Xa inhibition. [342 ] , [343 ] During in vitro extracorporeal circulation,
LMW heparin strongly reduces complement activation and neutrophil elastase release.
[179 ]
Dermatan sulfate catalyzes heparin cofactor II activity and heparnoids, which are a
mixture of dermatan sulfate and heparin, [337 ] have been used for CPB in Europe but
are not approved for the United States. [344 ]
FACTOR XA INHIBITORS
Factor X is activated by both the intrinsic and extrinsic coagulation pathways, and both
these pathways are activated during open heart surgery. [21 ] , [49 ] , [345 ] , Factor Xa,
the active enzyme, catalyzes the conversion of prothrombin to thrombin; thus a
tight-binding inhibitor of factor Xa theoretically should prevent thrombin formation.
Specific factor Xa inhibitors have been isolated from leeches and ticks, and
recombinant versions have been developed to the stage of investigation. [346 ] [349 ]
Recombinant tick anticoagulant peptide and antistasin (a protease inhibitor derived
from leeches) inhibit factor Xa at nanomolar concentrations. [348 ] , [349 ] Recombinant
tick anticoagulant peptide has a K i for factor Xa of 0.5 n M [350 ] but fails to inhibit the
expected increase in fibrinopeptide A during simulated extracorporeal circulation. [179 ]
Platelet Anesthesia
Platelet anesthesia is a term used to describe a strategy to protect platelet adhesion

and activation during CPB by temporarily inhibiting platelets during the period of
extracorporeal perfusion. If the inhibitor is removed immediately after CPB, larger
numbers of functionally adequate platelets are available to normalize bleeding time and
to reduce postoperative blood losses.
Partial platelet anesthesia can be achieved by several methods. Intraoperative

plasmapheresis and preparation of platelet-rich plasma [351 ] remove a large aliquot of
platelets from the perfusate but are expensive and require a considerable amount of
blood processing. [352 ] This method is not cost-effective for routine open heart
patients but may be useful in high-risk patients who require prolonged CPB or
reoperations.
Platelets can be inhibited temporarily during CPB by several different drugs, including
phosphodiesterase inhibitors (dipyridamole), prostanoids (prostacyclin, iloprost), and
glycoprotein IIb/IIIa membrane receptor inhibitors (ticlopidine, tirofiban). Aspirin inhibits
platelet cyclooxygenase and is not reversible. Intravenous dipyridamole partially
protects platelets during CPB [121 ] but is not quickly reversible because of a long
plasma half-life (100 min). [353 ] Prostacyclin partially preserves platelet numbers and
attenuates -thromboglobulin release [354 ] but causes profound and unacceptable
hypotension. Iloprost, an analogue of prostacyclin, also protects platelets during CPB
but requires large doses of phenylephrine to maintain adequate blood pressures. [54 ]
In baboons, glycoprotein IIb/IIIa receptor inhibitors effectively protect platelets and
reduce postoperative bleeding times during and after CPB. [123 ]
Aprotinin
In 1989, Bidstrup et al. [114 ] introduced aprotinin for cardiac surgery and demonstrated
a 50 percent reduction in postoperative bleeding and a similar reduction in the need for
blood and blood product transfusions. They observed that the drug reduced
postoperative bleeding times but had no effect on platelet count. These observations
have been confirmed. [115 ] , [116 ] , [355 ] [357 ]
Aprotinin is a natural serine protease inhibitor that strongly inhibits plasmin and weakly
inhibits kallikrein. [358 ] Plasma concentrations of 4 to 10 kallikrein inhibitory units (KIU)
of aprotinin completely inhibit plasmin, but 250 to 400 KIU is required to completely
inhibit kallikrein. [358 ] The full-dose Hammersmith protocol administers 4 million KIU
before CPB and 0.5 million KIU/h during CPB and maintains blood concentrations
around 250 KIU. [359 ] The half-dose protocol maintains approximately 125 KIU blood
concentrations. Numerous studies have shown that aprotinin reduces fibrinolysis during
and after CPB [115 ] , [355 ] [357 ] and also has a platelet-sparing effect that is both
independent of plasmin [360 ] and also related to plasmin. Plasmin causes platelets to
selectively remove glycoprotein Ib receptors from the platelet surface but does not
cause infolding of platelet glycoprotein IIb/IIIa receptors. [361 ] These properties explain
the failure of aprotinin to prevent platelet adhesion during CPB and its ability to
attenuate expected increases in postoperative bleeding times as glycoprotein Ib
receptors return to the platelet surface. In addition, depending on temperature and
concentration, plasmin is both a platelet inhibitor and an agonist. [362 ] At 37°C, high
concentrations of plasmin activate platelets and low concentrations inhibit. However, at
22°C, low concentrations strongly stimulate platelets. [362 ] The agonist effect of low
concentrations during deep hypothermia combined with circulatory arrest may explain
the higher incidence of renal failure and death in patients who have aortic surgery with
aprotinin. [363 ]
The mechanism of action of aprotinin is not fully understood, but the drug appears to
directly inhibit plasmin. [364 ] The drug also reduces thrombin formation and activity
[365 ] and thus has anticoagulant properties independent of fibrinolysis. [366 ]
Nevertheless, clinical concerns that the drug may reduce coronary arterial bypass graft
patency and increase the incidence of perioperative myocardial infarction have been
raised. [367 ] These concerns have not been substantiated in subsequent clinical trials.
[368 ] [372 ]
Clinical doses of aprotinin only partially inhibit kallikrein. Despite low potency, the drug
partially inhibits kallikrein-mediated activation of the intrinsic coagulation pathway,
complement, and neutrophils [359 ] and thus attenuates the whole-body inflammatory
response. The drug also may attenuate neutrophil activation and myocardial damage
during aortic cross-clamping. [373 ]
Other Protease Inhibitors
Clinical experience with aprotinin has stimulated efforts to discover other protease
inhibitors to control activation of blood elements during CPB. Nearly all the enzymatic
proteins of the contact, coagulation, complement, and fibrinolytic systems are serine
proteases. A large number of reversible and irreversible serine protease inhibitors are
known, and one or more of these or other inhibitors may prove more efficacious than
heparin and aprotinin in controlling the activation of blood elements during CPB. These
inhibitors of factor XIIa, factor XII fragments, factor IXa, factor Xa, kallikrein, C1s, t-PA,
plasmin, thrombin, and neutrophil elastase have different rate and binding constants for
each target protease. The most inviting targets for selective inhibition are factor XIIa,
kallikrein, and factor Xa. Complete inhibition of these three serine proteases offers
good prospects for attenuating activation of blood elements and the production of
vasoactive substances and microemboli during CPB.
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INTRAOPERATIVE CARDIAC PHYSIOLOGY
Myocardial Oxygen Consumption
The heart represents less than 0.5 percent of body weight, yet it accounts for over 7
percent of resting oxygen consumption. Myocardial oxygen consumption (Mvo 2 ) can
be readily calculated using the Fick equation if coronary blood flow (CBF) and arterial
(Cao 2 ) and coronary sinus (Ccso 2 ) oxygen contents are known [Mvo 2 = CBF × (Cao
2 -Ccso 2 )]. Cardiac muscle extracts much more oxygen in the normal state than other
organs, and thus increased myocardial oxygen consumption is achieved primarily by
increases in coronary blood flow. The left ventricle consumes approximately 8 mL of 02
per 100 g of myocardium per minute in a normal human subject at rest. During
potassium-induced arrest, oxygen consumption falls to 1.5 mL per 100 g of myocardium
per minute, a decrease of over 81 percent. The three major determinants of Mvo 2 are
heart rate, stroke work (the area within the pressure-volume loop, which incorporates
afterload), and inotropic state. The relationship between Mvo 2 and heart rate, stroke
work, and inotropic state is almost linear. [6 ] , [7 ] Mvo 2 is greater when a low stroke
volume is ejected against high pressures than when large stroke volumes are ejected
against low aortic pressures.
During cardiac surgery, myocardial oxygen consumption varies widely. The lowest Mvo
2 occurs when the heart is arrested. Maximum Mvo 2 occurs shortly after weaning from
cardiopulmonary bypass when the heart is repaying the oxygen debt incurred during the
aortic cross-clamp period. In a series of classic experiments, Buckberg et al. [8 ]
examined myocardial oxygen consumption during different conditions of myocardial
activity: the empty beating heart, the fibrillating heart, and the arrested heart (Fig. 10-1) .
Myocardial oxygen consumption was greatest during normothermic (37°C) fibrillation
and least during hypothermic (22°C) arrest. Hyperkalemic arrest achieved a reduction
in Mvo 2 from 5.6 ± 1.95 mL/100 g per minute to 1.1 ± 0.4 mL/100 g per minute.
Hypothermia reduced Mvo 2 to 2.9 ± 0.9 mL/100 g per minute, while the combination of
potassium-induced arrest and moderate hypothermia reduced Mvo 2 to 0.3 ± 0.1
mL/100 g per minute.
Myocardial ischemia occurs when there is an imbalance of oxygen supply and demand.
This imbalance results in anaerobic myocardial metabolism. The end products of
anaerobic metabolism rapidly lead to acidosis, mitochondrial dysfunction, and myocyte
necrosis.
Aerobic versus Anaerobic Metabolism
Figure 10-2 illustrates myocardial metabolism of glucose. Aerobic glucose metabolism

involves the conversion of glucose to pyruvate, which is then converted into acetyl-CoA.
Acetyl-CoA enters mitochondria and is metabolized via the Krebs cycle into carbon
dioxide and water (Fig. 10-3) . The net result of glucose oxidation is the production of
36 moles of ATP (adenosine triphosphate) for each mole of glucose. Figure 10-4
illustrates the movement of metabolic substrates into the cell and into mitochondria. This
figure also illustrates the metabolic effect of hypothermia on membrane transport and
mitochondrial respiration.
Anaerobic glucose metabolism involves the conversion of glucose to lactate. The initial
phosphorylation of glucose consumes 2 moles of ATP to form fructose-1,6-diphosphate
(FDP). The conversion of FDP to lactate and water involves the production of 4 moles
of ATP. Thus the net energy production of glycolysis is 2 moles of ATP for each mole of
glucose. Unfortunately, the metabolic end products-dihydronicotinamide-adenine
dinucleotide (NADH), lactate, and hydrogen ions-act to inhibit phosphofructokinase and
thereby inhibit further glycolysis. This inhibition results in continuing energy consumption
from the initial stages of glycolysis without any energy production. Therefore, not only is
anaerobic metabolism a less efficient source of ATP production, but it is also
associated with the production of hydrogen ions. The resulting decreased intracellular
pH has detrimental consequences for membrane and mitochondrial stability. Impaired
function of the sodium-potassium ATPase pump increases cell membrane permeability
to extracellular calcium and results in an elevation of the intracellular calcium level.
Impairment of the ATP-dependent calcium pump produces decreased calcium ion
sequestration in the cytoplasm and organelle injury and myofibrillar contracture.
Myocardium is remarkably adept at utilizing any available substrate for energy

production. Important amino acids such as glutamate and aspartate are depleted during
ischemia. The resulting loss of these Krebs cycle intermediates deprives the heart of an
alternative source of ATP and may limit normal oxidative metabolism during
reperfusion.
Weiss et al. [9 ] found that in isolated rabbit hearts ATP generated from aerobic
metabolism was used preferentially for myocardial contractility, whereas anaerobically
produced ATP was used primarily for intracellular repair. This difference is teleologically
sound because the ischemic cell should conserve energy for survival functions only.
These results also explain the slow recovery in function seen after cardioplegic arrest in
acutely ischemic hearts. The initial periods of reperfusion clearly serve to replenish
cellular energy stores, which are used primarily for intracellular repair. Once the
intracellular energy stores are replenished, contractile function resumes. Stunned
myocardium recovers metabolism quickly and function slowly. This phenomenon can be
demonstrated by examining myocardial metabolism during and after cardioplegic
arrest. [3 ] During the aortic cross-clamp period, anaerobic metabolism predominates,
and there is a net release of lactate from the heart. After cross-clamp removal,
accumulated myocardial lactate is washed out; however, lactate release persists for 5
to 10 minutes before the myocardium gradually reverts to net lactate extraction. We
have observed that persistent lactate release during reperfusion predicts the
development of postoperative low cardiac output. Thus restoration of normal aerobic
metabolism is essential for normal recovery of ventricular function.
Stunned Myocardium
Ischemic myocardium may undergo a period of reversible dysfunction following

reperfusion. Braunwald and Kloner [10 ] originally described myocardial stunning as fully
reversible ventricular dysfunction following an ischemia-reperfusion injury of insufficient
magnitude to cause cellular necrosis. Stunned myocardium is characterized by both
reduced contractility and diastolic compliance that revert to normal following a time
span that is longer than but directly proportional to the duration of ischemia. Stunned
myocardium responds to increases in coronary flow and inotropic stimulation with an
improvement in myocardial function. A less severe form of stunning may be referred to
as hibernating myocardium . In this clinical phenomenon, regional wall motion
abnormalities revert to normal almost immediately following revascularization.
Hibernating, stunned, and infarcted myocardium represent an escalating scale of
ischemic myocardial injury.
Patients who present for surgery following a myocardial infarction or with unstable
angina are at increased risk for perioperative morbidity and mortality. This increased
risk may be due in part to stunned myocardium, which, despite adequate
revascularization, may remain dysfunctional for several hours or days following
operation. During this vulnerable period, patients may develop hypotension, malignant
arrhythmias, or neurologic complications. Inotropic support may augment perioperative
ischemic injury. [11 ] The use of an intraaortic balloon counterpulsation device provides
hemodynamic support during this vulnerable period but is associated with a risk of
peripheral leg ischemia and arterial embolization.
Although the incidence of perioperative myocardial infarction is as low as 2 percent in

some series, [12 ] the incidence of postoperative low-output syndrome may be as high
as 10 percent. At our institution, low-output syndrome is defined as the requirement for
inotropic medication or intraaortic balloon pump support for longer than 30 minutes to
maintain systolic blood pressure above 90 mmHg and a cardiac index greater than 2.2
liters/min per m 2 after returning the patient to the intensive care unit. Postoperative
low-output syndrome represents a failure of perioperative myocardial protection and
may be a clinical reflection of myocardial stunning. Operative mortality in patients who
develop low-output syndrome is as high as 17 percent. [12 ] Therefore, improved
methods of myocardial protection aimed at reducing the incidence of low-output
syndrome may have a significant impact on operative mortality.
Ischemia results in a rapid metabolic and ultrastructural derangement of myocardium.

High-energy phosphate depletion occurs almost immediately, with a 50 percent loss of
ATP stores within 10 minutes. Reduced contractility occurs within 1 to 2 minutes, with
development of ischemic contracture and irreversible injury after 30 to 40 minutes of
normothermic (37°C) ischemia. Cardiospecific isoforms of creatine kinase (CKMB),
lactate dehydrogenase (LDH), and aspartate transaminase (AST) can be detected as
necrotic myocytes release intracellular enzymes. The peak rise in CKMB level occurs
within 24 hours, but both AST and LDH remain elevated for 4 to 5 days. Other markers
of myocardial ischemic injury, such as cardiac troponin I, are now used to assess
perioperative myocardial protection. [13 ] Cardiac troponin levels rise within 4 hours of
myocardial cell death and stay elevated for up to 48 hours.
Histologic examination of ischemic myocardium reveals coagulation necrosis, edema,

and an early neutrophilic infiltrate as early as 4 hours following infarction. A heavy
neutrophilic infiltrate is seen within 24 hours and leads to myocyte disintegration,
proliferation of fibrocytes, and fibrin deposition within 7 days.
In the operating room, ischemic myocardium may exhibit pallor or even hyperemia 24
hours following infarction. Within 5 days, a distinct hyperemic border appears
surrounding a central yellow-brown area of soft myocardium. This discoloration denotes
the time period when ischemic myocardium is susceptible to transmural rupture.
Fibrous scarring usually is complete within 7 weeks, but the potential to progress to
aneurysmal formation continues over a period of months to years.
Reperfusion Injury
Reperfusion injury is characterized by abnormal myocardial oxidative metabolism. In

addition to structural changes created during ischemia, reperfusion may produce
cytotoxic oxygen free radicals. Figure 10-5 reveals possible intracellular sources of free
radicals. These oxygen free radicals play a significant role in the pathogenesis of
reperfusion injury by oxidizing sarcolemmal phospholipids and thus disrupting
membrane integrity. Das et al. [14 ] demonstrated a decrease in the activity of the free
radical-scavenging enzymes superoxide dismutase (SOD), glutathione peroxidase
(GPX), and catalase following ischemia and cardioplegia in the pig. We have shown
that phospholipid-conjugated diene concentrations increased within 5 minutes of
reperfusion in myocardial tissue [15 ] (Fig. 10-6) . These conjugated dienes are
chemical signatures of oxygen free radical lipid peroxidation. Oxidized free fatty acids
are released into the coronary venous blood and are a marker of myocardial membrane
phospholipid peroxidation. Protamine induces complement activation, [16 ] which
activates neutrophils. Activated neutrophils and other leukocytes are an additional
source of oxygen free radicals and other cytotoxic substances. Thus the deposition of
leukocytes and platelets seen after reperfusion [14 ] may contribute to the free
radical-induced reperfusion injury. Figure 10-7 illustrates the mechanism of
leukocyte-mediated free radical lipid peroxidation.
PERIOPERATIVE ASSESSMENT OF MYOCARDIAL FUNCTION
AND METABOLISM
Classic indices of left ventricular function include developed pressure, cardiac index,
and stroke work index. These indices are load-sensitive, and changes in preload and
afterload dramatically influence these measurements. Measurement of ventricular
pressures and volumes over a series of cardiac cycles with varying preloads provides a
better estimate of ventricular function. Figure 10-8 illustrates a series of
pressure-volume loops before and after volume loading. The area within each
pressure-volume loop represents the stroke work for that cardiac cycle. Utilizing these
pressure-volume loops, load-insensitive indices of ventricular function can be
constructed.
In patients, measurements of intraventricular volume are difficult. Radionucleotide

ventriculography, intracardiac tantalum markers, [17 ] and ultrasonic crystals only
provide rough estimates of intraventricular volume, and each technique has its
advantages and disadvantages. Nevertheless, accurate measurements of myocardial
contractility require an assessment of the ventricular pressure-volume relation.
Measurements of Systolic Function
We have employed gated nuclear ventriculography to estimate intraventricular volumes.

[18 ] In conjunction with intraventricular micromanometer catheters used to measure
ventricular pressures, we created pressure-volume relations before, during, and after
volume loading.
We employed the time-varying elastance model to calculate maximal systolic elastance.

[19 ] Isochronic points are created for each systolic pressure-volume coordinate from
three or more pressure-volume loops obtained at different preloads. Linear regression
of isochronic points at different preloads permits an estimation of systolic elastance at
each systolic time interval. The maximal systolic elastance (Emax) was defined by the
regression line with the greatest slope and usually occurred before end-systole (Fig.
10-9) .
End-systole is difficult to define; therefore, we prefer to calculate end-systolic elastance

(Ees) using three isochronic points closest to end-systole for each different volume
condition (Fig. 10-10) . End-systolic elastance determined by this method is more
reproducible than maximal elastance because it utilizes more points and is subject to
less variation.
Measurements of Diastolic Function
The relation between diastolic pressure and volume is considered monoexponential;

therefore, we have employed a logarithmic transformation of diastolic pressure to
assess diastolic compliance. We calculated the natural logarithm of the left ventricular
end-diastolic pressure (LVEDP) and correlated it with the left ventricular end-diastolic
volume index. The slope and intercept of this relation provide an estimate of diastolic
compliance. Diastolic pressure-volume coordinates are used to calculate the modulus
of chamber stiffness ( K P), which is also an index of ventricular diastolic function.
Measurements of Myocardial Metabolism
The insertion of coronary sinus catheters intraoperatively has enabled us to measure

myocardial metabolism during and after surgery. Using the Fick equation, we calculate
myocardial oxygen consumption, lactate flux, and acid production. Left and right
ventricular biopsies yield measurements of myocardial ATP, ADP, and AMP and their
metabolic products adenosine, inosine, xanthine, and hypoxanthine.
Measurements of Cardioplegic Distribution
Sonicated albumin microbubbles have been used in patients to define the distribution of
cardioplegic flow. [20 ] Transesophageal echocardiography demonstrated that
antegrade cardioplegia results in better delivery of cardioplegic solution to both the right
and left ventricles compared with retrograde delivery despite severe proximal coronary
artery stenoses or occlusions. [21 ] Following completion of the right coronary artery
graft, perfusion to the right ventricle improves significantly regardless of the direction of
cardioplegic delivery. This emerging technology should permit researchers to critically
evaluate new cardioplegic techniques and delivery systems.
Clinical Outcome Measures
The traditional clinical outcomes of operative mortality and perioperative myocardial

infarction are now insufficient to discriminate between cardioplegic techniques. Two
large randomized clinical trials [22 ] , [23 ] failed to show any difference in perioperative
mortality or myocardial infarction between treatment groups. Low rates of operative
mortality and problems inherent in identifying perioperative infarction have made these
outcome measures impractical in contemporary studies of myocardial protection.
However, the incidence of postoperative low cardiac output can be used to assess the
efficacy of perioperative myocardial protection. [12 ]
The ability to measure subtle differences in myocardial metabolism and function

enables many laboratories, including ours, to compare various techniques of
myocardial protection. Although these subtle differences usually do not correlate with
clinical events in low-risk patients, they may prove clinically relevant in patients who are
at high preoperative risk because of unstable angina or poor preoperative left
ventricular function. [24 ] We have demonstrated that lactate production at the time of
reperfusion predicts development of postoperative low-output syndrome, even in
low-risk elective coronary bypass patients. [25 ] As the number of high-risk patients
presenting for coronary bypass surgery increases, [26 ] subtle improvements in
myocardial protection may have a significant impact on morbidity and mortality following
surgery.
PRINCIPLES OF CARDIOPLEGIA
In 1955, Melrose et al. [2 ] first described the use of hyperkalemic blood cardioplegia to
electively arrest the heart in diastole to reduce metabolic demand, improve
visualization, and facilitate the conduct of surgery. This cardioplegic solution was given
via the aortic root shortly after a clamp was placed across the aorta. However, Melrose
et al. abandoned cardioplegia because of the cardiac injury it caused. Other
investigators questioned hyperkalemic solutions because of focal inflammatory lesions
in the myocardium. [27 ] Subsequently, these lesions were thought to be due to
abnormal calcium flux, but by reducing the potassium concentration in the cardioplegic
solution, Gay [28 ] eliminated them.
Following the important discovery of Melrose et al., several improvements were made in
the composition and delivery of cardioplegia. The fundamental precept of any
cardioplegic technique involves protection against ischemic injury during the aortic
cross-clamp period when normal antegrade coronary perfusion is absent.An optimal
metabolic supply/demand ratio requires both a reduction in high-energy phosphate
utilization and an increase in the delivery of oxygen and metabolic substrates. The
previous practice of intermittent aortic cross-clamping was abandoned by most
surgeons when it was realized that the ensuing ventricular fibrillation greatly increased
cardiac energy requirements. Hypothermic hyperkalemic cardioplegic solutions were
introduced to induce asystolic arrest to minimize cardiac energy requirements.
Intermittent doses of cardioplegia were administered every 15 to 20 minutes to provide
oxygen and metabolic substrates for the basal requirements of the arrested
hypothermic heart. These multidose cardioplegic infusions also were needed to prevent
rises in myocardial temperatures and displacement of intracoronary cardioplegic
solution by noncoronary collateral flow.
Newer technologies involving both the composition and delivery of cardioplegic

solutions continue efforts to improve the critical ratio between myocardial supply and
demand.
CONTEMPORARY RESULTS WITH HYPOTHERMIC
FIBRILLATORY ARREST
Several investigators continue to use the traditional technique of hypothermic fibrillatory

arrest for coronary bypass surgery. [29 ] [33 ] Akins [29 ] reported his results using this
technique in 3085 patients who had operations between 1980 and 1993. Overall
mortality was 1.6 percent, the prevalence of perioperative myocardial infarction was 2.5
percent, and the requirement for intraaortic balloon pump support was 2.5 percent. This
series includes 371 (12 percent) patients who underwent emergency surgery for
complications of cardiac catheterization. This technique is also safe for high-risk
patients such as those who have left ventricular aneurysmectomy. [33 ]
BLOOD VERSUS CRYSTALLOID
During the 1980s, surgeons at many institutions began to employ blood cardioplegia.
Feindel et al. [34 ] demonstrated that blood cardioplegia was superior to crystalloid in
reducing irreversible myocardial injury in a canine model of global myocardial ischemia.
At our institution, Fremes et al. [35 ] used a blood cardioplegic solution produced by
mixing oxygenated blood from the bypass circuit with crystalloid solution in a 2:1 ratio. In
a prospective, randomized trial these investigators showed that blood cardioplegia
enhanced aerobic myocardial metabolism during aortic cross-clamping, increased
myocardial oxygen consumption, reduced anaerobic lactate production, and preserved
high-energy phosphate stores. Blood cardioplegia also improved both systolic and
diastolic function following surgery. Since publication of that trial, all surgeons at The
University of Toronto switched to blood cardioplegia. In a subsequent study that
compared blood versus crystalloid cardioplegia in patients with unstable angina, blood
cardioplegia significantly reduced the incidence of perioperative myocardial infarction,
low-output syndrome, and operative mortality [36 ] (Fig. 10-11) .
THE OPTIMAL TEMPERATURE FOR CARDIOPLEGIA
The standard method of delivering either blood or crystalloid cardioplegia consisted of

intermittent hypothermic (10°C) infusions. Hypothermia is often supplemented by a
topical jacket or saline slush. However, topical saline slush may cause phrenic nerve
palsy, which increases the risk of prolonged postoperative ventilation and respiratory
complications. [37 ] , [38 ]
Hypothermia does not reduce myocardial oxygen requirements much beyond the
reduction achieved with hyperkalemic arrest. [8 ] In addition, hypothermic cardioplegia
delays recovery of both myocardial metabolism and ventricular function. [39 ] [42 ] In a
clinical trial evaluating the metabolic effects of hypothermic blood cardioplegia, we
found that myocardial levels of high-energy phosphates [ATP and creatine phosphate
(CP)] decreased despite a threefold increase in adenosine monophosphate (AMP). [40
] Thus intermittent infusions of cold, oxygenated blood cardioplegia did not permit
adequate mitochondrial energy production. Furthermore, reperfusion did not restore
mitochondrial energy production because ATP and total energy charge [EC = (ATP +
1/2 ADP)/(ATP + ADP + AMP)] did not recover 30 minutes after cross-clamp release.
Rosenkranz et al. [43 ] hypothesized that this metabolic dysfunction is due to washout of
Krebs cycle intermediates such as glutamate and aspartate and showed that a
normothermic induction of glutamate- and aspartate-enriched cardioplegia improved
metabolic recovery in energy-depleted hearts. Teoh et al. [44 ] demonstrated that a
terminal infusion of warm blood cardioplegia (a hot shot) immediately prior to
cross-clamp release resulted in prolongation of electromechanical arrest, improvement
in aerobic metabolism, and increased diastolic compliance. The beneficial effect of the
hot shot was thought to be due to early recovery of temperature-dependent
mitochondrial respiration and ATP generation. Patients who received a terminal warm
blood infusion had significantly higher ATP and glycogen stores compared with patients
who did not receive the hot shot. Since this technique resulted in a prolongation of
electromechanical arrest, the ATP produced was presumably used for repair of
intracellular ischemic injury and restoration of depleted energy stores.
Clinical data indicated that normothermic induction combined with normothermic

terminal blood infusion facilitated early recovery of myocardial metabolic function.
Lichtenstein et al. [4 ] extrapolated these findings and proposed that normothermic
perfusion throughout the cross-clamp period might be beneficial. However, the modest
increase in myocardial oxygen demand at 37°C necessitated continuous delivery of
cardioplegia to prevent normothermic myocardial ischemia. Lichtenstein et al. [4 ]
employed normothermic antegrade blood cardioplegia in 121 consecutive patients and
compared this experience with a historical cohort of 133 patients who received
hypothermic antegrade blood cardioplegia. Normothermic blood cardioplegia
produced a significant reduction in perioperative myocardial infarction and in the
requirement for postoperative intraaortic balloon pump support. A subsequent
prospective, randomized trial in 1732 patients revealed that normothermic blood
cardioplegia reduced the incidence of postoperative low output syndrome significantly
[22 ] but failed to show any differences in perioperative myocardial infarction (by ECG
criteria) or mortality. Another trial by the Emory group [45 ] confirmed similar efficacy of
normothermic and hypothermic cardioplegia for myocardial protection but raised the
possibility of an increased incidence of postoperative neurologic events.
However, systemic normothermia is not necessary to administer warm blood

cardioplegia. At the Toronto Hospital, systemic temperature is allowed to drift to 33 to
35°C to provide neurologic protection from cerebral emboli released during cannulation
and aortic cross-clamping. Furthermore, a single prolonged cross-clamp period
provides superior myocardial protection compared with the use of a partially occluding
clamp and may cause less embolic debris. [46 ] , [47 ] If a surgeon prefers to use a
partially occluding clamp, as in the Emory series, [38 ] systemic normothermia may
pose a risk for cerebral ischemia, and therefore, hypothermic perfusion should be used.
In addition, hyperglycemic crystalloid solutions employed in the Emory trial may have
exacerbated intraoperative neurologic injuries. Hyperglycemia worsens cerebral
acidosis and augments ischemic injury. [48 ]
Figure 10-12 shows intraoperative measurements of myocardial oxygen consumption

and lactate release performed during a prospective trial [49 ] comparing
high-hemoglobin (4 parts blood to 1 part crystalloid) versus low-hemoglobin (2:1)
cardioplegia and the effect of low cardioplegic flow (< 80 mL/min) and high flow (> 80
mL/min). Low-hemoglobin, low-flow cardioplegia significantly increases oxygen
consumption following cross-clamp release compared with high-hemoglobin, high-flow
cardioplegia. A statistically insignificant increase in lactate release is seen with
low-hemoglobin, low-flow cardioplegia. As a result of this trial, the ratio of blood to
crystalloid in our cardioplegic solution increased to 4:1 in 1991. Table 10-1 illustrates
the current composition of our crystalloid additive for 4:1 blood cardioplegia.
The benefits of blood cardioplegia prompted many investigators to maximize the

proportion of blood in their cardioplegic solutions, but we have not found significant
benefits of 8:1 over 4:1 blood-crystalloid mixtures. However, recently, Menasche et al.
[50 ] described a simplified method to deliver essentially whole-blood cardioplegia with
a potassium-magnesium additive. This delivery system reduced the amount of
crystalloid solution infused from approximately 750 mL to less than 100 mL. Future
refinements probably will maximize hematocrit, decrease the amount of crystalloid, and
carefully titrate potassium, magnesium, and other exogenous additives.
The inability to consistently perfuse all areas of the myocardium subjects some regions
to possible normothermic ischemia. Warm blood (37°C) cardioplegia increases
anaerobic lactate production compared with cold blood (10°C) cardioplegia. [51 ] In
addition, warm blood cardioplegia produces lower levels of high-energy phosphates at
the time the cross-clamp is removed compared with cold blood cardioplegia (Fig.
10-13) , but recovery of ventricular function is better following warm blood cardioplegia.
[41 ] Therefore, we postulated that tepid blood (29°C) cardioplegia may be optimal. In a
randomized trial of 72 patients, we found that tepid blood cardioplegia reduced lactate
and acid production during cardiac arrest as compared with warm blood cardioplegia
and improved postoperative left ventricular function as compared with cold blood
cardioplegia. [51 ] This tepid blood cardioplegia exploits the decreased myocardial
metabolism associated with hypothermia but utilizes relative normothermia to improve
recovery of ventricular function.
ROUTE OF CARDIOPLEGIC DELIVERY
Antegrade
Cardioplegia traditionally is delivered antegrade into the aortic root, a technique still
employed by many cardiac surgeons. At the Toronto Hospital, a purse-string suture is
placed immediately proximal to the aortic cannulation site, and a cardioplegic tack is
introduced into the aortic root. Other surgeons prefer a needle to cannulate the aorta
proximal to the cross-clamp. An initial arresting dose between 500 and 1000 mL of
cardioplegic solution is given immediately after the aorta is cross-clamped. Intermittent
doses of cardioplegic solution are given through the aortic root at the completion of
each distal anastomosis. We attempt to provide the initial antegrade cardioplegic
solution at a perfusion pressure of 70 mmHg. Although antegrade cardioplegic solution
can be given continuously, it usually floods the operative field and may compromise the
technical quality of the distal anastomoses. In patients with severe proximal disease,
coronary obstructions may reduce cardioplegic delivery and produce nonuniform
myocardial perfusion.
During valve surgery, antegrade cardioplegia has several limitations. In aortic stenosis,
the initial cardioplegic infusion can be delivered via the aortic root. In aortic
regurgitation, the aorta is opened promptly after the cross-clamp is applied. The left
coronary ostium is cannulated directly for delivery of cardioplegic solution. The right
ostium is then cannulated and perfused to provide homogeneous arrest. A continuous
infusion is given unless the field becomes obscured; in this circumstance, the
cardioplegic infusion is interrupted. However, trauma to the coronary ostia caused by
cannulation can produce ostial stenosis.
Antegrade cardioplegia during mitral valve surgery requires interruption of the surgical
procedure because the mitral retractor causes aortic incompetence. This requires
removal of the retractor and deairing of the aortic root before antegrade cardioplegia
can be resumed. During combined aortic and mitral valve surgery, the aortotomy can be
performed prior to mitral valve replacement/repair. The coronary ostia are cannulated
directly, and perfusion catheters are left in for the duration of both valve procedures.
Retrograde
Retrograde delivery of cardioplegic solution via the coronary sinus was described as
early as 1957. [52 ] The advent of warm heart surgery has increased interest in
retrograde cardioplegia for coronary bypass surgery. [5 ] Retrograde cardioplegia is
employed to circumvent inhomogeneous distribution of antegrade cardioplegia in the
presence of severe proximal coronary artery stenoses. Unfortunately, evidence is
mounting that retrograde perfusion does not adequately perfuse the right ventricle and
does not provide as adequate capillary perfusion of the left ventricle as antegrade
delivery. [53 ] [56 ]
At the Toronto Hospital we use a right atrial cannulation technique for retrograde
delivery of cardioplegia. A purse-string suture is passed in the right atrium, and the
retrograde cannula is placed into the coronary sinus. The position of the cannula is
confirmed by observing distension of the posterior interventricular vein, monitoring
coronary sinus pressure (a sudden drop in pressure suggests that the cannula has
slipped into the right atrium), and palpating the coronary sinus.
Right atrial retrograde cardioplegic infusion involves placing tapes on both cavae and
clamping the pulmonary artery. Cardioplegia is delivered into the right atrium and flows
passively into the coronary sinus, with the aortic root vented. Unfortunately, valves in the
orifice of the coronary sinus may prevent adequate retrograde delivery when this
technique is used. [57 ] , [58 ]
Various techniques are proposed to improve perfusion with retrograde delivery. A

single Prolene snare placed at the base of the coronary sinus just proximal to the
posterior interventricular vein is advocated to prevent dislocation of the perfusion
cannula into the right atrium; however, there is a concern that the coronary sinus and/or
right coronary artery may be injured when this suture is placed (Fig. 10-14) . Rudis et al.
[59 ] found that coronary sinus occlusion during retrograde cardioplegia significantly
improved perfusion of the right ventricle and posterior intraventricular septum and
reduced the overall volume of cardioplegic solution administered. Menasche [60 ]
proposed a manually inflatable retrograde cannula to secure its position. The ideal
position of the retrograde cannula is still unknown. Some surgeons insert the cannula as
far distally as possible into the coronary sinus, while others prefer a more proximal
position. We prefer to place the cardioplegic cannula as far distally as possible and
then withdraw the cannula slowly until the posterior interventricular vein distends.
When retrograde cardioplegia solution is given at normothermic temperatures, it must

be given continuously to avoid ischemia. Proponents of continuous retrograde delivery
claim that this technique does not flood the operative field to the same extent as
continuous antegrade delivery. Nevertheless, most surgeons inevitably interrupt delivery
of retrograde flow to complete the distal anastomoses. Maatsura et al. [61 ] have shown
in a porcine model that three 7-minute interruptions during a 45-minute period of
cardioplegic arrest result in a larger infarct, more myocardial acid production, and
reduced echocardiographic wall motion compared with intermittent cold
antegrade/retrograde cardioplegia. Our clinical experience also indicates that warm
cardioplegia interrupted for greater than 7 minutes results in ischemic myocardial
metabolism.
Continuous retrograde cardioplegia is not truly continuous, and the optimal rate of
delivery is not well defined. In a prospective, randomized trial [62 ] we found that
retrograde flows of less than 100 mL/min at normothermia were associated with
myocardial lactate release and acid production following cross-clamp removal. Flow
rates of 200 mL/min minimized lactate production and maintained coronary venous pH
within the physiologic range. Flow rates of 300 mL/min or higher did not confer any
additional benefit, and thus we concluded that a minimum flow rate of 200 mL/min
should be used during retrograde cardioplegia to optimize distribution. To compensate
for periods of interruption, catch-up infusions of cardioplegia are given following each
interruption to maintain an average delivery of 200 mL/min.
Unfortunately, the major encumbrance to delivering high rates of retrograde flow is

pressure in the coronary sinus. Coronary sinus pressures above 40 mmHg may cause
perivascular hemorrhage, edema, and direct injury to the sinus. [63 ]
Retrograde cardioplegia is ideally suited for aortic valve operations. [64 ] , [65 ]
Near-continuous delivery can be achieved by placement of a coronary sucker tip at the
left coronary orifice, which permits a dry operative field. Effluent from the right coronary
orifice should be monitored to ensure proper oxygenation of the right coronary
vasculature. A desaturated right coronary effluent suggests inadequate right ventricular
perfusion, and antegrade delivery via a right coronary artery perfusion catheter should
be employed.
During mitral valve procedures, the aortic valve is made incompetent by the mitral
retractor, and venous effluent drains into the left ventricular cavity from the coronary
ostia. A left ventricular suction catheter effectively drains this effluent and permits
continuous delivery of cardioplegic solution until the prosthesis is inserted. When a
biatrial approach is used for mitral valve operations, the coronary sinus orifice can be
cannulated directly, and a purse-string suture can be placed around the ostium to
secure the cannula in place.
Combined Antegrade/Retrograde Delivery
Distribution of antegrade cardioplegia solution may be compromised by proximal

coronary artery stenoses. Distribution of retrograde cardioplegia solution may be
unreliable, particularly to the right ventricle. Thus combination of both techniques may
provide optimal distribution of cardioplegic solution. [66 ] [69 ]
One technique to provide combined antegrade and retrograde cardioplegia involves

alternate infusions controlled by a stopcock in the cardioplegia line. Continuous
retrograde delivery is attempted during construction of the distal anastomosis. Distal
and proximal anastomoses are completed in alternate fashion. Following completion of
each proximal anastomosis, the stopcock is turned to provide antegrade perfusion via a
cannula in the aortic root. Subsequent antegrade infusions perfuse both the native
coronary circulation and all completed vein grafts. The aortic root must be deaired prior
to each antegrade infusion; thus this technique is time-consuming and risks coronary air
emboli. However, in a recent study of 75 patients undergoing isolated coronary artery
bypass surgery, [70 ] we observed that this technique with normothermic blood
cardioplegia reduced lactate production, preserved high-energy phosphate stores, and
provided superior perfusion of the heart during the cross-clamp period than either
antegrade or retrograde cardioplegic delivery alone.
A modification of this technique eliminates the requirement to repeatedly deair the

aortic root. Following completion of each distal anastomosis, the proximal end of the
vein graft is connected to a manifold system in parallel with the retrograde delivery
catheter. This technique simultaneously and continuously perfuses the coronary sinus
and each completed vein graft (Fig. 10-15) . To conserve saphenous vein, a proximal
anastomosis is usually made following the second distal anastomosis. This
anastomosis usually is made to the smallest vessel that requires a graft, since this
arterial territory will not be perfused by antegrade flow after completing the proximal
anastomosis. Simultaneous retrograde perfusion drains via thebesian channels, and
the aortic root is vented to prevent venous congestion. Ihnken et al. [71 ] examined the
safety of simultaneous antegrade/retrograde perfusion in both animal and clinical
models and did not demonstrate myocardial edema.
The optimal technique for delivering cardioplegic solution is still controversial. A

combination of antegrade and retrograde delivery probably provides the most uniform
distribution of cardioplegia. New techniques of cardioplegic delivery will undoubtedly
improve perfusion to areas such as the right ventricle and posterior interventricular
septum that are not adequately perfused with current techniques.
SUBSTRATE-ENHANCED CARDIOPLEGIA
Glucose-Insulin-Potassium
In 1965, Sodi-Pollares et al. [72 ] used a glucose-insulin-potassium solution to decrease

electrocardiographic abnormalities in acutely infarcting myocardium. Since this initial
report, several investigators have used glucose and insulin solutions either
preoperatively, intraoperatively, or postoperatively to improve the results of surgery. [73 ]
Hearse et al. [74 ] described a detrimental effect of exogenous glucose infusions during
ischemic cardiac arrest but used a single-bolus cardioplegic infusion. The deleterious
effects were attributed to an accumulation of metabolic end products, such as lactate,
and acidosis. Neely and Grotyohann [75 ] demonstrated a beneficial effect of multidose
intermittent cardioplegic infusions of high glucose-insulin cardioplegia.
Glucose and insulin (GI) solutions are used to elevate myocardial glycogen levels [76 ] ,
[77 ] and increase myocardial metabolic reserves. Iyengar et al. [77 ] found that patients
with low myocardial glycogen levels have a higher incidence of arrhythmias, low-output
syndrome, and perioperative infarction.
Several mechanisms may explain the beneficial effects of GI solutions. GI solutions may
promote aerobic myocardial metabolism by increasing myocardial glucose uptake and
by stimulating the phosphorylating enzymes phosphofructokinase and hexokinase. GI
solutions also reduce circulating levels of free fatty acids that exert toxic effects on
mitochondrial membranes and on the metabolic pathways of the hypoxic heart. [78 ] [81
] After cardioplegic arrest, we demonstrated that fatty acid uptake is increased, but
beta-oxidation to acyl-CoA is decreased. [81 ] Lastly, hypertonic GI solutions may have
an osmotic effect similar to mannitol that decreases cell size and increases intracellular
calcium to improve myocardial contractility.
Kobayashi and Neely [82 ] showed that the activity of pyruvate dehydrogenase (PDH)
was inhibited at the onset of reperfusion. PDH converts pyruvate into acetyl-CoA, which
then enters the Krebs cycle during oxidative metabolism. Insulin stimulates PDH activity
in smooth muscle cells and in vascular endothelial cells, but in contrast to isolated rat
myocardium, [83 ] there is little evidence of insulin-mediated PDH stimulation in human
myocardium. If insulin is capable of stimulating PDH activity during early reperfusion, the
transition from anaerobic to aerobic metabolism should accelerate. This increase in
efficiency and compartmentalization of ATP production should improve postoperative
functional recovery.
Animal models suggest a direct inotropic effect of insulin that also may occur in
patients. [84 ] Gradinac et al. [85 ] administered insulin to patients who required
intraaortic balloon pump (IABP) support following coronary bypass surgery and found
improvement in cardiac function. Svedjeholm et al. [86 ] used a glucose, insulin, and
glutamate solution for patients who could not be weaned from cardiopulmonary bypass.
These authors identified 16 patients who could not be weaned and gave glutamate-GI
solution before inserting an intraaortic balloon. Only 3 patients required the IABP for
weaning, and all 3 died of irreversible cardiac injury. The authors concluded that
administration of glutamate-GI solution may reverse transient myocardial dysfunction
and avoid the need for mechanical support.
The role of exogenous glucose and insulin solutions in cardiac surgery remains unclear
due to the lack of properly designed, prospective, randomized trials. However, basic
science research combined with anecdotal clinical evidence suggests that insulin may
be an important component in future cardioplegic formulations.
Glutamate-Aspartate for Urgent Surgery
Teoh et al. [87 ] used a glutamate- and aspartate-enriched cardioplegic solution in

patients who had isolated coronary bypass surgery. Although low-risk elective patients
did not benefit, glutamate-aspartate solution provided a slight benefit to those patients
who underwent urgent surgery for unstable angina. Similarly, Rosenkranz et al. [43 ]
showed a benefit of glutamate-enriched blood cardioplegia in high-risk patients with
cardiogenic shock. These authors hypothesized that patients who present for surgery
shortly after an ischemic event have depletion of Krebs cycle intermediates such as
glutamate and aspartate. They suggested that restoration of these metabolites may
improve perioperative preservation of high-energy phosphates. However, the myocyte
is remarkably adept at utilizing any available substrate. Thus, in the presence of oxygen,
a normally functioning mitochondrial system is able to meet the energy requirements of
the cell. The role of Krebs cycle intermediates may be to stimulate normal mitochondrial
respiration as opposed to supplementing intracellular substrate stores. The relationship
between amino acids and mitochondrial metabolism is not fully understood.
Clarification of the mitochondrial metabolic defects caused by ischemia and
reperfusion may permit development of more site-specific compounds for restoring
normal aerobic metabolism.
Calcium-Channel Blockers
Experimental studies show that calcium-channel antagonists such as verapamil,

nifedipine, and diltiazem preserve myocardial function and metabolism after
normothermic ischemia, [88 ] crystalloid cardioplegia, [89 ] [92 ] and blood cardioplegia.
[93 ] These agents prevent calcium influx and adenosine triphosphate hydrolysis during
cardioplegic arrest. Calcium antagonists also may improve cardioplegic delivery by
coronary vasodilation.
Unfortunately, calcium antagonists depress cardiac function and may induce heart
block. [94 ] , [95 ] In a prospective, randomized trial [96 ] we found that diltiazem
cardioplegia reduced perioperative ischemic injury, improved myocardial metabolic
recovery, and prevented postoperative tachycardia and hypertension. However,
diltiazem cardioplegia was also associated with depression of systolic function and
atrioventricular block for a variable period after cross-clamp removal. After this trial, we
concluded that cardioplegic solutions enhanced with calcium-channel blockers may be
beneficial for patients with normal preoperative left ventricular function who are at risk
for postoperative hypertension, tachycardia, coronary spasm, or ischemia but that they
may be detrimental for patients with poor ventricular function. A very narrow
dose-response relationship limits application of this cardioplegic additive.
Newer calcium-channel antagonists such as amylodopine and felodopine may produce

less myocardial depression and provide beneficial effects when added to cardioplegic
solutions. These agents need to be evaluated in prospective, randomized clinical trials.
Antioxidants
Free radical-induced lipid peroxidation of the cell membrane occurs during cardiac
surgery. Weisel et al. [15 ] showed a bimodal release of free radicals (see Fig. 10-6 ).
The first burst occurs immediately following cross-clamp release. The second release of
conjugated dienes, a by-product of lipid peroxidation, occurs shortly after protamine
administration and is probably due to neutrophils activated by complement. [97 ]
Numerous laboratory and clinical studies have tried to assess the efficacy of a wide
variety of antioxidant agents. In a cultured human cardiomyocyte model, we showed that
water-soluble analogues of the antioxidants ascorbic acid and -tocopherol limited free
radical-induced damage. [98 ] Both agents also reduced infarct size in a canine model
of regional myocardial ischemia. [99 ]
Vitamin E (-tocopherol) and the cytosolic enzyme glutathione peroxidase are important
endogenous inhibitors of free radical-induced injury. Unfortunately, a water-soluble form
of vitamin E is not available. In a prospective, randomized trial, Yau et al. [100 ] reduced
free radical injury by a 2-week course of high-dose vitamin E. Unfortunately, this
protocol is impractical in high-risk patients who require urgent or emergent surgery and
do not have the luxury of time to orally increase vitamin E stores. Compounds such as
Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid, a water-soluble
analogue of -tocopherol) or other water-soluble antioxidants may prove beneficial in
these patients.
Nitric Oxide
Myocardial ischemia and reperfusion produce a myriad of physiologic responses

designed to limit irreversible injury. Coronary endothelial cells may have an important
role in the pathogenesis of ischemic and reperfusion injury. [101 ] [103 ] Endothelial
cells are metabolically highly active and produce a potent vasodilator previously known
as endothelium-derived relaxing factor (EDRF) but now identified as nitric oxide (NO).
[104 ] In addition to its vasodilatory properties, NO inhibits platelet aggregation, [105 ]
reduces neutrophil adherence, [105 ] and acts as an antioxidant. [106 ]
NO is synthesized from the amino acid L -arginine by NO-synthetase in the membranes

of endothelial cells. During ischemia, L -arginine levels may be reduced, and there may
be direct damage to the coronary endothelium. As a result, levels of NO may be
drastically reduced and exacerbate an ischemic injury.
The use of L -arginine or other NO donors to prevent ischemic injury yields conflicting
results because of the negative inotropic effects of nitric oxide. [107 ] [111 ] The role of
NO donors as an additive to cardioplegic solutions remains unclear and requires further
clinical investigation.
Ischemic Preconditioning
In 1986, Murry et al.[112 ] reported that brief episodes of ischemia conferred protection
against a subsequent prolonged ischemic insult. They termed this phenomenon
ischemic preconditioning , and subsequently, the characteristics, physiology, and
molecular mechanisms of this phenomenon have been investigated extensively.
Ischemic preconditioning is perhaps the most powerful endogenous protective
mechanism discovered for the heart to date. In the experiments of Murry et al.,
preconditioning decreased infarct size from 20 to 5 percent. Similar reductions in infarct
size have been reproduced by a variety of investigators. So far preconditioning has not
been shown to improve functional recovery following an ischemic insult, but preliminary
results in our laboratory have revealed that preconditioning may improve left ventricular
functional recovery after 20 minutes of global ischemia in rabbit hearts.
While preconditioning was described initially in a variety of animal models,

considerable evidence now suggests that a similar effect exists in humans. [113 ] , [114
] Yellon et al. [115 ] demonstrated a protective effect of brief episodes of
cross-clamping and reperfusion prior to a prolonged cross-clamp period in patients
undergoing coronary bypass surgery. Ikonomidis et al. [116 ] demonstrated that isolated
monolayer cultures of human ventricular cardiomyocytes were capable of producing a
preconditioning effect and that this effect is transferable, possibly by a humoral
mediator. Preconditioning seems to retreat to the era of intermittent aortic
cross-clamping, but newer protocols with brief periods of aortic cross-clamping have
not been compared with myocardial protection produced by cardioplegic arrest.
Several pharmacologic agents mimic the preconditioning effect, and these include
adrenergic agents, bradykinin, adenosine, and amiloride. Unfortunately, most of these
agents are either toxic or produce undesirable side effects when administered to
patients. Adenosine is most widely believed to induce a preconditioning response [117
] , [118 ] ; however, its use in humans is limited by potent vasodilatory effects. [119 ]
Acadesine is an adenosine analogue that causes less severe hypotension. A large
clinical trial suggests that acadesine may be beneficial in cardioplegic formulations. [23
]
As the molecular mechanisms of the preconditioning effect are clarified, new

pharmacologic agents may become available for better protection of ischemic
myocardium.
Aprikalim
Traditional cardioplegic protocols involve hyperkalemic arrest achieved by depolarizing

the cellular membrane and inhibiting propagation of an action potential. Recently,
potassium channel openers, such as aprikalim, have been proposed as an alternative
to hyperkalemic arrest. [120 ] These agents produce hyperpolarization of the cell
membrane, which causes cardiac arrest. Hyperpolarizing arrest has the advantage over
depolarizing arrest because energy-consuming processes such as ATP-dependent
calcium and sodium pumps are inhibited. However, these agents may not be as
effective as depolarizing arrest in eliminating myocardial fibrillatory activity. The
proarrhythmic nature of potassium channel openers needs further investigation prior to
widespread clinical application in standard cardioplegic formulations.
Coenzyme Q10
Ubiquinone, alternatively known as coenzyme Q10 , is a naturally occurring component

of the mitochondrial respiratory chain. [121 ] Several reports suggest that endogenous
levels of coenzyme Q10 are reduced in patients with a wide variety of cardiac
disorders, including those with coronary artery disease undergoing revascularization.
[115 ] [119 ] Chen et al. [122 ] randomized 22 patients who had coronary bypass
surgery to receive Q10 (11 patients) or placebo (11 patients). Although there were
statistically significant improvements in mitochondrial ultrastructure observed in biopsy
specimens, there were no appreciable hemodynamic benefits. Thus the role of
coenzyme Q10 as a cardioplegic additive remains unclear.
Summary of Cardioplegic Additives
Numerous cardioplegic additives have been investigated in an effort to improve

perioperative myocardial protection. Undoubtedly, many more compounds will be
introduced as potentially beneficial additives. Each may have specific indications for
use in a tailored fashion for individual patients. However, it must be emphasized that
regardless of the composition of the cardioplegic solution, homogeneous delivery to the
entire myocardium is required to achieve optimal perioperative myocardial protection.
SYSTEMIC TEMPERATURE MANAGEMENT
The Q10 law of chemical processes defines change in kinetics of reactions as a 10°C
change in temperature. Cardiac surgeons utilize this law of nature when they
contemplate systemic temperature management during cardiopulmonary bypass.
Figure 10-16 illustrates the effects of progressive degrees of hypothermia. At a core
temperature of 32.8°C, loss of consciousness occurs; at 30°C, the body loses the ability
to thermoregulate, and poikilothermia sets in; at 28.5°C, slow atrial fibrillation ensues;
and ventricular fibrillation begins at approximately 25°C. Below 25°C, brain stem
reflexes are absent and patients are clinically comatose. By reducing cerebral
metabolic demand, hypothermia protects against neurologic injury following cardiac
surgery. However, hypothermia also produces a delay in recovery of myocardial
metabolism and function. Thus the surgeon must weigh the balance between cerebral
protection and improved hemodynamic performance when contemplating systemic
temperature management during cardiopulmonary bypass.
pH-stat versus Alpha-stat Blood Gas Management
During systemic hypothermia, the patient's pH is usually kept at 7.40 by adding carbon
dioxide to the perfusion circuit (pH-stat management). However, evidence has
accumulated that a pH of 7.40 during systemic hypothermia may be detrimental. [127 ] ,
[128 ] In fact, in ectothermic (cold-blooded) animals, a pH of 7.40 is considered
acidotic. Becker et al. [127 ] studied 12 dogs subjected to systemic hypothermia
(22°C). Six dogs had pH maintained at 7.40 by adjusting the pco 2 during cooling and
rewarming. In the second group of 6 dogs, pH was allowed to vary as in ectothermic
animals (i.e., pH of 7.90 at 17°C). These investigators found that keeping pH at 7.40
caused a 50 percent depression of postischemic myocardial performance. In contrast,
postischemic myocardial performance was normal in animals whose pH varied
appropriately. The approach to systemic acid-base management is less important
when relative normothermia is employed (systemic temperature between 32 and 35°C).
However, when profound hypothermia is required for cerebral protection, alpha-stat
management of pH may be important for postoperative myocardial functional recovery.
In contrast, the hypercarbia produced during pH-stat blood gas management has
beneficial effects on cerebral blood flow by direct cerebral vasodilation. Kirshbom et al.
[129 ] demonstrated a protective effect of pH-stat management in a porcine model of
circulatory arrest. These authors found that cerebral metabolism and high-energy
phosphate stores were better preserved when a pH-stat protocol was employed prior to
circulatory arrest. They attributed this beneficial effect to an increase in cerebral blood
flow caused by the hypercarbic-induced vasodilation. Thus, once again, it appears that
the surgeon must make a tradeoff between cerebral protection and improved
hemodynamic performance.
CEREBRAL PROTECTION
Profound Hypothermia
Routine coronary bypass surgery does not require profound hypothermia for neurologic
protection. At our institution, systemic temperature is allowed to drift to 33 to 35°C. We
rewarm to 38°C to wean from bypass and begin the rewarming process during
construction of the distal left internal mammary artery (LIMA) to left anterior descending
arterial (LAD) anastomosis. This approach reduces the incidence of postoperative
shivering in the intensive care unit. Shivering creates a large metabolic demand and is
usually treated by sedating the patient with either morphine or Demerol. Unfortunately,
sedation prolongs ventilation and increases the duration of stay in the intensive care
unit. Avoiding deep hypothermia during cardiopulmonary bypass reduces postoperative
shivering.
However, for surgery of the aortic arch or aortic dissection, circulatory arrest usually is
required to adequately visualize the operative field. Hypothermia effectively reduces
brain metabolism. [130 ] [133 ] At normothermic temperatures, irreversible neuronal
damage occurs after 4 minutes of cerebral ischemia. Cerebral oxygen consumption is
reduced by approximately 5 percent per degree Celsius between 37 and 22°C. At
20°C, cerebral oxygen consumption is 20 percent of normothermic levels. Thus at 20°C
one can achieve safe periods of circulatory arrest of at least 20 minutes.
The successful use of profound hypothermia encouraged Griepp et al. [134 ] to employ
this technique for repair of ascending and transverse aortic arch disease. However,
Svensson et al. [135 ] have shown that cerebral ischemic times greater than 45 minutes
are associated with an increased risk of stroke and that after 65 minutes of cerebral
ischemia there is a higher risk of mortality. Often, complicated aortic arch repair
requires this period of circulatory arrest. Profound hypothermia (core temperature <
18°C) has been instrumental in allowing safe circulatory arrest times of up to 45
minutes. [136 ] The Boston Circulatory Arrest Study suggests an upper limit of safe
circulatory arrest of 30 to 45 minutes when systemic temperature is lowered to 15°C.
[137 ] However, even at these profoundly hypothermic temperatures, excess cerebral
lactate production that suggests the possibility of neurologic injury occurs. In addition,
profound hypothermia has other detrimental effects such as platelet dysfunction and
impairing recovery of mitochondrial oxidative enzymes.
Low-Flow Cardiopulmonary Bypass
Swain et al. [138 ] reported their experimental results with low-flow cardiopulmonary
bypass during deep hypothermia as an alternative to circulatory arrest. These authors
found that a flow rate of 5 mL/kg per minute depleted high-energy phosphates and
produced intracellular acidosis similar to hypothermic circulatory arrest. However, a flow
rate of 10 mL/kg per minute preserved intracellular pH and high levels of high-energy
phosphates. Hypothermia itself increased levels of high-energy phosphates as animals
were cooled from 37 to 18°C. Animals that were made hyperglycemic had significantly
more acidosis that did not resolve until after 1 hour of reperfusion. In contrast,
nonhyperglycemic animals had a milder intracellular acidosis that returned to baseline
within 30 minutes of reperfusion. Presumably, hyperglycemia stimulated anaerobic
metabolism and led to an accumulation of lactate and hydrogen ions. A similar finding in
the heart was reported by Hearse et al. [74 ] in 1978. Swain et al. also found that
barbiturates such as sodium thiopental prevented the normal increase in high-energy
phosphates induced by hypothermia. Thus administration of barbiturates to patients
who are at risk of cerebral ischemia during deep hypothermic, low-flow
cardiopulmonary bypass may be deleterious. Use of low-flow cardiopulmonary bypass
largely has been replaced by cerebroplegia.
Cerebroplegia
To extend the safe period of circulatory arrest during profound hypothermia, Swain et al.
[139 ] introduced intermittent hypothermic crystalloid cerebral perfusion (cerebroplegia)
in 1990. In a sheep model of circulatory arrest for 2 hours at 15°C, these authors found
that intermittent perfusion of cerebral arteries with a modified dextrose solution
improved preservation of cerebral high-energy phosphates measured by nuclear
magnetic resonance. A recent report by Aoki et al. [140 ] suggests that the University of
Wisconsin solution further improves recovery of cerebral blood flow and metabolism.
Several other compounds such as coenzyme Q10, insulin, and adenosine may prove
more effective for protecting the brain than the myocardium. Clearly, the composition,
temperature, and flow requirements of cerebroplegia require further investigation before
widespread clinical application.
Retrograde Cerebral Perfusion
The use of retrograde cerebral perfusion was first described by Mills and Ochsner [141
] as treatment for intraoperative air embolism. Since their original description, many
centers, including ours, now employ a similar approach for cerebral protection during
total circulatory arrest. [142 ] [146 ] Despite relatively widespread use of this technique,
optimal flow rates and temperature of retrograde cerebral perfusion require further
investigation.
At our institution, we employ low-flow, near-continuous retrograde cerebral perfusion via

the superior vena cava (Fig. 10-17) . Using this technique, we observe dark venous
effluent from the carotid arteries that suggests successful cerebral oxygen delivery.
Lytle et al. [142 ] recently reported results of a similar approach to cerebral protection in
a series of 43 adult patients who required deep hypothermia and circulatory arrest for
repair of the thoracic aorta. In 36 patients, a separate roller pump system was used for
retrograde cerebral perfusion via the superior vena cava. In this report, the authors
maintained central venous pressure between 25 and 30 mmHg with a mean flow rate of
250 mL/min. In their high-risk patients, they had 3 nonfatal and 1 fatal cerebral
complication. All 3 nonfatal injuries resolved completely by late follow-up.
Usui et al. [147 ] evaluated the optimal retrograde cerebral perfusion pressure. They
found that cerebrospinal fluid pressure and cerebral blood flow varied directly with
external jugular venous pressure. However, cerebral blood flow did not increase when
external jugular pressure rose over 25 mmHg, probably because of the increased
intracranial pressure. They recommend limiting retrograde cerebral perfusion to venous
pressures below 25 mmHg.
Hyperglycemia commonly occurs during cardiopulmonary bypass. Crystalloid solutions

used for priming the pump and for myocardial protection often produce severe
hyperglycemia (arterial blood glucose level > 25 mmol/liter). Glucose originally was
used in crystalloid cardioplegia solutions as an osmotic agent to prevent cellular
edema. Many centers continue to use high glucose concentrations in cardioplegic
solutions despite a change toward blood cardioplegia. Evidence from animal models
strongly suggests that hyperglycemia augments ischemic neurologic injury. [148 ] [153 ]
Since cardioplegic solutions eventually reach the systemic circulation, reducing glucose
concentrations in the formulation may be important for reducing neurologic injury during
cardiac surgery.
MANAGEMENT OF THE DISEASED AORTA
During routine cardiac surgery, hypoperfusion of the cerebral cortex is rarely the cause
of perioperative neurologic injury. Rather, intraoperative emboli from atherosclerotic
aortic debris is the main cause of perioperative stroke. In a recent review from our
institution, we found that the presence of triple-vessel coronary artery disease was a
significant predictor of postoperative neurologic injury. [154 ] The presence of severe
coronary artery disease identifies patients who are at risk for atherosclerotic disease of
the ascending aorta. Several studies have documented extensive disease in the
ascending aorta in patients who undergo coronary bypass. [155 ] [157 ] Strategies to
reduce stroke in these patients revolve around perioperative management of the
diseased aorta.
Intraoperative management of the diseased aorta may have the greatest impact on
prevention of neurologic injury. We prefer a single prolonged aortic cross-clamp to the
use of a partially occluding clamp. Recently, Aranki et al. [158 ] reported improved
myocardial and cerebral protection by using the single-clamp technique to construct
both proximal and distal anastomoses. This technique minimizes intraoperative
manipulation of the aorta and reduces the risk of propagating emboli. Barzilai et al. [155
] reported the use of intraoperative ultrasound to detect atherosclerotic plaques in the
ascending aorta and to identify nondiseased segments for cannulation. Alternative sites
for arterial cannulation also have been employed. [159 ] In patients with documented
disease of the ascending aorta, a decision to replace the diseased segment with a
Dacron graft arises. Our experience suggests that replacement can be performed with
minimal additional morbidity and greatly reduces the risk of embolic injury. An
alternative approach advocated by Bonchek et al. [160 ] is to refrain from applying the
aortic cross-clamp. Local isolation of the coronary artery permits adequate visualization
for the distal anastomosis without the need for cardioplegic arrest. This technique is
gaining popularity with the introduction of minimally invasive coronary bypass surgery.
Studies show that despite a normal-appearing aorta, many patients have cerebral
microemboli during cardiac surgery. Although most of these emboli remain
asymptomatic in terms of sensory or motor function, they may contribute to the
neuropsychologic alterations, as reported by several authors. [161 ] [166 ]
SUMMARY
The contemporary results of coronary bypass surgery are excellent, with overall mortality
under 3 percent. Unfortunately, the proportion of high-risk patients presenting for surgery
is increasing with time. New strategies of myocardial protection allow surgeons to
operate on these patients with acceptable levels of morbidity and mortality.
Refinements in myocardial protection now provide surgeons with several options for
clinically difficult situations. We currently employ a tepid (29°C) 4:1 blood-to-crystalloid
mixture for our cardioplegic solution and deliver it near continuously via the coronary
sinus. This is supplemented with antegrade perfusion via completed vein grafts.
High-risk patients require an integrated myocardial management protocol that may
involve a higher ratio of blood to crystalloid, substrate enhancement, or more efficient
delivery techniques. [167 ]
Improvements in the delivery of cardioplegic solutions will lead to improved perfusion to

regions that are inadequately protected with current methodologies. Improvements in
the composition of cardioplegic solutions and new pharmacologic therapies will further
reduce perioperative ischemic injury. All these improvements will require rigorous
clinical investigation using sensitive measures of myocardial function and metabolism
and will be based on continued investigation of cardiac physiology and biochemistry.
In addition, the role of cerebral protection will become more important as surgeons
contemplate more complicated procedures that require total circulatory arrest. In the
future, the need for deep hypothermia may be reduced with further improvements in
cerebral perfusion or cerebroplegia. Continued research into cerebral protection during
cardiac surgery undoubtedly will define the optimal route, pressure, flow rate, and
composition of a cerebroplegic formulation. In a word of caution, the benefits of any
neuroprotective strategy must be weighed against possible detrimental effects on
myocardial protection.
The ability to perform more complex operations on an increasingly high-risk patient

population depends on adequate intraoperative protection of vital organs. The breadth
and depth of clinical and basic science research already underway will inevitably offer
cardiac surgery to patient populations that were once considered inoperable.
COUNTERPULSATION
Historical Notes
The concept of increasing coronary blood flow by retarding the systolic pressure pulse
was demonstrated by Kantrowitz and Kantrowitz in 1953 in a canine preparation and
again by Kantrowitz and McKinnon in 1958 using an electrically stimulated muscle wrap
around the descending thoracic aorta to increase diastolic aortic pressure. [3 ] [5 ] In
1961 Clauss and colleagues used an external counterpulsation system synchronized to
the heart beat to withdraw blood from the femoral artery during systole and reinject it
during diastole. [6 ] One year later Moulopoulos, Topaz, and Kolff produced an inflatable
latex balloon that was inserted into the descending thoracic aorta through the femoral
artery and inflated with carbon dioxide. [7 ] Inflation and deflation were synchronized to
the electrocardiogram to produce counterpulsation that reduced end systolic arterial
pressure and increased diastolic pressure. [7 ] In 1968 Kantrowitz reported survival of
one of three patients with postinfarction cardiogenic shock refractory to medical therapy
using an intra-aortic balloon pump. [8 ] These pioneering studies introduced the
concept of supporting the failing circulation by mechanical means. Currently intra-aortic
balloon counterpulsation is used in an estimated 70,000 patients annually. [4 ]
Physiology
The major physiologic effects of the intra-aortic balloon pump (IABP) are reduction of
left ventricular afterload and an increase in aortic root and coronary perfusion pressure.
[9 ] [11 ] Important related effects include reduction of left ventricular systolic wall tension
and oxygen consumption, reduction of left ventricular end systolic and diastolic volumes,
reduced preload, and an increase in coronary and collateral vessel blood flow. [9 ] , [12 ]
[15 ] Cardiac output increases because of improved myocardial contractility owing to
increased coronary blood flow and the reduced afterload and preload, but the IABP
does not directly move or significantly redistribute blood flow. [9 ] , [16 ] , [17 ] IABP
reduces peak systolic wall stress (afterload) 1419 percent and left ventricular systolic
pressure approximately 15 percent. [9 ] , [12 ] , [16 ] , [18 ] , [19 ] Since peak systolic
wall stress is related directly to myocardial oxygen consumption, myocardial oxygen
requirements are reduced proportionately. [20 ] [22 ] Coronary blood flow is subject to
autoregulation and in experimental animals the IABP does not increase flow until
hypotension reduces flow to less than 50 ml/100 gm ventricle/min. [10 ] However, as
measured by echocardiography and color flow Doppler mapping, peak diastolic flow
velocity increases by 117 percent and the coronary flow velocity integral increases 87
percent with counterpulsation. [23 ] Experimentally collateral blood flow to ischemic
areas increases up to 21 percent at mean arterial pressures >90 mmHg. [24 ]
Several variables affect the physiologic performance of the IABP. The position of the
balloon should be just downstream to the left subclavian artery (Fig. 11-1) . Diastolic
augmentation of coronary blood flow increases with proximity to the aortic valve. [25 ] ,
[26 ] The balloon should fit the aorta so that inflation nearly occludes the vessel. [26 ]
Experimental work indicates that for adults balloon volumes of 30 or 40 ml significantly
improve both left ventricular unloading and diastolic coronary perfusion pressure over
smaller volumes. [25 ] , [26 ] Inflation should be timed to coincide with closure of the
aortic valve, which for clinical purposes is the dicrotic notch of the aortic blood pressure
trace (Fig. 11-2) . Early inflation reduces stroke volume, increases ventricular end
systolic and diastolic volumes, and increases both afterload and preload. [9 ] Diastolic
counterpulsation is visualized easily as a pressure curve in the arterial wave form and
indicates increased diastolic perfusion of the coronary vessels (and/or bypass grafts).
[23 ] , [27 ] , [28 ] Deflation should occur as late as possible to maintain the duration of
the augmented diastolic blood pressure but before the aortic valve opens and the
ventricle ejects. [9 ] For practical purposes deflation is timed to occur with the onset of
the electrocardiographic R-wave. Active deflation of the balloon creates a suction effect
that acts to decrease left ventricular afterload (and therefore myocardial oxygen
consumption).
Biologic factors that influence the in situ hemodynamic performance of the IABP include
heart rate and rhythm, mean arterial diastolic pressure, competence of the aortic valve,
and the compliance of the aortic wall. [9 ] Severe aortic regurgitation is a
contraindication to the use of the IABP; very low mean aortic diastolic pressures reduce
aortic root pressure augmentation and coronary blood flow. A calcified, noncompliant
aorta increases diastolic pressure augmentation, but risks injury to the aortic wall.
By far the most important biologic variables are heart rate and rhythm. Optimal
performance requires a regular heart rate with an easily identified R-wave or a good
arterial pulse tracing with a discrete aortic dicrotic notch. Current balloon pumps trigger
off the electrocardiographic R-wave or from the arterial pressure tracing. Both inflation
and deflation are adjustable and operators attempt to time inflation to coincide with
closure of the aortic valve and descent of the R-wave. During tachycardia the IABP
usually is timed to inflate every other beat; during chaotic rhythms the device is timed to
inflate in an asynchronous fixed mode that may or may not produce a mean decrease in
afterload and an increase in preload. In unstable patients every effort is made to
establish a regular rhythm, including a paced rhythm, so that the IABP can be timed
properly.
Indications
The traditional indications for insertion of the intra-aortic balloon pump are cardiogenic
shock (see Chapter 21), uncontrolled myocardial ischemic pain, and postcardiotomy
low cardiac output. [17 ] , [29 ] [32 ] In recent years indications for IABP have broadened
to include patients with high risk or failed percutaneous transluminal coronary
angioplasty, atherectomy, or stents; poorly controlled ventricular arrhythmias before or
after operation; and patients with postinfarction ventricular septal defect or acute mitral
insufficiency after myocardial infarction (see Chapters 22 and 23). [31 ] , [33 ] [36 ] In
addition, the IABP occasionally is used prophylactically in high-risk patients with poor
left ventricular function with either mitral regurgitation or preoperative low cardiac output
owing to hibernating or stunned myocardium. These patients benefit from temporary
afterload reduction during weaning from cardiopulmonary bypass, particularly if
myocardial contractility is not immediately improved by revascularization. In some
institutions a femoral arterial catheter is inserted in anticipation of IABP use in patients
undergoing complex procedures who have myocardial dysfunction. [37 ] In exceptional
patients IABP is used with extracorporeal membrane oxygenation (ECMO) to unload
the left ventricle while providing circulatory assistance for postcardiotomy patients. [38 ]
[40 ]
Nearly 90 percent of patients who receive intra-aortic balloon counterpulsation have

various manifestations of ischemic heart disease, with or without associated valvular
heart disease. [29 ] , [30 ] , [35 ] , [41 ] [43 ] Patients with valvular heart disease without
coronary disease generally receive an intraoperative IABP and the majority of these
patients have mitral valve disease. [30 ] , [41 ] A few patients have insertion of the
balloon pump for end-stage cardiomyopathy, acute endocarditis, or before or after heart
transplantation. [31 ] , [32 ] , [44 ]
The vast majority of patients who receive the IABP on the medical service have
ischemic heart disease primarily manifested by cardiogenic shock or unstable,
refractory angina. [17 ] , [31 ] , [32 ] Of 231 patients who had IABP insertions at the
Cleveland Clinic, Eltchaninoff reports that 83 (34.6 percent) were for complications of
acute myocardial infarction. Forty-four (18.3 percent) were owing to failed angioplasty,
48 (20 percent) were for high risk angioplasty, and 31 (12.9 percent) were for
stabilization before cardiac surgery. [31 ] Only 13 (5.4 percent) were for end-stage
cardiomyopathy. [31 ]
The timing of IABP insertion varies widely between reports. The percentage of IABPs
inserted before cardiac surgery varies between 18 percent at St. Louis University
Medical Center and 57 percent in a group of community hospitals that do cardiac
catheterization. [29 ] , [30 ] , [32 ] , [41 ] , [45 ] , [46 ] This percentage appears to be
increasing in recent years (Fig. 11-3) . The percentage of IABPs inserted
intraoperatively varies: 4272 percent. [29 ] , [30 ] , [32 ] , [41 ] , [45 ] [46 ] The smallest
number are inserted early after operation: 314 percent. [30 ] , [32 ] , [41 ] , [45 ] , [46 ]
The overall incidence of IABP use varies between 6.1 percent of all cardiac surgical
operations at the Cleveland Clinic (Fig. 11-4) and 9.8 percent at Washington University
Hospitals in St. Louis. [30 ] , [32 ] , [41 ] When angioplasties are added to bypass
operations the incidence is 4.6 percent. [32 ]
The overwhelming reason for intraoperative use of the IABP is failure to wean from
cardiopulmonary bypass. [29 ] , [30 ] , [41 ] Approximately 75 percent of intraoperative
balloon insertions are for this reason. [29 ] , [30 ] , [41 ] Preoperative low cardiac output
and postinfarction angina are additional indications for intraoperative insertion of the
IABP. [41 ] [43 ] Approximately half of patients who require intraoperative IABP have
urgent or emergency operations. [41 ]
Techniques of Insertion
The intra-aortic balloon pump is usually inserted into the common femoral artery either
by the percutaneous technique or by surgical cutdown. [47 ] A cutdown is most often
used during cardiopulmonary bypass when the pulse is absent. The superficial femoral
artery is avoided because of its smaller size and increased possibility of leg ischemia.
For patients with small vessels an 8.5 Fr. catheter is recommended; however, this
catheter does not have the pressure monitoring channel contained within the 9.5 Fr.
catheter. The iliac and axillary arteries and, very rarely, the abdominal aorta, are
infrequently used alternate sites. [48 ] , [49 ] Direct insertion into the ascending aorta is
used for intraoperative insertions in patients with severe aortoiliac or femoral occlusive
disease that prevents passage of the balloon catheter. [50 ] [52 ]
The percutaneous method uses a guide wire and is faster than a cutdown. [31 ] , [45 ] ,
[53 ] Approximately two-thirds to three-quarters of all femoral arterial insertions utilize
the percutaneous method. [46 ] , [54 ] Although percutaneous insertion was associated
with a higher incidence of leg ischemia in the past, this is no longer true. [31 ] , [45 ] , [53
] , [55 ] In the catheterization laboratory both the guidewire and balloon are monitored by
fluoroscopy, but this is not essential if not readily available. The cutdown technique may
be done with local anesthesia outside of the operating room, but preferably is done in
the operating room with local or general anesthesia because the risk of contamination
is less. After the femoral artery is exposed, a guidewire is introduced followed by
dilating catheters and the balloon. The catheter can be inserted without the sheath in
some instances. [56 ] The balloon catheter usually fits snugly in the arterial wound, so a
pursestring suture is not needed. An earlier technique of sewing a prosthetic vascular
graft end to side to the femoral artery to form a sleeve is no longer used. [45 ] If bleeding
is present around the entrance site, sutures are used for control. The wound is closed
completely. Regardless of the method of insertion, whenever possible the tip of the
balloon is visualized by fluoroscopy or transesophageal echocardiography or palpated
to place the balloon in the optimal position just downstream to the left subclavian artery.
[57 ]
The timing of inflation and deflation of the balloon must be monitored closely during
counterpulsation. This usually and easily is done by observing the continuously
displayed arterial pressure tracing; a second systolic pulse should appear with every
heart beat and begin just after the smaller first pulse begins to decay. Timing the balloon
for irregular rhythms is difficult and the circulatory support provided by the balloon is
compromised; in these patients attempts are made to convert the patient to a sinus or
paced rhythm or to slow (8090 beats/min) atrial fibrillation using appropriate drugs or
cardioversion. For tachycardias over 110120 beats/min the balloon is timed to provide
inflation on alternate beats if the machine is not able to reliably follow each beat.
Generally patients are not given heparin for the IABP. Ten milliliters per hour of low
molecular weight dextran are recommended by some groups. The exit site of the
catheter must be kept clean with antiseptics and covered in an effort to prevent local
infection or septicemia.
A percutaneous IABP can be removed without exposing the femoral puncture site. The
exit site is prepped and securing sutures are cut. The balloon catheter is disconnected
from the pump and completely deflated using a 50-ml syringe. Using steady pressure
over the femoral puncture site the balloon catheter is withdrawn smoothly and removed.
Pressure is maintained over the puncture site for 30 minutes to insure that thrombus
closes the hole. [37 ] , [45 ] If the balloon is inserted via a cutdown, the balloon preferably
is removed in the operating room. The puncture site is closed with sutures. If blood flow
to the lower limb is impaired after removal, a local thromboembolectomy using Fogarty
catheters and an angioplasty procedure using a vein patch is done to restore full flow to
the limb.
If the percutaneous needle punctures the iliac artery above the inguinal ligament
intentionally or inadvertently in obese individuals, removal should be done through a
surgical incision in the operating room because the backward slope of the pelvis makes
pressure difficult to maintain after withdrawal and substantial occult retroperitoneal
bleeding may occur.
If the common femoral or iliac arteries cannot be used because of occlusive disease or
inability to advance the guidewire, the axillary artery usually is exposed below the
middle third of the clavicle for insertion. [48 ] , [49 ] This vessel is smaller than the
femoral artery, but generally more compliant. Fluoroscopy or transesophageal (not
transthoracic) echocardiography is recommended to insure that the guidewire does not
go down the ascending thoracic aorta into the heart.
Transaortic insertion is done only for postcardiotomy patients who have severe
peripheral vascular or aorto-iliac disease that precludes femoral insertion. The catheter
may be inserted through an 8- or 10-mm woven Dacron or polyfluorotetraethylene graft
that is beveled and sutured end-to-side to the ascending aorta using a side biting clamp
on the aorta. [52 ] The opposite end of the graft is passed through a stab incision in the
chest wall below but near the xiphoid. The incision in the fascia and soft tissues must be
large enough to accommodate the balloon catheter. The balloon is passed through this
sleeve into the aorta and guided into the proximal descending thoracic aorta so that the
balloon does not occlude the left subclavian orifice when inflated. The suture cuff of the
balloon catheter is trimmed so that it can be inserted into the graft and tied tightly to
achieve secure hemostasis. This connection is placed just beneath the skin so that
none of the graft protrudes. The catheter is secured in place and managed in the same
way as IABPs placed through other insertion sites.
A simpler method uses two aortic pursestring sutures to secure the aorta around the
balloon catheter. No graft is used, yet bleeding complications are minimal. [50 ] , [51 ]
Regardless of the technique of insertion balloon catheters inserted through the
ascending aorta are removed in the operating room to secure closure of the aorta. [50 ]
, [51 ]
Because aortic-iliac occlusive disease usually involves the abdominal aorta and
ilio-femoral vessels, an abdominal aortic insertion site, exposed retroperitoneally, is
more theoretical than practical.
Pulmonary arterial counterpulsation is recommended for right heart failure but has not
achieved wide use. [58 ] , [59 ] Because of the short length of the pulmonary artery either
a prosthetic graft (2025 mm) is sewn end-to-side to the main pulmonary artery and tied
around the balloon catheter placed inside. There are little data regarding the amount of
afterload reduction of the right ventricle.
Complications
Reported complication rates of the intra-aortic balloon pump vary between 12.9 and 29
percent and average approximately 20 percent. [1 ] , [32 ] , [54 ] , [60 ] Life-threatening
complications are rare. [30 ] , [61 ] Leg ischemia is by far the most common
complication (incidence 925 percent patients); other complications include balloon
rupture, thrombosis within the balloon, septicemia, infection at the insertion site,
bleeding, false aneurysm formation, lymph fistula, lymphocele, and femoral neuropathy.
[31 ] , [32 ] , [45 ] , [54 ] , [62 ] , [63 ] The development of smaller, sheathless catheters
may reduce the incidence of leg ischemia, although this fact has not been
demonstrated. [31 ] , [56 ] There is no significant difference in limb ischemia in the five
different types of IABPs clinically available. [60 ] , [64 ]
Balloon rupture occurs in approximately 1.7 percent of patients and usually is indicated
by the appearance of blood within the balloon catheter and only occasionally by the
pump alarm. [64 ] Rupture may be slightly more common with transaortic insertion. [50 ]
Although helium usually is used to inflate the balloon, gas embolism has not been a
problem. If rupture occurs the balloon should be deflated forcibly to minimize thrombus
formation within the balloon and promptly removed. If the patient is IABP-dependent, a
guidewire is introduced through the ruptured balloon, the original balloon is removed,
and a second balloon catheter is inserted over the wire. If the ruptured balloon is not
removed easily, a second balloon is inserted via the opposite femoral or iliac artery or
through the axillary artery to maintain circulatory support.
Removal of a kinked or thrombosed ruptured balloon that cannot be withdrawn by firm

traction requires operation. A thrombosed balloon can severely lacerate the femoral
artery. The catheter should be withdrawn as far as possible with firm traction. The
location of the tip should be determined by x-ray or ultrasound and an incision planned
to expose that segment of the vascular system. In the operating room thrombolytic drugs
may be considered if these drugs are not contraindicated by recent surgery. [65 ] The
trapped balloon is removed through an arterotomy after control of the vascular segment
is obtained.
Although the incidence of clinically significant lower leg ischemia varies from 925
percent of patients, up to 47 percent have evidence of ischemia during the time the
IABP is used. [31 ] , [46 ] , [54 ] , [62 ] , [63 ] Thus the preinsertion status of the pedal
pulses should be determined and recorded before the IABP is inserted in every patient.
After insertion, the circulation of the foot is followed hourly by palpating pulses or by
Doppler ultrasound. Foot color, mottling, temperature, and capillary refill are observed;
the appearance of pain, dullness to sensation, and minimal circulation indicate severe
ischemia that requires restoration of the circulation to the extremity as soon as possible.
There are three alternatives. If the patient is not balloon-dependent, it is removed

immediately. In the majority of patients this relieves the distal ischemia; a few patients
require surgical exploration of the puncture site, removal of thrombus and/or emboli, and
reconstruction of the femoral artery. [31 ] , [54 ] If the patient is balloon-dependent, a
second balloon catheter can be introduced into the opposite femoral or iliac artery and
the first removed. If this alternative is not available or attractive, circulation to the
ischemic extremity is restored using a cross leg vascular graft or, less commonly, an
axillo-femoral graft. [32 ] , [66 ] , [67 ] Prompt revascularization pre-empts development
of the compartment syndrome (incidence 13 percent) and the need for fasciotomy. [32 ]
, [54 ] , [67 ] Prompt and aggressive treatment of leg ischemia has reduced the
incidence of amputation to 0.51.5 percent, but if amputation is necessary the level often
is above the knee. [31 ] , [32 ] , [45 ] , [46 ] , [67 ] The majority of amputations occur in
women. [32 ]
Several risk factors for development of leg ischemia have emerged. Female gender,
[32 ] , [62 ] , [63 ] , peripheral vascular disease, [31 ] , [32 ] , [54 ] , [62 ] , [63 ] diabetes,
[31 ] , [63 ] , [68 ] cigarette smoking, [54 ] , [63 ] advanced age, [62 ] obesity, [32 ] and
cardiogenic shock [63 ] are reported to increase the risk of ischemic complications
after IABP. Since the IABP is inserted for compelling indications identification of risk
factors does not influence management, except to encourage removal of the device as
soon as the cardiac status of the patients allows. In some series longer duration of IABP
counterpulsation is associated with an increased risk of complications. [62 ]
Although most ischemic complications are owing to impairment of arterial inflow, severe
atherosclerotic diseases of the descending thoracic aorta may produce trash
embolization of atherosclerotic material that can cause the blue toe syndrome and
eventually require amputation. [32 ] , [62 ] Emboli may also reach the renal and visceral
arteries to produce ischemia of these organs. [32 ] The presence of aortic
atherosclerosis can be determined by echocardiography and if present, insertion
through the axillary artery may be considered. [23 ] , [69 ] The ischemic rate of axillary
insertions is not known because of the low number of cases reported.
Approximately 1 percent of patients develop false aneurysms at the femoral puncture

site either in the hospital or shortly after discharge and rare patients develop an
arterial-venous fistula. [32 ] , [54 ] Both conditions are confirmed readily by duplex
scanning and require elective operative repair; neglected false aneurysms can rupture.
The rare complication of lymphocele or lymph fistula preferably is treated surgically by
local exploration and suture control.
Bleeding produces a local hematoma that is not evacuated unless skin necrosis is
likely. If bleeding occurs in the wound, the wound is explored, bleeding is stopped, part
of the hematoma is evacuated without extending the dissection, and the wound is
reclosed. Bleeding from transaortic insertion is uncommon (34 percent). [50 ]
Retroperitoneal bleeding from an iliac artery puncture may not be obvious, but may
cause death. [62 ]
Septicemia occurs in up to 1 percent of patients, but the risk increases with the duration
of the IABP residence. Most catheters are removed within 4872 hours. [62 ] Septicemia
is an indication for IABP removal, but if the patient is balloon-dependent, a replacement
balloon catheter is inserted in a new site. Suspected septicemia is treated aggressively
after blood cultures are obtained with broad spectrum antibiotics that are switched to
one or more specific antibiotics when the organism is known. Local infections occur in
23 percent of patients and usually are treated by drainage, packing, antibiotics, and
secondary closure.
Acute aortic dissection from the catheter tip piercing the intima has been reported. [32 ]
This problem is prevented preferably by not advancing the catheter against resistance
and monitoring with fluoroscopy or transesophageal echocardiography. Occasional
femoral neuropathies resolve over time, but can be disabling. Transaortic IABP is
associated with a 23 percent incidence of cerebral vascular accidents. [51 ]
Results
Very few complications of IABP cause death. Rare instances of bleeding

(retroperitoneal or aortic), septicemia, central nervous system injury, or aortic dissection
may cause or contribute to a patient's death. [32 ] , [51 ] , [62 ] Mortality is higher in
patients with leg ischemic complications than in those without. [32 ]
Counterpulsation increases coronary arterial flow, reduces afterload and myocardial

oxygen consumption, and experimentally reduces infarct size early after infarction. [14 ] ,
[70 ] Without revascularization IABP produces a marginal increase in survival, but with
revascularization both short-term, long-term, and quality of life are substantially
improved. [17 ] , [71 ] [73 ]
However, mortality is high in patients who receive an IABP because of the cardiac
problems that led to the need for the device. Overall hospital mortality ranges 2650
percent (Fig. 11-5) . [29 ] , [41 ] , [44 ] , [75 ] , [76 ] Risk factors for hospital mortality
include advanced age, female gender, high NYHA class, preoperative nitroglycerin,
operative or postoperative insertion, and transaortic insertion in one study and age and
diabetes mellitus in another. [41 ] A third study correlates hospital death with acute
myocardial infarction, ejection fraction less than 3 percent, NYHA class IV, and
prolonged aortic cross-clamp and bypass times. [75 ] Time of insertion affects hospital
mortality: preoperative insertion is associated with a mortality of 18.8 percent (Fig.
11-6) and 19.6 percent. [44 ] Mortality for intraoperative insertion is 27.632.3 percent.
[44 ] Postoperative insertion produces a mortality of 3940.5 percent (Fig. 11-6) . [44 ]
Mortality is highest at 68 percent for patients with pump failure; is lowest at 34 percent
for patients with coronary ischemia; and is 48 percent for patients who had a cardiac
operation. [29 ] Risk factors available at the time of weaning from cardiopulmonary
bypass associated with the likelihood of hospital death are heart block, advanced age,
female gender, and elevated preoperative blood urea concentration. [74 ]
Long-term survival varies with the type of operation and is highest in patients who had
cardiac transplantation or myocardial revascularization. [44 ] Patients who received an
IABP and who required valve surgery with or without revascularization have a poorer
prognosis. [44 ] Creswell and colleagues find 58.8 percent of all patients alive at 1 year
and 47.2 alive at 5 years. Nauheim and associates find that nearly all survivors are in
NYHA class I or II. [41 ] Approximately 18 percent of hospital survivors have some
symptoms of lower extremity ischemia. [76 ]
DIRECT CIRCULATORY SUPPORT
Continuous Flow Pumps
The purpose of temporary circulatory support with centrifugal or roller pump circuits is to
maintain the circulation until the native heart recovers from a reversible injury. If the heart
does not recover sufficient function to maintain life, long-term circulatory support (see
Chapter 51) or transplantation (see Chapter 49) is needed.
Continuous flow pumps provide a universally available means to provide temporary

direct circulatory support in that the equipment and personnel trained in its use are
available in every hospital in which heart surgery is done. These pumps were the first to
be used for circulatory assistance and continue to be the most frequently used. [1 ] , [2 ]
, [77 ] Less than 1 percent of patients (range 0.21.0 percent) who have open heart
surgery cannot be weaned from cardiopulmonary bypass using drugs and
counterpulsation (Fig. 11-7) . [1 ] , [78 ] [84 ]
These systems are extracorporeal and use various components of the heart-lung
machine. Extracorporeal membrane oxygenation (ECMO) includes an oxygenator/heat
exchanger within the perfusion circuit and bypasses both the heart and lungs to provide
support for the entire circulation. ECMO is synonymous with ECLS (extracorporeal life
support). RVAD (right ventricular assist device) bypasses the right ventricle only and
LVAD (left ventricular assist device) bypasses the left ventricle; neither system
incorporates an oxygenator. BVAD (biventricular assist system) combines RVAD and
LVAD to support both ventricles without an oxygenator. ECMO, RVAD, LVAD, and
BVAD use transcutaneous cannulas, require some degree of anticoagulation, need a
means to reduce heat loss from the extracorporeal circuit, activate and destroy some
blood elements, and are generally limited to short-term use, usually less than 1 week.
PUMPS
There are two types of commercially available pumps for extracorporeal circulation:
roller pumps and centrifugal/impellor pumps. Roller pumps are used rarely for circulatory
support because of important disadvantages. Although inexpensive, roller pumps are
insensitive to line pressure if the outflow line becomes obstructed, require unobstructed,
inflow, cause spallation of tubing particles, and are subject to tubing failure at
unpredictable times. These systems require constant vigilance and are difficult to
operate for extended periods.
Centrifugal and impellor pumps spin concentric cones (Medtronic-Biomedicus, Eden

Prairie, MN) or blades (Sarns Inc., Ann Arbor, MI) at high rpm to impart rotational
momentum to blood that enters the center of the pump housing and exits through a
perimeter outlet. These pumps may generate negative pressure at the inlet port if inflow
is obstructed, but unlike roller pumps the momentary decrease in pump flow is
self-relieving as new blood reaches the system. Small amounts of air entering the inflow
line tend to remain within the pump, but large amounts deprime the pump and stop flow.
Centrifugal/impellor pumps tolerate outflow obstruction without a build-up in pressure
within the circuit. Centrifugal/impellor pumps require some degree of anticoagulation
and, if inadequate, clots may form within the pump. [82 ] , [85 ] Both roller and
centrifugal/impellor pumps cause some trauma to red cells to produce mild hemolysis.
Centrifugal/impellor pumps are disposable, require less vigilance in operation than
roller pumps, and are more suited for extended use.
EXTRACORPOREAL MEMBRANE OXYGENATION (ECMO)
ECMO circulates and ventilates blood and can temporarily substitute for the entire
circulation. However, like the heart-lung machine, ECMO activates blood elements to
cause the coagulation and inflammatory problems associated with cardiopulmonary
bypass (see Chapter 9). ECMO can be implemented using percutaneous or direct
insertion femoral cannulas or may use central cannulas placed in the heart or great
vessels at operation. The system requires an operator in constant attendance and
blood must be anticoagulated. ECMO is the only circulatory support system that does
not require thoracotomy. With preparation and training ECMO can be rapidly
implemented outside the operating room in critical care and cardiac catheterization
units. [40 ] , [86 ] , [87 ] For this reason ECMO has been used to maintain the circulation
during high-risk catheterization procedures such as angioplasty or stent deployment. [88
] However, the most common use for temporary circulatory support is for patients who
cannot be weaned from cardiopulmonary bypass after cardiac surgery.
ECMO unloads the right ventricle, but does not unload the ejecting left ventricle, even
though left ventricular preload is reduced. [38 ] , [89 ] In normal hearts the marked
reduction in preload and small increase in afterload produced by the arterial inflow from
the ECMO system reduces wall stress and produces smaller end-diastolic left
ventricular volumes because the heart is able to eject the blood it receives. However, if
the heart is dilated and poorly contracting, the marked increase in afterload provided by
the ECMO system offsets any change in end-diastolic left ventricular volume produced
by bypassing the heart. The heart remains dilated because the left ventricle cannot eject
sufficient volume against the increased afterload to reduce either end-diastolic or
end-systolic volume. [38 ] , [89 ] , [90 ] ECMO, therefore, may increase left ventricular
wall stress and myocardial oxygen consumption unless an intra-aortic balloon pump or
other means is used to mechanically unload the left ventricle and reduce left ventricular
wall stress. [91 ] Kolobow has devised a spring-loaded catheter introduced through the
femoral vein to render the pulmonary valve incompetent to decompress the left ventricle
during ECMO, but this has not been used clinically. [91 ]
The common femoral vessels are used for inflow and outflow cannulas in most patients.
Cannulas may be inserted percutaneously over a guide wire or by surgical cutdown. If
the guidewire is introduced successfully, a small skin incision is made to allow the
catheter to pass. The venous catheter (1824 Fr.) is passed from the groin to the right
atrium to permit unlimited venous inflow (Fig. 11-8) . [92 ] Inflow is restricted if the tip of
the catheter does not reach the right atrium. The tip of the arterial cannula (1723 Fr.)
reaches the external iliac artery for retrograde perfusion. If the guidewires cannot be
introduced percutaneously, the vessels are exposed by surgical cutdown and
cannulated over wires introduced by direct vision. Peripheral cannulation is used for
most applications of ECMO (see the following), for patients who are supported with
ECMO for respiratory support (see Chapter 9), and for certain minimally invasive
cardiac procedures.
The most common application of ECMO is for patients who cannot be weaned from
cardiopulmonary bypass after heart surgery. Since ECMO is merely a streamlined
version of the perfusion circuit of the heart-lung machine, the existing right atrial and
aortic cannulas can be used; however, we prefer to convert the system to peripheral
cannulas and to cannulate both the proximal and distal femoral artery. The cannulation is
done by surgical cutdown and a 10 Fr. cannula inserted downstream to the primary
arterial inflow cannula to perfuse the leg (Fig. 11-9) . [90 ] , [93 ] The distal cannula
directs flow into the leg and significantly reduces problems with leg ischemia.
Conversion permits chest closure and removal of perfusion catheters at the bedside in
intensive care.
In patients with severe peripheral vascular disease existing aortic and right atrial
catheters are used. The tip of the aortic cannula is advanced into the arch just beyond
the left subclavian artery to reduce the possibility of embolization of the cerebral
vessels. Reinforcing pursestring sutures are placed and tied over rubber chokers and
buttons for later tying at decannulation. The catheters are brought through the chest wall
through separate stab wounds and after bleeding is secured, the chest is covered, but
not closed, over mediastinal drainage tubes. [82 ]
The external iliac vessels exposed through a small retroperitoneal incision are an
alternative peripheral cannulation site. The axillary artery has been used but is
associated with progressive edema of the arm. [94 ]
The perfusion circuit consists of a venous cannula, arterial cannula, centrifugal pump
upstream to a membrane oxygenator-heat exchanger unit. A filter is not used in the
arterial line, but a flowmeter is included. For distal femoral arterial perfusion a
Y-connector(&frac38;, &frac38;, ¼) is placed in the arterial line near the wound (Fig.
11-9) . Depending on circumstances, the system is primed with Ringers lactate with or
without 500 ml of starch solution or homologous blood.
ECMO is the only method of direct circulatory support that can be implemented rapidly
using peripheral cannulas. Thus it is used for selected patients who suffer cardiac arrest
and who are thought to have reversible disease. [40 ] , [86 ] , [95 ] ECMO is prescribed
for patients in cardiogenic shock who cannot be safely moved to the operating room.
ECMO may be used after cardiac arrest or acute pulmonary embolus. It is also used
occasionally in the catheterization laboratory to support high-risk procedures. In the
operating room ECMO is the fastest method to reestablish an adequate circulation in
hypotensive patients who have had previous cardiac surgery. More recently ECMO,
which implies peripheral cannulation, is used to support some minimally invasive
cardiac operations.
The greatest use of ECMO is for the postcardiotomy patient who cannot be weaned
from cardiopulmonary bypass after correction of all operable problems (e.g., ungrafted
coronary arteries, paravalvular leak, residual aortic stenosis or mitral regurgitation, etc.),
maximum pharmacologic therapy, and insertion of the intra-aortic balloon pump.
Pharmacologic therapy includes correction of acidosis, hypoxemia and electrolyte
imbalance, catecholamines chosen by effectiveness and paucity of arrhythmias, drugs
needed to control arrhythmias, phosphodiesterase inhibitors (milrinone), and
nitroglycerine for patients with ischemic heart disease. Systemic vascular resistance is
manipulated to produce the lowest afterload that provides adequate coronary and
cerebral arterial perfusion; often the intra-aortic balloon pump is all that is needed for
this requirement.
Patients who have maximum cardiac indices of 1.8 ml/m 2 /min or less and are not
improving with time, who have an elevated left atrial or pulmonary diastolic pressure 46
mmHg greater than their prebypass pressure, who cannot maintain an arterial pressure
greater than 90 mmHg systolic (or higher if necessary for adequate coronary perfusion),
or who have intractable arrhythmias that cannot be controlled medically or by
cardioversion are candidates for postoperative direct circulatory support by BVAD or
ECMO. If right ventricular end diastolic pressure and central venous pressure is 15
mmHg or less, LVAD can be used.
Patients with right heart failure after maximal pharmacologic therapy may be candidates
for ECMO, BVAD, or RVAD. In the absence of left heart failure right heart failure is
primarily manifested by left atrial or pulmonary arterial diastolic pressures 24 mmHg
less than prebypass pressures in patients with hypotension and low cardiac output.
Efforts are made to reduce pulmonary vascular resistance; the most important
determinant is an elevated (above 20 mmHg) left ventricular end diastolic pressure. If
left ventricular end diastolic pressure is elevated, BVAD or ECMO is needed if right
ventricular end diastolic pressure or central venous pressure exceed 20 mmHg.
Dobutamine and isoproterenol tend to increase myocardial contractility and reduce
pulmonary vascular resistance, but both drugs also have systemic effects and
isoproterenol is arrhythmogenic. Prostaglandin E1, adenosine, and inhaled nitric oxide
dilate pulmonary arteries, but successful use immediately after cardiopulmonary bypass
is usually limited to patients with mitral valve disease, heart transplantation or pulmonary
thromboendarterectomy (see Chapters 45 and 96). We do not recommend pulmonary
arterial counterpulsation. [58 ] , [59 ]
Despite problems we prefer ECMO over RVAD, LVAD, or BVAD for postcardiotomy
patients who cannot be weaned from cardiopulmonary bypass and have modified our
anticoagulation protocols (see the following) to reduce bleeding problems associated
with postoperative ECMO. ECMO supports both ventricles, is easily implemented after
generally prolonged operations and does not require a return to the operating room for
decannulation.
A priori direct circulatory support is not indicated in patients who cannot be restored to
cognitive life. In some patients the decision to do a cardiac operation is made without
knowledge of irreversible brain or other organ damage suffered during cardiac arrest or
a period of cardiogenic shock. More information may be available after bypass to
influence the decision to proceed to direct circulatory support. Intraoperative events
including stunned myocardium and reperfused myocardial infarctions often are
reversible to some degree. Oliguria during cardiopulmonary bypass, intractable
post-bypass coagulopathy, and bleeding and age over 70 years are associated with
poor survival. [97 ]
The use of full dose systemic heparin dose (34 mg heparin/kg body weight) for
postcardiotomy ECMO is associated with severe bleeding problems that necessitate
multiple transfusions of blood products that often produce renal failure and death. [98 ]
When heparin uncoated perfusion circuits are used, the smallest amount of heparin
needed to prevent clotting in the circuit or patient is used after ECMO is established
and all surgical wound bleeding is controlled. With heparin coated circuits no heparin or
very small amounts during periods of low flow are used in an attempt to reduce
nonsurgical bleeding. [89 ] , [90 ]
Heparin coated perfusion circuits offer the prospect of improved survival and reduced
postoperative bleeding and transfusions, but there are dangers. [89 ] , [99 ] Protamine
administration after starting ECMO can precipitate intracardiac clot. [90 ] If the left
ventricle does not eject and blood remains static within the ventricle, clot formation is
more likely. [90 ] Intracavity clot is more likely in patients with myocardial infarction due
to expression of tissue factor by the injured cells. Protamine may bind to the heparinized
coating of the new circuit and negate an anticoagulant effect. [100 ] It may be wise to
give some protamine while still on cardiopulmonary bypass before switching to the
ECMO circuit.
During ECMO bleeding is treated by transfusion of packed red cells, platelets, fresh
frozen plasma and cryoprecipitate as necessary. [82 ] , [89 ] A high percentage of
patients require reoperation for bleeding. [82 ] , [90 ] Epsilon aminocaproic acid may be
given, but aprotinin is not. After bleeding stops we typically start heparin and target an
activated clotting time of 175225 seconds.
The patient's lungs are lightly ventilated (10 ml/kg; 8 breaths/min; 5 cm h 2 o end
expiratory airway pressure) and periodically inflated fully to prevent atelectasis and
pneumonia. The lungs are ventilated with 50 percent oxygen or sufficient inspired
oxygen to maintain oxygen saturation of blood ejected from the left ventricle above 90
percent. If poorly oxygenated blood is ejected from the left ventricle, this desaturated
blood may perfuse the coronary arteries and add hypoxic damage to the already injured
heart. [86 ] Because blood samples are obtained at sampling sites perfused by the
ECMO system, this possibility may not be appreciated unless a sample is obtained
from a left atrial catheter.
The patient is generally managed as for other cardiac surgical patients in the intensive
care unit. The electrocardiogram, arterial, pulmonary arterial, and central venous
pressures are monitored in addition to blood, urine, and fluid losses and fluid intake.
Inotropic drugs are weaned except for renal dose dopamine. Pump flows average
approximately 4 l/min, but often range 1.56 l/min. [82 ] Transesophageal
echocardiography is used to monitor recovery of left and right ventricular function. Broad
spectrum antibiotics are given for the duration of ECMO; central catheters are changed
every 35 days or if fever or other signs of infection emerge. The circulation of the
cannulated leg is monitored hourly. If renal failure occurs, either continuous ultrafiltration
or hemodialysis is used.
Five thousand units of systemic heparin are given with heparin coated circuits during
periods of low pump flow (e.g., changing an oxygenator or pump head) and during
weaning from ECMO. Weaning attempts are made with transesophageal
echocardiographic monitoring. [82 ] Patients, who are eligible for cardiac
transplantation, are transferred to a long-term assist device (e.g., HeartMate ®, Thermo
Cardiosystems, Inc., Woburn, MA) as soon as it is clear that the native heart will not
recover. Patients eligible for weaning are decannulated in the intensive care unit and, if
necessary, cannulated vessels are repaired. Patients with intrathoracic catheters are
decannulated in the operating room.
LEFT, RIGHT, AND BIVENTRICULAR ASSIST DEVICES
LVAD, RVAD, and BVAD circuits incorporate centrifugal or impellor pumps and do not
contain an oxygenator. These configurations require cannulation of the heart or great
vessels in most instances although methods have been developed to implement RVAD
and LVAD without thoracotomy. [94 ] , [101 ] The major advantage of ventricular bypass
systems is that they volume unload the ventricle bypassed and reduce activation and
damage of blood constituents because the surface area of the perfusion circuit is
reduced greatly by the absence of an oxygenator (see Chapter 9). If the bypassed
ventricle continues to eject, end diastolic volume decreases dramatically and end
systolic volume also decreases. [102 ] With separate bypass of one or both ventricles
either pulmonary or systemic afterload can be separately manipulated by drugs to
reduce ventricular wall tension and myocardial oxygen demand. As end systolic volume
decreases contractility may actually increase perhaps because myocardial creep is
reversed. [102 ] , [103 ] Separate bypass of an ejecting ventricle actually rests the
ventricle and may enhance functional recovery (see Chapter 51).
For RVAD a single, inflow cannula is placed in the right atrium and the outflow cannula
is placed, usually through pursestring sutures, into the main pulmonary artery. Care is
taken to direct flow into both lungs as opposed to a single lung. For LVAD usually the
left atrium is cannulated between the junction of the right superior pulmonary vein and
left atrium or through the left atrial appendage (Fig. 11-10) . Left atrial catheters are
carefully positioned within the atrium to avoid damage to the mitral valve and to avoid
partial obstruction by the atrial wall. Extracorporeal flow often is very sensitive to
chamber volume and transfusions or volume expanders often are required to maintain
desired flow rates. Right ventricular cannulation is not used for RVAD or BVAD and left
ventricular cannulation infrequently is used for LVAD to reduce damage to the
compromised left ventricle. A right angled catheter usually is used for cannulation of the
left atrial appendage; either a straight or angled 1824 Fr. catheter is used for the
right-sided, left atrial cannulation site. The inflow catheter is placed through concentric
pursestrings in the ascending aorta, but the tip of the catheter is advanced beyond the
origin of the left subclavian artery to reduce the risk of cerebral emboli.
The Dennis technique of left atrial cannulation without thoracotomy uses a transseptal
approach. [101 ] The interatrial septum is pierced by a catheter introduced through the
femoral vein or by special needles from the right jugular vein. [94 ] , [104 ] A wire guide
is advanced into the atrium under fluoroscopic or echocardiographic control and the 18
or 20 Fr. catheter is inserted into the atrium over the wire. The arterial cannula may be
inserted into a femoral artery or via cutdown into an iliac artery through a small
retroperitoneal incision if the patient is ambulatory. After the transatrial catheter is
withdrawn the atrial septal defect appears to heal spontaneously. [94 ] Kolobow has
described a technique for right heart bypass without thoracotomy that uses a pulmonary
artery inflow catheter inserted into the femoral vein and passed through the right atrium
and ventricle into the pulmonary artery. This method has not been used clinically.
Bypass of single ventricles requires only inflow and outflow cannulas and the centrifugal
or impellor pump. [79 ] , [80 ] , [105 ] , [106 ] A flowprobe and pressure transducer is
incorporated into the circuit. Some circuits also include a T connector to a reservoir in
the venous line to facilitate regulation of volume. Cannulation sites for the various
circulatory configurations are described above.
If recovery of the native heart is expected, LVAD is used primarily to support the left
ventricle after cardiac surgery in patients with exclusively left heart failure as defined
above for ECMO. The right ventricle must function satisfactorily to adequately load the
LVAD circuit and central venous pressure should remain below 15 mmHg. The
reduction in left ventricular volumes and oxygen requirements and the reduced bleeding
problems make LVAD attractive if the right ventricle is functioning satisfactorily.
Similarly, RVAD is indicated in patients with good function of the left ventricle; these
patients are less common since often both ventricles experience the same
intraoperative injuries. Exclusive right ventricular dysfunction may occur if retrograde
cardioplegia is used and fails to protect the right ventricle. If pulmonary hypertension is
present, RVAD may not adequately load the left ventricle; ECMO or BVAD are better
choices.
BVAD usually is implemented when right ventricular dysfunction is discovered after

LVAD is started. ECMO is used preferably if both ventricles are known to function
poorly during efforts to wean the patient from cardiopulmonary bypass or in patients with
intractable ventricular arrhythmias that severely compromise native heart function. [83 ]
Anticoagulant requirements are less stringent with perfusion systems that do not require
an oxygenator because less thrombin is produced (see Chapter 9). If heparin coated
surfaces are not used, protamine is given after beginning perfusion with the circulatory
support system. [107 ] LVAD with centrifugal pumps has been used successfully without
any systemic heparin, but clots can occur. [85 ] , [105 ] , [107 ] , [108 ] Curtis does not
use heparin during the first 24 hours of perfusion and usually not until 48 hours after
starting circulatory support. [107 ] Magovern gives systemic heparin to increase the
activated clotting time to 150170 seconds while maintaining high flow rates. If heparin
coated circuitry is used, systemic heparin is not given. At high flow rates the risk of
clotting within these circuits or heart is probably less than within ECMO circuits because
the surface area of the system is smaller, but experience with groups of patients has not
been reported.
Blood transfusions may be harmful to patients with just LVAD support. Blood
components appear to increase pulmonary edema, hypoxemia, and pulmonary
hypertension and produce right heart failure that creates the need for an RVAD. These
observations contributed to our decision to increase our use of ECMO.
Management of perfusion is similar to that of ECMO. The patient must be ventilated and
efforts are made to reduce left atrial pressure to control pulmonary edema and
development of acute respiratory insufficiency. Minimum ventilatory pressures and
volumes and inspired oxygen concentrations that provide adequate arterial blood gases
are chosen. If RVAD or LVAD is used, function of the working native ventricle is
carefully monitored and drugs and volume are given to optimize performance.
Decreases in flow rates into the system usually require additional volume and may
threaten the performance of the unbypassed ventricle. Bleeding is controlled surgically
by transfusion of blood products and tight control of the activated clotting time. Heart
rate and rhythm are monitored; arrhythmias are treated aggressively. Other supportive
care is not unique to this type of circulatory support. Heparin is given during weaning as
pump flows are progressively reduced. [107 ]
COMPLICATIONS
The major complications reported by a voluntary registry for temporary circulatory

assistance using primarily LVAD, RVAD, and BVAD are bleeding, low cardiac output
with BVAD, renal failure, infection, neurologic deficits, thrombosis, and emboli,
hemolysis and technical problems (Table 11-1) . The incidence of these complications
in 1279 reported patients differed significantly between continuous perfusion systems
and pneumatically driven systems (see the following) with respect to bleeding, renal
failure, infection, and hemolysis (Table 11-1) , but except for bleeding were higher in the
pulsatile group. Neurologic deficits occurred in approximately 12 percent of patients
and in Golding's experience noncerebral emboli occurred equally often. [78 ] Golding
also found that 13 percent of patients also developed hepatic failure. [78 ] An autopsy
study found anatomic evidence of embolization in 63 percent of patients even though
none had emboli detected clinically. [109 ]
The experience in adults with ECMO for postoperative cardiogenic shock is more
limited because of nearly universal bleeding problems associated with the chest wound
in combination with heparin anticoagulation with the ECMO circuit. [98 ] Pennington
reported massive bleeding in six of six adults supported by ECMO following cardiac
surgery. [98 ] Even without the chest wound, bleeding was the major complication in a
large study of long-term ECMO for acute respiratory insufficiency. [110 ]
Recently, Magovern and Muehrcke reported experience with ECMO using heparin
coated circuitry with no or minimal heparin. [82 ] , [89 ] , [90 ] The incidence of
reexpoloration was 52 percent in the Cleveland Clinic experience; transfusions
averaged 43 units of packed cells, 59 units of platelets, 51 units of cryoprecipitate, and
10 units of fresh frozen plasma. Magovern reported somewhat fewer use of blood
products, but treated persistent bleeding by replacement therapy and did not observe
evidence of intravascular clots; two patients developed stroke after perfusion stopped.
Other important complications associated with ECMO using heparin coated circuits
included renal failure requiring dialysis (47 percent), bacteremia or mediastinitis (23
percent), stroke (10 percent), leg ischemia (70 percent), oxygenator failure requiring
change (43 percent), and pump change (13 percent). [90 ] Nine of 21 patients with leg
ischemia required thrombectomy and one amputation. Half of the patients developed
marked left ventricular dilatation and six patients developed intracardiac clot detected
by transesophageal echocardiography. [90 ]
Intracardiac thrombus may form within a poorly contracting, nonejecting left ventricle or
atrium because little blood reaches the left atrium with good right atrial drainage. [40 ] ,
[82 ] , [89 ] , [109 ] We have observed intracardiac thrombus in heparinized patients and
those perfused with pulsatile devices and a left atrial drainage cannula. The problem,
therefore, is not unique to ECMO or the location of the left-sided drainage catheter, but
is related to left ventricular function. In patients on ECMO with a left ventricular thrombus
we have removed the thrombus at the time a HeartMate LVAD was implanted for a
bridge to transplantation. [82 ]
RESULTS
The voluntary registry reported the experience with 604 LVAD, 168 RVAD, and 507
BVAD experiences; approximately 70 percent were with continuous flow pumps and the
remainder with pulsatile pumps. [1 ] There were no significant differences in the
percentage of patients weaned from circulatory assistance or the percentage
discharged from the hospital according to the type of perfusion circuitry. Overall 45.7
percent of patients were weaned and 25.3 percent were discharged from the hospital.
[1 ] Golding reported an identical hospital survival rate for 91 patients in 1992 using only
centrifugal pumps and Noon reported that 21 percent of 129 patients were discharged.
[78 ] , [111 ] Patients who received pulsatile circulatory assistance were supported
significantly longer than those supported by centrifugal pumps, but there were no
differences in the percentage of patients weaned or discharged. [1 ] Survivors were
supported an average of 3.1 days using continuous flow pumps. Patients supported for
acute myocardial infarction did poorly; only 11.5 percent survived to be discharged.
Recent experience shows improving results. Joyce reports that 42 percent of patients
supported by Sarn impellor pumps were eventually discharged, some after
transplantation. [112 ]
Magovern recently reported improved results in 14 patients supported by a heparin

coated ECMO circuit after operations for myocardial revascularization. [89 ] Eleven of
14 patients (79 percent) with revascularization survived, but none of three patients with
mitral valve surgery and none of four patients who underwent elective circulatory arrest
survived. Overall, 52 percent of the whole group survived, but two developed
postperfusion strokes that were probably from thrombi produced during perfusion. [89 ]
Although the Cleveland Clinic experience with heparin coated ECMO circuits produced
a survival rate of 30 percent, the patient population was more diversified and
represented only 0.38 percent of cardiac operations done during the same time period.
[90 ]
The registry reports that long-term survival of patients weaned from circulatory support
is 46 percent at 5 years. [1 ] Most of the mortality occurs in the hospital before
discharge or within 5 months of discharge. [1 ]
Hemopump
The Hemopump® (Medtronic-DLP, Grand Rapids, MI) is a novel method to provide

temporary, continuous, circulatory support with an intracorporeal device. [57 ] The pump
functions on the principle of an Archimedes screw and provides continuous axial flow.
[113 ] The device is driven at 25,000 rpm by a transcutaneous drive cable and is
located at the base of a catheter that is placed within a cardiac chamber or a great
vessel (Figure 11-11) . Blood inflow occurs at the tip of the catheter and is ejected from
the pump at the base of the catheter near the junction with the drive cable. The 21 Fr.
device provides three liters of flow per minute against a pressure of 100 mmHg. [113 ]
The 24 Fr. device pumps 5 liters/min but is inserted at thoracotomy. A smaller 14 Fr.
pump circulates 1.5 l/min and is designed for supporting cardiac catheterization
procedures. The 21 Fr. device may be inserted through a 12-mm Dacron graft sewn
end to side to the external iliac or common femoral artery or through a pursestring
suture. [114 ] , [115 ] The pump and leading cannula are advanced retrograde up the
descending thoracic aorta until the cannula tip crosses the aortic valve and enters the
main body of the left ventricle. [116 ] , [117 ] Blood is pumped from the tip of the catheter
to the base and down the descending thoracic aorta. The pump is cooled with a slow
infusion of glucose solution and the patient is anticoagulated with systemic heparin to
increase the activated clotting time to 1.52.0 times control. [114 ] , [117 ] , [118 ]
Either the 21 Fr. or 24 Fr. pumps may be inserted into the aorta or main pulmonary
artery. [118 ] Dacron grafts (12-mm) are sewn end-to-side to the selected vessel to
introduce the cannula tip into either the left or right ventricle. The catheter base and
pump reside in the great vessel. The drive line exits through a stab wound in the neck.
[118 ] Heparin is used.
The Hemopump is an investigational device with restricted use in the United States. It
has been used to provide LVAD, RVAD, or BVAD support for failing ventricles after
cardiopulmonary bypass, [114 ] , [115 ] , [117 ] [120 ] after acute myocardial infarction
[121 ] and during rejection of heart transplants [122 ] ; to support coronary angioplasty
[123 ] ; and to support the native heart during myocardial revascularization without
cardiopulmonary bypass. [118 ] , [120 ] , [123 ] , [124 ]
In an experience with 29 patients who could not be weaned from cardiopulmonary

bypass, Lonn and colleagues were not able to place the device in five patients because
of femoral arteriosclerosis or cable fracture. [2 ] , [3 ] , [119 ] Ten patients developed
biventricular failure despite adequate left ventricular decompression and died in the
operating room or shortly thereafter. Fourteen patients were supported an average of
2.4 days and all survived and were discharged. [119 ] All patients developed reversible
renal insufficiency, but none needed hemodialysis. Peak plasma hemoglobin
concentrations reached 0.32 gm/l; average platelet count fell to 53,000 × K/ul. In Meyns'
experience four of 16 patients, who could not be weaned, were supported with the
Hemopump and survived to discharge. [115 ]
Temporary Pulsatile Pumps
Pulsatile pumps are designed for temporary use, generally less than 1 week, or for
long-term use as a bridge to transplantation. Long-term applications of circulatory
support devices are presented in Chapter 51. As noted earlier most temporary
circulatory support devices are used for postcardiotomy ventricular failure or to support
the circulation for hours or a few days. The majority are centrifugal or impellor pumps
that remain outside the body. Temporary pulsatile pumps are also extracorporeal and
must be distinguished from long-term, implanted pulsatile pumps that primarily are used
for bridging patients to transplantation or, more recently, as permanent left ventricular
assist devices (see Chapter 51). For patients initially supported by ECMO or other
continuous flow pumps we convert to a long-term device when it is clear that the native
heart will not recover and that the patient is eligible for cardiac transplantation. [82 ]
Although pumps used for bridging are preferably implanted, many extracorporeal,
temporary pulsatile pumps have also been used for this purpose.
ABIOMED BVS 5000
The Abiomed BVS 5000 system (Abiomed Cardiovascular, Inc., Danvers, MA) is
designed to provide univentricular or biventricular support and was introduced in 1987.
[125 ] The device was approved by the United States Food and Drug Administration in
November 1992 for postcardiotomy support and has been used in over 500 patients for
a variety of indications. [126 ] The pump is a fully automatic, external, pulsatile, dual
chamber device with an upper, atrial (filling) chamber and a lower, ventricular (pumping)
chamber housed in a polycarbonate jacket (Figure 11-12) . The pump is placed on a
pole near the patient. Both inflow and outflow chambers contain 100-cc smooth
polyurethane bladders and are separated by a polyurethane trileaflet valve. Another
polyurethane trileaflet valve is used as an outflow valve from the ventricular chamber.
The pump is pneumatically actuated by an external drive console and pump filling is by
gravity that simplifies operation. As the inflow bladder fills, the console senses the
displacement of air around the inflow bladder and sends a bolus of compressed air to
the chamber around the outflow bladder to eject the contained blood.
Vascular access is similar to patients with centrifugal pump support via thoracotomy. A
46-Fr. wire reinforced lighthouse tipped cannula is used for drainage from either the
right atrium; the left atrium, via the interatrial groove; the dome of the left atrium; or the
left atrial appendage and secured with double pursestring sutures. [125 ] The outflow
cannula uses a 14-mm Dacron graft that typically is sewn onto the ascending aorta or
pulmonary artery. The cannulas usually are passed through stab wounds in the chest
wall and tunneled into the mediastinum to permit sternal closure.
The drive console for the Abiomed BVS 5000 is simple to operate. The control system
automatically adjusts the duration of pump diastole and systole, primarily in response to
changes in preload. Pump rate and flow are visible on the display monitor. During
automated operation the device can be managed by the bedside nurse.
Indications for Abiomed BVS 5000 circulatory support include postcardiotomy patients
who meet criteria (see above) for left, right, or biventricular ventricular failure. [125 ] The
device also has been used effectively in patients after acute myocardial infarction, with
myocarditis and following cardiac transplantation. [125 ] Two-thirds of patients require
biventricular support, 30 percent require LVAD, and 5 percent RVAD. [126 ] In
postcardiotomy patients heparin is reversed with protamine after implementation of the
BVS system. Postoperative bleeding is controlled and, when controlled, systemic
heparin is started to maintain activated clotting times 180200 seconds. [125 ]
During operation monitoring, lung ventilation, management of fluids and transfusions,

samples for blood gases, constituents and chemistries, and general care of the patient
does not differ from care of other patients on circulatory support systems (see above).
Transesophageal echocardiography is used to monitor ventricular function and with
chamber pressures to determine when to begin weaning from the assist device. No
universally accepted weaning protocols are established. We begin weaning when
cardiac recovery appears by progressively decreasing pump flow as long as the patient
maintains left atrial pressures below 20 mmHg and systemic arterial systolic pressure
over 100 mmHg. The device is removed when the patient is able to maintain a cardiac
index of 2.2 l/m 2 /min. [82 ]
As with all patients who require postcardiotomy mechanical support, complications are
frequent. [125 ] Seventy-six percent of patients have bleeding complications, respiratory
failure occurs in 54 percent, renal failure in 52 percent, and permanent neurologic deficit
in 26 percent. Thirteen patients (28 percent) developed infection while on the device,
but only three cases were considered device-related. Embolism occurs in 13 percent
and hemolysis in 17 percent. Mechanical problems related to the atrial cannula occur in
seven patients (13 percent). [125 ] No major changes in platelet count or blood
chemistries occur during the period of circulatory support. [125 ] Cardiomyopathy
patients experience fewer bleeding and other complications than postcardiotomy
patients. [126 ]
Fifty-five percent of 55 postcardiotomy patients enrolled in a multicenter study of 55

postcardiotomy patients were weaned from support and 29 percent were discharged
from the hospital. [125 ] However, 47 percent of patients who had not experienced
cardiac arrest before being placed on circulatory support were discharged. Of 14
patients who had presupport cardiac arrest, only one (7 percent) was discharged. A
more recent report of 500 patients treated with the BVS 5000 system included 265 (53
percent) who could not be weaned from cardiopulmonary bypass. Overall, 27 percent of
patients were discharged from the hospital, but the discharge rate was higher at more
experienced centers. [126 ]
THORATEC VENTRICULAR ASSIST DEVICE
The Thoratec VAD (Thoratec Laboratories Corp; Berkeley, CA) was introduced
clinically in 1976 under an investigational device exemption (IDE) and recently was
approved by the United States Food and Drug Administration for postcardiotomy
support or as a bridge to transplantation. The device is a pneumatically driven pulsatile
pump that contains two polyurethane, seamless bladders within a rigid housing. [127 ]
The inlet and outlet ports contain Bjork-Shiley convexo-concave tilting disc valves to
provide unidirectional flow. The effective stroke volume of each prosthetic ventricle is 65
ml. The pneumatic drive console applies alternating negative and positive pressures to
fill and empty each prosthetic bladder. Driveline vacuum and positive pressures can be
adjusted to improve filling and to improve systemic arterial pressure. The pump eject
time (equivalent of ventricular systole) also can be adjusted depending on preload and
afterload conditions. One or both pumps may be used to provide univentricular (LVAD
or RVAD) or biventricular support (BVAD).
The prosthetic ventricles are placed on the upper abdomen (Figure 11-13) and are
connected to the heart and great vessels by large bore, wire wrapped, polyurethane
cannulas that traverse the chest wall. [128 ] , [129 ] For temporary circulatory support of
the left ventricle the 51 Fr. right angled cannula is inserted into the left atrium via the
atrial appendage, the interatrial groove or the superior wall and secured by pursestring
sutures. [128 ] The outflow cannula is inserted into a 14-mm Dacron graft that is sewn
end-to-side to the ascending aorta. For right ventricular support the outflow cannula
usually is placed first. [128 ] A 14-mm Dacron graft is sewn end-to-side to main
pulmonary artery just above the pulmonary valve and connected to the wire- wrapped
catheter that crosses the chest wall. The 51 Fr. right angled, bullet tipped inflow catheter
is inserted directly into the right atrium through concentric pursestring sutures. The
exiting cannulas are anchored securely to the skin. The left ventricular apex is not used
for temporary circulatory support.
The pumps can be operated three control modes. [127 ] The fixed rate mode operates
independently of the patient's heart and the rate is set by the operator. In the external
synchronous mode the pump empties when triggered by the patient's R-wave on the
electrocardiogram. The usual mode for most patients is the full to empty mode in which
ejection occurs when the device senses that the prosthetic ventricle is filled. In this
volume mode heart rate is determined by the rate of prosthetic ventricular filling.
Unlike the Abiomed BVS 5000 the Thoratec pumps reside on the upper abdominal wall
and are connected to a large, wheeled console containing compressed air tanks.
Patients may be ambulatory, but the large console and external configuration of the
drive tubes and cannulas make ambulation more difficult, but unlike continuous flow
pumps, possible.
Most temporary use of the Thoratec VAD is for postcardiotomy patients, but the device
has also been used for patients after myocardial infarction and during cardiac transplant
rejection. [127 ] , [130 ] , [131 ] The Thoratec pump has also been used to support a
patient with myocarditis who eventually recovered adequate native heart function. [132 ]
Patients are initially anticoagulated with heparin, but can be anticoagulated with
coumadin for applications longer than a few days. [127 ] Complications are similar to
those experienced with other temporary circulatory support devices and include
persistent biventricular failure, bleeding, respiratory failure, renal failure requiring
dialysis, infection, stroke, and thrombosis. [1 ] , [131 ] The device can be changed
without returning to the operating room. [133 ] Bleeding complications are slightly less
than with continuous flow pumps, but the rates of renal failure, infection, and hemolysis
are slightly higher. [1 ]
After cardiotomy, results are similar to those obtained with continuous flow devices and
the Abiomed BVS 5000. [1 ] , [2 ] , [78 ] [80 ] , [105 ] , [125 ] , [126 ] In a recent review of
145 patients with non-bridge use of the Thoratec device 37 percent of patients were
weaned and 21 percent were discharged. [67 ] More experienced centers have
achieved hospital survival rates over 40 percent. [130 ] , [131 ] Renal failure and
myocardial infarction are poor prognostic events for survival. [131 ]
MECHANICAL VENTRICULAR COMPRESSION
A cup-shaped device designed to fit over both ventricles of the heart originally was
introduced in 1965, extensively studied for several years, and then abandoned for
failure to achieve long-term survivors. [134 ] Because this approach effectively produces
cardiac outputs of 80110 percent of control values, does not require anticoagulation
and can be implemented rapidly through an emergency left anterior thoracotomy
incision, interest in producing an improved modern version for temporary circulatory
support has returned. [135 ] , [136 ]
An elliptically contoured cup (sizes range from 90150 mm in transverse diameter) fits
over both ventricles and extends to the base of the heart. The outer shell is
noncompliant or rigid; the inner shell is a distensible diaphragm made of silicone rubber
or other suitable material. [136 ] A continuous vacuum (approximately -70 mmHg) is
applied to the apex of the cup to maintain its position over the ventricles. A pneumatic
console using positive and negative pressures alternately inflates and deflates the inner
diaphragm to compress and release both ventricles. Flow is directed by the patient's
heart valves; the pulse rate is set by the operator. Pulmonary arterial wedge pressure is
monitored to avoid overdistending the left ventricle by complete emptying of the right
ventricle and incomplete emptying of the left.
This device is under development and experience is extremely limited. One patient
supported by the device for 56 hours survived after cardiac transplantation. [136 ] The
device does not appear to cause significant trauma to the heart muscle and has
successfully supported animals with ventricular fibrillation up to 7 days.
OVERVIEW OF MAJOR DERANGEMENTS
Major physiologic derangements must be treated in patients recovering from a cardiac

surgical operation. These fall into two types: those existing preoperatively and those
which occur as a consequence of the operation and cardiopulmonary bypass (CPB).
The goal is to restore normal homeostasis. The most important factor contributing to
this restoration, of course, is proper conduct of a well-conceived operation.
Because so many systems may be deranged, a systems-oriented approach is

necessary to deal with problems in an orderly fashion. [1 ] The cardiac system, usually
the most perturbed, is the primary determinant of recovery, and consequently requires
the greatest effort to restore normal function. Measured cardiac output, clinical signs of
cardiac adequacy, and blood pressure must be maintained, and cardiac distension and
ischemia must be avoided. A low cardiac index during the early postoperative period
markedly increases the probability of death. [2 ] , [3 ] With the physiologic trauma of
recent cardiopulmonary bypass, hearts are susceptible to ventricular arrhythmias early
after operation and to atrial arrhythmias later.
Fluid accumulation in the perioperative period and interstitial edema cause pulmonary
dysfunction. The goal is to wean the patient from mechanical ventilation and high oxygen
concentrations as quickly as commensurate with adequate spontaneous ventilation,
ability to protect the airway, and satisfactory oxygenation.
High urine output usually results from operations performed on cardiopulmonary bypass;
anything less raises the alarm of renal insufficiency and requires immediate evaluation
and treatment. Renal dysfunction occurs commonly after heart operations, and early and
aggressive treatment reduces the otherwise high mortality accompanying this
complication. [4 ]
Neurologic complications occur more commonly after heart operations than after most
other types of surgery. Early, careful assessment and documentation of the return of
mental and central and peripheral neurologic function are required. Although many
central deficits occurring in the perioperative period cannot be treated, others can be,
and early diagnosis allows treatment before changes become irreversible.
Excessive bleeding complicates heart operations more often than other operations.
Consistent, systematic intraoperative control of bleeding contributes more than any
other factor to tolerable postoperative blood loss. Even then, excessive bleeding occurs
with a frequency higher than with most other operations. Bleeding may be from surgical
bleeding sites or caused by the temporary coagulation disorder that accompanies
nearly all heart surgery.
INFLAMMATORY RESPONSE OF CARDIOPULMONARY BYPASS
Cardiopulmonary bypass (CPB) harms patients, even while it enables life-preserving

operations. In a time-dependent fashion, CPB activates plasma proteins and blood and
endothelial cells. [5 ] [12 ] These complex reactions activate the complement, clotting,
and fibrinolytic cascades and cause a bleeding tendency, microemboli, fluid retention,
and perturbation of the hormonal milieu. [13 ] [16 ] A detailed description of these
events is provided in Chapter 9.
COMPLICATIONS: ANTICIPATION AND TREATMENT
A protocol for postoperative care is useful if it anticipates and prevents complications

while minimizing utilization of hospital resources. Many complications, such as renal
failure, pulmonary dysfunction, and bleeding, that occur from cardiac operations may be
anticipated. Accordingly, early and aggressive treatment mitigates morbidity and
shortens convalescence.
Hemodynamic malfunction may be caused by the underlying heart disease, but to

assume so precludes correcting mechanical complications of the operation at a time
when damage may be minimized. Postcardiac surgical units routinely monitor the
electrocardiogram (ECG), arterial blood pressure, and filling pressures (right atrial, left
atrial, and/or pulmonary artery pressure) and also utilize continuous displays of arterial
and mixed venous oxygen saturations (via pulse oximetry and oxymetric pulmonary
artery catheters, respectively). These indices allow minute-to-minute assessment of
cardiopulmonary physiology. Deviations from expected normal ranges prompt
immediate reevaluation of heart and lung function (Table 12-1) . As a working policy,
therefore, all hemodynamic malfunctionslow cardiac output, low blood pressure,
elevated left or right atrial pressuresare first considered a direct mechanical
complication of the operation performed or a result of mechanical ventilation or drug
administration. Reparable maladies such as coronary artery graft occlusion or spasm,
prosthetic paravalvular leak, mechanical valve leaflet immobility, pericardial tamponade,
pneumothorax, hemothorax, endotracheal tube malposition, and incorrect doses of
intravenous infusions are considered first.
Examples of standard postoperative orders and overall goals for the management of
uncomplicated patients are included in Appendix 12A. The protocol that works best at
an individual center must be subject to continual reevaluation as new knowledge and
therapeutic agents become available and as patient profiles change. The protocol
offered is the latest version at our institution and takes into account a recent emphasis
on decreased utilization of hospital resources by patients who may not need them.
Details of patient care are included in the following sections.
HEART
Minimal Requirements
Adequate cardiac function is an absolute requirement for successful recovery from any
operation, including one on the heart itself. During the immediate postoperative period,
minimum requirements of systemic and pulmonary blood flow must be met to avoid
organ dysfunction. Normal renal, gastrointestinal, and neurologic functions are the best
indices of adequate systemic circulation, but other parameters, including
measurements of cardiac output and oxygen utilization (vo 2 ), are also useful.
Under basal conditions, oxygen consumption can be measured directly; taken from
tables that correct for age, sex, and size; or estimated utilizing calculations based on
the patient's size (125 ml o 2 per minute per m 2 ). [17 ] A value for oxygen consumption
provides a means of estimating cardiac output from measurements of mixed venous
and arterial oxygen content using the Fick equation (Table 12-2) . Frequently,
measurements of mixed venous oxygen saturation (Svo 2 ) are used to determine
whether the cardiac output meets systemic demands. An Svo 2 greater than 60 percent
is acceptable for an awake normothermic patient. Following cardiac surgery, a number
of factors may affect the oxygen content of blood, the ability of blood to release oxygen
where it is needed, and the body's demand for oxygen (Table 12-3) . The essence of
postoperative critical care is to ensure the adequacy of systemic oxygen supply relative
to demand. [18 ] , [19 ]
Determinants of Cardiac Output
The cardiac output, expressed as liters per minute per square meter (cardiac index), is
the most commonly used measure of cardiac performance in the immediate
postoperative period. Although other methods are possible, the thermodilution
technique using a pulmonary artery catheter and room temperature injectate is simple
and sufficiently precise. [20 ] A normal value for cardiac index after surgery is between
2.2 and 4.4 liters/min per m 2 . [21 ]
Dietzman et al. [3 ] first reported the association between low cardiac output and
mortality after adult cardiac surgery, and this observation was confirmed subsequently
by Parr et al. in children. [22 ] A normal recovery from cardiac surgery can be expected
when the cardiac output is maintained within this range. [23 ] Treatment of low cardiac
output is predicated on manipulation of its primary determinants (Table 12-4) .
The determinants of cardiac output are heart rate and stroke volume. The latter is
influenced by the cardiac rhythm, ventricular preload and afterload, and myocardial
contractility. Although the heart rate is usually slightly increased immediately after
surgery, patients using large amounts of beta blockers preoperatively or with an intrinsic
rhythm disturbance may have a slow heart rate. Conversely, some patients, particularly
younger ones or those with profound left ventricular dysfunction, may be tachycardic.
The optimal heart rate balances coronary blood flow (which takes place mainly during
diastole) with cardiac output and is usually between 80 and 100 beats per minute. [24 ]
Normal sinus rhythm ensures atrioventricular synchrony and maximizes cardiac
efficiency. [25 ] Loss of sinus rhythm (junctional rhythm or atrial fibrillation) usually
reduces cardiac output by 10 to 25 percent. [26 ] Patients with slow sinus rhythm (less
than 70 beats per minute) or junctional (AV nodal) rhythm usually can be paced via atrial
pacing wires placed at the time of surgery to improve cardiac output. [27 ] Slowing a
rapid rhythm (>110 beats per minute) is important to reduce the likelihood of developing
myocardial ischemia in the immediate postoperative period when coronary flow reserve
is limited. Reduction of exogenous catecholamines; administration of narcotics,
sedatives, antipyretics, or intravenous fluids; and the use of antiadrenergics such as
beta blockers are employed to slow a rapid heart rate.
Ventricular preload refers to sarcomere length at end-diastole when both passive filling
and the contribution of atrial contraction are complete. Sarcomere length cannot be
measured directly, and therefore, a number of surrogate measurements are used.
These include left ventricular end-diastolic volume (LVEDV), which is related to left
ventricular end-diastolic pressure (LVEDP). The relationship LVEDV/LVEDP is
referred to as ventricular compliance , a combination of active relaxation of the
actin-myosin complex and the passive viscoelastic properties of the myocardium. [28 ] ,
[29 ] Hearts with reduced ventricular compliance (a frequent finding after heart surgery
[30 ] ) exhibit diastolic dysfunction and therefore require a higher LVEDP to achieve a
given preload. For example, patients with left ventricular hypertrophy secondary to aortic
stenosis have poor left ventricular compliance. Left atrial pressure closely approximates
LVEDP and should be measured directly in patients undergoing complex operations or
with preexisting left ventricular dysfunction. Pulmonary capillary wedge pressure or
pulmonary artery diastolic pressure provide good estimates of the left atrial pressure
when pulmonary congestion, edema, and inflammation are absentconditions rarely met
immediately after cardiac surgery. [31 ]
To maintain adequate preload, volume replacement frequently is necessary

immediately after heart surgery due to loss of arterial and venous vasomotor tone,
increased capillary permeability, bleeding, and high volumes of urine. [32 ] Often,
judicious fluid administration is all that is required to maintain hemodynamic stability or
to treat low cardiac output accompanied by vasoconstriction. Lactated Ringer's solution
is appropriate initially, but infusion of hydroxy-ethyl starch (hetastarch) or blood products
may be indicated. Hetastarch is at least as effective as albumin solutions for volume
expansion [33 ] , [34 ] and costs less than half as much. Coagulation abnormalities may
accompany any acute volume expansion because of hemodilution rather than specific
anticoagulant effects. Transfusion of packed red blood cells should be governed by
logical protocols and good clinical judgment with regard to the rate of blood loss. In
general, blood is not necessary unless the hematocrit is less than 25 percent.
Ventricular afterload refers to systolic wall stress, which is determined by intraventricular

systolic pressure and ventricular wall thickness. [35 ] Ventricular wall thickness changes
minimally during heart surgery, and therefore, changes in ventricular systolic pressure
have the most impact on afterload. In the absence of left ventricular outflow obstruction,
systolic blood pressure determines afterload and thereby influences both stroke volume
and myocardial oxygen demand. [36 ] , [37 ] Manipulations of systemic vascular
resistance can improve cardiac output and the adequacy of coronary blood flow. [38 ] ,
[39 ]
Hypertension, or at least systemic vasoconstriction, is common after cardiac surgery.

[40 ] Increased arterial resistance has been associated with low Po 2 in skeletal muscle
and secondary metabolic acidosis despite adequate cardiac output and oxygen content
of arterial blood. [41 ] The microcirculatory changes that produce inadequate tissue
perfusion appear to resolve after a period of 6 to 8 hours, but this interval does not
correlate with rewarming following moderately hypothermic cardiopulmonary bypass.
[42 ] Humoral factors may play a role, since a number of circulating mediators are
present and produce the whole-body inflammatory response to CPB. [43 ] , [44 ]
Regardless of etiology, sodium nitroprusside is an effective means to reduce afterload
during and after cardiac surgery. [40 ] , [45 ] , [46 ] The administration of this and other
drugs via computer-controlled systems offers several advantages [47 ] [49 ] but cannot
substitute for a competent bedside clinician.
Some patients have a lowered systemic vascular resistance (SVR) during and
immediately after cardiopulmonary bypass. The accompanying hypotension sometimes
requires treatment with vasoconstrictors that are usually agents with pronounced
alpha-adrenergic effects such as phenylephrine or norepinephrine. Christakis et al. [50 ]
reported the incidence of low SVR to be more common in patients undergoing
normothermic perfusion and in those with longer cardiopulmonary bypass times. [50 ]
Diabetics, patients with peripheral vascular disease, and those with a left ventricular
ejection fraction of less than 0.40 are less likely to develop low systemic vascular
resistance and associated hypotension. Treatment with phenylephrine is not associated
with an increased incidence of stroke or complications related to inadequate internal
mammary arterial graft flow.
Most surgeons assess myocardial contractility before, during, and after a cardiac
operation by indirect methods. Measurements of ejection fraction, ventricular wall
motion, and cardiac output all depend on loading conditions present at the time, as well
as intrinsic myocardial contractility. In the research laboratory, changes in the ventricular
pressure/volume relationship during a cardiac cycle can be used to generate a
load-independent assessment of contractility, [51 ] but this methodology is impractical
for routine clinical use. Thus appropriate assumptions regarding contractility are made
when changes in cardiac output are not explained by the other determinants.
Following heart surgery, dysfunction of either ventricle may limit overall cardiac
performance. Measurement and comparison of right and left atrial pressures (reflective
of respective ventricular end-diastolic pressures) provide important information. [52 ]
When the atrioventricular valves are normal, the ventricle with the highest corresponding
atrial pressure is the one limiting cardiac performance. Therapeutic interventions,
including but not limited to the use of inotropes, are aimed at supporting that ventricle.
Perioperative Causes of Left Ventricular Dysfunction
The factor that contributes the most to depressed postoperative cardiac function is the
pathology that existed immediately prior to operation. Even when reconstructive surgery
is successful, it is rare to see an immediate improvement in contractile function (without
the administration of inotropes). Thus adequate cardiac reserve must be present to
withstand the demands of heart surgery. Preoperative cardiac abnormalities are not
limited to systolic function but may involve diastolic, valvular, electrophysiologic, and
vascular function. Optimal periopoperative care is aimed at compensating for this
impaired preoperative function.
The operation itself may cause left ventricular dysfunction and low cardiac output.
Contributors to cardiac dysfunction include inadequate protection of the myocardium
during periods of aortic cross-clamping, myocardial and pulmonary edema, acute left
ventricular distension or other trauma, uncorrected valvular lesions, and reduced
coronary blood flow. The investigation as to whether the operation has been adequate
to correct preexisting pathology begins as soon as the aortic cross-clamp is removed.
Search for graft occlusion, valvular incompetence, cardiac compression, or intracardiac
shunting continues throughout the postoperative period. Useful tools include
assessment of wall motion abnormalities by direct visualization or echocardiography
(usually transesophageal), the electrocardiogram, cardiac enzymes, blood gases
obtained from the pulmonary and systemic vasculature, and right and left atrial pressure
measurements. Discovery of an inadequate operation usually demands immediate
reoperation.
THYROID HORMONE
Although still controversial, some literature suggests that low serum levels of thyroid
hormone immediately after cardiopulmonary bypass depress cardiac function. [53 ] , [54
] Free triiodothyronine (T3) augments cardiac output via nucleus-mediated mechanisms
and direct stimulation of calcium-ATPase in the sarcolemma and sarcoplasmic
reticulum. [55 ] Enhancement of calcium transport at this level reduces cytoplasmic
calcium levels, which are elevated in postischemic stunned myocardium.
Triiodothyronine also may benefit some patients immediately after heart surgery by
acutely decreasing systemic vascular resistance. [56 ]
Although levels of thyroid hormone are decreased in both children and adults for up to a
week after cardiopulmonary bypass, [53 ] , [57 ] the myocardial cell may not be depleted
of thyroid hormone. [58 ] Concerns regarding enhanced myocardial oxygen demand
and the propensity for atrial arrhythmias have limited widespread use of this hormone at
heart surgery centers. [59 ] , [60 ] In one study of patients undergoing coronary artery
bypass surgery, intravenous triiodothyronine did not significantly change hemodynamics
other than increasing heart rate. [61 ] Further investigation in impaired ventricles may
yield different results.
PERICARDIAL TAMPONADE
Compression of the heart, especially the right atrium and ventricle, can reduce overall
cardiac function dramatically. Increased right-sided heart pressures impair venous
return and consequently diminish left ventricular preload. This process does not require
significant accumulation of blood or fluid in the pericardial space and can occur
immediately after chest closure. Delayed sternal closure is an accepted technique for
avoiding compression of the seriously impaired heart in the immediate postoperative
period. [62 ] [64 ] Infectious complications are minimized by covering the wound with an
occlusive dressing [62 ] and instituting immediate irrigation of the mediastinum with a
diluted povidone-iodine solution. [65 ] , [66 ] Closure of the sternum is usually possible
after onset of negative fluid balance. [63 ]
Pericardial tamponade also can cause deterioration of cardiac output in patients who
initially demonstrate adequate ventricular performance but have heavy bleeding in the
initial hours after surgery. Subsequent correction of their coagulation profile, formation
of pericardial clot, and decreased chest tube drainage may lead to pericardial
tamponade. Tamponade is usually associated with a rapid increase in right and left
atrial pressures, which tend to equalize. Tamponade is almost invariably associated
with widening of the mediastinal silhouette on chest roentgenogram. The association of
rising atrial pressures, diminished cardiac output, and a widening mediastinum is
sufficient to prompt surgical exploration.
Although the majority of patients develop some degree of pericardial effusion in the
days following heart surgery, only a minority develop signs and symptoms of
tamponade. [67 ] Pericardial tamponade may develop insidiously. It can occur as late
as several weeks after operation and is more common in patients receiving
anticoagulants. [68 ] , [69 ] Delayed tamponade is not associated with the
postpericardiotomy syndrome (fever, pain, friction rub) [70 ] but rarely may be caused
by chylopericardium. [71 ] , [72 ] Prolonged drainage of the pericardial space does not
prevent subsequent development of delayed tamponade. [73 ]
The use of echocardiography to diagnose early or delayed tamponade has been well
described, [74 ] [76 ] and this technique is indicated in patients with unexplained poor
cardiac performance following heart surgery. [77 ] Measurement of an exaggerated
pulsus paradoxus (a decrease in systolic blood pressure during inspiration) remains a
reliable clinical indicator and, together with adequate radiologic examination, indicates
the need for drainage. Although a catheter is useful for preoperative effusions, the
safest method for delayed tamponade after median sternotomy is surgical, usually by a
simple subxyphoid approach. [78 ]
Support of Cardiac Performance
PHARMACOLOGIC SUPPORT
If ventricular function is depressed following a cardiac operation, treatment with

vasodilators and volume loading may not be sufficient to ensure adequate circulation.
Ventricular contractility should be augmented, usually with inotropic agents. There are
excellent reviews on this subject, [79 ] [81 ] and a thorough understanding of the
pharmacology involved is required to care for postoperative cardiac patients. Inotropic
agents may be divided into catecholamines and noncatecholamines. The former
include natural or synthetic adrenergic agents that stimulate alpha and beta receptors in
the heart, lungs, and peripheral vasculature (Table 12-5) . Noncatecholamines include
calcium, digoxin, amrinone, and milrinone.
Patients likely to benefit from catecholamine support are those with low cardiac output
(cardiac index less than 2.0 liters/min per m 2 ), with optimized heart rate, rhythm,
ventricular preload, and afterload, and without evidence of acute cardiac tamponade.
Dopamine and dobutamine enhance heart rate and cardiac output equally, but
dobutamine produces greater reductions in left ventricular preload and afterload. [82 ]
Dobutamine augments myocardial coronary blood flow more than dopamine. [83 ]
Dopamine works well in conjunction with vasodilators for low cardiac output after heart
surgery. [84 ] , [85 ] As with all adrenergic agents, the hemodynamic effects of these
drugs depend on dosage. When dopamine is administered at less than 8 µg/kg per
minute, beta and dopaminergic receptor stimulation predominates and enhances
cardiac output and renal blood flow. [86 ] At doses greater than 10 µg/kg per minute,
alpha vasoconstrictor effects predominate, and tachycardia may ensue. The underlying
pathophysiology and age of the patient may alter the expected response.
The effect of epinephrine on both alpha- and beta-adrenergic receptors makes it a

useful agent following cardiac surgery. The effects of epinephrine vary by dosage. At
low doses (< 0.02 µg/kg per minute) epinephrine stimulates peripheral beta 2 receptors
and causes vasodilation. Higher doses cause increasing cardiac effects, and the
highest doses can cause vasoconstriction via peripheral alpha-receptor stimulation.
The response of an individual patient's peripheral and pulmonary hemodynamics is
somewhat unpredictable, especially after cardiopulmonary bypass. Steen et al. [87 ]
investigated the effects of epinephrine after cardiac surgery and discovered a
consistent increase in cardiac output but variable changes in mean arterial pressure.
Stephenson et al. [88 ] demonstrated similar increases in cardiac output with
epinephrine infusions after heart surgery and showed that hypertension and tachycardia
occurred when higher doses were used.
Norepinephrine, another naturally occurring catecholamine, is used after heart surgery

when blood pressure is low. In addition to pronounced effects on peripheral alpha
receptors, norepinephrine is a potent beta1 agonist and therefore increases myocardial
inotropy. The increased blood pressure that these two effects provide must be balanced
against increased myocardial oxygen consumption and reduced renal, mesenteric, and
peripheral perfusion that may ensue, especially at higher doses.
Isoproterenol stimulates beta1- and beta 2 -adrenergic receptors but has little alpha
action. Isoproterenol increases heart rate and contractility and decreases systemic
vascular resistance. Isoproterenol is potentially useful when reactive pulmonary
hypertension and right-sided heart failure contribute to postoperative low cardiac output,
as may occur following mitral valve surgery or cardiac transplantation. Its nonselective
beta-adrenergic stimulation, which may cause tachyarrhythmias and systemic
vasodilation, limits its utility in other situations.
Calcium, in its ionized form, is critical for excitation-contraction coupling in cardiac

muscle. [89 ] Low calcium ion concentrations depress ventricular function and
peripheral resistance and contribute to hypotension and low cardiac output. In addition,
adequate calcium is necessary for the action of many cardiovascular drugs, including
catecholamines. Drop and Scheidegger [90 ] demonstrated that a calcium bolus
injection is associated with increased myocardial contractility, an effect that is directly
related to the initial calcium level (Fig. 12-1) . Shapira et al. [91 ] also showed that a
bolus of calcium can cause transient hemodynamic improvement in patients after
cardiopulmonary bypass but that a continuous infusion of calcium does not sustain the
beneficial effect. Because of these and similar [92 ] , [93 ] observations, many surgeons
administer a bolus of calcium (500 to 1000 mg) immediately before weaning from
cardiopulmonary bypass when serum ionized calcium levels are generally low.
Amrinone is a noncatecholamine bypyridine derivative that inhibits phosphodiesterase

to slow the degradation of cyclic AMP. [94 ] Amrinone has slightly positive inotropic and
marked vasodilating properties. [95 ] , [96 ] Amrinone increases cardiac output and
lowers pulmonary and systemic vascular resistance. A dose-dependent decline in blood
pressure limits its use in markedly hypotensive patients, and the relatively long plasma
half-life (6 hours in heart failure) hampers dose titration and control of the clinical effect.
[81 ] Deleterious side effects of amrinone include occasional thrombocytopenia and
hepatic function abnormalities. However, amrinone is useful in cases of right ventricular
and biventricular failure due to its ability to reduce right ventricular afterload. Since the
mechanism of action complements that of catecholamines, which stimulate production
of cyclic AMP, these drugs can be used in combination to achieve a synergistic effect.
Milrinone is a second-generation congener of amrinone with similar effects. The

positive inotropy of milrinone may be greater [97 ] than that of amrinone, and the
likelihood of precipitating thrombocytopenia is less. [98 ] Phosphodiesterase inhibitors
appear to improve myocardial relaxation [99 ] as well as coronary, [100 ] skeletal
muscle, [101 ] and mesenteric blood flow. [102 ] Their use is not associated with an
increase in myocardial oxygen consumption, [103 ] a finding that contrasts with all the
catecholamines. Unfortunately, the cost of these agents can be 100 times greater than
that of traditional inotropes.
Once acute problems have subsided, some patients in sinus rhythm require chronic
augmentation of contractile function. The use of digitalis in this setting has long been
argued, but there is evidence that it increases contractility. [104 ] Newer agents such as
enoximone, another type III phosphodiesterase inhibitor, and vesnarinone, a quinalone
with immunomodulatory properties, are also available for treatment of chronic heart
failure. [105 ] Their role in the immediate postoperative period is not defined.
MECHANICAL CIRCULATORY SUPPORT
Intraaortic balloon counterpulsation
Some patients arrive in the intensive care unit (ICU) following heart surgery with
enhanced circulatory support from an intraaortic balloon pump (IABP) or ventricular
assist device (VAD). [106 ] , [107 ] The use of mechanical assist devices is predicated
on the concept that myocardial function improves over time. As with any postcardiac
surgical patient, the goals of these devices are to minimize ventricular wall tension while
maintaining adequate coronary and systemic perfusion. Special routines for these
patients include careful monitoring for signs of leg ischemia, which is present in about 5
percent of patients with transfemoral placement of an IABP. [108 ] Assiduous
monitoring of peripheral pulses, ankle-brachial indices, and neuromuscular function
promptly identifies patients with threatened legs. Identification of these patients initiates
a discussion of treatment options that include removal by open or closed techniques,
possible reinsertion on the opposite side or via a transthoracic approach, and
axillofemoral or femoral-femoral bypass. [109 ] Continous infusion of dextran or heparin
should be considered for patients with intraaortic balloon catheters as soon as
mediastinal drainage has slowed.
Intraaortic balloon pumping was first performed clinically by Kantrowitz et al. in 1968.
[110 ] IABP uses the principle of diastolic counterpulsation, in which the balloon inflates
in synchrony and out of phase with the cardiac cycle. Benefits of this technique include
augmentation of diastolic coronary perfusion pressure, reduced systolic afterload, and
increased cardiac output with an improvement in the myocardial oxygen supply/demand
ratio. IABP is used in patients with inadequate cardiac performance that has not
responded to manipulations of heart rate and rhythm, preload, afterload, and
contractility. The decision to implement IABP is usually made in the operating room
during weaning from cardiopulmonary bypass. If moderate doses of inotropic drugs are
not sufficient to improve cardiac performance, an IABP is indicated, especially in
patients with preoperatively impaired left ventricular function and in those with evolving
myocardial infarction, destabilizing arrhythmias, or uncorrected mitral valve
insufficiency. [111 ] [113 ] Historically, a mortality rate of at least 50 percent is reported
for patients who had IABP inserted at the time of surgery [111 ] , [114 ] , [115 ] Higher
survival rates are now reported, even in elderly patients, especially in the absence of
important comobidity such as renal failure. [116 ] [118 ] Female sex is a consistent
independent predictor of mortality in patients who require IABP in association with
cardiac surgery. [116 ] , [119 ]
The only major contraindication to IABP use is atherosclerotic disease of the aorta and
iliofemoral arteries. Vascular complications of femoral IABP placement have been well
documented [120 ] [123 ] and are discussed in detail in Chapter 11. Arterial obstruction
occurs as a result of embolization of thrombi derived from the balloon surface,
cholesterol emboli due to intimal injury, or mechanical obstruction by the IABP catheter
itself. Thus low-molecular-weight dextran is recommended for postoperative patients,
while heparin administration is routine for patients who have not had operation.
Transthoracic placement of the IABP is associated with higher mortality rates. [124 ]
[126 ] A femoral-femoral or axillary femoral bypass graft may be necessary to save an
extremity.
Ventricular assist devices
Temporary ventricular assist devices (VADs) are placed after cardiac operations if
weaning from cardiopulmonary bypass remains impossible despite the use of an
intraaortic balloon pump and for patients in profound heart failure awaiting cardiac
transplantation. In both these circumstances, cardiogenic shock is either established or
imminent, and death is nearly certain without additional circulatory support. The most
important determinant of survival is the extent of irreversible myocardial damage
suffered prior to device implantation.
Patients with VADs demand a balance between control of bleeding, which often is
significant, and avoidance of intracardiac thrombosis. Our protocols is to utilize a
heparin-coated system and begin continuous heparin infusion as early as possible. In
patients supported with a right ventricular assist device (making thermodilution cardiac
output measurements unreliable), continuous measurements of mixed venous oxygen
saturation as well as right and left atrial pressures guide management decisions about
VAD flow rates, volume repletion, inotropic support, and alternations in systemic and
pulmonary vascular resistance.
Ventricular assist devices commonly used to support cardiac performance for a limited
time after surgery include centrifugal pumps, the Abiomed BVS system, [128 ] and the
Hemopump. The Abiomed BVS system is a tethered device with a pneumatically driven
external pump and polyurethane three-leaflet valves. Its pumping chambers are filled
passively from the patient's atria (it may be used as a left, right, or biventricular assist),
and blood is pumped back to the aorta or pulmonary artery. [128 ] The system yields an
overall 29 percent hospital discharge rate in patients who did not have presupport
cardiac arrest. [129 ] The Hemopump catheter is passed retrograde across the aortic
valve via a femoral artery approach. [130 ] Ventricular unloading with this device is
superior to that of IABP alone, especially when ventricular dysfunction is severe. [131 ]
Survival rate is similar to that with other VAD systems. [132 ] The Hemopump also has
been used in lieu of CPB for unstable patients undergoing coronary artery bypass
grafting. [133 ]
The controlled vortex centrifugal pump is the same that is commonly used during
cardiopulmonary and left-sided heart bypass and therefore offers the advantage of wide
availability without additional expense. It is use widely in both adults and children. [134 ]
[138 ] The use of a centrifugal pump as a VAD does not mandate anticoagulation,
particularly if a heparin-bonded circuit is used. Intracardiac thrombus formation,
however, remains a considerable problem, particularly if atrial cannulation is used and if
the bypassed ventricle has suffered a recent myocardial infarction. Low-dose heparin,
maintaining the activated clotting time at 150 to 200 seconds, [139 ] together with some
blood ejection from the bypassed ventricle, reduces this complication.
Other device-related complications include hemorrhage from cannulation sites (often

requiring early reexploration), thromboembolism, air embolism from a dislodged
cannula, and device malfunction. It is rare to wean a centrifugal assist device within 48
hours of its placement for severe ventricular dysfunction, but most are weaned within 4
days. Transesophageal echocardiography can be useful in assessing wall motion
abnormalities, overall cardiac function, and the presence of thrombus within the heart
but is not required daily. [140 ] When the patient is able to maintain cardiac index
greater than 2.0 liters/min per m 2 over several hours with a VAD flow rate of 1000
mL/min or less, the device is removed. It has been our experience that 1 to 2 days of
negative fluid balance, sometimes achieved with the use of ultrafiltration, are necessary
before a VAD can be removed successfully.
Although centrifugal pumps can be used effectively as a temporary assist device in

patients with potentially reversible ventricular failure, long-term survival rates remain low,
at approximately 20 percent in three reported series. [137 ] , [138 ] , [141 ] Recovery of
adequate cardiac function or transition to a long-term assist device before the onset of
sepsis and multiorgan failure is the race that must be won for survival.
BLEEDING
Bleeding after heart operations remains a common and frustrating complication. Its
treatment consumes countless hours and dollars. More important, bleeding contributes
to morbidity and death.
Causes
PREDISPOSITION TO BLEEDING
Although infrequent, preoperative disorders may cause postoperative bleeding. Acute

myocardial infarction treated with thrombolytic therapy within hours before surgical
revascularization causes a profound bleeding diathesis that can be controlled with
fibrinogen replacement and/or aprotinin. [142 ] , [143 ] Aspirin taken within 1 week
before operation may increase the bleeding time but infrequently increases
postoperative blood loss. [144 ] , [145 ] Other intrinsic clotting abnormalities are
encountered occasionally; however, almost all can be ruled out in the absence of a
history of unusual bleeding with lacerations, operations, or dental procedures. We do
not recommend a routine preoperative bleeding time but do obtain a careful bleeding
history.
MECHANICAL, ANATOMIC, OR SURGICAL CAUSES
In the presence of excessive bleeding (over 500 mL in the first hour), the first question is
whether or not bleeding is coming from an anatomic source. Such sources include
vascular anastomoses, side branches of saphenous veins or internal mammary
arteries, cannulation sites, aortotomies or cardiotomies, left ventricular aneurysm
resection lines, the distal transsected end of an internal mammary artery, edges of
pericardium, the coronary sinus and great coronary vein, and pleural or pericardial fat. If
bleeding is exceptionally brisk or an anatomic source is suspected, the remedy is
immediate operation.
BLEEDING DIATHESIS
Cardiac surgery causes a postoperative bleeding tendency. [146 ] [151 ] The primary
cause appears to be fibrinolysis caused by blood contact with the biomaterial
components of the heart-lung machine and by blood suctioned from pericardial and
pleural wells. (See Chapter 9 for a detailed discussion of the pathogenesis.) The
degree of fibrinolysis correlates with the duration of cardiopulmonary bypass. [147 ]
Platelet dysfunction and heparin [152 ] also contribute to postoperative bleeding.
Hemodilution decreases platelet numbers. Most cardiac operations use moderate
hypothermia, and persistent or recurrent hypothermia commonly occurs early after
operation. Hypothermia-induced dysfunction of platelets and coagulation enzymes also
causes a bleeding diathesis. Heparin reboundthe recurrence of measurable heparin
activity after complete neutralization with protamineoccurs frequently and is probably
caused by elution of heparin from plasma proteins. [153 ] Because this problem is
easily managed by additional protamine, it has little clinical significance. [154 ]
Diagnosis
Definition of excessive bleeding must precede diagnosis. We consider bleeding

excessive when the chest tube effluent exceeds 500 mL/h in the first hour, 400 mL/h
during the first 2 hours, 300 mL/h during the first 3 hours, or 200mL/h during the first 6
hours. In addition, sudden increases in bleeding rate signify excessive bleeding and
suggest a new arterial or intracardiac source. Massive bleeding is considerably in
excess of these parameters and usually is accompanied by hemodynamic
compromise.
At times, blood accumulates in the pericardial space but does not drain because clots
fill the chest tubes. In these instances, clot fills not only the chest tube but also the
pericardium. Vigorous chest tube stripping can create high negative pressures but
rarely succeeds in clearing clot from the tube. Clot cannot be removed in this manner
because the tube is surrounded by mediastinal clot that has the consistency of Jello.
The high vacuum created by stripping can suck a saphenous vein graft into the chest
tube and kink or occlude the graft. Chest tubes should not be stripped! Reexploration of
the wound and manual removal of the clot are required.
Our routine postoperative laboratory test to screen for clotting disorders is an activated
partial thromboplastin time (PTT). For patients with excessive bleeding or a markedly
elevated PTT, other tests are performed. These include a prothrombin time (PT),
thrombin time (TT), fibrinogen determination, and platelet count. Elevated fibrin
degradation products (FDP) or d-dimer indicates fibrinolysis, but a low plasma
fibrinogen concentration is sufficient to initiate antifibrinolytic therapy. If inadequate
heparin neutralization exists, it may be identified by an elevated PTT or TT and a normal
reptilase test. An analysis of the causes of bleeding and recommended treatments are
given in Table 12-6 . In addition to these tests, a comparison of the blood hematocrit
with one from a freshly drawn sample from the chest tube differentiates fresh bleeding
and excessive serum reflux or lymphatic drainage. Finally, if pericardial tamponade is
suspected, the chest x-ray taken immediately after operation should be compared with
that taken several hours later; tamponade in the absence of widened mediastinum is
rare.
Treatment
INTRAOPERATIVE TECHNIQUE: PREVENTION
The vast majority of excessive postoperative bleeding episodes can be prevented by a

meticulous, systematic operation and sternal closure. At the completion of an orderly,
carefully performed operation, and after neutralization of heparin with protamine, a
compulsively thorough search for bleeding should be done. Beginning superficially, the
skin and suprasternal tissues are inspected, followed by the sternum and periostium.
The internal mammary bed comes next, followed by reinsertion of the sternal retractor
and examination of the pericardial and pleural fat and the veins in the region of the left
innominate vein. Finally, all anastomoses, aortotomies, and cardiotomies and the
lengths of all grafts are examined. Excessive bleeding during this inspection often
precludes finding specific bleeding sites. Patience must be available to continue a
systematic search for bleeding. Because some patients do not tolerate lifting the heart,
the surgeon must be assured that the posterior surface is not bleeding before bypass is
terminated. This routine was clearly advocated by Najafi, who stated, The surgeon's
determination to gain reliable hemostasis is the prerequisite for preventing reoperation
for bleeding after cardiac operations. [155 ]
INTRAOPERATIVE: PHARMACOLOGIC MANIPULATION
Regardless of efforts to prevent bleeding, a bleeding diathesis may still produce

excessive blood loss after complex and long operations. Pharmacologic therapy of this
nonsurgical clotting disorder is often helpful. Antifibrinolytic agents such as
epsilon-aminocaproic acid and tranexamic acid and the protease inhibitor aprotinin
reduce postoperative blood loss after heart operations. [156 ] [160 ] However, aprotinin,
the most effective of these agents, may contribute to renal dysfunction and early
coronary artery graft thrombosis. [161 ] [163 ] For this reason, and because of its
considerable cost (about $1000 per patient), we reserve aprotinin for long operations
with predictable excessive bleeding. We recommend, and routinely administer,
epsilon-aminocaproic acid: 10 g with the skin incision, 10 g during the operation, and
the final 10 g immediately before heparin reversal with protamine for other operations.
Desmopressin acetate (DDAVP) also has been given to reduce postoperative

bleeding, but its effectiveness is controversial. [164 ] [166 ] However, the drug appears
to be effective in reducing postoperative bleeding in patients who receive preoperative
aspirin. [167 ] [169 ]
REINFUSION OF SHED BLOOD
During cardiac operations, blood in the pericardium or pleural spaces is routinely

aspirated back into the perfusion circuit. This admixture of circulating and shed blood
probably contributes to some of the clotting disorders that occur after heart operations.
[170 ] Before heparin and after protamine, many centers reinfuse packed cells
separated from washed blood aspirated from the field. After operation, chest tube
effluent may be reinfused. This blood has already clotted in the mediastinum and hence
contains high levels of fibrin degradation products and low levels of fibrinogen.
Accordingly, fibrinolysis appears after reinfusion of shed blood, but this does not lead to
a significant clotting disorder. [171 ] [176 ] Nevertheless, in most patients (in whom
average postoperative blood loss over the first 24 hours is between 500 and 750 mL)
we find that reinfusion is neither necessary nor cost-effective.
VOLUME REPLACEMENT
Volume replacement should satisfy two seemingly opposing goals: (1) maintenance of
adequate intravascular volume for adequate blood circulation (2) without increasing
diffuse organ edema that accompanies heart operations. Blood oxygen-carrying
capacity also must be adequate. If oxygenation and mixed venous o 2 saturation are
adequate, we do not transfuse patients unless the hematocrit falls below 25 percent.
BLOOD FACTOR REPLACEMENT
Component factor replacement is unnecessary unless bleeding is excessive and

recommended tests (Table 12-6) indicate a bleeding diathesis. For patients who
require replacement, the usual clotting disorder demonstrates an elevated PT, PTT, and
TT and a depressed fibrinogen concentration and platelet count. If the reptilase time is
normal, heparin excess is present, and extra protamine should be given. If the reptilase
test is elevated, fibrinogen deficiency and fibrinolysis are present in most cases.
Continued bleeding and continued red cell replacement exacerbate this deficiency.
Fibrinogen must be replaced after calculating the deficit. Although normal serum
fibrinogen levels are between 200 and 400 mg/dL, a fibrinogen concentration of above
100 mg/dL should be sufficient to prevent bleeding due to hypofibrinogenemia. The
deficit is calculated by subtracting the patient's serum fibrinogen concentration from 100
mg/dL and multiplying this by the patient's serum volume in deciliters. Volume
replacement is calculated by dividing the deficit by the amount of fibrinogen in 1 unit of
replacement. Fresh-frozen plasma contains about 500 mg per unit, and cryoprecipitate
contains about 150 mg per unit. After replacing the deficit amount, serum fibrinogen
should be remeasured. Continued bleeding further reduces the fibrinogen and must be
treated with additional replacement.
In patients with excessive bleeding and a bleeding diathesis or a low platelet count, we
replace platelets empirically and usually administer 6 to 10 units before assessing the
response.
OTHER METHODS OF CONTROLLING BLEEDING
Increasing positive end-expiratory pressure (PEEP) may control excessive bleeding,

but pressures approaching 20 cmh 2 o may cause hypotension and reduced cardiac
output. [177 ] [179 ]
Other mechanical methods include placing a tamponading pack in the mediastinum,

either with the chest closed or open. Sometimes the pack is covered with a rubber
glove to reduce the possibility that bleeding will restart when the pack is removed.
Lastly, high vacuum applied through a catheter to a specific bleeding area that cannot
be controlled with sutures may facilitate clot formation. [180 ] , [181 ]
Reexploration for Bleeding
Excessive bleeding, as defined above, requires reexploration if clotting studies are

normal. Delays in reexploration only increase morbidity by requiring more blood
transfusions that increase the bleeding tendency, increase organ edema, and
exacerbate heart, lung, and renal dysfunction.
The decision to reexplore is more difficult if clotting studies are abnormal. If the bleeding
rate does not produce hemodynamic compromise, and if pericardial tamponade is
absent, replacement of clotting factors and protamine administration may be pursued
aggressively. When clotting studies have returned to normal, or nearly so, the bleeding
rate may be reassessed by criteria listed above to determine the need for
reexploration.
When the clotting abnormality persists despite treatment, and if bleeding persists,
reexploration should be performed. The likelihood of finding nonsurgical bleeding is
high, but the likelihood of stopping the bleeding even without an anatomic source is also
high. Evacuation of mediastinal clots seems to facilitate cessation of bleeding.
Massive bleeding demands immediate reexploration, as does pericardial tamponade.

LUNG
The goal of pulmonary management after heart surgery is a rapid transition from a
patient who is anesthetized, intubated, and ventilated to one who is awake, extubated,
and breathing spontaneously with adequate oxygenation.
Initial Assessment
In postcardiotomy patients who have extensive and invasive monitoring, there is a

tendency to observe and treat the numbers rather than to rely on clinical assessment.
On arrival to the ICU, most patients will be intubated and still asleep. Skin color and feel
give early warning of poor cardiac output and poor oxygenation. Chest auscultation
confirms adequate air exchange in both lungs.
Arterial blood gases (ABGs) should be obtained on admission to the ICU even though
subsequent ventilator weaning may be monitored by pulse oximetry. A chest x-ray
confirms proper endotracheal tube position and reveals pleural effusions, pulmonary
edema, and atelectasis. The film also serves as a baseline for comparison of
mediastinal width should a question of pericardial tamponade be raised.
Pulmonary Dysfunction
PULMONARY EFFECTS OF CARDIOPULMONARY BYPASS
Cardiopulmonary bypass (CPB) injures most organs, including the lung. Extracorporeal
perfusion produces multiple emboli of gas, fibrin, fat, cells, and other biologic debris.
Bypass activates coagulation, contact, complement and fibrinolytic systems, and
leukocytes, monocytes, platelets, and endothelial cells (see Chap. 9).
The combination of microemboli and activated blood enzymes leads to increased

functional residual capacity (FRC), pulmonary shunting with an increased
alveolar-arterial oxygen gradient, ventilation/perfusion mismatch, microatelectasis,
endothelial cell swelling, and increased total-body and lung fluid. [182 ] , [183 ] The
degree of damage increases with the time on CPB and is worse with bubble
oxygenators than with membrane oxygenators. [184 ] , [185 ] The pulmonary damage
also correlates with the amount of pulmonary extracellular water and the degree of
complement activation (as measured by C3a), and both these changes correlate with
the duration of CPB. [7 ] , [184 ] , [186 ]
Several methods to minimize this lung injury have been proposed. Intraoperative
leukocyte depletion (by filtration) has produced inconsistent results. [187 ] [189 ]
Prostaglandin E1 (PGE 1 ) or a synthetic analogue reduces the duration of ventilation
and improves oxygenation postoperatively. [190 ] , [191 ] Pharmacologic inhibition of
platelet-activating factor decreases pulmonary vascular resistance, increases
oxygenation, and decreases histologic lung damage. [192 ]
The use of positive end-expiratory pressure (PEEP) postoperatively increases FRC but
may not reduce intrapulmonary shunting. [193 ] However, in our experience, increasing
levels of PEEP usually improve oxygenation in patients with excessive shunting. Very
high levels, above 10 to 15 cmh 2 o, may impair cardiac function.
PHRENIC PALSY
Left lower lobe atelectasis or infiltrates are quite common after heart operations. [194 ]
Part of the reason is wound pain, sedation, the supine position, hesitancy to cough, and
general weakness of the patient. Partial palsy of one or both phrenic nerves may
contribute. [194 ] [196 ] More severe or complete phrenic palsy can be caused by
topical cold or iced slush in the pericardium. Phrenic nerve palsy, particularly if bilateral,
can lead to severe or even fatal pulmonary dysfunction. [197 ] [199 ]
OTHER CAUSES
Preoperative pulmonary dysfunction contributes to postoperative dysfunction. [200 ] In

patients with poor pulmonary function, both the incidence of pulmonary complications
and the duration of intensive care increase. Patients with obstructive pulmonary disease
fare less well than those with restrictive disease.
Persistent left ventricular failure after cardiac operations increases end-capillary

hydrostatic pressure and favors fluid extravasation into alveoli. Interstitial and alveolar
fluid inhibits oxygen transfer, increases shunting, decreases compliance, increases
secretions, and facilitates atelectasis and pneumonia. Excessive pain, by inhibiting
deep breathing, also leads to atelectasis and pneumonia. Epidural anesthesia
effectively relieves severe pain and may be helpful in the uncommon patient who
develops sternal fractures during operation. [201 ]
Ventilation
INITIAL MANAGEMENT: VENTILATOR SETTINGS
The ventilator is adjusted to achieve adequate oxygenation (Po 2 of 80 to 100 mmHg),

carbon dioxide elimination (Pco 2 of 35 to 45 mmHg), and normal pH (7.3 to 7.5).
Higher tidal volumes with lower rates help reduce atelectasis without hyperventilation.
PEEP also helps to maintain lung volumes and prevent atelectasis. Low amounts of
PEEP are tolerated well by all patients except those with emphysematous air trapping;
in these patients, PEEP may be contraindicated. Typical initial ventilator settings are
minute volume, 120 mL/kg per minute; tidal volume, 15 mL/kg; rate, 8 breaths per
minute; and PEEP, 5 cmh 2 o. The inspired initial oxygen concentration (Fio 2 ) is usually
0.9 but is quickly lowered to 0.5 or less as permitted by an initial ABG measurement.
Subsequently, Fio 2 is progressively reduced and monitored by transcutaneous o 2
saturation.
MAINTENANCE
Intermittent mandatory ventilation (IMV) with PEEP of 5 mmHg maintains alveolar

expansion, facilitates weaning by gradual reduction in the ventilatory rate, but may not
always prevent postoperative atelectasis. [202 ] Fio 2 is rapidly reduced as tolerated.
Excessive secretions are removed by suction. An in-line suction catheter reduces
airway contamination that may occur with repeated insertions of an independent suction
catheter into the endotracheal tube. When the secretions are due to pulmonary edema,
however, PEEP and addressing the cause constitute the best method of controlling
them.
Shivering following hypothermic CPB increases systemic oxygen consumption and

predisposes to respiratory and metabolic acidosis. [203 ] Shivering is best treated by
rewarming with radiant heat but may be arrested temporarily with narcotics or muscle
relaxants. [204 ] , [205 ]
VENTILATOR WEANING
Whereas we once deferred extubation until the day after the operation, we now wean
patients from the ventilator and extubate them as quickly as possible after (and
occasionally before) leaving the operating room. This requires modification of the
high-dose narcotic anesthesia protocol that is often used to blunt the sympathetic
response in patients with ischemic heart disease. [206 ] , [207 ] Perioperative
myocardial infarctions increase if anesthesia is insufficient to prevent sympathetic
discharge. [206 ] , [207 ] However, other factors besides anesthesia also must be
considered in a decision for early extubation. These include duration of
cardiopulmonary bypass, extent of rewarming, preoperative pulmonary status, age,
comorbidity, and adequacy of hemodynamics and hemostasis. The efficacy of the
operation itself is a major factor in the decision for early extubation. Early extubation is
safe and improves cardiac function by increasing preload as capacitance blood volume
shifts into the chest. [208 ] [210 ] Early extubation allows shorter stays in the ICU and
decreased costs.
WEANING CRITERIA
If the initial ABGs are adequate, weaning the Fio 2 to 0.5 or less may be performed by
monitoring arterial o 2 saturation (Sao 2 ) by pulse oximetry. Weaning from controlled
ventilation to spontaneous unassisted ventilation may be monitored similarly. However,
adequate o 2 saturation does not ensure absence of co 2 retention. Careful clinical
assessment usually indicates satisfactory co 2 elimination. Rising blood pressure, rapid
or shallow ventilation, and agitation suggest inadequate co 2 elimination; ABGs must be
measured if there is any question of the adequacy of alveolar ventilation or co 2 removal.
Even if ventilator weaning proceeds smoothly, ABGs should be remeasured prior to
extubation to confirm the absence of co 2 retention and acidosis. Contraindications to
extubation include inadequate ABG values, inadequate ventilatory mechanics, early
pneumonia, unstable hemodynamics, and systemic complications.
For extubation, ABG criteria are
Po 2 > 80 mmHg with Fio 2 0.5
pH (on CPAP) 7.35 (no respiratory acidosis)
Pco 2 45 mmHg
Vital capacity (VC) 15mL/kg
Mean inspiratory flow rate (MIF) 35 liters/min
Alert, awake
Absence of excessive bleeding, hemodynamic instability, or dangerous arrythmia
Ventilator weaning, in uncomplicated cases, is quite simple. The IMV rate is

progressively decreased until the patient is on 5 mmHg of PEEP and an Fio 2 of 0.5 or
less. If the preceding criteria are met, the endotracheal tube is removed and replaced
with humidified mask oxygen.
POSTEXTUBATION SUPPORT
Immediately after extubation, administer humidified oxygen at 10 liters/min and at a

concentration 10 percent greater than the patient received while intubated. Oxygen
delivery may be decreased safely if the o 2 saturation remains above 97 to 98 percent.
Usually by the second postoperative day supplemental oxygen may be given via nasal
prongs at progressively decreasing rates as long as the o 2 saturation remains above
90 percent. Sao 2 is maintained over 95 percent during the first 2 to 3 days after
extubation and over 90 percent thereafter. Incentive spirometry helps the patient to
visually assess and improve his or her ventilatory effort. Lobar collapse either before or
after extubation may be treated by tracheal suctioning but usually requires
bronchoscopy. Chest physiotherapy is particularly helpful in raising secretions and
encouraging cough. During these first few postextubation days, several pulmonary
complications may occur; anticipating problems allows earlier treatment and preempts
an extended convalescence.
REINTUBATION
A few patients are too weak to sustain adequate ventilatory efforts despite having
satisfied extubation criteria. They develop retained secretions and atelectasis and may
progress to pneumonia. Treatment consists of chest physical therapy, nasotracheal
suctioning, and occasionally bronchoscopy. Should these measures not restore
adequate ventilatory mechanics, or should excessive weakness persist, reintubation is
necessary.
This step must not be delayed to the point that more severe pulmonary complications
ensue. The same clinical factors that predict failure to wean also predict the need for
reintubation. Air hunger, feeble ventilatory effort, tachypnea, shallow breathing, or gross
inability to clear secretions requires reintubation and mechanical ventilation. Other
reintubation criteria include a rising paco 2 from a normal value to 50 mmHg over a few
hours, hypoxia despite an increasing Fio 2 , and a falling cardiac output. [212 ] A venous
Pco 2 can be measured in lieu of an arterial sample. Venous Pco 2 is invariably 6 or 7
mmHg higher than the simultaneous paco 2 .
Complications
Prolonged mechanical ventilation predisposes to pneumonia. The endotracheal tube

not only bypasses defenses of the upper airway and tracheal cilia but also allows direct
ingress of bacteria. The importance of strict asepsis in the ventilator maintenance and
endotracheal suctioning cannot be overemphasized. The drawbacks of endotracheal
intubation and predisposition to pneumonia strengthen the argument for early
extubation.
Noncardiogenic pulmonary edema develops from an allergic reaction, probably to

blood or its products or to protamine. [213 ] , [214 ] The edema presents as fulminating
pulmonary edema with normal left atrial or pulmonary capillary wedge pressures and
usually occurs either in the operating room or in the immediate postoperative period.
The copious fluid bubbling from the endotracheal tube has a high protein content. When
this edema occurs after cardiopulmonary bypass, the turgid, edematous lungs develop
such severe air trapping that ventilation may cause the lungs to tamponade the heart,
especially if sternal closure is attempted. Effective treatment consists of
bronchodilators, corticosteroids, isoproterenol, and positive-pressure ventilation with
high levels of PEEP. Because of tamponade, sternal closure is deferred. An intraaortic
balloon may be required to support cardiac function despite the absence of intrinsic
cardiac abnormalities.
Barotrauma occurs most commonly in patients who require high levels of PEEP or high
peak inspiratory pressure during mechanical ventilation. Sudden hypoxia suggests
pneumothorax, either simple or tension, and demands immediate investigation. If
present, prompt chest tube insertion is required. This complication is most common
early after operation in elderly patients who cannot be extubated early and usually is due
to rupture of apical blebs.
With an open pleural space, as often occurs from harvesting the internal mammary
artery, postoperative bleeding may produce hemothorax rather than excessive blood
drainage. An unexplained fall in hematocrit or hemodynamic instability suggests this
possibility. Hemothorax also requires chest tube insertion.
Late pleural effusions occur more commonly on the left than on the right, as does left
lower lobe atelectasis. This predilection remains even without harvesting the left internal
mammary artery. Effusions may require thoracentesis or occasionally a chest tube.
Pulmonary embolism occurs infrequently after heart operations (incidence 0.56 percent)
but carries a high mortality of 34 percent. [215 ] Risk factors include preoperative bed
rest or hospitalization of more than 1 day, groin cardiac catheterization within 15 days of
operation, and postoperative congestive heart failure or bed rest of more than 3 days.
Long-Term Ventilator Support
CAUSES OF FAILURE TO WEAN FROM MECHANICAL VENTILATION
An infrequent postoperative patient requires prolonged ventilator support for more than
several days. Failure to wean has two causes: failure of gas exchange at the alveolar
level and failure to ventilate adequately. The two most common reasons for deficiency in
gas exchange are left-sided heart failure with pulmonary congestion and the adult
respiratory distress syndrome (ARDS).
Failure to adequately ventilate has several venues. These include chronic illness with
poor nutrition (cachexia) and ventilatory (diaphragm and chest wall) muscle weakness,
central nervous system dysfunction, pain, mechanical disruption of the bony chest wall,
chronic lung disease with stiff lung parenchyma, and sepsis. Muscle weakness also
may be caused by hypothyroidism and deficiencies of magnesium, potassium, calcium,
and phosphate. [216 ] , [217 ]
WEANING AFTER PROLONGED MECHANICAL VENTILATION
In patients who need prolonged ventilator support, weaning attempts must be preceded
by elimination of the causes of ventilator dependence. When excessive lung water
impedes weaning, negative fluid balance is required. In the patient with renal
dysfunction, a compromise must be struck between the pulmonary and renal systems,
usually in the favor of the lungs. During mild dehydration, the blood urea nitrogen (BUN)
level may rise temporarily. Likewise, pneumonia must be resolved by appropriate
antibiotics and airway toilet. When the disorders promoting ventilator dependence are
corrected, the same weaning criteria as for the acute postoperative patient are used.
WEANING TECHNIQUES
The process of weaning from long-term ventilator support may be considered

endurance training for the chest wall muscles and diaphragm. This consists of
progressively increasing ventilatory load until mechanical ventilation is discontinued.
This is usually accomplished by a weaning schedule that progressively increases
periods of spontaneous ventilation. In the absence of tachypnea, small spontaneous
tidal volumes, fatigue, or respiratory distress, progression may be rapid. During
weaning trials, the patient should be pushed to the point of fatigue. If none occurs, the
weaning period should not be terminated arbitrarily. The three types of weaning
methods used are T-piece, synchronized intermittent mandatory ventilation (SIMV), and
pressure-support ventilation (PSV). No convincing evidence suggests the superiority of
one method over another. In difficult weaning cases, if one method does not succeed,
another should be tried. With all methods, weaning in an upright or sitting position
optimizes the likelihood of success.
T-piece
In T-piece weaning, glottic expiratory resistance is eliminated by the endotracheal tube,

and this decreases end-expiratory lung volume. This adverse effect should be abolished
by adding 5 cmh 2 o of continuous positive airway pressure (CPAP). With T-piece
weaning, the patient should be monitored for fatigue, respiratory distress, respiratory
rate, heart rate, and blood pressure. Weaning proceeds if these parameters are
satisfactory. ABGs should be obtained before extubation.
SIMV
With this method, the ventilator is programmed to give a preselected number of breaths
per minute but is synchronized with the beginning of a spontaneous breath. Thus a set
number of mechanically ventilated breaths of predetermined volume are superimposed
on the patient's spontaneous ventilatory rate. CPAP is usually added to the
spontaneous breaths. Weaning is achieved by progressive, gradual decrements in the
SIMV rate until the patient is on CPAP without mechanical support. The same
parameters as with T-piece weaning should be monitored. Because even a few
mechanical breaths per minute can produce normal ABGs and thus conceal inadequate
spontaneous ventilation, high spontaneous rates with low tidal volumes preclude
extubation and predict weaning failure.
PSV
With PSV weaning, every spontaneous breath is mechanically assisted to a preset level
of pressure support. Weaning is accomplished by gradually reducing the level of
support, usually to about 5 to 10 cmh 2 o, before switching to CPAP of 5 cmh 2 o and
extubating. The same parameters as with the preceding two methods should be
monitored.
TRACHEOSTOMY
If, after 7 to 10 days of ventilation, weaning does not seem imminent, a tracheostomy or
cricothyroidotomy is performed. Tracheostomy offers several advantages over an
endotracheal tube. The time constraints of an endotracheal tube may force premature
weaning. With tracheostomy, weaning can be managed independently of extubation.
Tracheal toilet is more easily performed via tracheostomy. The dead space of a
tracheostomy is less than that of an endotracheal tube, and this may facilitate weaning
in a patient with marginal ventilation. Tracheostomy is more comfortable. Once
established, tracheostomy offers greater security than an endotracheal tube in case of
accidental extubation because a tracheostomy tube is more easily inserted.
One disadvantage of tracheostomy, whether performed by standard or percutaneous

techniques, is accidental extubation during the first several days after initial placement.
Hasty attempts to replace the tube easily lead to insertion outside the trachea. The
possibility of contamination and infection of the median sternotomy incision exists if the
tracheostomy is too close. The tracheostomy incision is placed as far above the median
sternotomy as practicable, and the tracheal stoma is established no lower than the
second tracheal ring. With either a tracheostomy or endotracheal tube, obstruction of
the tracheal end of the tube may occur from inspissated secretions. Adequate
humidification helps prevent this complication. Difficulty passing a suction catheter
through the tube suggests the problem, which may require changing the tube.
Cricothyroidotomy has advantages and disadvantages over tracheostomy. [218 ] [220 ]

It is more easily performed and therefore makes it easier to secure an airway during
emergency conditions (when an endotracheal tube cannot be inserted). Because the
incision and tracheal entry are further from the median sternotomy, cricothyroidotomy
may reduce the risk of mediastinal infection. Cricothyroidotomy, however, risks possible
subglottic stenosis, and in about half of recipients, voice abnormalities develop.
GENERAL CARE
Multiple problems may develop in the patient who requires long-term ventilation, and
these are best prevented by prophylaxis.
In an immobile patient, skin breakdown may occur over pressure points. A mattress
designed to eliminate constant pressure focused over these pressure points should be
used. Pooling of body fluids may cause skin maceration and breakdown. Assiduous
nursing care must be employed to prevent pooling of urine, stool, or other fluids.
Inadequate nutrition impairs the ability to wean from the ventilator. Nutritional
maintenance is started if the patient has not been extubated by the second
postoperative day. Most cardiac patients have an intact gut; enteral feeding has many
advantages over parenteral feeding. In these patients, and especially in those receiving
narcotics, stool impaction may easily occur. This possibility should be assessed
frequently by rectal examination if necessary. Stool softeners are used routinely.
Physical therapy is started to maintain joint mobility through range-of-motion exercises

and muscle mass through resistance exercises. Contractures in patients with neurologic
dysfunction are prevented with stretching exercises and splinting.
Infection constantly threatens these patients. Assiduous, aseptic care must be given to
intravenous lines and all catheters. Intravenous catheters are changed on a regular
schedule, usually every 5 days, or immediately if abrupt fever develops. Pulmonary toilet
is maintained with strict asepsis.
KIDNEY
Adequate Postoperative Renal Function
Urine volume, blood urea nitrogen (BUN) level, and plasma creatinine level are the
principal measures of adequate renal function following cardiac surgery. Adults are
expected to make a relatively large amount of urine, usually 0.5 to 1.0 mL/kg per hour or
greater after heart surgery. When urine volume is less, the clinician should suspect poor
renal function caused by low cardiac output, low blood pressure, or obstruction to renal
blood flow.
Mild elevations of BUN and creatinine are common after cardiac surgery and may be
associated with an adequate or even large urine volume. [221 ] These changes are
nearly always transient, with complete return of normal renal function. In cardiac surgical
patients with normal preoperative renal function, 15 percent have an increase in serum
creatinine above 1.5 mg/dL postoperatively. Only a fraction of these patients develop
acute renal failure (oliguria, creatinine > 2.5 mg/dL), a complication associated with a
high mortality rate. New azotemia reflects hypoperfusion of the kidney, and its degree
depends on the severity and duration of decreased glomerular filtration.
The insensitivity of BUN and plasma creatinine levels for predicting the onset of acute
renal failure has led to other analyses of renal function that are related primarily to renal
concentrating capacity. [222 ] , [223 ] Free water clearance is a simple and accurate
method of identifying early, subclinical renal dysfunction. [224 ] , [225 ] Free water
clearance ( C H20) can be determined according to the method of Smith [226 ] : C H20
= V(1 - U osm /P osm ) where U osm and P osm are urine and plasma osmolality in
mmoles per liter, and V is urine volume. Free water clearance values range from -100
(or more negative) to -20 mL/h; pathologic values range from -20 to 0 mL/h or more
positive. Abnormal free water clearance is a constant finding that precedes elevations
of BUN or creatinine in patients who develop renal failure [222 ] (Fig. 12-2) . However,
abnormal free water clearance is also detectable in patients with mild reversible renal
insufficiency and therefore is not predictive of renal shutdown. Baek et al. [224 ] and
Brown [225 ] used free water clearance measurements and the response to furosemide
to prospectively determine which patients would experience frank renal failure. A
response to furosemide correlated with a better prognosis. Thus free water clearance
measurements allow earlier detection and treatment of incipient renal failure.
Acid-base alterations also follow cardiac surgery and can reflect the adequacy of renal
function. [227 ] Development of metabolic acidosis or a base deficit parallels abnormal
free water clearance (and precedes elevations of BUN and creatinine) in patients who
eventually develop renal failure (Fig. 12-3) . At our institution, marked metabolic
acidosis following heart surgery is associated with increased mortality, morbidity, and
hospital stay, independent of the development of renal failure. Thus metabolic acidosis
and impaired free water clearance forebode development of renal failure and
independently correlate with negative outcomes. Often, these clinical findings are
sequelae of perioperative low cardiac output. Metabolic acidosis and impaired free
water clearance may unexpectedly follow a period of relatively normal urine flow and
acid-base balance during cardiopulmonary bypass, but mechanical perfusion may have
masked poor postoperative cardiac performance and postponed metabolic acidosis
and impaired free water clearance.
Criteria for Postoperative Renal Dysfunction
Renal dysfunction in the postoperative cardiac patient covers a spectrum from mild
azotemia without important consequences to oliguric renal failure that requires dialysis
and confers a mortality rate of at least 50 percent. [228 ] , [229 ] Associated morbidity
varies with the degree of renal dysfunction and often with the severity and duration of the
low cardiac output state that may have precipitated it. Acute renal failure is usually not
evident immediately after surgery but becomes evident within the first 48 hours.
Abnormalities in free water clearance and acid-base balance are the earliest laboratory
markers of renal insufficiency. Patients with inadequate renal function sequester more
fluid than normal and exhibit a fractional excretion of sodium (FENa) that is greater than
1.0. [230 ] FENa is calculated from the following formula: FENa = (U Na /S Na )/(U Cr /S
Cr ) × 100 where U Na is urine sodium concentration, S Na is serum sodium
concentration, U Cr is urine creatinine concentration, and S Cr is serum creatinine
concentration. Although hypertension is common after cardiac operations and may be
triggered by the renin-angiotensin system, it does not correlate with acute postoperative
renal insufficiency. [231 ] , [232 ]
About one day after early manifestations of renal dysfunction, rises in BUN and
creatinine levels are detectable. In one series, 17 percent of cardiac patients
demonstrated an increase in serum creatinine above 1.5 mg/dL, and 1.5 percent
progressed to oliguric renal failure (urine output less than 400 mL/day). [233 ]
Hyperkalemia is an important complication of renal failure that must be recognized and
controlled quickly to avoid serious cardiac dysfunction. Progressive oliguria and
azotemia ensue in those who develop frank renal failure; most of these patients require
temporary renal support.
Causes of Postoperative Renal Dysfunction
Perioperative cardiac output is an important determinant of postoperative renal

function. Similar to all experimental models of acute renal failure, the pathophysiologic
process that leads to most postoperative renal insufficiency is a reduction in total renal
blood flow and a secondary decrease in glomerular filtration. [223 ] Tubular obstruction
with cellular casts and leakage of filtrate across damaged tubular epithelium are
sequelae. The degree of tubular obstruction determines whether anuric renal failure
develops. Only a small number of patent tubules are needed to maintain adequate urine
output. [234 ] The recovery phase of acute renal failure is marked by improved free
water clearance and a gradual return of renal concentrating ability after relief of tubular
obstruction. [234 ]
Preoperative renal dysfunction and advanced age predispose to postoperative renal

failure. [221 ] , [228 ] , [235 ] However, a hemodynamic insult is superimposed on these
factors to initiate acute renal failure. [236 ] , [237 ] Although cardiopulmonary bypass
may temporarily impair renal function, acute renal insufficiency is not an expected
outcome of a well-conducted cardiac operation. After routine cardiopulmonary bypass,
patients with normal preoperative renal function have only mild disturbances of tubular
function and unchanged glomerular filtration. [228 ] , [238 ] Pulsatile flow, [239 ] , [240 ]
high systemic perfusion pressure, and high cardiopulmonary bypass flow rates have
been used to improve postoperative renal function. [241 ] , [242 ]
Other factors that may play a role in the development of acute renal failure include
hemolysis with the liberation of free hemoglobin during prolonged cardiopulmonary
bypass, [243 ] , [244 ] circulatory arrest, [245 ] , [246 ] and perioperative sepsis.
Temporary Renal Support
Because oliguria worsens prognosis, initial therapy of postoperative renal dysfunction is

aimed at preventing oliguric renal failure or converting the dysfunction to nonoliguric
renal insufficiency. Beyond this effect, the goal is to prevent complications of renal
dysfunction that include hypervolemia, electrolyte imbalance, acidosis, encephalopathy,
infection, and bleeding. The timing of renal support with dialysis or ultrafiltration is an
important decision in cardiac surgical patients. Specific guidelines are not universally
accepted, but initial drug therapy is the first step.
PHARMACOLOGIC SUPPORT
Mannitol and diuretics
Most centers use mannitol in the priming solution for cardiopulmonary bypass, and it is
the agent of choice for prevention of renal dysfunction when periods of decreased
glomerular filtration are anticipated. Pretreatment with intravenous mannitol, continued
throughout any ischemic episode, improves subsequent renal blood flow and glomerular
filtration. [229 ] A strong solute diuresis relieves tubular obstruction and reduces tubular
cellular swelling. [229 ] , [247 ] Mannitol increases renal blood flow in both dogs and
humans during CPB. [248 ] , [249 ]
The renovascular and functional effects of loop diuretics are similar to those of mannitol.
Furosemide increases renal blood flow and promotes solute excretion. [250 ] The
theoretical benefit of furosemide in the patient with incipient acute renal failure is to
convert oliguric to nonoliguric renal failure. Although this may not improve chances of
recovery, [251 ] , [252 ] it avoids some of the complications associated with complete
renal shutdown. Furosemide early in renal dysfunction, when only abnormalities in free
water clearance are apparent, improves medullary blood flow and free water clearance
and identifies patients who are likely to require dialysis by their failure to respond. [224 ]
, [225 ]
Dopamine and other drugs
The use of dopamine to enhance renal blood flow and forestall renal failure deserves
consideration. The synergistic effects of dopamine and furosemide (administered after
an acute renal injury) have been studied with the conclusion that the combination is
more effective than either drug alone. [253 ] The combination of drugs prompts a brisk
diuresis and reduces serum creatinine levels, possibly by enhancing vasodilatation to
allow increased delivery of furosemide to the distal tubule. [254 ]
Other drugs that have some protective effect in experimental models include calcium
channel blockers [238 ] , [255 ] and PGE 1 . [256 ] , [257 ] None of these agents has
found clinical application. The mainstay to early support is improvement in renal blood
flow and maintenance of tubular patency by ensuring adequate cardiac output and
blood pressure while promoting renal vasodilatation and glomerular filtration with
dopamine, mannitol, and furosemide. If successful, continuous infusion of these agents
should be considered.
DIALYSIS AND ULTRAFILTRATION
Once renal failure is established, early and aggressive dialysis decreases mortality in
surgical patients. [258 ] , [259 ] A choice must be made among the methods available:
hemodialysis, peritoneal dialysis, or continuous arteriovenous hemofiltration.
The goals of dialysis include removal of excess fluid, reduction of serum potassium
level, removal of toxic metabolites including nephrotoxins, and correction of metabolic
acidosis. These goals can be achieved with any method but are accomplished more
slowly with peritoneal dialysis. Approximately the same results can be achieved in 1 day
of peritoneal dialysis as can be achieved in 4 hours of hemodialysis. [260 ] Other
disadvantages of peritoneal dialysis include the requirement of a minor surgical
procedure to place the catheter (a technique that may be precluded by previous
abdominal surgery), a low but measurable risk of peritonitis, and the possible
exacerbation of respiratory insufficiency by raising intraabdominal pressures during
dwell periods. Patients who have had recent abdominal procedures or who may require
them in the immediate future and those with low peritoneal clearances (due to shock,
diabetes, lupus erythematosus), as well as those with compromised pulmonary status or
high BUN levels, are not good candidates for peritoneal dialysis. The advantage of
peritoneal dialysis is that it does not require vascular access nor utilization of
hemodialysis staff and equipment.
Hemofiltration, or continuous arteriovenous hemofiltration (CAVH), was first described

for correcting hemodilution following CPB [261 ] , [262 ] but now is used to treat acute
renal failure. [263 ] , [264 ] Hemofiltration can be monitored by intensive care nurses
rather than by dialysis technologists. CAVH can improve hemodynamics as well as fluid
and electrolyte balance. More than 90 percent of the nitrogen eliminated by CAVH is
urea nitrogen; albumin and leukocytes are not removed. [265 ] [267 ] There does not
appear to be significant complement activation by the capillary hemofilter, [265 ] and the
risk of bleeding can be reduced by titrating heparin into the arterial (inflow) side of the
circuit to minimize its systemic effect. The principal advantage of hemofiltration is a low
risk of cardiovascular complications because slow, continuous ultrafiltration produces a
more physiologic alteration of intravascular volume. A mean arterial pressure greater
than 70 mmHg is all that is required for adequate filtration, and the circuit can be
connected to that of a ventricular assist device to augment fluid removal in these critical
patients. [268 ] The major disadvantages of CAVH are the requirement for vascular
access and its unpredictable effect on plasma drug levels.
Conventional hemodialysis is rarely used in the immediate postoperative period

because it requires anticoagulation and can induce hemodynamic instability. Patients
with an ongoing requirement for dialysis are converted from continuous ultrafiltration to
the more efficient hemodialysis when their cardiopulmonary status is stable.
Renal Failure: Prognosis
Despite all supportive measures available today, the prognosis for patients with
established acute renal failure after CPB remains poor. Survival is 90 percent in
patients who maintain nonoliguric renal insufficiency, [269 ] but those who progress to
oliguric renal failure have a mortality over 50 percent. [269 ] [271 ] Most patients who
develop acute renal failure have sustained hypotension during the perioperative period
and develop failure of several organ systems. Infection becomes a common terminal
event in patients who die with renal failure. Age is a significant prognostic factor in
determining survival from acute renal failure after heart surgery, [269 ] although Lange et
al. [271 ] did not find age, sex, preoperative renal dysfunction, severity of underlying
heart disease, cardiopulmonary bypass time, or oliguria to be significant influences in a
univariate analysis of patients who required hemodialysis after heart surgery. They did
find that the number and types of complications were significant predictors of outcome;
the highest mortality rate was associated with respiratory failure, central nervous system
dysfunction, persistent hypotension, and infection. Bhat et al. [270 ] noted a marked
increase in mortality in patients whose serum creatinine rose higher than 6 mg/dL.
The best survival occurs in patients who can be maintained in nonoliguric renal failure.
Early dialysis and nutritional support in patients with oliguric failure minimize metabolic
complications, but the prognosis remains poor because of late septic complications.
Although many recover renal function after a brief period (days to weeks) of oliguria, the
incidence of chronic dialysis dependency in these patients is significant.
NERVOUS SYSTEM
Postoperative neurologic dysfunction occurs with disturbing frequency. This group of

complications can be divided into three categories: central neurologic,
neuropsychologic, and peripheral neurologic. Because of differences in definitions, in
tests to measure deficits, and in the diligence of postoperative examinations and
testing, the medical literature is inconclusive.
Central Neurologic Complications
Cerebrovascular accidents (CVAs) that result in lasting deficits occur after heart
operations in 2 to 5 percent of patients. [272 ] [274 ] These may appear after recovery
from anesthesia but usually are obvious when the patient awakens. Perioperative
strokes kill one-eighth of all patients afflicted. [275 ]
After a stroke, a computed tomographic (CT) scan demonstrates the cerebral infarction
within a day or two. However, no treatment exists, and accordingly, there is little need to
document cerebral damage early if the patient is hemodynamically unstable. However,
in the comatose patient, other causes may be present and may be treatable; therefore,
a CT scan should be performed as soon as possible.
Although carotid artery disease does not appear to be a major factor for stroke in
patients without preoperative neurologic symptoms , [273 ] , [276 ] , [277 ] we are wary
of performing cardiac operations in the presence of critical (> 75 percent stenosis) and
bilateral carotid stenoses without prior or concomitant carotid endarterectomy.
Symptomatic carotid stenoses increase the risk of stroke and usually require
prophylactic or concomitant carotid endarterectomy.
Perioperative strokes have multiple causes. Operations performed at normothermia

have a higher incidence of CVA than those performed at moderate (28 to 32°C)
hypothermia. [278 ] Open-heart operations may cause cerebral embolic infarction from
air boluses, intracardiac clot, calcified debris, or foreign material (such as felt pledgets).
However, the most probable cause of most strokes is atheromatous emboli from the
ascending aorta and aortic arch. Increasing age, incidence of aortic atheroma,
incidence of peripheral embolization (in autopsy series), and incidence of CVA are
closely correlated. [272 ] , [274 ] , [275 ] , [279 ] If aortic atheroma are documented by
echocardiography in older patients, operation is tailored to reduce aortic manipulation
and embolization. [274 ] Some authors find a correlation between low perfusion
pressure (50 to 60 mmHg) during CPB and CVA and recommend higher perfusion
pressures (between 80 and 100 mmHg). [280 ]
Neuropsychological Complications
A large number of symptoms fall into this category and range from alterations of mood,
to bizarre behavior, to quantifiable deficits in intellectual function. Postoperative
depression occurs commonly, may last 2 to 3 months, and may be sufficiently severe to
disrupt families and, rarely, cause patients to become suicidal. Usually, mild symptoms
of depression disappear spontaneously and require no treatment other than
reassurance. Early postoperative delirium follows a lucid period and presents as
paranoia or hallucinations. Together with depression, these disorders occur in about 40
percent of patients. [281 ] The reported incidence of delirium varies widely from 7 to 57
percent of cardiac surgical patients. [282 ] , [283 ] Delirium usually disappears within 1
week; patient management is facilitated by small doses of haloperidol.
In some studies, deficits in intellectual function such as memory and cognition occur in
as many as 75 percent of patients in the early postoperative period, decline to half that
number by 8 weeks, and decline minimally over the next year. [284 ] [287 ] Others,
however, report little change between preoperative and postoperative assessments of
intellectual function. [288 ] , [289 ] The changes seem to be caused by cerebral
microemboli and correlate with the duration of CPB. [273 ] , [284 ] [287 ] , [289 ]
Membrane oxygenators as compared with bubble oxygenators reduce the production of
microemboli. [290 ] The incidence of transcranially detected microemboli correlates
with both stroke and behavioral change, as well as with cardiac and pulmonary
complications and mortality. [291 ] These neurologic changes also correlate with new
cerebral abnormalities detected by magnetic resonance imaging. [292 ] Increasing age
also predicts neuropsychologic deficits. [285 ] , [289 ]
Peripheral Deficits
Intraoperative femoral arterial bleeding (usually from a recent cardiac catheterization)

can compress the femoral nerve. Foot drop can occur from pressure on the perineal
nerve as it wraps around the fibula. This complication of leg positioning for saphenous
vein harvesting can be prevented by proper padding or use of a cushion designed to
protect the nerve.
Upper extremity deficits are more common and are related to the median sternotomy.
[293 ] [296 ] The incidence increases with wide retraction or placement of the retractor.
[293 ] , [294 ] Upper extremity deficits produce sensory deficits in the fourth and fifth
fingers and usually disappear within 2 to 3 months. In severe cases, deficits involve a
wider area, result in permanent sensory and motor deficits, and can lead to sympathetic
dystrophy. These injuries are not completely preventable. In mild forms, sensory deficits
occur in as many as 24 percent of patients [294 ] and are caused by brachial plexus
injury from a first rib fracture or from the plexus stretching over an intact first rib. Nerves
C8 and T1 are damaged most commonly.
Injuries of the nerves around the elbow-especially the ulnar nerve-may be confused with
brachial plexus injuries. Proper padding prevents these cubital nerve injuries.
GASTROINTESTINAL SYSTEM
Major gastrointestinal complications occur more frequently after cardiac operations than
after noncardiac, nonintestinal surgery. The incidence is reported from 0.5 to 3 percent.
[297 ] [300 ] Decreased visceral blood flow occurring during episodes of hypotension
contributes to such complications. [301 ] [303 ] Pancreatitis, mesenteric ischemia,
gastroduodenal ulceration and inflammation, cholecystitis, and hepatic failure have all
been attributed to hypotension, shock, or cardiopulmonary bypass. [301 ] , [304 ] [309 ]
The most common major complications are upper gastrointestinal (GI) bleeding from
gastritis or ulcer disease, pancreatitis, hollow viscus perforation, mesenteric ischemia,
and cholecystitis. [298 ] [301 ] , [309 ] [311 ] In aggregate, these complications have a
frighteningly high mortality between 20 and 70 percent; mesenteric ischemia is nearly
always fatal. [300 ] , [305 ]
Risk factors for these complications include older age, perioperative hypoperfusion,
emergency operation, longer CPB times, need for high-dose vasopressors and
intraaortic balloons, and valve operations. [297 ] , [300 ] , [301 ] , [309 ] More than 800
mg of calcium chloride per square meter of body surface area is an independent risk
factor for pancreatitis. [308 ]
An elevated amylase level postoperatively occurs far more often than does clinical
pancreatitis. About 30 percent of patients develop an elevated amylase level
postoperatively, but only 10 percent have an increased lipase or pancreatic amylase
level; 20 percent have a nonpancreatic source for the increased amylase. [312 ] Only
0.04 to 1 percent of patients develop severe pancreatitis. [308 ] , [310 ]
Treatment and diagnosis must be pursued vigorously for all these complications,
without regard to the recent heart operation. Delayed diagnosis may initiate a chain
reaction that culminates in multiorgan failure.
Careful clinical assessment and physical examination raise the possibility of GI disease
and indicate the need for specific tests. Mesenteric ischemia can only be diagnosed by
looking directly at the bowel, but an elevated serum lactate level indicates the
possibility. An elevated amylase level is nonspecific but may suggest the possibility of
pancreatitis. Pancreatic ultrasound or CT scan demonstrates edema or fluid collection.
Hollow viscus perforation usually produces free peritoneal air (which should not be
confused with air introduced during a median sternotomy incision that extended too far
caudally). An ultrasound or HIDA (radionuclide) scan supports the diagnosis of
cholecystitis. GI bleeding requires endoscopy.
Anticoagulants are stopped temporarily for patients with GI bleeding who are on
prophylactic anticoagulants for prosthetic valves, thrombophlebitis, pulmonary
embolism, or atrial fibrillation. The severity of bleeding must be weighed against the
danger from discontinuing the anticoagulant. When the danger of prolonged stoppage
is unacceptable, early operation is performed to arrest the bleeding. Tissue valves are
preferred for patients at high risk for postoperative upper GI bleeding.
Pancreatitis is usually treated with nasogastric tube decompression and antibiotics.

When severe, it may require laparotomy and drainage.
Mesenteric ischemia is treated at the diagnostic laparotomy. Dead bowel is resected;

marginal bowel may be left in situ, with a second look operation performed for
reassessment.
Ulcer or bowel perforation requires operative treatment. Cholecystitis may be treated by

cholecystotomy if the patient cannot withstand cholecystectomy. With acalculous
cholecystitis or possible gallbladder gangrene, resection is indicated. Sometimes this
can be done by laparoscopy.
Minor GI complications are more frequent than major complications. Mild postoperative
ileus is common and is best treated by extending the duration of nasogastric tube
suction. Forcing oral intake while ileus persists only lengthens hospitalization. Diarrhea
suggests Clostridium difficile enteritis. A stool swab for fecal leukocytes and
enterotoxin secures the diagnosis. Treatment requires specific antibiotics
(metronidazole or oral vancomycin) and, when necessary, nutritional support.
PROPHYLACTIC ANTIBIOTICS
Operations performed using cardiopulmonary bypass cause major derangements of

multiple body systems and of the mediators of inflammation. Immunocompromise
seems to be one of the derangements; the incidence of infection without prophylactic
antibiotics is as high as 50 percent. Prophylactic antibiotics reduce this rate
substantially. [313 ] To be effective, antibiotics must be circulating at the start of the
operation and must be maintained in an adequate concentration during the entire
operation. [314 ] [317 ] In the immediate postoperative period, antibiotic treatment
should be continued for 24 to 48 hours. Administration for longer periods of time affords
no better protection against infection. [314 ] [316 ] , [318 ] The choice of antibiotic
generally varies with recommendations of hospital epidemiologists or infectious
disease committees and varies among institutions.
Because of the lability of heart disease, all patients who have cardiac surgery undergo
additional risks related to anesthesia management. [1 ] [3 ] Skilled cardiac anesthesia
is essential for a successful operation, and much depends on the experience,
knowledge, preparations, and vigilance of the anesthesiologist. Anesthetic
management requires invasive procedures to assure monitoring and an unobstructed,
reliable airway and also demands complex pharmacologic support to control the
volatility of the circulation. A particularly vigilant and balanced anesthetic approach is
needed in patients who begin with depressed cardiac function to avoid detrimental
hemodynamics and subsequent complications. [4 ] , [5 ]
Timing Invasive Monitoring
Central venous and peripheral arterial catheters are invasive procedures that require
limited sedation at the time of insertion to avoid patient discomfort and stress. Most
contemporary anesthetic agents directly affect circulatory stability and cannot be used
without continuous monitoring of the electrocardiogram and central pressures. Induction
of anesthesia, therefore, is delayed until complete hemodynamic monitoring is
available. During insertion of catheters, reassuring words with the patient, sedation,
local anesthetics, and careful, expedient placement of invasive lines minimize
discomfort and hemodynamic lability until general anesthesia is induced. After induction
of anesthesia other monitors (e.g., temperature probes, Foley catheter) are placed, and
the patient is positioned and prepped.
The selection of monitors also is important in anticipation of possible intraoperative and

postoperative problems. If postoperative low cardiac output is a possibility or if the
operation is expected to be long and complex, a Swan-Ganz catheter with an oximetric
electrode is selected to monitor mixed venous oxygen saturation. A transesophageal
echocardiographic probe is placed in patients with poor left ventricular function or mitral
valve disease.
Airway
The first priority of anesthesia management is to obtain and maintain an adequate

airway to ensure adequate ventilation and oxygenation throughout the procedure.
Patients with cardiac disease are particularly sensitive to impaired ventilation and
oxygenation. [6 ] Although loss of airway control (dislodgement, kinking, obstruction
from secretions, etc.) may occur at any time, the highest risks occur at the time of
intubation and at extubation. [7 ] , [8 ]
Careful preoperative evaluation of the patient's anesthetic history and a physical

examination of the mouth, teeth, jaw, and upper airway assure early identification of
problems that might impede rapid endotracheal intubation. At the time of induction, 100
percent oxygen, a pulse oximeter to monitor peripheral arterial oxygenation, and rapidly
metabolized induction agents reduce the risk of a cardiac complication during a difficult
or failed intubation. Selected patients at risk for a difficult intubation may benefit from
local anesthetic blockade of the glossopharyngeal and superior laryngeal nerves,
intravenous sedation, and subsequent awake oral or nasotracheal intubation. [9 ] , [10 ]
Airway manipulation may produce a sympathetic response that increases heart rate
and blood pressure at the time of intubation. [11 ] , [12 ] Careful management and
adequate anesthesia prevent this problem. [13 ]
A pediatric fiberoptic bronchscope may aid a difficult intubation or assure the proper
location of the endotracheal tube. If apnea exceeds 3060 seconds or if peripheral
oxygen saturation falls below 85 percent, an oral airway should be inserted and mask
ventilation given manually until adequate oxygenation is restored. Control of the airway
should never be lost. Airway obstruction caused by stricture, tumor, or unusual anatomy
may require more invasive means to establish a reliable airway; however, these
patients are exceedingly rare in the practice of cardiac surgery. An algorithm for
establishing an airway without serious complication is presented in Figure 13-1 .
Simple auscultation, observation of chest wall movements, and monitoring oxygen
saturation and end-tidal co 2 confirm the correct position and function of the
endotracheal tube. [14 ] Postoperatively, the position of the endotracheal tube can be
determined by chest X-ray. Proper insertion, location, and fixation of the endotracheal
tube reduce the chance of intraoperative dislodgement, single lung ventilation, and
vocal cord damage secondary to cuff insufflation at the laryngeal level.
Careful handling of the laryngoscope and endotracheal tube minimizes the risk of injury
to the oropharynx, larynx, and tracheal-bronchial tree. Insertion and manipulation of the
laryngoscope, particularly in patients with difficult airways, always are done under direct
vision. If used improperly, the laryngoscope may injure the tongue, dentition, or posterior
pharynx. More commonly, the larynx is injured by the tip of the endotracheal tube. [10 ] ,
[15 ] An appropriately sized tube placed carefully under direct vision minimizes direct
cord injury. Cord swelling and dysfunction usually follow prolonged intubation but may
occur after overnight intubation. [8 ] , [16 ] Therefore foods and fluids are limited for 46
hours after extubation to assure that the airway can be protected. The risk of tracheal
and bronchial injury associated with intubation is quite small. Soft pressure cuffs have
significantly decreased the risk of local ischemia and subsequent stenosis of the
trachea.
Finally, the risk of gastroesophageal reflux and its consequences always must be
recognized. Improvements in the medical management of gastric acid secretion reduce
the risk of perioperative aspiration of gastric contents, but a temporary nasogastric tube
is the most effective means of prevention. [17 ] [19 ]
Anesthetic Agents
The cardiovascular effects of anesthetic induction are most commonly manifested by

hypotension and brady- and/or tachyarrhythmias, and both may have profound effects
on the diseased heart. [10 ] , [20 ] [22 ] Hemodynamic changes associated with
anesthetic agents are attributed to both depression of myocardial function and changes
in peripheral vascular tone. Agents that alter preload, afterload, and myocardial inotropy
and chronotropy must be used carefully with direct hemodynamic monitoring to assure
early recognition and prompt counteractive measures. A more detailed discussion of
anesthetic agents for cardiac surgical anesthesia is provided in Chapter 7.
Allergic Reactions
Allergic reactions to anesthetic agents are uncommon, but cardiac patients

occasionally develop allergic reactions to antibiotics, the heparin-protamine complex,
aprotinin, and rarely other drugs during and immediately after cardiac operations. [23 ]
[28 ] A careful and thorough allergic history is an essential part of the admission
work-up, and drugs to which the patient is allergic should be prominently displayed in
the hospital chart and on order sheets. Overdoses, side effects, toxic effects, and drug
interactions are more common causes of drug-related complications. Since these
adverse drug reactions are too numerous to list and remember, some
not-too-uncommon examples serve to emphasize their importance. Intravenous
potassium can cause cardiac conduction disturbances and asystole and, therefore,
must be carefully monitored and given slowly. Overdoses of lidocaine and other local
anesthetics may cause convulsions. Acetyl cholinesterase inhibitors may produce
hyperkalemia in patients with impaired renal function. Procainamide and other
antiarrhythmics that slow conduction may cause torsade de pointes. A sound working
knowledge of drugs that are commonly used in the care of cardiac surgical patients is
the best protection against overdosage, toxic effects, and adverse drug interactions.
Drugs commonly used in cardiac surgery and postoperatively are presented in
Chapters 7, 8, and 25.
Monitors
Peripheral arterial and central venous catheters, chest and mediastinal tubes, the
intra-aortic balloon pump, and temporary pacemaker leads are part of open heart
surgery; yet each of these monitors involves a risk of complications.
ARTERIAL CATHETERS
Radial and femoral arteries are most commonly cannulated for pressure monitoring and
arterial blood samples. The most common problems with radial arterial cannulation
involve infection, embolization, and hand ischemia. [29 ] [31 ] Radial arterial cannulas
are inserted as atraumatically as possible, with minimal injury to the cannulation site and
avoidance of hematoma. The cannula tip should advance easily to avoid injury to the
arterial wall. The arterial waveform provides evidence of an intraluminal position. The
cannula site should receive daily dressing changes and local cleansing and care.
Bacteremia and septicemia from a radial cannula are rare, but superficial infections at
the cannulation site may approach 10 percent. With good local care, radial arterial
cannulas can be used for extended periods with minimal risk of systemic infection. [32 ]
Slogoff et al. reported evidence of early radial arterial thrombosis in 25 percent of 1,699
patients, but none developed permanent injury or required interventional treatment. [31 ]
Nevertheless, sporadic case reports describe devastating injuries associated with
radial arterial cannulation. [33 ] Removing the cannula successfully reverses ischemic
symptoms or embolization to the hand in most instances. Occasional patients with
recalcitrant symptoms may require chemical sympathectomy of the arm or local
vascular surgery, but the rarity of these patients precludes any estimation of the efficacy
of these remedies. [29 ] [31 ]
The time-honored Allen's test and duplex scanning of the artery are ineffective for
predicting ischemic injury from radial arterial cannulation, and no association has been
demonstrated between peripheral vascular disease and radial arterial complications.
Only patients with documented CREST variant of scleroderma are known to have an
increased risk for ischemic injury. [30 ]
The incidence of femoral arterial injuries from cannulation is estimated at less than 1
percent. Complications include bleeding, false aneurysm, arterial venous fistula, and
injury to the femoral nerve. Early removal of femoral arterial catheters with conversion to
the radial artery facilitates ambulation and reduces the risk of local or systemic infection
and distal emboli. [34 ] [36 ]
CENTRAL VENOUS CATHETERS
Central venous catheters usually are inserted via the jugular or subclavian vein; the
femoral vein is used only as a last resort. Puncture of both the jugular and subclavian
veins involves risks of complications. With jugular vein puncture, the risk of
pneumothorax is approximately 1 percent, but because the risk is low the diagnosis is
often delayed. [37 ] , [38 ] Puncture of the carotid artery usually produces arterial,
pulsatile back bleeding, but if the needle is against the wall, this safeguard may be
absent. The incidence of carotid artery injury is estimated at 4 percent. [38 ] With
subclavian venous puncture, the risk of pneumothorax increases to 4 percent, but it may
be lower with experienced operators. [37 ] , [39 ] [41 ] The incidence of major bleeding
from subclavian punctures is less than 1 percent, and the vein is the most common
source of bleeding after insertion of catheters, dilators, and even guidewires. [37 ] , [42 ]
If subclavian artery penetration is suspected, measurement of pressure may rule the
injury in or out; pressure below the clavicle against both subclavian vessels is
recommended to control bleeding. [39 ] , [42 ] An upright chest X-ray may indicate
bleeding by showing depression of the apical parietal pleura. If injury occurs, the
catheter should be removed and compression held at the site of vascular injury. A
catheter should be placed at a distant site, and unless bleeding is poorly controlled, the
operation may continue despite the need for systemic heparinization.
Suspicion of an arterial or bleeding venous injury should be investigated in the

operating room. Pneumothorax may be apparent on opening the chest. Unexplained
volume loss should prompt exploration of the pleural cavity and search for a bleeding
site. If found, the site should be controlled by appropriate sutures as soon as feasible.
More often blood loss is not discovered until weaning from cardiopulmonary bypass
when reexpansion of the lung suggests fluid in the ipsilateral chest. The postoperative
chest film always should be inspected for evidence of subclavian, jugular, or carotid
injury and hematoma at the root of the neck. [43 ]
Infection is the most common complication of central venous catheters. If they are left in
place only a few days, infection is rare. However, if catheters are maintained for longer
periods, changing over a wire is recommended every 35 days along with local site care.
If bacteremia or septicemia occurs and a central venous catheter is required, puncture
of a new site is recommended. Prudent catheter care and early removal are particularly
important for patients with implanted prostheses, such as valves, grafts, or transplants.
[37 ]
Air embolism from central venous catheters is rare but may occur if stopcocks are left
open or if the catheter is removed with the patient in an upright position. Hypovolemic,
spontaneously breathing patients are most susceptible to air embolism because of low
central venous pressure and cyclic negative intrathoracic pressures. Catheter air
embolism usually is successfully treated by observation, but on occasion is
catastrophic. It is best prevented. [37 ] , [44 ]
PULMONARY ARTERIAL MONITORING
Pulmonary arterial catheters provide invaluable information regarding central venous

and pulmonary arterial pressures, thermodilution, continuous cardiac output, or
continuous mixed venous oxygen saturation, and estimations of left atrial diastolic
pressure. However, pulmonary arterial catheters are associated with a risk of
complications in 0.050.2 percent of cardiac surgical patients. [45 ] , [46 ] The most
significant risks involve injury to valves, ventricular arrhythmias, and ventricular or
pulmonary arterial rupture. [47 ] , [48 ]
Insertion of a pulmonary catheter via the jugular or other vein should be done with
electrocardiographic and systemic arterial pressure monitoring. During insertion the
pressure at the tip of the pulmonary arterial catheter also is monitored. Placement is
aided by a balloon near the tip of the catheter. This balloon should not be overinflated,
and the catheter should not be pulled back with the balloon inflated because of possible
pulmonary or tricuspid valve injury. Passage of the catheter through the right ventricle
may produce arrhythmias that usually subside when the catheter is withdrawn.
Lidocaine or other intravenous antiarrhythmic agents may facilitate catheter passage
through the right ventricle in hypersensitive individuals.
The incidence of ventricular rupture is small and rarely causes sufficient intrapericardial
bleeding to produce tamponade. When ventricular rupture occurs, usually only a small
amount of intrapericardial blood is discovered when the heart is exposed, and often a
ventricular bleeding site cannot be located. An active bleeding site is obviously sutured
closed.
Pulmonary arterial rupture is the most serious complication, and cardiac surgical
patients are at higher risk because the catheter tip may move during manipulation of the
heart or with changes in temperature. [45 ] , [46 ] , [49 ] , [50 ] Advanced age, pulmonary
hypertension, female gender, and hypothermia are factors associated with an
increased risk of pulmonary arterial rupture. The wedge position of the catheter also
increases the risk of rupture and, if used, wedge pressures should be checked
intermittently to be sure the tip has not moved and that blood can be withdrawn. This is
particularly important after transfer to the intensive care unit when the patient's
temperature returns to normal. [46 ] , [47 ] , [50 ] If a wedge pressure is obtained without
balloon inflation, the catheter should be repositioned.
Pulmonary arterial rupture most commonly is associated with hemoptysis, impaired

oxygenation, and intrathoracic hemorrhage. If an injury is suspected before operation,
end-expiratory pressure is increased to 10 mmHg and an intraoperative chest film
obtained to determine the location of the catheter tip. Bronchoscopy is done to locate
the source of any bleeding, and if bleeding is found, the lung segment is isolated from
the rest of the lung by a balloon tip angioplasty catheter. [47 ] , [51 ] If the amount of
bleeding precludes lateralization of the source, the chest film indicates the main
bronchus to block to prevent drowning the uninvolved lung. Only the nonbleeding lung is
ventilated. A chest tube is inserted into the hemothorax of the bleeding lung. If the
patient is stabilized and bleeding is controlled adequately, the patient is transferred to
the intensive care unit without operation for careful monitoring. Coughing, straining, and
endotracheal tube suctioning are avoided for at least 48 hours as delayed bleeding is
not uncommon. [46 ]
Patients with persistent bleeding require surgical exploration via median sternotomy
that allows adequate exposure of both pleural cavities. The position of the pulmonary
arterial catheter is determined or confirmed by digital palpation. An engorged
pulmonary segment or torn visceral pleural membrane are indications for
segmentectomy or lobectomy. Planned cardiac surgery is delayed. [46 ] , [49 ]
Patients with suspected pulmonary arterial rupture during and after weaning from
cardiopulmonary bypass require a different approach. Usually the injury presents as
unexpected airway bleeding that may be massive. First bypass is resumed, and
bronchoscopy is done to locate the bleeding and to isolate the bleeding bronchus or
lung. The affected lung is exposed, and the algorithm outlined in Figure 13-2 is followed.
[46 ]
In the intensive care unit pulmonary arterial rupture usually presents with hemoptysis but
may not be recognized immediately. Initial management is conservative with
bronchoscopy, isolation of the bleeding airway, and placement of a chest tube in the
ipsilateral hemothorax. If bleeding persists or if ventilation is compromised, operation
may be needed for control. [46 ] , [51 ] When the lesion is suspected, a chest X-ray is
obtained to determine the side of the injury.
Mortality from pulmonary arterial catheter rupture reaches 41 percent and is particularly
high in debilitated cardiac patients and those with pulmonary hypertension. [46 ] , [52 ] ,
[53 ] Prevention is the most prudent policy. During cardiopulmonary bypass the
pulmonary arterial catheter is often withdrawn to the superior vena cava as it is easily
advanced again after bypass ends. Pulmonary arterial diastolic pressures frequently
can substitute for pulmonary wedge pressures, with a significant reduction in the risk of
rupture.
NONSPECIFIC COMPLICATIONS
Thoracostomy Tubes
Potential complications of thoracostomy tubes placed after or during operation include

intercostal arterial bleeding, bleeding from the superior epigastric artery from a deep
skin incision, disturbance of epicardial pacemaker leads, and rarely, intra-abdominal
injury. [54 ] , [55 ] Thoracostomy tubes may also cause postoperative pain that
disappears with removal of the tube. Intercostal or superior epigastric arterial bleeding
is controlled by cautery or occasionally a deep suture, and the absence of bleeding at
chest tube sites should be confirmed before the chest is closed. [56 ] Rarely persistent
bleeding from the site of a thoracostomy tube may be found owing to an intra-abdominal
injury. [57 ]
Removing chest tubes may allow air to enter the chest if not done properly. A previously
placed U stitch, an occlusive dressing, and removal during exhalation prevent air entry.
Fracture of a chest tube is very rare; if a segment remains in the chest, it should be
removed by thoracoscopy.
Temporary Epicardial Pacemaker Leads
Temporary epicardial pacemaker leads are routinely left to facilitate control of

postoperative arrhythmias after nearly every cardiac operation. The most common
problem is failure to function when needed owing to poor sensing or capture and
dislodgement. Occasionally metabolic and acid/base abnormalities impede capture,
but mechanical causes are most common. [58 ] , [59 ] Placement of the leads
approximately 2 cm apart and into a superficial layer of myocardium assures proper
sensing and capture if the leads remain intact. Separation by large distances
sometimes interferes with sensing because the leads act as an antenna. [58 ] Failure to
capture postoperatively initially is treated by reversing polarity; if this fails, extension
cables and the pacemaker generator are replaced. If failure to capture persists and the
patient's circulation is unstable, a transvenous or transcutaneous lead is needed
promptly. [58 ]
The reported incidence of major complications of epicardial pacemaker leads is

approximately 0.4 percent. [58 ] Bleeding can occur during insertion or at the time of
removal. Deep bites into the myocardium enhance bleeding, particularly at the time of
removal. Ventricular leads preferably are placed superficially in the longitudinal axis of
the ventricle. At least one atrial lead is placed within the ligature closing an atriotomy to
reduce the chance of bleeding. Placement of leads prior to administration of protamine
is recommended to reduce the likelihood of overlooking myocardial bleeding before
chest closure. [58 ] Bleeding may also occur from spearing an upper abdominal wall
vessel during exteriorization of the leads.
Removal of temporary pacing wires may cause lacerations of the atrium or ventricle,
injury to nearby coronary bypass grafts, and even strangulation of the heart by a
surrounding loop of wire. [60 ] Bleeding significant enough to cause pericardial
tamponade and require emergency thoracotomy may occur at the time of wire removal,
particularly in anticoagulated patients.
Pacemaker wires are removed with the patient supine by gentle traction after cutaneous
securing sutures are cut. [61 ] Patients remain at bedrest for a least 30 minutes
afterwards, and vital signs are monitored. Whenever possible, leads are removed
before the patient is fully anticoagulated and are not removed until coagulation times
above the therapeutic range are returned to the targeted range. Excessive pull on lead
wires is painful, may cause serious damage, and should be avoided. Preferably wires
which are difficult to remove should be sterilized with betadine or alcohol at the skin,
gently pulled and cut off at the skin with sterile scissors. The retained wire rarely causes
subsequent problems.
Great Vessel and Thoracic Duct Injuries
VENA CAVA AND LEFT INNOMINATE VEIN
Either the left innominate vein or the junction of the innominate vein with the subclavian
and jugular to form the superior vena cava can be injured during median sternotomy,
particularly in patients who have had previous operation through this incision. The injury
most often occurs when the sternal retractor is opened without first freeing the
innominate vein from the overlying chest wall. The incidence of the injury is not known
since this complication rarely is reported. The injury may produce dramatic bleeding
that may require accelerated administration of heparin and institution of
cardiopulmonary bypass by femoral cannulation.
If the injury to the left innominate vein is distant from the superior vena cava, the vessel
can be ligated with little concern since collateral channels usually are sufficient to relieve
elevated venous pressures. If, however, left jugular and subclavian venous pressures
are elevated above 25 mmHg, reconstruction of the injured left innominate vein should
be considered and undertaken if possible. [62 ]
If the innominate vein is separated from the superior cava at its junction, usually repair is
needed to prevent upper body venous hypertension. If measured pressures in the left
jugular and subclavian veins are below 25 mmHg, ligation and permanent separation
are an option. If repair is needed, a patch of saphenous vein or pericardium is used to
avoid tension on the suture line even after the vessels are freed from the chest wall and
surrounding tissues. [62 ]
Direct injuries to the superior or inferior vena cava occasionally occur during dissection
of the heart for cannulation or from insertion of a cannula. Usually tears in the superior
vena cava are easily repaired because exposure is good. Tears at the diaphragmatic
inferior vena cava are more difficult, particularly if the posterior or medial cava is torn. In
such cases a cannula should be passed into the inferior cava beyond the tear if
possible to reduce bleeding and sustain life. Insertion of a femoral venous catheter is
done to permit temporary occlusion of the diaphragmatic cava while a repair using
saphenous vein or pericardium is made.
PULMONARY VESSELS
Direct injuries to the proximal pulmonary arteries or veins during repeat cardiac
operations are not common but do occur. In most instances these can be sutured
closed easily by occluding bleeding by forceps, Allyce clamps, or finger and suturing. If
the site of injury is not exposed easily, cardiopulmonary bypass is started to reduce
bleeding. The artery is repaired either directly or, occasionally, with a pericardial patch
during bypass using 5-0 prolene suture. Veins are repaired directly.
AORTIC FALSE AND MYCOTIC ANEURYSMS
Although endocarditis involving the aortic valve may produce a mycotic aneurysm of the
aortic root, surgical incisions into the ascending aorta that for any reason leak or
become infected produce a sterile false or mycotic aortic aneurysm. [63 ] The incidence
of this serious complication is less than 0.8 percent, but the problem may account for up
to 3 percent of late deaths after cardiac surgery. [64 ] The wall of the false or mycotic
aneurysm is formed by fibrous tissue and does not contain tissue from the aorta.
Although thrombus may be present within the lumen of the aneurysm, unclotted blood
also is present and communicates with the true aortic lumen through an opening that
may be narrow but often is quite large. Typically the false or mycotic aneurysm extends
to the anterior chest wall by the time it is recognized.
Pseudo or mycotic aortic aneurysms usually present late, but the interval after the
original operation in which the aorta was incised ranges from 1 month to 9 years. Chest
pain; venous obstruction; dysphagia; hoarseness; stridor; an enlarging, palpable,
pulsatile mass in the sternal notch, high interspace, or the root of the neck; or
myocardial ischemia from compression of bypass grafts direct attention to the problem.
Occasionally aortic false aneurysms are asymptomatic and are detected by discovering
a widened mediastinum or mediastinal mass on chest X-ray.
If infection is present, the patient may have fever, lethargy, anorexia, anemia, and
leukocytosis in addition to other symptoms and signs. [65 ] Infection may develop from a
mediastinal infection or from septicemia. The most-common infecting organisms are
Staphylococcus aureus and S. epidermidis and various streptococci. Sustained
bacteremia over several weeks after cardiac surgery warrants further investigation for
possible mycotic false aneurysm.
The aneurysm may be imaged by transthoracic echocardiography (TTE), computerized

axial tomography (CT scan), magnetic resonance imaging (MRI), and aortography. [64 ]
, [66 ] The mass must be differentiated from mediastinal abscess, postoperative
hematoma, or an unrelated neoplasm. The initial examination is usually with TTE and
color flow Doppler velocity mapping to establish the presence of an aneurysm. [67 ] MRI
has the advantage over CT scan in that fluid and clotted blood are distinguished easily
and good images of the neck of the aneurysm usually are obtained. Both CT scans and
MRI identify the size, anatomic location, and structures adjacent to the aneurysm
satisfactorily and generally provide more information than aortography.
The presence of pseudo or mycotic aortic aneurysms is an indication for prompt

operation because of the possibility of rupture. Often these aneurysms abut against the
anterior chest wall beneath the sternotomy incision; therefore, femoral vessels are
cannulated for partial cardiopulmonary bypass before the sternum is opened. If the
femoral venous catheter reaches the right atrium, nearly the entire venous inflow can be
diverted into the extracorporeal perfusion system. Most commonly the patient also is
cooled to 20°C or less so that a short period of circulatory arrest can be used to open
the aneurysm, locate the true and false lumens, and differentiate the edges of the neck.
Alternatively in uninfected patients with small diameter communications a balloon
catheter can be inserted into the distal aorta to control back bleeding while the
aneurysm is repaired. A patch of bovine pericardium or synthetic material is used to
close the opening into the false aneurysm so that the true aortic lumen is not
compromised.
If the aneurysm is infected, all infected prosthetic material and necrotic, inflamed host
tissue must be excised, and all abscesses must be discovered and completely drained.
[65 ] , [68 ] After debridement the surgical field is thoroughly irrigated with antiseptic
solution. The aorta is reconstructed using synthetic material or bovine pericardium.
Sometimes the new patch is covered with transposed omentum to further reduce the
risk of continuing infection. Intravenous antibiotics, started before operation, are
continued afterwards but may be changed according to organisms cultured from the
surgical field. Approximately 7080 percent of patients treated for mycotic false
aneurysms of the ascending aorta survive. [65 ] , [68 ] Without infection, mortality is
approximately 10 percent. [64 ]
AORTIC DISSECTION
Mechanical injury to the aortic intima from incision, cannulation, clamp compression, or
torsion may produce an aortic dissection. [69 ] [71 ] Femoral or iliac artery cannulation
without a wire guide or incomplete incision of the intima during aortic cannulation may
create an intimal flap that initiates a dissection when cardiopulmonary bypass starts.
For this reason it is important to test for pulsatile backflow after every arterial
cannulation using large bore cannulas. Dissections also begin at intimal tears produced
by the aortic cross-clamp or the heel of a side-biting clamp, at the sites of a proximal
aortic vein graft, or at a poorly closed aortotomy site. Patients who are predisposed to
dissection include those with congenital syndromes associated with an abnormal wall,
severe atherosclerosis or calcification, or post-stenotic aneurysmal dilatation and
thinning. The complication may also involve a normal aorta. [71 ]
The incidence of acute aortic dissection during or shortly after cardiac surgery ranges
from 0.03 to 0.35 percent. [71 ] The majority are identified in the operating room, and
prompt recognition is fundamental to successful management. [69 ] [71 ] Occasionally a
dissection is first identified by transesophageal echocardiography during femoral
cannulation or intra-aortic balloon insertion. Rarely, an intraoperative aortic dissection
may present several days after operation. Development of bluish discoloration beneath
the adventitia of an aortic segment is often the first sign of dissection. The tense
adventitia usually is not pulsatile because of cardiopulmonary bypass and is
distinguished from an intramural hematoma by the extent and location of the involved
aorta. If cardiopulmonary bypass is not satisfactorily established, it may be possible to
stop bypass and resume the native circulation to permit transesophageal
echocardiographic examination of the extent of the dissection. If the native circulation
cannot be resumed rapidly, the inflow cannula should be relocated rapidly to another
undissected site to establish an adequate circulation. The damage then is assessed by
direct inspection and echocardiography, and an operative plan to rectify the
complication and to complete the planned operation is formulated.
A localized dissection that involves a small segment of the aortic wall or less than 15
percent of the aortic circumference often may be treated by plication. Larger localized
dissections that involve less than 50 percent of the aortic circumference may be excised
with reconstitution of the aortic edges and closure using a Dacron or pericardial patch.
[72 ] , [73 ] The dissected layers are reunited as a sandwich between two stripes of
Teflon felt. More-extensive dissections are best treated by resection and graft
replacement of the proximal aorta. Usually iatrogenic dissections do not involve the
aortic root, coronary ostia, or aortic valve; therefore, composite grafts are rarely
necessary. The arch, however, may be involved and require partial or complete
replacement during deep hypothermia and circulatory arrest with or without retrograde
cerebral perfusion (Chapter 38). If the dissection is recognized after proximal coronary
bypass graft anastomoses are made, the segment of aorta containing the anastomoses
can be patched onto the ascending aortic graft. [72 ] , [73 ]
Early descriptions of this complication of cardiac surgery reported a mortality between

33 and 62 percent. More-recent experience reports a mortality of approximately 15
percent. [73 ] , [74 ] Measures to prevent iatrogenic acute aortic dissection include
cannulation over a guide wire, complete incision of the intimal layer for aortic
cannulation, application and removal of clamps during brief periods of reduced flow,
careful inclusion of all aortic layers in suture lines, and avoidance of multiple aortic
clamp applications. [71 ] , [75 ]
ATHEROSCLEROTIC AORTIC EMBOLI
Moderate or severe atheromatous disease of the ascending aorta may be present in

513 percent of patients who have open heart surgery. [76 ] , [77 ] The extent of the
disease is variable. Normal aorta or minimal atherosclerotic disease involves less than
3 mm of intimal thickening; moderate disease includes focal areas of intimal thickening
that exceed 3 mm; severe disease includes multiple or circumferential areas of
significant intimal thickening with pedunculated or mobile atheromatous plaque (Fig.
13-3) . [78 ] The consistency of the atheromatous material varies among severe,
porcelain calcification; ragged, diffuse solid atheromatous material; and yellow
semiliquid toothpaste material within the aortic wall. Unfortunately, gross inspection of
the outside of the aorta does not provide clues to the degree of atheromatous
involvement. However, the disease is most common in patients with symptomatic
disease of other major arteries, smoking, hypertension, and increasing age. [77 ] , [78 ]
Moderate or severe atheromatous disease of the ascending aorta may be a marker of
generalized atherosclerosis, and these patients are at increased risk of morbidity and
mortality. [77 ] [80 ]
Moderate and severe disease may be suggested by calcification of the ascending

aorta in the perioperative chest X-ray. The disease also is identified by intraoperative
epiaortic echocardiography using a hand-held probe within a sterile sleeve. [78 ] , [79 ]
These images can provide excellent maps of the areas of severe involvement of the
ascending aorta but do not image the aortic arch well. Transesophageal
echocardiography produces satisfactory images of the ascending aorta and part of the
arch but has a blind spot owing to the left main bronchus; nevertheless, this method is
convenient and does not delay operation. [81 ] Aortic atheromata may be demonstrated
by CT scanning and MRI, but these studies are seldom ordered because
echocardiography can be used during operation.
Aortic atheromata may cause stroke, coronary arterial emboli, or emboli to the kidneys,
gastrointestinal tract, or extremities. Once the problem is identified, operation is
modified according to the algorithm presented in Figure 13-4 . The aorta should not be
manipulated until dislodgement of atheromatous material can be controlled. Cannulation
and aortic cross-clamping are maneuvers that are associated with embolization. [76 ] ,
[78 ] , [80 ] , [82 ] The incidence of emboli in patients with severe disease is reported as
high as 58 percent. [77 ] Proper management of the problem substantially reduces the
morbidity and mortality of these emboli. [76 ] , [83 ]
If the ascending aorta cannot be cannulated safely, sometimes the medial surface of the
arch can be used with introduction of a long soft-tipped cannula that is advanced
beyond the left subclavian artery. Femoral cannulation may be necessary, but
retrograde perfusion may dislodge atheromata in the descending thoracic aorta into
cerebral and coronary vessels. If the aorta must be clamped because of severe aortic
insufficiency, the most-proximal aorta that is usually least diseased is used. In patients
with moderate disease, areas relatively free of disease may be selected for placement
of the aortic cross-clamp. If the distal aorta can be clamped, the ascending aorta can be
opened for removal of the atheromatous material, for excision of the most diseased
areas with patch closure, or for replacement with a tube graft. [78 ] , [79 ] , [83 ]
If the ascending aorta cannot be safely cross-clamped, deep hypothermia with a period
of circulatory arrest is advised. This is used with retrograde cerebroplegia, which
washes out embolic material from the cerebral vessels, and an open anastomosis of a
Dacron graft to the distal ascending aorta or proximal arch. An 8-mm Dacron graft sewn
to the side of the ascending aortic graft permits antegrade flow when perfusion is
restarted after the period of circulatory arrest. This prevents emboli from retrograde
perfusion via the femoral artery. [83 ]
In patients with generalized vascular disease or poor or absent peripheral pulses, no

attempt is made to introduce catheters into the descending thoracic aorta because of
the likely presence of atherotoma. Transesophageal echocardiography reliably
identifies descending thoracic aortic atherotoma, and inspection prior to femoral
insertion of the intraaortic balloon pump is recommended to avoid trash emboli to the
lower extremities, gastrointestinal tract, and kidneys.
THORACIC DUCT
Thoracic duct injuries during cardiac surgery are extremely rare in adults but are
uncommon but not rare in children. [84 ] [86 ] Branches of the thoracic duct infiltrate
thymic tissue that may be transected during exposure of the aorta. The complication is
recognized postoperatively by persistent, milky chest tube drainage that contains fat
globules, chylomicrons, triglyceride concentrations greater than 110 mg/dL, and a high
lymphocyte cell count. [87 ] Initial management is dietary; oral fats are limited to
medium-chain triglycerides supplemented by intravenous feedings. [87 ] , [88 ] The
majority of leaks close without surgery. Should surgery be necessary, injection of heavy
cream into a nasogastric tube may facilitate location of the leaks. [89 ]
Complications associated with cardiopulmonary bypass are presented in Chapter 9.
Pulmonary Embolism
The incidence of pulmonary embolism after open heart surgery ranges between 0.56
and approximately 2 percent. [90 ] , [91 ] Nearly half the patients develop deep vein
thrombosis of calf veins after myocardial revascularization, but nearly all are
asymptomatic, are equally distributed between the donor leg and the opposite, and are
only visible by duplex scanning. [92 ] The incidence of pulmonary embolism after
coronary arterial bypass operations is 3.2 percent; risk factors include prolonged
postoperative recovery, previous venous thromboembolism, obesity, and
hyperlipidemia. Interestingly, valve surgery is not associated with as high an incidence
of pulmonary embolism. [91 ] Hospital mortality in patients with pulmonary emboli
ranges between 19 and 34 percent. [90 ] , [91 ]
Wounds
STERNAL WIRES
Occasional patients, usually but not always thin individuals, complain of chronic pain in
the region of palpable sternal wires in the absence of inflammation or infection. Rare
patients present with a visible sternal wire protruding through the skin. In both instances
removal of the wire or all wires during brief general anesthesia using small skin
incisions over each wire relieves the problem. If pus is encountered, it is cultured, and a
search for a deep sternal wound infection is begun after the procedure. It is unwise to
extend the exploration without first obtaining a complete evaluation for deep infection.
STERILE WOUND DEHISCENCE
Sterile dehiscence of a median sternotomy may be owing to technical factors or to

inability of sternal wires to maintain edge approximation because the sternum is soft
and osteoporetic. [93 ] , [94 ] If soft sternum is recognized at the time of operation or
after dehiscence, closure may be reinforced using the Robicsek technique. [94 ] This
method weaves a heavy wire vertically around the costal sternal junction of each rib by
passing the wire anterior to posterior to anterior up and down each side of the sternal
plate (Fig. 13-5) . Horizontal wires are placed around the vertical wires to approximate
the divided sternal edges.
Sterile sternal dehiscence usually develops within the first week or 10 days after
operation. Patients complain of pain and the sensation of movement, and sterile wound
drainage may exit the wound. Often instability can be palpated when the patient coughs
or moves. Drainage should be cultured and antibiotics given. The patient is returned to
the operating room promptly for exploration, irrigation, and reclosure of the entire
wound. These patients are at increased risk of a deep sternal infection or mediastinitis,
but the vast majority heal without infection.
SUPERFICIAL WOUND INFECTION
Superficial wound infections are defined as those that do not penetrate the
subcutaneous tissue layer. Approximately 1 percent of patients who have median
sternotomy develop a superficial wound infection, usually 79 days after operation. [95 ]
The wound may exhibit erythema and a small amount of drainage that contains bacteria.
The skin and subcutaneous layer are opened promptly and packed to allow secondary
wound closure. Antibiotics are not indicated, and extension to deeper layers is
uncommon unless treatment is delayed.
DEEP WOUND INFECTION
Deep sternal wound infections include acute mediastinitis with sternal dehiscence and
osteomyelitis of the sternum. The incidence of deep wound infections ranges 0.45
percent. [95 ] [98 ] Immunosuppressed patients who receive a heart or lung transplant
have a reported incidence of 3.4 percent. [96 ] Reexploration for bleeding and insulin
diabetes with simultaneous harvest of both mammary arteries also increase the
incidence of deep wound infection, but other putative risks factors including obesity,
transfusion, prolonged ventilatory support, emergency surgery, prolonged operation,
and renal insufficiency are no longer considered contributory. [96 ] , [99 ] [104 ]
The costs of deep wound infections are high, and every effort to reduce the incidence is
worthwhile. [93 ] These include strict observance of sterile technique, careful
hemostasis, operating room air filtration, reduced traffic in the operating room, and
periodic surveillance cultures.
Deep sternal wound infections arise from direct contamination of the wound, from the
bloodstream, or from direct extension of an adjacent infection. [96 ] Staphylococcal
organisms are the most common agents, but other organisms including pseudomonas,
enterobacter, serratia, acinetobacter, klebsiella, legionella, apergillus, and fungi have
been isolated from infected wounds. [96 ] [105 ] [108 ] Presenting symptoms and
findings include wound drainage, fever, sternal instability, excessive wound pain,
leukocytosis, and dehiscence. [95 ] , [97 ] , [98 ] Usually a deep wound infection
becomes apparent 24 weeks after operation, but a few may present months or years
later. [98 ] Any drainage from the wound should be cultured and the sensitivity of the
organism or organisms to antibiotics determined. Usually the plain chest X-ray is not
diagnostic and often does not suggest a deep infection.
A CT scan may show fluid or gas collections or inflammatory changes in part of the
sternum and rules in or out involvement of the aortic wall, cardiac chamber, or bypass
grafts. [108 ] Sternal wires somewhat impair interpretation of signs of sternal
inflammation and additional tests such as radionuclide scanning using Indium-labeled
[111 ] white cells may be needed. This test has a specificity of 95 percent. [109 ] The
clinical signs, CT scan, and location of wound drainage usually suffice for both the
diagnosis and localization of the infected tissues.
Appropriate antibiotics are given intravenously before and up to 4 or 6 weeks after the
wound is opened. Past therapy prescribed opening the wound, debriding necrotic
tissue, and allowing the open wound to granulate in with multiple daily packing. This
method was associated with a 25 percent rate of recurrence, prolonged hospital stays,
considerable patient discomfort, and significant mortality. [110 ] , [111 ] Rarely aortic or
coronary arterial bypass graft pseudoaneurysm or right ventricular rupture may develop
during or after open wound management. [112 ] [114 ]
If osteomyelitis is absent or is totally excised, exploration and debridement followed by

continuous irrigation and drainage of the reclosed wound may be an option. Both supra-
and infrasternal drains are used (Fig. 13-6) , and the wound is irrigated with dilute
povidine-iodine or Dakin's solution at 20110 mL/hr for 57 days or until the effluent
drainage is sterile. [115 ] , [116 ] The mediastinal drains are removed over a 48- to
72-hour period. This method is associated with recurrence rates up to 2 percent but is
less traumatic than the use of muscle flaps or omentum and nearly as efficacious. [117 ]
Additional advantages include a single operative procedure and early extubation and
ambulation. [115 ] [117 ]
An alternative method uses mobilized muscle flaps or omentum to sterilize and close
the infected wound (Fig. 13-7) . The wound is opened, debrided of necrotic tissue and
bone, and thoroughly irrigated. It then may be packed for 4 or 5 days to permit
granulation tissue to form. After that interval, the sternal edges are reapproximated, and
the sternum is covered by mobilizing both pectoralis muscles as flaps sewn over the
wound. If the wound is prepared for irrigation prior to closing the sternum, the muscle
flap procedure may be done immediately. [111 ] Occasionally a rectus muscle flap or
omentum is needed to cover the caudad portion of the wound. [118 ] , [119 ] Omentum
is useful for filling dead space beneath the sternum or for policing inflamed mediastinal
tissues but is associated with significant discomfort and temporary ileus.
The recurrence rate of muscle flap procedures is approximately 10 percent. The

most-common complication is bleeding beneath the flaps or dehiscence of the flap
suture line. Postoperative functional testing indicates minimal disruption of chest wall
mechanics and no significant impairment in breathing or activity. [120 ] The mortality
associated with deep wound infections ranges from 10 to 15 percent. [93 ] , [95 ] , [97 ] ,
[98 ]
COMPLICATIONS SPECIFIC TO ORGAN SYSTEMS
Heart and Pericardium
Postoperative complications involving the heart and pericardium are common after
cardiac surgery primarily because of arrhythmias, conduction disturbances, and
manifestations of ischemia. Prevention and control of these complications have had a
major role in the evolution of cardiac surgery and in the successful outcome of most
operations.
Supraventricular Arrythmias
Atrial arrhythymias, primarily atrial fibrillation or, less commonly, atrial fluttter, occur in
1040percent of patients after open cardiac surgery. [121 ] [123 ] The usual onset is 13
days after operation, with a peak incidence at 48 hours; however, the arrythymia may
occur at any time, including shortly after discharge. [121 ] , [123 ] Increasing age is the
most consistent predisposing factor; less-constant antecedent conditions include valve
surgery, history of rheumatic fever, duration of aortic cross-clamp time and
cardiopulmonary bypass, method of cardioplegia, and abrupt stoppage of -blocking
agents. Acidosis, hypokalemia, or hypoxemia may contribute to the onset of the
arrhythmia and should be corrected prior to initiating definitive therapy. [121 ] , [123 ]
[125 ]
In postoperative patients the diagnosis of atrial fibrillation or flutter is usually made from
the electrocardiographic monitor or occasionally from a postoperative
electrocardiogram. [123 ] , [126 ] A few patients experience symptoms of
lightheadedness or palpitations, and inferequently a patient develops hypotension and
reduced cardiac output from very rapid atrial fibrillation or flutter and requires prompt
resuscitation. The diagnosis is made by electrocardiogram; in equivocal cases the
atrial electrogram obtained from temporary atrial wires is helpful. [127 ] Immediate
electrical cardioversion is recommended for unstable, symptomatic patients. Stable
patients with atrial flutter usually are converted to lower ventricular rates by overdrive
pacing followed by anti-arrhythmic drugs. [121 ] In all patients antiarrhythmic drugs are
given first to control ventricular rate by slowing intranodal conduction and second to
achieve conversion to sinus rhythm. Class Ia drugs (e.g., Procainamide), and
calcium-channel blockers frequently are prescribed, but all depress myocardial
contractility to some degree. Digoxin is effective for chronic control. Amiodarone may
be needed for refractory patients.
Attempts to prevent atrial fibrillation and flutter by prophylactic therapy are only partially
successful. Large studies suggest that -blockers, such as propanalol, atenolol, and
metoprolol, reduce the incidence of postoperative arrhythmias to some degree, but
digoxin, calcium-channel blockers, and amiodarone are ineffective. [121 ] , [128 ] [132 ]
, [134 ] Treated postoperative atrial arrhythmias are usually well tolerated, and many
patients revert to sinus rhythm during the first month after hospital discharge and no
longer need drugs prescribed for rate control. [130 ] , [131 ] , [135 ] Patients who remain
in atrial fibrillation have a two- or threefold increase in the risk of stroke, and long-term
anticoagulation is recommended in the absence of contraindications. [123 ] , [126 ]
Despite the morbidity of atrial fibrillation, early and late mortality rates do not appear
increased by the dysrhythmia.
VENTRICULAR ARRHYTHMIAS
Postoperative ventricular arrhythmias range from occasional premature beats,

bigeminy, trigeminy, and nonsustained ventricular tachycardia to sustained ventricular
tachycardia and ventricular fibrillation. The benign arrhythmias occur in 2060 percent of
patients and infrequently produce symptoms or require treatment. [121 ] The incidence
of sustained tachycardia or ventricular fibrillation after cardiac surgery ranges 0.41.4
percent. [121 ] , [136 ] These potentially lethal arrhythmias often are unexpected and
may occur at any time during hospitalization and soon after discharge.
Predisposing factors include myocardial ischemia, low cardiac output, metabolic

derangements, drug interactions, and severe left ventricular dysfunction (ejection
fraction less than 40 percent). [121 ] , [137 ] Prophylactic correction of hypoxemia,
acidosis, hypokalemia, and hypomagnesemia is particularly important in the immediate
postoperative period. Development of ventricular arrhythmias should prompt evaluation
for ongoing myocardial ischemia. [121 ] , [136 ] , [138 ]
Immediate cardioversion followed by resuscitation and antiarrhythmic therapy is

essential for sustained ventricular tachycardia and ventricular fibrillation. Once the
patient is resuscitated, a cause for the event should be sought and corrected if possible
(e.g., hypoxemia, hypercarbic, etc.). Because these arrhythmias are lethal,
electrophysiologic testing is necessary to determine effectiveness of specific drugs in
individual patients. This should be done before hospital discharge, and occasional
patients may require an implanted automatic internal cardiac defibrillator prior to
hospital discharge. [137 ] Sustained ventricular tachycardia and fibrillation have an
associated mortality up to 44 percent that can be substantially reduced by aggressive
therapy. [121 ] , [136 ] [137 ]
CONDUCTION DISTURBANCES
Transient conduction disturbances after open cardiac surgery are very common, and
most do not require treatment other than transient pacing via temporary pacing wires.
[139 ] The incidence of permanent disturbances varies widely but is as high as 3455
percent in subsets of patients with coronary arterial disease. [140 ] [142 ] Hemiblock
and bundle branch blocks are rarely symptomatic, but atrioventricular block and sinus
node dysfunction that occur in 0.54 percent of patients usually require a pacemaker.
[121 ] , [140 ] Possible contributing factors to the development of postoperative
conduction disturbances include the severity of coronary arterial disease, particularly of
septal vessels, duration of aortic cross-clamping and cardiopulmonary bypass, method
of cardioplegia, depth of myocardial hypothermia, patient age, and specific operation.
[121 ] , [140 ] [142 ] Persistence of sinus node dysfunction or atrioventricular block
beyond 4 or 5 days is an indication for a permanent pacemaker. [121 ] Other
indications for permanent pacemakers are presented in Chapters 25 and 27.
PERIOPERATIVE MYOCARDIAL INFARCTION
The reported incidence of perioperative myocardial infarction varies widely (230

percent) because of differing definitions and criteria for infarction but in most series is
37 percent. [143 ] , [144 ] Possible causes of infarction include incomplete myocardial
protection during aortic cross-clamping, incomplete revascularization, vasospasm,
atheromatous emboli from previous bypass grafts or the aorta, air embolism, and
thrombosis of either a native vessel or a new graft. [145 ] [147 ] Myocardial
revascularization patients are at higher risk of perioperative infarction than patients
having other cardiac procedures. With revascularized patients risk factors for infarction
include extensive coronary arterial disease, prolonged aortic cross-clamp and
cardiopulmonary bypass times, older age, and preoperative depressed left ventricular
function. [143 ] , [144 ]
Studies suggest that up to 80 percent of newly infarcted areas are supplied by patent
bypass grafts. [147 ] , [148 ] Improvements in cardioplegia have reduced the number of
infarcts in areas supplied by bypass grafts, however, many infarcts are associated with
reduced flow in the bypass conduit. [144 ] , [149 ] The reasons for reduced flow may be
mechanical obstruction, limited runoff within the supplied vascular bed, emboli, or
vasospasm of downstream native coronary vessels.
Perioperative infarction traditionally is diagnosed by the electrocardiogram and

elevated serum levels of creatine kinase isoenzyme (CK-MB). [150 ] [152 ] ST
depression, T wave inversion, and particularly new Q waves with a significant increase
in CK-MB are suggestive of perioperative myocardial damage, but often patients do not
have evidence of compromised cardiac function. [153 ] In patients with ECG and
enzyme evidence of infarction and hemodynamic instability, bedside echocardiography
may be helpful in localizing areas of reduced wall motion that may indicate ongoing
myocardial ischemia that is potentially reversible. [145 ] , [146 ] Emergency coronary
angiography may show coronary vasospasm that may be responsive to
calcium-channel blockers or nitrates or conduit complications that may require
interventional cardiology or surgical exploration. [154 ] [158 ]
The risk of additional morbidity and mortality in patients who suffer perioperative
infarction may be 2.5 times greater than with comparable patients who do not have
infarction. [144 ] Patients with low cardiac output following perioperative infarction
should have aggressive diagnostic evaluation and also mechanical circulatory support
with an intra-aortic balloon pump. Past experience with more advanced methods of
circulatory support, such as left ventricular assist devices, generally has not been very
successful, but more-recent experience is considerably better (Chapter 21). [159 ] [161
] Patients below age 65 who suffer massive myocardial infarction may be candidates
for mechanical circulatory bridging to transplantation (Chapter 11). In our experience,
bridging patients with recent myocardial infarction without explanting the native heart
and providing total mechanical support is associated with significant morbidity and
mortality.
EARLY AND LATE PERICARDIAL TAMPONADE
Although the majority of patients develop small, posterior pericardial effusions after
open cardiac surgery, 36 percent develop early tamponade that requires reoperation.
[162 ] [164 ] Early pericardial tamponade is directly related to persistent mediastinal
bleeding and may progressively reduce cardiac output despite adequate filling
pressures. Typically, right atrial, pulmonary arterial, and wedge pressures trend toward
equality. [162 ] [164 ] However, loculated clot or fluid compressing the heart may prevent
equalization of filling pressures but still compromise cardiac output. [166 ] , [167 ]
Patients usually have excessive blood loss from chest tubes or a sudden decrease in
previously brisk chest tube drainage. Chest X-rays may not show a widened
mediastinum in the AP view, and chest tube suction may fail to relieve the tamponade.
The condition must be distinguished from perioperative infarction, right ventricular
infarction, or severe left ventricular dysfunction from other causes. Although these
conditions may be differentiated from tamponade by careful evaluation of pulmonary
arterial catheter tracings, transthoracic or preferably transesophageal
echocardiography reliably makes the diagnosis but may not be quickly available if the
circulation deteriorates rapidly. [164 ] , [165 ] , [168 ] If tamponade is even a remote
possibility, transfer to the operating room and emergency exploration of
hemodynamically deteriorating patients with or without a definitive diagnosis may be
lifesaving and is unlikely to harm patients with other causes of low cardiac output that
may need mechanical circulatory assistance.
Symptoms of tamponade that develop more than 1 week after operation usually are
categorized as delayed or late tamponade. [169 ] , [170 ] The reported incidence of late
tamponade varies 0.52.0 percent. [171 ] , [172 ] Symptoms delayed. [171 ] , [172 ] The
classical symptoms of constrictive pericarditis usually are absent; typically patients
present with low cardiac output and refractory heart failure and complain of progressive
dyspnea, orthopnea, and fatigue. [166 ] , [173 ] Neck veins may be distended; heart
sounds are rarely attenuated, and heart size is not enlarged by chest X-ray. The
electrocardiogram is not diagnostic. The diagnosis is made by echocardiograms that
demonstrate the effusion. [166 ] , [172 ]
The mechanism of late tamponade is incompletely understood but may be related to

anticoagulation, the postpericardiotomy syndrome, excessive perioperative mediastinal
drainage, chyle leak, and infectious pericarditis. [162 ] , [173 ] Although effusions
causing late tamponade usually present within 1 month of operation, delays as long as 6
months have been reported. [171 ] , [172 ]
Late effusions may be aspirated by needle with ultrasound guidance to reverse the
impaired hemodynamics. The rate of recurrence is low. [172 ] , [174 ] Patients on
anticoagulants or with loculated effusions may require subxiphoid exploration and finger
dissection of loculations. [175 ] Reexploration and pericardial stripping are rarely
needed. [176 ]
CONSTRICTIVE PERICARDITIS
Constrictive pericarditis following cardiac surgery was first reported in 1975 and now
complicates 0.20.3 percent of all operations without predilection to the type of
procedure. [177 ] [180 ] The disease progresses from pericardial hemorrhage and
inflammation to eventual organization into a fibrotic, pericardial shell that may contain
calcium. The etiology of the process is unclear; postoperative wound infection, irrigation
with povidine-iodine or antibiotics, dry pericardium, and bleeding plus pericardial
trauma have been blamed. Nearly half of the patients have a history of post-cardiotomy
syndrome. [180 ]
Patients complain of dyspnea with minimal exertion, fatigue, and peripheral edema and
present 2 weeks to 17 years after operation. [170 ] , [180 ] Symptoms and signs are
non-specific, and the ECG often shows nonspecific ST segment changes. The chest
X-ray may show cardiomegaly, however. Echocardiography, MRI, and CT scan all
demonstrate pericardial thickening, effusions, and occasional pericardial calcium. [176
] The most-common echocardiographic findings show biatrial dilatation, small to normal
ventricular size, and an unyielding shell of pericardium. [166 ]
Corticosteroids and nonsteroid anti-inflammatory agents generally are ineffective in

preventing constrictive pericarditis in patients with the post-pericardiotomy syndrome,
but a tapered dose of corticosteroids is recommended in patients with evidence of
constrictive pericarditis within 2 months of operation if they are clinically stable. [178 ] ,
[181 ] Persistent symptoms after 2 weeks of steroids, presentation after 2 months, or a
compromised circulation are indications for surgery. Ideally the fibrotic pericardium is
stripped from the epicardium without injury to either the heart or any bypass grafts. The
heart is decorticated as completely as possible and usually responds with immediate
improvement in performance. Sometimes hemodynamic recovery is delayed, possibly
because of myocardial atrophy beneath the fibrotic peel. Any threats of recurrence may
respond to corticosteroids. [180 ] The mortality associated with late stripping ranges
515 percent. [170 ] , [178 ] [180 ]
POSTCARDIOTOMY SYNDROME
The postcardiotomy syndrome or postpericardiotomy syndrome was first described

after closed heart operations in 1953 and recognized to be similar in presentation to the
syndrome described by Dressler after myocardial infarction. [182 ] In adults the
incidence after open heart surgery is approximately 18 percent and decreases with
advancing age. [183 ] The etiology is not totally clear, but the disease appears to be an
autoimmune phenomenon associated with high titers of heart-reactive antibodies that
develop in all patients who have open heart surgery. [183 ] Two-thirds of patients with
the syndrome also have antibodies that react with a panel of eight common viruses.
[183 ] The disease may progress to pericardial effusion and infrequently constrictive
pericarditis. [184 ] , [185 ]
The most-common presentation includes fever, pleuritic pain, malaise, and a pericardial
friction rub. Occasional patients develop pleural or pericardial effusions or have pain
with swallowing. Symptoms usually develop within the first month after operation and
usually after the first week. [186 ] Late presentations up to 190 days after operation are
described. [167 ] , [187 ] The disease must be differentiated from other postoperative
fevers including atelectasis, pneumonia, endocarditis, and wound and urinary tract
infection. A mild leukocytosis may be present, and the ECG may show nonspecific ST
changes. [187 ]
The disease is self-limited with a mean duration of symptoms lasting 1 month. Patients
are encouraged to limit activity, and analgesics (oxycodone, codeine) may be needed
for pain relief. Nonsteroidal anti-inflammatory agents usually are prescribed; patients
with severe or persistent symptoms may require a tapered dose of corticosteroids. [188
] , [189 ] Up to 20 percent of patients develop a recurrence. [186 ] The syndrome is not
associated with increased mortality.
Chest, Lung, and Airway
Although many advances have been made in anesthetic management, cardiopulmonary

bypass, chest physiotherapy, assessment of pulmonary function, intrathoracic imaging,
and infection control, pulmonary complications are common after open heart surgery
and are reported in as many as 30 percent of patients. [190 ] , [191 ] The incidence is
higher in older, sicker patients and those with compromised pulmonary function.
Prevention of pulmonary complications and prompt effective therapy impact directly on
length of hospital stay and mortality after cardiac surgery.
PNEUMOTHORAX
One to two percent of patients may develop pneumothorax after cardiac surgery. [192 ]
The cause may be direct lung injury during division of the sternum, insertion of venous
catheters, internal mammary artery harvest, insertion of a chest tube for effusion or
hemothorax or from sternal wires during closing. Patients with apical blebs,
emphysema, or bullae may develop pneumothorax during mechanical ventilation. Air
may enter the hemithorax from chest tube removal or enter the opposite hemithorax
across the anterior mediastinum from a pneumothorax of one lung. [193 ] All except very
small pneumothoraces are identified readily by plain chest X-ray.
The clinical presentation varies. Pneumothorax may be discovered as an incidental

finding on chest X-ray or cause cardiovascular collapse owing to tension pneumothorax
in patients who are mechanically ventilated. Between these two extremes patients may
develop dyspnea, pleuritic chest pain, hypoxia, arrhythmias, increased airway
pressures, or hypotension. In stable patients the diagnosis is suspected by absent
breath sounds and confirmed by chest X-ray. [192 ] , [194 ] With tension pneumothorax
respiratory distress is present, and the trachea is deviated away from the affected lung.
Tension pneumothorax requires immediate relief by insertion of a sterile thoracostomy

tube in the second anterior interspace in the midclavicular line. Closed suction is
maintained until the patient is able to breath spontaneously. Lung leaks nearly always
close spontaneously with reexpansion and adhesion to the chest wall. Very rare patients
may require multiple chest tubes, thorascopic surgery with bleb or bulla removal, or
pleurodesis. [192 ] , [195 ]
HEMOTHORAX
Accumulation of blood or irrigation fluid in one pleural cavity, usually the left, is not
unusual after open heart surgery. If the hemithorax is opened during operation, a chest
tube is placed prior to closure. However, small unnoticed holes and tears may allow
entry of mediastinal blood or irrigation fluid that is discovered on the postoperative
chest X-ray. These collections should be treated by thoracostomy tube to allow the lung
to completely expand and to remove the fluid.
Bleeding into the hemithorax occurs most often from the harvest site of the internal
mammary artery. [195 ] , [196 ] These collections usually are not substantial and do not
often affect hemodynamics, but occasionally an insidious, persistent bleeding vessel
produces a large hemothorax over time. These patients may develop hypovolemia from
the unrecognized bleeding and require several transfusions in addition to chest tube
drainage and often reexploration. More-localized, undrained blood accumulations in the
chest reduce pulmonary function by direct compression of the lung, increase the risk of
infection in the compressed lung, and over 2 or 3 weeks' time produce a fibrinous peel
that must be removed eventually. [197 ] , [198 ] Decortication is most easily done by
thorascopic surgery early before the fibrinous peel is completely organized; fibrous
peels discovered 3 to 4 weeks after hemothorax may require decortication. [197 ] , [198
]
LATE AIRWAY INJURIES
The endotracheal tube is involved in most postoperative airway injuries, and

complications associated with its insertion are presented above. Late laryngeal
complications are uncommon and may be produced by abrasion of the vocal cords or
cuff injuries to the recurrent laryngeal nerve. [199 ] [202 ] The mobility of the larynx
increases the likelihood of abrasive irritation of the cords and temporary swelling and
hoarseness. [200 ] A nasogastric tube combined with an endotracheal may cause
posterior ulceration of the arytenoid cartilage. [200 ] , [203 ] Recurrent laryngeal nerve
injuries are related to endotracheal cuff pressure and rarely, cannulation of the jugular
vein or harvesting an internal mammary artery. [204 ] [206 ] The recommended position
of the endotracheal tube cuff is at least 1.5 cm below the true vocal cords; the tip should
be 2 cm above the tracheal carina. [202 ] Last, prolonged intubation may produce
swallowing difficulties and laryngeal aspiration following extubation, particularly in older
patients. Most laryngeal and swallowing problems resolve with time, but many increase
length of stay and costs.
Injuries produced by prolonged overdistention of the endotracheal cuff are uncommon

because of improved cuff designs that prevent ischemic injury to the tracheal wall and
eventual stricture formation. Rarely, inflation of the cuff may cause posterior wall rupture
that can be extended toward the carina by mechanical ventilation. [207 ] , [208 ] This
injury may produce subcutaneous emphysema immediately and prompt immediate
bronchoscopic examination to evaluate the injury; if possible, the operation should be
delayed. Lacerations greater than one-third the circumference of the trachea should be
closed at operation; small lacerations may be treated conservatively with antibiotics.
[209 ] [211 ] The trachea rarely is injured during cardiac operations but may be injured
during aortic surgery near the isthmus and aortic arch. If injured, the trachea should be
repaired primarily and covered with a muscle flap or adjacent tissue for reinforcement.
PNEUMONIA
Up to 4 percent of patients undergoing cardiac surgery develop postoperative

pneumonia. The incidence is increased in patients with underlying pulmonary disease,
smokers, and aged patients with the potential for aspiration and is highest in patients
who require prolonged ventilatory support. [190 ] , [212 ] [218 ] Cardiopulmonary bypass
activates and weakens the whole body defense system (Chapter 9), and chronic
obstructive lung disease and smoking weaken the intrinsic pulmonary defense system
to increase the risk of lower airway infection.
Fever, productive sputum, pathogenic organisms identified by gram stain or culture in

airway secretions or blood, together with chest X-ray signs of a new or progressive
infiltrate, an area of consolidation, or a cavity establish the diagnosis. Immediate
treatment with one or more broad spectra or preferably organism-specific antibiotics is
indicated. In addition chest physiotherapy, encouragement of cough, and effective
tracheal-bronchial suctioning are initiated to help remove secretions. Occasionally
bedside bronchoscopy may be done to obtain a specimen for culture or to clear an
airway of obstructing mucus. Concomitant pleural effusions are drained dry by needle
aspiration or chest tube and cultured to prevent empyema. [215 ] , [217 ] , [218 ] If
empyema develops, thorascopic surgery to completely drain the infection and reexpand
the underlying and adjacent lung is mandatory. [214 ] , [215 ] , [217 ] , [219 ]
Preventive measures to reduce the incidence of postoperative pneumonia include chest

physiotherapy, incentive spirometry, preoperative antibiotic prophylaxis, and
bronchodilators in patients with chronic bronchitis. Unfortunately, smoking must be
stopped at least 2 months prior to operation to significantly reduce postoperative
pulmonary complications, but cessation for this length of time is effective. [220 ] , [221 ]
Treatment of chronic bronchitis and surveillance cultures before operation is prudent,
and only emergency procedures proceed without this preparation. The value of chest
physiotherapy and incentive spirometry has been questioned on a cost basis, but both
activities help to mobilize patients, increase tidal volume, and overcome fear of
breathing-induced wound pain. [222 ] [224 ] Use of antacids and H2-blockade for stress
ulcer prophylaxis does not appear to predispose cardiac patients to aspiration
pneumonitis, although other patients may be at risk. [215 ]
PHRENIC NERVE INJURY
The exact incidence of unilateral phrenic nerve injuries during cardiac surgery is not
clear but appears greater than 2 percent of patients. [225 ] [231 ] Likewise the causes
of the injury are not clearly understood. Direct injury during harvest of the internal
mammary artery, cold injury owing to pericardial ice slush, and inadvertent stretch
injuries during intrapericardial manipulations of the heart are documented causes, but
the injury also occurs in some patients without apparent reason. [228 ] Cold reduces
nerve conduction and causes direct injury to the nerve in animals, and intrapericardial
ice slush increases the incidence of phrenic nerve, particularly left phrenic nerve,
paralysis in patients. [225 ] , [231 ] The effectiveness of insulating partitions and cooling
jackets recommended to prevent cold injury is not clearly established. [232 ] , [233 ]
Bilateral phrenic nerve palsy occurs much less frequently, but the consequences of the
complication are more serious.
The diagnosis usually is suspected by noting a high diaphragmatic shadow or lower

lobe atelectasis on chest X-ray. [227 ] , [234 ] , [235 ] Nerve conduction and fluoroscopic
and ultrasonic studies, each with limitations, are used to confirm the diagnosis in
patients with persistent abnormal chest X-rays or pulmonary dysfunction. Although often
benign, unilateral phrenic nerve paralysis increases the likelihood of atelectasis,
pneumonia, and prolonged respiratory dependence, particularly in patients at risk for
postoperative pulmonary complications. [227 ] , [228 ] , [234 ] , [235 ] Bilateral phrenic
nerve injuries may be devastating and necessitate tracheostomy and prolonged
mechanical ventilation. [226 ] , [227 ] , [236 ] These patients have a high incidence of
cardiorespiratory arrest, nosocomial pneumonia, and eventual death. [225 ] Eventually
nearly all phrenic nerve palsies associated with cardiac surgery resolve, but delays up
to 18 months are described.
CHRONIC VENTILATORY DEPENDENCE
The vast majority of cardiac surgical patients are extubated within 24 hours of
operation, and younger, low-risk patients often are extubated within a few hours of
operation. [237 ] , [238 ] A subset of patients requires ventilatory support for more than 3
days for a variety of reasons. Often comorbidity, such as perioperative myocardial
infarction, stroke, or renal failure, as opposed to pulmonary problems, is the reason for
continuing mechanical ventilation.
Prolonged mechanical ventilation exposes the patient to the risks of nosocomial

infections, airway injuries, debilitation, stress ulceration, despondency, and even
adverse cardiac events. [225 ] Nearly one-third of those ventilated for more than 3 days
die of the primary event that necessitated continued ventilation.
Management of these patients is a team effort and usually includes critical care
specialists, infectious disease specialists, respiratory and physical therapists, and
speech physiotherapists. Provision must be made for nutritional support and infection
control. Intravenous catheters must be changed every 34 days, and entry sites must
receive daily cleansing. Prophylactic measures are needed against stress ulceration,
decubitus ulcers, and muscular atrophy. Usually the endotracheal tube using large
volume, low pressure cuffs to reduce airway injury is used for the first 2 weeks (Fig.
13-8) . Patients who still require ventilation after 2 weeks generally have tracheostomy
with little risk of sternotomy wound contamination. [239 ] [241 ] A weaning protocol is
established as soon as possible, and every effort is made to help the patient retain
respiratory muscle strength and prevent atrophy. A variety of weaning protocols,
including intermittent mandatory ventilation, continuous pressure support, and
continuous positive airway pressure, are used. The inspired oxygen tension should be
reduced as low as possible to maintain peripheral oxygen saturations > 95 percent.
Ventilatory gases must be heated and humidified and ventilators and connecting tubing
cleaned or changed frequently. High frequency or jet ventilation is used rarely in
postoperative cardiac patients. Care requirements for prolonged chronic ventilation
incur major costs in both time and money, and unfortunately a high percentage of
patients, particularly aged patients, fail to survive.
Adult Respiratory Distress Syndrome (ARDS)
ARDS is a syndrome characterized by refractory hypoxemia, noncompliant lungs, and

diffuse and sometimes homogenous infiltrates throughout both lungs on chest X-ray.
The hypoxemia is due to a diffuse high permeability pulmonary edema that usually
involves the entire lung and fills the alveoli with plasma and scattered red cells. Alveolar
surfactant is inactivated by the proteinaceous exudate. Patients develop a high
alveolar-arterial oxygen difference and large shunt fraction but do not have high left atrial
pressures. The etiology of the syndrome, which may affect up to 1.5 percent of cardiac
surgical patients, is not known, but the inflammatory reaction associated with
cardiopulmonary bypass is a contributing factor in that extracorporeal perfusion initiates
a massive inflammatory response and the production and release of a host of
vasoactive substances capable of increasing pulmonary capillary permeability (Chapter
9). [242 ] [245 ] ARDS may occur in sporadic patients after severe trauma, septicemia,
acute transient increases in pulmonary venous pressure, and other conditions that fill the
alveoli with a proteinaceous fluid. ARDS is associated with severe morbidity and a
mortality approaching 50 percent. [242 ]
Treatment is preventive and supportive. Inspired oxygen is reduced to the lowest levels
capable of maintaining adequate oxygen-carrying capacity. Diuresis is vigorously
pursued. Cardiac output is maintained at high levels; high filling pressures are avoided.
Lungs are ventilated with elevated end-expiratory pressures, reduced tidal volumes, and
as low inspired oxygen concentrations as possible. Reduced arterial oxygen tensions
are tolerated to reduce inspired oxygen concentrations. Bronchodilators are used to
relieve bronchospasm, and secretions are removed by frequent aspiration. Infection is
prevented by prophylactic broad spectrum antibiotics, surveillance cultures, and
pulmonary toilet. With recovery alveolar fluid and protein are gradually cleared; both the
alveolar-arterial oxygen difference and chest X-ray improve concomitantly.
Kidney
ACUTE RENAL FAILURE
During cardiac surgery the kidneys may be damaged by hypoperfusion because of low
systemic blood pressure, low cardiac output, and vasoconstriction from circulating
vasoconstrictors and hypothermia and from bombardment by microemboli. Although
attenuated by hemodilution, cardiopulmonary bypass reduces renal and plasma flow
and creatinine and free water clearance. Severe hemolysis, nephrotoxic drugs, or
atheromatous emboli are other uncommon injuries to the kidneys during open heart
surgery. Not surprisingly, up to 15 percent of patients develop some evidence of renal
dysfunction following cardiac surgery. [246 ] , [247 ] Mild renal dysfunction is defined as
an increase in blood creatinine of 100150 percent over baseline without the need for
dialysis. [248 ] , [249 ]
More-severe renal failure occurs in 1.54.0 percent of patients and is primarily related to
preoperative renal function, postoperative cardiac output, ischemic periods during
operation, microemboli, preoperative administration of radiographic contrast materials,
and toxic drugs. [248 ] , [249 ] The need for several transfusions, use of vasopressors,
episodes of cardiac arrest or low cardiac output, use of the intra-aortic balloon pump,
older age, insulin-dependent diabetes, reduced urine output during cardiopulmonary
bypass, and deep hypothermia also correlate with postoperative acute renal failure.
[250 ] Acute renal failure generally is defined as oliguria (urine output less than 400
mL/day), an increase in serum creatinine above 5 mg/dL, glomerular filtration rate less
than 30 mL/min/m 2 , or the need for dialysis. [248 ] , [249 ] , [251 ] The need for dialysis
is estimated to be as high as 1.5 percent of patients who have cardiac surgery, but this
incidence undoubtedly reflects the age and preoperative renal status of operated
patients. Polyuric renal failure usually develops after recovery from oliguric renal failure
and is identified by a high urine volume containing increased concentrations of sodium
associated with a rising serum creatinine.
Treatment of acute renal failure requires careful management of fluid balance,

avoidance of nephrotoxic drugs, reduction in doses of drugs cleared or excreted by the
kidneys, measurements of blood concentrations of potentially toxic drugs, and
prevention of infection and other complications. Every effort should be made to optimize
cardiac output. Initially if urine is being made, tubular diuretics are given in an attempt to
increase urine output. However, if early postoperative fluid accumulation is excessive,
fluid may be removed rapidly by continuous arterial venous hemofiltration using femoral
percutaneous cannulas if cardiac output is adequate. [252 ] Venovenous
hemodiafiltration is a newer method to correct fluid and electrolyte imbalances and is
not dependent on cardiac output. [253 ] [255 ] Plasma potassium concentrations are
monitored carefully, and potassium usually is removed from intravenous fluids. High
potassium concentrations (> 6.0 meq/L) are aggressively treated with bicarbonate, 50
mL of 50 percent glucose with 10 units of insulin, and 0.5 gm of calcium. Kayexalate ion
exchange resins in 25 percent sorbitol given by nasogastric tube or enema are used
occasionally, but more often progressive increases in potassium are managed by
hemodialysis. Elevated potassium, excess fluid, creatinine over 5 mg/dL, and lethargy
generally are indications for hemodialysis on a daily or alternate-day basis. Peritoneal
dialysis is now used uncommonly.
Every effort is made to prevent infection, and if unexplained fever, leukocytosis, or

reduced cardiac output with peripheral vasoconstriction develops, blood, sputum, and
urine cultures are obtained and effective, broad spectrum antibiotics are started or
changed without proof of infection. Renal failure patients frequently die of infection
before renal function returns and frequently develop serious unrelated complications.
Perioperative myocardial infarction is associated with 20 percent of patients with renal
failure. [246 ] The mortality in patients who develop acute renal failure is approximately
45 percent. [250 ] Mortality also is elevated in patients with mild renal dysfunction
(creatinine > 1.5, < 2.5 mg/dL). [250 ]
COMPLICATIONS ASSOCIATED WITH CHRONIC RENAL FAILURE
Patients who receive chronic dialysis or have a renal transplant often are eligible for
open cardiac surgery but require special management to avoid complications and
mortality. Progression of coronary arterial occlusive disease is accelerated by dialysis
dependency, and the longevity of bioprosthetic heart valves is substantially reduced.
[256 ] , [257 ] Chronic dialysis patients are susceptible to metabolic and hematologic
derangements and require special care of dialysis access catheters and grafts and fluid
management. Dialysis patients with azotemia have reduced platelet function,
coagulation abnormalities, anemia, and reduced blood protein concentrations and are
more susceptible to infection because of suppression of the immune system. [249 ] ,
[257 ] , [258 ] , [260 ] , [261 ] Transplant patients, of course, receive immunosuppressive
therapy and also are more susceptible to postoperative infection.
Bleeding is the most common intraoperative complication and occurs in up to 10

percent of patients. [249 ] , [262 ] Bleeding is primarily related to platelet dysfunction
and mild to moderate thrombocytopenia that produces an increase in preoperative
bleeding times. Abnormalities in the structure of von Willebrand factor, an adhesive
protein for platelets, also occur in uremic patients. Thus uremic patients require
intraoperative and postoperative transfusions of platelets and fresh frozen plasma and
may also benefit from desmopressin, which increases factor VIII-von Willebrand factor
concentrations. Chronic dialysis patients often receive recombinant erythropoetin to
correct chronic anemia. A hematocrit over 25 percent is recommended before
operation, and patients may require transfusion. [261 ]
During operation a dialysis unit in the extracorporeal circuit permits control of potassium
and fluid balance. Patients usually are dialyzed the day before operation and also the
day afterwards. [262 ] Venovenous hemodiafiltration also may be useful in these
patients if their indwelling arteriovenous fistulas are not serviceable temporarily. [252 ]
[255 ] , [263 ] During operation these shunts are carefully padded and protected, and no
intravenous catheters are inserted in that arm. Renal transplant patients usually need
stress dose corticosteroids in the perioperative period, and systemic blood pressure is
maintained above 70 mmHg (mean) during cardiopulmonary bypass. Urine output is
maintained postoperatively at 50100 mL/hr by adequate perfusion pressures and
diuretics.
A review reports that the overall survival rate for cardiac surgery in chronic dialysis
patients is 9 percent. [261 ] More-recent experience reports hospital mortalities 45
percent for both revascularization and valve operations. [257 ] , [261 ] Mortality is
increased by the preoperative presence of congestive heart failure and emergency
surgery; long-term survival is adversely affected by age above 60 years (Fig. 13-9) .
[257 ] , [261 ] Actuarial survival at 5 years is 55 percent for chronic dialysis patients;
3-year survival is over 80 percent for renal transplant patients who have open heart
surgery. [238 ] , [259 ] , [260 ]
Peripheral Vascular Complications
Peripheral vascular complications in the femoral region are not uncommon because the
easy access and size of these vessels encourage insertion of necessary cannulas for
monitoring, cardiac catheterization, blood processing (e.g., hemofiltration), and
circulatory support. Local hematomas occur frequently if pressure control of removed
catheters and cannulas does not stop blood egress. With the rare exception of pending
skin necrosis, these hematomas should not be drained; reabsorption may require
several weeks. If a large catheter is inserted through a cutdown into the femoral or iliac
artery, surgical closure of the artery is recommended at the time of withdrawal.
Occasionally arteriovenous fistulas complicate cardiac catheterization. This
complication is identified by ultrasound and requires surgical closure. Thrombotic
occlusion from percutaneous catheterization or cannulation requires operation to
reestablish flow to the lower extremity. A needle, catheter, or cannula may raise an
atherosclerotic plaque to compromise or obstruct the vascular lumen. Because these
complications occur relatively frequently and are managed relatively easily with few
long-term complications, the incidence is not known. Patients who have generalized
vascular disease and those who are active smokers are at increased risk of lower
extremity vascular complications after open heart surgery. [264 ]
Lower extremity vascular complications occur in approximately 20 percent of patients

who require the intra-aortic balloon pump (IABP), and the IABP is responsible for
approximately 85 percent of lower leg ischemia after open heart surgery. [264 ] Distal
ischemia is more common in patients with low cardiac output or cardiogenic shock and
those who require high doses of vasopressors. [265 ] The status of the dorsalis pedis
and posterior tibial pulses should be monitored frequently using a portable Doppler
probe in patients with an IABP (Fig. 13-10) . Loss of sensation, poor capillary filling, and
absence of venous filling are signs of ischemia and prompt steps to immediately relieve
the ischemia. If the balloon catheter cannot be removed, it sometimes can be
transferred to the other leg. If the preoperative vascular system is normal, the transfer is
well tolerated without ischemia in most individuals and reverses the ischemia in the
affected leg and foot without operation in approximately 30 percent of patients. [264 ] ,
[265 ] The majority of patients require surgery to fully restore the circulation. [265 ] This
may involve a vascular patch at the site of insertion if the intra-aortic balloon catheter is
transferred or removed. More commonly the IABP is not transferred and a cross leg or
axillary-femoral prosthetic graft is performed under local anesthesia to restore
circulation to the ischemic leg (Fig. 13-5) . [265 ] [268 ] Twenty-five to thirty percent of
patients with ischemia due to the IABP require amputation; overall mortality in this group
of patients is approximately 45 percent as opposed to a mortality of 11 percent in
postoperative patients with leg ischemia who do not need the IABP. [264 ]
Symptoms of lower leg ischemia also may occur without an IABP in a minority of
patients. Approximately two-thirds are caused by thrombotic occlusion secondary to
arterial puncture and may be aggravated by vasopressors. [264 ] About one-third of
patients develop embolic occlusions, particularly trash emboli from dislodgement of
atheromata from insertion of catheters into the femoral or iliac arteries and the aorta. If
femoral and popliteal pulses are reasonably strong, the foot usually survives, and
attempts to remove distal emboli usually are unrewarding. If proximal pulses are
diminished or absent, operation is needed. Most of these patients require operation to
restore adequate circulation to the lower extremities.
Rarely, heparin-induced thrombocytopenia and thrombosis cause the white clot

syndrome and vascular occlusion of the small arteries of the extremities (Chapter 9).
Gastrointestinal Tract
Gastrointestinal (GI) complications following cardiac surgery range 0.412 percent of

patients. [57 ] , [269 ] [271 ] Often GI complications are part of a constellation of
problems in patients with low cardiac output, respiratory failure, renal failure, and/or
central nervous system deficits. [272 ] A period of low cardiac output and reduced blood
flow to the viscera is thought to contribute to the development of most postoperative GI
problems. Although these complications also occur in noncardiac patients, the
complications appear more severe after heart operations and are associated with
increased morbidity and mortality. [273 ] [275 ] This severity may, in part, be a result of
delays in diagnosis because of anesthetic agents, inability of the sedated, intubated
patient to complain, and metabolic disturbances. Early recognition and treatment is
imperative for control of GI complications, and postoperative cardiac patients are better
able to tolerate early effective operation than to survive major bleeding or abdominal
sepsis. [276 ] , [277 ]
GASTROINTESTINAL BLEEDING
The incidence of gastrointestinal (GI) bleeding after open heart surgery ranges 0.353
percent. Patients usually bleed during the first month after operation and usually near the
end of the first postoperative week. [269 ] , [271 ] , [273 ] , [274 ] Gastritis or peptic ulcer
are the most-common causes, although esophagitis, ischemic bowel disease,
diverticulitis, and A-V malformations may be responsible. Age and a prior history of GI
bleeding are the most reliable predictors of postoperative bleeding. [278 ] H 2 blockade
and H + , K + -ATPase inhibitors are recommended for prophylaxis. [278 ]
Melena is the most-common symptom, although hematemesis occurs. [277 ] Upper GI

endoscopy is done first because of the prevalence of upper GI bleeding sources. [273 ]
, [279 ] Bleeding points are either sclerosed or cauterized, and high doses of H 2
blockers are started. If the patient is stable, gastric resection with or without vagotomy is
recommended for rebleeding, but lesser procedures, including reendoscopy, may be
done if the age or clinical condition of the patient precludes immediate operation. [274 ]
[276 ] , [278 ] , [279 ] Postcardiotomy bleeding is associated with a high mortality that
ranges 7.775 percent. [273 ] [279 ]
PERFORATED ULCER
Perforated ulcer after heart surgery occurs in 0.020.08 percent of patients and in half
the patients is found by free abdominal air on a routine chest X-ray. [273 ] , [276 ] , [277
] , [280 ] Other patients complain of upper abdominal pain and distention. Many patients
have a previous history of ulcer disease. These patients are usually treated with an
omental patch repair. Mortality ranges 3050 percent and reflects delay in diagnosis and
the general debilitated condition of the patient. [273 ] , [276 ] , [277 ] , [280 ]
BILIARY COMPLICATIONS
Cholecystitis is the second most common GI complication and has an incidence of

0.20.5 percent after cardiac operations. These patients usually develop symptoms 515
days after operation and complain of fever, nausea, and vague, diffuse abdominal pain
associated with a leukocytosis. The pain often is not localized to the right upper
quadrant; therefore, the diagnosis often is delayed. Abdominal ultrasonography and
nucleotide scanning in combination are more likely to be diagnostic than either test
alone. [271 ] , [273 ] , [277 ] , [279 ]
Cholecystitis preferably is treated medically with intravenous fluids, bowel rest, and
broad spectrum antibiotics. Because of a high incidence of ischemic injury to the gall
bladder, cholecystectomy often is necessary. This is done preferably by laparoscopy.
Cholecystostomy seldom suffices. Mortality is high, probably because of delay in
diagnosis and the general condition of most afflicted patients soon after cardiac
surgery. [273 ] , [274 ] , [276 ] , [279 ]
PANCREATITIS/HYPERAMYLASEMIA
Twenty-five to thirty-five percent of postoperative cardiac patients develop

asymptomatic hyperamylasemia, but only 12 percent develop symptomatic pancreatitis,
and 0.130.6 percent have necrotizing pancreatitis. [281 ] [283 ] The etiology is unclear;
hypoperfusion, microemboli, and hypovolemia have been blamed. [274 ] Autopsy
studies of patients who die 1 or more days after operation show evidence of pancreatic
injury in 1625 percent of patients. [283 ] Pancreatitis generally occurs within a few days
after operation with symptoms of fever, nausea, epigastric pain, and a leukocytosis and
elevated serum amylase and lipase. [271 ] , [283 ] Elevated enzyme levels may not
always be specific for pancreatitis; therefore, the diagnosis is confirmed by computed
tomography or ultrasound. [283 ]
Patients with hyperamylasemia are monitored to be sure enzyme levels trend lower and
symptoms do not occur. Patients with mild pancreatitis are treated by intravenous fluids,
nasogastric drainage, and bowel rest until serum amylase levels return to baseline.
Necrotizing pancreatitis requires immediate operation with mobilization and
debridement of the pancreas, wide drainage, and gastrostomy and feeding
jejunostomy. The postoperative course often is complicated. [277 ] , [280 ] Mortality of
severe postcardiac pancreatitis is over 50 percent in large series. [273 ] [275 ] , [277 ] ,
[282 ] , [283 ]
ISCHEMIC COLITIS
Older age and generalized peripheral vascular disease may contribute to the
development of ischemic colitis, but the complication also seems related to the need for
emergency surgery and a period of perioperative hypotension. Evidence of emboli are
lacking in pathologic specimens, and the disease typically presents 6 or more days
after operation. The incidence of ischemic colitis is estimated to be 0.020.3 percent.
[57 ] , [273 ] , [277 ] , [279 ] , [280 ] Symptoms usually are insidious with abdominal
distention and vague complaints of discomfort and nausea. Severe pain, abrupt
distention, vomiting, extreme leukocytosis, melena, and rapid deterioration are late
manifestations of the condition. Sigmoidoscopy may provide the diagnosis;
laparoscopy is more definitive. Arteriography may show vasospasm of mesenteric
vessels, and occasionally individuals without gangrenous bowel benefit from a direct
and continuous infusion of papaverine through an angiocatheter placed in the superior
mesenteric artery.
At laparoscopy or operation large segments of bowel may be gangrenous or

alternatively only patches of bowel ischemic. Necrotic bowel must be excised, but not
infrequently the extent of the gangrene precludes salvage of the patient. [272 ] , [274 ] ,
[277 ] , [279 ] Since many afflicted patients are very old, mortality ranges 5095 percent.
[272 ] , [274 ] , [277 ] , [279 ]
DIVERTICULITIS
The incidence of divericulitis after open cardiac surgery is 0.130.25 percent, and most
patients have a prior history of the disease. Perioperative splanchnic hypoperfusion is
believed a contributing factor. [269 ] , [272 ] , [279 ] Typically these patients develop
fever, leukocytosis, left lower quadrant pain, and abdominal distention; endoscopy or
CT scanning may aid the diagnosis. Nearly 50 percent of patients develop abdominal
free air and are misdiagnosed as having perforated ulcer. [279 ] Operation is required
for perforated diverticulitis; limited colectomy and diverting colostomy are
recommended. Without perforation the disease is treated with intravenous antibiotics
and bowel rest, usually with successful resolution of the inflammation. [279 ] Patients
with perforated diverticulitis face a mortality rate of nearly 25 percent. [279 ]
LIVER
Fifteen to twenty percent of patients develop transient increases in liver enzymes

between the second and fourth postoperative days after cardiopulmonary bypass. The
cause is not known but is probably related to blood trauma, hepatic congestion, and
perhaps hypoperfusion during bypass. [270 ]
The incidence of hepatic dysfunction after heart surgery is 0.4 percent, but the incidence
increases markedly to as high as 35 percent in patients who develop another
intra-abdominal complication. [270 ] , [271 ] Progressive hepatic dysfunction manifested
by cholestatic jaundice, increasing blood enzyme levels, and refractory coagulopathy
develops in 0.030.23 percent of patients and usually is associated with multiple organ
system failure and is essentially a terminal event. [271 ] , [284 ]
Blood
Three to five percent of patients require reexploration for bleeding after open heart
surgery, and although up to one-third of patients do not need transfusion of homologous
blood, bleeding is a persistent and serious complication that contributes to morbidity
and, in debilitated patients, mortality. [285 ] [285 ] In approximately two-thirds of patients
a surgical bleeding source is found. [285 ] Common sites of ongoing hemorrhage
include side branches of the internal mammary and gastroepiploic arteries and
saphenous vein grafts, graft anastomoses, cannulation sites, aortic and cardiotomy
incisions, insertion sites of pacing wires, mammary arterial harvest sites, thymus, and
around sternal closure wires. Rarely extraordinary measures, such as packing the chest
or girdling the aorta with Teflon felt, are necessary to staunch the bleeding. [289 ] , [290 ]
Reexploration for bleeding is more common (7 percent) in patients with previous
operations and in patients having valve procedures. [285 ]
Chest tubes are monitored carefully immediately after operation, and blood is sent for
measurement of platelet count, prothrombin time, and partial thromboplastin time unless
these measurements were made in the operating room after cardiopulmonary bypass.
The patient is warmed, and if bleeding appears somewhat brisk, airway end expiratory
pressure is raised to 1015 cm h 2 o in an attempt to tamponade bleeding sites. [291 ]
[294 ] Hypertension also is controlled. Chest tubes are stripped to prevent obstruction
and to insure drainage.
Reexploration is indicated if sudden massive bleeding occurs, if chest tube drainage

suddenly accelerates to suggest a surgical cause, or if chest tube drainage persists
during the first few hours after operation. If bleeding exceeds 500 mL in the first hour
after operation, 400 mL during each of the next 2 hours, 300 mL during each of the first
3 hours, or 1,000 mL in 4 hours, a return to the operating room is recommended.
Although a surgical source is found in the majority of patients, one-third appear to have
generalized, nonsurgical bleeding that is apparently related to a defect in coagulation.
[285 ]
Nonsurgical bleeding problems related to open heart surgery are conveniently

categorized as heparin related, platelet related, fibrinolysis, or due to lack of a soluble
coagulation protein and are considered in detail in Chapter 9. [295 ] [310 ] Deficiency of
a soluble coagulation protein is rare and is primarily related to preoperative
deficiencies; dilution and consumption during cardiopulmonary bypass seldom reduce
concentrations to levels that fail to support coagulation. [311 ] Heparin- and
platelet-related causes of nonsurgical bleeding are identified by measuring the
prothrombin time, partial thromboplastin time, and platelet count immediately after
operation. Excess heparin increases the partial thromboplastin time and is treated by
additional protamine without fear of a protamine anticoagulation effect. An elevated
prothrombin time indicates a defect in the extrinsic coagulation pathway and is treated
with fresh frozen plasma (1015 mL/kg). [366 ] Platelet transfusions (1 U/10 kg) are
prescribed in bleeding patients for counts under 80,000/µmL, but platelet transfusions
are recommended for bleeding patients soon after operation because of a functional
deficit in most of the circulating platelets. Cardiopulmonary bypass routinely increases
template bleeding times because of platelet dysfunction for several hours afterward.
[303 ] Preoperative aspirin also inhibits platelet function. [307 ] , [312 ]
Fibrinolysis begins with the surgical incision and increases markedly with the onset of
cardiopulmonary bypass. [309 ] Heparin fails to completely suppress thrombin
formation; therefore, thrombin circulates and converts fibrinogen to fibrin, which is lysed
by plasmin. [313 ] The most-effective management of fibrinolysis is prophylaxis by
tranexamic acid, epsilon amino caproic acid, or aprotinin (Chapters 8 and 9). [314 ]
[332 ] Antifibrinolytic prophylaxis significantly reduces postoperative blood loss and the
need for transfusions in both first time and reoperative patients. [324 ] Because of an
abundance of fibrinogen, hypofibrinogemia rarely occurs, and supplemental fibrinogen
(cryoprecipitate) usually is used with thrombin to produce topical fibrin clots.
Antifibrinolytics preferably are given with the surgical incision; administration after
bypass is less effective. [325 ]
The risk of blood-borne pathogens, particularly hepatitis and the human immune
deficiency virus (HIV), has progressively decreased (Chapter 9), and modern cardiac
surgery uses several different means to reduce postoperative anemia and the need for
transfusion. These methods, antifibrinolytics and the availability of recombinant
erythropoietin have increased the safety of cardiac operations for Jehovah's Witnesses.
[326 ] [328 ]
Nervous System
CENTRAL NERVOUS SYSTEM
Except for death, central nervous system (CNS) injuries are the most devastating
complications of open heart operations. The reported incidence of central nervous
system complications varies widely (0.75.0 percent) because of differences in
definitions, heterogeneity of patient cohorts, timing of evaluations, and other factors.
[329 ] [337 ] Age is a specific risk factor for a postoperative neurologic deficit, and the
incidence in patients over 75 years approaches 9 percent. [332 ] , [334 ] , [335 ]
Patients with a preoperative history of cerebrovascular disease have a three-fold
increased risk of a new neurologic deficit or worsening of a previous deficit. [329 ] ,
[337 ] The most-common permanent deficit is stroke, but reversible ischemic deficits,
encephalopathy and coma, cognitive deficits, and seizures all may occur.
Cerebral macro- and microemboli or a period of hypoperfusion are the most common
causes of postoperative CNS injuries. Sources of macroemboli include the ascending
thoracic and arch aorta, the carotid arteries, thrombus, calcium, and debris from
intracardiac surgery, and air. [329 ] , [332 ] , [336 ] , [337 ] Microemboli are generated
by cardiopulmonary bypass (Chapter 9) and by specific surgical maneuvers such as
cannulation and lifting the heart. [331 ] , [338 ] , [339 ] Hypoperfusion may occur
preoperatively in hypotensive emergency patients but occurs infrequently during
cardiopulmonary bypass. [332 ] , [334 ] Postoperatively prolonged hypotension and low
cardiac output may cause cerebral dysfunction. [337 ] However, the combination of
significant carotid arterial stenosis and hypotension may combine to produce an
ischemic injury. The relationship between preexisting carotid disease and open heart
surgery is presented in Chapter 20. Currently the possibility of an increase in
postoperative CNS injuries during normothermic cardiopulmonary bypass is under
intense investigation and is as yet unresolved. [340 ] [345 ] Neurologic deficits
associated with deep hypothermia and circulatory arrest are related to the duration of
arrest, the temperature at the time of arrest, hyperglycemia, and possibly the
management of blood pH and co 2 (Chapters 9, 10, 38, and 40). Intracranial bleeding is
less common and usually complicates an embolus.
Postoperative neurologic deficits are determined early postoperatively initially by gross

neurologic examination and later by more-detailed examination. Suspicion of a new or
worse neurologic deficit is reason for a neurologic consultation and detailed inventory of
the degree of abnormal nervous system function. Invariably either a CT scan or MRI of
the brain is ordered. These studies help to differentiate new lesions from old, provide
evidence of the probable mechanism of the deficit (embolus with or without associated
bleeding, generalized hypoxia, or edema, etc.), and are helpful in formulating a
prognosis. [330 ] , [333 ]
Aside from steps to reduce the incidence of macroemboli and to prevent postoperative
hypotension and hypoperfusion, attempts to reduce postoperative neurologic
dysfunction following open heart surgery are not proven. [330 ] However, during deep
hypothermia, retrograde cerebroplegia and limiting the duration of circulatory arrest
reduce postoperative neurological deficits (Chapters 9, 10, and 40). The consequences
of permanent or severe deficits may be devastating, and patients with permanent
lesions face an in-hospital mortality of 1530 percent. [329 ] [331 ]
PERIPHERAL NERVE INJURIES
The reported incidence of upper extremity peripheral nerve injuries ranges 1.918.3
percent and reflects differences in the evaluation and definition of these injuries. [346 ]
[348 ] A collective review suggests that the true incidence approximates 10 percent.
[347 ] Most of these injuries involve the C8 and T1 roots of the brachial plexus, which
are injured primarily by stretch or compression during sternal retraction. [349 ] The
brachial plexus also can be injured directly from the fractured end of the first rib or by
needle trauma from a jugular vein cannulation. Harvest of an internal mammary artery
does not increase the likelihood of a brachial plexus injury. Less-common injuries
involve the ulnar or, rarely, the radial nerve owing to poor protection during anesthesia.
The median nerve may be injured by swelling at the wrist after attempted radial arterial
cannulation. [346 ] , [350 ] , [351 ]
Most of these injuries become apparent in the first postoperative week when the patient
calls attention to numbness, decreased sensation, or motor deficits of the affected part.
Although distressing to patients, nearly all of these injuries resolve spontaneously over 6
to 8 weeks. [347 ] , [349 ] A few are permanent and require more-detailed study and
treatment.
Harvesting the saphenous vein often severs or stretches the saphenous nerve that
provides sensation to the medial forefoot and ankle. The sensory deficit disappears
within a few months and rarely bothers the patient. [346 ] However, injuries to the sciatic,
femoral, or common perineal nerves may cause considerable disability. These injuries
are reported in 0.1 percent of patients and are owing to needle stick, compression from
an improper position of the leg, or lack of protection over the head of the fibula. Injures
also are thought to occur from poor perfusion of the lower extremity owing to vasoactive
drugs or the intra-aortic balloon pump and may become permanent if the circulation is
improved rapidly. [346 ] , [347 ] , [352 ] , [353 ]
NEUROPSYCHIATRIC CHANGES
Behavioral changes, cognitive dysfunction, sleeplessness, changes in dream patterns,

and psychological abnormalities may be documented shortly after operation by careful
examination and testing in up to one-half of patients who undergo open heart surgery.
[339 ] , [354 ] [359 ] These changes are more common in older patients and those with
previous central nervous system dysfunction and do not correlate with variables in
extracorporeal perfusion protocols or equipment [354 ] , [360 ] but roughly correlate with
the numbers and size of microemboli detected by carotid ultrasonography during
operation. [339 ]
Studies suggest that up to 13 percent of patients develop postoperative psychological

disturbances that are clinically manifested by atypical behavior, disorientation, or
reduced cognitive functions. [354 ] , [356 ] , [360 ] , [361 ] Hallucinations or delusions
may occur in 0.9 percent of patients. Sleep disorders, nightmares, or changes in dream
patterns may affect more than one-half of postoperative patients. [357 ] , [362 ] In most
patients the changes are transient and gone within a few days or weeks. Changes in
cognitive function determined by testing may affect up to 75 percent of patients shortly
after operation, but late studies show that the vast majority of patients regain full
cognitive function within 6 months to 1 year. [359 ] , [363 ] , [364 ] , [365 ] However, as
many as 6.6 percent of patients may demonstrate moderate to severe psychometric
abnormalities at late follow-up, and in approximately 1 percent of patients the changes
preclude a return to work and normal daily activities. [355 ] , [359 ] , [363 ]
The behavioral changes that are associated with intensive care unit stays longer than
48 hours and that disappear within 48 hours after transfer from the intensive care unit do
not appear to have an organic basis but are more likely in postoperative cardiac
patients, particularly elderly patients, because of cardiopulmonary bypass,
microembolization, and probable metabolic factors.
BACKGROND
Cardiovascular disease is the leading cause of death in the United States, resulting in
nearly 1 million deaths annually. Over 6 million people in the United States have
significant coronary artery disease (CAD), and up to 1.5 million will have an acute
myocardial infarction (AMI) annually. [1 ] An estimated 478,000 deaths in 1991 were
due to coronary artery disease. [1 ] Forty-five percent of MIs and one-third of related
deaths occur in persons less than 65 years of age. [1 ] Although the death rate from
cardiovascular disease decreased 25.7 percent between 1981 and 1991, the actual
number of deaths decreased only 6.1 percent because of the aging U.S. population. [1 ]
, [2 ]
Sudden cardiac death is the unexpected, nontraumatic abrupt cessation of effective

cardiac function in a patient with either no symptoms or acute symptoms for less than 1
hour. [3 ] , [4 ] Prodromal symptoms such as chest pain, palpitations, and fatigue may
be present within the preceding 24 hours. [4 ] One-half to two-thirds of deaths
secondary to coronary artery disease (CAD) occur suddenly (approximately 300,000
per year), usually within 2 hours of the onset of symptoms. [1 ] , [5 ] [7 ] Each year
250,000 victims of sudden cardiac death die before reaching a hospital. [1 ] Of note,
the percentage of deaths that are sudden has not changed as the mortality rate due to
CAD has decreased. [8 ] Although the vast majority of sudden deaths in this country are
secondary to CAD, other etiologies may be responsible (Table 14-1) .
Cardiopulmonary resuscitation (CPR) was developed as a means to reverse sudden

cardiac death. Since the introduction of modern CPR in the 1960s, resuscitation
attempts have become common occurrences. CPR is performed on 1 to 2 percent of all
patients admitted to teaching hospitals. In all, about 30 percent of patients who die in
teaching hospitals undergo resuscitation attempts. [9 ] , [10 ]
The goal of CPR is to restore circulation before permanent neurologic damage occurs.
[11 ] Although many lives have been saved by CPR, current resuscitation techniques still
yield relatively low survival rates. Furthermore, there are still many survivors who are
severely neurologically impaired, particularly following out-of-hospital arrest. [12 ] , [13 ]
Although it was thought originally that closed chest massage would allow survival of
prolonged periods of arrest, [14 ] this is rarely the case. It must be emphasized that
CPR is a temporizing measure, and rapid, definitive treatment is vital to achieve
long-term survival. [15 ]
HISTORY OF CARDIAC RESUSCITATION
CPR as now practiced dates back only about 35 years, but interest in reviving the dead
and dying dates to ancient times. Resuscitation of the dead is a recurrent theme in
ancient mythology. [16 ] Biblical accounts of resuscitations by the prophets Elisha and
Elijah are well documented. [16 ] , [17 ] Rolling the chest over a barrel and lying the
victim across the back of a galloping horse are among the more interesting techniques
used in the past. [18 ] In 1744 Tossach successfully resuscitated a drowning victim
using mouth-to-mouth breathing, [19 ] but this technique was abandoned for mechanical
methods of artificial respiration. [20 ] Koenig described survival after closed chest
massage in humans in 1885. [21 ] However, open cardiac massage became the
preferred technique following the report of its success by Tuffier and Hallion in 1898. [20
] , [22 ] Prevost and Batelli in 1899 reported termination of ventricular fibrillation in the
open-chested dog using alternating current. [23 ]
In the early years of this century Crile described both open and closed techniques of
cardiac masssage. Crile recognized the importance of achieving adequate coronary
perfusion pressure and the value of epinephrine. [24 ] [26 ] Interest in ventricular
fibrillation grew during the first half of the twentieth century because of the increasing
use of electricity. High fatality rates among electrical workers led Con Edison to support
development of the electrical defibrillator by Hooker, Kouwenhoven, and Langworthy at
Johns Hopkins. [27 ] Wiggers also made significant contributions to understanding the
pathophysiology of ventricular fibrillation. [28 ] Beck reported the first successful case of
open defibrillation in 1947, [29 ] and in 1956 Zoll reported successful closed chest
defibrillation using alternating current. [30 ]
In the late 1950s Safar and Elam demonstrated that mouth-to-mouth rescue breathing
was superior to mechanical techniques, such as the Shafer prone-pressure method. [31
] [33 ] Around this time interest in closed cardiac massage was rekindled. While
working on the electrical defibrillator, Kouwenhoven and Knickerbocker noted femoral
pulsations when defibrillator paddles were pressed firmly on the sternum. [27 ] Further
work by these investigators along with Jude led to the development of modern closed
chest resuscitation. [14 ] In 1958 Bahnson used the newly developed closed cardiac
massage to resuscitate a small child. [27 ] The report of closed chest cardiac massage
combined with mouth-to-mouth ventilation and electrical defibrillation by Kouwenhoven
et al. [14 ] in 1960 marked the beginning of the modern era of CPR.
CARDIOPULMONARY RESUSCITATION (CPR)
Basic life support (BLS) attempts to provide adequate ventilation and blood flow to
sustain life until advanced cardiac life support (ACLS) measures can restore
spontaneous circulation. BLS uses an ABC algorhithm (airway, breathing, circulation) to
provide a standardized approach to the patient in cardiac arrest [34 ] (Fig. 14-1) .
Airway
BLS AIRWAY MANAGEMENT
Management of the unconscious patient
After unresponsiveness is verified and the emergency medical system (EMS) system is
activated, the initial step is to ensure a patent airway. [34 ] The patient is positioned
supine on a firm surface. The preferred method of opening the airway is the
head-tilt-chin-lift maneuver. [34 ] An alternative technique is the jaw-thrust technique,
which is recommended for patients with suspected head and neck trauma. [34 ]
However, the jaw-thrust is technically difficult and more fatiguing than the
head-tiltchin-lift. [35 ] Posterior displacement of the tongue is the most common cause
of airway obstruction in an unconscious patient. [36 ] , [37 ] Either of these techniques
relieves obstruction due to the tongue. [35 ]
Once an open airway is established, the rescuer looks for signs of breathing, using the
look, listen, feel method: Look for chest movement, listen for sounds of air flow, and feel
for air movement. If no signs of respiration are present after 3 to 5 seconds, rescue
breathing is initiated. If unable to ventilate the patient, the rescuer should reposition and
attempt to ventilate again. If still unable to ventilate, airway obstruction from a foreign
body should be suspected. [34 ]
Foreign-body airway obstruction
The Heimlich maneuver, or subdiaphragmatic abdominal thrust , is the recommended

method for relief of airway obstruction secondary to foreign bodies. [38 ] The rescuer
administers rapid upward thrusts to the subxiphoid region with his or her fists from
behind the victim. This produces a forced expiration with high airway pressures, which
may dislodge an obstructing foreign body. [39 ] This maneuver is repeated up to five
times if necessary. After performing the thrusts, the mouth is opened, a finger sweep is
performed, and ventilation is reattempted. The sequence is repeated until ventilation is
established. The chest thrust is recommended for markedly obese patients and women
in the late stages of pregnancy. [34 ] Back blows are not recommended for adult
resuscitation. [39 ] Use of instruments, such as Magill forceps, to retrieve foreign bodies
should be performed only by trained personnel. [34 ]
ADVANCED AIRWAY MANAGEMENT
Masks and oral and nasal airways

Masks should form a tight seal and have a one-way valve to divert exhaled air. They
may be used for mouth-to-mask ventilation or with bag-valve devices. Mannequin
studies have shown that mouth-to-mask breathing is more reliable in providing
adequate tidal volumes than bag-valvemask respiration. [40 ] [42 ] Bag-valve devices
may be used with masks, endotracheal tubes, or other airway devices, but only when
two or more rescuers are present. [43 ] An oropharyngeal or nasopharyngeal airway
should be used for nonintubated patients. Oropharyngeal airways are not used in
conscious patients because of the risk of laryngospasm and regurgitation. [43 ]
Endotracheal intubation
Endotracheal intubation (ETT) is the preferred method of airway management. In

addition to maintaining an open airway, an endotracheal tube decreases the risk of
gastric distension and aspiration. [43 ] ETT also provides a route for administration of
drugs if no intravenous access is available. [44 ] Indications for endotracheal intubation
are (1) inability to ventilate an unconscious patient, (2) inability to protect the airway, (3)
cardiac arrest with ongoing CPR, and (4) inadequate ventilation in a conscious patient.
[43 ] Orotracheal intubation is preferred for the cardiac arrest victim. If a neck injury is
suspected and the victim is breathing spontaneously, nasotracheal intubation is
indicated. Once proper tube placement is confirmed, a 10 to 15 ml/kg tidal volume is
delivered at the rate of 10 to 12 breaths per minute. [43 ] End-tidal co 2 monitoring may
be used as an adjunctive measure to confirm tube placement. If co 2 is not detected with
expiration, esophageal intubation is the most likely cause. [45 ] , [46 ] Complications of
endotracheal intubation include esophageal intubation, oral trauma, pharyngeal
laceration, vocal cord injury, pharyngeal-esophageal perforation, main-stem bronchus
intubation, and aspiration. [47 ] [49 ]
Esophageal airways
The esophageal obturator airway and the esophageal gastric tube are used commonly
in the prehospital setting but are associated with significant rates of serious
complications, including esophageal perforation or laceration, inadvertent tracheal
placement, and aspiration. [50 ] , [51 ] Esophageal airways should be replaced with an
ETT as soon as possible. The pharyngotracheal airway and esophageal-tracheal tube
are double-lumen tubes that are inserted blindly into the pharynx. Placement is
assessed, and the proper lumen is then ventilated. [52 ] , [53 ]
Transtracheal catheter ventilation
Transtracheal catheter ventilation (TTC) is a temporizing method for use when ETT
cannot be done. A catheter is passed through the cricothyroid membrane and attached
to a high-pressure oxygen source (30 to 60 lb/in [2 ] ). Air flows into the lungs under
positive pressure. Exhalation occurs passively when a valve is released. TTC provides
adequate oxygenation, but ventilation is usually inadequate and leads to a respiratory
acidosis. [54 ] Complications of TTC include pneumothorax, hemorrhage, and
esophageal perforation. [55 ]
Cricothyroidotomy
Cricothyroidotomy is an alternative when attempts at endotracheal intubation are
unsuccessful. [56 ] Possible complications of cricothyroidotomy include hemorrhage,
esophageal perforation, and mediastinal and subcutaneous emphysema. [57 ]
Tracheostomy is rarely indicated for acute management of cardiac arrest.
Breathing
For basic lifesaving with no airway device in place, mouth-to-mouth breathing is

recommended. It is easily learned, rapidly applied, and effectively provides oxygen. [33 ]
Exhaled air has an FIo 2 of 0.16 to 0.17, resulting in an alveolar Po 2 of approximately
80 mmHg. [43 ] Two slow breaths (2 seconds each) are given initially. A tight seal
between rescuer and patient is essential. Chest movement during inspiration and air
movement during passive exhalation are confirmed. In adults, 800 to 1200 ml of air are
needed to move the chest wall. The recommended rate of rescue breathing is 10 to 12
breaths per minute. [43 ] Maintaining an open airway during both phases of respiration
and giving breaths slowly minimize the risk of gastric distension and aspiration. [42 ] ,
[57 ] , [58 ] Mouth-to-nose breathing is recommended when the mouth cannot be
opened or a tight mouth-to-mouth seal is not achieved. Cricoid pressure, the Sellick
maneuver, may be used to decrease the risk of gastric distension and regurgitation
when two rescuers are involved. [59 ] Barrier devices, such as face shields and mask
devices, may be used when available to protect medical personnel from exposure.
Supplemental oxygen is administered in the highest concentration feasible when it is
available.
Closed Chest Massage
TECHNIQUE
Closed cardiac massage (CCM) is indicated when the unresponsive patient is

pulseless. Absence of a pulse is confirmed by palpation of the carotid or femoral artery.
Peripheral pulses, i.e., in the radial artery, are unreliable. CCM is performed with the
victim supine on a flat, firm surface. If the patient is in bed, a backboard is placed
beneath him or her. The heel of one hand is placed on the lower half of the sternum, and
the other hand is placed on top of it. The thrust of compression is delivered directly
downward (Fig. 14-2) . The recommended rate is 80 to 100 compressions per minute,
and the recommended depth in an adult is 4 to 6 cm (1.5 to 2 in). [34 ] The compression
phase should occupy 50 percent of the cycle. [60 ] Pressure is released completely
after each downstroke to allow ventricular filling and coronary blood flow. The hands
should maintain contact with the chest wall during the release phase to avoid having to
reposition them between compressions. [43 ]
HEMODYNAMICS
Cardiac output during closed cardiac massage is only approximately 25 to 30 percent

of normal. [61 ] [64 ] Standard CPR generates systolic blood pressures of 60 to 80
mmHg, but diastolic pressures are commonly less than 20 mmHg. [65 ] Mean carotid
pressure is typically less than 40 mmHg, which produces cerebral blood flows of 10 to
15 percent of baseline. [65 ] Coronary blood flow is even more compromised, usually
being only 1 to 5 percent of normal with standard CPR techniques. [66 ] [68 ] Alternative
techniques of CPR have been shown in the laboratory setting to provide better
myocardial blood flows. Maier et al. [64 ] showed that high-impulse CPR at a rate of 120
compressions per minute could generate coronary flows up to 75 percent of normal in
the canine model. Yet cardiac output was still only 36 percent of normal with this
technique. Although superior to outputs noted in most studies, this cardiac output is
inadequate to sustain vital organ function for prolonged periods. CCM as currently
practiced is strictly a temporizing maneuver that only delays the inevitable deterioration
from cardiac arrest. Hemodynamics are marginal early in the resuscitation and quickly
deteriorate. However, CCM does provide valuable time, albeit brief, during which the
institution of definitive treatment may be lifesaving.
ASSESSMENT OF ONGOING CARDIAC MASSAGE
There are no perfect clinical indicators of the efficacy of ongoing CPR. In particular, the
femoral pulse is unreliable, for it merely indicates a difference between systolic and
diastolic pressures. [69 ] It does not indicate effective blood flow and, in fact, may be
due to pressure changes in the femoral vein rather than in the artery. [70 ] Signs of
neurologic function, such as pupillary reaction and spontaneous respiratory efforts,
indicate good perfusion but are insensitive. [71 ] The best indicator of effective CPR is
the aortic diastolic pressure. [72 ] Unfortunately, this information usually is not available
in the clinical setting. If arterial and central monitoring lines are in place at the time of
arrest, they should be used to maximize coronary perfusion pressure
(aortic-diastolic-right-atrial pressure). If they are not in place, CPR must proceed without
them.
Recently, interest has focused on end-tidal co 2 (ETco 2 ) as an indicator of the efficacy

of resuscitative efforts. ETco 2 correlates with cardiac output during CPR and provides
information regarding endotracheal tube position. [46 ] , [73 ] , [74 ] It also may be
predictive of survival. [75 ] , [76 ] A low ETco 2 is indicative of insufficient support and
may be due to esophageal intubation, airway obstruction, inadequate CPR, massive
pulmonary embolus, or hypothermia. [77 ] A major advantage of ETco 2 is that it is
noninvasive.
COMPLICATIONS OF CLOSED CHEST MASSAGE
The most common injuries from chest compressions are rib fracture (30 percent) and
sternal fracture (20 percent). [78 ] Other common complications include aspiration,
gastric dilatation, anterior mediastinal hemorrhage, epicardial hematoma,
hemopericardium, myocardial contusion, pneumothorax, coronary air embolus,
hemothorax, lung contusion, and oral and dental injuries. [78 ] [80 ] The liver is the most
commonly injured intraabdominal organ, with rupture occurring in about 2 percent of
cases. The spleen is infrequently injured and ruptures in less than 1 percent of
resuscitation attempts. [78 ]
Rare injuries (incidence less than 1 percent) include tracheal injuries, esophageal
rupture, gastric rupture, cervical spine fracture, vena caval injury, retroperitoneal
hemorrhage, and myocardial laceration. [78 ]
Complications may occur even with properly performed CPR, especially rib and sternal
fractures. The possibility of injury should not deter the vigorous application of CPR,
since the outcome without effective resuscitation is certain death. Life-threatening
injuries from CPR, such as laceration of the heart or great vessels, are rare. Proper
techniques will lessen the incidence of serious complications.
CARDIAC ARREST
Cardiac arrest is the final manifestation for three different pathophysiologic conditions:
ventricular fibrillation/tachycardia (VF/VT), asystole, and electromechanical dissociation
(EMD), also called pulseless electrical activity . These three dysrhythmias have
different etiologies, priorities of treatment, and prognoses. Early identification of the
underlying dysrhythmia is vital for successful resuscitation.
Ventricular Fibrillation/Ventricular Tachycardia
Ventricular tachycardia (VT) is a reentrant arrhythmia characterized by three or more

premature ventricular depolarizations at a rate greater than 100 beats per minute.
Cardiac arrest may occur with rapid, sustained VT. Ventricular fibrillation (VF) is
characterized by uncoordinated, continuous contraction of the ventricular myocardium,
which does not produce forward blood flow. Holter monitor studies have shown that 80
to 90 percent of nontraumatic cardiac arrests originate with VF/VT. [81 ] Over 90
percent of survivors in most series have VF/VT as the initial rhythm. [82 ] , [83 ] Rapid
defibrillation is the most important determinant of survival after cardiac arrest. [84 ] [86 ]
Therefore, the overriding priority of treatment of cardiac arrest is early identification and
treatment of ventricular fibrillation. Defibrillation should precede BLS maneuvers if a
defibrillator is available. [43 ] Time is the major determinant of successful defibrillation.
[87 ] , [88 ] The mortality from ventricular fibrillation increases 4 to 10 percent for every
minute that the first defibrillation attempt is delayed. [86 ] , [87 ] , [89 ] If the first
countershock is delivered more than 10 to 12 minutes after the onset of the arrest, the
survival rate approaches zero. [90 ] These facts led the American Heart Association
(AHA) to recommend that the first responder to a cardiac arrest call for emergency
medical assistance prior to initiating CPR so that a defibrillator can be brought to the
patient's side promptly. [11 ]
TREATMENT
The treatment of VF follows the AHA guidelines, beginning with immediate defibrillation
if possible [43 ] (Fig. 14-3) . If no defibrillator is available, CPR is initiated until one
arrives. The recommended energy for the initial defibrillation attempt is 200 J. The
electrodes should remain in place on the chest between defibrillation attempts. If the
monitor continues to show VF, no time is taken to perform a pulse check, and a second
shock of 200 to 300 J is given immediately. If VF persists, a third countershock of 360 J
is delivered. It is vital that the three shocks be given consecutively and without delay for
ventilations, chest compressions, or other interventions. [43 ] The European
Resuscitation Council recommends giving four sets of three consecutive shocks with a
1-mg bolus of epinephrine after each set before any other drugs are considered. [91 ]
After a failed third defibrillation attempt, CPR is performed, the patient is intubated, and
intravenous (IV) access is obtained. Epinephrine 1 mg IV (2.5 mg via endotracheal tube
if IV access is not available) is given, and defibrillation is attempted once again with
360 J. The ACLS (advanced cardiac life support) provider may choose to use three
stacked shocks again at this point. Subsequently, epinephrine is given every 3 to 5
minutes throughout the resuscitation. Refractory VF is treated with the class IIa
(acceptable, probably helpful) antiarrhythmic agents lidocaine, bretylium, and
magnesium sulfate, giving a 360-J shock within 30 to 60 seconds of each drug. [43 ]
PROGNOSIS
VF/VT has a better prognosis than asystole or electromechanical dissociation (EMD),

with up to 30 percent of patients resuscitated successfully. [92 ] , [93 ] Early defibrillation
has been shown conclusively to improve survival in out-of-hospital arrest. [84 ] , [85 ]
Eisenberg et al. [84 ] reported an increase in survival to discharge from 7 percent with
standard CPR to 26 percent with defibrillation in the field. Stults et al. [85 ] found a 19
percent survival rate with defibrillation in the field compared with a 3 percent rate with
standard CPR and defibrillation in the emergency room. Failure to respond to the initial
series of shocks is a poor prognostic sign, but efforts should continue. At this point
attention should be directed to correcting metabolic problems and providing effective
ventilation and circulation, with attempts to defibrillate at appropriate times during the
resuscitation. [43 ]
Asystole
Asystole is the complete absence of electrical and mechanical cardiac activity and is
usually a terminal event. [43 ] However, some patients with asystole survive, and initially,
every effort should be made to resuscitate them. The priorities of treatment of asystole
are to confirm the rhythm and to establish effective coronary perfusion. [94 ] One animal
study has shown that fine VF may have an isoelectric vector, thereby masquerading as
asystole in certain electrocardiographic (ECG) leads. [95 ] However, evidence indicates
that this phenomenon may be rare in human cardiac arrest victims; it occurred in only
2.5 percent of patients with an initial diagnosis of asystole in a study by Cummins and
Austin. [96 ] More common causes of the erroneous diagnosis of asystole are incorrect
lead placement and equipment misuse or malfunction. [96 ] In any case where asystole
is identified, a quick check of all leads and connections and confirmation of asystole in
more than one ECG lead are indicated. There is no benefit to countershock in true
asystole, and it is not recommended. [97 ] , [98 ] In fact, countershocks induce a
parasympathetic discharge, which may diminish chances of restoring circulation. [99 ] ,
[100 ] Nevertheless, if there is any possibility that the rhythm is fine VF, defibrillation
should be attempted.
TREATMENT
After securing the airway and providing ventilation and chest compressions,
epinephrine 1 mg IV should be administered to raise aortic diastolic and coronary
perfusion pressures [43 ] , [101 ] (Fig. 14-4) . Epinephrine is repeated every 3 to 5
minutes during the resuscitation. Atropine 1 mg IV repeated every 3 to 5 minutes to a
total dose of 0.03 to 0.04 mg/kg is given because high parasympathetic tone underlies
some bradyasystolic arrests. [99 ] , [100 ] , [102 ] In rare cases, transcutaneous or
transvenous pacing therapy may be effective if applied early. [103 ] However, if applied
after myocardial high-energy phosphates are depleted, mechanical work will not occur
even if electrical capture is possible. [104 ]
PROGNOSIS
Asystole has a grim prognosis, with less than 2 percent of patients surviving to
discharge. [105 ] If asystole occurs after countershock of VF early during a
resuscitation, the patient may survive; however, if asystole occurs after prolonged CPR,
it is typically fatal. [106 ]
Electromechanical Dissociation/Pulseless Electrical Activity
Electromechanical dissociation (EMD) is characterized by organized electrical activity

without effective cardiac contractions. The AHA now uses the term pulseless electrical
activity (PEA) to encompass EMD, as well as pulseless idioventricular, bradycardic,
and ventricular escape rhythms. [43 ] Pulseless idioventricular, bradycardic, and escape
rhythms have an extremely poor prognosis. [107 ] , [108 ] PEA is the most common
proximate cause of death in delayed or difficult resuscitations. [94 ]
TREATMENT
The priority of treatment of EMD is identification and treatment of reversible causes.

These are listed in Table 14-2 . A rapid, narrow-complex rhythm is often an indicator of
a treatable etiology of EMD. [94 ] , [109 ] Patients are rarely resuscitated from EMD if a
reversible cause is not found. After reversible causes have been ruled out, the focus is
directed toward providing adequate ventilation and effective chest compressions in an
attempt to provide effective coronary perfusion (Fig. 14-5) . In addition to BLS
maneuvers, epinephrine is given to improve cerebral and coronary perfusion pressures.
[108 ] , [110 ] [112 ] Atropine is indicated if bradycardia is present. [43 ] Patients with
EMD following penetrating chest trauma should undergo emergency left anterolateral
thoracotomy. [113 ] Thoracotomy allows identification and management of reversible
causes of EMD, such as tension pneumothorax, cardiac tamponade, and hypovolemia,
as well as open cardiac massage and occlusion of the descending thoracic aorta.
DEFIBRILLATION
Defibrillation is the application of an electric current to the heart in an attempt to

terminate a nonperfusing rhythm and restore a perfusing rhythm. It is the only effective
treatment for ventricular fibrillation (VF). Defibrillation depolarizes the entire heart,
resulting in temporary asystole. [100 ] , [114 ] Then pacemaker cells resume normal
rhythmic activity. Sufficient myocardial high-energy phosphate (HEP) stores must be
present for contractions to resume. [115 ] , [116 ] HEP stores are rapidly depleted
during global ischemia [118 ] ; therefore, it is imperative to defibrillate the heart early,
before HEP levels are reduced.
The probability of successful defibrillation is as high as 90 percent when it is performed

immediately at the time of arrest. [117 ] [119 ] This probability declines rapidly with time.
The rate of return of spontaneous circulation decreases 7 to 10 percent per minute
during cardiac arrest. [90 ] If a defibrillator is not immediately available, CPR is
performed in an attempt to maintain vital organ perfusion until a defibrillator becomes
available. Although CPR maneuvers may slow the rate of deterioration, they do not
prevent or reverse it. Once a defibrillator is available, it should be attached immediately
to look for VF/VT. Quick-look paddles allow rescuers to evaluate the underlying rhythm
by placing the paddles on the chest. If VF or pulseless ventricular tachycardia is
present, defibrillation is performed immediately. Blind defibrillation is rarely needed due
to this ability to determine the rhythm with the quick-look method. When cardioverting
VF or pulseless ventricular tachycardia, the shocks are delivered asynchronously.
Cardioversion should be synchronized for more stable rhythms such as atrial fibrillation
or flutter and monomorphic VT. [43 ] If an asynchronous countershock is given for one of
these rhythms and comes during the relative refractory period, VF may result. [120 ]
Energy Requirements
The energy level used for defibrillation is of the utmost importance. If the energy level is
too low, the current delivered to the heart will be inadequate to convert it into a stable
rhythm. On the other hand, myocardial injury may occur if the energy is excessive. [121 ]
, [122 ] In general, the lowest energy level that will reliably defibrillate the heart is
preferred in order to minimize the risk of myocardial injury. A prospective study
demonstrated that 175 J was as effective for the first attempt as 320 J. [123 ] Based on
these data, the recommended energy for the first shock is 200 J. [43 ] Approximately 90
percent of adults will defibrillate with 200 J if it delivered early enough. [124 ] , [125 ] The
range of energy for the second countershock is 200 to 300 J. The decrease in
transthoracic impedance that occurs with repetitive shocks supports the use of 200 J for
the second attempt. [126 ] , [127 ] Therefore, the current passing through the heart will
be greater with the second shock even though the energy is the same. However, some
investigators believe that the decrease in transthoracic impedance in humans is
relatively small and that increasing the energy level to 300 J provides a more reliable
increase in the delivered current. [126 ]
Defibrillation depends on passing sufficient current through the heart within a brief time
period. [128 ] Modern defibrillators deliver a single pulse of direct current with a
damped half-sinusoidal waveform. [129 ] Although defibrillation is dependent on current,
defibrillators are configured to allow the operator to select the energy level. The actual
current delivered depends on the energy applied and the resistance (transthoracic
impedance) through which it travels. The energy-current relationships are shown in
Table 14-3 . [129 ]
Transthoracic Impedance
Because there is no precise correlation between body size and energy requirements in
adults, the AHA guidelines specify energy levels, i.e., 200 J, to be used for all adults
rather than basing the energy level on body weight. [43 ] The optimal current for
defibrillation is 30 to 40 A. [130 ] [132 ] For adults with an average transthoracic
impedance of 70 to 80 , a 200-J countershock will deliver a current of approximately 30
A. [129 ] However, the range of impedance in humans varies from 15 to 150 . [126 ] ,
[127 ] , [130 ] [132 ] Transthoracic impedance depends on many factors, including the
energy selected, chest size, electrode size, interelectrode distance, paddle-skin
coupling, phase of respiration, and antecedent countershocks [126 ] , [127 ] , [133 ] ,
[134 ] (Table 14-4) . The technique used for defibrillation is important in minimizing
transthoracic impedance. The electrodes are positioned to maximize current flow
through the heart.
There are three acceptable external paddle placement options. The most commonly
used placement is one electrode to the right of the sternum below the clavicle, with the
other in the left midaxillary line at the level of the nipple. Equally acceptable alternatives
are anteroposterior and apical-posterior. [43 ] The electrodes must not touch, and there
should be no contact between the conductive gel of the two electrodes. If there is
contact between the electrodes or the gel, current will travel through the path of least
resistance, the chest wall, and not pass through the heart. During open chest
resuscitation, one internal paddle is placed over the right ventricle, and the other is
placed behind the apex. Larger paddle size results in lower resistance. [126 ] , [134 ]
Most adult paddles are 8 to 12 cm in diameter. Smaller, pediatric paddles have high
impedance and should be used only if adult paddles will not fit on the chest, e.g., in
children less than 10 kg or about 1 year of age. [136 ]
Defibrillation Threshold
The defibrillation threshold (DFT) is the amount of current required to defibrillate the
heart. The DFT increases with time. The most important factor affecting the DFT is
coronary perfusion pressure. Catecholamines decrease the DFT. [142 ] [144 ] It was
once thought that epinephrine decreased the DFT by increasing the coarseness of VF.
Currently, it is understood that epinephrine's beneficial effect on DFT is due primarily to
increased coronary perfusion pressure (alpha-adrenergic receptor stimulation) not
increased amplitude of VF (beta-adrenergic effect). [145 ] The underlying mechanism of
the time-dependent increase in DFT during VF is not completely understood. The DFT
is not affected by metabolic or respiratory acidosis. [146 ] , [147 ] Recent work
implicates adenosine, via adenosine A1-receptor antiadrenergic effects, as a possible
mediator of the increase in DFT with time. [148 ] Aminophylline, an adenosine receptor
antagonist, decreases the defibrillation threshold. [149 ] [151 ]
Special Situations
In patients with pacemakers, the paddles should not be placed directly over the
generator. [137 ] The pacemaker must be interrogated and pacing thresholds
determined after the defibrillation episode. In recent years many patients at high risk for
sudden cardiac death have had placement of automatic internal
cardioverter-defibrillators (AICDs). If VF or pulseless VT is present in a patient with an
AICD, external defibrillation should be performed immediately. [128 ] AICDs are
shielded to withstand external countershocks. If the AICD discharges when the rescuer
is in contact with the patient, a shock may be felt, but it poses no danger to the rescuer.
AICD patches may increase transthoracic resistance. [138 ] Therefore, if the patient
fails to respond to 360 J, the electrode position should be changed and shocks
readministered. After successful external defibrillation, the AICD unit should be tested.
New Techniques of Defibrillation
The automated external defibrillator (AED) is being used increasingly by emergency

medical technicians. The AED uses an algorithm to analyze the ECG pattern for VF.
When VF is present, the device sounds an alarm and then discharges. AEDs require
less training than conventional defibrillators, and there is less delay in administering the
countershock. [90 ] , [152 ] , [153 ] Several studies with AEDs have shown equivalent or
improved survival compared with early defibrillation using manual defibrillators. [154 ]
[156 ] AEDs are endorsed by the AHA for use in out-of-hospital arrest. [157 ]
Because current delivered depends on impedance, the recommended energy levels

may be excessive or inadequate for a given patient. In an attempt to maximize the
potential for defibrillation and minimize the risk of myocardial damage, current-based
defibrillators have been developed. [130 ] , [131 ] , [139 ] These devices allow the
operator to select the amount of current. The transthoracic impedance is measured by
the device, which then delivers the appropriate amount of energy to generate the
desired current. Other areas of investigation include delivery of biphasic (bidirectional)
or multipulse, multipathway shocks. [129 ] These techniques are in use for internal
defibrillators, but their efficacy for external defibrillation has not been established. [140 ]
, [141 ]
Precordial Thump
The precordial thump may be used in witnessed arrests when a defibrillator is not
immediately available. The 1992 AHA guidelines classify the precordial thump as a
class IIb intervention (acceptable, possibly helpful). [43 ] It has been reported to convert
VT to sinus rhythm in 11 to 25 percent of cases. [158 ] , [159 ] However, it may convert
VT to VF, asystole or EMD. [159 ] , [160 ] It is rarely effective in converting VF. A
precordial thump is contraindicated for unwitnessed or out-of-hospital arrests. [43 ]
PHYSIOLOGY OF CLOSED CHEST CARDIAC MASSAGE
Mechanism of Blood Flow
The mechanism by which closed cardiac massage (CCM) generates forward blood
flow has been the subject of numerous investigations and great debate. Kouwenhoven
originally postulated that CCM generated flow by compressing the heart between the
sternum and the spine. [14 ] , [161 ] According to this theory, compression of the heart
decreases ventricular volume with a corresponding increase in intraventricular pressure,
forcing blood into the aorta and pulmonary artery with the cardiac valves directing flow.
This mechanism was widely accepted at the time and has become known as the
cardiac pump . Of note, it now has been demonstrated that compression of the heart
against the spine posteriorly is not mandatory and that the inertia of the heart may
provide the counterforce to allow cardiac compression.[162 ]
However, the cardiac pump hypothesis was challenged when Criley et al. [163 ]
observed that patients who fibrillated during cardiac catheterization could maintain
consciousness by coughing. Direct cardiac compression cannot explain cough CPR.
Therefore, an alternative explanation was sought, leading to the formulation of the
thoracic pump hypothesis. According to this theory, chest compression generates
uniform increases in the pressures in all intrathoracic structures. Forward blood flow
results from pressure gradients between the intrathoracic aorta and the extrathoracic
systemic arteries. Venous backflow is prevented by venous valves at the thoracic inlet.
[164 ] , [165 ] In the thoracic pump model the heart functions as a passive conduit. The
mitral valve remains open, and there is antegrade flow across the mitral valve during the
compression phase of CPR.
Proponents of each theory have cited circumstances in which the other mechanism
cannot account for the effectiveness of resuscitation. [66 ] The ability to resuscitate
individuals with open pneumothoraces is often cited as an exception to the thoracic
pump model. In addition, some have questioned how the thoracic pump could be
effective for intubated patients in whom the airway is vented. Halperin et al. [166 ] have
countered these arguments with their finding that increased intrathoracic pressure
occurs secondary to air trapping in small airways even when the upper airway is open.
Another criticism of the classic thoracic pump hypothesis is that it does not provide a
mechanism for coronary flow. Advocates of the thoracic pump theorize that during the
release phase, a small pressure gradient develops between the aorta and right atrium,
generating the coronary perfusion pressure. A small amount of backflow in the aorta
during the release phase, when intrathoracic aortic pressure falls below peripheral
arterial pressure, provides myocardial flow. [18 ]
The cardiac pump hypothesis has been criticized for being unable to explain cough
CPR. Another example used against the cardiac pump model is the ineffectiveness of
CPR in patients with flail chest. According to thoracic pump proponents, the mobility of
the chest wall with flail chest should allow more effective resuscitation if the cardiac
pump mechanism were operative. However, Feneley et al.[162 ] have argued that flail
chest actually may decrease the effectiveness of the cardiac pump mechanism by
allowing displacement of the heart in reaction to the compression force.
Investigations into the mechanism of flow in experimental animal models have yielded
conflicting results. Some investigators have found equal increases in central venous,
right atrial, pulmonary arterial, aortic, and pleural space pressures during the
compression phase of CCM. [65 ] , [168 ] In addition, Niemann et al. [169 ]
demonstrated open mitral and aortic valves and forward flow into the aorta during
compression using cineangiography. Furthermore, Halperin et al. [170 ] found that vital
organ perfusion depended more on the duration of compression than on the rate, which
supports the thoracic pump model.
In contrast, investigators at Duke University found that changes in intrathoracic vascular

pressures were two to four times greater than changes in pleural pressures during chest
compression in a chronically instrumented canine model.[64] This finding is not
consistent with the thoracic pump mechanism. Further studies by this group have shown
that the thoracic pump mechanism is operative only with low-force, prolonged
compressions. Otherwise, direct cardiac compression generates blood flow. [171 ] ,
[172 ] Echocardiographic studies demonstrate that the mitral valve closes and there is
no antegrade flow across the valve during compressions. In addition, the left ventricle
deforms asymmetrically, a finding consistent with the cardiac pump hypothesis. [172 ]
Hackl et al. [173 ] also demonstrated mitral valve (MV) closure with echocardiography.
Furthermore, they found that MV closure is associated with improved cardiac output,
cerebral perfusion pressure, and blood flow. Further work demonstrated a relatively
constant stroke volume with different heart rates during external massage. [174 ]
Deshmukh et al. [175 ] demonstrated MV closure during the compression phase of
CCM in minipigs. Cardiac output and coronary and cerebral pressures were higher in
animals with MV closure, and MV closure was associated with successful resuscitation.
Survival studies have shown that high-impulse CPR, a technique that augments the
cardiac pump mechanism, improves survival compared with standard CPR. [176 ]
The discrepancies in the findings of these studies may be due to methodology. As

Feneley et al. [162 ] pointed out, many major studies supporting the thoracic pump
theory used mechanical chest compression. [61 ] , [164 ] , [168 ] , [169 ] It may be
inappropriate to extrapolate data from mechanical compression techniques to manual
ones. Mechanical devices have been shown to favor the thoracic pump mechanism and
to be less effective in generating cardiac compression than manual techniques. [64 ]
Studies that support direct cardiac compression were performed utilizing manual
compression. The rate of chest compressions also may be a critical factor in
determining the operative mechanism in a given study. When force is applied to the
chest, the heart may either be compressed or displaced. [162 ] Low-velocity
compressions favor displacement and hence the thoracic pump mechanism.
High-impulse compressions favor cardiac compression, since the inertia of the heart
resists displacement over a short time period. [162 ]
Attempts to determine the operative mechanism of blood flow in humans have

predominately utilized echocardiography. The key differentiating features of the cardiac
and thoracic pump mechanisms are the position of the MV leaflets and whether
antegrade flow through the MV occurs during compression. Some investigators have
disputed the reliability of MV closure as a distinguishing feature, since Halperin et al.
[167 ] have demonstrated that MV closure can occur secondary to increased
intrathoracic pressure. Two studies using transthoracic echocardiography (TTE)
support the thoracic pump theory. They found that the MV was open throughout CCM,
while the aortic valve opened during compression and closed during release. [177 ] ,
[178 ] However, these studies have significant limitations. In addition to the inherent
difficulty in performing TTE during active CCM, all patients were studied late in the
resuscitation attempt, CPR was performed at a rate of 60 compressions per minute,
and none of the patients survived.
Recently, TEE has been used to evaluate CCM. Some studies have demonstrated an
open MV during compression. [179 ] Porter et al. [180 ] performed TEE in 17 adults in
cardiac arrest. The MV closed in 12 of the 17 during compression, but MV closure was
not related to left ventricular (LV) fractional shortening. The authors concluded that MV
closure was likely due to increases in intrathoracic pressure, not direct cardiac
compression. Of note, MV closure was a positive prognostic sign for successful
resuscitation. It is unclear why MV closure would be favorable if the thoracic pump were
operative. The major shortcomings of this study were that the patients underwent
variable periods of CPR in the field before arrival in the emergency room and
compressions were done with a mechanical piston device. On the other hand, Redberg
et al. [181 ] demonstrated direct cardiac compression in 18 patients studied with TEE
within 7 minutes of initiating CPR. Other investigators also have noted MV closure
during CCM. [182 ] , [183 ]
Without question, both the cardiac pump and thoracic pump mechanisms can occur
with CCM. Which mechanism predominates depends on the technique and rate of
compressions, as well as on individual patient characteristics, such as size, chest wall
stiffness, the presence of chronic obstructive pulmonary disease, and the duration of the
resuscitation. Both mechanisms may be present to varying degrees within the same
patient at different times during the resuscitation. The cardiac pump is the more efficient
mechanism, and techniques that augment the cardiac pump, e.g., high-impulse CPR,
provide superior hemodynamics, particularly coronary blood flow. [63 ] , [171 ] , [174 ] ,
[175 ] Whether these techniques improve resuscitation and survival rates in controlled
clinical trials remains to be determined.
ALTERNATIVE TECHNIQUES AND MECHANICAL ADJUNCTS TO
CPR
Simultaneous Compression/Ventilation
This technique is designed to augment the thoracic pump mechanism of blood flow. In
animal models, superior vena cava (SVC) CPR increased systolic pressure and carotid
blood flow. However, clinical trials of SVC-CPR have shown that survival was better with
standard techniques. [184 ] , [185 ] According to the 1992 AHA guidelines, SVC-CPR
is not recommended. [43 ]
Interposed Abdominal Compression (IAC) CPR
The technique of IAC-CPR involves standard chest compressions with a second person
applying compressions to the abdomen during the relaxation phase of the chest
compressions. [186 ] The theoretical advantage of this technique is that the abdominal
aorta is compressed during diastole, augmenting aortic diastolic pressure, and
released during systole, improving forward flow (analogous to an intraaortic balloon
pump). In contrast to abdominal binding, in which the liver is forced upward beneath the
sternum, with IAC-CPR the liver can move downward during chest compressions,
decreasing the likelihood of serious hepatic injury. IAC-CPR is not associated with
increased rates of intraabdominal injuries or aspiration. [186 ] Human studies of
IAC-CPR have yielded mixed results. [187 ] , [188 ] However, in two recent trials,
IAC-CPR was found to increase resuscitation rates and survival to discharge for
inpatient cardiac arrests. [189 ] , [190 ] Presently, this technique is still classified as
experimental by the AHA.
High-Impulse CPR
High-impulse CPR is a technique in which compressions are delivered with high force
at high rates. Animal studies have shown dramatic increases in coronary blood flow and
cardiac output using high-impulse CPR. [64 ] , [171 ] In addition, early and late survivals
are significantly better than with standard CPR. [162 ] The AHA still classifies
high-impulse CPR as an experimental technique. [43 ] However, the current
recommendation of a rate of 100 compressions per minute with a 50 percent
compression cycle is, in essence, a high-impulse technique. Further study is needed to
determine if high-impulse CPR improves survival clinically.
Pneumatic Antishock Garment/Abdominal Binder
These devices also are designed to augment the thoracic pump. They increase
intrathoracic pressure by limiting downward movement of the diaphragm during
compression. [191 ] Although animal studies have shown increased aortic pressures
and carotid blood flow with these devices, [195 ] their use may increase right atrial and
intracranial pressures, limiting blood flow to the heart and brain. [193 ] In addition, some
investigators have noted an increased incidence of serious intraabdominal
complications, particularly liver lacerations, with abdominal binding and a pneumatic
antishock garment. [194 ]
Pneumatic Vest
The pneumatic vest is designed to augment the thoracic pump mechanism. The device
consists of a vest containing a bladder. Air is forced into and out of the vest by a
pneumatic drive system. Preliminary human trials of vest CPR were reported in 1993.
[195 ] Vest CPR was shown to increase aortic diastolic and coronary perfusion
pressures and the rate of return of spontaneous circulation. However, no patients
survived to discharge. Vest CPR may lower the risk of traumatic complications,
however.
Active Compression Decompression (ACD)
The concept of the ACD device originated from the observation that a man was
resuscitated successfully from cardiac arrest on two separate occasions by family
members using a plunger. [196 ] The device consists of a hand-held suction cup with a
central piston and handle. ACD CPR has been shown to improve aortic and coronary
perfusion pressures, as well as cerebral, coronary, and renal blood flow. [197 ] [200 ]
ACD is thought to improve ventricular filling and coronary flow by creating a negative
intrathoracic pressure during the release phase. [201 ] Two clinical studies have
reported significant increases in the rates of return of spontaneous circulation and
24-hour survival with the ACD device. Survival to discharge was higher with ACD in
both studies but did not reach statistical significance. [202 ] , [203 ] The ACD device is
portable, easy to use, and inexpensive, making it an attractive adjunct to standard CPR.
Cardiopulmonary bypass (CPB) has been used successfully in cardiac arrest patients.
[204 ] [206 ] Hemodynamics, survival, and neurologic function are improved in animals
treated with early CPB versus those treated with standard CCM. [207 ] [209 ] However,
this technique is limited to tertiary care centers.
Intraaortic Balloon Pump (IABP)
The IABP has been shown to be effective in improving hemodynamic parameters

during closed chest resuscitation in animal models. [210 ] , [211 ] At present, no
randomized studies of the IABP in the setting of cardiac arrest have been performed.
Direct Mechanical Ventricular Actuation (DMVA)
The technique of DMVA was devised in the 1960s for the treatment of victims of
cardiac arrest. The device consists of a cup that is placed directly on the heart via a left
anterior thoracotomy. The cup has a semirigid outer shell and a pliable inner
diaphragm. Air is alternately insufflated and withdrawn from the space between the
inner diaphragm and the outer shell. As the diaphragm expands, the heart is
compressed, forcing blood out of the ventricles. Forward flow is directed by the cardiac
valves. During diastole, the diaphragm remains in contact with the epicardial surface
and enhances diastolic filling. DMVA provides similar hemodynamics and superior
ischemic tolerance and neurologic outcome compared with CPB. [212 ] [214 ] The utility
of the device for cardiac arrest is limited by the time required to place it, which, although
short, necessitates a thoracotomy and interruption of chest compressions. More likely
the future role for DMVA is bridging transplantation candidates, which has been done
successfully, or bridging to a long-term implantable LV assist device. [215 ]
OPEN CARDIAC MASSAGE (OCM)
OCM was the preferred technique prior to the introduction of modern CPR in 1960. [20 ]
Presently, open chest massage is indicated for cardiac arrest associated with
penetrating thoracic trauma and arrest during a thoracic surgical procedure. [43 ] OCM
also is indicated when chest wall deformity or recent sternotomy precludes effective
CCM. [43 ] Other situations in which to consider OCM include cardiac arrest due to
hypothermia, massive pulmonary embolism, pericardial tamponade, or intraabdominal
hemorrhage. The 1992 AHA guidelines also recommend consideration of OCM when
CCM fails to provide adequate support, [43 ] but OCM is seldom performed for this
reason. It is important to note that OCM is not indicated as a last effort after prolonged
closed chest CPR. [216 ] , [217 ]
Technique
OCM is performed via a left lateral thoracotomy unless the patient has a fresh
sternotomy. The chest is entered through the fifth intercostal space. The pericardium is
opened longitudinally, anterior to the phrenic nerve, if pericardial tamponade and/or a
penetrating cardiac injury is present. Otherwise, the pericardium may be left intact. The
heart is compressed with two hands or, alternately, with one hand while the other is
used to occlude the thoracic aorta (Fig. 14-6) .
Hemodynamics
In recent years there has been a resurgence of interest in OCM because of the
continued low survival rates with CCM. This renewed interest is based on the superior
hemodynamics of open massage compared with CCM (Table 14-5) . Although Redding
[221 ] found no difference in aortic pressure, carotid blood flow, or ability to defibrillate
between two groups of dogs subjected to 20 minutes of open or closed chest massage,
the majority of other studies demonstrated superior hemodynamics with open chest
massage. [69 ] , [219 ] [224 ] While systolic pressures may be similar with the two
techniques, diastolic pressures are higher and central venous pressure is lower with
OCM. [69 ] , [221 ] , [224 ] Therefore, coronary perfusion pressure and myocardial blood
flow are superior with OCM. Cardiac output and cerebral blood flow are also higher
during OCM. [222 ] , [223 ]
There are few studies comparing open and closed cardiac massage in humans. Del
Guercio et al. [225 ] reported their findings in six patients who underwent OCM after a
period of ineffective CCM. Cardiac output more than doubled with open compressions.
In addition, five of the six patients were defibrillated successfully after open massage,
whereas none had been defibrillated during closed chest CPR.
Results of OCM
Early reports of OCM had impressive success. Briggs et al. [226 ] reported a 55
percent survival for in-hospital arrests. Stephenson et al. [227 ] reported an overall
survival of 28 percent in 1953. However, when events under anesthesia are excluded in
the Stephenson et al. report, the survival rate was only 17 percent, which is comparable
with that found in many recent series of CCM.
The only prospective trial of open versus closed chest massage was stopped after 49
patients because no patients in either group survived, [228 ] but inferences are limited
because of the small number of patients and long prehospital downtime (220 minutes).
Open chest CPR after prolonged downtime is unlikely to improve results. Animal
studies suggest that OCM may improve results if applied early after a short period of
ineffective CCM. [229 ]
Complications
Complications of OCM include right ventricular perforation, hemorrhage, lung laceration,

phrenic nerve injury, esophageal and aortic injury, cardiac lacerations, and empyema.
[227 ] However, the rate of infection is relatively low, approximately 5 percent, given the
emergent nature of the procedure on an unprepped chest. [230 ]
Role of OCM in Cardiac Resuscitation
Currently, the role of OCM is limited to specific unusual circumstances. Given the poor
survival with standard CCM, early application of OCM may improve survival
significantly. For results to be meaningful, this question needs to be addressed in a
prospective trial. Downtime prior to thoracotomy must be minimized. Besides survival,
the possibility of successful resuscitation of neurologically impaired patients is a major
concern.
PHARMACOLOGY OF RESUSCITATION
Route of Administration
If no intravenous access is available, a peripheral intravenous line is placed at the time

of arrest. Peripheral access is preferred for both speed and safety and because CPR is
not interrupted. Recommended sites are the antecubital and external jugular veins.
Drugs take 1 to 2 minutes to reach the central circulation after peripheral injection
during CPR [231 ] ; therefore, peripheral boluses are followed with a 20-mL saline flush
and elevation of the extremity. [232 ] Peak concentrations of drugs are lower with
peripheral than with central venous injection. [233 ]
If a central line is in place, it should be used. A central line may be placed during the
resuscitation if there is no response to peripherally administered drugs. The internal
jugular vein and supraclavicular approach to the subclavian vein causes less
interference with CPR than infraclavicular subclavian placement. Short femoral venous
lines are not effective because venous return from the infradiaphragmatic IVC is
markedly impaired during CPR. [234 ] A femoral approach may be used to place a long
line that extends above the diaphragm.
If venous access cannot be obtained, atropine, lidocaine, and epinephrine may be

administered via an endotracheal tube. The medications are given via a catheter
passed beyond the tip of the ETT. The dose is 2 to 2.5 times the recommended
intravenous dose, diluted in 10 mL of saline or distilled water. [235 ] Water provides
better absorption but has a greater adverse effect on pao 2 than saline. [236 ] Several
rapid insufflations are given after the bolus to disperse the drug.
Intracardiac injection is not recommended for routine use during CPR. [43 ] It may be
used for epinephrine during OCM or when no other access can be obtained during
CCM. Disadvantages of intracardiac injection are the need to stop CPR and the high
rate of complications. Complications include coronary artery laceration, cardiac
tamponade, and pneumothorax.
Resuscitation Medications
SUPPLEMENTAL OXYGEN
Supplemental oxygen is provided in the highest possible concentration during CPR.

The optimal method of delivery is via a properly placed endotracheal tube.
INTRAVENOUS FLUIDS
Intravenous fluids are not indicated for routine cardiac arrest without hypovolemia. [43 ]
Fluid administration may adversely affect coronary perfusion pressure and myocardial
blood flow by raising right atrial pressure. [237 ] Fluid administration is beneficial in
certain cases of electromechanical dissociation (EMD), such as hypovolemia and
cardiac tamponade.
ALPHA-ADRENERGIC AGONISTS
Alpha-adrenergic agonists are the only class of drugs that have been shown to improve
outcome definitively in CPR. [238 ] [240 ]
Epinephrine
Epinephrine is a class I agent for cardiac arrest [43 ] (Table 14-6) . The
AHA-recommended dose of epinephrine for resuscitation is 1.0 mg IV every 3 to 5
minutes throughout the resuscitation attempt. [43 ] Epinephrine improves resuscitation
success and survival in animal models [238 ] [240 ] and is the pressor agent of choice
for resuscitation. The minimum coronary perfusion pressure and myocardial blood flow
needed to achieve successful defibrillation are 15 mmHg and 15 to 20 mL/min per 100
g, respectively. [65 ] , [94 ] Standard CPR techniques cannot meet these minimum
requirements in the absence of pressor agents. Epinephrine stimulates both alpha- and
beta-adrenergic receptors, but beneficial effects in CPR are predominately due to
alpha-adrenergic receptor stimulation. [145 ] , [239 ] [241 ] Alpha-adrenergic stimulation
increases aortic diastolic pressure and peripheral vascular tone and shunts blood to the
coronary and cerebral circulations. [241 ] , [242 ] Beta effects are less desirable
because of increased myocardial oxygen demand and decreased subendocardial
blood flow. [242 ] , [254 ] Successful defibrillation after epinephrine administration is
due to improved coronary perfusion (alpha effect), not to increasing the amplitude of
fibrillation (beta effect). [145 ]
Recently, the recommended dose of epinephrine during CPR was questioned because
it is based on intracardiac injections in small dogs. When corrected for body weight, the
doses used were equivalent to 3 to 14 mg in a 70-kg adult. [243 ] [245 ] Anecdotal
reports of the efficacy of high-dose epinephrine generated enthusiasm for the
technique. [246 ] [248 ] High-dose epinephrine has now been studied in several clinical
trials. [249 ] [253 ] Although these trials showed higher rates of successful resuscitation,
no significant survival benefit was demonstrated. In one trial, high-dose epinephrine had
an adverse effect in patients in VF and those over 65 years of age. [250 ] A trend
toward improved survival was noted for patients in asystole and EMD in another trial.
[249 ] The failure of high-dose epinephrine to improve results may be due to increases
in oxygen demand secondary to beta-adrenergic receptor stimulation. [254 ] Another
reason for the failure of high-dose epinephrine is that most survivors are patients who
cardiovert with the initial countershocks, before epinephrine is given during the
resuscitation. [251 ] High-dose epinephrine (5 mg, 0.01 mg/kg) is a class IIb
intervention [43 ] and may be tried if the standard dose fails.
Phenylephrine/methoxamine
Specific alpha1-adrenergic agonists might be preferable to epinephrine in cardiac

arrest because they do not stimulate beta-adrenergic receptors. [101 ] However,
investigations of alpha1 agonists fail to demonstrate a benefit compared with
epinephrine. Myocardial and cerebral blood flows are lower with phenylephrine and
methoxamine than with epinephrine in animal studies. [255 ] [257 ] Furthermore,
epinephrine resulted in a higher rate of successful defibrillation than methoxamine in a
clinical study. [258 ]
ANTIARRHYTHMICS
All antiarrhythmics are class IIb interventions in VF. None of these agents improved
survival in a placebo-controlled trial. [259 ]
Lidocaine
Lidocaine is the first-choice antiarrhythmic during cardiac arrest. It is given when VF/VT
persists despite initial countershocks, epinephrine, and repeated attempts to
defibrillate. Lidocaine suppresses ventricular arrhythmias by decreasing automaticity
(reduced slope of phase 4 depolarization of the action potential). [260 ] In addition, it
may terminate reentrant arrhythmias by changing the conduction velocity of the reentry
pathway. [261 ] Lidocaine increases the fibrillation threshold [262 ] , [263 ] but may
increase the defibrillation threshold as well. [264 ] [267 ] The recommended initial bolus
dosage during CPR is 1.0 to 1.5 mg/kg. [43 ] Defibrillation is attempted following the
bolus. The dose is repeated after 3 to 5 minutes up to a total dose of 3.0 mg/kg. If
defibrillation is successful after lidocaine, an infusion of 2 to 4 mg/min is administered. If
VF persists, additional boluses of 0.5 mg/kg may be given every 8 to 10 minutes. [43 ]
Excessive doses of lidocaine may cause disorientation, auditory disturbances,
paresthesias, muscle twitching, and seizures.
Bretylium
Bretylium tosylate is indicated for the treatment of VF/VT resistant to defibrillation,

epinephrine, and lidocaine. Bretylium is a quaternary ammonium compound that acts as
an adrenergic neuronal blocking agent. [268 ] It increases the fibrillation threshold but,
unlike lidocaine, does not increase the defibrillation threshold. [269 ] [271 ] Bretylium
lengthens the duration of the action potential and the effective refractory period in
normal myocytes. [272 ] It does not suppress phase 4 depolarization. Randomized trials
show similar efficacy for lidocaine and bretylium, [273 ] , [274 ] but bretylium has the
potential to produce adverse hemodynamic effects. Injection causes an immediate
catecholamine release. [275 ] After 15 to 20 minutes, hypotension may occur secondary
to postganglionic antiadrenergic actions. [276 ] The dose of bretylium in refractory
cardiac arrest is 5 mg/kg. If unable to defibrillate after the initial bolus, repeated boluses
of 10 mg/kg are given every 5 minutes to a maximum of 30 to 35 mg/kg. If the patient is
defibrillated after receiving bretylium, the drug is infused at a rate of 1 to 2 mg/min. [43 ]
Procainamide
Procainamide may be considered when VF/VT persists despite trials of lidocaine and
bretylium. Procainamide is a ganglionic blocker that slows phase 4 depolarization and
intraventricular conduction. The AHA guidelines recommend infusing procainamide at a
rate of 30 mg/min to a total dose of 17 mg/kg, [43 ] but at this rate it takes approximately
40 minutes to reach the full loading dose in an adult. More rapid infusion rates are
associated with hypotension [277 ] ; thus the drug offers little during cardiac arrest.
Procainamide also may worsen ventricular arrhythmias in the presence of hypokalemia
and hypomagnesemia.
Magnesium
Magnesium sulfate, 1-to-2-mg IV bolus, is given for hypomagnesemia or torsade de
pointes. It is considered a class IIb agent for treatment of refractory VF/VT. [43 ]
Hypomagnesemia is associated with ventricular arrhythmias and sudden cardiac death
[278 ] and may hinder potassium replenishment in hypokalemic patients. Common side
effects of magnesium sulfate include flushing, mild bradycardia, and hypotension with
rapid infusions. Hypermagnesemia can cause flaccid paralysis and cardiorespiratory
arrest.
Amiodarone
Amiodarone was useful for refractory VF in one study. Eleven of 14 patients

unresponsive to conventional therapy were defibrillated after amiodarone was given,
and 8 of the 14 survived to discharge. [279 ] Further studies are necessary before
amiodarone is recommended routinely.
OTHER AGENTS
Atropine
Atropine is a parasympatholytic agent that enhances atrioventricular node conduction

and sinus node automaticity. It is indicated for symptomatic bradycardia and asystolic
arrest. [99 ] , [100 ] , [102 ] , [280 ] Asystole secondary to prolonged ischemia is almost
uniformly fatal, and although atropine is unlikely to be of real benefit, there is no
evidence that it is harmful under these dire circumstances. [106 ] The dose of atropine
in cardiac arrest is 1 mg as an IV bolus, repeated every 3 to 5 minutes to a total dose of
3 mg. For symptomatic bradycardia, the dose is 0.5 to 1 mg (maximum of 2 to 3 mg).
[43 ] Doses lower than 0.5 mg are avoided because they may cause paradoxical
bradycardia. [281 ] , [282 ] Adverse effects of atropine include tachycardia and
anticholinergic effects.
Sodium bicarbonate
Sodium bicarbonate is a buffer agent. Bicarbonate ions bind hydrogen ions to form
carbonic acid. Carbonic acid is converted to co 2 and eliminated by the lungs according
to the following equation: H + + HCO 3 µrl H 2 CO 3 µrl h 2 o + co 2 Due to inadequate
perfusion, anaerobic metabolism, and inefficient co 2 removal during CPR, co 2
accumulates rapidly, leading to a hypercarbic venous acidemia. [283 ] , [284 ] Since co
2 is diffusible across membranes, it leads to a paradoxical intracellular acidosis [285 ]
that may decrease the likelihood of successful resuscitation. At the same time,
hypocarbic arterial alkalemia [284 ] or the so-called venoarterial paradox may develop.
Lactic acidosis does not occur until relatively late in the resuscitation effort. Sodium
bicarbonate may increase co 2 levels, worsen the venoarterial paradox, and exacerbate
intracellular acidosis. [286 ] , [287 ] Other potential adverse effects of NaHCO 3 include
alkalemia with a leftward shift of the oxyhemoglobin desaturation curve (less O 2 release
to tissues), hyperosmolality, hypernatremia, and decreased coronary perfusion
pressure. [288 ] [291 ] Bicarbonate has not been shown to improve results in cardiac
arrest. [289 ] , [290 ] , [292 ]
Sodium bicarbonate is definitely indicated (class IIa) for patients with preexisting
acidosis, hyperkalemia, and tricyclic antidepressant overdose. Otherwise, bicarbonate
is a class IIb agent for prolonged resuscitations. It is considered class III (not indicated,
possibly harmful) for treatment of lactic acidosis secondary to poor tissue perfusion.
The initial dose of bicarbonate is 1 meq/kg as an IV bolus. Subsequent doses of 0.5
mg/kg may be given every 10 minutes. [43 ]
Calcium
Calcium chloride administration produces a positive inotropic response. [293 ] In

addition, there is potential for coronary and cerebral vasoconstriction. Calcium
carbonate 8 to 16 mg/kg IV is indicated in the presence of hyperkalemia,
hypocalcemia, and calcium-channel blocker overdose. [105 ] Otherwise, calcium has
not been shown to be beneficial in the setting of cardiac arrest. [294 ] [296 ]
Isoproterenol
Isoproterenol is contraindicated in cardiac arrest except in patients with refractory

torsade de pointes (class IIb) and as a temporizing measure for cardiac transplant
patients with hemodynamically significant bradycardia. [43 ]
CEREBRAL PROTECTION/RESUSCITATION
The objective of CPR is to restore circulation in a neurologically intact individual. The

main priority during CPR is to provide sufficient myocardial and cerebral blood flow to
prevent irreversible damage prior to definitive intervention. Unfortunately, this goal often
is not achieved. Less than 10 percent of CPR attempts result in survival without
neurologic damage, whether in or out of a hospital . [297 ]
During global ischemia, consciousness is lost within 10 seconds. [298 ] Brain-stem

function ceases within 1 minute of cardiac arrest, producing agonal respirations and
fixed and dilated pupils. Anaerobic glycolysis, which is the only means of energy
production, is incapable of meeting the brain's basal metabolic demands. As a result,
high-energy phosphate and glycogen stores are depleted within 5 minutes. [299 ] Lactic
acid accumulates in neurons and has a direct cytotoxic effect. [300 ] The limited
cerebral blood flow generated by CPR may actually exacerbate intracellular acidosis by
supplying low levels of glucose for continued anaerobic metabolism. [301 ] , [302 ]
Because cerebral blood flow is inadequate during CPR, the likelihood of neurologically
intact survival diminishes rapidly with time. Irreversible brain damage begins to occur
within 4 to 5 minutes of cardiac arrest if there is no intervention. [303 ] , [304 ]
Restoration of circulation after 5 to 20 minutes of ischemia is accompanied by variable
degrees of neurologic damage. [305 ] , [306 ] The neurologic complications that follow
cardiac arrest and resuscitation are listed in Table 14-7 . [307 ]
An arterial-venous pressure gradient is necessary for flow to occur. During chest

compressions, this gradient is maintained by venous valves at the thoracic inlet that
prevent the transmission of high intrathoracic pressures to the jugular venous system.
[165 ] Autoregulation normally maintains a global cerebral blood flow of approximately
50 mL/min per 100 g for cerebral perfusion pressures (mean arterial
pressure-intracranial pressure) from 50 to 150 mmHg. [297 ] When cerebral perfusion
pressure falls below 50 mmHg, cerebral blood flow decreases. Even under optimal
conditions, cerebral perfusion pressure seldom exceeds 40 mmHg during CCM. [65 ]
Accordingly, cerebral blood flow during CPR is only 10 to 15 percent of normal. [221 ]
Studies show that this trickle blood flow is more harmful than complete no-flow
ischemia. [302 ]
Although irreversible neuronal injury begins to occur after about 5 minutes of global
ischemia, [308 ] some neurons maintain function in vitro for up to 60 minutes of
ischemia. [309 ] This finding has led to a search for ways to revive neurons that may be
potentially viable at the time circulation is restored. As with the heart, reperfusion
following global cerebral ischemia may be accompanied by additional cellular injury and
accelerated cell death. Reperfusion injury following successful resuscitation has been
termed the postresuscitation syndrome . The cause of reperfusion injury in the brain is
multifactorial. Calcium overload in the mitochondria, free-radical injury, and the
no-reflow phenomenon may all play a role in reperfusion injury. [297 ] The no-reflow
phenomenon is continued hypoperfusion of the brain that lasts up to 3 hours. [310 ] It is
caused by platelet aggregation, altered calcium flux, vasoconstriction, and pericapillary
edema. [311 ] No-reflow is not due to increased intracranial pressure, which usually
returns to normal soon after cardiac arrest. [312 ] , [313 ] Cerebral blood flow remains
depressed for 18 to 24 hours following a severe ischemic insult. [314 ] This delayed
hypoperfusion phenomenon is believed to be secondary to calcium-induced
precapillary vasoconstriction. [315 ]
Postresuscitation Cerebral Care
Autoregulation of cerebral blood flow is ineffective following ischemic injury [316 ] ;

therefore, blood flow is completely dependent on arterial pressure. Any degree of
hypotension severely compromises cerebral perfusion. [317 ] Every effort must be
made to maintain normotension, and some advocate mild hypertension in the
postresuscitation period. [318 ] , [319 ] Moderate hyperoxia (Po 2 ±g2 100 mmHg) and
mild hyperventilation (paco 2 = 30 to 35 mmHg) are desirable. [43 ] Arterial pH is
maintained in the normal range. Sedation and anticonvulsant medication are given as
needed. Seizures are common and occur in up to 30 percent of arrest victims. [320 ]
Although sometimes subtle, seizures are serious because of greatly increased O 2
demand and should be treated aggressively. [321 ] Body temperature is kept at or
below normal, since hyperthermia increases cerebral metabolic rate 8 percent per
degree centigrade. [321 ] Mild hypothermia may be beneficial. [322 ] , [323 ]
Many different protocols have attempted to lessen the effects of reperfusion injury.
Hemodilution reduces blood viscosity, but the cost is decreased oxygen-carrying
capacity. Barbiturates lower cerebral oxygen demands, but a randomized trial revealed
no improvement with routine thiopental. [324 ] Calcium channel-blocking agents have
been advocated to lessen calcium-mediated cellular injury, but trials of lidoflazine,
nimodipine, and fluzarizine fail to demonstrate improvement over standard post-CPR
management. [325 ] , [326 ] Corticosteroids also have not proven beneficial. [327 ]
Other agents under investigation include free-radical scavengers and excitatory amino
acid antagonists. [297 ] Currently, there is no definitive evidence that any therapy
improves neurologic outcome in humans. Hypoxia, hypotension, and hypercapnia
aggravate cerebral injury and must be corrected. [328 ]
OUTCOME
In-Hospital Cardiac Arrest
A disappointing aspect of CPR is that survival rates for inpatient cardiac arrest
remained poor over the past 30 years despite widespread training in CPR techniques.
[329 ] , [330 ] McGrath [329 ] reviewed 42 series encompassing over 12,000 patients
between 1961 and 1984. Twenty-four-hour survival rates ranged from 13 to 59 percent,
with a mean of 38.5 percent. Mean survival to hospital discharge was 14.6 percent
(range 3 to 27 percent). Of note, there was no substantial difference between survival
rates for studies published in the 1960s and those from the 1980s. Another review of
in-hospital arrest reports published between 1987 and 1991 found a combined
long-term survival rate of 11 percent (range 5 to 29 percent). [330 ] Several theories
exist to explain this failure to improve survival. One is that no dramatic advances have
been made since the introduction of CCM combined with ventilation and defibrillation in
the 1960s. [330 ] A second theory is that although CPR techniques and training have
improved, the inpatient population is older and sicker than in years past. [335 ] Despite
the trend toward older patients with more comorbidities in the inpatient population as a
whole, there is no definitive proof that the subset of patients undergoing CPR is different
from those in years past. [330 ]
PREDICTORS FOR IN-HOSPITAL CARDIAC RESUSCITATION
Many factors have prognostic significance for survival following in-hospital arrest.
Presenting rhythm is an important factor; VF/VT has a much better prognosis than
asystole and EMD. [9 ] , [331 ] , [332 ] , [334 ] , [335 ] , [338 ] , a significant negative
prognostic indicator in several early series. [338 ] , [339 ] However, age has no
independent predictive value when comorbid diseases and other factors are
considered. [9 ] , [10 ] Location of the arrest (ICU versus non-ICU) is a significant
predictor in some studies but not others. [9 ] , [10 ] , [329 ] , [338 ] , [340 ] Although early
studies showed a benefit for ICU patients, many of these patients had acute myocardial
infarctions. More recently, 32 percent of patients in a surgical intensive care unit for
noncardiac disorders survived to discharge after CPR if their overall clinical status was
stable prior to cardiac arrest, but no patients survived if their condition was deteriorating
prior to CPR. [341 ] Comorbid conditions associated with more than 95 percent
mortality after cardiac arrest are renal failure, metastatic cancer, pneumonia, sepsis,
hypotension, stroke, and homebound lifestyle. [9 ] , [331 ] , [332 ] , [334 ] , [335 ]
Survival is more likely for patients who have a witnessed arrest, CPR initiated within 5
minutes, and duration of CPR of 15 minutes or less. Mortality increases from 44 percent
for resuscitations lasting less than 15 minutes to 95 percent for those longer than 15
minutes. [9 ] Long-term survival is minimal after 30 minutes of resuscitation. [9 ] , [336 ] ,
[342 ]
Out-of-Hospital Cardiac Arrest
In contrast to inpatient arrest, where comorbid diseases play a major role in outcome,
time outweighs all other factors for out-of-hospital arrest. Key determinants of survival
include initial rhythm, whether the arrest is witnessed, the interval before CPR starts,
and the period before definitive treatment. Survival rates are highly variable among
reported studies. Becker et al. [343 ] reported a 2 percent overall survival to discharge
in metropolitan Chicago. This low survival primarily reflected the long interval from arrest
to defibrillation (average 16 minutes). Likewise, in New York City Lombardi et al. [344 ]
found that only 1.4 percent of cardiac arrest victims and only 5.3 percent of those with
witnessed VF arrest survived to discharge (Fig. 14-7) . In contrast, Eisenberg et al. [345
] reported an overall survival of 22 percent for patients with witnessed arrests who had
much shorter downtimes. Other studies of out-of-hospital cardiac arrest between 1973
and 1990 demonstrate survival rates ranging from 0 to 18 percent [343 ] , [346 ] [358 ]
(Table 14-8) .
PREDICTORS FOR OUT-OF-HOSPITAL CARDIAC RESUSCITATION
Eisenberg's study revealed the importance of early intervention for survival. Survival for
witnessed arrest was 22 percent versus 4 percent for unwitnessed arrests. If the time to
CPR was less than 4 minutes, survival improved from 12 to 28 percent. And if definitive
care, i.e., defibrillation, was provided within 8 minutes, survival was 40 percent
compared with 13 percent if the first shock was given more than 8 minutes from the time
of cardiac arrest. [345 ] As with in-hospital arrest, presenting rhythm was a major
determinant for survival; VF/VT had the best prognosis. [359 ]
Bystander CPR improves survival to discharge rates for victims of cardiac arrest [351 ] ,
[354 ] , [356 ] , [358 ] , [360 ] [364 ] (Table 14-9) . In addition, several studies found less
neurologic morbidity in cardiac arrest victims who received bystander CPR. [361 ] ,
[362 ] , [365 ] , [366 ] The decrease in hospital mortality from bystander CPR is primarily
due to fewer deaths from anoxic encephalopathy during the postresuscitation
hospitalization. [362 ] , [366 ] Return of consciousness within 24 to 48 hours of arrest is
a positive neurologic prognostic sign. [9 ] , [367 ] , [368 ]
Physiologic Predictors of Outcome
Most myocardial blood flow occurs during the release phase of CCM and depends on
coronary perfusion pressure (CPP = aortic diastolic pressure - right atrial pressure).
CPP is the principal physiologic determinant of successful CPR. [72 ] CPP must be
sufficient to provide a blood flow of 16 to 20 mL/min per 100 g of myocardium. [94 ] A
CPP of 15 mmHg is the minimal threshold for successful resuscitation. [65 ] , [369 ] ,
[370 ] To achieve this CPP, aortic pressure during the release phase must be 30 to 40
mmHg. These values are rarely attainable with standard CCM without the aid of pressor
agents. [62 ] , [101 ] , [111 ] , [112 ] , [371 ] Higher coronary perfusion pressures are
associated with improved rates of defibrillation. [65 ] One must bear in mind that many
humans have advanced coronary artery disease and may require significantly higher
CPPs to generate adequate myocardial blood flow.
Long-Term Outcome
SURVIVAL
Of the few patients who survive to discharge after out-of-hospital arrest, long-term
survival is relatively good. The reported 1-year survival rate ranges from 75 to 85
percent, and approximately 50 percent are still alive 4 years postarrest [372 ] (Table
14-10) . The majority of these patients ultimately die of cardiac causes. [13 ] , [380 ] ,
[381 ] Positive predictors for long-term survival are cardiac arrest associated with acute
MI, no prior history of MI, and short time intervals to CPR and definitive care. [375 ] ,
[378 ] , [382 ] Patients with primary arrhythmic events, congestive heart failure, impaired
LV function, extensive CAD, and complex premature ventricular depolarizations are
less likely to survive long term after discharge. [383 ]
MORBIDITY
Approximately 90 percent of survivors of CPR return to home, while 5 to 10 percent are

institutionalized. [372 ] Between 20 and 30 percent of those who return home are
home-bound. Only 60 percent return to their prearrest level of function, and less than 30
percent of those employed before arrest return to work. [372 ] The rate of significant
mental impairment is variable (Table 14-11) . Longstreth et al. [12 ] studied 459
out-of-hospital cardiac arrest victims who survived to admission. Ultimately, 41 percent
of these patients were discharged home with no gross neurologic deficits. One-third of
the survivors had permanent neurologic damage (Fig. 14-8) . Liberthson et al. [381 ]
found normal neurologic function in only 25 percent of 301 patients who survived to
admission. However, many patients with neurologic damage at admission died in the
hospital. Of the 42 patients who survived to discharge, 12 percent had severe and 28
percent had partial neurologic deficits. In another study, 41 percent of patients surviving
to discharge had significant neurologic impairment. [374 ] For patients who did not
receive early intervention, the outlook was more dismal. Abramson et al. [15 ] reported
that only 15 percent of 40 patients in whom CPR was delayed for more than 5 minutes
after arrest had good cerebral function. Earnest et al. [13 ] evaluated the neurologic
status of survivors 3.5 years after cardiac arrest. They found that 8 of 17 patients
examined were normal or had mild deficits. Nine of 17 had severe neurologic
dysfunction. Survivors of in-hospital arrest generally have better neurologic outcomes
because downtimes prior to CPR and defibrillation are shorter. However, major
functional disability is common, and many patients are confined to home. Other patients
are fearful of another arrest and limit their activities accordingly. [9 ] Depression is
common among survivors at the time of discharge but usually resolves within a few
months. [9 ]
CHRONIC STABLE ANGINA
CABG Surgery versus Medical Therapy
SURVIVAL
Three major randomized studies, the Coronary Artery Surgery Study (CASS), [12 ] the
Veterans Administration Cooperative Study Group (VA), [13 ] , [14 ] and the European
Coronary Surgery Study (ECSS), [15 ] , [16 ] and four smaller randomized trials [17 ] [19
] conducted between 1972 and 1984 provide the most reliable outcome data
comparing medical and surgical therapy. The overall survival benefit at 12 years for the
three large and four smaller randomized trials is shown in Figure 15-1 . [20 ]
The indications for coronary revascularization are based on trials of coronary bypass
surgery versus medical therapy in the 1970s. To avoid extrapolation of these data to the
relative effects of transcatheter techniques (including PTCA versus medical therapy) in
the 1990s, one needs additional current, prospective, randomized trials. Although many
aspects of the randomized trials of bypass surgery and medical therapy render these
early trials obsolete by current standards, these studies are remarkably consistent in
regard to their major findings, and their qualitative conclusions can be generalized to
current practice. The major message of these older multicenter and multinational trials
is that the relative benefits of bypass surgery over medical therapy on survival are
greatest in sicker patients at higher risk, as defined by severity of angina and/or
ischemia, the number of diseased vessels, and the presence of left ventricular
dysfunction. [13 ] , [20 ] , [21 ] It also should be emphasized that these were trials
primarily of patients with moderate chronic stable angina, and therefore, the conclusions
do not apply to patients with unstable angina pectoris or to patients with more-severe
degrees of chronic stable angina. For patients with single-vessel disease, no study has
shown a survival benefit for CABG surgery over medical therapy. [5 ] , [21 ] , [22 ]
Patients with left main equivalents (proximal left anterior descending and proximal
circumflex artery stenosis), three-vessel disease (irrespective of left ventricular
dysfunction), and double-vessel disease with left ventricular dysfunction all appear to
have a survival benefit from surgical revascularization. [23 ] A recent meta-analysis [20 ]
of the seven randomized trials cited above shows that surgically treated patients at high
risk (4.8 percent annual mortality) and moderate risk (2.5 percent annual mortality)
experience clinically and statistically enhanced survival at 5, 7, and 10 years, but there
is no evidence of a survival benefit for those at low risk (1.2 percent annual mortality).
The survival benefit occurred primarily in the sicker patients, as defined by severity of
symptoms and ischemia determined by history or exercise testing, the presence of left
ventricular dysfunction, and the extent of coronary occlusive disease, including
involvement of the proximal portion of the left anterior descending coronary artery.
Nonrandomized studies also demonstrate a beneficial effect of surgery on survival in
patients with multivessel disease and severe ischemia regardless of left ventricular
function. [23 ] [26 ]
The early concern that operative mortality was higher in patients with impaired left
ventricular function has been superseded by recognition that survival of patients on
medical therapy was much worse and that the relative survival benefits of surgical
revascularization, when compared with medical therapy, are greatest in this patient
subgroup. Left ventricular dysfunction in patients with documented ischemia is now
considered an important indication, rather than a contraindication, for surgical
revascularization. [12 ] , [20 ] , [23 ] , [27 ] , [28 ] The recent evidence that ischemic,
viable, hypokinetic (hibernating or stunned) myocardium, as detected preoperatively by
echocardiographic, nuclear, and positron-emission tomographic techniques, regains
stronger contractile function following effective revascularization has prompted
expansion of the indications and enhanced benefits of surgical revascularization in
patients with severe left ventricular dysfunction, including patients who would otherwise
be considered candidates for cardiac transplantation. Figure 15-2 provides an
excellent overview of the survival benefits of coronary artery bypass surgery; survival
after 10-year follow-up in seven randomized trials is depicted for each subgroup. [20 ]
OTHER BENEFITS
In patients in whom a survival benefit cannot be expected, CABG surgery is indicated

for
1. Relief of symptoms and improved quality of life.
Reduced incidence of subsequent nonfatal events such as myocardial infarction.

This is considered a reasonable indication even though the effect of operation on
such events has been more difficult to quantitate. [24 ]
Between 80 and 90 percent of patients who are symptomatic on medical therapy

become symptom-free following CABG surgery, and this benefit extends to low-risk
patients, for whom a survival benefit from surgery is not likely. [20 ] Relief of
symptoms appears to relate to both the completeness of revascularization and
maintenance of graft patency. The completeness of revascularization in patients with
triple-vessel disease particularly important with respect to survival in the presence of
the combination of severe ischemia and/or angina and left ventricular dysfunction.
[29 ] In patients with milder degrees of ischemia and/or angina and well-preserved
left ventricular function, complete revascularization, although desirable, may not be
essential. Symptom benefits of CABG diminish with time because of graft occlusion
and progression of disease in both bypassed and nonbypassed coronary arteries.
[13 ] Recurrence of angina following CABG surgery occurs at rates of 3 to 20
percent per year. In two systematic studies of graft patency, the patency rate was 93
percent for the internal thorasic artery graft and 52 percent for saphenous vein grafts
at 7.5 years [30 ] and 84.1 percent compared with 52.8 percent at 10 years. [31 ]
Although enhanced survival is reported when an internal thorasic artery rather than a
saphenous vein is used to graft the left anterior descending coronary artery, there is
no significant difference in postoperative freedom from angina. [32 ] Thus, while flow
preservation to the left anterior descending coronary artery appears important for
survival, [27 ] other factors, including vein graft occlusions to other arteries and
progression of disease in grafted and nongrafted coronary arteries, influence the
return of angina. Current surgical practice increasingly employs one or both internal
thorasic arteries to enhance patency rates (see Chap. 17).
Few, if any, gains in work rehabilitation can be demonstrated for surgically treated
patients in comparison with those managed medically. Generally, employment
declines in both groups and is determined nearly as much by socioeconomic factors
such as age, preoperative unemployment, and type of job (i.e., laborer versus white
collar) as by type of therapy or clinical factors such as postoperative angina.
Furthermore, surgical revascularization does not reduce the incidence of nonfatal
events such as myocardial infarction. This outcome is primarily due to perioperative
infarctions that offset the lower incidence of infarction in extended follow-up. [24 ]
PTCA versus Medical Therapy
Although angioplasty has been employed increasingly in patients with multivessel

disease as technology has improved and operator experience has been gained, the
majority of angioplasty procedures are still performed on a single coronary artery. [4
] Immediate symptomatic success rates for PTCA of 85 to 90 percent are reported,
similar to those obtained following CABG surgery. Only two small randomized
studies have compared PTCA with medical therapy in single-vessel disease. In the
ACME (A Comparison of Angioplasty with Medical Therapy) study, Parisi et al. [33 ]
reported 212 patients with documented ischemia and a single, greater than 70
percent diameter, coronary artery stenosis randomly assigned to medical therapy or
angioplasty. At 6 months, there was no mortality in either treatment group of these
low-risk patients. PTCA provided more complete anginal relief with fewer
medications, better quality of life scores, and longer exercise duration on stress
testing than medical therapy. [33 ] However, initial angioplasty therapy in the 100
patients was followed by an additional 19 repeat angioplasty procedures and 7
CABG surgical procedures over the first 6 months of follow-up compared with 11
angioplasty procedures and no CABG surgery in the patients randomized to
medical therapy. [33 ] Moreover, nearly half of all patients assigned to initial medical
therapy were asymptomatic at 6 months. Because this modest symptomatic benefit
was achieved at such a large procedural and financial cost, patients who are either
asymptomatic or have mild symptoms should have objective evidence of ischemia
prior to PTCA. [34 ] In many patients, an initial trial of medical therapy is certainly
appropriate.
A second small study of medical versus PTCA therapy for 88 patients with
single-vessel disease found no significant difference in clinical outcomes after 2
years, essentially supporting the recommendations of the ACME investigators. [35 ]
Despite the findings in these two trials, Topol et al. [36 ] found in a large insurance
database study that less than one-third of patients undergoing single-vessel PTCA
had a prior stress test. What is unclear, however, is the proportion of patients in this
study with moderate to severe angina in whom stress testing was not necessary. In
the only randomized study comprising all three treatment options, the Medicine,
Angioplasty or Surgery Study (MASS), [5 ] there were significantly fewer
revascularization procedures over 3 years of follow-up in medically treated patients,
but significantly fewer medically treated patients experienced angina relief. In this
small trial with a high proportion of low-risk patients, the incidence of nonfatal
myocardial infarction and mortality was low, and no significant differences in these
events were detected among treatment groups.
A brief 4-year follow-up report from the ACME investigators indicates that patients
initially randomized to PTCA had significantly fewer episodes of unstable angina
and repeat PTCA and CABG and a better quality of life in the 6-month to 4-year
follow-up period than patients initially treated medically. Thus the much-higher early
procedural numbers and costs for the PTCA-treated patients are considerably offset
by fewer procedures and lower costs in an extended follow-up period. The early and
late reports from the ACME study underscore the importance of an adequate
duration of follow-up in order to gain a reliable understanding of longer-term
outcomes. There are no prospective, randomized trials underway or completed
involving patients with multivessel disease treated medically and by PTCA.
PTCA versus CABG Surgery
SINGLE-VESSEL DISEASE
For patients with single-vessel coronary artery disease whose angina is not well
controlled on medical therapy or who are intolerant of their medications,
revascularization offers a reasonable alternative. Both PTCA and CABG are
associated with high rates of procedural success. Critical evaluation of outcomes for
PTCA and CABG surgical revascularization was first reported in a single-center
Swiss study of patients with single-vessel left anterior descending stenosis in 1994.
[22 ] One hundred and thirty-four patients were randomized to PTCA or internal
thoracic artery bypass grafting and were followed for 2.5 years. There were no
significant differences in combined outcomes of myocardial infarction and cardiac
deaths between the CABG surgery and PTCA treatment groups ( p = 0.21). There
was a greater need, however, for subsequent revascularization in the initial PTCA
treatment group. Seventeen patients (25 percent) required a second
revascularization procedure compared with only three patients (4.4 percent) in the
initial CABG-treated group. Although the PTCA patients were taking significantly
more antianginal medication, the clinical impairment level, stress test performance,
and quality-of-life indices did not differ between groups at 2 years.
The Medicine, Angioplasty or Surgery Study (MASS) from Brazil compared medical
therapy, PTCA, and CABG surgery using an internal mammary artery bypass at a
single center in 214 patients with stable angina, normal left ventricular function, and
proximal stenosis of the left anterior descending coronary artery. [5 ] In this relatively
small but nonetheless important randomized trial, the combined endpoint of cardiac
death, myocardial infarction, or refractory angina requiring revascularization was
statistically significantly less in surgically treated patients. Moreover, there was no
significant difference between patients treated medically or with PTCA. In
comparison with medical therapy, both PTCA and CABG surgery were shown to
provide improved relief of severe symptoms of angina pectoris and a lower
frequency of inducible ischemia on treadmill exercise testing. Nonetheless, there
was no difference among the three strategies at the end with respect to mortality or
late myocardial infarction, although the trial lacked statistical power to answer this
question. Similar findings were obtained at the 3-year follow-up. Since late (> 6
months after angioplasty) restenosis and internal thoracic artery graft occlusion are
both infrequent in single-vessel disease, further cardiac events or therapy are likely
to depend more on progression of the disease in other arteries than on the original
mode of revascularization.
In the RITA (Randomized Intervention Treatment of Angina) trial [37 ] of 1011

patients randomized to PTCA or CABG surgery, 456 (45 percent) had single-vessel
disease. As in the Swiss and MASS trials, no statistically significant difference in
death and myocardial infarction was detected between treatment groups at 2.5
years of follow-up, but the need for subsequent revascularization was much higher in
the patients treated initially by PTCA, due to restenosis. Late follow-up of the RITA
trial demonstrated a similar benefit from both PTCA and CABG surgery in terms of
quality of life, as assessed by a number of subjective and objective indices, and in
terms of costs. [38 ] Patients undergoing PTCA reported a slightly diminished
impairment of quality of life, attributed to a higher recurrence of angina pectoris at 6
months. Nonemployment due to cardiac reasons was similar between the two
groups. [39 ]
INDICATIONS FOR CORONARY REVASCULARIZATION IN PATIENTS WITH

SINGLE-VESSEL DISEASE
The indications for coronary revascularization in patients with single-vessel disease

and chronic stable angina are relatively clear-cut, since no study demonstrates an
unequivocal survival advantage of bypass surgery or PTCA in comparison with
medical therapy. Pending the results of ongoing studies, the objectives of
revascularization for patients with single-vessel disease are the alleviation of
symptoms and arguably the elimination of objective measures of ischemia in the
absence of angina. [34 ] Several studies emphasize the flaws in the assumption that
one can identify future culprit lesions in the absence of symptoms or documentation
of ischemia. [40 ] These studies demonstrate that among patients undergoing serial
coronary angiograms [40 ] [43 ] who subsequently develop an acute myocardial
infarction or unstable angina, the severity of the stenosis (at the time of the initial
angiogram) that ultimately became the site of the culprit lesion causing the acute
ischemic syndrome was less than 50 percent in the majority of cases and in many
patients was not present on the initial angiogram. These data strongly suggest that
among patients with single-vessel disease, prophylactic revascularization of a lesion
(in the absence of symptoms or documented ischemia) is unjustified on the premise
that the specific lesion will ultimately be the cause of an acute ischemic event. The
lack of benefit of prophylactic revascularization raises concern regarding the number
of patients undergoing single-vessel angioplasty who did not have stress testing to
document objective evidence of ischemia if severe symptoms at the time of
presentation were absent. [36 ]
MULTIVESSEL DISEASE
Although initially restricted to single-vessel disease or a procedure limited to one

vessel, the increasing use of PTCA in patients with multivessel disease has
prompted critical evaluation of its efficacy in comparison with CABG surgery in
patients with multivessel disease. Several randomized trials have been reported
recently [44 ] , [45 ] (Table 15-1) , but as evident in Table 15-1 , few enrolled patients
had significant left ventricular dysfunction despite the marked heterogeneity in the
clinical and angiographic spectrum of coronary disease. Coexistent disease was
not consistently reported, and importantly, only a small minority (4 to 9 percent) of
those undergoing clinically indicated angiography and screening for trial eligibility
were randomized to PTCA or CABG surgery. The majority of randomized patients
had one- or two-vessel disease (55 to 88 percent) and well-preseved left ventricular
function with mean ejection fractions ranging from 56 to 63 percent (see Table 15-1
). In the RITA trial, approximately one-third had single-vessel disease, and the
adequacy of revascularization had to be deemed equivalent by both techniques
prior to randomization. [37 ] Among clinically eligible patients in the BARI [6 ] and
EAST [22 ] trials, approximately two-thirds were excluded on appropriate
angiographic grounds that included chronic total occlusions (35 to 37 percent), left
main coronary artery disease, diffuse disease, and anatomic factors or the
perception that PTCA would be dangerous. [6 ] , [46 ]
Consequently, these randomized trials contain only a portion of the spectrum of
patients with coronary artery disease encountered in clinical practice. Further, a high
proportion of the randomized patients are in the lowest-risk groups, in whom no
survival advantage could be demonstrated when CABG surgery was compared with
medical therapy in the earlier CASS, ECSS, and VA surgery randomized trials. [12 ]
, [13 ] , [15 ] Therefore, it is possible that the potential survival benefit of CAGB
surgery over PTCA in high- and moderate-risk groups may be masked by inclusion
of low-risk patients, which reduces the power to detect a mortality difference
between the two treatment strategies. [45 ]
RESULTS
The success of a revascularization procedure depends extensively on the criteria

employed and the individual interpretation of the criteria by both patient and
physician. In the 19851986 National Heart, Lung, and Blood Institute PTCA registry
(Table 15-2) , 99 percent of patients were discharged alive from hospital and 92
percent did not sustain a myocardial infarction or require CABG surgery. [3 ] In the
more recent BARI trial, 99 percent of patients survived hospitalization and 88.6
percent of PTCA-treated patients did not have myocardial infarction or require
repeat revascularization by angioplasty or surgery during the initial hospitalization. [6
] Employing event-free criteria (death, myocardial infarction, CABG) for the initial
hospitalization, PTCA can be fairly judged successful. However, if a repeat
revascularization procedure within 5 years is regarded as a negative outcome, then
only 45.5 percent of all PTCA-treated patients are treated successfully. [6 ]
However, it should be emphasized that the lack of differences between the two
groups in mortality or myocardial infarction rates permits individuals to select one or
the other procedure without catastrophic penalty.
In the BARI, EAST, CABRI, GABI, and RITA multivessel PTCA versus CABG
surgery trials [6 ] , [37 ] , [46 ] [48 ] (Table 15-3) , mortality and recurrent myocardial
infarction were generally low and similar between 1 and 5 years of follow-up in both
the PTCA and CABG treatment groups, as anticipated from the patient composition
in these trials (see Table 15-1 ). Mortality ranged from 3 percent in the CABRI trial at
1-year follow-up [46 ] and 3.4 percent in the RITA trial at 2.5 years [37 ] to 13 percent
in the BARI trial at 5 years. [6 ] A similar but slightly higher incidence for myocardial
infarction was noted in some of these trials. The incidence of repeat
revascularization in the PTCA-treated patients ranged from 36.5 percent in the
CABRI trial at 1-year follow-up to 62 percent in the EAST trial at 3 years (Figure
15-3) . The repeat revascularization rate in the EAST trial for angioplasty-treated
patients was much higher than that noted in the BARI, CABRI, and RITA trials. There
was a concentration of repeat revascularization procedures in trials that required
stress thallium and angiography studies at 1 year; thus some of these procedures
may have occurred in the EAST trial as a consequence of protocol-mandated tests
rather than clinical indications. [46 ]
The incidence of repeat revascularization procedures in multivessel patients

randomized to CABG surgery ranged from 3.5 percent in the CABRI trial to 13.5
percent in the EAST trial. Generally, repeat revascularization procedures were
required five to eight times more often in patients with multivessel disease initially
treated by angioplasty, in comparison with those randomized to initial CABG
surgery. The incidence of angina at follow-up also was generally greater in the
PTCA-treated patients than in those randomized to CABG surgery.
In the recently reported Bypass Angioplasty Reperfusion Investigation (BARI), at 5

years, 54.5 percent of patients initially assigned to PTCA had undergone a repeat
revascularization procedure. [6 ] Of these, 23.2 percent had repeat PTCA (a single
procedure in the majority), 20.5 percent underwent CABG surgery, and 10.8 percent
had both PTCA and CABG. [6 ] Sixty-nine percent of PTCA-treated patients who
were angina-free at 5 years had not required CABG surgery. Among angina-free
patients at 5 years, only 48 percent of the angioplasty-treated patients compared
with 94 percent of the CABG surgery patients had not had an additional
revascularization procedure after their initial procedure.
These randomized trials are extremely useful, but only if results are interpreted in the
context of patients entering or eligible to enter these trials. [44 ] , [45 ] PTCA is a
reasonable alternative to CABG surgery, provided the patient understands that there
is a higher incidence of recurrent angina and need for repeat revascularization
procedures. For most patients similar to those included in these published trials, it is
reassuring that a nonsurgical revascularization procedure does not place them at
increased risk of myocardial infarction or death in comparison with the outcomes of
surgical therapy. To extrapolate these results to patients who are not eligible for
entry is intellectually flawed and potentially misleading.
BARI is the largest trial and the only one with sufficient power to detect a significant
difference in mortality. In a subset analysis of 353 diabetic patients receiving oral or
parenteral diabetic therapy, the 5-year survival with CABG surgery was substantially
better than with PTCA (80.6 versus 65.5 percent, p = 0.002). In the 1476
nondiabetic, randomized BARI patients, the 5-year survival rates were high and not
significantly different between the two groups (89.2 percent for CABG versus 86.3
percent for PTCA, p = 0.19). [6 ] Although the initial procedural complication rates
associated with PTCA and CABG surgery were similar for treated diabetics and
other patients, the apparent superiority in the long term of CABG surgery may be
explained in part by the sicker status of treated diabetics (e.g., greater prevalence of
triple-vessel disease, left ventricular dysfunction, a history of congestive heart failure,
and diffuse disease) (RL Frye, personal communication). Moreover, patients with
severe, diffuse disease and left ventricular dysfunction comprise a high-risk group in
whom complete revascularization is advisable, and the apparent survival benefit
from bypass surgery in these patients is explicable. Whether there are other factors
intrinsically related to diabetes that account for these differences in survival is
unclear, [49 ] as is the possibility that the long-term coronary vascular response to
PTCA in the treated diabetic differs from that noted in nondiabetics. A preliminary
analysis from the CABRI study found that mortality at 2 years was 15.6 percent in
PTCA-treated diabetics and 3.5 percent in diabetics undergoing CABG surgery.
At this stage, the BARI results do not justify CABG surgery over PTCA for all
patients who are diabetic. Further analysis of the subgroups with and without treated
diabetes is needed, with particular attention to the angiographic anatomy and the
distribution of other characteristics delineating patients at high risk.
LEFT VENTRICULAR DYSFUNCTION
Patients with left ventricular dysfunction also may be at higher mortality risk following
revascularization by PTCA than by CABG surgery, but the survival benefits of CABG
surgery do not become evident because these patients are underrepresented in
these prospective, randomized studies. The average ejection fraction reported in
these trials was 64 percent. In a multicenter study of patients with left ventricular
dysfunction (ejection fraction < 40 percent), slightly more than one-quarter of the
patients were dead in the 2 years following multivessel angioplasty. [50 ] Similar
results have been reported from other studies of PTCA in patients with multivessel
disease and left ventricular dysfunction, and overall, the outcome appears less
favorable than that obtained after CABG surgery. [28 ] This may be a function of the
more complete degree of revascularization in patients with left ventricular
dysfunction and multivessel disease. [29 ]
Completeness of revascularization may significantly influence the outcomes of

angioplasty in patients with left ventricular dysfunction. For PTCA, completeness of
revascularization of target arteries ranged from 57 to 61 percent in the prospective,
randomized trials in which complete revascularization was not a protocol
requirement (BARI, EAST, CABRI; see Table 15-1 ). In the GABI and RITA trials,
complete revascularization by PTCA was targeted and was achieved in 86 percent
in GABI and in 81 and 63 percent of patients with two- or three-vessel disease in
RITA. [37 ] , [48 ] In community clinical practice, completeness of revascularization by
PTCA is likely to be much lower than that achieved by experienced centers in highly
selected trial patients. In community practice, it is estimated that complete
revascularization is achieved in only 25 percent of patients with triple-vessel disease
by PTCA or in approximately 45 percent of patients with multivessel disease overall.
In most patients with chronic, totally occluded coronary arteries, revascularization of

occluded arteries is not possible by current angioplasty techniques. As evident in
Table 15-1 , 35 to 37 percent of the patients excluded from the randomized
multivessel PTCA versus CABG trials were excluded because of the presence of a
chronic total occlusion of a coronary artery serving viable myocardium. Thus the high
proportion of trial patients with less-than-three-vessel disease, well-preserved
ventricular function, and absence of chronically occluded rteries produces a study
population that favors a higher incidence of complete revascularization by PTCA
and attenuated consequences of incomplete revascularization than expected in
community practices. In patients with severe angina, triple-vessel disease, and
ventricular dysfunction, survival is greater in those with three or more coronary
arteries bypassed than in those with only two vessels bypassed. [20 ] , [29 ] CABG
surgery improves survival in patients with three- and two-vessel disease with left
ventricular dysfunction compared with medical therapy. Although angioplasty may
have a similar survival benefit, its influence on this high-risk subgroup has not been
fully tested or reported.
Additional information on the long-term outcomes of coronary angioplasty and

CABG surgery in patients may be obtained from large, prospectively managed,
nonrandomized database studies. In the Duke Cardiovascular Disease Databank,
9263 patients undergoing clinically indicated coronary angiography between 1984
and 1990 were followed a mean of 5 years after nonrandomized treatment by CABG
surgery, PTCA, or medical therapy. [4 ] Patients with valvular disease, prior
revascularization, significant (> 75 percent) left main disease, and congenital and
nonischemic cardiomyopathy were excluded. Overall, 39 percent of the patients had
single-vessel disease, two-vessel disease was present in 31 percent, and 30
percent had three-vessel disease. Medical therapy was provided in 3053 patients,
PTCA was performed initially in 2788 patients, and CABG was performed as initial
therapy in 3422 patients. To correct for baseline differences among the three
treatment groups, a standard covariate adjustment was performed that included all
identified prognostic factors in a multivariate survival model. Complete follow-up
was obtained in 97 percent of patients.
In this database study, as in the randomized trials, the effects of revascularization on

survival depended largely on the extent of the coronary artery disease. For the least
severe (one-vessel disease), there were no survival advantages of revascularization
over medical therapy in up to 5 years of follow-up. [4 ] For intermediate levels of
coronary artery disease severity (i.e., two-vessel disease), there was a higher
5-year survival rate for patients undergoing revascularization than for those treated
medically. For patients with the most-severe coronary artery disease (i.e.,
three-vessel disease), CABG surgery provided a significant and consistent survival
advantage over medical therapy. PTCA appeared prognostically equivalent to
medical therapy in these patients, but only a small number of patients in this
subgroup underwent angioplasty. In comparing PTCA with CABG surgery, PTCA
demonstrated a small survival advantage over CABG surgery for patients with
less-severe two-vessel disease, whereas CABG surgery was superior for
more-severe two-vessel disease (i.e., proximal left anterior descending artery
involvement). Although a nonrandomized study of PTCA and CABG surgery for
patients with two-vessel disease at Emory did not stratify the severity of two-vessel
disease, the overall adjusted 5-year survival rate of 93 percent was identical in the
two groups and was similar to the 91 percent in the Duke study. [28 ]
The mortality hazard ratios derived from the Cox regression model to evaluate
relative survival differences in this database study are shown for medicine versus
CABG surgery in Figure 15-4 , PTCA versus medicine in Figure 15-5 , and PTCA
versus CABG in Figure 15-6 . [4 ]
This database study confirms the survival advantage of CABG surgery over medical
therapy for more-severe coronary artery disease noted in the major randomized
trials one decade earlier and indicates that in this patient subset the survival
advantage for CABG surgery persists relative to PTCA as well. For less-severe
coronary artery disease, the survival advantages of PTCA over medical therapy are
modest, and there was no survival advantage for CABG surgery. In these patients, in
whom overall mortality risks are lower, decisions for treatment are usually based on
patient preference, symptom relief, and quality of life in addition to survival
considerations.
As evident from the foregoing analysis, most coronary artery disease treatment trials
have focused on chronic stable angina and the outcomes and considerations for
elective medical therapy or revascularization, generally employing anatomic (i.e.,
one-, two-, or three-vessel disease) subgroups rather than clinical or functional
classifications that may more reliably identify high-risk and low-risk patients. [51 ]
CURRENT INDICATIONS FOR PTCA AND CABG IN PATIENTS WITH

MULTIVESSEL DISEASE
For the overwhelming majority of patients with left main coronary artery disease,
CABG surgery is the preferred option, but it is also the procedure of choice for most
patients with triple-vessel disease, left ventricular dysfunction, diffuse disease, and
perhaps diabetes. These groups comprise the patients at highest risk, with
complete revascularization an important objective in many and essential in some.
This subset also includes patients with preexisting left ventricular dysfunction, for
whom the adverse consequences of acute PTCA failure are greater.
These trials also demonstrate a very clear and important role for PTCA and other
transcatheter technologies in patients with multivessel disease. These procedures
are particularly attractive for patients with preserved left ventricular function and
primarily double-vessel disease and patients with advanced age. Furthermore, as
time passes, newer interventional techniques can be expected to widen the pool of
patients amenable to transcatheter technologies.
It is evident that we are dealing with a constantly moving target as advances in

medical therapy, CABG surgery, and transcatheter technologies continue. In
perspective, however, it is important to emphasize the consistency of these trials to
date and the value of a large body of prospectively obtained, objective data that
provide the basis of educated recommendations for individual patients.
ACUTE CORONARY SYNDROMES
Acute coronary syndromes include unstable angina, postinfarction angina, and

Printzmetal's angina and denote acute, symptomatic changes in the myocardial oxygen
supply-demand ratio over a short time span. Printzmetal's angina , or coronary
vasospasm, is diagnosed definitively by electrocardiograms obtained during the
episode of pain and is treated medically. Unstable angina is not a uniform clinical entity
but describes a spectrum of myocardial ischemia between chronic stable angina and
myocardial infarction. Unstable angina implies a recent change in the severity,
character, or trigger threshold of chronic stable angina or new-onset angina.
Approximately 5.6 million Americans have chronic angina and about 350,000 develop
new angina each year. [52 ] Unstable angina develops in approximately 750,000
Americans each year and is associated with subsequent myocardial infarction in
approximately 10 percent. Postinfarction angina is defined as the presence of angina
or other evidence of myocardial ischemia in a patient with a recent (< 2 weeks)
transmural or subendocardial myocardial infarction.
The role of myocardial revascularization for acute myocardial infarction and cardiogenic
shock is presented in Chapter 21.
Unstable and postinfarction anginas are classified into nine subsets according to the
triggering stimulus (A to C) and frequency of pain (I to III) [53 ] (Table 15-4) . Class A
indicates angina precipitated by an extracardiac or indirect stimulus such as an
arrhythmia or hypotension that can be reversed by medical management. Class B
indicates angina without an extracardiac or indirect stimulus, and class C indicates
angina in the presence of acute (< 2 weeks) myocardial infarction. Class I is new or
accelerated angina without rest pain. Class II is angina at rest within 1 month but not
within 48 hours. Class III is angina at rest within 48 hours.
Unstable angina is a compelling symptom indicating an acute imbalance between

myocardial oxygen supply and demand. There are no recent trials of medical
management versus PTCA or CABG surgery for the treatment of unstable angina, and
the natural history of the syndrome was recorded before the introduction of modern
medical therapy that includes intravenous heparin, nitrates, beta blockers,
calcium-channel blockers, thrombolytics, platelet inhibitors, and the intraaortic balloon
pump. In the classic report by Gazes et al. [54 ] in 1973 of 140 patients with unstable
angina the 1-, 5-, and 10-year mortality rates were 18, 39, and 52 percent, respectively.
The 1-year mortality was 8 to 10 percent, and the 1-year nonfatal myocardial infarction
rate was 12 to 14 percent.
All patients who present with unstable angina are initially managed medically to alleviate
ongoing ischemia and to prevent acute myocardial infarction. More than 80 percent of
patients become asymptomatic within 48 hours. Myocardial infarction is ruled in or out
by serial electrocardiographic and enzyme studies. In general, patients without rest pain
(class I) are successfully managed medically, and a decision to perform coronary
angiography is optional or may be made after provocative testing for ischemia. [55 ] In
patients who have had angina at rest but are not having rest angina in hospital (class II),
coronary angiography is recommended for those with evidence of easily provoked or
ongoing ischemia (class IIB) and may be done optionally to discover left main, tight (>
95 percent) left anterior descending, or three-vessel coronary artery disease in classes
IIB and IIC. [55 ] , [56 ] Patients with class III unstable angina nearly always require
coronary angiography and revascularization.
CABG versus Medical Therapy
Two multicenter trials and one single-center randomized trial involving a total of 823
patients evaluated the relative merits of CABG surgery and medical therapy in unstable
angina between 1972 and 1982. [57 ] [59 ] Patients with left main disease, poor left
ventricular function (ejection fraction < 30 percent), and age greater than 70 years were
not included. In the largest trial of 468 men, recurrent angina was significantly greater in
the medically treated patients, and there was high crossover (34 percent in 24 months)
to surgical therapy. There was no difference in progression to Q-wave infarction, but
patients with impaired left ventricular function had substantially higher 2-year survival
rates when treated surgically in comparison with medical therapy. [57 ] In the patient
subset with three-vessel disease, 5-year survival was higher in the surgical group
regardless of left ventricular function. [56 ] Mortality correlated with the extent of
ventricular impairment in the medical group but not in the surgical group. At both 5 and 8
years, there were fewer subsequent hospitalizations in the surgical group for cardiac
reasons, [57 ] but by 10 years the survival advantage of CABG surgery was insignificant
except in patients with the lowest ejection fractions. [60 ] All patients in this study
received only saphenous vein grafts, but the data indicate that patients with
more-extensive coronary artery disease or impaired left ventricular function have both a
survival advantage and fewer cardiac rehospitalizations with early surgical therapy.
The single-center study (113 patients) demonstrated less subsequent angina, fewer
infarctions, and a survival benefit for surgery in short-term follow-up. [59 ]
The National Cooperative Study Group trial of 288 patients [58 ] showed no difference
in progression to Q-wave infarction and less-severe subsequent angina with operation,
but unlike the VA trial and Bertolasi report, there was no survival difference at 2 years
between surgical therapy (90 percent) and medical therapy (91 percent), but 32 percent
of the medical group crossed over to surgery by 24 months. Since current medical
therapy was not available to these patients, there is significant difficulty in extrapolating
the results of these trials to current clinical practice.
Revascularization for Unstable Angina
The initial success rate for PTCA of significant stenoses in patients with unstable
angina is between 83 and 93 percent. [61 ] [64 ] Acute complications, particularly early
after the onset of unstable angina, are higher (up to 10.5 percent) [62 ] than in patients
with stable angina, but late outcomes are similar. [65 ] , [66 ] These patients are also at
a slightly higher risk of developing a periprocedural acute myocardial infarction. Risk
factors for procedure-related complications include very severe anatomic stenosis,
presence of thrombus, ST-segment elevations, persistent T-wave inversions, and the
number of lesions dilated. [62 ]
The incidence of restenosis is the same or slightly higher after PTCA for unstable
angina as compared with chronic angina. [63 ] , [64 ] , [67 ] Five-year survival rates
exceed 90 percent, and approximately 75 percent of patients are asymptomatic. [61 ]
[64 ] , [68 ] The incidence of late myocardial infarction is similar to that following PTCA
for chronic angina. [68 ]
In patients with unstable angina or non-Q-wave myocardial infarction, medical

management followed by early or delayed PTCA or CABG surgery produced 6-week
mortality and nonfatal infarction rates of 2.1 and 6.1 percent in a trial involving 1473
patients. [56 ] The TIMI IIIB trial compared two strategies for managing unstable angina
after a period of initial stabilization. The aggressive arm involved routine angiography
followed by revascularization in the presence of suitable anatomy. In the conservative
arm, angiography was performed only in the event of recurrent pain or a positive stress
test. Over a 1-year follow-up there was no difference in death or myocardial infarction
between the two groups and, somewhat surprisingly, revascularization rates were
similar, but the timing was differentearlier revascularization in the aggressive arm with
more frequent repeat hospitaliations and later revascularization and higher costs in the
conservative arm. The results of this major trial provide an intellectual justification for
either strategy depending on patient preference and the availability of facilities for
cardiac catheterization and PTCA/CABG. The lack of any difference in mortality and
myocardial infarction rates between the two groups is an important outcome of this
study.
The addition of thrombolytic therapy in these patients is not beneficial and may be
harmful. In patients with a non-Q-wave or Q-wave infarct already treated with
thrombolysis, aggressive revascularization with PTCA or CABG surgery does not
improve early morbidity or mortality. [69 ]
In a database study of CABG surgery for progressive angina, angina at rest, and
postinfarction angina in 1282 patients, actuarial 5- and 10-year survival rates were 92
and 83 percent, respectively. Operative mortality was 1.8 percent. [70 ] Risk factors for
operative mortality in patients with unstable angina did not differ from those of chronic
stable angina and included advanced age, clinical and laboratory evidence of left
ventricular dysfunction, and preoperative use of the intraaortic balloon pump. [71 ] For
patients with postinfarction angina, risk factors for operative mortality were anterior
transmural infarction and preoperative intraaortic balloon pump. [72 ]
PTCA for Acute Myocardial Infarction
Both thrombolytic therapy and direct or primary angioplasty can restore coronary artery
patency and flow during acute myocardial infarction. In the absence of hemorrhagic
concerns, thrombolytic therapy is more widely available and is standard early therapy
for acute transmural myocardial infarction. Several early myocardial reperfusion trials
assessed the role of adjunctive angioplasty in recognition that not all arteries could be
reopened by thrombolysis, that reocclusion occurred in some arteries initially opened,
and that reocclusion was associated with increased morbidity and mortality. [73 ] , [74 ]
The addition of angioplasty to thrombolytic therapy does not enhance patency, improve
left ventricular function, or reduce early mortality but does increase expense and
vascular bleeding problems. [75 ] [77 ] A recent meta-analysis of adjunctive PTCA and
thrombolysis versus thrombolysis only shows no early benefit of PTCA except in
patients who have clinical indications for early revascularization (e.g., postinfarction
angina). [78 ]
The use of angioplasty as an alternative to thrombolytic therapy is the subject of several

recent trials. The PAMI (Primary Angioplasty in Myocardial Infarction) multicenter trial
randomized 395 patients by PTCA ( n = 195) or conventional dosing tissue-type
plasminogen activator (t-PA) ( n = 200). [73 ] A higher initial patency rate was noted for
angioplasty (97 percent) than for thrombolysis (80 percent at 90 minutes), and a
significantly lower ( p = 0.02) composite endpoint of death or reinfarction occurred in the
angioplasty group (5.1 percent) than in the thrombolytic group (12.0 percent). A
retrospective subgroup analysis of high-risk patients reported a 10.4 percent mortality
rate for those treated with t-PA versus a 2.0 percent mortality rate in the angio-plasty
group ( p = 0.01). There were fewer hemorrhagic strokes and the 6-month mortality rate
also was lower (8.5 versus 16.8 percent) in the angioplasty group. [73 ]
In a Mayo Clinic randomized study of 108 patients, there was no difference in mortality
or in myocardial salvage determined by pre- and posttreatment technetium-99m
(99mTc) sestamibi scans, but lower hospital costs, lengths of stay, and late costs were
noted in the angioplasty group.
In a more-recent report of 1137 patients randomized to PTCA versus accelerated t-PA

in a subgroup of the GUSTO II trial, a nonsignificant trend toward an improvement in
mortality and morbidity was noted in the angioplasty group. Differences in patient
selection, timing of therapy, operator experience, and t-PA infusion protocols may
contribute to the differing outcomes and conclusions reached in the PAMI and GUSTO
subgroup trials. Further multicenter trials on acute revascularization in myocardial
infarction are underway, and hopefully, this issue will be clarified in future years.
A meta-analysis of seven trials comparing PTCA and thrombolysis for acute myocardial
infarction found a significant reduction in early mortality (within 6 weeks) and the
combination of early mortality and nonfatal myocardial infarction with PTCA, but
because of the lack of long-term information, the authors recommend caution in the
interpretation of these data. [78 ]
Reperfusion by emergency CABG surgery in acute myocardial infarction is generally not

performed (except possibly for cardiogenic shock; see Chapter 21) because of the
more readily available and less-expensive thrombolytic and angioplasty therapeutic
options.
INDICATIONS FOR REVASCULARIZATION
Despite the underrepresentation in the recent reperfusion trials of patients at high risk
and those with chronically occluded arteries, enough evidence has emerged to allow
formulation of general indications for revascularization. These indications are provided
with the caveat that significant temporal changes in the reperfusion procedures and
adjunctive therapy that may alter efficacy occur continuously. Examples of such changes
are the widespread use of internal thoracic artery grafts, microinvasive CABG surgery,
newer antiplatelet agents such as the IIB-IIIA glycoprotein inhibitors, and percutaneous
intracoronary stents. It also must be emphasized that the recommendations below are
based on fairly short-term (1- to 5-year) outcome reports and that the long-term efficacy
of CABG surgery and angioplasty probably will require 10 years of follow-up for
adequate assessment.
Patients with the most advanced coronary artery disease, such as left main,
three-vessel, or two-vessel disease with proximal left anterior descending
artery involvement, or with significant left ventricular impairment have the
most to gain in survival benefit from CABG surgery in comparison with both
medical therapy and angioplasty. The recent BARI trial suggests that
diabetics also may benefit from early CABG surgery, but further data on the
clinical and angiographic characteristics of diabetics versus nondiabetics
are needed before firm recommendations can be made.
For patients with less-extensive atherosclerosis and preserved left

ventricular function, no distinct advantage in terms of survival has been
demonstrated for one therapy (medical, angioplasty, or surgery) over
another. A high proportion of lower-risk patients included in
revascularization trials are alive and angina-free regardless of the initial
mode of revascularization for up to 5 years after initial therapy. However,
patients who initially undergo CABG surgery have fewer subsequent
revascularization procedures, antianginal medicines, or cardiac
rehospitalizations than those on medical therapy or those treated initially by
angioplasty.
Among patients with unstable angina, some groups are at higher risk [4 ] ,
[55 ] based on response to therapy, dynamic electrocardiographic changes
during pain, and evidence of left ventricular dysfunction. These descriptors
are all indicative of severe ischemia and/or left ventricular dysfunction and
strongly warrant consideration for revascularization depending on coronary
artery anatomy.
Patients with postinfarction angina, in general, are another high-risk group

with severe ischemia and left ventricular dysfunction for whom the likelihood
that revascularization will be beneficial is strong and logical.
THROMBOLYSIS FOR ACUTE MYOCARDIAL INFARCTION
Background
Thrombolytic therapy for acute MI evolved from early attempts in the 1970s to treat
patients with MI on an emergent surgical basis. [6 ] Because cardiac catheterization
was required to delineate the coronary anatomy before undertaking coronary bypass,
soon it became apparent that thrombotic coronary occlusion was present in most of
these patients. Still, many investigators remained unconvinced that total thrombotic
occlusion was a significant factor in acute MI. Although thrombolytic therapy was widely
tested in Europe throughout the 1970s, it was not uniformly accepted. Interventional
studies during that period provided further evidence that thrombotic occlusion was the
cause of acute MI and opened the way for the study of both intracoronary and
intravenous thrombolytic therapy.
The modern era of thrombolytic therapy began in the late 1970s with the observation by
Rentrop [7 ] that intracoronary streptokinase provided effective thrombolysis for the
infarct-related coronary artery and, in the early and mid 1980s, when intravenous
streptokinase therapy was shown to reduce mortality in patients with myocardial
infarction in the clinical trial Gruppo Italiano per lo Studio della Streptochinasi
nell'Infarcto Miocardio (GISSI). [8 ] Since that time, numerous clinical trials have been
undertaken to test the efficacy of various thrombolytic agents in the treatment of acute
myocardial infarction. The results have shown definitively that timely administration of
thrombolytic agents reduces infarct size, preserves left ventricular function, and
improves short- and long-term survival in patients with acute MI. Despite the irrefutable
evidence that thrombolytic therapy is beneficial, controversial issues regarding this
therapy remain, such as the specific drug to be used, the need for heparin, the relation
between time to treatment and outcome, and risk: benefit considerations. As we gain
more information from ongoing clinical trials, these issues will become more clearly
defined.
Thrombolytic Agents
Complete thrombotic coronary occlusion usually results from ulceration or fissuring of

vascular endothelium at the site of an atherosclerotic plaque. As a response to vessel
injury, platelets adhere to the damaged endothelium and activate coagulation factors.
This results in fibrin formation and thrombotic coronary occlusion. Thrombolytic drugs
work by activation of plasminogen to the active enzyme plasmin, which digests the fibrin
component of the clot.
Thrombolytic agents may be divided into two general groupsthe fibrin-specific and
non-fibrin-specific activators. The specific group consists of tissue-type plasminogen
activator (t-PA) and its mutants (r-PA and others) and, to a lesser extent, single-chain
urokinase plasminogen activator (scu-PA); the relatively nonspecific proteases include
streptokinase (SK), urokinase (UK), and anistreplase (APSAC). [9 ] Four of these
drugs, SK, t-PA, urokinase, and APSAC are commercially available and widely used in
the treatment of acute MI. The drugs vary according to their clearance, fibrin selectivity,
plasminogen binding, in the potential to induce allergic reactions, and in costs. [10 ] ,
[11 ]
Streptokinase
Streptokinase was the first thrombolytic protein discovered, and it has been studied
more extensively than any other thrombolytic agent. It works by joining to plasminogen in
a complex that converts neighboring plasminogen to plasmin. [12 ] As a product of
B-hemolytic streptococci, streptokinase is antigenic and may produce allergic reactions
in patients with recent streptococcal infections. The recommended dose of
streptokinase (1.5 million units) is usually sufficient to overcome the neutralizing effect of
antibodies; therefore, most patients will develop systemic fibrinolysis. The
pharmacologic half-life of streptokinase is 30 minutes; depletion of fibrinogen usually
lasts for 24 hours. Antibodies develop approximately 4 days after streptokinase therapy
and persist for 6 months to 1 year; therefore, it is recommended that patients not be
retreated with streptokinase (or APSAC) during that time.
Streptokinase has been tested in thousands of patients and has shown the ability to
improve left ventricular function and save lives. Also it is less costly than other agents.
However, it does have the potential for allergic reactions [13 ] and hypotension. [14 ]
Tissue Plasminogen Activator (Activase)
t-PA is a naturally occurring serine protease that is nonantigenic and may be

readministered immediately in the event of reinfarction. [12 ] Unlike SK and APSAC,
t-PA is relatively fibrin-specific and clot-selective, producing more local thrombolysis.
One disadvantage of t-PA is that its short half-life (5 minutes) may contribute to infarct
vessel reocclusion. This limitation has led to the development of t-PA mutants with
glycosylation and other defects that delay the clearance of t-PA, and, in experimental
animal models, result in more rapid thrombolysis and reduction in the risk of
reocclusion. [15 ] [17 ] Originally, the recommended dose of t-PA was 100 mg over a
3-hour period (60, 20, and 20 mg over hours 1, 2, and 3, respectively). In 1989,
Neuhaus and colleagues [18 ] , [19 ] initiated front-loaded or accelerated t-PA dosing,
by demonstrating that higher patency could be achieved with a regimen of a 15-mg
bolus, 50 mg given in the first 30 minutes and the remainder (35 mg) infused over the
next 60 minutes. More recently, an initial 20-mg bolus is administered, with the
remainder of the t-PA being given over 1 hour. With the doses at which t-PA is usually
given, the decline in fibrinogen is approximately 50 percent; therefore, there is less
generation of fibrinogen split products.
Even though t-PA is clot selective, it does not cause fewer bleeding complications than
the other drugs. Increased bleeding complications have been noted particularly in
patients of smaller body size (<65 kg). Therefore, in these patients, the recommended
dosage is lowered to 1.25 mg/kg over 3 hours, with 10 percent as a bolus, 50 percent
for the first hour, and 40 percent for the last 2 hours. Although acute reperfusion rates
have been shown to be higher with t-PA than with streptokinase ( Tables 16-1 and 16-2
), [20 ] reocclusion also may be higher. In addition, because of its higher fibrinolytic
potency, t-PA may induce hemorrhagic stroke at a higher rate than streptokinase. It is
also more costly than other thrombolytic drugsabout 5 to 10 times more costly than
streptokinase. [21 ] , [22 ]
Anisoylated Plasminogen Streptokinase Activator Complex (Eminase)
Anisoylated plasminogen streptokinase activator complex (APSAC) is a new

second-generation thrombolytic agent that was developed to overcome some of the
limitations of streptokinase therapy. [12 ] With APSAC, the active enzymatic site of the
plasminogen streptokinase complex is temporarily protected by acylation, therefore
allowing rapid intravenous injection of the drug. This results in prolonged fibrinolytic
action. Compared with streptokinase, APSAC has greater fibrin binding and a longer
duration of action (half-life of 90 minutes). This simplifies intravenous administration of
the drug, with improved coronary reperfusion and reduced reocclusion rates. The entire
bolus of the drug can be administered over a period of 25 minutes, and its expense is
moderate compared with the other fibrinolytic agents. APSAC is not superior to other
drugs, however, in improving ventricular function or reducing mortality.
Urokinase
Another thrombolytic agent, urokinase, has been approved by the FDA for intravenous
administration, but is not available for intracoronary use. Urokinase is a proteolytic
enzyme produced from human fetal kidney tissue cultures. [12 ] The usual dosage is 3
million units, which usually is sufficient for depletion of fibrinogen. The dosage consists
of 1.5 million units as a bolus, with 1.5 million additional units given over a 1-hour
period.
Clinical trials have shown that after intravenous urokinase, the rate of coronary patency
is approximately 5070 percent; reocclusion is 510 percent. [23 ] [25 ] Compared with
streptokinase, urokinase has much less antigenicity, can be given in a bolus dose, and
has a relatively low rate of reocclusion. There are fewer allergic reactions and less
hypotension associated with this drug. The disadvantages include its relative expense
compared with other agents and the relative lack of experience with it in the United
States. It has been more widely used in Europe.
Prognostic Criteria
INDICATIONS FOR THROMBOLYSIS
The current consensus is that thrombolytic therapy is greatly underutilized in patients

with acute MI, despite a broader application of the therapy. [26 ] The criteria for
appropriate patient selection for thrombolytic intervention have evolved as more
knowledge is gained through clinical trials. All patients presenting with MI should be
considered candidates for intravenous thrombolytic therapy if they are seen less than 6
hours after the onset of symptoms and have no potential bleeding problems. Because
the extent of myocardial damage occurring during acute MI is time-dependent, mortality
reduction is greatest in those patients treated early with thrombolytic agents, although
beneficial effects have been shown with treatment initiated up to 12 hours after the
onset of symptoms. [27 ] [29 ] It is agreed generally that patients presenting with ST
segment elevation or bundle-branch block will benefit by thrombolytic therapy. Those
with ST depression only should be excluded.
CONTRAINDICATIONS
Late presentation after symptom onset and older patient age are the most common
contraindications to thrombolytic therapy. Within the past several years, elderly patients
with MI have been treated more routinely, however. [30 ] In a meta-analysis of eight large
clinical trials, with regard to older patients, thrombolytic therapy was shown to have the
greatest margin of benefit in patients aged 65 to 74 years. [31 ] In patients older than 75
years, only 18 lives were saved per 1,000 patients; this is owing, in part, to an increase
in bleeding complications in this patient subset.
In 1990, Muller and Topol [32 ] critically reviewed the recommendations regarding
patient eligibility for thrombolytic therapy after acute MI by examining studies published
during a 10-year period. They examined only randomized, controlled trials of
intravenous thrombolysis in acute MI and unstable angina. This study revealed that
relatively few patients with MI were considered eligible for the therapy. Those excluded
from thrombolysis, however, had a high early mortality. The findings suggested that
selected, high-risk subgroups might benefit from thrombolytic therapy. Such groups
would include otherwise healthy elderly patients, certain patients presenting more than 6
hours after the onset of symptoms, and those with a history of controlled systolic
hypertension, or brief nontraumatic cardiopulmonary resuscitation. Their data did not
support the use of fibrinolytic therapy as primary treatment for patients with unstable
angina or suspected myocardial infarction in the absence of confirmatory
electrocardiographic changes.
More recently, investigators from the Global Utilization of Streptokinase and Tissue
Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial developed a
multivariable statistical model for risk assessment in candidates for thrombolytic
therapy. [33 ] They used criteria from the large population of 41,021 patients in this trial
to analyze the relationship between baseline clinical data and 30-day mortality. They
concluded that multiple characteristics of the patient must be considered for an
accurate prognosis to be determined. These characteristics include age, medical
history, physiological significance of the infarction, and medical treatment. Specifically,
multivariable analysis identified age as the most significant factor influencing 30-day
mortality, with rates of 1.1 percent in the youngest decile (<45 years) and 20.5 percent
in older patients (>75 years). Other factors most significantly associated with increased
mortality were lower systolic blood pressure, higher Killip class, elevated heart rate, and
anterior infarction. These five factors comprised 90 percent of the prognostic
information in the baseline clinical data. Other less significant factors included previous
myocardial infarction, height, time to treatment, diabetes, weight, smoking status, type
of thrombolytic, previous bypass surgery, hypertension, and prior cerebrovascular
disease.
CHOICE OF THROMBOLYTIC AGENT
Information regarding drug selection has become available from three large-scale
randomized trials directly comparing the risks and benefits of various thrombolytic
agents in acute MI. [34 ] [36 ] These include the Gruppo Italiano per lo Studio della
Sopravvivenze nell'Infarcto Miocardico (GISSI-2) trial and its International Extension, the
Third International Study of Infarct Survival (ISIS-3), and the GUSTO-1 trial (mentioned
earlier). In the interpretation of results from these trials, it is agreed generally that the
agents most commonly used in the United Statest-PA, SK, and APSACall reduce
mortality when given to patients with acute evolving MI.
In addition, when the therapy is given to patients presenting up to 12 hours after onset of
symptoms, the mortality rate is reduced by approximately 20 percent. When aspirin
therapy is used in patients presenting up to 24 hours after symptoms begin, there is a
23 percent reduction in mortality. The combination with aspirin enhances the
thrombolytic efficacy of streptokinase and, probably, of all thrombolytic interventions.
Heparin (or another thrombin inhibitor) given intravenously in adequate dosage is
required to allow t-PA to exert a maximal thrombolytic effect. Aspirin is a
cyclo-oxygenase inhibitor and reduces the availability of thromboxane A2, a potent
promoter of platelet aggregation. Thrombin is formed at sites of vascular injury and
constriction, and it promotes platelet aggregation and vasoconstriction. Thrombolytic
therapy activates platelets and the addition of aspirin and thrombin inhibitors
counteracts the platelet activation and local effects of thrombin.
The most important finding in the analysis of randomized trials is that earlier
administration, as well as more widespread use of thrombolytic therapy and aspirin,
would save many more lives. In several studies, patients who received streptokinase
had slightly fewer strokes than those who received t-PA or APSAC, but the biological
difference is small.
One important contribution of the GUSTO trial, according to Habib, [11 ] is that it
provided compelling evidence for the open artery theory. [37 ] Regardless of which
thrombolytic drug was used, 30-day mortality was substantially higher (8.9 vs 4.4
percent, p = 0.009) in patients with a nonperfused infarct-related artery. According to
the theory, rapid and complete coronary reperfusion is associated with improved
clinical outcome (improved survival and improved ventricular function). [37 ] These
results have provided impetus for further clinical and basic research trials in this area.
Thrombolysis with Other Treatment Strategies
EARLY INVASIVE VS EARLY CONSERVATIVE STRATEGIES: TIMI IIIB
Thrombolytic therapy has been compared with other treatment strategies in recent
years in several clinical trials. The Thrombolysis in Myocardial Ischemia (TIMI)-IIIB
clinical trial, which included 1,473 patients, was designed to compare the efficacy of
t-PA with early invasive versus early conservative strategies in patients with unstable
angina and non-Q wave myocardial infarction. [38 ] In this large study of patients with
unstable angina and non-Q-wave MI, the incidence of death and nonfatal infarction or
reinfarction was low but not trivial after 1 year (4.3 percent mortality, 8.8 percent nonfatal
infarction). An early invasive management strategy was associated with slightly more
coronary angioplasty procedures but equivalent numbers of bypass surgery procedures
than a more conservative early strategy of catheterization and revascularization only for
signs of recurrent ischemia. No difference was seen in death or nonfatal infarction, or
both, after 1 year, according to strategy assignment, but fewer patients in the early
invasive strategy group underwent later repeat hospital admission (26 vs 33 percent, p
< 0.001). According to these results, either strategy appears to be acceptable for
treatment of patients with unstable angina and non-Q-wave MI; in this regard, physicians
have latitude in individualizing care for such patients. In the patients with unstable
angina and non-Q-wave infarction, thrombolytic therapy did not reduce mortality or
morbidity. [38 ]
Angioplasty and Thrombolytic Therapy
Percutaneous transluminal coronary angioplasty (PTCA) often is performed in patients

with acute MI after thrombolytic therapy or in lieu of thrombolysis. An early trial by
Ribeiro and associates [39 ] compared the benefit of thrombolytic therapy utilizing
streptokinase with that of direct coronary angioplasty in 100 patients who presented
with acute MI at a single interventional center. They excluded patients who were older
(75 years), or had prior bypass surgery, Q-wave infarction in the region of ischemia, or
excessive risk of bleeding. There were no major differences in the baseline
characteristics of the two treatment groups in this study. Results showed no difference
in 48-hour infarct-related artery patency or LV-ejection fraction. Also, there were no
major bleeding events, and mortality was similar. The investigators concluded that
intravenous therapy might be preferred over coronary angioplasty because of the
shorter time to treatment.
Several prospective clinical trials in the United States and Europe have been
undertaken to test the role and timing of angioplasty after intravenous thrombolytic
therapythe Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) study, [40 ] the
European Co-operative Study, [41 ] and the Thrombolysis in Myocardial Infarction (TIMI)
II-B [42 ] , [43 ] study. These early trials revealed the detrimental effects of aggressive
treatment for MI patients. Invasive therapy after intravenous thrombolytic therapy with
recombinant tissue-type plasminogen activator (rt-PA) resulted in no additional
preservation of ventricular function and no improvement in survival probability.
Furthermore, this aggressive approach was associated with greater morbidity and a
trend toward higher mortality.
A meta-analysis of randomized clinical trials examining the benefits of PTCA alone and
PTCA after thrombolysis revealed less convincing evidence for the superiority of one
therapy over another for treatment of acute MI. [44 ] The analyses of the various
categories of trials have suggested that primary PTCA may be more beneficial than
thrombolytic therapy in acute MI. [10 ] According to Ross, the current overall impression
is that direct PTCA for acute infarction is an effective method of reperfusion so long as
it can be accomplished in the same time frame as can pharmacologic reperfusion. [10 ]
Based on several large-scale trials, however, there has been failure to confirm a lower
reocclusion rate for PTCA as compared with plasminogen activator therapy. [10 ]
GENDER
Stone and coworkers [45 ] compared in-hospital outcomes in men versus women who
were treated by either thrombolytic therapy or primary coronary angioplasty for acute MI.
Their study comprised 395 patients (288 men, 107 women) in 12 centers who were
prospectively randomized to treatment with t-PA or primary PTCA. The in-hospital
mortality in women was 3.3-fold higher than in men (9.3 vs 2.8 percent, p = 0.005).
Women were older, more often had diabetes mellitus, systemic hypertension, prior
congestive heart failure, and presented later after symptom onset. In contrast, after
primary PTCA, women and men had similar in-hospital mortality (4.0 vs. 2.1 percent,
respectively, p = 0.46). Multiple logistic regression analysis of 15 clinical variables
showed that treatment with PTCA, as well as younger age, were independently
predictive of in-hospital survival in women.
COST
As greater numbers of clinical trials have been undertaken to compare the efficacy of
thrombolysis versus primary angioplasty for acute MI, comparisons regarding cost
effectiveness of these separate strategies have been made by several investigators.
According to a study by Goldman, [21 ] the incremental cost for thrombolysis with
streptokinase in patients with acute myocardial infarction ranges from approximately
$3,500 to approximately $21,000 per year of life saved. The incremental
cost-effectiveness of tissue-type plasminogen activator (t-PA) compared with
streptokinase ranges from approximately $16,000 to $60,000 per year of life saved.
Combined data from three randomized trials suggest that primary angioplasty can
reduce mortality by as much as 63 percent without any increase in cost. This reduction
is much greater than that shown by early administration of thrombolytic therapy or by
accelerated t-PA versus streptokinase. Further studies are needed, however, to confirm
the superiority of PTCA as primary therapy with regard to quality-of-life and cost
benefits.
PERCUTANEOUS TRANSLUMINAL CORONARY ANGIOPLASTY
Indications for PTCA
The role of PTCA in the treatment of coronary artery disease continues to evolve. [46 ]
The original indication for PTCA was the presence of angina pectoris with failure of
maximal medical therapy in a patient with an anatomically appropriate lesion (de novo,
type A) of a single diseased coronary artery. [47 ]
Today, PTCA is used in patients with multivessel disease, calcified and/or eccentric
lesions, distal coronary stenosis, complex or multiple lesions within the same vessel, or
saphenous or internal mammary bypass grafts. [48 ] PTCA also is used as primary
therapy for patients with acute myocardial infarction (Figure 16-1) . [10 ] , [49 ] In
patients with stable angina and single-vessel disease, PTCA alleviates symptoms more
completely than medical therapy alone. It may also reduce the development of unstable
angina and result in fewer hospitalizations.
In acute MI, PTCA applied sequentially, that is, after early administration of thrombolytic
agents, is not considered a beneficial treatment since poor results have been shown in
clinical trials. In selected patients, however, PTCA as an adjunctive therapy (several
days after the occurrence of MI) is a common choice and is probably applied in up to
one-third of patients first treated with a plasminogen activator. [10 ]
The decision of whether to utilize PTCA is dependent on several criteria: lesion

classification, the number of lesions or diseased vessels involved, and the patient's
history and clinical status. The American College of Cardiology (ACC) and the
American Heart Association (AHA) have developed a classification system for patients
undergoing PTCA, based on the likelihood of a successful procedure (Table 16-3) . [49
]
Contraindications
The Task Force also has outlined contraindications to coronary angioplasty ( Table
16-4 and Table 16-5 ).
Surgical Backup for PTCA
Early trials showed that angioplasty during the first hours after onset of MI is associated
with a lower incidence of reinfarction, intracranial hemorrhage, and death than
thrombolysis. [50 ] For this reason, the procedure has been approved in hospitals that
do not have coronary bypass backup programs. However, according to the current Task
Force guidelines, the national standard of accepted medical practice for coronary
angioplasty requires that an experienced cardiovascular surgical team be available
within the institution to perform emergency coronary bypass surgery should the clinical
need arise. [49 ] Surgical consultation is advisable in cases in which the extent of
disease indicates that surgery may be a more effective means of therapy than
angioplasty. [51 ]
Single-Vessel Coronary Artery Disease
Patients with single-vessel coronary artery disease with significant symptoms are still
one of the largest groups undergoing angioplasty. In this group of patients, a 9095
percent success rate can be expected. [52 ] , [53 ]
Several studies have been undertaken in recent years to compare the outcome of
PTCA with other therapeutic measures in patients with single-vessel disease. The
Department of Veterans Affairs Angioplasty Compared with Medical Therapy (ACME)
Study addressed 212 patients who had single-vessel lesions of 7099 percent diameter
stenosis and myocardial ischemia by treadmill testing for whom continued medical
therapy was still an option. [54 ] This study showed that PTCA offers earlier and more
complete relief of angina than medical therapy and is associated with better
performance on the exercise test. The drawbacks of PTCA are its initial higher costs
and an association with a higher frequency of complications.
Angioplasty vs Surgery
The role of angioplasty in treatment for multivessel disease has become increasingly
common, yet the benefits of this approach versus bypass surgery have not been
determined. Coronary bypass surgery offers the advantage of more complete
revascularization regardless of the coronary anatomy at the time of the procedure, yet it
carries the risks of general anesthesia, mechanical ventilation, midline sternotomy,
extracorporeal circulation, and a prolonged recovery time. [49 ] Coronary angioplasty
carries the risks of abrupt vessel closure and early restenosis, and it does not
guarantee complete revascularization at the time of the procedure. [49 ] Randomized
trials of surgical therapy have shown that the benefits of surgical revascularization are
proportional to the amount of myocardium affected by, or at risk for, ischemic injury. [48 ]
Comparisons between angioplasty and bypass surgery in select populations with
single- and multivessel coronary artery disease have shown that PTCA is not as
effective as surgery for long-term symptomatic control, and that it often requires repeat
PTCA or cross-over to bypass surgery; however, long-term outcomes (i.e., death and
myocardial infarction) are similar. [55 ] The critical outcome measures of these
procedures will be functional status, quality of life, employment, and health care costs.
[56 ]
The Coronary Artery Surgery Study (CASS) showed no survival benefits for
revascularization among patients who received PTCA without having failed medical
therapy. Certainly, the advantages of PTCA would have to be measured by symptom
relief, functional improvement, or reduced cost in this patient subset. [57 ]
The Emory Angioplasty vs. Surgery Trial (EAST) [58 ] recently assessed the 5-year
outcome in 392 patients randomized to coronary surgery ( n = 194) or coronary
angioplasty ( n = 198). Each group had an in-hospital mortality of 1 percent. Survival
was 91.2 percent in the CABG group versus 87.9 percent in the PTCA group ( p =
0.29). Whereas at 3 years there was no difference in mortality, by 5 years there was a
slight but not significant separation of the curves favoring surgery. Most of the additional
revascularization procedures occurred in the first year and there were more additional
revascularization procedures in the PTCA group. The study is continuing.
In a similar trial, the Bypass Angioplasty Revascularization Investigation (BARI), 1,800
patients from 16 centers across the United States have been enrolled for a 5-year study
period. [59 ] , [60 ] This trial is designed to evaluate whether the strategy of PTCA is as
safe (regarding mortality) as the strategy of starting with bypass surgery. The surgical
cohort of this trial represents the largest group of patients with multivessel coronary
artery disease who have been randomly assigned to surgical treatment. Patients were
eligible for BARI if they had multivessel coronary artery disease, had a clinical indication
for revascularization, and were suitable for both coronary angioplasty and bypass
surgery. The end-point of mortality will be examined at 5 years.
Another trial, the Randomized Intervention Treatment of Angina (RITA), was established
to compare angioplasty with surgical therapy in stable and unstable angina. [61 ] This
trial differs from BARI and EAST in that the lesions in each patient must be suitable for
both angioplasty and surgery. The goal for both strategies is to achieve complete
revascularization. At the 2 1/2-year follow-up in RITA, there was no difference between
PTCA and bypass surgery for survival on myocardial infarction. [61 ] Additional
revascularization procedures, myocardial infarction, and death were more common
among PTCA patients (38 percent) than among bypass surgery patients (11 percent)
within 2 years of randomization. Repeat coronary angiography was four times more
common among PTCA patients (31 vs 7 percent). Follow-up will continue to at least 5
years.
Other clinical trials underway in Europe will include angiography and thallium stress
testing in their follow-up evaluations. [62 ] , [63 ] In the German Angioplasty Bypass
Surgery Investigation (GABI), [62 ] at the end of one year PTCA and CABG showed
equivalent improvement in angina. The patients treated with PTCA were more likely to
require further interventions and antianginal drugs, whereas the patients treated with
bypass surgery were more likely to sustain an acute MI at the time of the procedure.
In the Coronary Artery Bypass Revascularization Investigation (CABRI), 183 Dutch

patients with multivessel disease were randomized to treatment with PTCA or coronary
artery bypass surgery between 1988 and 1992. [63 ] The CABG group consisted of 88
patients with a total of 255 vascular obstructions, the PTCA group of 95 patients with
294 vascular lesions. Within 30 days after intervention, the clinical results of the two
treatments were the same. The differences in death rate and myocardial infarctions
were not significant, in contrast to the difference in the numbers of reinterventions. The
death rates were 1.1 and 2.1 percent for CABG and PTCA, respectively. The proportion
of transmural, non-fatal myocardial infarctions was 2.3 percent in the CABG group
versus 3.1 percent in the PTCA group. The proportion of reinterventions was higher in
the PTCA group, 11.4 percent versus 1.1 percent. Early results with CABRI indicate that
PTCA is a reasonable alternative to coronary surgery in patients with multiple vessel
coronary disease.
In a recent review of surgery versus angioplasty for coronary artery disease, Wilson and
Ferguson [55 ] concluded that surgical bypass remains the mainstay of therapy for
patients with severe disease and a poor prognosis for survival, and it is warranted in
patients in whom PTCA has failed repeatedly. Revascularization should be offered on
the basis of symptom severity (in the presence of medical therapy) in accordance with
the prognosis for survival, as judged by the extent and severity of disease.
Complications of Angioplasty
Procedural success in angioplasty relates to certain patient characteristics, such as

younger age and male gender, and to clinical variables such as diabetes, prior
myocardial infarction, prior bypass surgery, and impairment of left ventricular function.
[49 ] Of major importance in predicting the success of the procedure are the
angiographic characteristics of the lesion (or lesions) to be dilated. [64 ] Long, calcified,
or ostial lesions; tortuosity of the vessels; and degenerative vein grafts are particularly
challenging for the interventionalist. The risk of abrupt vessel closure and early
restenosis must be carefully weighed when determining which patients will most benefit
from angioplasty. Other risks associated with the procedure include stroke, myocardial
infarction, arrhythmias, and vascular complications at the catheter entry site.
ABRUPT VESSEL CLOSURE
It is estimated that an acute ischemic complication will develop in approximately 7

percent of patients undergoing coronary angioplasty. [65 ] In more than half of these
patients, thrombus, dissection, or both can be identified angiographically as the
underlying cause of abrupt closure. [65 ] Predictors of dissection-mediated closure
include degenerated vein graft, de novo stenosis, proximal tortuosity, high lesion grade,
eccentricity, longer lesion length, and angulation. [65 ] Yellow plaque identified by
angioscopy confers a heightened risk of major complications. Lesions containing areas
of calcium adjacent to areas of soft plaque have been identified by ultrasound as a
powerful predictor of major dissection. The presence of thrombus in the artery to be
dilated is associated with a higher risk of post-procedural thrombotic occlusion.
Tan and associates [66 ] recently examined the determinants of coronary angioplasty
success and complications by evaluating the American College of
Cardiology/American Heart Association ABC lesions classification scheme and its
modifications. They assessed the lesion morphologic determinants of immediate
angioplasty outcome in 729 consecutive patients who underwent coronary angioplasty
of 994 vessels and 1,248 lesions. Angioplasty success was achieved in 91 percent of
lesions, and abrupt closure occurred in 3 percent. They found that longer lesions,
calcified lesions, diameter stenosis of 8099 percent, and presence of thrombus were
predictive of a lower success rate. Longer lesions, angulated lesions, diameter stenosis
of 8099 percent, and calcified lesions were predictive of an abrupt closure.
Despite the various interventions used to prevent abrupt closure, it remains a highly
unpredictable occurrence, with a substantial incidence of myocardial infarction and
angioplasty-related morbidity and mortality. [67 ] Intracoronary visualization by
angioscopy can help to identify important characteristics that identify lesions at risk for
abrupt closure. [67 ] Repeat dilatation is often successful in the treatment of abrupt
closure. [68 ]
In one study examining the impact of new devices on the incidence and reversal rate of
abrupt closure, [69 ] abrupt closure occurred in 80 (4.2 percent) of 1,919 consecutive
coronary angioplasty procedures; 389 procedures (20 percent) were performed with the
use of stents, coronary atherectomy, or laser balloon angioplasty. Abrupt closure was
less frequent following newer coronary interventions (1.8 percent) compared with
standard balloon angioplasty (4.9 percent, p < 0.01). Although this may have reflected
case selection, the results indicated that new interventional devices were associated
with a lower incidence of abrupt closure. Most catheterization laboratories administer
heparin for 1224 hours after angioplasty to reduce the risk of abrupt closure. [70 ]
RESTENOSIS
Restenosis has been deemed the Achilles' heel of angioplasty. [71 ] Despite many
innovations in interventional techniques for coronary disease in recent years, restenosis
remains the most common complication following PTCA. Restenosis may be described
simply as the chronic renarrowing of the dilated vessel in response to the balloon (or
other interventional device) injury that typically occurs over 3 to 6 months after the
procedure. In other words, coronary arteries that have been subjected to balloon
angioplasty or other interventions will be traumatized and undergo wound healing, which
culminates in the formation of stenotic lesions.
In 1992, the average restenosis rate reported in the literature was 30 percent [72 ] ;
recent reports have estimated a range of 2055 percent occurrence of restenosis in
arteries subjected to percutaneous interventions. [73 ] , [74 ] Studies of serial
longitudinal angiographic evaluations [75 ] after successful PTCA have shown that 11
percent of patients will have restenosis within the first month; 39 percent will have
restenosis at the end of the first 3 months; and an additional 6 percent will have
restenosis 36 months after PTCA. A small number of patients will have angiographic
evidence of restenosis at the end of 1 year.
Renarrowing within the first few days after an angioplasty procedure usually represents
abrupt closure rather than restenosis. This is often caused by thrombosis superimposed
on vessel wall dissection or intimal flap. Asymptomatic angiographic renarrowing (>50
percent diameter stenosis) has been shown to occur in as many as 7.8 percent of
lesions treated. [76 ] Some researchers [77 ] have noted that although anginal symptom
recurrence is the hallmark of restenosis, approximately 25 percent of patients are
asymptomatic. Also noteworthy is the fact that among those with recurring angina, up to
44 percent are not found to have restenosis. [77 ] , [78 ] After the first several days,
further renarrowing probably reflects chronic recoil, vessel remodeling, and neointimal
proliferation. [74 ]
Although restenosis does not result in increased mortality (because patients with
restenosis develop angina rather than myocardial infarction or sudden death),
restenosis does lead to repeat PTCA or coronary artery bypass grafting; thus, it
increases morbidity and costs. [79 ]
MECHANISMS OF RESTENOSIS
The pathophysiology of restenosis is not understood completely. Findings from

angioscopic, atherectomy, and autopsy studies have supported the hypothesis that
early restenosis is a local vascular manifestation of the general response to injury and
wound healing. Restenosis early after angioplasty usually consists of immediate elastic
recoil, platelet deposition and thrombus formation, followed by smooth muscle cell
proliferation and matrix formation. [80 ] , [81 ]
The time course of restenosis can be determined from studies of injury in rat carotid
arteries, from other animal models, and from autopsy studies. [82 ] [89 ] Within seconds
of injury, endothelial removal, and endothelial death, as well as some smooth muscle
death, smooth muscle separation, and smooth muscle stretch occur. For the next
several minutes, there is platelet attachment, release, aggregation, and coagulation.
Within a few days after injury, endothelial and smooth cells and macrophages proliferate
and migrate. Over several weeks, synthesis, maturation, and contraction of the
extracellular matrix occur, in addition to the remodeling process, during which the vessel
may enlarge or decrease in size.
PREVENTION OF RESTENOSIS
Angiographic results have shown that all arteries undergoing any type of
interventionballoon angioplasty, atherectomy, stent placement, or laser balloon
angioplastyshow a similar extent of restenosis at 6 months. [90 ] Use of angiography to
predict the long-term success or failure of PTCA is of limited value, however, because
these images provide only a circumscribed view of the arterial lumen and offer little
insight into underlying plaque morphologic characteristics. [91 ] Intravascular ultrasound
has been used with more success to identify patients in whom restenosis is likely to
develop, because it does provide information about the morphologic features of the
atheroma and its composition. [92 ] , [93 ] With ultrasound, the interventional strategy
may be modified to optimize lumen size and possibly reduce the risk of restenosis. [93 ]
The process of wound healing after balloon angioplasty begins within minutes after the
procedure and may continue for weeks or months. This process is dependent not only
on the release and complex interaction of cytokines and growth factors, but also on the
extent of healing and the type of injury. [91 ] Therefore, therapies have to be targeted at
processes that occur early after balloon injury to combat the early release of growth
factors and cytokines and for processes that occur late (24 weeks) when factors that
induce substance deposition are at their peak. [91 ] Although a variety of agents
designed to reduce the risk of restenosis have been successful in animal studies, no
pharmacological agent has clearly proved to be successful in reducing restenosis in
humans. This, after more than 50 published major clinical trials randomizing greater
than 12,000 patients with the goal of limiting restenosis by pharmacologic means. [94 ]
In addition, few risk factors for restenosis have stood the test of time, and their
predictive power is relatively weak, [95 ] including such factors as lipoprotein (a), low
high-density lipoprotein (HDL), prior restenosis, total occlusion, diabetes, or location of
the left anterior descending coronary artery. [79 ] , [96 ] [102 ]
Two new therapies have shown significant promise in reducing restenosis, including the
administration of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa
receptor and the placement of a stent, and new modes of therapy are being sought
based on the role of smooth muscle cell proliferation, inflammatory cells, and humoral
factors in the restenotic process. [103 ] [111 ] Many of the new studies are being
conducted in animal models of restenosis and are in the investigational stage. Other
new forms of therapy under clinical investigation will be discussed.
Arterial Remodeling
One avenue of research in prevention of restenosis involves arterial remodeling.

According to a recent report by Currier and Faxon, [80 ] restenosis can be thought of not
merely as neointimal formation in response to balloon injury, but as arterial remodeling
in response to balloon injury and neointimal formation. This remodeling may consist of
actual constriction of the artery, as has been described in some animal models and in
preliminary fashion in humans, or of compensatory enlargement as has been described
in de novo atherosclerosis and in the hypercholesterolemic rabbit iliac artery model.
Compensatory enlargement and chronic constriction may represent two ends of the
spectrum of arterial remodeling in response to balloon angioplasty. Thus, therapeutic
strategies to alter arterial remodeling in conjunction with altering intimal formation may
be required to reduce restenosis after coronary interventions.
LIPID-LOWERING AGENTS
Omega-3 fatty acids, in addition to lowering triglyceride level, also affect platelet
aggregation and coagulation, which are important in restenosis. Conflicting results have
been found in five clinical trials addressing the effect of omega-3 fatty acid
supplementation on the risk of restenosis. [112 ] [117 ] The weight of the evidence
suggests, however, that they do not generally reduce the risk of restenosis after PTCA.
In one early trial, a beneficial effect on restenosis was shown with the lipid-lowering
agent lovastatin [118 ] ; however, subsequent trials were unable to confirm this
observation. [119 ] , [120 ] The ongoing lovastatin Restenosis Trial after PTCA [121 ]
should provide more data on the efficacy of hypocholesterolemic therapy for reducing
the risk of restenosis.
PLATELET INHIBITORS
After coronary angioplasty, patients usually are treated with aspirin, nitrates, calcium
channel antagonists, and heparin. Such medications are given specifically to interfere
with coronary artery vasoreactivity and platelet function. These drugs are useful in
treating coronary vasospasm and preventing abrupt closure. Platelet inhibitors have
shown promise for prevention of restenosis in recent clinical studies. One large-scale
trial, Evaluation of c7E3 for the Prevention of Ischemia Complications (EPIC), was
designed to examine the role of thrombosis, angiotensin II, and oxidation in restenosis.
The platelet glycoprotein IIb/IIIa integrin is the receptor that mediates the final common
pathway of platelet aggregation. According to EPIC investigators, agents that block this
platelet receptor represent a promising new approach to preventing cardiovascular
ischemic complications and late restenosis after PTCA. [122 ] , [123 ] In the trial, which
includes high-risk patients undergoing coronary intervention procedures, a monoclonal
antibody Fab fragment (c7E3) directed against glycoprotein IIb/IIIa integrin was
administered as a bolus dose and through infusion (Fig. 16-2) . In early results of the
trial, c7E3 significantly reduced the 30-day incidence of major ischemic events relative
to aspirin and heparin, as well as decreasing the need for repeat revascularization
during the 6-month follow-up period. The major complication has been bleeding, [124 ]
the risk of which appears to be inversely related to body weight. [125 ]
At The University of Texas Health Science Center and the Texas Heart Institute, we
have tested the hypothesis that c7E3 can abolish or attenuate cyclic flow variations in
coronary blood flow after angioplasty procedures. [126 ] After angioplasty, flow
variations occur as a result of repetitive accumulation and dislodgment of platelet
aggregates at sites of coronary stenosis with endothelial injury. [127 ] In animal models
of coronary thrombosis, cyclic alterations in flow have often preceded thrombotic
occlusion or reocclusion. [128 ] c7E3 was shown to eliminate cyclic alterations in
coronary blood flow in four of five patients who developed cyclic flow variations in our
observations of 27 patients undergoing angioplasty procedures. [126 ] Studies are
ongoing to elucidate the role of the 7E3 antibody in the prevention of restenosis.
A recent economic analysis of the EPIC trial [73 ] demonstrated that the 26 percent
reduction in the 6-month rate of restenosis achieved with c7E3 treatment translated into
a saving per patient of more than $1,000 in medical costs, not counting the cost of the
drug itself. This reflects a reduced incidence of rehospitalization and substantial
declines in the need for repeat angioplasty and bypass surgery.
ALTERNATIVE APPROACHES TO CONVENTIONAL BALLOON
ANGIOPLASTY
Since balloon angioplasty was developed 17 years ago, improvements in the

procedure have kept it the primary interventional therapy for patients with ischemic heart
disease. [129 ] However, research has indicated that certain lesion types and patient
populations may be treated more effectively with other newer technologies, such as
intracoronary stents and coronary atherectomy and ablation devices. These new
devices appear to be more effective than conventional angioplasty in treating calcified,
eccentric, or ulcerated lesions; ostial stenosis or stenosis of the left anterior descending
(LAD) artery; disease in older saphenous vein grafts; restenotic lesions after prior
interventions; and dissected vessels with actual or threatened abrupt closure. [130 ] The
challenge for the clinician is deciding the optimal application for these technologies in
specific clinical settings.
Stents
The use of vascular endoprostheses or stents developed as a result of complications

seen in percutaneous transluminal angioplasty. Appropriate indications for stent
placement include restenosis, dissection, abrupt closure, residual stenosis, or
re-opened total occlusion (Fig. 16-3) . Intracoronary stenting has proved to be a
successful method of circumventing emergency bypass surgery after acute vessel
closure in angioplasty procedures.
The problem of thrombosis associated with angioplasty is not resolved by stent

placement. Stents are themselves thrombogenic, [131 ] and their use requires some
form of anticoagulation therapy; recent data suggest that aspirin or aspirin and
ticlopidine may be adequate. [132 ] , [133 ] In addition, a clinical trial involving a
heparin-coated Palmaz Schatz stent is underway in Europe (BENESTENT II). This new
strategy may obviate the need for prolonged anticoagulant treatment [134 ] and
decrease vascular access complications and length of hospital stay. The early results of
the BENESTENT II trial also suggest that a heparin-coated stent reduces the risk of
restenosis to approximately 13 percent. An earlier trial, BENESTENT I, suggested that
stents themselves reduce the risk of restenosis from the anticipated 3040 percent to 22
percent. [135 ]
Though it is a rare occurrence, loss of the stent from its delivery system into the
peripheral circulation is another possible complication of the stent procedure. In such
cases, magnetic resonance imaging may be useful for locating the misplaced device.
[136 ]
There are few reports of stent implantation after myocardial infarction. [137 ] [139 ]
Acute MI and associated intracoronary thrombus are usually considered
contraindications to stenting. [141 ] It is generally agreed that stents should be reserved
for situations in which balloon angioplasty fails; however, newer stent designs and better
anticoagulant regimens may make it possible to use coronary stenting in selected
cases of acute MI in the future.
In an editorial review of the implications of stent placement, Topol [142 ] acknowledged

that the practical implications of elective stenting are formidable, but he emphasized
that long-term follow-up is needed to determine the efficacy of adjunctive pharmacology
(i.e., platelet inhibitors) and adjunctive strategies (i.e., atherectomy and rotoblation), the
practicality of coated stents versus uncoated stents, and the impact of better stent
deployment. These questions should be answered as we gain more clinical experience
with stent applications.
PALMAZ-SCHATZ STENT
Publication of randomized trials of the Palmaz-Schatz stent (Johnson & Johnson

Interventional Systems, Warren, NJ) [135 ] , [143 ] in 1994 led to Food and Drug
Administration approval of this device for elective placement (Fig. 16-4) . These trials
showed a 30 percent reduction in major eventschiefly defined by the need for repeat
revascularization after 6 months of follow-up.
The Palmaz-Schatz stent consists of two 7-mm rigid, slotted stainless steel tubes
connected by a 1-mm central bridging strut. [144 ] The diameter of the stent is 1.6 mm in
the unexpanded state. It is deployed by use of a standard 20-mm length angioplasty
balloon catheter. When expanded, the rectangular slots take on a diamond-shaped
configuration with a large free-space-to-metal ratio. Individual metallic struts are 0.12
mm wide and 0.06 mm thick.
Stent implantation is accomplished with a stent delivery system. With a PTCA balloon,
the stent is advanced easily through an 8-F guiding catheter into the target vessel over a
previously placed exchange length 0.14-inch guidewire, eliminating the need for
recrossing the lesion. A modified stent delivery system is available as a
factory-preassembled unit, with a two-segment stent crimped on a specific diameter
balloon between two radiopaque balloon markers and preloaded onto a transparent
delivery sheath containing a proximal, internal radiopaque marker.
In the randomized trials involving almost 1,000 patients, the Palmaz-Schatz stent
significantly reduced restenosis compared with conventional balloon angioplasty. [145 ]
, [146 ] The mechanism of stent benefit in reducing restenosis rate seems to be the
wider initial lumen, which can accommodate a greater degree of intimal hyperplasia
and an inhibition of the elastic recoil that follows angioplasty.
In a comparison of Palmaz-Schatz stent implantation for failed angioplasty (60

consecutive patients) and elective stent placement (100 consecutive patients), stent
implantation was successful in all of the failed group and in 99 percent of the elective.
[147 ] However, in cases of failed angioplasty, stent placement was associated with a
greater frequency of stent thrombosis and restenosis. Stent thrombosis occurred in 2
percent of the elective group and in 16.7 percent of the failed group. Greater than 50
percent restenosis was shown in 32 percent of the elective group and in 50 percent of
the failed group at 6-month+ angiographic follow-up.
Preliminary experience with the Palmaz-Schatz stent in prevention of restenosis in

saphenous vein graft lesions has also been favorable. In the multicenter registry of U.S.
Palmaz-Schatz experience, stent implantation for focal saphenous vein graft lesions
resulted in a high rate of procedural success (97.1 percent), acceptable major
complications, reduced angiographic restenosis, and favorable late clinical outcome
compared with the historical balloon angioplasty control series. [148 ]
GIANTURCO-ROUBIN STENT
In June 1993, the Gianturco-Roubin coronary stent (Flexstent, Cook Inc., Bloomington,
IN) became the first coronary stent to be approved by the U.S. Food and Drug
Administration for acute or threatened closure following unsuccessful coronary
intervention (Fig. 16-5) . The device design is based on consideration of specific
physical, anatomical, biologic, and procedural limitations, and it is compatible with
standard interventional techniques and equipment. Indications and contraindications for
use of the Gianturco-Roubin coronary stent are shown in Table 16-6 .
The Gianturco-Roubin coronary stent is composed of a surgical stainless steel

monofilament (0.006-in) folded in a series of 180-degree serpentine loops, which are
then folded around the delivery balloon in an interdigitating fashion. [149 ] The stent
comes premounted on the delivery balloon in a standard over-the-wire design (0.018-in
guidewire compatible), with proximal and distal radiopaque bands placed 12 mm from
the ends of the stent coils. The balloon material is compliant polyethylene. The delivery
balloon expands to 0.5 mm greater than the nominal stent size at deployment pressures
to accommodate intrinsic recoil of the stent material and to embed the stent struts into
the vessel wall.
Investigators in the multicenter registry of the Gianturco-Roubin intracoronary stent [150

] studied data from 639 serial patients undergoing emergency stenting for abrupt vessel
closure ( n = 415; 65 percent) or elective deployment for restenosis ( n = 224; 35
percent) to identify predictors for early ischemic events. The incidence of subsequent
ischemic events, including death, nonfatal myocardial infarction, and bypass surgery
referral (within 90 days of the procedure) was higher after acute deployment (20
percent) than after elective stenting (9 percent; p = .0004). The investigators believed
such events might be avoided with use of the appropriate size of stent, ensuring
adequate lesion expansion.
In another recent study of the Gianturco-Roubin coronary stent, the risk of stent
thrombosis was stratified by using three predictors: stent size, post-stenting residual
dissection, and residual filling defect. [151 ] Results from this multicenter trial of 1318
patients also showed that avoiding the use of small stents (<3.0 mm) and achieving
optimal angiographic results after stenting for acute or threatened closure are useful
strategies in reducing stent thrombosis.
One disadvantage of coronary stenting thus far is cost. Elective coronary stenting, as
performed in the randomized STRESS trial, increased total 1-year medical care costs
by approximately $800 per patient, compared with conventional angioplasty. [152 ]
Ongoing refinements in stent design, implantation techniques, and anticoagulation
regimens may narrow this cost difference by reducing stent-related vascular
complications or length of stay.
Directional Coronary Atherectomy
Directional coronary atherectomy (DCA) has been proposed as an alternative to

balloon dilatation for treatment of coronary artery disease, but the long-term efficacy of
this procedure is not known. DCA was introduced in 1986 and approved by the FDA for
clinical use in 1990. The goal of DCA is for debulking rather than dilating a coronary
artery lesion (Fig. 16-6) .
In directional atherectomy, a metal cylinder with a lateral window is positioned on the

end of a catheter. When introduced into the lesion, the atherectomy catheter's rotating
knife cuts into the atheromatous material and traps it inside the metallic reservoir.
Although its potential role is not clearly defined, it is believed that, with DCA, selective
removal of plaque potentially may minimize the vessel wall damage and lead to
subsequent better late outcome. One important advantage of DCA is its usefulness for
the in vivo study of coronary artery plaques. [153 ]
In a study of the clinical and angiographic outcome after directional coronary

atherectomy, the procedure was associated with a high procedural success rate (94.8
percent) and infrequent complications in selected lesion subsets. [154 ] Late clinical
events (death, Q-wave myocardial infarction, coronary bypass surgery, coronary
angioplasty) occurred in 69 patients (28 percent). Independent predictors of late clinical
events included diabetes mellitus, unstable angina, and a prior history of restenosis.
DCA for saphenous vein graft lesions was performed at 21 centers during a 2-year
period; 318 procedures were performed in 363 vein graft lesions. [155 ] Angiographic
success was achieved in 86 percent of lesions and clinical success was achieved in 85
percent. Restenosis was significantly lower in primary vein graft lesions than in vein
grafts with prior intervention. This initial multicenter investigation indicates that DCA is
safe and effective in selected cases of degenerative vein grafts.
Several studies have been undertaken to compare the results of angioplasty with DCA
for treatment of coronary lesions. One recent study involving complex lesions showed
that DCA is limited by a modest degree of lumen enlargement, frequent need for
adjunctive angioplasty, and a high restenosis rate, and appears to offer no advantage
over conventional balloon angioplasty for such lesions. [156 ]
Investigators in the Coronary Angioplasty Versus Excisional Atherectomy Trial

(CAVEAT I) examined the efficacy of DCA for ostial coronary lesions. [157 ] For ostial
left anterior descending (LAD) coronary artery stenosis, procedures yielded similar
rates of initial success and restenosis, but atherectomy was associated with a higher
incidence of non-Q-wave-MI. The predominant angiographic benefit in this study was
shown in proximal nonostial lesions of the LAD. At 1-year follow-up in CAVEAT I, of
1,012 patients randomized to either angioplasty or DCA, a statistically significant
excess of deaths after DCA was revealed that was not evident at 6-month follow-up.
[158 ]
A review of acute and long-term results of coronary stenting and atherectomy in women
and the elderly has shown that both techniques can be performed safely and effectively
in these patient subsets, despite a somewhat lower success rate and higher rates of
acute complications. [159 ]
Rotablator
The Rotablator, which encompasses an olive-shaped high-speed burr coated with

diamond chips, is used primarily for debulking lesions (Fig. 16-7) . When introduced
into the stenosed area of the vessel, the rotablator attacks preferentially hard resistant
material and is thus indicated for calcified lesions. Its fine elliptoid tip rotates at 180,000
rpm, grinding atheroma into millions of tiny fragments. Whereas DCA is used to
physically remove plaque from the vessels, the Rotablator is used to ablate the plaque
in situ. Its use is contraindicated in irregular or thrombus-containing stenoses, highly
angulated stenoses (and possibly right coronary artery stenoses), or in those
associated with impaired distal runoff caused by a recent MI or manifest by a fixed
thallium defect. [160 ] The primary success rate with this device is 95 percent. [161 ] In
most Rotablator procedures, concomitant balloon angioplasty is necessary, however,
for creation of a suitable lumen.
Data from the Multicenter Rotablator Registry of two [161 ] rotational atherectomy
procedures in single lesions were analyzed to determine the efficacy of rotational
atherectomy for 1,078 calcified and 1,083 noncalcified lesions. [162 ] Adjunctive
coronary angioplasty was used in 82.9 percent of calcified and 66.9 percent of
noncalcified lesions. Procedural success (defined as >150 percent residual stenosis
without major complications) was achieved in 94.3 percent of calcified and 95.2 percent
of noncalcified lesions. In this large study, the success rate of rotational atherectomy
was not reduced by calcification despite the more frequently complex nature of the
calcified lesions. These results underscore the potential for the Rotablator as the
interventional device of choice for complex, calcified lesions.
THE FUTURE IN ALTERNATIVE CORONARY INTERVENTIONS
Other new technologies undergoing evaluation for treatment of coronary artery disease
include various types of stents, low-speed rotators, and transluminal extraction
catheters. Although laser angioplasty initially was greeted with enthusiasm, the current
consensus is that its use will be limited.
The adjunctive therapies in use today have made it possible for interventionalists to
treat long, calcified, ulcerated, and distal lesions that would not have been possible to
treat with balloon angioplasty alone. A lesion-specific approach is commonplace now.
The restenosis rate has not been significantly reduced with these adjunctive strategies,
although refinements in stent placement are promising.
Coronary angioplasty remains the cornerstone of interventional cardiology, currently

accounting for more than 90 percent of all coronary interventions. It is likely to remain the
primary procedure for coronary interventions and the standard against which we
measure new therapies in the future. The impact of any new device will depend to a
great extent on the technical experience and clinical judgment of the cardiology team.
To aid in evaluating the safety and efficacy of new percutaneous transluminal
interventional devices, the New Approaches to Coronary Intervention (NACI) voluntary
registry was founded in the early 1990s. [163 ] Reports from this registry should be
useful to all physicians interested in keeping abreast of evolving technologies.
ACKNOWLEDGMENTS
The excellent and dedicated assistance of Rebecca Teaff in preparing this manuscript
is gratefully acknowledged. Case illustrations were generously provided by Emerson
Perin, M.D.
VEIN GRAFTS
Sources of Vein
The greater saphenous is the primary source for vein grafts. This vein may be surgically
absent, varicose, rarely too small, and occasionally diseased with prior phlebitis. Many
patients with superficial varicosities have usable saphenous vein, but the superficial
varicosities may impair healing; therefore, the uninvolved leg is preferred if only one leg
has varicosities. Sometimes a varicose saphenous vein may have usable segments.
Occasionally, the distal saphenous vein is too small (< 2.5 mm in internal diameter), and
both veins from the thighs are needed. When a vein is arterialized, obligatory fibrous
intimal hyperplasia reduces the luminal diameter by 25 percent. [35 ] If a smaller vein is
used, this narrowing may limit blood flow. Finally, anastomosis of a small vein to the
aorta is problematic.
The saphenous vein between the groin and the knee may be duplicated or bifid with a
superficial branch that is close to the skin and a deeper branch that is inside or outside
the muscle fascia from high thigh to knee. In these instances, two adequate segments of
greater saphenous vein can be harvested.
When greater saphenous vein is not available or not suitable, the lesser saphenous vein
may be used. Because of limited length, frequently both veins are harvested.
Unfortunately, if the greater saphenous vein is too small to use, the lesser is also.
When a leg vein is known to be unavailable or is likely inadequate, the arms can be
prepared for harvest of one or both cephalic veins. The cephalic vein can be harvested
from the wrist to the clavicle, but the upper arm segment is usually best for size. The
basilic vein also can be used, even though it frequently branches. The patency rate of
arm veins is so poor [36 ] , [37 ] that arterial conduits should be given strong
consideration as an alternative. Arm veins should be considered a last resort.
Harvesting Techniques
The legs are surgically prepared circumferentially and draped so that the entire leg is
accessible except the foot. This allows manipulation of the leg to provide optimal
access to the greater saphenous vein and limited access to the lesser saphenous vein
with the patient supine. To facilitate exposure, both legs can be supported in a frog
position, or the harvested leg can be abducted with the knee flexed 45 degrees. When
the need for lesser saphenous vein is known in advance, some surgeons position the
patient prone and reposition after harvesting.
A single incision or multiple interrupted incisions can be made (Fig. 17-1) . It is easier
to harvest the vein through a single incision, but my preference is interrupted incisions
because I believe that healing is better. However, there are no data to indicate that
complications such as infection, wound hematoma, or lymphocele are reduced by
multiple incisions. Harvesting trauma to the vein may be greater if multiple incisions are
used unless the operator is experienced. The saphenous nerve should be preserved.
Only the adventitia and not the full thickness of the vein wall should be handled with
forceps. If the surgeon can feel tissue within the forceps, there is too much tissue in the
jaws. Pinching the full thickness of the vein wall with forceps damages the intima, and
since endothelium must be preserved , every step of the harvesting technique must be
directed toward this goal.
The vein is located through a modest (10-cm) incision and is much easier to find at the
ankle, particularly if the thigh is obese. After dissection is completed in that incision, the
skin is cut with scissors or a knife over the course of the vein. If multiple incisions are
made, the index finger dissects along the anterior surface of the vein, and the next skin
incision is started 2 to 4 cm from the previous incision with the surgeon's finger
beneath. Some surgeons prefer to use an external vein dissector (Fig. 17-1C,D) and
make small incisions wherever the stripper meets resistance. In the leg, this technique
may avulse small branches and is more satisfactory in the thigh, where branches are
fewer and larger and more fatty tissue that facilitates dissection surrounds the vein.
Branches are ligated with small or medium clips or with fine silk ties. Both clips and ties
are placed no closer than 1 to 2 mm from the vein wall to avoid damage and to avoid
adventitial constriction of the vein.
Dissection begins either at the proximal or distal end of the vein, but in general, the
distal segment is more favorable. If there is concern over healing because of ischemic
peripheral vascular disease, dissection should begin proximally in the leg with the best
arterial supply. Similarly, if the patient has chronic venous insufficiency with stasis
changes, the dissection starts proximally and ends before reaching the level of stasis
changes. If the thigh is very obese, dissection is easier distally, and wound
complications are less frequent.
If the patient has peripheral vascular disease and may need femoral-popliteal-tibial
reconstruction, arterial conduits or veins from other sources are used to save the
greater saphenous vein for vascular reconstruction in the leg. A number of arterial
conduits are now available for myocardial revascularization, but fewer alternatives to the
greater saphenous vein are available for leg revascularization.
The lesser saphenous vein (Fig. 17-2A) can be accessed by flexing the hip and knee
and having an assistant rotate the limb medially (Fig. 17-2B) . Alternatively, the hip can
be flexed to 90 degrees and the knee extended (Fig. 17-2C) . Dissection begins distally
with an incision between the Achilles tendon and the lateral malleolus. The sural nerve is
spared.
Cephalic vein dissection is initiated at any level and depends on the length needed and
ease in locating the vein (Fig. 17-3) . If both arm and forearm vein is harvested, the
incision in the antecubital fossa is interrupted to avoid a bridging cutaneous scar.
The length of vein needed is estimated from the following guidelines: distal third of right
coronary artery, 12 to 15 cm; posterior descending artery, 15 to 18 cm; left anterior
descending artery, 10 to 15 cm, depending on level of the anastomosis; first obtuse
marginal artery, 10 to 15 cm; and posterolateral artery, 20 cm. These distances apply to
a normal heart and must be revised if chambers are enlarged. Some prefer to harvest a
single segment of vein and divide it after each successive distal anastomosis; others
prepare each segment to length by measuring the aortocoronary distance (with
umbilical tape or a suture) and placing a venous cannula in each segment.
After the desired length of vein is mobilized, it is divided proximally and distally. The
new proximal and distal ends are marked for identification. This can be done by placing
a soft bulldog clamp (Soft/Fibra, 6 mm, Applied Medical Resources, Laguna Hills,
Calif.) on the new distal end (old proximal end) or by cannulating the new proximal end
(old distal end) with a vein cannula that is tied into the vein. The vein is placed in a basin
containing 50 ml of physiologic saline solution at room temperature, 60 mg of
papaverine, and 100 mL of heparinized blood. The vein is prepared by the individual
who harvests the vein or by the surgeon; I prefer to prepare the vein myself. Only diluted
blood is placed in the vein, and after briefly flushing the vein, the vascular bulldog is
reapplied, and the vein is gently distended to no more than 150 mmHg pressure.
Uncontrolled branches are closed with small sutures of 7-0 polypropylene. Generally,
suture bites are placed only in adventitia parallel to the long axis of the vein to avoid
constriction. Some surgeons also mark the long axis of the vein with methylene blue, an
indelible marking pen, or a suture. The vein is returned to the basin of blood and saline
until used.
Harvest injuries usually are related to avulsion of small branches. Occasionally, larger
branches are torn where they join the vein, and rarely, these larger branches are
avulsed. When repaired, sutures must catch the full thickness of the vein wall for several
bites to produce a secure repair. Greater injuries are best managed by discarding the
injured segment.
Histology of Harvested Vein
The normal vein is surfaced by a monolayer of large polygonal endothelial cells

moderately adherent to a fenestrated basement membrane that lies on a poorly
developed internal elastic lamina. The media consists of two or more layers of
circumferentially arranged smooth muscle cells interlaced with collagen and elastin
fibers. The adventitia is a loose structure of collagen fibers and vasa vasorum. [38 ]
Intimal thickening, elastosis, and hypertrophy of the media due to phlebosclerosis may
affect 90 percent of saphenous veins in the sixth and seventh decades of life. [39 ] [41 ]
However, the influence of these preexisting changes on the patency of arterialized vein
grafts is unknown.
THE VEIN WALL
Veins are highly compliant over the normal range of venous pressures but are not over
the range of arterial pressures. [42 ] Compared with arteries, veins have more rapid
uptake of lipid, more active synthesis of complex lipids, and a slower rate of lipolysis.
[44 ] [46 ] Stump-tailed macaque monkeys have a vein cholesterol of 0.08 ± 0.01 mg/dL
and a B-aproprotein content of 2.27 ± 0.98 µg/dL that increases to 0.18 ± 0.04 mg/dL
and 21.3 µpm 12.8 µgmg/dL, respectively, after 30 weeks of an atherogenic diet. [46 ]
Freshly harvested human vein has an adenosine triphosphate (ATP) content of 470 ±
60 nmol/g wet weight and an adenosine diphosphate (ADP) content of 180 ± 20 nmol/g
with an ATP/ADP ratio of 2.50 ± 0.13. [47 ] Canine saphenous vein has a total protein
of 1100 ± 100 mg/mm of length or 255 ± 40 mg/g of weight and an actomyosin content
of 122 ± 16 mg/g of total protein or 24 ± 2 mg/g of weight. [48 ]
ENDOTHELIUM
Furchgott and Zawadski [49 ] in 1980 made the key observation that endothelium is
necessary for the vasodilating effect of acetylcholine. This factor, initially called
endothelium-derived relaxing factor (EDRF), proved to be nitric oxide (NO). [50 ] NO is
produced from L -arginine after conversion to citrulline by NO synthase. Importantly, NO
has other activities that include inhibition of platelet aggregation and inhibition of
neutrophil adhesion, release, and chemotaxis. [50 ] Additionally, NO directly inhibits
smooth muscle growth, [50 ] which may relate to intimal hyperplasia in arterialized vein
grafts. [51 ] Endothelium-derived relaxation is also mediated by prostaglandin I2 (PGI2)
(prostacyclin) and hyperpolarization factor. [52 ] Although produced by both endothelium
and vascular smooth muscle and not proved an important relaxing factor, [52 ]
prostacyclin strongly inhibits platelet aggregation on damaged or denuded endothelium.
[53 ] Additionally, endothelium produces a plasminogen activator that mediates local
thrombolysis [54 ] and secretes heparinlike compounds [55 ] and antithrombin, the
heparin cofactor. [56 ]
Endothelium-dependent contractions are not as well characterized as NO-induced

vasodilation, and decreased production of NO may be the most important factor. [51 ]
The major mediators of smooth muscle contraction are oxidative stress and/or
decreased reducing potential. These mediators also may lower the effective availability
of NO, products of cyclooxygenase metabolism (thromboxane A2 and prostaglandin
F2), and the vasoconstrictor peptide endothelin. [50 ]
It is now apparent that the endothelium plays a critical role in vasomotion. Loss of
endothelial function removes vasodilator activity and causes vasoconstriction. Loss of
endothelium stimulates platelet and leukocyte adherence and their secondary effects.
The necessity for endothelial cell preservation in all vascular systems is apparent for all
varieties of vascular conduits. Had we understood the role of endothelium, the radial
artery might not have failed as a conduit in 19721974.
Harvesting the vein is associated with loss of endothelium in proportion to the

gentleness of the harvesting technique. Gentle surgical technique is critical, but an
incremental endothelial cell injury is related to the irrigating solution, storage solution,
duration of storage, storage temperature, and distending pressure used to overcome
harvest spasm. Finally, additional endothelial loss occurs when the vein is placed within
the arterial system.
Physiologic saline has an acid pH, causes endothelial dysfunction [57 ] , [58 ] and cell
loss, [57 ] , [59 ] leads to vein edema, [60 ] and contributes to late pathologic changes in
the vein wall. [61 ] Saline has been replaced with lactated Ringer's solution, [62 ] other
balanced electrolyte solutions, [58 ] tissue culture medium, [63 ] , [64 ] or plasma protein
fraction (Plasmanate). [65 ] The latter two solutions have been abandoned because of
expense and risk of bacterial contamination. Heparinized blood preserves endothelium
and late vein integrity [58 ] , [66 ] [69 ] ; but its use is not uniformly recommended. [70 ] ,
[71 ]
Storage at 4°C injures endothelium [57 ] , [58 ] , [72 ] ; room temperature (20 to 23°C)
[58 ] or 37°C [58 ] , [73 ] better preserves endothelial cells. Cold-induced contraction of
flat endothelial cells produces a spherical shape that detaches the cell from the
basement membrane and deranges internal cellular structure. [74 ]
Duration of storage has not been analyzed systematically, but storage for 60, 90, [58 ]
and 125 [75 ] minutes has been studied. Although 1 hour of storage appears well
tolerated, construction of proximal anastomoses first minimizes storage time and brings
the endothelium into contact with heparinized blood at the earliest opportunity. [76 ]
Hydrostatic dilation to overcome spasm may produce high intraluminal pressures (300
to 600 mmHg). [77 ] , [78 ] Data suggest that distending pressures should be less than
300 mmHg [43 ] , [58 ] , [65 ] and optimally less than 150 mmHg. [47 ] , [70 ] , [75 ] , [76 ]
Devices for measuring the distending pressure are available. [81 ] A simple alternative
is to dilate the graft with arterial pressure by doing the proximal anastomosis first or by
filling the graft from the aortic cardioplegia cannula. Unfortunately, exposure to arterial
pressure following grafting causes additional endothelial injury [57 ] , [66 ] , [78 ] even in
nondissected portions of arterialized in situ vein grafts in the legs. [57 ] , [78 ]
Papaverine is added to the distending medium to reverse harvest spasm. [65 ] Others
prefer to infiltrate the tissues around the vein with papaverine solution [61 ] , [66 ] before
dissection and to fill the vein with papaverine in balanced salt solution as it is harvested.
[61 ] , [71 ] As supplied (30 mg/mL), papaverine has a very acid pH (around 2.0); the pH
of the final distending solution should be checked for a pH in the physiologic range. My
solution contains 60 mg papaverine, 50 mL physiologic saline, and 100 mL heparinized
blood and has a pH of 7.42.
REACTIVITY TO CHEMICAL AGONISTS
Relaxation of preconstricted (phenylephrine) human vein segments with calcium

ionophore A23187, an endothelial-dependent relaxing agent, reveals excellent
preservation of vein segments stored in heparinized blood at room temperature for 90
minutes or 37°C oxygenated Krebs-Henseleit solution or room temperature
Plasma-Lyte for 75 minutes. [58 ] Relaxation with A23187 or acetylcholine decreases (
p < 0.05) when the storage temperature is 2 to 4°C or when the medium is saline at
room temperature. [58 ] Distension of vein segments to 400 mmHg results in decreased
relaxation. [58 ] Addition of nitroglycerin, papaverine, or verapamil to the Plasma-Lyte
solution before distension does not improve the relaxation response. [58 ] In the study
by Angelini et al., [72 ] human veins were excised, studied, and surgically prepared for
grafting or stored up to 250 minutes at room temperature in blood or Hartmann's
solution. Surgical preparation (uncontrolled manual distension and room temperature
storage in blood or Hartmann's solution) or storage in blood but not Hartmann's solution
reduced relaxation of serotonin-preconstricted human saphenous vein segments. [72 ]
In freshly harvested saphenous vein, histamine produces weak or absent relaxation and
in higher concentrations causes vasoconstriction; when endothelium is removed,
histamine causes less relaxation. [82 ] Thus endothelial H1 histaminergic receptors
linked to the release of NO are sparse or absent in human saphenous vein. Histamine
may be released from endothelial cells, mast cells, or platelets. Serotonin
(5-hydroxytryptamine) evokes significant contraction in veins that is not affected by
endothelium removal. [82 ] Serotonin is released during activation and aggregation of
platelets. Additionally, vein grafts have a variable and poor basal release of NO into the
lumen, and this favors platelet aggregation and adhesion. [83 ] Thus vein grafts are at
risk for release of histamine and serotonin that favor graft spasm and thrombosis.
Although this may be a mechanism to explain a higher rate of early graft closure
(compared with arterial grafts), vein graft spasm rarely is documented. [84 ]
Canine femoral veins studied 6 weeks after grafting into femoral arteries did not
demonstrate smooth muscle relaxation to acetylcholine but did to A23187. However, the
chemical nature of the endothelium-derived relaxing substance(s) was not identified. [85
] , [86 ]
The effects of the vasoconstrictors thromboxane analogue U46619, serotonin,

endothelin, leukotriene C4, and norepinephrine were studied on surgically harvested,
distended and nondistended segments of saphenous vein placed as aortocoronary
grafts and recovered short term (up to 1 year) and long term (1 to 10 years). [87 ] Vein
grafts were more responsive to U46619, norepinephrine, and leukotriene C4. For all
agents, an agonist-specific profile of response was found up to 10 years after grafting.
An age-related decrease in response probably was due to venous stiffening and loss of
mechanical contractile ability. [87 ] Assessment of human coronary bypass grafts 7
months to 12 years after grafting for endothelium-dependent vasodilation (acetylcholine,
A23187, thrombin, histamine, and NO) did not reveal an age-related response but
showed variable relaxation within each graft that appeared to correlate inversely with
development of intimal proliferative lesions. [88 ]
Venous arterial grafts have reduced basal luminal release of NO when harvested and a
further reduction after surgical preparation and grafting. Increased responsiveness to
vasoconstrictors may reflect this decrease in NO production. Reduced NO production
may be important in early [83 ] and late [52 ] vein graft failure.
Distal Anastomosis
ARTERIOTOMY SITE
Ideally, the anastomosis is made at a site that is readily accessible, has no intimal
disease, and has a luminal diameter of 2 mm or greater. The average coronary artery
decreases in caliber but tends to be more healthy as one moves distally. I do not
bypass 1-mm vessels (unless inadvertently opened) because the patency rate is so
poor. Vessels with a 1.5-mm lumen have reduced patency with saphenous vein unless a
side-to-side anastomosis is made and a larger vessel is used for the end anastomosis.
The presence of intimal disease, if moderate, reduces early patency and clearly
influences long-term patency, as may the presence of even mild intimal disease.
Because the bifurcation of the right coronary artery (the crux) is frequently diseased,
even when the distal third appears normal, I rarely graft to the distal right coronary artery
but go to the posterior descending artery. Occasionally, the posterior descending artery
is small and unsuitable for grafting; in this instance, the graft is placed into the
posterolateral artery on the ventricular wall or, if too small, in the atrioventricular groove.
ARTERIOTOMY INCISION
The coronary artery can be dissected with a no. 15 Bard-Parker disposable blade, but I
prefer a no. 10A blade (Becton Dickinson Acute Care, Franklin Lakes, N.J.) with a
round end. The anterior wall of the artery is incised with a disposable sharply pointed
blade (Becton Dickinson, Beaver Blade, catalog no. 377513) and then opened with
coronary scissors to provide a 3- to 5-mm arteriotomy that depends on the vessel
diameter and the planned conduit. The arteriotomy should be at least twice the diameter
of the artery and must be at least as long as the diameter of the vein.
END-TO-SIDE ANASTOMOSIS
Most vein grafts can be transected sharply at a right angle to the long axis, and this
yields an adequate diameter to mate with the arteriotomy (Fig. 17-4) . This results in
what I call a universal anastomosis in that the vein can then leave the anastomosis in
any direction. If the vein is small, it must be beveled or cut transversely and fish-mouthed
to achieve an anastomosis with a diameter twice the diameter of the coronary artery or
one and one-half times the diameter of the vein, whichever is greater (see Fig. 17-4) .
This creates an anastomosis with a heel and toe. The two vessels generally come
together in line, but if desired, the vein can be angled to one side or the other by placing
sutures in the heel of the vein several bites away from the apex of the arterial incision.
Most anastomoses are started at the heel beginning several bites away from the apices
of both the artery and the vein (see Fig. 17-4) . My preference is to continue the suture
line along the side farthest away from the surgeon, or the one most difficult to access.
When five or more bites have been placed around the heel, the suture line is tightened
to pull the two vessels together. The far suture line is completed with or without tension
on the suture. The toe of the anastomosis is finished without tension to give an
unobstructed view of the coronary arterial lumen. The critical areas of a coronary
anastomosis are the toe and heel. By not placing a sufficient number of small bites in
these two areas the coronary lumen can be constricted to cause early or late stenosis.
Thus I believe that the toe and heel should be constructed with five bites that are 1 mm
apart and 1 mm in depth. After completion of the toe, the suture line is tightened. The
anastomosis is then gently probed. The final lateral segment of the anastomosis is
completed with either suture. When the anastomosis is to the distal third of the right
coronary artery, it may be easier to start the anastomosis at the toe rather than at the
heel so that the surgeon sews toward himself or herself.
The choice of continuous or interrupted sutures is a matter of preference. The vast

majority of surgeons use continuous 70 or 80 polypropylene, and very few use
interrupted sutures. The two major arguments for interrupted sutures are more-precise
suture placement and absence of a purse-stringing effect on the anastomosis. It is
argued that continuous sutures can be placed just as precisely as interrupted sutures
and that if sufficient suture bites are placed, a purse-stringing effect is absent.
ORDER OF PREFERENCE FOR DISTALS
The order of distal anastomoses may be based on a plan to deliver cardioplegia

through each conduit after completing each anastomosis. In this approach, the most
ischemic or underperfused area is revascularized first and less compromised
myocardial beds in succession. I follow this strategy when operating for acute ischemia
(infarction, failed PTCA) but not routinely. If delivery of cardioplegia is not a concern, I
begin with branches of the circumflex system and proceed to branches of the right
coronary artery and then to the left anterior descending coronary artery and its
branches. If the anterior descending anastomosis is performed first, retraction of the
heart may damage this anastomosis, particularly if an ITA is used.
Y ANASTOMOSIS
The Y or bifid anastomosis is occasionally useful when a bifurcation lesion extends into
two branches that are relatively small and not suitable for direct grafts. The anastomosis
is accomplished using a natural Y in the vein graft or by creating two flaps of vein wall
using a longer incision in the front wall and a shorter incision in the back wall (Figure
17-5) . The suture line begins near the toe of one limb and continues toward the toe of
the second limb and then to the heel and back.
VEIN-PATCH ANGIOPLASTY
This technique is sometimes useful for treating coronary ostial stenosis without more
distal coronary disease (isolated ostial stenosis). This occurs in 17 percent of patients
(of whom 75 percent are female) with ostial disease. [89 ]
Because the aortic wall is frequently calcified, the incision must be generous (1.5 to 2.0
cm) to open the lesion and create a patulous channel with a large vein patch (Figure
17-6) .
Left ostial stenosis may be associated with left main disease. If only the left ostium is
involved, the pulmonary artery usually can be mobilized and retracted to provide
adequate exposure (Figure 17-7) . If left main disease is present, it may be necessary
to carry the incision to the bifurcation or beyond; in this instance, division of the
pulmonary artery is required for adequate exposure (Figure 17-8) . After placing the
patch and testing by infusing antegrade cardioplegia, the pulmonary artery is
reconstructed with running 5-0 polypropylene.
I believe that ITA bypass for left ostial stenosis is better than ostialplasty. Left ostial
stenosis without left main disease can be treated with a single bypass using the left ITA
to the left anterior descending coronary artery.
SIDE-TO-SIDE ANASTOMOSIS
Side-to-side coronary anastomoses appeared early in the history of saphenous vein

coronary bypass grafting. [24 ] , [25 ] These anastomoses are divided into either parallel
or crossing anastomoses. A parallel side-to-side anastomosis is technically simpler
because the anastomosis can be made as small as two times the diameter of the artery
or much longer and it is simple to match incisions in the two vessels with respect to
length. The anastomosis is initiated at the apex or one suture bite removed and at the
apex that is farthest from the surgeon. Generally, suture placement follows the standard
rule of going from the outside of the vein to the inside and from inside of the artery to
outside, although on the far side some surgeons prefer the opposite. My choice is to
keep the two vessels several centimeters apart (parachute technique) until the entire
backside and near apex are completed before pulling the suture line tight. This must be
done in segments to achieve smooth tightening of the suture (Figure 17-9AC) . The
near side of the anastomosis is finished with either suture. The artery may be
appropriately probed before completing the anastomosis.
When the side-to-side anastomosis is crossing (perpendicular), the incisions in the

artery and vein are parallel to the long axis as for the parallel anastomosis and are the
same length (Figure 17-9G) . If the vein is large, it is possible to make a transverse
incision in the vein and produce an acceptable anastomosis; however, if the vein is
small and the incision too large, the vein may be flattened at the anastomotic site
(seagull deformity) (Figure 17-9F) . Suture placement is identical to that for the parallel
side-to-side anastomosis and is started one bite from the proximal apex in the artery
and the midpoint of the venotomy. The suture line is continued using the parachute
technique to the near arterial apex, at which point the suture line is tightened. A diagonal
anastomosis can be made by making longitudinal incisions in the artery and vein and
starting the suture line several bites from the apex of the artery and at the apex in the
vein. Alternatively, the longitudinal incision in the vein can be made diagonally and the
suture line initiated at the apex of the vein or several bites removed from the apex to
create up to a 45-degree angle of the anastomosis.
Either the proximal or distal anastomosis can be done first. For the diagonalleft anterior
descending arterial sequence, I prefer to do the diagonal anastomosis first, which
allows better access to the toe of the side-to-side anastomosis. For anastomoses to
two obtuse marginal branches, or for the posterior descending-posterolateral
sequence, it is practical to do the end-to-side anastomosis first, but the portion of the
side-to-side anastomosis adjacent to the distal anastomosis is done next because
access will be limited when the suture line is pulled up (Fig. 17-10) .
Y GRAFTS
The two usual reasons for construction of Y grafts relate to the aorta or to the vein. The
aorta may be diseased, or the available area for an anastomosis may be small and
cluttered. If the supply of good vein is limited, vein can be conserved with sequential
grafts and Y grafts. If conduit length is not a problem, it is relatively easy to make the Y
anastomosis close to the aortic anastomosis of the primary vein graft, but if the vein is
short, the anastomosis must be more distal. The proximal (aortic) anastomosis of the
primary or donor graft is completed before the Y anastomosis is made. When
determining the anastomotic site for the Y anastomosis, the aorta should be unclamped
and the vein grafts and heart filled. This allows selection of an appropriate anastomotic
site that does not create tension, angulation, or axial distortion of either graft. It is
important to determine the circumferential location of the longitudinal incision in the long
axis of the primary graft to avoid axial distortion of the primary graft and angulation of
the side graft at the anastomosis. Once this is determined, the two vein grafts are
isolated with soft vascular bulldog clamps, and a 5- to 8-mm longitudinal venotomy is
made at the appropriate site in the donor vein (Fig. 17-11) . The recipient vein is cut
diagonally at approximately 45 degrees, or if it is small, the vein is fish-mouthed for a
distance equal to the donor venotomy. The 7-0 polypropylene suture line starts several
bites from the recipient vein heel on the near side and carries through the heel to the far
side. The suture line is tightened. The far side of the anastomosis is completed beyond
the toe, and the suture line is tightened again. The remainder of the anastomosis is
completed with either suture. Air is usually evacuated by releasing a distal vascular
bulldog, but if valves prevent filling, it may be necessary to release the proximal bulldog
with the distal bulldogs clamped or to use a 25-gauge needle to evacuate air after the
sutures are tied.
Natural Y graft
This application must be anticipated when the vein is harvested and a bifurcation with
two comparably sized limbs is encountered. When the limbs are parallel in the leg or
thigh, length is usually adequate, but bifurcation branches may vary considerably in size
and length. Depending on the length of the two venous limbs, the two grafted arteries
may be close to or distant from one another. It is important to very carefully position the
Y graft and to cut one limb while filled with blood with the heart in its natural position to
maintain proper intercoronary distance. One anastomosis is completed, and the
position of the graft is checked again while filled with blood (Fig. 17-12) .
SELECTION OF AORTIC SITES
If the ascending aorta is healthy, the proximal anastomosis may be at any site. It is
simplest to place the anastomoses on the anterior surface, although some prefer the
right lateral wall or greater curvature or a combination. It is common to place the most
distal graft on the aorta to the circumflex system, the middle graft to the left anterior
descending (LAD) system, and the most proximal graft to the right system. A few
surgeons prefer to route left-sided grafts through the transverse sinus and make the
proximal anastomosis on the lateral wall of the aorta. The disadvantage of this method
is that the entire graft cannot be seen readily to detect bleeding or axial torsion.
A major problem arises when the aorta is atherosclerotic. Calcification in the aortic wall
can be assessed by palpation, but intimal thickening and intimal ulcerative lesions are
very difficult to palpate. Palpation is facilitated by lowering blood pressure with
vasodilators or by inflow (caval) occlusion. If the calcification is only focal and the
remaining aorta is relatively healthy, it is often possible to place a side-biting clamp
away from the calcium.
Some surgeons routinely use intraoperative echocardiography (surface or

transesophageal) to assess the quality of the ascending aorta, and with experience, this
is a reliable technique to detect aortic atherosclerosis. [90 ] , [91 ] If the ascending aorta
is unsuitable for a proximal anastomosis, another site must be selected. If the
ascending aorta is diseased, usually the aortic arch is also diseased. Occasionally,
grafts are placed on the lesser curvature of the arch, but a partial occlusion clamp is
hard to apply. The innominate artery can be used but is often atherosclerotic. Rarely, the
ascending aorta is replaced, and vein grafts are attached to the Dacron graft. Other
alternatives include basing vein grafts on in situ ITA grafts or on a proximal native
coronary artery or use of in situ arterial grafts as described below.
TIMING PROXIMAL ANASTOMOSIS
Proximal anastomoses are usually made after performing distal anastomoses, but
some surgeons prefer to perform proximal anastomoses first, and others make each
proximal anastomosis after each distal anastomosis.
There are two advantages to performing the proximal anastomoses first. Cardioplegia
can be delivered through the graft immediately after each distal anastomosis. The graft
can be dilated with physiologic arterial pressure to minimize the time that vein
endothelium is not in contact with blood. Although delivery of cardioplegia can be
accomplished by cannulation of each individual vein graft, it is simpler to perfuse each
graft via the aortic root. It should be noted that crystalloid cardioplegia is associated
with endothelial injury, [92 ] , [93 ] which does not occur with blood cardioplegia. [94 ]
PROXIMAL ANASTOMOTIC TECHNIQUE
Using a padded partial occlusion clamp or cross-clamp, 3- to 4-mm incisions are made
in the ascending aorta, and a 4- to 5-mm aortic punch is used to remove circular
segments of the aortic wall (Fig. 17-13) . If the distal anastomosis is made first, care
must be taken to estimate the length of the conduit and to verify axial orientation. A soft
vascular bulldog clamp (Applied Vascular Devices) is placed on the graft to prevent
backflow during the anastomosis. The vein is spatulated for 5 to 7 mm with preservation
of the entire vein wall to create a cobra-hood anastomosis. A single 6-0 polypropylene
suture begins a running anastomosis. Approximately one-third of the anastomosis is
done in open fashion before the graft is pulled down to the aortic wall to complete the
final two-thirds. The anastomosis may be marked for subsequent angiographic study by
a metal washer, a large clip, or a radiopaque marking device.
In some patients the aorta can be safely cross-clamped, but it may be unwise to place a
partial occlusion clamp because of possible embolization or damage to the aortic wall.
In this circumstance, proximal anastomoses are performed with the aorta clamped after
each distal anastomosis or after completion of all the distal anastomoses. The
disadvantage of this technique is that cross-clamp time is prolonged, but with better
cardioplegia, this protocol is used more commonly.
The aortic wall may be diseased with only a limited area suitable for an anastomosis. If
only one proximal anastomosis is feasible, a second vein graft can be anastomosed to
the hood of the first vein graft by making a 5-mm incision in the hood of the graft and
connecting the second graft to the first using running 6-0 or 7-0 polypropylene (Fig.
17-13 and Fig. 17-14 ). A third graft can be attached to the second hood in a similar
fashion (see Fig. 17-13 ). It is also possible to anastomose a second or third vein graft
to the side of the primary graft using the Y-graft technique (see Fig. 17-11 and Fig.
17-14 ).
Occasionally, after the initial punch it is apparent that the aortic wall is too diseased for
a satisfactory anastomosis. One solution is to enlarge the aortotomy and cover the
defect with a pericardial patch using running 5-0 or 6-0 polypropylene (see Fig. 17-27 ).
The vein graft is anastomosed to the pericardial patch by making an incision or
punching a hole in the center of the patch. More rarely, the aorta may be too diseased
for patch repair and must be resected and replaced with a Dacron graft. The vein
conduits are anastomosed to the Dacron tube graft.
SOLUTIONS TO PROBLEMS
Aortic tear
Aortic tears may result from application of non-padded clamps to the ascending aorta.
The best management is to avoid this problem. Tears vary from a limited transmural
lesion to aortic dissection. Local tears are usually repaired with a 4-0 polypropylene
running horizontal mattress suture without additional supporting tissue. If the aorta is
fragile, two strips of pericardium are added. Alternatively, interrupted horizontal
mattress sutures of 2-0 Dacron or 4-0 polypropylene with felt pledgets or with strips of
felt are used to close the tear. If the injury is related to the aortic cannula, the cannula
may have to be moved to the femoral artery to allow satisfactory repair of a tear or
localized dissection. If the aorta cannot be repaired under arterial pressure, or if a
partial exclusion clamp or cross-clamp does not give clear access to the injury,
profound hypothermia with circulatory arrest may be necessary to repair the aorta. In
this setting, direct suture may be inadequate, and a pericardial or Dacron patch or tube
graft may be needed.
Pericardium is easier to work with than Dacron for suturing to the aorta or vein graft.
However, because long-term data on pericardial patches apply only to small patches,
[95 ] and because of concern about aneurysm formation, Dacron is used for large aortic
patch repairs.
Root dissection
When aortic root dissection occurs, the ascending aorta must be resected. This
requires cardiopulmonary bypass with femoral artery cannulation and provision for
profound hypothermia (18°C or less) and an open distal anastomosis. Usually the aortic
valve can be resuspended. Vein grafts are attached to the Dacron graft after it has been
placed. If vein grafts were anastomosed to the aorta before the dissection occurred and
are not involved in the dissection, an island patch can be placed in the anterior wall of
the Dacron tube graft.
No-touch aorta
When the aorta is calcified (porcelain aorta) or so diseased that it cannot be clamped
or cannulated, a no-touch technique must be employed. This includes femoral artery
cannulation and cold (25 to 28°C) fibrillatory arrest with ventricular venting and local
control of the coronary arteriotomy. Alternatively, circulatory arrest (18°C) with or without
retrograde cardioplegia can be used. Normothermic bypass, local coronary control, and
ultra-short-acting beta blockade to slow cardiac activity also have been used
successfully. This method also can be used without cardiopulmonary bypass for
accessible coronary arteries. Conduit inflow must be from the innominate artery or in
situ arterial conduits. [96 ] , [97 ] On occasion, inflow can be provided by a native,
undiseased proximal coronary artery (coronary-to-coronary graft) [98 ] (Fig. 17-15)
Single versus Multiple Touchdowns (Sequential Grafts) versus Y Grafts
ADVANTAGES
The major advantages of sequential grafting are conservation of vein, since a single
vein can revascularize the entire heart (snake graft) (Fig. 17-16) , and decreased
operative time, since only one proximal anastomosis is required. Side-to-side
anastomosis often takes more time than end-to-side anastomosis, so the time saved
may be small. More conservative sequential grafts use one segment of vein for each
major coronary artery and sequential anastomoses for branches. This approach
conserves vein if four to six anastomoses are needed but saves little time. Similarly, Y
conduits conserve vein.
DISADVANTAGES
The major disadvantage of a single sequential graft is that proximal conduit failure
compromises blood flow to the entire heart. A technical error at the proximal
anastomosis or the first side-to-side anastomosis jeopardizes the entire graft. A similar
result may occur late from atherosclerotic degeneration of the proximal vein graft. For
this reason, I limit sequential grafting to one graft for each major coronary system or for
a portion of two adjacent coronary systems unless conduit is not available. If the vein is
small, side-to-side anastomoses are technically more difficult and have a greater
potential for a faulty anastomosis.
The aorta may have to be clamped to facilitate exposure for Y anastomoses located on
the left side. Although not technically difficult, the Y anastomosis must be performed
more carefully than vein anastomoses to the aorta.
PATENCY RATES
There is one report of long-term follow-up of 212 double sequential grafts studied at 1
and 5 years postoperatively and compared with 424 single grafts anastomosed to the
same vessels. [99 ] Patency rate of side-to-side anastomoses (85 percent) was better
than that of end-to-side anastomoses (66 percent) for sequential grafts at 5 years ( p <
0.005). As a group, 5-year patency of all side-to-side anastomoses was better than that
of all the single end-to-side anastomoses (85 versus 76 percent; p < 0.05). Patency of
sequential end-to-side anastomoses, however, was less than that of single end-to-side
anastomoses (66 versus 76 percent; p < 0.05). When the authors studied sequential
grafts to the diagonal-anterior descending arteries, they found that patency was better
at both sites than for sequential grafts placed to other coronary arteries. Thus
side-to-side anastomoses of double sequential grafts have better patency than do
end-to-side anastomoses. Single grafts have better patency than end-to-side
anastomoses of sequential grafts, and therefore, single grafts are recommended unless
there are other considerations such as limited availability of graft material. This
particularly applies to the left anterior descending artery because the distal
anastomosis of a sequential graft is usually to this artery. Reversing the anastomotic
sequence is an alternative, but there are no data to support this procedure.
Early experience with 1 year of angiographic follow-up revealed no significant

difference in patency for simple grafts and Y grafts. [100 ] Similarly, a contemporary
series of 18 Y grafts studied at 1 year had a patency rate that was not different for single
grafts, and this did not change at 3 years. [101 ] Another current series of 6 Y grafts
studied at 1 year revealed 100 percent patency. [102 ] Thus, on the basis of limited
data, Y grafts appear to have patency rates comparable with those of single venous
coronary bypass grafts.
Occlusion of Vein Grafts
EARLY GRAFT CLOSURE (1 MONTH)
Closure of 10 to 15 percent of saphenous vein grafts in the first month, followed by

another 5 to 10 percent in the next 11 months, is secondary to anastomotic errors, injury
to the conduit, low flow, and disease of the coronary artery, aorta, or vein graft. Failure
at the aortic anastomosis can be due to large suture bites in the vein that cause
stenosis of the neck of the anastomosis. This complication is more likely later when
fibrointimal hyperplasia develops. Angulation at the neck due to improper alignment of
the anastomotic axis with the course of the vein can lead to early or late closure. Linear
tension due to insufficient graft length is associated with graft closure. [103 ] This also
produces tenting of the coronary artery with angulation of the vessel, usually proximal but
sometimes distal to the anastomosis. A redundant graft may become kinked but can be
positioned properly after fibrin forms or by suturing adventitia to the epicardium.
Sequential grafts are prone to angulation at side-to-side anastomoses and axial
torsion; either or both can cause stenosis or occlusion. Suture placement in the
coronary artery is obviously more critical than suture placement in the vein; large bites in
the coronary artery at the heel and toe may constrict the vessel by everting the wall and
reducing diameter (compression). [104 ] Graft failure was attributed to this mechanism
in 40 percent of autopsied hearts, [104 ] and following this early misadventure, technical
refinements improved graft patency. [103 ] , [105 ]
Aortic atherosclerosis and increased wall thickness may produce a ragged

anastomosis due to intimal disease. This leads to early local thrombus and/or a healing
stenosis related to a narrow tunnel in the thick aortic wall that closes as it heals.
Coronary atherosclerosis at the anastomosis reduces lumen diameter, can produce an
intimal flap or more serious wall separation, hinders precise suture placement, and may
result in intimal fragmentation as the suture line is tightened.
Conduit injury related to harvest and preparation (see above) is associated with
endothelial dysfunction and loss but has decreased since the 1970s with improved
endothelial preservation using current techniques. [106 ] However, graft patency has not
improved commensurately, and grafts continue to thrombose in the first month. This is
probably secondary to reduced graft flow, [107 ] which is related to limited outflow
(coronary diameter of 1.5 mm or less and flow of less than 40 mL). [108 ] , [109 ] Intimal
fibrin deposition is common 24 hours after grafting [110 ] [112 ] and may progress to a
layering of thrombus. Mural thrombus is common in autopsied patients and often is
associated with venous valves. [110 ] , [111 ] Platelet activation by cardiopulmonary
bypass may contribute to local thrombosis. Decreased levels of nitric oxide due to
endothelial injury or loss diminish inhibition of platelet activation and adherence and
reduce downstream vasodilation and flow. Early thrombus formation is enhanced by
reduced blood flow (stasis) and local factors that favor blood clotting
(hypercoagulability).
GRAFT FAILURE FROM 1 TO 12 MONTHS
Fibrous intimal hyperplasia is the primary cause of graft failure in this period and has
produced graft stenosis as early as 6 weeks postoperatively. This process is uniformly
distributed throughout the graft but may be focally or segmentally prominent in early
stages and is usually complete by 12 months. The cells associated with fibrous intimal
hyperplasia have ultrastructural features of smooth muscle cells with a matrix of acid
mucopolysaccharide. [113 ] Scarring and thick collagen bundles develop in the media
as smooth muscle cells are replaced. [114 ]
In the 1970s, 5 to 10 percent of vein grafts developed symptomatic stenosis or closed

due to progressive intimal hyperplasia that occurred in the first year. However, in the
1980s it was rarely possible to attribute graft closure to this process. Presumably this
change was due to more careful harvesting, preparation, and handling, but uniform wall
thickening secondary to fibrous intimal hyperplasia continues to occur in all grafts. [115 ]
Despite investigation, it has not been possible to define the exact cause, [38 ] but
exposure to the arterial system is clearly involved. Removal of the vein from its in situ
location is not a factor. [116 ]
GRAFT BEHAVIOR FROM 1 TO 5 YEARS
This interval is the golden period for vein grafts, with a failure rate of 2 to 3 percent per
year. [114 ] Although microscopic features of atherosclerosis are noted as early as 6
months after operation, [117 ] the disease generally appears after 1 year and causes a
few grafts to close around 5 years.
Fibrous intimal hyperplasia is relatively stable between 1 and 5 years, but cellularity
decreases. Medial fibrosis and loss of cellularity frequently progress as the graft is
converted to a stiff fibrous tube. [118 ] In a few grafts the intimal hyperplasia may
progress to occlusion, or more likely, a thrombus forms and becomes organized. [119 ]
GRAFT FAILURE BEYOND 5 YEARS
Graft failure after the fifth year occurs at a rate of 5 percent per year, so at 10 years, 50
percent or more of all grafts have closed and 25 percent have significant atherosclerotic
lesions. [120 ] , [121 ] Graft closure in this interval is almost always secondary to
atherosclerosis and its complications.
GRAFT ATHEROSCLEROSIS
Histology
Some smooth muscle cells of fibrous intimal hyperplasia have foamy cytoplasm early,
but fat stains are usually negative. [122 ] Normally, monocytes enter the intima,
differentiate into macrophages, and participate in physiologic scavenging. With
atherosclerosis this process accelerates, and intimal macrophages become lipid-rich
foam cells of the atherosclerotic plaque. [123 ] It is not clear whether or not sites of
prevalent foam cells precede complex atherosclerotic plaques. However, most
investigators, [124 ] [126 ] but not all, [127 ] believe that fibrous intimal hyperplasia is the
substrate for atherosclerotic change and that vein graft atheromatous disease is not
distinct from that found in arteries. [111 ] , [128 ] Some investigators find that vein
atheromas show more foam cells extending into the media and resembling
experimentally induced lesions. [115 ] , [129 ] Vein grafts also may have increased
erosion and undermining of the thickened intima with formation of a fibrous cap.
Rupture of atheromatous plaques is probably the most common mechanism of graft
occlusion. [130 ] Older atherosclerotic vein grafts show calcification, aneurysmal
degeneration, and plaque ulceration. [131 ] , [132 ]
Some work suggests that progressive graft atherosclerosis may be immune mediated.
[129 ] Vein graft atherosclerosis is often associated with a prominent intimal
inflammatory reaction that may extend through the media into the adventitia. [129 ]
Prevention
Risk factors for arterial atherosclerosis would be expected to contribute to vein graft
atherosclerosis, but some studies do not show a correlation. [105 ] However,
apolipoproteins (apo[a] and apoB) accumulate in long-standing vein grafts. [133 ]
Patients with elevated lipoprotein[a] levels have an increased risk of developing vein
graft disease. [134 ] Others find that plasma apoB levels correlate with graft
atherosclerosis more strongly than either low-density lipoprotein (LDL) cholesterol or
total cholesterol. [135 ] In one report, an elevated plasma triglyceride level was most
strongly associated with the need for repeat bypass grafting. [136 ]
The role of lipid modification has not been well defined, but patients with established
hyperlipidemia should have vigorous management of this problem (if only to prevent or
slow progression of coronary disease). [137 ] Treatment of lesser lipid elevations has
not proved beneficial. [127 ] , [138 ] Vigorous dieting and use of lipid-reducing drugs
soon after coronary artery grafting to prevent graft atherosclerosis may be helpful. [123 ]
In a clinical trial, therapeutic reduction of total plasma and LDL cholesterol significantly
reduced the percentage of patients with new lesions in vein bypass grafts as compared
with controls. [139 ] The hypothesis that lipid control improves graft patency is not
proven, [140 ] , [141 ] but such measures are entirely appropriate. Vein graft patency is
enhanced by platelet inhibition with aspirin or dipyrimadole (in patients unable to
tolerate aspirin or who have contraindications such as peptic ulceration). One of these
drugs should be started postoperatively and continued indefinitely. [142 ] [144 ]
PEDICLED ARTERIAL GRAFTS
Internal (Mammary-Thoracic) Artery (ITA)
HARVESTING TECHNIQUES
After midline sternotomy, periosteal hemostasis is obtained with electrocautery. Bone

wax is not used, but if marrow bleeding is a problem, it can be controlled with a paste
made from microfibrillar collagen and topical thrombin that is pressed into the marrow.
The pericardium is not opened. The sternal leaf may be elevated using a table-mounted
or spreading type of retractor. [145 ] The former opens the sternum asymmetrically,
which may cause stretch injuries of the brachial plexus that are frequently reversible but
occasionally lasting. [146 ] , [147 ] Either retractor, if applied too vigorously, may
produce costochondral or costal-transverse separation or fracture of the sternum or first
rib. [147 ] Postoperative discomfort is reduced with less vigorous retraction. To avoid
problems, the sternal leaf should be elevated in several stages and only enough to allow
adequate visualization. The table is elevated to suit the seated or standing surgeon and
is rotated away from the surgeon. Mediastinal contents are separated from the sternum
using medium-current cautery, during which mediastinal branches of the ITA are
controlled with cautery or clips. The pleura is left intact or opened widely. If opened, the
lung is packed out of the field with a gauze pad; occasionally, tidal volume is reduced to
facilitate exposure.
Pedicle mobilization
Using 2.5× surgical loupes and low-current electrocautery with a rubber-covered or

insulated blade bent 45 to 60 degrees, the endothoracic fascia and sternocostalis
muscle are incised in a line at the edge of the sternum along the middle third of the ITA
(Fig. 17-16) . In this segment the ITA and the vein are visible, and the incision is placed
just medial to the vein. If the vein is not visible, the artery is identified by palpation. Using
blunt dissection with a cold cautery tip, occasional current to divide dense tissue and
blood vessels, and the vein as a guide, dissection begins in the middle third and
continues distally as the ITA passes beneath the thick sternocostalis muscle. Forceps
grasp only endothoracic fascia or muscle as pedicle tissue is separated from
intercostal muscle fascia and the costal cartilages where the artery and vein may be
adherent. Use of the cautery to separate the artery from the costal cartilages may
damage the ITA. Too much traction on the pedicle may tear or avulse branches of the
ITA. Avulsions lead to serious bleeding that requires repair with 7-0 or 8-0
polypropylene and may seriously injure the vessel.
Dissection continues distally to the bifurcation of the ITA, usually in the sixth interspace,
where the musculophrenic (lateral) and superior epigastric arteries begin. Francel et al.
[148 ] suggest that preservation of the bifurcation (proximal division of the ITA) improves
circulation to the lower sternum and xiphoid. Extension of the harvest to the proximal 1
to 3 cm of the superior epigastric artery is controversial. The internal diameter of the
superior epigastric artery is usually 1.5 mm or less and may be less than the grafted
coronary artery; use of this segment has been associated with reduced patency. [149 ]
Other surgeons harvest below the bifurcation when additional length is needed and
obtain good conduit patency. [150 ] Still others believe not only that the bifurcation
should not be used but also that the distal 2 to 3 cm of the ITA should be discarded
because more smooth muscle is present in this segment [151 ] and spasm is more
likely. [152 ] I routinely use the distal ITA, and I use the proximal superior epigastric
artery when additional length is needed and the vessel is adequate.
The ITA is divided at this time between two medium-sized clips at the bifurcation
(unless greater length is needed). Although many believe that the ITA should not be
divided before systemic heparinization, I have not observed clotting in the vessel in the
last 1500 cases unless it was injured. In fact, lack of clotting in the ITA ensures an
atraumatic harvest. Heparin is given at the time of cannulation.
After distal dissection, the lateral border of the pedicle is developed (2 cm width of
pedicle), and dissection continues proximally to the anterior surface of the subclavian
vein. The anterior plane of dissection is the intercostal muscle fascia and
perichondrium. Branches are only controlled with cautery; if a branch bleeds, a small
hemostatic clip is applied (average of one per conduit). Branches are clipped after
aortic cross-clamp release and before bypass is stopped.
On the right side, because more length is usually needed, dissection continues beneath
the subclavian vein to the thoracic outlet. The internal thoracic vein is divided at the
junction with the subclavian vein after placing two medium proximal clips and one distal
clip. After the vein is divided, the cautery is not used because of proximity to the phrenic
nerve. Sharp and blunt dissection with scissors is used to separate the pedicle from the
medially placed subclavian vein. Several arterial and venous branches in this area
(dorsal and cephalad to the internal thoracic vein) are controlled with small clips. The
phrenic nerve approaches the pedicle from below (posterior) and usually can be
identified easily. The nerve is adherent to the pleura and posterolateral surface of the
subclavian vein, and both nerve and pleura are bluntly dissected off the vein (the sucker
tip works well). The nerve remains close to the ITA and may exit the thorax in any
relationship to it; if the ITA is divided as a free graft, the nerve must be identified
carefully before double clipping the ITA. The nerve usually lies medial to the ITA at the
highest point in the thorax, but it may lie posterior, anterior, or rarely lateral.
Skeletonization of the ITA
Some prefer to harvest the ITA without associated tissue and without the venae
comitantes. The ITA is exposed by incising the overlying endothoracic fascia and
sternocostalis muscle with scissors, or the dissection can be initiated medially with
cautery. Blunt dissection with the cold cautery tip is used to tease the artery from its
bed. Electrocautery can injure the skeletonized ITA; branches must be divided between
small clips. With magnification it is possible to see the anatomy of arterial branches and
place clips to maximally preserve collateral sternal blood flow by dividing
sternal/perforating and sternal/intercostal branches upstream to their division [153 ]
without injuring the ITA. Those who utilize the skeletonized ITA believe that there is less
reduction in sternal blood flow, less mediastinal wound infection, longer length of the
ITA, easier construction of sequential anastomoses, and easier recognition of
persistent spasm or harvesting-related ITA injury. [154 ] , [155 ] Although preservation of
collateral sternal blood flow is theoretically possible based on anatomic studies, [153 ]
this benefit has not been proved. Sequential grafting is facilitated by a skeletonized ITA
because pedicle tissue may interfere with construction of a side-to-side anastomosis.
Spasm and injury are recognized more easily, but the harvest technique is more difficult,
and the potential for damage is greater. Skeletonization also requires twice the time
needed for pedicle mobilization.
Phrenic nerve injury
The phrenic nerve is usually injured at the thoracic outlet or when the pericardium is
incised to create a pericardial window. When the proximal ITA dissection stops at the
anterior surface of the subclavian vein, injury is rare. Right phrenic nerve injury is more
common because ITA mobilization extends proximally to gain additional length. After
the lessons of visual identification of the nerve and avoidance of cautery for the proximal
dissection were learned, right phrenic nerve injury became rare (< 1 percent) in my
experience.
Phrenic nerve injury related to ITA harvest is confounded by the widespread use of ice
slush for topical cardiac cooling. This cause of phrenic nerve injury was recognized
early [156 ] and was later shown to be reversible with time in many instances. [157 ] ,
[158 ] However, this problem persists because surgeons are reluctant to abandon what
they believe is an important part of myocardial protection. Omission of topical
hypothermia reveals a rare occurrence of phrenic nerve injury when the ITA is harvested
carefully.
Although reported by others, [159 ] in over 500 personal cases I have not found that
division of ITA branches to the phrenic nerve impairs nerve function. [159 ]
Pleural management
It is possible to dissect the ITA with the pleura intact in many patients. I prefer to open
the pleura widely to facilitate dissection and to provide an intrapleural course for the ITA
parallel and adjacent to the phrenic nerve. This course can be developed with an intact
pleura in most patients by mobilizing the mediastinal pleura to the phrenic nerve and
dropping the ITA into this trough. This technique requires more time and creates the
potential for mediastinal bleeding, which, if significant, may displace and/or compress
the ITA.
Pleural opening may create pleural/pulmonary complications postoperatively. [160 ] ,

[161 ] Pleural drainage is greater after ITA harvest as compared with saphenous vein,
and there is a higher incidence of late pleural effusion. [160 ] , [161 ] Other data suggest
that chest wall retraction for ITA harvest causes more postoperative pain that worsens
pulmonary function but does not necessarily cause complications. [162 ] If the drainage
tube is placed anteriorly and subcostally rather than intercostally, it produces less
discomfort. The pleural drainage tube may fail to drain all blood and fluid from the
pleural space, and as red cells break down and osmotic forces increase, pleural fluid
may increase and require late thoracentesis if diuretic therapy is not adequate.
Conduit spasm
All conduits develop harvest spasm. The ITA has less spasm than the other arterial
conduits, perhaps because there is less smooth muscle in the media [151 ] and
possibly because there is less trauma when it is harvested as a pedicle. Harvest spasm
of the ITA usually resolves with time and frequently requires no treatment. In the ideal
and common scenario, restoration of conduit flow produces shear stress that stimulates
endothelial elaboration of NO [163 ] and vasodilation within minutes.
Treatment of conduit spasm
Harvest spasm has been treated with a variety of drugs applied topically, intraluminally,
and systemically and with hydrostatic or mechanical dilation. I prefer intraluminal
papaverine (2 mg/mL) in heparinized blood (pH of 7.3) to gently fill the conduit using a
2-mm olive-tipped needle (DLP, Inc., Grand Rapids, Mich.) or the 1-mm version if the
lumen is too small. Proximal occlusion is not used because it is difficult to estimate
intraluminal pressure; I have caused an ITA to dissect with hydrostatic dilation.
After measuring free ITA flow for 10 years, it is not apparent that this flow correlates with
long-term patency. Green [164 ] recommends that 50 mL/min is the minimal acceptable
free flow. Mills and Bringaze [165 ] recommend 120 mL/min, but their technique of
intraluminal papaverine and hydrostatic dilation achieves significantly greater
vasodilation than other methods. I believe that a stream of blood projecting 3 to 4 in
from the end of the ITA is adequate. If the stream appears inadequate, intraluminal
papaverine should be used. Patency has not correlated with IMA free flow. [166 ]
Although papaverine (pH 3.5) is commonly diluted in saline or physiologic salt solution,
these solutions have little buffering capacity and produce a mixed pH of 4.17 to 5.83
that varies with the solution and dilution. [165 ] The acidic pH that injures endothelium is
not known, but at some level of acidity endothelium is injured and unable to produce and
release NO. Blood is an appropriate buffer for intraluminal delivery of papaverine.
Topical nitroprusside is also an effective vasodilator, [167 ] , [168 ] but rapid systemic
absorption may produce systemic hypotension. Other agents also have been tried, but
they are not as effective or pragmatic as intraluminal papaverine for intraoperative use.
[168 ] Nifedipine is effective in treating induced ITA spasm (induced by potassium
chloride or norepinephrine) and is clinically useful when used sublingually or
intravenously. [168 ] Intravenous nitroglycerin and nitroprusside are not as potent or
effective. [168 ]
Balloon catheter dilation of the ITA injures endothelium [169 ] and may cause
dissection, although this is rare. Probes also may cause dissection and impair
endothelial function. [170 ]
Criteria for rejection of the ITA
The most common cause for rejection of the ITA is injury during harvest. If the injury is
distal, this segment can be discarded; if the injury is proximal, the remaining ITA can be
used as a free graft. Dissection that originates proximally may extend the length of the
conduit and is a compelling reason for rejection.
Intrinsic atherosclerosis is a rare (< 1 percent) cause for rejection, although autopsy
studies indicate a low but higher incidence of the disease. [171 ] [173 ] Uniform mild
intimal thickening or yellow plaques are occasionally found at operation, but these are
not flow-restrictive lesions. Most flow-restrictive lesions involve the ostium of the ITA.
The most common atherosclerotic lesion that compromises ITA flow is subclavian
stenosis or occlusion. This lesion or ostial stenosis can be managed by relocating the
ITA to the aorta or to the contralateral in situ ITA. Subclavian stenosis or occlusion can
be recognized preoperatively by comparing brachial blood pressures; a difference of
more than 20 mmHg requires investigation. Routine preoperative angiographic study
for subclavian or ITA disease is not justified because the yield is low.
Late development of reduced subclavian flow that causes coronary-subclavian steal

after ITA grafting can be managed by carotid-subclavian bypass, [174 ] balloon
angioplasty, [175 ] atherectomy of the subclavian lesion, [176 ] carotid-ITA bypass, [177
] or relocation of the ITA to the aorta. [150 ]
The ITA is rarely (< 1 percent) too small but sometimes appears small because of
spasm. This is best treated with intraluminal papaverine (see above). The average ITA
has a diameter of 2 mm just proximal to the bifurcation. Smaller patients (< 60 kg) may
have a 1.5-mm ITA at this level, but their coronary arteries are usually no larger. Some
ITAs have a large branch one interspace, rarely two, above the bifurcation and are
narrow and unusable beyond this branch. I have not recognized hypoperfusion from
grafting a 1.5-mm ITA to a 2-mm left anterior descending coronary artery.
The most common cause of inadequate length-diameter proportions is related to the

shape of the chest and position of the heart within the thorax. Although a long chest is
associated with a long ITA, the heart is nearer the diaphragm and further from the origin
of the ITA. When the chest is short, the diaphragm is relatively higher, and the heart is
more cephalad and horizontal so that the relative length of the ITA is greater. A long
chest may be associated with poor ITA length-diameter proportions. This problem can
be solved by using the ITA as a free graft or by lengthening it with another arterial
conduit.
Histology
The ITA is lined with typical arterial endothelium that lies on a basement membrane,
subendothelial substrate, and an internal elastic lamina that may have a few small
fenestrations. The media is between the internal and external elastic laminae. The
media contains smooth muscle, a small amount of collagen, and five to nine elastic
lamellae with more lamellae in the middle two-thirds of the artery. The proximal and
distal 10 to 20 percent contains fewer lamellae, and usually none are distal to the
bifurcation. [150 ] The adventitia contains dense collagen fibers and fine elastin fibrils
close to the external elastic lamina and progressively less dense material as the layer
transits to loose alveolar tissue that contains vasa vasorum that do not penetrate the
media. [178 ] Wall thickness from the endothelium to external elastic lamina is about
200 µm, which is well under the 350 µm that can be nourished by diffusion from the
lumen. [179 ]
Sims [180 ] , [181 ] has compared the internal elastic lamina of the ITA with that of
coronary arteries and found that fenestrations were larger and more prevalent in the
latter. [180 ] , [181 ] He proposes that medial smooth muscle cells migrate through
fenestrations to initiate intimal thickening that evolves into the atherosclerotic plaque.
Because of the solidarity of the internal elastic lamina, the ITA is protected.
RESPONSE TO AGONISTS
Vascular tone is controlled by endothelial release of vasoactive substances. The most

important is endothelial-derived relaxing factor (EDRF), which appears to be nitric
oxide (NO). [49 ] , [50 ] The ITA endothelium releases more prostaglandin I2
(prostacyclin) [182 ] and shows greater NO-mediated vasodilation than does
saphenous vein. [183 ] Extraluminal release of NO causes relaxation of adjacent
vascular smooth muscle. Release of NO into the lumen inhibits platelet aggregation
[184 ] and adhesion [185 ] and promotes platelet disaggregation as well. [186 ]
Downstream travel of NO from the ITA may cause coronary vasodilation. [187 ] Because
NO inhibits mitogenesis and smooth muscle proliferation, the chemical may inhibit
development of atherosclerosis in the ITA. [188 ]
To minimize endothelial injury, only very soft vascular bulldogs are placed on the ITA
(Soft/Fibra, 6 mm, Applied Medical Resources, Laguna Hills, Calif.).
Acetylcholine, adenosine diphosphate, and thrombin achieve greater vasodilation in the

ITA than in saphenous vein by endothelial release of NO. [183 ] Histamine is a potent
stimulus for NO release in the ITA but not in saphenous vein, where histamine evokes
endothelial-dependent contraction. [82 ] Serotonin-induced vasoconstriction is inhibited
but not abolished by basal endothelial release of NO in the ITA, whereas contraction is
not inhibited in saphenous vein. [188 ] Thus serotonin and histamine, which can be
released from platelets, mast cells, and endothelium, are implicated in coronary spasm,
[190 ] may contribute to venous graft spasm, but are unlikely to cause ITA spasm if the
endothelium is intact and functional. Recovery of regional wall motion in myocardium
revascularized by ITA grafts is impaired when the endothelium is removed and appears
to be enhanced by prostanoid secretion. [191 ] Activated neutrophils cause more
vasoconstriction in saphenous vein than in the ITA. [192 ]
In a systematic study of induced vasoconstriction in the ITA the most powerful agents in
decreasing order were the thromboxane mimetic U46619, norepinephrine, serotonin,
phenylephrine, and potassium chloride. [193 ] In potassium-precontracted arteries,
nifedipine, verapamil, and diltiazem caused full relaxation, but nifedipine was 15 times
more potent. [192 ] Although beta 2 receptors are abundant on endothelium and more
sparse on smooth muscle, [194 ] relaxation to beta agonists is mediated by smooth
muscle receptors and not by endothelial cell release. Dobutamine and dopexamine
produce active ITA vasodilation, whereas dopamine in low doses has no effect and
causes vasoconstriction at high concentration. [195 ] , [196 ] These catecholamines
have beta 2 -agonist properties, and their effects are not related to the functional status
of endothelium. Age and gender do not affect the reactivity of the human ITA. [197 ]
Although it is difficult to extrapolate in vitro drug concentrations to patients, some clinical
data verify the in vitro studies.
ITA flow after termination of cardiopulmonary bypass declines when phenylephrine (an
alpha1 agonist) is infused sufficiently to produce a 20-mmHg increase in blood
pressure. [198 ] An epinephrine bolus in normovolemic dogs increases ITA flow, but
with hypovolemia the same bolus causes a 40 percent further decrease in flow beyond
that produced by hypovolemia alone. [199 ]
Flow Capacity
In contrast to the saphenous vein, ITA flow capacity is limited and relates to the
diameter (2 versus 5 mm) or cross-sectional area of the conduit. This obvious
difference raises concern as to whether or not the ITA can supply adequate flow,
particularly at times of increased need (i.e., after cross-clamp release or during
exercise). Intraoperative measurements with an electromagnetic flowmeter or more
recently with a transit-time flowmeter demonstrate that basal flows are comparable for
the ITA and saphenous vein but that reactive hyperemic flows or those induced by
intracoronary papaverine are significantly greater for saphenous vein. [200 ] In other
reports, ITA flow is less than for saphenous vein, probably because of competitive flow
in the native coronary artery. [166 ]
When the ITA and saphenous vein are both grafted to the same left anterior descending
artery, blood flow is lower in the ITA. [201 ] Postoperative studies of ITA and vein graft
flow using dye-densitometric techniques reveal significantly greater vein graft flow. [202
] Nevertheless, flows at rest and during stress are comparable for both conduits using
xenon-133 washout, [203 ] digital subtraction, [204 ] myocardial scintigraphy, [205 ] and
microspheres. [206 ] However, there are clinical reports suggesting inadequate ITA
flow. [207 ] , [208 ] I measured ITA flows intraoperatively for 15 years and found no
correlation with long-term patency, and this also has been the experience of others.
[166 ] Patients studied 1 month postoperatively had an appropriate flow increase in ITA
grafts, but exercise-induced abnormalities of segmental wall motion suggest
inadequate flow. [207 ] When ITA and vein grafts were studied early (1 month) and late
postoperatively (1 year) by Doppler guidewire, coronary flow reserve was reduced (1.8
± 0.3) at 1 month but not at 1 year (2.8 ± 0.5 for ITA versus 3.0 ± 0.6 for vein). [209 ]
Another study at 8 ± 2 days and 19 ± 15 months postoperatively revealed a coronary
flow reserve of 2.70 ± 0.62 early versus 3.66 ± 0.81 late for the ITA and 4.05 ± 0.96 for
normal coronary arteries. [210 ] Significant ITA vasodilation both early and late occurred
after papaverine and isorbide dinitrate administrations. The diminished early coronary
flow reserve was attributed to perioperative injury of the coronary microvasculature. [210
]
These two serial clinical studies and earlier observations that ITA grafts enlarge over
time in accordance with flow demand indicate that ITA grafts have the capacity to grow
to meet physiologic demands of the myocardium. Nevertheless, there may be
perioperative situations or times of stress in the postoperative interval when myocardial
flow requirements are not met by an ITA graft. A well-documented instance occurs
during reoperative coronary bypass. If a diseased but patent vein graft to an occluded
left anterior descending coronary artery is ligated and replaced with an ITA graft, the
new graft may not immediately provide adequate perfusion of affected myocardium.
[211 ]
Distal Anastomosis
CORONARY VESSELS
Ideally, the distal anastomosis is made into a normal segment or the healthiest segment
(if diffusely diseased) of the target artery. For the left ITA, the target artery is usually the
anterior descending artery, but it may be the ramus intermedius or a branch of the
circumflex. The right ITA will reach the posterior descending artery in 30 to 40 percent of
patients and the anterior descending, ramus intermedius, or near branches of the
circumflex system. From 1984 to 1986, I used the transverse sinus route for the right ITA
to the circumflex but abandoned this procedure because two vessels developed string
signs and because the entire conduit cannot be inspected for bleeding, torsion, and
tension. Subsequently, the right ITA has been used only as a free graft when connected
to branches of the left coronary artery because of the possibility of injury during
reoperation. However, Joyce et al. have shown that a crossing right ITA connected to
left coronary arteries can be protected from injury during reoperation. [212 ] When two
ITAs are used, they are connected to the two most important diseased coronary arteries
(i.e., the largest vessels serving the largest mass of healthy muscle). A right coronary
anastomosis is usually made to the posterior descending artery (85 to 90 percent)
rather than to the distal right artery because disease at the bifurcation may not be
apparent on angiograms.
TECHNIQUE
A 3- to 5-mm coronary arteriotomy (at least two times the diameter of the vessel) is
made where the diameter is 1.5 mm or greater. The ITA is spatulated after trimming the
pedicle proximal to the bifurcation. An end-to-side anastomosis is constructed with 7-0
polypropylene and a small (8-0) needle. Some prefer 8-0 suture, but I find this difficult to
work with and believe the small needle causes less trauma (Fig. 17-17) . The suture is
started at the heel, where 2 or 3 bites are taken toward the surgeon and 2 or 3 taken
away; the suture line is pulled tight. The suture on the far side of the anastomosis is run
to the toe, with the suture pulled tight until the toe is reached. The next 5 bites are not
pulled up to provide an unobstructed view into the distal coronary artery. The suture is
then pulled tight, and usually the anastomosis is probed for 5 to 10 mm in each
direction. The anastomosis is completed, and the vascular bulldog is released to flush
out air before the suture line is tightened and tied. A running suture may have a
purse-string effect, but this is overcome by many small bites (15 to 20) that also serve to
prevent stenosis of the inflow or outflow coronary artery. Some surgeons prefer an
interrupted suture technique; this is entirely suitable and avoids the potential
purse-string effect.
After the anastomosis is completed and hemostasis is secured, the ITA pedicle is
tacked to the heart with one or two fine polypropylene sutures. Care is taken to reduce
linear tension on the pedicle and to avoid angulation at the anastomosis.
SIDE-TO-SIDE ANASTOMOSIS
Sequential ITA anastomoses were only attempted after several years of experience with
this technique using saphenous vein and then with careful angiographic control. [33 ]
Initial use was with the left ITA to one or two diagonal arteries and the left anterior
descending artery or to the middle and distal segments of the anterior descending
artery. After experience and demonstration of excellent patency, the technique was
extended to the ramus artery and obtuse marginal arteries.
I strongly believe that all side-to-side anastomoses with arterial conduits should be
made in parallel and that crossing anastomoses (diamond anastomoses) should never
be used. Although the latter are successful with venous grafts, the small diameter and
reduced compliance of the fragile arterial wall dictate the use of small incisions, which
raises the potential for stenosis and occlusion. I believe that perioperative
hypoperfusion can be a consequence of this type of anastomosis. When undertaking
sequential anastomoses, it must be recognized that a technically faulty proximal
anastomosis may compromise flow into the distal anastomosis, which may be the more
important anastomosis of the two.
The coronary arteriotomy site must be selected on the basis of the amount of disease in
the coronary artery, a diameter of 1.5 mm or more, the length of the ITA, and the location
of the distal anastomosis. The coronary arteriotomy is 3 to 4 mm in length, as is the
incision in the ITA. The entire length of the ITA between the two anastomoses is
exposed before the proximal anastomosis is begun. The two vessels are brought within
1 to 2 cm of each other, and the suture line is started proximally at the apex and
continued on the far side to the distal apex in parachute fashion (Fig. 17-18) . After
taking two bites beyond the distal apex, the suture line is tightened by pulling the fourth
or fifth loop from the proximal end. After this segment is tight, loops are pulled up until
the entire suture is tight. The other end of the suture is run on the near side from
proximal to distal.
It is my practice to construct proximal anastomoses first and distal anastomoses last

with arterial conduits. If the distal end of the conduit is unattached, the toe of
side-to-side anastomosis is better exposed. It is important to suture the ITA pedicle to
the epicardium at the heel of the anastomosis and on the far side where the pedicle
may catch the pericardial edge when the heart is replaced in its usual position.
INDICATIONS AND CONTRAINDICATIONS
Sequential grafting has been utilized to extend the utility of arterial conduits and the
advantage of better patency. Because of limited length and the need to perform parallel
sequential anastomoses (see above), target arteries and anastomotic sites on these
arteries must be selected carefully so that (1) the length of the conduit is adequate (no
tension) and (2) there are sigmoid curves or loops between anastomoses without
angulation or kinking. If these criteria cannot be met, sequential grafting is not
advisable. Anatomic situations that mitigate against this procedure include a very
proximal first diagonal. This situation requires more length because the ITA must literally
dip posteriorly before curving anteriorly to the anterior descending artery. If a diagonal
pursues a lateral course, the ITA is directed away from the anterior descending artery
by the parallel anastomosis, and more length is needed to produce an appropriate
curve back to the anterior descending artery. The proximal and middle thirds of the
diagonal may have significant atherosclerosis that mandates a distal anastomosis; the
length of the ITA may not allow it to reach back to the anterior descending artery.
It is desirable that the ITA be 2 mm in diameter at the side-to-side anastomosis for

technical reasons, but this is rarely a cause for rejection. Occasionally it may be
appropriate to place the side-to-side anastomosis to the anterior descending artery and
the end anastomosis to the diagonal; this depends on coronary anatomy and lesion
location.
Y Grafts
As an alternative to sequential grafting, a short segment of distal ITA can be resected

and used as a Y graft to the diagonal, a ramus artery, or even a first marginal artery if
the anastomosis is made to the proximal third of these latter vessels so that only a short
segment of free graft is needed. If an in situ ITA is directed to the circumflex branches, a
Y graft can be constructed to one or more of these branches. Ideally, this is planned,
and the Y anastomosis is performed prior to starting cardiopulmonary bypass.
However, the intended anastomotic sites must be inspected and even dissected to
determine feasibility, graft lengths, and the position of the Y. This frequently requires
initiation of bypass, which is discontinued while the Y is constructed. If the free segment
of ITA is directed to a ramus artery or first marginal, the Y anastomosis is placed on the
posterior aspect of an ITA pedicle directed to the left anterior descending coronary
artery. If the free segment is planned for a diagonal, it can be placed anteriorly,
posteriorly, or laterally on the pedicle.
The Y anastomosis is made with a 4- to 5-mm arteriotomy and appropriate spatulation

of the free segment (Fig. 17-19) . The anastomosis is started at the heel (Fig. 17-19D)
and constructed with 7-0 polypropylene and the small needle. If the free segment retains
pedicle tissue, the two pedicles can be tacked together with fine polypropylene. If the
free segment is skeletonized, tacking sutures usually are not helpful. The coronary
anastomoses are constructed as described above.
The natural Y graft entails harvest of the ITA bifurcation with preservation of appropriate
lengths of the musculophrenic and superior epigastric arteries (Fig. 17-20) . These two
branches are usually anastomosed to a diagonal artery and the anterior descending
artery, but any two adjacent coronary branches are suitable. Because the limbs are
short (1 to 3 cm), this method is limited anatomically. It is also limited by the fact that
each branch usually has a diameter of 1.0 to 1.5 mm so that anastomoses may be
technically difficult and flow may be restricted. Because of minimal elastic tissue at and
beyond the bifurcation, [151 ] spasm and flow restriction are more likely. [152 ]
T GRAFTS
The T graft can be viewed as a variant of the Y graft, or vice versa, but the unique role of
the T graft (a milestone in the evolution of coronary surgery) as a means to completely
revascularize the heart with only two conduits deserves special comment. Both ITAs are
harvested (the left as pedicle and the right free as a pedicle or skeletonized). The
pericardium is incised transversely at the level of the pulmonic valve to the left phrenic
nerve and for 2 to 3 cm parallel to the nerve. The distance to the tip of the left atrial
appendage is marked on the left ITA pedicle, and the right ITA is anastomosed to the
posterior aspect of the left ITA at this level after systemic heparinization and before
cannulation. [150 ] Tector et al. [150 ] perform the anastomosis as a true T (Fig. 17-21) ,
whereas I perform it as a Y anastomosis using running 7-0 or 8-0 polypropylene. The
heel is constructed in parachute fashion with five suture bites before pulling the suture
up. The far side is sutured to the toe before completing the near side. Pedicle tissue of
the two conduits is tacked together with two sutures of fine polypropylene. If the right ITA
is not skeletonized, the endothoracic fascia is incised down to the adventitia of the
artery to provide more length and to facilitate side-to-side anastomoses. If the left ITA is
to be used for sequential anastomoses or is short, it is treated similarly.
The right ITA is anastomosed to one or more branches of the circumflex artery and one
or more branches of the right coronary artery using parallel positioning for side-to-side
anastomoses and gentle simple or sigmoid loops between anastomoses. The end
anastomosis is performed last and usually is to the posterior descending artery. The left
ITA is anastomosed to the left anterior descending artery and to appropriate diagonal
arteries with parallel side-to-side anastomoses.
Although there was initial concern whether the proximal left ITA could provide adequate
flow for this configuration, the experience of Tector et al. [213 ] with more than 600
patients reveals a 1 percent incidence of hypoperfusion that is managed with
supplementary vein grafts. Only 1 of 27 T anastomoses was closed by angiography 6 to
30 months later.
Angioplastic Anastomosis
Tandem lesions with an intervening coronary artery segment containing branches that
should be perfused can be managed with the sequential technique. A side-to-side
anastomosis is made between the two lesions, and an end-to-side anastomosis is
placed distal to the second lesion. If the intervening segment has a branch of adequate
size, the side-to-side anastomosis (or a Y anastomosis) can be made to that branch. A
third option is to perform an angioplastic anastomosis across the distal lesion to
provide perfusion into the intervening coronary segment. The advantage of this
approach is that a single anastomosis suffices.
The coronary arteriotomy is made across the distal lesion and extends to relatively
healthy or normal artery proximal and distal to the lesion. The ITA is spatulated
appropriately (10 to 40 mm), and a long anastomosis that opens the stenosis and
provides bidirectional perfusion is performed (Fig. 17-22) . If the ITA is not sufficiently
long, a vein patch can be used to close the coronary arteriotomy, with the ITA
anastomosed to the proximal end of the vein patch (Fig. 17-23) .
Composite Graft with Vein
If the aorta is too diseased to accept proximal anastomoses and two pedicled ITA
grafts are used, supplemental vein grafts may be needed. The proximal vein can be
anastomosed to the ITA graft(s) [96 ] (Fig. 17-24) . It is easier to perform the proximal
anastomosis before the distal anastomoses. This allows the pedicle grafts to be
brought into the anterosuperior mediastinum to anastomose the vein to the posterior
aspect of the left ITA or to the anterior or posterior surfaces of the right ITA. After
systemic heparinization, an arteriotomy equal to the diameter of the vein is made in the
ITA to create a T anastomosis (see Fig. 17-21 ). Alternatively, a longer Y anastomosis
(see Fig. 17-19 ) can be constructed by beveling or spatulating the vein and making a
corresponding arteriotomy. The anastomosis is made with 7-0 polypropylene,
beginning at the heel as described for the ITA Y graft (see Fig. 17-19 ). This
anastomosis can be supported by toe and heel sutures placed from the fascia of the
ITA pedicle to the adventitia of the vein using fine polypropylene.
Conduit Failure
CONDUIT PATENCY
Patency for the left ITA grafted to the left anterior descending artery is 92 to 97 percent
at 1 year, [213 ] , [214 ] 88 to 96 percent at 5 years, [213 ] , [216 ] and 88 to 93 percent
at 10 years. [213 ] , [214 ] , [216 ] Right ITA patency is less than that reported for the left
ITA by 5 to 10 percent, [213 ] , [215 ] but if only grafts to the left anterior descending
artery are considered, patency is comparable for the two conduits. [217 ] In more recent
experience, 1-year patency for the right and left ITA is comparable (95 to 96 percent)
regardless of the vessel grafted. [218 ]
The failure rate for ITA grafts is 0.5 to 1.0 percent per year between years 1 and 10.
Beyond the tenth year only anecdotal data are available.
TECHNICAL ERRORS
Some conduits fail because unrecognized harvest injury or injury sustained during
preparation (intraluminal instrumentation, hydrostatic dilation) leads to early thrombosis.
Technical anastomotic errors include large suture bites (too deep or too wide) and
forceps trauma to the ITA. Anastomoses that are too small in diameter may become
stenotic when the suture is tightened and tied, or stenosis may occur with healing and
contraction of scar tissue in the anastomosis. Angulation or kinking adjacent to the
anastomosis may lead to stenosis or occlusion. Linear tension may cause narrowing
and occlusion. Conduits placed to coronary arteries with less than 50 to 70 percent
stenosis may develop generalized narrowing (string sign, slender sign) that is inversely
related to the degree of coronary stenosis. [220 ] Some of these narrow conduits may
occlude, but others that appear to be occluded can dilate when flow is needed. [221 ] ,
[222 ]
Some conduits fail because of coronary atherosclerosis that involves the anastomosis
or occludes the coronary artery proximal and distal to the anastomosis. Established ITA
grafts can remain patent even with proximal and distal occlusions with runoff through
very small branches of the patent segment adjacent to the anastomosis. [222 ]
Atherosclerosis of the ITA is not present in conduits functioning for 15 to 21 years, [223 ]
and intimal hyperplasia does not occur.
OTHER PEDICLED ARTERIAL CONDUITS
Gastroepiploic
HARVEST TECHNIQUE
The median sternotomy incision is extended 4 to 6 cm inferiorly to harvest the

gastroepiploic artery, which is done before or after harvest of the ITA(s). The peritoneal
cavity is entered after pulling the sternal retractor inferiorly or turning it around so that the
crossbar is out of the field. A nasogastric tube is used to add or remove air from the
stomach to facilitate exposure. The stomach is pulled anteriorly and cephalad with
Babcock clamps to bring the greater curvature in view. The artery is palpated to
determine the presence of a reasonable pulse and adequate size. To prevent axial
torsion, some prefer to mark the pedicle with a marking pen or a suture. [224 ]
Dissection begins in the middle third of the conduit, and as with the ITA, two basic
techniques are available: a bulky pedicle or a skeletonized conduit (Fig. 17-25) . I prefer
the latter technique and use the cold cautery tip to dissect the artery and venae
comitantes from the fatty gastrocolic omentum. Unlike the ITA, only the smallest
branches are controlled by coagulation because cauterized, thin-walled, larger
branches continue to bleed. Small clips provide secure hemostasis for all branches. A
bulky pedicle produces short gastric stumps from which clips slip. Attempts to control
bleeding from gastric stumps with cautery may cause a thermal gastric injury; 4-0 silk
ties are better. [225 ] Dissection continues proximally to the level of the pylorus and may
continue almost to the gastroduodenal artery if the conduit is a free graft. The distal
extent of the dissection depends on conduit diameter (minimum of 1.5 mm) and the
length required. After dissection is completed, the conduit is filled with blood containing
papaverine (2 mg/mL) using a 1- or 2-mm olive-tipped needle without hydrostatic
dilation and is returned to the peritoneal cavity until needed.
ROUTES TO THE PERICARDIUM
The gastroepiploic artery may pass anterior or posterior to the stomach (more properly,
the pylorus), anterior or posterior to the left lobe of the liver, and through or anterior to
the diaphragm (Fig. 17-26) . Considerations for routing include the distance to the
anastomotic site, the relationship between the diaphragmatic opening and the coronary
artery anastomosis, and the potential for injury to the conduit by future upper abdominal
operations. When these distances were measured in a small number of cadavers, there
were no significant differences between ante-and retrogastric or anterior and posterior
to the left lobe of the liver for either the right or circumflex coronary arteries. [226 ] If the
left lobe of the liver was enlarged, the posterior pathway was shorter. [226 ] For the left
anterior descending artery (the most uncommon destination [227 ] ), the shortest route
is anterior to the pylorus and the diaphragm. [226 ] Routing the artery over the pylorus
avoids tension on the conduit by a full stomach. Pedicle bleeding may be difficult to
manage with the posterior position. For an anastomosis to the distal right coronary
artery or posterior descending artery, the opening in the diaphragm is frequently to the
left, and the gastroepiploic artery approaches the anastomosis opposite to the direction
of coronary flow. The opening in the diaphragm can be a simple incision, a cruciate
incision, or an excision with the size proportional to the bulk of the pedicle. A large
defect may produce hernia. [228 ] Locating the diaphragm incision is based on the
preceding considerations and the ultimate location of the anastomosis when the heart is
full. Several centimeters of conduit are placed within the pericardium. This occurs
automatically for circumflex or anterior descending artery locations but may require
planning for the right coronary artery. The pedicle is sutured to the epicardium to prevent
anastomotic angulation and kinking and may be sutured to the diaphragm.
The case for retrogastric routing to avoid injury at a future laparotomy has been made,
[229 ] but the most important consideration is prior knowledge of the conduit. [230 ]
Thus the patient must be informed of this conduit and the importance of telling future
treating physicians.
Ten-year results and substantial experience [230 ] [235 ] are now available.
Intraabdominal complications related to the conduit are rare (one instance each of
pancreatitis, [235 ] gastric necrosis, [225 ] splenectomy, [235 ] and diaphragmatic
hernia [228 ] ). Gastric mucosal blood flow is not reduced. [232 ] Prior upper abdominal
operations with gastric resection, ligation of the gastroepiploic artery, or extensive
scarring preclude its use. Severe atherosclerosis of the gastroepiploic artery, [236 ]
which is rare, or celiac axis is an absolute contraindication.
Occasionally, the gastroepiploic artery is too small, particularly if the coronary bed is
large. Hypoperfusion occurs in 8 percent of patients 2 years after operation at maximum
exercise by thallium scintigraphy. [234 ] The gastroepiploic artery is long enough (1.5
mm or greater in diameter) to reach the right coronary artery in 97 percent of instances
and in 88 percent for the left anterior descending coronary or circumflex artery. [237 ] Its
length varies from 16 to 26 cm (mean 19.2 cm) with a free flow (after intraluminal
papaverine) of 42 to 660 mL/min (mean 180 mL/min). This is less consistent than for
the ITA. [238 ] If the abdomen is particularly obese, harvesting may be tedious and a
longer conduit may be needed. Excessive fat increases the distance to the heart.
Postoperative angiography shows that this vessel has a tendency to spasm;

perioperative diltiazem and postoperative oral therapy are recommended. [232 ]
Initially, the gastroepiploic artery was used in the absence of other conduits. [231 ] With
experience and proven patency, it is chosen for the second [232 ] or third arterial
conduit [234 ] in initial operations. This conduit is avoided in emergency operations,
severe impairment of the left ventricular function (ejection fraction of less than 25 to 30
percent), or excessive cardiac enlargement because of inadequate conduit length and
/or flow. Associated cardiac disease is a relative contraindication. The possibility of
coronary steal has been raised if the coronary stenosis is less than 90 percent, [239 ]
but this is unlikely unless there is stenosis in the celiac axis or beyond causing a
reduction in perfusion pressure. With less severe stenoses, gastroepiploic patency is
reduced due to competitive flow. [240 ]
HISTOLOGY AND RESPONSE TO AGONISTS
The media of alternative arterial conduits lack the 6 to 12 elastic lamellae found in the
ITA, [151 ] but otherwise the histology and wall thicknesses are similar.
As compared with the ITA, in vitro studies show stronger contractility to depolarizing
agents, [241 ] [243 ] adrenergic stimulation, [241 ] , [242 ] and serotonin [241 ] , [244 ] in
the gastroepiploic artery. However, others find similar responsiveness to serotonin for
both conduits [245 ] or that the ITA reacts more vigorously. [243 ]
Endothelium-dependent relaxation to methacholine and endothelium-independent
relaxation to sodium nitrate are comparable for both vessels. [245 ] In in vivo studies (6
to 36 months postoperatively), the gastroepiploic artery is more responsive to
ergometrine and nitrates than the grafted coronary artery, [247 ] but the ITA is less
reactive. [248 ] Ergometrine activates serotonergic receptors in vascular smooth
muscle cells. The same agent activates endothelial serotonergic receptors to release
nitric oxide to counteract the vasoconstrictive effects of activating smooth muscle
receptors. [249 ] The net result of direct vasoconstrictor and indirect
endothelium-dependent vasodilator effects depends on the distribution and sensitivity of
serotonergic receptors and the ability of endothelial cells to relax the vasoconstrictor
response of smooth muscle. Activated platelets cause endothelial-mediated relaxation
in precontracted porcine and human ITAs and contraction in porcine and human
gastroepiploic arteries. [244 ]
These data suggest that control of vasomotor tone by endothelial cells is less effective
in the gastroepiploic artery and that this may be responsible for reported instances of
spasm at angiographic follow-up. [232 ] , [250 ] This observation may have implications
for the use of vasoactive medications in patients grafted with this vessel.
PATENCY RATES
Three substantial series reported consistent patency rates. The largest series had a
2-month patency rate of 96 percent (350 of 365) and a 2- to 5-year patency rate of 92
percent (57 of 62). [232 ] For free grafts anastomosed to the aorta, patency was 80
percent (12 of 15). [232 ] Eighty-eight of 300 patients had angiograms at a mean of 10
months after operation. With experience, patency improved from 77 to 95 percent from
the first to the fourth quartile. [233 ] Of 240 patients studied the fifteenth day following
operation, 51 had a 96 percent patency rate. [234 ] In one report patency was the same
(80 percent) for free and in situ grafts studied 6 days to 65 months after operation. [235
]
FREE ARTERIAL GRAFTS
STORAGE AFTER HARVEST
The harvested ITA is gently flushed from proximal to distal with 5 mL of heparinized
blood containing 2 mg/mL papaverine using the 2-mm olive-tipped needle. A soft
vascular bulldog is placed on the distal end, and the artery is filled gently (to avoid
hydrostatic dilation) and a proximal bulldog placed. The ITA is stored in
room-temperature lactated Ringer's solution until used.
TECHNIQUE OF PROXIMAL ANASTOMOSIS
The proximal anastomosis may be performed before or after the distal anastomosis
and is made to the aorta or to another in situ arterial conduit (usually the left ITA).
If the aorta is healthy and not thickened, the free ITA may be anastomosed to the aorta
using a 4-mm punch and 7-0 polypropylene. The ITA is spatulated with a 6-mm incision
and not trimmed (Fig. 17-27) . The suture is started at the heel, with the first bite placed
in the aorta in the precise direction of the final conduit to avoid angulation. Three to six
bites are taken to the surgeon's left, followed by a similar number to the right, and the
suture line is tightened. The anastomosis is made with multiple small bites to avoid
gathering the ITA and to create as much hood as possible. If this anastomosis is
performed last, air can be flushed from the conduit and aorta by retrograde flow before
tying the suture line.
If the aorta is thick-walled or atherosclerotic, a 4-mm opening is at risk of stenosis with

healing or progression of disease. In this situation, the ITA is anastomosed to the hood
of a vein graft or to a patch of vein or pericardium in the aortic wall. If the aorta is
atherosclerotic, a 20-mm incision is made or a 10 × 15 mm defect is created with
multiple bites from a large punch. The patch is placed with a running 6-0 polypropylene
(see Fig. 17-27 ). The patch is incised 5 or 6 mm, or a 4-mm hole is made for the
anastomosis of the ITA. If the patient has had previous surgery, it is usually possible to
anastomose the ITA to the hood of an old vein graft.
It is easier to construct an anastomosis to an in situ arterial conduit (usually the right ITA
to the left) by bringing the left ITA into the anterior mediastinum (before it is tethered by
a distal anastomosis). This can be done without cardiopulmonary bypass. The
procedure for joining a free right ITA to an in situ left ITA is described on page 509 and
illustrated in Fig. 17-21 . If the free conduit is used for a sequential anastomosis, the
smooth (pleural) side of the pedicle is oriented to face the heart; this means the initial
spatulation must be on the rough side. An anastomosis larger than the diameter of
either conduit is achieved by spatulation of the right ITA. Skeletonization of the right ITA
facilitates sequential anastomoses, since the presence of a pedicle is cumbersome;
however, the pedicle stabilizes the conduit and reduces the possibility of angulation and
kinking.
PATENCY RATES
Intermediate-term patency of aorta-based free ITAs is not as good as for in situ ITAs
(75 to 92 percent), [214 ] , [219 ] , [251 ] even though early patency is reported to be 96
to 100 percent. [252 ] , [253 ] When the free right ITA is based on the in situ left ITA,
patency is 91 percent (31 of 34). [150 ]
Inferior Epigastric Artery
HARVEST TECHNIQUE
The skin incision extends from the umbilicus to symphysis pubis. A midline incision
allows harvest of both inferior epigastric arteries by entering the rectus sheath medially
and retracting the muscle laterally. A paramedian incision 2 cm lateral to the midline
with lateral retraction of the muscle places the surgeon closer to the artery. An incision 3
to 4 cm from the midline with lateral entry into the rectus sheath and medial retraction
places the surgeon nearer the origin of the artery and is preferred.
After the rectus sheath is entered, the muscle is mobilized by blunt and sharp dissection
laterally and retracted medially by a hand-held retractor initially and later by a
self-retaining retractor (Fig. 17-28) . Initial retraction must be gentle to avoid tearing
arterial branches. The artery and its venae comitantes lie in a small amount of fatty
tissue behind the retracted muscle on the posterior rectus sheath. Dissection begins in
the midsegment by creating a small pedicle of fat, veins, and artery using sharp
dissection and low-current electrocautery. Branches are controlled with fine clips.
Dissection continues distally (cephalad) until the artery enters into the rectus muscle or
increasing muscular arterial branches slow dissection. Dissection is then directed
proximally (caudad) as the artery courses laterally and posteriorly. Exposure is
facilitated by a sponge stick to push the peritoneum and preperitoneal fat posteriorly
and by a small hand-held retractor placed anteriorly. The two accompanying veins form
a single trunk within 1 to 2 cm of the external iliac vein. An anomalous obturator artery
may arise from the inferior epigastric artery as a large branch within 1 cm of the external
iliac artery. Some surgeons have used this branch to extend the length of the inferior
epigastric artery. [254 ] The inferior epigastric artery is divided within 1 cm of the
external iliac artery by two medium clips or a ligature of 2-0 silk. The inferior epigastric
artery, although visibly pulsatile when first exposed, rapidly develops spasm and loses
pulsation with initiation of dissection.
After dividing the artery, the length is measured, and distal dissection is resumed. With
increasing difficulty of dissection, the distal artery may run posterior to the muscle, in a
groove in the muscle, or deep within the muscle [255 ] (Fig. 17-28E) . The latter position
makes dissection very difficult and at times hardly worthwhile. In addition, the artery may
bifurcate into two equal-sized branches that often reduce the diameter to less than 1.5
to 2.0 mm. Occasionally this variant can be used as a natural Y graft. Distal dissection
is facilitated by extending the incision, rotating the table away from the surgeon, and
further retraction of the rectus muscle. Dissection of the artery within the muscle is
facilitated by an anterior approach through the rectus muscle. The length of useful artery
varies from 6 to 16 cm, with a mean of 12 cm. [256 ] The harvested conduit is placed in
room-temperature lactated Ringer's solution and flushed with heparinized blood
containing 2 mg/mL papaverine using the 2-mm olive-tipped cannula. Soft vascular
bulldogs placed on both ends retain blood in the conduit, but hydrostatic dilation is not
used.
Most surgeons use this conduit as a free graft from the aorta and harvest the maximal
length. Calafiore et al. [257 ] have used it differently by deliberately harvesting a short
segment (4 to 8 cm) and attaching the graft to an situ left ITA or to a radial artery graft
anastomosed to the left ITA. The inferior epigastric artery is anastomosed distally to a
diagonal artery, ramus marginalis, or marginal artery. This approach avoids an aortic
anastomosis, and it is simpler to harvest a short segment than a long segment.
Alternatively, the inferior epigastric artery can be anastomosed to an in situ right ITA to
extend its length by end-to-end anastomosis or to make a Y graft (Fig. 17-29) .
The abdominal wall incision is packed with a laparotomy pad. After protamine is given,
the incision is rechecked for bleeding and closed in layers with absorbable sutures.
Some prefer a closed drainage system that I have not found necessary.
HISTOLOGY AND RESPONSES TO AGONISTS
The histology of the artery wall is similar to that of the other alternative arterial conduits
in that the media has few or no elastic fibers. [151 ] Wall thickness from the lumen to the
outermost media is significantly less than for the ITA. [151 ] Fenestrations of the internal
elastic lamina are fewer than in the ITA, [258 ] , [259 ] but the significance of this finding
is not clear.
In vitro response of vessel rings to alpha-adrenoceptor stimulation (norepinephrine) is

less than in the ITA in one report [260 ] and comparable in another. [261 ] Similarly, the
constrictor response to serotonin is either greater in the inferior epigastric artery [260 ]
or comparable with the ITA. [261 ] Histamine produced greater contraction in the ITA
[261 ] or comparable responses. [260 ] Endothelium-dependent vasodilation in
response to acetylcholine and substance P is significantly greater in the inferior
epigastric artery than in the ITA in one report [261 ] but is reduced in another. [262 ]
Endothelium-independent relaxation is comparable in the two conduits in response to
nitroglycerine [261 ] but reduced in the inferior epigastric artery for other vasodilators.
[262 ] A third group found that contractility, endothelium-independent relaxation, and
receptor-mediated endothelium-dependent relaxation are similar for the two conduits.
[263 ] Because of lack of consistency, clinical application of these data is problematic.
A prior midline lower abdominal incision does not preclude harvesting the inferior
epigastric artery, but a paramedian incision commonly damages the artery. Groin
incisions for hernia and aortofemoral bypass produce scarring around the proximal
portion of the inferior epigastric artery, and this segment (1 to 3 cm) may not be
available. Early bifurcation or small size may prohibit use except as a short graft from
another arterial conduit. This anatomy can be determined by Duplex scanning. [264 ]
Atherosclerosis of the proximal 1 to 3 cm is rarely flow restrictive but may preclude use
because of medial calcification. [256 ]
This conduit is used infrequently, and only one group has provided significant follow-up.
[265 ] Most usage relates to absent or poor-quality vein or prior use of one ITA. With
experience, some surgeons have expanded indications to achieve complete
revascularization with arterial conduits in younger, low-risk patients. [257 ] , [265 ] , [266
] The inferior epigastric artery is a reasonable choice to achieve revascularization with
only arterial conduits. Limitations are short length, inconsistent availability due to early
branching and occasional small size, and tedious dissection if the vessel enters the
muscle. Bilateral availability is a potential advantage, but I have had abdominal wall
necrosis in 2 of 17 patients after harvesting both ITAs and both inferior epigastric
arteries. [266 ]
PATENCY RATES
Patency data, except after early catheterization in a few patients, are available from one
source [265 ] and another when the inferior epigastric artery was anastomosed to an
arterial conduit. [257 ] Aortic-based conduits are intact in 88.9 percent (120 of 135) at
day 11, 75 percent (36 of 48) at 6 to 12 months, 86.2 percent (25 of 29) at 13 to 43
months, and 100 percent (5 of 5) at 16 to 60 months for a midterm patency rate of 79
percent. [265 ] Arterial conduitbased conduits have patency of 95.7 percent ( N = 70) at
a mean of 3.3 months and 100 percent ( N = 25) at a mean of 25.2 months. [257 ]
Radial Artery
HARVEST TECHNIQUES
For simplicity, I use the Allen test, which entails vigorous opening and closing of the
hand 20 times while the radial and ulnar arteries are occluded at the wrist. With release
of the ulnar artery, capillary refilling of the palm and digits occurs in 3 to 4 seconds in
most patients, with 10 seconds or less acceptable for harvesting. Subclavian stenosis
or occlusion is excluded by less than 20 mmHg systolic difference in brachial blood
pressure between the arms. Subclavian stenosis or occlusion raises concern for use of
an in situ left ITA but not the radial artery if the Allen test is negative. Doppler
assessment of collateral circulation in the forearm and hand is not used in my
experience but may reduce the incidence of false-positive Allen tests. [267 ] Five
percent of patients have a bilateral positive test, and 11.6 percent have a unilateral
positive test. [268 ] The nondominant forearm is used as donor unless the Allen test is
positive; if so, the radial artery is harvested from the dominant arm. Perioperative
arterial blood pressure is monitored from the opposite radial artery or the femoral
artery.
The arm is abducted to 90 degrees and prepared and draped on an armboard. A

curved incision is made over the course of the artery with the convex side placed
medially to place the lateral antebrachial cutaneous nerve in the lateral soft tissue flap
that includes the middle third of brachioradialis muscle (Fig. 17-30) . The artery is
dissected with its venae comitantes and a small amount of adjacent fatty areolar tissue,
and branches are controlled with small clips. The electrocautery is avoided except for
low current on the skin and subcutaneous tissue. Dissection begins in the midsegment
and continues proximally to the origin and then distally to the proximal wrist crease (Fig.
17-31) . In addition to preserving the lateral antebrachial cutaneous nerve, the
superficial radial nerve may be encountered in its lateral position along the proximal and
middle thirds of the artery. [269 ] Both nerves are sensory to the dorsal skin of the
forearm and hand, and injury results in minor symptoms in less than 3 percent of
patients. The artery is ligated proximally and distally with nonabsorbable suture to yield
a length of 20 to 24 cm in males and 18 to 22 cm in females. [268 ]
The artery is placed in room-temperature lactated Ringer's solution and later flushed
using the 2-mm olive-tipped needle with heparinized blood containing 2 mg/ml
papaverine and filled without hydrostatic dilation. If the proximal anastomosis is
performed prior to cardiopulmonary bypass, the radial artery is filled with blood
containing papaverine and dilates from the arterial pressure in 10 minutes. In 5 percent
a second injection is needed to achieve maximal dilation.
HISTOLOGY AND RESPONSE TO AGONISTS
The radial artery has a muscular media with minimal elastic tissue similar to other
alternative arterial conduits. [151 ] It differs from the others, including the ITA, in that
medial thickness is significantly greater. [151 ]
Consistent with the thicker media, the radial artery has a greater contraction force to
potassium chloride than the ITA or gastroepiploic artery and a higher contraction force
to norepinephrine and serotonin than the ITA but not the gastroepiploic artery. [270 ]
Equal responses of the three conduits to norepinephrine and serotonin, [270 ]
endothelial-dependent relaxation, and sodium nitroprusside were observed. [270 ]
Precontracted radial artery relaxed fully when treated with a vein graft solution
containing verapamil and nitroglycerin or diluted papaverine (30 mm), but the full
response to papaverine required 10 minutes versus 1 minute for other arteries. [271 ]
Calcium-channel blockers are commonly used intraoperatively and postoperatively by

most groups using the radial artery, [272 ] [274 ] but I have not used them. Perioperative
use of calcium-channel blockers is associated with depression of myocardial
contractility, bradyarrhythmias, and hypotension unless very low doses are used. The
therapeutic benefit of low-dose therapy for lysis of radial artery spasm has not been
demonstrated.
The radial artery is surprisingly consistent in length and diameter, and less than 1
percent have medial calcification (which is more prevalent distally). Another 5 percent of
patients have a bilaterally positive Allen test, and the vessel cannot be used. Prior
operation for carpal tunnel syndrome causes periarterial fibrosis of the most distal
segment, and prior arterial cannulation at the wrist may cause both periarterial and wall
fibrosis but does not usually preclude use of the vessel.
The radial artery was used by several groups in the early 1970s and abandoned
because of poor early patency. [275 ] , [276 ] It was returned to clinical use in 1989 after
several patients from the early series [275 ] had angiographic studies showing patent
conduits after 15 or more years. [272 ] Others reported similar results. [274 ] , [277 ]
Calafiore et al. [273 ] applied the radial artery with multiple other arterial conduits to
achieve complete revascularization with arterial conduits and placed the proximal radial
arterial anastomosis to an in situ left ITA rather than the aorta. After an initial learning
experience, I use it as the second arterial graft of choice (after both ITAs). When it is
used in conjunction with the in situ left ITA to which it is attached as a Y graft (Fig. 17-32)
, most patients receive complete arterial revascularization with two conduits as with
Tector's T graft. [150 ] , [213 ]
Total experience with the radial artery remains limited, but at least five centers have
experience with 200 to 400 patients. [257 ] , [268 ] , [272 ] , [274 ] , [277 ] Until there is
more information on patency, reservations remain.
PATENCY RATES
Patency for the aorta-based conduit is 85 percent at a mean of 12 weeks [274 ] and
93.5 percent at a mean of 9.2 months. [272 ] When based on an in situ ITA, patency is
98.7 percent (75 of 76) at a mean of 3.6 months and 94.3 percent (33 of 35) at a mean
of 21.2 months. [257 ]
Preinfarction Ischemia
It is generally agreed from the results of several randomized trials that surgery provides
an advantage in survival when compared with medical therapy for the following
conditions: left main coronary artery stenosis, triple-vessel disease, double-vessel
disease with proximal left anterior descending (LAD) artery stenosis, and in patients
with impaired left ventricular function. [2 ] [4 ]
Acute Myocardial Infarction
Patients presenting with chest pain and an evolving myocardial infarction of less than 6
hours' duration deserve special consideration. Many centers reserve operative therapy
in this setting for complications that demand it, namely, ventricular septal or free wall
rupture and acute mitral regurgitation from papillary muscle rupture. [5 ] Currently, it is
our belief that early operation should be considered for any patient with less than 6
hours of ischemia (or longer if extensive collaterals are seen on angiography). [6 ] An
additional subgroup of patients that should have emergent revascularization are those
with acute proximal LAD artery occlusion associated with refractory pain, even if the
duration of pain is greater than 6 hours. The continued presence of pain indicates that
viable myocardium is at risk. Intractable ventricular arrhythmias may be an additional
indication for emergent surgical intervention, since control of arrhythmias and ultimate
survival may occur despite the grave prognosis.
Emergent operative intervention is preferred over techniques of medical reperfusion

(thrombolytics, percutaneous transluminal angioplasty, atherectomy, and laser), since
several studies show improved myocardial function following surgical reperfusion after
acute myocardial infarction. [7 ] [14 ] Medical reperfusion has the disadvantage of
reperfusing the heart with unmodified whole blood with the heart fully loaded and in the
working condition. A canine model utilizing 2 hours of regional ischemia compared
reperfusion that simulated thrombolysis or PTCA (percutaneous transcoronary
angioplasty) versus controlled cardioplegic surgical reperfusion. Myocardial necrosis
was greater in the medically reperfused group (medical 44 percent necrosis of area at
risk versus surgical 21 percent, p < 0.05). [14 ] This study also showed decreased
preservation of myocardial contractile function in the medically reperfused group. [14 ]
An additional canine study demonstrated decreased recovery of contractility with
medical reperfusion following an ischemic insult after both 1 hour and 1 week (medical
reperfusion 19 percent segmental shortening compared with baseline versus surgical
52 percent, p < 0.05). [7 ] Surgical reperfusion has the unique advantage of controlling
both the composition of the reperfusate and the conditions of reperfusion. As evidence
mounts that the majority of injuries following ischemia and reperfusion occurs during
reperfusion, [15 ] it is logical that modification of reperfusion could have a dramatic
beneficial effect on myocardial function. [16 ] In a recent multicenter clinical trial [8 ]
involving 156 patients with acute coronary occlusion who had acute revascularization,
there was a clear survival advantage in the group that underwent controlled surgical
reperfusion compared with five previously reported series of patients medically
reperfused with percutaneous transluminal angioplasty. [9 ] [13 ] In these series,
multivessel disease, LAD artery occlusion, and cardiogenic shock were independent
predictors of a higher mortality for both methods of reperfusion. The surgically treated
patients were revascularized at longer intervals (6.3 hours surgical versus 3.9 hours
medical, p = < 0.05) and had a higher incidence of left interior descending artery
occlusion, multivessel disease, and cardiogenic shock, yet survival at 30 days was
improved (surgical 30-day survival 96.1 percent versus medical 91 percent, p = < 0.05).
Regional wall motion was likewise improved in the surgically reperfused group (wall
motion scoring: 0 = normal wall motion to 4 = dyskinetic). Eighty-seven percent of the
surgical group had a score of < 2 versus only 42 percent of the medically reperfused
group ( p = < 0.05). Although not yet widely adopted, the results of this study argue
strongly for surgical intervention early in the course of myocardial ischemia and
infarction. The specifics of intraoperative management of the patient who presents with
acute myocardial infarction and cardiogenic shock are considered in Chapter 21 and
are not further considered here.
POSTTHROMBOLYTIC OPERATIVE INTERVENTION
As the relative and absolute contraindications for thrombolytics shrink, we are

increasingly asked to operate on patients with evolving myocardial infarction less than 6
hours old who have failed to reperfuse after thrombolytics. This can be done safely
provided pharmacologic agents to control plasmin activity are administered and
attention is paid to preservation and repletion of functioning platelets. [17 ] Depleted
coagulation factors also must be replaced as needed. Aprotinin has been used very
effectively in this setting to inhibit plasmin and to protect both the number and function of
available platelets. [17 ] This approach has markedly decreased both shed mediastinal
blood and transfusion requirements in a small number of study patients [18 ] as
compared with published outcomes of patients undergoing surgery following
thrombolytic therapy without aprotinin. [19 ] Epsilon-aminocaproic acid (AMICAR) can
be given under similar circumstances, although it has a less potent effect. [20 ]
The newer platelet IIb/IIIa receptor antagonist (Rheopro), given to inhibit platelet
aggregation, further increases the complexity of operation following medical
interventional failures. Although the half-life of Rheopro is relatively short (12 hours),
platelet dysfunction can be overcome acutely only by platelet transfusion, which has
inherent risks. [21 ]
EFFECT OF AGE
Another consideration for evaluating patients for early surgical revascularization

following acute myocardial infarction is that patients older than 75 years who present
with a non-PTCA-related infarction and unstable hemodynamics have a uniformly poor
outcome in our experience. For this reason, compelling evidence is needed to go
emergently to the operating room for surgical revascularization, in this elderly
population.
PREOPERATIVE DATA GATHERING
The first step in the evaluation of a patient referred for revascularization is acquisition of
data. This helps with risk stratification, preoperative planning, operative planning, and
postoperative care.
History and Physical Examination
The history and physical examination are the mainstays of preoperative data gathering.
A thorough history of the events leading to the presentation for revascularization can be
very helpful. Dr. J. Willis Hurst warns that we should not fail to listen when the diagnostic
clues are pouring out from the patient. [22 ] Chest discomfort is the single most
important symptom preoperatively; however, this symptom can be misleading, since 28
percent of patients in the CASS study with typical angina had no coronary artery
disease after further investigation. [4 ] The character, location, duration, precipitating
events, and response to intervention (i.e., nitroglycerin) can help differentiate ischemic
cardiac pain from other causes of chest pain (see Table 18-1 for conditions producing
symptoms that may simulate those caused by atherosclerotic coronary artery disease).
[22 ] Congestive heart failure (CHF) is an extremely important finding because its
presence drastically alters the prognosis even in patients with a normal ejection fraction
(6-year survival 82 percent with a history of CHF versus 91 percent in those without, p <
0.0001). [23 ] , [24 ] Other organ systems should be reviewed systematically to allow for
risk stratification and possible preoperative therapy (see below).
Physical examination may confirm extracardiac organ system involvement and therefore
influence preoperative management and decisions based on assessment of risk. As
mentioned previously, signs of congestive heart failure are crucial because this is both
a risk factor for perioperative mortality and an indication for further evaluation of
myocardial viability to determine which patients will likely benefit from surgical
revascularization [24 ] (see Preoperative Viability Testing below). Physical examination
may reveal the presence of concomitant valvular disease, carotid bruit, peripheral
vascular disease, or previous operation that may limit conduit availability (e.g., vein
stripping, peripheral revascularization, amputation, etc.); all these influence operative
planning. In the absence of concomitant disease, most patients have a normal physical
examination.
Risk Factors/Risk Stratification
Multivariate analysis of 13,368 patients examined prospectively revealed that seven

preoperative factors significantly influenced postoperative survival. [25 ] These factors
are
1. Age
Ejection fraction
Clinical status (emergency operation)

Gender
Diabetes
Congestive heart failure
Other risk factors that clearly influence surgical morbidity, may be univariate
predictors of mortality, and are used to guide perioperative management are
previous stroke, history of significant bleeding (dental or gastrointestinal),
hypertension, angina class, history of previous myocardial infarction, concurrent
remote-site infection (UTI, dental abscess, sinusitis, etc.), significant obstructive
pulmonary disease, and renal insufficiency or renal failure.
Since preoperative pulmonary therapy can greatly benefit some patients with
pulmonary insufficiency, this should be quantitated and treatment instituted. Very
poor pulmonary function or wet tracheobronchitis may influence the operative
procedure [avoidance of an internal mammary artery (IMA) graft] or introduce
prohibitive risk.
Due to the significant morbidity associated with perioperative stroke and the
possibility of prevention based on preoperative screening and intervention, this
preoperative risk factor deserves special consideration. Risk of perioperative
stroke is age-related; while it is 1 to 3 percent for patients of all ages, it is 3.8 times
higher in patients more than 70 years of age. [26 ] [29 ] The incidence of
hemodynamically significant carotid artery stenosis (>170 percent diameter
narrowing) in patients who require coronary revascularization is between 2.8 and
11.8 percent depending on the screening method used. [30 ] [32 ] Patients who
present with symptomatic cerebrovascular disease, a history of previous carotid
endarterectomy, a history of previous cerebrovascular accident or carotid bruits, or
who have left main disease should undergo routine noninvasive carotid studies by
duplex scanning. Lesser indications include age over 65, heavy smoking history,
and peripheral vascular disease. In most institutions, a positive duplex scan is an
indication for cerebral arteriography to further delineate the anatomy of the lesion
before planning operative strategy. While there is no correlation between the
presence of a carotid bruit and the severity of carotid artery disease, presence of a
bruit mandates further diagnostic studies. Once significant extracranial
cerebrovascular disease is identified by either invasive or noninvasive means, the
presence or absence of neurologic symptoms and the severity of both the coronary
and carotid artery disease dictate the order of operative intervention. If the patient is
asymptomatic and has unilateral 70 percent or greater carotid artery stenosis,
several authors propose nonoperative management of the carotid disease and
proceeding with coronary revascularization. They have not noted a significant
increase in the incidence of stroke. [33 ] [37 ] However, we and other authors have
recommended prophylactic carotid endarterectomy to minimize the risk of late
neurologic events. [32 ] , [38 ] [40 ] We currently recommend staged operative
therapy under local anesthesia for the patient with significant unilateral stenosis;
coronary artery bypass grafting follows several days later. Patients with unilateral or
bilateral carotid disease who also have severe left main coronary artery obstruction
or diffuse multivessel disease and unstable angina should have a combined
operative procedure. (See Figure 18-1 for an algorithm outlining this
decision-making process.) A recent study by Coyle et al. [41 ] showed that the
combined cerebrovascular accident-mortality rate for patients undergoing combined
carotid-coronary revascularization procedures was 26.2 percent versus only 6.6
percent for those who had staged procedures. Although this figure may be
inordinately high, the combined approach is avoided if at all possible.
Medications
All current medications are discontinued from the time of admission until the time of
surgery with the exclusion of beta blockers, angiotensin converting-enzyme (ACE)
inhibitors, and calcium-channel blockers. Platelet-inhibiting agents (aspirin,
dipyridamole, ticlopidine) are discontinued as far preoperatively as is feasible
because of their prolonged therapeutic effect. Coumadin is discontinued 3 to 5 days
prior to elective surgery or treated with fresh-frozen plasma for emergent cases.
Vitamin K, either by intramuscular injection or intravenous infusion, is avoided due to
the extended period required to reverse anticoagulation. [42 ]
A history of allergy to medications is obtained and evaluated to differentiate side

effects from true allergic reactions.
Laboratory Investigations
In recent years an effort has been made to minimize preoperative laboratory

investigations to contain costs and to eliminate tests that do not directly affect
outcome. One such test is the bleeding time, which bears no relation to the
probability of significant postoperative hemorrhage or to the number of transfusions
required. [43 ] We no longer routinely obtain this test before operation.
Laboratory data from the referring hospital, if current, are adequate for electrolytes,
creatine, liver function tests, and urinalyses. A hematocrit and platelet count are
obtained routinely immediately before operation due to the lability of these blood
components following cardiac catheterizations and exposure to heparin.
Other Tests
A chest x-ray, if performed within 1 month in a patient without signs or symptoms of

congestive heart failure, is sufficient for preoperative screening. It should be
evaluated for cardiac size and conformation, pulmonary edema, extracardiac
pulmonary disease, and vascular calcification. An electrocardiogram is obtained
immediately preoperatively on all patients for postoperative comparison. An
electrocardiogram (ECG) from an outside institution is acceptable if obtained within
7 days and if the patient is clinically stable. Adjunctive tests to evaluate myocardial
ischemia (nuclear scintigrams, treadmill stress test, etc.), if performed previously,
are evaluated and used to confirm the preoperative diagnosis and to determine the
physiologic significance of borderline stenoses. Nuclear scintigrams and
positron-emission tomographic (PET) scans are also useful prognostically [22 ] ;
however, these tests are not ordered routinely in patients with adequate anatomic
indications for operation and normal ventricular function.
Blood Bank Protocols
We have modified our policies for typing and cross-matching blood for primary
surgical revascularization candidates. For patients who are less than 70 years old
without bleeding or complicating risk factors for bleeding and who have a hematocrit
greater than 35 percent for males and greater than 38 percent for females, a type
and screen is ordered routinely. If antibodies are discovered on the screen, 2 units
of packed red blood cells are fully cross-matched. For patients who do not meet
these criteria, 2 units of packed red blood cells are fully cross-matched, the screen
is performed, and the 2 units are held. Whole blood is no longer used routinely. No
platelets are reserved for individual patients preoperatively; however, our blood
bank maintains 24 units available for the cardiac surgical service on a continuous
basis and replaces them as they are used.
Preoperative Viability Testing
Patients with poor left ventricular function (an ejection fraction of < 25 percent) and
signs or symptoms of congestive heart failure should have hypocontractile areas
evaluated for viability to predict postoperative functional recovery following
myocardial revascularization. Patients who have large areas of nonviable scarring
are unlikely to benefit from surgical revascularization, and nonoperative therapy is
recommended. Patients with large areas of ischemic but viable myocardium that is
either hypo- or noncontractile (hibernating myocardium) have a high likelihood of
postoperative improvement in myocardial function, but they may have a difficult and
stormy course in the early postoperative period. [24 ] Positron-emission
tomographic (PET) scanning using [ [18 ] F] fluorodeoxyglucose (18-FDG) clearly
has been the gold standard for determination of viability [44 ] , [45 ] ; however, PET
is expensive and not universally available. Other isotope scans may be used if their
limitations are understood. Sestamibi scans accurately depict perfusion, but since
they do not redistribute, these scans incorrectly underestimate viability in 36 percent
of patients as compared with thallium or PET scanning. [46 ] Thallium scanning also
underestimates viability, since 50 percent of fixed defects show functional
improvement following surgical revascularization. [47 ] Thallium reinjection with
delayed imaging is more accurate than standard stress-rest images for predicting
myocardial viability except in severely hypoperfused areas and in areas of
increased isotope attenuation such as the inferior wall. [44 ] Image enhancement
with single photon emission technology (SPECT) with [129 ] I-labeled fatty acids 48
may provide more accurate viability scanning, but this, too, has limited availability.
Evaluation of regional wall motion with low-dose dobutamine stimulation and

echocardiography has shown good sensitivity (86.8 percent) and specificity (81.6
percent) in predicting viability but also is not universally available and is
operator-dependent. [49 ] Magnetic resonance imaging (MRI) indexing end-systolic
wall thickening or documenting contractile reserve with dobutamine stimulation also
shows promise. [50 ] Exercise-induced ST-segment changes, if present, are
indicative of myocardial viability (sensitivity 82 percent, specificity 100 percent);
however, even when ST-segment changes are absent, PET scanning shows viability
in 56 percent. [51 ] ST-segment changes with exercise do not predict the degree of
functional recovery because they do not indicate the size of the viable area.
In a patient with a severely impaired ventricle, all available information must be

considered when attempting to make the difficult clinical decision between coronary
revascularization and transplantation. In general, those favored for coronary arterial
bypass grafting (CABG) need a preoperative cardiac index of more than 2.0
liters/min per m 2 , a mean pulmonary artery pressure of less than 35 mmHg, and
evidence of viability by one of the preceding methods. [52 ]
All patients being considered for surgical revascularization need to have a recent
preceding cardiac catheterization to provide a road map for surgical
revascularization. The angiogram is reviewed to evaluate distal vessels for both size
and anatomic suitability for surgical revascularization. In addition, the relationship
between stenosed coronary arteries and regional wall motion abnormalities should
be analyzed. In general, grafts are not performed to small, diffusely diseased
arteries supplying areas showing no function and/or no viability. An assessment of
the amount of myocardium at risk supplied by each target vessel and the quality of
the vessel also should be made to allow prioritization of vessels to be anastomosed
in the event that limited conduit is available or an expeditious surgical procedure is
mandated for other reasons (i.e., comorbid factors, myocardial protection problems,
etc.). It should be emphasized, however, that an expeditious incomplete
revascularization is inferior to complete revascularization that takes only slightly
longer.
MYOCARDIAL BRIDGING
Between 0.5 and 7.5 percent of all coronary angiograms show significant systolic
arterial compression with a widely patent artery during diastole (myocardial
bridging). [53 ] Some authors feel this is not pathologic and requires no operative
intervention. [22 ] We and others feel that if the stenosis is greater than 75 percent, it
can be associated with chest pain, myocardial infarction, and ventricular fibrillation.
[54 ] , [55 ] Objective evidence of ischemia should be present prior to consideration
for surgery in this subgroup. More commonly, only a slight compression with systole
and a lack of tortuosity is seen, but this is a clue to the intramyocardial location of the
vessel and is used for surgical planning. An intramyocardial left anterior descending
artery may be difficult to find. Intraoperative techniques using a Doppler ultrasound
probe or elevation with elastic tapes placed under the artery have been used to
assist with locating the artery. [56 ] Alternatively, a 1-mm probe may be inserted
distally and passed proximally to locate the intramyocardial artery by palpation.
RIGHT VENTRICULAR INFARCTION
There are several findings on a coronary angiogram that demand further

investigation. A very large right coronary artery that has an abrupt occlusion shortly
after its origin (stump right coronary artery) places a large portion of the inferior wall
at risk. More important, when the stenosis is proximal to the right ventricular
branches, this may produce severe right ventricular dysfunction in the perioperative
period. Further investigation of right ventricular (RV) function in all patients with acute
inferior wall myocardial infarction and in those with this pathologic anatomy is clearly
warranted. Right ventricular infarction may complicate up to 50 percent of inferior
infarctions. [57 ] The presence of right ventricular infarction increases the risk of
hospital death from 6 to 31 percent. [58 ] Improvement in right ventricular systolic
function over time is the rule and is not dependent on reperfusion of the
infarct-related artery supplying the right ventricle. [59 ] Nonetheless, revascularization
of an acutely occluded right ventricular branch decreases the incidence of RV
infarction, [60 ] morbidity (2.4-fold, p < 0.0001), and mortality (3.7-fold, p < 0.0005).
[58 ]
Evidence of right ventricular infarction may be diagnosed on an electrocardiogram

as Q waves in a V 4R lead. Echocardiographic analysis of the right ventricle can be
very helpful preoperatively; however, this has only 82 percent sensitivity and may be
falsely negative. Radionuclide scans are superior as the gold standard for
estimating right ventricular impairment following infarction. [57 ] Distended neck
veins on physical examination or an elevated central venous pressure (CVP)
following placement of intravascular monitoring catheters (out of proportion to
elevated left ventricular filling pressures) indicates significant right ventricular
dysfunction. Preoperative evaluation should be made prior to the operation.
When surgery is performed during the acute phase of RV infarction, mortality can be
as high as 66 percent. [60 ] , [61 ] These patients clearly benefit from allowing the
RV infarction to recover before subjecting the heart to the increased pulmonary
vascular resistances and increased pulmonary pressures that follow
cardiopulmonary bypass. A recovery interval preoperatively of 4 to 6 weeks is
appropriate if the patient is clinically stable.
COEXISTING CONDITIONS
The angiogram also may delineate coexisting conditions; the evaluation and repair
of these is beyond the scope of this chapter. However, careful attention to valvular
dysfunction and signs of ventricular septal rupture may avoid intraoperative surprise
and added morbidity.
DETERMINATION OF GRAFTABLE VESSELS
The angiogram is used to critically evaluate each coronary artery for the presence of
significant stenoses and for arterial size; 1.2 mm is considered minimally
acceptable for surgical revascularization. Most angiographic catheters are 2 mm in
diameter and can be used as a standard to compensate for varying degrees of
magnification. Stenoses must be more than 50 percent in two views to be
considered significant. The area of myocardium supplied by each stenotic artery is
identified, and ideally, at least one graft is performed to each major area at risk. In
some cases complete revascularization requires multiple grafts to a single area,
and these may be performed as sequential anastomoses if the anatomic
configuration is favorable for this. It is our general practice and philosophy to have a
separate graft for each significantly stenosed vessel.
There does appear to be some benefit to performing sequential anastomoses when

the more proximal vessel is small and has insufficient runoff to maintain the patency
of a single vein graft. Another indication for sequential anastomoses is lack of
conduit (see alternative conduits below). When performing sequential anastomoses,
the more proximal anastomosis of the two sequential anastomoses is performed
first with careful planning of the orientation of the anastomosis; the graft is cut to
length, and the distal-most anastomosis is performed second. The same procedure
is used for sequential arterial anastomoses; however, these are performed more
rarely because arterial grafts show greater physiologic adaptability to small vessels
and the technical difficulty of a sequential arterial graft is greatly increased. In
general, the first vessel grafted with the proximal portion of a sequential
anastomosis should be smaller than the distal vessel and have a smaller area of
distribution to avoid a steal phenomenon. Flow may decrease distal to a large
proximal coronary artery that is anastomosed to a sequential graft. Also, the
arteriotomy should be kept small to avoid flattening a small vein graft or arterial graft
at the proximal anastomosis and compromising the flow to the distal anastomosis.
Anastomoses to right ventricular branches are performed when the vessels are
stenosed of adequate size with significant areas of the right ventricle at risk
(especially in the setting of increased metabolic demand on the right ventricle, such
as right ventricular hypertrophy, chronic obstructive pulmonary disease, and
pulmonary hypertension).
Coronary arteries with borderline stenoses of 40 to 50 percent require careful

consideration regarding bypass. If the internal mammary artery (IMA) is used as a
conduit beyond a noncritical stenosis (< 60 percent), clinical evidence indicates that
the mammary artery remains patent but atrophies (string sign). [62 ] [61 ] Although in
canines there is evidence that internal mammary artery flow does not decrease
acutely, even with a widely patent coronary artery, [64 ] caution is warranted in
extrapolating canine results to humans, since the canine IMA is three times the size
of the human IMA relative to body weight. [66 ] There is currently no evidence that
there is decreased venous conduit patency due to competitive flow. [67 ] Artifactual
occlusion has been seen in venous conduits in the presence of competitive flow, yet
the conduit is patent if studied properly by angiography. [68 ] Likewise, an additional
study shows that proximal native vessels that appear occluded angiographically in
the presence of a widely patent venous graft are, in fact, angiographically patent if
properly studied. [69 ] It is not known if these occluded native vessels can be
recruited at levels of flow adequate to meet myocardial demands following attrition
of the venous conduits. There are also anecdotal reports of mammary artery
recruitment with gradual native vessel stenosis; however, the reliability of the
observation and the physiologic adequacy of flow are unproven. Nonetheless,
venous grafting in the setting of noncritical coronary artery stenosis does accelerate
progression of the native coronary artery stenosis. [70 ] , [71 ] Thirty-eight percent of
bypassed vessels progressed from less than 50 to more than 70 percent stenosis
within 3 years versus only 3 percent for ungrafted arteries. [71 ] These grafts are then
subject to attrition secondary to atherosclerosis, which will result in recurrent
myocardial ischemia. For these reasons, we currently recommend not bypassing
minimally stenosed vessels unless there is additional objective evidence of
ischemia.
CHOICE OF CONDUIT
In Situ Arterial Grafts
Pedicled arterial grafts are used whenever feasible due to an impressive improvement
in survival, both early postoperatively [72 ] , [73 ] and late. [74 ] In patients less than 50
years of age, bilateral internal mammary arteries are used preferentially with no
increased risk of perioperative morbidity or mortality. [75 ] Although there is no
detrimental effect of bilateral mammary use, there is no proven survival benefit in
patients followed up to 15 years postoperatively. [76 ] , [77 ] In patients with bilateral
mammary artery grafts, a decreased rate of late postoperative infarction is found only in
patients less than 60 years old. [77 ] Wound infection rates following the use of single or
bilateral internal mammary artery grafts vary widely. Several studies show no increased
rate of wound infection with single [78 ] or bilateral grafts. [78 ] , [79 ] Others show that
bilateral internal mammary arteries increase the odds ratio for infection by a factor of 2
if diabetes is absent. When used in the presence of diabetes, the odds ratio increases
by a factor of 13.9. [80 ] Other risk factors shown to increase infection rates are obesity
[78 ] and prolonged mechanical ventilatory support. [81 ] In addition, patients with
impaired pulmonary function due to chronic obstructive disease are at increased risk
because of an incremental restrictive defect seen in the early postoperative period after
internal mammary artery use. [82 ] Therefore, we avoid bilateral arterial conduits in
obese or diabetic patients and in those with severe pulmonary disease unless no other
conduit is available.
Pedicled arterial grafts are used whenever feasible when patients present emergently;
however, in patients more than 80 years of age this practice probably has minimal
benefit. Pedicled arterial grafts are also avoided in patients with chronic renal failure on
hemodialysis due to the potential for blood flow steal from the internal mammary artery
graft by an ipsilateral arteriovenous fistula placed for hemodialysis. Additionally, these
patients have a limited life span once they begin hemodialysis (median 48 months) [83 ]
and only a 45 percent 2-year survival rate following coronary surgery [84 ] ; both these
observations negate any long-term benefits from pedicled arterial grafts.
INTERNAL MAMMARY PREPARATION
Our technique for internal mammary artery harvesting and preparation includes
harvesting the internal mammary artery on a very narrow (1- to 1.5-cm) pedicle to
diminish the risk of postoperative infection. [85 ] We utilize an Ancheney sternal
retractor for cardiac operations and do not utilize a special retractor for mammary artery
harvesting on the left side. For right IMA harvesting we use an Internal Mammary
Retractor (Model 4100, Rultract, Inc., Cleveland, Ohio) because once the sternum is
opened with the left side higher than the right, it is difficult to reverse the exposure with
the same retractor for the opposite side.
DeBakey forceps are used for downward traction on the pedicle (with the tips closed),
and the internal mammary artery itself is not touched directly at any time. If additional
exposure is needed, forceps are used to grasp and retract the endothoracic fascia
directly. Excess traction on the artery is avoided because this causes intimal tearing
and results in early failure of the graft. [86 ] Segmental arterial and venous branches are
individually clipped and divided distally with the electrocautery until the pedicle is freed
from the bifurcation (into the superior epigastric artery and the musculophrenic arteries)
to the level of the first rib. A lesser dissection fixes the mammary pedicle in a medial
position that exposes it to injury with reoperation, either by retraction or direct injury. The
junction of the internal mammary and subclavian veins generally can be seen at the
superior extent of the dissection but does not need to be divided on the left side for
visualization and does not provide additional usable length. This is unlike the right
internal mammary vein, wherein division of the vein allows better visualization of the
proximal portion of the dissection and mobilizes an additional 1 to 3 cm of usable
length. On the left side the phrenic nerve lies posteriorly and medially and is usually not
seen. Conversely, on the right side the phrenic nerve exits the thoracic cavity with the
mammary artery, and division of the mammary vein allows better visualization and
protection of the nerve. The patient is heparinized when the dissection is completed
above the second rib. An illustration of the dissection technique can be seen in Figure
18-2 .
After confirmation of anticoagulation, the mammary artery is clamped distally after its
bifurcation and divided just proximal to this point. The pedicle is occluded with a soft
rubber bulldog clamp (Fogarty softjaw 6-mm clamp, Model 614-06, Baxter-Edwards,
Santa Ana, Calif.). The mammary artery is cannulated with a 22-gauge Silastic cannula,
and the soft bulldog clamp is removed and blood withdrawn into a non-Luer-Loc
syringe. This avoids distal impingement of the catheter on the intima and dissection of
the artery during injection. Intraluminal papaverine solution (1:4 dilution in normal saline)
is injected intraluminally, the cannula is withdrawn, and the distal end is occluded with a
hemoclip. [87 ] This technique is illustrated in Figure 18-3 . This technique provides
superior dilatation with elimination of spasm and less chance for technical error. [88 ]
The distal end is beveled and cut just prior to its use and is anastomosed as the last
anastomosis to the most important vessel being revascularized; this is usually the left
anterior descending artery.
The suturing technique used for sequential arterial anastomoses is shown in Figure
18-4 , and a postoperative angiogram is shown in Figure 18-5 . The internal mammary
artery is not handled with forceps during any portion of the anastomosis, and if
retraction is required, the adventitia alone is grasped with fine-toothed coronary forceps
(no-touch technique). Running 7-0 Prolene is used for all anastomoses. Inverted
pedicled internal mammary grafts based on the superior epigastric and musculophrenic
branches are not recommended due to a predictably low flow through an inferiorly
based pedicle. We also do not recommend sequential division of the endothoracic
fascia of the internal mammary artery pedicle to gain extra length because this usually
indicates that the graft is too short. Traction places the graft under tension and
decreases long-term patency. [89 ] Under these circumstances, it is preferable to use
the internal mammary artery as a free graft (see below).
Other Arterial Grafts
INTERNAL MAMMARY ARTERY FREE GRAFT
If the internal mammary artery is of adequate caliber but lacks pulsatility or has reduced
flow (< 60 mL/min), [90 ] the artery is divided adjacent to the subclavian vein and utilized
as a free graft. Care is taken not to include the phrenic nerve in placing the clamp.
Some have recommended a minimum acceptable flow of 120 mL/min, [91 ] although, in
general, measurement of flow is not needed to recognize inadequacy. If the left anterior
descending artery is very large and the mammary artery has adequate pulsatile flow but
is small in caliber, an alternate site to a smaller coronary branch may be chosen for the
mammary pedicle (diagonal, anterior marginal, etc.).
If the arterial caliber is adequate but flow is inadequate as outlined above, use as a free
graft is preferable. The entire pedicle is soaked in papaverine solution prior to use. The
proximal portion is anastomosed directly to the aorta if the aortic wall is not thickened or
to the hood of an adjacent vein graft if the aorta is thickened or if the internal mammary
artery is small. [92 ] If the aorta is so thickened as to compromise the proximal
anastomosis of saphenous vein grafts, or if no venous grafts are performed, a patch of
bovine or autologous pericardium may be used to replace the anterior wall of the aorta
so that the proximal end of the graft can be anastomosed to this area. Use of the
mammary artery as a free graft does not affect endothelial function [93 ] or resistance to
atherosclerosis but does result in a decreased patency rate as compared with in situ
grafts. [94 ] However, patency remains superior to saphenous vein grafts, and most
failures are early. [94 ]
RIGHT INTERNAL MAMMARY ARTERY GRAFT
The right internal mammary artery (RIMA) can be used as an in situ graft to bypass the
proximal or middle right coronary artery. The posterior descending artery or a left
ventricular branch can be reached only with an exceptionally long right IMA pedicle. The
right IMA is used as a free graft more than 50 percent of the time. Grafts to the left
coronary circulation employing the RIMA are always performed as free grafts to avoid
the pedicle crossing the midline. This route places the graft in a treacherous position for
damage during reoperative surgery. We also do not advocate placement through the
transverse sinus because it is difficult to examine the pedicle for bleeding, it is likely to
be placed under tension, or the pedicle may develop unrecognized twisting or kinking
and have a decreased long-term patency. [89 ]
GASTROEPIPLOIC ARTERY GRAFT
The gastroepiploic artery (GEA) may be used as an in situ graft to either the inferior or
lateral portions of the heart; however, extreme care must be taken during both
harvesting and anastomosis to avoid twisting, kinking, and technical error at the
anastomotic site. These grafts have a great propensity to develop these problems. [95 ]
These vessels are very vasoactive and have an increased tendency to spasm during
harvesting; this necessitates compulsive use of vasodilating drugs (papaverine and
diltiazem) for preparation of the arterial pedicle. [96 ] A minimum acceptable diameter
is 1.5 mm, and the minimum flow is 120 mL/min; otherwise, in situ gastroepiploic
arterial (GEA) grafts have decreased patency rates. [96 ] The gastroepiploic artery
used as a free graft has a decreased long-term patency rate as well as an increased
propensity to spasm. [97 ] A GEA graft likewise should be avoided in the setting of
competitive flow because atrophy occurs rapidly. [96 ] Other relatively rare
complications described with the gastroepiploic artery include gastric perforation,
gastrointestinal hemorrhage, diaphragmatic herniation, and pancreatitis. [98 ] [100 ]
Due to the high incidence of technical problems with this graft, we do not use the GEA
routinely for primary revascularization unless another suitable conduit is not available.
INFERIOR EPIGASTRIC ARTERY GRAFT

The inferior epigastric arteries are an additional available arterial conduit, although
length is limited (11.9 cm average versus 16.5 cm for the IMA and 20 cm for the GEA).
Therefore, inferior epigastric artery grafts are used only for coronary vessels that require
short grafts (proximal LAD, diagonal, ramus intermedius) [101 ] or are used as a
composite graft with either a saphenous vein or another arterial conduit. Long-term
patency studies for the inferior epigastric artery are lacking, but its early patency (1 to 6
weeks) is disappointingly low (57 to 82 percent). [102 ] , [103 ] A recent study using
both papaverine and diltiazem to combat spasm shows improved results (cumulative
patency 95.7 percent with a mean follow-up of 25 months). [104 ] Decreased patency
also occurs in the setting of competitive flow. [104 ] , [105 ] In a recent review by
Califiore et al., [104 ] a hypoperfusion syndrome occurred in 2.5 percent of patients and
mortality was 50 percent (1 of 2) in those who developed the syndrome after transport to
the intensive care unit (ICU). Hematomas occur in 4 percent of patients, and complete
abdominal wall necrosis has been described after harvesting the inferior epigastric
artery and both internal mammary arteries. [89 ] , [105 ] With these limitations in mind,
this graft is not recommended unless no other conduit is available.
RADIAL ARTERY GRAFT
Initial results with radial artery free grafts were very disappointing [106 ] , [107 ] ;
however, with newer techniques of harvesting and early prophylactic calcium-channel
blockade to prevent spasm, patency has improved. [108 ] Late results are still pending,
although the 1-year patency rate recently reported by Tixier et al. [109 ] was a favorable
93 percent. Due to the unknown long-term benefit of this conduit, currently we do not use
it unless no other conduit is available.
GREATER SAPHENOUS VEIN
Saphenous vein grafts constitute the majority of grafts utilized for first-time
revascularization in our population (in conjunction with pedicled arterial grafts).
New techniques for endoscopic harvesting in hopes of decreasing peripheral wound

problems have been used recently in our institution for peripheral vascular procedures;
however, this technique has not been used for cardiac surgical procedures because of
the inordinately long time required to harvest the vein (usually > 2 hours).
Veins are harvested very quickly using an open technique by gentle elevation from the
anatomic bed without excess traction; this avoids endothelial damage that increases
early stenosis and occlusion. [110 ] Side branches are clipped initially and then ligated
with fine silk ligatures. Branches are tied flush with the vein, and constructive adventitial
tissue bands are carefully avoided. Although scattered reports recommend incubation
in sanguineous instead of crystalloid solutions for saphenous vein grafts, other
convincing evidence indicates that incubation in blood-containing solutions increases
endothelial and medial damage. [111 ] Plasmalyte preserves endothelium-dependent
relaxation better than does saline, [112 ] and there is no advantage to the University of
Wisconsin solution. [113 ] Excess distending pressure during saphenous vein graft
preparation is the one factor that clearly alters cellular matrix, decreases cellular ATP
levels, increases smooth muscle response to vasoconstrictors, stimulates medial
smooth muscle proliferation, and results in decreased patency. [111 ] , [114 ] , [115 ] A
distending pressure of less than 150 mmHg is safe, [111 ] and although we strictly avoid
overdistension, we do not employ pressure-limiting devices. [116 ] Nevertheless,
stenosis rates are clearly higher for vein grafts as compared with in situ mammary
grafts. [117 ]
LESSER SAPHENOUS VEIN
The lesser saphenous vein, although usually an excellent conduit that is easily
harvested, [118 ] is rarely needed for first-time coronary revascularization procedures
unless other conduits have been excised or utilized for other surgical procedures.
Despite reports claiming equal patency compared with greater saphenous vein grafts in
a small number of patients, [119 ] studies with long-term follow-up on large numbers of
patients are lacking.
Other Grafts
Arm veins, in general, should be avoided because of their tendency toward aneurysmal
dilatation in the late postoperative period. [120 ] In addition, angiographic patency of
cephalic veins is inferior to saphenous veins and was only 47 percent at 4.6 years in
one study [121 ] and less than 10 percent at 6 years in another. [122 ]
Intercostal arteries have been studied histomorphometrically, have been found suitable
for coronary revascularization, [123 ] and have been evaluated for pedicled in situ
grafting in a cadaveric model [124 ] ; these conduits have not been implemented or
evaluated clinically.
Although there are anecdotal reports of successful use of the splenic artery for coronary
revascularization, [125 ] we do not advocate this vessel because of its high incidence of
atherosclerosis, difficulty with mobilization, tendency to coil when harvested, and
tendency for the media to split with harvesting.
Cryopreserved human saphenous vein has an extremely poor long-term patency rate.
This is attributed to death of cellular components, including loss of all viable endothelium
following cryopreservation and immunologic rejection following implantation. [126 ]
Patency rates vary from 41 percent at 2 to 16 months to 0 percent at 6 to 30 months
postoperatively. [126 ] , [127 ] A recent study using modified freezing protocols and
cryopreservation solutions demonstrated preservation of both smooth muscle and
endothelial cellular function; however, it is not known if this advance will improve clinical
patency. [128 ]
Bovine internal mammary artery also has been used for coronary revascularization;
however, the 1-year patency rate is only 14 percent. [129 ] New methods of preservation
(poly-epoxy cross-linking) for xenografts are currently under investigation. [130 ]
Small-diameter polyurethane has been used experimentally with a 76 percent 3-month

patency rate for 1.5-mm internal diameter grafts with medium porosity. The low-porosity
grafts showed incomplete endothelialization and neointimal hyperplasia and early
occlusion. [131 ] This material has never been tested clinically.
A recent study using 5-mm endothelial cell-seeded polytetrafluoroethylene (PTFE)

grafts for below-knee femoral popliteal bypass demonstrated good short-term patency
(4 of 4 at 3 months). [132 ] Patency following coronary artery bypass grafting and
long-term results with this material are unknown. Nonseeded PTFE was used in one
patient with 3-month patency, but again, no long-term results are known. [133 ] There
are other scattered reports using small-diameter Dacron grafts seeded with omental
endothelial cells, [134 ] siliconized homologous vein, [135 ] and bovine sacral arteries,
[136 ] none of which have shown clinical long-term patency.
Endarterectomy
Endarterectomy can be used for severely diseased vessels, such as are encountered
frequently in patients with severe diabetes mellitus. If a short segment of artery is
endarterectomized and is repaired with a small vein patch, the internal mammary artery
can be anastomosed to the hood of the venous patch. However, if a long
endarterectomy is required, the overlay patch of saphenous vein graft can be quite
patulous and result in stasis of flow and occlusion unless an aortocoronary vein graft is
used for arterial inflow. [137 ] The immediate postoperative mortality, perioperative
myocardial infarction rate, and percentage of patients with low-output syndrome who
require intraaortic balloon pump placement appear comparable between a control
group and an endarterectomized group in one study, [137 ] but in another study
endarterectomy was an independent predictor of operative mortality by multivariate
analysis (4.5 percent mortality with endarterectomy versus 2.6 percent without, p <
0.05). [98 ] Endarterectomized vessels also show accelerated deterioration with time,
with a 19-month mean patency rate of only 64 percent. [138 ] Endarterectomy also
significantly increases pump time and cross-clamp time. [138 ] Aprotinin should be
avoided in the setting of extended endarterectomy and vein patching because
catastrophic thrombosis has occurred. [138 ] This procedure is reserved for vessels
that supply moderate or large areas of myocardium that are otherwise inoperable.
Intraoperative Angioplasty and Laser
Intraoperative angioplasty has been abandoned largely because of high rates of

restenosis and vessel occlusion. [139 ] There are no good long-term studies of patency
following intraoperative laser therapy. Clinical trials are needed, and these procedures
cannot be recommended without an investigative protocol.
General Strategy for Graft Usage
General operative strategy for first-time revascularization patients consists of single

internal mammary artery pedicled grafts for patients older than 50 years of age, bilateral
internal mammary artery grafts for patients less than 50 years of age, and segments of
reversed saphenous vein for the balance of required grafts. Although it is argued that
internal mammary artery grafts should not be performed in patients more than 80 years
of age due to their low 10-year survival rate of 30 to 35 percent, [140 ] other studies
show an improved survival both early and late regardless of the patient population. [74 ]
Therefore, we strive to use the internal mammary artery for elective cases without
regard to age. Comorbid factors (severe COPD, renal failure with hemodialysis, severe
diabetes mellitus) may mitigate enthusiasm for the IMA even in younger patients.
Because of the gravely increased morbidity of emergency operations in octogenarians,
we generally prefer an expeditious operation with saphenous vein grafts for this
circumstance.
CONDUCT OF THE PROCEDURE
Before Cardiopulmonary Bypass
ANTIBIOTICS
Preoperative antibiotics are given to all patients because the risk of infection with
cardiopulmonary bypass without prophylaxis was 44 percent in one study even though
these operations are clean cases (Altemeier class I). [141 ] Our current regimen calls for
a second-generation cephalosporin in the absence of allergy with doses continued for
24 hours postoperatively. This regimen is superior to first-generation cephalosporins,
and continuation of prophylaxis beyond 48 hours adds no benefit. [142 ]
CAROTID ENDARTERECTOMY
When a carotid endarterectomy is required in a combined carotid-coronary

revascularization procedure, it is generally performed prior to instituting
cardiopulmonary bypass (CPB). In an unstable patient, the chest is opened, and
preparations are made for rapid cannulation and institution of CPB if the patient
deteriorates during endarterectomy. Following carotid endarterectomy, the neck wound
is left open, packed with antibiotic-soaked gauze, and closed following the chest
closure and reversal of systemic heparin. Some authors recommend beginning
cardiopulmonary bypass to add the protective effects of hemodilution and hypothermia
to the cerebral protection protocol [143 ] ; others recommend deep hypothermia and
circulatory arrest as an additional protective measure. [144 ] Both studies show a low
incidence of perioperative stroke, but neither contained a randomized control group for
comparison. We currently do not advocate either of these techniques.
EPIVASCULAR ECHOCARDIOGRAPHY
Despite the importance of extracranial cerebrovascular disease in the etiology of

cerebrovascular accidents, most perioperative strokes occur in patients who do not
have significant carotid artery disease. This probably is due to atheromatous disease
with dislodgment of mobile debris from the ascending aorta or aortic arch. An autopsy
series of 500 patients with cerebrovascular disease or stroke revealed ulcerated
plaques in the ascending aorta and aortic arch in 26 percent. [145 ] Patients with severe
atherosclerosis in the ascending aorta and aortic arch have 2.4 times the risk for stroke.
[146 ] Intraoperative ultrasonographic scanning of the ascending aorta and aortic arch
is a sensitive technique for identifying atheromatous plaques within. [147 ] , [148 ] The
incidence of ascending aortic and aortic arch disease correlates directly with
increasing age. Modification of the procedure based on ultrasonographic findings was
required in only 8 percent of patients less than 70 years of age versus 32 percent of
patients more than 70 years of age in a study by Kouchoukos et al. [149 ]
Palpation alone clearly underestimates the presence of disease in the ascending aorta
compared with epiaortic echocardiography. [147 ] , [150 ] False-negative results may
occur with intraoperative ultrasonography as a result of loose atheromatous debris that
is hidden in shallow atheromatous craters. Alterations in operative technique include
change in position of the cannulation site within the ascending aorta, moving
cannulation to the femoral artery, retrograde delivery of cardioplegia, use of a
no-touch-no cross-clamp hypothermic fibrillatory arrest technique, adjustment in position
of the aortic cross-clamp for proximal vein grafts, and complete replacement of the
ascending aorta under profound hypothermia and circulatory arrest. These techniques
were used by Kouchoukos et al. in 500 patients who underwent complex cardiac
surgical procedures, of which 89 percent were coronary artery bypass grafting
procedures alone. In this population with these modifications of operative technique, the
incidence of cerebrovascular accident was only 1 percent.
Although multivariate analysis only reveals a correlation between increasing age and
positive ultrasonographic findings, we use the risk factors of age greater than 70 years,
severe peripheral vascular disease, severe long-standing hypertension, calcification of
the aortic knob on screening chest x-ray, and the presence of palpable disease within
the ascending aorta as indications for intraoperative epivascular ultrasonographic
investigation. This is performed following internal mammary artery harvesting and prior
to cannulation. The schema for modification of the operative procedure as outlined by
Kouchoukos et al. can be found in Figure 18-6 . [149 ] We modify this approach by
incorporating the more conservative method of Culliford et al. [151 ] to preserve the
ascending aorta using endarterectomy techniques and to patch the aortic wall with
bovine pericardium if disease of the ascending aorta is limited to a single crater filled
with atheromatous debris. For more extensive disease, aortic replacement as
advocated by Kouchoukos et al. is warranted.
Three patterns of severe ascending aortic atherosclerosis as described by Mills and

Everson [152 ] that require an alteration in intraoperative management by the
above-mentioned techniques can be seen in Figure 18-7 .
Our current preference for cardiopulmonary bypass equipment uses a roller pump,
membrane oxygenator, and open reservoir system. The alpha-stat method of pH
management and moderate (28 to 34°C) systemic hypothermia are used for all
operations. Since the numerous detrimental effects of cardiopulmonary bypass are
clearly time-dependent, operation is conducted as expeditiously as possible to limit the
duration of extracorporeal circulation. A schematic of our current setup is illustrated in
Figure 18-8 .
Cardioplegia
Both blood and crystalloid cardioplegia are used in our institution, with indications for
each determined by the presence or absence of ischemia and surgeon preference.
Intermittent antegrade hypothermic (4°C) oxygenated crystalloid cardioplegia or blood
cardioplegia is used for elective primary coronary revascularization procedures in those
patients without acute myocardial ischemia or infarction or concomitant valvular
disease.
Hypothermic (28°C) oxygenated blood cardioplegia is given both antegrade and

retrograde with control of reperfusion for primary coronary revascularization in the
setting of acute ischemia, reoperative coronary artery bypass, or associated valve
procedures. Surgery for acute myocardial infarction (MI) and cardiogenic shock is
covered in detail in Chapter 21 and will not be considered further here. Our preferences
for intraoperative myocardial protection in the setting of acute myocardial ischemia
have been reviewed recently. [153 ]
Ongoing investigation in our laboratory shows no advantage of blood versus crystalloid

cardioplegia for ventricular hypertrophy (MacDonald et al., personal communication,
unpublished data). Other published evidence indicates that hypothermic techniques
provide better right ventricular protection [154 ] and that continuous retrograde
cardioplegia via the coronary sinus poorly protects the right ventricle. [155 ] These data
become clinically relevant in patients with impaired right ventricular function, proximal
right coronary artery occlusion, or prolonged ischemic times or when metabolic demand
of the right ventricle is increased.
We do not routinely administer a normothermic amino acid-enriched blood cardioplegic

hot shot just prior to cross-clamp removal. Although this technique is superior to
crystalloid cardioplegia, it is not proven superior to continuous or intermittent blood
cardioplegia solution delivery. [156 ] In addition, carbon labels of amino acid substrates
in the normothermic hot shot are not incorporated into the Krebs cycle in studies using
magnetic resonance spectroscopy. [157 ]
A left ventricular vent is not utilized routinely if the ventricle remains nondistended
throughout the time on cardiopulmonary bypass. Significant ventricular distension
should be strictly avoided because it is clearly detrimental to postoperative ventricular
function. [158 ]
Myocardial temperature probes are not used routinely for either cardioplegic technique.
Approximately 100 mL of crystalloid cardioplegia at 4°C are delivered through each
saphenous vein graft as it is completed. Cardioplegic redosing via the aortic root is
performed every 20 minutes throughout the cross-clamp period and is accompanied by
strict vigilance to topical cooling, which ensures adequate maintenance of tissue
hypothermia during the cross-clamp period. This obviates the need for temperature
monitoring. We also do not measure temperatures routinely with continuous blood
cardioplegic techniques.
Leukocytes are the main effectors of reperfusion injury following an ischemic insult.
Depletion of leukocytes in blood cardioplegia decreases leukocyte accumulation,
lysosomal enzyme release, and free radical synthesis that reduce myocardial injury and
result in superior preservation function following ischemia and reperfusion in the
experimental laboratory. [159 ] [161 ] The clinical importance of these observations
remains unproved, and we do not routinely use a leukocyte filter in our blood
cardioplegia in the absence of ischemia.
Distal Anastomoses
Following cross-clamp application and administration of cardioplegia, distal

anastomoses are performed first. The vessels on the inferior surface of the heart are
grafted initially (right coronary artery, posterior descending artery, left ventricular
branch); then, proceeding in a counterclockwise direction, the posterior marginals,
midmarginals, anterior marginals, ramus-intermedius, diagonals, and lastly the left
anterior descending artery. Rewarming is begun with the next to last distal anastomosis.
Recently, only minimal systemic hypothermia (32 to 34°C) has been used to shorten the
postoperative stay in the ICU and hospital. The internal mammary artery anastomosis to
the left anterior descending artery (or alternately, to the most important distal target) is
performed last; after this anastomosis is complete, the soft bulldog is removed from the
pedicle, and the cross-clamp is released. The internal mammary artery pedicle is
tacked to the epicardium with two interrupted sutures to prevent torsion. In the absence
a of contraindication (see Epivascular Echocardiography above), a partial exclusion
clamp is placed on the ascending aorta, and proximal sites are made with a pointed
knife blade and enlarged with a 4-mm aortic punch. Proximal anastomoses are
performed with the most anterior grafted artery placed most proximally on the aorta.
Metal bulldog clamps prevent backbleeding through the vein grafts during performance
of proximal anastomoses and prevent air embolism down the coronary arteries
immediately following removal of the partial exclusion clamp. The vein graft that
occupies the most superior position on the aorta (usually a right-sided graft) is left
untied and used to evacuate air as the partial exclusion clamp is removed. The heart is
gently massaged and manually compressed to make this portion of the aorta the
uppermost structure to ensure complete evacuation of residual air. The aorta is then
gently balloted to expel any remaining air, and the suture is tied. Vein grafts are then
deaired using a 25-gauge needle, and bulldog clamps are removed. If arterial grafts are
used as free grafts, they are allowed to backbleed prior to clamp removal and are not
deaired using the 25-gauge needle because of the risk of injury. Stainless steel
washers are placed on the uppermost and lowermost saphenous vein grafts to assist
with later catheterizations; alternatively, each individual vein graft is marked with a
stainless steel washer according to the preference of the surgeon. Markers that
surround proximal anastomoses are strictly avoided due to the difficulties produced
during reoperative procedures. Distal anastomoses are checked for bleeding, and
preparations are made for weaning from cardiopulmonary bypass.
We do not advocate performing proximal anastomoses first. This technique does

prevent overdistension of the saphenous vein grafts by exposing the graft only to
physiologic arterial pressures; however, the method may result in increased afterload
and myocardial ischemia if done with the heart ejecting prior to institution of PCB. This
also increases shear stress placed on the aorta in the area of clamp placement and
thus increases the risk for dissection.
Immediately after cross-clamp removal, the perfusion pressure is held low at

approximately 50 mmHg for 2 minutes to help prevent postischemic edema, [162 ]
endothelial dysfunction, [163 ] and postreperfusion arrhythmias. [164 ] It is then
increased to 70 mmHg (or higher in the presence of cerebral vascular disease, [165 ]
chronic hypertension, or ventricular hypertrophy [166 ] ). Calcium is avoided during the
early reperfusion period after cross-clamp removal to prevent mitochondrial
accumulation of calcium, uncoupling of oxidated phosphorylation, and further
exacerbation of the reperfusion injury [167 ] ; however, ionized calcium levels must be
returned to normal during the weaning process to eliminate some of the detrimental
conduction disturbances associated with hyperkalemia during the early
post-cross-clamp period.
Weaning from cardiopulmonary bypass should be approached in a systematic, orderly

fashion and requires coordination, cooperation, and communication among the
surgeon, the perfusionist, and the anesthesiologist.
Preparation for separation from CPB may be divided into three parts: (1) preparation of
the heart, (2) preparation of the lungs, and (3) preparation of the overall patient. [168 ]
Steps for preparation of the heart are outlined in Table 18-2 ; preparation of the lungs is
outlined in Table 18-3 ; and overall patient physiological preparation is outlined in Table
18-4 . [168 ]
The heart is allowed to reperfuse in an empty beating state as electrolyte, acid-base,

and hematocrit values are corrected and inotropes are initiated if indicated.
The need for inotropes can be determined by preoperative or intraoperative factors.

Preoperative factors include advanced age, low ejection fraction, high pulmonary artery
pressures, high left ventricular end-diastolic pressure, or high central venous pressures.
Alternately, intraoperative factors that prompt the need for inotropic assistance include
incomplete revascularization, severe distal disease, prolonged CPB or cross-clamp
times, poor myocardial protection, and poor left ventricular contractility by visual
inspection following cross-clamp removal. Intraoperative transesophageal
echocardiography also can be very helpful in determining the need for inotropes for
separation from cardiopulmonary bypass (see Failure to Wean below).
CHOICE OF INOTROPES
Pharmacologic strategies to facilitate CPB weaning as practiced in our institution are

outlined in Figure 18-9 .
If there is a significant gradient between pulmonary artery diastolic pressure and

pulmonary capillary occlusion pressure, a left atrial line may be placed to measure left
atrial pressure directly and more accurately direct volume loading of the heart during the
weaning process. A second left atrial line may be placed adjacent to the first line and
vasopressors infused directly into the left atrium to produce a systemic effect without
first passing through the pulmonary vascular bed; however, a recent study in canines
demonstrates that this does not attenuate pulmonary vasoconstriction and carries the
added risk of left-sided air embolism. [169 ]
The heart is gently filled while maintaining adequate perfusion pressure and optimal
filling pressures and monitoring mixed venous saturation as extracorporeal perfusion is
weaned. Increased perfusion pressure may be required for patients with incomplete
revascularization, preoperative right ventricular failure, ventricular hypertrophy, or
renovascular or cerebrovascular disease to ensure adequate end-organ perfusion
during the weaning process.
FAILURE TO WEAN
If the patient fails to wean initially from cardiopulmonary bypass, reassessment of the
safety of ongoing cardiopulmonary bypass (i.e., adequate heparinization), possible
omission of one of the previously outlined steps for weaning, accuracy of information
determining failure to wean, adequacy of drug delivery, function of bypass grafts with
regard to both inflow and outflow, mechanical valvular or outflow problems, and
optimization of the five determinants of cardiac output (rate, rhythm, contractility,
preload, afterload) are reviewed. Factors that can impede successful weaning from
CPB are illustrated in Figure 18-10 .
Saphenous vein grafts can be inspected with Doppler sonography to evaluate patency.
A side-branch ligature also can be removed and a probe passed down a saphenous
vein graft to gauge distal anastomotic lumenal size and patency. This maneuver should
be done reluctantly and with extreme caution because of the risk of causing additional
damage to the native coronary artery. Pedicled arterial grafts are more difficult to
evaluate, but an index of the flow can be obtained using pulsed Doppler sonography.
[170 ] Pulsatility by palpation is a poor indicator of flow and may even be accentuated
with distal graft occlusion.
Transesophageal echocardiography (TEE) is extremely helpful in this setting. The heart

is gently volume loaded, and regional wall motion is assessed and compared with
preoperative data. The precise location of new postoperative regional wall motion
abnormalities directs evaluation of the involved graft(s) and allows for surgical
correction of dysfunctional grafts or placement of new grafts to additional regions that
were not grafted previously. TEE also helps to identify mechanical problems such as
valvular dysfunction, acquired ventricular septal defect, or other previously unrecognized
congenital mechanical defects that may interfere with successful weaning. A review of
the preoperative angiograms is mandatory at this point to complete data gathering so
that a decision can be made regarding a second cross-clamp interval and graft
placement or replacement.
Intraaortic balloon pumping
Failure to wean in the absence of correctable impediments to weaning is an indication

for an intraaortic balloon pump to augment diastolic pressure, increase coronary artery
perfusion, and reduce afterload. The decision to place this device is weighed against
clinical factors that increase the complication rate following device placement. In
general, these devices are avoided in patients with aortic insufficiency, although this is
not an absolute contraindication. [171 ] . Risk of complications is increased in patients
with severe peripheral vascular disease, in those with very shaggy altheromatous
disease in the descending aorta by TEE, in small women, in diabetics, and in those
requiring open placement of the device. [171 ] Although the incidence of mortality from
intraaortic balloon pump placement is less than 1 percent, the overall complication rate
remains 26.7 percent. [172 ] The majority of complications occur in patients with one or
more of the risk factors listed above. Nonetheless, a counterpulsation device should be
placed even in high-risk individuals who fail to wean from CPB. Counterpulsation of the
pulmonary artery to augment the right ventricle has been described [173 ] ; however, we
have not found this technique useful.
SECONDARY CARDIOPLEGIA
If the patient fails to wean from cardiopulmonary bypass with maximal inotropic and
mechanical support, the patient is returned to cardiopulmonary bypass and rested with
the heart empty, beating, and perfused for an additional 20 to 30 minutes. Secondary
cardioplegia is considered to help resuscitate the myocardium. A report indicates that
this has been successful in weaning the difficult patient, [174 ] but we have not been
able to corroborate this.
MECHANICAL VENTRICULAR ASSIST
Following a second failure to wean with maximal inotropic and mechanical support, a
ventricular assist device must be considered. We generally do not place assist devices
in patients more than 70 years of age, in those whose surgical procedure has been
technically unsuccessful, or in those who have infarcted versus stunned myocardium,
uncontrolled hemorrhage, CPB time greater than 6 hours, active infection, or end-organ
dysfunction (renal, hepatic, pulmonary). A full discussion of the indications for and
management of postoperative mechanical assist devices is discussed in detail in
Chapter 11.
Fortunately, nearly all patients are weaned successfully from cardiopulmonary bypass
using the preceding methods.
OPEN CHEST
There is a small subset of patients who can be weaned from cardiopulmonary bypass
but do not have enough room in the chest to allow closure without significant myocardial
compression and hemodynamic compromise. This is either due to a small chest cavity
or to severe myocardial edema or myocardial enlargement from cardiac failure. Severe
decompensation may occur with myocardial compression, and the circulation may not
recover by simply reopening the chest. Sometimes adequate cardiac function does not
return even with reinstitution of CPB, placement of an IABP, and additional attempts to
wean. In very small-framed females, in patients with right ventricular failure, and in those
with very enlarged hearts, we recommend that the sternum be left open to maintain
hemodynamic stability.
The sternal edges are held apart with Synthes orthopedic plates and sternal wires (Fig.
18-11) to prevent compression of the heart by elastic recoil of the chest wall. An
Esmarch latex bandage is used to close the wound by sewing it to the skin edges with a
running monofilament suture. Pleural drainage tubes and pacing wires are placed as for
patients with reapproximated sterni. In a recent review from our institution when the
chest was left open following cardiopulmonary bypass and primary surgical coronary
revascularization, operative mortality was 53 percent. The average interval to wound
closure was 3.7 days and was related to the onset and persistence of negative fluid
balance (Schmidt et al., personal communication, unpublished data). As shown
previously, presence of a negative fluid balance is the most accurate predictor of
successful sternal closure. [175 ] The incidence of wound infection was 7 percent, but
the incidence of deep mediastinal infection requiring flap closure was only 3.5 percent.
Although mortality is high, this is not unexpected in this severely ill subset of patients. Of
patients discharged from the hospital, 5-year survival was more than 65 percent, a
gratifying long-term survival for these desperately ill patients. Traction of the closed
sternum using sternal wires and an externally configured traction apparatus has been
proposed as an alternative to delayed sternal closure [176 ] ; we have no experience
with this method and do not currently recommend it.
Special Circumstances
There are several special circumstances in the perioperative period that deserve
mention, although full discussion of each of these entities is beyond the scope of this
chapter.
PREOPERATIVE STROKE
The optimal interval between an acute neurologic event (CVA) and safe anticoagulation
and institution of CPB is unknown. Some authors recommend use of a heparin-coated
CPB circuit and low-dose heparin when surgery is mandated soon after the insult [177 ]
; however, surgery usually can be performed safely with standard anticoagulation if an
acute bleed is not present in a preoperative computed tomogram. [178 ]
PREOPERATIVE GASTROINTESTINAL HEMORRHAGE
Similarly, no hard data are available for acute gastrointestinal hemorrhage. In general, a
decision must be made regarding the urgency of coronary revascularization, with
operation planned accordingly. An increase in angina caused by anemia secondary to
gastrointestinal hemorrhage should not be mistaken for ischemic instability. If surgery
must be performed acutely, a heparin-bonded circuit and low-dose heparin have been
recommended, but benefit is not proven. [177 ]
CRYOGLOBULINS
The presence of cryoglobulins detected preoperatively mandates normothermic

cardiopulmonary bypass and normothermic cardioplegia. [179 ] Although the incidence
of neurologic complications is increased with strict maintenance of normothermia
during cardiopulmonary bypass, [180 ] this risk is outweighed by the risk of the
sequelae of hypothermia in the presence of cryoglobulins.
RELIGIOUS OBJECTION TO BLOOD TRANSFUSION
Perioperative management of patients who refuse blood products can be particularly

challenging. Management recommendations and technical details of successfully
guiding these patients through the operative period have been detailed previously. [181
]
HEPARIN-INDUCED THROMBOCYTOPENIA AND THROMBOSIS
The syndrome of heparin-induced thrombosis and thrombocytopenia (HITT) is a rare but

potentially very devastating postoperative complication. This syndrome results from
antibody-mediated, uncontrolled platelet aggregation that leads to widespread platelet
aggregate thrombi (white clot syndrome). [182 ] The severity of the syndrome depends
on the extent of microvascular thrombosis, when recognized, and the organ systems
involved. If vascular occlusion is widespread and its recognition delayed, the disease
can be rapidly fatal. [183 ] There may be less prevalence with porcine heparin, [184 ]
although other studies show equal prevalence between beef and porcine heparin. [182 ]
We routinely limit exposure to heparin in the postoperative period by removing
heparin-bonded monitoring catheters as soon as feasible and using only heparin-free
saline for intravenous flushes and carrier fluids. Diagnosis is suspected by a low
postoperative platelet count (< 80,000). Diagnosis can be confirmed with an antiheparin
antibody assay, but treatment should begin presumptively. All heparin must be avoided.
Therapeutic options are limited and generally ineffective, although treatment protocols
using prostaglandin E1 and aspirin, [185 ] ancrod, [186 ] and low-molecular-weight
heparin [187 ] have been suggested. Iloprost [188 ] has been used along with heparin;
and ancrod has been used alone for anticoagulation during CPB in patients with a
previous history of HITT. [189 ] A routine platelet count is obtained in patients who are
discharged early after operation to identify this small subset of patients who may
develop this devastating complication.
Postoperative Bleeding
Much of the frustration of management of postoperative bleeding can be minimized by

an orderly and scientific approach to the patient with an excess of shed mediastinal
blood. To this end, we have developed a protocol for evaluating the bleeding patient
(Fig. 18-12) . We have found the thromboelastogram (TEG) clinically useful for directing
therapy despite conflicting reports regarding its predictive value. [190 ] [192 ] Despite
this limitation, a recent study showed both fewer transfusions and a lower rate of
reexploration for bleeding in patients whose anticoagulation and reversal were
managed by thromboelastography. [193 ] Quantifiable TEG variables and characteristic
TEG patterns associated with specific coagulation defects are found in Figures 18-13
and 18-14 . [194 ] Patients who are thought to be at high risk for bleeding (aspirin or
other antiplatelet drug use, recent thrombolytics, complex surgery, or thrombocytopenia)
or those who have excess bleeding before heparin is given should have samples for
plasma fibrinogen and platelet count sent during the last hour of cardiopulmonary
bypass. A TEG can be run during bypass if heparinase is added to the cuvette. [195 ]
Results are examined prior to weaning from CPB and appropriate blood products
obtained to avoid delaying corrective steps.
Patients who are not identified as being at high risk for bleeding but who continue to
have excess blood loss despite adequate heparin reversal with protamine should also
have plasma fibrinogen and a platelet count measured. Likewise, if the activated
clotting time does not normalize with protamine administration and an additional 50 to
100 mg of protamine is ineffective, blood is sent for platelet count and plasma
fibrinogen. Paired TEGs with and without heparinase are sent to identify residual
heparin effect or heparin rebound. If excess thrombolysis is seen on the TEG,
epsilon-aminocaproic acid (AMICAR), if not already instituted, is infused. Additional
surgical sites of bleeding are diligently sought and repaired while laboratory work is
pending and before initiation of therapy. If the TEG is abnormal in the sample without
heparinase, then additional protamine is given. If the platelet count is greater than
100,000 and the fibrinogen levels are greater than 150 mg/dL, no additional therapy is
begun. If the platelet count is less than 100,000, 8 units of platelets are infused. If the
fibrinogen level is less than 150 mg/dL, then 10 units of cryoprecipitate are infused to
correct hypofibrinogenemia. Excess fibrinolysis produces a characteristic TEG (Fig.
18-14) . If the maximum amplitude of the TEG is more than 45 and does not lyse,
surgical bleeding is suspected and should be found and corrected. If the maximum
amplitude is less than 45 and platelet and fibrinogen levels are normal, desamino
d-arginine vasopressin (DDAVP) 10 µgmg/m 2 is given to correct platelet dysfunction;
however, platelet transfusion may be required especially if the patient has been on
platelet-active medications preoperatively. Following elimination of surgical bleeding
and if the rate of blood loss is not massive, the wound is closed expeditiously to prevent
further cooling from an open chest and blood products infused to correct the
coagulopathy.
If excess mediastinal blood loss does not begin until the patient is admitted to the ICU,
an activated clotting time is performed first, and additional protamine is given if
indicated. A platelet count, fibrinogen level, and TEG are sent as previously outlined.
Laboratory results are handled in a similar manner as above. Patients are monitored
closely for hemodynamic compromise (not related to hypovolemia from bleeding), which
mandates a return to the operating room for surgical reexploration. In the postoperative
period the classic signs of tamponade may develop late; reexploration should not be
delayed until the patient is in extremis. If the patient with normal ventricular function
preoperatively has impaired hemodynamic function despite adequate volume
resuscitation, tamponade should be seriously considered. Indications for reexploration
include tamponade, blood loss greater than 1 liter in the first hour following return to the
ICU, more than 400 mL/h for 2 hours, more than 300 mL/h for 3 hours, or more than 200
mL/h for 4 hours, even though it is unusual for patients to continue to bleed once a level
of less than 200 mL/h is reached.
Aprotinin is generally not used in the postoperative period unless it has been started in
the operating suite, and in general, it is not given in the operating suite to patients
undergoing primary surgical revascularization.
Rational Use of Blood Products
Approximately 10 percent of the total blood transfused in the United States annually is
related to intraoperative or postoperative transfusion following coronary bypass surgery.
[196 ] Owing to the risk of antigen-mediated reactions and bloodborne infections, there
is great interest in limiting exposure to homologous blood transfusions. Patients at an
increased risk for transfusion are those with a low red blood cell mass, low body surface
area, increased age, female gender, and those receiving antiplatelet or anticoagulation
therapy. Conservation techniques to decrease transfusion rates can be implemented
before, during, and after coronary revascularization.
Autologous predonation is the mainstay of preoperative blood conservation programs

for all types of surgical procedures with or without pharmacologic erythropoietin.
Out-of-hospital predonation decreases the percentage of patients who require
transfusion from 46 to 12.6 percent ( p < 0.001) [197 ] but requires an average of 18
preoperative days to accomplish. In addition, total exposure to blood product is not
reduced because transfusion of other blood products (platelets, fresh-frozen plasma,
etc.) is not similarly decreased by autologous predonation. Another study showed a 22
percent incidence of preoperative ECG changes induced by predonation in the
presence of ventricular dysfunction.[198 ] Another had a 20 percent incidence of
hypotension associated with autologous predonation that was probably related to
inadequate volume replacement; this may not be tolerated by patients with critical
coronary artery stenoses. [199 ] Also, Birkmeyer et al. [200 ] showed that predonation is
not cost-effective. For these reasons, we do not recommend out-of-hospital
predonation. Erythropoietin decreases the chance for transfusion when coupled with
predonation; however, this drug requires administration over 3 weeks preoperatively to
be effective. [201 ]
Intraoperative predonation also results in fewer transfusion requirements. [202 ]

However, in this study the transfusion rate without predonation was extremely high (90
percent) and dropped only to 35 percent in those who predonated blood
intraoperatively. Furthermore, patients who were eligible to predonate intraoperatively
may have been at a lower risk for requiring transfusion. Nonetheless, the technique is
useful for suitable patients.
Other intraoperative methods of blood conservation include direct reinfusion of shed

blood, centrifugal cell salvage with reinfusion, and ultrafiltration followed by reinfusion.
No difference in effectiveness is noted between any of these methods, with the
exception that plasma colloid oncotic pressure and platelet counts are not sustained in
the ultrafiltration group. [203 ]
Intraoperative pharmacologic therapy for blood conservation has increased in popularity

following Food and Drug Administration (FDA) approval of aprotinin. Aprotinin is a
serine protease inhibitor that is isolated from bovine lung. It inhibits kallikrein, it may
decrease neutrophil elastase release, and it may diminish the inflammatory response to
cardiopulmonary bypass. The drug preserves platelet function by protection of
glycoprotein Ib (GPIb) receptor function. [17 ] There is a 0.5 percent incidence of
anaphylaxis with previous exposure; thus exposed patients require pretreatment with
antihistamines and steroids prior to drug administration. [204 ] Recombinant aprotinin
may be less antigenic. [205 ] Spurious increases in the activated clotting time (ACT)
occur with Celite tubes; therefore, kaolin tubes are used to monitor heparin. [206 ] If the
patient is adequately anticoagulated, there is no increased risk of myocardial infarction
with aprotinin. [207 ] Other pharmacologic agents currently in use that decrease
transfusion requirements are epsilon-aminocaproic acid (EACA), tranexamic acid, and
nafamostat mesilate. [208 ] [210 ] There is no proven decrease in transfusion
requirements associated with prophylactic administration of desamino d-arginine
vasopressin (DDAVP). [211 ]
Normovolemic hemodilution to a hematocrit of 21 to 23 percent shows no adverse

effects, [212 ] and this level of anemia is tolerated postoperatively without symptomatic
orthostasis in most younger individuals with normal ventricular function. Hematocrit
levels during cardiopulmonary bypass are allowed to fall as low as 15 percent if the
mixed venous saturation and oxygen delivery remain adequate.
Platelet-rich plasmapheresis either preoperatively or intraoperatively is expensive and

without proven benefit and therefore is not used. [213 ] Likewise, heparin coating of the
bypass circuit is without proven benefit, [214 ] adds extra cost, and also is not used.
There is a single study that reports improved postoperative platelet function and less
postoperative bleeding associated with warm heart surgery [215 ] ; however, we cannot
corroborate this observation in our experience with warm heart surgery.
Mediastinal blood shed postoperatively can be autotransfused as a blood conservation

measure. Earlier reports indicated fewer transfusions in patients who were
autotransfused [216 ] ; however, prospective, randomized trials fail to show any benefit,
[217 ] and other studies show an increased transfusion requirement with
autotransfusion. [218 ] , [219 ] This is thought related to reinfusion of blood with very high
fibrinolytic activity. This method of blood conservation is probably not effective when
used with modern hematologic drugs in older, sicker contemporary patients; however,
the practice remains widespread. [218 ]
POSTOPERATIVE HEMODYNAMIC MEASUREMENTS
An entire chapter is devoted to postoperative management, and there is nothing unique

to primary revascularization that must be individually addressed with regard to
postoperative hemodynamic management. As a cost-saving measure, patients with
normal preoperative ventricular function and no comorbid factors generally have only a
central venous (CV) and radial arterial line placed for intraoperative and postoperative
monitoring. Central venous pressure alone predicts a normal pulmonary capillary wedge
pressure 96 percent of the time in these patients. [220 ] No outcome data suggest that
this practice increases risk; however, a CV line alone does not detect early myocardial
ischemia. [221 ]
We do not routinely place oximetric Swan-Ganz catheters or routinely draw mixed

venous blood gas samples for patient management; however, with a low cardiac index
(< 2.0 liters/min per m 2 ) we use a mixed venous sample to guide therapy. A minimal
acceptable saturation is 60 percent, and this is modified by increasing inotropic therapy
and/or increasing blood hemoglobin levels to increase delivered oxygen. At the same
time, we initiate effective therapy to decrease metabolic demand (reduce pain, fever, or
shivering; increase ventilation to decrease the work of breathing; and the addition of
somatic paralysis). In many patients with an inadequate cardiac index (< 1.8 liters/min
per m 2 ), normal clinical parameters, and adequate output (urine output, acid-base
status, etc.), this test will reveal an adequate mixed venous saturation and hence that
oxygen delivery at the tissue level is adequate. If patients require prolonged inotropic
support, Swan-Ganz catheters help to guide the weaning rate of inotropes. Indwelling
monitoring catheters are changed routinely every 3 days to reduce the incidence of
contamination and sepsis.
POSTOPERATIVE RESPIRATORY MANAGEMENT
To increase efficiency, decrease length of hospital stay, and contain costs, we

developed a protocol for early postoperative extubation. Planning for this begins
preoperatively, continues with intraoperative anesthetic management, and culminates
postoperatively with early extubation and first-day transfer out of the ICU for
uncomplicated patients. Excluded patients are those with very poor left ventricular
function, end-stage chronic obstructive pulmonary disease, end-stage renal disease,
and those more than 70 years old (sometimes septuagenarians with a young
physiologic age are considered for early extubation). [222 ] Patients with suboptimal
revascularization, technical operative difficulties, or intraoperative complications also
may be excluded for early extubation.
Intraoperative anesthetic management is an important part of early extubation, and

several regimens have been devised to allow early weaning from the ventilator and
adequate pain control with minimal sedation. [223 ]
POSTOPERATIVE ICU CARE
Once in the ICU, sedative infusions are tapered if the patient is hemodynamically stable
(minimal or no inotropic support), chest tube output is less than 100 mL/h, temperature
is greater than 36°C, and the patient shows signs of awakening without a neurologic
deficit. Following arrival in the ICU, an arterial blood gas is drawn 15 minutes after the
patient is placed on mechanical ventilation. The ventilator is weaned using a
transcutaneous saturation monitor and an end-tidal carbon dioxide monitor. A minimal
saturation of 95 percent and an end-tidal co 2 of 35 to 40 mmHg is maintained as the
patient is weaned. Metabolic acidosis is treated with sodium bicarbonate, and repeat
arterial blood gases are obtained 30 minutes after infusion. Mechanical ventilation is
decreased to an IMV of 4 breaths per minute once the patient is awake and responsive.
If the patient's mechanical and spontaneous combined respiratory rate is more than 10
breaths per minute without continuous stimulation, and if the patient is able to lift his or
her head off the pillow, the ventilator is changed to continuous positive airway pressure
(CPAP). An arterial blood gas is checked after an additional 15 minutes. If the patient
has been intubated for less than 12 hours and has no significant pulmonary disease,
and if the FIO 2 is less than 0.4, arterial oxygen saturation is more than 95 percent, paco
2 is between 35 and 45 mmHg, and pH is 7.35 to 7.45, the patient is extubated directly
to a nasal oxygen cannula. Humidified face mask oxygen is used for patients who were
intubated for more than 12 hours or those with underlying pulmonary disease. The use
of morphine sulfate and benzodiazipines is minimized in the postextubation period, and
a follow-up blood gas is obtained 1 hour following extubation. Aspirin is given orally
following extubation unless contraindicated by severe allergy. Antiplatelet therapy
increases graft patency, especially in grafts to small vessels. [224 ] Aspirin is given with
an enteric coating to patients with a history of gastritis or peptic ulcer disease.
Patients are ambulated on the first postoperative morning. They are transferred from the
ICU later that same morning, and diuretics are administered routinely. Chest tubes are
removed later in the afternoon of the first postoperative day if drainage is less than 100
mL/8 h per tube. The Foley catheter is removed at 10 p.m. on the night of the first
postoperative day, and urine output is reevaluated at 6 a.m. the following morning.
Telemetry is discontinued 24 hours following admission to the floor unless otherwise
needed. Pacing wires are removed on the third postoperative day, and patients are
monitored for signs of tamponade for 4 hours. Patients are generally discharged on
postoperative day 4 if they have a room air oxygen saturation greater than 92 percent,
are ambulatory and afebrile, have a normal or decreasing white blood cell count, normal
sinus rhythm, stable creatinine, potassium level greater than 3.5, normal postoperative
chest x-ray, adequate control of systemic blood pressure, normally convalescing
wounds, normal neurologic function, and return of bowel function. Postoperative
teaching plays a major role in early discharge of these patients, and they are instructed
in dietary modification, smoking cessation, pulmonary toilet, activity level, and general
guidelines and expectations for convalescence. Dosing schedules and the purposes of
all medications are individually reviewed with patients, and they are given a written list
of current medications.
PATHOLOGY
The pathology and causes of vein graft failure are important not only to understand the
reasons for reoperation but also to understand the dangers of either interventional or
conservative treatment of patients with previous bypass surgery.
MURAL THROMBUS
The pathology of saphenous vein to coronary artery grafts (SVG) is different at different
intervals after operation. [8 ] [13 ] Histology of saphenous vein grafts examined within a
few months of operation often shows diffuse endothelial disruptions with attached mural
thrombus. The mural thrombus usually is not obstructing. When grafts become occluded
with thrombus early after operation, the occlusion is not a result of intimal changes but is
related to hemodynamic factors. Mural thrombus present early after operation, however,
predisposes to development of late pathologic changes.
INTIMAL FIBROPLASIA
Most saphenous vein grafts examined more than 2 to 3 months after operation have
proliferative intimal fibroplasia. This is a diffuse concentric process that extends the
entire length of the graft (Fig. 19-4) . Intimal fibroplasia initially is very cellular but
evolves to a relatively acellular fibrous lesion. It is not friable, and although intimal
fibroplasia involves most vein grafts, only a few develop stenoses or occlusions. The
process probably provides substrate for development of vein graft atherosclerosis.
VEIN GRAFT ATHEROSCLEROSIS
Vein graft atherosclerosis is a distinct pathologic process that often is observed as

early as 3 to 4 years after operation and is characterized by lipid infiltration of areas of
intimal fibroplasia (Fig. 19-4) . Therefore, the distribution of vein graft atherosclerosis
follows the diffuse, concentric distribution of intimal fibroplasia, but as the disease
progresses, eccentric stenotic lesions may develop. Vein graft atherosclerosis is a
superficial lesion, very friable, and often associated with overlying mural thrombus.
These characteristics are different from native vessel coronary atherosclerosis, that is
segmental, proximal, eccentric, encapsulated, usually not friable, and usually without
overlying mural thrombus. Vein graft atherosclerosis with or without stenosis is present
in a majority of grafts explanted more than 10 years after surgery, and almost all late
SVG stenoses result from these atherosclerotic lesions. The extreme friability of vein
graft atherosclerosis creates a substantial risk of distal coronary artery embolization
during percutaneous interventions and reoperations and probably produce spontaneous
coronary embolization. Last, atherosclerotic stenoses in vein grafts predispose to graft
thrombosis. Thus vein graft atherosclerosis is an active, event-producing lesion.
INCIDENCE OF STENOSIS
The exact incidence of late SVG stenoses and occlusions is difficult to determine even
in prospective studies because death and reoperation are non-random events that
remove patients available for late coronary angiography. However, by 10 years
approximately 30 percent of vein grafts are totally occluded and 30 percent of patent
grafts have some degree of stenosis or intimal irregularities characteristic of vein graft
atherosclerosis. [2 ] , [12 ] , [14 ] In a study of patients who had multiple postoperative
angiograms within 5 years of operation, we found that 19 percent of patent grafts
(initially angiographically perfect) restudied 5 to 12 years after operation had stenotic
lesions and 26 percent were totally occluded. [12 ]
Although not the only factor related to SVG occlusion, intrinsic SVG pathology probably
is the most important cause of late failure. Native vessel stenoses distal to the insertion
site may decrease SVG outflow, but late occlusion usually is associated with vein graft
atherosclerosis. Furthermore, when stenotic vein grafts are replaced at reoperation, the
late patency rate of these new vein grafts is good. [6 ] Virtually all late SVG stenoses
and most late SVG occlusions appear related to the intrinsic vein graft atherosclerosis.
We do not know how to prevent vein graft atherosclerosis. Perioperative and long-term
platelet inhibitors improve early patency rates of saphenous vein grafts but there are no
data (as yet) to indicate that platelet inhibitors decrease the incidence of SVG
atherosclerosis or improve late vein graft patency rates. [15 ] [17 ] Vein graft
atherosclerosis is more common in patients with severe hyperlipidemia and
randomized studies to test the effect of lipid lowering regimens on late vein graft
disease have been conducted. One randomized trial shows a diminished rate of native
vessel and SVG atherosclerosis after postoperative treatment of hyperlipidemia, but the
overall improvement is small. [18 ] So far, the only way to avoid vein graft
atherosclerosis is to avoid vein grafts.
ITA grafts rarely develop late atherosclerosis and late attrition rates of patent ITA grafts
are extremely low. Left ITA (LITA) to LAD (left anterior descending) grafts have a very
high late (20 years) patency rate and for most patients the LAD is a particularly
important coronary artery. [12 ] , [19 ] This observation explains why a LITA-LAD graft
not only decreases the rate of late death after primary bypass surgery but also
decreases the rate of reoperation. [20 ] Since ITA grafts do not develop vein graft
atherosclerosis, they do not embolize during reoperation. Although there is suggestive
evidence that bilateral ITA grafts further decrease the incidence of late reoperation (Fig.
19-3) , it is not known whether or not more extensive use of arterial grafts, such as the
gastroepiploic artery, inferior epigastric, and radial arteries, at primary operations
provide further protection against reoperation.
INDICATIONS FOR REOPERATION
Randomized trials of bypass surgery versus medical management initiated in the 1970s
provide information concerning indications for bypass surgery and subsequent
observational studies add further data. However, no randomized trials or comparative
observational studies include patients with previous coronary revascularization surgery.
The coronary arterial pathology of patients with previous bypass surgery is different than
that of patients with native vessel disease. Therefore, we cannot assume that the natural
history of, for example, triple atherosclerotic vein grafts is equivalent to the history of
triple vessel, native disease.
Does Reoperation Prolong Survival?
We conducted two studies that involved patients who had previous bypass surgery, to
address the issue of whether or not reoperation prolongs patient survival. [21 ] , [22 ]
Both studies were non-randomized and retrospective. Although all patients had
postoperative angiograms, patient and physician bias was a major factor in the choice
of medical versus surgical therapy. The first study attempted to determine if vein graft
stenoses were predictive of death in patients who were treated medically. [21 ]
Outcome was good and approximately the same in patients with and without stenotic
vein grafts that were documented less than five years after surgery (early vein graft
stenoses). Patients with early stenoses in LAD vein grafts had a slightly higher rate of
reoperation than patients without vein graft stenoses, but even early SVG-LAD
(saphenous vein graft-left anterior descending) stenoses were not associated with a
decreased rate of survival.
However, stenoses in vein grafts more than 5 years after operation (late vein graft
stenoses) predicted poor long-term outcomes, particularly if the stenotic graft supplied
the LAD coronary artery. Late survival rate was particularly dismal in patients with
stenotic LAD vein grafts who had other high risk factors. For example, patients with a
5099 percent LAD vein graft stenosis combined with abnormal left ventricular function,
triple vessel, or left main coronary stenosis had only a 46 percent chance of surviving
without reoperation. Interestingly, patients with more than 50 percent stenosis of the
native vessel had a significantly better long-term outcome than patients with a late,
greater than 50 percent stenosis of an LAD vein graft (Fig. 19-5) . This study showed
that early obstructions owing to intimal fibroplasia are associated with a different
prognosis than late obstructions owing to vein graft atherosclerosis and that late
stenoses in vein grafts are dangerous lesions.
The second study examined the question of whether or not reoperation improves
survival of patients with stenotic vein grafts. [22 ] Patients from the first study who had
stenotic vein grafts but were treated medically (MED group) were compared to patients
with stenotic vein grafts who had immediate reoperation (REOP group). In this
non-randomized, retrospective study, there were significant differences between groups
in that patients in the REOP group were older, more symptomatic, had worse left
ventricular function, and fewer patent grafts than patients in the MED group.
Survival of patients with early (<5 years) SVG stenoses was not different in the two
groups. Operative risk for the REOP group was low (no deaths in 59 patients) and
long-term survival was good, but late survival was just as good in patients treated
medically (Fig. 19-6) . However, patients in the REOP group were more symptomatic
initially and less symptomatic at late follow-up. Reoperation for patients with early vein
graft stenosis effectively relieved angina, but if symptoms were absent or mild, patients
could be safely treated medically, at least for a while.
Patients with late stenoses (>5 years) in vein grafts had worse outcomes without
reoperation. By multivariate testing (Table 19-1) a stenotic (2099 percent) LAD vein
graft predicted late death and reoperation increased late survival. Multivariate testing of
smaller subgroups showed a survival advantage for the REOP group with Class I or II
symptoms and that reoperation improved survival for the remaining patients when
patients with stenotic LAD vein grafts were excluded from analysis.
Univariate survival comparison for REOP and MED patients with stenotic LAD grafts,
as shown in Figure 19-7 , demonstrates improved survival for the REOP group. When
patients with stenotic LAD vein grafts are regrouped by severity of stenosis (Fig. 19-8A)
, patients with severely stenotic (5099 percent) vein grafts who had operation have
improved survival even early after surgery. For patients with moderate stenoses in LAD
vein grafts (2049 percent), patient survival of both groups is equivalent to about 2 years;
after that time, survival of patients in the MED group deteriorates rapidly so that by 34
years the survival benefit of reoperation is apparent.
The one subgroup of patients with late vein graft stenoses who do not have better
survival with reoperation are those with patent ITA to LAD grafts and stenotic SVGs to
circumflex and/or right coronary arteries (Fig. 19-9) . In both MED and REOP groups,
survival rates are good. However, in evaluating these data, it is important to remember
that reoperative patients are more symptomatic and/or have large areas of myocardium
at risk from stenotic vein grafts; therefore, we do not suggest that reoperation is not
indicated for patients with patent ITA grafts. Patients who do not have either a stenotic
LAD vein graft or a patent ITA-LAD graft have better survival with reoperation. Currently
these studies provide the only data that compare outcome of previously operated
patients with and without repeat surgery.
Interventional Cardiology
At the time most of these patients were treated, percutaneous interventions were not
available for patients with previous coronary bypass surgery. Once percutaneous
transluminal coronary angioplasty (PTCA) became available, interventional
cardiologists rapidly learned the importance of vein graft age. In an early study of PTCA
for stenotic vein grafts, Platko et al. found that balloon angioplasty of late stenoses in
saphenous vein grafts (more than 36 months after operation) had a 4 percent risk of
death, 12.5 percent risk of myocardial infarction, and 4 percent risk of bypass surgery
versus no procedure-related complications for 53 patients with early stenotic grafts less
than 36 months after operation. [23 ] In this study repeat angiography documented
restenosis in 42.3 percent of patients treated for early stenosis versus 82.6 percent of
those treated for late stenosis ( p < 0.01). Furthermore, late event-free survival was
substantially worse for patients with late SVG stenoses.
Technological changes in interventional cardiology have been rapid and multiple

percutaneous techniques have been introduced to open stenotic vein grafts. In a
randomized prospective study that compared directional coronary atherectomy (DCA)
with balloon angioplasty (PTCA) for stenotic SVG lesions, the risk of distal coronary
embolization was higher for patients undergoing DCA, but death, myocardial infarction,
and acute closure were equivalent for the two interventions. [24 ] The risk of death was 2
and 1.9 percent for DCA and PTCA, respectively. Six-month angiographic follow-up
documented a restenosis rate of 45.6 percent for DCA versus 50.5 percent for PTCA (
p = NS). Clinical follow-up indicated a six-month event-free survival of 59.7 percent for
DCA and 55.7 percent for PTCA ( p = NS), and survival rates of 95.3 percent (DCA)
versus 92.3 percent (PTCA). The authors concluded that DCA is not better than
angioplasty for stenotic SVG.
Intracoronary stents in stenotic vein grafts offer the possibility of larger lumen diameters
that can reduce post-intervention recurrence rates. A multi-center registry study finds
that treatment of focal SVG lesions with stenting is initially successful in 98.8 percent of
cases and that peri-procedure risks of death are 1.7 percent, emergent CABG, 0.9
percent, non-fatal Q-wave myocardial infarction 0.3 percent, and non-Q-wave infarction,
4.8 percent. [25 ] Bleeding complications caused by the intensive anticoagulant
regimen needed to prevent acute thrombosis of stents occur in 14.3 percent of patients.
Eight percent of these patients require operation to control bleeding and 6.3 percent
only require transfusion. Six months after the procedure 66 percent of eligible patients
had follow-up angiograms and 29.7 percent have greater than 50 percent restenosis.
Patients with larger vein grafts and SVG lesions not previously treated have less
restenosis. The event-free survival rate 1 year after stent placement is 76.3 percent.
Thus, the use of stents for SVG lesions appears to be an improvement over previous
interventional devices.
However, there is still uncertainty about the clinical role of percutaneous treatments of
stenotic vein grafts. Patients with stenotic vein grafts are an extremely heterogeneous
group; some subgroups are at low risk without any interventional treatment, and others
are at high risk without effective therapy. To date reported studies of percutaneous
treatment of SVG lesions do not include clinical risk stratifications that allow
comparison of patient survival rates. Another concern is the diffuse pathology of SVGs.
Although patients with vein graft atherosclerosis may have focal stenoses,
atherosclerosis almost always extends the entire length of the graft. If restenosis is
defined as a stenosis within the graft rather than at the site of the original native
coronary lesion, the restenosis rate is not likely to progressively decrease 612 months
after treatment as occurs for dilatation of native vessel lesions.
Summary of Current Indications
There are no randomized prospective studies that compare medical versus

interventional versus reoperative management for patients with previous bypass
surgery. In general, the presence of atherosclerotic vein grafts accelerates the natural
history of coronary artery disease because progression of these lesions often is rapid.
This observation combined with data from randomized studies of patients without
previous bypass surgery permits some logical conclusions.
Anatomic indications for reoperation include: (1) atherosclerotic (late) stenoses in vein
grafts that supply the LAD [22 ] ; (2) multiple stenotic vein grafts that supply large areas
of myocardium [22 ] ; and (3) multi-vessel disease with a proximal LAD lesion and/or
abnormal left ventricular function owing to either native vessel lesions or stenotic vein
grafts or a combination. [3 ] , [4 ] Reoperation also is effective in other anatomic
situations in which severe symptoms are the indication for invasive treatment. These
include patients with a patent ITA to LAD graft combined with other ischemia-producing
lesions and patients with multiple early vein graft stenoses.
Despite persistently high restenosis rates, percutaneous interventions often are

indicated for patients with previous bypass surgery. Realistically, percutaneous
treatments are best suited for situations where failure is not likely to be catastrophic.
These situations include symptomatic patients with (1) early vein graft stenoses; (2)
native coronary stenoses; and (3) focal late SVG stenoses in vein grafts not supplying
the LAD. Still, many patients with previous surgery stand in a middle ground where it is
not clear whether PTCA or reoperation yields the best outcome. The decision requires
weighing specific advantages and disadvantages of each treatment for each patient.
Factors making PTCA versus reoperation more attractive are listed in Table 19-2 .
TECHNICAL ASPECTS OF CORONARY REOPERATIONS
Reoperations are different from primary operations. Surgeons must recognize and
solve specific technical challenges that are either unique or more common during
coronary reoperation. These are (1) the danger of sternal re-entry; (2) stenotic or patent
vein or arterial bypass grafts; (3) aortic atherosclerosis; (4) diffuse native vessel
coronary artery disease; (5) locating coronary arteries amid old grafts and epicardial
scarring; and (6) lack of bypass conduits.
The overall problem of myocardial protection is also more difficult during reoperations;
peri-operative myocardial infarction still is the most common cause of in-hospital death.
[7 ] , [26 ] The metabolic concepts of contemporary myocardial protection are valid, but
anatomic reasons may cause myocardial protection to fail sometimes during
reoperation. Anatomic causes of perioperative myocardial infarction include injury to
bypass grafts, atherosclerotic embolization from vein grafts or the aorta to distal
coronary arteries, myocardial devascularization secondary to graft removal,
hypoperfusion through new grafts, failure to deliver cardioplegic solution, early vein graft
thrombosis, incomplete revascularization, diffuse air embolization, and technical error.
[7 ] , [27 ] [31 ] To be successful consistently, strategies for coronary reoperation must
be designed to avoid these causes of infarction.
Preoperative Assessment
A complete understanding of the patient's native coronary and bypass graft anatomy is
essential. Sometimes achieving this goal is not easy, particularly if the patient has had
multiple previous coronary operations. If bypass grafts, venous or arterial, are not
demonstrated by a preoperative coronary angiogram, usually they are occluded.
However, sometimes they are not occluded and the angiogram fails to demonstrate
their location. Often it is helpful to examine old angiograms performed prior to previous
operations and to review previous operative records to understand the coronary
anatomy. Two fundamental principles are: (1) coronary arteries rarely disappear; and
(2) functioning areas of myocardium need a blood supply. If an angiogram does not
account for all major coronary arteries and does not demonstrate the arteries supplying
functioning myocardium, repeat angiography may be needed to establish the precise
anatomy of the coronary vasculature.
It is helpful also to know that graftable stenotic coronary arteries supply viable
myocardium. Myocardial scar and viability can be differentiated by thallium scanning,
positron emission tomography, and stress (exercise or dobutamine) echocardiography.
The details of establishing myocardial viability are beyond this discussion but this is an
important consideration. Reoperative candidates often have areas of myocardial
infarction and scar and not all coronary arteries may be suitable for bypass grafting.
Before prescribing reoperation, it makes sense to be reasonably sure of a match-up
between graftable arteries and viable myocardium, so that grafting provides long-term
benefits.
It is wise also to have a preoperative plan for selection of bypass conduit and to
document that potential conduits are available. Even if ITAs were not used at a previous
operation, ITA angiography may be helpful to rule out partial dissection of the vessels or
injury during sternal closure. In addition, venous Doppler studies of the legs can assess
the presence and size of greater and lesser saphenous venous segments. Doppler
studies also can assess inferior epigastric and radial arteries and evaluate flow to
digits during temporary radial artery occlusion.
Median Sternotomy, Conduit Preparation, and Cannulation
Situations that increase risk during repeat median sternotomy include right ventricular or
aortic enlargement, a patent vein graft to the right coronary artery, an in situ patent right
ITA graft to a left coronary artery branch and multiple previous operations. In these
situations vessels for arterial (via the femoral or axillary artery) and venous access for
cardiopulmonary bypass are dissected out prior to sternal re-entry.
All bypass grafts except the internal thoracic arteries may be prepared prior to sternal
re-entry. Preparation of radial artery and greater and lesser saphenous vein segments
may be carried out simultaneously. For preparation of the radial artery the arm is
outstretched on a side table. Details of radial artery anatomy are complex and deserve
review prior to using this conduit. [32 ] , [34 ] We harvest accompanying veins with the
radial artery during dissection. Pulse oximetry is used to assess digital perfusion during
radial artery occlusion prior to removing the vessel. Once the artery is removed, only
subcutaneous tissue is closed and the arm is dressed and placed next to the patient's
side. Skin is closed after heparin is reversed to avoid hematoma.
Greater saphenous vein segments are removed with the legs externally rotated. When
dissecting the lesser saphenous vein, an assistant holds the leg in the air. Once the
lesser saphenous vein is removed and the incision is closed, the legs are returned to
the normal position. Then the inferior epigastric arteries and gastroepiploic artery may
be prepared, if they are included in the operative plan.
When re-opening a median sternotomy the incision is made to the sternal wires; the
wires are cut anteriorly and bent back, but are not removed (Fig. 19-10) . An oscillating
saw is used to divide the anterior table of the sternum. After this, ventilation is stopped
and assistants elevate each side of the sternum with rake retractors while the posterior
table of the sternum is divided in a caudal-cranial direction. The retained sternal wires
posterior to the sternum help protect underlying structures. Once the posterior table of
the sternum is divided, wires are removed and sharp dissection with scissors is used to
separate each side of the sternum from underlying structures. After the sternum is
divided, assistants must retract in an upward direction, not laterally. The right ventricle
that is still adherent to the sternum is more often injured by lateral retraction than by
direct saw injury.
In high-risk situations it is helpful to perform a small anterolateral right thoracotomy (Fig.

19-11) before repeat median sternotomy. Underlying structures such as the aorta,
patent bypass grafts, and the right atrium and ventricle, can be dissected from the
sternum via this approach and, with the surgeon's hand placed behind the sternum,
re-entry is safe. This small additional incision contributes little to morbidity.
Another technique for high-risk sternal re-entry is to cannulate and start cardiopulmonary
bypass prior to the incision. Advantages of this strategy are that the heart is emptied
and allowed to fall away from the sternum, and that cardiopulmonary bypass is already
started if an injury occurs. The disadvantage is that extensive mediastinal dissection,
including dissection of a planned right internal thoracic artery, must be done after
heparin. We rarely employ this approach except when an aortic aneurysm is adherent to
the sternum and renders sternotomy during deep hypothermia and circulatory arrest the
best approach.
Once the sternum is divided, the sooner the pleural cavities are entered, the better. A
general principle of dissection during reoperation is that starting at the level of the
diaphragm and proceeding in a cranial direction usually is safest. At the level of the
diaphragm few critical structures can be injured if the wrong plane is entered. Usually
we dissect along the level of the diaphragm to the patient's right side until the pleural
cavity is opened; we then detach the pleural reflection from the chest wall to the
innominate vein. The innominate vein is dissected from both sides of the sternum with
scissors, to prevent stretch injury.
Once the right side of the sternum is separated from cardiac structures, it is possible
usually to prepare a right ITA graft. Because of parietal pleural thickening, longer ITA
grafts during reoperation are harder to obtain than during primary procedures;
therefore, the right ITA is frequently used as a free graft. Once the right ITA dissection is
completed to the superior border of the first rib, an incision is made in the parietal
pleura to separate the proximal ITA from the phrenic nerve (Fig. 19-12) . Thus, if a right
ITA needs to be converted to a free graft during aortic cross-clamping, division is easier
because the proximal ITA is identified easily.
Although intrapericardial dissection of the left side of the heart is deferred until later,
freeing the left anterior chest wall from underlying structures (that may include a patent
ITA graft) is undertaken now. This is difficult only if a patent ITA graft is densely adherent
to the chest wall. Again, it is best to enter the left pleural cavity at the level of the
diaphragm and proceed cranially. The most difficult point usually is at the level of the
sternal angle where a patent ITA graft may approach the midline and adhere to the
sternum or aorta. There are no tricks for dissecting out a patent ITA graft except being
careful. The danger to a patent left ITA graft during sternal re-entry and mediastinal
dissection is entirely related to the strategy used at the primary operation. Ideally,
pericardium should be divided at the primary operation to allow the left ITA graft to run
posterior to the lung through the pericardial incision to the LAD or circumflex artery (Fig.
19-13) . When this is done, the lung lies anterior to the left ITA and prevents adherence
to the aorta or chest wall.
Once the left side of the chest wall is free, the left ITA is prepared, if it has not been
used previously. The sternal spreader is inserted and intrapericardial dissection of the
aorta and right atrium is accomplished. Again, in most cases it is safest to find the
correct dissection plane at the level of the diaphragm and to continue around the right
atrium to the aorta. This dissection may be dangerous if an atherosclerotic vein graft to
the right coronary artery lies over the right atrium. Manipulation of atherosclerotic vein
grafts may produce atherosclerotic emboli to distal coronary arteries; it is best to
employ a no touch technique with such grafts. If a vein graft to the right coronary artery
lies awkwardly over the right atrium, it is best to avoid the right atrium and use femoral
vein and superior vena caval cannulas for venous drainage (Fig. 19-14) . The
atherosclerotic vein graft can be disconnected once cardiopulmonary bypass is
established, the aorta is cross-clamped and cardioplegia is given.
During dissection of the ascending aorta the goal is to obtain enough length for
cannulation and cross-clamping, and to avoid the most common error of aortic
subadventitial dissection. It is important to leave the adventitia on the aorta. The correct
level of dissection on the aorta usually is found either by dissecting the overlapping right
atrium from the antero-lateral aortic root or by dissection under the innominate vein. By
identifying the innominate vein and leaving all tissue beneath the vein on the aorta, the
surgeon can avoid creating a subadventitial plane. At the level of the innominate vein
the pericardial reflection on each side of the aorta is identified easily. Division of the
pericardial reflection on the left side leads to the plane between the aorta and
pulmonary artery. Once the left side of the aorta is identified, the surgeon can dissect
posteriorly on the medial surface of the left lung toward the hilum. If a patent left ITA graft
is present, the pedicle of tissue between these two dissection planes usually includes
the graft and clamping occludes it. Last, the superior vena cava is separated from the
right side of the aorta and once this is done, the aorta can be cross-clamped.
When the aorta is dissected out heparin is given and cannulation is undertaken.
Although the ascending aorta is the most common site for arterial cannulation, aortic
atherosclerosis frequently is present in reoperative patients. Cannulation of an
atherosclerotic ascending aorta may produce emboli that cause stroke, myocardial
infarction, or multi-organ failure. If aortic atherosclerosis is present, alternative
cannulation strategies should be considered. [34 ] , [35 ] Although aortic atherosclerosis
sometimes may be palpated, the most effective identification is by echocardiography.
The femoral artery is the most widely used alternative arterial cannulation site. However,
arteriopathic patients often have severe femoral artery atherosclerosis that makes
cannulation difficult. Also when the descending aorta is atherosclerotic, retrograde
arterial perfusion risks cerebral embolization of atherosclerotic debris. The axillary
artery is an alternative arterial cannulation site that we use with increasing frequency.
Atherosclerotic disease usually is not present in the axillary artery and cannulation
allows antegrade perfusion (Fig. 19-15) . [36 ] Venous cannulation usually is
accomplished with a single two-stage right atrial cannula. A transatrial coronary sinus
cardioplegia cannula is inserted via a right atrial pursestring with the aid of a stylet. A
needle is placed in the ascending aorta for delivery of antegrade cardioplegia and for
use as a vent (Fig. 19-16) .
Cardioplegia
The myocardial protection strategy used by the author during most coronary
reoperations is a combination of antegrade and retrograde delivery of intermittent cold
blood cardioplegia combined with a dose of warm reperfusion cardioplegia (hot shot)
given prior to aortic unclamping. The principles of this strategy were developed by
Buckberg and colleagues. [37 ] , [38 ] Multiple types of cardioplegic solutions have been
described and most provide a metabolic environment that effectively protects
myocardium. Because potential anatomic difficulties in delivering cardioplegia during
reoperations, details of delivery are very important for adequate myocardial protection.
The cardioplegia era began with the strategy of delivering antegrade cardioplegia to
the myocardium via the aortic root and in most primary bypass operations this method
works well. During reoperations, however, antegrade cardioplegia is not effective for
areas of myocardium supplied by patent, in situ arterial grafts and may be dangerous
because of the risk of embolization of atherosclerotic debris into the coronary arteries
from old vein grafts. Development of techniques for delivery of cardioplegia into the
coronary sinus and through the cardiac venous system to the myocardium (retrograde
cardioplegia) is a major step forward in myocardial protection during reoperation. [39 ] ,
[40 ] Retrograde cardioplegia avoids atheroembolism from vein grafts and also can be
helpful in removing atherosclerotic debris and air from the coronary system.
Furthermore, it can deliver cardioplegia to areas supplied by in situ arterial grafts. The
biggest disadvantage of retrograde cardioplegia is that it is not always possible to
place a catheter in the coronary sinus that will deliver cardioplegia consistently. When
using retrograde cardioplegia, it is important to monitor the adequacy of delivery by
measuring coronary sinus pressure and noting distention of cardiac veins with arterial
blood, myocardial cooling, and return of desaturated blood from open coronary arteries.
Cardiopulmonary bypass is started; the perfusionist empties the heart and the patient is
cooled to 2832°C; the aorta is cross-clamped; and cardioplegia usually is induced
through the aortic root. It is helpful to occlude patent arterial grafts to induce and
maintain cardioplegic protection. If a patent arterial graft cannot be clamped
immediately, systemic perfusion temperature is decreased to 25°C until control of the
graft is achieved. Once antegrade cardioplegia is given for 23 minutes, we shift to
retrograde perfusion for another 23 minutes. Antegrade cardioplegia risks embolization
from atherosclerotic vein grafts, but if these grafts are not manipulated, the danger is
relatively small. Once adequate retrograde cardioplegia delivery is established, that
route is often used predominantly for maintenance doses.
Pericardial Dissection
When the heart is completely arrested, intrapericardial dissection of the left ventricle is
completed. Again, it is safest to start at the level of the diaphragm. The dissection is
extended along the diaphragm out to the left of the apex of the heart. Once the apex is
identified, the surgeon can divide the pericardium in a cranial direction on the left side
of the LAD coronary artery (Fig. 19-17) . A patent LITA (left internal thoracic artery) to
LAD graft will lie within the strip of pericardium over the LAD. Dissection of this pedicle
from the anterior aspect of the pulmonary artery allows an atraumatic clamp across the
patent ITA graft and also allows passing new bypass grafts from the aorta beneath the
patent ITA graft to left-sided coronary arteries. Advantages of waiting until after aortic
clamping and arrest to dissect out the left ventricle are more accurate dissection, less
damage to the epicardium, less bleeding, less risk of emboli from manipulation of
atherosclerotic vein grafts, and safer dissection of patent ITA grafts.
Once the heart is completely dissected out, target coronary arteries are identified,
needed lengths of bypass conduits are determined, and the final operative plan is
established. Old grafts and epicardial scarring present during reoperations makes
preoperative prediction of conduit length difficult, particularly for arterial grafts.
Therefore, the operative plan must be flexible because until the heart is completely
dissected out, it is not always clear which bypass grafts will reach which coronary
vessels. Patent, atherosclerotic vein grafts that will be replaced are disconnected
before anastomoses are made. The usual order of anastomoses used by the author is
distal vein grafts, distal free arterial grafts, distal in situ arterial grafts and, last, proximal
(aortic) anastomoses.
Stenotic Vein Grafts
When should patent or stenotic vein grafts be replaced and what should they be
replaced with? Atherosclerosis in vein grafts is common if grafts are more than 5 years
old, even if the grafts look normal by angiography. Although 2030 percent of vein grafts
continue to function 20 years after operation, leaving old vein grafts in place risks
embolization of atherosclerotic debris at the time of reoperation and also premature
graft stenoses or occlusions after reoperation. On the other hand, replacement of all
vein grafts extends operation and may use up all available bypass conduits.
Our general rule is to replace all vein grafts more than 5 years old at the time of
reoperation, even if those grafts are not angiographically diseased. However, this
strategy assumes that conduits are available. Inspection of vein grafts at reoperation
occasionally identifies a graft that appears angiographically normal and without
thickening or atherosclerosis by direct inspection. Often these pristine vein grafts are
left alone.
When old vein grafts are replaced with new vein grafts this is accomplished usually by
creating the new vein to coronary anastomosis at the site of the previous distal
anastomosis. Extension of native vessel atherosclerosis may make construction of
grafts at new sites difficult. When removing an old vein graft, only 1 mm or so of the old
vein is left in place (Fig. 19-18) , but that arteriotomy often provides the best access to a
heavily diseased native coronary artery. In addition, this strategy provides assurance
that removal of the old vein graft does not devascularize any area. If significant native
vessel stenoses have developed distal to the old vein graft, the new graft is placed to
the distal artery. Since many reoperative patients have proximal native coronary
occlusions and multiple stenoses throughout the vessel, it is important to realize that
proximal segments of coronary arteries and their branches may not be supplied by new
distal grafts. More than one graft to a major coronary artery may be desirable during
reoperation (Fig. 19-19) .
Sequential vein grafts are often very helpful during reoperation, as they allow more distal
anastomoses and fewer proximal anastomoses. Sites for proximal anastomoses often
are at a premium in the scarred reoperative aorta.
Arterial Grafts
Arterial coronary artery bypass grafts have many advantages at the time of reoperation.
First, they are often available. Second, the tendency of arterial grafts to remain patent
even when used as grafts to diffusely diseased coronary arteries, makes them
particularly applicable for reoperative candidates. Third, in situ arterial grafts do not
require a proximal anastomosis. If the left ITA has not been used previously, a strong
attempt should be made to use it as an in situ graft to the LAD coronary artery. The
importance of this graft is well-established for patients who have had a primary
operation and there is suggestive evidence that it also improves long-term outcomes of
patients who have repeat surgery. [6 ] Some reoperative candidates will have received
a left ITA graft during their first procedure but often the right ITA is available at
reoperation. During primary operations the right ITA usually can be brought across the
midline as an in situ graft to left-sided vessels, but this maneuver is more difficult during
repeat surgery and the right ITA usually is used as a free graft.
Arterial graft aortic proximal anastomoses are a problem at reoperation, because of

aortic scarring and thickening. However, when old vein grafts become occluded, a
bubble at the aortic end of the old vein graft often is a good spot for the proximal
anastomosis of a free aorta to coronary arterial graft (Fig. 19-20) . In addition, if new
vein grafts are used, the hood of a new vein graft is a favorable location for an arterial
graft anastomosis. Late angiographic data regarding this strategy are not available, but
the relative freedom of the vein graft hood from development of atherosclerosis strongly
suggests that these anastomoses will be successful.
Another effective strategy is to use either an old or newly constructed arterial graft as a
spot for the proximal anastomosis of a free arterial graft (Fig. 19-21) . Composite
arterial grafts, usually using a new in situ left ITA graft for the proximal anastomosis of a
free right ITA graft have been employed with increasing frequency and early outcomes
are favorable. [41 ] , [42 ] This concept is particularly useful during reoperations since an
aortic anastomosis is avoided and a shorter right ITA length is needed to reach distal
circumflex arteries. There are also advantages of using an old, patent ITA graft for the
proximal anastomosis of a new arterial graft, since an old graft often increases in size
and preoperative angiograms ensure patency. When an LITA to LAD graft is
compromised by a distal LAD lesion, a short segment of a new arterial graft can bridge
the stenosis to the distal LAD (Fig. 19-21) . Heavy scarring around a previously
performed arterial graft may complicate these strategies and it is important to avoid
technical misadventures. Damage to a previously well-functioning left ITA to LAD graft is
a serious adverse event.
Arterial Graft Replacement of a Vein Graft
Can an ITA graft be used to replace a vein graft during reoperation? When faced with
replacing a stenotic or patent vein graft during reoperation, a number of options, all with
potential disadvantages, are available.
The surgeon may leave the old vein graft in place and add an arterial graft to the same
coronary vessel. The dangers of this approach are that atherosclerotic emboli from the
old vein may occur during reoperation and competitive flow between the vein graft and
the arterial graft may jeopardize the ITA graft after reoperation.
The surgeon may remove the old vein graft and replace it with an ITA graft. This
decreases the likelihood of atherosclerotic embolization and competitive flow but risks
hypoperfusion if the arterial graft cannot immediately supply all of the flow previously
carried by the vein graft.
Replace the old vein graft with a new vein graft. The disadvantage of this is that the
coronary vessel remains dependant upon a vein graft.
When we examined these choices in a retrospective study of operations for patients

with atherosclerotic vein grafts supplying the LAD coronary artery, the worst outcomes
resulted from removing a patent (although stenotic) vein graft and replacing it with only
an ITA graft. [30 ] That strategy was associated with a significant incidence of
hypoperfusion and severe hemodynamic difficulties during reoperation and was treated
effectively by adding a vein graft to the same coronary artery. The incidence of
myocardial infarction associated with residual stenotic vein graft in place was low. Thus,
although atherosclerotic emboli from an old vein graft is a risk, it is rarely a catastrophe
with the use of retrograde cardioplegia. We usually remove atherosclerotic vein grafts
replaced with a new vein graft but leave stenotic vein grafts when the same vessel is
grafted with an artery (Fig. 19-22) .
Alternative Arterial Grafts
Alternative arterial grafts are often useful during reoperation. The radial artery has
particular advantages during repeat surgery because it is larger and longer than other
free arterial grafts. These qualities increase the range of coronary arteries that can be
grafted and make proximal anastomoses more secure. Disadvantages of radial artery
grafts are that some patients require the radial artery for digital perfusion, and the
uncertainty of long-term patency rates. In the early 1970s, radial artery grafts had poor
patency rates. With more meticulous harvesting and administration of calcium channel
blockers postoperatively, patency rates for radial artery grafts may be improved. Recent
early studies of radial artery grafts show favorable patency rates but there are few
long-term data. If high early patency rates are confirmed by tests of time, the radial
artery will be used extensively during reoperations.
The inferior epigastric artery is often too short to function as a separate aorta to
coronary graft during reoperation but can be extremely useful as a composite arterial
graft. We commonly use short segments of inferior epigastric artery between a patent
ITA graft and the distal LAD, as illustrated in Figure 19-21 .
The right gastroepiploic artery (RGEA) has good mid-term graft patency rates and often
is useful during reoperation because it is an in situ graft. [43 ] Furthermore, it can be
prepared prior to median sternotomy. It is most often used as an in situ graft to the
posterior descending branch of the right coronary artery or to the distal LAD.
The aortic anastomoses of vein and arterial grafts are performed last during a single
period of aortic cross-clamping. Sites for aortic anastomoses are often at a premium
because of previous scarring, atherosclerotic disease, or the use of Teflon felt during
the primary operation. Often proximal anastomoses of previous vein grafts are the best
sites for new anastomoses. Once proximal anastomoses are constructed, a hot shot of
substrate enhanced blood cardioplegia is given, first retrograde to remove air from
grafts and the aortic root and then antegrade. The aortic cross- clamp is then removed.
The advantages of constructing aortic anastomoses during a single period of aortic

cross-clamping are minimal aortic trauma and excellent visualization of proximal
anastomoses. Furthermore, if patent or stenotic vein grafts are removed and replaced,
aortic declamping does not re-establish perfusion until aortic anastomoses are
completed. The disadvantage of this approach is that the duration of aortic
cross-clamping is prolonged. However, our strategies for reoperation are not based on
minimizing the duration of myocardial ischemia. If cardioplegia can be delivered
effectively, the valid metabolic concepts of cardioplegia ensure myocardial protection.
Failure of myocardial protection is usually caused by anatomic factors. Our approach to
coronary reoperations (which are, by necessity, complex operations) is to use
cardioplegic myocardial protection to lengthen periods of aortic occlusion, to permit
strategies that avoid adverse anatomic events, and to improve blood flow to all viable
myocardium.
ALTERNATIVE APPROACHES TO CORONARY REOPERATIONS
Although most coronary reoperations are performed through a median sternotomy with
cardiopulmonary bypass, special situations that make either the incision or
cardiopulmonary bypass undesirable prompt consideration of alternative approaches.
The most common situation is the presence of severe pathology of the ascending aorta.
Management of the Bad Aorta during Reoperation
Severe ascending aortic calcification or atherosclerosis make aortic cannulation and

cardiopulmonary bypass dangerous and renders construction of aortic graft
anastomoses difficult. This problem has two solutions: a complex operation using deep
hypothermia, circulatory arrest with aortic replacement or endarterectomy, or a less
complex operation that avoids cardiopulmonary bypass.
MANAGEMENT WITHOUT CARDIOPULMONARY BYPASS
Reoperations can be done without cardiopulmonary bypass using in situ arterial grafts
to avoid aortic anastomoses. The disadvantages of this solution are that only a few
grafts can be accomplished without bypass and perfect anatomic results are more
difficult to achieve. Through a median sternotomy incision the left or right ITA can be
used as an in situ graft to the LAD-diagonal system. Once the median sternotomy is
completed and adhesions are taken down, an ITA graft is prepared. Multiple stay
sutures of 2-0 silk are placed in the left pericardial edge and are used to pull the edge
anteriorly. The pericardium is dissected off the LAD but remaining intrapericardial
adhesions are left to help dampen cardiac movement. Heparin is injected, tidal volume
is decreased to limit ventilatory motion and short acting beta blockers are given to slow
the heart rate. Elastic bands or 4-0 sutures are placed around the coronary artery to
control blood flow and the ITA to coronary anastomosis is completed.
The right coronary artery can be exposed by dissecting out the diaphragmatic surface
of the heart and placing stay sutures posteriorly in the pericardium. By drawing these
sutures anteriorly, the diaphragmatic surface of the heart rotates into view. This
maneuver exposes the posterior descending branch of the right coronary artery and that
vessel can be grafted with an in situ gastroepiploic graft.
DEEP HYPOTHERMIA AND CIRCULATORY ARREST
Unfortunately, most reoperative candidates need more extensive procedures than grafts
to major LAD and right coronary artery branches. Usually native vessels are so
diseased that accurate and complete revascularization cannot be accomplished reliably
without cardiopulmonary bypass. For patients who need extensive coronary
reoperations and who have severe ascending aortic disease, the best strategy usually
is to use deep hypothermia, circulatory arrest, retrograde cerebral perfusion, and to
replace the ascending aorta. Obviously deep hypothermia requires cardiopulmonary
bypass and cannulation of the right axillary artery often is the safest way to reach the
arterial system. After starting cardiopulmonary bypass, systemic temperature is lowered
to 20°C without aortic occlusion. The systemic circulation is arrested and retrograde
cerebral perfusion with arterial blood is begun through a superior vena caval cannula.
The calcific or atherosclerotic aorta is excised and replaced with a Dacron graft.
Retrograde (venous) cerebral perfusion of arterial blood removes atherosclerotic

emboli from the arterial circulation, maintains cerebral hypothermia, and prevents and
treats air emboli. [53 ] Once the distal aortic anastomosis is completed, systemic
arterial circulation is re-established, the Dacron graft is clamped and rewarming is
completed while the coronary bypass operation is completed. Proximal vein graft
anastomoses are made to the Dacron graft or to a pericardial patch on the Dacron
graft. This strategy complicates the operation but is a reliable method to avoid stroke
and myocardial infarction in patients with severe aortic atherosclerosis.
Reoperations via Left Thoracotomy
A left thoracotomy may provide access for reoperations when repeat median
sternotomy is extremely dangerous. [45 ] Examples include severe mediastinitis or
infection after a previous operation or a crossing right ITA graft to the LAD coronary
artery. Our most common indication for left thoracotomy is for limited reoperations to
circumflex vessels without cardiopulmonary bypass. Disadvantages of reoperations
through a left thoracotomy are inability to cross-clamp the aorta and use cardioplegia,
limited access to the right coronary artery and sometimes the anterior descending
coronary artery; cannulation of the femoral or left subclavian arteries, and unavailability
of the right internal thoracic artery. Mills et al. have used the subscapular artery as a
bypass conduit with a left thoracotomy. [46 ]
The left thoracotomy is usually made in the 5th intercostal space laterally. This incision
may be extended anteriorly to provide better access to the distal anterior descending
coronary artery. When using cardiopulmonary bypass, the femoral vein is cannulated.
Either the left femoral artery or the left subclavian artery also is cannulated. If cardiac
immobilization is needed, systemic hypothermia and ventricular fibrillation are used.
It is often possible to do limited operations on branches of the circumflex system without

cardiopulmonary bypass through a left thoracotomy. After heparin, a proximal vein
anastomosis is made to the left subclavian artery or to the descending thoracic aorta
using a partial occluding clamp. When grafting a native coronary artery, the artery is
isolated with sutures or tapes. If the operative mission is to replace an old circumflex
vein graft with another vein graft, often the old vein graft is cut off at its point of insertion
into the coronary artery. A small rim of vein is left to use in the anastomosis to the new
vein graft. This anastomosis usually can be accomplished without occluding arterial
inflow.
Minimally Invasive Reoperation
Today, concepts of limited incision surgery (optimistically, minimally invasive surgery)

are being considered for coronary arterial bypass. Adhesive fixation of cardiac
structures and difficult coronary access in patients with previous surgery limits
application of these concepts to reoperations. Nevertheless, the distal LAD can usually
be exposed through a limited anterior left thoracotomy by removing the 4th costal
cartilage. During primary minimally invasive surgery the left ITA is used usually as a graft
in situ to the LAD, but during reoperations intrathoracic adhesions restrict ITA
dissection when the vessel has not been used already. Alternatively, the gastroepiploic
artery may be prepared through a small upper abdominal incision and brought through
the diaphragm as an in situ graft to the distal LAD (Fig. 19-23) . Also, the right coronary
artery may be exposed by dividing the xiphoid. An off the pump anastomosis using an in
situ RGEA graft can be made to the posterior descending branch of the right coronary
artery through a limited incision. These are difficult anastomoses and, although these
techniques may be helpful in special circumstances, these operations are unlikely to
become common.
RESULTS OF CORONARY REOPERATIONS
Coronary reoperations are riskier than primary operations. The Society of Thoracic
Surgeons (STS) reports an in-hospital mortality of 6.95 percent associated with
reoperations in the hospitals contributing to their database for the years 19911993, and
a multivariate analysis of all isolated coronary bypass surgery identifies previous
operation as a factor increasing the mortality rate. [47 ] , [48 ] At the Cleveland Clinic
Foundation, the in-hospital mortality rate of a first reoperation ranged between 34
percent from 1967 through 1991 and was 3.7 percent for 1663 patients having repeat
surgery from 1988 through 1991. [5 ] [7 ] Recent mortality rates from other large series
range from 6.9 to 11.4 percent; most are in the range of 7 percent. [49 ] [53 ] All of these
figures are 23 times the risk of primary bypass surgery.
The reason coronary reoperations are associated with higher in-hospital mortality is
related to an increased risk of perioperative myocardial infarction. In the most recent
cohort of patients undergoing reoperation at the Cleveland Clinic Foundation, the cause
of perioperative death was cardiovascular in 85 percent of cases. This figure contrasts
with recent studies of primary operations in which non-cardiac causes of death are
increasingly important. [2 ] , [7 ] Furthermore, in the reoperative series, in-hospital
mortality is associated with a new perioperative myocardial infarction in 67 percent of
cases. The causes of these perioperative infarctions are sometimes difficult to
establish even at post mortem examination and not all patients who die after bypass
surgery undergo autopsy. However, the identified causes include incomplete
revascularization owing to distal coronary artery disease, vein graft thrombosis, ITA
graft failure, atherosclerotic embolization from vein grafts, injury to bypass grafts,
hypoperfusion from arterial grafts, preoperative myocardial infarction, and
complications of PTCA.
Multiple studies of patients undergoing reoperation identify increased age, female

gender, and emergency operation as clinical variables that have a high association with
in-hospital mortality. Although there is no standard definition of emergency, mortality
rates after emergency reoperations range from 13 to 40 percent. [7 ] , [26 ] , [47 ] , [51 ] ,
[52 ] Clearly, there is a major increment in risk associated with emergency
reoperationslarger than for patients undergoing primary surgery.
Age and gender interact as risk factors. Although males have a slight increase in
in-hospital mortality with increasing age, there is a dramatic increase in mortality for
women (Fig. 19-24) . [7 ] In many studies of primary bypass surgery, female gender
increases risk slightly, but the reasons for a dramatic effect during reoperation are not
clear. Other clinical variables associated with increased risk include descriptors related
to abnormal left ventricular function (prior myocardial infarction, history of congestive
heart failure, ejection fraction) and hypertension.
It is noteworthy that only variables that can be consistently identified and quantified are
designated as risk factors. For example, experience and logic dictate that severe
atherosclerosis of the ascending aorta is a major risk factor, but this is rarely cited in
large studies because patients do not routinely have echocardiography to identify aortic
atherosclerosis.
The presence of patent ITA grafts and atherosclerotic vein grafts is a suspected risk
factor for reoperation, but we have never documented an increased mortality rate for
patients with patent ITA grafts. We note that the risk of damage to the ITA dropped from
8 percent in our early experience to 3.7 percent more recently. This improvement is
almost entirely related to surgical experience. With proper positioning of an ITA graft at
the primary operation a patent LITA to LAD or circumflex graft does not impede
reoperation. A patent in situ right ITA graft that crosses the midline to supply the LAD or
circumflex system is more difficult and requires extreme care when reoperating through
a median sternotomy. Although these situations are uncommon and provide difficult
technical challenges, risks for these patients are not increased.
On the other hand, past studies indicate an increased perioperative risk for
atherosclerotic vein grafts. Perrault et al. document mortality rates of 7, 17, and 29
percent for patients with 1, 2, or 3 stenotic vein grafts, respectively. [27 ] In a previous
study of our patients with atherosclerotic vein grafts the presence of an atherosclerotic
vein graft to the LAD increased in-hospital risk. [22 ] However, more recently we find no
increase in mortality for atherosclerotic vein grafts, although patients with multiple
stenotic grafts have a nonsignificant trend toward increased risk. [7 ] These improved
results are related to improved technology, retrograde cardioplegia, and increased
surgical experience.
Although arterial grafts offer advantages at reoperation, their use prolongs an already
complex operation and may influence perioperative risk. However, we find that use of
single or double ITA grafts at reoperation does not increase perioperative risk and, in
fact, absence of an ITA graft (constructed at either the first or second operation) is
associated with increased in-hospital mortality. In that study, selection of grafts was not
randomized; thus the increased risk for patients who received only vein grafts may
relate to patient variables rather than surgical strategy. Nevertheless, the use of arterial
grafts does not increase risk.
Except for an increased incidence of perioperative myocardial infarction, in-hospital

morbidity is not increased for patients undergoing reoperation. One important
observation relates to wound complications. Multiple groups, including ours, find
increased risk of wound complications in diabetic patients who receive bilateral,
simultaneous ITA grafts. However, this risk is not increased for diabetic patients who
receive staged ITA grafts, one at the first and another at the second operation.
LATE RESULTS
Patients who have reoperation have more advanced native coronary atherosclerosis
than at the time of their primary surgery, and anatomic results of revascularization are
less perfect. Although the definition of complete revascularization varies widely, few
reoperative candidates receive bypass grafts to all diseased segments of all arteries.
Therefore, it is not surprising that long-term results of reoperation are not as favorable
as long- term results of primary procedures.
The likelihood of recurrent angina after any bypass operation is related to time, but
angina is more common after repeat surgery than after primary operation. Follow-up of
our reoperative patients at a mean interval of 72 months shows that 64 percent of
patients are in Class I, although only 10 percent of patients are in Class III or Class IV. [6
] Weintraub et al. also note that 41 percent of reoperative patients experience some
angina at 4-year follow-up. [26 ]
Late survival rates after reoperation are also inferior to those after primary surgery.
Weintraub et al. note a 76 percent 5- year and 55 percent 10-year survival rate and our
most recent follow-up study find a 10-year survival of 69 percent for in-hospital survivors
(Fig. 19-25) . [6 ] , [26 ] Predictors of late survival vary among studies but left ventricular
dysfunction, advanced age and diabetes are consistently associated with decreased
late survival. Variables related to decreased late survival for 2,429 hospital survivors of
a first reoperation identified by multivariate testing are listed in Table 19-3 .The
influence of ITA grafts on late survival is difficult to determine for reoperations. We find a
positive influence of a single ITA graft on late survival, but the effect is not as dramatic
as for primary operations. Weintraub et al. did not document improved survival
associated with ITA grafting.
MULTIPLE CORONARY REOPERATIONS
Patients with more than one previous coronary operation are like first reoperations only
more so. Many patients undergo multiple reoperations 1520 years after their first
procedure, and severe native vessel disease and lack of bypass conduits are common
problems. Selection criteria vary widely among institutions but in-hospital mortality rates
have been increased relative to first reoperations. [54 ] , [55 ] Through 1993 we
reoperated on 392 patients who had more than one previous bypass operation with an
in-hospital mortality rate of 8 percent. Follow-up of the in-hospital survivors finds a late
survival rate of 84 percent at 5 and 66 percent at 10 postoperative years, respectively.
Although in-hospital risks are increased for these patients, long-term outcome is
relatively favorable.
CONCLUSION
Coronary reoperations continue to present adult cardiac surgeons with very difficult
challenges, in part because of many technical pitfalls, but also because coronary
reoperations are so common. The population of patients who have had previous bypass
surgery is huge and patients who develop recurrent ischemic syndromes expect
effective treatment. Although we now understand the long-term implications of vein
grafts, technical and operative time considerations are unlikely to stimulate a wave of
exclusive arterial revascularization for primary coronary operations. Thus, reoperations
will continue to increase and improvements over the principles outlined in this chapter
will continue to be an important goal.
PERIOPERATIVE STROKE
Incidence of Perioperative Stroke
To better understand the magnitude of the problem of perioperative cerebrovascular

accidents, one need only review some of the current literature on the growing incidence
of stroke. In 1986 Gardner et al. [1 ] reported the risk of stroke in their coronary bypass
patients to be a clear function of patient age. For patients less than 45 years of age, the
risk of perioperative stroke was 0.2 percent, rising to 3.0 percent for patients in their
60s and then to 8.0 percent for patients over age 75. In that study the risk factors
associated with stroke were increased age, preexisting cerebrovascular disease,
atherosclerosis of the ascending aorta, prolonged cardiopulmonary bypass time, and
severe perioperative hypotension.
Similarly, Tuman et al. [2 ] in 1992 investigated the effects of age on the incidence of
low cardiac output, myocardial infarction, and neurologic injury in coronary bypass
patients. Whereas the incidences of both low cardiac output and myocardial infarction
were constant as patient age increased, the risk of neurologic damage rose
exponentially after age 65. The stroke rate in their patients rose from 0.9 percent for
patients less than age 65 to 8.9 percent for patients older than age 75.
To place this problem of increasing perioperative stroke risk with increasing patient
age into a contemporary context, at the Massachusetts General Hospital (MGH) the
mean age of patients having coronary artery bypass grafting has risen from 56 years in
1980 to over 67 years in 1994. During the same time interval, the percentage of
patients aged 70 years or older has risen from 6 percent in 1980 to over 40 percent in
1994.
Causes of Perioperative Stroke
Given, then, that the rate of perioperative stroke is an increasing function of patient age,
it is important to consider possible causes of perioperative neurologic injury (Table
20-1) . The most common cause of perioperative stroke is atherosclerotic or
thromboembolic debris from the heart or major vessels. Less commonly, entrained air
may be a cause of neurologic events but usually not focal deficits. Intracardiac emboli
can arise from mural thrombus secondary to myocardial infarction, left atrial thrombus
associated with mitral valve disease or atrial fibrillation, or suture lines in the left atrium
or left ventricle used for venting the left side of the heart or for access to left-sided
structures. Catheters placed in the left side of the heart also can be a source of
postoperative emboli.
The aorta has been recognized increasingly as a source of embolic debris. Cannulation
of the ascending aorta for cardiopulmonary bypass and the frequent use of aortic
occlusion clamps and intra-aortic cardioplegia delivery devices increase the risk of
dislodging any existing atherosclerotic material from the aortic wall. Wareing et al. [3 ]
have demonstrated clearly that aortic atherosclerosis is an important contributor to the
problem of perioperative neurologic injury. The use of intraoperative echocardiography
of the ascending aorta to identify the degree of atherosclerosis of the aorta and the
subsequent alteration of operative techniques to ameliorate identified problems have
led to an improved stroke risk in their patients.
Emboli from diseased carotid arteries are a well-defined contributor to the risk of
perioperative neurologic injury. Indeed, some evidence exists that the morphologic
nature of the carotid plaque can have an important impact on the risk of stroke for
patients with carotid artery stenosis. In a companion study to the North American
Symptomatic Carotid Endarterectomy Trial investigators found that ulcerated carotid
plaques were significant incremental risk factors for stroke across all degrees of carotid
stenosis. [4 ]
Neurologic injury also can result from the low-flow phenomenon on cardiopulmonary
bypass. The importance of maintaining an adequate perfusion pressure while on
bypass has been emphasized recently by Schwartz et al. [5 ] In their study they noted
that cerebral blood flow depends on arterial perfusion pressures and not on
cardiopulmonary bypass flow rates. Low cerebral blood flow occurred with perfusion
pressures of less than 60 mmHg and was not influenced by the pump flow rate.
Obviously, in the presence of a carotid stenosis the maintenance of adequate perfusion
pressure becomes even more important. When there is occlusion of one of the carotid
or intracerebral arteries, blood flow to portions of the brain depends on adequate
collateral circulation. Once again, the importance of perfusion pressure is obvious.
Whether or not carotid or intracerebral vascular spasm can be a contributor to low-flow
neurologic injury is still very much open to question.
Finally, the development of intracranial hemorrhage may be a contributor to neurologic

injury following cardiopulmonary bypass, but the fact that this does not occur more
frequently is truly amazing, given that all the patients are so intensely anticoagulated for
cardiopulmonary bypass. In fact, at MGH, where computed tomographic (CT) scans are
obtained routinely to guide the potential use of heparin following clinical suspicion of
perioperative stroke, the finding of intracerebral bleeding is extremely uncommon.
From a surgical point of view, of all the potential causes of perioperative neurologic
injury listed in Table 20-1 , carotid stenosis is the one anatomic situation about which
the surgeon can do something routinely to remove the pathology. Thus the importance
of defining carotid disease as a true potential risk factor for perioperative stroke is
obvious.
Relationship of Carotid Stenosis to Perioperative Stroke
Early studies that attempted to relate the presence of carotid stenosis to the
development of perioperative neurologic injuries used auscultatory evidence of carotid
disease as the method of diagnosis. In 1988 Reed et al. [6 ] from our institution
investigated the relationship between carotid bruits and perioperative stroke. They were
able to document a 3.9-fold increase in the odds ratio for stroke in the presence of a
carotid bruit.
Unfortunately, carotid bruits are not a very reliable indication of the presence of internal
carotid stenosis, let alone discriminatory in the degree of stenosis. In 1994 Sauve et al.,
[7 ] as a part of the North American Symptomatic Carotid Endarterectomy Trial,
investigated the ability of carotid bruits to predict the degree of carotid stenosis and
found poor correlation between auscultatory findings and the degree of carotid stenosis
as defined by carotid angiography. Indeed, it is well known that as carotid lesions
progress to very high degrees of stenosis, a carotid bruit may not be audible.
Much better definition of the degree of carotid stenosis can be obtained with the use of
noninvasive carotid testing with Doppler ultrasound techniques. The reliability of these
methods not only to quantify the degree of carotid stenosis but also to provide actual
visual images of the stenosis has made these methods the routine first step in
evaluating patients suspected of having carotid artery occlusive disease.
Brenner et al. [8 ] studied 4047 cardiac surgical patients and found a 9.2 percent rate of
stroke or transient ischemic attacks in patients found to have asymptomatic carotid
stenoses by noninvasive testing. This rate was significantly greater than the 1.3 percent
rate in patients with no carotid stenosis.
In 1990 Faggioli et al. [9 ] published a very important study on the usefulness of routine
carotid noninvasive testing in coronary artery bypass patients. In their study they
performed routine noninvasive carotid testing in myocardial revascularization patients
who had no ischemic neurologic symptoms. The odds ratio for stroke was increased
9.9-fold in the presence of a documented carotid stenosis of greater than 75 percent.
For patients over age 60 with a greater than 75 percent carotid stenosis, the stroke rate
was 15 percent, versus 0.6 percent for patients of the same age but without evidence of
carotid disease. In addition, perioperative strokes occurred in 4 (14.3 percent) of 28
patients who had a greater than 75 percent carotid stenosis who did not have
concomitant carotid endarterectomy. This experience compared with no strokes in 19
patients with greater than 75 percent carotid stenoses who had a prophylactic carotid
endarterectomy at the time of coronary artery bypass grafting.
In 1992 Berens et al. [10 ] reported their results with routine carotid duplex scanning for
all cardiac surgical patients aged 65 years or older. The risk of stroke was 2.5 percent
for carotid lesions that were less than 50 percent, 7.6 percent for carotid stenoses that
were greater than 50 percent, 10.9 percent for carotid stenoses greater than 80
percent, and 10.9 percent for unilateral carotid artery occlusion.
Thus, adequate evidence exists that significant carotid artery stenoses are an important
incremental risk factor for the development of perioperative neurologic injury following
coronary artery bypass grafting. In addition, the study by Faggioli et al. [9 ] suggests that
carotid endarterectomy performed with coronary grafting yields a lower stroke rate.
Mechanism of Perioperative Stroke with Carotid Stenosis
The actual mechanism of how carotid stenoses cause perioperative stroke is not fully
understood, especially in consideration of the fact that patients are fully anticoagulated
during cardiopulmonary bypass. Strokes due to carotid artery disease that occur during
operation may result from emboli from the carotid plaque itself. Possibly loss of pulsatile
perfusion or failure to maintain adequate perfusion pressure during bypass leads to
diminished flow distal to a significant stenosis and causes a watershed stroke.
However, the time of occurrence of perioperative strokes reported in the study by Reed
et al. [6 ] suggests that more than half the strokes occur following the immediate
postoperative period. These delayed strokes in patients with uncorrected carotid
stenoses may be related to the prothrombotic milieu that may occur in the early days
after cardiopulmonary bypass.
Relationship of Uncorrected Carotid Stenosis to Late Stroke
In 1985 Barnes et al. [11 ] assessed the late risk of untreated asymptomatic carotid
stenosis in 65 patients who had cardiovascular operations, of whom 40 had coronary
artery bypass grafting. At a mean follow-up of only 22 months, 10 percent of the
coronary bypass patients had died and 17.5 percent had suffered a stroke. Late
noninvasive carotid testing of the coronary bypass patients revealed progression of the
carotid artery disease in half the patients within 4 years.
CAROTID STENOSIS IN CORONARY ARTERY BYPASS PATIENTS
Incidence of Carotid Stenosis in Coronary Artery Bypass Patients
In 1977 Mehigan et al. [12 ] reported that routine noninvasive testing in 874 patients
prior to myocardial revascularization revealed a 6 percent incidence of significant
extracranial cerebrovascular disease. Ivey et al. [13 ] reported in 1984 that in 1035
patients having isolated coronary artery bypass grafting, routine screening for a history
of neurologic events and the presence of a cervical bruit revealed significant carotid
stenosis, as confirmed by ultrasonic duplex scanning in 86 patients (8.3 percent). In
addition, Faggioli et al. [9 ] evaluated 539 coronary artery bypass patients with no
symptoms of carotid ischemia using noninvasive methods. In their study, 8.7 percent of
the patients had a carotid stenosis of greater than 75 percent. The incidence rose from
3.8 percent for patients younger than age 60 to 11.3 percent for patients older than age
60.
Berens et al. [10 ] have reported their results with routine carotid duplex ultrasonography
in 1087 patients who were 65 years of age or older and who were candidates for
cardiac surgery (91 percent with coronary artery disease). Of their entire population,
with a mean age of 72 years, 186 (17.0 percent) had a greater than 50 percent carotid
stenosis and 65 (5.9 percent) had a greater than 80 percent carotid stenosis.
Predictors of severe carotid disease were female gender, peripheral vascular disease,
history of transient ischemic attacks or stroke, smoking history, and left main coronary
artery disease.
Diagnosis of Carotid Artery Disease
PHYSICAL EXAMINATION
Auscultation of a bruit over the neck may provide some suggestion of the presence of
carotid artery stenosis but is by no means diagnostic nor capable of revealing the
degree of carotid stenosis. [7 ] Indeed, as the degree of stenosis increases and
approaches total occlusion, the bruit will fade and may become inaudible. Palpation of
the carotid artery provides no useful information and theoretically can dislodge
thrombus or embolic debris.
NONINVASIVE TESTING
Given that auscultatory examination of carotid bruits is not reliable for assessing the
degree of carotid stenosis and that direct carotid angiography is both too expensive
and too invasive to serve as an initial test for all patients suspected of carotid artery
disease, noninvasive methods of assessing carotid stenosis have become the
procedures of choice for screening patients.
Indirect testing
One method of noninvasive indirect testing that has some usefulness in assessing the
degree of carotid stenosis is oculoplethysmography, an indirect measurement of the
pressure in the opthalmic artery, which in turn reflects the pressure in the distal internal
carotid artery. The test can compare pressure in the contralateral normal artery with
decreased pressures on the side of carotid stenosis and provide an estimate of the
severity of the carotid stenosis.
Another indirect testing method is transcranial Doppler, which assesses ophthalmic and
intracranial arterial flow and is especially useful in elucidating the status of collateral flow
above a lesion at the origin or in the siphon of the internal carotid artery. This method is
also useful for detecting additional disease in the intracranial extension of the internal
carotid system, especially the middle cerebral artery. Evaluation of the vertebral and
basilar arteries with this method can provide information about disease in those arterial
systems that may be contributing to neurologic symptoms.
Direct testing
Direct testing usually takes the form of either duplex or triplex ultrasound scanning. In
duplex ultrasound scanning a range-gated Doppler probe is directed at the bifurcation
of the common carotid artery, the origins of the internal and external carotid arteries,
and then the more distal portions of those vessels. The Doppler probe samples a small
volume of flowing blood in the artery at the point of maximum stenosis, just distal to the
point of maximal stenosis where turbulence is greatest, and then more distally in the
artery where laminal flow is reestablished. The higher the flow velocity, the tighter is the
stenosis, and the tighter the stenosis, the more turbulence is present. This mode of
testing provides information about the residual lumen diameter and plaque morphology.
Ulcerated areas in a plaque and calcification also can be identified. The value of the
study is very dependent on patient cooperation and the skill of the technician. Duplex
scanning cannot easily distinguish between complete occlusion and near occlusion with
a minimal residual lumen.
Triplex ultrasound scanning, or color-flow Doppler, combines the B-mode imaging of

duplex scanning with a multigated pulse Doppler, which allows flow measurements
across the entire vascular structure. As an added advantage over duplex scanning, the
data can be converted to color-coded flow displays over the B-mode image of the
vessel. Although the method can reveal turbulence over a larger area, this technique
also cannot differentiate near from total occlusion.
INDICATIONS FOR NONINVASIVE TESTING
Our current indications for performing noninvasive carotid testing are for those patients
with
1. An audible bruit in the neck
History of a prior stroke
History of transient ischemic attacks
Severe peripheral vascular disease

Advanced age
All the preceding are fairly self-explanatory, except the last. Because the incidence
of carotid stenosis rises dramatically in patients over 65, there certainly must be a
specific age at which it becomes cost-effective to screen all patients for carotid
disease. This statement has become particularly more pertinent since the
publication of numerous randomized trials that have verified the efficacy of carotid
endarterectomy as treatment for both symptomatic and asymptomatic severe
carotid stenoses. (These are discussed in detail below.) However, that age limit has
not yet been clearly determined. Such a determination will require demonstration of
cost savings obtained by performing carotid endarterectomy routinely versus the
cost of allowing uncorrected carotid stenoses to lead to expensive cerebrovascular
accidents in some patients.
DIRECT CAROTID ANGIOGRAPHY
Until recently at MGH, a noninvasive test suggesting severe carotid stenosis was an
indication for direct carotid angiography. For some patients who have neurologic
symptoms and an audible carotid bruit, direct carotid angiography was done without
noninvasive testing. Direct carotid angiography clearly yields the most detailed
images of the carotid arteries and their pathology. This technique can identify
ulcerative lesions, the degree of stenosis, and frequently the presence of mural
thrombus. It also provides the best information on the quality of the distal vessels
and collateral circulation. Unfortunately, carotid angiography is not without risks,
including aortic dissection or embolization of debris from carotid lesions that can
lead to procedure-related strokes. Cholesterol embolization due to catheter
manipulation in a diseased aorta also can cause severe embolic occlusions in other
vascular distributions, especially the renal arteries. Lastly, carotid angiography is
quite expensive.
MAGNETIC RESONANCE ANGIOGRAPHY
Beginning in the early 1990s, magnetic resonance angiography began to be used

increasingly to define the degree and location of carotid lesions. The principal
advantage of magnetic resonance angiography over direct carotid angiography is
that it is essentially noninvasive and eliminates the risk of procedure-related
cerebrovascular accidents. A severe stenosis is usually manifested by signal
dropout when the stenosis is greater than 70 percent. Unfortunately, this technique
cannot distinguish total from near-total occlusion. In addition, at MGH there is little
true cost savings over direct angiographic techniques.
Definition of Severe Carotid Artery Stenosis
The definition of a severe carotid stenosis has varied from study to study and also
has changed as the techniques used to investigate carotid artery disease have
changed. At MGH, when direct carotid angiography was used to define the degree
of stenosis, a severe stenosis was judged initially to be one that reduced the
residual diameter to less than 1.5 mm, as measured from a calibrated metallic bead
in the radiation field. Later, a severe stenosis on angiography was defined as one
that reduced the luminal diameter by more than 70 percent. More recently, as we
have begun to use magnetic resonance angiography more frequently, a severe
stenosis is judged to be that which causes signal dropout.
EFFICACY OF CAROTID ENDARTERECTOMY AS A TREATMENT
FOR CAROTID STENOSIS
Until recent years there has been considerable debate about the ability of carotid
endarterectomy to yield improved survival and a lower incidence of neurologic events in
patients with documented carotid stenosis. This controversy has existed both for
patients with symptomatic carotid stenoses and more particularly for patients with
asymptomatic carotid lesions. However, several studies and randomized trials have
now addressed this issue and have indicated that the operative approach is more
efficacious.
Carotid Endarterectomy for Symptomatic Carotid Stenosis
In 1986 Hertzer et al. [14 ] from the Cleveland Clinic studied 211 previously unoperated
patients who had transient ischemic attacks or strokes in conjunction with greater than
50 percent carotid stenoses on digital subtraction angiography. Nonoperative treatment
was continued in 126 patients, and 85 had carotid endarterectomy. Although there was
no difference in survival between the two groups at a mean follow-up of 36 months,
carotid endarterectomy yielded significantly better freedom from late neurologic events
for patients with greater than 70 percent unilateral stenoses, for patients with greater
than 50 percent bilateral stenoses, and for patients with greater than 50 percent carotid
stenoses in association with contralateral internal carotid occlusions.
In 1991 the results of a randomized study of medical treatment and carotid

endarterectomy in 659 patients enrolled in the North American Symptomatic Carotid
Endarterectomy Trial were reported. [15 ] All patients had either hemispheric or retinal
transient ischemic attacks or a nondisabling stroke within 120 days of entry into the trial
in association with a 70 to 99 percent stenosis in the symptomatic carotid artery. The
actuarial cumulative risk of any ipsilateral stroke at 2 years was significantly lower at 9
percent in the 328 surgical patients compared with 26 percent in the 331 medical
patients. For major or fatal ipsilateral strokes, the risk was 2.5 percent for surgical
patients compared with 13.1 percent for medical patients ( p < 0.001). When all strokes
and deaths were included in the analysis, carotid endarterectomy was better than
continued medical treatment.
The European Carotid Surgery Trial randomized 2518 patients to medical or surgical
treatment if they had a nondisabling stroke, transient ischemic attack, or retinal in
farction in conjunction with a stenotic lesion in the ipsilateral carotid artery. [16 ] For 778
patients with severe stenoses of 70 to 99 percent, the initial risk of stroke at carotid
endarterectomy of 7.5 percent was outweighed significantly by the reduced late stroke
rate at 3 years of 2.8 percent versus 16.8 percent for the medically treated patients. At 3
years the cumulative risk of operative death, operative stroke, ipsilateral ischemic
stroke, and any other stroke was 12.3 percent for the surgical cohort compared with
21.9 percent for the medical group ( p < 0.01). Finally, the risk of fatal or disabling
ipsilateral stroke at 3 years was 6.0 percent for the carotid endarterectomy patients
versus 11.0 percent for the medical control patients ( p < 0.05).
Therefore, one retrospective and two randomized trials have clearly established the
superiority of carotid endarterectomy over continued medical treatment for patients with
symptomatic severe carotid artery stenoses.
Carotid Endarterectomy for Asymptomatic Carotid Stenosis
Hertzer et al. [17 ] also studied operative and nonoperative treatment in 290 previously
unoperated patients who had greater than 50 percent asymptomatic carotid artery
stenoses identified by digital subtraction angiography. During follow-up to about 3
years, prophylactic carotid endarterectomy in 95 patients yielded a significantly reduced
incidence of subsequent neurologic events compared with continued medical treatment
in 195 patients ( p = 0.05).
The results of the Veterans Affairs Cooperative Study, which randomized medical
treatment and carotid endarterectomy in 444 men with asymptomatic carotid artery
stenoses that demonstrated greater than 50 percent reduction in diameter by
angiography, were reported in 1993. [18 ] At a mean follow-up of 4 years the combined
incidence of ipsilateral neurologic events was 8.0 percent for the surgical patients
versus 20.6 percent for the medical patients ( p < 0.001). There were no significant
differences between groups when all strokes and deaths were analyzed. Total mortality,
including operative deaths, was due mostly to coronary artery ischemic events.
In 1995 the results of the Asymptomatic Carotid Atherosclerosis Study, which

randomized 1662 patients to either carotid endarterectomy or continued medical
treatment, were published. [19 ] In that trial, the degree of stenosis defined as severe
was greater than 60 percent. After a mean follow-up of 2.7 years, the aggregate risk
over 5 years for ipsilateral stroke and any perioperative stroke or death for the surgical
group was 5.1 percent, which was significantly lower than the rate of ipsilateral stroke of
11.0 percent for the medical group.
In summary, one retrospective and two randomized trials have documented a significant
advantage of carotid endarterectomy over continued medical management for patients
with severe asymptomatic carotid artery stenoses.
MYOCARDIAL ISCHEMIC EVENTS IN PATIENTS WITH CAROTID
ARTERY DISEASE
Although this chapter is directed at management of the patient with known coronary
artery disease who is found to also have significant extracranial cerebrovascular
disease, some comment on the contribution of ischemic heart disease to the short-and
long-term risks of carotid endarterectomy patients is appropriate.
Incidence of Coronary Artery Disease in Carotid Endarterectomy Patients
Utilizing only clinical history and electrocardiographic studies, Mackey et al. [20 ]
evaluated 614 carotid endarterectomy patients and found that 324 had overt evidence
of coronary artery disease and 290 had no evidence of coronary disease. Assessing
coronary artery disease in 106 carotid endarterectomy patients with thallium exercise
testing, Urbinati et al. [21 ] found that 27 (25 percent) had significant defects on
myocardial scanning. In 1985 the Cleveland Clinic surgeons reported the results of
routine preoperative coronary angiography in carotid endarterectomy patients. [22 ] In
that study of 506 patients, 30 percent had advanced but compensated disease, 28
percent had severe, correctable disease, and 7 percent had severe, inoperable
coronary disease.
Risk of Myocardial Ischemic Events
SHORT-TERM RISKS
The significant contribution of coronary artery ischemic events to the short-term risks of
carotid endarterectomy has been well documented. In 1981 Hertzer et al. [23 ]
assessed myocardial risks in 335 carotid endarterectomy patients. Hospital mortality
occurred in 1.8 percent, of which 60 percent was due to coronary artery disease. Ennix
et al. [24 ] reported a 4.9 percent mortality rate following carotid endarterectomy and an
8.4 percent perioperative myocardial infarction rate. In the study by Mackey et al. [20 ]
cited above, carotid endarterectomy patients with clinically overt coronary artery
disease had an operative mortality of 1.5 percent and a myocardial infarction rate of 4.3
percent compared with no mortality and an infarction rate of 0.5 percent for patients
without overt coronary disease. The incidence of myocardial infarction following carotid
endarterectomy has been summarized to range from 1.5 to 5 percent. [25 ]
LONG-TERM RISKS
The Mackey et al. study [20 ] of carotid endarterectomy patients demonstrated that the
5- and 10-year survival rates of patients with clinically overt coronary artery disease
were 68.6 and 44.9 percent, respectively, versus 86.4 and 72.3 percent for patients with
no overt coronary disease. When Urbinati et al. [21 ] followed their carotid
endarterectomy patients, the 7-year freedom from all cardiac events was 51 percent for
patients with silent myocardial ischemia compared with 98 percent for patients with
normal thallium exercise testing.
In the study cited above by Hertzer et al., [23 ] the 5-year mortality rate in the patients
who survived hospitalization was 27 percent, and 37 percent of those late deaths were
due to myocardial infarction. In that study, 209 patients had clinically suspected
coronary artery disease. Actuarial survival and reduction in the late mortality rate at 11
years were significantly better by statistical analysis for the subgroup of patients with
coronary artery disease who had myocardial revascularization. A later study from the
same surgical group of 329 carotid endarterectomy patients followed for 10 years
confirmed that myocardial infarction caused more late deaths (37 percent) than stroke
did (15 percent). [26 ] Additionally, 10-year survival was significantly better for patients
having coronary artery bypass grafting.
TIMING OF CAROTID AND CORONARY SURGERY
If one accepts (1) that uncorrected carotid stenosis poses an important risk of
neurologic events for patients with severe carotid and coronary artery disease who have
only isolated coronary artery bypass grafting, (2) that carotid endarterectomy is the
indicated treatment for severe symptomatic and asymptomatic carotid stenosis, (3) that
coronary artery disease is a significant contributor to the short- and long-term risk for
carotid endarterectomy patients, and (4) that coronary artery bypass grafting is an
indicated treatment for severe coronary artery disease, then the important question
becomes not the indication for but the timing of the two operative procedures.
Staged Carotid and Coronary Operations
One approach that has been advocated by several surgical groups is to perform the
carotid endarterectomy and coronary artery bypass operations as staged procedures,
and there are situations where one can present a rationale for either operative
procedure being the intial operation. By convention, performing the carotid
endarterectomy before the coronary artery bypass grafting is referred to as a staged
procedure , while performing the coronary grafting followed by the carotid operation is
called a reversed staged procedure .
Most surgeons who advocate a sequential approach to the patient with severe
combined disease usually will do the carotid endarterectomy first, a staged operation, if
the patient is stable from a hemodynamic and ischemic standpoint. Improvements in
patient management during carotid endarterectomy, particularly anesthetic techniques
or operations performed under local anesthesia, have made some vascular surgeons
comfortable doing carotid endarterectomy on any patient who is not truly unstable from
a cardiac point of view. However, the risk of a perioperative coronary ischemic event
remains a real issue.
For patients with unstable cardiac symptoms, particularly those whose carotid stenosis
is asymptomatic, some cardiac surgeons have opted to perform an initial myocardical
revascularization followed by an interval carotid endarterectomy, a reversed staged
procedure. The principal risk with this approach is obviously the potential for neurologic
complications either during or shortly after the myocardial revascularization.
Although we currently advocate concomitant carotid and coronary bypass operations for
virtually all patients with severe combined disease, in patients found to have severe
bilateral carotid stenosis a staged approach may be appropriate, especially if the
patient is reasonably stable from a cardiac point of view. We would then arrange to
have the more severe of the two carotid lesions treated with initial isolated carotid
endarterectomy, followed by combined coronary artery bypass grafting and
endarterectomy of the other carotid artery within a couple of days. Utilizing a reversed
staged approach, namely, doing one carotid endarterectomy with the myocardial
revascularization followed several days later by the other carotid endarterectomy unless
anticoagulation is maintained between the two operations, would seem to be an
inappropriate approach because of the increased stroke risk with reversed staged
procedures (see below).
Concomitant Carotid and Coronary Operations
In 1972 Bernhard et al. [27 ] were the first to report successful performance of combined
carotid endarterectomy and coronary bypass grafting in 15 patients. Since then,
numerous groups have added their results to the published literature. The strategy of
performing both operative procedures during one anesthetic in patients with severe
combined disease is based on the premise that only with a combined approach can
one avoid the cardiac events that frequently complicate isolated carotid endarterectomy
and the neurologic events that complicate isolated coronary artery bypass grafting.
In today's medical environment one also can make a strong case for the fact that doing
the two operative procedures together is more cost-effective than a staged or reversed
staged approach, which requires two anesthetics and additional costs for extra days in
the hospital between operations.
OPERATIVE TECHNIQUES FOR CONCOMITANT CAROTID AND
CORONARY OPERATIONS
Standard Approach
The usual operative technique for concomitant carotid endarterctomy and coronary
artery bypass grafting has been to perform the carotid endarterectomy during the
harvesting of coronary bypass conduits prior to the institution of cardiopulmonary
bypass. This is the approach that we have used routinely at the MGH, where the carotid
operation is performed by a peripheral vascular surgeon as the cardiac surgical team
harvests whatever saphenous vein may be needed.
The actual technique of the carotid endarterectomy varies among our vascular
surgeons. Several surgeons desire constant electroencephalographic monitoring and
will place an intravascular shunt if changes are noted during the study. Others routinely
employ an intravascular shunt without electroencephalographic monitoring.
The decision to use a patch for closure of the carotid artery is usually based on the size
of the vessel. When vascular patches are used, they are usually saphenous vein.
After the carotid endarterectomy is completed, the neck incision is loosely

approximated with a towel clip over a sponge. Final closure of the neck incision, usually
over a temporary plastic drain, is performed after cardiopulmonary bypass is completed
and heparinization is reversed.
Alternate Approaches
Minami et al. [28 ] reported using some of the perceived advantages of

cardiopulmonary bypass, namely heparinization, hypothermia, and hemodynamic
control, to perform carotid endarterectomy in 116 patients during cardiopulmonary
bypass for myocardial revascularization. Operative mortality was 1.7 percent, and total
stroke risk was 4.3 percent. Weiss et al. [29 ] also published a report advocating
performance of the carotid endarterectomy during cardiopulmonary bypass with
systemic hypothermia to 20°C and with the heart protected during aortic cross-clamping
by retrograde blood cardioplegia. In a small series of 23 patients they had no
neurologic events and 1 postoperative death. Several surgical groups have adopted
this approach, with the thought that hypothermia during cardioplumonary bypass
provides an extra margin of ischemic protection for the brain during the endarterectomy
and avoids the need for an intravascular shunt. The level of systemic hypothermia
utilized has varied among the surgical groups that use this method.
Whether or not performing both operations during cardiopulmonary bypass saves total
operative time is not proven, but the protocol certainly prolongs aortic occlusion and
cardiopulmonary bypass times that most cardiac surgeons try to limit. The requirement
for deeper levels of hypothermia is another drawback, particularly since lesser degrees
of hypothermia are currently preferred for myocardial revascularization.
HIGHLIGHTS OF POSTOPERATIVE MANAGEMENT
At MGH postoperative management of patients following concomitant carotid

endarterectomy and coronary artery bypass grafting does not differ importantly from
management of patients after isolated myocardial revascularization. We believe that the
maintenance of a good coronary perfusion pressure and, by extension, good cerebral
perfusion pressure is beneficial in the early postoperative hours. Early diuresis to clear
perioperative edema also seems efficacious.
Routinely, myocardial revascularization patients receive aspirin beginning within 6 hours

of completion of the operation, unless the patient continues to bleed. This protocol is
also adequate for patients who have either primary closure of the carotid arterotomy or
closure with a vein patch. In some special cases where an artificial cloth patch is used,
where the patient has considerable residual disease higher in the carotid system that
cannot be removed, or where contralateral carotid disease, especially ulcerated plaque,
is uncorrected, some vascular surgeons prefer early anticoagulation with either heparin
or rheomacrodex, followed by long-term warfarin anticoagulation.
If a surgeon decides not to perform a staged or concomitant carotid endarterectomy for

a severe stenosis, the increased risk of stroke in the early days after isolated
myocardial revascularization suggests that heparin is appropriate once the risk of
perioperative bleeding is past.
RESULTS OF STAGED AND CONCOMITANT CAROTID AND
CORONARY ARTERY OPERATIONS
Early Results
STAGED CAROTID AND CORONARY OPERATIONS
There are few studies that report actual results of staged operations for concomitant
carotid and coronary disease. One very important study, however, was published by
Hertzer et al. [30 ] and contained a randomized subgroup of patients with unstable
coronary syndromes and incidental asymptomatic carotid stenoses. Over a 5-year
period they treated 275 patients with severe combined disease. Their criteria for
carotid endarterectomy was either symptomatic and/or severe (> 70 percent) carotid
disease.
Only 24 (9 percent) of the patients were judged to have coronary disease stable enough
to allow carotid endarterectomy prior to coronary artery bypass grafting. Of the 24
patients, 1 (4.2 percent) suffered a perioperative stroke after the preliminary carotid
endarteretomy and died of a myocardial infarction while awaiting myocardial
revascularization.
Symptomatic or severe bilateral carotid disease were treated with a combined carotid
and coronary operation in 122 patients with an operative mortality rate of 6.1 percent
and a perioperative stroke rate of 7.1 percent.
The remaining 129 patients with unstable coronary symptoms and unilateral,
asymptomatic, severe carotid stenoses were randomized to either a combined
operation (71 patients) or a reversed staged operation (58 patients). Patients having
concomitant carotid and coronary operations had a mortality rate of 4.2 percent
compared with a combined rate of 5.3 percent for the two operations in the staged
patients. The incidence of stroke in the combined operations was 2.8 percent, which
was significantly lower than the 14 percent risk of the reversed staged operations (6.9
percent during the isolated coronary bypass grafting and 7.5 percent during the delayed
isolated carotid endarterectomy). This study clearly emphasizes the advantage of
concomitant operations over reversed staged procedures.
CONCOMITANT CAROTID AND CORONARY OPERATIONS
Since the late 1970s, some cardiac surgeons in our group have utilized concomitant
operative repair as the standard therapy for patients with combined severe carotid and
coronary artery disease. Staged operations were reserved for a few patients with very
stable coronary artery disease. In 1995 we published our results of the first 200
consecutive patients who had combined operations between 1979 and 1993. [31 ]
The average age of our patients who had combined carotid and coronary operations
was 67 years, about 6 years older than the mean age for all coronary bypass patients
during that time period. Two-thirds of the patients presented with unstable angina
pectoris, and 42 percent had a prior myocardial infarction. Although the distribution of
single-, double-, and triple-vessel disease was expected at 6, 28, and 65 percent,
respectively, 43 percent of the patients had significant left main coronary artery disease.
Of the 200 patients in the study, 115 (58 percent) were neurologically asymptomatic, 32
percent had transient ischemic attacks, and 16 percent had a prior stroke. Unilateral
severe carotid stenosis was identified in 156 patients (78 percent), whereas 22 percent
also had some degree of disease in the contralateral carotid artery.
Urgent or emergency operations were required in 33 percent of patients, of whom 4

percent were on the intraaortic balloon pump. The average number of grafts per patient
was 3.8. Although only 50 percent received at least one internal mammary artery graft,
81 percent of the last 100 patients did.
Hospital mortality was 3.5 percent, the perioperative myocardial infarction rate was 2.5
percent, and the perioperative stroke rate was 4.0 percent, of which three-fourths were
permanent.
Significant multivariate predictors of hospital death were postoperative stroke, failure to

use an internal mammary graft, requirement for intraoperative intraaortic balloon
pumping, and nonelective operation. Both peripheral vascular disease and unstable
angina predicted postoperative stroke. Significant predictors of prolonged
postoperative hospital stay were postoperative stroke, advanced age, and nonelective
operation.
Vermeulen et al. [32 ] found that the only significant multivariate predictor of hospital
death in their study of 230 combined operations was left main coronary artery disease.
Postoperative neurologic events were predicted by the presence of severe left
ventricular dysfunction and preoperative stroke or transient ischemic attacks.
Some of the series of concomitant carotid endarterectomy and coronary artery bypass
grafting published since 1985 are noted in Table 20-2 . The results from our series are
provided for comparison with the combined results from the other reports. Our patients
were a little older than the mean for the other studies. Our hospital mortality, myocardial
infarction rate, total stroke rate, and permament stroke rate were all comparable with
the mean rates for the other series.
Late Results
Follow-up for the patients in our series of 200 combined operations was 99 percent
complete and revealed the following 10-year actuarial freedom rates for late events:
death, 59 percent; myocardial infarction, 81 percent; percutaneous transluminal
coronary angioplasty, 98 percent; reoperative myocardial revascularization, 94 percent;
total stroke, 96 percent; ipsilateral stroke, 96 percent; and carotid endarterectomy, 94
percent [31 ] ( Fig. 20-1 and Fig. 20-2 ). Ten-year actuarial freedom from all combined
cardiac and neurologic morbidity and mortality was 57 percent (Fig. 20-3) .
Vermeulen et al. [32 ] found their 10-year actuarial freedom from cardiac events to be
50 percent, freedom from neurologic events to be 81 percent, and freedom from all
events to be 41 percent. The only significant multivariate predictors of late cardiac
mortality in their study were the presence of severe left ventricular dysfunction and
advanced age.
In their study of 127 combined carotid and coronary operations, Rizzo et al. [35 ] had a
5-year survival rate of 70 percent, a freedom from myocardial infarction rate of 84
percent, and a freedom from all strokes rate of 88 percent. In their study, late survival
was worse in patients with lower ejection fractions. Late strokes were least common in
patients who had been neurologically asymptomatic at the time of operation, more
common in patients who were transiently symptomatic, and most frequent in patients
with a history of a prior stroke.
SUMMARY
The increasing risk of the devastating complication of perioperative stroke following

myocardial revascularization is directly related to the increasing age of the patients. An
increased incidence of carotid artery disease comes with this increasing age. Several
studies have now clearly shown that severe, uncorrected carotid stenosis is a major risk
factor for perioperative stroke. In addition, excellent randomized trials have established
the safety and efficacy of carotid endarterectomy as the most appropriate treatment for
both symptomatic and asymptomatic severe carotid stenosis. Also, a randomized trial
has demonstrated the advantage of concomitant carotid endarterectomy and coronary
artery bypass grafting over reversed staged operations. Thus I advocate combined
carotid and coronary operations for virtually all patients who present for coronary artery
bypass grafting who are also found to have significant carotid artery stenoses.
PATHOGENESIS OF ACUTE OCCLUSION
Myocardial ischemia due to coronary occlusion for as little as 60 seconds causes

ischemic zone changes from a state of active systolic shortening to one of passive
systolic lengthening. [6 ] Occlusions for less than 20 minutes usually cause reversible
cellular damage and depressed function with subsequent myocardial stunning.
Experiments by Jennings and Reimer [7 ] demonstrated that foci of necrosis in papillary
muscles developed in 50 percent of dogs subjected to 20 minutes of occlusion of the
circumflex artery. After 40 minutes, 70 percent of the muscle was necrosed (Fig. 21-1) .
Additional studies demonstrated that reperfusion of the infarct lead to variable amounts
of salvageable myocardium. After 40 minutes of ischemia followed by reperfusion, 60 to
70 percent of the ultimate infarct is salvageable, but this decreases dramatically to 10
percent after 3 hours of ischemia. [7 ]
The exact timing in humans is even more difficult to analyze because of collateral flow,
which is a major determinant of myocardial necrosis in the area at risk in humans. [8 ]
The collateral blood supply is extremely variable, especially in patients with
long-standing coronary disease. At the time of complete occlusion of a coronary artery,
the area supplied by the occluded artery may still receive blood flow from collaterals.
However, collateral flow will be jeopardized with arrhythmias, hypotension, or the rise of
left ventricular end-diastolic pressure above tissue capillary pressure. [7 ] Thus loss of
collateral flow to the infarct area may lead to the cellular death of salvageable
myocardium. Control of blood pressure and prevention of arrhythmias are vital during
this immediate time after infarction.
Animal model evidence has demonstrated that 6 hours of regional ischemia produces
extensive transmural necrosis. [9 ] Many clinical trials studying methods of reperfusion
after acute myocardial infarctions also have shown that 6 hours from the onset of
symptoms to reperfusion is critical. Reperfusion within 6 hours leads to a decrease in
infarct size and improved survival [10 ] (Fig. 21-2) .
However, aggressive management of infarctions older than 6 hours is also warranted to

preserve the border areas that may be underperfused during the early days after an
infarction. Although some of these patients may develop objective evidence of
ischemia, the clinical assumption that a hypotensive patient with a suddenly dilated and
pressure-overloaded ventricle is prone to losing more muscle mass in border zones of
the infarct is reasonable. This is true even in patients after complete revascularization.
Conservative measures, such as nitroglycerin and intraaortic balloon pumps, have
demonstrated their efficacy in this population of patients without clearly salvageable
myocardium by improving coronary blood supply and reducing the work demand of the
left ventricle. More radical approaches such as insertion of a left ventricular assist
device (LVAD) have been advocated as well. At our center, placement of long-term
assist devices into this group of patients has sometimes resulted in significantly
improved ventricular function at the time of device explantation months later.
Table 21-1 outlines the effects of anatomic, physiologic, and therapeutic variables on
the evolution of final infarct size. Anatomically, the location of the coronary obstructive
lesion and additional diseased vessels and the presence of collateral flow will
determine the extent of early injury following infarction. However, additional physiologic
factors such as malignant arrythmias, hypotension, and left ventricular distension with
subsequently increased wall stress can influence the viability of borderline areas. In
addition, ventricular remodeling of the infarct has important consequences influencing
ventricular function after myocardial infarction. [11 ] Thus appropriate and aggressive
invasive therapies such as PTCA, IABP, CABG, controlled reperfusion, and LVAD
insertion can mitigate myocardial injury and salvage borderline areas even if the
interventions occur many hours or days after the initial infarction.
Reperfusion injury also contributes to myocardial damage as free oxygen radicals are
released and destroy endothelial cells and produce interstitial edema. The timing and
management of reperfusion effects on myocardial damage may have an impact on both
survival and functional recovery of individuals following acute myocardial infarction. [12 ]
Some centers have argued convincingly that controlled reperfusion with specially
designed perfusate and a decompressed, energy-conserving ventricle resting on
cardiopulmonary bypass is the best means to preserve muscle mass. [13 ]
CARDIOGENIC SHOCK
Definition
Cardiogenic shock is defined clinically as a systolic blood pressure below 80 mmHg in

the absence of hypovolemia, peripheral vasoconstriction with cold extremities, changes
in mental status, and urine output of less than 20 mL/h. Hemodynamic parameters for
cardiogenic shock include cardiac index less than 1.8 liters/min per m 2 , stroke volume
index less than 20 mL/m [2 ] , mean pulmonary capillary wedge pressure greater than
18 mmHg, tachycardia, and a systemic vascular resistance of over 2400 dyn/cm5.
These patients are defined as type IV by the Killip classification, a widely used system
to classify myocardial infarctions. [14 ]
Prevalence
Shock is the most common cause of in-hospital mortality following myocardial infarction.
[15 ] The in-hospital mortality associated with cardiogenic shock has remained
unchanged at approximately 80 percent despite the development of new treatment
modalities. [15 ] Cardiogenic shock occurs in 2.4 to 12 percent of patients with acute
myocardial infarction. [16 ] Since 1975, the incidence of cardiogenic shock
complicating acute myocardial infarctions has remained constant at 7.5 percent,
ranging between 5 and 15 percent [15 ] (Table 21-2) . One reason these figures may
have remained constant is the increasing efficiency of emergency medical systems in
resuscitating patients in the community and bringing them to the hospital. Previously,
these patients would have died before reaching the hospital. Similarly, there has been a
decrease in the incidence of out-of-hospital deaths due to coronary disease between
1975 and 1988. [15 ] The key to success in patients in shock is early intervention and
revascularization, although debate surrounds the strategy and mode of therapy. Use of
mechanical circulatory support also may play a role by resting stunned myocardium to
allow its recovery and to prevent the irreversible end-organ injury that may result from
prolonged shock.
Infarct Size Relationship to Shock
Shock is directly related to the extent of the myocardium involved. Myocardial infarctions
resulting in loss of at least 40 percent of the left ventricle have been shown to result in
cardiogenic shock. [4 ] , [5 ] , [17 ] Autopsy findings also revealed marginal extension of
the recent infarct and focal areas of necrosis in those patients with cardiogenic shock.
[4 ] Extensive three-vessel disease is usually found in individuals with cardiogenic
shock, and extension of the infarct is an important determinant in individuals developing
cardiogenic shock. [4 ] , [5 ] , [17 ] Limiting the size of the infarct and its extension is the
key to therapeutic interventions in patients with myocardial infarction. By following
creatinine phosphate kinase (CPK) levels, Gutovitz et al. [18 ] have shown that the
progression/extension of myocardial damage results in cardiogenic shock. Patients
who develop shock have higher peak values.
MEDICAL MANAGEMENT MYOCARDIAL INFARCTION
The management of patients with acute myocardial infarctions demands expeditious

treatment and decision making. With the ultimate goal of reperfusing the ischemic
myocardium, treatment strategies should be directed toward reducing myocardial
oxygen demand, maintaining circulatory support, and protecting the threatened
myocardium before irreversible damage and expansion of the infarct occur. Infarct size
is affected by duration of ischemia, distribution of vessels, degree of obstruction, and
adequacy of collateral channels. As the area of ischemic and dysfunctional myocardium
approaches 40 percent of the ventricular mass, the likelihood of cardiogenic shock
increases dramatically. [4 ] , [5 ] , [17 ]
Both clinical and basic science research have demonstrated that reperfusion is the
main treatment option for acute myocardial infarction. Until reperfusion can be obtained,
treatment is medical. Unfortunately, the majority of patients with myocardial infarction
receive only medical management; only 40 percent of patients having an acute
myocardial infarction receive thrombolytic therapy, the most common means of
reperfusion. [19 ]
A major tenet of medical management is the provision of adequate arterial oxygenation,

defined as greater than 90 percent saturation. Supplemental oxygen and mechanical
ventilation, including positive end-expiratory pressure and endotracheal intubation, aid
in the management of pulmonary edema.
Nitroglycerin dilates epicardial arteries, increases collateral flow, and decreases

ventricular preload. Although clearly beneficial in the treatment of myocardial infarction,
nitrates may increase ventilation-perfusion mismatch and cause hypotension due to
preload reduction.
Adequate analgesia is also beneficial. Morphine sulfate, the most commonly used
analgesic, reduces preload and afterload, myocardial oxygen demand, anxiety, and
circulating catecholamines. Side effects include hypotension and respiratory
depression, each of which is treatable with basic resuscitative efforts.
Antiarrhythmic therapy, including lidocaine, is indicated under certain guidelines, along

with atropine and countershock therapy when arrythmias occur. Since arrhythmias are
one of the most common complications after myocardial infarction,
electrocardiographic (ECG) monitoring is recommended for the first 48 to 72 hours.
Arterial monitoring and the balloon flotation catheter aid in the management of patients
who are hemodynamically unstable, developing congestive heart failure, or developing
mechanical complications of a myocardial infarction. Long-term therapy for
uncomplicated myocardial infarction includes the use of beta blockers, calcium channel
blockers, and angiotensin-converting enzyme inhibitors.
Medical Treatment of Cardiogenic Shock
Medical management includes the use of vasopressors and inotropic agents as

first-line treatment strategies for cardiogenic shock. Optimizing filling pressure by
balancing fluid management and diuretics is essential. Pulmonary capillary wedge
pressures should be kept in the 16-to-22 mmHg range. [2 ]
The use of dobutamine and dopamine is part of the pharmacologic armamentarium.

These agents affect adrenergic receptors in different ways. Dopamine at doses of 5 to
8 µ/kg per minute stimulates beta-adrenergic receptors; at higher doses,
alpha-adrenergic receptors are activated. At rates of more than 10 µ/kg per minute, left
ventricular filling pressures rise and increase myocardial oxygen consumption.
Dobutamine affects beta-adrenergic receptors and thus decreases afterload while
stimulating the myocardium. Thus vasopressors, while necessary to maintain adequate
perfusion pressures, increase afterload of the heart and increase myocardial oxygen
demand, potentially worsening ischemia and extending the area of infarction.
While medical management of cardiogenic shock complicating acute myocardial

infarctions is associated with high mortality, early revascularization can reduce mortality.
As will be discussed later, mechanical support, including intraaortic balloon pumps and
artificial circulation with revascularization, is presently the treatment of choice for
patients in cardiogenic shock.
In contrast to using inotropic agents to improve circulation, beta blockers have been
used successfully to reduce death after infarction, probably due to their ability to reduce
myocardial oxygen demand and arrhythmias. In hypotensive patients or individuals
suffering bradycardia after infarctions involving the right coronary artery, beta blockade
is contraindicated. Other mainstay therapies mentioned earlierheparin, nitrates, and
morphinealso comprise the traditional medical management of these critically ill
patients.
STATES OF IMPAIRED MYOCARDIUM
Coronary insufficiency can result in three states of impaired myocardium: infarcted,

hibernating, and stunned. Each state requires separate clinical interventions and carries
different prognostic implications. Infarcted myocardium is irreversible myocardial cell
death due to prolonged ischemia. Hibernating myocardium is a state of impaired
myocardial and left ventricular function at rest due to reduced coronary blood flow that
can be restored to normal if a normal myocardial oxygen supply-demand relationship is
reestablished. [20 ] , [21 ] Hibernating myocardium is defined as contractility-depressed
myocardial function secondary to severe chronic ischemia that improves clinically
immediately following myocardial revascularization. Stunned myocardium is left
ventricular dysfunction without cell death that occurs following restoration of blood flow
after an ischemic episode. If a patient survives the insult resulting from a temporary
period of ischemia followed by reperfusion, the previously ischemic areas of cardiac
muscle eventually demonstrate improved contractility (Table 21-3) .
Hibernating Myocardium
Hibernation may be acute or chronic. Carlson et al. [22 ] showed that hibernating
myocardium was present in up to 75 percent of patients with unstable angina and 28
percent with stable angina. The entity also occurs after myocardial infarction. Angina
after myocardial infarction commonly occurs at a distance from the area of infarction.
[23 ] In fact, mortality is significantly higher in patients with ischemia at a distance (72
percent) compared with ischemia adjacent to the infarct zone (33 percent). [23 ] It is the
hibernating myocardium that may be in jeopardy and salvageable, although its
presence is usually incidental to the occurrence of the acute infarction. By distinguishing
between hibernating myocardium and irreversibly injured myocardium, a more
aggressive approach to restoring or improving blood flow to the area at risk is
reasonable. Function often improves immediately after revascularization of
appropriately selected regions.
Stunned Myocardium
In the 1970s it was observed that after brief episodes of severe ischemia, prolonged
dysfunction with gradual return of contractile activity occurred. In 1982 Braunwald and
Kloner [25 ] coined the phrase stunned myocardium . Stunning is a fully reversible
process despite the severity and duration of the insult if the cells remain viable.
However, myocardial dysfunction, biochemical alterations, and ultrastructural
abnormalities continue to persist after return of blood flow. Within 60 seconds of
coronary occlusion, the ischemic zone changes from a state of active shortening to one
of passive shortening. [6 ] Coronary occlusion lasting less than 20 minutes is the classic
model reproducing the stunning phenomenon. [24 ] [27 ]
The most likely mechanisms of myocardial stunning are calcium overload, generation of
oxygen-derived free radicals, and excitation-contraction uncoupling due to
sarcoplasmic reticulum dysfunction, or a combination thereof. Other mechanisms that
may contribute to the stunning phenomenon include insufficient energy production,
impaired energy use by myofibrils, impaired sympathetic neural responsiveness,
impaired myocardial perfusion, damaged extracellular collagen matrix, and decreased
sensitivity of myofilaments to calcium [26 ] , [28 ] , [29 ] (Table 21-4) .
Stunned myocardium can occur adjacent to necrotic tissue after prolonged coronary
occlusion and can be associated with demand-induced ischemia, coronary spasm, and
cardioplegia-induced cardiac arrest during cardiopulmonary bypass. Clinically these
regions are edematous and even hemorrhagic. They also have a propensity for
arrhythmias, which can lead to more extensive ventricular stunning and hypotension with
subsequent infarction of these regions.
In summary, infarcted myocardium is nonviable myocardium, while hibernating

myocardium is viable myocardium that is chronically dysfunctional due to impaired
blood supply. Stunned myocardium is viable myocardium that is acutely dysfunctional
after adequate blood supply has been restored.
Diagnosis of Viable Myocardium
Mechanisms to identify patients with myocardial stunning and hibernation include ECG
findings, radionuclide imaging, positron emission tomography (PET), and more
recently, dobutamine echocardiography. Thallium identifies perfusion-related defects of
the myocardium and can distinguish between viable and scarred myocardium as well.
However, early redistribution of thallium does not distinguish between hibernating and
scarred myocardium; one study demonstrated that 45 percent of segments with
irreversible defects by thallium improve after reperfusion. [30 ] Redistribution imaging
and reinjection imaging improve the predictive value of thallium imaging in
distinguishing hibernating myocardium.
PET measures the metabolic activity of myocardial cells. Its positive predictive value is
80 to 87 percent, and its negative predictive value is 82 to 100 percent. [31 ] These
values are similar to those for thallium scanning; however, these results are from limited
studies with few patients. Further assessments are needed before accepting this
diagnostic tool.
Both thallium scanning and PET can be used to distinguish stunned myocardium.
Perfusion and metabolic activity are present in stunned myocardium; thus each test is
useful for this identification.
Dobutamine echocardiography, a recently emerging technique, also has demonstrated

effectiveness in distinguishing hibernating myocardium. [32 ] To date, no one test has
yet proved sensitive and specific enough for routine use. Treatment decisions are still
educated guesses.
Treatment of Stunned Myocardium
Several approaches to management of this critically ill group should be taken. Blocking
the production of oxygen free radicals will reduce both additional cell death and edema
in stunned myocardium. By reducing inflammation, the prothrombotic effects on injured
endothelial cells also can be reduced and thus enhance ventricular recovery. Several
techniques attack the production or effects of these oxygen free radicals. Allopurinol
blocks the xanthine oxidase-hypoxanthine pathway and decreases superoxide anion
radicals; however, clinical trials have yielded conflicting results. [33 ] [35 ]
Iloprost, an analogue of prostacyclin, has demonstrated some effectiveness in reducing
stunning in animals. The proposed mechanism is inhibition of neutrophil and platelet
function and reduction in the production of oxygen free radicals. In the TAMI trial, Iloprost
did not show improved ventricular function after reperfusion with tissue plasminogen
activator (t-PA). [36 ]
Recombinant superoxide dismutase (SOD), an oxygen free radical scavenger, is a

hydrophilic enzyme that does not cross the cell membrane. Additionally, SOD works
most effectively if it is in tissue prior to reperfusion injury and oxygen free radical
production. [37 ] , [38 ] Perhaps because of these two limitations, the use of SOD has
not yet shown clinical effectiveness. [39 ]
Other pharmacologic agents including calcium antagonists, nitrates, beta-blocking

agents, and angiotensin-converting enzyme inhibitors also have been studied with
some beneficial results. [40 ] [44 ] Intracellular adhesion molecule blockers and
p-selectin blockers also may prove beneficial in the coming years.
The use of inotropic agents can overcome stunning in both animal experiments and
human observation. It is recognized that contractility of reversibly injured myocardium
can be enhanced by catecholamines. Thus inotropic agents may have a role in
supporting the patient with borderline function until the stunned myocardium can
recover. [38 ]
While stunned myocardium is recovering or being treated by one of the

above-mentioned means, hemodynamic stability must be maintained. Short-term
mechanical circulatory devices can aid in the support of patients until the myocardium
has sufficiently recovered.
Summary
Differentiation between infarcted, hibernating, and stunned myocardium guides

therapeutic options in patients with poor ventricular function. If adequate regions of
hibernating myocardium are present as documented by PET or 24-hour thallium
scanning, revascularization may allow ventricular recovery. In patients without evidence
of hibernating or stunned myocardium, medical management or transplantation is a
better option.
Further distinction is required between stunned and hibernating myocardium.

Hibernating myocardium requires revascularization to restore blood supply to this area.
Stunned myocardium requires only support, which may take the form of pharmacologic
manipulations, including addition of epinephrine, dobutamine, and/or amrinone. If
conservative measures fail, the intraaortic balloon pump (IABP) or short-term LVAD
support becomes necessary.
RATIONALE FOR AGGRESSIVE MANAGEMENT OF MYOCARDIAL
INFARCTION
Arguments supporting emergency surgery in patients within 6 hours of infarction have

been made successfully. Early reperfusion clearly reduces infarct size in the major
areas at risk. Controlled reperfusion may be even superior. The arguments are more
difficult to make for patients outside the golden 6-hour window; however, these patients
often have ischemic border regions that are prone to arrhythmias and necrosis. In
addition, patients are at risk for prolonged periods of hypotension with resulting
end-organ injury and further left ventricular dysfunction. Even if revascularization does
not appear critical, ventricular unloading with IABP or LVAD may provide the bridge to
recovery needed in patients dying after myocardial infarction. The major limiting factors
to aggressive surgical management are major comorbidities, which make continuation
of life undesirable or unlikely, and an unclear neurologic status, especially after a period
of cardiopulmonary arrest.
REPERFUSION
Although restoration of blood flow to ischemic regions is essential, the accompanying

reperfusion injury initially can worsen rather than improve myocardial dysfunction. The
area at risk is affected not only by reperfusion but also by the conditions of reperfusion
and the composition of the reperfusate. [12 ] Thus controlling reperfusion itself may aid
in reducing myocardial infarct size and ventricular injury.
At the cellular level, myocardial ischemia results in a change in energy production from
aerobic to anaerobic metabolism. The consequences of ischemia vary from decreased
adenosine triphosphate production and increased intracellular calcium to decreased
amino acid precursors such as aspartate and glutamate. These changes can only be
reversed by reperfusion.
However, as oxygen is reintroduced into a region, oxygen free radical generation

ensues with resulting cellular damage. Cellular swelling and/or contracture leads to a
no-reflow phenomenon that limits the recovery of myocytes and possibly adds to
irreversible injury of others. The production of oxygen free radicals during ischemia and
at the time of reperfusion is the leading mechanism proposed to explain cellular injury.
Four basic types of reperfusion injury have been described: lethal cell death,
microvascular injury, stunned myocardium, and reperfusion arrhythmias (Table 21-5) .
Buckberg et al. [12 ] , [13 ] , [45 ] [61 ] conducted studies of controlled reperfusion after
ischemia and produced a clinical application for controlled reperfusion. The conditions
of reperfusion and the composition of the reperfusate allow more muscle salvage, less
postischemic edema, and greater immediate recovery of systolic shortening than
uncontrolled reperfusion. [45 ] The composition of the reperfusate is designed to
provide oxygen, reduce calcium influx, reverse acidosis, mobilize edema, and replenish
substrates. To accomplish this, the cardioplegic solution is hyperosmolar and basic and
contains blood, a chelating agent, aspartate, and glutamate [46 ] (Table 21-6) . The
duration of reperfusion, 20 minutes, as well as the dose is critical. [53 ]
The surgical strategy of controlled reperfusion, especially as espoused by Buckberg

and colleagues, includes several elements. First, extracorporeal circulation is
established as expeditiously as possible with venting of the left ventricle as required.
Initially, antegrade cardioplegia is delivered using either a warm Buckberg solution to
rebuild ATP stores or cold, high-potassium cardioplegia to achieve rapid diastolic
arrest. We routinely add retrograde cardioplegia to ensure global cooling, even in areas
of active ischemia. The temperature of the anterior and inferior walls of the ventricle is
measured to ensure adequate cooling. After each distal anastomosis, cold
cardioplegia is infused into each graft and the aorta at 200 mL/min over 1 minute. This
is followed by retrograde infusion through the coronary sinus for 1 minute. After
completion of the final distal anastomosis, warm substrate-enriched blood cardioplegia
is given at 150 mL/min for 2 minutes into each anastomosis and the aorta. After
removal of the aortic cross-clamp, regional blood cardioplegia is given at 50 mL/min
into the graft supplying the region at risk for 18 minutes. The proximal vein grafts are
then completed, followed by reestablishment of normal blood flow. To decrease oxygen
demand, the heart is allowed to beat in the empty state for 30 minutes. After this time,
the patient is weaned off bypass.
Application of the Buckberg solution and technique have been shown to be effective in
improving mortality rates and myocardial function after acute coronary occlusion. With
ischemic times averaging 6 hours, a prevalence of multivessel disease, and
cardiogenic shock, the overall mortality in patients with acute coronary arterial
occlusions who underwent surgical revascularization applying this method of
reperfusion was 3.9 percent. Postoperative ejection fractions averaged 50 percent. [13
] Surgical revascularization in this series using controlled reperfusion compared
favorably with percutaneous transluminal coronary angioplasty (PTCA) in several large
series. [13 ] The superior results of this method for the treatment of cardiogenic shock, a
9 percent mortality, has brought this method to the forefront in the treatment of
cardiogenic shock [13 ] (Table 21-7) .
Methods of Reperfusion
ROLE OF THROMBOLYTIC THERAPY
Since myocardial salvage depends on reperfusion of occluded coronary arteries, rapid

dissolution of an occluding thrombus with thrombolytic therapy is an appealing
intervention. Intracoronary streptokinase in patients with acute myocardial infarction
demonstrates that thrombolytic therapy is a safe and efficient way to achieve the
desired early reperfusion. [62 ] Following this study, a number of multi-institutional
megatrials showed the effectiveness of thrombolytic therapy in treating acute
myocardial infarctions.
The trial of the Italian Group for the Study of Streptokinase in Myocardial Infarction
(Gruppo Itialiano per lo Studio della Streptochinasi nell'Infarto Miocardio, GISSI) [63 ]
and the Second International Study of Infarct Survival (ISSI-2) [64 ] found a reduced
hospital mortality in patients treated with streptokinase. The effectiveness of tissue-type
plasminogen activator (t-PA) also has been evaluated in randomized studies. The
Thrombolysis in Myocardial Infarction (TIMI) [65 ] study and the European Cooperative
Study Group [66 ] demonstrated the effectiveness of t-PA for the treatment of acute
When streptokinase and t-PA were compared, two studies failed to demonstrate any
difference in mortality. [67 ] , [68 ] A third study, however, the Global Utilization of
Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries
(GUSTO) trial, supported the use of t-PA by demonstrating a more rapid and complete
restoration of coronary flow that resulted in improved ventricular performance and
reduced mortality. [69 ] , [70 ] After 90 minutes, 54 percent of the group receiving t-PA
and heparin had normal flow, compared with less than 40 percent in the other groups.
While patency rates were similar after 3 hours, 30-day mortality was lowest in patients
whose flow was normal at 90 minutes (4.4 percent). [69 ] , [70 ] This supports the
importance of rapid restoration of flow. Although the actual difference in patient survival
between the two groups was small (6 versus 7 percent mortality), the number of lives
saved each year may justify the added expense of t-PA. [69 ] , [70 ] The mode of
delivery of t-PA has been credited for the differences in the outcomes in these trials.
Differences in methods of delivery between t-PA and streptokinase and adjuvant
therapy with aspirin and heparin, along with cost factors of each agent, have stimulated
a continuing debate over these two drugs. [19 ] Table 21-8 summarizes some of the
previously mentioned trials.
While thrombolyis improves survival and ventricular function, the patency of

infarct-related arteries is reported to be between 50 and 85 percent. [63 ] [70 ] Normal
flow should be achieved in 60 percent of patients by today's standards. Thrombolytic
therapy works well but is not without complications. [71 ] Complications of thrombolytic
therapy include bleeding and intracranial hemorrhage. Bleeding is usually minor and
occurs mostly at the sites of vascular puncture. Intracranial hemorrhage and stroke rates
are around 1 percent and are an acceptable risk.
Cardiogenic shock
Thrombolytic therapy for patients presenting in cardiogenic shock or heart failure does
not appear to improve survival in this population but may decrease the incidence of
patients developing heart failure after myocardial infarction. [72 ] A review of the
literature, however, demonstrates failure to include or analyze patients in cardiogenic
shock treated by thrombolytic therapy. [73 ] Further studies of thrombolytic therapy in
shock patients are needed before the efficacy of this method of therapy is determined.
Thrombolytics also must be evaluated with respect to the improved results
demonstrated by mechanical revascularization in this population.
Summary
Thrombolytic agents for the treatment of myocardial infarction have demonstrated

several important points. Survival is improved by decreasing time to reperfusion. The
GUSTO trial showed that patients treated within the first hour had the greatest
improvement in survival, with a 1 percent reduction in mortality for each hour of time
saved. [69 ] , [70 ] Thrombolytic therapy is easy to administer in the community by
trained personal. Since the time to reperfusion is a critical element in preserving
myocardium, thrombolytic therapy is ideal for most communities. One study evaluated
the use of prehospital-administered thrombolytics and found a trend toward improved
survival. [74 ] Further large-scale trials must be initiated before recommendations are
made. However, in communities, thrombolytics should be used for treatment of patients
with acute myocardial infarction.
ROLE OF PTCA
Since the first reported use of percutaneous transluminal coronary angioplasty (PTCA)
by Gruntzig et al. [75 ] in 1979, the efficacy of this procedure in the treatment of coronary
artery disease has been well recognized. A number of studies have evaluated the
efficacy of primary PTCA in the treatment of acute myocardial infarction. Overall, PTCA
hospital mortality rates range from 6 to 9 percent. [76 ] [81 ]
Several different strategies employing PTCA for acute myocardial infarction have been
developed and examined through clinical trials. Primary, rescue, immediate, delayed,
and elective PTCA are options for the treatment of acute myocardial infarction. Primary
PTCA uses angioplasty as the method of reperfusion in patients presenting with acute
myocardial infarction. Rescue, immediate, delayed, and elective PTCA all are done in
conjunction with or following thrombolytic therapy. Rescue PTCA is done following
recurrent angina or hemodynamic instability following thrombolytic therapy. Immediate
PTCA is performed in conjunction with thrombolytic therapy, and delayed PTCA occurs
during the intervening hospitalization. Finally, elective PTCA is done following
thrombolytic therapy and medical management when a positive stress test is obtained
during the same hospitalization or soon thereafter.
Primary PTCA functions in several roles for the treatment of acute myocardial
infarctions. Since there are some absolute and relative contraindications to
thrombolytics, PTCA is the best method of reperfusion in patients with acute myocardial
infarction, according to studies that evaluated PTCA as first-line therapy. Several
studies evaluated the role of PTCA compared with thrombolytic therapy. The Primary
Angioplasty in Myocardial Infarction Study Group trial concluded that immediate PTCA
without thrombolytics reduced occurrence of reinfarction and death and was associated
with a lower rate of intracranial hemorrhage. The trial did not show any differences in left
ventricular systolic function. [77 ] Myocardial salvage is similar for PTCA and
thrombolytic therapy [78 ] ; however, primary PTCA may be slightly less costly than
thrombolytic therapy. [79 ]
There are limits to the use of primary PTCA. Logistic and economic constraints apply to
invasive modes of therapy. Catheritization laboratories and personnel must be ready at
all times. This is not practical in most communities, and transportation to tertiary care
centers raises costs considerably.
Immediate PTCA following thrombolytic therapy does not improve clinical outcome and
is associated with increased complication rates. The European Cooperative Study
Group (ECSG), [66 ] the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI)
trial, [80 ] and the Thrombolysis in Myocardial Infarction (TIMI-IIA) trial [81 ] demonstrate
that immediate angioplasty does not improve clinical outcome or left ventricular function
compared with delayed angioplasty. [66 ] , [80 ] , [81 ] Immediate angioplasty is also
associated with a higher risk of bleeding and emergent bypass. The ECSG trial
demonstrates a lower incidence of bleeding, hypotension, and ventricular fibrillation as
well as lower mortality with delayed PTCA. [66 ] The TAMI trial, which compared
immediate versus delayed PTCA after thrombolysis, shows no difference in global
ventricular function at 1 week between the two groups in patients with angiographically
patent infarct arteries. [80 ] Overall, immediate angioplasty does not lead to better
ventricular function or clinical outcome compared with elective PTCA. Finally, TIMI-IIA
concludes that immediate PTCA after thrombolytic therapy for acute myocardial
infarction does not improve survival or ventricular function [81 ] and is associated with
increased bleeding, reinfarction, and emergency coronary artery bypass grafting
(CABG) (Table 21-9) .
Delayed PTCA does not improve clinical outcome either. The Treatment of
Post-Thrombolytic Stenoses (TOPS) study group concludes that there is no functional or
clinical benefit from routine late PTCA after acute myocardial infarction treated with
thrombolytic therapy in patients who do not have ischemia on stress testing before
hospital discharge. [82 ] However, the TIMI-IIB trial indicates that thrombolytic therapy
followed by angioplasty in individuals with symptomatic or provokable ischemia is
appropriate. [81 ]
Cardiogenic shock
Primary PTCA may play a greater role in patients presenting in cardiogenic shock. The
GISSI I and II trials demonstrates no benefit from intravenous thrombolysis, with mortality
rates of 70 percent. [63 ] , [67 ] In patients presenting in or developing cardiogenic
shock after acute myocardial infarction, PTCA improves survival to 40 and 60 percent.
[83 ] , [84 ] This improvement is even greater when angioplasty is successful; in-hospital
survival rates increase to 70 percent. In most of these series an IABP is used in
conjunction with PTCA. Even with improved in-hospital survival, long-term mortality rates
are still high, with only 18 percent of patients surviving 1 year after hospital discharge
following PTCA for cardiogenic shock. [84 ]
Summary
Presently, primary PTCA should be performed in patients with acute myocardial

infarction and contraindications to thrombolytic therapy. Patients with established or
developing cardiogenic shock should be treated with PTCA rather than thrombolytic
therapy. Specialized centers that have 24-hour catheterization facilities can provide
primary PTCA as a first-line therapy. Rescue PTCA after failed thrombolytic therapy for
patients with ongoing ischemia or clinical compromise is also recommended. Finally,
elective PTCA should be performed on patients who have recurrent or provokable
angina prior to hospital discharge.
STENTS AND ATHERECTOMY
The role of intracoronary stents and atherectomy for acute myocardial infarction is in its
infancy. Intracoronary stents and atherectomy catheters are useful for acute coronary
arterial dissections and long lesions, respectively. At this time, no large randomized
trials have evaluated the efficacy of these treatment options for acute myocardial
infarction.
ROLE OF CORONARY ARTERY BYPASS GRAFTING (CABG)
The role of surgical revascularization in the treatment acute myocardial infarction has
changed considerably over the past 30 years. Improvements in intraoperative
management and myocardial preservation techniques have strengthened the surgeon's
armamentarium. However, the development and use of thrombolytic therapy and PTCA
offer alternatives to surgery.
Early studies reported increased morbidity and mortality for patients undergoing
surgical revascularization within 30 days of the infarct. [85 ] A concern arose over a high
risk of extension and hemorrhage into infarction after surgical revascularization of acute
myocardial infarction. [86 ] Medical management was believed the more prudent
therapy. The only absolute indications for emergent operative intervention of acute
myocardial infarctions during this era were papillary muscle rupture, ventricular septal
defect, and left ventricular rupture. For these entities, surgery was the only hopeful
option.
During the 1980s, reports appeared recommending surgical revascularization in

preference to medical therapy for acute myocardial infarction. [10 ] , [87 ] [93 ] Mortality
rates under 5 percent were reported. Critics argued that these studies lacked
randomization or consecutive entry of patients, that preoperative stratification was
absent, and that enzyme levels were not included. Inherent bias that favored surgery in
low-risk patients was believed to be the reason for the excellent outcomes. [94 ]
At the time these reports surfaced, thrombolytic therapy and interventional cardiology
were emerging as alternative options for acute infarction. With the availability of
thrombolytics and PTCA, large multicenter trials began looking at the efficacy and
usefulness of these two techniques. Randomized trials using CABG were not done; thus
this option was never established as an option for acute myocardial infarction.
However, several centers continued to use surgical revascularization to treat acute

myocardial infarction. Excellent results were achieved by coordinated community and
hospital systems. However, practical, logistic, and economic constraints relegate
surgical revascularization to a third option behind thrombolytics and PTCA for the
primary treatment of acute myocardial infarction.
There continue to be several scenarios that require emergent or urgent surgical

revascularization. Failure of thrombolytics and PTCA with acute occlusion may require
surgical intervention. Additionally, CABG for postinfarction angina has became a critical
step in the pathway of treating acute myocardial infarction.
Timing after infarction
If surgical revascularization within 4 to 6 hours after the onset of symptoms is feasible,

the mortality rate is improved over that of medically treated patients. While these
studies were not controlled and were critized for selection bias, they did demonstrate
the feasibility of early operative intervention in acute myocardial infarction. Early
experiences demonstrated that time less than 6 hours from onset of pain, [89 ] degree
of collaterals, and degree of obstruction (subtotal versus total) [92 ] were important
factors ensuring low operative mortalities. With more recent developments in
myocardial protection and a better understanding of reperfusion injury, the results of
these early studies should improve if these protocols are repeated in the future.
However, if patients are already more than 6 hours after a large infarction, surgical
solutions can still be valuable. Revascularization may prevent further extension of
infarction, and mechanical support systems may be the only means to resuscitate a
moribund patient, thus preventing end-organ injury and allowing ventricular recovery.
Patients with postinfarction ischemia can undergo CABG within 30 days of myocardial
infarctions with little increased risk. In fact, the TAMI 1 to 3 and 5 trials revealed that
coronary bypass surgery improves global and regional left ventricular function following
thrombolytic therapy for acute myocardial infarction. In TIMI-II, the mortality following
surgical revascularization was 3.9 percent. These trials support the notion that CABG
has a role in the early treatment strategy for acute myocardial infarctions.
Angina occurs in up to 60 percent of patients following an acute myocardial infarction

due to continuing coronary insufficieny. Two categories of postinfarction angina have
been noted: ischemia in the infarct zone and ischemia at a distance. Ischemia at a
distance represents a higher risk of 1-month mortality: 72 percent compared with only
33 percent mortality for patients with ischemia only in the infarct zone. [23 ] Angina
occurring secondary to ischemia outside the infarct zone risks new myocardium and
should prompt aggressive revascularization of this area. Loss of greater than 40
percent of the myocardium leads to shock, heart failure, and death; this degree of
myocardial damage does not usually occur from just one occluded artery. [23 ] Thus
revascularization of additional areas at risk outside the infarct zone is strongly
recommended, and prompt workup of postinfarction angina is necessary to determine
the best means of revascularizing jeopardized areas of myocardium. [23 ]
Risk factors
Time after infarction has not been shown to be an independent risk factor for mortality
after CABG. [95 ] , [96 ] Risk factors include urgency of the operation, increasing
patientage, renal insufficiency, number of previous myocardial infarctions, hypertension,
[96 ] reoperation, cardiogenic shock, depressed left ventricular function and the need for
cardiopulmonary resuscitation, [97 ] left main disease, female sex, left ventricular wall
motion score, [98 ] IABP, and transmural infarction. [99 ] Characteristics associated
with better outcome early after myocardial infarction include preservation of left
ventricular ejection fraction, male gender, left main disease, younger patients, and
subendocardial versus transmural myocardial infarction.
Cardiogenic shock
Surgical revascularization in acute myocardial infarction complicated by cardiogenic

shock has been shown to improve survival. Cardiogenic shock, as discussed earlier, is
accompanied by 80 to 90 percent mortality rates. DeWood et al. [10 ] were the first to
demonstrate improved results with revascularization in patients in cardiogenic shock
complicating acute myocardial infarction. Patients who were stabilized with an IABP
and underwent emergent surgical revascularization had survival rates of 75 percent.
Early surgical revascularization is associated with survival rates of 40 to 88 percent in
patients in cardiogenic shock due to nonmechanical causes. Guyton et al. [100 ]
reported an 88 percent in-hospital survival and a 3-year survival of 88 percent, with no
late deaths reported. Thus, for patients in cardiogenic shock, surgical revascularization
offers a significant survival benefit.
Advantages of CABG
Reported survival rates are similar for CABG and PTCA in the treatment of acute
myocardial infarction. To date there have been no randomized clinical trials comparing
CABG with PTCA and thrombolytics. Presently, a trial comparing PTCA versus CABG
for the treatment of acute myocardial infarction is ongoing. No data from this trial have
yet been released. Due to the lack of prospective, randomized trials, recommendations
must be based on retrospective and observational studies. CABG offers several
potential advantages: First, surgical revascularization is the most definite form of
treatment of the occlusion. CABG offers the longest patency of revascularized stenotic
and occluded arteries in elective cases; 90 percent of internal mammary arteries are
patent at 10 years. Second, CABG also offers more complete revascularization, since
all the vessels are treated. Third, difficult distal obstructions can be reached. Fourth,
there is controlled reperfusion to reverse ischemic injury and reduce reperfusion injury.
Fifth, as with other forms of reperfusion. CABG interrupts the progression of ischemia
and necrosis and limits infarct size.
Disadvantages of CABG
Disadvantages of immediate surgical revascularization include the delay in the

institution of CABG, since less than 6 hours has been shown to be the critical time and
4 hours is the ideal. Rapid availability of catheterization and operating room personnel
for emergency procedures imposes logistic and economic constraints. Thus CABG is
not readily applicable to the vast majority of patients in the community, and to provide
this would strain health-care resources. Second, it is difficult to analyze published
results of CABG for acute myocardial infarction because randomized trials have not
been done. Comparisons thus far have used medically treated patients as controls.
Patients in the surgical group may be at lower risk; this might explain their progression
to operation rather than continuing medical treatment. Crossover of patients from
medical to surgical treatment also may have skewed the data.
Summary
Surgical revascularization following acute myocardial infarction can be performed with

excellent results in an appropriate patient population. Most patients do not need such
measures and would not benefit from this aggressive form of therapy. However, patients
with mechanical complications, those in cardiogenic shock, and those with
postinfarction angina who have left main disease or multivessel disease are likely to
benefit from early CABG.
USE OF THE INTRAAORTIC BALLOON PUMP
The early use of aortic counterpulsation with an intraaortic balloon pump (IABP)
demonstrated the safety but not efficacy of this device for patients in cardiogenic shock
following acute myocardial infarction. [101 ] While survival was not improved, aortic
counterpulsation did improve the myocardial oxygen requirements and myocardial
energetics were reduced in patients in shock. [101 ] As revascularization techniques of
occluded coronary arteries of patients in cardiogenic shock have improved, use of
aortic counterpulsation has found a role as an adjuvant to treatment protocols.
IABP counterpulsation in combination with reperfusion is effective in the treatment of

acute myocardial infarction complicated by cardiogenic shock. [10 ] , [102 ] While the
major improvement in survival is due to reperfusion, patients who had combined
reperfusion and IABP additionally have improved long-term survival. IABP improves
circulatory physiology and decreases end-organ damage in the early shock period
before the myocardium is reperfused and recovers function.
Aortic counterpulsation decreases the reocclusion rate, recurrent ischemia, and need
for emergency PTCA in patients who have coronary artery patency established by
emergency cardiac catheterization following acute myocardial infarction. [103 ]
Prophylactic counterpulsation for 48 hours sustains patency in coronary arteries after
patency is reestablished following myocardial infarction. No increase in vascular or
hemorrhagic complications is observed as compared with controls. [103 ]
Weaning from the IABP should take place only after there is clear evidence of
myocardial and end-organ recovery. In general, inotropic requirements should be
reduced first in order to minimize myocardial stress. The one exception is the
development of limb ischemia due to the IABP catheter.
ROLE OF CIRCULATORY ASSIST
Circulatory support devices are reserved for patients who are hemodynamically
unstable; however, intervention should not be delayed until after irreversible end-organ
injury occurs. This group of shock patients has a mortality rate of 80 percent, and
survival data with the use of assist devices reflect the critical condition of patients
treated. Mortality rates have changed very little in the last 20 years despite
improvements in medical and surgical therapy.
Patients in cardiogenic shock who are candidates for circulatory assist devices may be
divided into two groups: individuals who have stunned myocardium and need a bridge
to recovery and those who have irreversible myocardial damage and need a bridge to
cardiac transplantation. For example, if a patient with previously normal ventricle
develops a large myocardial infarction, we prefer short-term support, since enough
recovery may occur to allow a fruitful existence with the native heart. However, if a
patient with preexisting heart failure has another infarction, the need to definitively
bridge the patient to transplant with a long-term implantable device is apparent.
Difficulty arises in assessing the results of mechanical assistance for patients following
acute myocardial infarction and cardiogenic shock because of these different
objectives.
Mechanical assist devices augment systemic perfusion and prevent end-organ damage
while resting the stunned ventricle. [104 ] Early studies on implantable LVADs have
shown that end-organ function is an early predictor of mortality. Treatment of patients
prior to end-organ deterioration is essential for improving the odds for long-term
survival. In addition to affecting end-organ function, assist devices also may improve
myocardial contractility of postischemic hearts. [104 ]
Decisions regarding specific device use depend on the degree of circulatory support
needed and many other factors. Selection criteria for device placement include (1)
potential reversibility of cardiac dysfunction, (2) cause of the cardiac dysfunction, (3)
degree of right and left ventricular dysfunction, (4) amount of circulatory support needed,
(5) importance of the device for myocardial functional recovery, (6) patient size, (7)
geographic location of collapse or deterioration, (8) whether the patient is a candidate
for cardiac transplantation, (9) whether the patient can be anticoagulated, (10) expected
duration of support, and (11) advanced age and severity of comorbid conditions. [105 ]
At Columbia-Presbyterian Hospital, several circulatory assist devices are available to

aid treatment of each group. Short-term devices that can be placed percutaneously
include the IABP and extracorporeal membrane oxygenation. Devices that require
thoracotomy and are beneficial for short-term use include the Abiomed and Biomedicus
pumps. Both these devices primarily treat stunned myocardium, but they are capable of
bridging to transplant. These devices are easy to insert, do not require excision of
ventricular muscle, and do not compromise ventricular function following device
removal. These devices can be removed without the need to reinstitute
cardiopulmonary bypass. These devices are effective in patients who require
emergency support secondary to cardiogenic shock. The Dennis method of left
ventricular assist does not require a thoracotomy or special equipment and is safe,
effective, and potentially widely available, but experience with it is very limited. [106 ] ,
[107 ]
The TCI Heartmate (Thermo Cardiosystems Inc., Woburn, Mass.) LVAD is the
long-term implantable assist device that we use for bridging to transplantation.
Another device that requires thoracotomy is a direct mechanical ventricular actuation

device. This elliptically shaped cup that fits over both ventricles compresses and relaxes
the ventricles, simulating directed cardiac actuation. Reports document improved
cardiac outputs using this device and survival of several patients over prolonged
periods of support. Presently, a trial is underway to examine the use of a direct
mechanical actuation device in patients who develop cardiogenic shock. [108 ] (A
complete discussion of temporary and long-term ventricular assist devices is found in
Chaps. 11 and 51.)
Weaning of Circulatory Support
The first decision concerns whether or not the heart will recover. Clues to the answer to
this question include cardiac enzyme levels at the time of infarction, ECG changes, and
the preinfarction condition of the ventricle. If the ventricle is considered not likely to
recover, early use of a long-term device is rational. On the other hand, if recovery is
possible, the heart should be rested for 3 to 5 days, loaded with the institution's choice
of inotropic support, including a phosphodiesterase inhibitor, and allowed to beat and
eject. If a transesophageal echocardiogram demonstrates recovery, the short-term
support device should be removed in the operating room and kept available for 1 hour
as the patient is observed for signs of decompensation. If the device cannot be
removed within a week, the heart is not likely to recover. In this event, either a
longer-term device is placed or patient support is discontinued.
Ethical Considerations
Programs that aggressively pursue surgical approaches to high-risk patients also must
aggressively seek termination of care in futile cases. A liaison should be developed
with a medical ethics individual or group to provide support for primary caregivers;
however, the burden of medical decisions must rest with the attending physician. The
family should not be forced to sign declarations withdrawing care unless significant
controversy and/or the potential of legal action encumbers the decision. In the case of
mechanical circulatory support, each pump of the device can be interpreted as a new
intervention and therefore can be terminated if necessary. A precedent for this course of
action has been set with mechanical ventilation.
If significant neurologic or other end-organ dysfunction has developed and cardiac

function has not returned, termination of support is reasonable and appropriate.
SURGICAL MANAGEMENT
Columbia-Presbyterian Approach
Patients who are potential transplant candidates and who are dying of cardiogenic
shock after myocardial infarction are all candidates for placement of a long-term
implantable left ventricular assist device (LVAD). If at all possible, a coronary
angiogram is obtained to allow revascularization with or without LVAD insertion.
Surgery is delayed if the culprit vessel can be opened with angioplasty and the patient
stabilized in the catheterization laboratory. If hemodynamics continue to deteriorate, the
patient is taken directly to the operating suite, even if infarction occurred earlier than 6
hours before the planned procedure. Hemodynamic observations that favor early CABG
are pulmonary artery pressures of less than 60/30 mmHg and cardiac output of more
than 3 liters/min. If the hemodynamics are worse, early implantation of a long-term
implantable LVAD may be needed, especially if the mixed venous oxygen saturation is
less than 50 percent. The decision to place a long-term LVAD is influenced by the
patient score on a screening scale designed for this purpose (Table 21-10) . These
scores were selected to identify end-organ dysfunction (lung, liver, kidney) and
operative constraints (right-sided heart failure and bleeding). We have nearly a 90
percent survival if the summed scores are less than 5 points versus 30 percent survival
with summed scores of greater than 5 points. [109 ] For this reason, if the total score is
greater than 5 points, an attempt is made to stabilize the patient prior to beginning
long-term LVAD insertion. Patients with lower scores are offered temporary LVAD.
If a patient is not a potential transplant candidate, our approach is more conservative,

since we do not have a safety net if coronary revascularization fails and a temporary
support device is inserted. An angiogram must be obtained; if hemodynamics are not
favorable and no acute ischemia is present, we delay surgery until pulmonary arterial
pressures fall. If the patient is ischemic, we proceed with CABG as described below. If
the patient cannot be separated from bypass without high-dose inotropic support
including alpha agonists, if the cardiac index is less than 2 liters/min per m 2 , and if
left-sided filling pressures remain high with mixed venous oxygen saturations of less
than 50 percent, short-term LVAD support with the Abiomed system is instituted (Fig.
21-3) . IABP alone in this patient population often does not prevent death and almost
always results in significant renal, hepatic, and pulmonary dysfunction that significantly
complicates patient recovery even if adequate cardiac function returns. Most important,
stressing the heart with high-dose inotropic agents and high filling pressures when it is
weakest during the early reperfusion period after acute infarction may compromise
border zone regions. This concern is especially true of patients with older infarctions (>6
hours).
Operative Techniques for Acute Myocardial Infarction
PREOPERATIVE
Patients are prepared in the catheterization laboratory with a Swan-Ganz catheter, an

angiogram of the coronary arteries, and placement of a salvage catheter if possible and
necessary. The intraaortic balloon is inserted under fluoroscopic guidance. We do not
advocate blind revascularization and have always insisted on a preoperative coronary
angiogram to guide revascularization.
ANESTHESIA
Anesthesia is provided by a rapid narcotics-based regimen with perfusion and surgical

teams prepared to respond to catastrophic hypotension or cardiac arrest.
Transesophageal probes are always placed in these patients if possible. As the patient
is prepped, a test dose followed by a loading dose of aprotinin is given.
BLEEDING
Bleeding is a significant complication of emergency CABG and often results in further

myocardial depression and pulmonary hypertention. Cytokine release induced by
infusion of blood products and thromboxane A2 released by cardiopulmonary bypass
stimulate pulmonary hypertension, which can be catastrophic in the setting of right
ventricular ischemia. Use of aprotinin decreases bleeding during CABG [110 ] , [111 ]
and reduces right-sided heart failure and death after LVAD insertion. [112 ] There are
reported cases of aprotinin use following thrombolytic therapy for acute myocardial
infarction. [113 ] Successful use of aprotinin for reoperative, emergency, or high-risk
CABG is common in many institutions.
Epsilon-aminocaproic acid also has been used to decrease bleeding associated with
CABG. Studies have demonstrated its effectiveness in routine cases. [114 ] , [115 ] To
date, however, there are no large series on the use of aprotinin or epsilon-aminocaproic
acid for emergency CABG following thrombolytic therapy.
CHOICE OF CONDUITS
For emergency cases, the choice of conduit should not differ from elective cases in
most circumstances. The internal mammary artery is not associated with a higher
number of complications compared with saphenous vein grafting in emergent situations
and can be used in most circumstances. [116 ] , [117 ] There is one reported case of
successful use of polytetrafluoroethylene for coronary revascularization in a patient in
shock. [118 ]
INTRAOPERATIVE CONSIDERATIONS
Decompression of the ventricle during revascularization after acute coronary occlusion

decreases muscle damage and improves functional outcome by decreasing wall
tension and reducing oxygen consumption [55 ] ( Fig. 21-4 and Fig. 21-5 ). Indeed,
ventricular decompression reduces metabolic energy consumption by 60 percent.
Diastolic basal arrest, by avoiding the energy of contraction, is the second most
important means of minimizing oxygen consumption and further reduces metabolic
energy consumption by 30 percent. Cooling of the patient and heart only has an impact
on the final 10 percent of basal energy requirements.
Reduction of myocardial energy consumption is best achieved by early institution of

cardiopulmonary bypass to maintain a high perfusion pressure. If a coronary salvage
catheter has been placed across a tight coronary lesion, the catheter is left in place until
just before cross-clamping. Antegrade and retrograde catheters are placed prior to
cross-clamping to allow quick instillation of retrograde cardioplegia and protection of
the territory supplied by the occluded or compromised vessel. The standard Buckberg
protocol is followed, including warm induction to allow regeneration of depleted ATP
(adenosine triphosphate) stores.
If the territory at risk is grafted by saphenous vein, this anastamosis is performed first to
allow direct instillation of cardioplegia into the territory at risk. The proximal
anastomoses should be performed prior to removal of the cross-clamp to allow
complete perfusion of the entire heart upon removal of the cross-clamp.
While large ventricular aneurysms are treated by resection and patch, debate surrounds
smaller aneurysms. Our group does not resect small aneurysms, but some groups are
more aggressive. If an aneurysm is resected, the defect is repaired with a patch of
bovine pericardium sewn to the fibrotic rim of the endoaneurysm surface. The native left
ventricular wall is closed over the patch.
POSTOPERATIVE CARE
Routine postoperative care is usually adequate for patients undergoing emergent or

elective coronary bypass surgery. Aspirin is usually adequate for saphenous vein
protection. Patients with large anterior wall infarctions and attached thrombus require
anticoagulation with heparin and Coumadin. Sedation and antibiotic protocols are
institution-based and should be followed for operations on patients with acute infarction.
Following surgery for acute myocardial infarctions, patients should not be on fast track
protocols.
A higher incidence of complications in shock patients compared with nonshock

emergencies has been reported. Guyton et al. [100 ] report a 47 percent complication
rate associated with cardiogenic shock compared with 13 percent for patients with
nonshock emergencies. This increase in complications probably reflects the
preoperative condition of the patients rather than the treatment itself. Long-term
follow-up in patients following emergency surgical revascularization shows that survival
rates are closely correlated with postoperative ejection fraction. [119 ] , [120 ]
CONCLUSION
The treatment of acute myocardial infarction should be divided into two approaches
(Fig. 21-6) . Uncomplicated acute myocardial infarction can be treated in most
community hospitals. In most areas of the country, these patients are treated effectively
with thrombolytic therapy and medical management. For communities and facilities that
have catheterization laboratories, primary angioplasty may be more cost-effective and
produce similar results. At this time, emergency coronary artery bypass surgery is not
the most cost-effective approach; randomized, controlled studies to demonstrate
advantages of emergency CABG have not yet been performed.
The approach to acute myocardial infarctions complicated by cardiogenic shock

presents a more difficult problem. Mortality rates are high with medical management.
Reperfusion therapy is the only real hope for improved survival in this group of patients.
Thrombolytic therapy is associated with poor outcomes; thus PTCA and emergent
CABG are the primary alternatives. An ongoing randomized trial to assess these two
modes of therapy may indicate a preference. Mechanical circulatory assistance has an
important role for supporting patients until the myocardium recovers. Use of
pharmacologic agents and means to control reperfusion are important areas of current
research and development. Assist devices and the artificial heart programs also are
areas of important research.
In summary, treatment of acute myocardial infarctions is based on reperfusion of

ischemic myocardium and requires balancing time to reperfusion against reperfusion
injury. When assessing different modes of treatment, it is important to recognize several
factors. Outcomes differ depending on the success of reperfusion. Reperfusion is the
key for successful treatment of acute myocardial infarction. It is important to compare
outcomes for different modes of therapy after myocardial infarction and not only cases
that result in successful reperfusion. Thus, if all patients treated with thrombolytics,
PTCA, and CABG are fairly randomized and evaluated, tabulation of both successes
and failures will indicate the best therapy to apply.
DEFINITIONS
An acute postinfarction ventricular septal defect is a perforation of the ventricular

septum occurring in an area of acutely infarcted myocardium. Ventricular septal rupture
is chronic when it has been present for more than 46 weeks. Postinfarction ventricular
rupture is a perforation of the ventricular free wall occurring in an area of acutely
infarcted myocardium.
POSTINFARCTION VENTRICULAR SEPTAL DEFECT
History
In 1845 Lathum described a postinfarction ventricular septal rupture at autopsy, but it

was not until 1923 that Brunn first made the antemortem diagnosis. [2 ] , [3 ] Sager in
1934 added the 18th case to the world literature and established specific clinical
diagnostic criteria that stressed the association of postinfarction septal rupture and
coronary artery disease. [4 ]
The treatment of this entity was medical and strictly palliative until 1956 when Cooley et
al. performed the first successful surgical repair in a patient 9 weeks after the diagnosis
of septal rupture. [5 ] The initial patients who had similar repairs in the early 1960s
usually presented with congestive heart failure after having survived acute septal
perforation for more than 1 month. [6 ] , [7 ] The success of operation in these patients
and the precipitous, acute course of other patients with this complication gave rise to
the belief that operative repair should be limited to patients surviving for 1 month or
longer. [6 ] , [8 ] , [9 ] This purportedly allowed scarring at the edges of the defect that
was considered crucial for secure and long-lasting closure of the septal rupture. [10 ] ,
[11 ]
In the late 1960s, more rapid recognition of septal rupture following infarction led to the
recommendation that operation be attempted earlier in patients who were
hemodynamically deteriorating. [1 ] , [3 ] , [12 ] The use of improved prosthetic materials
accompanied the successful surgical repair of defects from 1 to 11 days old, as
reported by Allen and Woodwark in 1966, Heimbecker et al. in 1968, and Iben et al. in
1969. [12 ] [14 ] Notable among these reports was Heimbecker and associates' superb
study of infarctectomy in patients with postinfarction ventricular septal defects. Surgical
management of these patients was further refined by inclusion of infarctectomy and
aneurysmectomy and development of techniques to repair perforations in different
areas of the septum. [13 ] , [15 ] [20 ]
Over the last 15 years, it is increasingly clear that postinfarction ventricular septal
rupture constitutes a surgical emergency in the majority of cases. More recently,
improved surgical techniques, newer prosthetic materials, enhanced myocardial
protection, and improved perioperative mechanical and pharmacological support have
produced more favorable results in patients with postinfarction septal rupture. [21 ] , [22
]
Incidence
Postinfarction ventricular septal defects complicate approximately 12 percent of cases

of acute myocardial infarction and account for about 5 percent of early deaths after
myocardial infarction. [23 ] , [24 ] The average time from infarction to rupture is 24 days
but may be as short as a few hours or as long as 2 weeks. [24 ] [27 ] These
observations correlate well with pathological findings that demonstrate abundant
necrotic tissue and little ingrowth of blood vessels and connective tissue 421 days
following myocardial infarction. [28 ] , [29 ] Postinfarction ventricular septal defects occur
in men more often than women (3:2), but more women experience rupture than would be
expected from the incidence of female coronary artery disease. [8 ] The age of patients
with this complication ranges from 44 to 81 years, with a mean of 62.5 years. However,
there is some evidence that the average age is increasing. [22 ] , [24 ] , [30 ] , [31 ] The
vast majority of patients who experience ventricular septal rupture do so after their initial
infarction. [24 ] , [31 ] The overall incidence of postinfarction ventricular septal rupture
may have decreased slightly during the past decade as a result of aggressive
pharmacologic treatment of ischemia, thrombolytic therapy, and prompt control of
hypertension in patients with evolving myocardial infarction. [31 ]
Angiographic evaluation of patients with postinfarction ventricular rupture indicates that

septal rupture usually is associated with complete occlusion, rather than severe
stenosis of a coronary artery. [32 ] On average, they have slightly less extensive
coronary artery disease, as well as less developed septal collaterals than do other
patients with coronary artery disease. [33 ] The lack of collateral flow noted acutely may
be secondary to anatomical configuration, edema, or associated arterial disease. Hill
and associates, in reviewing 19 cases of postinfarction ventricular septal rupture, found
single-vessel disease in 64 percent, double-vessel disease in 7 percent, and
triple-vessel disease in 29 percent. [34 ] However, the frequency of single-, double-, and
triple-vessel coronary artery disease is more evenly distributed in other series. [27 ] ,
[35 ]
In approximately 60 percent of cases, postinfarction ventricular septal defects are

located in the anteroapical septum following a full-thickness anterior infarction. These
anterior septal ruptures are caused by occlusion of the left anterior descending artery. In
about 2040 percent of patients, rupture occurs in the posterior septum following an
inferoseptal infarction that usually is the result of occlusion of a dominant right coronary
artery or, less frequently, a dominant circumflex artery. [36 ] Thus, ventricular septal
perforations occur most frequently in 65-year-old men with single-vessel coronary
disease and poor collateral flow who present 24 days following their first anterior
Pathogenesis
The infarct associated with septal rupture is transmural, generally quite extensive, and
involves on average, 26 percent of the left ventricular wall in hearts with septal rupture as
compared with only 15 percent in other acute infarctions. [24 ] In an autopsy study,
Cummings et al. found that in patients with acute anterior or inferior infarctions, the
amount of right ventricular infarction is much greater in hearts with septal ruptures as
compared to those without septal defects. [37 ] Likewise, hearts with posterior septal
rupture have more extensive left ventricular necrosis than do hearts with inferior
infarctions and no septal defects.
Why certain hearts rupture and others do not is unclear at present. Slippage of
myocytes during infarct expansion may allow blood to dissect through necrotic
myocardium and enter either the right ventricle or pericardial space. [38 ] , [39 ] Hyaline
degeneration of cardiomyocytes with subsequent fragmentation and enzymatic
digestion may allow fissures to form and predispose to rupture. [40 ]
There are two types of rupture: simple, consisting of a direct through and through defect
usually located anteriorly; and complex, consisting of a serpiginous dissection tract
remote from the primary septal defect, which usually is located inferiorly. [41 ] Multiple
defects, which may develop within several days of each other, occur in 511 percent of
cases and are probably due to infarct extension. Since successful surgical outcome is
related to secure closure of septal defects, multiple defects must be sought
preoperatively if possible, and certainly at the time of operative repair.
Of the small number of patients who survive ventricular septal rupture, 3568 percent go
on to develop ventricular aneurysm by ventricular remodeling. [25 ] , [34 ] , [42 ] This
compares with a 12 percent incidence of aneurysm formation in patients who suffer
infarction without septal rupture. [43 ] The higher incidence of ventricular aneurysm with
septal rupture probably relates to transmural infarction. Postinfarction septal rupture,
especially in the posterior septum, may be accompanied by mitral valve regurgitation
owing to papillary muscle infarction or dysfunction. Approximately 33 percent of cases
of septal rupture have some degree of functional mitral insufficiency, secondary to left
ventricular dysfunction that usually resolves with repair of the defect. [33 ]
Pathophysiology
Following postinfarction ventricular septal rupture, the most important determinants of

early outcome are development of congestive heart failure and cardiogenic shock.
These conditions depend on the size of infarction and magnitude of the left-to-right
shunt. Left ventricular dysfunction, owing to extensive left ventricular necrosis, is the
primary determinant of congestive heart failure and cardiogenic shock in patients with
anterior septal rupture. Right ventricular dysfunction secondary to extensive right
ventricular infarction is the principal determinant of heart failure and cardiogenic shock
in patients with posterior septal rupture. [35 ] , [44 ] , [45 ] However, congestive heart
failure and cardiogenic shock are not solely explained by damage to the ventricle. [46 ]
The magnitude of the left-to-right shunt also contributes to hemodynamic compromise.
When the septal defect opens, pulmonary blood flow increases and systemic blood flow
decreases, as part of each stroke volume diverts to the pulmonary circuit. This sudden
increase in hemodynamic load further burdens a heart compromised by acute
infarction, and possibly ventricular aneurysm, mitral valve dysfunction or a combination
of these problems. Severe low cardiac output results. The normally compliant right
ventricle especially is susceptible to failure. [47 ] , [48 ] Patients with posterior
ventricular septal rupture and right ventricular dysfunction may have shunt reversal
during diastole because right ventricular end-diastolic pressure can be higher than left
ventricular end-diastolic pressure. [39 ] , [49 ] Ultimately, persistent low cardiac output
causes peripheral organ failure.
Diagnosis
The typical presentation of ventricular septal rupture is a patient with acute myocardial
infarction who develops a new systolic murmur, recurrent chest pain, and abrupt
deterioration in hemodynamics after convalescing for a few days. Development of a
loud systolic murmur, usually within the first week following acute infarction, is the most
consistent physical finding (present in over 90 percent of cases). The murmur usually is
harsh, pansystolic, and best heard at the left lower sternal border. The murmur often is
associated with a palpable thrill. Depending on the location of the septal defect, the
murmur may radiate to the left axilla, and mimic mitral regurgitation. [26 ] Up to half of
these patients experience postinfarction chest pain with appearance of the murmur. [24
] Usually the patient's clinical course also abruptly declines with congestive failure and
often cardiogenic shock. Acute cardiac failure is primarily caused by right heart failure.
Usually pulmonary edema is less prominent than in patients with acute postinfarction
mitral regurgitation. [50 ]
The electrocardiogram (ECG) reflects an antecedent anterior, inferior, posterior, or

septal infarction. Localization of infarction by ECG correlates highly with location of the
associated septal perforation. In our review of 55 patients, location of the defect
correlated with the ECG location of the infarct in all except three patients. [31 ] Up to 33
percent of patients develop some degree of atrioventricular conduction block (usually
transient) that precedes rupture, but no pathognomonic indicator predicts impending
perforation. [51 ] The chest radiograph usually shows increased pulmonary vascularity
consistent with pulmonary venous hypertension.
Acute mitral regurgitation caused by ruptured papillary muscle also produces a sudden
systolic murmur and hemodynamic deterioration following myocardial infarction. Several
points help to distinguish these two lesions clinically. First, the systolic murmur
associated with a septal rupture is more prominent at the left sternal border, whereas
the murmur of ruptured papillary muscle is best heard at the apex. Second, the murmur
associated with septal perforation is loud and associated with a thrill in over 50 percent
of patients; the murmur of acute mitral regurgitation is softer and without a thrill. [8 ]
Third, septal rupture often is associated with anterior infarctions and conduction
abnormalities; papillary muscle rupture is most commonly associated with an inferior
infarction and no conduction defects. [52 ] Finally, it should be noted that septal rupture
and papillary muscle rupture may coexist following infarction. [20 ] , [53 ] , [54 ]
Until recently, right heart catheterization using a Swan-Ganz catheter was the principal
means to differentiate septal rupture from mitral valve dysfunction. [55 ] With septal
rupture, a step-up in oxygen saturation develops between the right atrium and
pulmonary artery. A step-up greater than 9 percent confirms the presence of a
left-to-right shunt. [56 ] Pulmonary-to-systemic flow ratios (Qp/Qs), obtained from oxygen
saturation samples, range from 1.4:1 to greater than 8:1 and roughly correlate with the
size of the defect. [57 ] With acute mitral regurgitation secondary to papillary muscle
rupture, the pulmonary artery wedge pressure trace shows classic giant V-waves.
However, mild mitral regurgitation secondary to left ventricular dysfunction [58 ] is
present in up to 33 percent of patients with septal rupture.
Transthoracic and transesophageal echocardiography and color flow Doppler mapping

have revolutionized the diagnosis of ventricular septal rupture. [59 ] [61 ]
Echocardiography can detect the defect, localize its site and size, determine right and
left ventricular function, assess pulmonary arterial and right ventricular pressures, and
exclude coexisting mitral regurgitation or free wall rupture. Smyllie et al. [60 ] reported a
100 percent specificity and 100 percent sensitivity when color flow Doppler mapping
was used to differentiate ventricular septal rupture from acute severe mitral regurgitation
following acute myocardial infarction. The site of septal rupture was correctly
demonstrated in 41 of 42 patients. Echocardiography has replaced Swan-Ganz
catheter insertion for diagnosis of septal rupture, has accelerated surgical referral from
outlying hospitals and hastened operative repair. [22 ]
The necessity of preoperative left heart catheterization and coronary angiography is a

matter of debate. Left heart catheterization provides important information concerning
coronary artery disease, left ventricular wall motion, and valvular dysfunction. In most
series, over 60 percent of patients with septal rupture have significant involvement of at
least one vessel other than the one supplying the infarct. [62 ] , [63 ] Recently we
reported that bypassing associated coronary artery disease significantly increases
long-term survival when compared to patients with unbypassed coronary artery disease.
[64 ] For these reasons, we and others recommend preoperative left heart
catheterization, but recognize that the procedure is time-consuming and may contribute
to both the mortality and morbidity of these seriously ill patients. [22 ] , [62 ] Some
centers do not carry out preoperative left heart catheterization; others use it selectively
and avoid patients with septal rupture from anterior wall infarction because of a lower
incidence of multiple vessel coronary disease as compared to septal defects from
posterior infarctions. [22 ] , [65 ] , [66 ] In our studies, complementary bypasses at the
time of septal rupture repair increase longevity in patients with either anterior or
posterior septal rupture, but survival is greatest in patients with anterior septal rupture.
[64 ] Since hospital survival is not adversely influenced by complementary coronary
bypass grafting, [64 ] we confidently advocate coronary arteriography prior to surgery in
all patients, and revascularization of major stenotic vessels at the time of septal repair.
Natural History
Reviews by Oyamada and Queen, Sander et al., and Kirklin et al. reveal that nearly 25
percent of patients with postinfarction septal rupture and no surgical intervention die
within the first 24 hours, 50 percent die within 1 week, 65 percent within 2 weeks, 80
percent within 4 weeks, and only 7 percent live longer than 1 year. [8 ] , [67 ] , [68 ]
Lemery et al. report that of 25 patients with postinfarction ventricular septal defects
treated medically, 19 died within 1 month. [69 ] Thus, the risk of death is highest
immediately after infarction and septal rupture, then gradually declines. Despite many
advances in the nonoperative treatment of congestive heart failure and cardiogenic
shock, including the intra-aortic balloon pump and a multitude of new inotropic agents
and vasodilators, these methods do not supplant the need for operative intervention in
these critically ill patients.
Management
The early practice of delaying surgery for several weeks after ventricular septal rupture
only selects out a small minority of patients with less severe and better tolerated
hemodynamic insults. [19 ] , [35 ] , [70 ] Likewise, supportive management of most
patients, in hopes of deferring operation, deprives the great majority of definitive
surgery before irreversible damage due to peripheral organ ischemia occurs. [62 ] , [71
] We and others advocate early surgery, but some prefer to defer operation in patients
who are easily supported and are hemodynamically stable. [21 ] , [72 ] [74 ] Indications
for prompt operation include persistence of congestive heart failure or marginal
stabilization with rising blood urea nitrogen (BUN) and borderline urine output. The
intra-aortic balloon pump (IABP) frequently produces a transient reversal of
hemodynamic deterioration. This period of stability often makes it possible to complete
left-heart catheterization before operation but should not significantly delay operation.
Patients with septal rupture rarely die of cardiac failure per se, but die of end-organ
failure as a consequence of shock. Early operation shortens the duration of shock and
often yields dramatic results. [31 ] , [64 ] As long as one adheres to a policy of
proceeding with surgery before irreversible end-organ failure, no patient is too sick for
emergency operation.
Radford and associates reviewed 41 consecutive patients with postinfarction ventricular

septal rupture at the Massachusetts General Hospital between 1971 and 1975 and
found that the presence or absence of cardiogenic shock was the most important
determinant of operative mortality. [46 ] Thereafter, we employed intra-aortic balloon
pumping and immediate operative repair in all patients with cardiogenic shock. In 1982,
we again reviewed our experience and compared results achieved before 1975 with
those achieved after 1975. [31 ] Hospital survival was 59 percent for the group before
1975 and 75 percent for the group after 1975. However, the difference in hospital
survival was most dramatic for patients in cardiogenic shock: 27 percent survived
before 1975 versus 67 percent after 1975. Most other groups also report better
success with early operative repair and emphasize the importance of early operation
before development of multisystem failure. [45 ] , [72 ] , [75 ] [77 ]
These results suggest the following plan of surgical management for patients with
postinfarction ventricular septal rupture. Patients in cardiogenic shock represent a true
surgical emergency that requires immediate operative repair. The few patients who are
completely stable, without clinical deterioration and who require no hemodynamic
support, may undergo elective operative repair during that hospitalization. The large
group of patients who are intermediate between shock and stable hemodynamics
should be operated on early (usually within 1224 hours) after appropriate preoperative
evaluation. Since stable patients constitute less than 5 percent of the population with
postinfarction ventricular septal rupture, most patients require prompt surgical
treatment.
Rarely, because of a delayed referral, a patient is seen who already has multisystem
failure or has developed septic complications. This patient is unlikely to survive
emergency operation and thus may benefit from prolonged IABP support and an
attempt to reverse organ failure and control infection before operative repair. We have
treated three of 92 patients in this fashion. Baillot and colleagues report individual
successes with this approach, but success is the exception rather than the rule. [74 ]
Preoperative Therapy
Since the natural course of the disease is so dismal in unoperated patients, the
diagnosis of postinfarction ventricular septal rupture is an indication for operation. [71 ]
Preoperative management attempts to stabilize the circulation to maintain peripheral
organ perfusion while further diagnostic studies are obtained. Although the early clinical
course is variable, 5060 percent of patients with postinfarction ventricular septal rupture
present with severe congestive heart failure and low cardiac output that requires
intensive preoperative therapy. [78 ]
The goals of preoperative management are to (1) reduce systemic vascular resistance,
and thus, the left-to-right shunt; (2) maintain cardiac output and arterial pressure to
ensure peripheral organ perfusion; and (3) maintain or improve coronary arterial blood
flow. This is accomplished best by the intra-aortic balloon pump (IABP). As reported by
Gold and associates in 1973, counterpulsation reduces left ventricular afterload,
increases cardiac output, and decreases the left-to-right shunt. [79 ] In addition, IABP
support decreases myocardial oxygen consumption and improves myocardial and
peripheral organ perfusion. Although counterpulsation produces improvement, complete
correction of heart failure and low cardiac output cannot be obtained. [80 ] Peak
improvement occurs within 24 hours and no further benefit occurs with prolonged
balloon pumping. [81 ]
Pharmacologic therapy with inotropic agents and diuretics should be instituted

promptly. The use of vasodilators (i.e., sodium nitroprusside or intravenous
nitroglycerine) to decrease left to right shunting theoretically is sound, but often causes a
marked fall in mean arterial blood pressure and reduced coronary perfusion that are
poorly tolerated in these critically ill patients. It must be emphasized that pharmacologic
therapy is used to support the patient before operation and should not delay operation.
We now admit patients with postinfarction septal rupture directly to the surgical intensive
care unit rather than to the coronary care or medical intensive care unit.
Other techniques that have been tried in an effort to improve the hemodynamics of
patients with intraventricular septal rupture include veno-arterial extracorporeal
membrane oxygenation (ECMO), and inflation of a balloon in the right ventricular outflow
track to decrease the left-to-right shunt. [82 ] , [83 ] Neither procedure is reliable in
clinical application. Use of a catheter-mounted axial flow pump (Hemopump) to stabilize
these patients is controversial because pieces of necrotic tissue may acutely block
pump flow. [84 ]
The first repair by Cooley et al. of an acquired ventricular septal defect was done
through an incision in the right ventricular outflow tract. [5 ] This approach, which was
adapted for closure of congenital ventricular septal defects, was disadvantageous for
many reasons. Exposure of the defect, particularly for apical defects, frequently was
poor. The incision injured normal right ventricular muscle and interrupted collaterals from
the right coronary artery. Finally, the operation failed to eliminate paradoxical bulging of
the infarcted left ventricular wall. Subsequently,Heimbecker et al. introduced, and others
adopted, a left ventriculotomy with an incision through the area of infarction. [13 ] , [16 ] ,
[25 ] , [85 ] This incision frequently combines infarctectomy and aneurysmectomy with
repair of septal rupture.
Eight basic principles have evolved from our experience with a variety of techniques to
close postinfarction ventricular septal ruptures (Table 22-1) . These principles have led
to the development of separate approaches to apical, anterior, and inferoposterior
septal defects.
GENERAL TECHNIQUES
Patients are induced using Fentanyl-based anesthesia. Pancuronium is selected for

muscle relaxation to prevent bradycardia. Pulmonary vasodilators such as Dobutamine
are avoided to minimize left-to-right shunting. Preoperative antibiotics include both
Ancef and Vancomycin since prosthetic material is left in the patient.
Bicaval venous drainage is used for cardiopulmonary bypass. The patient is cooled to
25°C. Cardiac standstill is achieved with cold, oxygenated, dilute blood cardioplegia
using antegrade induction followed by retrograde perfusion via the coronary sinus. [86 ] ,
[87 ] A total of 1,2002,000 ml of cardioplegia solution is delivered depending on the
size of the heart and the degree of hypertrophy. [88 ] Although we have not employed
warm cardioplegic induction, we do give warm reperfusion cardioplegia before
removing the aortic cross clamp. [91 ] , [92 ] Patients with multivessel coronary disease
and critical coronary stenoses are revascularized before opening the heart to optimize
myocardial protection. In most of these patients, the left internal mammary artery is not
used.
APICAL SEPTAL RUPTURE
Apical amputation was described by Daggett and associates in 1970. [16 ] An incision
is made through the infarcted apex of the left ventricle. Excision of necrotic myocardium
back to healthy muscle amputates the apical portion of the left ventricle, right ventricle,
and septum ( Fig. 22-1A and Fig. 22-1B ). The remaining apical portions of the left and
right ventricular free walls are approximated to the apical septum. This is accomplished
by means of a row of interrupted mattress sutures of 0 Tevdek that are passed
sequentially through a buttressing strip of Teflon felt, the left ventricular wall, a second
strip of felt, the interventricular septum, a third strip of felt, the right ventricular wall, and a
fourth strip of felt ( Fig. 22-2A and Fig. 22-2B ). After all sutures are tied, the closure is
reinforced with an additional over-and-over suture, as in ventricular aneurysm repair, to
insure hemostasis (not shown).
ANTERIOR SEPTAL RUPTURE
These defects are approached through a transinfarct incision and infarctectomy in the
left ventricle (Fig. 22-3) . Small defects beneath anterior infarcts are closed by plication
as suggested by Shumaker. [93 ] This approximates the free anterior edge of the
septum to the right ventricular free wall using mattress sutures of 0 Tevdek over strips of
felt (Fig. 22-4A) . The transinfarct incision is closed with a second row of mattress
sutures buttressed with strips of felt ( Fig. 22-4B and Fig. 22-4C ). An over-and-over
running suture completes the ventriculotomy closure (not shown).
Most anterior defects require closure with a prosthetic patch (DeBakey Elastic Dacron
fabric made by U.S.C.I., Division of C.R. Bard, Inc., Billerica, MA) to avoid tension that
could lead to disruption of the repair (Fig. 22-5) . After debridement of necrotic septum
and left ventricular muscle, a series of pledgeted interrupted mattress sutures are
placed around the perimeter of the defect (Fig. 22-5A) . Along the posterior margin,
sutures are passed through the septum from the right side to the left. Along the anterior
edge of the defect, sutures are passed from the epicardial surface of the right ventricle
to the endocardial surface. All sutures are placed before the patch is inserted. Then, all
sutures are passed through the edge of a synthetic patch that is seated on the left side
of the septum (Fig. 22-5B) . Each suture is passed through an additional pledget and all
are tied. We use additional pledgets on the left ventricular side overlying the patch (Fig.
22-5) to cushion each suture as it is tied down to prevent cutting through friable muscle.
The edges of the ventriculotomy are approximated by a two-layer closure consisting of
interrupted mattress sutures passed through buttressing strips of Teflon felt and a final
over-and-over running suture (not shown).
POSTERIOR SEPTAL RUPTURE
Closure of inferoposterior septal defects, produced by transmural infarction in the

distribution of the posterior descending artery, poses the greatest technical challenge.
[20 ] Early attempts to close these defects by simple plication similar to those used for
anterior defects frequently were unsuccessful because sutures tore out of the soft,
friable myocardium closed under tension. This caused the defect to reopen or
catastrophic disruption of the infarctectomy closure. Analysis of our early efforts to close
these defects led to the evolution of the operative principles enumerated in Table 22-1 .
The following techniques have greatly improved operative survival. After establishing
cardiopulmonary bypass with bicaval cannulation, the left side of the heart is vented via
the right superior pulmonary vein. The heart is retracted out of the pericardial well, as for
coronary bypass, to the posterior descending coronary artery. The margins of the defect
may involve the inferior aspects of both ventricles or only the left ventricle (Fig. 22-6A) .
A transinfarct incision is made in the left ventricle, and the left ventricular portion of the
infarct is excised (Fig. 22-6B) , to expose the septal defect. The left ventricular papillary
muscles are inspected. Mitral valve replacement is performed only if there is frank
papillary muscle rupture. When indicated, we replace the mitral valve through a
separate, conventional left atrial incision, to avoid trauma to friable ventricular muscle.
After all infarcted left ventricular muscle is excised, less aggressive debridement of the
right ventricle is done to resect only as much muscle as is necessary to completely
visualize the defect. With this technique, delayed rupture of the right ventricle has not
been a problem. If the posterior septum has cracked or split from the adjacent
ventricular free wall without loss of much septal tissue, the rim of the posterior defect
may be approximated to the edge of the diaphragmatic right ventricular free wall using
mattress sutures buttressed with strips of Teflon felt ( Fig. 22-6C and Fig. 22-6D ).
Larger posterior defects require patch closure (Fig. 22-7) . Pledgeted mattress sutures
are placed from the right side of the septum and from the epicardial side of the right
ventricular free wall (Fig. 22-7B) . All sutures are passed through the perimeter of the
patch and then through additional pledgets and are then tied (Fig. 22-7C) . As for
closure of large anterior defects, the patch is secured on the left ventricular side of the
septum. Direct closure of the remaining infarctectomy rarely is possible because of the
tension required to pull the edges of the gaping defect together. A prosthetic patch
generally is required. Originally, we cut an oval patch from a Cooley low porosity woven
Dacron tube graft (Meadox Medicals, Inc., Oakland, NJ). Currently, we cut this patch
from a Hemashield woven Dacron collagen impregnated graft (Meadox Medicals, Inc.).
Pledgeted mattress sutures are passed through the margin of the infarctectomy
(endocardium to epicardium) and then through the patch (Fig. 22-7D) , which is seated
on the epicardial surface of the heart. After each suture is passed through an additional
pledget, all sutures are tied (Fig. 22-7E) . The cross-sectional view of the completed
repair (Fig. 22-8) illustrates restoration of relatively normal ventricular geometry that is
achieved by appropriately sized patches.
ENDOCARDIAL PATCH REPAIR WITH INFARCT EXCLUSION
The concept that preservation of left ventricular geometry plays a crucial role in
preservation of left ventricular function is the foundation of endocardial patch repair of
postinfarction ventricular septal defects described by David and Cooley, and later by
Ross. [19 ] , [76 ] , [77 ] , [89 ] , [94 ] [96 ] This operative technique, which applies Dor's
technique of ventricular endoaneurysmorrhophy to ventricular septal rupture repair,
places an intracavitary endocardial patch to exclude infarcted myocardium and maintain
ventricular geometry. [94 ] Instead of closing the septal defect, it is simply excluded from
the high pressure zone of the left ventricle. Recent impressive results obtained using
infarct exclusion mandate a detailed description of the technique. [45 ] The following
descriptions are taken from the work of David and colleagues (with permission). [39 ] ,
[45 ] , [89 ]
In patients with anterior septal rupture, the interventricular septum is exposed via a left
ventriculotomy that is made through the infarcted anterolateral wall starting at the apex
and extending proximally parallel to, but 12 cm away from, the anterior descending
artery (Fig. 22-9A) . Stay sutures are passed through the margins of the ventriculotomy
to aid in the exposure of the infarcted septum. The septal defect is located and the
margins of the infarcted muscle identified. A glutaraldehyde-fixed bovine pericardial
patch is tailored to the shape of the left ventricular infarct, as seen from the
endocardium, but is made 12 cm larger. The patch is usually oval and measures
approximately 4 × 6 cm in most patients. The pericardial patch is sutured to healthy
endocardium all around the septal infarct (Fig. 22-9B) . Suturing begins in the lowest
and most proximal part of the noninfarcted endocardium of the septum with a
continuous 3-0 polypropylene suture. Interrupted mattress sutures with felt pledgets are
used to reinforce the repair. [96 ] The patch also is sutured to noninfarcted endocardium
of the anterolateral ventricular wall. Stitches are inserted 57 mm deep in the muscle and
45 mm apart. Sutures in the patch are at least 57 mm from its free margin to allow the
patch to cover the area between the entrance and exit of the suture in the myocardium.
[39 ] This technique minimizes the risk of tearing muscle as the suture is pulled taught. If
the infarct involves the base of the anterior papillary muscle, the suture is brought
outside of the heart and buttressed with a strip of bovine pericardium or Teflon felt
applied to the epicardial surface of the left ventricle. Once the patch is completely
secured to the left ventricular endocardium, the left ventricular cavity becomes largely
excluded from infarcted myocardium. The ventriculotomy is closed in two layers over
two strips of bovine pericardium or Teflon felt using 2-0 or 3-0 polypropylene sutures as
illustrated in Figure 22-9C . No infarctectomy is performed unless necrotic muscle along
the ventriculotomy is sloughing at the time of closure. Minimal infarcted muscle is
removed since the infarct is not exposed to left ventricular pressures when the heart
begins to work (Fig. 22-9D) . Alternatively, sutures can be passed through the
ventricular free wall and through a tailored external patch of Teflon or pericardium (Fig.
22-10) . [76 ] , [95 ]
In patients with posterior septal defects, an incision is made in the inferior wall of the left
ventricle 1 or 2 mm from the posterior descending artery (Fig. 22-11A) . This incision is
started at the midportion of the inferior wall and extended proximally toward the mitral
annulus and distally toward the apex of the ventricle. Care is taken to avoid damage to
the posterolateral papillary muscle. Stay sutures are passed through the fat pad of the
apex of the ventricle and margins of the ventriculotomy to facilitate exposure of the
ventricular cavity. In most cases, the rupture is found in the proximal half of the posterior
septum, and the infarction involves the posteromedial papillary muscle. [45 ] A
triangular-shaped bovine pericardial patch, approximately 4 × 7 cm in most patients, is
cut. The base of the patch is sutured to the fibrous annulus of the mitral valve with a
continuous 3-0 polypropylene suture starting at a point corresponding to the level of the
posteromedial papillary muscle and moving medially toward the septum until
noninfarcted endocardium is reached (Fig. 22-11B) . At that level, the suture is
interrupted and any excess patch material trimmed. The medial margin of the
triangular-shaped patch is sewn to healthy septal endocardium with a continuous 3-0 or
4-0 polypropylene suture taking bites the same size as described for anterior defects.
The lateral side of the patch is sutured to the posterior wall of the left ventricle along a
line corresponding to the medial margin of the base of the posteromedial papillary
muscle. Because the posterior wall of the left ventricle is infarcted, it is usually
necessary to use full-thickness bites and anchor the sutures on a strip of pericardium or
Teflon felt on the epicardial surface of the posterior wall of the left ventricle, right at the
level of the posteromedial papillary muscle insertion as shown in Figure 22-11B . Once
the patch is completely sutured to the mitral valve annulus, the endocardium of the
interventricular septum, and the full thickness of the posterior wall (Fig. 22-11C) , the
ventriculotomy is closed in two layers of full thickness sutures buttressed on strips of
pericardium or Teflon felt (Fig. 22-11D) . The infarcted right ventricular wall is left
undisturbed. If the posteromedial papillary muscle is ruptured, mitral valve replacement
is necessary. [89 ]
There are several theoretical advantages of infarct exclusion: (1) It does not require
resection of myocardium that, if excessive, depresses ventricular function, and if
insufficient, predisposes to a recurrent defect; (2) it maintains ventricular geometry,
which enhances ventricular function [42 ] ; and (3) it avoids tension on friable muscle
and may diminish postoperative bleeding. [45 ]
OTHER TECHNIQUES
Most other successful operative techniques adhere to the same general principles
described above. For example, da Silva and associates report a technique whereby a
non-transfixing running suture is used to secure a large prosthetic patch to the left side
of the ventricular septum, with little or no resection of septal muscle. [97 ] Tashiro et al.
describes an extended endocardial repair in which a saccular patch of
glutaraldehyde-fixed equine pericardium is used to exclude an anterior septal rupture.
[98 ] Usui et al. report successful repair of a posterior septal rupture using two sheets of
equine pericardium to sandwich the infarcted myocardium, septal defect, and
ventriculotomy. [99 ]
PERCUTANEOUS CLOSURE
Successful transcatheter closure of postinfarction ventricular septal rupture has been

reported using a double umbrella prosthesis. [100 ] However, recent experience at the
Boston Children's Hospital and Brigham and Women's Hospital suggests that device
closure is not effective for acute postinfarction ventricular septal defects. It is likely that
friable myocardium surrounding the rupture prevents adequate seating of the device
and also tends to expand the defect. In contrast, device closure was successful in all six
patients treated for residual or recurrent septal defects discovered after primary
operative repair (Michael Landzberg, personal communication). Technical
improvements in experimental devices to obliterate intracardiac shunts may one day
make percutaneous treatment of postinfarction ventricular septal rupture a primary
option, especially in high-risk patients with multi-system failure. However, current
indications are limited to recurrent or residual defects after surgical repair (Lawrence
Cohn, personal communication).
Of note, Hachida et al. introduced a balloon catheter from the groin to abolish the shunt
in a poor-risk patient with acute postinfarction septal rupture. [101 ] Hemodynamic
improvement occurred immediately and was sustained; 3 weeks later the septal defect
was successfully closed operatively.
Simultaneous Myocardial Revascularization
The decision to perform concurrent coronary artery bypass grafting in patients

undergoing emergent repair of postinfarction ventricular septal rupture is controversial.
[25 ] , [30 ] , [64 ] , [66 ] , [102 ] Some argue that revascularization provides no benefit
and requires preoperative left heart catheterization that is time-consuming and
potentially dangerous. [65 ] , [66 ] Loisance et al. base their policy of not revascularizing
patients with acute postinfarction septal ruptures on the fact that none of 20 long-term
survivors (five of whom had bypass) had incapacitating angina or recurrent myocardial
infarction. [103 ] Piwnica and associates report a series of 28 survivors of early
operative closure of postinfarction ventricular septal rupture, and only one had coronary
artery grafting. [102 ] Among 24 patients for whom follow-up was complete, only two
died later of cardiac causes. However, their report does not include information
regarding concomitant coronary artery disease and concurrent revascularization in the
32 patients who did not survive operation.
Some groups use left heart catheterization and concurrent coronary bypass grafting
selectively. [22 ] , [30 ] Davies and colleagues found that of 60 long-term survivors
(median 70 months; range 1174 months), only five patients developed exertional angina
during follow-up and none required revascularization. [30 ] This group avoids left heart
catheterization in patients with an acquired septal defect owing to a first anterior
infarction, if the patient has no history of angina or electrocardiographic evidence of a
previous infarction in another territory. [30 ] This policy is based on the fact that
multivessel disease is much less prevalent in patients with apical septal rupture from
anterior infarction. [22 ]
We and others increasingly revascularize stenotic arteries. [35 ] , [45 ] , [64 ] , [76 ] [78 ] ,
[104 ] We place aortocoronary vein grafts to major epicardial coronary arteries that
have severe proximal stenoses. Recently we reviewed our experience in patients
undergoing repair of postinfarction septal rupture to investigate early and late effects of
coronary artery revascularization. [64 ] Between June 1968 and April 1991, 75 patients
underwent coronary angiography and repair of postinfarction septal rupture. Thirty-three
patients had two- or three-vessel proximal coronary artery disease and had complete
revascularization; 19 patients also had two- or three- vessel coronary disease but did
not have bypass grafting performed at the time the septal defect was closed; and 23
patients had only single-vessel coronary artery disease that corresponded to the region
of the infarct. These 23 patients underwent ventricular septal defect repair only.
Cumulative 30-day mortality was similar in all three groups (2126 percent); however,
patients who had revascularization demonstrated significantly improved long-term
survival as compared to patients who did not have concomitant revascularization, even
though the extent of coronary artery disease and preoperative hemodynamics were
similar (Fig. 22-12) . After 5 and 10 years, survival was 72.2 and 47.8 percent,
respectively, in the bypassed group, 29.2 and 0 percent, respectively, in the
unbypassed group, and 52.2 and 36.5 percent, respectively, in patients with
single-vessel disease. These data support the policy of concomitant revascularization
during repair of postinfarction septal rupture and preoperative coronary angiography in
all patients with acute postinfarction septal rupture.
In our series, patients with anterior septal defects benefit from concomitant coronary
bypass more than patients with posterior septal defects (Fig. 22-13) . In patients with an
anterior septal perforation, only 16 percent with unbypassed coronary disease survived
5 years, but 92 percent of those who were revascularized were alive. These data
strongly argue against not doing coronary angiograms in patients with apical septal
rupture caused by anterior myocardial infarction. [30 ]
Intraoperative transesophageal echocardiography is essential to assess ventricular

function, ventricular dimensions, residual shunt, and mitral regurgitation when weaning
from cardiopulmonary bypass. The two most common problems encountered in
separating from bypass following repair of a postinfarction ventricular septal defect are
low cardiac output and bleeding. Although the treatment of low cardiac output following
cardiac surgery is beyond the scope of this chapter, a few agents and principles are
worth mentioning. First, most patients have an intra-aortic balloon pump (IABP) inserted
before surgery. If not, one should be inserted in the operating room, especially if low
output is secondary to left ventricular dysfunction. IABP also may benefit patients with
right ventricular failure by improving right coronary artery blood flow. We find intravenous
milrinone, a phosphodiesterase inhibitor, very effective in reversing low output
secondary to left ventricular dysfunction. Milrinone has inotropic and vasodilatory
properties that together increase cardiac output and reduce right and left filling
pressures and systemic vascular resistance. It is less arrhythmogenic than dobutamine,
causes less hypotension than amrinone, and is not associated with thrombocytopenia.
[105 ]
Posterior defects commonly are associated with mitral regurgitation and right heart
dysfunction secondary to extensive right ventricular infarction. [37 ] Management of right
heart failure is aimed at reducing right ventricular afterload while maintaining systemic
pressure. [106 ] Initial steps to manage right ventricular dysfunction include volume
loading, inotropic support, and correction of acidosis, hypoxemia, and hypercarbia. If
patients remain unresponsive to these measures, we infuse prostaglandin E1 (0.52.0
mcg/min) into the right heart, and titrate norepinephrine into the left atrium. [107 ] Inhaled
nitric oxide (2080 ppm), which selectively dilates the pulmonary circuit, is also
efficacious in the treatment of right heart failure. [108 ] More recently, intravenous
adenosine (50 mcg/kg/min) has been shown to be as effective as nitric oxide in
diminishing pulmonary vascular resistance and increasing cardiac output, without
reducing systemic blood pressure. [109 ]
In our experience, inability to separate from cardiopulmonary bypass does not occur if
the repair is successful. However, if a patient cannot be weaned from bypass using
conventional therapy and is under 70 years old with no residual, hemodynamically
significant lesion, we consider a ventricular assist device. A cardiac index less than 1.8
L/min/m 2 , left atrial pressure above 1825 mmHg, right atrial pressure below 15 mmHg,
and aortic pressure below 90 mmHg peak systolic are indications for a left ventricular
assist device. A cardiac index less than 1.8 L/min/m 2 , aortic pressure below 90 mmHg
peak systolic and left atrial pressure less than 15 mmHg, despite volume loading to a
right atrial pressure of 25 mmHg with a competent tricuspid valve are indications for a
right ventricular assist device. Four important points to remember when instituting
ventricular assistance are: (1) right ventricular failure may not become evident until left
ventricular assistance is started; (2) once refractory ventricular failure is identified, delay
in beginning support increases morbidity and mortality; (3) closure of a patent foramen
ovale is mandatory prior to left ventricular mechanical support; and (4) postoperative
hemorrhage should be treated aggressively and completely controlled. [110 ]
Management of Bleeding
To prevent postpump coagulopathy, we begin antifibrinolytic therapy with either

aprotinin or ϵ-aminocaproic acid (Amicar) before commencing cardiopulmonary
bypass. Half-dose aprotinin is administered by first giving an intravenous test dose of
10,000 KIU over 10 minutes, then loading patients with 1 million KIU over 20 minutes
prior to bypass. Another 1 million KIU is given in the pump prime, and 250,000 KIU/h is
administered during surgery. Heparin is monitored with activated clotting times (ACT)
but kaolin, not Celite, is used to activate the clot. Since aprotinin raises issues of
increased renal dysfunction and perioperative thrombotic events, [111 ] we use Amicar
in patients who (1) require aortocoronary bypass grafts; (2) are diabetic; or (3) have
known renal dysfunction. Amicar is administered by loading patients with 10 grams
prior to commencing bypass and adding another 10 grams to the pump prime. During
the procedure Amicar is continuously infused at 1 g/h during surgery. Postpump suture
line bleeding may be reduced by applying a fibrin sealant to the ventricular septum
around the septal defect before formal repair. [112 ] Biological glue may be effective in
controlling bleeding suture lines following repair, but we have limited experience with
these compounds. [113 ] As a last resort, Baldwin and Cooley suggest insertion of a left
ventricular assist device solely to reduce left ventricular distention and, indirectly, control
bleeding. [114 ]
Highlights of Postoperative Care
Early postoperative diuresis and positive end-expiratory pressure ventilation are used
to decrease the alveolar-arterial (A-a) oxygen gradient induced by increased
extravascular pulmonary water associated with cardiopulmonary bypass. Once the
patient is warm, we commonly use an intravenous infusion of furosemide and mannitol
(1 gram of furosemide in 400 cc of 20 percent mannitol) at a rate of 120 ml/h to keep
urine output greater than 100 cc/h. If preoperative renal function is compromised,
continuous veno-venous hemofiltration (CVVH) is employed postoperatively and
managed by our intensive care unit nurses.
Intractable postoperative ventricular arrhythmias secondary to reperfusion injury

sometimes are difficult to control using standard therapy. We find intravenous
amiodarone efficacious in these patients (1020 mg/kg over 24 hours). [115 ]
Operative Mortality
By adhering to the policy of early operative intervention, we reported an overall hospital

mortality of 25 percent in patients treated since 1975. [71 ] Mortality varied with the
anatomic location of the septal defect. Mortality was 34 percent for correction of
posterior defects and 15 percent for closure of anterior defects. Using similar
techniques, Skillington et al. reported an overall early mortality of 20.8 percent in 101
patients who underwent surgical correction of postinfarction ventricular septal defects
between 1973 and 1988 (32.6 for posterior defects and 12.1 percent for anterior
defects). [22 ] However, mortality in their most recent experience with 36 patients
(19871988) declined to 11.1 percent. [22 ] Deville, Fontan, and colleagues [35 ]
reported a similar improvement in mortality.
Using the infarct exclusion technique, David's group in Toronto reported an operative
mortality of 10 percent in 31 patients between 1980 and 1989 [77 ] and 14 percent in 44
patients in an updated report. [45 ] This experience compares favorably with 2040
percent operative mortality figures for infarctectomy and Dacron reconstruction of the
ventricular wall in most series reported after 1990. [22 ] , [35 ] , [62 ] , [64 ] Importantly,
operative mortality for posterior defects in David's series was only 13.6 percent, no
worse than that for anterior ruptures. [45 ] David and colleagues suggest that their low
operative mortality, especially for posterior ruptures, is because infarct exclusion
causes less ventricular dysfunction than repairs that require infarctectomy. [45 ]
The single most important determinant of operative mortality is cardiogenic shock

which signifies extensive loss of ventricular mass. [35 ] , [45 ] , [77 ] , [78 ] , [82 ] , [116 ] ,
[117 ] Other factors also increase the risk of early death. Posterior location of the septal
rupture is associated with increased operative mortality. [35 ] , [37 ] , [47 ] , [49 ] This is
attributed to a more technically difficult repair and to associated right ventricular
dysfunction, which is an independent predictor of early mortality following posterior
infarction. [19 ] , [48 ] , [63 ] , [118 ] Interestingly, a recent retrospective analysis of 109
patients stratified the location of the septal defect into four sites: proximal, posterior,
distal, and anterior. Proximal location of the septal defect (not posterior) was the main
predictor of cardiogenic shock, which was, in turn, the strongest determinant of early
mortality (34.3 percent vs. 16.7 percent for distal septal defects). [117 ] A short time
interval between infarction and operation, which selects for sicker patients unable to be
managed medically, and patient age are also risk factors for early mortality. [21 ] , [82 ] ,
[117 ] , [119 ] Thus, the highest risk patient is an elderly individual with a proximal,
posterior ventricular septal defect who is in severe heart failure and is operated on 12
days after infarction. The most common cause of death following repair of acute
postinfarction ventricular septal defect is low cardiac output. Other causes include
cerebrovascular complications, intractable ventricular arrhythmias, and renal failure.
Long-Term Results
Both survival and functional rehabilitation are favorable long-term. Actuarial survival at 5
years for most recent series ranges between 6083 percent. [30 ] , [31 ] , [35 ] , [39 ] , [64
] Sixty-four percent of our patients treated since 1975 are long-term survivors. Eight of
19 long-term survivors are in New York Heart Association functional Class I, and 10 are
in New York Heart Association functional Class II. [31 ] In a recent review, we noted that
patients over age of 70 who survived closure of the ventricular septal defect survived
long-term and over 90 percent remained in New York Heart Association functional
Classes I or II (Fig. 22-14) . [94 ] As mentioned earlier, concomitant myocardial
revascularization in patients with postinfarction ventricular septal defects enhances
long-term survival (Fig. 22-12 and Fig. 22-13 ). [64 ]
Gaudiani and associates report similar long-term results using an early operative
approach. [78 ] In their series, 88 percent of hospital survivors are alive at 5 years, and
74 percent of survivors are in New York Heart Association functional Class I and 21
percent in functional class II. Piwnica and associates report 20 long-term survivors, of
whom eight are in New York Heart Association functional Class I, and 12 are in Class II.
[102 ] David et al. report a 66 percent 6-year survival rate in patients operated on since
1980. [45 ] Finally, in what is probably the largest follow-up study to date (60 long-term
survivors), Davies et al. report 5-, 10- and 14-year survivals of 69, 50, and 37 percent,
respectively. [30 ] Eighty-two percent of patients are in New York Heart Association
functional Classes I or II. Thus, aggressive management of postinfarction ventricular
septal rupture with early surgery yields excellent long-term survival and functional results.
Recurrent Ventricular Septal Defects
Recurrent or residual septal defects are diagnosed by Doppler color flow mapping early
or late after operation in 1025 percent of patients. [22 ] These may be caused by
reopening a closed defect, an overlooked defect, or to new septal rupture during the
early postoperative period. These recurrent defects should be closed for symptoms or
signs of heart failure or when the calculated shunt fraction is large (Qp:Qs > 2.0). When
defects are small (Qp:Qs < 2.0) and either asymptomatic or controlled with minimal
diuretic therapy, medical management is reasonable and late spontaneous closure may
occur. [22 ] Interventional cardiac catheterization using a clam-shell device may become
useful for closing symptomatic, postoperative residual, or recurrent defects.
Chronic Ventricular Septal Defects
In 1987 Rousou and associates reported successful closure of an acquired posterior

ventricular septal defect through the right atrium. [120 ] Filgueira and colleagues also
used the transatrial approach for delayed repair of chronic, acquired posterior septal
defects. [121 ] Transatrial exposure should not be used in acute patients because the
necrotic septum is friable and because the infarct is not removed or excluded and
compromises hemodynamics by paradoxical bulging. However, the right atrial
approach is suitable for chronic postinfarction ventricular septal defects since the
septum is well scarred and the patch can be securely sutured from the right atrium. We
emphasize that although transatrial exposure may be used selectively for chronic
defects, it is rarely appropriate for closure of acute defects, except perhaps when an
infarct is localized to the septum without evidence of necrosis of the left ventricular free
wall. [39 ]
POSTINFARCTION VENTRICULAR FREE WALL RUPTURE
History
William Harvey first described rupture of the free wall of the heart after acute myocardial
infarction in 1647. [122 ] In 1765, Morgagni reported 11 cases of myocardial rupture
found at autopsy. [123 ] Ironically, Morgagni later died of myocardial rupture. [124 ]
Hatcher and colleagues from Emory University reported the first successful operation
for free wall rupture of the right ventricle in 1970. [125 ] FitzGibbon and colleagues in
1971 and Montegut in 1972 reported the first successful repairs of left ventricular
rupture associated with ischemic heart disease. [126 ] , [127 ]
Incidence
Autopsy studies reveal that ventricular free wall rupture occurs about ten times more
frequently than postinfarction ventricular septal rupture, and happens in about 11
percent of patients following acute myocardial infarction. [23 ] , [128 ] Ventricular rupture
and cardiogenic shock are now the leading causes of death following acute myocardial
infarction and together account for over 66 percent of early deaths in patients with a first
acute infarction. [129 ] Postinfarction ventricular ruptures are more common in elderly
women (mean age 63 years) with a first infarction. [130 ] , [131 ] In the prethrombolytic
era, 90 percent of ruptures occurred within 2 weeks after infarction; the peak incidence
was at 5 days. [132 ] Thrombolysis and coronary reperfusion seem to accelerate the
time to cardiac rupture (not necessarily frequency of rupture); with thrombolysis, rupture
may occur within hours from the onset of symptoms. [133 ] Thus, free ventricular ruptures
occur most frequently in hypertensive women over the age of 60 who develop symptoms
within 5 days of their first transmural myocardial infarction.
Opinions differ as to the most common site of left ventricular rupture. The older literature
suggests that the anterior wall is the most frequent site. [134 ] However, more recent
series report a preponderance of lateral and posterior wall ruptures. [27 ] , [128 ] , [132 ]
David suggests that a lateral wall infarction is more likely to rupture than is an anterior or
inferior one, but since anterior infarctions are much more frequent than lateral
infarctions, the anterior wall is the most common site. [135 ] Like postinfarction
ventricular septal rupture, free wall ruptures may be simple or complex. [41 ] A simple
rupture results from a straight through-and-through tear that is perpendicular to the
endothelial and epicardial surfaces; a complex rupture results from a more serpiginous
tear that often is oblique to the endocardial and epicardial surfaces. [135 ] Batts et al.
report 100 consecutive cases of left ventricular free wall rupture and find that 50 percent
were simple ruptures and the rest were complex. [132 ]
Pathogenesis and Pathophysiology
Left ventricle free wall rupture can be divided into three clinicopathological categories,
acute, subacute, and chronic. [136 ] , [137 ] An acute or blow-out rupture is
characterized by sudden recurrent chest pain, electrical mechanical dissociation,
profound shock, and death within a few minutes caused by massive hemorrhage into
the pericardial cavity. This type of rupture probably is not amenable to current
management. A subacute rupture is characterized by a smaller tear that may be
temporarily sealed by clot or fibrinous pericardial adhesions. Usually these present with
the signs and symptoms of cardiac tamponade and eventually, cardiogenic shock.
Subacute rupture may mimic other complications of acute myocardial infarction, such
as infarct extension or right ventricular failure, and may be compatible with life for
several hours or days or even longer. [135 ] A chronic rupture with false aneurysm
formation occurs when blood leakage is slow and when surrounding pressure on the
epicardium temporarily controls the hemorrhage. Adhesions form between the
epicardium and pericardium to reinforce and contain the rupture. [29 ]
Congestive heart failure is the most common clinical presentation of patients with false
aneurysms of the left ventricle. [138 ] False aneurysms also are discovered by
echocardiography in an otherwise asymptomatic patient who is recovering from acute
myocardial infarction. Angina, syncope, arrhythmias, and thromboembolic
complications occur in a small percentage of patients. [138 ] There are four major
differences between a true and false aneurysm of the left ventricle: (1) the wall of a false
aneurysm contains no myocardial cells; (2) false aneurysms are more likely to form
posteriorly; (3) false aneurysms usually have a narrow neck; and (4) false aneurysms
have a great propensity for rupture. [138 ] [140 ] Rupture of the free wall of the left
ventricle may occur in isolation or with rupture of other ventricular structures such as the
interventricular septum, papillary muscles, or right ventricle. [138 ] , [141 ]
The pathogenesis of cardiac rupture remains poorly understood. However, cardiac

rupture occurs only with transmural myocardial infarctions, and infarct expansion
appears to play an important role in the pathogenesis. [38 ] , [42 ] , [142 ] Infarct
expansion is an acute regional thinning and dilatation of the infarct zone, seen as early
as 24 hours following acute transmural myocardial infarction, and it is not related to
additional myocardial necrosis. [143 ] This regional thinning and dilatation of the infarct
zone is a consequence of slippage between muscle bundles, that reduces the number
of myocytes across the infarct. [144 ] Infarct expansion increases the size of the
ventricular cavity, increases wall tension and predisposes the infarct to endocardial
tearing. [135 ] Systemic hypertension aggravates thinning and dilatation of the infarct
wall and increases the probability of rupture. [145 ] Lack of collateral blood flow may
also promote ventricular rupture. [146 ]
Since myocardial rupture occurs in complete transmural myocardial infarcts, usually

after extensive hemorrhagic transformation, [142 ] , [147 ] , [148 ] and since thrombolytic
therapy may convert a bland infarct into a hemorrhagic infarct, [149 ] the possibility that
thrombolysis may increase the likelihood of ventricular rupture arises. [150 ] Honan et al.
performed a meta-analysis of four large clinical trials (1,638 patients) in which
streptokinase was used to treat acute myocardial infarction. They concluded that the
risk of cardiac rupture is directly related to the timing of thrombolytic therapy. [147 ]
Early treatment (within 7 hours from the onset of symptoms) decreases the risk of
cardiac rupture, but late treatment (after 17 hours) increases the risk of this
complication, even though, surprisingly, overall mortality diminishes when streptokinase
is given late after acute infarction. In a prospective Late Assessment of Thrombolytic
Efficacy (LATE) ancillary study of 5,711 patients, Becker et al. were unable to show an
increased risk of cardiac rupture in patients treated with rt-PA (recombinant tissue
plasminogen activator) 624 hours after the onset of symptoms. [133 ] Thus, there was
general agreement that early, successful thrombolysis decreased the risk of cardiac
rupture, probably by limiting the extent of necrosis to produce a nontransmural instead
of a transmural infarct. However, the impact of late thrombolytic therapy on cardiac
rupture remained unclear.
Diagnosis
The clinical presentation of a subacute ventricular rupture is primarily that of pericardial

tamponade with pulsus paradoxus, distended neck veins, and cardiogenic shock. The
hemodynamics of tamponade include hypotension, right atrial and pulmonary capillary
pressures >10 mmHg, equalization of right atrial and pulmonary capillary pressures
(with a difference <5 mmHg between both pressures), and a right atrial pressure
waveform exhibiting a deep x descent and blunted y descent. [151 ] Identification of
clinical or hemodynamic findings of cardiac tamponade should be followed by a
transthoracic or transesophageal echocardiogram to confirm the presence of a
pericardial effusion. Although 537 percent of patients with acute myocardial infarction
without rupture may develop pericardial effusion, echocardiographic signs that increase
the sensitivity and specificity for cardiac rupture include: effusion thickness >10 mm;
echo-dense masses in the effusion; ventricular wall defects; and signs of tamponade
(e.g., right atrial and right ventricular early diastolic collapse and increased respiratory
variation in transvalvular blood flow velocity). [130 ] , [152 ] [154 ] Pericardiocentesis
and aspiration of uncoagulated blood is considered the most reliable criterion of
subacute ventricular rupture [155 ] , [156 ] ; however, false positive and false negative
diagnoses are reported. [130 ] , [153 ] Demonstration of clear pericardial fluid after
pericardiocentesis definitively excludes cardiac rupture. [153 ] Pericardiocentesis is
also therapeutic in some patients, by providing short-term circulatory improvement. [157
] However, echocardiography provides the most prompt diagnosis of cardiac rupture.
[130 ]
Oliva et al. retrospectively studied 70 consecutive patients with rupture and 100
comparison patients with acute myocardial infarction without rupture in an attempt to
define symptomatic, electrocardiographic, and hemodynamic markers that identified
patients prone to acute postinfarction ventricular rupture. [128 ] They found several
markers that were associated with a significant increase in the risk of rupture ( Table
22-2 ). Lateral infarction, especially with associated inferior or posterior infarction
increased the risk for rupture. Persistent, progressive or recurrent ST segment
elevation, persistent T-waves changes after 4872 hours, or gradual reversal of initially
inverted T-waves were associated with an increased risk of rupture. Finally,
development of pericarditis, repetitive emesis, or restlessness and agitation, especially
in combination, predicted the possibility. [128 ] In a similar study, Pollak et al. identified
lateral wall involvement, history of hypertension, and age >65 as risk factors for
subacute left ventricular rupture following acute myocardial infarction. [154 ]
Diagnosis of left ventricular false aneurysm can be made preoperatively by several

imaging techniques including, echocardiography, computed tomography, magnetic
resonance imaging, radionucleotide studies, and contrast ventriculography. [140 ] , [158
] , [159 ]
Natural History
Acute rupture of the free wall of the left ventricle invariably is fatal; death usually occurs
within minutes of the onset of recurrent hest pain. [132 ] , [135 ] , [146 ] In most cases,
the sequence of events leading to death is so rapid that there is not time for surgical
intervention. In contrast, patients with subacute rupture usually survive hours or days
and, rarely, weeks following the myocardial tear. [137 ] Pollak et al. found that in 24
cases of postinfarction subacute rupture, survival time (i.e., time from the critical event
to death) varied between 45 minutes and 6.5 weeks, with a median of 8 hours. [154 ]
Núñez and associates found that in 29 cases of subacute rupture, 20 (69 percent) died
within minutes of the onset of symptoms and nine (31 percent) lived several hours. [160
] Subacute ventricular ruptures occur less commonly than acute free wall ruptures, but in
recent studies with high autopsy rates, 2142 percent of all postinfarction free wall
ruptures followed a subacute course. [154 ] , [161 ] , [162 ]
Because of its rarity, the natural history of false aneurysms of the left ventricle is not
established. [135 ] They are believed to have a poor prognosis because of a high
probability of rupture [139 ] , [163 ] , [164 ] ; however, in some patients the diagnosis
was made many years after myocardial infarction. [138 ] , [165 ] , [166 ] Wide
application of echocardiography after acute myocardial infarction promises to improve
clinical outcomes for many patients with the various forms of ventricular wall rupture.
Preoperative Management
Usually, the sequence of events leading to death is so rapid in patients with acute, free
wall left ventricular rupture that surgery is not possible. [135 ] These patients usually die
within minutes of the onset of recurrent chest pain. [160 ] However, a high index of
suspicion, and percutaneous, intrapericardial infusion of fibrin glue immediately
following pericardiocentesis, may afford a chance for survival in these otherwise
untreatable patients. [167 ] , [168 ]
In contrast, patients with subacute left ventricular rupture can be saved with surgery.
Once the diagnosis of rupture of the free wall is established, the patient should be
immediately transferred to the operating room. No time should be wasted for coronary
angiography. [130 ] , [135 ] , [160 ] , [169 ] Inotropic agents and fluids should be started
while preparing for surgery. Pericardiocentesis often improves hemodynamics
temporarily, [169 ] and insertion of an intra-aortic balloon pump is usually beneficial,
even though the principal problem is cardiac tamponade. [156 ]
Timing of surgery following the diagnosis of false aneurysm of the left ventricle depends
on the age of the myocardial infarction. When a false aneurysm is discovered within the
first 23 months after coronary infarction, surgery is urgently recommended after
coronary angiography and ventriculography because onset of rupture is unpredictable.
[138 ] , [166 ] However, when the diagnosis is made several months or years after
myocardial infarction, the urgency and need for operation is determined by symptoms
and the severity of the coronary artery disease rather than the risk of rupture. [135 ] ,
[165 ]
SUBACUTE RUPTURE OF THE FREE WALL
As soon as the diagnosis of rupture of the free wall of the left ventricle is confirmed by
echocardiography, the patient should be transferred to the operating room. In patients
with tamponade, severe hypotension may result during induction of anesthesia. We
usually complete preparation and draping before inducing anesthesia. Others advocate
femoral artery cannulation before induction of anesthesia. [170 ] A median sternotomy is
performed and after the pericardium is decompressed, blood pressure often rises
quickly. This should be anticipated and controlled because hypertension may cause
ventricular bleeding to start again, or may even increase the size of the ventricular rent.
[135 ] In most cases, however, the ventricular tear is sealed off by clot, and there is no
active bleeding.
Traditionally, postinfarction rupture of the free wall of the left heart is repaired with
cardiopulmonary bypass [130 ] , [137 ] , [151 ] , [155 ] , [156 ] , [160 ] , [170 ] , [171 ] ;
however, recently, some surgeons question the need for cardiopulmonary bypass
except in patients with posterior wall rupture, severe mitral regurgitation, ventricular
septal rupture, or graftable coronary artery disease. [135 ] , [169 ] Although the
ventricular tear can be repaired without aortic cross-clamping, cardiac standstill and left
ventricular decompression facilitate the procedure when the rupture is in the posterior
left ventricular wall. [135 ]
Four surgical techniques are used to control ventricular rupture. The first technique
closes the rent with large horizontal mattress sutures buttressed with two strips of Teflon
felt. [125 ] , [172 ] This method is not recommended because sutures are placed into
necrotic, friable myocardium and easily tear. [130 ] The second method combines
infarct excision and closure of the defect with interrupted, pledgetted sutures [126 ] ,
[130 ] , [156 ] , [170 ] or a Dacron patch. [173 ] , [174 ] This method usually requires
aortic cross-clamping and is probably best reserved for patients who have an
associated ventricular septal defect. [160 ] The third technique, described by Núñez and
colleagues, [160 ] closes the defect with horizontal mattress sutures buttressed with two
strips of Teflon felt. This closure and surrounding infarcted myocardium are then
covered with a Teflon patch sutured to healthy epicardium with a continuous
polypropylene suture (Fig. 22-15) . This method provides good control of active
ventricular hemorrhage. [130 ] The fourth method consists of simply gluing a patch of
either Teflon [169 ] or autologous gluteraldehyde-preserved bovine pericardium [130 ] ,
[175 ] , [176 ] to the ventricular tear and infarcted area using a biocompatible glue of
either fibrin (Tissucol, Immuno AG, Vienna, Austria), butyl-2-cyanoacrylate monomer
(Histoacryl Blue, B. Braun, Melsungen AG, Germany) or gelatin-resorcin-formaldehyde
(Pharmacie Centrale, C.H.V. Henry Mondor, Créteil, France). This technique does not
require institution of cardiopulmonary bypass and may be the preferred repair when the
ventricle is not actively bleeding. [130 ] , [169 ]
FALSE ANEURYSM OF THE LEFT VENTRICLE
Acute false aneurysms are best repaired with an endocardial patch using the same
techniques used for repairing true ventricular aneurysms. [135 ] Chronic anterior false
aneurysms are usually closed primarily if the neck is fibrotic; however, primary closure
of the neck of a posterior false aneurysm may exacerbate mitral regurgitation.
Therefore, posterior aneurysms are reconstructed with a patch of Dacron graft or
glutaraldehyde-fixed bovine pericardium. [138 ] , [141 ]
Results
SUBACUTE RUPTURE OF THE FREE WALL
The surgical experience with this entity largely is anecdotal. The single largest
experience with surgical repair of postinfarction left ventricular free wall rupture was
reported by Padró and associates. [169 ] They treated 13 patients using a Teflon patch
glued onto the ventricular tear and surrounding infarcted muscle, and used
cardiopulmonary bypass in only one patient who had a posterior defect. All of their
patients survived and were alive at a mean of 26 months. Eleven were asymptomatic
and two had exertional angina. [169 ] Núñez et al. operated on seven patients, and four
survived. [160 ] Coletti and associates treated five patients and four survived. [130 ]
Pifarre et al. treated four patients successfully, whereas Pappas et al. treated four
patients with two survivors. [156 ] , [174 ]
Although operative risk can not be determined from these small numbers, without
surgery probably all these patients would have died. [135 ] It appears that, if patients
survive surgery, they tend to do well afterwards. [135 ]
FALSE ANEURYSM OF THE LEFT VENTRICLE
Komeda and David treated 12 patients with postinfarction left ventricular false
aneurysms; four also had mitral valve replacement, one had repair of a fistula between
the false aneurysm and the right ventricle, and nine had coronary artery bypass. [138 ]
There were three operative deaths; all occurred in patients who needed mitral valve
replacement. Of the eight patients who underwent isolated repair of a false aneurysm,
all were alive after a mean of 62 months. Seven patients were asymptomatic, and one
had angina pectoris. [138 ] Mackenzie and Lemole reported 14 cases of left ventricular
false aneurysm; 12 were related to a previous myocardial infarction. [140 ] There were
three operative deaths. Long-term follow-up was not reported. The literature suggests
that patients who have isolated repair of a left ventricular false aneurysm have a low
operative mortality. [135 ]
PREVALENCE
Between 17 and 55 percent of patients develop a mitral systolic murmur or

echocardiographic evidence of IMR early after AMI. [2 ] [9 ] [12 ] Thirty-five percent of
posteroinferior and 46 percent of anterior infarctions produce IMR that is detectable
within 48 hours of infarction by color-flow Doppler velocity mapping. [12 ] Of patients
who have cardiac catheterization within 6 hours of the onset of symptoms of AMI, 18.2
percent have IMR. [5 ] In 3.4 percent of these patients, the degree of mitral insufficiency
is severe. [5 ] Many of the murmurs early after AMI are transient and disappear by the
time of discharge, [2 ] , [10 ] probably as a result of ventricular remodeling.
Nineteen percent of 11,748 patients who had cardiac catheterization for symptomatic
coronary artery disease had ventriculographic evidence of mitral regurgitation. [13 ] In
most of these patients the degree of mitral insufficiency was mild, but in 7.2 percent of
all patients the degree of regurgitation was 2+ or greater, and in 3.4 percent MR was
moderate or severe with evidence of heart failure. [13 ] In another study of consecutive
cardiac catheterizations, 10.9 percent of 1739 patients with coronary arterial disease
had MR. [14 ]
Collectively, these data indicate that IMR is most frequent early after AMI, but in many
patients it is mild or disappears completely. The relatively high incidence of IMR (10.9 to
19 percent) in catheterized patients with symptomatic coronary artery disease suggests
that chronic IMR persists in many patients after acute infarction and may develop
subsequently in others. [10 ] Approximately 11,200,000 Americans have angina or a
history of myocardial infarction, and untold millions more have asymptomatic coronary
atherosclerosis. [6 ] Using these figures, [6 ] , [13 ] , [14 ] the incidence of IMR in the
United States is estimated to be 1.2 to 2.1 million patients. From Hickey's data,
approximately 381,000 patients have moderate or severe IMR with heart failure. [6 ] ,
[13 ]
PATHOLOGY
IMR may present suddenly in association with AMI, electively as a late or chronic
manifestation of myocardial infarction, or less commonly as regional episodic ischemia.
The pathology is that of myocardial infarction, which does not need review here.
However, some pathologic aspects of infarctions that cause IMR relate to the
pathophysiology of the disease and have considerable clinical relevance. These
features of IMR are discussed below.
In sheep, which have unvarying coronary arterial anatomy, [15 ] ligation of two circumflex
marginal arteries infarcts 21 percent of the LV mass, includes the posterior papillary
muscle, and produces progressively more severe MR as the left ventricle dilates over
the subsequent 8 weeks. [15 ] Ligation of two circumflex marginals and the posterior
descending coronary artery infarcts 32 percent of the LV mass and produces
immediate MR. [16 ] Comparable infarctions in other ventricular locations, including
those involving the anterior papillary muscle, do not produce significant (>1+) MR.
However, unlike sheep, human coronary arterial anatomy varies considerably between
patients. [17 ]
Frantz et al. [14 ] carefully studied a group of 189 patients with both chronic MR and
coronary artery disease by coronary angiography and ventriculography but could not
prove a relationship between the development of IMR and specific coronary arterial
obstructions. Moderate or severe MR was found in 19 to 28 percent of patients with
high-grade isolated circumflex, left anterior descending (LAD) plus circumflex, LAD plus
right coronary artery (RCA), RCA plus circumflex, and three-vessel coronary arterial
obstructions. [14 ] They also found that isolated high-grade obstructions of the LAD or
RCA did not cause moderate or severe MR. In the Hickey et al. series, [13 ] 58 percent
of patients with symptomatic moderate or severe IMR had left main or three-vessel
coronary artery disease. After AMI, 54 to 60 percent of patients with severe IMR have
three-vessel disease, and 24 to 30 percent have two-vessel disease. [3 ] , [5 ]
Papillary muscles are supplied by small penetrating vessels that enter the base of the
muscle from overlying epicardial arteries. [17 ] The blood supply of both papillary
muscles has multiple sources. The posterior papillary muscle is supplied by either the
RCA or the terminal circumflex marginal arteries. [17 ] In patients with right dominant
coronary arteries, all or part of the posterior papillary muscle is supplied from the RCA
in 68 percent. [4 ] The terminal branches of the left circumflex system supply the
posterior papillary muscle in the remainder as well as in patients with left dominant
systems. [4 ] , [17 ] The anterior papillary muscle is supplied primarily by the circumflex
coronary arterial system, but often vessels or collaterals from the LAD and diagonal
coronary arteries contribute. [10 ] , [17 ] A lateral position of the anterior papillary muscle
within the ventricle is more likely to be supplied by a circumflex branch. [14 ]
By auscultatory criteria, IMR is more common after posterior infarction, [10 ] and the
severity of MR tends to be greater. [4 ] , [10 ] , [18 ] , [19 ] Transmural infarctions are
more common with posterior infarctions (56 versus 26 percent), [10 ] and
posteroinferior wall infarctions nearly always involve the posterior papillary muscle [10 ]
(Fig. 23-1) . In a series of 60 patients with chronic IMR, Becker [4 ] observed that the
posterior papillary muscle was involved in all 37 posterior infarctions, whereas only 12
of 23 anterior infarctions reached the anterior papillary muscle. Thus, although anterior
infarcts are usually larger than posteroinferior infarcts, [20 ] nearly half of those which
cause chronic IMR do not involve the papillary muscle.
Ruptured papillary muscle causes acute, often life-threatening IMR after AMI. The
posterior papillary muscle is involved three to six times more commonly than is the
anterior muscle. [21 ] [25 ] Either the entire trunk of the muscle or one of the heads to
which chordae attach may rupture. In most series partial rupture is more common [22 ] ,
[23 ] , [25 ] ; in a few the reverse is true. [21 ] , [26 ] Subendocardial infarcts are found in
approximately half of patients with ruptured papillary muscle, and a few have healed
previous infarctions. [22 ] , [24 ] , [25 ] The extent of the infarct may be small (<6 cm 2 ),
[22 ] averaging approximately 20 percent [21 ] , [25 ] but varies widely from 1 to 50
percent of the LV mass. [21 ] The extent of coronary obstructive disease varies and is
usually less severe than in patients with chronic IMR [4 ] ; approximately 25 percent have
only one vessel involved. [22 ] , [26 ] Complete rupture occurs most commonly within the
first week after acute infarction. [21 ] , [25 ] Partial rupture may be delayed up to 3
months. [22 ] , [25 ]
AMI also may produce sudden, severe mitral insufficiency without rupture of a papillary
muscle. These patients usually are described as having papillary muscle dysfunction,
[10 ] , [21 ] , [22 ] , [25 ] and indeed, the papillary muscle does not contract. The
associated LV wall at the base of the affected papillary muscle is invariably infarcted
[23 ] , [25 ] and often is hemorrhagic and friable. [23 ] In a study of 19 patients who died
with IMR without a ruptured papillary muscle after AMI, Heikkila [10 ] found that 63
percent had posterior wall infarctions involving the posterior papillary muscle; the
remainder had anterior infarctions that damaged the anterior papillary muscle.
In chronic IMR, sizes and ages of infarcts vary widely, but little morphologic data are
available to document the amount and distribution of scarred myocardium. Both small
and large infarctions involving the posterior papillary muscle and adjacent LV wall can
produce chronic IMR. [4 ] , [19 ] , [27 ] [29 ] Anterior wall infarctions that produce chronic
IMR are usually larger and associated with greater dilatation of the ventricle and even
aneurysm formation. [4 ] , [10 ] , [27 ] , [29 ] Wall motion scores in patients with chronic
IMR vary widely [19 ] , [30 ] ; the more severe degrees of MR are associated with larger
areas of myocardial asynergy. [19 ] Kono et al. [31 ] noted that the LV is more spherical
in patients with IMR and heart failure than in patients with previous infarctions that do not
produce MR. In all patients with chronic MR, the leaflets and chordae of the mitral valve
are intact. [4 ] , [32 ]
Surgeons usually describe a dilated mitral annulus at reparative operations for chronic
IMR, [33 ] , [34 ] but detailed measurements and information regarding prior infarctions,
the electrocardiogram, and ventricular dimensions during the cardiac cycle are not
reported. Izumi et al. [19 ] observed significant annular dilatation (>3 cm) in 11 of 43
patients with chronic IMR and noted a high correlation with increased LV volume and
centralization of the regurgitant jet. Severe LV enlargement may occur without any
dilatation of the mitral annulus. [10 ] , [27 ] Unlike dilated cardiomyopathies [35 ] or
degenerative or connective tissue MR, [36 ] the mitral annulus may or may not be dilated
in chronic IMR. [10 ] The annulus tends to dilate in proportion to LV volume, [19 ] and in
these patients the left atrium is often enlarged.
PATHOPHYSIOLOGY
The mitral valve has six anatomic components: leaflets, chordae tendineae, annulus,
papillary muscles, left ventricle (LV), and left atrium (LA). The mitral annulus is
saddle-shaped with cephalad promontories near the middle portions of the anterior and
posterior leaflets and caudad depressions at the commissures. [37 ] Function of the
normal mitral valve is wonderfully complex and involves precisely timed interactions
between the six components. These interactions are most easily described by relating
the changes in each of the six components during a cardiac cycle. For this description,
the cardiac cycle is divided into four periods, systole, diastole, isovolemic relaxation
(IVR), and isovolemic contraction (IVC), as defined below.
End systole (ES) is defined as the maximum negative LV dP/dT , [38 ] and end
diastole (ED) is defined as the peak of the QRS complex. End isovolemic contraction
(EIVC) is defined as the first time point at which the aortic root dP/dT is greater than
zero. End isovolemic relaxation (EIVR) is defined as the time at which the LV pressure
(LVP) is 10 percent of LVPmax and the LV dP/dT is less than zero. [38 ]
During IVC, left atrial filling begins immediately after the mitral valve closes and before
the aortic valve opens. [39 ] Flow through the mitral valve briefly reverses as the leaflets
coapt and bulge toward the atrium. [40 ] During systole, the left atrium rapidly fills [39 ]
and reaches maximum near ES. The position of the annulus ascends slightly during
atrial contraction, [41 ] [43 ] which occurs during late diastole, does not change during
IVC, and descends progressively 1 to 1.5 cm toward the apex throughout systole. [39 ] ,
[43 ] , [44 ] The annulus contracts asymmetrically [41 ] , [44 ] during atrial and ventricular
systole and in humans reaches a minimal area (mean reduction of 27 percent) in
midsystole. [45 ] Immediately after atrial contraction, the mitral leaflets approach each
other and close within 20 to 60 ms after pressure crossover when LVP exceeds LA
pressure. [39 ] Since the total area of leaflet tissue is approximately twice the total area
of the annulus, [27 ] , [46 ] the apposition point of the two leaflets at the time of pressure
crossover is very near the plane of the annulus. [47 ] , [48 ] At closure approximately 30
percent of the anterior cusp and 50 percent of the longer posterior cusp are in
apposition. [47 ] Chordae tendineae attached to the free edges and body of the leaflets
[47 ] restrict the upward movement of the slightly compliant leaflets and produce a tight
seal along the line of apposition. Chordal tension peaks in early systole and begins to
fall slowly in late systole and rapidly during isovolemic relaxation (IVR). [49 ] Papillary
muscles begin to shorten during late IVC and throughout systole in synchrony with
shortening of the adjacent ventricular wall. [50 ] The actual distance papillary muscles
shorten is small and ranges between 2 and 4 mm. [38 ] , [51 ] During systole, the
directions and timing of left ventricular contraction are not necessarily uniform
throughout systole because of the complex anatomic arrangement of muscle bundles
[29 ] , [52 ] and the timing produced by the impulse conduction pattern. [53 ] LV
shortening is greater in both equatorial axes than in the long axis. [53 ] LV wall thickness
increases during IVC and decreases rapidly during IVR. [54 ] Peak wall thickness
occurs near ES, but timing of the exact peak varies slightly between ventricular wall
segments. During systole, the ventricle progressively twists counterclockwise (as
viewed from the apex) along its longitudinal axis to reach a maximum at ES. [55 ]
During IVR, the left atrium begins to empty when LA pressure crosses over and
exceeds LVP. [39 ] , [40 ] The atrium empties rapidly in early diastole and further
diminishes with atrial contraction in late diastole just before IVC. [56 ] The LV may
actually generate negative pressure in early diastole if LAPs are low. [57 ] During IVR,
the mitral annulus to LV apex distance lengthens as the mitral annulus ascends in early
diastole, descends slightly, and ascends again with atrial contraction. [39 ] , [42 ] The
area of the mitral orifice increases slightly during IVR and continues to increase during
diastole until it reaches a maximum just before the left atrium contracts. [41 ] , [45 ] In
humans, the annular area index reaches a maximum of 3.9 ± 0.7 cm 2 /m 2 . [45 ] As
annular area increases, its shape changes asymmetrically; most of the area increase is
due to lengthening in the posterior and lateral parts of the annulus. [41 ] During IVR, the
mitral leaflets separate approximately 30 ms before LA pressure exceeds LV
pressure. [39 ] Peak blood flow through the valve occurs early in diastole, but the mitral
leaflets reach their maximal open position before peak flow occurs and begin closing
while flow is still accelerating. [58 ] The papillary muscles may shorten very slightly
during early IVR [38 ] , [50 ] , [51 ] , [59 ] but do not begin to lengthen until the beginning
of diastole. Papillary muscles reach maximum length shortly after ED during IVC.
Chordal tension decreases rapidly during IVR and remains near zero until late diastole,
when a small increase occurs. [49 ] , [58 ] The left ventricle relaxes and dilates after ES
and reverses the complex deformations of LV shape produced by systole. During early
diastole and the period of rapid filling, the ventricle dilates primarily along both
equatorial axes and much less along the longitudinal base-to-apex axis. [53 ] Only a little
shape change occurs in middiastole and after atrial contraction. Ventricular wall
thickness decreases [54 ] primarily during IVR. Lastly, the ventricle rapidly untwists
(rotating clockwise) during early diastole and more gradually during middle and late
diastole. [55 ]
The pathogenesis of both acute IMR in the absence of papillary muscle rupture and
chronic IMR is not completely clear because the ventricular deformations that occur after
infarctions that produce IMR are not fully understood. [14 ] , [28 ] , [44 ] , [46 ] , [60 ] [62 ]
Myocardial infarction does not disturb leaflets or chordae, nor does it directly affect the
left atrium. The fibrous trigones that form the central fibrous body that joins part of the
aortic annulus and anterior portion of the mitral annulus do not stretch after infarction, but
infarction may involve the septal portion of the anterior annulus and all or part of the
posterior annulus. This analysis suggests that infarction produces MR by altering the
ventricle, one or both papillary muscles, and possibly the septal and mural (posterior)
parts of the annulus.
Numerous studies have demonstrated conclusively that loss of papillary muscle

shortening does not cause MR. [28 ] , [46 ] , [60 ] , [62 ] [64 ] With ischemia or infarction
the papillary muscle elongates by 2 to 4 mm in sheep and dog [50 ] , [51 ] ; the tip
moves 1.5 to 3 mm closer to the annulus. [51 ] , [65 ] With few exceptions, [65 ] , [66 ]
echocardiographic studies in dog and humans do not show mitral valve prolapse with
acute IMR in the absence of papillary muscle rupture. [3 ] , [31 ] , [48 ] , [67 ] Absence of
valve prolapse is probably due to the absence of acute annular dilatation, the fact that
the area of the valve leaflets is much greater than the area encompassed by the
annulus, [46 ] , [68 ] and the minimal amount of papillary muscle elongation produced by
infarction. In acute postinfarction MR, the annulus does not dilate at all. [16 ] , [21 ] , [36 ]
AMI that involves a papillary muscle invariably involves the adjacent ventricle to which
the papillary muscle attaches. It is now clear that infarctions in specific locations of the
ventricle produce changes in ventricular shape, size, twist, and segmental wall motion
that displace the papillary muscle base. [16 ] , [31 ] , [60 ] , [69 ] This papillary muscle
displacement away from a perpendicular through the centroid of the valve annulus and
the ventricular apex alters the spatial relationships of valve closure by restricting the
upward motion of part of one or both leaflets [16 ] , [44 ] , [48 ] , [60 ] , [62 ] , [66 ] , [67 ] ,
[69 ] (Fig. 23-2)
In chronic IMR, mitral valve prolapse has been described [66 ] in a few patients, but the
vast majority have incomplete mitral valve closure due to papillary muscle and chordal
restriction of leaflet motion. [31 ] , [60 ] , [66 ] , [67 ] Pathologic studies consistently show
fibrosis and atrophy of infarcted papillary muscles, [3 ] , [10 ] , [27 ] , [28 ] and none has
demonstrated papillary muscle or chordal elongation. Nevertheless, surgeons have
described elongated chordae in some patients with myocardial infarction and MR. [33 ]
, [34 ] In these patients, elongated chordae and mitral valve prolapse without MR
probably antedate the infarction. [7 ] , [8 ] In a patient with preexisting mitral valve
prolapse, ventricular infarction may cause the previously competent valve to leak. This
hypothesis explains the sporadic observations of mitral valve prolapse in patients with
chronic IMR but needs preinfarction echocardiograms for confirmation.
In chronic IMR, the annulus may or may not dilate, and when dilatation is present, it is
usually is restricted to a portion of the annulus. The largest dilated annuli are found in
markedly enlarged hearts or those with LV aneurysms. [10 ] , [14 ] Infarctions often
spare the base of the heart, but ventricular deformations produced by infarction can
deform the mural part of the annulus away from the central fibrous body. [16 ] The
changes in mitral valvular components in chronic IMR primarily involve the LV and
papillary muscles; dilatation and deformation of the annulus and enlargement of the left
atrium are secondary changes produced by the MR and ventricular remodeling during
healing.
To summarize, in acute postinfarction MR that does not involve papillary muscle rupture,
changes in ventricular shape, size, twist, and segmental wall motion are primarily
responsible for the MR, since the annulus is not dilated, papillary lengthening is trivial,
and papillary muscle shortening is zero or minimal. Myocardial infarction does not affect
the leaflets or chordae. In chronic IMR, atrophy and fibrosis of a papillary muscle [10 ] ,
[27 ] may contribute to restriction of upward leaflet motion, but the paramount cause of
MR is deformations of ventricular geometry, dilatation and incoordinate segmental wall
motion caused by the infarction, and subsequent remodeling to compensate for the MR.
[14 ] , [16 ] , [28 ] , [31 ] , [60 ] Enlargement of the LA occurs as a secondary
phenomenon and is usually associated with both annular and LV dilatation. [10 ] , [27 ]
Although the term papillary muscle dysfunction refers to alterations in muscle length,
shortening, and position, [46 ] , [61 ] , [70 ] it overemphasizes changes in function and
length and deemphasizes the more important ventricular component. Papillary muscle
displacement , which may be passive (dyskinetic) or dynamic, better describes the
mechanism that is responsible for IMR in most patients with acute or chronic
postinfarction MR without papillary muscle rupture.
A full understanding of the ventricular deformations that produce or fail to produce MR

after infarction is not yet available. [14 ] There is little or no information regarding
changes in LV twist after infarctions in various locations (Fig. 23-3) . Aside from overall
ventricular dilatation, the role of ventricular remodeling after infarction in the
development of chronic IMR is not known. The higher incidence of MR after posterior
infarctions that involve the posterior papillary muscle correlates with observations of
localized ventricular wall bulging (dyskinesis) [16 ] , [60 ] and a more spherical
ventricular shape during systole. [31 ] Experimentally, infarctions that involve the anterior
papillary muscle in sheep do not produce MR but are also not associated with
segmental dyskinesis at the papillary muscle base. Clinically, anterior infarctions usually
do not cause chronic MR until the LV to which the papillary muscle attaches dilates or
becomes aneurysmal. [4 ] , [10 ] Annular dilatation after infarction does not occur as an
isolated pathologic finding but is usually associated with subsequent regional or global
LV enlargement. [36 ]
NATURAL HISTORY
After AMI, approximately 15 percent of mitral murmurs disappear by hospital discharge

and another 15 percent are gone within several months. [10 ] In patients with AMI who
do not have an early mitral murmur, approximately 12 percent develop an MR murmur
later. [10 ] Thus roughly 15 percent of patients have some degree of MR months after
AMI. [13 ]
The presence of MR after AMI as determined by color-flow Doppler velocity mapping or

cardiac catheterization increases the likelihood of pulmonary edema, cardiogenic
shock, and death. [2 ] , [5 ] , [12 ] However, when adjusted for age, ejection fraction,
heart failure, and other variables that affect mortality, the presence of MR is not an
incremental risk factor for death. [5 ] Nevertheless, even mild or moderate MR after AMI
doubles the 30-day and 1-year mortality to approximately 15 and 20 percent,
respectively, [5 ] as compared with patients without MR.
Without surgery, median survival following rupture of a papillary muscle trunk is 3 to 4

days. [21 ] , [25 ] Some patients with partial rupture or rupture of one head survive
several weeks or a few months. [22 ] , [71 ] Overall acute moderate or severe (3 or 4+)
IMR has a 30-day mortality of 24 percent and a 1-year mortality of 52 percent. [5 ] The
onset of cardiogenic shock reduces survival to a few days.
Chronic IMR of 2+ severity discovered at cardiac catheterization for symptomatic

coronary artery disease has a 1-year mortality of approximately 17 percent (Fig. 23-4) ;
1+ severity increases mortality to approximately 10 percent from about 6 percent if MR
is not present. [13 ] The 1-year mortality for 3 and 4+ IMR is approximately 40 percent,
[13 ] which is only slightly less than for severe MR after acute infarction. [5 ]
Three distinct clinical syndromes describe most patients with symptomatic IMR. Except
for prognostic considerations, patients who develop transient MR or a persistent
low-grade mitral systolic murmur after AMI are managed medically for coronary
ischemia until symptoms of chronic IMR and heart failure arise. The clinical spectrum of
IMR of interest to surgeons is presented below under the headings Acute Postinfarction
Mitral Regurgitation (acute IMR), Episodic Ischemic Mitral Regurgitation, and Chronic
Ischemic Mitral Regurgitation.
Acute Postinfarction Mitral Regurgitation
As noted above, MR is extremely prevalent after AMI. In most patients, the presence of
MR does not affect management of the AMI. Others develop postinfarction angina with
mild or moderate MR without symptoms or signs of heart failure. These patients are
managed similarly to patients with postinfarction angina without MR. A minority of
patients develop severe (3 or 4+) MR with symptoms of heart failure, low cardiac output,
or both.
Severe MR following AMI may be due to papillary muscle displacement as a result of an

infarct of specific size in a specific location or rupture of a papillary muscle trunk or tip.
Rupture of the trunk of a papillary muscle (Fig. 23-5) invariably results in rapid onset of
severe MR with pulmonary edema and cardiogenic shock and requires prompt
intervention for survival. Rupture of a papillary muscle tip usually produces severe MR
but is consistent with longer survival. [22 ] , [71 ] Acute severe postinfarction MR without
rupture is more common than papillary muscle rupture but may produce similarly severe
impairment of cardiac function. Although the specific pathology varies, acute severe
postinfarction MR is a distinct, highly lethal clinical entity that invariably requires surgery
or reperfusion of the infarct for survival.
Acute severe IMR occurs in 0.1 percent of patients with symptomatic coronary arterial
disease [13 ] and complicates 0.4 to 0.9 percent of all patients with AMI. [72 ] However,
in contemporary practice the incidence actually may be higher as more patients with
AMI survive. Wei et al. [21 ] observed papillary muscle rupture in 5 percent of all fatal
myocardial infarctions at Johns Hopkins Hospital. Approximately two-thirds of cases of
acute severe IMR involve the posterior papillary muscle, [10 ] , [21 ] , [25 ] , [73 ] even
though anterior myocardial infarctions are more common. An average of 20 percent of
the LV mass is infarcted, but in autopsy series the size of the infarct varies widely. [21 ]
PATHOPHYSIOLOGY
Acute severe MR produces acute LV volume overload and immediately increases LV

end-diastolic volume and decreases end-systolic volume. [74 ] Volume of reguritant flow
depends on the size of the incompetent valve opening during systole and the pressure
difference between the LV and LA. This pressure difference is influenced by LV
afterload, forward flow past the aortic valve, and myocardial contractile force. Acute MR
enhances early diastolic filling of the ventricle and decreases end-systolic wall stress
and end-systolic elastance. [75 ] Myocardial oxygen consumption does not change
because of reduced wall stress in late systole. [74 ] Stroke volume increases, and
initially, cardiac output may be maintained by a tremendous increase in stroke volume.
However, if the reguritant volume is very large, the amount of forward flow past the aortic
valve (i.e., cardiac output) decreases. With MR, ejection fraction increases in animals
without LV infarction; in patients with infarction, ejection fraction varies widely. [26 ] LA,
pulmonary capillary wedge, and LV end-diastolic pressures increase abruptly with acute
MR; end-diastolic wall stress also increases markedly, and end-diastolic wall thickness
and stiffness decrease slightly. [76 ] In patients with small atria, a prominent v wave
appears. [23 ] , [61 ] Pulmonary vascular resistance increases rapidly and may cause
right-sided heart failure. [74 ]
Acute severe IMR usually presents abruptly with an acute onset of chest pain and/or
shortness of breath. The age range of patients reflects the age range of myocardial
infarction; the mean age is around 60 years. The syndrome is slightly more common in
men than in women. Many have hypertension. Only a few patients have historical or
electrocardiographic (ECG) evidence of prior myocardial infarction, and less than half
have angina. [21 ] , [23 ] , [25 ] The disease presents as an AMI and occasionally may
be silent. [23 ] , [25 ] Papillary muscle rupture may occur as early as the first day after
infarction and nearly always within 7 days (mean approximately 4 days). [21 ] , [23 ] , [25
]
Typically, patients are short of breath, and many rapidly develop pulmonary edema
complicated by systemic hypotension. Most patients have a loud apical, holosystolic
murmur that radiates to the left axilla. [61 ] In some the murmur occurs in middle or late
systole; in others it may be absent [12 ] or difficult to hear because of pulmonary rales.
[23 ] The most compelling findings are those of low cardiac output and congestive
heart failure in the setting of AMI . Many patients develop cardiogenic shock
characterized by systemic hypotension, oliguria, acidosis, and poor peripheral pulses
and perfusion. [73 ] A few have cardiac arrest. [26 ]
DIAGNOSTIC STUDIES
Nearly all electrocardiograms are abnormal, [21 ] , [23 ] , [25 ] but only slightly more than
half are diagnostic of AMI. Some of the nondiagnostic changes include right or left
bundle branch block and nonspecific ST-segment and T-wave changes in the
anteroseptal, lateral, or inferior lead. [21 ] [23 ] , [25 ] , Most patients are in sinus rhythm.
[23 ] , [74 ] In autopsy series, the incidence of subendocardial infarctions is
approximately equal to the incidence of transmural infarctions. [21 ] , [25 ] Frequently,
patients with a ruptured papillary muscle have ECG evidence of an inferior infarction.
When the electrocardiogram (ECG) is diagnostic, inferior wall infarctions are much
more common than anterior and lateral wall infarctions. Conduction abnormalities are
relatively uncommon and are found more often in patients with postinfarction ventricular
septal defects. [77 ]
Chest x-rays nearly always show signs of pulmonary congestion, interstitial pulmonary
edema, and pulmonary venous hypertension. [23 ] The heart may or may not be
enlarged [21 ] and usually is not massively enlarged.
The differential diagnosis includes postinfarction ventricular septal defect, massive AMI
without significant MR, and ruptured chordae tendineae without AMI. Right-sided heart
catheterization from the bedside or in the catheterization laboratory usually shows
elevated pulmonary arterial pressures with prominent v waves reaching 40 mmHg or
higher. [23 ] , [26 ] Mean pulmonary artery wedge pressures are greater than 20 mmHg
unless cardiac output is very low. Mixed venous oxygen saturations are often well below
50 percent and reflect low cardiac output with indices that range from 1.0 to 2.9
liters/min per m 2 . [26 ] In the presence of a loud systolic murmur, absence of an oxygen
step-up in the pulmonary artery is strong evidence against the diagnosis of
postinfarction ventricular septal defect. ECG evidence of AMI distinguishes acute IMR
from ruptured chordae, but in some instances the two diseases cannot be distinguished
until after operation or death. [23 ]
Transthoracic echocardiography may show flail mitral leaflets but does not reliably
distinguish rupture of a papillary muscle from MR due to papillary muscle displacement
(dysfunction). [26 ] Typically, the LA is not enlarged, but the LV shows signs of volume
overload and segmental wall motion abnormalities. Color-flow Doppler velocity
mapping documents the presence of MR after myocardial infarction [12 ] and
semiquantitates its severity. [78 ] Ejection fractions vary widely but do not reliably reflect
the extent of myocardial damage or residual ventricular function. [26 ] Transesophageal
echocardiography, used primarily during operation, provides better detail of mitral valve
structures, segmental wall motion abnormalities, and the degree of MR. [79 ] , [80 ]
Despite hemodynamic instability, most patients have a diagnostic cardiac

catheterization primarily for definition of coronary arterial anatomy; however, the wisdom
of prescribing cardiac catheterization for patients in cardiogenic shock is highly
questionable in that revascularization of obstructed, remote coronary vessels is not
likely to improve a patient's chances for immediate survival. [73 ] Approximately half of
catheterized patients have single-vessel disease, often of the right coronary artery. [23 ]
, [26 ] Most of the remainder have three-vessel disease. [21 ] [23 ] , [25 ]
Ventriculography shows increased LV volume at both ED and ES, severe MR,
segmental wall motion abnormalities, [81 ] and a wide range of ejection fractions that
are generally over 40 percent and frequently over 60 percent. [22 ] , [26 ] LV
end-diastolic pressures are elevated with prominent left atrial v waves and moderate
pulmonary hypertension. Occasional patients have mild or moderate tricuspid
regurgitation. Cardiac output is low; the arteriovenous oxygen difference is often over 6
vol percent.
MEDICAL MANAGEMENT
The urgency and aggressiveness of initial management depend on the presence or

absence of cardiogenic shock and/or congestive heart failure. Because of the severity
of MR, definitive therapy means surgery or occasionally interventional cardiac
catheterization. Beyond the need for diagnosis and attempts to stabilize the circulation,
there is nothing to gain by deferring definitive therapy. In an intensive care unit setting,
patients are monitored by continuous ECG, measurement of peripheral oxygen
saturation, an arterial catheter with continuous display of arterial blood pressure, and a
Swan-Ganz catheter to monitor central venous pressure and pulmonary arterial
pressure and to obtain measurements of cardiac output (intermittently or ongoing) and
mixed venous oxygen saturation. An additional intravenous access may be needed. If
surgery is possible or probable, a blood sample should be sent for type and crossmatch
and routine blood work for hematology, electrolytes and glucose, renal function, and
coagulation studies. Blood gases for arterial oxygen saturation, paco 2 , and pH are
also obtained. Supplemental oxygen is provided by nasal prongs or mask. The decision
to intubate and ventilate the patient is made on the basis of clinical assessment of
respiratory distress, findings of pulmonary edema, low paco 2 or elevated paco 2 .
The adequacy or inadequacy of the circulation must be assessed early before

arrhythmias or cardiac arrest intervene. The criteria for cardiogenic shock vary slightly
between specialists, but systemic hypotension (peak pressure <80 mmHg; mean
pressure <55 mmHg), mixed venous oxygen saturation <50 percent, thermodilution
cardiac index <2.0 liters/min per m 2 , metabolic acidosis, oliguria, and poor peripheral
perfusion (pallor, cool extremities, faint peripheral pulses) are findings that collectively
or in various combinations indicate that the circulation is not adequate. Even if the
criteria for cardiogenic shock are not present, patients must be worked up promptly and
monitored carefully to avoid either progressive or abrupt deterioration of the circulation.
Necessary diagnostic studies are best performed as promptly as possible.
Circulatory performance must be optimized and monitored carefully. Arrhythmias should

be controlled promptly by drugs that least impair myocardial contractility (cardiac
glycosides) or cause hypotension. Electrical cardioversion is often the first choice for
tachyarrhythmias when cardiac output is low. Temporary pacing via skin electrodes or
an intravenous catheter may be the best treatment of bradyarrhythmias and atrial flutter.
Cardiac output is optimized by improving contractility using dobutamine alone or a
combination of dobutamine and epinephrine (or dopamine) if blood pressure is
unacceptably low. If cardiac output is low and the patient is hypotensive, the intraaortic
balloon pump is needed to maintain coronary perfusion pressure, unload the LV, and
slightly increase cardiac output. Newer methods of mechanically supporting the
circulation using intra- or extracorporeal circulatory devices may come into more
general use for younger patients who meet criteria for heart transplantation if the native
heart cannot be saved. For patients who are not hypotensive, pharmacologic reduction
of afterload using intravenous nitroglycerin, [82 ] adenosine, or nitroprusside improves
cardiac output. Management of fluid volume is critical and best guided by ongoing
measurements of central venous and pulmonary capillary wedge or diastolic pressures.
Additional volume must be given cautiously in critically ill patients to avoid volume
overload and acute decompensation of the ventricle. In less ill patients, additional
crystalloid or colloid may improve cardiac output and restore urine flow.
DEFINITIVE THERAPY
For most patients with acute severe postinfarction MR, prompt surgery is the best
chance for survival. A few, highly selected patients without papillary muscle rupture have
been treated by emergency percutaneous transluminal coronary angioplasty (PTCA)
and/or thrombolytic therapy in an attempt to reduce the size of the infarct and to reverse
leaflet restriction caused by papillary muscle displacement. [5 ] , [66 ] , [83 ] , [84 ]
PTCA or thrombolysis carried out within 4 hours of the onset of AMI may produce
spectacular reversal of both the infarction and MR, [66 ] , [83 ] , [84 ] and
intermediate-term follow-up of these patients indicates little or no MR. However, less
rapid PTCA may not succeed in preempting the infarct and aborting MR. [84 ] More
liberal application of PTCA and thrombolysis in patients catheterized within 6 hours of
AMI may restore mitral valve competence in some [85 ] and perhaps is worth trying if
patients are sufficiently stable and can be followed by echocardiography and color-flow
Doppler velocity mapping. However, in many patients PTCA and thrombolysis do not
provide a favorable outcome. [5 ] In patients with successful thrombolysis, 17 percent
died in hospital; in those with successful PTCA, 50 percent died shortly afterward and
77 percent were dead in 1 year. [5 ] Of the survivors, the majority continue to have 3 or
4+ MR. [5 ]
For patients who have acute postinfarction angina with 1+ or 2+ MR, urgent myocardial
revascularization is indicated to relieve angina and to prevent extension of the
infarction. It is important to prevent progression of MR and the development of
congestive heart failure or cardiogenic shock. This is usually accomplished by
thrombolysis, PTCA, or an intracoronary arterial stent. If these measures are
unsuccessful, operation is rarely completed in time to reverse the infarction, but early
operation may reduce the size of the ultimate infarct. [86 ] [88 ] The presence of mild to
moderate IMR does not increase operative mortality, [89 ] [91 ] but the presence of
congestive heart failure is a risk factor. [92 ] In these patients the mitral valve is not
exposed unless intraoperative transesophageal echocardiography indicates 3 or 4+
MR.
Indications for emergency surgery for acute severe postinfarction MR vary between
institutions [5 ] , [23 ] , [24 ] , [26 ] , [73 ] , [93 ] , [94 ] and probably explain wide
discrepancies in reports of hospitals mortality. [30 ] , [93 ] In this group of patients,
medical therapy does not produce survivors, [22 ] , [23 ] and patients denied operation
are not reported. [23 ] Aged patients are less likely to survive operation, [30 ] , [66 ] and
there are no reports of successful operation in octogenarians. Other risk factors for
hospital death are severe congestive heart failure, the number of comorbid diseases
such as renal or pulmonary problems, presence of the intraaortic balloon pump,
reduced ejection fraction, and greater number of diseased coronary arteries. [30 ]
Contemporary concerns regarding costs and longevity beyond immediate hospital
survival also influence indications for operation and reported mortality.
Operation for acute (within 30 days) severe postinfarction MR consists of mitral valve
repair or replacement with or without myocardial revascularization. Nearly all surgeons
recommend revascularization of all significantly obstructed coronary vessels away from
the site of the infarction, [93 ] and improved methods of cardioplegia support this
recommendation even in patients with preoperative cardiogenic shock who have had
cardiac catheterization. The wisdom of blind revascularization of remote coronary
vessels in patients who have not had preoperative cardiac catheterization and
revascularization of the infarct artery more than 4 to 6 hours after onset of pain is less
clear. [73 ] On a statistical basis, only half of patients with IMR have multivessel coronary
artery disease. [21 ] , [23 ] , [26 ] Revascularization of completed infarctions favorably
influences subsequent ventricular remodeling, [87 ] [89 ] and reperfusion arrhythmias
usually can be controlled.
OPERATION
Operation for acute severe postinfarction MR is often urgent or an emergency; a high

percentage of patients have the intraaortic balloon pump inserted before induction of
anesthesia. [26 ] , [73 ] Monitors include the ECG, arterial blood pressure, a Swan-Ganz
catheter with mixed venous oxygen electrode, nasopharyngeal and rectal (or bladder)
temperature, and a catheter for urine output. The heart is exposed through a midline
sternotomy, and needed saphenous vein is harvested simultaneously. Because of the
extra time needed and typically precarious condition of the patient, mammary arteries
are seldom used for revascularization. Both cavae are cannulated separately, and the
pericardial attachments around the superior and inferior cavae and the right pulmonary
veins are dissected back. Most patients with acute IMR have small left atria. During
cardiopulmonary bypass, the patient may or may not be cooled; the aorta is
cross-clamped; the heart is protected by cardioplegia (e.g., retrograde and antegrade
cold blood with myocardial temperature monitoring). After opening the left atrium for
decompression of the heart, planned coronary bypass grafts are constructed prior to
exposing the mitral valve.
The LA is usually opened posterior to the interatrial septum. The incision extends
behind the inferior vena cava. Often exposure is poor; better exposure may be obtained
by opening the RA just anterior to the interatrial septum and then cutting the septum
transversely toward (but not to) the anterior commissure of the tricuspid valve. Improved
exposure also may be obtained by extending the atrial incision superiorly behind the
superior caval-right atrial junction. The mobilized cava may be retracted strongly
anteriorly, or if it cannulated directly, it may be divided at the right atrial junction.
Replacement of the diseased valve, regardless of the pathology of the IMR, is

recommended with rare exception. It is important to preserve as many chordal
attachments to the annulus as possible without obstructing the left ventricular outflow
tract using any one of several techniques. In patients with a ruptured papillary muscle, a
single pledgetted mattress suture is passed through the chordal fibrous junction with the
infarcted muscle and then through the infarcted base and tied loosely over a large patch
of Teflon felt. This may or may not improve postoperative LV function but takes little
time. The prosthetic valve (usually mechanical) is sutured to the annulus with running or
interrupted sutures. The choice of a mechanical or bioprosthetic valve is optional, since
durability and anticoagulation issues are relatively minor concerns in these patients. The
atrial incisions are closed with running sutures, and any proximal anastomses are
completed before weaning the patient off cardiopulmonary bypass.
During weaning, transesophageal echocardiography is helpful for assessing LV

function and loading. Inotropic drugs and systemic and coronary arterial vasodilators
are used initially, but if the LV cannot easily maintain an adequate cardiac output,
mechanical circulatory assistance is instituted immediately. If the intraaortic balloon
pump is not adequate, left atrial to the aorta or femoral artery perfusion or other
temporary left ventricular assist device is used promptly and before the weakened heart
is subjected to injury from transitory volume or pressure overload or coronary ischemia.
RESULTS
Revascularization for postinfarction angina in patients with mild to moderate MR is not

reported separately from patients without MR because in most series acute MR is not
an incremental risk factor for operative death. [90 ] [92 ] Currently, most patients with
postinfarction angina with or without MR are treated by interventional cardiologic
methods; when revascularization surgery is necessary, the mitral valve is ignored. Other
indications for myocardial revascularization are usually delayed until after the infarction
has healed (see Chronic Ischemic Mitral Regurgitation).
Published reports of mitral valve replacement, which is recommended by many

surgeons for acute severe IMR, show poor results. [23 ] , [24 ] , [26 ] , [30 ] , [73 ] [93 ] ,
[95 ] , Hospital mortality ranges from 31 to 69 percent and probably reflects the
selection process more than quality of care. Variables that increase early mortality
include patient age, cardiogenic shock, comorbid conditions, the amount of infarcted
myocardium, and delay in operation. [22 ] , [23 ] , [26 ] , [30 ] More recent experience
may be better [96 ] because of prompt diagnosis, early surgery, complete
revascularization, and application of chordal preservation techniques that better
preserve LV function. [97 ] [101 ] Several techniques are available for preserving
chordae [97 ] , [102 ] , [103 ] (Fig. 23-6) , and in patients with a ruptured papillary muscle
it may be reasonable to reattach the muscle and then preserve the chordal attachments
to the annulus when replacing the valve. David [96 ] reports a hospital mortality of 22
percent in 18 patients using chordal preservation techniques.
Many surgeons do not recommend mitral valve repair for acute IMR, [24 ] , [73 ] , [94 ] ,
[96 ] but others do. [30 ] , [102 ] , [104 ] Kay et al. [104 ] report a 39 percent hospital
mortality in a group of 26 patients who had repair or replacement but does not
differentiate between operations. Repair of the valve in acute IMR poses difficult
problems. Intraoperative transesophageal ECG and color-flow Doppler velocity
mapping are essential adjuncts to the operation to assess the quality of the repair. [79 ]
, [80 ] Occasional patients with a ruptured tip of a papillary muscle may be amenable to
repair if the infarct is relatively small and if the LV is minimally deformed, but these
patients are uncommon and usually much less ill. Most patients with acute IMR are in or
near cardiogenic shock, and although the size of the infarct averages only 20 percent of
the LV mass, [21 ] , [25 ] the amount varies widely between patients. Unless present
before AMI, annular dilatation and chordal elongation are not part of the pathology.
Therefore, an approach through the LA does not address the problem of papillary
muscle displacement and LV dysfunction. Lastly, few surgeons are confident of their
ability to realign subvalvular components in a recently infarcted, geometrically deformed,
flaccid ventricle. [94 ] Even if a ruptured muscle is resutured, [30 ] dyskinesis of the
infarcted ventricular wall may prevent valve competency.
Nevertheless, Rankin et al. [34 ] report excellent results in a series of 13 patients with
mitral valve repair and acute IMR. [34 ] Their procedure for acute IMR consists of
reimplanting the ruptured papillary muscle or papillary muscle tip, shortening elongated
chordae, reducing the circumference of all or part of the mitral annulus, and exclusion of
the area of infarction in patients in whom the valve is exposed through an incision in the
infarcted ventricle. [34 ] The need to shorten chordae, also observed by others, [33 ] is
confusing because ischemia and infarction generally do not produce mitral valve
prolapse of normal valves. [28 ] , [60 ] Of 13 patients with acute IMR, only 3 (23 percent)
died early after operation compared with 9 of 13 (69 percent) who had valve
replacement. [30 ] Only one repaired valve failed, and this patient had successful
replacement. It is possible that the ventriculotomy and subsequent closure improved
both valve and LV function by reducing displacement of the posterior papillary muscle
as well as by stiffening the infarct. [105 ]
Episodic Ischemic Mitral Regurgitation
Occasional patients develop episodes of dyspnea or flash pulmonary edema with or

without angina. [106 ] In some of these patients, a murmur of mitral regurgitation
appears during symptomatic periods and disappears or softens during asymptomatic
periods. [106 ] Patients may or may not have had a prior myocardial infarction, but all
patients have coronary arterial disease. [107 ]
The mechanism of episodic ischemic MR is well understood and is due to transient

dyskinesis of one or more segments of the LV wall produced by ischemia. The
dyskinesis may occur spontaneously in patients with coronary arterial disease or be
induced by balloon occlusion during PTCA in some patients. [107 ] The phenomenon
may be much more common in patients with coronary arterial disease than generally
appreciated. [107 ] Segmental dyskinesis occurs with or without an increase in
end-systolic and end-diastolic volumes but is sufficient to cause incomplete mitral valve
closure and translocation of the coaption point of mitral valve leaflets toward the LV
apex in the patients who develop MR. [107 ] The annulus does not dilate, and mitral
valve prolapse does not occur. The magnitude of MR may be large, with dramatic
increases in left atrial v wave and mean pressure. [106 ] The MR decreases or
disappears with recovery from ischemia and restitution of segmental wall thickening.
[107 ]
An exercise ECG study with color-flow Doppler velocity mapping demonstrates the
episodic nature of the mitral and ventricular segmental wall dysfunction. [107 ] Because
the MR is reversible and due to transient ischemia, therapy that controls the causative,
localized ischemia is indicated. In some patients this means surgical revascularization
without exposure of the mitral valve.
Chronic Ischemic Mitral Regurgitation
Between 10.9 and 19 percent of patients with symptomatic coronary arterial disease
who have cardiac catheterization [13 ] , [14 ] and between 3.5 and 7 percent of patients
who have myocardial revascularization have IMR. [108 ] [111 ] The vast majority of
patients with IMR have chronic IMR, and most of these patients have 1 or 2+ MR without
heart failure. [13 ] , [14 ] , [108 ] [110 ]
In patients with chronic IMR, three major variables interrelate to produce the clinical
spectrum of patients with varying combinations of symptomatic ischemia and heart
failure. As with acute IMR, the three variables are (1) the presence and severity of
ischemia, (2) the severity of MR, and (3) the magnitude of LV dysfunction. Patients with
obstructive coronary artery disease may have no symptoms or have stable,
progressing, unstable, or postinfarction angina or its equivalent. Because of disabling
symptoms, threat to LV mass, or statistically shortened survival, ischemia is a
compelling problem that must be addressed therapeutically. The approach and
methods do not materially differ from similar patients who do not have IMR. The severity
of MR is the second variable. At present, 1 or 2+ MR in patients without symptoms of
heart failure does not compel invasive therapy for MR. More severe MR and/or
symptoms of heart failure require evaluation for possible operation irrespective of the
therapy needed for ischemia. The degree of LV dysfunction is the last variable and the
most difficult to assess in the presence of MR. Symptoms of heart failure may be due to
LV dysfunction, MR, or both (episodic ischemia notwithstanding). Preoperative
determination of the probability of adequate LV function when afterload is increased
and preload is reduced by restoration of mitral valvular competence is one of the most
difficult decisions in cardiology and cardiac surgery.
PATHOPHYSIOLOGY
Chronic MR with a normal LV is well tolerated for many years because end-systolic wall
stress is reduced by the MR, [112 ] and the heart readily increases stroke volume
without increasing myocardial oxygen consumption. [74 ] Chronic MR markedly reduces
the constant for LV chamber stiffness and thus increases LV compliance without
changing the constant for myocardial stiffness . [76 ] , [112 ] The LV dilates. Chronic
MR also decreases LV contractile strength (Fig. 23-7) due to deficient myocardial
hypertrophy and loss of sarcomere myofibrils. [113 ] The presence of an infarction
further reduces LV contractility, causes further dilatation and remodeling, [87 ] , [114 ]
and accelerates the onset of failure.
In patients with chronic IMR, LV volume and wall stress increase at ED, [12 ] , [14 ] , [76 ]
, [115 ] and LV mass increases progressively without an increase in end-diastolic wall
thickness. [115 ] Infarction contributes to LV dilatation by increasing diastolic wall stress
and by stimulating myocyte hypertrophy and myocyte slippage in uninfarcted, remote
areas. [114 ] In patients with IMR who maintain a near-normal ejection fraction, peak
systolic wall stress increases [114 ] and the velocity of shortening decreases, [116 ] but
end-systolic volume and stress remain near normal. [115 ] Cardiac output is reduced
but maintained at asymptomatic or minimally symptomatic levels by an increase in
preload (increased end-diastolic wall stress). [115 ] However, in patients with reduced
ejection fractions, both end-diastolic and end-systolic volumes and stresses increase
and cardiac output and stroke volume fall; the increase in afterload cannot be overcome
by increased myocardial contractility produced by the increased preload. [115 ] LA, LV,
end-diastolic, and pulmonary capillary wedge pressures increase to two or three times
normal values independent of ejection fraction [115 ] ; often the atrial v wave
disappears, [61 ] as does atrial contraction. The LA enlarges. [61 ] In patients with
chronic IMR, the LV enlarges asymmetrically, [10 ] , [14 ] particularly in infarcts and
borderzone myocardium around infarcts. [87 ] Over time, both the severity of MR [14 ]
and loss of myocardial contractile strength worsen. [10 ] , [14 ] , [116 ]
Because most patients with IMR have mild to moderate MR without heart failure, [13 ]
symptoms of ischemia are the most common presenting problem. In published series
weighted toward patients who had myocardial revascularization without mitral valve
surgery, [109 ] , [110 ] , [117 ] the mean age of patients is approximately 65 years, and
about two-thirds are men. Between 16 and 19 percent have had a recent infarction, and
all have had previous infarction. In one series, 53 percent of patients had unstable
angina. [110 ] Two-thirds of patients have three-vessel disease [109 ] ; approximately
20 percent have left main disease. Two series noted a preponderance of inferior wall
infarction and obstruction of the right coronary arterial system. [109 ] , [118 ] About 10
percent of patients have symptoms of failure [110 ] , [117 ] ; the ejection fraction is
typically normal [117 ] or slightly depressed. [110 ] Seventy percent of patients have wall
motion abnormalities by ventriculography, and up to 10 percent have LV aneurysms.
[109 ] , [117 ] Pulmonary capillary wedge pressures range between 15 and 18 mmHg;
resting cardiac index is around 2.6 liters/min per m 2 .
Most published series of myocardial revascularization weighted toward mitral valve

repair or replacement [30 ] , [33 ] , [94 ] , [118 ] [112 ] are heterogeneous with respect to
the etiology of MR and often do not separate acute and chronic IMR. From limited
information, patients with moderate or severe IMR tend to be older (around 70 years),
and 70 percent are men. [66 ] , [94 ] , [122 ] Between 70 and 75 percent are in New
York Heart Association (NYHA) class IV; average ejection fraction is about 35 percent.
[119 ] Over 90 percent have left main or three-vessel disease. [119 ] The murmur of
mitral insufficiency is apical, pansystolic and may vary in intensity and with time. [61 ]
Usually a fourth heart sound is not present. [61 ]
DIAGNOSTIC STUDIES
The primary purpose of diagnostic studies is to determine the severity of coronary

arterial disease and its anatomy, the severity of MR, the degree of LV dysfunction, and
the potential for LV function to improve after revascularization. It is also important to
determine the etiology of MR; the prevalence of coronary artery disease is such that
some patients with degenerative and other causes of MR may have symptomatic
coronary disease that is unrelated to MR. In most series, IMR represents a minority of
patients. [95 ] , [102 ] , [120 ] [122 ] In IMR, the ventricular geometry and function reflect
remodeling due to both the MR and infarction; therefore, these patients may require
diagnostic studies and perhaps operative procedures that are different from patients
with coronary arterial disease associated with MR. It is also important to define
comorbidity of other organs systems by appropriate diagnostic studies dictated by the
patient's history, physical examination, and routine laboratory findings.
In patients with IMR, the ECG usually shows evidence of a prior myocardial infarction.
[109 ] , [110 ] , [117 ] , [119 ] The incidence of arrhythmias varies; most patients are in
sinus rhythm, [109 ] but some are in chronic atrial fibrillation or have a pacemaker. In
patients without failure and mild MR, heart size by chest x-ray is normal or slightly
enlarged; the LA is seldom enlarged. In those with moderate or severe MR and/or
severe LV dysfunction, the heart is enlarged and usually the LA is also enlarged. [61 ]
Transthoracic echocardiography is useful in determining the etiology of MR.

Two-dimensional echocardiography reliably detects ruptured chordae, annular
calcification, and myxomatous degeneration, which are not features of chronic IMR, and
differentiates rheumatic valve disease, endocarditis, and congenital deformities. The
presence of mitral valve prolapse is generally not a feature of IMR but is observed in a
small subset of patients with the disease [66 ] (see Pathophysiology). The hallmark of
chronic IMR is restricted leaflet motion due to displacement of one or both papillary
muscles. [19 ] , [31 ] , [60 ] , [107 ] The annulus may or may not be dilated but almost
always is bigger if the LV is enlarged. [14 ] , [123 ] The echocardiogram is also useful
for determining chamber size, segmental wall motion abnormalities, wall thickness, and
ejection fraction. Transthoracic color-flow Doppler velocity mapping is the principal
method used to semi-quantitate the severity of MR but is less sensitive than
trans-esophageal color-flow Doppler velocity mapping. [79 ] , [123 ] Transesophageal
echocardiography and color-flow Doppler velocity mapping are necessary during
operation but sometimes may be needed preoperatively for the best definition of LV
function, severity of MR, and definition of the pathologic anatomy.
Cardiac catheterization defines the coronary arterial pathology, and ventriculograms are
helpful in assessing segmental wall motion abnormalities, areas of dyskinesis or
aneurysm, chamber size, the degree of MR, and overall LV function. Measurements of
chamber pressures and estimates of cardiac output contribute to the overall evaluation
of LV function. Pulmonary hypertension, when present, is typically moderate and
correlates with the degree of LV dysfunction and/or severity of MR.
Stress redistribution thallium tests, [124 ] rest redistribution thallium or sestamibi

studies, [125 ] and positron emission tomography (PET) [126 ] [128 ] are noninvasive
methods to differentiate viable, hypoperfused (hibernating) myocardium from scar.
Although still being evaluated, one or more of these imaging studies assess the
potential for recovery of LV function after revascularization with a specificity and
sensitivity between 75 and 90 percent. [128 ] Radionuclear ventriculography measures
ejection fraction and to some extent segmental wall motion but often is redundant to
echocardiographic and catheterization studies in these patients.
INDICATIONS FOR SURGERY
Patients with symptomatic coronary artery disease that is not amenable to interventional
cardiology are candidates for operation. The criteria for revascularization do not differ
from those for symptomatic patients without IMR; however, the presence of MR and/or
severe LV dysfunction increases the risk of operation. [109 ] [111 ] , [117 ] A decision
not to expose the mitral valve is generally made preoperatively if the severity of MR is 1
or 2+ and is confirmed in the operating room by transesophageal echocardiography
and color-flow Doppler velocity mapping before and after cardiopulmonary bypass and
after manipulating afterload and preload (see below).
The presence of severe IMR (3 or 4+) and/or moderate or severe LV dysfunction

increases the risk of operation and requires therapy for the mitral valve in addition to
any bypass grafts needed to ameliorate symptoms of coronary ischemia. These
patients have heart failure and may or may not be helped by operation. The presence of
regional areas of hibernating or chronically stunned myocardium by one or more
imaging studies offers hope, but not certainty, that LV function may improve after
revascularization. Dilated and aneurysmal LVs [30 ] , [85 ] and those with end-diastolic
volumes [14 ] approaching 200 mL/m [2 ] are poor candidates for operation. Other
negative prognostic findings include cardiac indices below 1.8 liters/min per m 2 ,
arteriovenous oxygen differences greater than 7 vol%, ejection fractions below 30
percent with severe MR, LV end-diastolic pressure greater than 35 mmHg, LV systolic
volume index > 160 ml/m 2 (chapter 32), pulmonary hypertension (mean > 50 mmHg),
tricuspid regurgitation, and right-sided heart failure. Important comorbid conditions such
as chronic renal failure, severe chronic obstructive pulmonary disease, previous stroke
with residual, etc. also must be considered in the prescription of operation in patients
with moderate or severe IMR and moderately or severely damaged LVs. Not only is the
operative risk very high in patients with severe LV dysfunction, survivors usually have
small benefit in terms of increased activity or longevity.
OPERATION
Operation is usually elective, except in patients with uncontrolled symptoms of coronary

ischemia, who may require emergency or urgent operation to prevent infarction.
Preoperative preparation and intraoperative monitors do not differ from other cardiac
operations with the exception of transesophageal echocardiography and color-flow
Doppler velocity mapping. After induction of anesthesia, the degree of MR, anatomy of
the valve, and dimensions and segmental wall motion of the LV are carefully assessed
to determine whether or not the mitral valve needs to be addressed. Since anesthesia
generally reduces systemic vascular resistance and afterload, assessment of the valve
after administration of phenylephrine may unmask more severe MR. If the amount of MR
is 2+, transfusion after aortic cannulation to increase preload to 1.5 to 2.0 times resting
pulmonary capillary wedge pressure may unmask more severe MR and prompt a
decision to expose and repair the valve. [85 ] In patients with marginal LV function, a
Swan-Ganz catheter with an oxygen electrode and a femoral arterial catheter for
possible intraaortic balloon insertion are recommended.
The heart is exposed via midline sternotomy; other incisions may be used to expose the
mitral valve, but these compromise the ability to revascularize the heart. For patients
who have only revascularization, cannulation, administration of cardioplegia, depth of
systemic hypothermia, choice of conduit, and conduct of operation do not differ from
revascularization operations without IMR. However, if there is any possibility that the
mitral valve will be exposed, separate cannulation of both cavae through the RA may
save time later.
For patients who require mitral valve repair or replacement, two venous cannulas are
preferred, and one of the specialized retractors for facilitating exposure of the mitral
valve is used after the sternotomy and mammary arterial dissection. Pericardial
attachments to both cavae and the right pulmonary veins are dissected away to
mobilize the heart. After starting cardiopulmonary bypass, the LA is opened for
decompression of the ventricle; the aorta is clamped, and cardioplegia is given. Both
antegrade and retrograde cold blood cardioplegia are recommended with myocardial
temperature monitoring to minimize myocardial stunning and postbypass LV
dysfunction. Distal coronary arterial anastomoses are done first to reduce manipulation
of the heart with possible rupture of the ventricle at the atrioventricular groove after mitral
valve repair or replacement.
The LA is usually enlarged and accommodates a generous incision behind the

interatrial septum. The atrial septum and RA are retracted to expose the valve. An initial
inspection reveals the amount of annular dilatation and may indicate segments of the
mural annulus that appear disproportionately elongated. Traction sutures in the annulus
at each commissure elevate the valve and facilitate exposure of the leaflets, chordae,
and papillary muscles. Careful inspection searching for ruptured, elongated, or
sclerosed chordae; fibrotic, atrophied papillary muscle; and redundant or defective
leaflet tissue is made. Most often the entire valve appears normal; sometimes the
posterior papillary muscle seems slightly more yellowish brown than the rest of the
ventricle, and the posterior part of the mural annulus seems slightly elongated. There is
little to fix, yet the valve leaks.
The decision to repair or replace the valve is often difficult. Replacement is

recommended in older patients with severe LV dysfunction, who do not easily tolerate
prolonged cardiopulmonary bypass with cardioplegic arrest. A short operation ending
with a competent valve offers the greatest chance of success. In other patients, repair is
preferred if a competent valve is produced. Since repair of IMR does not address the
primary pathology causing the MR, a decision to repair carries the caveat of immediate
replacement if unsuccessful.
Repair is made using techniques developed by Wooler et al., [129 ] Kay et al., [130 ]
Carpentier, [131 ] and others. [94 ] , [132 ] Abnormalities of the valve that are not due to
infarction, such as ruptured or elongated chordae and defects in leaflets, are corrected
using these well-established techniques. If the mural annulus is dilated or sags toward
the apex, a ring annuloplasty is performed. Ring annuloplasty reduces orifice
cross-sectional area more than suture annuloplasty, [119 ] but results are more
predictable and repair is more secure with a ring. [119 ] The choice between a rigid or
flexible ring is immaterial. [133 ] By filling the ventricle, an initial assessment of valve
competency is made. Final assessment is made using transesophageal
echocardiography and color-flow Doppler velocity mapping after restarting the heart
and stopping cardiopulmonary bypass either before or after rewarming is complete. It is
important to test the repaired valve at high afterload and increased preload to ensure
reliability of the repair.
Chordal-sparing techniques [97 ] [99 ] , [102 ] , [103 ] , [134 ] are used if the valve is
replaced. These methods have significantly reduced postoperative ventricular
dysfunction observed after valve excision in the past and produce no more LV
dysfunction than reparative operations. [103 ] Aged patients in sinus rhythm and
patients with a life expectancy of less than 5 or 6 years who otherwise do not need
anticoagulation are candidates for bioprosthetic valves; mechanical valves are
recommended for others. The valve is inserted after excising [98 ] , [103 ] or transposing
[102 ] anterior leaflet tissue using running over-and-over sutures. Pledgetted interrupted
mattress sutures are used only in patients with extremely friable atrial and annular
tissue. The mural leaflet is plicated into the valve insertion suture line to prevent
interference with the valve mechanism.
Prior to removing the aortic clamp, all air is evacuated from the ventricle, and the mitral
valve is kept incompetent using a transvalvular catheter with ventricular and atrial holes.
Absence of air is ensured and assessment of ventricular wall motion is done by
transesophageal echocardiography. Anticipated pharmacologic support is started, and
satisfactory LV contractility is established before loading the heart. After weaning,
cardiopulmonary bypass is restarted if the LV begins to dilate and wall motion
deteriorates; every effort is made to prevent any distension of the ventricle that might
reduce myocardial contractile force. [135 ] Decisions for using intraaortic balloon
pumping or even temporary LV assistance are better made early than made
desperately after multiple attempts to wean from cardiopulmonary bypass have failed.
RESULTS
Myocardial revascularization alone in patients with chronic IMR has a higher hospital
mortality than in patients without IMR. [111 ] Mild (1+) IMR increases operative mortality
to 3.4 to 4.5 percent, [109 ] [111 ] , [118 ] and moderate (2+) IMR raises operative
mortality to 6 to 11 percent. [109 ] [111 ] , [136 ] Revascularization improves the degree
of MR in up to half of patients, [137 ] particularly in patients with limited left ventricular
damage. Five-year survival is influenced by the severity of LV function at the time of
operation, age, and comorbid disease. [30 ]
Two-year survival for revascularization alone in patients with 1+ and 2+ MR is 88 and 78

percent, respectively. [138 ] Five-year survival rates for patients with mild MR range
between 70 and 80 percent. [13 ] , [109 ] , [117 ] , [136 ] For moderate IMR, 5-year
survival ranges between 60 and 70 percent [109 ] , [110 ] (Fig. 23-8) . There are little
data regarding the functional class and quality of life in revascularized patients with mild
to moderate MR and no data regarding rates of progressive worsening of MR.
Repair and revascularization of chronic IMR have an operative mortality that ranges
from 3 to 29.4 percent [33 ] , [34 ] , [94 ] , [119 ] , [136 ] , [139 ] , [140 ] and a rate of
reoperation of up to 14.7 percent. [102 ] , [139 ] , [141 ] Mitral valve replacement and
revascularization have a hospital mortality between 3 and 33 percent [34 ] , [94 ] , [96 ] ,
[109 ] [111 ] , [117 ] , [120 ] , [122 ] , [142 ] , [143 ] and average around 20 percent. Most
of this reported experience with valve replacement occurred before chordal sparing
became standard-practice. [109 ] , [110 ] , [120 ] , [122 ] , [142 ] , [143 ] In addition,
many series combine patients who have myocardial revascularization and mitral valve
replacement for all causes of mitral disease. [120 ] [122 ] , [141 ] , [143 ] , [144 ] In
general, operation for IMR has a higher mortality than for other causes of mitral valve
malfunction. [85 ] , [111 ] , [136 ] The choice of valve prosthesis does not appear to
influence results. Risk factors for hospital death include age, congestive heart failure,
severity of LV dysfunction, preoperative intraaortic balloon pump, ejection fraction,
number of diseased coronary arteries, and comorbid conditions. [30 ] , [81 ] , [85 ]
Rankin et al. [30 ] estimated hospital mortality of revascularization and mitral valve
replacement for chronic IMR to be between 4 percent for low-risk patients and 15
percent for medium-risk patients.
Most reports indicate that the 5-year survival after revascularization and mitral valve
repair or replacement is between 30 and 40 percent. [13 ] , [33 ] , [109 ] , [110 ] , [117 ]
Recently Cohn and colleagues [147 ] reported that the 5-year survival after myocardial
revascularization and repair of functional IMR is 43 ± 13 percent as compared to 91 ± 5
percent after revascularization and mitral valve replacement.
CONCLUSIONS
Ischemic mitral regurgitation is an extremely common complication of myocardial

infarction that significantly reduces short- and long-term survival. The disease involves
three variablescoronary arterial obstructive disease, MR, and LV dysfunctionand
therefore differs from combinations of nonischemic MR and coronary arterial disease.
Newer diagnostic methods permit differentiation of IMR from other causes of MR and
from IMR complicating mitral valve prolapse. Furthermore, the potential of recovery of
LV function due to ischemia can now be assessed with encouraging, but still imperfect,
reliability. The pathogenesis of both acute and chronic IMR is more clear and highlights
the need to address the ventricular deformations that cause papillary muscle
displacement and incomplete mitral valve closure.
The presence of even mild MR reduces long-term survival. Without ischemia, chronic
MR reduces LV contractile force on both a cellular and ventricular level [113 ] ; however,
with correction of the MR, contractile force recovers. [112 ] The addition of an infarct
further increases LV diastolic wall stress and accelerates LV dilatation and loss of
contractile force. [87 ] Revascularization alone for mild to moderate IMR improves
contractile function and reduces the severity of MR in some patients but fails to do so in
many others. Any degree of MR in an infarcted ventricle initiates LV remodeling
changes that gradually lead to progressive LV enlargement, loss of contractile force,
and more severe MR. Current therapy does not address this aspect of the disease.
Advances in cardioplegia and intra- and postoperative management, including more
sophisticated methods of temporary mechanical left ventricular assistance, provide an
opportunity to improve long-term results without negatively affecting short-term
outcomes. However, current reparative operations do not correct the pathologic
physiology of either acute or chronic IMR, and there are no operations that attempt to
favorably influence ventricular remodeling after myocardial infarction. Greater
understanding of LV stresses, strains, and material properties [105 ] after infarction and
of the ventricular deformations that produce IMR is needed to develop new and better
reparative operations. The valve is structurally normal; it need not be replaced, but
currently we do not know how to fix it. Thus this prevalent disease with its many faces
and variables offers cardiac surgeons and cardiologists a spectacular opportunity.
DEFINITION
Left ventricular aneurysm has been defined loosely as any large area of left ventricular
akinesia or dyskinesia that reduces left ventricular ejection fraction (Fig. 24-1) . More
strict definition requires that the aneurysm be a distinct area of abnormal diastolic
contour with systolic dyskinesia. [1 ] True left ventricular aneurysms involve bulging of
the entire left ventricular wall, while a false aneurysm of the left ventricle is, in fact, a
rupture of the left ventricular wall contained by surrounding pericardium.
HISTORY
Left ventricular aneurysms have long been described at autopsy, but left ventricular
aneurysm was not recognized to be a consequence of coronary artery disease until
1881. [2 ] The angiographic diagnosis of left ventricular aneurysm was first made in
1951. [2 ] A congenital left ventricular aneurysm was first treated surgically by Weitland
in 1912 by aneurysm ligation. In 1944, Beck [3 ] described fasciae latae plication to
treat left ventricular aneurysms. Likoff and Bailey [4 ] successfully resected a left
ventricular aneurysm through a thoracotomy in 1955 using a special clamp without
cardiopulmonary bypass. The modern treatment era began in 1958 when Cooley et al.
[5 ] performed a linear repair of a left ventricular aneurysm successfully using
cardiopulmonary bypass. More geometric ventricular reconstruction techniques were
subsequently devised by Stoney et al., [6 ] Daggett et al., [7 ] Dor et al., [8 ] Jatene, [9 ]
and Cooley et al. [10 ] , [11 ]
INCIDENCE
The incidence of left ventricular aneurysm in patients suffering myocardial infarction has
varied between 10 and 35 percent depending on the definition and the methods used.
Of patients undergoing cardiac catheterization in the CASS study, 7.6 percent had
angiographic evidence of left ventricular aneurysms. [12 ] The absolute incidence of left
ventricular aneurysms may be declining due to the increased use of thrombolytics and
revascularization after myocardial infarction. [13 ] , [14 ]
ETIOLOGY
Over 95 percent of true left ventricular aneurysms reported in the English literature result
from coronary artery disease and myocardial infarction. True left ventricular aneurysms
also may result from trauma, [15 ] Chagas' disease, [16 ] or sarcoidosis. [17 ] A very
small number of congenital left ventricular aneurysms also have been reported and have
been termed diverticula of the left ventricle. [18 ]
False aneurysms of the left ventricle result most commonly from contained rupture of the
ventricle 5 to 10 days after myocardial infarction and often occur after circumflex
coronary arterial occlusion. False aneurysm of the left ventricle also may result from
submitral rupture of the ventricular wall, a dramatic event that generally occurs after
mitral valve replacement with resection of the mitral valve apparatus. [19 ]
PATHOPHYSIOLOGY
The development of a true left ventricular aneurysm involves two principal phases: early
expansion and late remodeling.
Early Expansion Phase
The early expansion phase begins with the onset of myocardial infarction.
Ventriculography can demonstrate left ventricular aneurysm formation within 48 hours of
infarction in 50 percent of patients who develop ventricular aneurysms. The remaining
patients have evidence of aneurysm formation by 2 weeks after infarction. [20 ]
True aneurysm of the left ventricle generally follows transmural myocardial infarction due
to acute occlusion of the left anterior descending or dominant right coronary artery. Lack
of angiographic collaterals is strongly associated with aneurysm formation in patients
with acute myocardial infarction and left anterior descending artery occlusion, [21 ] and
absence of re-formed collateral circulation is probably a prerequisite for formation of left
ventricular aneurysm (Table 24-1) . At least 88 percent of ventricular aneurysms result
from anterior infarction, while the remainder follow inferior infarction. [2 ] Posterior
infarctions that produce a distinct left ventricular aneurysm are relatively unusual.
In experimental transmural infarction without collateral circulation, myocyte death begins

20 minutes after coronary occlusion. Infarctions that result in aneurysm formation are
almost always transmural and may show gross thinning of the infarct zone within hours
of infarction. Within a few days, the endocardial surface of the developing aneurysm
becomes smooth with loss of trabeculae and deposition of fibrin and thrombus on the
endocardial surface in at least 50 percent of patients. While most myocytes within the
infarct are necrotic, viable myocytes often remain within the infarct zone. In a minority of
patients, extravascular hemorrhage occurs in the infarcted tissue and may further
depress systolic and diastolic function of involved myocardium. Inflammatory cells
migrate into the infarct zone by 2 to 3 days after infarction and contribute to lysis of
necrotic myocytes by 5 to 10 days after infarction. Electron microscopy demonstrates
disruption of the native collagen network several days after infarction. Collagen
disruption and myocyte necrosis produce a nadir of myocardial tensile strength
between 5 and 10 days after infarction, when rupture of the myocardial wall is most
common. Left ventricular rupture is relatively rare after the ventricular aneurysmal wall
becomes replaced with fibrous tissue.
Loss of systolic contraction in the large infarcted zone and preserved contraction of
surrounding myocardium cause systolic bulging and thinning of the infarct. By Laplace's
law ( T = Pr /2 h ), at a constant ventricular pressure P , increased radius of curvature r
and decreased wall thickness h in the infarcted zone both contribute to increased
muscle fiber tension T and further stretch the infarcted ventricular wall.
Relative to normal myocardium, ischemically injured or infarcted myocardium displays

greater plasticity or creep , defined as deformation or stretch over time under a constant
load. [22 ] Thus increased systolic and diastolic wall stress in the infarcted zone tends to
produce progressive stretch of the infarcted myocardium (termed infarct expansion )
[23 ] until healing reduces the plasticity of infarcted myocardium.
Transmural infarction without significant hibernating myocardium within the infarct region
is necessary for subsequent development of a true left ventricular aneurysm.
Angiographic ventricular aneurysms with evidence of hibernating myocardium (lack of Q
waves or presence of uptake on technetium scan) may resolve over several weeks and
thus do not represent true left ventricular aneurysms by strict criteria. [24 ]
Due to increased diastolic stretch or preload and elevated catecholamines, remaining

noninfarcted myocardium may demonstrate increased fiber shortening and, ultimately,
myocardial hypertrophy in the presence of a left ventricular aneurysm. This increased
shortening and increased wall stress increase oxygen demand for noninfarcted
myocardium and for the left ventricle as a whole.
In addition to increased regional wall stresses, left ventricular aneurysm can increase
ventricular oxygen demand and decrease net forward cardiac output by producing a
ventricular volume load because a portion of the stroke volume goes into the aneurysm
instead of out the aortic valve. Net mechanical efficiency of the left ventricle (external
stroke work minus myocardial oxygen consumption) is decreased by reducing external
stroke work (volume times pressure) and increasing myocardial oxygen consumption.
Left ventricular aneurysms can produce both systolic and diastolic ventricular
dysfunction. Diastolic dysfunction results from increased stiffness of the distended and
fibrotic aneurysmal wall, which impairs diastolic filling and increases left ventricular
end-diastolic pressure.
Late Remodeling Phase
The remodeling phase of ventricular aneurysm formation begins 2 to 4 weeks after

infarction when highly vascularized granulation tissue appears. This granulation tissue is
subsequently replaced by fibrous tissue 6 to 8 weeks after infarction. As myocytes are
lost, ventricular wall thickness decreases as the myocardium becomes largely replaced
by fibrous tissue. In larger infarcts, the thin scar is often lined with mural thrombus. [25 ]
After acute myocardial infarction, animal studies show that ventricular load reduction
with 8 weeks of nitrate therapy may reduce expected infarct thinning, decrease infarct
stretch, and lessen hypertrophy of noninfarcted myocardium. [26 ] Interestingly, nitrate
therapy for only 2 weeks after infarction does not prevent aneurysm formation. This
observation emphasizes the importance of late remodeling from 2 to 8 weeks after
infarction. Angiotensin converting-enzyme (ACE) inhibitors also reduce infarct
expansion and subsequent development of ventricular aneurysm. Because animal
studies show that ACE inhibitors nonspecifically suppress ventricular hypertrophy, it is
not clear whether suppression of the compensatory hypertrophy of surrounding
myocardium is ultimately beneficial or harmful.
Lack of coronary reperfusion is probably prerequisite for development of left ventricular

aneurysm. In humans, reperfusion of the infarct vessel either spontaneously, [24 ] by
thrombolysis, [27 ] or by angioplasty [28 ] has been associated with a lower incidence of
aneurysm formation. It is speculated that coronary reperfusion as late as 2 weeks after
infarction prevents aneurysm formation by improving blood flow and fibroblast migration
into the infarcted myocardium. The role of delayed infarct healing in aneurysm
development is supported by observations that steroids after myocardial infarction may
increase the likelihood of aneurysm formation. [29 ]
Arrhythmias such as ventricular tachycardia may occur at any time during the
development of ventricular aneurysm, and all these patients have the substrate for
reentrant conduction pathways within the heterogeneous ventricular myocardium. These
pathways tend to involve border zones surrounding the ventricular aneurysm (see Chap.
5).
NATURAL HISTORY
The excellent prognosis of asymptomatic patients with ventricular aneurysms who were
treated medically was demonstrated in a series of 40 patients followed for a mean of 5
years. [30 ] Of 18 initially asymptomatic patients, 6 developed class II symptoms while
12 remained asymptomatic. Ten-year survival was 90 percent for these patients but
was only 46 percent at 10 years in patients who presented with symptoms (Fig. 24-2) .
Although earlier autopsy series reported relatively poor survival in patients with
medically managed left ventricular aneurysms (12 percent at 5 years), most recent
studies report 5-year survival from 47 to 70 percent. [12 ] [30 ] [32 ] Causes of death
include arrhythmia in 44 percent, heart failure in 33 percent, recurrent myocardial
infarction in 11 percent, and noncardiac causes in 22 percent. [30 ]
Factors that influence survival with medically managed left ventricular aneurysm include
age, heart failure score, extent of coronary disease, duration of angina, prior infarction,
mitral regurgitation, ventricular arrhythmias, aneurysm size, function of residual ventricle,
and left ventricular end-diastolic pressure. [30 ] , [33 ] Early development of aneurysm
within 48 hours after infarction also diminishes survival. [20 ]
In general, the risk of thromboembolism is low for patients with aneurysms (0.35 percent
per patient-year), [31 ] and long-term anticoagulation is not usually recommended.
However, in the 50 percent of patients with mural thrombus visible by echocardiography
after myocardial infarction, 19 percent develop thromboembolism over a mean
follow-up of 24 months. [34 ] In these patients, anticoagulation and close
echocardiographic follow-up may be indicated. Atrial fibrillation and large aneurysmal
size are additional risk factors for thromboembolism.
Angina is the most frequent symptom in most series of operated patients with left
ventricular aneurysm. Given that three-vessel coronary disease is present in 60 percent
or more of these patients, the frequency of angina is not surprising. [35 ]
Dyspnea is the second most common symptom of ventricular aneurysm and often
develops when 20 percent or more of the ventricular wall is infarcted. Dyspnea may
occur from a combination of decreased systolic function and diastolic dysfunction.
Either atrial or ventricular arrhythmias may produce palpitations, syncope, or sudden

death, or aggravate angina and dyspnea in up to one-third of patients. [35 ]
Thromboembolism is unusual but may produce symptoms of stroke, myocardial
infarction, or limb or visceral ischemia.
DIAGNOSIS
The electrocardiogram frequently demonstrates Q waves in the anterior leads along

with persistent anterior ST-segment elevation (Fig. 24-3) . The chest radiograph may
show left ventricular enlargement and cardiomegaly (Fig. 24-4) , but the chest
radiograph is not usually specific for left ventricular aneurysm.
Left ventriculography is the gold standard for diagnosis of left ventricular aneurysm. The
diagnosis is made by demonstrating a large, discrete area of dyskinesia, generally in
the anteroseptal-apical walls. Occasionally, left ventriculography also may demonstrate
mural thrombus.
Two-dimensional echocardiography is a sensitive and specific means of diagnosing left

ventricular aneurysm (Fig. 24-5) . Mural thrombus and mitral valve regurgitation are
detected most readily by echocardiography. Echocardiography is also useful for
distinguishing false aneurysm from true aneurysm by demonstrating a defect in the true
ventricular wall. Gated radionuclide angiography reliably detects left ventricular
aneurysms, and thallium scanning or positron emission tomography (PET) can be
helpful early after infarction to differentiate true aneurysm from hibernating myocardium
with reversible dysfunction. Magnetic resonance imaging (MRI) accurately depicts left
ventricular aneurysms and is a reliable means for detecting mural thrombus. [36 ]
Because of the relatively good prognosis for asymptomatic left ventricular aneurysm, [30
] no indications for repairing asymptomatic aneurysms are established. Yet, in low-risk
patients during operation for associated coronary disease, investigators report
repairing large, minimally symptomatic aneurysms. [2 ] , [37 ]
On the other hand, operation is indicated for symptoms of angina, congestive heart
failure, or selected ventricular arrhythmias (see Chaps. 25 and 26). For these
symptomatic patients, operation is more effective than medical therapy (Table 24-2) .
Operation is also indicated in viable patients with contained cardiac rupture, with or
without development of a false aneurysm. Because left ventricular pseudoaneurysms
have a definite tendency to rupture with or without symptoms, operation is indicated. [38
] Similarly, congenital aneurysms have a presumed risk of rupture and should undergo
repair independently of symptoms. Rarely, embolism is an indication for operation in
medically treated patients at high risk for repeated thromboembolism. The role of
operation in asymptomatic patients with very large aneurysms or documented
expansion of aneurysms is uncertain.
Relative contraindications to operation for left ventricular aneurysm include excessive

anesthetic risk, impaired function of residual myocardium outside the aneurysm, resting
cardiac index less than 2.0 liters/min per m 2 , significant mitral regurgitation, evidence
of nontransmural infarction (hibernating myocardium), and lack of a discrete, thin-walled
aneurysm with distinct margins. Ejection fraction per se, no matter how low, is not useful
in determining operability.
Angioplasty has an uncertain role in the treatment of left ventricular aneurysms but may
be indicated in patients with suitable coronary anatomy, one- or two-vessel disease, a
contraindication for operation, or asymptomatic status with inducible ischemia.
PREPARATION FOR OPERATION
All patients being considered for operation should undergo right- and left-sided heart
catheterization with coronary arteriography and left ventriculography. Patients with at
least 2+ mitral regurgitation at cardiac catheterization should have echocardiography to
assess the mitral valve and to look for intrinsic mitral valve disease not amenable to
annuloplasty.
Preoperative electrophysiologic study is clearly indicated in any patient with

preoperative ventricular tachycardia or ventricular fibrillation. The decision to perform an
electrophysiologic study in patients without preoperative ventricular arrhythmias is
controversial, since the incidence of postoperative ventricular arrhythmias is low and not
changed by endocardial resection at the time of operation. [2 ] Electrophysiologic study
is frequently not helpful in patients with polymorphic ventricular tachycardia occurring
within 6 weeks of myocardial infarction. [2 ]
General
Operation for left ventricular aneurysm requires cardiopulmonary bypass and a

balanced anesthetic technique, as generally used for coronary bypass grafting. After
induction of anesthesia and endotracheal intubation, an electrocardiogram monitor, a
Foley catheter, a radial arterial line, and a Swan-Ganz catheter are placed. A median
sternotomy is performed, and the patient is given heparin. Planned saphenous vein or
mammary artery conduits are prepared.
Cardiopulmonary bypass is begun after cannulating the ascending aorta and using a
single, two-stage cannula to cannulate the right atrium. Epicardial mapping is
performed if necessary. The left ventricle is inspected to identify an appropriate area of
thinned ventricular wall. A linear vertical ventriculotomy, generally on the anterior wall 3
to 4 cm from the left anterior descending coronary artery, is made (Fig. 24-6) . The left
ventricle is opened (Fig. 24-7) , all mural thrombus is carefully removed, and
endocardial mapping is performed if necessary. A left ventricular vent is now placed
through the right superior pulmonary vein-left atrial junction after mural thrombus is
removed. Coronary arteries to be grafted are identified. Endocardial scar, if present, is
resected, and afterwards, endocardial mapping is repeated. Body temperature is
maintained at 37°C until intraoperative mapping is completed; thereafter, temperature
is decreased to 28 to 32°C.
The ascending aorta is clamped, and the heart is arrested with cold anterograde
cardioplegic solution. Alternatively, the aorta is not clamped and the entire procedure is
done during hypothermic fibrillation. The left ventricular aneurysm is repaired using one
of the techniques described below. The distal coronary anastomoses are performed,
followed by releasing the aortic clamp. [39 ] Air is removed by venting the ascending
aorta and left ventricle while filling the heart and ventilating the lungs with the patient in
the Trendelenberg position. The patient is rewarmed, and proximal coronary
anastomoses are performed. Once normothermia is achieved, an electrophysiologic
study may be repeated if indicated. Temporary pacing wires are placed on the right
atrium and right ventricle, cardiopulmonary bypass is discontinued, and heparin is
reversed. The heart is decannulated, and the median sternotomy is closed with
mediastinal drains after hemostasis is achieved.
Weaning from cardiopulmonary bypass frequently requires some degree of inotropic

support. Typically 5 µg/kg per min of dopamine, nitroglycerin to prevent coronary
spasm, and nitroprusside for afterload reduction are used. An intraaortic balloon pump
may be needed in patients with borderline ventricular function. Transesophageal
echocardiography is useful for assessing left ventricular function and to detect residual
intracardiac air.
Additional inotropic support may not increase cardiac output significantly because of
abnormal ventricular compliance and may produce arrhythmias and poorly tolerated
tachycardia. Hypokalemia and hypomagnesemia are corrected immediately to
minimize arrhythmias. Intraoperative and postoperative ventricular ectopy is treated
aggressively with intravenous lidocaine and/or procainamide. Intravascular volume
shifts are poorly tolerated in these patients because of poor ventricular compliance;
therefore, rapid transfusions are avoided by meticulous hemostasis before closing.
Because the left ventricle is poorly distensible, stroke volume is relatively fixed, and a
resting heart rate between 90 and 115 beats per minute is not unusual to maintain a
cardiac index of approximately 2.0 liters/min per m 2 .
Plication
Plication without opening the aneurysm is reserved for only the smallest aneurysms that
do not contain mural thrombus. A two-layer suture line of 0 monofilament is placed
across the aneurysm using a strip of Teflon felt on either side. The suture line is oriented
to reconstruct a relatively normal left ventricular contour and does not exclude all
aneurysmal tissue.
Linear Closure
After removing all mural thrombus, the aneurysmal wall is trimmed, leaving a 3-cm rim of
scar to allow reconstruction of the normal left ventricular contour (Fig. 24-8) . Care is
taken not to resect too much aneurysmal wall and overly reduce ventricular cavity size.
Anterior aneurysm defects are closed vertically between two external 1.5-cm strips of
Teflon felt, two layers of 0 monofilament horizontal mattress sutures, and finally, two
layers of running 2-0 monofilament vertical sutures with large-diameter needles (Fig.
24-9) .
Circular Patch
Inferior or posterior aneurysms generally require circular patch closure, which also can
be applied to anterior aneurysms. After opening the aneurysm (Fig. 24-10) and after
debridement of thrombus and aneurysm wall (Fig. 24-11) , a Dacron (Hemashield)
patch is cut to be 2 cm greater in diameter than the ventricular opening. Interrupted,
pledgeted 0 monofilament horizontal mattress sutures are placed through the
ventriculotomy rim and then through the patch, leaving the pledgets outside the
ventricular cavity (Fig. 24-12) . Sutures are tied, and additional interrupted sutures or a
second layer of running 2-0 monofilament is placed for hemostasis.
Endoventricular Patch
The endoventricular patch technique is suitable for anterior aneurysms but is less suited
for inferior or posterior aneurysms, for which the standard (circular) patch technique is
used. After debridement of thrombus, a Teflon felt patch is cut to size sufficient to
restore normal ventricular size and geometry when secured to the aneurysmal rim (Fig.
24-13) . The patch is sutured to normal muscle at the aneurysmal circumference using a
running 3-0 polypropylene suture that is secured with single sutures at three or four
places around the patch circumference. Interrupted 3-0 sutures are placed as needed to
ensure good fit. Care is taken not to distort the papillary muscles. The aneurysmal rim is
trimmed to allow primary closure of the native aneurysmal wall over the patch using two
layers of running 2-0 monofilament suture without pledgets (Fig. 24-14) .
As compared with linear and circular patch techniques, the endoventricular patch
technique has technical advantages. An endoventricular patch preserves the left
anterior descending artery for possible grafting and leaves no external prosthetic
material to produce heavy pericardial adhesions. The technique facilitates patching the
interventricular septum, and is suitable for acute infarctions when tissues are friable. [2 ]
, [11 ]
Coronary Revascularization
Concurrent coronary revascularization is performed as in standard coronary bypass

procedures. Since the endoventricular patch technique does not encroach on the left
anterior descending coronary, the left internal mammary artery may be used to graft the
left anterior descending coronary artery.
The severity of mitral regurgitation should be evaluated before cardiopulmonary bypass

by intraoperative transesophageal echocardiography. The mitral valve is also inspected
from below after opening the aneurysm and beginning repair of the aneurysm.
Transventricular mitral valve repair may be done by placing pledgeted polypropylene
sutures at both mitral commissures to reduce the circumference of the annulus. [40 ]
This technique produces satisfactory short-term results, but long-term results are not
known. Usually the mitral valve is repaired via left atriotomy after completion of the distal
coronary anastomoses and before releasing the aortic cross-clamp. If mitral
regurgitation results from annular dilatation and systolic restriction of leaflet motion
(Carpentier type IIIB), Carpentier mitral annuloplasty is done. [41 ]
In symptomatic patients with sufficient depression of global left ventricular function to

preclude aneurysm repair, transplantation is a reasonable alternative. Relative
contraindications to cardiac transplantation in patients with left ventricular aneurysm
include current amiodarone therapy or prior placement of an internal defibrillation
device.
Ventricular False Aneurysm
Ventricular false aneurysms are repaired with the same techniques used for true
ventricular aneurysms based according to the location and size of the aneurysm. The
circular patch technique is particularly useful in that inferior false aneurysms are
common and typically have narrow necks. Usually the wall of the false aneurysm is
inadequate to close over the defect.
Ventricular Rupture
Any of the techniques described above may be used to manage a contained ventricular
rupture. Because infarcted tissue is particularly friable 5 to 10 days after rupture, closure
may be difficult. The endoventricular technique is particularly well suited for this
uncommon operation because the patch can be sewn to the margins of healthy
endocardium, which may be at some distance from the site of rupture. Patient survival
also has been reported by gluing a biologic patch to the ventricular epicardium over the
site of the rupture.
EARLY RESULTS
Hospital Mortality
In a compilation of 3439 operations for left ventricular aneurysm between 1972 and
1987, hospital mortality was 9.9 percent and ranged from 2 to 19 percent. [13 ] More
recent reports indicate that hospital mortality has fallen to 3 to 7 percent in the last
decade using either patch [2 ] , [11 ] , [42 ] or linear closures. [14 ] , [37 ] , [42 ] The most
common cause of hospital mortality is left ventricular failure, which occurs in 64 percent
of deaths. [37 ]
Risk factors for hospital mortality include increased age, [13 ] , [37 ] , [42 ] incomplete
revascularization, [37 ] increased heart failure class, [13 ] , [42 ] , [44 ] , [45 ] female
gender, [13 ] emergent operation, [13 ] ejection fraction less than 20 to 30 percent, [42 ]
, [44 ] concurrent mitral valve replacement, [2 ] , [13 ] and failure to use the internal
mammary artery. [45 ]
In-Hospital Complications
The most common in-hospital complications are shown in Table 24-3 and include low
cardiac output, ventricular arrhythmias, and respiratory failure. [13 ] , [14 ] , [42 ] Low
cardiac output may be more common in patients undergoing intraoperative mapping
due to perioperative cardiac injury. [46 ]
Left Ventricular Function
The preponderance of data from the last two decades have shown that left ventricular
function improves in most patients undergoing operation for left ventricular aneurysm.
Operation improves ejection fraction whether linear repair [43 ] [47 ] [49 ] or patch repair
[8 ] , [11 ] , [50 ] [52 ] is used (Fig. 24-15) . Both techniques decrease end-diastolic and
end-systolic volumes [48 ] , [51 ] and improve exercise response [11 ] , [49 ] (Fig. 24-16)
. Aneurysmal patch repair also improves diastolic filling as compared with preoperative
values. [52 ]
Controversy remains strong regarding whether patch techniques provide results

superior to those achieved with linear closures. Stoney et al. [6 ] , [53 ] noted lower left
ventricular end-diastolic pressure when more geometric reconstructions were
performed. Hutchins and Brawley [54 ] first noted at autopsy that some patients had
severe reduction and distortion of ventricular volume after linear repair. The authors
proposed that a more geometric repair might avert these problems. Although very
experienced groups attribute improved outcomes and function to a switch to patch
techniques, [2 ] , [11 ] no controlled studies compare results from the two procedures. A
small, uncontrolled comparison by Kesler et al. [48 ] reported no differences in
postoperative symptoms, ejection fraction, or echocardiographic ventricular dimensions
between linear and patch repairs. In an animal model of simulated aneurysm repair,
Nicolosi et al. [55 ] found no difference in left ventricular systolic or diastolic function
between linear and patch techniques. Indeed, Salati et al. [56 ] reported that 8 percent
of patients with endocardial patch reconstruction had significant postoperative diastolic
dysfunction that contributed to in-hospital death in 4 of 6 patients who had severe
postoperative diastolic dysfunction. Salati et al. suggested that contributing factors were
excessive reduction of ventricular volume and creation of a base-apex diameter of less
than 7 to 7.5 cm. To avoid postoperative diastolic dysfunction with the endoventricular
patch technique, Salati et al. recommended a large circular patch, instead of an
endoventricular patch, in patients with recent myocardial infarction, pulmonary
hypertension, or unusually elevated preoperative left ventricular end-diastolic pressure.
Although minor technical differences exist between patch and linear repairs, good
functional results are possible with either technique. Suboptimal outcomes result from
either technique when left ventricular cavitary volume is overly reduced and causes
decreased stroke volume and impaired diastolic filling. [54 ] , [56 ] Excessively small
patches reduce stroke volume and impair diastolic filling, but excessively large patches
reduce ejection fraction and increase wall stress (Fig. 24-17) .
LATE RESULTS
Survival
Survival after operation for left ventricular aneurysm is variable, largely due to
differences between patient populations. Five-year survival in recent series varies
between 58 and 80 percent, [43 ] , [44 ] 10-year overall survival is 34 percent, [44 ] and
10-year cardiac survival is 57 percent [37 ] (Fig. 24-18) . Cardiac causes are
responsible for 57 percent of late deaths, [46 ] and most cardiac deaths result from new
myocardial infarctions. In aneurysm patients randomized to medical or surgical therapy
in the CASS study (most of the patients had minimal symptoms), survival was not
different between medical or surgical therapy, except for patients with three-vessel
disease. [33 ] These patients had better survival with surgery (Fig. 24-19) .
Preoperative risk factors for late death include age, heart failure score, ejection fraction
less than 35 percent, cardiomegaly on chest radiograph, left ventricular end-diastolic
pressure greater than 20 mmHg, and mitral regurgitation [33 ] , [37 ] , [46 ] (Fig. 24-20) .
Symptomatic Improvement
Studies consistently demonstrate improvement in symptoms after operation relative to

preoperative symptoms [43 ] , [47 ] (Fig. 24-21) . In the study of Elefteriades et al., [47 ]
using a linear repair, mean angina class improved from 3.5 to 1.2 and mean CHF class
improved from 3.0 to 1.7. In the randomized CASS study, the subset of patients with left
ventricular aneurysm achieved a better heart failure class with surgical therapy than with
medicine, and rehospitalization for heart failure was less common for the surgical
therapy group than for the medicine group. [33 ]
ABNORMALITIES OF CARDIAC IMPULSE FORMATION AND
CONDUCTION
Physiology and Anatomy of the Cardiac Conduction System
A short review of the heart's intrinsic electrical system is useful when considering
pathogenesis and therapy of disorders of cardiac impulse formation and transmission.
The functions of the conduction system are not only initiation and regulation of rat¸e of
the heartbeat but also its coordinated transmission to the entire heart resulting in
maximum mechanical efficiency.
CELLULAR PHYSIOLOGY [1]
Cardiac electrical activity is determined by transmembrane potential -the voltage

difference between the intracellular and extracellular environments. This potential
difference can only exist because of the selectively permeable cardiac cell membrane,
composed of a lipid bilayer in which are situated specialized proteins that allow
passage of selected ions at certain times between the intra- and extracellular spaces.
Normally, the intracellular compartment has more negative than positive ions and is thus
polarized to a negative potential relative to the extracellular space (about 85 to 90 mV
for most cardiac cells). Changes in cell membrane potential are due to flow of positively
charged ions that may occur directly to and from the extracellular space through
specialized channels in the membrane or between adjoining cardiac cells through
so-called gap junctions. These latter connections are critical for the normal rapid spread
of electrical activity throughout the heart.
Each membrane channel is selective for its particular ion (na + , k + , ca 2+ ). How much
of each ion passes through its own channel at any time (its current) depends on both
voltage and chemical gradients. Resting membrane potential for most cells is
determined by potassium current. Following depolarization, the resting potential is
restored by an energy-dependent na + -k + exchange pump. Until a certain amount of
this repolarization process has been completed (which requires 150 to 250 ms), the cell
cannot depolarize again; it is said to be refractory to stimulation. The cell regains full
capacity to depolarize once this refractory period is over.
The cellular action potential (AP) is the curve of voltage change over time during
depolarization/repolarization of the cardiac cell (Fig. 25-1) . The sodium current is
turned on and then off very quickly at the beginning of the action potential; na + thus
mediates the rapid upstroke (phase 0) of the AP. Calcium influx occurs slightly later and
lasts longer, accounting for the plateau (phase 2) of the AP, and mediates cardiac
muscle contraction. These are followed by k + efflux from the cell, leading to
repolarization (phase 3) back to the resting membrane potential (phase 4). Cells in
which this type of fast-response AP is operative comprise most of the heart (atrium,
ventricles, His-Purkinje system); other specialized cells (in the sinoatrial and
atrioventricular nodes) have slow-response APs, in which na + is less important and ca
2+
more important in mediating phase 0.
CONDUCTION SYSTEM ANATOMY [2] (Fig. 25-2)
Sinus node and atrium
The heartbeat normally originates in cells of the 5 × 15 mm teardrop-shaped sinoatrial,

or sinus, node located in the high lateral right atrium where it adjoins the superior vena
cava (embryonic sinus venosus region). Cells in the center of the sinus node have the
ability to depolarize spontaneously (phase 4 depolarization), reaching a threshold
voltage at which time the cell as a whole is electrically activated. Although cells in other
portions of the conduction system are also capable of spontaneous depolarization, their
discharge rates are typically slower than that of the sinus node, and thus the heart rate is
controlled in most individuals by the sinus node. Impulses spread from the sinus node
over the atria, from right to left, top to bottom, completing atrial depolarization in about
80 to 100 ms. This accounts for the morphology of the normal P wave on a standard
ECG (upright in leads I, II, and III). Although bundles of atrial tissue exist to which some
have ascribed enhanced conduction properties (Bachmann's bundle, Thorel's tract,
etc.), there are really no specialized interatrial tracts. Rather, particular arrangements of
atrial cells, such as those in the crista terminalis, facilitate impulse transmission along
their long axis. Congenital defects in the region of the sinus node, such as a sinus
venosus atrial septal defect, can be associated with an absence of sinus rhythm per se;
instead, subsidiary pacemaker cells from other areas of the atrium control the heartbeat
at a rate lower than would be expected in the presence of an intact sinus node. Blood
supply to the sinus node is from the right coronary artery in 55 percent of cases and the
circumflex branch of the left coronary artery in 45 percent; occlusion of the artery
supplying the sinus node can result in significant bradycardia. The sinus node is richly
innervated by both sympathetic and parasympathetic fibers and responds with
acceleration or deceleration of its intrinsic discharge rate depending on the balance of
autonomic tone.
Atrioventricular (AV) node
The AV node is situated in the inferomedial right atrium and forms the entrance to the
only normal electrical connection between atria and ventricles. Special cells transmit
impulses very slowly, requiring 60 to 130 ms to traverse about 1 cm of compact node.
The AV node's slowing of the impulse facilitates optimal filling of the ventricles afforded
by atrial contraction (since it takes a small but finite amount of time for the blood to be
propelled through the AV valves and distend the ventricular walls). This slowing also
protects the ventricles to a variable extent from racing in response to rapid atrial
arrhythmias (atrial fibrillation) by not allowing all impulses through; it also can fail to let
any impulses through and is the most common location of heart block. The AV node is
profoundly influenced by autonomic tone, having rich innervation from both the
sympathetic and parasympathetic fibers; blood supply is from the right coronary artery
in 90 percent of cases and the left circumflex in the rest. Under most clinical
circumstances, AV nodal cells do not have the capacity to depolarize spontaneously;
so-called nodal rhythms are in fact generated in the infranodal portion of the conduction
system (His bundle).
His-Purkinje system (HPS) and ventricles
Rapid spread of impulses through the ventricles is mediated by cells of the His-Purkinje
system. The AV node terminates in the top of the His bundle, which then branches into a
left and right bundle branch; the left bundle branch soon divides again into an anterior
and posterior fascicle, and each fascicle further ramifies into the rest of the Purkinje
network. This network is situated just beneath the endocardial surface. Conduction is
especially rapid through these cells, activating the left side of the interventricular
septum, then the apex, and finally the base, from endocardium to epicardium. In this
way, ventricular contraction starts at the apex, and blood is propelled efficiently toward
the semilunar valves. The entire mass of ventricular myocardium is depolarized in about
80 to 100 ms, the same as in the atria. Blood supply to the His and main bundle
branches is almost entirely from the left anterior descending artery; the very proximal
His bundle may have a variable right coronary arterial supply. Cells within the HPS are
capable of spontaneous depolarization at rates from 30 to 50 beats per minute
depending on autonomic tone; consequently, the pacemaker function of these cells is
suppressed in the presence of a faster rhythm from the sinus node but may become
manifest if extreme sinus bradycardia or AV block occurs.
An electrode catheter placed in the region of the AV node and His bundle can record
the His deflection, or potential; the amount of time taken to traverse the AV node is
approximated by the AH interval (local atrial deflection to His spike, normally 60 to 125
ms), and the duration of activation of the proximal HPS is reflected in the HV interval
(from His spike to QRS onset, normally 40 to 55 ms) (Fig. 25-3) .
Abnormal connections: Wolff-Parkinson-White (WPW) syndrome [3]
Additional atrioventricular connections (aside from the normal AV node-HPS) exist in

about 1 to 3 in 1000 individuals. These are generally comprised of fibers of
myocardium from 5 to 20 cells thick, histologically indistinguishable from normal atrial or
ventricular cells, that traverse the AV groove extrinsic to the valve ring tissue. [4 ] , [5 ]
These fibers, present from birth, typically have properties similar to normal myocardial
tissue (i.e., rapid conduction) and connect directly between atrium and ventricle-not
using the HPS. They can conduct anterogradely (atrium to ventricle), leading to the
unusual and characteristic ECG appearance of WPW syndrome (the delta wave), since
ventricular depolarization occurs (1) without the usual AV nodal delay and (2) without the
rapid spread of impulses mediated by the HPS (Fig. 25-4) . These bypass tracts also
can conduct retrogradely (ventricle to atrium) and participate in tachycardias (see
below). Some bypass tracts cannot conduct anterogradely (from atrium to ventricle) but
only in the retrograde direction; these are termed concealed bypass tracts, and
although patients with this type of tract have normal PR intervals and QRS complexes in
sinus rhythm rather than the characteristic ECG findings of WPW, they are still
susceptible to supraventricular tachycardia (SVT) because only retrograde conduction
in the bypass tract is necessary for this arrhythmia to occur.
Bradyarrhythmias
ABNORMAL IMPULSE FORMATION
Normal sinus rhythm is defined as a regular rhythm originating in the sinus node with a
rate between 60 and 100 beats per minute. However, the use of normal must be
interpreted within the context of patient activity. For instance, a heart rate of 70 would be
normal for a middle-aged person reading a book but very abnormal in a teenager
playing soccer. The maximum rate of discharge of the sinus node (i.e., maximum heart
rate) decreases with age following this relation: maximum sinus heart rate = 225 - age
in years. Sinus node dysfunction, manifested as inappropriate sinus bradycardia, is a
major cause of fatigue, weakness, and syncope in the elderly due to the combination of
suboptimal cardiac output and poor vascular compliance. Other manifestations of sinus
node dysfunction include the brady-tachy syndrome, in which atrial fibrillation or flutter
bombards the sinus node with impulses, suppressing its capacity for spontaneous
depolarization; when the atrial arrhythmia ceases, the sinus node may be abnormally
sluggish in recovering from this suppression and take several seconds to resume
functioning. If there is no His bundle (junctional) escape beat to support the circulation,
syncope can result. Medications that normally slow the sinus discharge rate (beta
blockers, ca 2+ blockers) can have dramatically enhanced effects in susceptible
individuals.
ABNORMAL IMPULSE TRANSMISSION
The cardiac impulse may fail to conduct from one point in the heart to another in one of
three ways: delayed conduction (first-degree block), intermittent conduction
(second-degree block), and no conduction (third-degree block). These are best
illustrated in disorders of atrioventricular (AV) conduction, but the same principles apply
to practically all other portions of the conduction system. These types of disordered
conduction will first be considered within the AV conduction system and then
generalized to other parts of the conduction apparatus.
Atrioventricular block (AVB)
This is the most common location for clinically important conduction disturbances and
serves as a model for conduction abnormalities in other locations within the heart.
First-degree (1°) AV block (Fig. 25-5)
This is actually a misnomer, since there is really no block; all impulses do get to the
ventricles, but with a longer-than-normal PR interval (>200 ms). Accordingly, it is
sometimes called 1° AV delay. The most common location for 1° AVB to occur is within
the AV node, correlating with an increased AH interval on intracardiac recordings; in
some cases, the HPS is responsible (yielding a long HV interval). Medications
(particularly beta and Ca [2 ] + blockers) can slow AV nodal conduction enough to
produce 1° AVB within the AV node. Figure 25-6 is an example of 1° AV delay due to
prolongations in both the AH (AV node) and HV (HPS) intervals.
Second-degree (2°) AVB (see Fig. 25-5 )
The hallmark of 2° AVB is an intermittent, sudden lapse of AV conduction. This takes

two forms, named after Mobitz:
Mobitz type I 2° AVB . This is characterized by a gradual increase in the PR interval that
eventually leads to a nonconducted P wave, after which conduction resumes for another
cycle; most often a 3:2 or 4:3 ratio of P waves to QRS complexes is observed. An
additional feature of this type of AVB is that the increment in the PR interval on
successive beats gradually decreases, and if the PP interval remains constant, the
resulting RR intervals decrease progressively. Usually known as Wenckebach block ,
this type of AVB is relatively common and is almost always localized to the AV node.
Accordingly, it is less serious than block at a lower level, since if condution through the
AV node fails entirely, the discharge rate of the subsidiary pacemaker (His bundle) is
sufficient to prevent asystole and death.
Mobitz type II 2° AVB . This is manifested as 1:1 AV conduction with a constant PR

interval until a P wave suddenly fails to conduct, after which P waves are once again
conducted faithfully until another QRS is dropped. This type of AVB is less common
than type I but more serious; the location of the block is in the HPS, and if conduction
fails entirely, the rate of the escape focus (lower HPS) is less reliable and may not
support the circulation.
Third-degree (3°) AVB (see Fig. 25-5 )
In this disorder, also known as complete heart block (CHB), there is no electrical
communication between atria and ventricles; each beats at its own rate (ventricles
typically slower, driven by an escape focus in the HPS). The location of the block may
be in either the AV node or the HPS. Symptoms are related to the decrease in cardiac
output caused by the slow rate; some individuals have relatively rapid escape focus
rates (55 to 65 beats per minute) and are largely asymptomatic, while others who have
little or no escape rhythm may have syncope or die suddenly when CHB develops.
Sinus nodal exit block
In addition to abnormal impulse formation, sinus node dysfunction may be manifested

by abnormal transmission of the impulse from the sinus node to the surrounding atrium.
First-degree sinus exit block cannot be diagnosed from the ECG; it is even difficult to
make direct intracardiac recordings from the sinus node itself (in order to observe
delayed conduction from it to the atrial muscle). However, 2° sinus exit block is
occasionally observed on ECG strips, manifested as either type I 2° sinus exit block (a
gradual decrease in the PP interval culminating in lack of a P wave) or type II 2° sinus
exit block (constant PP interval followed by sudden absence of a P wave). Complete
(3°) sinus exit block would appear as sinus arrest on the ECG, and intracardiac
recordings would be necessary to confirm the presence of sinus nodal depolarization
without spread to the surrounding atrium. It is important to note that abnormalities of
conduction exiting the sinus node may exist independently of other conduction system
disease.
Bundle branch block
Delay or block of the cardiac electrical impulse also can occur in the HPS distal to the
His bundle itself. The clinical significance of these disturbances (bundle branch or
fascicular blocks) is generally much less than that of block in the AV node or His bundle.
Most of the conduction disturbances within this group can be viewed as complete (3°);
although delayed conduction can occur in a bundle branch or fascicle, it is very difficult
to diagnose and of minimal clinical significance if found. The different types of bundle
branch and fascicular blocks are as follows:
Right bundle branch block (RBBB)
This abnormality is characterized by a prolongation of the overall QRS duration to

approximately 0.12 s with a tall R wave forming the terminal portion of the QRS in lead
V 1 . Other features, such as a prominent terminal S wave in leads I and V 6 , are
corroborative. Since ventricular activation during the initial portion of the QRS complex
is mediated by the left bundle branch, disturbances of conduction in the RBB have
minimal influence on the initial QRS deflection. RBBB is seen in 1.7 percent of standard
ECG recordings and of itself has little prognostic importance. (If a terminal small R wave
is present in V 1 but the QRS duration is 0.10 to 0.12 s, an incomplete RBBB is
diagnosed.)
Left bundle branch block (LBBB)
This type of block is manifested by a prolongation of the overall QRS duration to

approximately 0.12 s with a deep S wave forming the terminal portion of the QRS in
lead V 1 . Additional helpful features are lack of a Q wave in leads I and V 6 , as well as
a delay in the intrinsicoid deflection (initial R-wave development) in V 5 and V 6 ; this
occurs because of the dependence of normal initial ventricular activation on impulse
propagation in the LBB. Observed in 1.2 percent of routine ECGs, LBBB likewise has a
poor correlation with the subsequent development of heart block due to disturbances in
other portions of the conducting system.
Nonspecific interventricular conduction disturbance (IVCD)
This relatively uncommon abnormality is diagnosed when the QRS complex is

prolonged to approximately 0.12 s, but specific criteria for both LBBB and RBBB are
absent. This generally suggests the presence of disordered intramyocardial conduction
rather than disease of the main bundle branches. There does not appear to be a
significantly increased risk of development of CHB with this disorder.
Left anterior fascicular block (LAFB)
Also known as left anterior hemiblock , this abnormality consists of interruption of

conduction in one of the two branches of the LBB. Because of this, the anterolateral
portion of the left ventricular free wall is activated slightly later than normal; the QRS
duration, however, is rarely prolonged to a measurable extent. The diagnosis is made
largely on the basis of a frontal plane axis of -60 to -90 degrees (marked left axis
deviation); additional criteria are presence of a small Q wave in leads I and V 6 , RS
waves in leads II, III, and aV F , and the inscription of the peak of the R wave in lead aVL
prior to that of lead aVR (corresponding to a counterclockwise direction of the loop
inscribed in a vectorcardiogram). This abnormality is observed in an isolated form in up
to 1.5 percent of routine ECGs and, like other disorders in this group, has little
prognostic value.
Left posterior fascicular block (LPFB)
This disorder, also known as left posterior hemiblock , is diagnosed based on a frontal
plane axis of +120 to +170 degrees (marked right axis deviation) and the presence of a
small R wave in lead I with small Q waves in leads II, III, and aVF. The diagnosis is
difficult to make because a variety of other disorders can cause a similar degree of
right axis deviation (right ventricular hypertrophy, posterior wall infarction); it is likewise
rare, occurring in only about 0.3 percent of routine ECGs as an isolated abnormality.
The fascicular blocks can occur in combination with another form of conduction block;
for instance, a commonly occurring abnormality is the presence of RBBB plus LAFB. It
would seem that in situations like this (with only a single fascicle still conducting),
complete heart block would develop in many patients. While there is a slight increase in
incidence of CHB in such individuals, it is not high enough to warrant prophylactic
implantation of permanent pacemakers. [6 ]
Tachyarrhythmias
Twenty years ago, only two mechanisms of arrhythmia were recognized: automaticity ,
in which a cell or group of cells autonomously discharge at an inappropriately rapid rate,
and reentry , in which an impulse travels within a circuit in a continuously repetitive
fashion. Of these, automaticity was felt to be the predominant cause of clinical
arrhythmias; within this construct, an entire group of arrhythmias now recognized as
distinct entities was termed paroxysmal atrial tachycardia , with the implication that an
automatic focus was responsible for the rapid firing. Subsequent studies in basic
science laboratories, as well as in animal models and in humans, have led to the
description of subtypes of both these mechanisms of arrhythmia as well as others.
These additional mechanisms include triggered activity (two subtypes),
postrepolarization refractoriness, boundary currents, and others. This chapter will deal
only with the more clinically relevant mechanisms, according to our current
understanding.
AUTOMATICITY
This mechanism, defined as the spontaneous (unstimulated) discharge of cells once

threshold potential has been reached, is responsible for sinus rhythm as well as a
variety of rhythm disturbances. At least three subtypes of automaticity exist: normal,
enhanced normal, and abnormal ( Fig. 25-7 ). Sinus rhythm is based on normal
automaticity; the cells of the sinus node are capable of spontaneous depolarization,
which occurs because of progressive decay of the polarized resting membrane
potential toward a threshold value (a process known as phase 4 depolarization ). Once
this threshold has been reached, a rapid depolarization of the cell can occur, followed
by spread of the impulse to adjacent cells and beyond. Enhanced normal automaticity
occurs generally when some extrinsic agent modifies the resting membrane potential,
the rate of phase 4 depolarization, or both. An example of this is adrenergic stimulation.
The final subset, abnormal automaticity, occurs in partially depolarized cells and
appears to be a calcium-dependent phenomenon. [7 ] Ischemic myocardial cells may
exhibit this mechanism on occasion, but it is likely that clinical arrhythmias related to it
are rare.
Supraventricular arrhythmias due to automaticity include ectopic atrial tachycardias and

junctional ectopic tachycardia, occasionally observed after valve surgery. Ventricular
arrhythmias due to automaticity are rare but probably include some cases of
idioventricular rhythm following myocardial infarction and some ventricular tachycardias
(VTs) occurring in normal hearts (such as those originating in the right ventricular outflow
tract).
REENTRY
Research over the last two decades-much of which was conducted in the operating
room-has produced an overwhelming body of information showing reentry to be the
most frequent mechanism of arrhythmias in humans, whether supraventricular or
ventricular. [8 ] It is thus worthwhile to consider in some detail the essential elements of
reentrant arrhythmias in general, which are (1) the presence of a closed loop of
electrically excitable tissue, (2) heterogeneity of electrophysiologic properties
(conduction velocity and refractoriness), and (3) an initiator to begin the reentrant
process. Occasionally, additional factors such as increased adrenergic effect (neural or
humoral) are required to facilitate the development of reentry. The prototype for all
reentrant arrhythmias is the WPW syndrome ( Fig. 25-8 ). In this condition, an additional
strand of normal working myocardium connects atrium to ventricle on the epicardial
surface of the AV valve rings. As noted above, the PR interval is short because there is
little or no delay of conduction as the electrical impulse traverses the bypass tract (as
would normally be encountered in the AV node). The initial portion of the QRS complex,
mediated by conduction over the bypass tract, is abnormally wide (the delta wave)
because of relatively slow muscle-muscle spread of impulses once activation of the
ventricular myocardium begins.
In the absence of a bypass tract (i.e., a normal individual), an impulse beginning in the
sinus node spreads through atrial myocardium and penetrates the AV node.
Conduction of the impulse slows, allowing the mechanical distension of the ventricles
following the atrial contraction, and then rapid spread of the impulse occurs over the
HPS starting near the apex and ending at the base. At this point the impulse stops,
since there is normally no additional excitable tissue to electrically activate. The
presence of the bypass tract provides a complete circuit of electrically excitable tissue,
incorporating the atrium, AV node, His bundle, ventricle, and bypass tract. The mere
presence of this complete loop does not suffice for reentry to take place, however. One
of the other features that also must be present is a disparity between the refractory
periods, or duration of inexcitability between two successive beats, of two portions of
the circuit. In WPW, this typically takes the form of a longer refractory period in the
bypass tract than in the AV node, such that a premature beat in the atrium fails to
conduct over the bypass tract but still finds the AV node ready to transmit the impulse
(see Fig. 25-8 ). This still does not suffice for reentry to occur; an additional necessary
factor is slow conduction, which in this case occurs in the AV node and allows enough
time for recovery of excitability in the bypass tract that had been found refractory initially.
If the impulse then approaches the bypass tract from the ventricular aspect and the
bypass tract can conduct (recovered excitability), the atrium can be activated
retrogradely; at this point, the impulse has returned to its point of origin, and a single
cycle of reentry has occurred. Assuming the AV node and all other parts of the circuit
can again conduct the impulse, a sustained tachycardia (orthodromic) can ensue.
Several subtypes of reentry have been described. These are (1) anatomic reentry , in
which the impulse circulates around a fixed, anatomically determined path, (2)
functional reentry , in which the impulse circulates within a circuit whose size is
determined by refractory periods of the participating cells, [9 ] (3) anisotropic reentry ,
in which both anatomic and functional properties participate in determining the path
taken by the circulating wavefront, [10 ] and (4) reflected reentry , in which the impulse
retraces its steps along a linear path to return to or reflect on its point of origin. [11 ]
Clinical supraventricular arrhythmias due to reentry include
1. Orthodromic tachycardia in patients with bypass tracts (mentioned above)

2. Antidromic reentry in WPW (conduction in the opposite direction using the same
circuit, leading to a very wide QRS complex and retrogate conduction over the AV
node)
3. AV nodal reentry (intranodal circuit with slow and fast pathways)

4. Some cases of atrial tachycardia
5. Atrial flutter
6. Atrial fibrillation (multiple small circuits with changing locations)
Clinically important ventricular arrhythmias due to reentry include
1. Uniform-morphology VT (each beat looking the same as others) in the setting of

prior myocardial infarction, [12 ] cardiomyopathy, arrhythmogenic RV dysplasia, [13 ]
or after tetralogy of Fallot repair, [14 ] as well as others
2. Some cases of polymorphic VT (constantly changing QRS complex)

3. Ventricular fibrillation (multiple small circuits with changing locations)
TRIGGERED ACTIVITY
This arrhythmia mechanism was well-characterized in laboratory preparations long

before evidence of its clinical occurrence was discovered. The important features of this
cause of arrhythmia are that a cell or group of cells depolarize normally but during or
after the repolarization process, small-amplitude disturbances in the membrane
potential are observed (in the direction of depolarization). Since these depolarizations
occur following the normal period of cellular depolarization, they are called
afterdepolarizations . Two types of afterdepolarizations exist ( Fig. 25-9 ): early (EADs,
occurring during repolarization) and delayed (DADs, following complete repolarization).
Both EADs and DADs appear to be caused by abnormalities of cellular calcium
homeostasis. Evidence indicates that EADs are observed in cells of patients with
polymorphic VT associated with a long QT interval (very often as an idiosyncratic
consequence of treatment with type IA antiarrhythmic drugs), [15 ] whereas DAD-related
arrhythmias appear to include digitalis-toxic atrial, junctional, and ventricular
tachycardias, [16 ] as well as perhaps some cases of VT originating in the right
ventricular outflow tract in individuals without structural heart disease.
To summarize, reentry, although requiring a complex set of conditions for its initiation
and perpetuation, accounts for the majority of arrhythmias observed in humans.
Automaticity accounts for a small but important group of tachycardias, and triggered
activity in one of its forms is most likely responsible for a scattered variety of
arrhythmias. The distinction is of considerable importance in that both automatic and
triggered arrhythmias behave as though there is a point source of the abnormal
impulses from which all electrical activation originates; the remainder of the heart is
merely passively activated. Locating this very small focus is essential to successfully
eradicate the arrhythmia during surgical or catheter ablation. On the other hand, in a
reentrant arrhythmia, large areas of the heart may participate in the circuit, making
removal of the entire circuit impractical. Instead, one must locate smaller areas of tissue
that are absolutely critical to the maintenance of reentry and target these for ablation. In
the case of WPW reentry, for example, complete excision of the circuit would involve
removing half the heart, whereas eradicating the bypass tract will cure the arrhythmia
but leave the rest of the heart intact. (In principle, dividing the AV node or His bundle
also will cure the arrhythmia but will leave the patient pacemaker-dependent and is thus
not a satisfactory option.)
COMMON TYPES OF CLINICAL ARRHYTHMIAS
Although it is not possible to undertake a detailed review of even the most commonly
encountered clinical arrhythmias, important features of some typical varieties are
discussed below ( Fig. 25-10 ).
SVT in patients with WPW syndrome/concealed bypass tracts
In this disorder, as noted above, a reentrant circuit is present; during the most common
form of clinical arrhythmia in these patients (orthodromic SVT), the impulse travels in the
normal fashion over the AV node-His bundle, through the ventricles, and then
retrogradely over the bypass tract, through the atria, and back to the AV node for
another cycle. Impulses less commonly circulate in the opposite (antidromic) direction:
down the bypass tract, through the ventricles, up the AV node-His bundle, through the
atria, and back to the bypass tract. Patients may have multiple bypass tracts that may
participate in various combinations (anterogradely or retrogradely) during SVT
episodes.
AV nodal reentry
Once again, a reentrant circuit is present, in this case comprised largely (or, in some
cases, wholly) of AV nodal tissue. Patients with this disorder most often manifest the
phenomenon of dual AV nodal pathways , denoted by a discontinuity in the curve of AH
intervals resulting from delivery of progressively premature atrial extrastimuli. During the
common variety of this arrhythmia, impulses proceed toward the His bundle over a very
slowly conducting AV nodal pathway (the slow pathway) and retrogradely via a faster
pathway (that may be intra- or extranodal). It happens that in most cases the time it
takes for the impulse to traverse the lower portion of the node and His bundle is very
nearly the same as the fast-pathway conduction time, such that the P wave during AV
nodal reentrant SVT often occurs in the middle of the QRS complex and cannot be seen
distinctly on the ECG. As in WPW, the AV nodal circuit can in some patients be
reversed, with anterograde conduction proceeding via a fast pathway and retrograde
conduction proceeding over a slow pathway.
Atrial flutter
Reentry is again the operative mechanism; in the most common variety of atrial flutter,
the wavefront appears to circulate in a relatively large circuit comprised of the region of
the coronary sinus os (inferior and posteromedial right atrium), the posteromedial right
atrial free wall, the right atrium near the junction with the superior vena cava, the
posterolateral right atrial wall, and finally, the isthmus of atrial muscle between the
tricuspid annulus and the inferior vena caval (IVC) orifice. Some cases may involve
revolution of the wavefront around the atrial rim of the tricuspid annulus itself; in either
case, the isthmus of atrium between the annulus and the IVC appears to be of critical
importance for perpetuation of the arrhythmia. As was the case in other reentrant
arrhythmias, the same circuit can be traversed in the opposite direction (atypical flutter).
Automatic atrial tachycardia
In this example of an automatic arrhythmia, an autonomous focus of perhaps just a few

atrial cells discharges independently; although any region of the atria can be
responsible, foci of atrial tachycardia seem to be concentrated in several confined
areas. These include the pulmonary vein orifices, the mouths of the left and right atrial
appendages, and the crista terminalis in the right atrium. These arrhythmias cannot be
initiated with pacing or premature impulses, as can reentrant arrhythmias; thus studying
them in the electrophysiology (EP) laboratory can be somewhat haphazard, depending
on the presence of the arrhythmia at the time of the study. In many cases, however,
catecholamine infusion (such as isoproterenol) can facilitate spontaneous tachycardia
onset.
Postinfarction uniform sustained VT
Reentry is again responsible for this important arrhythmia, [8 ] which occurs in from 2 to
10 percent of survivors of large myocardial infarctions. The circuit appears to be
comprised of surviving sub-endocardial cells at the periphery of the main infarct zone,
probably also including some deeper tissues in many cases. [17 ] The length of the
circuit is likely 4 to 8 cm in most instances, with the impulse taking a meandering course
in many. Although ultimately due to an ischemic basis (postinfarct scar interspersed
among residual living fibers), this form of VT does not depend on active ischemia either
for its onset or for perpetuation; i.e., periods of ischemia (such as on a stress test or
during anxiety) rarely provoke VT episodes, whereas pacing and premature beats
reliably do so. Most patients with this type of arrhythmia manifest more than one ECG
morphology of VT [18 ] ; whether these different morphologies represent distinct circuits
or (as has been noted before) different directions of wavefront propagation within the
same circuit is not certain.
Bundle branch reentrant VT
A special variety of VT has been described that involves the HPS; this disorder is
observed most commonly in patients with dilated cardiomyopathy. In this reentrant
arrhythmia, significant disease of the conduction system enables an impulse to travel
anterogradely down the RBB, cross the interventricular septum, and travel retrogradely
up the LBB and back down the RBB. [19 ] VT in these cases has a LBBB pattern on the
ECG, and intracardiac recordings typically show His potentials inscribed prior to each
QRS complex. Another hallmark is an HV interval during VT the same or slightly longer
than in sinus rhythm. As with most other reentrant arrhythmias, it is possible in rare
cases for the wavefront to traverse the same circuit in the opposite direction.
DIAGNOSIS OF CARDIAC ARRHYTHMIAS
Clinical Symptoms
Arrhythmias may produce a wide variety of symptoms, ranging from a complete

absence of awareness of the episode to mild palpitations, light-headedness, syncope,
and even sudden cardiac death. Additional symptoms include chest pain, throat
tightness, or dyspnea, any of which may occur alone or in combination with others.
Unfortunately, the severity of the symptom has only a weak correspondence with the
arrhythmia diagnosis; for instance, the combination of severe light-headedness and
dyspnea may be due to SVT with a heart rate of 230 beats per minute in one individual,
while the same symptoms in another person may result from complete heart block with
a heart rate of 30 beats per minute. Some general guidelines can be formulated,
however, as to how to make use of clinical symptoms in patients with known or
suspected arrhythmias.
The symptom produced depends as much or more on the heart's contractile state than
on the heart rate during the arrythmia episode; a heart rate of 180 beats per minute may
result in syncope in an individual with severe depression of myocardial function, while a
young patient without heart disease may not even experience so much as palpitations.
The presence of chest discomfort during an arrhythmia episode does not necessarily
indicate the presence of inadequate coronary arterial supply.
The more the severe symptom, the greater should be the effort to establish the casual
diagnosis and begin effective treatment (see below).
The more frequently a symptom occurs, the greater should be the effort to establish the
diagnosis and the more likely it is a diagnosis can be found.
Episodes of symptoms that the patient can self-terminate by Valsava, squat, cough, etc.
generally involve the AV node integrally (although occasional atrial and even ventricular
tachycardias will terminate in response to these vagal maneuvers).
If a patient notes a relationship between stress or exertion and onset of symptoms, it is

likely that endogenous catecholamines play a role in development of episodes and that
either beta-blocking agents may be useful in treatment or exercise testing or
administration of agents such as isoproterenol during electrophysiology study may be
needed to elicit the arrhythmia.
Noninvasive Methods
THE RESTING ELECTROCARDIOGRAM
The routine ECG during resting rhythm may provide some clues as to the etiology of
arrhythmia symptoms. The presence of delta waves in WPW syndrome is a strong clue
that symptoms suggestive of arrhythmia are related to an AV bypass tract; similarly, the
presence of pathologic Q waves raises the possibility of postinfarction VT as the cause
of symptoms such as palpitations or syncope. T-wave inversion in leads V 1 to V 4 and a
pattern of incomplete RBBB suggest right ventricular dysplasia with the possibility of VT
causing arrhythmia symptoms. The presence of a long PR interval and bundle branch
block suggests the possibility of both intra- and infranodal conduction defects that might
cause intermittent heart block with associated symptoms. The presence of stimulus
artifacts from a permanent pacemaker raises the possibility of pacemaker malfunction
or a role for the pacemaker in producing an abnormal tachycardia. Finally, a prolonged
P-wave duration suggests atrial disease of a degree that atrial arrhythmias could be
responsible for clinical symptoms (atrial tachycardias, flutter, and fibrillation). Aside from
these and other occasional examples, in the majority of patients, the resting ECG (i.e.,
between episodes) provides relatively few clues as to the cause of the symptomatic
episodes.
The ECG obtained during a symptomatic episode is of immense diagnostic value, in

that it affords the opportunity to make a determination of the presence of P waves and
their relationship to QRS complexes. Rather specific diagnoses of various types of SVT
can be made based on particular timing relationships between P waves and QRS
complexes, and distinctions between VT and SVT can be solidly drawn by carefully
evaluating the ECG for specific QRS configurations; however, such precise diagnostic
points are beyond the scope of this chapter. As useful as the full 12-lead ECG can be in
leading the clinician to the proper arrhythmia diagnosis, it is relatively unusual that one
is recorded during a spontaneous episode (unless the patient seeks medical attention
while the symptom is still occurring).
AMBULATORY ELECTROCARDIOGRAM (ALSO KNOWN AS HOLTER

MONITORING )
Because of the rarity of opportunity to record an actual arrhythmic episode with a full
12-lead ECG, other methods to make more limited but still diagnostic ECG recordings
during symptomatic episodes have been developed. The ambulatory electrocardiogram
(AE) [20 ] was among the first of these to come into widespread use. This diagnostic
tool consists of a battery-powered compact cassette tape recorder and ECG leads that
the patient wears continually for 24 to 48 hours; during this period, two to three leads of
the ECG are recorded to the tape continuously. The patient may make a notation of the
occurrence of a particular symptom with an event marker and likewise note symptoms
in a diary (Fig. 25-11A) . Once the recording period is over, the tape is played back and
analyzed for the presence of arrhythmias and their correlation with symptoms.
EVENT MONITORS (EM)
This device, of which there are several forms, fundamentally consists of a relatively
small apparatus for collecting a limited amount of ECG information (30 seconds to 2
minutes) on demand. Generally, only one ECG lead can be recorded, and the quality of
the transmission is occasionally poor; however, there can be a direct correspondence
between the symptom and the associated rhythm (see Fig. 25-11B ). Once the patient
has finished recording the episode, he or she may, at his or her leisure, transmit the
data over standard telephone lines to a center capable of receiving them, from which
the processed information can be distributed to the ordering physician. In contrast to the
short-term AE recorders, EMs are kept for a month or more by the patient in order to be
able to capture less frequent events. Obviously, the AE is very useful in obtaining
recordings from patients who have nearly daily episodes (which might well be captured
on any given day) or ones that last only seconds or quickly lead to incapacitating
symptoms such that an EM could not be readily hooked up or activated. On the other
hand, the EM is most useful in patients whose episodes are relatively rare and not
associated with such severe symptoms that they could not reliably operate the device.
[21 ]
EXERCISE (STRESS) TESTING
Occasionally, symptomatic episodes can be reproduced by having the patient perform

a graded exercise test during which endogenous catecholamines may modulate the
cardiac electrophysiologic milieu such that arrhythmias may be provoked. As noted
earlier, this is more likely to occur if there is a history of an association between exertion
or stress of other forms and onset of symptoms. Otherwise, the exercise test is much
less likely to facilitate initiation of arrhythmia episodes and is thus not a routine part of
the evaluation of patients with symptoms suggestive of arrhythmia episodes. It can,
however, provide other useful types of information in selected patients, such as an
indication of the presence or absence of myocardial ischemia as well as estimating the
patient's functional capacity.
SIGNAL-AVERAGED ECG (SAECG)
Patients with reentrant ventricular arrhythmias typically do not manifest either slow
conduction or block on the resting ECG; however, even in the baseline condition there
are usually some tissues that exhibit slow conduction. Tissues in which slow conduction
is present would be expected to be depolarized after the rest of the heart had been
activated; i.e., these signals would be present during the ST segment but in very low
amplitude. The presence of this abnormality can be determined (and the potential for
reentrant ventricular arrhythmias inferred in many cases) by using special tools such as
the SAECG. [22 ] This technique draws on the theory of signal averaging, in which a
low-amplitude repetitive signal can be magnified many times by summation of
repeated, gated recordings such that its amplitude on an averaged beat exceeds the
ambient noise level (which is assumed to be random and is thus effectively diluted by
the process). In practice, this entails recording approximately 200 fairly identical beats
using specially designed filters and processing algorithms and eventually yielding an
aggregate signal for the average QRS complex. Normal values have been determined
for filtered QRS duration, as well as area under the curve (root-mean-square, or RMS,
voltage) in the terminal 40 ms of the filtered QRS complex (during which low-amplitude
signals reflecting slow conduction are inscribed), as well as other parameters. A
positive SAECG is one that shows an abnormality in one or more of these parameters
(Fig. 25-12) . In recent years, the use of this technique has fallen into some disfavor
because of lack of adequate sensitivity and specificity to replace other diagnostic tools;
very often the information provided by the SAECG simply corroborates what is already
known about the patient's potential for developing ventricular arrhythmias.
Invasive Methods
ELECTROPHYSIOLOGIC (EP) STUDY
Shortly after the development of percutaneous catheter techniques to record the His
bundle potential in animals, similar tools were applied to diagnosing the causes of ECG
abnormalities and symptomatic arrhythmias in humans. During the EP study, thin
catheters with 2 to 12 electrodes near the tip are inserted percutaneously into veins
(and occasionally arteries) and advanced under fluoroscopic guidance to strategic
locations within the heart, in contact with the endocardium. Patients are generally lightly
sedated for these studies, which can take up to several hours to complete. Common
sites for vascular access include the femoral veins (which can usually each
accommodate up to three standard vascular sheaths), as well as the brachial, internal
jugular, and subclavian veins. Which, if any, of these latter sites is used depends on
individual preference. Free access to all right-sided structures can be obtained from
these approaches, including the coronary sinus (which yields recordings from the
junction of the left atrium and ventricle along the mitral annulus). Left atrial recordings,
when needed, may be obtained from the venous approach either by passing a catheter
through a preexisting interatrial communication (patent foramen ovale or atrial septal
defect) or by performing an atrial septal puncture with specially designed catheters and
needle. Left ventricular access may be gained by passing a catheter retrogradely
through the aortic valve from the femoral arterial approach or by using the transatrial
septal approach.
The intracardiac catheter positions vary according to the indication for the EP study;
most studies include a right atrial, AV junction (to record the His potential), and right
ventricular apical recording sites (Fig. 25-13) . Studies performed for evaluation of SVT
usually also include a coronary sinus recording catheter; those designed for
investigating ventricular arrhythmias usually include a second right ventricular catheter,
typically in the outflow tract. In catheter ablation procedures (see below), an additional
special mapping and ablation catheter is inserted and positioned at the location of the
tissue targeted for ablation (determined after the diagnostic portion of the study or
based on data collected at a previous EP study). Once stable catheter positions have
been obtained, the catheters are connected to amplifiers and recording equipment, and
signals are recorded from the various locations within the heart simultaneously. The
same catheters can be used to stimulate the heart. EP studies were originally applied
to diagnose the cause of bradyarrhythmias (level of block, etc.) but quickly showed
potential for aiding in diagnosis and management of tachyarrhythmias. This is so
because the catheters used for recording also could be used to stimulate (pace) the
heart and thereby provoke tachyarrhythmias that depended on rapid rates or (more
typically) premature beats for their initiation. In patients with rare episodes of
palpitations, the cause of which could never be adequately documented
electrocardiographically, programmed electrical stimulation at EP study could recreate
the circumstances of arrhythmia occurrence in the controlled laboratory setting, thereby
compressing time; not only could an accurate diagnosis be made as to the arrhythmia
mechanism, but the same techniques could be applied to acutely test the efficacy of
drug or surgical therapy designed to suppress episodes of arrhythmia. [23 ] , [24 ]
ENDOCARDIAL MAPPING
At the time of EP study, the tissues responsible for several different types of arrhythmias
often can be localized by the process of catheter endocardial mapping. This technique
involves moving a catheter from point to point within the heart and making recordings
during either sinus rhythm or a tachycardia. [25 ] The catheters used for this procedure
are of a special design that allows deflection of the catheter tip (bearing the mapping
electrode) in all three spacial axes by manipulating mechanical controls on the handle of
the catheter, outside the patient's body. The timing of sampled electrograms obtained
during mapping is compared with a reference recording (either a surface ECG lead or
another intracardiac recording), seeking the location from which the recorded
electrogram precedes the reference electrogram by the maximal amount of time. The
underlying arrhythmia mechanism largely determines what this optimal amount of time
is; in arrhythmias based on an automatic mechanism, the interval between the firing of
the automatic focus and the onset of the surface P wave or QRS may be relatively short
(15 to 40 ms). For instance, when mapping an automatic atrial tachycardia, one would
manipulate the mapping catheter within the atria searching for a site from which the
recorded electrogram preceded the onset of the surface P wave during the tachycardia
by 20 to 50 ms or more [26 ] (Fig. 25-14) . In contrast, a much longer presystolic interval
is sought during reentrant arrhythmia, since electrical activity is ongoing throughout the
cardiac cycle-even during what appears to be electrical diastole on the surface ECG.
Electrograms can still be recorded from the small number of cells responsible for
continued propagation of the electrical impulse during the diastolic interval, and sites
are then sought during mapping from which markedly presystolic or even middiastolic
electrograms can be recorded. An example of this type of arrhythmia is postinfarction
sustained VT; during mapping studies, sites are sought from which electrograms can
be recorded during middle to late diastole (Fig. 15-14) . The morphology of the mapped
electrogram also can be useful in analyzing the quality of sites; markedly abnormal
electrograms are often recorded from arrhythmogenic sites, regardless of arrhythmia
mechanism.
Other methods of localizing arrhythmogenic areas also have been devised in specific
arrhythmias. In both WPW syndrome and postinfarction VT, analysis of the surface ECG
morphology can provide information adequate to regionalize the location within the
heart responsible for the arrhythmia. [27 ] [29 ] Several complex algorithms have been
developed to assist in this process, but none is completely accurate and all are difficult
to remember in detail. In addition, the algorithms cannot localize the arrhythmogenic
tissue with the precision necessary to undertake catheter or surgical ablation based
solely on the ECG. These techniques are useful, however, in directing attention to
certain areas of the heart where more extensive mapping should be performed if
possible. Another technique, catheter endocardial pacemapping , has been used
successfully in VT (as well as to a lesser extent in atrial tachycardias). [30 ] The principle
behind this technique is that pacing from the site within the heart from which the
arrhythmia arises should replicate the ECG morphology of the arrhythmia. In the case of
VT, pacing at an endocardial site should produce a 12-lead ECG identical in all leads
to that of the VT being mapped (Fig. 25-16) . This technique, however useful, lacks
adequate sensitivity and specificity to substitute for standard activation mapping as
described above but can provide corroborative information in many cases.
THERAPEUTIC CHOICES FOR CARDIAC ARRHYTHMIAS
As with all aspects of medicine, therapy of arrhythmias should be individualized, tailored

to the needs of specific individuals. Examples of this are a young person with WPW
needing catheter ablation rather than long-term drug therapy; a traveling salesperson
with postinfarction VT needing preventive therapy (drugs, catheter or surgical ablation)
instead of rescue therapy from an implantable cardioverter-defibrillator, in order that he
or she can operate an automobile and maintain his or her livelihood; and a
jack-hammer operator with extreme sinus bradycardia needing a rate-responsive
pacemaker based on a mechanism other than piezoelectric transduction (vibration
sensor).
Continuing advances in research have led to alterations in the both the indications for
and the methods of treatment of a variety of arrhythmias. Currently, a large array of
therapeutic options is available in the management of arrhythmias, the details of which
are well beyond the scope of this discussion; in this chapter we will therefore attempt to
address general concepts. It is worthwhile to remember that treatment of one rhythm
disorder may exacerbate another; for instance, control of ventricular rate during
paroxysms of atrial fibrillation may require a dosage of beta or calcium blockers that
produce unacceptable sinus bradycardia between episodes of fibrillation.
Pharmacologic
HISTORICAL OVERVIEW
The history of pharmacologic treatment of arrhythmias can be traced to Dr. William

Withering, who used an English woman's recipe for tea made from the digitalis plant to
treat heart failure in the 1780s; many of his patients so treated appear to have suffered
from rapid heart rates during atrial fibrillation, and the action of the digitalis preparation
may have been as much in controlling the heart rate (allowing for more efficient
ventricular filling) as in enhancing myocardial contractility. The properties of atropine
and catecholamines (natural and synthetic) were studied prior to the turn of the century;
practical use of oral medication awaited the application of quinidine in the 1920s and
procainamide in the 1950s. Beta blockers became available in the 1960s, and their
utility in treating a wide variety of tachyarrhythmias became apparent. By the
mid-1970s, lidocaine and disopyramide were used to treat ventricular arrhythmias, and
verapamil was released for supraventricular arrhythmia treatment. Use of these
medications for treating even the most serious arrhythmias was largely empirical; i.e.,
the physician simply chose a medication and a dose and hoped for a good outcome,
since there was no reliable method for predicting efficacy. Development and refinement
of electrophysiology studies and other methods of testing drug efficacy enabled a more
rational use of these medications in many instances. [31 ] It also became clear that
some of these medications could promote arrhythmiaseither increasing the frequency of
arrhythmias they were supposed to treat or causing serious arrhythmias never
experienced by the patient. [32 ] [35 ] In particular, the form of ventricular tachycardia
known as torsades de pointes , characterized by rapid, continually changing QRS
complexes in the setting of a long QT interval on the ECG, was recognized as a rare
and unpredictable side effect of antiarrhythmic medications, especially those in the type
IA group (see below).
In the 1980s, as pharmacologic agents proliferated and their use increased, concern
began to develop as to the degree to which patients in various subgroups benefited
from antiarrhythmic therapy. Several studies were designed to answer these questions.
The results of one such study, the Cardiac Arrythmia Suppression Trial (CAST), [36 ]
dramatically changed the way antiarrhythmic medications are used. [37 ] In brief, this
study showed an increased mortality (many sudden deaths) in the group of patients
treated with flecainide and encainide, agents that profoundly slow conduction but have
minimal effect on refractoriness (see below). After these findings were published, the
use of empirical antiarrhythmic therapy markedly declined and development of new
agents slowed. In the last 10 years, several relatively effective medications have been
released for treatment of arrhythmias; among these are amiodarone, propafenone, and
sotalol. Despite their enhanced efficacy compared with previously available
medications, many of these newer agents are being used less frequently than might be
indicated because of concerns about possible side effects.
The continued development, testing, and release of new antiarrhythmic agents signify
the lack of a perfect medication. Such an agent would be one that has (1) very high (and
predictable) efficacy rates for treating a variety of rhythm disturbances, (2) low rates of
side effects, especially toxic ones, (3) low cost, and (4) a convenient dosing schedule
(daily or even less frequent). The pharmacologic industry continues to seek an
approximation of this elusive combination of attributes.
BRADYARRHYTHMIAS
It is rare that a patient with a bradyarrhythmia can be treated successfully with

medications. Heroic efforts can be expended in administering large enough doses of
either anticholinergic agents (e.g., scopolamine patches) to counter high vagal tone or
methylxanthines (theophylline) as sympathetic stimulants. In practice, it is difficult to
achieve the desired therapeutic endpoint without encountering significant side effects.
One relatively frequent means of treating bradyarrhythmias using medications is to

withdraw agents from the patient's regimen that might be responsible for the slow rates,
such as beta or calcium-channel blockers, amiodarone, and propafenone; other
medications less commonly recognized as possibly causing bradycardia include
cimetidine and lithium.
TACHYARRHYTHMIAS
Goals of drug therapy
Complete suppression of the index arrhythmia is the ideal endpoint, but in many cases
practice falls short of this ultimate goal. Other, lesser endpoints are often quite
acceptable; among these are a marked decrease in the frequency of symptomatic
recurrences of arrhythmia; a reduction in the severity of symptoms during recurrences,
largely due to a decrease in the heart rate in the arrhythmia, [38 ] making initiation in the
EP laboratory setting more difficult [39 ] ; a shortening of the absolute duration of
episodes (changing sustained into nonsustained episodes) [40 ] ; and changing the
arrhythmia's behavior such that it can be terminated by the antitachycardia pacing
function of an implanted defibrillator rather than requiring shocking. [41 ]
Classes of drugs and modes of action
Over the years, several classification schemes have been proposed to attempt to group
antiarrhythmic medications according to common effects. Each method has strengths
and weaknesses; the classification of Vaughan Williams, [42 ] proposed in 1970, has
remained a useful means of considering the actions of antiarrhythmic drugs on cardiac
cellular electrophysiology and applying that information to the intact human heart. It is
important to keep in mind that antiarrhythmic medications rarely have a single, pure
mechanism of action; most agents of one class described below possess features of
another class or classes. General features of these medications will be outlined briefly;
a full discussion of the benefits and problems associated with the clinical use of these
medications is well beyond the purview of this chapter.
Class I antiarrhythmic agents
Medications in this group have depression of the fast sodium current as a common
feature. As such, they cause a slowing in the conduction velocity of the cardiac impulse
in tissues that rely on the sodium channel for depolarization (i.e., all cells except those in
the sinus node and AV node).
Class IA agents . Drugs in this subgroup, such as procainamide, quinidine,

and disopyramide, cause a marked decrease in conduction velocity as well
as an independent prolongation of repolarization. [43 ] These effects
translate into a prolongation of the QRS duration and QT interval on the
ECG. These medications are used most frequently in either preventing or
slowing the heart rate during episodes of VT, atrial fibrillation and flutter, and
other arrhythmias to a lesser degree. These drugs are occasionally
associated with the development of rapid polymorphic VT (torsades de
pointes) in patients who often have no history of such arrhythmias; this
potentially lethal side effect appears to be due to the prolongation of
repolarization effected by these medications (drug-related long-QT
syndrome). [44 ] This latter idiosyncratic reaction is entirely reversible upon
withdrawal and washout of the offending medication and may or may not
occur upon rechallenge of the patient with the same drug or another in this
class. [45 ]
Class IB agents . Members of this group, which include lidocaine and

mexiletine, cause moderate slowing of conduction but have minimal effects
on repolarization (and may even shorten it). [46 ] , [47 ] This results in little or
no change in the contour of ECG complexes. These medications have
practically no utility in controlling supraventricular arrhythmias and are only
moderately effective in controlling ventricular arrhythmias (often in
combination with other medications [48 ] ). Side effects are mainly
gastrointestinal upset and neurologic; because these agents have little
effect on repolarization, torsades de pointes is rare.
Class IC agents . Flecainide and propafenone are members of this group,

the effects of which are marked decreases in conduction velocity (more so
than with class IA agents) but minimal effect on repolarization. These effects
lead to QRS widening but minimal prolongation of the QT interval in sinus
rhythm. These medications potentially have wide applicability in treating
almost all types of supraventricular and ventricular arrhythmias, [49 ] , [50 ]
but their use has been limited due to concerns about possible proarrhythmic
effects, as noted above. [35 ] Currently, these medications are used with
caution mainly in patients with atrial fibrilation as well as some with VT; other
types of arrhythmias are treated less commonly with these drugs. [51 ] , [52 ]
Class II antiarrhythmic agents
This class includes beta-adrenergic blocking drugs, which act by antagonizing the
effects of epinephrine and norepinephrine at nerve terminals in the heart and elsewhere.
These agents are most useful in treating arrhythmias that depend on the AV node for
perpetuation (i.e., many forms of SVT); they may be used adjunctively in ventricular
arrhythmias but have little independent efficacy in this setting. Side effects include sinus
bradycardia or AV block; provocation of heart failure, peripheral vascular disease, or
reactive airways disease; and destabilizing diabetic control.
Class III antiarrhythmic agents
Medications in this class, including amiodarone, bretylium, and sotalol, have the
common feature of blocking intracellular currents responsible for repolarization (mainly k
+
). [53 ] As such, these agents prolong the QT interval on the ECG; amiodarone and
sotalol also exhibit significant non-class III actions as well. While bretylium has efficacy
generally limited to ischemic ventricular arrhythmias and is only available parenterally,
amiodarone and sotalol are useful in treating almost all types of supraventricular and
ventricular arrhythmias. [53 ] [56 ] Significant side effects are associated with each,
including development or aggravation of preexisting sinus bradycardia and AV
conduction disturbances, heart failure, proarrhythmia, and a variety of noncardiac
abnormalities. In the case of amiodarone, some of the latter are of particular concern in
that the medication has an extremely long tissue half-life (measured in months), and
whatever side effects are produced by the drug may linger for some time after the drug
is stopped. [56 ] , [57 ] Rare side effects, such as amiodarone-related pulmonary
fibrosis, occasionally can be fatal. Because of these problems, use of these
medications has been limited to more refractory cases.
Class IV antiarrhythmic agents
These agents, such as verapamil and diltiazem, block the cardiac calcium channels; not
all types of calcium-channel blockers have electrophysiologic effects. These
medications may be used almost interchangeably with the beta blockers in
supraventricular arrhythmias because of their actions on the AV node (slowing
ventricular rates during atrial flutter or fibrillation, preventing episodes of AV nodal
reentry or orthodromic SVT, etc.). [58 ] Cardiac side effects include production or
worsening of heart failure and bradyarrhythmias, as is also true of beta blockers; a
number of noncardiac side effects are also observed.
Disadvantages of drug therapy
As noted previously, drug therapy of arrhythmias is less than ideal in many cases
because of the side effects and cost of many of the medication, as well as the
inconvenience of dosing (three to four times a day for some drugs) and finally the
unpredictable efficacy under varying clinical circumstances. On this last point, a number
of studies have shown that several different antiarrhythmic medications may
demonstrate effective suppression of inducibility of supraventricular or ventricular
arrhythmias in the laboratory setting or resting state, but the beneficial effects of the
medication can be almost entirely reversed by infusion of small amounts of exogenous
catecholamines such as isoproterenol. [59 ] In the clinical setting, this correlates with
successful suppression of arrhythmia recurrences at rest but return to almost baseline
frequency of arrhythmia occurrence when the patient is vigorously exercising or under
significant psychological stress. Since the occurrence of these circumstances cannot
always be predicted accurately, patients may suddenly find themselves in situations in
which their medications are of borderline efficacy. Thus, while medications can be
extremely useful in treating patients with a wide variety of rhythm disturbances, they are
not free of disadvantages, and the physician must stay vigilant especially for
development of side effects or decrease in efficacy that may signal the need to
consider alternate forms of therapy. [60 ] , [61 ]
Pacemakers
BACKGROUND AND INDICATIONS
Bradycardias can be treated effectively in one of two ways: removing the cause of the
bradycardia (sinus or heart block), often by altering medications, or else implanting a
permanent pacemaker. These devices have been in existence since the late 1950s, at
which time only a single chamber could be paced (ventricle), only a single paced rate
was available, sensing capacity did not exist, and battery life was but a few months.
Pacemakers are now quite sophisticated; they can pace not only the ventricle but also
the atrium, respond to intrinsic cardiac electrical activity by following each P wave with a
paced QRS, and even record and telemeter electrical signals from the heart, report how
much of the time the heart is paced, and modulate the pacing rate to adjust for
metabolic needs. Battery life is now in excess of 8 to 10 years in many units.
Specific guidelines have been established for determining whether a pacemaker is

indicated for a particular patient's needs. In brief, these are
Class I: Pacing definitely indicated . Examples are complete heart block

with an escape rate of less than 40 beats per minute, symptomatic type I or
II second-degree AV block, and sinus bradycardia of less than 40 beats per
minute during waking hours.
Class II: Pacing potentially indicated . Examples include asymptomatic

complete heart block with a ventricular rate of more than 40 beats per
minute and asymptomatic type II second-degree AV block.
Class III: Pacing not indicated . Examples include prolonged PR interval

and asymptomatic type I second-degree AV block (Wenckebach).
TYPES AND MODES OF PACING
The majority of pacemakers currently implanted are so-called dual-chamber models;

i.e., one permanent electrode resides in contact with atrial myocardium and another
with ventricular tissue. Most electrodes are placed via the transvenous approach,
entering the venous system from the right or left subclavian, cephalic, or even jugular
vein; preformed atrial J leads are shaped to retroflex into the right atrial appendage.
Occasionally, epicardial screw-in wires are still used when the endocardial approach is
problematic or impossible (venous thromboses, tricuspid valve prosthesis, etc.).
Dual-chamber pacing is indicated mainly for patients with complete or high-grade AV
block who derive significant benefit from the atrial component of ventricular filling.
Single-chamber ventricular pacing is used in patients who only occasionally need
pacing (such as those with intermittent complete heart block or sinus bradycardia but
with normal sinus rates and AV conduction most of the time) [62 ] or in patients with
chronic atrial fibrillation.
Many patients with preserved left ventricular function and no ventricular hypertrophy who
also have chronic complete heart block (and require ventricular pacing at all times) will
have a normal functional capacity with rate-responsive single-chamber (ventricular)
demand pacing. This latter pacing feature modulates the paced rate in response to a
perceived physiologic need, such as physical activity. Thus, as the patient exercises,
the pacemaker's physiologic sensor alerts the unit's processor, which gradually
increases the paced rate according to the level of sensed physiologic need. The
threshold amount of activity required to be registered as such, the rapidity of increase of
pacing rate, and maximum paced rate are all programmable parameters. A number of
physiologic sensors have been evaluated and commercialized, including piezoelectric
crystals, chest wall impedance sensors, and quartz accelerometers.
Modern pacemakers have several modes of functioning; a four-letter internationally

agreed standard code is used to describe pacemaker operating mode as follows:
First letter : Chamber(s) paced [A (atrial), V (ventricular), D (both or dual),

and O (no pacing)]
Second letter : Chamber(s) sensed [A, V, and D as above; O (no sensing)]
Third letter : Mode of response [I (inhibited), T (triggered), D (dual), and O

(no response)]
Fourth letter : Additional functions, such as R (rate-responsive)
Thus, in the VVI-R pacing mode, the pacemaker paces and senses in only the ventricle,
a sensed event inhibits pacing output till the next cycle, and rate responsiveness is
present. A DDD pacemaker paces both atrium and ventricle, senses both atrium and
ventricle, and exhibits both inhibited and triggered responses to sensed events; e.g., an
atrial event (P wave) occurring prior to completion of the pacemaker's programmed
escape interval will inhibit the atrial pacing function but can trigger a ventricular paced
beat if no native QRS is sensed prior to the end of the programmed AV delay.
Pacemakers currently have a large number of programmable parameters, including not

only rate and amount of current or voltage applied for each beat but also the AV delay
(for paced as well as sensed P waves), lead polarity (uni- or bipolar), hysteresis (a
delay after a sensed event before pacing begins at the lower rate limit), and
rate-responsiveness features. Many devices are also able to determine pacing lead
impedance (an indicator of the integrity of the lead), automatically check the pacing
threshold, telemeter real-time and even stored electrograms, record histograms of
sensed and paced events, report battery voltage and/or impedance, and be used as
implanted electrophysiologic stimulators through which programmed stimulation or
burst/overdrive pacing can be performed to terminate or even stimulate arrhythmias.
Pacemaker-mediated or endless loop tachycardia, in which a ventricular paced beat
was conducted retrogradely over the patient's AV node and activated the atria, which
the pacemaker sensed as a normal P wave and responded with another ventricular
paced beat, was at one time a significant problem in early dual-chamber pacemakers.
[63 ] This rhythm disturbance, which was unique to these devices, has largely been
relegated to the past with upgrades in pacemaker algorithms that either prevent the
initiation of this arrhythmia or terminate it after only a few beats by temporarily
suspending atrial sensing.
More specific information on indications for particular types of pacemakers, their

implantation, and follow-up is given in Chap. 27.
Catheter Ablation
HISTORICAL OVERVIEW
By 1980, treatment of arrhythmias had advanced from diagnosing the cause of

bradycardias to both diagnosis and control of tachyarrhythmias. While medications
were moderately effective, long-term treatment of relatively young individuals with
medications such as amiodarone, which has a very long tissue half-life, was not
attractive. Similarly, several surgical procedures had been developed to effectively treat
both supraventricular and ventricular tachyarrhythmias by this time (see below), but
these of course required sternotomy, cardiopulmonary bypass, and a significant
recovery time as well as incurring a small but definite operative mortality and morbidity.
As other methods were being sought to control especially supraventricular
tachyarrhythmias in young patients, a serendipitous finding opened the way for a new
technology, catheter ablation. A patient undergoing EP study required cardioversion to
restore sinus rhythm; at the time of the external shock, a catheter was situated in the His
bundle region. While previously there had been no transfer of such shock energy to an
intracardiac catheter, in this case some energy was shunted down the His bundle
catheter, and for several minutes after the cardioversion, complete heart block was
present. Workers at several centers began studying this phenomenon in the animal
laboratory, and intentional catheter ablation of the His bundle for control of SVT (either
AV nodal reentry or rapid ventricular rates during AF) began in 1981. [64 ] , [65 ] This
first iteration of technology coupled a standard EP catheter (three or four poles) with a
standard direct-current (dc) cardioversion apparatus; the shock (50 to 250 J) was
delivered from catheter tip to a large metal backplate that was positioned such that the
target (the His bundle) was directly between the two shocking poles. After a successful
procedure, the patient was in CHB and required a pacemaker but had no further
episodes of supraventricular arrhythmia.
Direct-current catheter ablation of the His bundle was highly successful (>85 percent),
[66 ] and it use eventually was extended to other types of arrhythmias, including VT and
those related to WPW (with at best 30 to 40 percent success rates). [67 ] Direct-current
ablation produced a relatively homogeneous scar of variable size, depending on where
in the heart it was given; as much damage may have been effected by barotrauma from
the high-energy discharge as was due to temperature injury. As useful as dc ablation
was in many cases, it had several disadvantages. Because of the discomfort produced
by the shock, general anesthesia was necessary during the actual ablation portion of
the procedure. The amount of damage produced by the shock was not easily
predictable; in addition, some patients suffered marked deterioration of left ventricular
function immediately after the ablation. In some patients who underwent the procedure
for WPW, shocks administered in the region of the coronary sinus os caused
myocardial rupture and cardiac tamponade. Of even greater concern was the 2 percent
sudden death incidence among otherwise healthy individuals who underwent His bundle
ablation, presumably from malignant ventricular arrhythmias in some way engendered
by the ablation procedure. [66 ]
In the mid-1980s, several investigators began evaluating the application of

radiofrequency (rf) energy to ablation. [68 ] , [69 ] Similar to electrocautery, rf energy
uses the tissue in immediate contact with the catheter tip as a resistive element that
generates heat upon application of current (which it cannot readily pass). The tissue
heats to a temperature that denatures proteins and kills the cells while also passively
heating surrounding cells. Energy is applied between the catheter tip and a large
indifferent electrode (similar to the dc backplate) at a far lower power setting but for
longer durations (20 to 50 W for 30 to 60 s) than for dc ablation. This results in a more
easily controlled and fairly reproducible amount of homogeneous damage in normal
tissue. The use of rf energy required several adaptations of equipment, among which
were a change in catheter design such that the tip electrode had a larger surface area
for energy delivery, as well as special filtering for the ECG and intracardiac recordings
to prevent interference during applications of current. Radiofrequency energy has
several advantages over direct current; the lower power settings produce minimal or no
discomfort, and thus there is no need for general anesthesia; rf energy rarely, if ever,
causes myocardial stimulation or contraction. The amount of damage effected by rf
energy is generally easier to gauge than for dc energy; and rf energy appears to have a
better safety profile than dc, with only rare reports of sudden death after procedures and
minimal change in myocardial contractility. Because of these advantages, rf has now
almost entirely supplanted dc as the standard form of ablation energy.
TECHNIQUES
Mapping techniques have been refined for catheter ablation procedures; since the
amount of tissue that can be destroyed reliably by rf energy typically has a radius of 3 to
5 mm, the spatial resolution of mapping information must be within this tolerance in
order to ablate the target tissue successfully. The principles of mapping have largely
remained the same-in most cases, suitable target sites for ablation are those having
electrical activation prior to all other sites during the rhythm being studied. Specific
examples include
WPW and concealed bypass tracts . [70 ] , [71 ] In these cases, the bypass
tract is the target and can be localized either by mapping the site of earliest
ventricular activation during sinus rhythm or by mapping the site of earliest
atrial activation during retrograde conduction (SVT or ventricular pacing).
Since bypass tracts bridge the AV groove on the epicardial aspect of the
tricuspid or mitral annulus, the mapping electrode must be positioned along
either the atrial or ventricular aspects of the annulus. This is most readily
accomplished in right-sided, anterior septal, or posterior septal tracts from
the atrial aspect. Left-sided tracts can be approached from either the
ventricular aspect (retrograde aortic approach, with the catheter tip
positioned behind the mitral leaflet) or the atrial aspect (after crossing the
atrial septum via a patent foramen ovale or following septal puncture). Once
the location of the bypass tract has been established as outlined above and
the catheter is in a stable position at that location, rf energy may be applied;
this is usually performed such that a successful result will be evident
immediately. This can be during sinus rhythm or atrial pacing (observing for
sudden disappearance of the delta wave; see (Fig. 25-17) or during
ventricular pacing (observing for a change in retrograde atrial activation
pattern or loss of retrograde conduction). Ordinarily, a short (15- to
30-minute) waiting period is observed following successful ablation of the
tract to ensure that its conduction does not return due to its having merely
been damaged rather than destroyed. During this waiting period, pacing
maneuvers can be performed to evaluate for the coexistence of other
bypass tracts or different arrhythmias such as AV nodal reentry (each
present in 5 to 10 percent of patients with WPW), which can likewise be
ablated at the same session. These procedures take from 2 to 8 hours to
complete; patients most often are discharged from the hospital the following
day. Initial success rates for bypass tract ablation exceed 95 percent;
conduction resumes over approximately 5 percent of tracts within 6 months
after an initially successful procedure. Repeat ablation is typically successful
in such cases if attempted. Significant morbidity and mortality rates are
under 1 percent.
AV nodal reentry . [72 ] , [73 ] This very common form of SVT is also highly
curable; approximately 95 percent of patients with AV nodal reentrant SVT
can expect permanent freedom from recurrences of SVT following catheter
ablation while maintaining normal AV conduction. This is accomplished
most commonly by targeting the slow AV nodal pathway, which typically
appears to exist along the tricuspid annulus anterior to the coronary sinus
os. Controversy remains as to whether discrete potentials can be recorded
from this area. Some workers take an anatomic approach to ablation of the
slow pathway, whereas others target an area from which relatively
characteristic potentials consistent with slow-pathway conduction can be
recorded; in most cases, both point to the same area. Radiofrequency
energy applied to this area during sinus rhythm typically results in an
accelerated junctional rhythm for a few seconds, followed by sinus rhythm.
After a successful procedure, AV nodal reentry is no longer inducible; in
many instances, there is no longer any evidence of residual slow-pathway
conduction (absence of discontinuous AV nodal conduction curves). Since
only a small portion of AV nodal tissue is ablated in an area separated from
the compact AV node by up to 1 to 1.5 cm, significant degrees of heart
block or even prolongation of the PR interval is a rare outcome;
approximately 2 percent of patients undergoing this procedure eventually
require permanent pacemakers due to unintended heart block.
Atrial flutter . [74 ] , [75 ] The current understanding of this arrhythmia is that
the isthmus of atrial tissue between the IVC and tricuspid annulus
constitutes a critical portion of the reentry circuit in most patients. Mapping
during atrial flutter typically shows middiastolic electrograms from this
region; the requirement of this tissue for continued tachycardia can be
demonstrated using pacing maneuvers. The object of ablation in such cases
is to create a line of electrical discontinuity spanning this isthmus of atrial
tissue such that there can be no reentry incorporating this area. This is
effected by placing the ablation catheter tip on the tricuspid annulus and
beginning power delivery during either sinus rhythm or atrial flutter. Because
of the dimensions of the area requiring ablation, either several applications
of rf energy are required in sequence (spot welding) or a linear drag lesion
may be made by gradually withdrawing the catheter tip into the IVC as
power delivery is continued. If the energy is applied during flutter, the
tachycardia often slows in rate for a few beats prior to terminating. Using
this technique, about 80 percent of patients with atrial flutter can be
discharged from the hospital without inducible atrial flutter; approximately 20
percent of these will have subsequent recurrences of atrial flutter, most of
whom will respond favorably to a second attempt at ablation.
Automatic atrial tachycardia . [26 ] , [76 ] This relatively rare arrhythmia also
can be ablated successfully in the majority of patients. Mapping studies are
performed seeking the site of earliest atrial activation during tachycardia,
which typically precedes the onset of the surface P wave by 15 to 40 ms.
Application of rf energy to such sites often leads to a transient increase in
tachycardia rate just prior to termination. Approximately 80 percent of
patients with automatic atrial tachycardia can be cured of the arrhythmia
using these techniques. A significant problem during some of these studies
is encountering enough of the tachycardia to map and ablate; since by
definition these automatic tachycardias cannot be induced, patients must
either have spontaneous episodes or have tachycardia facilitated by
catecholamine infusion (isoproterenol).
Uniform sustained postinfarction VT . [77 ] , [78 ] Among the more

challenging types of ablation procedures are those which attempt to
eradicate sustained VT in patients who have suffered prior myocardial
infarction. Several factors make these procedures difficult, including
marginal hemodynamic stability during VT, vascular access problems, a
tortuous aorta, and presence of left ventricular thrombus. In addition to these
problems, the presence in most patients of multiple morphologies of VT
(which may result from the same or different circuits [18 ] ) makes the
procedure more arduous; while mapping during one VT morphology, the VT
may change to another, leading to confusion as to what sites in the heart
have characteristics of potential ablation targets. During mapping, sites are
sought that show reproducible middiastolic activity or markedly presystolic
electrogram components. Pacing maneuvers are typically employed to
validate the characteristics of these electrograms. Ablation is usually
performed during an episode of VT, if possible; the VT generally slows
slightly and terminates if the catheter is at a good target site (Fig. 25-18) . In
about 30 percent of patients, no more VT can be initiated at the conclusion
of the procedure, which may target from one to eight VT morphologies.
Another 40 percent of patients have some form of VT inducible (uniform or
polymorphic, sustained, or nonsustained) after eradicating other
morphologies. At least some degree of success can be obtained in most
patients (e.g., elimination of at least one VT morphology), although perhaps
not enough to be of significant clinical benefit. Although results are slowing
improving, most patients still require some form of antiarrhythmic drug or
ICD therapy following attempts at catheter ablation for VT.
Bundle branch reentrant (BBR) VT . [79 ] This relatively uncommon subset

of VT is particularly amenable to catheter ablation, since a critical
constituent of the reentrant circuit is the anatomically discrete and easily
targeted right bundle branch. For a variety of reasons, it is considerably
more difficult to firmly establish the diagnosis of BBR (as distinct from more
common myocardial) VT than it is to ablate the arrhythmia successfully.
Once the VT is diagnosed correctly, however, the operator may simply
position the tip of the ablation catheter along the right ventricular aspect of
the septum in order to record a clear right bundle branch electrogram;
energy application at such a location readily yields RBBB on the surface
ECG, after which BBR VT can no longer be initiated. Many of these patients
have a baseline LBBB due to their underlying conduction system disease; in
such cases, iatrogenic RBBB produces complete heart block, and a
pacemaker is necessary. BBR VT can be treated successfully in this
manner in more than 90 percent of patients with the arrhythmia [80 ] ; up to
30 percent of these individuals have other forms of VT (myocardial-based)
inducible at the end of the procedure, the clinical significance of which
remains unclear.
Use of rf energy for catheter ablation has had a tremendous impact on the treatment of
a variety of arrhythmias. Patients can enter the hospital on the same day as the
procedure, can go home the next day in most cases, and can resume normal activities
(including athletics) in a week or less. Success rates of rf ablation in SVT patients
exceed 90 percent for most diagnoses (WPW with concealed bypass tracts, AV nodal
reentry, His ablation, atrial flutter ablation, and atrial tachycardia). Currently, if patients
with these forms of SVT who need chronic treatment cannot be managed readily by
medications that produce practically no side effects, catheter ablation should be
strongly considered. VT ablation is generally reserved for patients who have frequent
recurrences of the arrhythmia despite drug and/or ICD therapy (with the exception of
BBR VT, for which ablation is a first-line option in many centers).
Implantable Defibrillators
HISTORICAL OVERVIEW
The implantable cardioverter-defibrillator (ICD), pioneered by Mirowski et al. [81 ] at

Johns Hopkins University, was first successfully implanted in 1980. This event was the
culmination of many years of careful and often frustrating research. The device and its
derivatives added another major class of therapeutic options for patients with
life-threatening ventricular arrhythmias. The original devices were simply shock boxes,
capable of little more than charging capacitors and shocking the heart at a fixed energy
using two epicardial mesh electrodes once an arrhythmia was detected. Open
thoracotomy was required for implantation, and operative mortality was up to 5 percent
in some series; morbidity was high as well, with infection a very serious threat to survival
of both system and patient. New lead, battery, and capacitor technologies have been
combined in more recent models to greatly facilitate implantation procedures and
thereby decrease operative risk. [82 ] Increasingly sophisticated features have been
incorporated into subsequent generations of devices, which has led to the expansion of
the indications for and types of arrhythmias that can be treated successfully in this
manner. A typical ICD system implanted today requires 1 to 2 hours of operative time
and a 2- to 3-day in-hospital convalescence and incurs less than 1 percent mortality with
more than 95 percent efficacy of successful defibrillation.
The primary indication for ICD therapy is a history of sustained VT or ventricular

fibrillation (VF), recurrent episodes of which cannot be prevented reliably by
medications, surgery, or catheter ablation. Some workers include syncope or frequent
nonsustained VT in patients at high risk of sustained VT/VF among the indications for
these devices. Inducible VT or VF at EP study is no longer required, since some
patients (especially those with cardiomyopathy and syncope or cardiac arrest) may be
at high risk of recurrence and yet have no inducible arrhythmias in the laboratory setting.
Contraindications to ICD therapy are few and self-evident: patients who have very
frequent episodes of VT/VF (requiring shocks on a daily or weekly basis), those with
active intrathoracic or intravascular infection, and those who are too ill to likely to survive
the implantation procedure. These characteristics exclude very few patients from
consideration of a device. In most centers, ICD therapy is currently the default form of
treatment for all patients with life-threatening ventricular arrhythmias. [83 ]
FEATURES
The level of sophistication incorporated into current ICDs continues to expand. Several
innovations have had dramatic impacts on the effectiveness of these devices. The
addition of antitachycardia pacing (ATP) capability [84 ] has extended the application of
ICDs to patients who have only hemodynamically stable VT, in whom shocks for
terminating the arrhythmia would be unnecessary and extremely unpleasant (Fig. 25-19)
. The use of biphasic shocks (as opposed to monophasic) has increased the efficacy of
defibrillation significantly and has decreased energy requirements. Single-wire lead
systemsthe tip at the RV apex, with proximal pacing electrodes near the tip and other
shocking electrodes further back on the lead so as to be near the right atrial-superior
vena caval junction when in positionhave greatly simplified system implantation.
Thoracotomy is currently required in only 1 to 2 percent of implants using these
techniques. Devices small enough to be implanted pectorally rather than abdominally
are now being tested. Most current devices offer a wide array of programmable
functions, including rate cutoff for detecting VT or VF, multiple rate zones of arrhythmia
detection and device response, ATP algorithms that are indexed to the rate of the
sensed arrhythmia, amount of delivered shock energy, means of discriminating VT/VF
from supraventricular arrhythmias, episode-triggered electrogram storage and replay,
and bradycardia backup pacing. Follow-up of these devices can be an extensive
procedure, especially if there are indications of device malfunction or inappropriate
shocks for nonventricular arrhythmias (see below). [85 ]
PROBLEMS ASSOCIATED WITH ICD THERAPY
Despite all the capabilities of ICDs, they are not free of problems. [86 ] A large
proportion of patients eventually will have one or more inappropriate shocks, [87 ]
generally due to detection of a supraventricular arrhythmia that meets rate criteria for
device activation; occasionally, episodes of nonsustained VT cause device activation
and shock delivery after the arrhythmia has ceased. Concomitant medications may slow
the rate of recurrent VT such that it falls below the rate cutoff and is not detected;
medications also can increase pacing and defibrillation thresholds, as well as altering
the appearance of the intracardiac electrogram used for sensing. Lead migration may
cause the device to falsely sense and ineffectively treat VT/VF; other devices, such as
pacemakers, may interact with the ICD to cause sensing errors. Device infection may
be indolent and extremely difficult to diagnose and eradicate, even after removal of all
hardware. Despite this daunting litany of potential problems, most patients have rather
benign courses following ICD implantation.
RESULTS
A number of long-term follow-up studies have shown that ICDs reliably prevent the most
severe consequence of recurrent ventricular arrhythmiassudden death. [85 ] , [88 ] , [89 ]
Over 95 percent of patients with ICDs remain free of sudden death (although having
recurrent arrhythmias treated successfully by the devices) over a 2- to 5-year follow-up
interval. More patients are being managed with ATP as opposed to only shocking VT or
VF, which not only prolongs battery life but is also less uncomfortable to the patient. It is
still not certain, however, that ICD therapy is significantly better than medical therapy or
that it in fact prolongs life. [90 ] Studies are currently in progress to attempt to answer
these questions, which have considerable public health policy ramifications in light of
the expense of various forms of therapy as well as the economic loss incurred by failure
of therapy (sudden death). [91 ]
Surgery
HISTORICAL OVERVIEW
The first report of surgical cure of a serious arrhythmia was by Couch [92 ] in 1959, who
reported eradication of ventricular tachycardia (VT) following left ventricular
aneurysmectomy. Although aneurysmectomy alone has since been shown to have a
disappointing success rate in this setting, [93 ] , [94 ] the report nonetheless generated
interest in the possibility of a nonpharmacologic option for treating such patients. In the
years that followed, a number of surgical techniques were developed to excise or
isolate the tissues responsible for initiation or continuation of VT, including encircling
endocardial ventriculotomy, [95 ] cryoablation, [96 ] and subendocardial resection. [97 ]
These techniques underwent continued refinement during the 1970s and 1980s and
currently provide a very highly effective means of controlling VT with an acceptable
operative risk. This type of direct surgical intervention (i.e., techniques that mechanically
deal with the tissues actually responsible for the arrhythmia) remains applicable to a
relatively small proportion of patients with VT, as will be discussed further below.
The first successful surgical treatment of supraventricular tachycardia (SVT) occurred in

1968, [98 ] in a patient with incessant SVT related to Wolff-Parkinson-White (WPW)
syndrome. Thereafter, an increasing number of patients with WPW as well as
concealed bypass tracts underwent surgical therapy, which led to the description of
anatomic classification schemes. Recognition of these surgical subtypes facilitated
development of specific techniques that enhanced the success rates of surgery. A key
ingredient to the success of surgery to eradicate bypass tracts is the ability to precisely
localize the bypass tract in order to effect the ablation (mapping). The endocardial
approach to bypass tract surgery has been highly refined, and an epicardial approach
also has been shown to have excellent efficacy and safety. Based on the good
experience in bypass tract surgery, electrophysiologists and surgeons began applying
the same principles of mapping and surgical ablation to other forms of SVT, including
AV nodal reentry, atrial tachycardias, and atrial flutter and fibrillation.
Direct, curative surgical therapy for arrhythmias reached its zenith in the middle to late
1980s when a number of techniques for treatment of a variety of both supraventricular
and ventricular arrhythmias had become highly refined and were in widespread use.
Since that time, ICDs have become more sophisticated and simpler to implant,
resulting in a decrease in the number of patients undergoing direct surgical therapy for
VT; in addition, the development, refinement, and dissemination of catheter ablation
techniques for treatment of supraventricular arrhythmias have constrained the use of
surgical therapy to patients refractory to one or more catheter ablation attempts. As
noted earlier, these developments, as well as continued release of new types of
antiarrhythmic medications and reformulations of old ones, have led to a significant
decrease in the use of direct surgical methods for treating arrhythmias.
Surgical procedures for selected specific arrhythmias are outlined below; for a more
in-depth discussion, the reader should refer to Chap. 26. Despite differences in the
details of the surgical approaches, practically all so-called direct surgical procedures
designed to eradicate arrhythmias share some common features. In almost all cases,
the heart is exposed through a median sternotomy, and a pericardial cradle is
constructed. The great vessels are cannulated for cardiopulmonary bypass, and
pacing/recording electrodes are affixed to the epicardial surface of chambers to be
mapped or stimulated. Epicardial mapping can be performed thereafter; this generally
can be accomplished off bypass, but in patients in whom substantial mapping is
required on the inferoposterior surfaces (which requires lifting the heart and decreasing
ventricular filling), institution of normothermic cardiopulmonary bypass may be
necessary. The target arrhythmia can then be initiated with pacing maneuvers, after
opening the heart as indicated for the planned procedure. Mapping is continued until all
arrhythmogenic areas have been localized satisfactorily; thereafter, the tissues so
identified are incised, excised, isolated, or cryoablated depending on the nature of the
target arrhythmia. This may be performed on the normothermic, beating heart or after
instillation of cold cardioplegia into the aortic root. Following the direct surgical attack
on the arrhythmogenic area, the heart is rewarmed and stimulation is repeated to
assess the adequacy of the surgical procedure. If more arrhythmias are encountered,
mapping is repeated, followed by more surgical exploration of the indicated areas.
Once all arrhythmias appear to have been eradicated successfully, the patient is
weaned off bypass. Epicardial temporary pacing wires are left in place for pacing in the
postoperative period.
WOLFF-PARKINSON-WHITE SYNDROME AND CONCEALED BYPASS TRACTS
Once the heart has been exposed and temporary pacing and sensing electrodes
affixed to the epicardial surface, mapping of the atrium and ventricle on each side of the
AV groove is carried out using either a roving bi- or quadripolar probe electrode or a
multielectrode strip with which activations can be recorded simultaneously from 15 to 25
locations over the entirety of the AV groove. In the presence of overt preexcitation on the
surface ECG, mapping of the ventricular aspect of the groove is performed during sinus
rhythm or atrial pacing, seeking sites of earliest ventricular activation (prior to the onset
of the surface delta wave), which would indicate proximity to the ventricular insertion site
of the bypass tract. The same principles are used in mapping the atrial aspect of the AV
groove during either ventricular pacing or SVT, looking for the site or sites of earliest
retrograde atrial activation (the location of the atrial connection with the bypass tract).
Mapping during SVT is more reliable than during ventricular pacing, since many
patients also have retrograde conduction over the normal pathway, and atrial mapping
in such patients shows an activation wavefront proceeding from the septal area as well
as the actual bypass tract's location (if different).
Once mapping has been completed and all bypass tracts have been localized
satisfactorily, surgical dissection of the relevant portion of the AV groove (except at the
aortomitral continuity, which has atrium above but no ventricular muscle below) is
undertaken. The groove has been divided into four separate surgical regions: left
lateral, right lateral, anterior septal, and posterior septal. The surgical approach differs
slightly depending on the region involved.
In the endocardial approach for left lateral bypass tracts, [99 ] the heart is cooled and
cardioplegic solution administered; some surgeons prefer to cool the heart for
endocardial dissection of bypass tracts in other locations as well. In the specific case of
left-sided bypass tracts, the left atrium is entered posteriorly as for a mitral valve
operation, after which an incision is made in the left atrial wall 3 to 4 mm above the
mitral annulus and is extended from the left fibrous trigone to the posteromedial portion
of the septum. This reveals the epicardial fat pad, which is then carefully dissected with
a nerve hook in a manner such that all material is cleaned off the epicardial aspect of
the mitral annulus and adjacent ventricular and atrial myocardium. Any bypass tract
fibers crossing the AV groove in this region are disrupted; meticulous care is necessary
because these fibers are not large enough to be macroscopically distinct. Once the
entire extent of the incision in the atrial wall has been so treated, the atrial incision is
finished by making an additional cut from the ends of the incision perpendicularly down
to the mitral annulus to eliminate the possibility of spread of impulses to the rest of the
atrium from residual bypass tract material connected to the rim of atrial tissue beneath
the incision (i.e., not severed by the dissection). After this, the incision in the atrial wall is
repaired with running sutures, the left atrium is closed and air evacuated, and the heart
is rewarmed. Both atria and ventricles are paced to confirm elimination of conduction
over the bypass tract, and the operation is concluded. The same principles apply to
dissection of the AV groove for treatment of bypass tracts in other locations within the
heart.
Using the epicardial approach, cooling of the heart is not required; in fact, in many
cases, cardiopulmonary bypass is also not necessary. [100 ] An incision is made in the
visceral pericardium, and the AV groove is dissected down to the mitral annulus, which
is cleaned of all adherent fat and other material. Care must be taken to avoid undue
traction or injury to a coronary artery or the coronary sinus. This procedure has the
additional advantage of being able to determine when the bypass tract has been
disrupted successfully during the dissection. Areas not easily addressed by the
dissection may be treated with cryoablation using a 0.5- to 1.5-cm freezing probe at
-70°C. This causes a homogeneous area of cellular death without disrupting the
structural integrity of surrounding connective tissue. Once the dissection is completed,
the visceral pericardium is closed and pacing is performed to ensure absence of
conduction over the bypass tract. As in the endocardial dissection method, the same
principles can be applied to treatment of bypass tracts in other locations.
The choice of which approach to use in bypass tract surgery depends largely on local
preference; each procedure is highly effective (>98 percent cure rates), and each
carries very low morbidity and mortality rates. Far fewer procedures are being
performed currently because of the success rates of catheter ablation in these patients;
those operations which are performed are either on patients undergoing other types of
heart surgery at the same time (bypass surgery, valve repair or replacement) or on
those in whom catheter ablation has failed. These latter patients can present particular
problems, in that the catheter ablation procedure may have resulted in significant
scarring and distortion of the anatomy of the AV groove. In addition, many patients who
have undergone failed attempts at catheter ablation have anatomic anomalies such as
coronary sinus diverticula or variable degrees of Ebstein's anomaly. Due to the special
skills required for this type of surgery, it probably should be performed in only a few
centers with extensive experience with such procedures.
AV NODAL REENTRY
Following the successes of surgery for WPW, many investigators sought a means of
surgically curing AV nodal reentry without causing severe damage to normal AV nodal
conduction. Two different approaches have been found to yield good clinical results;
each requires exposure of the atrial septum following right atriotomy, after which the
location of the His bundle is determined by activation mapping. One approach involves
careful sharp dissection of the triangle of Koch (formed by the medial tricuspid annulus,
the coronary sinus os, and the tendon of Todaro) from both an epicardial and
endocardial aspect. [101 ] The epicardial portion is performed much like dissections for
treating anterior and posterior septal bypass tract. The right AV groove is opened
widely, exposing the tricuspid annulus; the anterior extent of the dissection is carried
into the right coronary fossa, while the posterior extent is carried into the pyramidal
space formed by the posteromedial portions of both atria and the posterosuperior
process of the left ventricle. Thereafter, the right atrium is opened and an incision made
along the borders of the triangle of Koch, in effect isolating the posterior and superficial
approaches from the atrium to the AV node. The other type of surgical procedure
involves placing a series of cryolesions around the perimeter of the triangle of Koch
(with a 5-mm probe), effecting a similar disconnection of atrial inputs to the AV node.
[102 ] Each procedure carries a success rate of more than 92 percent, with no reported
cases of heart block requiring pacemaker insertion.
ATRIAL FIBRILLATION (AF)
This common arrhythmia has been addressed surgically using a variety of approaches.
One involved disconnection of the left atrium from the right, with the hope that spread of
fibrillation from one atrium to the other would not occur; this has met with limited
success. Another procedure, termed the corridor operation , consisted of isolating a
path of atrium between the sinus node and AV node, excluding the remaining mass of
atrial muscle. [103 ] This resulted in maintenance of normal heart rate variations with
activity but did not obviate other problems associated with AF such as loss of the atrial
contribution to ventricular filling and the thromboembolic potential of a fibrillating left
atrium. Many of these shortcomings have been addressed by the maze procedure , one
which involves an extensive set of incisions in both right and left atria designed to
electrically subdivide the atrial mass into portions too small to support fibrillation. [104 ]
Success at preventing electrocardiographic AF has been quite good (>90 percent), but
the degree of recovery of mechanical functionand thus hemodynamic benefit and
freedom from thromboemboliis less uniform.
POSTINFARCTION UNIFORM SUSTAINED VT
Direct surgical therapy for patients with postinfarction sustained VT presents particular
challenges to the electrophysiologist and surgical team because of both the complexity
of the arrhythmia and the degree of LV dysfunction present in most patients. The
majority of institutions performing surgery for VT utilize endocardial mapping to guide
most aspects of the surgical attack, although some centers simply resect or encircle all
visible endocardial scar tissue. Despite its increasing the complexity of the procedure,
mapping appears to offer significantly better antiarrhythmic efficacy in most cases. [105
] During such a procedure, the heart is exposed and cannulated for bypass; electrodes
are affixed to both ventricles for pacing and sensing. The LV is incised through an
aneurysm or infarct area to gain access to the endocardium, from which the vast
majority of arrhythmias arise in these patients. Endocardial mapping is performed
during induced VT (in some cases during sinus rhythm as well) using a roving probe
electrode or multipolar electrode array; several systems are available for computerized
acquisition and analysis of signals. As in other reentrant arrhythmias, sites are sought
from which markedly presystolic or even middiastolic electrograms can be recorded. In
most cases, several VT morphologies can be initiated, and each should be mapped to
the extent possible, since there is no certainty that a single circuit is responsible for
more than one VT morphology. After mapping has been completed, one of several
types of surgical procedures can be performed to eliminate the areas responsible for
VT. Many centers use subendocardial resection (SER), in which a 2- to 3-mm-thick
sheet of endocardium and subjacent tissue is removed; this specimen is felt to contain
at least a critical portion of the mapped VT circuits. Another procedure, encircling
endocardial ventriculotomy (EEV), is carried out by making a 3- to 4-mm-deep incision
perpendicularly into the myocardium in such a fashion as to partially encircle or isolate
the mapped regions; this appears to be effective by either incising actual circuits or
preventing spread of persistent VT impulses to the rest of the ventricular myocardium.
Some centers also use cryoablation, either alone or in combination with one of the other
techniques. [106 ] These procedures can be performed on the normothermic beating
heart or after cooling/cardioplegia administration. After having performed this part of the
operation, the ventricles may be restimulated to assess the efficacy of the ablative
procedure; if VT can still be initiated, further mapping and resection, cryoablation, or
incision may be performed and these cycles repeated until no further VT can be
initiated. [107 ] These procedures are roughly comparable as far as operative mortality
(5 to 15 percent) and success at eliminating inducible VT at postoperative EP study (70
to 85 percent) are concerned. [108 ] [110 ]
VENTRICULAR FIBRILLATION (AND RAPID POLYMORPHIC VT)
In the case of many arrhythmias, such as AF or SVT, therapy can be considered

adequate if most recurrent episodes are prevented; VF allows no margin for error,
however. Thus one must be as certain as possible that the treatment used will be
effective at preventing all recurrences, and this in turn depends on correctly ascertaining
the cause of the arrhythmia. If it can be demonstrated that VF episodes are ischemic in
origin, revascularization is the treatment of choice; outcomes in these patients are quite
good. [111 ] , [112 ] It should be noted that this is the singular circumstance in which
revascularization can be expected to exert a direct beneficial effect on ventricular
arrhythmias. [113 ] In other cases, in which severe active ischemia does not appear to
be present at the time of VF initiation, revascularization will be of little help, and other
forms of direct surgical therapy are of uncertain benefit. VF cannot be mapped using
current technology in order to localize and eradicate responsible tissues. Some workers
have relied on so-called fragmentation mapping or intraoperative endocardial mapping
during sinus rhythm, during which sites with markedly abnormal electrograms are
sought, to serve as a guide for subendocardial resection (SER) or encircling
endocardial ventriculotomy (EEV). [114 ] Experience in such cases is relatively limited;
it appears likely that a majority of patients in this subgroup lack both discrete areas of
epicardial abnormality that could be incised in order to gain access to the endocardium
and a well-demarcated endocardial scar to resect or encircle and that ICD therapy will
afford the best protection from recurrent VF episodes.
ARRHYTHMIAS RESULTING FROM CARDIAC SURGICAL
PROCEDURES
A variety of arrhythmias and conduction disorders can result from cardiac surgery,
whether or not the operation was designed to alter rhythm. Most are benign and
self-limited, causing no clinical concern after the hospital phase of the postoperative
recovery period. Some, however, can be life-threatening, and others may not become
manifest until yearts later; it is thus worthwhile to mention these types of abnormalities.
[115 ]
Bradyarrhythmias and Conduction Disturbances
SINUS NODE INJURY
Occasionally, during the process of cannulation of the right atrium for cardiopulmonary
bypass in the adult, inadvertent trauma to the sinus node occurs. This, as well as
postoperative pericarditis on occasion, can lead to postoperative sinus bradycardia.
[116 ] Early experience with both the Senning and Mustard procedures for correction of
transposition of the great arteries showed a high incidence (>50 percent) of
postoperative sinus node dysfunction. [117 ] This was presumably due to damage to
either the sinus node or its vascular supply by the creation of intraatrial baffles to
redirect intracardiac blood flow.
DAMAGE TO AV CONDUCTION
AV nodal injury may result from surgical repair of an atrial septal defect or mitral valve
replacement/implantation of a annuloplasty ring. [116 ] This is usually a transient
phenomenon probably related to edema in the perinodal region and, like other causes
of AV nodal conduction disturbance, tends not to proceed to complete heart block
(CHB) or produce enough compromise that a pacemaker is indicated. Aortic valve
replacement operations may engender damage to the infranodal conduction tissues by
a similar mechanism, but since the level of block is at or below that of the subsidiary
pacemaker cells in the HPS, patients with postoperative conduction disturbances within
the HPS bear more careful monitoring.
Occasional patients with congenital membranous ventricular septal defects may require
surgical repair as young adults. Since the His bundle courses along the inferior aspect
of the membranous portion of the interventricular septum, care must be taken to avoid
inadvertent injury to the His bundle during placement of patching material and sutures.
An electrode probe may be used to map the location and course of the His bundle so
as not to injure it during the repair.
BUNDLE BRANCH BLOCK
A small proportion of patients develop RBBB (less commonly LBBB) following cardiac
surgery; these may develop despite there having been no direct contact with the
endocardial HPS during surgery. A cause is more readily identified in some cases,
such as procedures requiring right ventriculotomy (e.g., tetralogy of Fallot repair) or
following extensive SER. Although the latter procedure would be anticipated to produce
marked changes in the postoperative sinus rhythm ECG because of removal of the
endocardial layers that contain the HPS, relatively minor ECG changes are the rule.
[118 ]
Supraventricular Tachyarrhythmias
POSTOPERATIVE ATRIAL FIBRILLATION
From 15 to 30 percent of patients undergoing heart surgery of any type will have at least
one episode of postoperative AF. For the vast majority, there will be no further
recurrences of this arrhythmia following hospital discharge. These arrhythmias often
may be best managed with beta blockers, since many patients have had these agents
held or withdrawn entirely around the time of the surgery and adrenergic receptor
density on the atria is high. [119 ] Overdrive pacing is not effective in restoring sinus
rhythm in this arrhythmia characterized by multiple small reentrant wavefronts.
ATRIAL FLUTTER AND INTRAATRIAL REENTRANT TACHYCARDIA
Much less commonly than in the case of atrial fibrillation, atrial flutter or slower reentrant
atrial tachycardias may result from a variety of surgical procedures. These generally
involve atrial incisions of greater extent than in a standard procedure using
cardiopulmonary bypass; examples are closure of atrial septal defect, closure of
ventricular septal defect from an atrial approach, and valve repairs. Each of these
procedures incorporates a relatively large atrial incision that can serve as an anatomic
barrier and substrate for reentry. Atrial flutter and reentrant atrial tachycardias generally
can be terminated by overdrive pacing.
ACCELERATED JUNCTIONAL RHYTHM/JUNCTIONAL TACHYCARDIA
These rhythm disorders originate in the His bundle rather than the AV node. Patients
who undergo aortic valve surgery are most prone to develop accelerated junctional
rhythm with rates from 60 to 90 beats per minute, which is generally benign and
self-limited. This is probably related to edema and irritation in the tissues near the His
bundle. A far more dangerous arrhythmia, junctional ectopic tachycardia, with rates in
excess of 150 beats per minute, is largely confined to the postoperative pediatric
population. [120 ]
Ventricular Tachyarrhythmias
UNIFORM SUSTAINED VENTRICULAR TACHYCARDIA
Uniform-morphology VT may occur after cardiac surgery for a variety of reasons. In

patients who have a history of VT and in whom the arrhythmia was not specifically
addressed during surgery (such as by mapping-guided SER or EEV), VT is quite likely
to recur in the early postoperative period and carries a high mortality rate. [121 ] , [122 ]
VT episodes in some such patients are far more frequent than preoperatively; the
reasons for this are unclear, but restoring blood flow to marginally supplied
arrhythmogenic regions may play a role. Patients who suffer perioperative myocardial
infarction also can have episodes of uniform sustained VT, but this is relatively rare. In
patients who undergo right ventriculotomy (most commonly for repair of tetralogy of
Fallot), the resulting scar in the free wall may form a discrete anatomic barrier around
which a wavefront could conceivably circulate. This uncommon occurrence generally
does not become evident until some years after the initial procedure. [123 ]
VENTRICULAR FIBRILLATION
In the first few hours after cardiac surgery, VF occasionally may occur during rewarming
or due to electrolyte shifts; such episodes appear to have no adverse prognostic
significance. Episodes of VF that occur after the first 12 postoperative hours are
uncommon, occurring in less than 0.5 percent of all operated patients. [121 ] , [122 ]
Potential causes that must be evaluated include ischemia due to occlusion of a
coronary artery bypass graft or spasm of a native coronary artery, myocardial infarction
due to graft occlusion or atheromatous or air emboli, cardiac tamponade, severe
acid-base derangements (including marked acidosis or alkalosis), administration of
high concentrations of exogenous catecholamines, severe hypokalemia, and
cardiogenic shock with high left ventricular end-diastolic pressure. If one of these
causes can be diagnosed and rectified, recurrences of VF are uncommon; if, however,
no cause is identified, VF episodes may continue to complicate the postoperative
recovery and require EP evaluation.
CONCLUSIONS
The understanding of mechanisms and pathogenesis of arrhythmias has grown

dramatically over the last 20 years; much of what is known about cardiac arrhythmias in
humans was learned in the operating room, during attempts to treat very ill patients in
whom all other treatment options had been exhausted. A wide variety of innovative and
highly successful surgical procedures has been devised in recent years to offer curative
therapy for many types of rhythm disturbances, in addition to providing the means for
implantation of pacemakers and defibrillators. The advent and refinement of new
nonsurgical methods of treating arrhythmiasnew medications, implantable defibrillators,
and catheter ablation techniqueshave displaced many of these curative surgical
procedures. It is ironic that direct surgical operations designed to cure arrhythmias,
once reserved for only the most refractory cases, had grown to become standard
treatment in many institutions but now have been relegated to secondary therapy for a
small number of, again, the most refractory cases. As fewer such surgical procedures
are performed and maintenance of specific surgical skills becomes difficult, it would
seem advisable to constrain the number of institutions at which these procedures are
performed to those with considerable experience in them.
Cardiac Anatomy
EMBRYOLOGY OF THE CONDUCTION TISSUES
The sinus node probably first appears at the stage of cardiac looping and is located at
the junction of the superior vena cava with the right atrium. [1 ] The nodal tissue is
discrete from the adjacent myocardium at this stage and extends across the crest of the
atrial appendage medially and down toward the orifice of the inferior vena cava laterally
(Fig. 26-1) .
The development of the normal junctional area is more complicated. [2 ] It is probable

that as soon as the heart tube is formed, a ring of histologically discrete tissue
separating the atrial myocardium from the ventricular myocardium throughout the
atrioventricular canal is identifiable as atrioventricular ring specialized tissue (Fig. 26-2)
. An additional specialized (ventriculobulbar) ring between the inlet and outlet parts of
the ventricular loop becomes draped over the trabecular septum during the looping
process to form the primordium of ventricular conduction tissue. The joining of these two
specialized rings into intact conduction tissue depends on normal septation of the
developing heart (see Fig. 26-2 ). The sandwich of atrioventricular sulcus tissue,
atrioventricular ring tissue, and endocardial cushion tissue on the inside of the heart is
retained as the inlet septum and makes contact with the trabecular septum. [3 ] Thus at
all times the developing nodal bundle has endocardial cushion tissue on its endocardial
surface and is separated from the ventricular myocardium by extensions of the
epicardial atrioventricular sulcus tissue. In this way, penetration of the atrioventricular
bundle occurs.
EMBRYOLOGY OF THE ATRIOVENTRICULAR (AV) GROOVE
Direct physical (and presumably electrical) continuity is present between atrial and
ventricular myocardium during the early phases of embryogenesis. Atrioventricular
specialized ring tissue is normally lost along the lateral (free) wall aspects of the heart
by ingrowth of AV sulcus tissue and formation of the annulus fibrosis. Normally, this
ingrowth produces separation of atrial and ventricular myocardial tissue everywhere
around the AV groove except at the site of the penetrating atrioventricular bundle.
The histologic structure of accessory connections is thought to be composed of normal

myocardium, except where atrioventricular specialized ring tissue has been
demonstrated. [4 ] Defects in the annulus are present in term infants; however,
correlation between anatomically present accessory connections and functional
electrophysiologic pathways does not exist. Accessory musclular connections are
present between the right atrium and either the anterior or the posterior right ventricle in
both prenatal and postnatal specimens; however, all demonstrated accessory
connections were in infants less than 6 months of age. This observation suggests that,
on the right side at least, final separation of the right atrium from the right ventricle
occurs as part of normal postnatal development. The increased frequency with which
defects are seen in the tricuspid annulus fibrosis as opposed to the mitral annulus is
used to argue that left-sided pathways originate in a different manner from right-sided
pathways, but this is probably not the case.
In summary, atrioventricular connections appear to be present during normal

cardiogenesis and appear to be composed of normal myocardium or specialized ring
tissue. These connections are uncommon in infants older than 6 months of age and are
not present in asymptomatic adults; as such, it is clear that these connections between
the atrium and ventricle normally regress. It is currently thought that failure to lose these
accessory atrioventricular connections during development is the morphologic basis of
the most common form of ventricular preexcitation.
EMBRYOLOGY OF THE ATRIAL SEPTUM AND VENTRICULAR SEPTUM
The atrial septum develops during displacement to the right of the three large venous
systems draining via the sinus venosus into the primitive atrium of the cardiac tube and
occurs simultaneously with development of a pulmonary venous tract. The sinoatrial
junction is shifted to the right side of the primitive atrium, while the left sinus venosus
horn becomes the coronary sinus, originally a muscular structure. The pulmonary venous
connection is made with the intrapulmonary venous connection by development of the
posterior portion of the primitive left atrium.
The atrioventricular canal is separated by fusion of the endocardial cushions.

Development of the atrial septum involves formation and regression of the septum
primum, followed by growth of the septum secundum, the inferior and posterior margins
of which circumscribe the foramen ovalis (Fig. 26-3) . Fusion of the septum primum and
septum secundum occurs normally after birth; failure to close produces a patent
foramen or a septum secundum defect. Following closure, the foramen ovalis becomes
the fossa ovalis, and the free border of the septum secundum becomes the limbus
fossa ovalis.
At the same time, the ventricular septum is formed between the septum of the
endocardial cushion of the arterial outflow tract and the frontal portion of the septum of
the trabecular zone; a small portion of the posterosuperior part is left open, to be closed
later by the membranous septum. This develops from coronary sulcus tissue and is in
contact with the low right anterior atrial septum. [5 ]
Anatomy of the Mature Conduction System
Anatomically, the node is a spindle-shaped structure with the head extending toward the
interatrial groove and the tail extending toward the orifice of the inferior vena cava (Fig.
26-4) . In a small number of cases (approximately 10 percent), the head extends across
the crest of the atrial appendage into the interatrial groove, giving rise to the so-called
horseshoe node. [6 ]
The sinus node artery originates from the initial portions of the right coronary artery in
about 55 percent of cases and from the left coronary artery in the remainder. A small
percentage of patients appear to have a dual supply. The artery passes up through the
interatrial groove and may be either epicardial or intramyocardial. Most commonly, the
artery passes posterior to the superior cavoatrial junction to enter the inferior end of the
sulcus terminalis. Alternatively, the artery may course anteriorly across the crest of the
atrial appendage to enter the superior end of the node, or infrequently, an arterial ring
may be present.
In the normal sinoatrial node, beta-adrenergic activation increases the rate of action
potential development, and increased parasympathetic activity decreases the rate. [7 ]
This innervation arises from the cardiac plexus surrounding the arch of the aorta.
Sympathetic fibers arise from the upper thoracic spinal cord, and parasympathetic
fibers arise from the medulla. Superior, middle, and inferior cardiac nerves from the
superior, middle, and inferior cervical ganglia of the sympathetic nerves join the vagus
nerve from both sides to form this cardiac plexus. In addition to supplying the sinoatrial
(SA) node, the plexus supplies the approaches to the SA node, the atrial septum, the
approaches to the AV node, the AV node itself, and to a lesser degree, the AV bundle.
The SA node is especially responsive to parasympathetic adrenergic stimulation, while
the AV node is preferentially sensitive to sympathetic adrenergic regulation.
Endocardial mapping studies indicate that normal atrial activation begins in either the
high or midlateral right atrium, with the former more likely to occur at sinus rates above
100 beats per minute and the latter more likely at rates below 60 beats per minute.
These different activation patterns may reflect different exit routes either from a single
nodal focus or, more likely, from a sinus node complex consisting of multiple
pacemaker regions. [8 ]
Activation spreads to the right AV junction in about half the time needed to reach the left
atrial free wall. Faster conduction on the right side produced a controversy, present
since the early part of this century, over the nature of internodal atrial myocardial tissue.
It is generally agreed that there is preferential conduction but not discrete anatomic
pathways for the spread of excitation from the sinus to the AV node. Spach [9 ] was the
first to emphasize the importance of the geometric arrangement of myocardial cells
involved in impulse propagation in atrial tissue. He determined that conduction velocity
was faster parallel to the long axis of muscle fibers and slower along the plane
transverse to muscle fiber orientation, so-called uniform anisotropy. Well-oriented atrial
muscle tracts made up of fibers running in parallel are found in the anterior limbus of the
fossa ovalis, the crista terminalis, and its continuation into the sinus septum; activation
of adjacent myocardium along these bands as broad wavefronts explains preferential
atrial conduction. The ultimate substrate for preferential conduction within these bands
remains to be established.
The triangle of Koch is bounded by the annulus of the tricuspid valve inferiorly, the
tendon of Todaro superiorly, and a line drawn between the coronary sinus and the
tricuspid annulus posteriorly (Fig. 26-5) . The apex of the triangle is the central fibrous
body and the supraannular portion of the membranous intraventricular septum. The atrial
portion of the junctional area is contained entirely within the triangle. [6 ] As seen in Fig.
26-6 , the atrial component of the triangle is an interatrial structure, not a right atrial
structure. The tendon of Todaro is the most easily recognized landmark when looking at
the right atrial septum. The point of attachment of the septal leaflet of the tricuspid valve
to the atrioventricular septum is also easily recognized (except occasionally in patients
with Ebstein's anomaly). Note that the attachment of the tricuspid valve to the septum is
lower than the attachment of the mitral valve so that a small area of muscular septum
separates the right atrium from the left ventricle. The compact AV node lies on the atrial
surface of this septum, separated from the ventricular myocardial fibers by the annulus
fibrosus. In the adult heart, the AV node measures approximately 5 to 7 mm in length
and 2 to 5 mm in width. The node is usually far removed (anteriorly) from the coronary
sinus; the transitional cell zones extend backward and superiorly from the compact node
but are contained within the boundaries of the triangle. However, the position and size
of the node may be quite variable from patient to patient.
The approaches to the AV node from the right atrial, tricuspid valve, midseptal, and left
atrial tissue merge gradually into the superficial layer of nodal cells. An intermediate
layer of cells, still loosely arranged, lies within the superficial layer and surrounds the
compact nodal cells. Each layer contains fibers closely related to the right ventricular
myocardium, the tricuspid annulus, the central fibrous body, the left atrial myocardium,
and the atrial septum. Because the nodal fibers differ in their orientation and structure in
these various parts, these differences are probably related to functional differences in
the speed of conduction.
In addition, nodelike cells are often seen at or near the annuli of the tricuspid, aortic, and
mitral valves, in the parietal wall of the right atrium, or near the annulus of the tricuspid
valve. The functional significance of this feature of nodal tissue is unknown.
The compact AV node becomes the penetrating bundle at the apex of the triangle and
passes into the ventricular septum beneath the attachment of the tendon of Todaro to
the central fibrous body. [6 ] The AV bundle at its penetrating portion measures about
1.5 to 2.0 mm in greatest diameter and varies greatly in length (Fig. 26-7) . The
nonbranching and branching bundles are sandwiched between the muscular ventricular
septum and the membranous septum; branching of the bundle takes place on the
muscular septum beneath the commissure between the right coronary and noncoronary
cusps of the aortic valve. Importantly, the compact node, penetrating bundle, and
branching bundle form a continuous axis of cells that runs the length of the muscular
ventricular septum. The atrial component lies above the annulus, the penetrating bundle
passes through the annulus, and branching bundles lie beneath the annulus fibrosus of
the heart. In general, the left bundle branch fibers are quite superficial and
subendocardial. The branching bundle lies at the lower confines of the membranous
part of the ventricular septum on top of the summit of the ventricular septum beneath the
noncoronary aortic cusp. This main left bundle branch in general gives off a larger
posterior radiation and a smaller anterior radiation. In normal hearts, retrograde
conduction after right apical endocardial activation proceeds via the left bundle in
two-thirds of individuals.
Finally, the atrioventricular node is an epicardial structure, lying within the posterior
atrioventricular sulcus. [6 ] The arterial input to the AV node is dual in nature. [10 ] From
the posterior aspect, the atrioventricular nodal artery takes origin from the characteristic
U-turn of the dominant coronary artery at the crux of the heart. In 90 percent of
individuals this dominant artery is the right coronary artery. This artery passes beneath
the coronary sinus in a plane that extends into the atrioventricular septum to supply the
AV node (Fig. 26-8) . This artery is of importance when surgical ablation of posterior
septal pathways are considered.
The second source of arterial supply to the junctional area is via the first or second
septal perforating arteries of the anterior descending branch of the left coronary artery,
which ramify to supply the bundle branches within the ventricular septum.
Anatomic Principles Pertaining to Ablative Therapies for Supraventricular

Arrhythmias
THE HORIZONTAL PLANE
Anatomically, the heart can be transected at the level of the AV groove and divided into
four discrete areas defined in this horizontal plane (Fig. 26-9) . These four discrete
areas are the left free wall, the right free wall, the posterior septal spaces, and the
anterior septal spaces. [11 ] The two fixed boundaries defining these spaces are the left
and right fibrous trigones of the skeletal structure of the heart; the other boundaries are
defined by adjacent anatomic landmarks. These include the left free wall to left posterior
intraventricular septum junction separating the left free wall and posterior septal spaces,
defined endocardially 1 cm posterior to the medial commissure of the mitral valve, and
the right free wall to right posterior intraventricular septum junction separating the right
free wall and posterior septal spaces, defined endocardially 1 cm anterior (onto the free
wall) to the os of the coronary sinus. The right free wall to pulmonary infundibulum
junction separating the right free wall and the anterior septal spaces is arbitrarily
defined. It is important to recognize, however, that the posterior and anterior septal
spaces are in fact epicardial spaces that abut the atrial septum posteriorly and
anteriorly. Surgically, these two spaces must be distinguished from the parietal right and
left free wall spaces, and thus they are designated as septal.
The mitral and aortic valve annuli contribute significantly to the structural integrity of the
fibrous skeleton and are further strengthened at their left junction to form the left fibrous
trigone. The AV groove between the left fibrous trigone and the right fibrous trigone (the
anterior portion of the central fibrous body) represents the site of continuity between the
anterior leaflet of the mitral valve and the aortic valve annulus (see Fig. 26-9 ). This is the
only area in the AV groove where atrial muscle is not in juxtaposition to ventricular
muscle, and for this reason, accessory atrioventricular pathways are not found between
the left and right fibrous trigones. This part of the fibrous skeleton lies in the horizontal
plane of the AV groove.
A second important anatomic fact, however, is that the fibrous skeleton of the heart is
not completely horizontal. [6 ] , [11 ] , [12 ] The cardiac skeleton is strongest at the
central fibrous body, where the annuli of the mitral, tricuspid, and aortic valves meet
(see Fig. 26-9 ). The tricuspid annulus is more apical in position than is the mitral
annulus and not on the same horizontal plane. Because of this, the anterior part of the
central fibrous body extends into the ventricles beneath the attachment of the tricuspid
valve, and the interventricular component of the membranous septum between the aortic
outflow tract and the right atrium actually lies cephalad to the tricuspid annulus. This is
an important anatomic landmark because the bundle of His penetrates the central
fibrous body just posterior to the membranous septum.
THE ATRIAL SEPTUM
The true atrial septum is quite small. [13 ] The anterior limbus of the fossa ovalis is
separated from the aortic root by the transverse pericardial sinus, and the portion
anterior to the right fibrous trigone constitutes the free wall of the right atrium. The fossa
ovalis itself and the posteroinferior limbus constitute true atrial septal tissue. However,
because of the apical position of the tricuspid valve, the posteroinferior portion of the
inferior limbus separates the right atrial chamber from the left ventricular outflow tract
(see Fig. 26-6 ). The atrial tissue surrounding the coronary sinus and the proximal sinus
itself constitute epicardial structures, lying in the posteroseptal atrioventricular groove.
THE VERTICAL PLANE
Conceptualization of the anatomic relationships of these pathways in the vertical plane

is more difficult. [12 ] Electrophysiologically, accessory pathways are the equivalent of
an electrical cable that is capable of conducting electrical impulses between the atrium
and ventricle. Histologically, these pathways resemble normal atrial myocardium.
Because of the anatomic limitations imposed by the valve annulus on the inside of the
AV groove and the epicardium on the outside of the AV groove in the vertical plane, all
accessory pathways must connect atrium to ventricle somewhere between these two
boundaries (Fig. 26-10) . No accessory pathway in a human being has ever been
shown to pass through the tissue of the valve annulus (mitral or tricuspid) itself. In the
vertical plane, therefore, accessory pathways are theoretically confined to locations (1)
adjacent to or near the valve annulus, (2) within the fat pad of the AV groove, or (3) just
beneath the epicardium overlying the AV groove. Surgically, the depth of the pathway
within the AV groove in the vertical plane must be considered to be variable. [14 ] The
experience with radiofrequency (rf) ablation has demonstrated that most left-sided
pathways are juxtaannular; the relative ease of localization, the small size of rf lesions,
and the low incidence of complications related to the circumflex coronary artery, whose
depth within the atrioventricular groove is variable, all suggest this. Most true left
free-wall pathways that were missed at surgery resulted from failure to completely
dissect the mitral annulus or failure to perform some type of isolation of the rim of atrial
tissue attached to the annulus. Moreover, relatively few left-sided pathways could be
interrupted surgically with the epicardial dissection technique without accompanying
cryoablation of the mitral annulus. It is likely, however, that right free-wall pathways are
located more frequently at some distance from the endocardium of the right atrium or
ventricle. The evidence for this is the higher failure rate with right-sided pathways, the
requirement for larger amounts of rf energy for right- as compared with left-sided lesions
(e.g., the necessity to ablate a larger amount of tissue), and the anatomic folding over of
the atrium onto the ventricle on the right side of the heart (Fig. 26-11) that is quite
prominent at the time of endocardial surgical dissection. This gives the impression that
right-sided pathways are more separated from the annulus than left-sided pathways.
This folding over is most prominent in those patients with both the true form and the
forme fruste of Ebstein's anomaly and may account for the high incidence of accessory
pathways in patients with this congenital lesion. [14 ]
Finally, when the horizontal and vertical planes are combined, these accessory
pathways can traverse this three-dimensional space tangentially. [15 ] A manifest left
free-wall pathway may connect the atrium 1 cm from the left fibrous trigone to the
ventricle in the midportion of the left free-wall space, 3 cm from the left fibrous trigone. In
this situation, the pathway passes obliquely across the vertical plane of the AV groove
and encompasses a 2-cm area of the left free-wall space in the horizontal plane. In
addition, data from sophisticated computerized intraoperative mapping systems verify
the suggestion that many of these accessory pathways are broad bands of tissue rather
than fine, hairlike structures. In this situation, the reason electrophysiologic data indicate
a precise pathway is that electrical conduction occurs predominantly over only one
specific and precise portion of the broad band.
THE POSTERIOR SEPTAL SPACE
The posterior septal space is perhaps the most difficult to conceptualize for both the
electrophysiologist and the surgeon. [16 ] Accessory pathways in this location may be
associated with several special conditions, including (1) Ebstein's anomaly, (2)
Mahaim-type accessory connections, (3) anomalous coronary sinus/coronary sinus
diverticulum, (4) the permanent form of reciprocating junctional tachycardia, and (5)
concealed pathways at the left free wall-posterior septal junction, often referred to as the
left posterior paraseptal space . It is helpful to recognize that the posterior septal space
is, in fact, an epicardial space. A supraannular incision made in the endocardium of the
left or right atrial free wall penetrates the heart; similarly, an endocardial incision in the
posterior half of the triangle of Koch penetrates the right atrial chamber into the
posteroseptal atrioventricular groove fat pad. [17 ]
Sealy and Gallagher [18 ] have described the posterior septal space as a toppled
trihedral pyramid. As shown in Fig. 26-12 , the posterior septal space sits on top of the
posterior intraventricular septum, extends onto both the left and right parietal-septal
junctions and abuts the posterior aspect of the right and left atrial septa. The difficulty
that has existed in conceptualizing this anatomic space results from the fact that (1) it is
a three-dimensional space, (2) the terminology used to describe the space is confused,
and (3) two-dimensional illustrations cannot adequately represent the three-dimensional
aspects of the dissection.
The epicardium of the posterior septal space extending across the crux of the heart
constitutes the caudal aspect of the dissection in the surgeon's orientation (see Fig.
26-12 ). As in the other endocardial procedures, the fat pad is dissected off the top of
the ventricle to the epicardial reflection. After operation, dissection of the fat pad off the
top of the ventricle is evident at least several centimeters to the left of the posterior
descending coronary artery, which marks the midpoint of the crux of the heart. When
viewed from outside the heart, the posterior septal space extends approximately 1.5 cm
to either side of the crux. If the site of earliest atrial or ventricular activation during
mapping is outside this area, particularly on the left side, then the accessory connection
is considered to traverse both the free wall and posterior septal spaces.
Following the completed dissection, the fat pad that has been dissected away from the
top of the posterior ventricular septum contains the entire contents of the pyramidal
space within the AV sulcus at the crux of the heart: the coronary sinus, the arterial supply
to the AV node, and the AV node and proximal His bundle (see Fig. 26-12 ). As
mentioned, the AV node is an epicardial structure that becomes the penetrating bundle
and passes into the central fibrous body anterior to the most posterior extent of this
structure. [6 ] During dissection of the posterior septal space, it is extremely important to
gently sweep away the fat pad from the posterior aspect of the central fibrous body,
since this is the most cephalad extent of the dissection. Failure to terminate the
dissection at this fibro-fatty junction is the source of complete heart block previously
associated with this dissection. In addition, great care should be exercised in retracting
the elevated fat pad because it contains the AV node and proximal bundle tissues.
In all patients, the posterior arterial supply to the AV node is frequently associated with
accessory atrioventricular connections and should be divided during the course of the
dissection if the artery penetrates the top of the interventricular septum. [10 ] , [16 ]
Temporary or permanent heart block from dividing this artery has not been encountered,
but a number of patients required reoperation under circumstances where this artery
was clearly the only remaining connection between the ventricular septal tissue and the
fat pad.
OTHER CONDITIONS
Right atriofascicular accessory pathways
Mahaim first described fibers that connect the nodal bundle to the ventricular septum,
so-called nodoventricular fibers. Although common in infant hearts, in the past these
fibers were thought to be associated with atypical preexcitation syndromes due to a
long antegrade conduction time over the accessory pathway coupled with decremental
conduction properties and with retrograde conduction occurring only over the AV node.
Careful mapping at electrophysiologic study shows that the majority of fibers exhibiting
Mahaim-type physiology are located along the right free wall (Fig. 26-13) . A few of
these fibers insert into the right ventricle close to the tricupsid annulus, but the majority
have an anatomic course greater than 4 cm and insert either into the apical region of
the right ventricular free wall, near the moderator band containing the disal components
of the right bundle branch, or directly into the distal components of the right bundle
branch at the apical ventricular free wall. [19 ] The atrial end inserts near the
posterolateral tricuspid annulus. The decremental conduction properties appear to
result from a duplication of the AV conduction system, with a proximal nodelike
component and a distal bundle branch-like structure. Anatomically, these pathways are
properly termed right atriofascicular accessory pathways .
Ebstein's anomaly
Ebstein's anomaly is a congenital malformation in which the origins of the septal and
posterior leaflets (or both) of the tricuspid valve are displaced downward into the right
ventricle. [20 ] These two leaflets of the valve are usually deformed, and the
anterosuperior leaflet is usually larger than normal. The septal and posterior leaflets are
attached to the right ventricular wall rather than to the atrioventicular ring (Fig. 26-14) . In
addition, there is an accentuation to the normal infolding of the atrial and ventricular
muscle at the level of the true annulus.
There is a wide spectrum of variability, with many patients having the forme fruste of this
disease. In the severest forms, the proximal portion of the right ventricle is atrialized and
may be so thin as to appear aneurysmal. The right atrium may be dilated, and an atrial
septal defect of any type may be present. The position of the AV node and conduction
bundles in patients with Ebstein's malformation is normal, although the right bundle
branch may be compressed by thickened endocardium. The incidence of arrhythmias
and conduction disturbances in this patient population is high, and approximately 5
percent of these patients have accessory atrioventricular connections responsible for
the Wolff-Parkinson-White (WPW) syndrome. An additional undetermined percentage
of patients with the WPW syndrome have the forme fruste of Ebstein's malformation.
A distinct association between patients with Ebstein's anomaly and the specific location
of the accessory pathways exists. [17 ] Most commonly, patients with this anomaly have
posterior septal accessory atrioventricular connections. However, in our series, a
majority of patients with Ebstein's malformation or the forme fruste of the disease are
found to have a combination of right free-wall and posterior septal accessory pathways
at intraoperative mapping. This correlation is so high that if a patient is found to have
this combination of pathways on the preoperative electrophysiologic study, an
echocardiogram is indicated to determine the status of the tricuspid valve.
Coronary sinus abnormalities
The coronary sinus is the portion of the cardiac venous system that begins at the origin
of the oblique vein of Marshall (that part of the cardiac venous system which drains the
left atrium) and ends at the ostium of the coronary sinus in the right atrium (Fig. 26-15) .
The great cardiac vein of Galen, the posterior vein of the left ventricle, and the marginal,
middle, and small cardiac veins all drain into the coronary sinus in the normal anatomic
configuration. [10 ] The coronary sinus is normally contained within the posterior
epicardial AV groove fat pad and does not come in contact with the top of the
ventricular septum. For this reason, it can be readily separated from the top of the
ventricle during dissection of the posterior septal space. Frequently, however, the
coronary sinus is covered by a thin band of atrial muscle, and if an accessory
atrioventricular connection is present, it is usually intimately associated with the
coronary sinus and its venous branches.
An anomalous coronary sinus is a rare congenital abnormality that probably results from
a malformation of the confluence of the middle cardiac vein and the sinus. [17 ] This
entity is usually associated with accessory pathways in the posterior septal space.
Abnormalities of the proximal sinus itself are even more uncommon and usually result in
a diverticulum. [21 ] Malformation of the os of the coronary sinus may accompany this
entity, including gross enlargement of the opening of the coronary sinus or the presence
of two channels within the os (one representing the true coronary sinus draining the
posterior left side of the heart and the second representing a greatly enlarged and
separate great vein). In these instances, the tight adherence of the inferior wall of the
coronary sinus abnormality to the postero-superior process of the left ventricle and the
posterior interventricular septum constitutes a problem encountered during ablative
therapy. These true diverticula are round or oval structures with a narrow mouth that
drains into the sinus. The body of the diverticulum is within the epicardial layers of the
posterior left ventricle at the septo-parietal junction. The epicardial surface is covered
by the epicardial reflection, and the diverticulum may occupy most of the posterior
septal space when viewed from the outside of the heart. Modification of the standard
endocardial technique is necessary in these circumstances, as described below.
The triangle of Koch and AV node-His bundle
The anatomy of the atrial septum and triangle of Koch is extremely important when
considering ablative treatment of AV nodal reentrant tachycardia (AVNRT). The true
atrial septum is comprised only of the tissue within the fossa ovalis and its inferior rim
when the heart is viewed from the opened right atrium. Anteriorly, superiorly, and
posteriorly (in the in situ position), the right and left atrial free walls infold to meet the
atrial septal tissue; inferiorly, in the in situ position, atrial septal tissue connects to and is
anterior to the central fibrous body. On the right atrial side of this connection lies the
triangle of Koch.
Multiple input approaches for atrial impulses to reach the AV node have been
described. [22 ] These include left atrial and right atrial approaches; the right atrial
approaches may be further subdivided into posterior (inferior), anterior (superior), and
anteroseptal approaches. Moreover, the anterior approaches curve posteriorly after
reaching the AV node to merge with the posterior approaches; these posterior
approaches course along the posterior limbus of the fossa ovalis, also known
anatomically as the crista terminalis (see Fig. 26-3 ). In general, conduction proceeds
faster along the anterior and superior approaches than along the posterior approaches.
However, this difference in conduction does not constitute the functional description of
AV node reentry comprising two pathways with distinct (fast and slow)
electrophysiologic properties. It remains unproven that these properties correspond to
the atrial inputs to the AV node; these functional properties may be related to distinct
anatomic pathways, longitudinal dissociation within the AV node, or functional
properties of the perinodal myocardium. The presence of a lower common pathway
remains plausible, since structures below the His bundle are not actively involved in the
reentrant circuit. The location of the upper portion of the reentrant circuit is probably
extranodal, but this is not yet proven. During common (slow-fast) AVNRT, the earliest
site of atrial activation is at the anterosuperior aspect of the interatrial septum, close to
the His bundle recording site. During uncommon (fast-slow or slow-slow) AVNRT, the
earliest site of atrial activation is more toward the posteroinferior aspect of the
interatrial septum, in close proximity to the coronary sinus ostium. This suggests the
presence of distinct anatomic sites for fast and slow pathways, either extranodal with
distinct atrial inputs or intranodal with two separate atrial breakthrough points. Ablation
techniques (rf, cryosurgical modification, or surgical dissection) are directed at one or
both of these anatomic sites.
Atrial tachycardias of ectopic origin
Anatomically, ectopic or automatic atrial tachycardias can originate from foci occurring
anywhere within the left or right atrial tissue or atrial septum. In addition, there may be
multiple foci. Lowe et al. [23 ] collected 125 patients reported in the literature; of the 89
cases in which the location was specified, 61 (68 percent) originated in right atrial
tissue (Fig. 26-16) , 5 (6 percent) in the atrial septum, and 23 (26 percent) in left atrial
tissue.
These arrhythmias may arise from reentrant circuits or from abnormal foci of activation
within the atrium. Reentrant arrhythmias are found most commonly in patients who have
undergone surgical correction of congenital heart defects, most commonly tetralogy of
Fallot, transposition of the great vessels, tricuspid atresia, and simple atrial septal
defect (ASD) closure. Suture lines, patch material, and conduits can produce a fixed
anatomic barrier around which the reentrant circuit can form.
Atrial flutter
Multiple studies show that the common type of atrial flutter most likely occurs from a
single macroreentrant circuit in right atrial tissue that is dependent on fixed anatomic
obstacles (e.g., the venae cavae or surgical incisions) to create areas of conduction
block. [24 ] , [25 ] This reentrant circuit commonly involves the atrial septum. In typical
flutter (flutter rate of 250 to 350 per minute, inverted flutter waves in ECG leads II, III, and
aVF, upright waves in V 1 ), the circuit involves atrial excitation over the interatrial
septum followed by activation of the roof of the right atrium and crista terminalis. The
region between the tricuspid annulus and the inferior vena cava appears to be the zone
of critical slow conduction, and ablation in this region is effective in the long term in
approximately 50 percent of patients (Fig. 26-17) . Using sophisticated multipoint
computerized mapping, intraoperative localization of the reentrant circuits responsible
for several clinical atrial flutter circuits has been possible, including left-sided circuits
around the pulmonary veins.
Atrial fibrillation
Atrial fibrillation is distinct from atrial flutter and macroreentrant circuits responsible for
the WPW syndrome in that no discrete anatomic obstacles (or pathways) are part of the
reentrant circuit and from ectopic atrial tachycardias because there is no single
dominant focal area of atrial tissue. In macroreentrant circuits, if the length of the circuit
is longer than the wavelength of the electrical impulse, the arrhythmia is stable; the
difference between the anatomic length and the wavelength is the excitable gap. In atrial
fibrillation (according to the leading-circle concept of reentry responsible for fibrillation),
the microreentrant circuits do not involve a gross anatomic obstacle and are
determined by electrophysiologic properties; the size of the circuit is approximately
compatible with the wavelength, which is determined by the product of the refractory
period and the conduction velocity. [26 ] [28 ] The wavelength of refractoriness is the
product of the functional refractory period and the conduction velocity. In the absence of
an excitable gap, the cycle length of the circuit is expressed as follows: CL = L/CV ,
where CL is cycle length of the circuit, L is the anatomic length of the circuit, and CV is
the conduction velocity. If the wavelength equals the anatomic length of the circuit, cycle
length is equal to the refractory period: CL ( RP × CV )/ CV = RP , where RP is the
refractory period. Therefore, alterations in the (effective) refractory period of the
circuit(s) affect propagation and termination of fibrillation. Prolongation of the
wavelength (e.g., prolongation of the refractory period) is associated with spontaneous
termination of atrial fibrillation.
Experimental studies confirm that atrial fibrillation is due to intraatrial reentry, where
multiple reentrant wavelets present in the atrium are maintained by the inhomogeneity of
tissue refractoriness in atrial myocardium. [27 ] This uneven refractoriness slows the
activation wavefront in some areas but not in other areas and results in uneven
conduction that causes a single wavefront to be dissociated into multiple reentrant
waves. Clinically, the dispersion of refractoriness in atrial fibrillation intervals, defined as
the variance of the fibrillation intervals at the multiple recording sites, is up to three times
larger in patients with a history of paroxysmal atrial fibrillation as compared with control
patients. [29 ] , [30 ]
As atrial size increases, the number of wavefronts during atrial fibrillation and the
duration of atrial fibrillation increase. [31 ] , [32 ] As cycle lengths decrease and become
more variable, various regions of the atria become completely dissociated from one
another, permitting multiple simultaneous wavefronts that are transient in both time and
space. [33 ]
Anatomic Principles Pertaining to Ablative Therapies for Ventricular

Arrhythmias
Similarly, the anatomic considerations for ablative treatment of ventricular

tachyarrhythmias are for the most part independent of the technique used to perform the
ablation.
NONISCHEMIC VENTRICULAR TACHYCARDIAS
Ventricular tachycardia in infants and children amenable to surgery is unusual and is

most often associated with a cardiomyopathy, prior surgery for congenital heart defects,
and cardiac tumors. There are anatomic considerations that relate to each of these
entities.
Arrhythmogenic right ventricular dysplasia (ARVD) is a congenital myopathy remarkable

pathologically for transmural infiltration of adipose tissue. Anatomically, this results in
weakness and aneurysmal bulging of three pathologic areas of the right ventricle: the
infundibulum, apex, and posterior basilar region. [34 ] Ventriculography demonstrates
diffuse dilatation of the right ventricle with a significant reduction in contractility and
marked delay in right ventricular emptying. Ventricular bulges or frank aneurysms occur
in one or all of the three pathologic areas, and hypertrophic muscular bands in the
infundibulum and anterior right ventricular wall result in apparent pseudodiverticula, the
so-called feathering appearance of the right ventricular outflow tract.
Cardiac tumors can be localized to the left or right ventricle or septum in association
with isolated arrhythmogenic tissue, or they can diffusely involve cardiac muscle and
conduction tissue. Localized tumors may be epicardial, intramyocardial, or on the
endocardial surface of the heart. [35 ]
Finally, patients with congenital heart defects, especially tetralogy of Fallot, have
developed ventricular arrhythmias long after the corrective procedure. [36 ] The
occurrence of these arrhythmias appears to be in part related to the hemodynamic
result achieved with the operative procedure. Some of these arrhythmias originate from
the right ventriculotomy site.
ISCHEMIC VENTRICULAR TACHYCARDIAS
Ventricular tachyarrhythmias in adults are most commonly secondary to ischemic

coronary artery disease. [37 ] In most patients with these arrhythmias, there is
progression of acutely ischemic tissue to cell death that leaves a fibrous scar in place of
the injured myocardium. The interlacing anisotropic pattern of the remaining scar and
normal myocardium may harbor local areas of slow conduction, uni-directional block,
uneven refractoriness, and nonuniform repolarization, the electrophysiologic substrates
for development of reentrant circuits associated with ventricular aneurysm formation.
These same substrates are also produced by tension and/or compression forces of
ventricular aneurysmthe most common anatomic correlate of ischemic ventricular
tachycardia. Most commonly these substrates occur in the anteroapical position
secondary to complete obstruction of the left anterior descending coronary artery, but
they also occur posteriorly in the distribution of the posterior descending coronary
artery. The presence of an aneurysm has a significant bearing on the outcome of direct
surgery for ventricular tachyarrhythmias. Moreover, the presence of an aneurysm directly
contributes to overall impairment of left ventricular function, both in the short and the long
term. Multiple studies demonstrate that long-term survival following either direct surgery
or internal cardiac defibrillation (ICD) therapy for ventricular tachycardia is almost
exclusively dependent on the degree of left ventricular dysfunction, the natural history of
that dysfunction, and the functional outcome following surgical reconstruction of the
ventricular chamber. [38 ]
INTRACARDIAC AND EPICARDIAL MAPPING OF ARRHYTHMIAS
Epicardial Intraoperative Mapping Techniques
The availability of a computerized mapping system in recent years has led to the
elucidation of even the most complex supraventricular arrhythmias (Fig. 26-18) .
Cardiopulmonary bypass is usually not necessary for the intraoperative mapping of

patients with the WPW syndrome. After safe induction of general orotracheal
anesthesia, a median sternotomy is performed. If cardiopulmonary bypass is used, the
heart is suspended in a pericardial cradle, and the ascending aorta is cannulated for
cardiopulmonary bypass. The right atrial appendage is cannulated with a right-angled
cannula placed into the superior vena cava (SVC) for venous return; the inferior vena
cava (IVC) is not cannulated until after completion of all presurgical intraoperative
mapping to avoid iatrogenic trauma to the pathway.
Epicardial pacing and sensing electrodes are sutured onto the atrium and ventricle near
the suspected site of the accessory pathway. [11 ] A 16-point band electrode is placed
around the ventricular side of the AV groove, and electrograms are recorded
simultaneously from the 16 bipolar electrodes during normal sinus rhythm and atrial
pacing. After computer selection of activation times, the electrogram recorded from the
electrode located nearest the site of ventricular insertion of the accessory pathway
shows the earliest activation (Fig. 26-19) .
The band electrode is then moved to the atrial side of the AV groove, and reciprocating
tachycardia is induced with programmed electrical stimulation. Only a few cycles of
tachycardia are allowed, since hemodynamic compromise is common and patients are
not on cardiopulmonary bypass. If reciprocating tachycardia cannot be induced
intraoperatively, retrograde atrial mapping is performed during ventricular pacing. Since
retrograde conduction is faster across the accessory pathway than through the AV
node-His bundle complex, the atrium activates earliest at the site of atrial insertion of
the accessory pathway.
If a septal pathway is detected during epicardial mapping, the patient is placed on

cardiopulmonary bypass, a right atriotomy is performed, and endocardial mapping of
the right atrium and atrial septum is completed using a hand-held, single-point mapping
system prior to proceeding with surgical dissection. [39 ]
When the epicardial approach is used, intraoperative mapping most often involves
single-point mapping to localize the pathway around the AV groove. After the epicardial
dissection is performed, additional mapping may be performed just adjacent to the
annulus to identify appropriate locations for the annular cryolesions.
For ectopic atrial arrhythmias, the atrial electrode is placed on the atrial tissue (left or
right) found to contain the ectopic focus preoperatively (Fig. 26-20) . Intraoperative
localization is often difficult due to suppression of the arrhythmia by general anesthesia
and the inability to induce the arrhythmia with programmed stimulation. [40 ] If the
arrhythmia does persist intraoperatively so that it can be localized with a single-point
system, or if a multipoint system is available so that the atria can be mapped from only
a few beats of tachycardia, then a localized surgical procedure can be performed. Most
often, a combination of both single-point and computerized mapping is performed in
these patients utilizing atrial epicardial plaque electrodes with 156 bipolar electrode
points (Fig. 26-21) .
Because of the transient nature of the reentrant circuits and lack of dependence on
anatomic considerations in atrial fibrillation, intraoperative mapping is not performed
routinely for surgical ablation of atrial fibrillation.
Ventricular Arrhythmias
Intraoperative mapping for patients with ventricular tachyarrhythmias can be performed

with both single-point and multipoint systems. In infants with localized arrhythmogenic
sites due to tumors, the site of earliest activation is readily identified; occasionally, the
tumor may be seen on the epicardial surface of the heart. In patients with ARVD, the
three pathologically abnormal regions of the right ventricle may exhibit electrical silence
on epicardial mapping; the actual site of origin of the tachycardia may be in the
electrically silent region and only appear to arise from the border of the silent region
because a critical mass of synchronously depolarized myocardium is necessary to
produce an electrogram large enough to be detected by the exploring electrode.
In adults with ischemic ventricular tachycardias, two reference ventricular (one left, one
right) electrodes are placed for intraoperative mapping. [41 ] Epicardial mapping with a
sock electrode or hand-held electrode is performed, and the results are correlated with
the preoperative electrophysiologic study. Since most ventricular tachycardias arise
from within myocardial tissue (and not on the endocardium or epicardium), transmural
activation sequences can be obtained with plunge needle electrodes safely and
efficiently, yielding a three-dimensional representation of activation to guide the surgical
resection and to delineate sites of intramural origin and endocardial and epicardial
breakthrough.
All 160 channels of the computerized system are used to map the heart in patients with
ventricular tachycardia.[12] This system can record 160 simultaneous signals, analyze
the data, and display them in various forms within 2 minutes after data acquisition for
editing. An epicardial map employing a 96-electrode sock array (Fig. 26-22) is
recorded, and this information is used to guide subsequent placement of plunge needle
electrodes to further delineate the specific site of arrhythmogenesis.
Subsequently, multiple plunge needle electrodes containing four bipolar pairs of

electrodes are inserted into the ventricle in the region of earliest epicardial activation. If
the tachycardia appears to arise from the intraventricular septum, a right atriotomy is
performed, and up to 15 plunge needle electrodes are inserted into the septum from the
right side. A total of up to 160 endocardial, intramural, and epicardial data points can
be recorded simultaneously from the septum and free wall. A ventriculotomy, which can
prevent further inducibility of the ventricular tachycardia and necessitate performance of
a procedure that is not map-guided, does not have to be performed in order to obtain
an endocardial map.
THERAPY FOR SUPRAVENTRICULAR ARRHYTHMIAS
As with any application of technology in medicine, failures occur due to (1) operator
error or inexperience, (2) technology failure, or (3) anatomic or pathologic deviation
from the norm. Recently, the incidence of radiofrequency (rf) catheter ablation failure for
WPW syndrome and AVNRT has continued to decline as nuances of anatomy are
elucidated.
AV Reentrant Tachycardia
The objective of surgery for WPW syndrome is to divide the accessory pathway(s)
responsible for the syndrome. [11 ] Two surgical approaches are employed commonly
to divide these accessory pathways. The endocardial technique is designed to divide
the ventricular end of the accessory pathway, and the epicardial technique has been
directed toward division of the atrial end of the pathway.
LEFT FREE-WALL ACCESSORY PATHWAYS
If the endocardial technique is employed, accessory pathways on the left side of the
heart are approached through a left atriotomy after the heart is arrested. A supraannular
incision is placed 2 mm above the mitral valve annulus, extending from the left fibrous
trigone to the posterior septum (Fig. 26-23A,B) . The entire space is dissected
completely in every patient, regardless of the precise location of the accessory pathway
within that space. After placing the supraannular incision, a plane of dissection is
established between the underlying AV groove fat pad and the top of the left ventricle
throughout the length of the supraannular incision (Fig. 26-23C,D) . It is important to
carry this plane of dissection all the way to the epicardial reflection from the posterior
left ventricle to divide any accessory pathway that might be located in the subepicardial
position in the AV groove. Following this dissection, it is still theoretically possible for an
accessory pathway located immediately adjacent to the valve annulus to remain intact
unless the annulus is cleaned meticulously with a sharp nerve hook or knife. To preclude
this possibility, the two ends of the supraannular incision are squared off (Fig. 26-2F) to
the level of the mitral annulus so that even if a juxtaannular pathway survived the
previous dissection, the small rim of atrial tissue to which it would attach would be
isolated from the remainder of the heart and the potential conduction circuit would be
interrupted. This dissection exposes the entire left free-wall space and each of its
boundaries so that no accessory pathway can reach the ventricle.
The epicardial dissection exposes the AV junction via a direct incision in the fat pad
along the ventricular wall. [42 ] , [43 ] The epicardium of the fat pad is incised
longitudinally along the left ventricular edge anterior to the coronary sinus in the inferior
segment of the coronary sulcus. For the majority of cases, cardiopulmonary bypass is
required. A plane of cleavage is found over the left ventricular wall, and the AV junction
is identified. This technique requires (1) identification, ligation, and division of the
obtuse margin cardiac vein and (2) dissection of the obtuse marginal coronary artery
and other ventricular branches of the circumflex coronary system over a 1- to 2-cm
segment; the long-term effects of this skeletonization are not known at present. Finally,
the great cardiac vein and the AV groove fat pad including the left circumflex coronary
artery are mobilized and isolated on a large stay suture to expose the entire left
free-wall space except for the region near to the left fibrous trigone; this area cannot be
exposed adequately from either epicardial approach and requires either closed heart
endocardial cryoablation of the region, which is near the origin of the left main coronary
artery, or an endocardial dissection. After completion of direct epicardial dissection,
epicardial mapping is performed with a hand-held electrode, and cryolesions are
placed along the AV groove. This direct approach divides the ventricular end of the
accessory atrioventricular connection in similar fashion to the standard endocardial
dissection technique.
POSTERIOR SEPTAL ACCESSORY PATHWAYS
With the endocardial approach to posterior septal accessory pathways, normothermic

cardiopulmonary bypass is instituted, and a right atriotomy is performed after
conventional epicardial mapping. [16 ] , [17 ] Following mapping, a supraannular
incision is placed 2 mm above the posterior medial tricuspid valve annulus, beginning
at least 1 cm posterior to the His bundle beneath the coronary sinus (Fig. 24) . The
supraannular incision is extended in a counterclockwise direction well onto the free wall
of the posterior right atrium (Fig. 26-2C) . This latter extension is important for two
reasons: (1) it provides a larger incision for better exposure into the depths of the
posterior septal space near the posterosuperior process of the left ventricle, and (2) it
simplifies identification of the epicardial reflection off the posterior right ventricle, a
landmark to follow across the crux of the heart to the posterior left ventricle during
dissection of the posterior septal space. Once the fat pad occupying the posterior
septal space is identified through the supraannular incision, a plane of dissection is
established between the fat pad and the top of the posterior ventricular septum (Fig.
26-24D,E) . Prior to cardioplegic arrest, this plane is developed in the anterior portion
of the posterior septal space closest to the His bundle and approaches the central
fibrous body from the posterior aspect. The junction of the posteromedial mitral and
tricuspid valve annuli forms an inverted V at the posterior edge of the central fibrous
body, and the fat pad comes to a point at the apex of that V (Fig. 26-2F) . The apex of
the V is always posterior to the His bundle, although the distance between the apex of
the V and the pathway of the bundle through the central fibrous body is variable.
However, as long as the dissection in this region remains posterior to the central fibrous
body, the His bundle will not be damaged. Once the anterior point of the fat pad is gently
dissected away from the apex of the V (i.e., away from the posterior edge of the central
fibrous body), the mitral valve annulus comes into view at the point where it joins the
tricuspid valve to form the central fibrous body. The heart is usually arrested at this point,
but this is not absolutely necessary. If the plane of dissection is relatively bloodless and
easily identified, the entire posterior septal space can be dissected with the heart
beating. On the other hand, if the plane is extremely vascular, the entire dissection is
done under cardioplegic arrest.
Since the epicardial reflection off the posterior right ventricle is already identified,
visualization of the mitral valve annulus in the anterior portion of the posterior septal
space completes identification of the dissection boundaries of the space. The plane of
dissection between the fat pad and the top of the posterior ventricular septum is
developed completely by following the mitral annulus over to the posterosuperior
process of the left ventricle and by following the epicardial reflection from the posterior
right ventricle, across the posterior crux, and onto the posterior left ventricle (Fig.
26-24G) . It is absolutely essential to divide all structures penetrating the posterior
ventricular septum and the posterior septal space, including, if necessary, the AV node
artery.
If the epicardial approach is used for posterior septal pathways, [42 ] , [43 ] the posterior
septal region, the adjacent inferior right ventricular region, and the left posterior
paraseptal region are all dissected from the atrial epicardial aspect (see Fig. 26-12 ).
The inferior AV groove fat pad is mobilized en bloc, and the inferior right ventricular
wall-AV junction is exposed. The right coronary artery and its branches are identified.
The midcardiac vein is ligated and divided. The right atrial-left ventricular fat pad is
mobilized, and the posterosuperior process of the left ventricle is exposed. Complete
exposure requires cauterization of small arteries and veins coursing over the ventricular
process, including the AV node artery. The pericardium is incised anterior to the
coronary sinus and the left AV junction, and the left posterior septal region is exposed.
The right and left AV junctions are dissected, especially in the posterior septal region, to
expose the whitish AV lamina. Ablation of epicardial pathways is secured by epicardial
cryoablation of the exposed AV junction using overlapping applications of a cryoprobe
while monitoring antegrade AV nodal conduction. If preexcitation exists after placement
of these cryole sions, then blind endocardial cryoablation is necessary, with a cryoprobe
placed into the right atrium through a small purse-string suture in the right atrial
appendage. This epicardial dissection is performed without cardiopulmonary bypass,
with the heart retracted by a large traction suture passed through a sterile piece of
cardboard and the acute margin of the heart. Occasionally, the posterolateral branch of
the right coronary artery must be divided to obtain adequate exposure and complete
mobilization of the coronary sinus. If a left paraseptal pathway is present,
cardiopulmonary bypass is necessary to connect the left free wall and posterior septal
epicardial dissections.
In patients with Ebstein's anomaly, the true location of the tricuspid annulus is frequently
difficult to define. [12 ] This is best accomplished by first identifying the AV groove fat
pad on the right free wall epicardially. This fat pad is always located in the plane of the
true tricuspid annulus. Therefore, an endocardial incision is placed exactly opposite the
AV groove fat pad on the right atrial free wall and extended clockwise in that plane into
the posterior septal space. Since conduction tissue lies in the normal location in
patients with Ebstein's anomaly, the endocardial incision is stopped beneath the os of
the coronary sinus (see Fig. 26-24 ). Once the supraannular incision is made, the
remainder of the operative procedure is identical to that described earlier for posterior
septal pathways. If valve replacement or placement of an annuloplasty ring is necessary
for severe Ebstein's malformation, the valve or annuloplasty ring should be placed
below the coronary sinus by sutures placed through the true tricuspid annulus. [20 ]
Plication of the atrialized ventricle may or may not be necessary.
To ablate accessory pathways associated with coronary sinus abnormalities, the

standard endocardial technique must be modified. [12 ] In patients with an anomalous
coronary sinus and/or coronary sinus diverticulum, the inferior wall of the sinus or
diverticulum is fused with the posterior interventricular septum, with no intervening fat
pad. Since the coronary sinus itself can be intimately associated with accessory AV
connections, the coronary sinus must be isolated in some way from the ventricular
surface to interrupt the accessory pathway. In dissecting the coronary sinus off the
septum, a small rim of the inferior coronary sinus wall must be left attached to the
posterior septum. Although this maneuver interrupts the accessory connection in most
instances, complete dissection of the entire posterior septal space is still performed.
Closure of the endocardial incision is done in standard fashion, as described earlier.
Coronary sinus drainage is unimpeded because the defect quickly becomes
readherent to the ventricular surface of the dissection. Closure of the defect in the
coronary sinus is neither necessary nor advisable.
RIGHT FREE-WALL ACCESSORY PATHWAYS
Both endocardial and epicardial dissections can be performed without cardioplegic

arrest in these circumstances. [44 ] One advantage to the endocardial technique may
be to permit endocardial mapping; there is frequently a large amount of fat in the AV
groove on the right side, making epicardial mapping difficult. A supraannular incision is
placed 2 mm above the tricuspid valve annulus and extends around the entire right free
wall (Fig. 26-25) . A plane of dissection is established between the underlying AV
groove fat pad and the top of the right ventricle throughout the length of the supraannular
incision. This dissection plane is developed all the way to the epicardial reflection off
the ventricle so that the entire right ventricular free wall that is in contact with the AV
groove fat pad is free of any penetrating fibers from the fat pad. [12 ]
In the epicardial dissection approach, an incision is made in the epicardium at the site
of its reflection off the atrium to cover the AV groove fat pad of the right atrial free wall. A
plane of dissection is established between the external right atrial wall and the AV
groove fat pad down to the level of the tricuspid valve annulus. This plane of dissection
is established throughout the entire length of the right atrial free wall. Numerous anterior
cardiac veins opening into the right atrium and variability in the anatomic course of the
right coronary artery and its branches may complicate the dissection.
Regardless of the surgical approach employed, there is an additional problem with right
free-wall dissections that does not exist on the left side. The atrium and ventricle tend to
fold over onto one another at the tricuspid annulus much more than they do on the left
side at the level of the mitral annulus (see Fig. 26-11 ). Because of the folding over of
right atrial and ventricular walls at the annular level, the AV groove fat pad does not
actually touch the true tricuspid valve annulus as it does the mitral annulus on the left.
Therefore, when the fat pad is dissected away from the tricuspid annulus using the
epicardial technique, ventricular preexcitation usually does not disappear. To interrupt
such right free-wall accessory pathways that reside too close to the valve annulus, one
of three adjunctive measures must be added to the dissection: (1) mechanical unfolding
of the atrium and ventricle so that the true valve annulus can be seen and freed of any
adjacent fibers connecting the atrium and ventricle (applicable to both the epicardial
and endocardial techniques), (2) application of a cryolesion to the tissues near the valve
annulus to destroy the juxtaannular accessory pathway (applicable to both techniques),
or (3) squaring off of the supraannular incision at both ends to isolate the atrial rim of
tissue to which a juxtaannular accessory pathway may connect (applicable to the
endocardial technique). This folding over of the atrium and ventricle at the level of the
tricuspid annulus is much more pronounced in patients with Ebstein's anomaly; this is
true whether the patient has the classic Ebstein's anomaly or only forme fruste.
Accessory pathways with Mahaim-type physiology are approached using these same
techniques. Depending on the spatial separation of the Mahaim fiber and His bundle,
these accessory connections are interrupted using standard endocardial surgical
dissection techniques (right free wall or posterior septal) in combination with
cryosurgery. The operation performed depends on the location of the accessory
connection determined by preoperative and intraoperative mapping.
ANTERIOR SEPTAL ACCESSORY PATHWAYS
Epicardial mapping is excellent for documenting an anterior septal pathway but does
not localize these pathways very precisely because of the large fat pad covering the
atrium and ventricle and the anterior septal space. [44 ] Therefore, endocardial mapping
is especially important because these pathways are more frequently located adjacent to
the His bundle (anteriorly) than are posterior septal pathways (posteriorly) (Fig. 26-26) .
After performing retrograde endocardial mapping through a right atriotomy with the
patient on cardiopulmonary bypass, the endocardial dissection begins with a
supraannular incision placed just anterior to the His bundle, 2 mm above the tricuspid
annulus, and extended in a clockwise direction well onto the right anterior free wall. The
initial endocardial incision frequently abolishes ventricular preexcitation, but regardless,
the entire anterior septal space should be dissected. After the initial supraannular
incision is completed, a plane of dissection is established between the fat pad
occupying the anterior septal space and the top of the right ventricle. This dissection is
developed completely to the aorta medially and to the epicardial reflection off the
ventricle anteriorly. During this dissection, the fat pad must be retracted very gently to
avoid injury to the proximal right coronary artery, which courses through the fat pad
before entering the AV groove of the anterior right free wall. In addition, when the
anteromedial portion of the anterior septal space is dissected, extreme care should be
taken to avoid injury to the aorta. This area is actually the external surface of the right
coronary sinus of Valsalva beneath the right coronary arterial orifice, and it is therefore
quite thin.
The anterior septal space cannot be dissected from an epicardial approach.
RESULTS
Successful surgical correction of WPW syndrome now approaches 100 percent, with an
operative mortality that ranges from 0 to 0.5 percent with either technique [45 ] , [46 ] (
Table 26-1 ). Complication rates following these operations are likewise extremely low (
Table 26-2 ). Both early and late recurrences following surgery, utilizing either the
endocardial or epicardial technique, are extremely unusual. The surgical treatment of
WPW syndrome has and continues to illustrate the paradigm for effective cure of
supraventricular arrhythmias.
SURGICAL iNTERVENTION FOLLOWING FAILED RF ABLATION
Surgical intervention following radiofrequency (rf) ablation is most often for right-sided
lesions, since they are associated with (1) more complex anatomy, (2) more anatomic
variability, and (3) a higher failure rate than left-sided lesions. In general, the surgical
approaches are the same. At the time of surgery, previously applied rf lesions may or
may not be apparent, depending in part on the number of lesions and the amount of rf
energy used. [46 ] , [47 ]
When the recent surgical experience at Washington University with rf catheter ablation
failures for tachycardias due to accessory connections was examined, two major points
became apparent. There were 15 patients referred to Washington University between
1990 and 1993 for surgery following unsuccessful ablation attempts ( Table 26-3 ). The
first point was that the majority of rf catheter ablation failures were a result of anatomic
abnormalities that were documented at surgery; these included Ebstein's anomaly,
anomalous coronary sinus/aneurysm, persistent left superior vena cava, iatrogenic
perforation of the right ventricle with pericarditis, or broad bundles of muscle (8 to 10
mm) adherent to the coronary sinus tissue that in fact was the accessory connection. All
these anatomic variants complicate the anatomic localization of the accessory
pathway(s); similarly, knowledge of these anatomic variations is important at the time of
surgical intervention. In the remainder of cases, operator error was presumed to be the
cause of failure, as manifest by a clinical history of multiple applications of rf catheter
ablation lesions but no visible lesions in the appropriate region at the time of surgery.
The second and most important point is that it was possible to render a patient
surgically incurable by inappropriately aggressive rf catheter ablation therapy.
Excessive application of rf energy obliterates the normal tissue planes that exist in the
AV groove of the heart and, in the worst case, renders the tissues so friable as to
prohibit surgical correction altogether. In these circumstances, appropriate judgment
must be used by the electrophysiologist to determine when maximal rf catheter ablation
efficacy has been reached.
With this one exception, surgical results and morbidity for WPW syndrome surgery are
identical to pervious experience with this arrhythmia.
AV Nodal Reentrant Tachycardia
CRYOSURGICAL MODIFICATION OF THE AV NODE
The objective of surgery for AV nodal reentry tachycardia is to interrupt one of the two
conduction pathways through the AV node while leaving the other conduction pathway
intact. [44 ] , [48 ] The perinodal cryosurgical procedure ablates the slow conduction
pathway and preserves the fast conduction pathway. The right atrium is opened during
normothermic cardiopulmonary bypass (Fig. 26-27) . After localizing the His bundle,
atrial pacing is instituted, and the AV interval is monitored on a beat-to-beat basis as
described above. [49 ] A nitrous oxide cryoprobe with a 3-mm-diameter tip is placed
over the tendon of Todaro at the upper edge of the os of the coronary sinus (see Fig.
26-27 ). Cryothermia is applied at a temperature of -60°C for 2 minutes. Three or four
more cryolesions are placed along the tendon of Todaro, moving sequentially toward
the apex of the triangle of Koch near the His bundle. Cryolesions are then placed along
the annulus of the tricuspid valve, beginning just beneath the os of the coronary sinus.
Usually, the AV interval increases progressively during cryothermia as the AV node is
approached from the posterior aspect. This allows the electrophysiologist to notify the
surgeon of the degree of AV interval prolongation with each succeeding beat.
Cryothermia is terminated instantly with development of incomplete AV block; AV
conduction resumes invariably within 2 or 3 beats, and the AV interval returns to its
control value during the ensuing 10 to 15 beats. The cryoprobe is then moved slightly
more peripherally until cryothermia can be applied for the full 2 minutes to a given site
without causing heart block. Using the onset of temporary block to terminate each
cryolesion, cryolesions are placed at multiple sites within the triangle of Koch without
creating permanent AV block. The objective of the operation is to cryoablate as much of
the perinodal tissue within the triangle of Koch as possible without causing permanent
AV conduction block. Cryosurgery produces a definitive but reversible endpoint
(complete heart block).
In patients with AV node reentry tachycardia and concomitant WPW syndrome, the
WPW syndrome must be corrected first before any attempt is made to treat AV node
reentry. This sequence is essential because the discrete cryo-surgical procedure for AV
node reentry depends on the ability to monitor exclusive conduction through the AV
node-His bundle complex on a beat-to-beat basis. If the patient has a functioning
accessory pathway that conducts antegrade, it is impossible to monitor the effects of
cryosurgical modification of normal AV conduction during atrial pacing because the
atrial impulse travels preferentially across the accessory pathway to the ventricles.
SURGICAL DISSECTION
Operative dissection for AV nodal reentry tachycardia is performed through the same
surgical approach. [50 ] , [51 ] Intraoperative mapping is usually performed prior to
surgical dissection with normothermic cardiopulmonary bypass. Using a hand-held
bipolar electrode, earliest atrial activation during AV nodal reentry tachycardia occurs
just superior and medial to the AV node in those patients with type A tachycardia and
just superior and lateral to the AV node near the os of the coronary sinus in those
patients with type B tachycardia. Under cardioplegic arrest, stay sutures are placed in
the posterior tricuspid annulus to facilitate dissection and exposure. An incision is made
through the right atrial wall immediately behind the tricuspid valve annulus, commencing
just inferior and lateral to the os of the coronary sinus and extending superior and
medial over the central fibrous body. The right atrial wall is reflected superiorly, using a
knife to expose the posterior septal space. The AV node and central fibrous body are
identified.
For type A AV nodal reentry tachycardia, the superolateral connections of the AV node
to the atrium via the coronary sinus are left undisturbed (Fig. 26-28A,C) . The tendon of
Todaro is traced forward to the central fibrous body and then the tendon, along with all
muscle over the central fibrous body and intraatrial septum superior and medial to the
AV node and down to the submucosa or fat, and the atrial septum are resected with a
knife as far superiorly as the level of the coronary sinus. Inferior and lateral dissection
stops before the AV node, but more posteriorly, the dissection exposes the mitral
annulus and the superior process of the left ventricle. Care is used not to dissect
between the AV node and the central fibrous body because this may divide the His
bundle.
In type B AV nodal reentry tachycardia, the superior and medial connections of the AV
node to the atrium are left undisturbed (Fig. 6-28A,D) . The free wall of the right ventricle
is dissected with a knife from just inferior and lateral to the os of the coronary sinus to
just lateral to the AV node and posterior to the AV nodal artery onto the interventricular
septum and extends in depth to just beneath the epicardium. The inferior and posterior
walls of the coronary sinus are dissected to clean the epicardium from the os of the
coronary sinus to the level of the left atrial wall to expose the right coronary sinus. This
dissection divides all connections between the AV node and the right atrium superior
and lateral to the AV node.
Although the surgical techniques designed to cure AV nodal reentry tachycardia have
been employed for only a short period, results are excellent. There are no operative
deaths in any series. Following the perinodal cryosurgical procedure, smooth AV node
conduction curves through the remaining single conduction pathway are demonstrated
in all patients, and none has had inducible AV nodal reentry tachycardia
postoperatively. Moreover, all patients maintain normal conduction through the AV
node-His bundle complex without recurrent AV nodal reentry tachycardia. The surgical
dissection technique is associated with a low incidence of permanent complete heart
block and a low incidence of recurrent AV nodal reentry tachycardia.
Automatic Atrial Tachycardia: Surgical Ablation
Surgery is reserved for symptomatic patients who fail rf catheter ablation or those with
multiple foci; the ablative surgical therapy available depends on the ability to map the
foci successfully intraoperatively, which in turn depends on the ability to reproduce the
arrhythmia under general anesthesia. Failing this, isolation procedures based on the
results of the preoperative electrophysiolgic study are available for both the right and left
sides of the atrium or the atrial septum.
If the tachycardia focus can be localized, a number of techniques are advocated for
surgical treatment. [23 ] , [44 ] Cryoablation of the ectopic focus, with or without
cardiopulmonary bypass, is utilized. Alternatively, wide excision of foci located on the
right atrial free wall with a pericardial patch repair may be used. Foci located on the
atrial appendage may be treated by simple excision and oversewing of the line of
resection. Others use a combination of cryoablation and resection.
Foci on the left atrium tend to be near the left superior pulmonary vein; localized
isolation procedures are described for these tachyarrhythmias, but with limited success.
In addition, a significant number of these ectopic foci are localized on preoperative
study to the left atrium but cannot be localized intraoperatively, and therefore, a localized
isolation procedure cannot be done. In both instances, ectopic foci should be excluded
from the remainder of the heart using the left atrial isolation procedure (described
below). Following the left atrial isolation procedure, patients remain in normal sinus
rhythm despite the presence of an incessant tachycardia confined to the left atrium. No
adverse sequelae are noted over a 7-year follow-up period with this procedure. This
therapy is preferable to the alternative of elective His bundle ablation and pacemaker
insertion.
Right atrial tachycardias are usually confined to the body of the right atrium and may be
multifocal. If the arrhythmia circuit or focus cannot be localized at surgery, a right atrial
isolation procedure that isolates the body of the right atrium while leaving the atrial
pacemaker complex in continuity with the atrial septum and ventricles should be
performed.
If the focus of origin for ectopic atrial tachycardias can be localized adequately in the
operating room, operative procedures for isolation and/or ablation of the arrhythmia
should be uniformly successful.
Atrial Flutter
Surgery for atrial flutter in the past has been sporadic, limited by the infrequency of this
arrhythmia in patients coming to operation, in terms of both mapping and application of
ablative techniques. [44 ] Interruption of large macroreentrant right-sided circuits
responsible for type I flutter (see Fig. 26-21E ) by a right atrial free-wall incision
experimentally and clinically results in recurrence of a new flutter circuit that often
involves the surgical incision as a focus of reentry. [52 ] More recently, patients with
flutter coming to operation for concomitant procedures receive cryolesions to the area
of critical slow conduction in the lower right atrium, where rf ablation is performed.
Atrial Fibrillation
Atrial fibrillation (AF) is a common arrhythmia that is associated with significant

symptoms and morbidity. The symptoms of palpitations, presyncope, dyspnea, and
exertional intolerance may be caused by poorly controlled ventricular response rates at
rest or with exercise or by an irregular ventricular response to the rapid atrial rhythm that
results in beat-to-beat variability of ventricular filling. [53 ] A minority of patients, such as
those with dilated or ischemic cardiomyopathy, also have exacerbation of congestive
heart failure due to loss of the atrial contribution to ventricular filling. The major morbidity
of AF is attributable to left atrial thrombus formation and subsequent thromboembolic
events, especially embolic stroke. [54 ] Although the risk of stroke may be reduced with
warfarin anticoagulant therapy, it is still higher than observed in the general population.
[55 ] The goals of ablation therapy in atrial fibrillation, therefore, are to either improve
symptoms or decrease atrial thrombus formation and subsequent embolic events.
PREVIOUS SURGICAL THERAPIES FOR ATRIAL FIBRILLATION
Atrial fibrillation is associated with three detrimental sequelae, namely, loss of atrial
transport function, loss of a regular cardiac rhythm, and thromboembolism. Each of
these may be an indication for intervention for this arrhythmia; the most important of the
three is prevention of thromboembolism.
In the past, the only therapeutic option available when medical therapy failed to control
the ventricular response to rapid AF was surgical ablation of the His bundle and
implantation of a VVI pacemaker. [56 ] In many series, however, patients with the
combination of VVI pacing and congestive heart failure experienced a 50 percent
3-year mortality. This is a slightly more effective option with transvenous rf or
direct-current (dc) ablation of the His bundle and implantation of a rate-response
ventricular inhibited pacemaker. This approach still does not address problems of
thromboembolism or loss of transport function.
The ideal ablative procedure for AF accomplishes five goals: (1) elimination of atrial
fibrillation as a clinical arrhythmia, (2) restoration of sinus rhythm, (3) maintenance of AV
synchrony, (4) restoration of atrial transport function, and (5) by virtue of goals 1 to 4, a
decrease in or elimination of the risk of thromboembolism by eliminating passive stasis
of blood in either or both atria. [57 ] The appropriateness of any intervention should be
judged against these five criteria; ablative therapy is less than optimal to the degree that
one or more are not achieved.
The traditional ablative paradigm involves identification of the clinical arrhythmia,

accurate electrophysiologic definition and anatomic localization of the arrhythmia circuit
and/or origin, followed by application of an ablative technique. However, specific
application of ablative therapy based on electrophysiologic and anatomic information is
not considered possible in AF. The concept of a surgically created maze is the only
approach that meets these five criteria.
THE MAZE PROCEDURE
The surgical goals of the Maze III procedure [58 ] , [59 ] are to (1) reduce the critical
number of reentrant circuits available to maintain the fibrillatory process and (2) reduce
the surface area of the atrium available to maintain the fibrillatory process. Importantly,
the success of the operation depends on newly created anatomic relationships between
surgical incisions and fixed anatomic obstacles in the atria: the superior and inferior
cavae and tricuspid valve annulus on the right side and the pulmonary veins and mitral
valve annulus on the left side. Paradoxically, the Maze procedure reestablishes the
relationship between electrophysiology and anatomy in this arrhythmia.
Prior to cardiopulmonary bypass, the ascending aorta is cannulated for arterial inflow,
and the superior vena cava and extreme low right atrium are directly cannulated for
venous return. Complete mobilization of the heart including the SVC and IVC, the aorta
and aortopulmonary window, the transverse sinus, and Waterston's groove is
performed. The operation is currently performed under a single cross-clamp interval,
utilizing warm induction antegrade blood cardioplegia for cardiac arrest, with
maintenance continuous cold retrograde delivery throughout the remainder of the
procedure. Intraoperative mapping is not performed.
Following cardioplegic arrest and right-sided heart isolation, the right atrial appendage
is transected, and lateral free-wall and posterior incisions parallel to the interatrial
groove are made. The posterior incision is carried well onto the SVC and IVC (Fig.
26-29) . The lower posterior incision is then fashioned as a T anterior to the IVC, down
to the AV groove on the right side of the heart (Fig. 26-30) . This transmural incision is
completed from inside the right atrium using an endocardial dissection technique
similar to that employed for accessory pathway ablation (Fig. 26-30C) . Atrial fibers
along the tricuspid annulus are ablated with a cryolesion (Fig. 26-30D) , and this
incision is closed, first endocardially and then epicardially to the level of the AV groove
(Fig. 26-30E) . The lower posterior longitudinal incision is closed up to the T to prevent
tearing the proximal IVC with retraction.
A counterincision is made on the medial aspect of the right atrium (Fig. 26-31) down to
the anterior tricuspid annulus; again, this dissection is performed endocardially once the
anterior AV groove is met. Endocardial dissection and cryoablation of the annulus are
performed, and this incision is closed to the base of the excised appendage. This
completes the right-sided incision sequence, which isolates the majority of the right
atrial free wall from the atrial septum anteriorly and posteriorly.
The left-sided incisions are created as follows (Fig. 26-32) . A standard left atriotomy in
Waterston's groove is performed, with extension of the lower end between the right
inferior pulmonary vein and the posterior aspect of the IVC. An atrial septal incision is
then made, beginning approximately at the level of the right superior pulmonary vein and
extending in a curvilinear fashion toward the os of the coronary sinus. It is critical that
this incision not extend across the tendon of Todaro. This exposes the entire left atrium
transseptally. Encirclement of the pulmonary veins is completed inferiorly and superiorly
to a point beneath the orifice of the left atrial appendage. Tissue orientation is
maintained by excising the appendage from within, leaving a 1-cm bridge of tissue
connecting these three incision lines (Fig. 26-33) . A cryolesion is placed at this junction
to complete the pulmonary vein isolation. The transsected orifice of the atrial
appendage is closed from within, and isolation pulmonary vein incisions are closed
approximately halfway.
To isolate the bridge of tissue between the lower aspect of this encircling incision and
the posterior mitral annulus, an incision is made first transmurally and then endocardially
into the posterior left ventricular AV groove down to the mitral annulus (Fig. 26-34) .
After dissection of the atrial muscle from the AV groove fat pad, a cryolesion is placed
at the level of the annulus. The AV groove fat pad is carefully dissected, and the
coronary sinus at this location is isolated and frozen with the cryoprobe over a distance
of approximately 1 cm. At this point, mitral valve repair or replacement is performed, if
necessary. The vertical annular incision is closed, and the remainder of the pulmonary
venous encircling incisions are closed to the level of the left side of the atrial septum
(Fig. 26-35) . The atrial septal incision is then closed from the right side, followed by
closure of the pulmonary venous encircling incision. Closure of the septal incision is
completed on the right side to the level of the posterior longitudinal incision (Fig. 26-36)
. Prior to removing the cross-clamp, air is evacuated from the left side of the heart using
usual maneuvers. This completes the operative procedure. The remainder of the
right-sided incisions are closed as illustrated in Fig. 26-37 . Perioperative temporary
atrial and ventricular pacing wires are placed prior to closing the sternotomy incision.
Transesophageal echocardiographic evaluation along with visual inspection of the

contracting atria after bypass documents left and right atrial transport function during
sinus rhythm and during atrial pacing.
After completion of the Maze procedure, reentrant circuits cannot form because
distances between incisions, the nonconducting fibrous skeleton of the heart, and fixed
anatomic obstacles of the right and left atria prevent formation of reentrant circuits. The
circuits become extinguished by an excision or obstacle before a reentrant loop is
established. The only sustained conduction pathway originates from the sinus nodal
area, proceeds anteriorly around the right atrial tissue, enters the atrial septum
anteriorly, and depolarizes the AV nodal tissue; this anterior atrial depolarization carries
across to the anterior left atrium and then around posteriorly to depolarize the tissue
beneath the pulmonary veins (Fig. 26-38) . Conduction down the atrial fibers contained
within the coronary sinus is interrupted, however, by placement of a cryolesion on the left
atrial side of the sinus. The remainder of the posterior atrial free walls are depolarized
from the wavefront exiting the atrial septum posteriorly. Thus normal AV conduction is
maintained, and the entire atrium is depolarized in sequential fashion after this
operative procedure.
RESULTS OF TECHNICAL MODIFICATIONS TO THE MAZE PROCEDURE
The first Maze procedure was performed in September of 1987. That patient was
followed for 6 months, and then the second procedure was performed. This observation
process was repeated until the safety and efficacy of the initial operative approach were
documented. The early follow-up in Maze patients documented four sequelae of the
initial operative approach [60 ] :
1. Inability to achieve maximal heart rates with exercise, termed a blunted

chronotropic response to exercise
Inability to document left atrial transport function in 30 percent of patients despite the
presence of right atrial transport in all patients
A requirement for new pacemaker implantation in over 40 percent of patients
Technical difficulty with performing the procedure in patients who had undergone
previous cardiac surgery because of the necessity to alter placement of the suture
lines
The inappropriate response to exercise and the pacemaker requirement were

attributed initially to possible devascularization of the SA node by surgical incisions
in this region. Elimination of one incision and movement of the medial SVC incision
more posteriorly were the modifications made ( Fig. 26-39 and Fig. 26-40 ), and
these were tested and verified in the experimental laboratory. Subsequent analyses
suggested alternative explanations for each of these findings.
The results of the Maze I procedure indirectly confirmed the findings of Boineau et al.
[61 ] regarding the atrial pacemaker complex. These findings documented in dogs
an area of SA nodal tissue extending along the SVC-right atrial junction; pacemaker
cells capable of firing at a lower rate were located at the caudal end of this complex,
while pacemaker cells capable of more rapid intrinsic depolarization rates were
located more superiorly and anteriorly. Neurocardiogenic influences were thought to
play an important role in influencing the dominant pacemaker site at any given time.
[7 ] The Maze I operation surgically eliminated conduction of impulses arising in this
anteromedial area and explained the blunted response to exercise.
Pacemaker implantation was required initially in approximately 40 percent of

patients. [62 ] While DDDR devices were implanted, patients required only atrial
chamber pacing for junctional rhythm with a slow or absent SA response or for a
chronotropically incompetent SA node response, usually below 40 beats per minute
at rest. In addition, a small number of patients had previous pacemaker implantation
(usually a VVIR device following AV node ablation) in conjunction with paroxysmal or
chronic AF, and in these patients, pacemakers were upgraded to dual-chamber
systems. Careful analysis of preoperative electrophysiologic data (Holter and/or
event monitoring, preoperative electrophysiologic study, hospital monitoring)
documented evidence of sick sinus syndrome in the majority of patients who
required a pacemaker for atrial pacing postoperatively. This analysis encompassed
the first 103 patients in the series, 47 of whom had undergone the Maze I or II
procedure and 56 of whom had undergone the Maze III procedure (Table 26-4) .
Impairment of atrial transport function on the left side following the Maze I and II
procedures was thought to be related to impairment of right-to-left atrial conduction.
Both procedures divided Bachmann's bundle, a thick bundle of atrial tissue that runs
across the top of the atrial septum posterior to the aorta to rapidly (approximately 40
ms) conduct the SA impluse to the left side of the atrium. Surgical interruption of the
bundle slowed conduction through the maze from the right to the left to 350 to 400
ms. In some cases at least, this initiated left atrial systole when the mitral apparatus
was closed during isovolumic contraction or ventricular systole. Eliminating division
of Bachmann's bundle prevented this intraatrial conduction delay and was
incorporated into the Maze III procedure.
In the early experience, primarily with the Maze I procedure, a total of nine patients
had had a variety of prior cardiac surgical procedures, including ASD closure, aortic
and mitral valve replacement, myocardial revascularization, or ablation of
supraventricular arrhythmias. The Maze operation in these patients required
modifications of the procedure that were individualized for each patient. The inability
to perform a standardized operation prompted the recommendation that the Maze
procedure not be performed in reoperative patients.
CURRENT RESULTS WITH THE MAZE III PROCEDURE
The following analysis compares results with the Maze I and II procedures with those
from the currently performed Maze III procedure. [58 ] , [63 ] The Maze II operation
was an intermediate modification between Maze I and III used in only 15 patients.
This was technically more complicated and was modified further into the technically
straightforward Maze III procedure.
A total of 139 patients have undergone surgical intervention through January of 1995
at our institution. [86 ] Mean age was 52 ± 11.5 years. Fifty-five percent of patients
had paroxysmal fibrillation or flutter, while 45 percent had chronic AF. Arrhythmia
intolerance was the indication for surgical intervention in 65 percent of patients,
while drug intolerance was present in 11 percent. A previous thromboembolic event
prompted surgery in the remaining 24 percent. Only a small percentage of patients
had abnormal ventricular function preoperatively. Thirty-one percent of patients had
a concomitant cardiac surgical operation at the time of the Maze procedure. There
have been 3 perioperative deaths in the overall series (2.2 percent), 1 in the Maze I/II
group and 2 in the Maze III group. There has been 1 late death, at 4 years.
Forty-seven patients underwent the Maze I/II procedure, while the remaining 92 had
the Maze III procedure. Except for the 9 patients who underwent reoperation, the
patient demographics are similar in both groups (Table 26-5) . Postoperative
complications for the two groups are listed in Table 26-6 . The incidence of atrial
arrhythmias is similar. These are thought to be related to shortening of atrial
refractoriness as a result of surgery; as the atrium heals, refractoriness returns to
normal, and reentrant circuits are extinguished by atrial surgical suture lines and
fixed anatomic obstacles. The incidence of the remaining complications in each
group is low and similar between the two groups and similar to other open heart
antiarrhythmia procedures. [45 ]
Table 26-7 illustrates the follow-up data for these patients. All operative survivors
were at risk for pacemaker implantation; this requirement was reduced from 54.3
percent (25 of 46) in the Maze I/II group to 27.8 percent (25 of 90) in the Maze III
group. The vast majority of patients who require pacemaker implantation have
evidence of sick sinus syndrome preoperatively or have already undergone
pacemaker implantation. Only two pacemaker patients overall have sustained
iatrogenic injury, one patient in the Maze I/II group with devascularization of the sinus
node and one patient in the Maze III group with an anomalous coronary sinus repair
and postoperative complete heart block. This patient is the only patient in the entire
series who requires ventricular pacing.
Late follow-up (> 3 months) is available for all but one patient in the Maze I/II and in
78 of 92 patients in the Maze III group (see Table 26-7 ). Transient ischemic attacks
(TIAs) have occurred in 3 percent of the Maze I/II group and in 1 percent of the Maze
III group. The incidence of a blunted response to exercise has been reduced from 65
to 8 percent, most likely for the reasons outlined above. The remaining incidence of
chronotropic abnormality is probably related to underlying SA nodal disease. Nine of
46 patients had a late recurrence of fibrillation ( n = 3) or flutter ( n = 6) in the Maze
I/II group. All have been controlled effectively with medication. There have been no
late recurrences following the Maze III procedure.
Postoperative atrial transport function was documented in the majority of patients by

any one of five tests: intraoperative visualization, transesophageal
echocardiography, transthoracic echocardiography, three-dimensional magnetic
resonance imaging (MRI) scanning, and hemodynamic assessment of
atrioventricular pacing compared with ventricular pacing. A positive study with any
evaluation constituted demonstration of transport function.
Forty-three of 46 Maze I/II patients underwent postoperative evaluation for transport

function; 53 of 98 Maze III patients were evaluated. Right atrial transport function was
present in all Maze I/II patients. In the Maze III group, 52 patients (98 percent) had
right atrial transport present.
In the Maze I/II group, 30 of 43 patients (70 percent) had left atrial transport, while 48
of 53 patients (90 percent) in the Maze III group had left-sided atrial function. The
Maze III modification increases right- and left-sided transport to 98 and 90 percent of
patients, respectively. The reason for failure of left-sided atrial systole remains
uncertain. It is not clear whether operated patients will have a reduced risk of
thromboembolism as compared with a control population, because of the low
incidence. However, the procedure does not increase the incidence of
thromboembolism.
MODIFICATIONS OF THE MAZE PROCEDURE AND RHEUMATIC MITRAL

VALVE DISEASE
A number of investigators have modified the Maze procedure for combined

procedures. [66 ] [76 ] The majority are for rheumatic mitral disease; presumably, the
motivation is to simplify the overall operation. Others suggest on the basis of
preliminary mapping studies that the fibrillatory mechanism associated with valvular
heart disease primarily involves the left side of the atria, and therefore, surgical
procedures that address only the left atrium are all that are required. [70 ] , [73 ]
Several variations in surgical technique are described by investigators in this

country. First, patients who had mitral valve repair for degenerative disease had the
Maze procedure only after successful mitral repair was demonstrated
intraoperatively. [69 ] Second, patients with markedly enlarged atria had partial
resection of both atria as part of the Maze procedure. Still others performed a
left-sided Maze procedure with concomitant valve repair; interestingly, this patient
had an occurrence of atrial flutter postoperatively. Finally, the Washington University
experience with concomitant valvar disease and the Maze procedure has been
increasing. It currently is recommended that patients with concomitant disease
should be less than 70 years of age, have normal ventricular function, have
experienced embolic events related to long-standing (>1 year) fibrillation, be
medically refractory and severely symptomatic, have a left atrial dimension greater
than 60 mm, and have an easily reparable valve lesion. [69 ] , [77 ]
The largest experience with combined antifibrillatory and valve procedures is in

Japan, where a nationwide response to a survey was reported at the recent meeting
of the International Society of Cardiothoracic Surgeons (Japan). From 30 institutions
a total of 230 patients were reported; 196 patients underwent some form of
combined mitral plus (modified) Maze procedure. Twenty-one patients had
concomitant repair of an atrial septal defect, and only 3 of 230 had idiopathic atrial
fibrillation.
The majority of these procedures were modifications of the Maze technique ( Table
26-8 ). In a comparison between 51 patients who had a modified Maze procedure
plus valve surgery and historical controls without an antifibrillatory procedure,
morbidity and mortality were similar in both groups; recurrence rate for fibrillation in
the antifibrillatory surgical group was 8 percent, as compared with 90 percent in the
control group. A modified left-sided Maze technique that isolates the pulmonary
veins, amputates the left atrial appendage, and uses cryolesions to regionally isolate
a large portion of the posterolateral left atrial tissue has been used in 13 patients
with mitral valve disease. At late follow-up, 11 of 13 patients demonstrated sinus
rhythm and atrial transport; interestingly, all 11 patients had right atrial contraction by
echocardiography, and 9 (82 percent) had left atrial contraction. An atrial
compartment procedure was performed in 22 patients (16 with rheumatic heart
disease) in combination with mitral valve surgery; this procedure was either a left
atrial isolation procedure or a biatrial isolation procedure. Fourteen of 22 patients
were in sinus rhythm at 6-month follow-up; all 14 (the majority with rheumatic
disease) had evidence of both left and right atrial mechanical function at this time,
although in many patients detectable function took 2 to 6 months to return.
Another series of 15 patients underwent a combined Maze/mitral valve procedure.

Postoperative echocardiographic findings in this group demonstrated that in elderly
(> 60 years) patients with large left atria (up to three times normal), effective left
atrial systole could not be demonstrated despite sinus rhythm; in younger patients
with smaller atria, contractions were readily apparent.
THE LEFT ATRIAL ISOLATION PROCEDURE
A number of investigators have used the left atrial isolation procedure [78 ] for AF.
This operation was designed for ectopic atrial tachycardias originating on the left
side of the atrium that could not be localized during intraoperative mapping. After
cardioplegic arrest, the left atrium is opened, and the entire left atrial free wall is
surgically isolated from the atrial septum and mitral annulus. The appendage is
oversewn from within. Surgeons in Italy performed a left isolation procedure in 100
patients with AF secondary to mitral valve disease who had operative intervention;
70 percent of patients maintained sinus rhythm at follow-up. [79 ] Preoperative
duration of fibrillation longer than 6 months was a risk factor for recurrence. The risk
of thromboembolism is not addressed by isolation of the left atrium, which continues
to fibrillate; therefore, left atrial isolation does not meet the criteria for an ideal
ablative procedure. Sinoatrial function was satisfactory in all patients who
maintained persistence of sinus rhythm; during the same time interval, 80 percent of
a nonrandomized group of patients with AF who had mitral procedures without the
left atrial isolation had persistent fibrillation postoperatively.
There is interest in applying the concept of the Maze procedure to eliminate AF at

the time of mitral valve surgery throughout the world. At this time, it is not clear if
various modifications are as effective as the Maze operation in patients with mitral
valve disease. It is also unclear whether or not a higher recurrence rate of AF is
justified, particularly since many patients with rheumatic mitral disease have
impaired ventricular function and would benefit from restoration of sinus rhythm and
atrial transport. [80 ] Similar considerations apply to prospective and prophylactic
Maze procedures in other cardiac disease states. [81 ] , [82 ]
ABLATIVE THERAPY FOR NONISCHEMIC AND ISCHEMIC
VENTRICULAR TACHYCARDIA
Because of the electrophysiologic complexity of ventricular arrhythmias and difficulties

with preoperative and intraoperative mapping, development of ablative procedures for
ventricular tachycardia proceeded more slowly than for supraventricular arrhythmias.
The efficacy of surgical treatments for these arrhythmias has been demonstrated
recently by analysis of results with greater than 10-year follow-up. [83 ]
Patients with both ischemic and nonischemic ventricular tachycardia who are surgical
candidates for ablation operations undergo complete electrophysiologic, angiographic,
and ventriculographic evaluation. The catheter electrophysiologic study is performed (1)
to confirm that the arrhythmia is ventricular and not supraventricular in origin, (2) to
demonstrate that the arrhythmia is reentrant using induction and termination
programmed electrical stimulation techniques, and (3) to identify the earliest site of
origin of all morphologically distinct tachycardias using catheter mapping techniques.
[12 ] , [41 ]
Angiographic and ventriculographic evaluation is particularly helpful in the evaluation of

three nonischemic forms of ventricular tachycardia. Tumors are rare causes of
medically refractory ventricular tachycardia in children and adults. In patients with diffuse
cardiomyopathy, due to patchy myocardial fibrosis, angiographic and hemodynamic
data usually indicate abnormal myocardial contractility associated with recurrent
tachycardia. Ventriculography demonstrates diffuse dilatation of both ventricles.
Biventricular dilatation due to repeated bouts of tachycardia also can be present with
idiopathic ventricular tachycardia; however, pathologic evidence of primary cardiac
disease is absent. In arrhythmogenic right ventricular dysplasia due to transmural
infiltration of adipose tissue that causes weakness and aneurysmal bulging of three
areas of the right ventricle, ventriculography demonstrates diffuse dilatation, depressed
contractility, and delayed right ventricular emptying. Frank aneurysms of the
infundibulum, apex, and/or posterior basilar region occur, and hypertrophic muscular
bands in the infundibulum and anterior right ventricular wall result in a feathering
appearance of the outflow tract. Since the tachycardia originates in the right ventricle,
the 12-lead ECG shows a pattern consistent with left bundle branch block during
tachycardia. Right ventriculography should be performed in any patient with ventricular
tachycardia and this QRS-complex configuration.
The final decision regarding ablative therapy for ventricular tachycardias of both
ischemic and nonischemic origin is based on a variety of preoperative factors. The
primary indication for ablation is life-threatening arrhythmias that are refractory to
medical therapy.
Nonischemic Ventricular Tachycardia
SURGICAL TECHNIQUES
These tachycardias usually arise in the right ventricular free wall or septum and in
general are extremely resistant to medical therapy. Localized surgical isolation
techniques are usually employed for tachycardias arising in the right ventricular free
wall, while multipoint map-guided cryoablative techniques are used for arrhythmias
localized to the septum.
The surgical procedure developed for arrhythmogenic right ventricular dysplasia is

designed to isolate the arrhythmogenic myocardium from the remainder of the heart. [84
] For well-localized ventricular tachycardias, focal isolation or ablation procedures are
recommended. When the area of arrhythmogenic myocardium is larger, a transmural
encircling ventriculotomy is created with the surgically isolated pedicle based on
vessels originating from the right coronary artery. Two cryolesions are placed at the
proximal and distal aspects of the incision at the level of the tricuspid annulus to ensure
complete separation of all ventricular muscle fibers on either side of the incision.
Successful isolation has been achieved in a small number of patients. In certain
instances, intraoperative mapping indicates that the entire right ventricular free wall may
be arrhythmogenic to cause multiple morphologic types of tachycardia. Surgical
isolation of the entire right ventricular free wall was done in the past for these patients,
but occasionally, the right ventricle developed progressive dilatation. Today cardiac
transplantation is recommended over surgical isolation of the entire right ventricular free
wall.
Patients with ventricular tachycardia in association with the long-QT-interval syndrome

frequently have torsades de pointes. Medical therapy consists of beta-adrenergic
blockade coupled with permanent atrial or ventricular pacing. Surgical therapy consists
of left cervicothoracic sympathectomy with removal of the left stellate ganglion and the
first three to four left thoracic sympathetic ganglia. This procedure is associated with
early success but late failure; consequently, implantation of an internal cardiac
defibrillator (ICD) at the time of (or in lieu of) sympathectomy is recommended.
Ischemic Ventricular Tachycardia
The status of treatment for ventricular tachycardia and fibrillation is more complicated
than for supraventricular arrhythmias for several reasons: (1) the arrhythmias are
electrophysiologically more complicated and less well understood, (2) curative surgical
interventions are more complicated and historically associated with a higher morbidity
and mortality, (3) an alternative, palliative therapy exists that is associated with a high
degree of efficacy, and (4) catheter ablation techniques are still in the developmental
stages for many forms of ischemic ventricular arrhythmias.
Direct Surgery: Indications
Ventricular tachyarrhythmias in adults are most commonly secondary to ischemic

coronary artery disease. A current algorithm for the optimal surgical treatment of
refractory ischemic ventricular tachycardia is shown in Fig. 26-40 . With this algorithm
as a guide, the following points can be emphasized [12 ] , [41 ] :
The evaluation regarding surgical intervention for medically refractory ischemic

ventricular tachycardia should be made prior to the institution of amiodarone therapy.
The depressant effect of amiodarone on left ventricular function is aggravated by
ischemic cardioplegic arrest in the majority of patients; thus amiodarone therapy prior
to surgical intervention significantly complicates the operative procedure.
Surgical intervention is based primarily on the determination of sufficient left ventricular

function to permit survival after operation. Because most patients with ischemic
ventricular tachycardia have left ventricular aneurysm, accurate determination of ejection
fraction is difficult, and the result is not an accurate predictor of operative mortality.
Patients with discrete apical or posterior aneurysms and normal or near-normal
myocardium in the remainder of the heart are the best candidates for operation.
If the patient has global ventricular dysfunction and is not a clear surgical candidate, an
ICD should be implanted. ICD implant criteria are described below. If the patient is not
an ICD candidate, amiodarone therapy should be started.
If the patient's tachycardia is uncontrolled with an ICD or amiodarone, cardiac

transplantation should be considered. If the patient is not a transplant candidate, surgery
for ventricular tachycardia is the only therapeutic option available.
If the patient's left ventricular function is adequate for surgery, the surgical approach
outlined below is recommended.
Surgical Techniques
After intraoperative mapping during normothermic cardiopulmonary bypass is

completed (Fig. 26-41) , the ventricle is opened through the infarct or aneurysm. [84 ] ,
[85 ] This is performed with the heart beating at normothermia and preferably during
ventricular tachycardia. All associated endocardial fibrosis is resected except that
which extends onto the base of the papillary muscles. Approximately 10 percent of
patients still have inducible tachycardia following resection of endocardial fibrosis; this
indicates that the actual site of origin of the tachycardia is deeper in the myocardium
than the visible, fibrotic border. Endocardial cryolesions are applied with a 2.5-cm
nitrous oxide cryoprobe to the site(s) of origin of the tachycardia(s) as determined by
intraoperative mapping, and these ablate the myocardium responsible for the
tachycardia. Arrhythmogenic tissue at the base of the papillary muscles is cryoablated,
not resected. These techniques apply to both anterior and posteroinferior
infarcts/aneurysms (Fig. 26-42) .
Following resection and cryoablation procedures, programmed electrical stimulation is

applied in an attempt to reinduce the arrhythmia. If ventricular tachycardia is still
inducible, mapping is performed, and the remaining arrhythmogenic myocardium is
again cryoablated. If the arrhythmia is no longer inducible, there is a 98 percent chance
that is has been permanently ablated. If coronary artery bypass grafting or other
procedures are required, they are performed after mapping and endocardial resection.
The reason that cardioplegic solution should not be administered until the antiarrhythmic
portion of the operative procedure has been completed successfully is that cardioplegia
may temporarily alter delicate reentry circuits to cause tachycardia. If the
antitachycardia procedure is performed during cardioplegic arrest, it is impossible to
determine intraoperatively whether or not the surgical procedure has ablated the
arrhythmias. Following cardioplegia, the ventricle is revascularized and remodeled
using one of several ventriculoplasty techniques (see Chap. 24).
Surgical Results: Pre-ICD
The success rate for patients who survive surgery for ventricular tachycardia using these
techniques is 87 percent at 9 years in our series. Long-term survival in our series is 72
percent at 9 years following successful operative intervention. [83 ]
The pre-ICD (before 1988) experience with direct surgical intervention

(aneurysmectomy plus endocardial scar resection, with or without intraoperative
mapping) for ventricular arrhythmias from five centers that each reported over 50
patients with over 5-year follow-up has been reviewed ( n = 258). All medically refractory
patients presenting both electively and emergently were reported, including a relatively
high percentage of patients for whom no other therapy was available at the time )(Table
26-9)A . In this compiled series, operative mortality was 14 percent. Recurrence rate for
ventricular tachycardia demonstrated at late postoperative electrophysiologic study was
20 to 25 percent (ranging from 2 to 38 percent) in survivors after surgery alone. When
recurrence was demonstrated at late postoperative study, antiarrhythmic drug therapy
reduced the reinducibility rate to less than 5 percent. The sudden death rate in survivors
was 0.7 percent per year, and overall survival at 5 years was 70 percent in patients who
survived surgery. Importantly, this survival is not different from that for patients with
ischemic coronary disease and moderately severe ventricular dysfunction without
ventricular tachycardia. Thus, in patients who survived surgical intervention, the overall
cure rate was 95 percent, with survival determined by the underlying degree of ischemic
ventricular dysfunction. The incidence of sudden cardiac death (SCD) was extremely
low. Similar data have been compiled by others more recently (see Table 26-9B ).
Surgical Results: Post-ICD
Direct surgery for ventricular tachycardia continues to be performed in selected centers

after the ICD became widely available in 1988. [46 ] At Washington University, the
difference between this population and the earlier population is that the ICD is now
available to treat patients who are considered high risk for direct surgical intervention
because of global ventricular dysfunction, lack of a ventricular aneurysm, polymorphic
and/or multiple morphologic types of tachycardia, or comorbidity.
Patient selection reduced operative mortality at our institution from 14 to 5.7 percent for
35 patients operated on between 1988 and 1992 using surgical techniques that were
identical to our earlier experience (see Table 26-9C ). In patients with anterior
aneurysms, mortality was 4 percent. [86 ] These results are nearly the same as those
reported by others for similar operations in similar patients. Surgical cure rates are 97
and 89 percent, respectively. The incidence of sudden death is zero after surgery.
Thus patients who currently undergo successful surgery have an extremely high
probability of cure of their arrhythmia and a life expectancy determined by the underlying
ischemic disease process and degree of ventricular dysfunction.
Role of the ICD in Direct Surgical Candidates with Ventricular Tachycardias
The current role for device therapy in patients considered or undergoing direct surgical
ablation for ventricular tachycardia is as follows:
1. If an institution does not have the capability of performing computerized

intraoperative mapping or cryosurgery, if a procedure that is not dependent on
intraoperative mapping is performed, or if the surgical procedure is performed
under cardioplegic arrest, it is appropriate to implant ICD patches in these patients
at the time of surgery for ventricular tachycardia. The rationale for this
recommendation is that under these circumstances, approximately 25 percent of
patients have inducible tachycardia following operation.
If the tachycardia is inducible at the time of postoperative electrophysiologic study,

implantation of the ICD device should be performed.
The only absolute contraindications to ICD implantation include patient inability to

tolerate implantation and an episodic rate of tachycardia that can rapidly exhaust the
battery supply of the device or make the patient's life prohibitively uncomfortable due
to an excessive number of device discharges.
Operative and long-term follow-up results for surgery for ventricular tachycardia
argue strongly against routine implantation of an ICD device and coronary bypass
surgery for ventricular tachycardia in patients who are otherwise candidates for a
map-directed, wide-resection/cryoablative procedure as described above.
The ICD device provides a therapeutic option for patients with extreme degrees of
ventricular dysfunction. Judicious selection of these patients for ICD implantation
should reduce operative mortality for the surgery of ventricular tachycardia and
reduce the overall mortality rate for interventional therapy of ventricular tachycardia.
ICD Therapy in Ischemic Ventricular Tachycardia
Techniques for ICD implantation without thoracotomy at Washington University and

other institutions under clinical investigation protocols produce excellent
electrophysiologic outcomes and improved mortality and less morbidity as
compared with implantation via thoracotomy. In over 150 nonthoracotomy implants
using several devices under investigation, no operative deaths have occurred in
patients similar to those who had previously undergone thoracotomy implantation
without concomitant revascularization. Postoperative morbidity is considerably
reduced, and most patients were discharged within 24 hours of implantation.
However, a new set of late complications has developed that includes lead
dislodgment and fracture, device malfunction, and infection. [87 ] The advantages of
nonthoracotomy devices outweigh the disadvantages, and these are now preferred.
Patients with ischemic disease still need to be screened clinically and
angiographically for the need for treatable coronary arterial disease because all
long-term survival studies indicate that survival following direct ventricular
tachycardia surgery or ICD implantation is dictated primarily by the degree of
ventricular dysfunction. Myocardial revascularization should be undertaken whenever
possible. Furthermore, recent data suggest that revascularization reduces the
frequency of episodes of ventricular tachycardia/ventricular filbillation (VT/VF) in
patients with ICDs. Currently, ongoing trials are examining prophylactic implantation
of ICD devices in patients with myocardial ischemia who are undergoing
revascularization.
Currently, there are three management options for combination

revascularization/ICD therapy. In patients with only moderate degrees of ventricular
dysfunction, concomitant revascularization and implantation of the generator device
are often feasible. For patients with greater degrees of ventricular dysfunction,
placement of extrapericardial patches with or without epicardial rate-sensing
electrodes can be performed at the revascularization operation, with placement of
the remaining endocardial hardware and the generator at a second operative
procedure. Finally, if biphasic devices are available, the ICD can be implanted in its
entirety at a second nonthoracotomy operative procedure after the patient has
recovered from the revascularization; the success with biphasic endocardial
implants makes this the favored approach in patients with severe degrees of
ventricular dysfunction.
VT Surgery versus ICD Therapy versus Catheter Ablation
The operative mortality of 4 to 5 percent for direct VT surgery is not significantly

different from the experience with thoracotomy implantation of ICDs during the same
time interval. In those patients with ventricular tachycardia, the benefit of VT surgery
as compared to ICD placement via thoracotomy is the probability for cure in the VT
surgery group with similar risk of morbidity and mortality. These VT patients should
be treated with direct VT surgery whenever possible. Catheter ablation may be
attempted initially if the current limitations of this technique are understood.
How does the nonthoracotomy ICD experience affect this argument? With an
operative mortality that is nearly zero, and with significantly reduced postoperative
morbidity, these short-term results discourage prescription of direct surgery for
appropriate patients but fetter them to a lifetime of dependence on the ICD. In
patients with discrete aneurysms and VT that is amenable to intraoperative mapping
and ablation, the discharges and restrictions associated with nonthoracotomy ICD
technology diminish the quality of life that can be attained with direct surgery. In
recognition of these facts, the German Cardiac Society and the European Society of
Cardiology recently took the position that ICD implantation is only acceptable if the
patient is not a candidate for a possibly curative procedure (direct surgery or
catheter ablation).
Cost Issues: VT Surgery versus ICD Therapy
A number of reports have examined the cost efficacy of ICD therapy, with varying
results. Recently, a preliminary comparison of hospital costs associated with
specific therapies for ventricular arrhythmias between 1991 and 1993 was
undertaken at Washington University. [86 ] In this analysis, fully loaded hospital costs
for the inpatient admission during which the therapy was performed were compared
for patients undergoing direct VT surgery, good risk patients undergoing VT surgery
from within that group, thoracotomy implantation of an ICD, nonthoracotomy
implantation, and battery change (23-hour admission). While the numbers in each
group are small and statistical comparison is not possible, Table 26-10
demonstrates that when fully loaded costs (not charges) are examined, the cost of
device implantation as compared with surgery is not significantly different. For good
risk surgical patients, mean costs are actually less than those for either type of ICD
implant. Furthermore, ICD patients are subject to additional follow-up costs of
approximately $20,000 every 3 or 4 years for defibrillator battery change, even when
the generator change is performed as an outpatient procedure. These results cast
an unfavorable financial light on ICD therapy as compared with direct VT surgery in
appropriate patients.
As these ICD devices become smaller and easier to implant, assessment of the
benefits of ICD therapy will become even more difficult for the following reasons: (1)
the ease of implantation, low morbidity, and no mortality will make it easy to
consider application of this therapy to all patients with VT, VF, and SCD, with
abandonment of other forms of therapy, including antiarrhythmic drug therapy; (2) the
diminishing size and ease of implantation increase the tendency to compare ICD
therapy with pacemaker therapy; the danger in this comparison is that a system
malfunction, lead dislodgment, or infectious complications have a much higher risk
of patient death with ICD therapy than with pacing therapy; (3) from a medicolegal
standpoint, formal training programs for this rapidly evolving technology do not exist;
and (4) cost analyses must consider the high initial device cost and costs of
follow-up and replacement devices. [87 ] When one considers that only a small
fraction of patients with sudden death have been identified out of the total sudden
death population amenable to treatment, these considerations become even more
important. For these reasons, regulation of ICD device implantation seems
imminent, whether by government, third-party reimbursement agencies, or
physicians themselves.
PACEMAKERS
History
The early history of cardiac surgery includes the lethal complication of iatrogenic heart
block. Transthoracic pacing was available using Zoll cutaneous electrodes;
percutaneous pacing with endocardial electrodes was described in 1959. [4 ] , [5 ] An
implantable pacemaker using epicardial electrodes was described in 1960. [6 ] The
subsequent evolution of pacemakers and implantation techniques reflects successes
and failures of bioengineering and technology. Notable improvements in miniaturization,
power supply, electrical efficiency, pacing algorithms, programmability, lead fixation,
engineering of lead tips, materials durability, circuit reliability, venous access, device
telemetry, and transtelephonic telemetry have occurred. Inadequacies persist in lead
durability, chronic inflammatory responses to pacemaker materials, infection,
programming complexity, and cross-manufacturer programmer incompatibility.
International Pacemaker Code
A five-letter code describes pacemaker function. [7 ] The first three letters are in
common usage and must be understood by all clinicians dealing with pacemakers
(Table 27-1) . The first letter is the chamber paced, the second the chamber sensed.
The third letter describes the algorithm used to integrate pacing and sensing functions.
Thus, fixed-rate ventricular and atrial pacemakers are VOO and AOO, respectively.
Demand (rate-inhibited) pacers for the same chambers would be VVI and AAI. VDD
refers to a pacemaker that paces the ventricle only but senses both the atrium and the
ventricle. [8 ] DVI involves both atrial and ventricular pacing but only ventricular sensing.
DDD is the most flexible of current designs. Rate-responsive pacemakers are identified
by the letter R, as in VVIR.
Anatomic Factors
The conduction system is vulnerable to injury during heart surgery. Complete heart block
may occur as a result of suture placement during aortic, mitral, or tricuspid valve
surgery, during closure of septal defects, or during myotomy for idiopathic hypertrophic
subaortic stenosis (IHSS). The sites of these lesions are indicated schematically in
Figure 27-1 .
Physiology
CELLULAR ELECTROPHYSIOLOGY
Cellular membrane depolarization and repolarization, described elsewhere in this book,

are essential to automaticity of the cardiac chambers and the conduction system. The
mechanism of action of antiarrhythmic drugs is reflected in the Vaughan Williams
classification; the bradyarrhythmic effects of medications for control of atrial and
ventricular tachyarrhythmias may result in the need for chronic pacing by aggravating
sinus bradycardia or atrioventricular (AV) block. [9 ]
In the resting state, the outer surface of the cell is positive, and the interior of the cell is
negative. This suggests that a negative current applied to the outside of the cell
produces a greater potential difference and is more successful in depolarizing the cell
than a positive current.Empirically, such a relation is observedunipolar pacing
thresholds are lowest when the negative terminal (cathode) of a pacing system is
connected to the heart and the positive terminal (anode) is connected to the ground. [10
] Pacing thresholds are more sensitive to polarity than is the amplitude of the
electrogram.
AV BLOCK
First-, second-, and third-degree blocks are recognized. First degree block represents
prolongation of the PR interval. Second-degree block involves incomplete dissociation
of the atria and ventricles, which results in either progressive P-R prolongation and
dropped beats (Wenckebach, Mobitz I, usually AV nodal block) or frequently dropped
beats without prior progression of the P-R interval (Mobitz II, usually in the His-Purkinje
system). [11 ] Third-degree block involves complete atrioventricular dissociation.
First-degree block at a low atrial rate may progress to a Wenckebach rhythm as atrial
rate is increased. Left and right bundle branch blocks and left anterior and posterior
hemiblocks complete the spectrum of conduction system blocks recognizable by
electrocardiogram. The etiology of AV block includes ischemic heart disease,
idiopathic fibrosis, cardiomyopathy, iatrogenic damage, AV node ablation, Lyme
disease, bacterial endocarditis, lupus erythematosis, and congenital heart disease.
SINUS NODE DYSFUNCTION
Sinus bradycardia and sinus arrest may require pacemaker therapy. Sinus pauses in
excess of 30 seconds were documented in our hospital in otherwise healthy medical
students and residents. Whether pacemaker insertion is warranted depends on whether
the sinus node dysfunction is symptomatic or whether symptoms are likely to occur
based on planned administration of bradyarrhythmic drugs required for ancillary
conditions. Causes of sinus node dysfunction include coronary artery disease,
cardiomyopathy, and reflex influences.
The spectrum of reflex problems is broad and includes carotid sinus hypersensitivity,
vasovagal syncope, and oddities like micturation induced and deglutition syncope. [12 ]
Both cardioinhibitory (asystole >13 seconds) and vasodepressor (marked fall in blood
pressure despite adequate heart rate) components of reflex-mediated syncope are
recognized. Whether pacemaker insertion is indicated is determined by clinical
judgment based on the duration of asystole. Objective data is provided by tilt-table
testing with and without temporary pacing. Current trends favor pacemaker insertion for
asystolic intervals greater than 3 seconds; medical therapy is favored for
vasodepressor syncope even with substantial sinus bradycardia. [13 ] Dual-chamber
pacing is strongly favored for this population because of beneficial effects of AV
synchrony on stroke volume and symptomatology. [12 ] Retrograde conduction may
require special pacing algorithms in patients with cardioinhibitory syncope.
DUAL-CHAMBER PACING AND AV SYNCHRONY
At normal atrial rates at rest and during exercise, AV synchrony is important for
maintenance of ventricular filling and stroke volume. In the normal heart, stroke volume
increases 515 percent with AV synchrony versus the asynchronous state. [14 ] In the
presence of left ventricular (LV) hypertrophy or heart failure, atrial contraction is of
greater clinical significance. Apical pacing the right ventricle (RV) disrupts the normal
sequence of activation, because depolarization propagates slowly over the ventricular
walls; propagation through the His-Purkinje network is faster and more symmetrical.
Disruption of the activation sequence probably reduces mechanical efficiency, and
explains why cardiac output and ejection fraction are worse during DDD than AAI
pacing and why the ventricular-aortic pressure gradient in IHSS (idiopathic hypertrophic
subaortic stenosis) is reduced by DDD pacing. [15 ] , [16 ]
Loss of AV synchrony not only decreases stroke volume and cardiac output but also
produces other symptoms that are particularly disturbing to some patients, related to
contraction of the atria against closed AV valves and other physiologic changes. The
resulting constellation of symptoms, known as pacemaker syndrome, is relieved
immediately by dual-chamber pacing. [17 ]
RATE RESPONSE TO INCREASED METABOLIC DEMAND
At times of high metabolic demand, cardiac output normally increases, and is

potentiated physiologically by increased myocardial contractility, increased venous
return, and increased heart rate. In patients with a normal sinus node rate response to
exercise and complete AV block, dual-chamber pacemakers restore both AV
synchrony and, by tracking the atrium, a normal rate response. With dual-chamber
pacing and sinus-node incompetence (no atrial rate increase with exercise) or with
single-chamber ventricular pacing, alternate methods of sensing and compensating for
metabolic demand are needed. In marketed-rate responsive pacemakers, body
vibration or respiratory rate are employed to estimate metabolic demand. [18 ] , [19 ]
Other indicators under evaluation include body temperature, venous oxygen saturation,
Q-T interval, RV (right ventricular) systolic pressure, and RV stroke volume. [20 ] [24 ] All
proposed and implemented sensors may produce aberrant increases in heart rate. [25 ]
For example, a pacemaker that senses body vibration may be confused by a truck ride
on a bumpy road; a fever will cause excessive heart rate if the sensor tracks body
temperature.
Clinical Considerations
INDICATIONS FOR PACEMAKER INSERTION
With nearly 150,000 pacemakers inserted annually in the United States, insurance
carriers have a strong incentive to regulate pacemaker insertion. Two indications for
pacemaker insertion are importantone is based on clinical criteria, the other is based
on insurance carriers' criteria. If the latter are not met, neither the hospital nor the
physician is reimbursed. Medicare's guidelines are presented in Table 27-2 .
Documentation supporting the putative indication may be required. Medicare divides
indications into three categoriesjustified, never justified, and possibly justified. The
justified category is not problematic if documentation is adequate. The intermediate
category is problematic, particularly in relation to sinus bradycardia; a number of
ambiguities are apparent in this category. A common area of contention is whether a
patient's symptoms are related to an underlying bradyarrhythmia and whether that
association is adequately documented. Medicare allows pacemakers in support of
long-term, necessary drug therapy for conditions including supraventricular arrhythmias,
ventricular arrhythmias, hypertension, and angina. Although clinical research may
support new indications for pacemaker therapy such as IHSS, recognition of such
advances by Medicare often is slow.
The common clinical indications for transvenous pacemakers are symptomatic

atrioventricular block, sinus arrest, and sinus bradycardia. Attempts should be made not
only to document the arrhythmia but also to document that the arrhythmia is the cause of
the patient's symptoms. An example of a potential conflict is the elderly patient with near
syncope, coronary disease, carotid hypersensitivity, and nonsustained ventricular
tachycardia. The patient's symptoms could be owing to either of the two observed
arrhythmias, and an electrophysiology (EP) study may be necessary to define the
proper treatment. [26 ] When clinical and insurance carrier indications conflict, there is
no certainty that payment will be approved.
CHOICE OF PACING TECHNIQUE
Increasing acceptance and enthusiasm of cardiologists for dual-chamber pacing and a

high rate of success with current technology makes the recommendation of anything
other than a dual-chamber pacemaker for the patient in sinus rhythm increasingly
unpopular. Even paroxysmal atrial fibrillation, which prior to mode switching (described
in the following) prohibited dual-chamber pacing, is no longer a contraindication
because sinus rhythm may be maintained better by atrial than ventricular pacing. [27 ]
Similarly, dual-chamber pacing is now recommended for reflex-mediated syncope with
cardioinhibitory features. [12 ] Most cardiologists are not content with AAI, AAIR, VVI, or
VVIR pacing for patients with coronary artery disease and sinus bradycardia.
Dual-chamber pacing is the clear standard for all forms of atrioventricular block. For
example, a cardiologist colleague recently argued for DDD instead of VVI pacing in an
80-year-old demented woman with intermittent complete heart block.
VVI or VVIR pacing is indicated for patients in chronic atrial fibrillation with bradycardia,
and AAIR is generally accepted at our institution for cardiac allograft recipients with
sinus arrest or sinus bradycardia. Beyond that, cardiology opposition to single-chamber
pacing must be fought on a case-by-case basis.
Technical Considerations
TEMPORARY PACING
Profound bradyarrhythmias after cardiopulmonary bypass require urgent correction.

Ideally, in patients who are not in atrial fibrillation, temporary wires and temporary
external AV sequential pacemakers are used. We employ two pull-out teflon-coated
myocardial wires for RV pacing and two bare wire loops sewn to the right atrial (RA)
surface with 6-0 Prolene for atrial pacing. These wires are removed with gentle but
persistent traction when they are no longer needed; they generally function adequately
for 714 days. A period of bed rest and monitoring should be employed after the wires
are removed, to rule out the possibility of bleeding and tamponade. If the wires cannot
be easily removed, they are usually cut off at the skin level.
Acute bradycardia after temporary wires are removed may be treated with a
transthoracic pacemaker, temporary transvenous wires inserted under fluoroscopy, or
with chronotropic drugs such as atropine or isoproterenol. Percutaneous wire kits that
are designed for direct insertion into the right ventricle with a transthoracic needle
puncture in a dire emergency are available.
Problems with temporary epicardial wires include loss of RA or RV capture and loss of
RA sensing. Competition between an atrial pacemaker and the patient's intrinsic rhythm
may precipitate atrial fibrillation or atrial flutter. If atrial sensing is not adequate,
competition can be reduced by pacing the atrium considerably faster than the intrinsic
rate. If temporary lead dysfunction is owing to a short circuit between the wires near the
heart, pairing one wire with a cutaneous ground wire solves the problem.
POLARITY AND RATE IN TEMPORARY PACING
Reversing the polarity of temporary wires may reduce the problem of a rising pacing
threshold from unmanageable to manageable levels. A rigorous protocol for
management of temporary wires includes daily testing of pacing thresholds and testing
the effect of reversed polarity if the threshold is increasing. The most expedient way to
reverse polarity is to reverse the connector to the external generator. Output of the
generator should be increased before this is done, since the threshold after reversing
polarity may be substantially worse rather than better. The output of the external
generator in volts or milliamps should be at least twice as high as the measured
threshold.
For patients with hemodynamic compromise following cardiac surgery, pacing rate and
AV delay are variables that may importantly affect hemodynamics. Mean arterial
pressure is more closely related to cardiac output than peak systolic pressure. To
optimize cardiac output, mean pressure is examined as rate is increased in 10-bpm
increments and then decreased in similar increments. Rate adjustments are examined
over less-than-20-second time periods to minimize the importance of compensatory
reflex changes on the observations. The rate producing the highest sustained mean
arterial pressure generally is associated with the highest cardiac output.
Permanent Pacing
DEVICE DESCRIPTION
A permanent pacing system consists of pacing leads and a pacemaker generator. The
leads generally contain one or two conductors of stainless steel or special alloys
insulated from each other and their surroundings by silicone or polyurethane. The lead
tips are commonly platinum-iridium, carbon, or special alloys and may be modified to
increase the surface area or retain pellets of elutable chemicals. [28 ] The generator is
usually hermetically sealed and contains a battery, a telemetry antenna, and integrated
circuits. The power source generally is lithium iodide, but many other battery types are
used commercially, including rechargeable and nuclear batteries. The integrated
circuits, a marvel of miniaturization, include programmable microprocessors and
extensive memory functions as well as oscillators, amplifiers, and sensing circuits. [29 ]
The integrated circuits employ CMOS (complementary metal oxide semiconductor)
technology and VLSI (very-large-scale integrated) circuits that can be damaged by, and
must be protected from, ionizing radiation. [30 ] Available pacemakers are highly
programmable and can telemeter their internal status, the condition of their external
connections, their programmed settings, and recent activity. Unfortunately, no universal
programmer is availableeach device only responds to the programmer of its
manufacturer.
DUAL-CHAMBER PACING ALGORITHM
The basic functional algorithm of DDD pacemakers is rather complex and much of it is
not intuitive. [31 ] The critical programming parameters are the lower rate, the upper
rate, and the AV delay. The rate settings define the way the pacemaker responds to the
atrial rate. If the atrial rate falls between the upper and lower rate limits, the pacemaker
maintains a 1:1 response between the RA and RV. The pacemaker does not allow the
atrial rate to fall below the lower rate limit, and paces the atrium at that rate, if
necessary. If the atrial rate is faster than the upper rate limit, the pacemaker will
maintain the ventricular rate at the upper rate limit, but no faster, and loss of AV
synchrony results.
The algorithm for ventricular pacing depends on a programmable AV delay. The timer
starts when an atrial electrogram or pacing stimulus is detected. If ventricular
depolarization is not detected within the allowed interval, the ventricle is paced. With
atrial pacing, the atrial stimulus is recorded earlier in the cardiac cycle than the atrial
electrogram of spontaneous beats. This is compensated by allowing a longer AV delay
after paced beats.
A signal on the ventricular channel immediately after an atrial pacing stimulus may be
either a ventricular depolarization or far-field sensing of an atrial depolarization. Many
pacemakers deal with this ambiguity by pacing the ventricle at a very short (100 msec)
AV delay. Observation of a very short AV delay, known as safety pacing, indicates that
the pacemaker is detecting a signal during the longer AV delay. [31 ]
Most complexities of dual-chamber pacemaker programming relate to blanking and

refractory periods intended to neutralize crosstalk, to compensate for the onset of atrial
fibrillation, and to prevent retrograde AV conduction from producing
pacemaker-mediated tachycardia (see the following).
EPICARDIAL/ENDOCARDIAL LEADS
Early experience with cardiac pacing involved epicardial leads. [6 ] Applying leads to
the exposed surface of the heart is direct and intuitively appealing, but the epicardial
approach is associated with inferior long-term results. [32 ] Problems with epicardial
leads include fatigue-related lead fractures, and fixation methods that are more
traumatic and contact surfaces that tend to be larger than those employed with
endocardial leads. Smaller contact surfaces are associated with better pacing
thresholds and inferior sensing function; lead designs generally embody some
compromise to balance these attributes. [28 ] Permanent pacing from the epicardial
approach is particularly daunting in the presence of fibrosis and trauma associated with
reoperations. Recent progress in epicardial lead design is encouraging, and steroid
eluting leads may prove valuable. [28 ] Commercial leads for epicardial atrial and
ventricular pacing include sutureless (screw-in) and sutured varieties.
Epicardial leads present additional problems when they become infected. Although this
is a rare event, infection requires thoracotomy and adds trauma, risk, and morbidity
during lead removal. In practice, epicardial leads are required rarely, as for example in
patients with congenital heart disease in whom there is an unacceptable hazard of
systemic emboli with endocardial leads, because of right-to-left shunts (tetralogy of
Fallot) or single-ventricle physiology. The Fontan operation also may require epicardial
pacing.
An alternative method of inserting endocardial leads uses an epicardial approach. For

implantation of a DDD pacemaker during open-heart surgery, one preferred scheme is
depicted in Figure 27-2 . Endocardial atrial and ventricular fixed-screw, positive fixation
leads are introduced into the heart through small atrial punctures and passed to
appropriate cardiac chambers. They are fixed into position by axial rotation and tested.
When a tricuspid prosthesis or ring is inserted, one option is to pass the leads between
the sutures in the prosthetic ring and the valve annulus. A useful method of attaching
pacing leads directly to the epicardial atrial surface is illustrated in Figure 27-3 . Other
epicardial approaches for lead insertion in a patient with limited venous access are
described in the following.
UNIPOLAR/BIPOLAR
Pacemaker systems are either unipolar or bipolar. In bipolar systems, both conductors
are contained within an integrated bipolar lead. In unipolar systems, the patient's body
is used as a ground for anodal conduction; leads containing only a single conductor
carry negative current to the heart. Bipolar pacing systems are resistant to electrical
noise (oversensing) and adventitious diaphragm or chest-wall pacing. Bipolar systems
also are more resistant to interference from monopolar electrocautery and are
mandatory when a pacemaker and defibrillator are implanted in the same patient.
These advantages are offset by the increased engineering complexity of two
conductors in a single structure. Structural breakdowns of insulation or conductors are
more likely with bipolar leads and cause serious pacemaker malfunction. [28 ] , [33 ]
In comparison with unipolar leads, bipolar leads are larger, stiffer, and less easily
maneuvered than unipolar leads. My preference is for unipolar leads, however, because
the smaller size is advantageous for venous access and reduces bleeding in case of
venous or cardiac perforation. The increased flexibility of unipolar leads appears to
increase the stability of loops (Fig. 27-4) or J bends and may reduce the probability of
perforation through the right ventricular apex. A single lead design can be used for atrial
or ventricular pacing; specially shaped and stressed J leads are not needed for atrial
pacing.
Others see the increased stiffness of bipolar leads as an aid to maintaining the lead tip
firmly wedged into the RV apex and argue that conversion to unipolar pacing often is
possible if the anodal conductor fails. Recently, several small-diameter bipolar leads
have been marketed (Fig. 27-5) ; only time will prove their long-term stability in the
hostile environment of the human body.
LEAD FIXATION
Satisfactory retention of each lead tip in the location selected at the time of insertion is
essential to satisfactory long-term pacemaker function. In our experience, positive
fixation techniques are superior to other methods of lead fixation, particularly in
locations with minimal trabeculation. Most current positive fixation mechanisms involve
a small corkscrew at the tip of the lead ( Fig. 27-5A to Fig. 27-5F ) that is screwed into
the myocardium as is a corkscrew is screwed into a cork. The simplest screw-in lead
involves a fixed screw that is covered with soluble material to facilitate venous passage
and minimize chances of the lead tip perforating or impaling the cephalic vein (Fig.
27-5D) . The fixed screw provides tactile feedback on the firmness and reproducibility
of the fixation site. The Bisping lead incorporates a retractable screw, which is
extended or retracted by rotation of the pin at the lead tip with a plastic vise (Fig. 27-5C)
.
An alternate and equally popular form of lead fixation uses plastic tines analogous to a
sea anchor (Figs. 27-5A, 27-5B, 27-5E, and 27-5F) . The tines, which come in a variety
of shapes and sizes, are designed to wedge between and grip myocardial trabeculae.
Tined leads generally require larger introducers than screw-in leads and are not as
secure in ventricles that are smooth-walled (e.g., corrected transposition of the great
vessels) or massively dilated. Tined leads are less secure in the atrium, particularly if
the atrial appendage is obliterated. Nevertheless, excellent clinical results are reported
with tined leads. [34 ] , [35 ]
Technique of Pacemaker Insertion
EQUIPMENT/ENVIRONMENT
Properly functioning equipment is essential for pacemaker insertion. Pacemakers,

leads, a programmer, and a sterile magnet are basic. Mandatory accessories include
an assortment of Allen wrenches, adapters, silicone glue, and strip-away introducers.
Sterile plastic sleeves or camera bags should be available to allow programming
wands to be brought to the surgical field to retrieve electrograms or adjust generator
settings. Because of the dire consequences of infection, operating room standards for
air quality should be enforced if an electrophysiology (EP) laboratory is used for
pacemaker insertion. Monopolar cautery is potentially hazardous during pacemaker
insertion. To avoid confusion, we allow only bipolar cautery for routine cases.
ANESTHESIOLOGY
Pacemakers can be inserted in an EP laboratory by one skilled surgeon and one skilled
circulating nurse. My experience with this arrangement indicates that, for most
situations, it is quite satisfactory. When a problem such as angina, transient ischemic
attack, patient disorientation, or lidocaine toxicity arises, however, this approach
becomes problematic. Also, certain patients are simply too unstable because of
dementia, myocardial ischemia, heart failure, anxiety attacks, or ventricular tachycardia
(VT) to undergo pacemaker insertion without the presence of an anesthesiologist or an
equivalent, full-time advocate. Vancomycin reactions (Red Man syndrome),
pacing-induced ventricular fibrillation (VF), air embolism, Stokes-Adams attacks, and
uncontrollable dementia are additional clinical problems that arise without warning and
require the assistance of a skilled specialist. Colleagues have reported intraoperative
deaths during pacemaker insertion owing to hemorrhage and myocardial infarction.
Attempting to do these procedures in a fragile population without the presence of an
anesthesiologist is a gamble that often is not worth the risk.
MONITORING
Pulse monitoring until recently was based on R-wave detection from the
electrocardiogram (ECG). This is hazardous for pacemaker insertion because pacing
artifacts that fail to capture may not be distinguished from those that do capture. Thus,
subthreshold pacing may elicit a regular beeping sound from the monitor in an asystolic
patient. This problem is solved by oxygen-saturation monitors that beep only during
blood flow. However, ECG sounds must be turned off and the saturation monitor turned
up to make this solution workable. Direct monitoring by the anesthesiologist of the pulse
in the temporal, facial, or radial artery is still valuable for detecting asystole.
ANTIBIOTIC PROPHYLAXIS
Antibiotic prophylaxis is indicated before insertion of a prosthetic device. [36 ] We

prefer cefazolin, 1 gram, IV. We also irrigate the operative field with a portion of a
solution of 1 gram of cefazolin in a liter of warm saline. Patients who have a valve
prosthesis or who have a penicillin or cefazolin allergy receive vancomycin (500 mg)
and gentamycin (1 mg/kg).
Whether patients with implanted pacemakers should receive antibiotic prophylaxis at

the time of dental work and other procedures that cause transient bacteremia is
controversial. We recommend prophylaxis for 3 months after pacemaker insertion, to
allow some time for exposed endocardial portions of the pacing system to become
endothelialized.
PACING-SYSTEMS ANALYZER
Pacing thresholds and electrogram amplitudes are measured in the operating room
using a pacing systems analyzer. Some advocate examining the electrogram
characteristics and slew rate with an oscillograph before implanting a pacemaker, but
this is not essential if electrogram telemetry is available from the pacemaker (see the
following). The analyzer must function properly, and should be serviced and tested
periodically. The batteries must be checked and replaced when depleted. Any
discrepancies between measurements by the analyzer and the pacemaker should be
noted and related functions of the analyzer rechecked.
A skilled operator is needed to run the analyzer and record results. Alternatively, the
analyzer can be placed in a sterile bag and operated from the surgical field.
CABLES
The cables connecting the analyzer to the leads are the patient's lifeline. Even with
excellent quality control, defective cables may be delivered to the operating room.
Errors may also occur in connecting cables to the analyzer to produce open or
intermittent connections. A routine for testing cables and the integrity of their connection
to the analyzer is essential. After passing cables from the operating table, we initiate
pacing from the analyzer at maximum output. The alligator connectors are then briefly
brought into contact, to short-circuit the system. Current, measured in the analyzer,
should rise to the maximum measurable by the analyzer. If high current is not observed,
the circuit is faulty. The operation should not proceed until the problem is corrected, as
the analyzer is undependable. Connections to the analyzer should also be checked,
since inadvertent reversal of polarity may make measured pacing thresholds
inappropriately high.
FLUOROSCOPY
The fluoroscope is essential for transvenous device implantation; operating room

personnel need to be familiar with the fluoroscope. Needlessly distracting and
troublesome problems with resetting timers and releasing or locking brakes with
movement of the C arm can be avoided by a knowledgeable nurse or physician's
assistant. A backup unit should be available in case of sudden failure of fluoroscopy
equipment at a critical point in an implant; otherwise the options are blind lead insertion
or canceling surgery.
VENOUS ACCESS
Obtaining venous access is the first essential step in pacemaker insertion. The plan for
this affects preparation and the initial steps of the procedure. Important choices include
which side to employ and whether a cutdown or percutaneous venipuncture is used.
Cutdown approaches to the cephalic, external jugular, and internal jugular systems are
described. [37 ] The anatomy of subclavian vein puncture was described recently in an
effort to reduce the frequency of complications related to this approach (Fig. 27-6) . [33
] , [38 ]
In some patients, central venous access is effectively impossible. One recurring

example is the superior vena cava syndrome. Another is subclavian/innominate vein
thrombosis after chronic dialysis, mediastinal tracheostomy, or pacemaker lead
insertions. Although access from below is possible in these patients, the potential for
venous thrombosis and pulmonary embolism is a concern. [37 ] , [39 ] An approach
described by others, which we have found useful for DDD or VVI pacing, is a right
parasternal mediastinotomy at the level of the fifth or sixth rib. Through this, small
introducers are inserted into the right atrium through atrial purse-string sutures. The
leads are positioned under fluoroscopy. [40 ]
For reoperations, we use an earlier lead as a locater lead to identify the location of the
subclavian vein by fluoroscopy. The exploring needle from an introducer set is attached
to a syringe containing lidocaine, and the needle is walked along the course of the
locater lead. Local anesthesia is infiltrated as the needle is advanced, and fluoroscopy
confirms that moving the tip of the needle laterally moves the locater lead; this indicates
that the position of the needle and the locater lead are congruent in three dimensions.
The needle is advanced along the course of the locater lead until aspiration yields blood
and confirms entry into the deep venous system. If a guidewire cannot be advanced into
the vena cava, iodinated contrast is injected to visualize the anatomy and rule out
venous stenosis or thrombosis.
PACEMAKER INSERTION
Our preference is to approach the patient from the left. The fluoroscope is positioned on
the patient's right. The right arm is extended on an arm board. Drapes are suspended
from IV poles. One pole is caudad to the arm board. Careful positioning exposes the left
clavicular region while still leaving the patient adequate light and air. After skin
preparation, towels are aligned with the deltopectoral groove and clavicle to define
essential landmarks. The region of the incision and generator are infiltrated with 1
percent lidocaine to produce a field block. A 56 cm horizontal incision is made 4 cm
beneath the clavicle; the lateral extent of the incision just reaches the deltopectoral
groove. This places the generator away from the deltopectoral groove and axilla, to
avoid interference with left arm motion at the shoulder. An alternate incision, directly
over the deltopectoral groove, facilitates exposure of the cephalic vein, particularly in
obese females, but makes optimal positioning of the generator more difficult.
When the deltopectoral groove is exposed, additional anesthesia is infiltrated into the
lateral margin of the pectoralis and laterally into the deltopectoral fat. The dissection
proceeds into the deltopectoral groove, following the lateral edge of the pectoralis, until
the cephalic vein or another venous branch is exposed. Failure to find a vein may mean
the incision is too far cephalad or caudad or not lateral enough. The incision can be
deepened into the subpectoral fat, if necessary. If the vein is too small to pass a
pacemaker lead, the curved end of the guidewire for a 7 Fr introducer is extended and
advanced. [41 ] The method, illustrated in Figures 27-7 and 27-8 , can be used to
enlarge the vein at the point of access. If the guidewire will not pass centrally, a m;16
angiocath is advanced over the guidewire and used to inject a small amount of
iodinated contrast to visualize the venous system fluoroscopically. If the cutdown attempt
must be abandoned, precise localization of the subclavian vein by venogram reduces
the risk of subclavian puncture. If dual-chamber pacing is planned, the guidewire should
be reinserted through the introducer before the introducer is stripped away. This
provides venous access for the duration of the procedure. [42 ] A purse-string suture in
the muscle usually provides adequate control of bleeding and stabilizes the lead(s). [43 ]
, [44 ]
From the left side, a gentle spiral in the distal 10 cm of the stylet guides the lead across
the tricuspid valve to the apex. Ideally, the lead is advanced into the pulmonary artery
outside the cardiac silhouette to confirm that it is not in the coronary sinus. For
fixed-screw positive fixation leads, the stylet is withdrawn 35 cm before screwing the
lead into the myocardium with axial clockwise rotation. It is important to feel the reverse
torque as the lead is rotated; this torque is a guide to the security of fixation. We fix the
lead with a sequence of three consecutive 360° clockwise rotations of the lead shaft
and then release the torque. This fixation sequence is repeated as many times as is
necessary, until the lead is secure. If the tip is secure, significant reverse torque is felt
after the first 360° rotation. No more than three complete axial rotations are employed in
any sequence. When the lead is secure, the stylet is withdrawn and thresholds tested.
The patient is asked to hyperventilate and cough to confirm fixation. Ventricular pacing
thresholds should be less than 0.7 volts and R-wave amplitude should be more than 5
mv. For unipolar leads, impedance should be roughly 500 ohms. There should be no
diaphragmatic pacing at an output of 10 volts.
If the lead is dislodged by hyperventilation and coughing, or if thresholds are not

adequate, the lead should be relocated. A positive fixation lead can be unscrewed by
counterclockwise axial rotation until it floats free. Positive fixation leads can be secured
almost anywhere along the margins of the RV silhouette (Fig. 27-9) , including the RV
outflow tract (Fig. 27-10) . [45 ] In difficult cases, we relocate these leads as many as 15
times. The geographic center of the RV silhouette is not desirable, as the lead may
become entangled in the chordae tendineae (Fig. 27-9) .
For dual chamber pacing, the atrial lead is introduced next. A J or S stylet shape is best
for finding the atrial appendage from the left side. [44 ] The S shape also is useful for
passing a positive fixation lead to the right margin of the atrium near the junction of the
right atrium and inferior vena cava (Figs. 27-9 and 27-11) . P-wave amplitude often is
better in this location than at other atrial sites. The atrial pacing threshold should be less
than 2 volts. In the presence of complete heart block, it may be difficult to confirm atrial
capture from the surface ECG. Pacing the atrium at 150 beats/minute produces rapid
motion of the lead tip, which is readily recognized fluoroscopically and can be used to
determine atrial pacing threshold. This technique is only used safely if the high atrial rate
is not conducted to the ventricle. It is important also to be aware of the possibility that
atrial pacing in this situation may inhibit temporary VVI pacing and cause asystole.
The atrial P-wave electrogram is the Achilles' heel of dual-chamber pacing. If atrial
sensing is not satisfactory, a DDD pacemaker will not function properly. The P-wave
amplitude should be at least 1.62.0 mv. Measurement of atrial P-wave amplitude with
unipolar leads can be confusing. Crosstalk or far-field sensing of ventricular
depolarization from the atrium can occur, so that a 2-mv signal measured through a
pacemaker analyzer from the atrium is not a P-wave but a QRS complex. The optimum
way to resolve this is simultaneous measurement and display of atrial and ventricular
electrograms and the surface ECG. An alternate, expedient solution involves
preprogramming the generator as a P-wave detector: The lower rate is set below the
patient's intrinsic atrial rate, the A-V delay is set shorter than the patient's PR interval,
and atrial sensitivity is set at 2 mv. When the generator is connected to the atrial and
ventricular leads, every P-wave is followed immediately by a ventricular pacing spike if
P-wave amplitude is greater than 2 mv. Of course, the pacemaker must be
reprogrammed to clinically appropriate settings at the conclusion of surgery.
Telemetry of atrial and ventricular electrograms by pacemakers is a valuable adjunct to

proper dual-chamber pacing. For example, inability to pace the atrium or to measure
atrial electrograms in the operating room may be an indication of low-amplitude atrial
fibrillation that is invisible on the surface ECG but may be detectable as rapid salvos of
electrogram activity on the atrial channel of a dual-chamber pacemaker (Fig. 27-12) .
We use electrogram telemetry frequently in the operating room to confirm proper
function of DDD pacing systems (Fig. 27-13) .
PACEMAKER GENERATOR REPLACEMENT
Pacemaker generator replacement, usually innocuous, involves pitfalls including

infection, lead damage, connector problems, and asystole during the transition from the
old generator to the new. Ambulatory surgery is appropriate. For patients who are
anticoagulated with coumadin, the options are to stop the coumadin, to maintain
anticoagulation during surgery, or to admit and heparinize the patient while coumadin is
weaned. As a practical matter, generator insertion, even in fully anticoagulated patients,
should not be a problem, although some extra care is needed for hemostasis. If lead
replacement is anticipated, reversal of coumadin may be necessary.
Some practitioners insert a temporary transvenous pacing wire during pacemaker

generator replacement; the justification for this is unclear. The output of the replacement
unit must be high enough to match the pacing threshold of a chronically implanted lead.
This is problematic if the generator is an older type with a fixed output of 5.4 volts. Lack
of programmability prevents preoperative threshold testing, and the 5.4 volt output is
considerably higher than nominal for most current generators. The standard approach is
to test the pacing threshold with a pacemaker analyzer and program the new generator
to a higher output if necessary before connecting it. Before disconnecting the old
generator, be sure that the pacemaker analyzer, cables, and connections are intact and
that personnel in the operating room are aware of where the cables run. Some place the
analyzer in a sterile bag on the operative field. With many generators, an Allen wrench
placed in the header establishes electrical continuity with the ventricular lead; the pacing
threshold can then can be established before disconnecting the old generator. The old
generator should be kept within reach as a backup in case of trouble with the new
generator, the analyzer, or the connectors.
There are three common sizes of lead connector for permanent pacing: 6, 5, and 3.5
mm (VS-1 or IS-1). Ideally, the new generator should be an exact match for the patient's
lead size. A selection of step-up and step-down adapters also should be available in
the operating room. The contacts do not always line up correctly across VS-1 and IS-1
connectors, even though the connector diameter is the same. It is important to be
certain in advance whether connections can be made safely across the VS-1/IS-1
barrier.
Lead dysfunction can occur coincident with battery depletion. Patients with leads more
than 10 years old and increasing pacing threshold should be queried carefully for
symptoms of pacemaker dysfunction; a Holter monitor should be obtained prior to
surgery if lead dysfunction is suspected. If unsuspected lead problems are discovered
during generator replacement, the option of lead replacement should be available.
WOUND CARE
Our approach includes water-tight two-layer skin closure for primary implants, three
layers in some generator replacements. Patients are advised to keep their wound dry
until an office visit 714 days postoperatively. Any wound drainage at the postoperative
visit is cultured, and prophylactic antibiotics are started until culture results are available.
Unless infection is an issue, we have abandoned our former practice of aspiration of the
rare postoperative hematoma in favor of close observation.
Length of Stay After Pacemaker Implantation
AMBULATORY SURGERY
With current techniques, early discharge from the hospital after pacemaker insertion is
feasible in most patients. With positive fixation leads, we perform DDD, AAI, or VVI
pacemaker insertion on an ambulatory basis in patients with an adequate escape
rhythm. After surgery, patients are ambulated in the outpatient surgery unit and are
instructed in range of motion exercises for the shoulder. Patients are discharged 23
hours after surgery, after a chest x-ray has documented stable lead position and ruled
out hemo/pneumothorax or pericardial enlargement. Lead displacement in our hands in
ambulatory patients is not more frequent than in hospitalized patients.
PACEMAKER-DEPENDENT PATIENTS
The incidence of lead displacement in our experience overall is approximately 1.5

percent. Roughly a third of this is owing to technical errors, including inadequate length
of lead loops. Another third is related to struggling of inadequately sedated patients,
including infants and restrained, demented adults. The remainder is owing to causes
that cannot be defined in retrospect but presumably are related to inadequate fixation at
the myocardial end of the lead. Since a small percentage of lead displacement appears
unavoidable, patients who could suffer death or serious injury with abrupt pacemaker
failure should be observed in the hospital overnight on telemetry. [34 ] , [35 ]
Whether or not a patient is pacemaker-dependent is determined intraoperatively by

pacing the ventricle at 90 beats per minute, and abruptly withdrawing the pacing
stimulus. If a spontaneous ventricular rhythm is not observed within 5 seconds, or if the
patient becomes dizzy while recumbent, pacemaker dependence is proven.
Pacemaker dependence is most severe with iatrogenic heart block after open-heart
surgery and after radiofrequency ablation of the atrioventricular node is performed for
atrial fibrillation. High-dose antiarrhythmic therapy for VT or VF also may result in a poor
escape rhythm.
Results
MORTALITY
Technical issues
A review of 650 pacemaker insertions at our institution between January 1984 and April
1993 found one perioperative death (Table 27-3) . [46 ] The cause was heart failure
provoked by general anesthesia in a patient with congenital heart disease. Death is
rare in pacemaker insertion. Potential causes are technical and physiologic. Potentially
lethal technical problems include lead displacement, venous or cardiac perforation, air
embolism, and VT or VF.
Cardiac perforation related to permanent lead insertion is now rare with designs that
allow the lead to become soft and flexible once the stylet is removed. [28 ] Certainly it is
possible to perforate the thinned-out RV apex of the elderly patient (Table 27-3) .
Techniques that reduce the chance of perforation include avoiding the apex entirely
(Fig. 27-10) . When positive fixation leads are used, the stylet should be pulled back
from the tip of the lead before the lead is screwed into the RV apex. Temporary wires
also can cause cardiac perforation; undersensing and diaphragmatic pacing suggest
the possibility of this complication. Appropriate monitoring and safeguards should be
instituted when temporary wires are removed.
Serious potential problems during pacemaker insertion are hemopneumothorax and

pericardial tamponade owing to injury to the heart or arterial or venous systems; death
is not uncommon with these complications. The Seldinger technique may cause such
injuries when applied incorrectly. With this in mind, a large introducer never should be
passed over a guidewire unless the operator is certain the guidewire is properly placed.
This must be judged by the anatomic path of the guidewire visualized by fluoroscopy
and aided by contrast injection, if necessary. It is also critically important to slide the
introducer over the guidewire. The introducer and the guidewire should never be pushed
in together, as this neutralizes the function of the guidewire. Movement of the guidewire
and introducer also should be observed fluoroscopically as the introducer is advanced,
particularly if increased force is needed. The introducer should never be advanced if the
guidewire buckles, since buckling indicates that the pathfinding function of the
guidewire has been lost.
Heart rate
An increase in heart rate may be detrimental to patients with coronary artery disease.
Following pacemaker insertion, death may occur from myocardial infarction,
precipitated by an increased heart rate. Since bradycardia is an increasingly common
indication for pacemaker insertion in patients with inoperable coronary artery disease,
this hazard should be borne in mind both intraoperatively and in the early postoperative
period. When a pacemaker is inserted in a patient with a history of VT or VF,
disposable external defibrillation leads should be applied to the patient before surgery
begins.
COMPLICATIONS
Lead displacement Incidence
The incidence of endocardial lead displacement in early series was greater than 10
percent. [47 ] With the availability of tined and positive-fixation leads, the incidence has
fallen to the range of 2 percent. [28 ] , [34 ] , [35 ] , [48 ] , [49 ] The overall incidence of
this complication was 1.5 percent for both atrial and ventricular leads in all locations in a
recent review of experience at the Columbia-Presbyterian Medical Center (Table 27-3
and 27-4) . Secure placement of pacemaker leads is a learned skill. Four prime factors
in the stability of a newly inserted lead may be identified, as follows:
Length adjustment
Lead length should be adjusted between too short, where a deep breath in the upright
position produces lead displacement, and too long, where a cough in the supine
position may cause loop formation that effectively shortens the lead and pulls it out of
the apex.
Patient cooperation
We ask patients to perform maximal inspiration and maximal expiration under

fluoroscopy to aid in length adjustment. We also ask them to cough vigorously to test the
firmness of lead tip fixation. Patient response also is helpful in evaluating whether or not
symptomatic pacemaker syndrome will occur with VVI pacing and necessitate a
dual-chamber device. All of this feedback is lost if the patient is too heavily sedated or
cannot cooperate for other reasons.
Tip movement
There should be no fluoroscopic displacement of the tip relative to the atrial or

ventricular myocardium during the cardiac cycle. When movement suggests lead
bouncing, the electrogram and pacing threshold should be evaluated for changing
electrical properties. Electrical instability requires repositioning. Swiveling or rocking of
the lead body around the lead tip also invites careful assessment of lead stability with
hyperventilation, coughing, and electrical testing.
Lead torque
The use of this property to assess the security of lead attachment was described in
detail earlier.
Lead entrapment
Entanglement of a pacemaker lead in the chordae tendineae can produce such firm
entrapment that the force required to remove the lead jeopardizes the integrity of the
chordal apparatus. When this problem occurs, options include escalation of force,
application of lead extraction techniques, or an open procedure. [50 ] , [51 ] Our
experience involves two firmly entangled leads in 616 patients (Table 27-3) . Both leads
were capped and abandoned in place rather than escalate the risk of the procedure.
There were no untoward consequences of abandoning these leads. This experience
taught us to avoid the anatomic center of the RV when implanting positive fixation leads
(Fig. 27-9) , and this problem has not recurred in more than 500 subsequent
pacemaker implants.
Infection/erosion
Established infection around implanted prosthetic devices may be suppressed but is

rarely is eliminated by antibiotics. Antibiotic therapy not infrequently causes temporary
resolution of drainage from a pacemaker or ICD pocket, but the problem usually recurs
several months later. [51 ] Frequently, negative cultures from a sinus tract or erosion of a
pacemaker generator encourages the clinician to move the generator to a fresh,
adjacent site. The ultimate clinical response to such maneuvers, however, is almost
always recurrent erosion. Unless continual antibiotic suppression is advisable,
successful treatment of recurrent device erosion almost always requires removal of all
hardware and insertion of new hardware from the opposite side. [50 ] , [51 ] The
incidence of erosions, infections, hematoma, and lead displacement early after
pacemaker insertion is increased by operator inexperience. [49 ]
Premature battery depletion
The accepted standard for pacemaker output is a pulse width delivered to the
ventricular lead that is twice the threshold value. Pacemaker generator longevity can be
prolonged by adjusting generator output to this minimum value. Because early pacing
thresholds are unstable, this adjustment should be made somewhere between six
weeks and one year following generator insertion.
Generator dysfunction
Electrical component failures still occur, even in pacemaker generators that have an
established track record of reliability. [52 ] We have seen generators that functioned
normally at the time of implant fail within a few weeks. In my experience with more than
1,000 implants over the past 10 years, this occurred on three occasions; generator
replacement was necessary in all instances.
Despite extensive testing and FDA approval, new pacemaker products may contain
systematic flaws that do not become apparent for years after clinical use. [28 ] , [53 ]
Pacemaker dysfunction
Pacemaker dysfunction can be caused by mechanical defects in leads or errors in

connecting the lead and generator. Most commonly it represents scarring at the
lead-myocardial interface, changes in myocardial properties caused by tissue necrosis
or drug effects, or a poor choice of lead position.
Undersensing
Undersensing is defined as failure to sense atrial or ventricular electrograms. The

problem appears on the ECG as an atrial or ventricular pacing artifact that should have
been inhibited by the preceding (unsensed) beat. In a dual-chamber pacemaker,
undersensing may also appear as failure to pace the ventricle after an atrial P-wave.
The problem may be correctable by programming to increase generator sensitivity, but
oversensing may result. The tolerance for reprogramming can be estimated by
examining telemetered electrograms (Figs. 27-14 and 27-15) .
Oversensing
Oversensing (inappropriate pacemaker inhibition or triggering) in unipolar systems may

result from detection of muscular activity in the chest wall. This can occur without
compromise of lead integrity and may be correctable by reprogramming to reduce
pacemaker sensitivity (Figs. 27-15) . Oversensing can be life-threatening in patients
with poor escape rhythms (Figs. 27-16) .
Exit block
Exit block (rising pacing threshold) owing to edema or scarring at the lead
tip-myocardial interface usually develops gradually and may be correctable by
reprogramming the generator to increase the amplitude or pulse width of the
pacemaker impulses (Figs. 27-17 and 27-18) . Increasing output and pulse width
shortens battery life. In unipolar systems, adventitious pacing of chest wall and/or
diaphragm may result from high generator output.
Pacing threshold is expected to increase over 714 days after lead insertion, then
stabilize at about 6 weeks. This phenomenon, which appears related to inflammatory
changes at the lead tip-myocardial interface, is ameliorated by steroid-eluting leads. [28
] , [54 ]
Lead fracture
Lead fracture, whether owing to insulation or conductor breaks, may be visualized

directly in many cases by chest x-ray. Changes in lead impedance may suggest lead
defects that are not obvious by inspection. Low lead impedance (less than 300 ohms)
suggests an insulation break, while high lead impedance (more than 1000 ohms)
suggests conductor problems. Telemetered electrograms, if available, should be
monitored for noise while the patient hyperventilates, coughs, bends, and swings his
arms. Pacemaker malfunction related to body movement is an indication for lead
replacement or repair.
After capping dysfunctional leads, we do not necessarily remove them, but this area is
in dispute. The probability of lead fracture differs markedly from lead to lead. Bipolar
construction, certain forms of polyurethane insulation, and some types of epicardial lead
are particularly prone to breakdown (Fig. 27-16) . Technical factors also may be
implicated in lead fracture. These include tight ligatures applied to the lead without an
anchoring sleeve, kinking or excessive lead angulation, and subclavian crush. [28 ] , [33
] , [38 ]
Accufix lead
Recently, a new and unusual form of lead fracture was described. This affects the
Telectronics Accufix lead, a bipolar, Bisping-type, atrial screw-in lead. A J-shape was
integrated into the design to direct the tip to the atrial appendage. The engineers
welded a J-shaped retention wire to the indifferent anodal ring electrode near the tip
and then bonded the rest of the retention wire to the lead body with polyurethane. In
clinical use, the retention wire is susceptible to fracture, followed by extrusion. The
extruded retention wire is analogous to an open safety pin inside the right atrium (Fig.
27-19) . Deaths were reported from cardiac tamponade, possibly related to puncture of
the atrium or aorta by the protruding retention wire. More than 45,000 of these leads
have been implanted. The manufacturer recommends periodic lead surveillance by high
resolution fluoroscopy to look for retention wire fracture. If a fracture is detected, the
lead should be removed. Lead removal utilizes the Byrd technique, employing Cook
catheters or an open-chest procedure. [55 ] [57 ]
These recommendations are controversial, since the difficulty of percutaneous

extraction is increased both by retention-wire fracture and the duration of lead
implantation. In addition, many patients with these leads are not content to wait for
fluoroscopic evidence of lead fracture. It is difficult to recommend that these leads be
left in place in otherwise vigorous patients, even without overt retention wire fracture;
however, mortality has occurred during extraction of this lead.
Subclavian crush
This refers to entrapment of a pacemaker lead between the clavicle and first rib in the
costoclavicular ligament. The lead is believed to be subjected to high levels of stress
during body movement, and early lead failure results. This problem pertains exclusively
to leads implanted by percutaneous puncture of the subclavian vein, and in theory can
be avoided completely by cephalic vein cutdown. Refinements in technique intended to
minimize this problem have been defined. [28 ] , [33 ] , [38 ]
Pneumothorax/hemothorax
These complications are almost exclusively owing to technical problems related to

percutaneous subclavian vein puncture. In our experience with pacemaker insertion in
more than 1,000 patients by cephalic cutdown, hemopneumothorax has not occurred. In
a recent review of 1,088 consecutive implants by subclavian puncture, the overall
incidence of pneumothorax was 1.8 percent. [49 ] However, informal discussion
suggests that complications of subclavian puncture are the most common cause of
mortality during pacemaker implantation.
POSTOPERATIVE TESTING/FOLLOW-UP
Office/clinic versus telephone
Pacemakers require periodic testing to confirm that sensing and pacing are
appropriate and to detect declining battery voltage indicative of approaching battery
depletion. Current standards involve testing these functions at 2-week to 2-month
intervals, depending on the age of the device. Whether this follow-up should be done by
transtelephonic monitoring, clinic, or office visits is a matter of dispute. [58 ] [60 ] My
routine involves transtelephonic monitoring, using a commercial service. This is
convenient and cost-effective for both the physician and the patient but generates less
revenue for the physician and hospital than clinic/office visits or a physician-operated
monitoring operation. In addition to reduced travel for patients and reduced office
volume and time saved for the physician, a good transtelephonic monitoring system
provides emergency service on a 24-hour basis. The ability of a service to
independently check a pacemaker in a patient with palpitations or dizzy spells provides
critical information for triage, including emergency room referral. A monitoring service
with 24-hour coverage is almost indispensable for management of the apprehensive
patient with a new implant.
Pacemaker Programming
Programming pacemakers of even a single manufacturer is daunting because many

functions must be mastered. The practitioner must be familiar with the testing
equipment and protocol to allay patient concerns. Although programmers are
increasingly intuitive and user-friendly, each manufacturer's programming routine and
nomenclature is unique. One manufacturer's programmer will not program another
manufacturer's pacemaker. If the practitioner is not familiar with new equipment and the
programming problem is complex, assistance from a manufacturer's representative is
preferable to risking patient injury.
The basic programming parameters for DDD pacing include electrogram sensitivity
and amplitude/pulse width of the pacing stimulus for both atrium and ventricle. Lower
rate, upper rate, atrioventricular delay, and refractory periods for atrial and ventricular
sensing are important in defining limits on the pacemaker's view of the cardiac cycle.
Rate responsiveness is another important programmable parameter. Many other
programmable features, including unipolar/bipolar choices when bipolar leads are
used, are available on most current generators.
Because of the increasing emphasis on ambulatory surgery and early discharge, we

initially program newly inserted pacemakers to a stimulation amplitude and pulse width
higher than nominal. When the patient comes in for an initial office visit, pacing
thresholds are retested and, if appropriate, amplitude and pulse width are adjusted to
nominal levels.
We seek to make pacemaker programming for outpatients as reproducible and routine

as possible. We begin by interrogating the pacemaker to obtain and print initial
settings. These are later compared to final settings to be certain that unintended
parameter changes do not occur. Telemetry is examined to determine the 24-hour
variation in heart rate, the relative time the pacemaker spends sensing and pacing, the
quality of the electrograms, lead impedance, and battery voltage.
Automated pacing threshold testing is performed and the pacemaker is adjusted to

leave at least a 150-percent safety margin for stimulation pulse width(s). The pulse
width is more finely tuned at the 1-year follow-up visit, but the safety margin is
maintained at no less than 100 percent. Pacing mode, rates, refractory periods,
rate-responsive features, and delays are adjusted to optimize patient comfort and
battery life. For example, if a patient with a DDD pacemaker inserted for complete heart
block is found to be pacing the atrium 25 percent of the time and this occurs at night, it
may be reasonable to reduce the lower pacing rate or adjust diurnal cycling of the
pacemaker (if this is adjustable) to eliminate atrial pacing.
Specific pacing problems detected by transtelephonic or Holter monitoring are

corrected, if possible. Adjustments for patient symptoms should also be considered.
These adjustments may include not only correction of sensitivity or pacing output but
also pacing mode for problems such as new-onset atrial fibrillation (Fig. 27-12) or
sinus-node incompetence related to medication changes (Fig. 27-20) . If pacemaker
problems are not correctable by programming, the patient is counseled regarding the
nature of the problem and the advisability of a corrective reoperation.
The full spectrum of problems that may be discovered and corrected at routine
pacemaker follow-up is not within the scope of this chapter. [61 ] A great deal of
experience, background, and training are necessary to become comfortable with all the
capabilities of the current generation of pacing devices.
Computer Support
The large amount of information that must be managed about pacemakers and/or
defibrillators makes sophisticated computer support almost mandatory. Information is
needed not only for billing but also for generating operative notes, tracking serial
numbers of leads and generators, keeping records of programming information, and
managing follow-up visits, telephone or clinic follow-up, and patient education. A variety
of commercial and home-grown software packages are available for this purpose. [62 ]
We developed our own system, using an intuitive, object-based multiuser relational data
base and a networked computer system accessible both throughout the hospital and by
remote connection from home or remote sites.
Innovations and Special Problems
ATRIAL FIBRILLATION/MODE SWITCHING IN DUAL-CHAMBER PACING
Many candidates for dual-chamber pacing suffer not only from sinus bradycardia but
also from supraventricular tachycardia and paroxysmal atrial fibrillation. A standard
DDD pacemaker responds to atrial fibrillation by pacing at the upper rate limit of the
pacemaker. This situation requires either programming to a slow, restrictive upper-rate
limit or else accepting a high pacing rate during atrial fibrillation. Neither choice is well
received by patients, and the problem is potentially hazardous for patients with coronary
disease. Initially DDD pacemakers were not recommended in patients with a history of
atrial fibrillation. Paradoxically, however, the frequency of atrial fibrillation may be
decreased by atrial pacing. The concept of mode switching permits use of DDD
pacemakers in patients with a history of atrial fibrillation. [63 ] This programmable
feature requires the DDDR mode. The pacemaker continuously compares the observed
atrial rate to an anticipated rate based on the patient's activity level. If the atrial rate
appears excessive for the activity level, an atrial arrhythmia is assumed and the
pacemaker switches to VVIR pacing until the atrial rate again appears appropriate.
PACEMAKER-MEDIATED TACHYCARDIA IN DUAL-CHAMBER PACING

Another peculiarity of DDD pacing is pacemaker-mediated tachycardia (PMT), an
iatrogenic reentrant arrhythmia. [61 ] PMT requires retrograde conduction through the
AV node, as may occur following a premature ventricular depolarization. The atrium
then depolarizes. If this atrial depolarization is sensed by the pacemaker and the
ventricle is paced, a re-entrant cycle is set up that can continue indefinitely at the
upper-rate limit of the pacemaker. This problem can be minimized by avoiding high
upper-rate limits in patients with retrograde conduction and adjusting the post
ventricular atrial refractory period (PVARP) so that the pacemaker ignores atrial
depolarizations for 300350 msec after the QRS complex. Current pacemaker circuits
also have built-in safeguards that attempt to break reentrant arrhythmias by periodic
interruption of continuous pacing at the upper-rate limit. In addition, pacemaker
telemetry provides notification when upper-rate limit pacing suspicious of PMT occurs.
DDI pacemakers are immune to this problem.
EVALUATION/IDENTIFICATION OF PACEMAKERS BEFORE GENERAL

SURGERY
Proper identification and evaluation of a functioning pacemaker in a patient about to

undergo general anesthesia and surgery is mandatory. If the surgical and anesthesia
teams lack expertise, a consultant is needed. Life-threatening pacemaker emergencies
may occur intraoperatively, and proper preparation can be life-saving. First, the
manufacturer and model of the pacemaker must be identified. This information is most
readily obtained from the patient's pacemaker card. If this is not available, records of
the service or physician performing pacemaker follow-up may be helpful. Alternatively,
an x-ray showing the pacemaker may be helpful. Most pacemaker generators have
unique radioopaque markers that identify the manufacturer and model. If an appropriate
reference source is available, the x-ray appearance is sufficient to identify the
pacemaker. [62 ] After the pacemaker is identified, reference material or a call to the
manufacturer identifies the pacemaker type, programmability, polarity, end-of-life
indicators, and other critical information. For programmable units with telemetry, the
currently active program can be retrieved by interrogation with the manufacturer's
programmer.
Recently, an important compendium of information about contemporary pacemakers

and ICDs (internal cardiac defibrillators) became available in the form of a book and
related software. [62 ] The publisher, Droege Computing Services, Inc., has a web site
on the internet (www2.interpath. net/devcomp/guide.htm) that downloads device
information and a limited selection of radiographs at no charge on a 24-hour basis.
The next issue is to identify whether or not the patient is pacemaker-dependent; if the
pacemaker fails, does the patient have a dependable and adequate intrinsic rhythm? If
the answer to this question is no, or if the answer cannot be determined because the
pacemaker is not programmable, a backup method of maintaining heart rate must be
defined, because the electrocautery may cause pacemaker failure (see the following).
In the past 5 years, at least two avoidable life-threatening incidents involving

pacemakers occurred in our medical center. In one, unipolar cautery produced
complete and irreversible loss of pacing in a pacemaker-dependent patient. In the
other, a patient with a DDD pacemaker developed atrial fibrillation and began pacing at
the upper-rate limit (110). With the patient hypotensive, more than 20 minutes were
needed to determine the pacemaker type, locate the responsible physicians, and take
corrective action. No permanent injury to either patient resulted, but the experience
proved the need for intraoperative management guidelines for pacemakers and
defibrillators.
ELECTROCAUTERY
Management of a pacemaker recipient during orthopedic, general, or thoracic surgery

is complicated and vexing. [65 ] , [66 ] Pacemaker manufacturers recommend against
using electrocautery in such patients, but this is impractical. Unipolar cautery is far more
hazardous than bipolar cautery. Nevertheless, many surgeons insist on unipolar cautery
when planned surgery is extensive. Unipolar pacemakers are more susceptible to
interference from electrocautery than bipolar pacemakers.
A spectrum of escalating problems can be caused by electrical interference from the

electrocautery. This noise most commonly is misinterpreted by pacemaker sensing
circuits as a rapid heart rate, and produces inhibition of the pacemaker that is
reversible when the interference stops. Less frequently, high-level noise may cause
pacemaker reprogramming or reversion of the pacemaker to a backup mode. Backup
modes differ for different units; members of the surgical team should know what to
expect if this problem occurs. A common mode characteristic of backup pacing is
VOO.
The most severe problem that electrocautery may cause is complete and permanent
loss of pacing. We observed this in a generator about one year short of battery
depletion. The first application of unipolar cautery during a planned hip replacement
caused complete loss of pacing. The patient's intrinsic heart rate was less than 20, and
emergency measures, including pacemaker generator replacement, were required. The
planned procedure was canceled and successfully carried out one week later. The
manufacturer noted that with decreasing battery voltage the pacemaker oscillator
became increasingly susceptible to destruction by electrocautery.
Perhaps the best way to manage a pacemaker during use of electrocautery is to

program the generator to VOO or DOO at a rate sufficient to minimize competition with
the intrinsic heart rate. This strategy creates the possibility of competition with
spontaneous ventricular beats; therefore, the pacemaker should be returned to a
sensing mode as soon as possible after operation. No strategy can protect the patient
from the possibility of permanent loss of pacemaker function except providing an
alternate means of maintaining heart rate.
MAGNET MODE
When a permanent magnet is placed over a pacemaker, it closes a magnetic reed

switch and converts the pacemaker to magnet mode. [60 ] Magnet-mode behavior is
not predictable except by reference to lookup tables or information from the
manufacturer. [62 ] In most instances, a magnet converts a pacemaker to the VOO
mode, preventing inhibition by electrocautery. Other pacemakers convert to VOO for a
few beats and then revert to the underlying program. With a magnet, most current
generators perform a threshold margin test; this test investigates the adequacy of the
pacing margin by decreasing output by a predetermined amount during a specific beat
after the magnet is applied. If capture is maintained on that beat, an adequate safety
margin is confirmed. The rate of a pacemaker in magnet mode usually decreases as
the end of battery life approaches.
STEROID-ELUTING LEADS
A pellet of dexamethasone incorporated into the lead tip addresses the problem of
fibrosis at the lead-myocardial interface. This produces reproducible improvement in
early lead pacing thresholds that is superior to conventional leads. [28 ] The clinical
performance of these leads makes them the best choice for patients who require lead
replacement for early exit block. Currently, steroid-eluting leads are only available with
tined leads ( Figs. 27-5B and 27-5C ); but steroid-eluting, positive-fixation endocardial,
and suture-type epicardial leads are undergoing clinical trials and appear promising.
Our experience with steroid-eluting leads is limited to patients with exit block. In most of
these patients the lead worked well; in some, pacing threshold increased but remained
usable beyond one year. When compared to positive fixation leads, steroid-eluting
endocardial leads impose a need for larger veins and decrease the range of
anatomically acceptable pacing sites.
ADULTS WITH CONGENITAL HEART DISEASE
Preoperative echo-Doppler or angiographic studies may help to define abnormal caval

and coronary sinus anatomy in patients with congenital heart disease. Persistent left
superior vena cava often is associated with aberrant location of the subclavian vein that
makes percutaneous lead insertion futile and hazardous. In these patients, insertion of
leads through a cephalic vein cutdown is advisable. In the presence of persistent left
superior vena cava, a pacemaker is more easily inserted from the right side. Leads can
be inserted from the left side, but often a loop is required to enter the ventricle. Situs
inversus and corrected transposition are particularly confusing if undetected prior to
operation.
Positive fixation leads are particularly valuable in patients who need atrial pacing after a
Mustard operation or a caval-pulmonary anastomosis. The smooth-walled right ventricle
of corrected transposition of the great vessels also makes positive fixation leads
advantageous. [43 ] In some adults who have the Fontan operation, a small diameter,
positive-fixation lead may be passed far enough into the coronary sinus to successfully
pace the right ventricle (Fig. 27-21) . We also found ventricular pacing via the coronary
sinus possible in a patient with a mechanical valve in the tricuspid position.
PACING IN INFANTS AND CHILDREN
Transvenous pacing can be facilitated in this population by leaving an intracardiac loop

to allow for growth (Fig. 27-4) . Unipolar, positive-fixation leads are ideal for this
purpose but other approaches are described. [43 ] , [44 ] , [67 ] We prefer a cephalic
vein cutdown with optical magnification if needed. A flexible guidewire is passed
centrally and a 7 French introducer is used to introduce the lead. A longitudinal split of
the cephalic vein facilities advancing the introducer Fig. 27-7 . In very small infants, the
external jugular vein at the thoracic inlet may be useful. Others prefer a subclavian vein
puncture guided by a catheter introduced via the femoral vein. [67 ] Thoracotomy
provides a third option for pacing in this group. [40 ]
DEMENTIA
Demented patients may require physical restraint or heavy sedation in the operating
room. Such patients will not cough or hyperventilate on request and may require general
anesthesia, which increases surgical risk. In our experience, restraint for dementia on
the night after surgery often is associated with lead displacement. Every effort, including
a vigil by family members at the bedside, should be made to avoid the need for
postoperative restraint in these patients. Of the problems commonly encountered in
prospective pacemaker recipients, dementia is among the most daunting and is a
possible contraindication to surgery.
AV NODE ABLATION
AV node ablation is used to control the ventricular rate response in patients with atrial
fibrillation refractory to medical management. Our cardiologists ablate the AV node and
then transport patients to the operating room for pacemaker insertion and hospital
discharge the following day. However, in these patients the ventricular escape rhythm
often is so poor that the risk of serious injury or death is substantial if the pacemaker
system fails. Secure positioning of positive fixation leads and high pacemaker output in
the early postoperative period are recommended for these patients.
TRANSPLANT RECIPIENTS
The most common indication for pacemaker insertion in cardiac transplant recipients is
sinus bradycardia or sinus arrest. This can be managed successfully by AAIR pacing.
[68 ] , [69 ] In our experience, most recipients outgrow the need for pacing within two
years. [68 ] The surface ECG may be quite misleading and suggest atrioventricular
dissociation, because there are two sources of P-wavesthe atria of the donor and the
recipient. Whether or not ventricular pacing is needed is evaluated intraoperatively by
pacing the atrium at a rate of 150. If a 1:1 response of the ventricle is observed, the AV
node essentially is normal. The location of the atrial appendage is more medial than
usual in these patients, and positive fixation leads are useful for secure lead positioning
(Fig. 27-22) .
IMPLANTABLE CARDIAC DEFIBRILLATOR (ICD) RECIPIENTS
Transvenous pacing in ICD recipients has the most stringent requirements for lead
performance in the entire spectrum of pacemakers. At issue is the possibility of
crosstalk between devices. Crosstalk can cause inappropriate ICD shocks or failure of
the ICD to detect and correct a potentially lethal ventricular arrhythmia. [70 ] , [71 ]
Recently marketed ICDs are capable of VVI pacing, but this capability is really
designed for occasional backup pacing. If frequent pacing is needed, battery depletion
is accelerated. It is not cost-effective to deplete a $20,000 ICD generator by VVI pacing
when a VVI generator costs $3,500. Furthermore, pacing circuits of current ICDs are
not capable of rate-responsive (AAIR or VVIR) or dual chamber pacing.
There are two ways in which detection of permanent pacemaker artifacts by an

implanted ICD can cause problems. The first involves double or triple counting. [71 ] The
most extreme example is when an ICD, operating with high sensitivity and short
refractory periods, detects and counts both atrial and ventricular DDD pacemaker
spikes and the native QRS complex. This triple counting scenario makes a heart rate of
70 appear to be 210 to the ICD, and leads to inappropriate ICD firings that cycle
repetitively. A more lethal problem may result if a pacemaker fails to detect VF and
continues to pace at a regular rate in the physiologic range. If the ICD detects
large-amplitude, regular-pacing artifacts, it may not distinguish this signal from a normal
rhythm and may not sense VF or resuscitate the patient. [71 ]
For this reason, pacemaker artifacts essentially must be invisible to an ICD. This
problem was challenging when ICD systems were implanted by thoracotomy (Fig.
27-23) , but is far more difficult with transvenous ICD leads ( Figs. 27-24 and 27-25 ).
[70 ]
A successful solution to this problem first requires a bipolar pacemaker system. A

dedicated bipolar pacemaker generator that can never be programmed or revert to
unipolar pacing is preferred; units with extra circuit protection against high-energy
shocks are available. Next, both electrodes of the bipolar pacemaker lead must be
placed as far as possible from the ICD leads used for rate sensing. Unfortunately, in the
Endotak system, the anode for rate sensing is the physically large distal coil for ICD
shocks ( Figs. 27-24 and 27-25 ). If a standard in-line bipolar lead is used for the
pacemaker (Fig. 27-23) , proximity of the pacemaker lead anode and the ICD
rate-sensing lead anode is so close that electrical isolation of the two systems is
extremely difficult. Ideally, the size of ventricular and/or pacing artifacts should be less
than 0.2 mv or less than 10 percent of R-wave size in the rate-sensing leads. [70 ] We
use two methods to achieve this ideal; both involve insertion of extra hardware.
The least complex and controversial solution is to insert a separate bipolar lead for ICD
rate sensing (Fig. 27-24) . Positive fixation leads are made for this purpose; they have a
small ring anode similar to a standard pacemaker lead and a fixed-screw configuration
that allows the lead to be placed at any convenient site within the right ventricle. A more
effective method is to create bipolar ventricular and/or atrial leads by linking two
unipolar leads with an in-line Y connector ( Figs. 27-25 through 27-27 ). The latter
method, most effective in reducing the size of pacemaker artifacts in the rate-sensing
leads, can be combined with the former method if necessary. The use of a unipolar
pacing lead as an node, valuable in this specific application, involves theoretical
disadvantages, including an increased possibility of pacemaker-induced VT. [28 ]
However, we have not observed this problem in our patients.
With objective measurements supporting ICD-pacemaker compatibility, ICD immunity

to double counting and the ability of the ICD to detect VF should be tested. The latter is
best done during magnet-forced VOO pacing ( Figs. 27-28 and 27-29 ). When a
pacemaker is inserted in a patient with a previously placed ICD, amplitude of pacing
artifacts can be tested without opening the pocket if electrogram telemetry is available.
LONG Q-T SYNDROME
This is a genetically determined repolarization problem that is associated with a high

incidence of sudden death. Recommended therapy includes stellate ganglionectomy
and/or adrenergic blockade. [69 ] , [72 ] In severe cases, the pacing threshold may be
too high for rapid ventricular pacing, and atrial pacing may be the only option. [69 ]
IDIOPATHIC HYPERTROPHIC SUBAORTIC STENOSIS (IHSS)
IHSS or obstructive cardiomyopathy is characterized by left-ventricular hypertrophy and

outflow obstruction sufficient to cause symptoms of angina, syncope, and sudden death.
[16 ] Fananapazir and others report that DDD pacing in patients in sinus rhythm at AV
intervals sufficient to pre-excite the right ventricle decreases outflow gradients in IHSS.
[16 ] , [69 ] Dramatic examples of acute reductions in pressure gradients occur, and
over time (Fig. 27-30) further reductions and reversal of septal hypertrophy may develop
(Fig. 27-31) . [16 ] A reduction in the incidence of sudden death also is claimed in
patients with a history of syncope. In our experience, substantial immediate reduction of
the outflow gradient with DDD pacing occurs in about half the patients we have studied
intraoperatively; apical pacing is more effective than RV outflow-tract pacing. In one of
our patients, pacing dramatically reduced anginal symptoms, but the patient suffered
sudden death several months later.
Environmental Issues
ELECTROMAGNETIC INTERFERENCE
Concerns about electrocautery are described in the preceding. An increasing variety of

other sources of electromagnetic, radioactive, and mechanical energy that are present
in the environment can damage pacemakers. [65 ] , [66 ] Electromagnetic influences
include electrocautery, AV-node ablation, cellular telephones, magnetic resonance
imagers (MRI), microwaves, diathermy, arc welders, powerful radar and radio
transmitters, and theft detectors in department stores. [73 ] Strong magnets also may be
problematic. It is generally recommended that patients with pacemakers should not
undergo MRI examination because of the possibility of severe tachyarrhythmias; but
recent evidence suggests this risk may be exaggerated. [66 ] , [73 ]
Any defective electrical appliance or motor, including electric razors, lawn mowers, or
even an electric light can be problematic if it causes interference with radio or television
reception. The extent to which such sources of electrical noise should be feared by
pacemaker recipients is directly related to the degree of pacemaker dependence. The
vast majority of pacemaker recipients are not pacemaker-dependent, so that a brief
period of pacemaker dysfunction does not cause loss of consciousness. These patients
can move away from a source of interference, lie down, or call for help before
developing serious symptoms. Patients who are truly pacemaker-dependent, however,
must avoid loss of pacing for more than a few seconds. Patients who are
pacemaker-dependent and work in electrically noisy environments are candidates for
bipolar pacing systems because of added noise protection. Patients using cellular
telephones should separate the telephone antenna and the pacemaker generator by
several inches. [74 ]
MECHANICAL INTERFERENCE
Mechanical problems can be caused by lithotripsy, mechanical trauma, dental

equipment, and even bumpy roads. [66 ] At one end of the spectrum, the mechanical
shock of the lithotripter may cause serious damage to pacemaker circuits. An
automobile accident and assault with a baseball bat reportedly caused pacemaker
generator failure. [75 ] Vibration in subways or on bumpy roads produces less serious
but annoying symptoms when vibration sensors in rate-responsive units are stimulated
to inappropriately accelerate heart rate.
The American Heart Association recommends that children with pacemakers should
not engage in contact sports. [76 ] However, life is a perpetual contact sport for many
children, and one of my patients was punched in his pacemaker pocket as soon as he
went back to school. In reality, many pacemaker recipients engage in very vigorous
sports without mishap. Patients with poor escape rhythms, who could suffer death or
injury in the event of abrupt pacemaker failure, should be strongly discouraged from
participating in sports or recreational activities likely to result in deceleration injury.
These include traditional contact sports as well as basketball, handball, downhill skiing,
surfing, diving, mountain climbing, and gymnastics. Others who are not
pacemaker-dependent and participate in these activities should be warned that abrupt
pacemaker failure can occur in the event of trauma-induced lead displacement/fracture
or generator failure.
RADIOACTIVITY
The CMOS integrated circuits of most current pacemakers and implantable

defibrillators are subject to permanent damage by radiotherapy. [30 ] , [66 ] If the
pacemaker cannot be shielded adequately from the radiation field, it may be necessary
to remove and replace it or move the pacing system to a remote site.
Pacemaker Lead Extraction
Indications for pacemaker lead extraction are chronic infection or a life-threatening

mechanical defect, as described previously for Accufix leads. Some suggest that any
dysfunctional pacemaker lead should be removed, but this may be excessive. [38 ] , [50
] , [51 ] Until recently, the only available techniques for extraction of a transvenous lead
were external traction or thoracotomy with cardiotomy, during inflow occlusion or
cardiopulmonary bypass. The difficulty with pacemaker lead extraction is owing to
fibrosis of the lead tip to the myocardium and fibrosis of the lead body to the vena cava,
innominate, and subclavian veins.
The armamentarium of methods for removal of infected or defective pacemaker leads

has been substantially advanced by techniques described by Byrd and marketed by
Cook. [38 ] , [50 ] , [51 ] The system consists of locking stylets and a series of metal and
plastic sheaths. The objective is to pass a locking stylet inside the central channel to the
tip of the lead where it locks; this allows stronger and safer traction to extract the lead.
The external sheaths are then manipulated to pass a long plastic sheath just slightly
larger than the external diameter of the pacing lead to the lead-myocardium interface.
This allows countertraction against the myocardium while traction is applied to the lead
tip with the locking stylet (Fig. 27-32) . The success of lead extraction with this technique
is reported to be more than 90 percent, with a three-percent chance of serious
morbidity or death.
We perform pacemaker lead extraction under general anesthesia with an arterial

monitoring line in place. The patient is draped for a median sternotomy, and a pump
team is on call. The consent for lead removal includes consent for an open procedure
with cardiopulmonary bypass. If catastrophic bleeding were to result from an injury
during lead extraction, we would proceed immediately to sternotomy. We have not had
this problem to date and may change our methods, if the chance of injury proves to be
remote.
Our experience with the Cook extractor involves 15 leads aged 215 years after
implantation. The difficulty of extraction was related to the age of the lead. All leads
were removed successfully, but thoracotomy, cardiotomy, and inflow occlusion were
required in two patients. There were no complications and no deaths. In patients with
lead systems more than 10 years old, extensive, calcified adherence of the leads to the
subclavian and innominate veins was encountered, and metal trocars from the Cook
system were passed tediously and with difficulty to the level of the vena cava. In one of
these patients, a sternotomy was required to remove an Accufix atrial lead and a
ventricular lead that were fibrosed together. At median sternotomy, a clotted hematoma
was found tracking along the left innominate vein.
We find Accufix leads particularly difficult to remove with the Cook system. [55 ] [57 ] A
number 26 locking stylet is recommended, but the central channel of the lead narrows at
the proximal ring electrode, to make passage through the last two cm of the lead
particularly difficult. Silicone oil and every available trick should be employed to get the
locking stylet to the tip of the lead. If the stylet does not pass to the lead tip, forceful
attempts at lead extraction result in internal disruption of the lead structure, partial
extraction of the inner coil, and failure of the technique (Figs. 27-33) . Also it is important
to retract the screw at the tip of the lead before extracting the lead. If the screw does not
retract, the tip can be unscrewed from the myocardium by rotating the shaft of the lead
counterclockwise. This should not be done, however, until a sheath has been passed
over the lead to its tip. Rotation of the lead body without an external sheath in place can
extrude the retention wire (Fig. 27-19) . At that point, passage of the external sheath is
probably impossible, and a thoracotomy may be necessary.
Pacemakers for Atrial and Ventricular Arrhythmias
Overdrive pacing techniques of variable efficacy are described for VT,

Wolff-Parkinson-White syndrome, and atrial flutter. [77 ] [78 ] Implantable
pacemaker-defibrillators are under development for atrial fibrillation. Antitachycardia
ventricular pacing for VT is integrated into implantable cardioverter-defibrillator (ICD)
therapy because of a hazard of accelerating VT or converting it to VF with overdrive
pacing. The indications and the role of antitachycardia pacing techniques are likely to
expand in the coming decade.
EMBRYOLOGIC DEVELOPMENT
During the early stages of development of the cardiovascular system, the primordial
cardiac chamber is connected to the main arterial trunk (the truncus arteriosus) via the
truncoconal channel. The truncoconal channel eventually develops into the pulmonary
arteries and aorta. As seen in Figure 28-1 , a septum develops within the truncoconal
segment and subsequently fuses with the underlying ventricular septum. At the point of
fusion between these two septal components, separation of the ventricular chamber is
accomplished by development of the aortic valve.
The right and left cusps of the aortic valve develop from the aortic side of the
truncoconal septum. Opposing this septum, the embryonic posterior aortic valve
develops from the truncoconal lining. As development continues, the aortic valve leaflets
grow to become nearly uniform in size and dimensions.
ANATOMY
The aortic valve may be described as having a passive valve mechanism that is quite
different from the mitral valve. The mitral valve has an active component consisting of
papillary muscle contraction that aids alignment of the leaflets. The aortic valve has no
active component. Because of its passive mechanism, the structure of the aortic valve
must open and close with minimal pressure differences between the ventricle and aorta.
During closing, this same mechanism must prevent backflow by perfectly aligning the
cusps, which must have enough structural integrity to withstand systemic pressures.
In its simplest form, the aortic valve is composed of three leaflets. However, other
components also provide structural integrity and allow proper function. There is no true
aortic valve annulus in contrast to the mitral valve. The surgical annulus of the aortic
valve is the ventricular arterial junction defined by the semilunar attachments of the
aortic valve leaflets. If the leaflets were attached to a true annulus, it would not be
possible for the leaflets to open properly during systole. The commonly designated
annulus of the aortic valve is actually an aortic ring and is the last impediment to flow
prior to blood reaching the aorta. The ratio of the diameter of the aorta just downstream
to the aortic ring is approximately 1.17. [1 ]
The junction between the ventricular chamber and the aorta is designated as the
ventricular arterial junction . This may be viewed as either an anatomic or physiologic
junction. The physiologic junction is marked by attachments of the semilunar valves that
define the separation between the ventricular outflow chamber and the proximal aorta.
However, there is a discrepancy between this physiologic junction and the anatomic
junction due to, in part, muscular tissue of the ventricle and, in part, fibrous tissue of the
septum and mitral valve. As can be seen in Figure 28-2 , the commissures are above
the anatomic junction, but the bases of the semilunar attachments of the aortic leaflets
are at the true anatomic junction. [2 ]
The fibrous skeleton of the heart forms the posterior wall of the outflow tract where the
leaflets are in fibrous continuity with those of the mitral valve (see Fig. 28-2 ). These two
ends of the fibrous skeleton that lie on either side of the noncoronary leaflet are
thickened and form the left and right fibrous trigones. The right fibrous trigone is
continuous with the membranous part of the septum and forms the central fibrous body
through which atrial ventricular conduction tissue passes to the crest of the ventricular
septum. The central fibrous body is at the junction between the noncoronary and right
coronary leaflets. [2 ]
Another component of the aortic valve is the sinus of Valsalva. The sinus of Valsalva is
defined as the area between the aorta and the valve leaflet edge when the valve opens.
A cross-section of the aorta at this point reveals that the wall of the aorta is thinner than
the aortic wall distal to the sinus. [3 ] In addition, this cross section also demonstrates a
cloverleaf pattern to the aorta showing the ballooning of the sinuses of Valsalva. This
space between the aortic surface of the valve cusp and the wall of the aorta behind the
cusp is bounded caudally by the basal attachment of the aortic valve cusp and cephalad
by the sinotubular junction, which is the beginning of the aorta just downstream to the
sinus. This space provides a reservoir of blood when the valve leaflets are open and
also, as discussed later, functions to billow the valve leaflets to accelerate apposition
during diastole.
The valve leaflets are classically described as semilunar valves. This description
reflects the fact that leaflet attachments to the aorta are in one plane but are
crescent-shaped. Each valve cusp is approximately equal in size and weight. Each
leaflet is approximately 308 mm 2 and weighs approximately 0.08 g with a volume of 1
mL. [4 ] Although the normal aortic valve appears to have three equally sized leaflets,
over 50 percent of patients have one valve leaflet slightly larger than the others. In
addition, there is a trend for larger-sized hearts to be associated with larger valves. [4 ]
A valve leaflet is composed of collagen, elastin, and glycosaminoglycans. These

components form the three principal layers of the leaflet: the fibrosa or arteriosa, the
spongiosa, and the ventricularis ( Fig. 28-3 and 28-4 ). As can be seen in Figure 28-3 ,
the arterial and ventricular side of the aortic leaflet is associated with the corresponding
aortic and ventricular wall. There is no demarcation between the outer layers of the
leaflet and the corresponding wall. The outer layers of the leaflet form a continuum with
the aortic endothelium or ventricular endocardium.
The ventricular side of each aortic valve cusp contains elastin-rich fibers aligned in a
radial direction, perpendicular to the leaflet free margin. In addition, there is a collagen
component lying parallel to the free margin in a circumferential direction. The aortic side
contains a collagen-rich layer referred to as the corrugated fibrosa . These fibers are
arranged in a circumferential direction and, in a relaxed state, assume a wave form
pattern. The middle layer, referred to as the spongiosa , consists of mainly loose
connective tissue or mucopolysaccharides. These principal layers of the aortic leaflet
provide the necessary biomechanical properties for proper valve function. [5 ]
On the arteriosa (fibrosa) side of the valve leaflet, endothelial cells are present.
Endothelial cells normally align in the direction of stress. In an artery, endothelial cells
are aligned in the direction of blood flow because flow stress is the major stress.
However, endothelial cells on the aortic valve leaflet are arranged in a circumferential
pattern; i.e., they are arranged perpendicular to the blood flow. Therefore, shear stress
of blood flow across the aortic valve is not the major stress. The major stress across the
aortic valve is in a circumferential direction and is perpendicular to blood flow. [6 ]
BIOMECHANICAL PROPERTIES
The mechanical properties of the aortic valve must allow the valve to open with minimal
transvalvular pressure differences and to close completely with minimal flow reversal.
Although these functional requirements are simple, the mechanical properties also must
provide durability. The pressure drop across the aortic valve generates large stresses
within the leaflets. These stresses are too great for the leaflets and must be distributed
to the fibrous skeleton of surrounding structures by the valve anatomy. [5 ]
The valve leaflets demonstrate anisotropic properties because equal leaflet strains in all
directions would not allow the valve to close properly during diastole. Differences in
strain properties allow the cusps to stretch during closure to completely coapt along the
free margins. Strain distribution is in two directionscircumferential and radial. The radial
vector is perpendicular to blood flow, and the circumferential vector is in the direction of
blood flow. Circumferential stiffness is increased relative to radial stiffness. These
anisotropic properties allow the valve leaflet to stretch in a radial direction, whereas
downward movement is relatively restricted. This facilitates leaflet coaptation and
sealing during diastole. As seen in Figure 28-4 , the fibrosa layer of the valve leaflet is
corrugated. This property allows the fibrosa layer to stretch in a radial direction and
allows each leaflet to billow toward the other leaflets. Although this layer is the principal
load-bearing layer, these properties do not prevent it from stretching. The ventricularis
layer determines the stiffness in the circumferential direction. [5 ] These properties are
demonstrated in Figure 28-5 , where different layers of the valve leaflet are severed and
strain properties measured.
Because the principal stresses are oriented in a radial direction, endothelial cells on the
fibrosa layer of the leaflets are oriented in a radial direction. Most of the stress on the
leaflets occurs at the interface between the two coapting edges of the cusp. These
stresses are reduced by several factors. By mutual coaptive support, each leaflet
reduces the stress of the other. These stresses are then distributed along the leaflet
edges to corners of the commissures.
Further stress reduction is also accomplished by the interaction of the sinus of Valsalva
with the leaflet assembly. The sinus of Valsalva changes its radius of curvature from
systole to diastole, decreasing approximately 16 percent. [3 ] This change in radius of
curvature allows distribution of stresses within the sinus in accordance with the Laplace
formula. By coaptation of the valve leaflets in diastole, there is an inward bending of
each sinus at the commissural attachments and outward bowing of the aortic wall within
the sinus between commissures. This decreases the radius of curvature of the aortic
wall of the sinus and verifies that each sinus of Valsalva shares the stresses during
diastole.
These mechanisms of stress reduction are important for valve durability. If stresses are
unabated due to abnormalities, such as improper coaptation of the valve leaflets or
congenital anatomic abnormalities, the normal mechanism of stress reduction cannot
operate. Stress reduction is important because endothelial damage on valve leaflets is
directly proportional to the amount of stress. With turnover of endothelial cells and
fibroblastic activity, repair of the valve incorporates calcium, which further reduces the
mechanical efficiency of the valve. Inability to manage stresses efficiently explains why
abnormal leaflets produce progressive deterioration of valve function.
Mechanics of Movement
The opening and closing of the aortic valve constitute a passive mechanism responding
to the pressure fluctuations of the cardiac cycle and pressure differences between the
ventricular chamber and the aorta. Although pressure changes during the cardiac cycle
may create some structural changes of the valve mechanism to facilitate opening or
closing, the principal component is the pressure difference between the ventricle and
the aorta. Under normal circumstances, the valve leaflets offer little impediment to flow
because the specific gravity of the leaflets is equal to that of blood. [7 ] Proper function
depends on rapid closure in response to minimal forces moving the valve leaflets.
OPENING
During diastole, the pressure difference between the aorta and the ventricle creates
stresses on the valve leaflets. These stresses toward the central portion of the aortic
opening constrict the base of the aortic root. In addition, the elastic properties of the
aortic root contribute to this decrease in diameter. During late diastole, as the blood fills
the ventricle, a 12 percent expansion of the aortic root occurs approximately 20 to 40
ms prior to aortic valve opening. [8 ] This slight dilatation of the aortic root flattens the
valve leaflets to reduce their apposition to a minimum. As pressure rises in the
ventricular outflow tract, tension across the leaflets lessens. As pressure continues to
rise, the pressure difference across the valve leaflets is minimal, and no tension is
present within the leaflet. [9 ] At this point, without constriction of the aortic root at the
leaflet attachments due to redistributed stress during diastole, the aortic root expands to
allow the valve to open rapidly at the beginning of ejection. Ejection takes place with a
brisk upward movement of straightened leaflets, and the angle at their bases becomes
more acute. [10 ] These mechanisms permit the valve to open quickly and to offer
minimal resistance to ejection.
CLOSING
Closure of the aortic valve is one of the more elegant mechanisms of the valve
apparatus. [11 ] A principal theory involved in closure is the vortex theory. The vortex
theory recognizes the importance of the sinus of Valsalva in providing a reservoir of
blood for small developing vortices. These small vortices allow full expansion of the
opened valve leaflets. However, by maintaining a space between the edge of the leaflet
and the aortic wall, reversal of flow at the end of systole provides rapid closure. As
ejection occurs, deceleration of blood at the stream edge creates small eddy currents
or vortices. These small vortices along the aortic wall gradually move toward the base of
the ventricular arterial junction to the edge of the leaflet and top of the sinus of Valsalva.
As flow declines at end-systole, the pressure difference across the opened aortic valve
leaflet decreases. At the end of ejection and prior to valve closure, the vortices within
the sinus of Valsalva balloon the valve leaflets toward the center of the aorta. The angle
at the base of the leaflet becomes more obtuse and rounded, in contrast to the very
sharp angle at maximal valve opening. This point of flexure begins to move up the valve
leaflet and eventually terminates at the free margin of the valve cusp. [10 ] Therefore, the
mechanics of valve closure begin during ejection with development of vortices within the
sinus of Valsalva priming the leaflets for valve closure. When pressure between the
ventricular outflow tract and aorta equalizes, a small reversal of flow occurs due to the
deceleration of ejected blood. This small flow reversal causes the leaflets to close
rapidly.
Apposition of the valve leaflets occurs briskly. The second heart sound occurs after
complete closure of the aortic valve. [12 ] The valve leaflets act as an elastic membrane,
with stretch and recoil producing the sound; the sound is not produced by physical
apposition of the valve leaflets. The second heart sounds depends on the elasticity of
the valve leaflet and diastolic blood pressure to cause reverberation of the valve leaflet.
Rheology
Blood flow across the aortic valve is pulsatile and differs from classic laminar flow such
as flow through a pipe at a constant rate. Analysis of flow characteristics is also difficult
because structural components above and below the aortic valve differ from patient to
patient. In addition, the dynamics of the valve mechanism and rate of ejection force vary
considerably. However, while recognizing these limitations, certain characteristics of
normal aortic flow rheology can be described.
As ventricular contraction occurs, blood pressure within the chamber increases. As the
pressurized blood moves through the ventricular outflow tract, velocity increases until the
blood is ejected at the aortic valve. The ventricular outflow tract acts as a funnel to
increase blood flow velocity. As blood passes through the relatively fixed aortic valve
ring to the slightly larger aorta, laminar flow is not present, and a ventricular flow profile
develops.
The ejected blood produces a skewed peak systolic velocity profile that varies in its
location along the aortic wall [13 ] and during the course of ejection. This velocity profile
becomes more blunt at the end of the ejection. Because the effective valve orifice is
normally smaller than the aorta, the ejection flow pattern interacts with the blood column
along the aortic wall that has a relatively low velocity. This interaction between blood
moving at varying velocities causes turbulence. Turbulence is defined as random
velocities in more than one plane. Therefore, it is normal to have some turbulence;
however, the degree of turbulence is directly proportional to both the velocity of ejected
blood and the interface between ejected blood and the relatively stagnant blood in the
aorta.
Figure 28-6 demonstrates that as blood is ejected through the valve orifice, the position
of the leaflets helps to reduce turbulence by masking the dilatation of the sinuses to
produce an aortic root of nearly uniform diameter. Under these normal circumstances,
the effective valve orifice is minimally smaller than the aorta. Once the flow profile
reaches the aortic wall, the interaction between stagnant blood and high-velocity blood
no longer occurs, and turbulence is diminished.
When high-velocity blood interacts with low-velocity blood, energy transfer occurs and
contributes to turbulence. This energy density can be up to 14 times greater in highly
turbulent blood as compared with normal blood turbulence. This energy density is
obviously transferred to the surrounding structures, particularly the endothelium of the
aorta, but this high turbulence may initiate damage to intimal surfaces to produce intimal
thickening and platelet deposition with subsequent thrombosis. [14 ]
Throughout systole and early diastole, a bidirectional velocity profile is present.

Retrograde velocities present around the wall of the aorta subsequently contribute to
closure of the aortic valve leaflets. Bidirectional velocity is present under normal
circumstances; however, if it is severe, it may contribute to early systolic closure of the
aortic valve.
AORTIC STENOSIS
In the adult population, the principal cause of aortic stenosis is deposition of calcium
within the aortic valve leaflet. A lifetime of leaflet stress with each cardiac contraction
causes shearing stresses that produce small deposits of calcium within the collagen
framework that increase with time. This aging process is accelerated by rheumatic
fever. Although rheumatic fever has declined over the past few years, it still remains a
cause for aortic stenosis. In the adult population, bicuspid valves are common. Although
many patients with bicuspid valves require operation at a younger age, these patients
represent only about 1 percent of the general population. [15 ] Bicuspid valve leaflets
tend to calcify as early as ages 20 to 30 years and may become symptomatic between
the ages of 30 and 60 years.
Despite the underlying cause for the aortic stenosis, the pathophysiologic
consequences are essentially the same. With a decrease in the effective valve orifice,
there is progressive obstruction to flow from the left ventricle. Disturbance of the flow
profile through the aortic valve contributes to further deterioration of the valve and
decreases valvular mechanical efficiency. In addition, ventricular adaptations to the
abnormal resistance occur and, if untreated, lead to ventricular dysfunction.
Rheology
An appreciation of the velocity profile in aortic stenosis is needed not only to understand
the consequences of high-velocity ejection but also because noninvasive measures of
velocity are used to assess the degree of stenosis. The velocity of blood ejected
through the aortic valve is determined by several factors. [16 ] The first factor is the
degree of contractile force transferred to blood within the left ventricle. With normal
ventricular function, aortic stenosis is associated with a highly asymmetric flow profile.
Because this flow profile is asymmetric, different velocities, depending on location,
occur within the ejection stream. [17 ] A low ejection fraction demonstrates a lower
velocity profile and more symmetry. In this situation, the flow velocity profile at any point
is similar despite the same degree of stenosis as a normally ejecting heart. A higher
degree of asymmetric flow may be due to septal angulation of the ventricular outflow
tract. As the ventricle hypertrophies, the septum may change to create changes in the
velocity patterns in the outflow track. [18 ] As blood moves through the aortic outflow
tract, it reaches maximum velocity at the minimal cross-sectional area of the valve. [19 ]
At this point of maximal velocity, static pressure is minimal. Static pressure of blood
above the aortic ring is greater than the pressure of blood at the valve orifice.
Pressure differences occur within domains of blood, within the valve orifice, and above
the valve. These pressure differences are important because blood with high velocity
and relatively low pressure interacts with fluid with lower velocity and higher pressure
and may produce turbulence. The critical Reynold's number that depends on flow
velocity determines whether turbulence will occur. [20 ] As blood velocity increases, from
an increase in either ejection force or more severe stenosis, the critical Reynold's
number is reached and turbulence occurs. This turbulence may be relatively short in
length or may extend considerably, although dampened to below the diaphragm. [20 ]
As mentioned previously, a high degree of turbulence causes deterioration of the
valvular intimal lining and induces changes within the aortic wall.
As the effective valve orifice decreases with increasing aortic stenosis, flow separation
occurs at the junction between the ejection stream and nonejected blood present in the
aorta. This flow separation may cause stagnation and sometimes flow reversal.
Retrograde flow in the ascending aorta occurs during both systole and diastole and is
enhanced by both the degree of aortic stenosis and the ejection velocity. Retrograde
flow also occurs along the wall of the aorta and in regions of vortex formation. These
deviations from normal flow characteristics can cause dramatic changes within aortic
endothelium and in aortic size. High shear stress causes normally oval endothelial cells
to narrow and align in the direction of shear stress forces. Where the ejection stream
interacts with the aortic wall downstream from the valve, endothelial cells align in the
direction of flow. As the degree of stenosis increases, the ejection may interact with the
aortic wall further downstream. Thus, as stenosis increases, endothelial cells are not
aligned in the direction of flow just above the valve, but are aligned further downstream.
[21 ] , [22 ]
Prolonged aortic stenosis may produce post-stenotic dilatation. Two factors determine
the diameter of a vesselthe distending pressure acting perpendicular to the vessel wall
and the intrinsic elastic properties of the wall itself. Pressure fluctuations caused by
aortic stenosis produce a wide range of fluid movements that vibrate the vessel wall [23
] at various frequencies. [17 ] Vibrations modulate the properties of aortic elastin. In
older vessels, a higher frequency of vibration is required to produce changes within the
elastin nets joining the lamella. [23 ] With deterioration of elastic properties, the aortic
wall tends to dilate more at any given distending pressure. Post-stenotic dilatation is
usually seen distal to the aortic valve and most likely where the ejection stream interacts
with the aorta directly to modulate elastin. Since older vessels require a higher
frequency to dilate, the duration and quality of the vibration (murmur) are critical for
modulation of elastin.
Hemodynamics
Aortic stenosis may be defined simply as a point of resistance between the left
ventricular cavity and the aorta that prevents proper ejection of blood. Because of this
resistance, pressure is greater within the left ventricle than in the aorta and causes
structural changes within the left ventricle over time. Pressure differences across the
valve assess the degree of stenosis and influence the clinical decision for surgical
intervention. However, pressures in the ventricular chamber and outflow tract are not
equal during systole. Since the outflow tract is tapered, flow velocity is increased as
compared with that in the left ventricle. [25 ] Because of this increase in flow velocity,
measured pressure is less than pressure measured in lower portions of the ventricle.
[18 ] Thus the location of the ventricular pressure measurement is critical in determining
the pressure difference across the valve. The most accurate measurement for
determining aortic valve area using the Gorlin formula is that taken just below the valve.
Both principal methods of measuring transvalvular pressure gradients have technical

difficulties. The first method obtains simultaneous pressures on both sides of the aortic
valve. The second technique uses a pullback catheter to measure left ventricular
pressure first and then the pressure above the valve. The simultaneous pressure
gradient is more accurate, but with both methods the catheter itself can add to the
stenosis, particularly if the aortic valve area is less than 0.6 cm 2 . Catheter pullback can
increase the distal pressure as much as 5 mm/Hg in patients with critical aortic
stenosis. [26 ] However, despite the catheter contribution to stenosis, the simultaneous
technique is more reliable in patients with a low transvalvular pressure gradient and/or
rhythm problems. [27 ] As mentioned previously, the transvalvular pressure gradient is
important for calculating aortic valve area using the Gorlin formula, but the correlation
between the calculated area and the degree of stenosis varies depending on the
pressure gradient. As the transvalvular pressure gradient increases, the correlation with
degree of aortic stenosis also increases so that a mean gradient of 50 mmHg is
approximately 90 percent accurate in predicting the severity of stenosis, whereas a
mean gradient of 30 mmHg is only 60 percent accurate. [28 ]
Calculation of Valve Area
There are two principal methods for determining valve area. The Gorlin formula uses
invasive measurements of pressure and flow to determine valve area; a second
technique, referred to as the continuity equation , utilizes Doppler-derived data to
determine valve area. The Gorlin formula is used during cardiac catheterization,
whereas the continuity equation is used with echocardiography. The advantage of the
continuity equation is that it is a noninvasive technique so that the severity of aortic
stenosis may be followed easily over time.
THE GORLIN FORMULA
The Gorlin formula was used originally to determine the severity of mitral valve stenosis.
The correlation studies were done only with a mitral valve; however, the same formula is
used to calculate aortic valve area. The Gorlin formula is
where AVA is aortic valve area, AVF is aortic valve flow, and AVG is the mean
difference across the aortic valve. All values are for systole only.
The Gorlin formula has two componentsflow and pressure gradient. Aortic flow is
measured during systole to determine aortic valve area. Systolic aortic flow is
calculated from heart rate and cardiac output, measured by the Fick equation or
thermodilution. The most common measurement is by thermodilution. Errors in the
measurement of cardiac output have a direct effect on calculations of aortic valve area.
The thermodilution technique is less reliable in low-flow states, particularly less than 3
liters/min. During low flow, temperature of the fluid bolus dissipates to erroneously
indicate higher flows. The difference between the thermodilution and Fick techniques
during low flow can be 35 percent.
The Gorlin formula contains intrinsic assumptions. It assumes that no aortic insufficiency
is present. With aortic insufficiency, the effective ejection of blood is greater than the
calculated cardiac output, and the calculated valve area is too large. A second
assumption is that the valve area is constant under all conditions; however, with an
increase in left ventricular pressure, calculated valve area increases. In addition, a
thickened aortic leaflet may distend more with higher left ventricular pressures. In some
patients, the degree of aortic stenosis is affected by the dynamic variables of the left
ventricle. Conversely, left ventricles with decreased ventricular function may not fully
open thickened leaflets so that the calculated valve area is smaller than the anatomic
valve area. The third assumption of the Gorlin formula is that the correction constant of
44.5, extrapolated from mitral valve data, is accurate for the aortic valve even though it
has not been derived from aortic valve data.
There are intrinsic problems with the Gorlin formula. For the most part, the Gorlin
formula has a tendency to overestimate valve size by approximately 15 percent. [17 ]
The exact cause for this overestimation is not known. In addition, valve area increases
with increasing cardiac output. This may be due to distensibility of the aortic valve
apparatus in relation to the velocity and pressure of blood moving through the valve.
Despite these difficulties, the Gorlin formula is used widely to determine aortic valve
area in clinical practice, but the limitations must be realized, particularly in patients with
marginal calculated areas for surgical intervention or with low ejection fractions. [30 ]
THE CONTINUITY EQUATION
The continuity equation uses data from noninvasive techniques to determine aortic valve
area. Echocardiography can measure stroke volume and the velocity of blood just distal
to the aortic valve. [31 ] These two variables with the calculated ejection time provide the
data for calculation of the aortic valve area. The aortic valve area correlates with left
ventricular ejection times better than that produced from stroke volumes. [32 ] The
continuity equation is based on the Bernoulli equation, but assumptions are made to
facilitate the calculation. The first is that flow is fractionalized within the valve orifice. The
second assumption is that maximal velocity is minimal proximal to the obstruction as
compared with blood flow velocity distal to the stenosis. With these assumptions, the
continuity equation is simplified [33 ] to
where SV is stroke volume, ET is ejection time, and V is flow velocity. Thus the
continuity equation measures the effective orifice area and not the anatomic area.
In clinical practice, there are additional assumptions and limitations of the continuity
equation. In the presence of large amounts of calcification within the valve and
surrounding aorta, measurement of velocity distal to the valve may be difficult. Because
of basal septal hypertrophy, flow velocity may be low in the left ventricular outflow tract,
and the assumption that the blood velocity is minimal just proximal to the aortic valve is
erroneous. [33 ] The angle of the Doppler probe influences measurements of velocity. If
the Doppler angle deviates more than 30 degrees, the error in the velocity calculation
may be squared. [35 ] Because blood flow velocities are asymmetric past the valve,
sampling errors of peak velocity may impair determination of a true mean velocity.
Finally, because of time differences between determination of stroke volume and aortic
flow velocity, an error in the time variable may be produced that greatly affects
calculation of effective valve area. [36 ] The continuity equation is useful for determining
effective valve area but has a tendency to underestimate valve area when compared
with the Gorlin formula. [37 ]
Development of left ventricular hypertrophy is the principal pathophysiologic

consequence of aortic stenosis. This is a normal adaptive response to increased work
demands imposed by valvular stenosis and may be considered beneficial. However,
over the long term, the combination of increased work and the effects of hypertrophy on
cardiac function is detrimental. These changes include a decrease in diastolic function,
an increased need for coronary flow, a decrease in coronary flow reserve, and
myocardial biochemical changes such as a decrease in ATPase. These adaptive
changes are adverse and contribute to the onset of congestive heart failure and/or
angina. Relief of the mechanical obstruction partially reverses adverse ventricular
adaptations.
Left ventricular hypertrophy is induced by either pressure or volume overload. As seen

in Figure 28-7 , Grossman [38 ] hypothesized that with an increase in pressure, the
increase in systolic pressure leads to an increase in midmyocardial stress. Increased
wall stress induces development of hypertrophy by an unknown mechanism to increase
wall thickness and reduce wall stress. This is called concentric hypertrophy and is
defined as an increase in wall thickness with near-normal intraventricular volume.
Consequently, the radius-to-wall-thickness ratio is smaller than normal. Eccentric
hypertrophy is induced by volume overload such as aortic insufficiency. In concentric
hypertrophy, new myofibrils are added to remodel the left ventricle, but the number of
myocytes is not increased. Cells are thicker, and myofibrils are added in parallel. [39 ]
Cells are not longer, so the length-width ratio is decreased compared with normal
myocytes. [40 ] This remodeling has the effect of normalizing peak systolic wall stress.
The increase in intracavitary pressure stress caused by ventricular outflow obstruction is
compensated by concentric hypertrophy. Since wall stress is directly proportional to
pressure and chamber radius (Laplace formula) and inversely proportional to two times
the wall thickness, an increase in wall thickness compensates for an increase in left
ventricular pressure.
MOLECULAR EFFECTS
Shortly after birth, cardiac myocytes no longer replicate. Any increase in myocardial
mass is produced by an increase in the size of each individual myocyte. The stimulus
for inducing hypertrophy is, in effect, a stimulus for changing the gene expression of
each myocardial cell. These changes occur almost immediately after increasing
pressure load and have both short- and long-term adaptive roles. These adaptive
mechanisms recapitulate a fetal pattern of gene expression and alter both cellular
contractile elements such as myosin and the biochemistry that affects the relaxation
capabilities of the left ventricle. The stimulus for reexpression of a fetal gene type
appears to be development of increased left ventricular stress. The exact mechanisms
by which increased stress induces genetic reexpression are under active investigation.
Stressed myocytes are thought to upregulate protein kinase A and C. These kinases
activate transcription factors that stimulate promoter genes to produce hypertrophy and
normalize stress. [41 ] [43 ] A change in transcriptional activation probably upregulates
cardiac genes [44 ] [46 ] to increase protein synthesis and the total concentration of
cardiac RNA. [47 ]
Within the contractile unit, actin and myosin interact to generate the force necessary for
contraction. Myosin is the major molecule and consists of two heavy chains, two light
chains, and two regulatory chains. The heavy chain of myosin contains the site for
ATPase activity and exists in two isoforms, alpha and beta myosin heavy chains
(MHCs). Both alpha- and beta-MHCs are present in atria and ventricles. Hemodynamic
overload is accompanied by permanent induction of the beta-MHC gene. Increased
expression of the beta-MHC gene (isoform transition) causes a slower rate of ATP
cycling by myosin and a lower velocity of contraction to produce an improved efficiency
of force generation. [48 ] , [49 ] Because the beta-MHC gene is normally the
predominant isoform in the left ventricle, pressure overload has very little effect on the
ventricle; however, with increased production of the beta-MHC gene in the atria, atrial
efficiency of force generation is improved. The actin components of the contraction unit
are not affected by pressure overload. Therefore, the functional consequence of cardiac
hypertrophy cannot be explained fully by an induction of beta-MHC gene, and other
components, such as noncontractile proteins, may explain the observed physiologic
changes.
Contractile parameters that are depressed in hypertrophy include peak isometric

tension, maximum rate of rise of tension, and maximum rate of relaxation. These are
functional consequences of perturbed excitation-contraction coupling. [48 ] , [50 ]
Myocardial relaxation is controlled by sarcolemmal sodium-calcium exchange in the
sarcoendoplasmic reticulum by ATPase (SERCA). In hypertrophy, calcium transit times
are prolonged significantly and lead to major changes in excitation-contraction coupling.
With hypertrophy, SERCA is not upregulated and is depressed. [51 ] It is hypothesized
that there are a fixed number of SERCA molecules per cell. With hypertrophy, because
the number of cells does not increase and the number of contractile units in the
myofibrils increases per cell, the relative amount of SERCA to myofibrils decreases. In
addition, calcium release channels such as dihydropyridine and ryanodine receptors in
the sodium-calcium exchange show reduced expression. [51 ] These changes
contribute to prolonged calcium transit times. The change in receptors and a relative
change in SERCA density prolong calcium transit time and the disequilibrium between
contraction and relaxation. These changes may have a minor effect on the inotropic
state of each individual contractile unit. The major changes appear to be in relaxation
capability of the sarcomere. Abnormal regulation of calcium in cardiac hypertrophy may
explain the more frequent malignant arrhythmias and sudden cardiac death that occur
with hypertrophy. [52 ]
The mechanism by which these changes are induced at the molecular level is just
coming to light. There are growth-related genes including protooncogenes c- fos , c- jun
, and c myc . c- fos and c- jun are activated by pressure overload and other growth
stimuli such as stretch, endothelin, angiotensin, alpha and beta agonists, and hypoxia.
[45 ] The products of these two protooncogenes form the transcription factor complex
TRE/AP-1 motif. [53 ] This complex combines with DNA to cause structural changes or
flexing that allows individual genes to be available for transcription. Cardiac related
genes, such as the gene for atrial natriuretic factor, are associated with TRE/AP-1
binding domains. The secondary relationship between protooncogenes and
reexpression of fetal phenotypes is not fully elucidated at this time. However, external
stimuli known to be responsible for development of hypertrophy induce protooncogenes
that begin the cascade of events leading to the cellular changes responsible for
hypertrophy.
DIASTOLIC FUNCTION
One of the purposes of diastole is to allow filling of the left ventricle with enough blood to
produce an adequate stroke volume by the next contraction. Although this is elementary,
it is an often ignored component of cardiac function. In fact, diastolic dysfunction is a
major cause of congestive heart failure and occurs in as many as 15 to 40 percent of
cases. [54 ] [56 ] Proper diastolic function or lusitropy has both an active and passive
phase. The active phase involves iso-volumic relaxation, which is dependent on
energy-dependent calcium uptake in the sarcoplasmic reticulum. The second
component is a passive mechanism and is dependent on left ventricular compliance.
These two phases, referred to as early (active) and late (passive) diastole , can have
dramatic effects on the ability of the left ventricle to maximize preload.
An increase in the time required for isovolumic relaxation occurs in patients with aortic
stenosis and ventricular hypertrophy. [57 ] The prolonged relaxation time after aortic
valve closure impedes rapid left ventricular filling that usually occurs in early diastole. [58
] This reflects actin-myosin cross-bridge inactivation that depends on calcium uptake by
the sarcoplasmic reticulum. Because of a relative decrease in SERCA per myofibril,
relaxation is prolonged, as confirmed by the decrease in the rate of rapid filling during
early diastole observed by echocardiography. [59 ] Abnormal relaxation also may
contribute to a relative decrease in endocardial coronary blood flow due to a delay in
pressure decay.
The passive elastic properties of the left ventricle during diastole do not depend on
preload or afterload but are directly proportional to the degree of hypertrophy present.
[60 ] Close correlation exists between left ventricular wall thickness, peak filling rate,
thinning rate, the time constant of left ventricular isovolumic pressure decay, and wall
stiffness. [61 ] During late diastole, the passive elastic properties are defined by a
curvilinear pressure-volume relationship. With increased chamber stiffness, the slope of
this curvilinear relationship increases. With severe forms of hypertrophy, the steeper
portions of this pressure-volume relationship are reached. This, in effect, causes
diastole dysfunction by several mechanisms. The first is that by increasing filling
pressure in late diastole, symptoms of congestive heart failure may develop. Second,
with increasing end-diastolic pressure, coronary blood flow to the endocardium may be
impaired in late diastole. [62 ] A reduction may exacerbate diastolic dysfunction. [63 ]
Third, when the steeper portions of the diastolic pressure-volume relationship are
reached, the preload reserve of the left ventricle is reduced. [64 ] , [65 ] This, in effect,
limits the ability of the left ventricle to increase stroke volume by increasing end-diastolic
volume via the Starling mechanism. When the limit of the preload reserve is reached,
afterload mismatch occurs and leads to a decrease in clinical indices of ventricular
function such as ejection fraction.
Pressure hypertrophy creates more diastolic stiffness compared with volume-overload

hypertrophy due to the greater wall thickness. [66 ] In addition, there is an increase in the
diastolic pressure-volume relationship as the age of the patient increases. [61 ] Late
diastolic function and compliance correlate with the size of the myocardial cell and not
the degree of fibrosis in hearts, as seen with volume overload. [67 ]
Therefore, diastolic function is impaired in hypertrophy secondary to the physical and

chemical changes brought on by the hypertrophic process. Not only does this process
limit preload reserve, but it may have secondary effects such as limiting endocardial
coronary flow and/or inducing symptoms of congestive heart failure despite normal
systolic ventricular function. In patients with aortic stenosis, diastolic dysfunction usually
occurs before systolic dysfunction.
SYSTOLIC FUNCTION
No index of left ventricular contractile state is totally satisfactory. Clinically, ejection

fraction is the index used most frequently to evaluate left ventricular systolic function.
Other indices such as the end-systolic pressure-volume relationship (ESPVR) are used
in both laboratory and clinical settings but have drawbacks. Although the ESPVR
provides a more detailed view of ventricular function, it is difficult to determine this
relationship in patients and depends on afterload, which, of course, is increased in
aortic stenosis. The concept of systolic myocardial stiffness proposed by Mirsky et al.
[68 ] is an attempt to further refine the end-systolic pressure-volume relationship.
Ejection fraction provides a single number for the clinicial evaluation of systolic function.
However, ejection fraction is affected by both preload and afterload, and since disease
states affect both preload and afterload, ejection fraction may not truly represent the
degree of ventricular contractility. [69 ] Figure 28-8 shows the effect of varying afterload
with a fixed preload on ejection fraction. When preload is fixed, as afterload increases,
ejection fraction decreases to an isovolumic contraction or zero ejection fraction. [70 ]
Conversely, with afterload fixed, by varying preload, ejection fraction varies
proportionately. Therefore, ejection fraction, although useful as a clinical index, is very
dependent on preload and afterload and must be viewed within these parameters to
fully assess ventricular function.
The ESPVR proposed by Sagawa et al.[70a] is a linear relationship of the end-systolic

pressure-volume points at varying preloads. In isolated hearts, this relationship is linear.
However, chronic animal studies as well as human studies reveal that the ESPVR is
affected by afterload. Despite these limitations, it is still used as an index of myocardial
contractile function. In aortic stenosis, as shown in Figure 28-9A , this relationship is not
useful for the following reasons: With hypertrophy an increase in left ventricular pressure
with only small increases in end-diastolic volume shifts the ESPVR to the left. Using this
criterion, one assumes that the inotropic state of the left ventricle is increased above
normal. However, this is not accurate because, as mentioned previously, the major
determinant for developing hypertrophy is myocardial stress. With the development of
hypertrophy, midmyocardial wall stress is normalized. If one plots for midmyocardial wall
stress versus ventricular volume as shown in Fig. 28-9B , the end-systolic stress-volume
relationship is nearly identical. By these criteria, the inotropic state of the left ventricle
does change with the development of hypertrophy.
Mirsky et al. [68 ] modified the ESPVR to include myocardial stiffness. This requires a
complex mathematical formula that, in brief, converts the pressure element of the
ESPVR to stress. With stiffness included, the linear relationship between ventricular
volume and pressure is converted to a curvilinear relationship, and the inotropic state is
defined by the slope of this curvilinear function. By further mathematical manipulation,
ejection fraction can be calculated for a fixed preload and afterload. Ejection fraction
may be used as a single number utilizing Mirsky's myocardial stiffness formula, and
ventricular function or ejection fraction can be compared in different hearts and different
disease states. This obviates some of the intrinsic deficiencies of ejection fraction and
the ESPVR. Intrinsic myocardial performance independent of both preload and
afterload can be measured, and a truer picture of intrinsic ventricular function can be
obtained. Although clinical evaluation utilizing this technique is limited, Mirsky's data
reveal that ventricular function is not significantly decreased in aortic stenosis; however,
there is a slight trend downward.
Therefore, although a perfect index of ventricular contractile function is not available, an

estimation of the contractile state of the left ventricle can be obtained from other indices.
Clinicians are still left with the decision as to whether or not intrinsic myocardial damage
is too severe to premit valve replacement. When ejection fraction is normal or
supernormal, this decision is easy. However, with ejection fractions of 10 to 15 percent,
there is legitimate concern over the ability of the patient to survive aortic valve
replacement. However, an understanding of afterload mismatch reduces much of this
concern in patients with low ejection fractions.
Afterload mismatch can be demonstrated by rapidly transfusing volume into a normal

heart. An end-diastolic volume is eventually reached where further increases in
end-diastolic volume no longer increase stroke volume. At this volume, sarcomeres are
stretched maximally. Any further increase in afterload with maximal distension of
sarcomeres decreases stroke volume. In essence, preload is fixed, and any further
increase in afterload reduces ejection fraction. This is shown schematically in Figure
28-8 . When maximal preload is reached and afterload is increased, afterload
mismatch occurs. Also, if preload reserve cannot be reached due to a decrease in
venous return (effective preload is reduced), or if preload reserve is reached and
afterload is increased, afterload mismatch occurs. Stroke volume and calculated
ejection fraction decrease. The ultimate extension of increasing afterload at a fixed
preload is an isovolumic contraction and a zero ejection fraction.
Therefore, a clinically determined ejection fraction cannot be used to estimate

ventricular function, and a low number may be reflective of afterload mismatch due to
aortic valve stenosis. In aortic stenosis, if one assumes, in the absence of contrary data,
that intrinsic myocardial function is not reduced severely, a decreased ejection fraction
is assumed due to afterload mismatch. This is important clinically because by
correcting the mismatch (i.e., aortic valve replacement), normal or improved ejection
fraction should return. Consequently, ejection fraction in the absence of intrinsic
myocardial disease should not be used to deny operation in patients with pure aortic
stenosis.
CORONARY BLOOD FLOW
Angina occurs in approximately 35 to 50 percent of patients with aortic stenosis. [71 ]

The risk of acute myocardial infarction is also increased. In experimental animals,
infarct size is greater with hypertrophy. [57 ] Coronary artery disease, myocardial
bridging, septal perforator compression, coronary vasospasm, and small-vessel
disease [72 ] are causes for angina or acute myocardial infarction with left ventricular
hypertrophy.
Increased oxygen demand due to increased muscle mass causes the coronary arteries
to increase in diameter in hearts with left ventricular hypertrophy secondary to aortic
stenosis. Data demonstrate that the circumflex and left anterior descending (LAD)
coronary arteries are both increased in diameter. This increase is greater in the
circumflex coronary artery as compared with the LAD artery, and this observation may
explain the propensity for sudden death and increased episodes of ventricular ectopy in
patients with aortic stenosis. [72 ] The cross-sectional area of the coronary arteries is
increased in proportion to the left ventricular mass in asymptomatic patients with left
ventricular hypertrophy, but this proportional increase is not present in patients with left
ventricular hypertrophy and angina. [73 ] The cause for the increase in coronary artery
diameter is not totally known, but vessel growth factors are supposedly responsible. The
larger coronary cross-sectional diameters decrease after aortic valve replacement. [74 ]
, [75 ] Patients with angina have a higher peak systolic pressure that may reflect
possible reverse flow or markedly decreased systolic coronary blood flow. [76 ] Patients
with angina also have a higher diastolic peak coronary artery flow velocity that may be
reflective of a relative functional stenosis of the coronary arteries. In addition, the
possibility that higher velocity leads to higher shear stresses and release of endothelial
vasoactive mediators may contribute to angina-like symptoms. [73 ]
A decrease in the driving pressure of coronary blood flow also may be responsible for
angina. The pressure in the sinus of Valsalva, particularly during systole, may be
depressed due to rheologic factors (Bernoulli theorem). This contributes to a decrease
in the driving pressure of blood flow, particularly during systole and early diastole, when
intraventricular pressures are elevated. Coronary blood flow is further reduced by
abnormal relaxation during diastole, and this may contribute to early diastolic
dysfunction. [73 ]
The coronary vascular bed does not keep pace with the increase in myocardial mass.
The density of capillaries is reduced in hypertrophied hearts, and this may explain the
development of angina with exercise. The distribution of capillaries is usually not altered
unless left ventricular muscle grows 75 percent or more. The greatest coronary blood
flow occurs in midwall layers, with lesser but approximately equal flow to the
endocardium and epicardium. With left ventricular hypertrophy, particularly in aortic
stenosis, coronary arteries may be dilated maximally under resting conditions. [77 ] With
little reserve from further coronary dilatation, coronary artery flow may be further
hampered by shortened diastole due to increased systolic ejection time. [78 ]
One of the major physiologic consequences of hypertrophy is decreased coronary

reserve. As shown in Figure 28-10 , the normal hyperemic response after a 10-second
coronary artery occlusion is severely blunted in a coronary artery distributing blood to
hypertrophied myocardium. [79 ] The peak velocity of coronary blood flow following
coronary artery occlusion is decreased by more than 50 percent. [80 ] These changes in
flow reserve are reversed after surgery. [65 ] , [81 ] , [82 ]
Left ventricular hypertrophy impairs subendocardial blood flow. There is a decrease in

the endocardial-epicardial flow ratio from 1.2 to 0.9. This accounts for an increase in the
oxygen extraction that is highest in the endocardium. [83 ] , [84 ] The change in the
endocardial-epicardial flow ratio is due to hypertrophy and is not due to an increase in
left ventricular pressure. [85 ] Thus endocardium is more vulnerable to ischemia
because most of its blood supply occurs during diastole. [77 ]
Aortic stenosis prevents normal vortex formation in the ascending aorta, and this
causes low pressure, particularly in the sinus of Valsalva. During systole, retrograde
coronary artery blood flow to the left ventricle may occur. This suggests that increased
intracavitary stress is the main cause of flow reversal. [78 ] Reversal of flow in the first
half of systole corresponds to the peak left ventricular-aortic pressure gradient.
Coronary flow is also reduced by decreased diastolic flow after the aortic valve closes.
This decrease is due to increased resistance from systolic compression of
intramyocardial vessels and decreased coronary artery filling from impaired diastolic
relaxation or both. [86 ] The ratio of systolic-to-diastolic coronary artery blood flow is
decreased compared with nonhypertrophied hearts.
All these factors contribute to the development of angina with left ventricular hypertrophy.
The increased oxygen requirements of the hypertrophied myocardial mass demand
maximal coronary artery blood flow. Coronary artery flow reserve is severely depressed,
and therefore, any exercise may induce angina and contribute to the observed
decrease in ejection fraction noted during exercise in patients with aortic stenosis.
Coronary artery disease occurs with aortic stenosis, and any further limitation of flow is
poorly tolerated. The relative decrease in coronary artery flow in left ventricular
hypertrophy induces myocardial metabolic changes. At times, anaerobic metabolism is
present in the subendocardium. Lactate and the lactate-pyruvate ratio are higher in
endocardium, and the ATP content is lower. [71 ] However, ATP content is lower in both
epicardium and endocardium. With normalization of systolic wall stress, myocardial
oxygen consumption per unit of muscle mass returns to control values. [80 ] However,
because the total amount of myocardium is greater, total oxygen consumption is also
greater.
The electrocardiogram (ECG) may be diagnostic of an increase in left ventricular

muscle mass. Voltage increases and is probably due to increased muscle mass but
also may be due to a change in conduction properties. [88 ] The mean QRS axis shifts
posteriorly, superiorly, and to the left due to hypertrophy of the basal portion of the
ventricle. Depolarization is prolonged due to the larger muscle mass. Purkinje activation
is increased but with localized intraventricular conduction delays. ST segments may be
shifted with the T-wave inverted opposite to the QRS complex. Activation is prolonged,
and repolarization proceeds from endocardium to epicardium, possibly because of
relative coronary artery insufficiency caused by hypertrophy without an increase in the
coronary capillary bed. The Purkinje system is outpaced by the growing muscle mass,
and more activation occurs in the myocardium and contributes to change in the T-wave
vector. ST-segment depression may be present due to repolarization before completion
of depolarization. Left ventricular ejection time is prolonged to a high-normal ratio of
0.43. [89 ] ECG sensitivity is reduced in the presence of coronary artery disease,
particularly when a point system is used to diagnose left ventricular hypertrophy. Criteria
for left ventricular hypertrophy are specific but, unfortunately, insensitive.
Echocardiography not only determines the degree of stenosis but also detects the
presence of calcification. Reduced excursion of leaflets and thickening are both
ascertained by echocardiography. [88 ] Noninvasive parameters such as left ventricular
end-diastolic volume, left ventricular end-systolic volume, ejection fraction, and left
ventricular wall motion can be determined. The severity of hypertrophy or wall thickening
can be measured. When the stenosis is not critical, blood velocity determined by
Doppler echocardiography is less than 3.0 m/s, [90 ] except when ejection fraction is
low (i.e., <50 percent). With a low ejection fraction, a velocity of 3.0 to 3.5 m/s may
indicate critical stenosis. Both right ventricle size and contractile function can be
evaluated. Right ventricular wall thickening in the absence of pulmonary hypertension
indicates that undefined factors are responsible for hypertrophy. [91 ] Left atrial
enlargement occurs in 73 percent of patients with an aortic valve area less than 0.8 cm
2
, and it reflects an increase in the left ventricular diastolic dimension. [92 ]
Cardiac catheterization measures the peak-to-peak left ventricular to aortic pressure

difference. Cardiac outputs are obtained by thermodilution or the Fick equation. With
catheterization, the coronary arteries are evaluated, and this is the major reason for the
study. If ejection fraction is low, sodium nitroprusside may be infused to decrease
afterload so as to increase cardiac output. This may provide more accurate
assessment of the severity of the aortic valve disease. [93 ]
Aortic valve stenosis may remain asymptomatic for years. During this time, hypertrophy
normalizes left ventricular wall stress. Ultimately, continued hypertrophy produces
adverse effects, and symptoms begin as progression of stenosis continues and
ventricular stress cannot be reduced. The classic symptoms of aortic stenosis are
angina, syncope, and congestive heart failure. Most patients with moderate to severe
aortic stenosis develop symptoms. Average survival after onset of angina is
approximately 4 years; after syncope, 3 years; and after congestive heart failure,
approximately 2 years. Most patients with untreated aortic stenosis die of congestive
heart failure, although a small subset succumbs to sudden death, presumably from
malignant ventricular arrhythmias. Aortic valve replacement is usually recommended for
patients who have any symptoms due to aortic stenosis.
Aortic valve replacement in patients without symptoms is controversial. Many authors

recommend surgery only for symptomatic patients, since ventricular changes are
reversible. However, others argue that an aortic valve area of 0.75 cm 2 or less is an
indication for valve replacement. In older patients, the prevalence of coronary artery
disease may be as high as 60 percent; therefore, patients with angina need evaluation
of both coronary artery and aortic valvular disease.
Syncope is characteristically related to exertion and usually occurs when left ventricular
function is normal and without decreased cardiac output or depressed ventricular
function. Dysrhythmias may produce syncope, but although cardiac vagal efferent
activity is depressed in patients with aortic stenosis, studies show that the initial event in
all syncopal episodes is a drop in blood pressure that is caused by an arrhythmia. The
primary event appears to be an acute reflex producing arterial and venous dilatation.
This reflex is caused by sudden changes in left ventricular pressure. Patients who suffer
from syncopal symptoms have increased left ventricular cavitary pressure, particularly
during systole. This increased pressure probably affects ventricular baroreceptor
activity to produce vasodilatation and subsequent syncope.
Symptoms of heart failure may be due to circulatory or myocardial failure. Circulatory

failure, secondary to decreased cardiac output, can produce systemic acidosis from
anerobic metabolism in skeletal muscle. Lactic acidosis induces hyperventilation to
produce symptoms of dyspnea and fatigue. Myocardial failure also causes dyspnea
and fatigue that may reflect diastolic dysfunction, which usually precedes depressed
systolic function. Filling pressures increase, and cardiac output falls.
Depressed ventricular function may be due to afterload mismatch or an intrinsic

depression of contractility. Both the safety and prognosis of aortic valve replacement
relate to distinguishing between these two causes of reduced ventricular function.
Patients with a true afterload mismatch do well after aortic valve replacement despite
very low preoperative ejection fractions. Depressed contractility from myocardial
disease does not respond as well to aortic valve replacement. Nevertheless, patients
with low ejection fractions and low wall stress often do well. Other factors that correlate
with persistent postoperative low ejection fractions include acute myocardial infarction
and coronary artery disease that was not bypassed.
Overall, ejection fraction should not be a contraindication to aortic valve replacement.

Although patients with low ejection fractions have increased perioperative mortality, no
methods are available to separate intrinsic myocardial dysfunction from afterload
mismatch.
Midmyocardial wall stress is dramatically reduced by aortic valve replacement. This

decreases induction of hypertrophy and prompts resolution. Biochemical as well as
mechanical changes are reversed, and these changes occur fully within approximately 6
to 12 months after operation. All parameters indicating left ventricular hypertrophy are
reversed. [81 ] These include a better isovolumic relaxation time, a more compliant left
ventricle, normalization of the diameter of the coronary arteries, and improved
ventricular function.
The inability of aortic valve leaflets to coapt fully provides an effective opening between
the aorta and the left ventricle during diastole that allows previously ejected blood to flow
retrograde into the left ventricular chamber. Effective stroke volume is less than the
volume ejected each heartbeat. Both volume overload and pressure overload occur; the
combination produces eccentric hypertrophy. Volume overload is due to regurgitant
flow, and pressure overload is due to the increased volume of blood ejected.
Consequently, the performance of the left ventricle with eccentric hypertrophy is different
from the concentric hypertrophy of pure aortic stenosis.
The causes of aortic insufficiency can be grouped according to the structural

components of the valve. There may be distortion of valve leaflets that prevents proper
coaptation. Calcific aortic valve disease and rheumatoid disease may prevent an
inflexible valve from closing properly. The integrity of the valve leaflet may be
compromised by endocarditis with destruction of leaflet components. Enlargement of
the aortic root with dilatation of commissures causes the effective valve orifice to be
greater than the area of the leaflets. [94 ] Rheumatoid diseases, degenerative disease,
collagen-vascular disease, and loss of commissural support from aortic dissection [95 ]
may all produce an incompetent valve and similar hemodynamic consequences.
Aortic regurgitation may be acute or chronic with different ventricular and hemodynamic
responses. With acute aortic regurgitation, the left ventricle does not have the
opportunity to adapt to the increased volume load. Disease processes that may present
in this fashion are endocarditis, aortic dissection, and traumatic disease.
With acute aortic regurgitation, the ventricular chamber cannot dilate rapidly and cannot
accommodate a large volume of reverse flow. Even with a smaller regurgitant volume,
left ventricular diastolic pressure increases dramatically. Diastolic aortic and ventricular
pressures equalize earlier in diastole. The mitral valve may close earlier in late diastole
to reduce the amount of left atrial blood entering the ventricle and to prevent backflow
into the left atrium and pulmonary veins. The rapid rise in diastolic pressure in acute
regurgitation attenuates the aortic pulse pressure as compared with the widened pulse
pressure in chronic aortic regurgitation. The normal decrease in effective area of the
aortic valve annulus may slightly reduce the regurgitant volume. [96 ] Effective cardiac
output is less as compared with chronic regurgitation because of the smaller left
ventricular volume. Heart rate increases and is higher than in chronic aortic
regurgitation. Overall, the hemodynamic effects of acute aortic regurgitation produce a
low effective cardiac output with an elevated diastolic ventricular pressure and heart
rate and lead to early congestive heart failure.
Patients with chronic aortic regurgitation gradually accommodate reverse flow through
the aortic orifice. Consequently, large end-diastolic volumes are present and are the
largest seen in any form of heart disease. Despite these volumes, compliance of the left
ventricle is normal so that end-diastolic pressure is not elevated in well-compensated
chronic aortic regurgitation. Left ventricular end-diastolic pressure does not reach aortic
diastolic pressure, as may occur in severe acute aortic regurgitation. Aortic
insufficiency impairs early diastolic function, and left ventricular relaxation is impaired in
aortic insufficiency. Abnormalities in early diastolic filling are common, and valvular
regurgitation is likely related to impaired left ventricular relaxation. [97 ] During
regurgitation, there may be flutter of the anterior leaflet of the mitral valve (Bernoulli
effect). Premature closure of the mitral valve does not occur, and diastolic time is
essentially normal.
Owing to changes in diastolic perfusion pressure, coronary artery flow may be reduced,
and many patients have angina pectoris. Oxygen demand in hearts with aortic
insufficiency is extremely high because of very large stroke volumes and slightly
increased ejection pressures. With a moderate reduction in aortic diastolic pressure,
myocardial blood flow is adequate due to normal coronary reserve. However, with a
severe reduction in diastolic perfusion pressure, a decrease in diastolic coronary artery
flow occurs. This is somewhat compensated by an increase in coronary artery flow
during systole, but an overall severe reduction inadequately perfuses the endocardium.
In experimental models, diastolic aortic pressures of 40 mmHg or less dramatically
reduce coronary artery blood flow and increase myocardial lactate production. [98 ]
Coronary artery flow reserve decreases during aortic insufficiency due to the reduced
diastolic perfusion pressure. When diastolic perfusion pressures are corrected to
control values, hyperemic flow returns. If the coronary artery is stenotic, the impact of
diminished diastolic flow reserve may be exacerbated considerably. In severe aortic
insufficiency, regurgitant aortic flow may reverse diastolic coronary artery flow. Left
ventricular hypertrophy also reduces coronary vascular reserve in direct proportion to
the degree of left ventricular hypertrophy. [104 ]
Peripheral vasodilation occurs with exercise and increases effective forward cardiac
output and heart rate. For a given regurgitant orifice, peripheral vascular resistance and
not arterial compliance is the main component for determining the amount of regurgitant
volume. Therefore, any intervention that decreases systemic vascular resistance
improves effective cardiac output. [105 ]
In addition to size, the morphology of the regurgitant orifice is important. [106 ]

Degenerative and bicuspid orifice shapes have a higher contraction coefficient and
allow more regurgitant flow than rheumatic, incompetent valves. [106 ] An increase in
heart rate reduces the duration of diastole and regurgitant flow and enhances effective
forward cardiac output. Conversely, bradycardia may cause pulmonary congestion.
[109 ] Because diastolic aortic pressure approaches left ventricular end-diastolic
pressure, pulse pressure is wide. Quincke's sign and Corrigan's pulse are indicative of
a widened pulse pressure. If the compliant left ventricle remains compensated, the third
heart sound is usually not heard in chronic aortic insufficiency.
Flow reversal increases left ventricular diastolic stress. With the increase in diastolic
stress, myocytes add myofibrils in series that extend the full length of each myocyte. The
length-to-width ratio of each myocyte increases to accommodate increasing left
ventricular volume. However, the addition of myofibrils in series increases left ventricular
internal diameter. Because wall thickness does not change initially, systolic stress
increases in accordance with Laplace's law. Hypertrophy develops in response to the
elevation in systolic stress and increases to normalize stress. [110 ] Similarly, the
radius-to-wall-thickness ratio remains in the normal range, although this concept has
been challenged recently. [111 ] The adaptive process of progressive left ventricular
dilatation and increasing wall thickness creates a very large left ventricular chamber.
This large chamber can eject large amounts of blood, and total cardiac output (not
effective cardiac output) can be as high as 20 liters/min in well-compensated chronic
aortic regurgitation. The ejection fraction may be normal.
With continued dilatation from untreated aortic regurgitation, fibrosis develops within the
myocardium, possibly as a result of subclinical ischemia or myofibrillar degeneration.
Compliance of the left ventricle diminishes, and with continued fibrosis, the likelihood of
postoperative improvement in cardiac function diminishes. Severe interstitial fibrosis
also correlates with metabolic deficiencies that include the mitochondrial enzymes ATP
and succinyl dehydrogenase. These enzyme deficiencies and increased myocardial
fibrous tissue portend poor postoperative outcomes but are not reliably predictive. [112
]
Evaluation of ventricular function in aortic regurgitation depends on two variables. The

first is the diastolic pressure-volume relationship. In chronic aortic regurgitation, the
diastolic pressure-volume curve is shifted to the right ( Fig. 28-11 ). This accommodates
an increase in left ventricular volume secondary to the regurgitant flow. Despite an
increase in left ventricular end-diastolic volume, left ventricular end-diastolic pressure
increases only slightly if the ventricle remains compensated.
The end-systolic pressure-volume relationship (ESPVR) is the second component. In

compensated chronic aortic regurgitation, the ESPVR is shifted to the right, indicating
reduced myocardial contractility. Ejection fraction is essentially normal and often
overestimates true myocardial function. [113 ] Because of a large end-diastolic volume
and normal ejection fraction, stroke volumes are large. Peak systolic and diastolic wall
stresses are elevated as compared with normal hearts. This provides an environment
for afterload mismatch; therefore, ejection fraction may not be a good indicator of
ventricular function. [114 ]
As aortic insufficiency progresses, the preload reserve of the left ventricle is eventually
reached. Thereafter, any further increase in afterload creates afterload mismatch. In
general, patients with aortic insufficiency have slightly depressed ventricular function
when the ESPVR is compared with that of normal patients. [115 ] A near-normal
ESPVR with depressed ejection fraction indicates afterload mismatch. However, a
depressed ESPVR with a low or moderate ejection fraction usually indicates intrinsic
myocardial disease, particularly in patients with large end-systolic and end-diastolic
volumes.
As aortic insufficiency continues, irreversible ventricular dysfunction occurs. Diastolic

wall stress continues to increase without a further increase in wall thickness, and
myofibrillar slippage may develop. Ventricular function deteriorates with the loss of
mechanical advantage at the myofibrillar level. Further reductions in ventricular function
and increases in diastolic stress produce myocardial damage and more myocardial
fibrosis. This provides a spiral of events that leads to further deterioration and
subsequent death.
A point is reached in the natural history of aortic insufficiency when valve replacement
will not improve cardiac function. Identifying these patients is somewhat difficult.
Ejection fraction alone is a poor indicator of postoperative functional recovery because
it depends on preload and afterload. Irreversible changes decrease both the ejection
fraction and the ability to develop peak systolic stress in relation to chamber size.
Patients with left ventricular end-systolic volumes exceeding 60 ml/m 2 have reduced
fractional shortening after operation and remain in functional class IV. Gaasch et al.
[116 ] suggest that when the ratio of chamber volume to wall thickness exceeds 3.8,
postoperative recovery is compromised. This ratio is indicative of progressive dilatation
with myofibrillar slippage.
Myocardial oxygen consumption (M vo 2) is much greater than in normal hearts due to

the large stroke volume and slightly increased ejection pressure. Endocardial and
epicardial blood flow ratios may change remarkably to as low as 0.76. The
endocardial-to-epicardial M vo 2 ratios may decrease to as low as 0.54 in severe forms
of aortic insufficiency compared with control values of 1.44. Therefore, aortic
insufficiency increases myocardial oxygen consumption, but the endocardium becomes
ischemic with increasing demand due to the decreased diastolic perfusion pressure.
[117 ]
Although interstitial fibrosis occurs in aortic regurgitation, left ventricular function

correlates with the contractile material lost and not the amount of interstitial fibrosis.
[118 ] Myofibrillar protein synthesis in aortic regurgitation is dissimilar to hypertrophy
with pressure overload. Myocyte hypertrophy in response to acute pressure overload is
due to an increase in the rate of myofibrillar protein fractional synthesis and occurs
within 3 days. However, in chronic aortic regurgitation, the increase in myofibrillar
protein content at 1 month is not due to an increased rate of synthesis but is caused by
a decrease in the rate of degradation. [119 ]
Chronic aortic regurgitation results in left-axis deviation. Q waves in leads I, V 1 , and V

3 to V 6 are indicative of diastolic volume overload. [120 ] Left ventricular conduction
defects are usually associated with left ventricular dysfunction. The QRS amplitude is
linearly correlated with left ventricular mass. The finding of a strain pattern in relation to a
reduction in the QRS amplitude is indicative of severe depression of ejection fraction
and contractility. [121 ] Overall, the ECG is not an accurate predictor of the severity of
aortic regurgitation.
Echocardiography is helpful in aortic regurgitation because of its ability to evaluate

other valves. Vegetations present on the aortic valve indicate possible endocarditis.
Severe aortic insufficiency may cause premature opening of the aortic valve. The
etiology of aortic regurgitation is defined by failure of leaflets to coapt versus stiffness of
fibrotic or calcified leaflets. The quality of the regurgitant murmur is evaluated by
color-flow techniques. [122 ] [124 ] Measurements of end-systolic and end-diastolic
volumes, as well as measurement of wall thickness, can be obtained. These
measurements are useful for determining possible irreversible changes in the left
ventricle. A reduction in the EA slope indicates that the left ventricle is volume
overloaded and is operating on the steep portion of the diastolic pressure-volume
curve. Premature closure of the mitral valve, as seen in acute aortic regurgitation, can
be recognized. Fluttering of the anterior mitral leaflet from regurgitant flow may occur
during diastole. This is a sensitive indicator of both acute and chronic aortic
regurgitation. Although fluttering of the open mitral valve classically is seen during
diastole, fluttering also may occur with the mitral valve closed. Fluttering of the posterior
mitral valve leaflet is also described. [127 ]
More important, echocardiography is a useful noninvasive technique to follow aortic

insufficiency over time. With noninvasive techniques to evaluate ejection fraction, left
ventricular diameters in systole and diastole, and wall thickness, patients may be
followed to determine when aortic valve replacement is most appropriate. [128 ] Any
deterioration detected by echocardiography is an indication for aortic valve
replacement.
Cardiac catheterization is important to estimate the severity of aortic insufficiency and

concomitant coronary artery disease. The amount of regurgitant flow can be determined
by calculating the angiographic stroke volume minus a measured fixed stroke volume.
The difference between these two measured volumes divided by the angiographic
stroke volume determines the regurgitant fraction. In general, a regurgitant fraction less
than 20 percent is one-plus (1+) aortic insufficiency. An increase in regurgitant fraction
to 60 percent corresponds to four-plus (4+) insufficiency. [129 ] Left ventricular
end-diastolic pressure is measured directly, and ejection fraction is estimated roughly.
Indications for Surgery
Acute aortic regurgitation is treated by early valve replacement. With inadequate time
for the left ventricle to compensate, progressive congestive heart failure, tachycardia,
and diminished cardiac output ensue rapidly.
Compensated chronic aortic regurgitation is well tolerated by most patients. [130 ] ,

[131 ] Aortic valve replacement is not currently recommended for patients who are
asymptomatic, even with severe chronic aortic regurgitation. These patients, however,
must have normal ventricular function and good exercise tolerance. In asymptomatic
patients, aortic valve replacement is indicated for deteriorating ventricular function. [132
] An ejection fraction of less than 55 percent with a diastolic diameter approaching 75
mm or an end-systolic diameter approaching 50 mm is an indication for operation. [133
] [136 ]
Predictive indicators of impending symptoms in asymptomatic patients are not

available. One potential indicator is measurement of left ventricular wall stress at rest
and after exercise. Although the number of patients was small in this study, three of
three patients with increased wall stress developed symptoms of decompensated left
ventricular volume overload within a mean of 3.6 years. [137 ] Aortic valve replacement
is indicated if patients develop symptoms of congestive heart failure or decreased
exercise tolerance. Nonoperative management of patients with severe aortic
regurgitation and abnormal left ventricular function is associated with a 50 percent
mortality in 1 year. [138 ]
Ideally, aortic valve replacement should be performed before irreversible myocardial

damage occurs. Although patients with impaired ventricular function are at an increased
perioperative risk, survival is prolonged when compared with patients undergoing
medical management. Risk factors for postoperative death include a
radius-to-wall-thickness ratio of 3.8 or greater. [116 ] , [139 ] However, despite aortic
valve replacement, impaired left ventricular dysfunction may continue. In patients whose
ventricular function does not return to normal, the left ventricle shows fiber hypertrophy
and increased interstitial fibrosis.
The regression of left ventricular dimension and cross-sectional area can take as long
as 3 years. The best predictor for persistent, postoperative left ventricular enlargement
is preoperative enlargement of the end-diastolic dimension, but this descriptor is not
always predictive of outcome. The peak systolic pressure to end-systolic volume ratio is
also used as a predictor of postoperative outcome. Six months after operation, 8
percent of patients with a ratio of peak systolic pressure divided by an end-systolic
volume of less than 1.72 mmHg/mL/m 2 died and 31 percent were in functional class III.
This index, although not corrected for stress in the study, may be useful with other
parameters for predicting postoperative outcome. Duration of symptoms of left
ventricular dysfunction preoperatively is also an indicator for poor reversibility of
ventricular function postoperatively. [142 ]
Early postoperative studies of left ventricular size and function reveal that end-diastolic
volumes decrease significantly with valve replacement. With the decrease in pre-load,
subsequent ejection fraction decreases; however, if the operation is correctly timed,
ejection fraction eventually recovers to near-normal values in selected patients. [143 ] ,
[144 ] Further recovery includes regression of myocardial hypertrophy, reduction in left
ventricular size, and normalization of the mass/volume ratio. [145 ] If improvement is
going to occur after aortic valve replacement, it occurs within the first 6 months as the
ventricular end-diastolic dimension decreases. A decrease in the peak systolic wall
stress and an increase in ejection fraction also occur within the first 6 months. [146 ] ,
[147 ] After aortic valve replacement, the amount of coronary artery flow during systole
decreases by 36 percent, whereas diastolic flow increases by 81 percent. Overall, the
ratio of the diastolic flow over total coronary flow increases from 63 to 82 percent. [148 ]
CONCLUSION
The two classic forms of aortic valve disease are aortic stenosis and aortic
regurgitation. Aortic stenosis is manifested by a pressure-overloaded ventricle that
develops left ventricular hypertrophy to compensate. Ventricular function is
characterized by an afterload mismatch between the ventricle and the systemic
circulation. In patients with poor ventricular function as measured by ejection fraction,
measurements are needed to accurately determine the severity of aortic stenosis.
Careful assessment is also needed to differentiate between poor ejection fraction
caused by afterload mismatch versus intrinsic myocardial disease. With this
differentiation, low ejection fraction is not a contraindication to aortic valve replacement
because of afterload mismatch.
Aortic insufficiency is a mixture of pressure and volume overload. Volume overload is

the major component and is responsible for the compensating ventricular dilatation.
Patients with aortic insufficiency that is well compensated tolerate aortic regurgitation
for months or years. With serial echocardiograms, aortic valve replacement can be
recommended in these patients before severe ventricular dysfunction develops.
A subset of patients does not benefit from aortic valve replacement because of left
ventricular dilatation with concomitant fibrosis and myofibrillar slippage. These patients
are not identified by a single index, but careful assessment of the duration of symptoms,
ventricular dimensions, and wall stresses provides some prognostic information
regarding postoperative outcome. Despite poorer long-term outlooks, medical
management produces poor results, and unless there are other contraindications, aortic
valve replacement may be advisable.
MORPHOLOGY
Aortic Stenosis
CALCIFIC CONGENITAL AORTIC STENOSIS
Calcific aortic stenosis is caused by dystrophic calcification of the congenitally

abnormal bicuspid valve (Figure 29-1) . Calcification progresses to produce significant
stenosis by the fifth and sixth decades of life. Calcification presents as mass lesions
within the leaflets and is maximal at sites of commissural fusion or congenital buttress
formation. The calcification invariably extends into the ventriculo-aortic junction or
annulus and to the adjacent aorta often near the coronary ostia. Calcification of the
right-non-coronary commissure at the membranous septum may cause complete heart
block. The valve orifice is nearly fixed and slit-like.
DEGENERATIVE AORTIC STENOSIS
Degenerative or arteriosclerotic aortic stenosis occurs on a normal tricuspid valve. The

calcific deposits develop as part of the atheromatous process of the leaflets and cause
the leaflets to remain essentially closed. Significant stenosis develops in the sixth,
seventh and eighth decades of life. Calcification may involve the sinuses of Valsalva
and occasionally the ascending aorta. Mitral annular calcification may accompany this
senile degenerative process of the aortic valve.
RHEUMATIC AORTIC STENOSIS
Rheumatic aortic stenosis is the least common cause and usually occurs in conjunction
with mitral valve disease. The pathological process produces fibrous leaflet thickening
of the tricuspid valve with fusion of one or more commissures. Calcification can occur
and usually is most severe at sites of commissural fusion. A history of rheumatic fever is
elicited in approximately 50 percent of patients. The prevalence of rheumatic aortic
stenosis fell in the 1980's.
Rheumatic aortic regurgitation is caused by cicatricial leaflet shortening with minimal

thickening and calcification of the leaflets. The central regurgitation through the rolled
leaflet margins produces aortic root dilatation.
ANNULOAORTIC ECTASIA
Annuloaortic ectasia is a feature of Marfan syndrome and the pathologic process is

cystic medial degeneration. Annuloaortic ectasia can occur in the absence of Marfan
syndrome but may still be hereditary. The aortic dilatation causes varying degrees of
aortic regurgitation even when cusps are normal. The process can cause aneurysmal
enlargement of the ascending aorta with involvement of the sinuses of Valsalva and the
sinotubular junction. Regurgitation is due to tightening of the free leaflet edges and loss
of coaptation in diastole. Regurgitation worsens as dilatation progresses. The
ventricular-aortic junction is not involved in the process and consequently larger
prostheses are not required. The aneurysmal process usually terminates upstream to
the innominate artery.
The major complication of annuloaortic ectasia is aortic dissection. Approximately 30

percent of surgical patients with Marfan syndrome and annuloaortic ectasia with
proximal aortic aneurysm have aortic dissection. Acute aortic dissection can destroy
the commissural attachment of the valve to produce leaflet prolapse.
MYXOMATOUS DISEASE OF AORTIC VALVE
Myxomatous degeneration of aortic leaflets can cause prolapse from redundancy of the
leaflets. In this floppy valve syndrome the aortic root may be normal or dilated and mitral
valve prolapse also may be present.
NATIVE VALVE ENDOCARDITIS
Native valve endocarditis may occur on both normal and diseased valves. Aortic
regurgitation can occur from leaflet perforation or leaflet prolapse from commissural
destruction. The aortic root may be destroyed by a periaortic abscess which can extend
to the anterior leaflet of the mitral valve or to adjacent chambers especially the right
atrium. Mitral regurgitation from perforation of the anterior leaflet may occur.
CONGENITAL REGURGITANT VALVE
Regurgitation may occur from prolapse of a redundant leaflet of a congenital unicuspid

or bicuspid valve.
MISCELLANEOUS
Aortic dilatation from numerous other causes may produce aortic regurgitation.
Atherosclerotic and syphilitic ascending aortic aneurysms, aortitis from rheumatoid
arthritis, Reiter syndrome, and ankylosing spondylitis are uncommon causes of aortic
regurgitation. Spontaneous cusp rupture or blunt trauma may cause rupture and
regurgitation of a myxoid degenerative valve. Other causes of regurgitation are related
to hypertension, psoriasis and Takayasu disease.
Combined Aortic Stenosis and Regurgitation
The etiology and morphology of combined aortic lesions are produced by essentially
the same causes as isolated lesions.
CLINICAL FEATURES AND DIAGNOSIS
Aortic Stenosis
Patients with rheumatic aortic stenosis may be asymptomatic for over 40 years,
whereas those with congenital bicuspid disease may become symptomatic anytime
between the ages of 15 and 65 years. [1 ] Calcification of the valve is usual in the
seventh and eighth decade of life. The onset of symptoms is ominous and indicates a
life expectancy of less than 5 years. The classic triad is angina, syncope, and
congestive heart failure. The life expectancy in half of the patients with angina is less
than 5 years, those with syncope less than 3 years and those with congestive heart
failure less than 2 years. Angina pectoris is the initial symptom in 5070 percent of
patients with severe aortic stenosis. [2 ] Angina usually occurs with exertion; rest angina
indicates associated coronary artery disease. [3 ] Syncope is the presenting symptom
in 1530 percent of patients. [4 ] [6 ] All patients with aortic stenosis are at increased risk
of sudden death, but only 5 percent of asymptomatic patients die suddenly. Symptoms
of congestive heart failure are those of pulmonary venous hypertension (dyspnoea,
orthopnea, paroxysmal nocturnal dyspnoea or frank pulmonary edema). End-stage
aortic stenosis causes secondary right ventricular failure.
The physical findings of aortic stenosis are an ejection systolic murmur (heard in right
and left intercostal spaces near the sternum and apex with radiation to carotids),
expiratory splitting of the second heart sound, and prominence of the apical beat. The
murmur may be barely audible in the terminal stages of heart failure or in patients with
emphysematous lungs.
The chest radiograph shows calcification of the aortic valve and convexity of the left
ventricular silhouette due to left ventricular hypertrophy. The electrocardiogram reveals a
strain pattern from hypertrophy with or without inverted T-waves in V 6 . The
electrocardiogram may show right or left bundle branch block. Continuous-wave
Doppler echocardiography is the best means to establish the diagnosis; the Doppler
gradient correlates closely with the mean catheter gradient. A systolic gradient of 50
mm Hg is clinically significant. Coronary angiography is indicated for patients over the
age of 40 years to determine the presence or absence of coronary artery disease.
Valve area is measured at cardiac catheterization or by echocardiography.
Patients with aortic regurgitation usually are asymptomatic for years. The dominant
symptoms are those of pulmonary venous hypertension, namely, dyspnoea, orthopnea,
and paroxysmal nocturnal dyspnoea. Angina pectoris is the presenting symptom in 25
percent of cases. [2 ] Syncope is very rare in aortic regurgitation.
The physical findings include a displaced prominent apex, collapsing or water hammer
pulse in advanced disease, wide pulse pressure and very low diastolic pressure. An
early diastolic murmur radiates to the apex, and often an apical, mid-diastolic murmur
caused by fluttering of the anterior mitral leaflet (Austin-Flint murmur) is present. The
murmur may be difficult to distinguish from that of mitral stenosis. Two-dimensional
echocardiography differentiates the hemodynamic lesions.
The chest radiograph documents left ventricular enlargement. An enlarged ascending

aorta shows aneurysmal disease. The electrocardiogram reveals left ventricular
enlargement with high-peaked T waves and prominent Q-waves. Color flow Doppler
echocardiography distinguishes the diagnosis of aortic regurgitation from ruptured
aneurysm of the sinus of Valsalva or a large patent ductus arteriosus with pulmonary
regurgitation. Coronary angiography is indicated for patients over 40 years of age.
Many patients have combinations of both lesions, more commonly severe aortic
stenosis with mild regurgitation rather than severe regurgitation with mild stenosis.
PATHOPHYSIOLOGY
Aortic Stenosis
The natural progression of aortic stenosis is from mild to moderate to critical severe
stenosis. The normal adult valve area is 2.63.5 cm 2 , which corrects for size to an index
of 2 cm 2 /m 2 . As stenosis progresses, normal stroke volume is associated with an
increasing systolic pressure difference between the left ventricle and aorta. Left
ventricle pressure may reach 300 mm-Hg with a normal aortic systolic pressure and
relatively normal stroke volume. The higher pressure gradient produces compensatory
left ventricular hypertrophy (Chapter 28). There is increased muscle mass without
chamber dilatation. The accompanying increase in left ventricular end-diastolic
pressure (LVEDP) is an indication of decreased diastolic function or reduced
compliance.
Development of symptoms indicates moderate aortic stenosis with reduction of the

orifice area to 0.70.9 cm 2 and valve index of 0.5 cm 2 /m 2 . [7 ] LV dilatation may
accompany hypertrophy with increases in both left ventricular end-diastolic volume
(LVEDV) and LVEDP. [8 ] Ejection fraction may decrease with compromise of left
ventricular contractility. Symptoms may appear with the onset of atrial fibrillation since
atrial contraction supplies up to 40 percent of ventricular filling during diastole in aortic
stenosis. In a normal heart atrial contraction contributes approximately 20 percent of
stroke volume. The loss of sinus rhythm may cause rapid clinical deterioration in
moderate aortic stenosis.
Critical aortic stenosis develops with reduction of the aortic valve index to below 0.5 cm
2
/m 2 and is accompanied by increases in LVEDP and further decreases in ejection
fraction. [9 ] In the early stages of compensation, LV end-systolic volume remains
normal although LVEDP and LVEDV are elevated. In the late stages of the disease with
marked elevations of LVEDP and LVEDV, LV end-systolic volume increases and
stroke volume falls.
Angina pectoris occurs when there is an imbalance between myocardial oxygen supply
and demand and reduction in coronary reserve. A subnormal increase in blood flow in
proportion to the increase in left ventricular mass in aortic stenosis creates a mismatch
between oxygen supply and demand. In the early stages of aortic stenosis increases in
LV pressure are offset by increases in wall thickness and wall stress remains normal.
As the disease progresses LV pressure increases beyond the ability of the ventricle to
hypertrophy and wall stress rises. [10 ] Angina occurs at this stage because oxygen
supply is reduced by impaired coronary blood flow reserve and demand is increased by
elevated wall stress.
The mechanism of syncope is controversial. [6 ] Syncope may occur during exercise

with a normal reduction in systemic vascular resistance without an ability to increase
cardiac output through the stenotic aortic valve. Development of cardiac dysrhythmias
during exercise is a possible cause of syncope. [5 ]
Congestive heart failure occurs when both diastolic and systolic dysfunction develops.
Diastolic dysfunction occurs as increased wall thickness reduces ventricular chamber
compliance. Reduced compliance requires higher pressures to fill the ventricle and
symptoms of pulmonary congestion. Systolic dysfunction occurs from afterload
mismatch and decreased contractility. Ventricular ejection is impaired as wall stress or
afterload increases when left ventricular pressure rises and wall thickness cannot
match. The fall in ejection performance reduces cardiac output and increases LV
pressure and pulmonary congestion. The development of left ventricular hypertrophy
may be associated with depressed contractility. Left ventricular hypertrophy influences
the geometry of the ventricle. [11 ]
A pressure-volume flow loop for aortic stenosis is illustrated in Figure 29-2A . [12 ]
Peak pressure generated during systole is much higher in aortic stenosis owing to the
transvalvular peak gradient. The slope of the diastolic segment is steeper in aortic
stenosis and reflects reduced LV diastolic compliance. Small changes in diastolic
volume produce relatively large increases in ventricular filling pressure.
The systolic segment of the pressure-volume loop is maintained by satisfactory pump

function with maintenance of stroke volume and ejection fraction. The compensatory
mechanisms of forward flow are preload reserve and left ventricular hypertrophy.
Ejection performance is maintained at the expense of ventricular hypertrophy and wall
stress remains normal. However, severe afterload stress and extensive concentric
hypertrophy can decrease subendocardial perfusion to produce ischemia.
The load independent indices of contractility (end-systolic stress-end-systolic dimension

relationship) usually are the same before and after development of hypertrophy and
suggest that the increase in chamber thickness compensates for afterload stress to
maintain normal contractility. The end-systolic pressure-volume relationship (E max,
elastance) shifts upward and to the left with development of concentric hypertrophy and
pressure overload. Loss of preload reserve with maintenance of ventricular contractility
leads to congestive failure.
Chronic aortic regurgitation is a long-standing adaptive process that increases left

ventricular end-diastolic volume (LVESV) in relation to the regurgitant volume. The
ventricle adapts by eccentric hypertrophy similar to normal physiologic growth of the
heart. Regurgitation of blood during diastole does not initially increase the LV
end-diastolic pressure. During this phase of the disease the patient remains
asymptomatic.
Severe LV volume overload creates a vicious cycle with disproportionate increases in

LVEDV in relation to regurgitant volume that decrease LV ejection fraction. Clinical
decompensation occurs when left ventricular enlargement leads to increased afterload.
Severely increased afterload further enlarges the left ventricle and extends the vicious
cycle of increasing end-systolic and end-diastolic volumes, increasing afterload and
decreasing ejection fraction. Even though adequate hypertrophy normalizes afterload,
ventricular hypertrophy cannot keep pace with excessive ventricular dilatation; eventually
marked hypertrophy decreases compliance, elevates LV end-systolic pressure, and
produces exertional dyspnoea. [13 ] When the ventricle can no longer dilate, the reversal
point of preload reserve is reached and the ventricle decompensates.
At this stage both diastolic and systolic left ventricular wall stresses are elevated and
ejection fraction decreases at rest. [13 ] , [14 ]
The pressure-volume flow loop for both chronic and acute aortic regurgitation are shown
in Figure 29-2B . [12 ] In chronic regurgitation the diastolic pressure-volume curve is
shifted far to the right with a tremendous increase in LVEDV and a marginal change in
filling pressure; diastolic compliance is high. Preload reserve maintains the total stroke
volume that includes systemic and regurgitant flow. Assessment of contractile function is
crucial as ejection phase indices are unreliable. The Starling mechanism continues to
support stroke volume even in the presence of myocardial depression as demonstrated
by the ability of left ventricular dilation and minimal afterload to normalize ejection
fraction even with depressed contractility.
When compensated the dilated ventricle maintains stroke volume and ejection fraction
by using preload reserve. When the limit of preload reserve is reached, ventricular
dysfunction occurs and shifts the end-systolic wall stress relationship to the right. Stroke
volume and ejection fraction decline with higher wall stress.
LVESV is independent of preload but is influenced by contractility and afterload. In

chronic aortic regurgitation end-systolic volume is determined by wall stress. Myocardial
oxygen supply is compromised by diastolic hypotension and shortened diastolic time
for coronary perfusion because of a compensatory tachycardia.
Acute aortic regurgitation in the pressure-volume loop shows a precipitous rise in

LVEDP. Systemic resistance is high and stroke volume falls. Heart rate increases;
coronary arterial flow reserve decreases, and myocardial ischemia may occur.
NATURAL HISTORY
Aortic Stenosis
Aortic stenosis has a long asymptomatic period. The average duration of life is
markedly reduced when symptoms develop, especially those of congestive heart failure.
The natural history of severe, symptomatic aortic stenosis (aortic valve area <0.7 cm 2 )
is well documented. Mean survival after angina pectoris occurs is nearly 4 years, after
syncope slightly over 2 years, and after congestive heart failure 1 year. [19 ] The same
study reveals that the age of onset of symptoms is related to the etiology of aortic
stenosisrheumatic aortic stenosis, 39 years; congenital bicuspid stenosis, 48 years;
and degenerative calcific stenosis of tricuspid valves, 66 years (Fig. 29-3) .
The natural history of moderate aortic stenosis (aortic valve area 0.71.2 cm 2 ) is not
well documented. Patients with moderate aortic stenosis are at significant risk of
developing complications, but, approximately 60 percent remain asymptomatic 4 years
after diagnosis. [7 ] Valve area is not the only prognostic factor; overall mortality is
similar for patients with symptomatic moderate and severe stenosis. Absence of
symptoms does not necessarily guarantee absence of left ventricular dysfunction, and
moderate increases in left ventricular pressure and left ventricular volume indexes.
Complications develop in one-third of patients with ejection fractions 50 percent but are
higher in those with ejection fraction <50 percent. The same center [7 ] reports that
patients with asymptomatic, hemodynamically significant aortic stenosis have a
significant risk of cardiac events within 2 years but low risk of sudden death.
Survival of patients after recommendations for surgery is only 18 percent at 5 years and
no patient survives 12 years. [19 ] The sudden death rate remains high with advanced
aortic stenosis. [20 ] The rate of sudden death is >10 percent/year in symptomatic
patients but 2 percent/year in asymptomatic patients.
In a pediatric population, a ventricular-aortic pressure of 50 mm-Hg increases the risk of

serious arrhythmias and sudden death; if the gradient is 80 mm-Hg surgical intervention
is clearly indicated. [21 ] The intermediate group, 5079 mm-Hg, should not have
intervention delayed.
The study by Horstkotte and Loogen [19 ] indicates that prognosis of aortic stenosis
correlates only with signs and symptoms of disease. These authors do not recommend
surgery for mild stenosis (AVA >1.5 cm 2 ) and moderate stenosis (AVA 1.50.8 cm 2 ,
gradient <80 mm-Hg) until development of symptoms. For patients with severe aortic
stenosis (0.81.4 cm 2 ) and symptoms mean survival is 4.5 years after onset of angina
with all patients dead within 10 years; 2.6 years after first syncope and all patients dead
at approximately 5 years; and <1 year with the first episode of congestive heart failure
with all patients dead within 2.5 years.
Chronic aortic regurgitation is usually tolerated for a long period of time with no
symptoms but once symptoms develop deterioration may be rapid. The natural history
of chronic regurgitation is determined by development of progressive heart failure that
may continue despite aortic valve replacement. The natural history is less well
documented in comparison to aortic stenosis. Onset of symptoms or left ventricular
dysfunction are general indications for operation.
The relationship between left ventricular function and onset of symptoms in chronic
aortic regurgitation is evaluated by echocardiographic diastolic and systolic diameters,
ejection fraction, shortening fraction, systolic stress, volume-mass ratio and contractility
index. Development of symptoms identifies patients with more advanced eccentric
hypertrophy. [22 ]
The natural history is known for asymptomatic patients with normal systolic function. [23 ]
, [24 ] The prognosis is excellent with an annual mortality <1 percent; less than 4
percent/year require surgery after symptoms and left ventricular dysfunction develop. [25
] Patients who require surgery over this extended time frame are identified by
increasing age, progression of LV dimensions and decreased resting ejection
fractions. The risk of sudden death increases with extreme LV dilatation; diastolic
diameter >80 mm and end-systolic diameter >55 mm.
The natural history of aortic regurgitation is influenced by both medical and surgical
therapy. Lin and colleagues [26 ] evaluated the long-term efficacy of enalapril versus
hydralazine on left ventricular volume, mass, and function and on the renin-angiotension
system. Both drugs significantly reduced left ventricular mean wall stress and mildly
increased exercise tolerance. Enalapril significantly reduced left ventricular mass, and
left ventricular end-diastolic and end-systolic volumes and suppressed the
renin-angiotension system. This study suggests that early unloading with enalapril may
influence the natural history of chronic aortic regurgitation. Schön [27 ] confirmed the
benefit of ACE inhibitors by demonstrating that long-term quinapril provides sustained
reductions in LV loading and LV mass. The decrease in systemic vascular resistance
reduces regurgitant volume and at least partially explains a decrease in left ventricular
end-diastolic volume.
Aneurysmal dilatation of the aorta is a common complication of Marfan syndrome and

may manifest at an early age. [28 ] There is a relationship between fibrillin depletion of
connective tissue microfibrils, hemodynamic factors and changes in annular diameter.
Rapid progression of aortic dilatation to aortic root diameters in excess of 50 mm may
produce aortic dissection and aortic insufficiency from sinotubular enlargement and loss
of leaflet coaptation.
INDICATIONS FOR AORTIC VALVE REPLACEMENT
Aortic Stenosis
Development of symptoms with moderate and severe aortic stenosis is an indication for
aortic valve replacement. [29 ] Surgery also is indicated for the asymptomatic patient
with severe aortic stenosis who is at increased risk of ventricular ectopy and sudden
death.
The majority of patients with aortic stenosis and left ventricular dysfunction dramatically
improve after aortic valve replacement. Patients with severe aortic stenosis, congestive
heart failure and greatly impaired ventricular function also benefit from surgery because
left ventricular afterload is reduced. This immediately improves ejection fraction and
hemodynamic performance.
In a minority of patients with low transvalvular gradients ventricular performance may not
improve after surgery. Smucker et al [30 ] studied prognostic indicators in aortic
stenosis and concluded that neither poor ventricular function nor low mean aortic
gradient always predicted a poor surgical outcome. Nevertheless, low mean valve
gradient, aortic valve area >0.8 cm 2 and advanced age are relative contraindications to
aortic valve replacement. Patients with low transvalvular gradients and reduced valve
areas should have inotropic augmentation at catheterization to determine if higher
cardiac outputs can increase valve area above the critical range (>1 cm 2 ). If so, these
patients probably have cardiomyopathy and only mild aortic stenosis and may benefit
from vasodilator therapy. [29 ]
The elderly patient with aortic stenosis may have remarkable improvement after aortic
valve replacement. Risk is somewhat increased in elderly patients but is confined
primarily to patients with concomitant coronary artery disease.
The indications for aortic valve replacement are summarized in Table 29-1 [25 ] , [31 ]
and the indications are based on symptoms, severity (mean gradient 50 mmHg and
aortic valve area (0.75 cm 2 , or aortic valve area index (0.4 cm 2 /m 2 ), progression of
ventricular enlargement and decline of ventricular contractility.
Optimal timing of aortic valve replacement for chronic aortic regurgitation remains
challenging. [32 ] Operation is mandatory in symptomatic patients but is more
questionable in asymptomatic patients and patients with severe left ventricular
dysfunction. Symptomatic patients who are NYHA III or IV are definite candidates for
aortic valve replacement. Asymptomatic or minimally symptomatic patients usually are
followed until the onset of resting left ventricular dysfunction.
In the early 1980s the asymptomatic patient with severe aortic regurgitation was
followed until heart size increased and resting ejection fraction decreased to 20 percent
on exercise. [33 ] However, Louagie and colleagues [34 ] found that late survival differed
significantly between patients with NYHA I and II, and III and IV and recommended that
severe regurgitation with altered left ventricular function was an indication for surgery
regardless of the presence or absence of symptoms.
Optimal timing of surgery has evolved over the past decade. [25 ] , [35 ] [38 ] In 1984
Bonow [35 ] reported criteria for left ventricular dysfunction as end-systolic diameter >50
mmHg, decrease in left ventricular ejection fraction during exercise, progressive
increase in end-systolic and end-diastolic diameters, rapid decrease in fractional
shortening (<29 percent) or ejection fraction (<50 percent). Kress and co-authors [37 ]
attempted to identify the limits of compensatory mechanisms and recommended aortic
valve replacement when end-diastolic volume exceeded 300 mL with clinical symptoms,
and/or moderately depressed left ventricular ejection fraction, and LVEDV/residual
volume within the normal range.
Indications for surgery for asymptomatic aortic regurgitation were reviewed by Bonow
[25 ] in 1994 (Table 29-2) . Patients who undergo aortic valve replacement with
preoperative LV dysfunction have greater risk of postoperative heart failure and death
than those with normal function. Patients who are asymptomatic with definite or
reproducible evidence of impaired LV function should undergo surgery without waiting
for symptoms or more severe LV dysfunction. Asymptomatic patients with normal LV
systolic function can be managed conservatively with only a gradual rate of
deterioration. Patients likely to require operation over 10 years because of symptoms
or LV dysfunction are identified by older age, progressive increase in LV dimensions or
decrease in resting ejection fraction. Patients at risk of sudden death are identified by
extreme LV dilatation (diastolic dimension >80 mm; systolic dimension >55 mm).
The combined lesions have both volume and pressure overload of the left ventricle.
Indications for operation are based on whether stenosis or regurgitation are
predominant. Severe aortic stenosis with mild regurgitation is more common than aortic
regurgitation with mild stenosis.
The response of left ventricular function following aortic valve replacement has been
assessed by postoperative exercise tolerance. [38 ] [40 ]
TECHNIQUE OF OPERATION
Choice of Operation and Replacement Devices
The surgeon has a wide range of aortic valvular substitutes. [41 ] This chapter discusses
bioprostheses and mechanical prostheses; allografts and autografts are presented in
chapter 30 and complex operations of the aortic root are detailed in chapter 31.
Available operations include simple valve replacement, aortic inclusion cylinder, and
aortic root replacement. Prostheses for simple aortic valve replacement are mechanical
prostheses (bileaflet, monoleaflet, and caged-ball), stented porcine and pericardial
bioprostheses, stentless porcine bioprostheses, and allografts. Choices of prostheses
for an inclusion cylinder are stentless porcine bioprostheses and allografts. Prostheses
for aortic root replacement are mechanical valved conduits, homografts, autografts,
stentless porcine roots, and porcine bioprosthetic conduits. An additional option for
aortic root disease is synthetic root replacement with retention of the native aortic valve.
Annular enlarging and reduction procedures are supplementary procedures.
The choice of prosthesis is based on patient age; pathological process; aortic valve
and root anatomy; compliance with anticoagulation; anticipated durability of the
prosthesis to expected longevity, and comfort level of patient, surgeon, and cardiologist.
Small stented porcine bioprostheses and mechanical prostheses are intrinsically

obstructive. The general rule is that 19- and 21-mm prostheses are not suitable for body
surface areas over 1.5 m 2 . Small obstructive prostheses cause high transvalvular
gradients and inadequate regression of left ventricular mass. Annular enlargement or
stentless prostheses are possible alternatives for these patients.
A pulmonary autograft usually is reserved for children to facilitate growth and for young
adults for extended durability. [42 ] Porcine bioprostheses are definitely suitable for the
elderly because durability is better. [43 ] [52 ] Stentless porcine bioprostheses are
currently implanted in elderly patients. Stentless porcine bioprostheses have reduced
fatigue-related stress and potentially extended durability.
Allografts are recommended for native and prosthetic valve endocarditis, small aortic
annuli and patients less than 5055 years of age. [53 ] [56 ] Subcoronary allografts are
contraindicated for large aortic annuli (30 mm). Allografts are also contraindicated for
malalignment of coronary ostia or porcelain aortic walls.
Mechanical prostheses are recommended for younger adults if allografts or autografts

are not available or suitable. Mechanical prostheses are also recommended for elderly
patients by a significant proportion of cardiologists and surgeons.
Anatomy and pathology determine the type of prosthesis for aortic root reconstruction.
With endocarditis and annular abscess, chamber fistula or aortoventricular discontinuity,
root replacement with an allograft is best. [55 ] [57 ] A mechanical valved conduit or an
allograft, if available, usually is used for Type A aortic dissection. Ascending aortic
replacement with a synthetic cylinder and preservation of native aortic leaflets with or
without sinuses is now recommended for aortic aneurysm and/or annulo-aortic ectasia
with normal aortic leaflets. This procedure is advocated by Yacoub (personal
communication) and David and colleagues. [58 ] All aortic root reconstructions require
coronary arterial, ostial button anastomoses.
The majority of aortic valve replacement procedures are performed with mechanical
prostheses and xenograft (porcine and pericardial) bioprostheses. [41 ] , [46 ] [49 ] , [51
] , [52 ] , [59 ] [133 ]
Perioperative Preparation
AORTIC STENOSIS
The patient's circulation must be maintained. [134 ] Left ventricular preload may require
augmentation to maintain stroke volume; nitroglycerine may endanger cardiac output.
Loss of sinus rhythm may seriously compromise preload augmentation. Heart rate
should be maintained at 5070 per minute because low rates limit cardiac output while
rapid rates decrease coronary perfusion and reduce the time for systolic ejection. Beta
blockade is avoided because of a possible increase in LVEDV and decrease in
cardiac output. Even though afterload is fixed, systemic vascular resistance must be
maintained to support adequate systemic diastolic perfusion pressure and coronary
perfusion. Alpha-adrenergic agonists may be required to maintain systemic vascular
resistance. Pulmonary vascular resistance usually is normal and should not require
manipulation except for end-stage aortic stenosis.
Left ventricular preload must be maintained because of the increased left ventricular
volumes. Any pharmacological intervention that produces venous dilatation may reduce
cardiac output. Heart rate of 90 per minute is optimal because reduced diastole
decreases the regurgitant fraction. Tachycardia improves subendocardial blood flow
with a higher systemic diastolic pressure and lower LVEDP. Increased heart rate does
not induce myocardial ischemia because cardiac output is improved. Sinus rhythm is
not as important as in aortic stenosis since many patients are in atrial fibrillation.
Although left ventricular function is impaired, left ventricular contractility must be
maintained. Pure beta-adrenergic agents may increase stroke volume by increasing
contractility and peripheral dilatation. Systemic vascular resistance should be reduced
with afterload-reducing agents; any increase in afterload increases stroke work and
LVEDP. Pulmonary vascular resistance is normal except in end-stage left ventricular
dysfunction.
Anesthetic Considerations
The anesthetic considerations must be influenced by the hemodynamic lesion, both for
aortic stenosis and aortic regurgitation. [134 ] , [135 ]
AORTIC STENOSIS
Premedication must prevent tachycardia and must be light to maintain preload and
afterload. A thermodilution cardiac output pulmonary arterial catheter is required
postoperatively but dysrhythmias may occur during placement. The anesthetic agent
should be narcotic-based to avoid myocardial depression, reduced blood pressure,
and dysrhythmias. During induction and maintenance of anesthesia, a potent
alpha-adrenergic agent, such as phenylephrine, may be needed to maintain systemic
pressures. Any evidence of ischemia is treated cautiously with nitroglycerine.
Supraventricular dysrhythmias are treated with synchronized DC cardioversion because

either tachycardia or loss of atrial contraction can rapidly reduce cardiac output.
Emergency cardiopulmonary bypass may be necessary if the circulation deteriorates
rapidly. Transesophageal echocardiography (TEE) is necessary for evaluation of the
replacement prosthesis and for maintaining ventricular function.
Premedication should be light to maintain myocardial contractility and heart rate.

Moderate tachycardia is not harmful in aortic regurgitation. The anesthetic may be
isoflurane or a synthetic narcotic with pancuronium but should maintain preload
peripheral arterial dilatation, contractility, and a heart rate at approximately 90 beats per
minute. Transesophageal echocardiography is recommended.
Myocardial protection techniques
Myocardial protection techniques for aortic valve replacement incorporates the

integrated myocardial management philosophy and techniques of Buckberg and
colleagues. [136 ] Intermittent cold cardioplegia is recommended for perfusion to avoid
compromising visualization. Myocardial temperature is maintained between 10 and
15°C and systemic temperature is between 32 and 35°C.
Antegrade and retrograde cardioplegia is used for aortic valve surgery. [136 ] , [137 ]
Perfusion cannulae are placed in the ascending aorta and coronary sinus with the
commencement of cardiopulmonary bypass. The bypass system utilizes an ascending
aorta infusion cannula, two-stage venous cannula, and a left-sided venting cannula
placed via the right superior pulmonary vein. In aortic stenosis cardioplegic induction is
antegrade via the aorta, followed by retrograde delivery. In aortic regurgitation induction
cardioplegia is given retrograde while the aorta is opened and simultaneously with
ostial antegrade cardioplegia afterward. Both left and right coronary ostia are perfused
to ensure right ventricular protection. In general, during operation cardioplegia is
maintained with retroperfusion via the coronary sinus. Intermittent right coronary ostial
perfusion is given if the right coronary effluent blood is very desaturated.
Hypothermic cardioplegia is used for aortic valve procedures using high-potassium,

low-potassium or non-cardioplegic blood as required. Myocardial temperature is
monitored by a septal thermistor. Delivery of cardioperfusion may be continuous cold
retroperfusion or intermittent delivery every 1020 minutes. To maintain a dry operative
field a coronary sucker tip may be placed in the coronary ostium. Any electromechanical
activity is controlled by altering the potassium concentration in the cardioplegic
perfusate.
During aortotomy closure cold blood with cardioplegia is delivered retrograde. Prior to
completing closure aortic warm blood cardioplegia is recommended for 68 minutes and
is followed by 3 minutes of warm blood without cardioplegia given retrograde.
Electromechanical activity resumes momentarily following retroperfusion with
non-cardioplegic blood.
Several steps are used to deair the heart using the Buckberg technique. [136 ] The
aorta remains vented while the aortotomy is closed. As the aortotomy suture line is
secured, lungs are inflated, the left ventricle is compressed, and antegrade perfusion is
continued to evacuate all air from the aorta. Antegrade infusion is continued with an
empty beating heart with the LV vent on gravity suction. This period is limited to 5
minutes because right ventricular function deteriorates without ejection.
The aorta is declamped with the vent on high suction; the cross clamp is partially
removed to create a dome for purged retained air. The LV vent is clamped and
removed with gentle manipulation of the ventricle to expel trapped air bubbles. The
aortic clamp is completely removed. With the heart ejecting well and aortic vent on high
suction, the aortotomy is inspected and cardiopulmonary bypass is discontinued.
Buckberg maintains the antegrade aortic vent cannula for protamine administration and
arterial pressure recording if pressures do not agree with the radial arterial cannula.
The deairing procedure of Buckberg [136 ] is complicated and the author uses an
alternative method. The author deairs the heart and aorta with the heart arrested. The
aorta is deaired by antegrade infusion of cardioplegia solution during final closure of the
aortotomy. The heart then is perfused with 300400 mL of potassium-containing
cardioplegic infusate and 200 mg of lidocaine administered systemically. The LV vent
then is stopped and the ventricle is deaired with the ventricle elevated using a simple
apical cannula with full and intermittent inflation of the lungs and inversion of left atrial
appendage. The cross-clamp is removed and the aortic antegrade catheter site is
allowed to bleed for any residual air. When the heart resumes electromechanical
activity, LV vent suction is discontinued and vent is removed. Cardiopulmonary bypass
is discontinued. The site of the antegrade catheter is closed when systemic pressure is
at least 7080 mmHg systolic.
Combined aortic valve and coronary procedures require special consideration. Distal
coronary anastomoses are always constructed first in combined procedures.
Cardioplegic and non-cardioplegic solutions are administered antegrade via the aorta
and vein introducers in completed coronary grafts and retrograde through the coronary
sinus. Myocardial perfusates can be delivered simultaneously via grafts and the
coronary sinus. The resuscitation and deairing procedures are similar to those
described earlier using special precautions to prevent air in the coronary grafts.
Postoperative Care
AORTIC STENOSIS
Following aortic valve replacement for aortic stenosis, pulmonary capillary wedge
pressure, and LVEDP immediately decrease and reduce stroke volume. Myocardial
function improves rapidly, but the hypertrophied ventricle requires an elevated preload
to function normally. LV hypertrophy regresses in the several months post-operatively if
the residual pressure gradient is small. [138 ] [140 ] If myocardial preservation is
adequate, most left ventricles function well after aortic valve replacement.
AORTIC INSUFFICIENCY
LVEDP and LVEDV decrease immediately following aortic valve replacement but LV
hypertrophy and dilatation obviously persist. In the immediate postcardiopulmonary
bypass period, preload augmentation must be maintained to fill the dilated left ventricle.
In the early postoperative period, inotropic or intra-aortic balloon pump support may be
required to offset a temporary decline in left ventricular function.
AORTOTOMY
Aortotomy for aortic valve procedures can vary depending on the replacement
prosthesis and surgical preference. The standard aortotomy is transverse with the
incision 24 mm above the sinotubular junction and 46 mm above the origin of the right
coronary artery (Fig. 29-4A) . Alternatively the incision may begin transversely and then
extends obliquely toward the non-coronary sinus if a posterior annular enlarging
procedure is necessary for a larger prosthesis (Fig. 29-4B) . This incision is also used
for placing allograft and autograft valves. The inside of the aortic root is seen through
the initial transverse incision, and the final decision to insert a prosthesis, allograft, or
autograft is made. A longitudinal incision can also be extended obliquely toward the
mid-point of the non-coronary sinus (Fig. 29-4C) .
Another incision is described in Chapter 30 for an allograft or autograft. The incision is

a reversed lazy S, which begins well above the right coronary artery and proceeds
above the anticipated allograft commissural pillar, and then extends obliquely to the
midpoint of the non-coronary sinus. This aortotomy does not compromise suspension of
the commissural pillars and allows space for the pillar between the right and
noncoronary cusps.
OPERATION
The anatomic features of the aortic valve, sinuses, sinotubular junction, and anterior
leaflet of the mitral valve are determined. The morphological features of tricuspid and
bicuspid diseased valves are shown in Figure 29-5 . Calcification involving the annulus,
aortic wall, and extension into the anterior mitral leaflet is an important consideration.
The diseased valve is excised and the aortoventricular junction or annulus is completely
debrided of calcific deposits (Fig. 29-6) . Calcium over the bundle of His at the
membraneous septum must be carefully debrided. The valve is completely removed,
without damage to the left aortoventricular junction, ventricular septum or aortic wall.
Excision of the valve is accomplished with scissors and rougeurs and frequently with a
scalpel. Calcification may be abundant in the area of the right coronary-noncoronary
cusp commissure and extend onto the ventricular septum, membraneous septum, or
onto the aortic wall. The left coronary-right coronary commissural area may also be
heavily calcified. The commissure between the left coronary and noncoronary cusps is
near the aortic wall and left atrioventricular junction. Calcific deposits involving the
annulus, commissures, or anterior leaflet of the mitral valve are removed by small
rougeurs, scalpel, or curettes. Small calcific emboli are controlled by placing a small wet
radio-opaque gauze through the valve into the ventricle, using high-vacuum suction,
wiping the valve bed with wet gauze and vigorously irrigating the ventricle following
removal of the wet gauze. The annulus and commissural areas must be very pliable
after the valve is excised and the annuluis is debrided.
Sizing the aortic annulus is conducted with sizing devices used with the chosen
prosthesis. The aortic annulus is usually sized by disc for bioprostheses and
mechanical prostheses and by Hegar dilator for allografts.
MECHANICAL PROSTHESES
Currently marketed bileaflet and monoleaflet mechanical prostheses are satisfactory for
aortic valve replacement. Annular sutures are placed through the sewing ring of the
prosthesis and lowered and secured in position with tied sutures (Fig. 29-7A,B,C,D) .
The bileaflet prostheses should be placed with the central axis parallel to the septum
(Fig. 29-8) . Monoleaflet prostheses are positioned so the greater orifice opens toward
the aortic arch.
STENTED PORCINE OR PERICARDIAL BIOPROSTHESES
Sizing supra-annular stented porcine or pericardial bioprostheses requires

consideration of both the annulus and aortic sinuses. The author prefers to size the
annulus with a disc and then the supra-annular sinus area with a prosthetic valve replica
sizer such as that provided for the Carpentier-Edwards supra-annular porcine
bioprosthesis and the investigational Medtronic Mosaic porcine bioprosthesis. Annular
sutures are placed in the sewing ring of the scalloped supra-annular prosthesis to
conform to the native annulus and commissural areas.
STENTLESS BIOPROSTHESES
The stentless porcine bioprostheses can be implanted as a subcoronary, inclusion

cylinder or as replacement of the aortic root. Subcoronary implantation is similar to an
allograft using two suture layers. (Chapters 30 and 31). Root replacement with a
stentless porcine bioprosthesis is implanted as for allograft root replacement (Chapter
30).
The inclusion cylinder technique places a cylinder within a cylinder and preserves
orientation of the commissures. [141 ] A transverse aortotomy is made 25 mm above
the sinotubular junction and 56 mm above the orifice of the right coronary artery. The
aortotomy transects approximately three-quarters of the aortic circumference. Exposure
and preparation of the annulus is the same as described earlier for mechanical and
stented bioprostheses. The annulus is sized to achieve a snug fit between the porcine
aortic cylinder and the host valve sinuses. The valve must not be oversized; oversizing
causes distortion of the valve inflow. The sinotubular junction is tailored to fit the aortic
sinotubular junction. The outflow circumference of the porcine cylinder is preserved to
prevent distortion of the valve commissures.
The inflow suture line is made with simple 2-0 polyester sutures in a single plane
incorporating annulus and subcommissural areas. These sutures are passed through
the cylinder wall below the leaflets to orient the porcine coronary arteries opposite the
patient's coronary ostia. The porcine coronary sinuses are excised to fully expose the
coronary ostia and the height of the cylinder is trimmed to the level of the patient's aortic
sinuses. The outflow suture line uses a continuous 4-0 polypropylene suture and joins
the proximal edge of the partially transected aorta above the noncoronary sinus to the
edge of the porcine cylinder. The outflow suture line is completed beneath each
coronary ostium to the commissural pillars.
The Cryolife-Bravo stentless porcine bioprosthesis is designed for single suture line
implantation ( Figs. 29-9 and 29-18C ).
ALLOGRAFT AORTIC VALVE
The surgical techniques for implantation of an allograft aortic valve are described in
Chapter 30. The three techniques for valve replacement are: (1) subcoronary with 120°
counterclockwise rotation; (2) subcoronary with intact non-coronary sinus; and (3) aortic
root inclusion cylinder. The optimal technique is controversial but all are feasible for a
relatively normal aortic root. [54 ] , [142 ] Sizing is particularly important for an allograft to
fit a dilated, pressurized aortic root without incompetence. It is acceptable to use an
allograft of the same size or up to 2 mm less than the size of the host. Sizing should be
performed at both the basal and commissural levels. Measurements are made by
pre-operative echocardiography in centers that do not maintain a large bank of
allografts.
Replacement of the Aortic Valve and Ascending Aorta
Aortic root reconstruction with replacement of the aortic valve and ascending aorta can
be performed either with a prosthetic valve cylinder, allograft aortic valve cylinder or
pulmonary autograft cylinder.
The pulmonary autograft is indicated in children and adolescents because of growth

potential and adaptation to a growing patient. [42 ] An autograft is desirable for young
adults because of resistance to degeneration.
An allograft aortic root replacement is usually reserved for a deformed root due to
endocarditis with annular abscess or aortoventricular discontinuity, or a congenital
anomaly with a small annulus and dilatation of the root and sinotubular junction.
A prosthetic valve cylinder is often used for reconstruction in Marfan syndrome and in
acute type A dissection. A mechanical valved conduit is preferred to a bioprosthetic
valved conduit because of the risk of degeneration of the bioprosthesis.
PROSTHETIC VALVE CYLINDER
The technique for placement of a mechanical valved conduit is shown in Figure

29-10A,B . The preoperative preparation and cannulation techniques are similar for
standard aortic valve procedures except in cases of type A aortic dissection. In cases
of dissection, femoral artery cannulation is utilized with profound hypothermia,
circulatory arrest, and retrograde cerebral perfusion if the aortic arch is involved
(Chapter 38). Patients for prosthetic valved conduits may have annuloaortic ectasia with
dilated sinuses and displaced coronary ostia.
The ascending aorta is opened longitudinally; the aortic valve is excised; and coronary
ostial aortic wall buttons are prepared. The valved conduit need only be 2729 mm in
diameter. The proximal anastomosis can be performed with interrupted pledgeted 2-0
multifilament polyester everted mattress sutures or interrupted continuous 3-0
polypropylene sutures. The prosthesis is pressurized with blood cardioplegic solution to
evaluate hemostasis. The site for the anastomosis of the left coronary button is chosen
and a hole is made with a cauterizing coil. The anastomosis is performed with a
continuous 4-0 polypropylene suture. The site for the right coronary button is chosen, a
hole is made, and the anastomosis is done. The graft conduit is pressurized and both
coronary anastomoses are evaluated for hemostasis. The distal anastomosis to the
native aorta is completed with a continuous 3-0 polypropylene suture. The residual
aortic wall may be closed over the prosthetic graft but kinking the coronary arteries must
be avoided.
ALLOGRAFT AORTIC VALVE CYLINDER
Allograft root replacement is indicated for any abnormality of the aortic root that involves
the native aortic valve and distorts the aortic sinuses. O'Brien and colleagues [57 ] ,
[142 ] provided evidence that cryopreserved allograft root replacements may be
preferred, because immediate and late results at 8 years are the same as non-root
procedures. Fewer technical difficulties are encountered with allograft root procedures.
The technique for allograft root replacement is detailed in Chapter 30 and is similar to
that for prosthetic valved conduit insertion.
PULMONARY AUTOGRAFT CYLINDER
The operative procedure for harvesting and placement of the pulmonary autograft is
given in Chapter 30. A cryopreserved pulmonary allograft is recommended for
reconstruction of the right ventricular outflow tract. An aortic allograft becomes calcified
in the pulmonary outflow tract.
Replacement of the Ascending Aorta and Preservation of Aortic Valve
Preservation of the aortic valve during replacement of the ascending aorta and
reconstruction of the aortic root is detailed by David in Chapter 29. David and
colleagues [58 ] popularized two procedures for preservation of the aortic leaflets. The
first suspends the aortic leaflets with sinuses excised within a Dacron graft of the normal
sized annulus. Criterion for the operation is stated: if the valve is trileaflet and the
leaflets do not prolapse, i.e., the length of the free margin is shorter than the length of the
base in all three leaflets, a valve-sparing operation is feasible. The measurements for
formation of the Dacron graft have been evaluated with a computer model by
Kunzelman and colleagues. [143 ]
The operation was further refined to create pseudosinuses by longitudinal cuts in the
Dacron graft for insertion of commissural pillars. This operation was performed by
Yacoub for over a decade (personal communication), was recently reported by David,
and was successfully performed at the author's center and elsewhere. [58 ] These
procedures require reimplantation of coronary ostial aortic buttons.
The reconstruction of the aortic annulus for annuloaortic ectasia with a root diameter of
230 mm aortic annuloplasty techniques were developed to reduce the diameter of the
left ventricular outflow beneath the commissures of the non-coronary leaflet. [15 ] , [144 ]
Reoperative Replacement of the Prosthetic Aortic Valve
Reoperative aortic valve replacement is performed for several reasons: thrombosis of

the prosthesis, periprosthetic leak, prosthetic valve endocarditis and structural valve
deterioration. [64 ] , [131 ] Not all reoperations require re-replacement of the prosthesis.
Acute thrombosis may be treated by thrombectomy and periprosthetic leak by simple
resuture of the area of dehiscence. Prosthetic valve endocarditis, structural valve
deterioration and extensive periprosthetic leak nearly always requires re-replacement.
The technique of operation involves principles of all cardiac reoperative procedures.

The sternotomy can be complicated by right ventricular injury; therefore, preparations
are made for emergency cardiopulmonary bypass with femoral artery and vein
cannulation. The sternotomy is performed with a vibrating saw and usually is uneventful.
The procedure can be performed with limited lysis of adhesions to expose only the
ascending aorta, a portion of the right atrium and the right superior pulmonary vein.
Some surgeons prefer to fully mobilize the heart, especially for deairing. After
cardiopulmonary bypass is started, the remainder of the operation, including myocardial
protection, is conducted as previously described. [136 ]
Stented bioprostheses and mechanical prostheses are excised by sharp dissection

with removal of previous sutures and the prosthesis. Injury to the annulus is avoided by
identifying the junction between the sewing ring and the aortoventricular junction or
annulus. If this is not possible, the surgeon should err on the side of leaving portions of
the sewing ring. If injuries to the annular junction occur, interrupted suture repair is
necessary.
A free-hand or inclusion cylinder may be more difficult to remove. Remnants of an

allograft aortic wall may be calcified and require extensive care in removal. Removal of
the allograft should leave the aortic root in satisfactory condition for replacement with
another allograft or a different prosthesis.
Reoperative Replacement of the Ascending Aortic Graft and Prosthetic Valve
Reoperation for a Dacron valved conduit requires modification because of the risk of
massive hemorrhage from the prosthetic graft at the time of sternal re-entry. Re-entry is
also complicated if aortic regurgitation is present. Cardiopulmonary bypass is initiated
by cannulating the common femoral artery and vein and core cooling to 20°C. When
aortic regurgitation is significant, a limited left anterolateral thoracotomy through the fifth
intercostal space is indicated to vent the left ventricular apex and to monitor left
ventricular end-diastolic pressure to prevent ventricular distension. Adequate
hypothermia allows sternotomy with the vibrating saw without fear of uncontrolled
exsanguinating hemorrhage. If the Dacron tube is cut, cardiopulmonary bypass is
discontinued and blood is retrieved by cardiotomy suction. Cardiopulmonary bypass is
restarted after the graft is controlled distal to the tear and a right atrial venous cannula is
inserted. The operation continues using standard techniques of myocardial protection. If
the prosthetic valve is infected, all prosthetic material must be removed and replaced
with an allograft. If the pathology is not related to infection, prosthetic material can be
preserved and an interposition technique used for the graft.
Aortic Valve Replacement with Myocardial Revascularization
Aortic valve replacement and concomitant coronary artery bypass is recommended

when significant coronary arterial lesions are documented at cardiac catheterization.
Following commencement of cardiopulmonary bypass, the aortic valve is excised; the

replacement device is selected; and distal vein graft anastomoses are completed.
Myocardial preservation techniques include retrograde coronary perfusion and
perfusion of each individual vein graft. Following insertion of the aortic valve and
deairing the aortic cross-clamp is removed but the vein grafts are still perfused.
Proximal anastomoses are performed using a partial aortic clamp distal to the
aortotomy.
There are alternative operative strategies. Proximal vein anastomoses can be

performed prior to beginning of cardiopulmonary bypass to shorten total perfusion time,
but the grafts cannot be used to deliver cardioplegic solution. If distal grafts are
performed initially, proximal anastomoses can be performed following the valve
procedure with the aorta still clamped, but this prolongs cardiac ischemia. An internal
mammary artery graft can be used with the anastomosis performed after valve insertion.
However, this does not allow delivery of cardioplegia solution to that vessel during either
the valve or root procedure. The sequence of operative steps is the preference of the
surgeon but must include a satisfactory method to protect the myocardium. Care must
be taken after aortic declamping to prevent air from reaching the coronary vasculature.
Predictors of Operative Risk
Evaluation of early and late mortality following aortic valve replacement reveals that
predictors are primarily related to the functional and physiological status of the patient
(Table 29-3) . The predictors of early mortality have been studied for patients with aortic
valve replacement with or without concomitant coronary artery bypass, and patients with
either isolated aortic stenosis or aortic regurgitation. From several reported
studies,predictors of early mortality for aortic valve replacement are advancing age,
emergency operation, atrial fibrillation, left ventricular dysfunction, advanced NYHA
class, physiological group, renal dysfunction, acute endocarditis and previous aortic
valve replacement. [110 ] , [126 ] , [145 ] [147 ] Hwang et al. [146 ] reported predictors of
early mortality for aortic stenosis are reduced preoperative ejection fraction, myocardial
infarction, small valvular gradient and incomplete myocardial revascularization. Scott
and colleagues [126 ] report advanced functional class, older age, renal dysfunction,
prosthetic valve dysfunction and absence of angina as predictors of early mortality.
Craver and colleagues [148 ] also report advancing age and emergency surgery as
predictive for early mortality in aortic stenosis.
The predictors of early mortality after aortic valve replacement for aortic regurgitation
are reduced pre-operative ejection fraction, decreased LV systolic pressure, higher
functional class, atrial fibrillation and year of surgery. [126 ] , [146 ] , [149 ]
The major study reported by Scott and colleagues [126 ] from Stanford University in
1985 found no influence on early mortality from concomitant coronary artery bypass,
ascending aortic replacement, previous operation or endocarditis. Late mortality
predictors are reported by a few investigators. [50 ] , [149 ] , [150 ] Reported predictors
of late mortality are advanced age, moderate to severe left ventricular dysfunction and
preoperative renal dysfunction.
Preoperative criteria do not provide predictors of irreversible left ventricular dysfunction

after aortic valve replacement for aortic regurgitation. Stone and colleagues [151 ] found
that the quality of life can improve significantly in patients with serious preoperative
clinical disability and grossly impaired left ventricular function. However, Borer et al.
[152 ] , [153 ] observed that aortic valve replacement in symptomatic patients with aortic
regurgitation can improve but does not usually normalize left ventricular function during
exercise. Schuler and co-authors [154 ] provided support for early aortic valve
replacement for symptomatic aortic regurgitation before severe myocardial
decompensation. With early operation clinical status improved and was associated with
significant regression of myocardial hypertrophy, reduction in left ventricular size,
evolution of normal LV mass/volume ratio, recovery of septal dyskinesia, and
improvement in left ventricular function.
The effect of simultaneous aortic valve replacement and myocardial revascularization

on early and late mortality has received some consideration. [43 ] , [147 ] , [155 ] [161 ]
Predictors of early mortality for combined procedures are advanced age, advanced
New ork Heart Association Class, renal failure, and emergency operation. Czer and
colleagues [155 ] also showed that coexistent coronary disease has a detrimental
impact on early mortality but that revascularization does not increase operative risk
when associated coronary artery disease is present. Magovern et al. [160 ] also
reported that a combined operation has no independent predictive effect on early
mortality.
Factors associated with late mortality following combined operations are advanced
age, advanced New York Heart Association functional classification, male gender,
compromised left ventricular function with reduced cardiac index and ejection fraction,
elevated left ventricular end-diastolic pressure, and renal failure. [34 ] , [147 ] , [150 ] ,
[160 ] Czer et al. [155 ] also showed that untreated coexistent coronary atherosclerosis
increases late mortality, as well as early mortality. These authors documented that
combined revascularization with aortic valve replacement reduced the occurrence of
late sudden death. Karp and investigators [158 ] reported multicenter studies that show
aortic valve replacement without revascularization in the presence of coronary artery
bypass reduced long-term survival as compared to patients without coronary artery
disease or those with combined valve replacement and coronary artery bypass.
Special Surgical Considerations
AORTIC ROOT ENLARGEMENT
The aortic annulus can be enlarged by either posterior or anterior techniques. Posterior
patch enlargement procedures were initially described by Nicks and colleagues [162 ]
and later by Manouguian and Seybold-Epting [163 ] to enable placement of a prosthetic
valve two to four sizes larger than the original annulus. The anterior annular enlargement
or aortoventiculoplasty was first described by Konno and colleagues [164 ] and 1 year
later by Rastan et al. [165 ] for management of complex congenital lesions including
annular hypoplasia and subaortic stenosis. There have been several modifications to
the original surgical procedures.
Posterior patch enlargement
The Nicks operation (Fig. 29-11) extends the aortic incision downward through the
non-coronary sinus across the aortic ring to the attachment of the mitral valve leaflet and
places a Dacron fabric gusset to accommodate implantation of a larger size
mechanical prosthesis. [162 ] The Manougian procedure is more radical; the transverse
aortotomy is extended into the commissure between the left and non-coronary cusps
across the intravalvular trigone and central fibrous origin of anterior mitral leaflet. [163 ]
The defect is reconstructed with a fusiform Dacron or pericardial patch to allow
implantation of a larger prosthesis. The incision in the left atrial wall is extended
superiorly and is closed by running sutures by incorporating the atrial edges as the
patch is sutured to the defect in the anterior leaflet of the mitral valve. Alternatively, the
defect in the left atrial wall may be closed primarily with a pericardial patch and then
incorporated with the annular enlarging patch. [166 ] The aortotomy can be extended
into the anterior mitral leaflet and the left atrial wall with the Nicks approach also. This
technique enlarges the aortic annulus by 1025 mm. David and Uden [167 ] recommend
sizing the width of the patch for the Nicks noncoronary sinus enlargement by multiplying
the desired increase in annular diameter by and adding 8 mm for the suturing margin.
The posterior enlarging procedure is usually sufficient for adults.
Anterior patch enlargement
Anterior aortic annular enlargement, the aortoventriculoplasty, is performed for various

types of left ventricular outflow tract obstruction. The procedure was described by Konno
and colleagues [164 ] primarily for subaortic and annular stenosis and is more
commonly utilized in pediatric patients than in adults.
The decision to perform the Konno procedure must be made before the aorta is
opened. A longitudinal incision is placed in the anterior wall of the aorta and the valve is
evaluated. The incision continues slightly to the left of the right coronary artery and into
the right ventricle across the aortic annulus below the pulmonary valve. The incision
across the aortic annulus also extends into the ventricular septum below the subaortic
stenosis (Fig. 29-12A) . An elliptical piece of Dacron is cut to size and used as a patch
to close the septal defect and to close the aorta following placement of the valve (Fig.
29-12B) . The Dacron patch is sutured on the left ventricular side of the septal defect
utilizing interrupted pledgeted polypropylene sutures that are tied over pledgets on the
right ventricular side (Fig. 29-12C) . The patch is continued to the aortic annulus and the
widened annulus is sized for the replacement prosthesis. The native annulus comprises
5065 percent of enlarged annulus. The prosthesis, usually mechanical, is sutured to the
native annulus by any appropriate technique and to the Dacron patch by horizontal
mattress sutures. The remaining patch is sutured using running, horizontal mattress
polypropylene sutures to close the ascending aorta. The Dacron patch can be extended
up the ascending aorta to enlarge any narrowing of the proximal aorta. A running
polypropylene suture is used to reinforce the patch suture line to the aorta.
The defect in the right ventricular outflow tract is closed with pericardium using running
polypropylene suture (Fig. 29-12D) . The pericardial patch is sutured to the completed
Dacron patch over the valve annulus to complete closure of the right ventricle.
Results of annular enlargement procedures
The posterior enlarging procedures have been reported by several centers. [137 ] , [169
] [176 ] Blank et al. [169 ] reported successful use of the Nicks procedure in eight
patients in 1976. The Nicks operation was performed in approximately 20 percent of
aortic valve replacements by Mori et al. [175 ] and the net increase in diameter was
over 3 mm. The Manouguian procedure was reported by cofounder Seybold-Epting
[177 ] and Hoffmeister with no procedure-related mortality. In 1985 Dalichau et al. [171 ]
documented successful use of pericardium for reconstruction in the Manouguian
procedure. Mechanical prostheses are recommended with aortoventriculoplasty
reconstructions but not necessarily for posterior enlargements. Kawachi and co-authors
[173 ] reported that late reoperations for bioprostheses structural failure caused no
difficulty with the Manouguian operation. These authors also reported that mitral
regurgitation does not develop over time.
Posterior enlargement of the aorta annulus can be combined with homograft

replacement of the aortic valve and ascending aorta. The anterior leaflet of the
homograft fills the gap in the native mitral valve and the noncoronary sinus of the
homograft fits into the aortic incision to enlarge the annulus and proximal ascending
aorta. [178 ] Ahmad and Nazem [179 ] used double annular incisions at both ends of the
left coronary cusp or both sides of the left coronary ostium to enlarge the aortic annulus.
These authors used this technique in 43 patients with one death. Mayumi et al. [180 ]
has altered the standard Manouguian procedure by extending the incision through the
commissure of the left coronary cusp and noncoronary cusp to the intervalvular trigone
behind the anterior mitral leaflet and dividing the left atrial attachment, to preserve both
the anterior mitral leaflet and left atrial roof, as done in the Nicks procedure.
The Konno aortoventriculoplasty has also produced favorable results. [181 ] [185 ]
Misback et al. [186 ] reported on 18 patients with one death. Rastan and colleagues
[187 ] reported 21 patients and recommended aortoventriculoplasty for complex left
ventricular outflow tract obstructions. Reddy and colleagues [188 ] reported 11
reoperative patients between 4 days to 17 years in whom aortoventriculoplasty was
combined with a pulmonary autograft.
The apicoaortic composite conduit was reported in 1979 and 1984 as an alternative to
annular enlargement procedures for left ventricular outflow tract obstruction. However,
this procedure is not generally recommended in adults. [168 ] , [169 ]
AORTIC ROOT REDUCTION
Aortic root reduction procedures are described for accommodating allograft placement
and for reducing ventriculoaortic diameter in annuloaortic ectasia. [15 ] , [144 ] , [190 ]
Barratt-Boyes described a technique of tailoring a large aortic root for allograft
implantation. [15 ] The aortotomy is extended into the non-coronary sinus across the
base of the non-coronary cusp into the mitral-aortic annulus for a distance of
approximately 8 mm. The incision involves dissection of the left atrium, which may be
inadvertently entered and is immediately posterior and to the right of the central fibrous
trigone, which contains the bundle of His. A second incision is made posteriorly and
parallel to the first incision, to facilitate removal of an ellipse of aortic root with the
widest diameter at the annulus. The posterior edge of the defect must be placed slightly
away from the left coronary-noncoronary commissure to prevent interference with
sutures suspending the allograft commissure. The defect is closed with interrupted
figure-of-eight or simple polyester or polypropylene sutures and the left atrial wall is
incorporated in the sutures. The last suture is used to close the aortotomy following
insertion of the allograft.
REPARATIVE AORTIC VALVE SURGERY
Duran and co-authors, [191 ] [193 ] Cosgrove and colleagues, [194 ] and Carpentier
and colleagues [195 ] have explored reconstructive techniques for aortic regurgitation.
A fiberoptic cystoscope with a 30° angle lens [196 ] has been used to inspect aortic
valve repair during operation. The techniques include commissurotomy, unrolling free
edges of each leaflet, annuloplasty with pledgetted U sutures at the base of each
commissure, resuspension of prolapsed free margins and enhancement of the
supra-aortic ridge (Fig. 29-13A,B) . The leaflet extensions are performed with
glutaraldehyde treated pericardium. Duran et al. [191 ] and Fabiani et al. [197 ] have
also used glutaraldehyde preserved pericardium to totally reconstruct the aortic valve.
Ultrasonic debridement of the aortic valve may slow progression of stenosis by

decalcification but causes central regurgitation from tissue fibrosis and leaflet
retraction. [194 ] This procedure is not recommended.
Only short-term follow-up is available for aortic valve reconstructive techniques. The
reoperative rate for early regurgitation is 6 percent. [193 ] Cusp extension appears
more reliable than annular and leaflet plasties; however, long-term results are not
reported.
PERCUTANEOUS BALLOON AORTIC VALVULOPLASTY
The role of percutaneous balloon aortic valvuloplasty was evaluated in the 1980s. The
procedure is palliative and is used only for patients who are not candidates for surgery
or for brief hemodynamic improvement in selected patients before valve replacement.
Balloon valvuloplasty is not an alternative to aortic valve replacement because
hemodynamic improvement is limited and not sustained. [198 ] [202 ]
FUNCTIONAL MITRAL INCOMPETENCE WITH AORTIC VALVE DISEASE
Appropriate mitral valve surgery, either repair or replacement, must be performed for
co-existent organic mitral valve stenosis or regurgitation. The issue of functional mitral
regurgitation requires considered judgement. [203 ] Grade two or three mitral
regurgitation from mitral annular dilatation is usually abolished or considerably reduced
with aortic valve replacement. Grade three mitral regurgitation should be evaluated by
transesophageal echocardiography after stopping cardiopulmonary bypass. If grade
three mitral regurgitation persists, repair with an annuloplasty ring should be
considered; replacement of the mitral valve is rarely indicated.
CALCIFIED PORCELAIN ASCENDING AORTA
The calcified, porcelain aorta can complicate aortic valve surgery and necessitate a
more complex operation such as apicoaortic valved conduit. The porcelain aorta may
require deep hypothermic circulatory arrest and replacement of the ascending aorta
with a tube graft or a composite valved conduit. Severe calcification of the aorta usually
precludes placement of an allograft, autograft, or stentless porcine bioprosthesis.
Svensson and colleagues, [204 ] report endarterectomy of calcific plates. The
endarterectomy leaves the outer adventitia intact and removes plates of calcification
involving predominantely aorta subintima and media. These authors used periosteal
elevators to perform the endarterectomy. Closure of the residual adventitial aorta
provides hemostasis when interrupted horizontal pledgeted 4-0 or 5-0 polypropylene
sutures are utilized. Long-term follow-up with computerized tomography or
echocardiography in a limited number of patients does not reveal aortic dilatation.
CONDUCTION DEFECTS
Intraventricular conduction defects are relatively common with aortic valve disease and
after aortic surgery. The bundle of His at the membranous septum may be injured
requiring pacing. In some patients serious consideration of prophylactic permanent
pacemakers must be given because sudden death may occur from tachyarrhythmias or
possibly from progression of left bundle branch block to complete heart block or
trifasicular block. [205 ]
RIGHT CORONARY ARTERY INJURY
Right ventricular failure may be owing to air or particulate emboli, ostial injury from
perfusion cannulas or entrapment during closure of the aortotomy. Salerno and
co-authors [206 ] recommended right coronary artery bypass with saphenous vein when
acute right ventricular failure occurs after an aortic valve procedure.
Aortic Valve Replacement Devices
MECHANICAL PROSTHESES
The principle mechanical prostheses available worldwide are listed in Table 29-4 . The
first successful mechanical prosthesis was the Starr-Edwards caged-ball valve, which
was the gold standard for over 20 years until the early 1980s. [207 ] Mechanical
prostheses subsequently were either monoleaflet or bileaflet prostheses with Pyrolite®
carbon leaflets, and titanium or Pyrolite carbon housings. Tungsten is utilized to
radiopacify leaflets and occasionally a metallic reinforcing band. The leaflet or leaflets
can be rotated within the housing in most prostheses. Retrograde washing reduces
blood stasis and thrombus formation. Monoleaflet prostheses have crossing bars or
central guides to control leaflet travel; in general bileaflet prostheses have pivot
recesses in the orifice to control leaflet travel.
St. Jude Medical mechanical prosthesis
The St. Jude Medical mechanical prosthesis (St. Jude Medical Inc, Minneapolis,
Minnesota) is a bileaflet prosthesis with pyrolytic carbon over graphite substrate for
housing and leaflets (Fig. 29-14A) . The leaflets are flat and impregnated with tungsten
for radiopacity. The two semicircular leaflets open to 85°, resulting in central, near
laminar flow. Leaflets are orifice orientated and closing forces are supported by the
pivot system. The pivot guards are raised above the housing, and leaflet motion is by
rotation. Relatively high velocity blood jets and approximately 1015 percent regurgitant
flow wash the pivot recesses. In the original prosthesis, leaflets could not be rotated.
The prosthesis has been altered in the Masters series to rotate within the housing and
to radio-opacify the annular rotating mechanism. The St. Jude Medical HP (high
performance) prosthesis was recently introduced and is designed to optimize
hemodynamics.
Carbomedics mechanical prosthesis
The CarboMedics (Austin, TX) mechanical prosthesis is a bileaflet prosthesis with a

solid Pyrolite housing and flat leaflets of pyrolytic carbon coated over tungsten loaded
graphite substrate (Fig. 29-14B) . The prosthesis has excellent radiopacity with a
radiopaque titanium stiffening ring and increased tungsten content in the leaflet
substrate. The opening angle of the leaflet is 78°, which encourages synchronous
closure. The leaflet pivot retention mechanism is within the housing without pivot guards,
struts or orifice projections. Leaflet motion is by rotation. The leaflets can be rotated
within the housing. The recently introduced CarboMedics Top Hat prosthesis is
designed for supra-annular implantation and improved hemodynamic performance in
small sizes.
Edwards Tekna mechanical prosthesis
The Edwards-Tekna mechanical prosthesis (Baxter Healthcare Corp.) is a bileaflet

prosthesis with a solid pyrolytic housing and curved leaflets with pyrolytic carbon coated
over tungsten loaded graphite substrate (Fig. 29-14C) . Housing stability is increased
by a Stellite stiffener ring over a solid pyrolytic valve housing. The pivot hinge
mechanism is located within the housing, and leaflet motion is by rotation and
translation. The opening angle of the aortic prosthesis is 77°. The curved leaflets
enhance central flow and rapid closure. Aortic leaflets can be rotated within the housing
and the housing has a low profile. The pivot ball and slot mechanism facilitate
retrograde washing by relatively high velocity jets. Leaflets close on a circular ledge
within the housing to reduce regurgitation and stress on the hinge mechanism. The pivot
ball hinge closes by rotation and translation.
Bicarbon mechanical prosthesis
The Bicarbon (Sorin Biomedica, Saluggia, Italy) mechanical prosthesis is a bileaflet

prosthesis with a titanium alloy housing coated with a thin film of pyrolytic carbon and
curved leaflets with pyrolytic carbon coated over a graphite and tungsten substrate (Fig.
29-14D) . A titanium housing strengthens the prosthesis and the minimal thickness
increases the effective orifice. The hinge cavity supports a constantly varying, single
point contact between pivot and housing, and two effluent passages provide continuous
washing even in the closed position. The curved leaflets separate the orifice into three
sections with similar resistances to flow, very low pressure gradients and minimal
turbulence. The hinge mechanism supports a rolling motion. The opening angle of both
the aortic and mitral prosthesis is 70 percent and both prostheses can be rotated within
the housing. The sewing ring is made with Dacron and carbon coated Teflon.
ATS (Advancing the Standard) mechanical prosthesis
The ATS mechanical prosthesis (ATS Medical Inc., Minneapolis, Minn.) is a bileaflet
prosthesis with a pyrolytic housing and pyrolytic carbon leaflets containing graphite
substrate. The prosthesis has a convex hinge mechanism with protrusions on the inner
aspect of the housing that support the leaflets. The prosthesis has no protruding struts
with this hinge mechanism. The convex hinge mechanism is designed to facilitate
retrograde washing. The opening angle is 85°. The aortic prosthesis can be rotated
within the housing.
Björk-Shiley Monostrut mechanical prosthesis
The Björk-Shiley Monostrut prosthesis (Sorin Biomedica, Saluggia, Italy) is a

monoleaflet prosthesis (Fig. 29-15A) . The orifice ring and integral struts are
constructed from a single piece of cobalt-chromium alloy. A pyrolytic carbon disc
contains a radiopaque tantalum marker. The opening angle is 70° and the valve can be
rotated within the sewing ring. Leaflet motion is by rotation and translation. Retrograde
washing is by relatively low velocity blood flow between leaflet edge and orifice.
Sorin Allcarbon monoleaflet mechanical prosthesis
Sorin Allcarbon monoleaflet mechanical prosthesis (Sorin Biomedica, Saluggia, Italy) is

a monoleaflet prosthesis constructed of a chromium alloy housing coated with a thin film
of pyrolytic carbon with single monoleaflet of pyrolytic carbon (Fig. 29-15B) . The strut
mechanism is integral with the housing. The sewing ring is carbon coated.
Medtronic Hall mechanical prosthesis
The Medtronic Hall prosthesis is a monoleaflet prosthesis with a central guide for leaflet
travel (Fig. 29-15C) . The housing and central guide are made of titanium and the disc
is pyrolytic carbon. The prosthesis can be rotated within the sewing ring. Leaflet motion
is by rotation and translation. The opening angle is 7075°. The disc has tungsten-loaded
substrate for radiopacity.
Omnicarbon mechanical prosthesis
The Omnicarbon prosthesis (Medical Inc., Grove Heights, Minn.) is a monoleaflet

prosthesis with a titanium orifice ring and a pyrolytic carbon disc (Fig. 29-15D) . Disc
motion is controlled by short struts. The opening angle is 80°.
STENTED BIOPROSTHESIS
Biological valvular prostheses are constructed from porcine aortic valves or bovine
pericardium (Table 29-5) . The natural aortic valve possesses unique architectural and
material characteristics consistent with functional requirements (Chapter 28). Porcine
bioprostheses are preserved with glutaraldehyde at high pressure, low, or no pressure.
Tissue preservation methods and stent designs define the anatomical characteristics
and biomechanical properties of the leaflets.
The first generation porcine bioprostheses, Hancock standard and Carpentier-Edwards

standard, fixed the porcine tissue with glutaraldehyde at high pressure (6080 mmHg).
Current generation porcine prostheses are either low (2 mmHg) pressure or zero
pressure glutaraldehyde-fixed prostheses. Bovine pericardial prostheses use
pressure-free fixation with glutaraldehyde and in the current generation advanced
engineering was used to determine the tissue-stent relationship. Glutaraldehyde
cross-links collagen and as fixation pressures approach zero the collagen crimp
framework is maintained to varying degrees in the valve cusps and cords. [208 ] The
authors and Flomenbaum and Schoen [209 ] have shown that zero-pressure fixation
preserves normal collagen crimp in all regions of the cusp.
Studies of the physical and chemical properties of glutaraldehyde preserved tissue

valves discovered the need to ensure synchronous leaflet opening at low flows and to
reduce commissural bending strains. [210 ] Calcification of bioprostheses is related to
tissue stresses. [128 ] The highest stresses occur at areas of greatest flexion, and
calcification occurs at areas of mechanical stress and compressive forces. In porcine
bioprostheses stresses are at the commissural regions while with pericardial
bioprostheses shear deformation is in the zone of flexion. Preserved tissues have been
treated with various surfactants in an attempt to reduce calcification. Investigational
techniques to minimize calcification include chemical control of residual aldehydes,
extraction of cellular tissue components, and alternative cross-linking agents. [211 ] [215
] Valve fixation after permanent predilatation has been investigated to reduce
open-leaflet bending deformations. [216 ] , [217 ] A fresh aortic root subjected to
predilatation increases root diameter 19 percent but glutaraldehyde-fixed tissue dilates
only 6 percent.
Carpentier-Edwards Supra-annular porcine bioprosthesis
The Carpentier-Edwards Supra-annular porcine bioprosthesis (Baxter Healthcare

Corp., Irvine, Calif.) has a supra-annular configuration, mounted on a flexible Elgiloy®
wire frame for stress reduction (Fig. 29-16A) . The prosthesis has a reduced stent
profile and the tissue is preserved with glutaraldehyde at low fixation pressure (2 to 4
mmHg). The tissue is treated with the calcium mitigation agent polysorbate 80. Note
that the Carpentier-Edwards standard porcine bioprosthesis remains in use in the
United States but with low pressure fixation substituted for high pressure fixation.
Hancock II porcine bioprosthesis
The Hancock II porcine bioprosthesis (Medtronic Inc., Irvine, Calif.) is a supra-annular

prosthesis (Fig. 29-16B) . The prosthesis has a Delrin® stent, scalloped aortic sewing
ring, reduced stent profile, and is fixed with glutaraldehyde at low pressure and
subsequently for a prolonged period at high pressure. The prosthesis is treated with
sodium dodecyl sulfate to retard calcification.
Medtronic Intact porcine bioprosthesis
The Medtronic Intact porcine bioprosthesis (Medtronic, Inc., Irvine, Calif.) is an

intra-annular prosthesis with high stent posts and low stent rails. The prosthesis is
designed to retain leaflet relationships and dimensions, retain maximal areas of
coaptation, and provide natural stress relief. The tissue is pressure-free fixed with
glutaraldehyde and treated with the calcium mitigation agent toluidine blue. The fixation
process is thought to conserve leaflet architecture and biomechanics with preservation
of the natural collagen crimp pattern to duplicate the normal stress-strain relationship.
The high profile stent is made of an acetal copolymer resin.
Medtronic Mosaic porcine bioprosthesis
The Medtronic Mosaic® porcine bioprosthesis (Medtronic, Inc., Irvine, Calif.) is a third
generation investigational prosthesis. The prosthesis has a supra-annular configuration
with a Delrin® stent, scalloped aortic sewing ring and reduced stent profile. The tissue
is pressure-free fixed with glutaraldehyde and the aortic wall is predilated to reduce
deformation of the commissures. The prosthesis is treated with alpha oleic acid to
retard calcification.
Hancock modified orifice porcine bioprosthesis
The Medtronic modified orifice prosthesis (Medtronic, Inc., Irvine, Calif.) is similar in
configuration to the Hancock standard porcine bioprosthesis except for composite
leaflet placement (Fig. 29-16C) . In this composite configuration the non-coronary leaflet
from another porcine root is used to replace the right coronary leaflet that contains a
muscle shelf. The prosthesis is designed to optimize hemodynamics in small aortic
roots.
Biocor porcine bioprosthesis
The Biocor porcine biprosthesis (Biocor Industria e Pesquisa Ltda, Belo Horizonte, MG
Brazil) is a zero pressure, glutaraldehyde fixed porcine bioprosthesis.
St. Jude Medical Bioimplant porcine bioprosthesis
The St. Jude Medical Bioimplant (formerly Liotta) porcine bioprosthesis (St. Jude
Medical, Inc., Minneapolis, Minn.) is an early generation valve (Fig. 29-16D) . The
prosthesis has a very low profile supra-annular configuration with low pressure
glutaraldehyde fixed tissue.
St. Jude Medical X-Cell porcine bioprosthesis
The St. Jude Medical X-Cell porcine bioprosthesis (St. Jude Medical, Inc., Minneapolis,
Minn.) is a third generation investigational prosthesis. The prosthesis is mounted on a
polymer stent with a stent-tissue interface designed to optimize hemodynamics (Fig.
29-17A) . Valve sizes 25 mm and smaller are composite valves with the right coronary
cusp and muscle-shelf replaced with a non-coronary leaflet. The porcine tissue is zero
pressure fixed with glutaraldehyde and cellular components are removed to decrease
sites for calcification.
Carpentier-Edwards pericardial bioprosthesis
The Carpentier-Edwards pericardial bioprosthesis (Baxter Healthcare Corp., Irvine,

Calif.) is constructed with an Eligoy stent at the orifice and commissures for flexibility
and pericardium fixed without pressure in glutaraldehyde (Fig. 29-17B) . Leaflets are
single and produced by computer-aided design for optimal leaflet to stent matching.
Leaflets achieve satisfactory coaptation without stent post sutures.
Mitroflow pericardial bioprosthesis
The Mitroflow pericardial bioprosthesis (Mitroflow International Inc., Richmond, British

Columbia, Canada) is made with a Delrin stent for flexibility and pericardium fixed
pressure-free with glutaraldehyde (Fig. 29-17C) . Pericardium is utilized as a single
component without critical stent-post sutures. The Dacron cloth of the prosthesis
(current version) has the smooth, rather than ribbed Dacron in contact with the
pericardium.
Sorin Pericarbon pericardial bioprosthesis
The Sorin Pericarbon pericardial bioprosthesis (Sorin Biomedica, Saluggia, Italy) is a

stentless pericardial valve made of two separate sheets of glutaraldehyde-treated
bovine pericardium. The first sheet is shaped to form the three leaflets by means of a
process of atraumatic tissue fixation without the use of molds. It is then sutured to the
second sheet using a pyrolite carbon-coated suture. The suture line is especially
designed to dampen the mechanical stress at the level of the commissures.
Pericarbon pericardial bioprosthesis
The Pericarbon (Sorin Biomedica, Saluggia, Italy) pericardial bioprosthesis is made

with two sheets of pressure-free fixed pericardium over a Delrin acetal resin stent (Fig.
29-17D) . One sheet forms three cusps with zero stress on the commissures and a
cylindrical shape in the open position. The other sheet coats the inner surface of the
stent. The prosthesis is low profile, has a radiopaque metal wire marker and has carbon
coated Dacron fabric in the sewing ring.
STENTLESS BIOPROSTHESES
St. Jude Medical-Toronto SPV stentless porcine bioprosthesis
The Toronto SPV stentless porcine bioprosthesis (St. Jude Medical Inc., Minneapolis,
Minn.) is a subcoronary stentless porcine bioprosthesis with the external surface,
including muscle shelf covered with fine Dacron mesh (Fig. 29-18A) . The proximal
sewing ridge is covered with fine Dacron. Porcine tissue is preserved with low-pressure
glutaraldehyde fixation.
Medtronic Freestyle® stentless porcine bioprosthesis
The Medtronic Freestyle® stentless porcine bioprosthesis (Medtronic, Inc.,

Minneapolis, Minn.) is fashioned as a porcine aortic root for implantation using the
subcoronary (allograft freehand-like), miniroot cylinder or aortic root technique (Fig.
29-18B) . Tissue is pressure-free fixed with glutaraldehyde and the aortic wall
predilated to reduce deformation of the commissures. Tissue is treated with alpha
amino oleic acid to retard calcification. Dacron mesh covers the muscle shelf and forms
a thin proximal sewing cuff.
Cryolife Bravo stentless porcine bioprosthesis

The Cryolife Bravo stentless porcine bioprosthesis (Cryolife Inc., Atlanta, Georgia) is an
investigational stentless prosthesis with composite leaflets (Fig. 29-18C) . The
prosthesis is designed only for distal suture line implantation, in contrast to other
stentless porcine bioprostheses that require two suture lines. The prosthesis is fixed in
glutaraldehyde without pressure.
Baxter Prima stentless porcine bioprosthesis
The Baxter Prima® stentless porcine bioprosthesis (Baxter Healthcare Corp., Irvine,
Calif.) is designed as a cylinder with prefashioned coronary openings (Fig. 29-18D) .
The prosthesis has a Dacron mesh that covers the muscle shelf, supports the coronary
openings, and forms a thin proximal cuff. The prosthesis is investigational and only
implanted in selected non-North American locations. A newly designed prosthesis,
Prima Plus, is an investigational prosthesis that features a more versatile cylinder,
unfashioned coronary areas and Dacron mesh only over the muscle shelf and proximal
sewing cuff. The porcine tissue is glutaraldehyde-fixed at low pressure with sinus area
dilatation. The prosthesis can be implanted by freehand subcoronary, miniroot cylinder
or aortic root replacement technique (Chapter 30).
Biocor stentless porcine bioprosthesis
The Biocor stentless porcine bioprosthesies (Biocor Industria e Pesquisa Ltda, Belo
Horizonte, MG Brazil) is a stentless prosthesis with individual porcine cusps to mount a
composite bioprosthesis, avoiding leaflets with muscular bands. The leaflets are treated
under no pressure and are tanned with different glutaraldehyde solutions for a period of
3 months. The leaflets are sutured to a conduit of glutaraldehyde-treated bovine
pericardium. The conduit is then shaped in a scalloped manner to mimic the natural
aortic valve.
HEMODYNAMIC CHARACTERISTICS
The hemodynamic performance of the various aortic replacement prostheses is

summarized in Tables 29-4 and 29-5 . [52 ] , [114 ] [117 ] , [172 ] , [218 ] [234 ] The
hemodynamic performance of aortic prostheses have been reported by other
investigators. [77 ] , [224 ] , [235 ] [77 ] The beneficial response to annular enlargement
procedures has also been documented. [171 ] , [181 ] , [184 ] Supra-annular
bioprostheses are hemodynamically superior to intra-annular bioprostheses. Size 19-
and 21-mm Medtronic Intact® intra-annular bioprostheses have inferior hemodynamics
to supra-annular bioprostheses (Jamieson and colleagues, personal communication).
Pericardial bioprostheses and stentless porcine bioprostheses provide better
hemodynamics in small sizes. The bileaflet mechanical prostheses provide better
hemodynamics than other mechanical prostheses in the small sizes. The basal surface
area of the patient dictates whether a prosthesis will be satisfactory or whether an
annular enlarging procedure is needed to accommodate a larger prosthesis. The
hydrodynamic assessment of prostheses have been reported both by Butterfield [247 ]
and Yoganathan [248 ] and their colleagues evaluating forward flow, regurgitant
volumes, and total energy loss.
Regression of left ventricular hypertrophy after aortic valve replacement is extremely

important for reduction of sudden, unexpected death. [20 ] Monrad and colleagues [249
] reported a 31 percent regression of left ventricular mass within 1.6 years and a further
13 percent within eight years. Aoki [235 ] found that 25 mmHg was the upper limit of
acceptable pressure gradients for aortic valve prostheses. The greatest reduction in left
ventricular mass occurred in patients who received a 21-mm or larger prosthesis. [140 ]
Pericardial and stentless porcine bioprostheses, allografts, and bileaflet mechanical
prostheses provide the best prosthetic valves for reducing left ventricular mass with
small prostheses. Stentless prostheses have a significantly larger aortic valve area as
compared with stented prostheses. [77 ]
Implantation of various bioprostheses and mechanical prostheses requires special

considerations. The risk of disc immobilization from suture ends or intracardiac
structures must be minimized. Suture ends can entrap the disc or full orifice closing
prostheses, such as the Medtronic Hall and Björk-Shiley Monostrut valves. Sutures used
with these prostheses must exit the sewing ring near the equator so that suture ends
project away from the discs. Long suture ends must be avoided with bioprosthesis
because of the risk of leaflet injury.
Prostheses must not be oversized in the aortic position. Annular decalcification is

important to prevent paravalvular leaks and damage to leaflet tissue with supra-annular
prostheses. Interrupted horizontal mattress sutures are recommended for aortic
replacement. Horizontal mattress sutures can be placed with or without pledgets from
the aortic side or ventricular side of the annulus.
Septal hypertrophy requires special consideration in aortic valve replacement.

Rotatable mechanical prostheses should be used to orientate the moving parts after
implantation. A monoleaflet prosthesis may be best in these circumstances. The tilting
technique of implantation (Chapter 31) of aortic prostheses for small aortic annuli, as an
alternative to annular enlarging procedures, should be performed with a monoleaflet
mechanical prosthesis or with a bioprosthesis.
There are two recommended techniques for implanting an aortic bileaflet mechanical
prosthesis. One technique is to locate the septum beneath one leaflet by positioning
one pivot at the center of the left coronary cusp and the other at the junction of the right
coronary and non-coronary cusps. The other method places the leaflets perpendicular to
the septum with one pivot at the center of the right coronary cusp and the other at the
junction of the left coronary and non-coronary cusps. [69 ] , [227 ]
Stentless porcine bioprostheses require special techniques for valve and root
replacements. [223 ] , [250 ] [252 ] A vertical hockey stick aortotomy to the noncoronary
sinus is generally recommended. The annular inflow suture line is made with interrupted
sutures in a horizontal, nonscalloped plane and the second outflow suture line uses
continuous sutures. In root replacement coronary ostia are sutured to coronary windows
and the outflow end of the prosthesis is secured during closure of the transverse
aortotomy.
CELLULAR AND IMMUNOLOGIC CHARACTERISTICS OF
ALLOGRAFTS
The aortic valvular cellular/molecular structure includes endothelial cells and fibroblasts
that produce collagen, elastin, and mucopolysaccharides. Constant production,
remodeling, and adaptation of these cells and matrix ensure the functional integrity of
the aortic valve. Endothelial cells cover the collagen matrix, provide nutrition for
fibroblasts, and ensure a nonthrombogenic surface. The goal of preservation
techniques is to ensure that these cells and molecules remain intact and properly
functioning once the valve is implanted. This goal does not necessarily mandate
viability, however. Pulmonary autografts and, for that matter, valves of transplanted
hearts are characterized by dense cellularity and preserved stromal architecture (i.e.,
normal collagen and elastin). [1 ] , [2 ] These attributes are seen occasionally in the
preserved allograft. Anecdotal evidence indicates that fibroblasts from donor allografts
have survived for many years after implantation, but their presence is sporadic and their
architecture is dissimilar to that of the normal aortic valve. [3 ]
Variation in cusp cellularity raises questions regarding long-term function. It is likely that
preservation of the fibroblast serves as a marker of the structural integrity of ground
substance. Observations of antibiotic-preserved allografts indicates that this valve
progressively loses ground substance and develops cusp thinning and subsequent
perforations approximately 7 to 8 years after implantation. [3 ] , [4 ] With few exceptions,
this problem does not occur with cryopreserved allografts or with fresh allografts; both
have preserved fibroblasts. Nevertheless, animal models and human experience
demonstrate that while leaflets implanted within 2 hours of collection are clearly viable,
cells gradually disappear after implantation. [5 ] Cell viability at the time of implantation
does not necessarily mean that the valve will remain viable. Lack of viability, however,
does not necessarily mean that the valve will not remain functional.
Preserving the integrity and viability of cells has a potential disadvantage of inducing an
allograft rejection reaction. Major histocompatability complex (MHC) antigens are the
primary target of the immune response of allograft rejection. Expression of MHC
antigens is not a constant feature of the cell but can be up-regulated by cytokines and
down-regulated by substances that counteract or inhibit cytokine production.
Quantitative changes in expression alter the magnitude of the immune response.
Originally, HLA class I antigens were thought to be ubiquitous, and although
constitutively present on many nucleated cells, these antigens are weakly expressed or
absent on endocrine cells, hepatocytes, smooth muscle, normal skeletal, and cardiac
muscle cells. [6 ] Class II antigen (HLA-DR, -DP, and -DQ), originally thought to be
restricted to macrophages, dendritic cells, monocytes, and activated T cells, also has
been described on endothelial and epithelial cells. [7 ] However, endothelial cells that
express a class II antigen are only typical of primates. In rat hearts, endothelial cells do
not constitutively express class II antigen, and the majority of class IIpositive cells are
dendritic. Although most data related to the immunogenicity of aortic allografts are
derived from nonprimate experiments, Rose et al. [8 ] demonstrated that 85 percent of
human endothelial cells express class II antigen; this raises the possibility that allografts
may be immunogenic. These investigators also found that expression of class II antigen
by endothelial cells varies with the site of endothelial cell origin. Whereas smaller
vessels tend to have cells positive for class II antigen, larger vessels (including aorta) do
not express class II antigens. It is not clear at this time whether or not preservation of
endothelial cells and their potential immunologic characteristics is advantageous.
Histologically, minimal infiltrates unrelated to any immune reaction are found in the
ground substance of antibiotic-preserved allografts explanted after a 6- to 7-year period
and also in specimens of cryopreserved allografts. [3 ]
MECHANICAL CHARACTERISTICS OF ALLOGRAFTS
Mechanical characteristics are important in understanding the superior hemodynamic

performance of aortic allografts and problems associated with durability. From a
rheologic point of view, experience shows that pressure gradients measured in vivo
after implantation of free-hand aortic allografts and aortic root allografts are minimal and
only slightly different from those of native aortic valves and considerably better than
those of alternative devices (Fig. 30-1) . The distensibility of leaflets and the aortic wall
is a unique mechanical characteristic of the allograft valve. This characteristic is
important in two respects: durability of the valve and physiologic interaction within the
aortic root.
Using biaxial testing techniques on explanted free-hand aortic allograft valves, Christie
and Barratt-Boyes [9 ] demonstrated that the cusp loses a significant amount of natural
tissue extensibility. Using computer simulations to investigate changes in cusp
biomechanical characteristics on valve function, they predicted progressive
incompetence as cusp extensibility is lost and sharply increased commissural stress
levels with reduced leaflet coaptation. As the pressure applied to the model of an aortic
root increased from 0 to 80 mmHg, cusp tissue extended and coaptation area
increased. The diameter of the aortic root expanded at the commissures by 25 percent
relative to the flaccid state. The model predicted that a fully loaded fresh allograft has a
coaptation area of about 40 percent of the loaded cusp surface area at implantation.
This prediction was in good agreement with direct measurement and with aortic cusp
morphology. Stress throughout the coaptation surface was small, and maximum stress
was aligned in the circumferential direction through the cusp belly.
In this model of freshly implanted aortic allografts, there was substantial central cusp
redundancy consistent with anatomic measurements of the human aortic root. The data
showed that coaptation also was reduced progressively over time and that the greatest
influence was due to loss of radial extension. These measurements were done in
antibiotic-preserved valves that were defined as nonviable. The results of the computer
model were in good agreement with clinical results in that antibiotic-preserved valves
seem to develop incompetence 8 to 10 years after implantation.
Recently, the distensibility of cryopreserved aortic allografts and so-called fresh

allografts was studied and was found to be better than that of nonviable grafts in both
(Fig. 30-2) . This result also was inferred by the differing histology of explanted
allografts. [10 ] Distensibility of the aortic cusp and wall relates to the deterioration
process but is even more important for ensuring improved rheologic characteristics of
the aortic root complex. It is well known that the arterial system acts both as a conduit for
distribution of blood and as a capacitor that transforms intermittent stroke volumes into
continuous flow that is essential for metabolic exchange at the tissue level. [11 ] This
damping effect is mostly attributable to the viscoelastic properties of the aorta that
largely determine shapes of aortic pressures and flow waveforms. Accordingly, an
important consideration for choosing allograft aortic valves is maintenance of aortic root
distensibility, which in turn optimizes blood flow in the coronary arteries during both
systole and diastole.
ALLOGRAFT PROCUREMENT AND PRESERVATION
TECHNIQUES
Three techniques for allograft preservation are used today. Antibiotic preservation was
the first to be tested and produced satisfactory results (see Table 30-2) ; however, with
the advent of cryopreservation, antibiotic preservation has become obsolete. More
recently, with the development of cardiac transplantation, the so-called fresh (homovital)
allograft became available.
Regardless of preservation protocols, techniques for allograft procurement are similar.

Valves are removed from nondiseased hearts of donors aged 6 months to 55 years.
The heart is procured using sterile technique, as for heart transplantation. The heart is
rinsed in cold Ringer's lactate solution, packaged in a sterile plastic bag, and kept cold
by iced slush. Generally, the aortic allograft is retrieved from heartbeating cadavers that
are unsatisfactory cardiac donors but are satisfactory for other organ transplants.
Cadaveric hearts up to 12 hours after death also can be used. All preservation
techniques attempt to preserve cell viability. Figure 30-3 shows the effect of
temperature on the viability of fibroblasts and endothelial cells. Therefore, during
procurement, it is important to limit warm ischemic time as much as possible.
The aortic valve and the ascending aorta block are removed from the heart in a
controlled, clean environment. The innominate artery marks the distal border of the
block; the proximal border is the portion at the base of the left ventricle containing the
anterior leaflet of the mitral valve and the aortic ring (Fig. 30-4) . The coronary ostia are
ligated in the event that the allograft is used as a valved conduit. A portion of ventricular
muscle is removed from the base of the allograft, but most of the attached ventricular
muscle is trimmed at the time of implantation. After harvest, the sterile allograft block is
stored in a culture medium (RPMI m;1640) that contains a low concentration of
broad-spectrum antibiotics (lincomycin 120 µg/mL, cefoxitin 240 µg/mL, polymyxin B
100 µg/mL, and vancomycin 50 µg/mL) [12 ] and stored at 4°C for 24 hours. The culture
medium is changed, and the tissue is stored for a second 24 hours at 4°C in a new tube
with fresh culture medium and antibiotics. The allograft can be used directly at this time
as a homovital graft or stored further with controlled-rate freezing to achieve
cryopreservation. Cultures are obtained before storage and at 24 and 48 hours.
Controlled-rate freezing is the hallmark of the cryopreservation technique and is

designed to prevent cellular damage created by the freezing process itself. Prior to
actual freezing, the allograft is transferred from the antibiotic solution into a vinyl pouch,
into which RPMI solution containing 10% fetal calf serum and 10% DMSO is added.
This solution is designed to nourish the tissue and protect the specimen from
crystallization during the freezing process. Using a microprocessor controlled-rate
freezer, the tissue is frozen at 1°C per minute to -40°C. The freezer is programmed to
overcome the heat of crystallization so that during this phase change the specimen is
exposed for no more than 2.5 to 3 minutes to solution effects of freezing. Once the
specimen reaches -40°C, it is transferred into a nitrogen storage refrigerator and kept
at approximately -195°C until used. After microbiology cultures are reported (72 hours)
and serology tests (4 to 6 weeks)* are completed, the allograft specimen is ready for
use when needed.
The appropriately sized packaged allograft is placed in warm sterile saline and
transported to the operating room. The partially thawed allograft is removed from the
sterile foil container and placed in RPMI with 10% DMSO solution. By graduated
dilutions, the DMSO is removed and the graft is thawed and rinsed. The graft is
maintained in a culture medium solution without DMSO until trimmed.
The primary variables that affect cryopreservation are enumerated in Table 30-3 in
order of occurrence during the cryopreservation process. The table also matches each
variable with a list of specific concerns for that variable. The cooling rate of the tissue is
very important in the cryopreservation process. Prefreezed cooling refers to a change in
tissue temperature from 37 (donor body temperature) to 4°C (refrigerator temperature).
This is usually accomplished as a single-step transfer or at most a two-step transfer
from 37 to 22°C (room temperature) and from 22 to 4°C. During this period, gross
changes occur in cell membranes and in rates of biochemical reactions within cells.
Cells may not be able to produce sufficient energy to maintain isotonicity; this is
compensated by a storage medium that is isotonic for as many cellular constituents as
possible. Sufficient time is allowed for membrane shrinkage during the period of
temperature transition and is the main reason for a slow freezing rate of -1°C per
minute. The water state within the cell is related to final storage temperature and
duration of storage. At a storage temperature below the glass transition temperature (at
least -139°C and probably lower for water), no water movement and no ice
recrystallization occur to cause mechanical damage. Rates of chemical reactions in
biophysical processes are slow enough to yield satisfactory cell survival. Warming
frozen tissue also presents an opportunity for forming potentially harmful temperature
plateaus, unless the warming rate is adequately controlled throughout the tissue. Finally,
the choice of restoration and revitalization media is made on the basis of tissue
nutritional and osmotic needs. The cryoprotectant-containing medium must be dialyzed
out of the tissue at a rate that precludes osmotic damage. A two-step procedure of first
transferring tissue in 15% glycerol to a 7% solution and then to a 0% solution might be
employed. The definition of viability is based on preservation of adequate structure and
function but not necessarily prolonged endothelial cell and fibroblast survival.
One of the characteristics of the aortic allograft is its versatility for aortic valve
replacement. Allograft tissue is pliable and conforms well to irregular surfaces, but the
characteristics that make allograft valves desirable also make allograft implantation
more prone to technical errors that may affect immediate outcome and long-term
results. Differences of opinion persist among experienced surgeons regarding the best
technique for allograft implantation. For orthotopic placement, controversy exists with
respect to the classic three deep scallops versus the one shallow scallop technique.
There is also controversy over orthotopic versus no scallop (miniroot inclusion cylinder
aortic valve replacement) versus the use of total root replacement for all situations.
Other technical variations include continuous versus interrupted proximal sutures,
inversion of the graft, rotating the graft counterclockwise 120 degrees, position and
degree of tension of the commissure pillars, tailoring the host annulus and/or aorta,
amount of graft muscle trimming, and even the best way to perform the aortotomy. Table
30-4 outlines several critical points in ensuring appropriate technical results, regardless
of the technique chosen.
The free-hand technique is generally characterized by excision of two or three sinus

portions of the valve, often 120-degree rotation, and precise upstream (ventricular) and
downstream (aortic sinus) suture lines. This is considered the routine technique and is
favored for symmetric small and medium-sized roots.
Gross deformity of the aortic root due to infection or congenital anomaly, excessively
small root, and important root or sinotubular dilatation are indications for total root
replacement. Most of the aortic root is excised, and the allograft is attached to normal
tissue in the left ventricular outflow tract. The graft is placed as an interposed valve-aorta
complex between the left ventricular outflow tract and the ascending aorta. Coronary
ostia are reattached to the allograft. A variation of this technique is implantation of the
allograft aortic root as an inclusion cylinder within the native aorta (miniroot). Most
surgeons believe that this technique is more difficult than either the scalloped orthotopic
procedure or total root replacement. Thus four main surgical techniques are used to
implant aortic allografts: (1) 120-degree counterclockwise rotation free-hand
(scalloped), (2) intact non-coronary sinus free-hand; (3) aortic root replacement, and (4)
aortic root inclusion (cylinder or miniroot).
Assessment of the native aortic root and the sinotubular junction is critically important
for deciding which technique of allograft insertion is indicated. A distorted aortic root
may be a contraindication to allograft placement with the double-suture free-hand
technique because of difficulties in reconstituting normal geometric proportions
between the root and donor allograft. The aortic annulus must be debrided precisely to
achieve proper coaptation of allograft tissue with native annular tissue and for proper
placement of sutures. The native aortic root also must be made pliable. Secure
attachment of donor and recipient aorta is particularly necessary to prevent small
perivalvular leaks and hematomas behind valve pillars or leaflets. Measurement of the
annulus is critical for the choice of allograft size. In general, the largest allograft should
be inserted in the annulus without excessive redundancy to allow about 4 mm of cusp
tissue to coapt.
If the muscle shelf of the allograft is trimmed aggressively, the valve can be placed
without creating outflow obstruction. An excessive muscle shelf also can impair
movement of the anterior leaflet of the mitral valve and create other mitral valve
problems. When root replacement is chosen, enough tissue must remain on the allograft
to buttress the upstream suture line. It is important to realize that once the valve is
functional, suture-line stress is minimal, and the pressure of the blood column against
the aortic wall becomes the primary force holding the valve in position. One of the main
problems regarding the placement of an allograft aortic valve with the free-hand
two-suture-line method is the degree of tension placed on the commissural pillar by the
downstream suture line. This tension adjustment is critical because the goal is to
duplicate normal sinotubular junctional dynamics that use cusp tension to control valve
competency. In some centers, complete root replacement, which avoids this problem, is
routine. Complete root replacement helps prevent distortion and accommodates most
sizes of aortic roots. With this operation, the only geometric issue is positioning
reimplanted coronary arteries.
TECHNIQUES OF ALLOGRAFT AORTIC VALVE REPLACEMENT
Some authors suggest allograft or autograft valves for all aortic valve replacements.
However, limitations of availability and various technical demands preclude use in many
patients. In general, allograft aortic valve replacement is considered for the following
indications: (1) all replacements in patients with more than 10 years of life expectancy
for whom anticoagulation is undesirable, (2) small aortic annuli, (3) prosthetic and native
valve endocarditis, (4) composite replacement of the aortic valve and ascending aorta,
and (5) reoperation for failure of an aortic prosthetic or allograft valve. Relative
contraindications to insertion of an allograft valve include (1) lack of availability, (2)
severe annular calcification or aortic wall calcification (e.g., porcelain aorta), (3)
unfavorable coronary ostial anatomy that precludes proper geometric adjustment, (4)
large aortic annulus in excess of 30 mm, and (5) time-consuming, complex operations
in which aortic valve replacement is a small part. This last concern is particularly true for
patients with severe left ventricular dysfunction. In addition, we discourage use of
cryopreserved valves in patients with abnormal calcium metabolism or renal failure.
Indications for pulmonary autografts for aortic valve replacement are discussed below.
Preoperative evaluation of patients for aortic allograft implantation is not different from
the evaluation of any patient with aortic valve disease. Sizing the aortic root can be
done preoperatively to help determine the appropriate allograft valve size. Yankah and
Hetzer [13 ] recommend using angiographic measurements of the aortic annulus. This
method requires an angiogram obtained in the lateral position during systole and
diastole. Measurements are performed 1 mm above the sinuses. Although this
technique has some accuracy, in our experience and that of others, estimates are too
unreliable for routine use. Furthermore, angiography is not necessary in some patients.
We find echocardiography more reliable. [14 ] The measurement is made from a
parasternal long-axis view of the left ventricular outflow tract. The internal diameter of the
outflow tract is measured at the point of continuity of the anterior leaflet of the mitral
valve and the aortic annulus just beneath the valve leaflet attachment across to the
septum. Multiple measurements are made, but the most important are during early
systole. In our experience, this measurement correlates well with the measured annulus
size at operation ( (Fig. 30-5) . This technique is operator-dependent, so experience is
needed, with results substantiated in the operating room before the method becomes
reliable and useful. The problem of preoperative sizing is particularly important if the
supply of allograft valves is limited and grafts must be obtained from outside the
institution. Recently, transesophageal echocardiography has supplanted transthoracic
echocardiography for allograft sizing because of improved accuracy.
CANNULATION
Cardiopulmonary bypass is established using distal ascending aortic cannulation as

close to the innominate artery as possible. If the aortic root is short, the aortic arch is
cannulated. A single venous cannula is used for venous return, and a vent is inserted in
the right superior pulmonary vein.
Myocardial protection is achieved with a combination of antegrade and retrograde

blood cardioplegia. The initial cardiac arrest is obtained with antegrade cardioplegia if
the aortic valve is competent or with retrograde cardioplegia followed by direct
cannulation of the coronary arteries after aortotomy if the valve is not competent. The
temperature of the extracorporeal perfusate is stabilized at 28°C. Retrograde
cardioplegia is repeated every 20 to 30 minutes during the cross-clamp period.
AORTOTOMY
Although previously we used a horizontal incision, now a reversed lazy-S incision is

begun 4 to 5 cm above the right coronary artery and is brought down to a level that is
well above the expected top of the allograft commissural pillar (Fig. 30-6) . This is an
important point because a poorly placed incision may compromise proper suspension
of the commissure pillar and outcome of the operation. Once this point is reached, the
aorta is incised obliquely until the midpoint of the noncoronary sinus is reached; a
space is left for a suspended commissural pillar between the right and noncoronary
cusps. The incision is completed by extending the incision well into the noncoronary
sinus toward the anterior leaflet of the mitral valve but is stopped short of the annulus.
The aortotomy is retracted open by three silk sutures. The reversed lazy-S incision is
also suitable for aortic root replacement.
EXCISION OF THE NATIVE VALVE, DEBRIDEMENT OF THE ANNULUS, AND

SIZING
The aortic valve is resected without scattering calcific debris. Usually, this can be done
without rongeurs and by establishing a plane between the base of the cusp and the
aortic root in a way that the aortic ring becomes pliable. The aortic ring is measured
using any convenient prosthetic valve sizer or Hegar dilator. At this time, the
appropriately sized aortic valve allograft is brought from the nitrogen freezer and thawed
but not trimmed. If accurate estimates of root size are available by transesophageal
echocardiography, the allograft can be obtained and trimmed prior to cardiopulmonary
bypass. Previously, the allograft was sized using a Hegar dilator or a jeweler's ring
sizer, but this size corresponds to the internal orifice of the allograft aortic valve.
Therefore, the appropriate size of valve allograft is 2 to 3 mm smaller than the
measured internal diameter of the aortic root (Table 30-5) . The allograft is delivered,
and the surgeon or an assistant begins the rinsing and thawing process as described
previously. Subsequently, the valve is trimmed and made ready for insertion.
TRIMMING OF THE ALLOGRAFT
The main objective of trimming is to debulk the allograft but leave enough support for
suturing and commissural attachment of valve cusps. The muscle at the base of the
donor left ventricle and ventricular septum is trimmed from the allograft aortic ring (Fig.
30-7) . Care is taken not to buttonhole the aortic wall, particularly near the attachment of
the anterior mitral leaflet or near the membranous ventricular septum. The anterior mitral
leaflet is trimmed and shortened, and the ventricular muscle is shaved using scissors.
Finally, the tubular portion of the ascending aorta is transsected, and the sinus portions
of the ascending aorta are removed, to leave three columns of aorta supporting each
commissure of the aortic cusps (Fig. 30-8A) . For the two-suture-line technique with an
intact noncoronary sinus of Valsalva, this sinus is obviously not resected. About 5 mm of
tissue from the base of the aortic cusp is left on the upstream border, and about 4 mm
of aortic wall is left in the sinus of Valsalva beyond the base of the aortic cusp
downstream (Fig. 30-8B) .
Free-Hand 120-Degree-Rotation Two-Suture-Line Technique
The valve is sutured into place using two rows (upstream and downstream) of
continuous 4-0 polypropylene. The aortic allograft is rotated 120 degrees
counterclockwise to prevent the remaining muscle on the graft from opposing ventricular
septal muscle in the recipient (Fig. 30-8C) . The first row of continuous suture is placed
on the ventricular side of the aortic ring. This places the bulky portion of the graft
upstream to the narrowest diameter of the left ventricular outflow tract (i.e., the aortic
ring) and places the base of the aortic cusp in the same horizontal plane as the
orthotopic native aortic valve. To facilitate this suture line, three sutures are placed 120
degrees apart midway between the commissural pillars of the graft (Fig. 30-9) . The
graft, at this time, can be held away from the aortic root, either by fingertip or by a
noncrushing vascular clamp. With these sutures in place, the graft is delivered into the
aortic root and inverted. The suture line is made so that the upstream edge of the valve
is below the aortic ring (Fig. 30-10A) . This suturing is done precisely so that the needle
passes parallel to the long axis of the left ventricular outflow tract. In the area of the
membranous septum, the suture line dips slightly downstream and is a little more
superficial to avoid the conduction system. When this upstream suture line is
completed, two of the three commissural pillars are everted and positioned against the
old commissural attachments of the native valve using silk guy sutures. It is essential
that each commissural pillar not be placed under tension and that it is allowed to sink
into the bulbous sinus portion of the aortic root. The second suture line is begun,
generally in the right sinus of Valsalva (Fig. 30-10B) . A double-armed suture is used,
and the initial suture is placed in the midpoint of the sinus. For the first few bites, the
suture line is kept very close to the native valve aortic annulus.
The downstream suture line maintains a U-shaped (rather than a V-shaped)

configuration as it moves up and out of the sinus of Valsalva to attach the commissural
pillar against the aortic wall (Fig. 30-10C) . The left sinus Valsalva is completed in
similar fashion. Finally, the noncoronary sinus suture is completed, and the suture ends
are tied to one another at the top of the commissural pillar (Fig. 30-11) . This completes
the insertion of the aortic allograft. The aortic root is irrigated, and the aortotomy is
closed with a single layer of continuous 4-0 polypropylene.
Free-Hand Intact Noncoronary Sinus Two-Suture-Line Technique
Trimming, sizing, and preparing the allograft are identical to the preceding method,
except that the noncoronary sinus is not trimmed away. This technique is used for larger
aortic roots and also for mild distortions that are occasionally encountered in patients
with bicuspid aortic valves. For this technique, the valve is inserted in its anatomic
position (without rotation), the proximal suture line is usually placed with interrupted
sutures, and the valve is not inverted during placement of the upstream suture line. The
reason for placing interrupted sutures is that adjustment during insertion of the valve
may be necessary and can be accomplished more easily with interrupted sutures.
Simple interrupted 4-0 polyester sutures (Ethibond) are used and started under the
middle of the right coronary sinus where the right coronary artery ostium serves to
center the allograft valve in an appropriate position. The allograft valve is held above the
root without inversion as the sutures are continued toward the commissure between the
right and left leaflets. Usually, six to eight sutures are used for each sinus.* After all
sutures are placed, the valve is lowered into place, and the sutures are tied (Fig.
30-12A) The distal suture line differs slightly from the fully scalloped technique. The
intact noncoronary sinus method requires two additional steps. The first is to suture the
aortic wall of the allograft to the overlying margins of the recipient aortotomy incision
(Fig. 30-12B) . This is done with 4-0 polypropylene sutures and is followed by closing
the aortotomy. The aortotomy closure includes bites in the allograft aortic valve in the
sinus position up to the downstream border (Fig. 30-12C) . Once this is reached,
vertical mattress sutures are passed through the allograft noncoronary sinus and
brought outside the aorta to obliterate the space behind the allograft sinus. The
aortotomy is then closed completely.
Aortic Root Replacement Technique
This technique is used when an abnormality of the aortic root extends beyond that of the
native valvular tissue and when severe distortion of the sinus portion of the aorta or the
annulus is present. These characteristics make replacement of the aortic valve with a
free-hand two-suture-line technique more difficult, and in the hands of most surgeons,
results are unreliable. Aortic root replacement is a better option in these patients and
produces reliable, reproducible results. In many ways, aortic root replacement with
implantation of coronary ostia is simpler than free-hand aortic valve replacement. Root
replacement also solves some of the problems of sizing allograft valves. For root
replacement, allografts can be sized up or sized down 2 to 3 mm without problems. For
this reason, the technique has appeal for surgeons who have limited numbers of
allograft valves in stock. However, root replacement increases the chance of
hemorrhage and has a higher incidence of coronary problems.
The aortotomy and excision of the native valve proceed in the same manner as for the
free-hand two-suture-line technique. The coronary ostia must be examined carefully,
particularly for calcification near the right coronary ostium. Calcium may jeopardize
reimplantation of the coronary ostium into the allograft valve and is a relative
contraindication of the method. The allograft valve is trimmed as for the free-hand
two-suture-line technique, except for not removing the sinuses and for retaining a
greater length of ascending aorta. The upstream interrupted suture line is placed as for
the free-hand technique with preservation of the noncoronary sinus. Multiple interrupted
sutures starting in the middle of the right sinus of Valsalva are used (Fig. 30-13) .
Generally, we insert a narrow felt or pericardial gasket in the outflow tract, over which
sutures are tied (Fig. 30-14) . Alternatively, a continuous suture can be used, with the
posterior portion sewn from within the left ventricular outflow tract. Once the upstream
suture line is completed, the ostia of the coronary arteries are removed as buttons from
the recipient aorta with minimal mobilization. This is very similar to the technique used
for the arterial switch operation in infants. The coronary button is sutured to an
appropriate opening in the allograft root with running 5-0 polypropylene. This may or
may not correspond to the ostia of the allograft (Fig. 30-15A) . The left coronary artery is
usually sutured first, followed by the right coronary artery (Fig. 30-15B) . After the left
coronary anastomosis, the root is often distended by antegrade cardioplegia to align
the right coronary artery anastomosis (Fig. 30-15C) . The circumferential incision in the
recipient's distal ascending aorta is completed to match the diameter of the allograft
root. An end-to-end anastomosis is performed between these two structures. It is
important not to manipulate the allograft root during deairing maneuvers. Needles or
venting catheters are placed in the native aorta rather than in the allograft root. Similarly,
care should be taken to preserve homograft adventitia to minimize chances of tearing
the allograft.
Aortic Root Inclusion Technique (Miniroot)
This operation proceeds in a manner similar to total root replacement. The coronary
ostia are not mobilized and are sutured directly to openings in the allograft (Fig. 30-16) .
This can be done by suturing the recipient's coronary artery circumferentially to the
opening in the allograft or by partially resecting the appropriate sinus of Valsalva in
patients with a high origin of the coronary artery.
The downstream suture line is constructed with interrupted or continuous monofilament

sutures. The aortotomy closure is similar to that described for the free-hand
two-suture-line technique with intact noncoronary sinus.
Assessment of Competence of the Allograft Valve Replacement
The adequacy of the operation is assessed under appropriate loading conditions after
weaning from cardiopulmonary bypass using transesophageal echocardiography.
Anything more than trivial regurgitation is regarded with suspicion, and moderate
regurgitation is unacceptable and requires reestablishment of cardiopulmonary bypass
and reinspection and revision of the allograft valve.
AORTIC ROOT REPLACEMENT WITH PULMONARY
AUTOGRAFTS
Indications
Indications for the pulmonary autografts (in contrast to allografts or other valve
substitutes) are not fully determined. The pulmonary autograft may be preferred in
children and adolescents, since the valved autograft offers a potential for growth and
continuous adaptation to the patient's increasing size. Concerns about excessive
dilation of the pulmonary autograft from the systemic pressure have been raised but
have not been confirmed by long-term follow-up. [15 ] The pulmonary autograft is very
resistant to degeneration, particularly calcification. [16 ] This attribute makes the
autograft pulmonary valve especially desirable for patients less than 40 years of age.
Use of pulmonary autografts raises the issue of substitutes for the pulmonary valve and
artery. Aortic allografts appear to calcify quickly in the pulmonary position. [17 ] For this
reason, pulmonary allografts were introduced for reconstruction of the right ventricular
outflow tract. Results with pulmonary allografts indicate that these substitutes can be
expected to last over 20 years in more than 80 percent of patients. [16 ] In patients older
than 40 years of age, the advantages of pulmonary autografts are less evident as
compared with aortic allografts. In the older patients, indications for pulmonary
autografts should be evaluated carefully and individualized.
Contraindications
Contraindications to the use of pulmonary allografts are basically related to the quality of
the patient's pulmonary valve. The presence of even mild incompetence contraindicates
this operation, as does a mismatch in size between the pulmonary annulus and the
aortic annulus in excess of 2 to 3 mm. These criteria essentially rule out patients with
aneurysms or aortic annular ectasia for pulmonary autograft replacement.
Echocardiography is used to assess the functional status of the pulmonary valve and
any disparities in size between the aortic annulus and the pulmonary annulus that may
contraindicate the procedure. In addition, a large conal branch to the left anterior
descending artery, an infrequent finding at operation, contraindicates the autograft.
Operative Procedure
CANNULATION AND MYOCARDIAL PROTECTION
This operation requires bicaval cannulation and total cardiopulmonary bypass.

Cannulation of the ascending aorta is similar to that used for allograft aortic valve
replacement. A retrograde cardioplegia cannula is routine, and antegrade cardioplegia,
either by direct coronary cannulation or through the aortic root, if the aortic valve is
competent, is also used. After the initial dose of antegrade and retrograde
cardioplegia, retrograde cardioplegia is repeated every 20 minutes. The left ventricular
vent is inserted through the right superior pulmonary vein. The temperature of the
perfusate is stabilized at 28°C during most of the operation.
AORTOTOMY, EXCISION OF THE NATIVE AORTIC VALVE, AND PREPARATION

OF THE AORTIC ROOT
A cross-clamp is applied, and cardioplegia is given. Aor-totomy is performed in a

similar manner to the aortotomy used for allograft aortic valve replacement but must not
be placed distally. Excision of the aortic valve and preparation of the coronary artery
buttons proceed in the same way as for aortic root replacement with allograft valves.
HARVESTING THE PULMONARY VALVE
Mobilization of the proximal aorta and main pulmonary artery is done after institution of
cardiopulmonary bypass. The distal main pulmonary artery is divided as near the
bifurcation as possible. This approach reduces the risk of injury to the pulmonary valve
commissures and leaves the conduit long enough for root replacement. The pulmonary
valve is inspected to ensure normal architecture, and a blunt clamp is passed through
the valve to aid in location of the initial incision in the right ventricular outflow tract. A cuff
of muscle 3 to 4 mm wide is left below the lowest point of the leaflet attachment as the
right ventricular outflow tract is opened transversely with a fine blade first and then with
scissors. The conus branch of the right coronary artery is avoided when the incision is
extended toward the aorta.
Fibrous tissue between the aorta and pulmonary artery must be gently dissected to
avoid buttonholing the pulmonary artery while completing the incision (Fig. 30-17) .
Once this point is reached, the incision is directed toward the left side, where the left
anterior descending artery and its first septal perforating branch are at risk (see Fig.
30-17A ). By keeping the endocardial incision deeper than the epicardial dissection
(i.e., beveling the right ventricular edge), the pulmonary valve is removed without injuring
the perforating branch (see Fig. 30-17B ). Infusion of coronary ostial cardioplegia
identifies any small bleeding points at the resection margin, and these are controlled at
this time. The left main coronary artery and the left anterior descending branch are
posterior to the right ventricular outflow tract and 4 to 5 mm away. By dissecting carefully
from each side, the posterior attachment can be completed without injuring the coronary
artery. All the adventitia covering is left on the autograft. The autograft and base of the
remaining right ventricular outflow tract are measured with standard sizers so that an
appropriate allograft can be retrieved and thawed. Adventitial sutures are placed to
mark the locations of the commissures of the pulmonary autograft.
ALLOGRAFT ROOT IMPLANTATION
The upstream suture line is constructed with a 4-0 polypropylene continuous or

interrupted suture. Absorbable monofilament sutures are used in very young patients.
The pulmonary autograft is oriented so that the posterior pulmonary sinus becomes the
noncoronary sinus (Fig. 30-18A) . It is important to place the sutures in the muscle of the
left ventricular outflow tract. If the sutures are placed superficially or are attached to the
remnant of aortic wall, the autograft may not be supported adequately and may dilate
later. The suture line may be reinforced with a pericardial gasket to enhance
hemostasis. The coronary arteries are reimplanted as described for allograft aortic root
replacement (Fig. 30-18B) . The marking adventitial sutures placed at the commissures
of the pulmonary allograft guide placement of the circular openings in the pulmonary
autograft. The distal (downstream) suture line is completed after trimming and fitting the
aorta and distal portion of the autograft. After completion of the suture line, the aortic
root is deaired with retrograde cardioplegia; antegrade cardioplegia is used to test
suture lines and the exposed coronary arterial bed for leaks.
RECONSTRUCTION OF RIGHT VENTRICULAR OUTFLOW TRACT
Cryopreserved pulmonary allograft is the preferred conduit for the right ventricular
outflow tract reconstruction. The proximal (upstream) suture line is placed with
continuous 4-0 monofilament sutures. Posteriorly, a strip of pericardium is used to
improve hemostasis. The left coronary artery system is very close to the edge of the
incision posteriorly, and sutures must be placed precisely in ventricular endocardium to
prevent kinking the left main coronary artery or injury to the first septal branch of the left
anterior descending artery. After completing the upstream suture line, running 4-0 or 5-0
monofilament sutures are used to perform the distal (downstream) anastomosis at the
pulmonary arterial bifurcation (Fig. 30-18C) .
DEAIRING, WEANING FROM CARDIOPULMONARY BYPASS, AND TESTING

THE VALVE REPLACEMENT
Deairing maneuvers are similar to those for all other open cardiac procedures. After
weaning from cardiopulmonary bypass, competence of the valve is assessed with a
transesophageal echocardiogram.
ALLOGRAFT AND AUTOGRAFT RESULTS
Early and Long-Term Survival
Operative mortality is low and is comparable with that of mechanical or bioprosthetic

valvular replacement. In recent series, operative mortality ranged between 2 and 6
percent (Table 30-6) . Although some authors report a slightly higher operative mortality
for allograft root replacement, [18 ] [21 ] results of others are similar to those obtained
with the free-hand two-suture-line technique. In our own experience, early results are
similar for root replacement and free-hand two-suture-line techniques. In our opinion, it
is not appropriate to compare results with aortic allografts and pulmonary autografts
with the operative mortality and morbidity associated with bioprosthetic or mechanical
valve replacement. A patient-selection bias is probably present in all series of allograft
replacements. In general, patients are younger, their New York Heart Association
classification is less severe, and their left ventricular function is better than patients who
have aortic valve replacement with other devices.
These selection biases are also reflected in long-term results (Fig. 30-19) . Five-year
survival ranges between 80 and 95 percent and 10-year survival ranges between 75
and 85 percent after allograft valve replacement. No prospective, randomized studies
have been done to compare allograft, bioprosthetic, and mechanical valves.
Barratt-Boyes, [22 ] in a retrospective, nonrandomized study, reported better survival for
patients who received allograft aortic valves as compared with other devices. Analysis
of causes of death during long-term follow-up reveals a striking reduction in sudden
death as compared with mechanical aortic valve replacement. [19 ] [23 ] This decrease
in sudden death is the most consistent finding in all experiences with homograft aortic
valves. The reason is not clear, but it is possible that better hemodynamic performance
contributes to both fewer sudden deaths and less infective endocarditis.
Results of the pulmonary autografts are similarly encouraging. In this operation, bias in
patient selection is even more evident than in patients who receive allograft valves, so
direct comparison with other methods of valve replacement is not appropriate.
Notwithstanding this limitation, Ross et al. [1 ] observed that over 80 percent survived
20 years; however, this survival rate excludes operative mortality. [1 ] Other authors
report similarly excellent results for follow-up periods up to 4 to 6 years. [24 ] , [25 ]
Hospital mortality for pulmonary autografts is approximately 5 percent in recent years
(Table 30-7) . However, even the most recent series of the autograft operation report
operative deaths due to hemorrhage or coronary kinking that are not usually associated
with simple mechanical valve replacements.
Allograft Valve Failure
Allograft aortic valve failure almost always produces regurgitation. There are four
interrelated mechanisms that cause valve regurgitation (Fig. 30-20) : structural valve
degeneration (cusp rupture, usually in the belly, but sometimes in the commissure),
leaflet prolapse or distortion (technical error), central leak from progressive aortic
dilation (without leaflet rupture or technical error), and progressive loss of leaflet
extensibility. [26 ] These factors are difficult to separate from one another, but the latter
two mechanisms of deterioration are probably related to the intrinsic nature of the
allograft valve replacement, and the first two mechanisms are certainly related to more
controllable factors.
The technique of preservation historically has played a prominent role in the rate of
structural valve degeneration. Therefore, long-term results should be separated into
three different time periods: the early homograft era from the late 1960s to the late
1970s, the antibiotic-preserved homograft era from the late 1970s to the mid-1980s,
and the contemporary era, which includes cryopreserved allograft valves that began with
the O'Brien experience in 1975. The first era of allograft implantation included
tissue-preservation techniques such as freeze drying, multiple antibiotic incubations,
irradiation, and glutaraldehyde pretreatment. Within this early era as reported by the
Mayo Clinic group [27 ] and others, valve durability ranged from 40 to 60 percent after 5
or 6 years. With the advent of antibiotic sterilization, durability improved, and most
current reports relate to valves implanted using this preservation technique. Valves were
harvested from cadavers (with variable ischemic intervals), sterilized with antibiotics,
and stored at 4°C in nutrient media. Cell viability was not preserved, but this more
gentle method improved valve durability. Reports from this antibiotic era are primarily
from Ross' group at the National Heart Hospital, [28 ] from Khagani et al., [29 ] and from
Barratt-Boyes et al. [30 ] In 1980, Ross's group reported a series of 580 patients
followed for up to 15 years that included 202 patients who received antibiotic-sterilized
allografts and 179 pulmonary autografts. This study clearly demonstrated the superiority
of antibiotic-sterilized allografts over frozen, irradiated, or beta-propiolactoneprepared
valves. Freedom from valve deterioration was 75 percent after 10 years. In the United
States, the Stanford group reported their results in 1986 for 83 patients followed up to
19 years. [31 ] Freedom from valve failure was 83 ± 4 percent at 5 years, 62 ± 6 percent
at 10 years, and 43 ± 7 percent at 15 years. Yacoub summarized his experience in
1980. [32 ] One-hundred and forty patients had antibiotic-sterilized homografts and
were followed 10 to 13 years. Freedom from valve failure at 10 years was 72 percent.
Cusp degeneration caused failure in 19 percent of patients and endocarditis in 6
percent. The authors pointed out that prolonged warm ischemic time at procurement
(interval between death and dissection of the allograft) correlated with an increased risk
of valve degeneration.
Barratt-Boyes summarized his experience with 252 isolated aortic allograft valve
replacements followed for 9 to 16 years. [19 ] All valves in this series were inserted with
the same technique (orthotopic scalloped) by the same surgeon, so technical aspects
were constant. All valves were sterilized in antibiotic solution and stored in nutrient
medium at 4°C. Freedom from important valve incompetence was 95 percent at 5
years, 78 percent at 10 years, and 42 percent at 14 years. Three factors were
associated with valve deterioration: donor age greater than 55 years, young age of the
recipient, and aortic root diameter equal to or greater than 30 mm. In this series, aortic
insufficiency was rarely due to cusp rupture and more often was caused by a
combination of a technical problem at operation, dilatation of the aortic root, or central
incompetence related to less than perfect commissural suspension (Figure 30-21) .
Few series have distinguished between tissue-related problems and other causes of
allograft valve failure. [19 ] [23 ] In 1987, O'Brien et al. [33 ] reported the first
intermediate-term follow-up of cryopreserved valves and compared their results with
fresh antibiotic-treated allografts. Freedom from reoperation for degeneration was 89
percent at 10 years for antibiotic-treated allografts and 100 percent for cryopreserved
valves, [33 ] but the authors did not report important insufficiency in the absence of
reoperation. This omission underestimates the incidence of allograft degeneration
because some patients have moderate or severe allograft incompetence that is well
tolerated. If echocardiographic evidence of moderate and severe aortic insufficiency is
added to reoperative proof of allograft degeneration, Kirklin et al. [20 ] found that
freedom from leaflet degeneration after 8 years was 95 percent in reoperated patients
and 85 percent in reoperated and nonoperated patients (Figure 30-22) . An unresolved
issue is whether or not delayed tissue degeneration will increase slowly in
cryopreserved valves over time or abruptly increase at some point, as observed after 8
or 10 years in antibiotic-preserved allograft valves. In our experience with 96 patients
who received cryopreserved aortic allografts, we have not observed any progression of
aortic insufficiency in up to 10 years of follow-up, and no patient had explantation for
tissue degeneration (excluding calcification in one adolescent patient). Clearly, the
method of preservation is the most important issue for maintaining satisfactory valve
function in the long term if technical problems of implantation are avoided.
Contemporary Era
In 1975, O'Brien et al. [33 ] introduced the cryopreservation technique. In 1986, the first
report of long-term results of cryopreserved allografts became available. In this first
published series of 192 patients operated on between 1975 and 1986, all patients were
free from reoperation due to valve degeneration at 10 years. Freedom from reoperation
for all causes, particularly technical or endocarditis, was 92 percent at 10 years. (Figure
30-23) is the most recent report from the O'Brien group. [18 ] At 10 years, 93 percent
were free of structural deterioration. These results are, in general, better than results
published for antibiotic-preserved valves, as subsequently confirmed by others. [20 ] [34
] In our experience, no valve has deteriorated. The only instance of valve failure was
from aortic stenosis due to calcification in an adolescent patient.
Yacoub et al. [21 ] report results with fresh homovital valve allografts. These grafts are
obtained from recipient hearts of transplant patients and are stored for 24 to 48 hours at
4°C. They are implanted in the fresh, viable state. Freedom from graft deterioration is
about 90 percent after 10 years, but in patients younger than 30 years, accelerated
calcification of the valve seems to occur and causes aortic stenosis. This calcification,
which also occurs in cryopreserved allografts implanted in young patients, does not
develop in patients older than 40 years of age (Figure 30-24) .
Many authors have observed improved durability when the allograft is inserted as a root
replacement as compared with the free-hand two-suture-line technique. Daicoff et al.
[35 ] reported a small series with short follow-up in which results of free-hand insertion
were inferior to those of root replacement. Postoperative transvalvular gradients were
higher (17 versus 7 mm), and by 6 years, all 10 patients with free-hand allografts had
progressive regurgitation, and it was severe in 4. In contrast, no patient who had root
replacement had severe regurgitation, and only 50 percent had mild to moderate
regurgitation. Similar findings were reported by Elkins et al. [34 ] In 71 patients who had
root allograft valve replacement, freedom from significant aortic regurgitation was 88
percent at 6 years, and none had aortic valve deterioration. A comparison of root
replacement with the free-hand technique in mainly antibiotic-preserved allografts from
the Harefield group [36 ] showed less valve deterioration and better survival for patients
who had root replacement. However, O'Brien et al. [18 ] found no difference in the
incidence of reoperation between the two techniques during the first 8 years of follow-up
(Figure 30-25) .
In summary, results of cryopreserved and homovital allografts seem to be equivalent

and are far superior to those obtained with previous preservation techniques. With
satisfactory tissue survival to 10 years, technical factors during insertion are
increasingly important in the present era. It is premature to conclude that the free-hand
implantation technique is inferior to aortic root replacement, but the latter technique may
be less prone to technical problems and may provide more consistent results in the
hands of most surgeons.
Valve-Related Complications
Valve-related complications are rare after allograft aortic valve replacement and
basically are limited to progressive aortic regurgitation and endocarditis.
Thromboembolism is extremely uncommon and in most reported series is zero for as
long as 15 to 20 years. [18 ] [24 ] If thromboembolism occurs, it is associated with
tissue degeneration or infective endocarditis. In our experience of 96 patients followed
up to 10 years, there have been no episodes of thromboembolism, and no
anticoagulation has been necessary.
Tissue failure is apparent as early as during thawing. This is rare but emphasizes the
importance of very accurate thawing and rewarming of allograft valves. With refinements
of cryopreservation and better understanding of cryobiology, this problem should
disappear. However, a few details are important and begin with harvesting the allograft
valve. Key factors are warm ischemia time, controlled cryopreservation, and
maintenance of the intact adventitial layer on the allograft aorta.
Progressive calcification of valve cusps is uncommon. In our experience, this occurred

in one adolescent who had aortic root replacement and developed calcification and
aortic stenosis 7 years after operation. In Yacoub's experience with homovital grafts,
calcification appears more common but is limited to patients in their 20s or early 30s.
[21 ] In the experience of all surgeons with allograft valves, evidence of calcification of
the leaflets is minimal. [18 ] [21 ]
Calcification of the aortic wall of the allograft root replacements is another significant
issue. Available data are sparse, and follow-up is too short in most series to precisely
define this problem. [39 ] In the Harefield experience, the concern that progressive
calcification may decrease distensibility of the aortic root and create overwhelming
stress on the valve cusps after 7 or 8 years did not materialize. [39 ]
Another concern at the other end of the spectrum is progressive dilatation and loss of
root or allograft valve strength. This problem manifests early as an aortic regurgitation
murmur that tends to progress. An early aortic regurgitation murmur suggests a
possible technical problem, even though hemodynamic significance is negligible. These
murmurs usually progress to require valve replacement in 4 to 6 years. In our
experience, close follow-up of patients after aortic allograft valve replacement with
echocardiography indicates that 60 percent of patients do not have any evidence of
aortic regurgitation after the operation and 40 percent have trace or trivial regurgitation
without a diastolic murmur. In follow-up to a maximum of 9 years, we do not find any
progression of trivial aortic regurgitation detected echocardiographically. Thus the
presence of a murmur seems a more ominous sign than minimal regurgitation detected
by echocardiography.
Allograft aortic valves may be preferred even after failure of previous aortic valve
operations. [37 ] Yacoub reported 101 patients who had a previous allograft (i.e., a
failed allograft). The mean interval from first operation to reoperation was 9.48 years,
and reoperative mortality was 2 percent. This is significantly less than with other valve
replacements when reoperation is done for failed mechanical or bioprosthetic valves.
Thus reoperation for a failed allograft valve can be performed with low operative
mortality. Furthermore, as noted by Barratt-Boyes et al., [19 ] the operation is usually
elective because progression of aortic insufficiency is slow. Patients with previous
allografts also had better long-term survival after the repeat allograft operation. This
suggests that the allograft valve preserves left ventricular function better than does a
mechanical valve.
Infective endocarditis is rare after allograft valve replacement (Figure 30-26) .

Furthermore, there are data that indicate that recurrent endocarditis is less when an
allograft valve is used to replace an infected mechanical valve or bioprosthesis. [38 ]
Results with aortic allografts are shown in Figure 30-27 .
CONCLUSION
The cryopreserved aortic allograft valve is a suitable aortic valve substitute. Lack of
thrombogenicity, need for anticoagulants, and excellent mechanics make it superior for
young and middle-aged patients. Time-related acquired regurgitation and surgical
technical demands are drawbacks and limit universal application. However, experience
will overcome technical limitations, and perhaps further long-term follow-up may
demonstrate a low rate of valve degeneration.
AORTIC VALVE REPLACEMENT IN PATIENTS WITH A SMALL
AORTIC ANNULUS
Although the aortic valve has no fibrous annulus, surgeons use the term aortic annulus
to describe the aortoventricular junction where the aortic leaflets are attached. The
diameter of the normal aortic annulus in adults ranges from 23 to 27 mm depending on
the patient's size. Thus the definition of small aortic annulus is a relative one; an aortic
annulus of 23 mm is normal for a patient with a body surface area of 1.5 or 1.6 m [2 ] but
is small for a patient with a body surface area of 2.0 m [2 ] . In my experience,
approximately 20 percent of all patients who need aortic valve replacement have a
small aortic annulus when the preceding guidelines are used. [1 ] , [2 ]
A small aortic annulus is common in patients with rheumatic aortic valve disease or
non-bicuspid congenital aortic stenosis. Bicuspid aortic valve disease is frequently
associated with a larger than normal aortic annulus, particularly when aortic insufficiency
is the indication for valve surgery.
Because mechanical heart valves and stented biologic valves are intrinsically
obstructive, aortic valve replacement with small prosthetic valves may produce
unacceptably high transvalvular gradients. Experience with patients with systemic
hypertension and left ventricular hypertrophy [3 ] , [4 ] and, more recently, with aortic
valve replacement with small prosthetic valves [5 ] , [6 ] shows that persistent left
ventricular hypertrophy adversely affects long-term survival. Since most patients who
need aortic valve replacement have increased left ventricular mass, it is important to
implant a competent prosthetic valve that leaves minimal or no systolic gradient across
the left ventricular outflow tract and allows the left ventricle to return to a normal mass.
Based on hemodynamic data obtained from postoperative Doppler echocardiographic

studies in several hundred patients who had aortic valve replacement in my institution, I
developed Table 31-1 to assist the surgeon in matching the size of the patient to the
size of the prosthetic heart valve (mechanical or tissue).
There are various methods to deal with a small aortic annulus during aortic valve
replacement. They are as follows.
Aortic Valve Replacement with Stentless Biologic Valves
Aortic valve replacement with a pulmonary autograft, an aortic valve homograft,or a

stentless porcine valve is one alternative for patients with a small aortic annulus. These
stentless biologic valves have the lowest impedance to flow of all available valves used
for aortic valve replacement. However, if the aortic annulus is excessively small, an
enlargement procedure is also necessary before one of these stentless valves is
implanted. Pulmonary valve autografts and aortic valve homografts are discussed in
Chap. 30. Stentless porcine bioprostheses are discussed later in this chapter.
Implantation of a Prosthetic Valve in a Supraannular Position
The noncoronary aortic sinus is the largest of the three sinuses, and it often sags on the
roof of the left atrium in patients with aortic valve disease. The aortic annulus in this area
lies at a lower level than it does along the left and right aortic sinuses. The diameter of
the aortic root at the level of the aortic sinuses is larger than the diameter at the level of
the aortic annulus. One takes advantage of this anatomic feature to implant a larger
prosthetic aortic valve than the diameter of the aortic annulus by securing it in a
supra-annular position along the non-coronary aortic sinus. [1 ] , [7 ] To accomplish this,
the diseased aortic valve is excised,the annulus is debrided completely of all calcific
deposits, and multiple pledgeted sutures of a 2-0 multifilament polyester are passed
through the aortic annulus along the left and right sinuses and from the outside to the
inside of the aortic root a few millimeters above the aortic annulus along the
noncoronary aortic sinus, as shown in Figure 31-1 . These sutures are then passed
through the sewing ring of the prosthetic valve and tied down. Care must be exercised
to prevent tears in the non-coronary aortic sinus when sutures are tied. This technique is
very useful when bioprosthetic valves are implanted, and a valve one size larger than the
diameter of the aortic annulus usually can be implanted. I do not believe that this
technique is advisable when mechanical valves are implanted because the annulus
beneath the non-coronary aortic sinus may interfere with valve function immediately after
surgery or later due to pannus formation.
Patch Enlargement of the Aortic Annulus along the Noncoronary Aortic Sinus
The aortic annulus and the left ventricular outflow tract can be enlarged by extending the
aortotomy into the non-coronary aortic sinus and base of the anterior leaflet of the mitral
valve or by incising the right aortic sinus and the interventricular septum.
Enlargement of the aortic annulus along the non-coronary sinus was first described by
Nicks et al. [8 ] in 1970. Variations of this technique have been described by others. [9 ]
, [10 ] Basically, the aortotomy is extended into the non-coronary aortic sinus, through
the aortic annulus, and then into the anterior leaflet of the mitral valve, as illustrated in
Figure 31-2 . The incision is best directed toward the mid-mitral line (an imaginary line
that divides the anterior mitral leaflet into two equal halves). The depth of this incision
may be limited by the roof of the left atrium, which is attached to the fibrous curtain
between the aortic and mitral valves. If an incision down to this level does not provide
adequate enlargement of the aortic annulus, the roof of the left atrium may have to be
opened and the incision extended into the anterior leaflet of the mitral valve to
approximately one-third of its height, as shown in Figure 31-2C . The width of the patch
used to enlarge the aortic annulus is limited by the depth of the incision made in the
mitral valve. The width does not exceed double the length of the incision made below
the aortic annulus because it may produce mitral valve dysfunction. The patch material
is shaped as a tear-drop and sutured to the mitral valve and aortic walls with a
continuous 4-0 polypropylene suture. If the roof of the left atrium is opened, it is closed
with a separate patch sutured to the margins of the atriotomy and to the patch used to
enlarge the aortic annulus, as shown in Figure 31-2C .The prosthetic valve is then
secured to the aortic annulus and patch as in Figure 31-1C and D . Fresh autologous
pericardium, glutaraldehyde-fixed bovine pericardium, and Dacron or Teflon fabric can
be used as patch material. This operative technique usually permits implantation of a
prosthetic valve two sizes larger than the original size of the aortic annulus.
In patients who also need mitral valve replacement, fibrous tissue between the aortic
and mitral annuli may be divided completely and a patch sutured to this fibrous tissue to
further enlarge the aortic annulus. Details of this operation are presented later under
Endocarditis (Figure 31-4) .
Patch Enlargement of the Aortic Annulus along the Interventricular Septum
Another method to enlarge the aortic annulus is referred to as aortoventriculoplasty and

was first reported by Konno et al. [11 ] in 1975 and by Rastan and Koncz [12 ] in 1976. If
the decision to perform this type of enlargement of the aortic annulus is made before the
aortic valve is excised, the ascending aorta is opened through a longitudinal rather than
a transverse or oblique incision. The origin of the right coronary artery is identified by
dissecting the anterior wall of the aortic root, and a longitudinal aortotomy is made and
stopped just to the left of the origin of the right coronary artery. The aortic valve is
excised, and the aortotomy is extended into the right aortic sinus 8 to 10 mm away from
the orifice of the right coronary artery and into the interventricular septum and free wall of
the right ventricle, as shown in Figure 31-3A . The interventricular septum is incised for
a length of 2 to 5 cm depending on the size of the heart and on the desired degree of
enlargement of the outflow tract (Figure 31-B) . A patch of Dacron fabric or
glutaraldehyde-fixed bovine pericardium shaped as a tear-drop is used to close the
incision made in the interventricular septum with a continuous 3-0 polypropylene suture,
as shown in Fig. 31-3C . This suture is interrupted at the aortic annulus, and a 4-0
polypropylene suture with a finer needle is used to sew the patch to the aortic sinus and
aorta. The width of the patch at the level of the aortoventricular junction determines the
degree of enlargement of the aortic annulus. A prosthetic aortic valve is secured to the
aortic annulus and patch (Figure 3D,E) . The incision in the right ventricle is closed with
a separate triangular-shaped patch of Dacron fabric or bovine pericardium (Figure
31-3F) . It may be best to close the right ventricle before implanting the aortic valve
prosthesis because it saves one suture line by incorporating the right ventricular patch
in the sutures used to secure the prosthetic aortic valve to the left-sided patch, as shown
in Figure 31-3E . This method of patch enlargement of the aortic annulus allows for
implantation of a prosthetic valve three or four sizes larger than the original size of the
annulus.
Clinical Results
Patch enlargement of the aortic annulus along the non-coronary aortic sinus was
commonly performed in my unit before development of stentless porcine valves. [1 ] , [2
] Approximately one patient in five who had aortic valve replacement with a porcine
bioprosthesis also had patch enlargement of the aortic annulus. [2 ] I often use fresh
autologous pericardium or glutaraldehyde-fixed bovine pericardium as patch material
when bioprostheses are implanted and Dacron fabric when a mechanical valve is
implanted. In my experience, patch enlargement of the aortic annulus along the
non-coronary aortic sinus does not increase the operative mortality of aortic valve
replacement. [1 ] , [2 ] In a series of 32 patients who had patch enlargement of the aortic
annulus, I had only 1 operative death that was unrelated to the procedure. [1 ] However,
most surgeons believe that aortic annular enlargement during aortic valve replacement
increases operative mortality and morbidity. The principal problem with this operation is
bleeding along the suture lines. This can be avoided by careful suturing and prevention
of excessive tension along suture lines. Mitral regurgitation may be produced by this
procedure if the patch is not long enough and pulls the anterior leaflet upward to prevent
it from coapting with the posterior leaflet.This problem can be avoided by using a patch
of correct size and by securing the aortic valve prosthesis at a level that does not pull
the anterior leaflet of the mitral valve away from its plane of coaptation. In other words,
there must be enough patch material below the aortic valve to prevent upward distortion
of the anterior leaflet of the mitral valve.
Aortoventriculoplasty is a complex operation that should be performed only by

experienced surgeons. It is usually recommended for children with aortic stenosis and
hypoplastic left ventricular outflow tract. This type of patch enlargement of the aortic
annulus can produce serious problems if it is not executed carefully.Abnormal coronary
artery anatomy may further complicate this procedure. Bleeding along suture lines is a
common problem that can be avoided by careful suturing and avoidance of excessive
tension. The incision in the interventricular septum often severs the first septal perforator
artery with subsequent myocardial damage. In patients with a large first septal
perforator, the myocardial infarction can be fatal. [13 ] Although uncommon,
aortoventriculoplasty also may damage conduction pathways to cause left bundle
branch block, right bundle branch block, and even complete heart block. Another
problem is dehiscence of the patch from the interventricular septum with communication
between the left and right ventricles. This problem may require reoperation for
correction of the ventricular septal defect. Intraoperative Doppler echocardiography is
helpful in detecting interventricular communications,but it does not foretell late
dehiscence. Only meticulous operative technique avoids this problem.
Rastan et al. [13 ] reported 21 patients with 5 operative deaths. However,these authors
stated that with increased experience the operative mortality decreased to 5.8 percent
(1 death among 16 patients). [13 ]
ENDOCARDITIS OF THE AORTIC VALVE
Pathogenesis
Infective endocarditis is a disease whereby a microorganism colonizes a site in the

heart and produces fever, heart murmur, splenomegaly, embolic manifestations, and
bacteremia or fungemia. Early diagnosis of this condition is extremely important
because it almost invariably leads to devastating complications and death if not treated
promptly and properly.
Predisposing factors for infective endocarditis are cardiac abnormalities that damage
endocardium by a jet injury and a blood-borne microorganism that colonizes these
abnormal surfaces. Congenitally bicuspid aortic valve is the most common
predisposing lesion for endocarditis of the native aortic valve. Degenerative calcific
aortic stenosis, rheumatic aortic valve disease, and other congenital abnormalities of
the aortic valve are also predisposing lesions for infective endocarditis. Depending on
the virulence of the microorganism, normal aortic valves also can be infected.
It is impossible to determine the incidence and prevalence of native aortic valve

endocarditis in the general population because this disease is continuously changing.
Patients with prosthetic aortic valves have an ongoing risk of developing infective
endocarditis. The reported incidence ranges from 0.2 to 1.4 events per 100
patient-years. [2 ] , [14 ] [16 ]
Many studies demonstrate that dental extractions produce bacteremia. However, even
simple mastication, brushing teeth, and oral irrigation produce transient bacteremia.
Endoscopic procedures also produce bacteremia. Intravenous drug users are
particularly susceptible to infective endocarditis that often occurs in structurally normal
heart valves.
In 1928, Grant et al. [17 ] theorized that platelet-fibrin thrombi on heart valves served as
a nidus for bacteria adherence. In 1963, Angrist and Oka [18 ] introduced animal
evidence that supported this mechanism in the pathogenesis of endocarditis.
Experimental inoculation in animals with pre-existing nonbacterial thrombotic
endocarditis produced by mechanical abrasion of the endothelial covering of heart
valves causes a prompt leukocytic infiltration of the thrombi. [19 ] As the microorganism
multiplies, more leukocytes and thrombotic material accumulate in the area, and a
verrucous vegetation begins to form.
Depending of the virulence of the microorganism and the resistance of the host, the
aortic valve can be destroyed, and the infection may spread into the annulus and
surrounding structures with abscess formation. The abscess may rupture into the
pericardial cavity or into the heart.
Infective endocarditis of the aortic valve not only causes destruction of leaflets,
paravalvular abscess, and cardiac fistulas, but also causes coronary and systemic
embolization of vegetations. Cerebral infarction, either ischemic due to arterial
occlusion or hemorrhagic due to rupture of mycotic aneurysm, is common in these
patients. Mycotic aneurysms, infarcts, and abscesses of other organs such as spleen,
liver, kidneys, and limbs are also common.
Infection in a mechanical aortic valve is usually located in the sewing ring. [20 ] [22 ]
Infection in a porcine or pericardial valve may involve the leaflets and/or sewing ring. [23
] [25 ] Infection in aortic valve homografts and pulmonary autografts resembles that of
the native aortic valve; it begins in the leaflets and destroys them to produce aortic
insufficiency, and it also may extend into surrounding structures. [26 ] , [27 ]
Gram-positive cocci are the most common microorganisms responsible for native
aortic valve endocarditis. [20 ] , [28 ] [30 ] Staphylococcus aureus is presently the most
common agent, and it is extremely virulent and able to infect normal aortic valves. [20 ] ,
[30 ] Streptococcus viridans is the second most common microbe. It is not as virulent
as Staphylococcus and causes a more protracted infection. S. epidermidis and
various other streptococci also can cause endocarditis. Endocarditis due to
gram-negative bacteria is uncommon but is often resistant to antibiotic therapy and may
cause serious complications. Hemophilus , Actinobacillus , Cardiobacterium ,
Eikenella , and Kingella (HACEK group) are gram-negative bacilli grouped together for
their characteristic fastidiousness that requires prolonged incubation before growth.
Endocarditis by the HACEK group is also uncommon. Fungal endocarditis is rare but
extremely serious. Candida albicans and Aspergillus fumigatus are the usual agents.
The microbiology of prosthetic aortic valve endocarditis is different from that of the
native valve. [22 ] [24 ] , [30 ] [31 ] Prosthetic valve endocarditis is arbitrarily classified
as early when it occurs within the first 60 days after surgery and late when it occurs
after 60 days. [32 ] However, it is possible that many cases of prosthetic valve
endocarditis that occur during the first year after surgery are acquired at the time of
implantation of the artificial heart valve. This may be particularly true when the infection
is caused by the HACEK group of bacteria. Early prosthetic endocarditis is caused by
contamination at the time of implantation or by perioperative bacteremia. S. aureus , S.
epidermidis , and Enterococcus faecalis are among the more common
microorganisms responsible for early prosthetic valve endocarditis. [20 ] , [22 ] [25 ]
Sources of late prosthetic valve endocarditis are more difficult to determine.
Bacteremia is probably the principal cause of late endocarditis. Although streptococci
and staphylococci are commonly encountered in these patients, a myriad of
microorganisms causes late prosthetic valve endocarditis. [20 ] , [23 ] , [31 ]
Clinical Presentation and Diagnosis
It is helpful to classify infective endocarditis as acute and subacute because there are
major differences between these two clinical presentations. Subacute endocarditis is
often caused by a less virulent microorganism such as S. viridans : when this organism
affects a diseased aortic valve, the clinical course is protracted, and antibiotics alone
cure most cases. On the other hand, acute endocarditis is frequently caused by a
virulent microorganism such as the S. aureus , may affect a normal aortic valve, the
clinical course is acute, and antibiotics alone seldom cure.
The onset of subacute endocarditis in most cases is subtle, with low-grade fever and
malaise. Patients think they have the flu and are often treated with oral antibiotics for a
week to 10 days with improvement of symptoms. However, in most cases the
symptoms recur a few days after stopping antibiotics. In the majority of cases no
predisposing factor is identified. An aortic valve murmur is present in nearly all patients
because they have preexisting aortic valve disease. Splenomegaly is common.
Clubbing of the fingers and toes may develop in long-standing cases. Skin and mucous
membrane signs occur late in this form of endocarditis. Petechiae appear on any part
of the body. Small areas of hemorrhage may be seen in the ocular fundi. Hemorrhages
in the nail beds usually have a linear distribution near the distal end, hence the name
splinter hemorrhages . Osler's nodes are acute, tender, barely palpable nodular lesions
in the pulp of the fingers and toes. Bacteria have been cultured from these lesions.
Embolization of large vegetation fragments may cause dramatic clinical events such a
acute myocardial infarction, stroke, or splenic or hepatic infarcts. Any other organ also
may be involved. Destruction of the aortic leaflets causes aortic insufficiency and heart
failure. The blood picture is not distinctive in subacute endocarditis. Anemia without
reticulocytosis develops in patients untreated for more than a few weeks. The leukocyte
count is moderately elevated. Blood cultures frequently identify the offending
microorganism.
The clinical course of acute endocarditis is often fulminating. A preexisting source of

bacteremia may be identified. This form of endocarditis can present all symptoms and
signs described under subacute endocarditis, but these are more acute and patients
are often sicker with overwhelming signs of sepsis. Early metastatic infections are
common. Two physical signs are seen only in acute endocarditis: the Janeway lesion (a
painless red-blue hemorrhagic lesion of a few millimeters in diameter found in the palm
of the hands and in the soles of the feet) and the Roth spot (an oval pale area near the
optic disc surrounded by hemorrhage). Acute endocarditis is common in patients with
no pre-existing aortic valve disease. Early cardiac decompensation due to aortic
insufficiency is common. Paravalvular abscess is also common, and depending on its
location, the electrocardiogram may show an increased PR interval or heart block. The
blood picture is one of acute sepsis. Blood culture often isolates the infecting agent.
Prosthetic valve endocarditis may present as acute or subacute endocarditis.
Doppler echocardiography is extremely useful in the diagnosis and management of

infective endocarditis. [33 ] , [34 ] Transesophageal echocardiography is usually better
than transthoracic echocardiography, and multiplane is better than monoplane for the
diagnosis of endocarditis. Echocardiography can detect vegetations as small as 1 to 2
mm in size, but it is more reliable in native than in prosthetic valve endocarditis. It is
more useful for tissue than for mechanical valves because of acoustic shadowing and
ball, disk, or leaflet motion of mechanical heart valves. Echocardiography is also
extremely sensitive for detecting paravalvular abscess and cardiac fistulas.
Heart catheterization and coronary angiography increase the risk of embolization in

patients with vegetations.
Treatment
An appropriate antibiotic is the most important therapy in the management of patients

with infective endocarditis. [29 ] , [30 ] Antibiotic therapy should be started soon after
obtaining several blood cultures. The initial choice of antibiotics is based on clinical
circumstances and the suspected source of infection. Patients who had recent dental
work should receive antibiotics to cover bacteria from the oral cavity; those who had
recent urinary or colonic procedures should be treated with antibiotics that are effective
against gram-negative bacteria; intravenous drug users are usually infected with S.
aureus or S. epidermidis. Once the microorganism is identified by blood cultures and
its sensitivity to specific antibiotics is known, antibiotic therapy is adjusted accordingly.
A combination of two or three antibiotics that potentiate each other is often needed in
the treatment of endocarditis caused by virulent microorganisms. Intravenous antibiotic
therapy is continued for 4 to 6 weeks.
It is difficult to eradicate infection caused by virulent microorganisms with antibiotics

alone because they often destroy the native aortic valve very rapidly to cause aortic
insufficiency and congestive heart failure. These infections are usually caused by S.
aureus , Pseudomonas aeruginosa , Serratia marcescens , or fungi.
Surveillance blood cultures are performed in 48 hours to monitor the efficacy of

antibiotic therapy. The patient must be watched closely for signs of congestive heart
failure, coronary and systemic embolization, and persistent infection. Daily
electrocardiograms and frequent Doppler echocardiograms are performed during the
first 2 weeks of treatment. Any evidence of increasing aortic insufficiency, enlarging
vegetations, recurrent emboli, paravalvular abscess, or persistent infection constitute
indications for surgery. Patients with vegetations larger than 10 mm present a clinical
problem because they are more likely to develop serious complications [33 ] ; a more
aggressive approach in these patients appears justifiable. [20 ]
Anticoagulation is not effective in preventing embolization of vegetations and is

associated with an increased risk of neurologic complications. [33 ]
Early surgical treatment should be considered in patients with signs of congestive heart
failure, acute valve dysfunction, paravalvular abscess or cardiac fistulas, recurrent
systemic embolization when valve vegetations are present, and persistent sepsis
despite adequate antibiotic therapy for more than 4 to 5 days. Prosthetic valve
endocarditis is best treated by early surgery, particularly in patients with mechanical
valves. [20 ] , [22 ] , [29 ]
Surgery for Infective Endocarditis of the Aortic Valve
Patients with infective endocarditis who need surgery are often very sick, and
intraoperative myocardial protection is of utmost importance because they often require
complex operations and long aortic cross-clamp times. Another important aspect of
surgery for endocarditis is avoidance of contamination of the surgical field, instruments,
drapes, and gloves with vegetations and pus. Instruments used to extirpate
contaminated areas of the heart should be discarded before reconstruction of the aortic
valve and heart begin. In addition, local drapes, suction equipment, and surgical gloves
should be changed.
When infection is limited to leaflets of the native aortic valve or a bioprosthetic valve,
complete removal of the valve and implantation of a biologic or mechanical valve usually
resolve the problem. However, if the aortic annulus is involved by the infective process,
resection of the inflamed area is needed before a prosthetic valve can be implanted.
The defect created in the annulus can be repaired with fresh autologous pericardium. A
prosthetic aortic valve is secured to that patch and to the remaining normal aortic
annulus.
Patients with aortic root abscess and/or cardiac fistulas challenge cardiac surgeons
because of both the local problem and metastatic abscesses. The most important
aspect in the surgical treatment of these patients is radical resection of all infected
tissues. [20 ] , [22 ] , [27 ] , [36 ] [38 ] Although some surgeons reconstruct the aortic root
and surrounding tissues with Dacron fabric, [36 ] , [37 ] I favor glutaraldehyde-fixed
bovine pericardium because it is resistant to colonization by the offending
microorganism. [20 ] , [27 ] , [38 ] I use only bovine pericardium to reconstruct the left
ventricular outflow tract and the non-coronary aortic sinus. If left or right aortic sinuses
are completely excised, I reconstruct the left ventricular outflow tract with bovine
pericardium and use a valved Dacron conduit to replace the aortic root and proximal
ascending aorta. When this is done, coronary arteries may require Dacron, Gore-Tex,
or saphenous vein extensions before they can be reimplanted in the valved conduit.
Aortic homografts are ideally suited for this situation and may be more resistant than
Dacron to persistent infection; however, I firmly believe that radical resection of the
abscess is the key to eradicate infection in the aortic root. [22 ]
Patients with abscess in the fibrous tissue between the mitral and aortic valves are
among the more difficult ones to manage. This abscess is best approached through the
aortic root and roof of the left atrium. After removing the aortic valve (native or
prosthetic), the aortotomy is extended into the aortic annulus and roof of left atrium to
expose the fibrous curtain between the aortic and mitral valves. The abscess is excised
en bloc even if it is necessary to resect a considerable amount of normal tissue. Often
the infected anterior leaflet of the mitral valve requires excision. The proximal third of the
anterior leaflet of the mitral valve can be resected and reconstructed safely (see Figure
31-4 ), but it is safer to remove the entire anterior leaflet than to leave infected tissue
behind. If the entire anterior leaflet is excised, the base of the left ventricle becomes
widely open without separation between inflow and outflow tracts. A new aorto-mitral
fibrous curtain is necessary, and this is made by suturing a triangular-shaped patch of
bovine pericardium to the fibrous trigones. A mitral valve prosthesis is secured to the
posterior mitral annulus and the patch. The roof of the left atrium is closed with a
separate pericardial patch. An aortic valve prosthesis is implanted in the aortic position
by securing it to the triangular patch and normal aortic annulus. When aortic homografts
are used for this type of reconstruction, the anterior leaflet of the mitral valve of the
homograft can be used as patch material for the new fibrous curtain between the aortic
and mitral valves.
Postoperative complications are common after surgery for active infective endocarditis.
Septic patients may bleed excessively after cardiopulmonary bypass from a severe
coagulopathy. Antifibrinolytic drugs and clotting factors may be needed to obtain
hemostasis. Radical resection of an aortic root abscess may cause heart block that
requires a permanent pacemaker. Depending on the patients preoperative clinical
condition, multi-organ failure may develop after surgery. Neurologic complications are
also common. Although the majority of the cerebral lesions are ischemic infarcts,
hemorrhagic infarcts also may occur and complicate the perioperative course of these
patients. Cerebral abscess is uncommon but may occasionally require surgical
attention. Pulmonary, splenic, hepatic, and other metastatic abscesses seldom require
surgical treatment. Large metastatic abscesses may have to be drained. In the case of
the spleen, splenectomy should be performed because of the risk of rupture. [39 ]
Clinical Results
The prognosis of aortic valve endocarditis largely depends on when the disease is
diagnosed and how promptly it is treated. [30 ] Patients with prosthetic aortic valve
endocarditis have a more serious prognosis than patients with native aortic valve
endocarditis [20 ] , [29 ] ; however, the results of surgery for infective endocarditis have
improved significantly during the past three decades. [20 ] [22 ] , [29 ] , [32 ] , [36 ]
Operative mortality for patients with infection limited to the leaflets of the aortic valve is
as low as for uninfected aortic valve replacement [20 ] , [29 ] ; it is higher in patients with
prosthetic valve endocarditis and in those with aortic root abscess. [22 ] , [27 ] , [35 ] [36
] In a recent series of surgically treated patients, operative mortality for native valve
endocarditis was under 10 percent, and for prosthetic valve endocarditis it was 20 to 30
percent. [20 ] , [22 ] , [27 ] , [29 ] , [36 ]
My colleagues and I [40 ] reviewed our experience with surgery for active infective
endocarditis in 122 patients and found that actuarial survival at 10 years was 61 ± 6
percent. Late recurrent endocarditis is a potential problem. Patients operated on for
active infective endocarditis have a higher risk of developing endocarditis than other
patients with prosthetic valves. [29 ] , [40 ] In our experience, 8 of 122 patients
developed recurrent infection after a mean interval of 47 months; freedom from
recurrent endocarditis at 10 years was 79 ± 9 percent. [40 ] In most of these patients the
second episode of endocarditis was caused by a different microorganism.
AORTIC VALVE REPAIR IN PATIENTS WITH AORTIC ROOT
ANEURYSM
Certain anatomic and functional features of the aortic root have to be known to
understand the principles of reconstruction of the aortic root. Figure 31-5A shows a
diagram of a normal aortic valve leaflet. The length of the base is approximately 1.5
times that of the free margin. This difference in length prevents prolapse of the aortic
leaflet. The noncoronary leaflet is slightly larger than the right and left leaflets. The size of
the aortic sinus is directly related to the size of the leaflet. Thus the noncoronary aortic
sinus is larger than the right and left sinuses. Figure 31-5B shows a diagram of the
aortic root. The diameter of the aortic annulus is 10 to 15 percent larger than the
diameter of the sinotubular junction. The aortic leaflets are attached along a crescentic
line in the aortic root. The aortic valve commissures are located immediately below the
sinotubular junction. Thus the diameter of the sinotubular junction is smaller than the
average length of leaflet free margins; this allows the leaflets to coapt centrally. The
aortic and mitral valves share a segment of fibrous tissue. The right side of the aortic
root is attached to this fibrous tissue, which corresponds to approximately 55 percent of
the circumference of the aortic root. The left side of the aortic root is attached to
ventricular muscle, which corresponds to approximately 45 percent of the
circumference.
Although the aortic valve has no fibrous annulus, surgeons use the term aortic annulus
to describe the aortoventricular junction. Annuloaortic ectasia is a term used to
describe an increase in diameter of the aortic annulus. This ectasia occurs along the
fibrous tissue beneath the aortic root and increases the circumference of fibrous tissue
attached to ventricular muscle. Annuloaortic ectasia is seen in Marfan syndrome, forme
fruste Marfans, Ehlers-Danlos syndrome, osteogenesis imperfecta, and
pseudoxanthoma elasticum or may be idiopathic. Aortic sinuses become thinner and
dilated, the sinotubular junction increases in diameter, and commissures of the
noncoronary leaflet are pulled apart to prevent leaflets from coapting centrally. Aortic
insufficiency results. Dilatation of the aortic root increases tension on the leaflets so that
they may become overstretched and thinner.
Not all patients with aortic root aneurysms have annuloaortic ectasia. Degenerative
diseases of the aorta may cause dilatation of the ascending aorta and aortic sinuses
with minimal or no dilatation of the aortic annulus.
The aortic valve is often incompetent in patients with aortic root aneurysms (Figure
31-6A) ; however, leaflets are normal or minimally stretched in at least one-third of the
patients who come to surgery. In these patients, it is possible to reconstruct the aortic
root and preserve the native aortic valve.
Operative Technique
The ascending aorta is opened, and the aortic valve is carefully inspected. If the valve is
trileaflet and the leaflets do not prolapse (i.e., the length of the free margin is shorter
than the length of the base in all three leaflets), a valve-sparing procedure is feasible.
Next, the aortic sinuses are examined. If they are thinned and grossly dilated, all three
should be excised, leaving only 4 or 5 mm of arterial wall attached to the aortic annulus
and around each coronary artery orifice. To do this, the aortic root must be
circumferentially dissected from the pulmonary artery, right ventricle, and roof of the left
atrium (Figure 31-6B) . The diameter of the aortic annulus is measured. As mentioned
earlier in this chapter, a normal aortic annulus measures from 23 to 27 mm depending
on the patient's size. If the patient has annuloaortic ectasia with a diameter that often
exceeds 30 mm, aortic annuloplasty is needed as part of the reconstructive procedure.
This is accomplished by one of the two following operative procedures.
REIMPLANTATION OF THE AORTIC VALVE
Multiple horizontal mattress sutures of 4-0 or 3-0 polyester are passed from inside to
outside the left ventricular outflow tract in a single horizontal plane immediately below
the lowest level of the aortic leaflets, along the fibrous tissue, and following the
scalloped contour of the aortic annulus along its muscular insertion. In other words, the
sutures are in a single horizontal plane on the right side of the left ventricular outflow
tract and follow the insertion of the leaflets on the left side, as shown in Figure 31-6C .
Next, the length of the free margin of each leaflet is measured and averaged. A tubular
Dacron graft of diameter equal to the average length of the free margin of the leaflets is
selected. Three equidistant marks are made at one end, and one scalloped edge is
created to correspond to the commissure of the left and right leaflets, as shown in
Figure 31-6C . All sutures previously placed in the left ventricular outflow tract are
passed from inside to outside of the tailored end of the Dacron graft. It is important to
remember that one cannot plicate the muscular portion of the left ventricular outflow
tract, and sutures in this area must be carefully spaced. Most of the reduction in
diameter of the left ventricular outflow tract is done beneath the commissures of the
noncoronary leaflet. All sutures are tied outside the graft, and the aortic valve is now
within the graft (Figure 31-6D) . The three aortic commissures are suspended inside the
Dacron graft with interrupted pledgeted 4-0 polypropylene sutures. The remnants of the
arterial wall are sutured to the Dacron graft following the scalloped edge to mimic the
normal aortic root. This suture line is made with continuous 4-0 polypropylene sutures.
The aortic valve is tested by injecting saline into the Dacron graft and observing leaflet
coaptation. Coronary arteries are reimplanted into their respective sinuses with
continuous 5-0 polypropylene sutures (Figure 31-6D) . The upper end of the Dacron
graft is properly tailored and sutured to either the ascending aorta or to a graft used to
replace the transverse arch.
REMODELING THE AORTIC ROOT WITH ANGIOPLASTY
The aorta is transected, and the coronary arteries are detached from the aortic sinuses
(Figure 31-7A) . The aortic sinuses are excised, leaving a 3- to 4-mm rim above the
attachment of the leaflets. Multiple horizontal mattress sutures of 4-0 or 3-0 polyester
are passed from inside to outside the left ventricular outflow tract in a single horizontal
plane along its fibrous (nonmuscular) circumference only, as shown in Figure 31-7B .
These sutures are then passed through a strip of Dacron cloth in such way as to reduce
the diameter of the dilated fibrous circumference of the left ventricular outflow tract. Most
of the reduction in diameter should occur beneath the commissures of the noncoronary
leaflet. The sutures are tied down to produce an outflow tract in which the muscular
component represents approximately 40 percent of the circumference (Figure 31-7C) .
A tubular Dacron graft 2 or 3 mm smaller in diameter than the length of the free margin
of the leaflets is selected, and three equidistant marks are made at one of the ends.
Next, a longitudinal incision is made at each mark for a distance of approximately

two-thirds to three-fourths of the graft diameter. The graft end is scalloped as shown in
Figure 31-7D . Each aortic commissure is suspended at the end of these longitudinal
cuts in the graft by passing a 4-0 polypropylene suture from inside to outside the graft
end and then from inside to outside the arterial wall around the commissure. These
sutures are tied over a Teflon pledget. The scalloped end of the graft is sutured to the
remnants of the arterial wall close to the aortic annulus with a continuous 4-0
polypropylene suture, as shown in Figure 31-7E . All three commissures and
neosinuses are sutured in the same fashion, and the valve is tested by injecting saline
into the graft and observing the leaflets. Coronary arteries are reimplanted into their
respective sinuses, and the upper part of the Dacron graft is sutured to the ascending
aorta or transverse arch graft Figure 31-7E .
In patients who do not have annuloaortic ectasia, aortic annuloplasty is not needed;
remodeling the aortic root as described above is all that is required to correct aortic
insufficiency and the aortic root aneurysm and is illustrated in Figure 31-8 .
Certain patients with ascending aortic aneurysm and aortic insufficiency may have
normal aortic leaflets and fairly normal aortic sinuses but an enlarged sinotubular
junction that causes aortic insufficiency. In these patients, simple replacement of the
ascending aorta and reconstruction of the sinotubular junction with a tubular Dacron
graft of diameter 2 or 3 mm smaller than the length of the free margin of the aortic
leaflets correct the aortic insufficiency. This operation is shown in Figure 31-9 . In other
patients, only the noncoronary aortic sinus is involved by the aneurysm; reconstruction is
performed using the preceding rules to select the size of the Dacron graft and to tailor
one sinus at one end of the graft, as shown in Figure 31-10 .
Clinical Results
Although valve-sparing operations in patients with aortic root aneurysms have been
performed for over a decade, [44 ] , [45 ] no long-term information is available. [42 ] , [43
] As of June 1995, I reconstructed the aortic root with preservation of the valve in 65
patients. The reimplantation technique was used in 22 patients, remodeling of the root
with annuloplasty in 9, and remodeling without annuloplasty in 34. Twenty-two patients
had Marfan syndrome, and 12 had acute and 7 had chronic type A aortic dissection with
root aneurysm. There was one operative death due to extensive coronary artery
disease in a patient with acute type A dissection and one early and one late failure. The
remaining 62 patients are alive and have experienced no valve-related complication
during a mean follow-up of 19 months (range 3 to 82 months). Function of the aortic
valve remains unchanged in all these patients; one patient has moderate aortic
insufficiency, and all others have either mild or no aortic insufficiency. Freedom from
reoperation at 5 years is 95 ± 3 percent.
Because of these gratifying results, I have expanded the indication for surgery to
patients with aortic root aneurysms 5 cm in diameter who have incompetent but
structurally normal aortic valves by echocardiography.
MYECTOMY FOR HYPERTROPHIC CARDIOMYOPATHY
Hypertrophic cardiomyopathy (HCM) can be defined as left and/or right ventricular

hypertrophy of unknown etiology that is frequently asymmetric and associated with
histologic evidence of myocardial disarray. [46 ] , [47 ] HCM is an autosomal dominant
disease with variable penetrance. [48 ] , [49 ] It occurs either as a familial or as a
sporadic type due to genetic mutations with a low rate of genetic transmission. [48 ] ,
[49 ]
The most common form of HCM is asymmetric ventricular septal hypertrophy, followed
by midventricular and apical; the least common form is symmetric hypertrophy. The
extent of hypertrophy at any given site may vary and has an important role in the
manifestations of this disease. [47 ]
HCM often causes subaortic obstruction due to ventricular septal hypertrophy and
anterior displacement of the papillary muscles and mitral valve leaflets. The anterior
leaflet is subjected to Venturi and/or drag forces resulting in systolic anterior motion
(SAM) and contact with the hypertrophied septum to cause subaortic obstruction. The
anterior systolic motion of the anterior leaflet prevents coaptation with the posterior
leaflet; posteriorly directed mitral regurgitation results. The pressure gradient across the
left ventricular outflow tract is virtually simultaneous with the onset of anterior
leafletseptal contact. The time of onset and duration of anterior leafletseptal contact in
systole determine the magnitude of the pressure gradient and the degree of
prolongation of left ventricular ejection time.
Although left ventricular outflow tract obstruction is due to systolic anterior motion of the
anterior leaflet of the mitral valve in the vast majority of the patients with HCM, a few
patients have obstruction without systolic anterior motion. Obstruction in these patients
is believed to be caused by abnormal papillary muscles.
HCM also causes abnormalities in left ventricular relaxation and filling in about 80
percent of the patients. Reduced distensibility and increased diastolic stiffness are
associated with decreased stroke volume, increased filling pressure, and compression
of intramyocardial coronary arteries. This diastolic dysfunction is probably responsible
for symptoms of fatigue, exertional dyspnea, and angina pectoris.
HCM is often classified as obstructive and nonobstructive types. In obstructive HCM, the
subaortic obstruction may be latent, labile, or persistent. In nonobstructive HCM, there is
no systolic obstruction at rest or with provocation.
It is difficult to determine the natural history of HCM. The annual mortality rate due to
premature sudden death in hospital-based populations with HCM has been around 2 to
4 percent. [50 ] , [51 ]
Symptoms of obstructive HCM include dyspnea, angina pectoris, presyncope, and/or

syncope. A small proportion of patients develops atrial fibrillation. Doppler
echocardiography is the most useful diagnostic tool in this disease. Heart
catheterization and coronary angiography usually are reserved for patients who are
candidates for surgery.
The treatment of HCM is based on symptoms. Negative inotropes such as beta

blockers, calcium antagonists, and disopyramide decrease the degree of left ventricular
outflow obstruction. Patients who fail to respond to medical therapy may be treated with
dual-chamber pacing. [52 ] , [53 ] The mechanism by which the gradient is decreased
with dual-chamber pacing is poorly understood but may be related to decreased septal
motion, late activation at the base of the septum with right ventricular apical pacing, or
decreased left ventricular contractility. To work, ventricular capture that requires
optimization of the atrioventricular delay must be complete. Dual-chamber pacing
cannot be used for patients in atrial fibrillation.
Surgical myectomy for symptomatic subaortic obstruction due to HCM has been
performed for more than three decades. [54 ] Myectomy with complete relief of the
obstruction at rest and on provocation provides better symptomatic benefit than any
form of therapy currently available. [55 ]
Mitral valve replacement with a low-profile mechanical valve also has been used to
relieve subaortic obstruction in patients with HCM. [56 ] This operation removes the
offending mitral valve leaflets but condemns the patient to the hazards of having a
prosthetic mitral valve.
Septal Myectomy
This operation is performed with intraoperative transesophageal Doppler

echocardiography to precisely map the asymmetrically hypertrophic interventricular
septum and measure its thickness. The aorta is opened through a generous transverse
aortotomy, and the aortic valve is retracted and protected throughout the myectomy
(Figure 31-11A) . The hypertrophic septum is readily visible beneath the right aortic
leaflet and displays typical endocardial fibrosis in the area that is intermittently touched
by the anterior leaflet of the mitral valve. The septal myectomy is started by making an
incision in the interventricular septum 2 to 3 mm to the right of the center of the right
aortic leaflet directed toward the left ventricular apex. A second parallel incision is made
2 mm from the lateral fibrous trigone of the mitral valve and extended toward the apex.
The depth of these incisions varies with the thickness of the hypertrophied septum but
should be deep enough to reduce the thickness of the interventricular septum to 6 to 8
mm. A third incision is made 2 or 3 mm below the aortic annulus to join the two previous
incisions and then is deepened into the septum and toward the apex (Figure 31-11B) .
A rectangular block of muscle is excised. This block is usually 20 to 25 mm wide and 40
to 50 mm long, and its thickness varies with the original thickness of the hypertrophied
septum and is often 10 to 18 mm thick (Figure 31-11C) . After myectomy, the septum
should measure 6 to 8 mm by intraoperative echocardiography.
Clinical Results
Operative mortality associated with isolated septal myectomy for HCM is below 2
percent. [55 ] , [57 ] , [58 ] The operative risk is higher when myectomy is combined with
other procedures. [55 ] , [57 ] , [58 ] Transient complete heart block is common after
myectomy, and patients often need atrioventricular pacing after surgery during the first
few postoperative hours. Less than 5 percent of patients require permanent
atrioventricular pacing after septal myectomy. Ventricular septal defect is a rare
complication. The systolic gradient is consistently reduced to below 10 mmHg after
radical myectomy; anterior systolic motion of the mitral valve and mitral regurgitation are
abolished. Most patients become asymptomatic. The annual mortality rate is reduced to
1 to 2 percent. [55 ] , [57 ] [59 ]
THE NORMAL MITRAL VALVE
Anatomy
The mitral annulus is a pliable junctional zone of fibrous and muscular tissue joining the
left atrium and ventricle and anchoring the base of the anterior and posterior mitral
leaflets. [1 ] [11 ] The annulus has two major collagenous structures: (1) the right fibrous
trigone, which is part of the central fibrous body and is located at the intersection of the
atrioventricular membranous septum, the mitral and tricuspid valves, and the aortic root,
and (2) the left fibrous trigone at the posterior junction of the mitral valve and left
coronary leaflet of the aortic valve (Fig. 32-1) . The anterior mitral leaflet spans the
distance between the commissures (including the trigones) and is in direct fibrous
continuity with most of the left and part of the noncoronary aortic valve leaflets (Fig.
32-2) . Fine tendon-like collagen bundles, the fila of Henle, extend out circumferentially
from each fibrous trigone a variable distance around the corresponding side of the
mitral orifice. The posterior one-third to one-half of the annulus, which subtends the
posterior leaflet, is primarily muscular with little or no fibrous tissue. [10 ] This muscle is
arranged mainly perpendicularly to the annulus, but a less prominent group of muscle
fibers is arranged parallel to the annulus.
The mitral valve has two leaflets, the much larger anterior (or aortic) leaflet and the
smaller posterior (or mural) leaflet, which usually contains three (or sometimes more)
scallops separated by clefts. [12 ] The central portions of the leaflets on the atrial
surface are termed the rough zone , with the remainder of the free edge leaflet surface
being the bare, membranous , or clear zone . The ratio of the height of the rough zone
to the height of the clear zone is 0.6 for the anterior leaflet and 1.4 for the posterior
leaflet, since the clear zone on the posterior scallops is only about 2 mm high. [12 ] The
two leaflets are separated at the annulus by the posteromedial and anterolateral
commissures, which are usually quite distinct.
The histologic structure of the leaflets includes three layers: (1) the fibrosa, the solid
collagenous core that is continuous with the chordae tendineae, (2) the spongiosa,
which covers the atrial aspect and forms the leaflet leading edge (it consists of few
collagen fibers but has abundant proteoglycans, elastin, and mixed connective tissue
cells), and (3) a thin fibroelastic covering of most of the leaflets. [10 ] On the atrial aspect
of both leaflets, this surface (the atrialis ) is rich in elastin. The ventricular side of the
fibroelastic cover (the ventricularis ) is much thicker but is confined mostly to the
anterior leaflet; again, it is densely packed with elastin. The fibroelastic layers become
thickened with age due to elaboration of more elastin and collagen formation; similar
accelerated changes also accompany myxomatous valvular disease (floppy valve
syndromes). In addition to these complex connective tissue structures, the mitral leaflets
contain cardiac muscle fibers, blood vessels, and both adrenergic and cholinergic
nerves. [13 ] [16 ] Leaflet muscle, a direct extension of left atrial muscle fibers, is neurally
controlled and may play a role in mitral valve function. [6 ] , [16 ] [22 ] The atrial surface
of the anterior leaflet exhibits a depolarizing spike shortly before the onset of the QRS
complex, and the resulting contraction of leaflet muscle possibly may aid leaflet
coaptation as well as stiffen the leaflet in response to rising left ventricular (LV)
pressure. [16 ] , [21 ] , [23 ] [26 ] Mitral leaflet stretch of 10 percent or more also leads to
an action potential that initiates leaflet muscle contraction. [25 ]
Annular Size, Shape, and Dynamics
The average mitral annulus cross-sectional area ranges from 5.0 to 11.4 cm 2 in normal
human hearts (mean 7.6 ± 1.9 cm 2 ). [27 ] The annular perimeter of the posterior leaflet
is longer than that subtending the anterior leaflet by a 2:1 ratio; i.e., the posterior annulus
circumscribes about two-thirds of the mitral annulus. [12 ] Annular area varies during the
cardiac cycle and is influenced directly by both left atrial and LV size and pressure. [4 ] ,
[28 ] The magnitude of change in mitral annular area is in the 20 to 40 percent range. [4
] , [8 ] , [9 ] , [28 ] [35 ] Annular size increases beginning in late systole and continues
through isovolumic relaxation and into diastole;maximal annular area occurs around the
time of the electrocardiographic P wave. [4 ] , [8 ] , [30 ] , [32 ] , [33 ] Importantly, one-half
to two thirds of the total decrease in annular area may occur during atrial contraction
(thereby being presystolic); this component of annular area change is smaller when the
PR interval is short and is completely abolished when atrial fibrillation is present.
Annular area decreases further (if left ventricular end-diastolic volume is not abnormally
elevated) to a minimum in midsystole. [4 ] , [7 ] , [8 ] , [28 ] , [30 ]
The human mitral annulus is roughly elliptical or D-shaped in cross section, with greater
eccentricity (i.e., being less circular) in systole than in diastole. [3 ] , [4 ] , [8 ] , [27 ] , [28 ]
, [32 ] , [34 ] , [36 ] In its most elliptical configuration, the ratio of minor to major
diameters is approximately 0.75. In three-dimensional space, the annulus is somewhat
saddle-shaped (or, more precisely, a hyperbolic paraboloid), with the highest point (i.e.,
farthest from the LV apex) located anteriorly, the low points located posteromedially and
anterolaterally near the commissures, and another less prominent high point posteriorly.
[4 ] , [37 ] , [38 ] During the cardiac cycle, annular regions adjacent to the posterior
leaflet (where the leaflet attaches directly to the atrial and ventricular endocardium)
move toward (during systole) and away from (during diastole) the relatively immobile
anterior annulus. [4 ] , [34 ] Certain annular segments located near the left fibrous
trigone (or area of aortic-mitral continuity), however, may actually lengthen during LV
ejection, at least in canine and ovine hearts. [39 ]
The mitral annulus moves upward into the left atrium in diastole and toward the LV apex
during systole; the duration, average rate, and magnitude of annular displacement
correlate with (and perhaps influence) the rate of left atrial filling and emptying. [4 ] , [8 ] ,
[30 ] , [33 ] , [40 ] , [41 ] The annulus moves little during late diastole, e.g., 2 to 4 mm
toward the left atrium during atrial systole. This does not occur in the presence of atrial
fibrillation and thus may be due to atrial contraction. It moves a greater distance, e.g., 3
to 16 mm toward the LV apex, during isovolumic contraction and ventricular ejection.
This systolic motion, which aids left atrial filling, occurs in the presence or absence of
atrial fibrillation and is related to the extent of ventricular emptying; thus it is likely driven
by LV contraction. [4 ] , [8 ] , [32 ] , [33 ] , [40 ] , [41 ] [46 ] Subsequently, the annulus
moves very little during isovolumic relaxation but then exhibits rapid recoil back toward
the left atrium in early diastole. This recoiling increases the net velocity of mitral inflow
by as much as 20 percent. [9 ] , [33 ]
Dynamic Leaflet Motion
The posterior mitral leaflet is attached to thinner chordae tendineae than the anterior
leaflet, and its motion is restrained by chordae during both systole and diastole. [12 ] ,
[40 ] Both leaflets are concave toward the left ventricle during systole, [47 ] [49 ] but
leaflet shape is complex and some leaflet curvature may be convex to left ventricle
during systole. [37 ] , [38 ] Leaflet opening does not start with the free margin but rather
in the center of the leaflet [48 ] , [49 ] ; leaflet curvature initially flattens and then becomes
reversed (making the leaflet convex toward the left ventricle) while the edges are still
approximated. The leading edge then moves into the left ventricle (like a traveling
wave), and the leaflet straightens. The leaflet edges in the middle of the valve appear to
separate before those portions closer to the commissures, and posterior cusp opening
is delayed by 8 to 40 ms. [49 ] [51 ] Once reaching maximum opening, the edges exhibit
a slow to-and-fro movement (like a flag flapping in a breeze) until another less forceful
opening impulse occurs with the a wave. During late diastole, the leaflets move
gradually away from the LV wall. Valve closure starts with leaflet bulging toward the
atrium at its attachment point to the annulus. The closure rate of the anterior leaflet is
almost twice that of the posterior leaflet and thereby ensures arrival of both cusps at
their closed positions simultaneously (since the anterior leaflet is opened more widely
than the posterior leaflet at the onset of ventricular systole). [51 ] The anterior leaflet
actually arrives at the plane of the annulus in a bulged (concave to the ventricle) form,
but as the closing movement proceeds and the leaflet ascends toward the atrium, this
curvature appears to run through the whole leaflet, from the annulus toward the edge, in
a rolling manner. The leaflet edge is the last part of the leaflet to approach the annular
plane. Leaflet curvature becomes more pronounced with the onset of systolic ejection.
[48 ] , [49 ]
Mitral valve closure is completed 10 to 40 ms after the initial systolic rise of LV

pressure, but surprisingly, leaflet opening motion may actually precede the diastolic
pressure crossover point by up to 60 ms. [49 ] , [52 ] , [53 ] While the onset of mitral
valve closure at the end of diastole appears initiated by atrial contraction, competent
leaflet closure requires an increase in ventricular pressure above that in the atrium
(irrespective of whether or not a normal atrial electrical and mechanical sequence is
present) and a proper valve annular size to permit apposition of the valve leaflets at the
onset of and during ventricular ejection. [16 ] , [28 ] , [51 ]
Chordae Tendineae and Papillary Muscles
Left ventricular epicardial fibers descend from the base of the heart and proceed inward
at the apex to form the two papillary muscles, which are characterized by vertically
oriented myocardial fibers. [11 ] , [54 ] The anterolateral papillary muscle usually has
one major head and is a more prominent structure; the posteromedial papillary muscle
can have two or more subheads or bellies and is flatter. [12 ] A loop from the papillary
muscles to the mitral annulus is completed by the chordae tendineae continuing into the
mitral leaflets, which are attached to the fibrous annular ring. The posteromedial
papillary muscle is usually supplied by the right coronary artery (or a dominant left
circumflex artery in 10 percent of cases); the anterolateral papillary muscle is supplied
by both the left anterior descending and circumflex coronary arteries. [11 ] , [55 ] , [56 ]
The posteromedial and anterolateral papillary muscles give rise to chordae tendineae
going to both leaflets. [12 ] The chordae are classically and functionally divided into
three groups. [11 ] , [57 ] First-order chordae originate near the papillary muscle tips,
divide progressively, and insert on the leading edge of the leaflets; these primary
chordae prevent valve tip prolapse during systole. The second-order chordae (including
two or more larger and less branched strut chordae) originate from the same location
and tend to be thicker and fewer in number [12 ] , [57 ] ; they insert on the ventricular
surface of the leaflets in the rough zone and at the junction of the rough and clear zones,
which is demarcated by a ridge corresponding to the line of leaflet coaptation. The
secondary chordae (including the strut chordae on the anterior leaflet) serve to anchor
the valve and are more prominent on the anterior leaflet. The third-order chordae, called
tertiary or basal chordae , originate directly from the trabeculae carnae of the ventricular
wall and attach to the posterior leaflet near the annulus. Additionally, distinct
commissural chordae and cleft chordae (attached to the posterior leaflet) can be
identified by their fan-shaped patterns. [57 ] Some chordae, considered to be immature
forms, may contain muscle tissue. In total, about 25 major chordal trunks (range 15 to
32) arise from the papillary muscles in humans, equally divided between going to the
anterior and posterior leaflets [57 ] ; on the other end, over 100 smaller individual
chordae attach to the leaflets.
During diastole, the papillary muscles form an inflow tract; during systole, they create an
outflow tract, which later becomes obliterated and augments LV ejection by volume
displacement. [54 ] The contribution of the papillary muscles to LV chamber volume is 5
to 8 percent during diastole but 15 to 30 percent during systole. [54 ] , [58 ] The anterior
and posterior papillary muscles contract simultaneously; they are innervated by
sympathetic and parasympathetic (vagal) nerves. [59 ] , [60 ] Previous analyses of
papillary muscle function during the cardiac cycle yielded widely discordant results. [59 ]
, [61 ] [65 ] Although the papillary muscles shorten at some point during systole (by
upwards of one-fourth of their maximum length), [61 ] , [64 ] , [66 ] [69 ] some suggest
that this contraction may be isometric or substantially less than that of the LV free wall
fibers. [63 ] , [69 ] In addition, there is no consensus as to the exact timing of papillary
muscle contraction and elongation during the cardiac cycle. [59 ] [62 ] , [64 ] It is
reported that the papillary muscles contract before the LV free wall so that the mitral
valve leaflets are supported during early LV ejection [65 ] ; however, others find that the
papillary muscles lengthen during isovolumic contraction and shorten during ejection as
well as during isovolumic relaxation. [60 ] , [62 ] , [64 ] From the standpoint of
electromechanics, although papillary muscle excitation occurs simultaneously with the
rest of the endocardial surface of the ventricle, the papillary muscles may contract just
after the onset of LV contraction. [59 ] , [67 ] Marzilli et al. [67 ] , [68 ] suggest that
maximal shortening and elongation of the papillary muscle follow maximal shortening
and elongation of a segment of the LV free wall. Thus papillary muscle shortening
throughout isovolumic relaxation may play a role in opening of the mitral valve, and
elongation in late diastole may be necessary to permit proper valve closure. [67 ] In a
recent chronic canine study, Rayhill et al. [61 ] demonstrated that both papillary muscles
closely mimic general LV dynamics; i.e., the papillary muscles shorten during ejection,
lengthen during diastole, and change length minimally during the isovolumic periods
(Fig. 32-3) . These findings suggest that earlier studies purporting papillary muscle
lengthening during isovolumic contraction and shortening during isovolumic relaxation
may have been confounded by some form of myocardial injury or surgical trauma. [61 ]
MITRAL STENOSIS
Etiology
Mitral stenosis, in general, is due to rheumatic heart disease. [70 ] [77 ] Nonrheumatic
causes of mitral stenosis or LV inflow obstruction include severe mitral annular and/or
leaflet calcification, congenital mitral valve deformities, malignant carcinoid syndrome,
neoplasm, left atrial thrombus, endocarditic vegetations, certain inherited metabolic
diseases, and cases related to a previous commissurotomy (surgical or percutaneous)
or implanted prosthetic heart valve [74 ] , [76 ] [79 ] (Fig. 32-4) . A definite clinical history
of rheumatic fever can be obtained in only about 50 to 60 percent of patients; women
are affected more often than men by a 2 to 3:1 ratio. Nearly always acquired before age
20, rheumatic heart disease becomes clinically evident 10 to 30 years later.
Approximately 20 million cases of rheumatic fever occur in third world countries

annually, with a correspondingly high incidence of advanced mitral stenosis later in life.
[80 ] In the United States and other developed countries, the frequency of mitral stenosis
has decreased markedly. The etiologic agent for acute rheumatic fever is group A
beta-hemolytic streptococcus, but the specific mechanisms leading to the valvulitis are
unknown. [80 ] Streptococcal antigens cross-react with human tissues and can modify
immune mechanisms. Differences in the cellular and extracellular proteins in the many
strains of group A streptococcus may be important in the development of rheumatic
heart disease. The virulence of the organism may include the hyaluronic acid capsule
and the serotype of the antigenic capsular M protein, which resists phagocytosis and
opsonization. [80 ] Along with the individual patient's immune responsiveness, other
genetic factors are likely to be involved in the susceptibility to disease development or
progression.
Rheumatic heart disease involves more structures than just the cardiac valves; it is a
pancarditis affecting to various degrees the endocardium, myocardium, and
pericardium [70 ] , [73 ] , [74 ] (Fig. 32-5) . In rheumatic valvulitis, the mitral valve is the
one most commonly involved (isolated mitral stenosis is found in 40 percent of cases),
followed by combined aortic and mitral valve disease, and least frequently, isolated
aortic valve disease. Distinct pathoanatomic changes characteristic of mitral valvulitis
include commissural fusion, leaflet fibrosis with stiffening and retraction, and chordal
fusion and shortening. [73 ] One common finding is fusion of the valve cusps. Leaflet
stiffening and fibrosis become exacerbated by increased blood flow turbulence.
Associated mitral regurgitation (MR) can develop due to chordal fusion and shortening.
The chordae tendineae occasionally become so retracted that the leaflets appear to
insert directly into the papillary muscles. The amount of calcification varies; it is more
common and of greater severity in men, older patients, and those with a higher
transvalvular gradient. [74 ] Rheumatic myocarditis can lead to cardiac dilatation and
progressive heart failure.
Not uncommonly, mitral annular calcification progressing to mitral sclerosis and

eventually stenosis becomes clinically important in elderly patients. [71 ] , [79 ] In this
situation, the anterior leaflet remains relatively normal structurally but usually is thick and
immobile; LV inflow obstruction results from a calcified shelf beneath the posterior
mitral valve leaflet. Mitral stenosis also may result from protrusion of the calcific mass
into the ventricle, narrowing the valve orifice; additionally, extension of the calcium into
the leaflets may result in a rigid leaflet, leading to stenosis. [79 ] Anatomically, the left
ventricle is typically small, hypertrophied, and noncompliant.
Hemodynamics
With mitral stenosis, a diastolic gradient develops between the left atrium and ventricle
[75 ] , [81 ] [83 ] (Fig. 32-6) . As the degree of mitral stenosis worsens, a progressively
higher transvalvular pressure gradient becomes necessary to maintain adequate
cardiac output. The mean left atrial pressure in patients with severe mitral stenosis may
be in the range of 15 to 20 mmHg at rest, with a mean transvalvular gradient of 10 to 15
mmHg. [81 ] , [83 ] The high left atrial pressure and gradient rise substantially with
exercise. LV end-diastolic pressure is usually in the normal range.
An important physiologic measurement in patients with mitral stenosis is the (derived)

cross-sectional valve area, which is calculated from the mean transvalvular pressure
gradient and cardiac output. The transvalvular pressure gradient is a function of the
square of the transvalvular flow rate; for example, doubling the flow quadruples the
gradient. At a given flow rate, a smaller valve area corresponds to a higher pressure
gradient. Mitral transvalvular flow depends on cardiac output and heart rate; an increase
in heart rate decreases the duration of transvalvular LV filling during diastole, reducing
forward cardiac output; the transvalvular gradient increases and, consequently, so does
left atrial pressure [82 ] , [85 ] (Fig. 32-7) . A high transvalvular gradient may be
associated with a normal cardiac output; conversely, if the cardiac output is reduced, a
low transvalvular gradient may be present.
In patients with mitral stenosis and normal sinus rhythm, effective atrial contraction is
associated with a lower mean left atrial pressure compared with individuals in atrial
fibrillation. [86 ] , [87 ] In addition, sinus rhythm can augment flow through the stenotic
valve and thereby help to maintain adequate forward cardiac output. The development
of atrial fibrillation decreases cardiac output by 20 percent or more; atrial fibrillation with
a rapid ventricular response can lead to acute dyspnea and pulmonary edema. [70 ] ,
[86 ] , [87 ]
In patients with isolated mitral stenosis who have restricted LV inflow, LV chamber size
(end-diastolic volume) is normal or decreased, and LV end-diastolic pressure is
typically low. [75 ] , [88 ] , [89 ] LV peak filling rate is reduced, as is stroke volume.
Decreased cardiac output due to mitral stenosis is usually the result of inflow
obstruction rather than LV pump failure. [90 ] LV mass is normal or slightly subnormal in
the majority of patients with mitral stenosis [88 ] ; however, approximately 25 to 50
percent of patients with severe mitral stenosis have LV systolic dysfunction due to
associated diseases (e.g., mitral regurgitation, aortic valve disease, ischemic heart
disease, or rheumatic myocarditis and/or myocardial fibrosis). [75 ] , [83 ] , [89 ] In these
patients, LV end-systolic and end-diastolic volumes may be increased. Although LV
ejection fraction increases with exercise, LV filling is compromised by the shorter
diastolic periods at higher heart rates that cause smaller LV end-diastolic and stroke
volumes and a blunted increase (or even decrease) in cardiac output. [89 ]
Additionally, as right ventricular afterload increases secondary to the development of

pulmonary hypertension, right ventricular ejection performance may fall. [75 ] , [91 ]
Clinically, however, increased right ventricular afterload as a result of mitral stenosis is
frequently associated with normal right ventricular contractility. [75 ]
Atrial Adaptation
In patients with mitral stenosis who are in normal sinus rhythm, the left atrial pressure
tracing is characterized by an elevated mean left atrial pressure with a prominent a
wave, which is followed by a gradual pressure decline after mitral valve opening. [70 ] ,
[87 ] The a wave pressure largely reflects the kinetic energy dissipated in overcoming
the resistance across the valve. Because of the stenotic valve, left atrial contraction is
important in terms of maintaining transvalvular flow. [87 ] The high left atrial pressure
gradually leads to left atrial hypertrophy, atrial fibrillation, and mural thrombi formation.
[74 ] , [89 ] , [92 ] The degree of left atrial enlargement and fibrosis does not correlate
with the severity of the valvular stenosis; this is due in part to the marked variation in
duration of the stenotic lesion and atrial involvement by the underlying rheumatic
inflammatory process. [89 ] Disorganization of atrial muscle fibers is associated with
abnormal conduction velocities and inhomogeneous refractory periods. Premature
atrial activation due to increased automaticity or reentry eventually can result in atrial
fibrillation, which is present in over one-half of patients with either pure mitral stenosis or
mixed mitral stenosis and regurgitation. [92 ] , [93 ] Major determinants of atrial
fibrillation in patients with rheumatic heart disease include older age and larger left atrial
diameter. [92 ]
Pulmonary Changes
In patients with mild to moderate mitral stenosis, pulmonary vascular resistance may not
increase, and pulmonary arterial pressure may be normal at rest, rising only with
exertion or increased heart rate. [81 ] In severe chronic mitral stenosis with elevated
pulmonary vascular resistance, pulmonary arterial pressure is usually elevated at rest
and may exceed systemic pressure. A pulmonary arterial systolic pressure greater than
60 mmHg significantly elevates impedance to right ventricular emptying and produces
elevated right ventricular end-diastolic and right atrial pressures.
Left atrial hypertension produces pulmonary vasoconstriction and increased pulmonary

vascular resistance. [74 ] , [91 ] As mean left atrial pressure exceeds 30 mmHg above
oncotic pressure, transudation of fluid into the pulmonary interstitium occurs to cause
reduced lung compliance. Pulmonary hypertension develops due to passive
transmission of high left atrial pressure, pulmonary venous hypertension, pulmonary
arteriolar constriction, and eventual pulmonary vascular obliterative changes. Early
changes in the pulmonary vascular bed may be considered protective in that the
elevated pulmonary vascular resistance protects the pulmonary capillary bed from
excessively high pressures; however, the pulmonary hypertension progressively
worsens, which leads to right-sided heart failure, tricuspid insufficiency, and sometimes
pulmonic valve insufficiency. [75 ] , [91 ] Severe mitral stenosis ultimately causes
irreversible pulmonary vascular changes; cardiac output may be low at rest and remain
subnormal during exercise. [81 ]
Symptoms
Because of the gradual development of mitral stenosis, patients may remain

asymptomatic for years. [70 ] , [72 ] , [81 ] , [93 ] Characteristic symptoms of mitral
stenosis eventually develop and are associated primarily with pulmonary venous
congestion or low cardiac output, e.g., dyspnea on exertion, orthopnea, or paroxysmal
nocturnal dyspnea and fatigue. Dyspnea is often precipitated by events that elevate left
atrial pressure, such as physical or emotional stress or atrial fibrillation. In patients with
mild mitral stenosis, symptoms usually occur only with extreme exertion. With
progressive stenosis (valve area between 1 and 2 cm 2 ), patients become
symptomatic with less exertion. When mitral valve area decreases to about 1 cm 2 ,
symptoms become more severe. With pulmonary hypertension and right-sided heart
failure, the patient may have signs of tricuspid regurgitation, hepatomegaly, edema, and
ascites.
Although rare, hemoptysis can occur in patients with mitral stenosis. [70 ] , [91 ] As a
result of high left atrial pressure and increased pulmonary blood volume in the earlier
phases of the disease, massive hemoptysis may develop secondary to rupture of
dilated bronchial veins (or submucosal varices). Over time, pulmonary vascular
resistance increases and the likelihood of hemoptysis decreases. Hemoptysis also
may result from pulmonary infarction, which is a late complication of chronic heart
failure. Acute pulmonary edema with pink frothy sputum can occur due to rupture of
alveolar capillaries.
Systemic thromboembolism, occurring in approximately 20 percent of cases, may be

the first symptom of mitral stenosis; recurrent embolization occurs in 25 percent of
patients. [70 ] , [72 ] , [94 ] , [95 ] The incidence of thromboembolic events is higher in
patients with mitral stenosis or mixed mitral stenosisregurgitation than in those with pure
mitral regurgitation. At least 40 percent of all clinically important embolic events involve
the cerebral circulation, approximately 15 percent involve the visceral vessels, and 15
percent affect the lower extremities. [70 ] , [72 ] , [96 ] Embolization to coronary arteries
may lead to angina, arrhythmias, or myocardial infarction; renal embolization can result
in hypertension. [70 ] , [72 ] Risk factors for thromboembolic events include low cardiac
output, left atrial dilatation, atrial fibrillation, the absence of tricuspid or aortic
regurgitation, and the presence of left atrial echocardiographic smoke, an indicator of
stagnant flow. Patients with these risk factors should be considered for prophylactic
anticoagulation. [70 ] , [72 ] , [94 ] [96 ] If an episode of systemic embolization occurs in
patients in sinus rhythm, infective endocarditis, which is more common in mild than in
severe mitral stenosis, should be considered.
Patients with chronic mitral stenosis are often thin and frail (cardiac cachexia),
indicative of long-standing low cardiac output, congestive heart failure, and inanition. [70
] The peripheral arterial pulse is generally normal, except in patients with a decreased
LV stroke volume, in which case the pulse amplitude is diminished. Heart size is usually
normal, with a normal apical impulse on palpation; a forceful apical impulse suggests
LV hypertrophy secondary to associated mitral insufficiency, aortic valvular disease, or
hypertension. An apical diastolic thrill may be present. In patients with pulmonary
hypertension, a right ventricular lift can be palpable in the left parasternal region.
Characteristic auscultatory findings include a presystolic murmur, an increased first

sound, an opening snap, and an apical diastolic rumble. [70 ] , [97 ] [99 ] The presystolic
murmur, which occurs due to closing motion of the anterior mitral leaflet, is a consistent
finding and begins earlier in those in sinus rhythm compared with patients in atrial
fibrillation. [99 ] The first heart sound (S1) is accentuated in mitral stenosis when the
leaflets are pliable but diminished in later phases of the disease when the leaflets are
thickened or calcified. As pulmonary artery pressure becomes elevated, S 2 becomes
prominent. [100 ] With progressive pulmonary hypertension, the normal splitting of S 2
narrows because of reduced pulmonary vascular compliance. Other signs of pulmonary
hypertension include a murmur of tricuspid and/or pulmonic regurgitation and an S 4
originating from the right ventricle. Best heard at the apex, the early diastolic mitral
opening snap is due to sudden tensing of the pliable leaflets during valve opening and
is absent when the leaflets are rigid or immobile. [70 ] , [97 ] , [98 ] In mild mitral
stenosis, the diastolic murmur is soft and of short duration; a long diastolic murmur
indicates severe mitral stenosis. The intensity of the murmur does not necessarily
correlate with the severity of the stenosis; indeed, no murmur may be detectable in
patients with severe stenosis and calcified leaflets. [99 ]
CHEST RADIOGRAPHY
In patients with mitral stenosis, left atrial enlargement is the earliest change found on
chest radiography; it is suggested by posterior bulging of the left atrium, a double
contour of the right heart border, and elevation of the left mainstem bronchus. [71 ] , [81 ]
, [101 ] Overall cardiac size is often normal; prominence of the pulmonary arteries
coupled with left atrial enlargement obliterates the normal concavity between the aorta
and left ventricle to produce a straight left heart border. In the lung fields, pulmonary
congestion may be recognized as distension of the pulmonary arteries and veins and
pleural effusions. If mitral stenosis is severe, engorged pulmonary lymphatics are seen
as distinct horizontal linear opacities in the lower lung fields (Kerley B lines).
ELECTROCARDIOGRAPHY
The electrocardiogram (ECG) is not accurate in assessing the severity of the mitral
stenosis and in many cases may be completely normal. In patients with severe mitral
stenosis and in normal sinus rhythm, left atrial enlargement is the earliest change (a
wide notched P wave in lead II and a biphasic P wave in lead V 1). [81 ] , [102 ] Atrial
arrhythmias are more common in patients with advanced degrees of mitral stenosis. [81 ] In those with
pulmonary hypertension, right ventricular hypertrophy (RVH) may develop and is associated with
right-axis deviation, a tall R wave in V 1 , and secondary ST-T wave changes; however, the ECG is not a
sensitive indicator of RVH or the degree of pulmonary hypertension. [102 ] Because multivalvular disease
may be present in patients with rheumatic heart disease, signs of left and right ventricular hypertrophy
can be identified on the ECG in cases of combined mitral and aortic stenosis. However, right atrial
enlargement and right ventricular dilatation and hypertrophy also can mask the changes indicative of LV
hypertrophy in patients with multivalvular disease. [102 ]
ECHOCARDIOGRAPHY
Echocardiography has emerged as an invaluable noninvasive technique for assessing mitral valve pathology and pathophysiology. [71 ] , [103
] [106 ] Cross-sectional valve area and left atrial and LV dimensions can be quantified using two-dimensional
echocardiography. Best appreciated in the parasternal long-axis view, features of rheumatic mitral stenosis include reduced
excursion of the leaflets and thickening or calcification of the valvular and subvalvular apparatus ( Figs. 32-8 and 32-9 ).
M-mode findings include thickening, reduced motion, and parallel movement of the anterior and posterior leaflets during
diastole. The mitral valve area can be planimetered directly in the short-axis view, but this measurement does not have much
clinical importance, particularly in patients with heavily calcified valves and fibrotic commissures, in whom planimetered valve
areas are inaccurate.
Doppler echocardiography accurately determines maximal and mean transvalvular mitral pressure gradients that correlate
closely with cardiac catheterization measurements [71 ] , [104 ] (Fig. 32-10) . To obtain mitral valve area, the pressure half-time
(time required for the initial diastolic gradient to decline by 50 percent) is employed [104 ] ; the more prolonged the half-time,
the more severe is the reduction in orifice area. Using the pressure half-time determination, mitral valve area is equal to 220
(an empirical value) divided by the pressure half-time. In patients with combined aortic regurgitation and mitral stenosis, the
pressure half-time method may be unreliable because the regurgitant jet may interfere with the valve area calculation. [104 ]
Transesophageal echocardiography can provide even more information in the evaluation of mitral stenosis; it is better than
the transthoracic approach for visualizing details of valvular pathology, such as valve mobility and thickness, subvalvular
apparatus involvement, and extent of leaflet or commissural calcification. [104 ] [106 ] In addition, transesophageal
echocardiography is more reliable in detecting left atrial thrombi.
CARDIAC CATHETERIZATION
Cardiac catheterization is not necessary to establish the diagnosis of mitral stenosis nor essential prior to surgical intervention; however, it can
provide valuable data regarding secondary processes or associated cardiac diseases such as pulmonary hypertension or coronary artery
disease. [71 ] , [101 ] Left ventriculography permits assessment of the mitral valve, LV contractility, and the subvalvular
apparatus and calculation of ejection fraction but generally is unnecessary. Left-sided heart catheterization allows
determination of LV end-diastolic pressure; right-sided heart catheterization is performed to measure cardiac index and the
degree of pulmonary hypertension. In the past, fluoroscopy detected calcification of the mitral valve leaflets and annulus.
Today, the only real need for cardiac catheterization in patients with mitral stenosis is to study coronary arteries or, rarely, to
evaluate the reversibility of severe pulmonary hypertension.
Medical Therapy
Therapeutic options include medical therapy, commissurotomy (percutaneous balloon valvuloplasty or surgical), and mitral valve replacement
(MVR). [73 ] , [75 ] , [107 ] [111 ] Mild heart failure symptoms are managed with diuretics and salt restriction. If atrial fibrillation
develops, attempts should be made to reestablish normal sinus rhythm by pharmacologic means or cardioversion. Digoxin
remains the drug of choice for control of ventricular rate in patients with atrial fibrillation, although beta blockers and
calcium-channel blockers may be more effective during exercise or stress. Digoxin does not significantly alter the adverse
hemodynamics and usually is of no benefit to patients with mitral stenosis in sinus rhythm; however, it may be useful in
treating symptoms of right-sided heart failure. Measures that reduce pulmonary venous pressure, including sedation, an
upright posture, and aggressive diuresis, are used if the patient has hemoptysis. Endocarditis prophylaxis is mandated in all
patients with valvular disease and a murmur. Unless contraindicated, anticoagulation should be considered in patients with
atrial fibrillation and those with a history of embolism; however, anticoagulation-related mortality and morbidity increase with
age, and the relative risks versus benefits should be weighed on an individual basis. [71 ] , [75 ]
Indications for Surgery and Postoperative Outcome
Whereas indexes of LV function are used to determine the natural history and surgical outcome of patients with other valvular lesions, there
are few data linking LV function to outcome in those with mitral stenosis. The best indicator is likely related to the amount of clinical
impairment. From the time of diagnosis, the natural history of medical management of patients with mitral stenosis includes a survival
estimate of roughly 45 to 50 percent at 5 years, 34 percent at 10 years, and 14 percent after 20 years. [ 107 ] , [108 ] In patients without
symptoms (New York Heart Association class I), the expected 10-year survival rate is 85 percent. [ 75 ] For patients in
functional class II, the 10-year survival estimate is 50 percent; however, for individuals in class III, only 20 percent are alive
after 10 years. For patients who have deteriorated markedly (NYHA class IV), none can be expected to be alive at 5 years.
[75 ] Survival is lower in older patients, since increasing age generally implies more advanced disease. Surgical intervention
(mitral valvotomy or MVR) substantially improves the functional capacity and long-term survival of patients with mitral
stenosis; over 90 percent of patients (functional class III and IV preoperatively) are alive at 10 years and 89 percent at 15
years. [112 ] , [113 ]
Although the mildly symptomatic patient may be managed medically for years, this valvular disease is relentlessly
progressive, and there is a constant risk of systemic embolization. Prophylactic operation should be considered in an
asymptomatic female patient who wishes to become pregnant. In those who have sustained systemic emboli, operation
should be performed because of the high risk of recurrent thromboemboli with potentially catastrophic complications. [75 ] ,
[94 ] With current diagnostic and surveillance modalities, e.g., transesophageal echocardiography, however, a suggested
alternative is to detect left atrial thrombi, institute anticoagulation, and defer operation if resolution of the thrombus is
documented. [75 ]
Once patients with mitral stenosis become symptomatic, they become candidates for operation. In general, a valve area of 1
cm 2 is considered critical and is associated with significant symptoms and morbidity. In physically active or larger patients,
somewhat larger valve areas (>11.2 cm 2 ) may produce symptoms. [75 ] Intervention in elderly patients is individualized;
although a small minority in this age group may benefit from percutaneous mitral balloon valvuloplasty, most are better served
by MVR. [109 ] [111 ] In mitral stenosis, the LV may become foreshortened and more globular; these morphologic changes,
however, rarely dictate operative timing and do not influence surgical outcome. Despite a higher operative risk in those with
pulmonary hypertension and right-sided heart failure, these patients usually improve postoperatively with a reduction in
pulmonary vascular pressures. [ 75 ] , [114 ]
Summary
Mitral stenosis is generally due to rheumatic heart disease. Rheumatic heart disease is a pancarditis affecting the endocardium, myocardium,
and pericardium; the mitral valve is most commonly involved in rheumatic valvulitis, followed by combined aortic and mitral valve disease.
Rheumatic myocarditis can lead to cardiac dilatation and progressive heart failure. In mitral stenosis, a diastolic gradient develops between the
left atrium and the left ventricle. With worsening mitral stenosis, a progressively higher transvalvular pressure gradient becomes necessary to
maintain adequate cardiac output. Mitral transvalvular flow depends on cardiac output and heart rate; an increase in heart rate decreases the
duration of transvalvular LV filling during diastole and reduces forward cardiac output. Decreased cardiac output due to mitral stenosis is
usually the result of inflow obstruction rather than LV pump failure. In mild to moderate mitral stenosis, pulmonary vascular resistance may not
be increased, and pulmonary arterial pressure may be normal at rest and rise only with exertion or increased heart rate. In severe mitral
stenosis with elevated pulmonary vascular resistance, pulmonary arterial pressure is usually elevated at rest and may exceed systemic
pressure. Characteristic symptoms of mitral stenosis are primarily associated with pulmonary venous congestion or low cardiac output.
Dyspnea is often precipitated by events that elevate left atrial pressure, such as stress or atrial fibrillation. Echocardiography (transthoracic
and transesophageal) has emerged as a valuable noninvasive technique for assessing mitral valve pathology and pathophysiology. The
cross-sectional valve area and transvalvular gradients can be quantified using echocardiography. Therapeutic options include medical therapy,
commissurotomy (percutaneous balloon valvuloplasty or surgical), and mitral valve replacement. Endocarditis prophylaxis is mandated in all
patients with valvular disease. Once patients with mitral stenosis become symptomatic, they become candidates for operation. Surgical
intervention (mitral valvotomy or mitral valve replacement) can substantially improve the functional capacity and long-term survival of
patients with mitral stenosis. Intervention in elderly patients is individualized; although a small minority in this age group may benefit from
percutaneous mitral balloon valvuloplasty, most are better served by valve replacement. Despite a higher operative risk in those with
pulmonary hypertension and right-sided heart failure, these patients usually improve postoperatively, and pulmonary vascular pressures
decrease.
MITRAL REGURGITATION
Etiology
The functional competence of the mitral valve relies on proper, coordinated interaction
of the mitral annulus and leaflets, chordae tendineae, papillary muscles, left atrium, and
left ventricle. [11 ] , [55 ] , [115 ] , [116 ] Normal left ventricle shape and papillary muscle
and chordae tendineae alignment prevent mitral valve leaflet prolapse during ventricular
systole. Dysfunction of any one or more components of this valvular-ventricular complex
can lead to mitral regurgitation. Regurgitation can occur in systole as well as diastole;
diastolic regurgitation results from delayed ventricular contraction, but this phenomenon
appears to have few clinical implications. [117 ]
Systolic mitral regurgitation is important from the hemodynamic and clinical standpoint.
In contrast to mitral stenosis, in which rheumatic heart disease accounts for the vast
majority of cases, the etiology of pure mitral regurgitation is variable, including
myxomatous degeneration or floppy mitral valve (in 29 to 70 percent of cases),
rheumatic valve disease (1 to 31 percent), papillary muscle dysfunction (11 to 27
percent), infective endocarditis (2 to 8 percent), mitral annular calcification, idiopathic
chordal rupture (1 to 14 percent), congenital anomalies (4 percent), dilated or
hypertrophic cardiomyopathies, endocardial fibrosis, and collagen-vascular disorders
[71 ] , [76 ] , [77 ] , [101 ] , [116 ] , [118 ] [122 ] (Fig. 32-11) . In developed countries, the
incidence of rheumatic mitral regurgitation is very small; the leading cause of mitral
regurgitation is degenerative. Four different types of structural changes of the mitral
valve may produce mitral regurgitation: leaflet retraction from fibrosis and calcification,
annular dilatation, chordal abnormalities (including rupture, elongation, or shortening),
and papillary muscle dysfunction. [11 ] , [55 ] , [115 ] , [116 ] Carpentier et al. [123 ] , [124
] classified mitral regurgitation into three pathoanatomic types based on leaflet and
chordal motion: (1) normal leaflet (chordal) motion, (2) leaflet prolapse (excessive
chordal motion), and (3) restricted leaflet or chordal motion (Fig. 32-12) . Mitral
regurgitation with normal leaflet motion is caused by annular dilatation, which is often
secondary to ventricular dilatation; as a rule, insufficient leaflet coaptation is present.
Normal leaflet motion is also associated with leaflet perforation secondary to
endocarditis. Leaflet prolapse typically results from a floppy mitral valve with chordal
elongation and/or rupture but can be seen in patients with coronary artery disease who
have papillary muscle rupture. Mitral regurgitation due to restricted leaflet motion usually
is associated with rheumatic heart disease, [124 ] but interestingly, similar leaflet
morphologic motion patterns also have been described in patients with ischemic mitral
regurgitation. [124 ] , [126 ]
MYXOMATOUS DEGENERATION
Myxomatous or degenerative valve disease (floppy mitral valve or mitral valve prolapse)
has become the leading cause of mitral regurgitation during the past decades in the
United States, primarily as a result of the decline in rheumatic heart disease. [11 ] , [118
] , [119 ] , [127 ] The cause of mitral valve prolapse is likely congenital with defective
fibroelastic connective tissue in the leaflets, chordae, and annulus [74 ] , [128 ] [130 ]
(Fig. 32-13) . Some degree of echocardiographic mitral valve prolapse is seen in 5 to 6
percent of the normal female population [128 ] , [129 ] , [131 ] ; it is most common in
young and middle-aged women, can be familial, and is associated with hypertension.
Although mitral valve prolapse appears to be more widespread in women, severe mitral
regurgitation due to mitral valve prolapse is actually more common in men. The risk of
endocarditis is increased only if valvular regurgitation is substantial and accompanied
by a murmur. This syndrome includes palpitations, chest pain, syncope or dyspnea, and
a nonejection click (with or without a murmur of mitral regurgitation). [128 ] , [129 ]
Auscultation most often reveals the characteristic midsystolic click and middle to late
systolic murmur. Heart failure may be the presenting complaint in 25 to 40 percent of
symptomatic elderly patients with mitral valve prolapse.
Pathologically, the atrial aspect of the prolapsed mitral leaflet is often focally thickened.
[74 ] , [128 ] , [130 ] The changes on the ventricular surface of the leaflet consist of
connective tissue thickening or pads forming primarily on the interchordal segments,
with proliferation of fibrous tissue extending into adjacent chordae and occasionally
onto the ventricular endocardium. [74 ] The myxomatous degeneration may extend into
the annulus. The leaflets become thickened and opaque, occasionally with yellow
plaque formation. Histologically, elastic fiber and collagen fragmentation and
disorganization are present; acid mucopolysaccharide material accumulates in the
leaflets.
Only 5 to 10 percent of patients with mitral valve prolapse develop progression of mitral
regurgitation, and the majority remain asymptomatic. [71 ] , [128 ] , [129 ] Mechanisms
accounting for severe mitral regurgitation in persons with mitral valve prolapse include
annular dilatation and chordal rupture (58 percent), annular dilatation without chordal
rupture (19 percent), and chordal rupture without annular dilatation (19 percent). [130 ]
Chordal rupture is probably related to defective collagen, underlying papillary muscle
fibrosis or dysfunction, or bacterial endocarditis [11 ] , [55 ] , [74 ] , [76 ] , [77 ] , [119 ] ,
[121 ] , [132 ] [134 ] (Fig. 32-14) . It is typically the culprit when mitral insufficiency
develops acutely in patients without any previous symptoms of heart disease and in
those with known mitral valve prolapse in the absence of an acute myocardial infarction.
[71 ] , [76 ] , [77 ] Chordal rupture was evident in 14 to 23 percent of surgically excised
purely regurgitant mitral valve specimens; in 73 to 93 percent of these cases, the
underlying pathology was degenerative or floppy mitral valve syndrome. [76 ] , [77 ] ,
[121 ] Posterior chordal rupture was the most frequent finding, followed by anterior
chordal rupture and then combined anterior and posterior chordal rupture. [76 ] , [77 ] ,
[119 ] , [121 ]
RHEUMATIC DISEASE
Although the incidence is decreasing, rheumatic fever remains a common cause of

mitral regurgitation. [11 ] , [76 ] , [77 ] , [116 ] , [120 ] [122 ] It is unknown why rheumatic
fever leads to valvular stenosis in some instances and pure regurgitation in others. The
pathoanatomic changes of the purely regurgitant rheumatic valve differ from those in a
stenotic valve; regurgitant rheumatic valves have diffuse fibrous thickening of leaflets
with minimal calcific deposits and nonfused commissures; chordae tendineae are
rarely extremely thickened or fused. [76 ] , [77 ] There also may be shortening of the
chordae tendineae, infiltration of the papillary muscle, and asymmetric annular dilatation
that develops primarily in the posteromedial portions.
PAPILLARY MUSCLE DYSFUNCTION
Papillary muscle dysfunction causing mitral regurgitation is the consequence of

coronary artery disease. [11 ] , [55 ] , [56 ] , [76 ] , [77 ] , [135 ] Some degree of mitral
regurgitation resulting from papillary muscle injury and/or annular dilatation is found in
approximately one-third of patients with coronary disease who are being evaluated for
revascularization. The papillary muscles, which are perfused by the terminal branches of
the coronary arteries, are particularly susceptible to ischemia; the posteromedial
papillary muscle (generally supplied by the posterior descending artery) is more
vulnerable to the effects of acute ischemia than is the anterolateral papillary muscle
(which is customarily supplied by branches of the left anterior descending and
circumflex arteries). [11 ] , [55 ] , [56 ] , [136 ] The posteromedial papillary muscle is
perfused by one major coronary artery in 63 percent of cases and by two vessels in the
remainder; on the other hand, the anterior papillary muscle has two-vessel perfusion in
71 percent of normal individuals. [56 ] In patients with a previous inferior wall myocardial
infarction, mitral regurgitation developed only in those with a single papillary muscle
blood supply. Thus myocardial infarction leading to papillary muscle dysfunction occurs
more frequently when the blood supply to the papillary muscle is provided by one vessel,
as is more frequently the case with the posteromedial papillary muscle. [56 ] It also has
been observed that coronary artery disease involving both the right and circumflex
coronary arteries (as opposed to single-vessel disease) can contribute to the
development of posteromedial papillary muscle dysfunction. [136 ]
Mitral regurgitation due to acute myocardial infarction occurs in about 15 percent of

cases of anterior myocardial infarction but up to 40 percent of patients with inferior
infarcts. [76 ] , [77 ] The severity of the mitral regurgitation is generally proportional to the
area of LV akinesia or dyskinesia. LV dilatation and papillary muscle fibrosis resulting
from chronic ischemic heart disease can cause papillary muscle malalignment, leading
to valvular regurgitation. Although papillary muscle necrosis frequently complicates
myocardial infarction, frank rupture of a papillary muscle is very rare. Total papillary
muscle rupture is usually fatal due to the resulting severe mitral regurgitation and LV
pump failure; survival is possible with rupture of one or two of the apical subheads of a
papillary muscle, which is associated with a lesser degree of mitral regurgitation.
Papillary muscle rupture usually occurs 2 to 7 days after myocardial infarction; without
urgent surgery, approximately 50 to 75 percent of such patients may die within 24 hours.
[137 ] [138 ]
MITRAL ANNULAR CALCIFICATION
Mitral annular calcification is a degenerative disease that is essentially limited to the

elderly. [11 ] , [71 ] , [79 ] Most patients are older than 60 years of age, and more women
are affected than men. The pathogenesis of mitral annular calcification is not known, but
it appears to be a stress-induced phenomenon; annular calcification is associated with
systemic hypertension, hypertrophic cardiomyopathy, and aortic stenosis. Other
predisposing conditions include chronic renal failure and diabetes mellitus. Aortic valve
calcification is an associated finding in 50 percent of patients with severe mitral annular
calcification.
The gross appearance of mitral annular calcification may vary from small, localized
calcified spicules to rigid bars up to 2 cm in thickness. [71 ] , [79 ] Initially, calcification
begins at the midportion of the posterior annulus; as the process progresses, the
leaflets become upwardly deformed, stretching the chordae tendineae, and a rigid
curved bar or complete ring of calcium may encircle the mitral orifice. Invasion of the
calcific spurs into the myocardium and impingement on the conduction system can
result in atrioventricular and/or intraventricular conduction defects. Annular calcification
causes mitral regurgitation by displacing the mitral leaflets, immobilizing the peripheral
portion of the mitral leaflets (thereby preventing their normal diastolic excursion and
systolic coaptation), or impairing the systolic sphincteric action of the annulus. [71 ] , [79
] As the degree of mitral regurgitation escalates, LV volume overload can lead to heart
failure. Systemic embolization can occur if annular calcific debris is extensive and
friable.
Hemodynamics
The pathophysiology of acute mitral regurgitation differs markedly from chronic mitral
regurgitation. Acute valvular regurgitation usually results from spontaneous chordal
rupture, infective endocarditis, chest trauma, or myocardial infarction. [11 ] , [55 ] , [133 ]
, [134 ] , [137 ] , [138 ] , The clinical impact of acute mitral regurgitation is modulated by
the compliance of the left atrium. In a normal left atrium with a relatively low compliance,
acute regurgitation results in high left atrial pressure, which can rapidly lead to
pulmonary edema. Such is not the situation in patients with chronic mitral regurgitation,
in whom compensatory changes over time increase left atrial and pulmonary venous
compliance so that the symptoms of pulmonary congestion can be negligible for years.
In the setting of mitral regurgitation, the impedance to LV emptying is decreased

because the mitral orifice is in parallel with the LV outflow tract. [11 ] , [83 ] , [139 ] The
regurgitant volume ejected into the left atrium depends on the mitral orifice size, the
LV-atrial pressure gradient, and the heart rate. Regurgitation into the left atrium
increases left atrial pressure and reduces forward systemic flow. Left atrial pressure
rises significantly during ventricular systole, followed by an abrupt decline in early
diastole (Fig. 32-15) . At end-diastole, left atrial pressure may remain elevated with a
transient 5 to 10 mmHg transvalvular gradient, representing a flow gradient associated
with the increased diastolic flow rate. The volume of mitral regurgitation depends on the
square root of the systolic pressure gradient between the LV and the atrium, the time
duration of regurgitation, and the effective mitral orifice area. [11 ]
If the mitral annulus is not rigid, various diagnostic and therapeutic interventions can
alter the size of the regurgitant orifice. Altered loading conditions (elevated preload and
afterload) and decreased contractility result in progressive LV dilatation and a larger
regurgitant orifice. [140 ] When LV size is reduced by medical management (e.g.,
digoxin, diuretics, and most important, vasodilators), the regurgitant volume is reduced.
[141 ] , [142 ]
In terms of cardiac energetics, reduced LV impedance in patients with mitral

regurgitation allows a greater proportion of contractile energy to be expended in
myocardial fiber shortening than in tension development. [11 ] , [139 ] Because this
increased shortening is less of a determinant of myocardial oxygen consumption than
other components, such as tension development and heart rate, mitral regurgitation
causes only small increases in myocardial oxygen consumption. [139 ] , [143 ]
Simultaneous reductions in developed tension due to lower systolic LV wall stress (or
afterload) associated with mitral regurgitation allow the ventricle to adapt to the
substantial regurgitant volume by increasing total cardiac output to maintain adequate
forward output. Conversely, along with this lower afterload, a substantial increase in
preload (LV end-diastolic volume or, more precisely, end-diastolic LV wall stress)
occurs. [11 ] , [144 ] , [145 ] A fundamental response of the ventricle to augmented
preload is to increase stroke volume and stroke work, although effective forward stroke
volume may be normal or actually subnormal. High LV preload eventually leads to LV
dilatation and shape changes of the ventricle, i.e., more spherical, due to replication of
sarcomeres in series as a consequence of chronic elevation of end-diastolic LV wall
stress. [144 ] , [145 ] This is in contrast to LV hypertrophy secondary to chronic pressure
overload (elevated systolic wall stress), which is due to sarcomere replication in
parallel. [144 ] , [145 ]
In patients with chronic mitral regurgitation, LV mass also increases; however (and
unlike the situation in LV pressure overload), the degree of hypertrophy correlates with
the amount of chamber dilatation so that the ratio of LV mass to end-diastolic volume
remains in the normal range. [145 ] [148 ] Whereas LV dilatation is caused by
sarcomeres being added in series due to the elevated end-diastolic wall stress, [145 ]
the contractile dysfunction that ultimately evolves is accompanied by increased myocyte
length as well as reduced myofibril content. [146 ] The basic changes are a combination
of myofibrillar loss and the absence of compensatory hypertrophy in response to the
progressive decrease in cellular and ventricular pump function; recent experimental
work indicates that the defect is intrinsic to the myocyte per se. [149 ] Conversely, in
acute mitral regurgitation, the ratio of LV mass to end-diastolic volume is reduced
because the chamber dilatation occurs rapidly and the LV wall becomes acutely
thinned; this increase in left ventricular end-di-astolic volume (LVEDV) is associated
with sarcomere lengthening along the length-tension curve. [150 ]
After the initial compensatory phase, LV systolic contractility becomes progressively

more impaired with chronic mitral regurgitation. [147 ] [150 ] Because of the low
impedance during systole, however, clinical indexes of cardiac pump performance,
such as ejection fraction and fractional circumferential fiber shortening (FSc), can still
be normal even with severely depressed LV systolic function. [149 ] , [151 ] , [152 ] An
ejection fraction of less than 40 to 50 percent or %FSc under 28 percent indicates
severe myocardial dysfunction if mitral regurgitation is severe. These commonly used
ejection-phase indexes of LV performance, e.g., ejection fraction, %FSc, cardiac
output, stroke volume, stroke work, etc., are affected by changes in preload and
afterload that accompany all forms of valvular heart disease.
To avoid these pitfalls, load-independent indexes of LV contractility (e.g., end-systolic

elastance derived from the end-systolic pressure-volume relationship) have been used
to measure LV systolic functional mechanics in the face of mitral regurgitation. [147 ] ,
[148 ] , [153 ] , [154 ] In hypertrophied and dilated hearts, as seen in chronic mitral
regurgitation, however, the utility of end-systolic elastance may be limited; using the
end-systolic stress-volume relationship is more precise. One other problem inherent in
the use of end-systolic elastance or stress-volume data is that end-systole and
end-ejection are dissociated in patients with mitral regurgitation; end-ejection is
defined as minimum LV volume and end-systole is defined as the instant when LV
elastance reaches its maximal value. Because of this dissociation of end-systole from
minimal ventricular volume, end-ejection pressure-volume relations do not correlate with
maximal elastance values derived using isochronal methods. [153 ]
LV end-systolic volume (LVESV) (or echocardiographic diameter) is a widely employed

surrogate that reflects changes in LV systolic function; it is independent of preload and
varies directly and linearly with afterload. [155 ] [158 ] The larger the LVESV, the worse
is the systolic contractility. Correcting LVESV for afterload [i.e., mean or peak systolic
wall stress (or aortic dicrotic notch pressure or mean pressure)] and body size [LV
end-systolic volume index (LVESVI)] provides an excellent index of systolic function that
is less influenced by loading conditions and variation in patient size. Preoperative
LVESV or LVESVI is a better predictor of postoperative outcome in terms of LV
performance and cardiac death than is ejection fraction, LV end-diastolic volume
(LVEDV), or LV end-diastolic pressure (LVEDP). [158 ] In patients with mitral
regurgitation, an LVESVI greater than 90 mL/m 2 presaged a higher likelihood of
operative mortality; an LVESVI exceeding 30 mL/m 2 was associated with diminished
postoperative LV function, which was proportional to the degree of elevated
preoperative LVESVI. [158 ] All patients with a normal preoperative LVESVI had
preserved LV function postoperatively. As would be expected, LVESVI corrected for LV
wall stress, a single-point ratio of end-systolic wall stress to end-systolic volume index,
or ESS/LVESVI, was a good predictor of LV systolic function and an accurate predictor
of surgical outcome in patients with mitral regurgitation. [155 ] , [156 ] In patients with
mitral regurgitation undergoing operation, of the many different variables (including
NYHA functional class, age, cardiac index, mean right atrial pressure, mean pulmonary
wedge pressure, LVEDVI, LV stroke volume index, ejection fraction, end-systolic wall
stress, and ESS/LVESVI), LVESVI and the single-point ESS/LVESVI ratio were the
only independent determinants of an untoward outcome. [156 ] An ESS/LVESVI ratio
less than 2.6 portended a poor medium-term prognosis; conversely, a normal or high
ESS/LVESVI ratio was associated with a favorable outcome, suggesting that LV
contractile function had been relatively normal preoperatively. [156 ]
Using precise indexes of LV contractility, Yun et al. [147 ] examined changes in LV

systolic mechanics in an experimental canine model of chronic mitral regurgitation.
Three months after creation of mitral regurgitation, the (normalized for increase in LV
mass) end-systolic pressure-volume relationships decreased by 36 percent, and
normalized end-systolic stress-volume relationships declined by 21 percent [147 ] (Fig.
32-16) . There was a 26 percent reduction in LV preload-recruitable stroke work
(PRSW, the relation of stroke work to LVEDV) and a 14 percent drop in
preload-recruitable pressure-volume area (the relation of stroke work to LV
pressure-volume area) [147 ] (Fig. 32-17) . The efficiency of energy transfer from
pressure-volume area to external pressure-volume work at matched LVEDV decreased
by 25 percent. Furthermore, there was a deterioration in ventriculovascular coupling
over time; i.e., a mismatch developed between the ventricle and the total (forward and
regurgitant) vascular load. Although the overall (systemic plus left atrial) effective arterial
elastance decreased, there was a proportionally greater reduction in LV end-systolic
elastance. Thus LV systolic mechanics were impaired, global LV energetics and
efficiency deteriorated, and a mismatch in coupling between the left ventricle and
arterial bed emerged. [147 ]
LV diastolic function is also affected by chronic mitral regurgitation. [159 ] [163 ]

Diastolic inflow into the ventricle must increase as total stroke volume increases during
the evolution of mitral regurgitation. To compensate, the ventricle dilates (LV preload
increases). Early on, mitral regurgitation enhances LV diastolic function vis-à-vis
increasing the early diastolic filling rate and decreasing stiffness. Flow across the mitral
valve during early diastole is chiefly determined by the left atrial-ventricular pressure
gradient, [159 ] even though other factors, such as diastolic restoring forces and
isovolumic relaxation, also influence early LV filling. In middle and late diastole, the
lower ventricular chamber stiffness found in patients with acute mitral regurgitation
(evidenced by a shift of the LV diastolic pressure-dimension or pressure-volume
relationship to the right) allows LV mean and end-diastolic pressures (and stresses) to
remain in the normal range. On the other hand, in patients with chronic mitral
regurgitation and preserved ejection fraction, a decrease in LV chamber stiffness
(similar to that expected during acute mitral regurgitation) is observed; however, in
those with impaired systolic function, chamber stiffness is normal. [161 ] During the
period of passive filling, maximal rates of circumferential fiber lengthening and strain
are increased only in the group with preserved ejection fraction. [161 ] The absence of
augmented filling rate in patients with depressed LV systolic function probably reflects
underlying myocyte abnormalities. In general, chronic mitral regurgitation causes a
decrease in LV systolic contractile function but an increase in early diastolic function (as
evidenced by an increase in early diastolic filling rate and a decrease in chamber
stiffness). [162 ] , [164 ] The reduced chamber stiffness may be the result of altered
ventricular geometry (the more spherical or less eccentric shape) [161 ] ; however, this
shape change can exacerbate the degree of mitral regurgitation by altering annular
shape and producing papillary muscle malalignment. [115 ] , [165 ] Although the left
ventricle becomes less stiff due to the change in geometry, the myocardium may
actually be stiffer due to myocyte hypertrophy and interstitial fibrosis. [161 ] , [162 ]
Experimentally, the changes in LV diastolic properties (including early diastolic filling

rate, myocardial relaxation, chamber stiffness, myocardial stiffness, and end-diastolic
pressure) are reversible after MVR. [162 ] , [164 ] MVR normalizes LV volume and the
volume-to-mass (or dimension-to-thickness) ratio, but mild LV hypertrophy persists.
[162 ] If surgical correction of mitral regurgitation is carried out before the
volume-overload myopathy reaches an irreversible stage, LV diastolic filling
characteristics and systolic contractile function return toward normal values.
Atrial Adaptation
Regurgitant flow into the left atrium leads to progressive atrial enlargement, the degree
of which does not correspond directly with the severity of mitral regurgitation. [88 ] , [139
] Also, the left atrial v wave in mitral regurgitation does not correlate with left atrial
volume. [88 ] Compared with mitral stenosis, left atrial size can be larger in patients with
long-standing mitral regurgitation; conversely, thrombus formation and systemic
thromboembolization occur less frequently because of the absence of atrial stasis. [88 ]
, [91 ] Also, atrial fibrillation occurs less often in those with mitral regurgitation and does
not affect the clinical course as dramatically as in individuals with mitral stenosis. [91 ]
Left atrial compliance is an important component of the patient's overall hemodynamic

status with mitral regurgitation. [11 ] , [133 ] , [139 ] , [166 ] , [167 ] With sudden
development of mitral regurgitation due to chordal rupture, papillary muscle infarction, or
leaflet perforation, left atrial compliance may be normal or reduced. The left atrium is not
enlarged, but the mean left atrial pressure (and the v wave) is elevated. Gradually, the
left atrial myocardium becomes hypertrophied; proliferative changes develop in the
pulmonary vasculature, and pulmonary vascular resistance rises. As the mitral
regurgitation becomes chronic and more severe, left atrial compliance increases, as
reflected by left atrial enlargement and increased left atrial pressure. In patients with
severe, long-standing mitral regurgitation, the left atrium is markedly enlarged, atrial
compliance is increased, the atrial wall is fibrotic, but left atrial pressure is normal or
slightly above normal. [166 ] In this situation, pulmonary artery pressure and pulmonary
vascular resistance are also usually still in the normal range or only modestly elevated.
Atrial fibrillation and a low cardiac output, however, are often present.
Pulmonary Changes
Because chronic mitral regurgitation is associated with left atrial enlargement and mild
elevation in left atrial pressure, pronounced increases in pulmonary vascular resistance
usually do not develop. In those with acute mitral regurgitation with normal or reduced
left atrial compliance, a sudden increase in left atrial pressure initially may modulate an
elevation in pulmonary vascular resistance and acute right-sided heart failure. [11 ] ,
[133 ] Acute pulmonary edema occurs less frequently in patients with chronic mitral
regurgitation than in those with mitral stenosis because a sudden increase in left atrial
pressure is uncommon. Pulmonary vascular resistance is increased more often in
patients with mitral stenosis than in those with mitral regurgitation due to the chronically
high left atrial pressure.
From the standpoint of pulmonary parenchymal function and mechanics in patients with
chronic mitral regurgitation, there is a decline in vital capacity, total lung capacity, forced
expiratory volume, and maximal expiratory flow at 50 percent vital capacity. [168 ] These
patients also may have a positive response to methacholine challenge; this bronchial
hyperresponsiveness may result from increased vagal tone due to chronic pulmonary
congestion.
Symptoms
Patients with mild to moderate mitral regurgitation may remain asymptomatic for many
years as the left ventricle adapts to the increased workload. During this time,
susceptibility to bacterial endocarditis is the major hazard. Gradually, symptoms
reflective of decreased cardiac output and/or pulmonary congestion develop, such as
weakness, fatigue, palpitations, and dyspnea on exertion. If right-sided heart failure
appears, hepatomegaly, peripheral edema, and ascites occur associated with rapid
clinical deterioration. Hemoptysis and systemic thromboembolization are less frequent
than in cases of mitral stenosis. [93 ] , [95 ]
With acute mitral regurgitation, pulmonary congestion and pulmonary edema are
prominent. Clinically, acute papillary muscle rupture may mimic the presentation of a
patient with a postinfarction ventricular septal defect. [169 ] Transthoracic Doppler
echocardiography is particularly useful to differentiate quickly between these two
emergency conditions. In patients with an acute ventricular septal defect, right-sided
heart catheterization demonstrates an oxygen step-up in the right ventricle and high
thermal dilution blood flows.
On physical examination, the peripheral pulse of patients with mitral regurgitation often
exhibits a brisk upstroke with a normal pulse pressure. The cardiac impulse is
hyperdynamic and displaced to the left; the forcefulness of the apical impulse is
indicative of the degree of LV enlargement. In patients with chronic mitral regurgitation,
S1 is usually diminished. S2 may be single, closely split, normally split, or even widely
split [170 ] ; as a consequence of the reduced resistance to LV ejection, a common
finding is a widely split S2 that results from shortening of LV systole and early closure of
the aortic valve. An S3 may be appreciated due to the increased transmitral diastolic
flow rate during the rapid filling phase. The apical systolic murmur is blowing,
moderately harsh, and radiates to the axilla and the inferior angle of the scapula, left
sternal border, occasionally to the neck, and to the vertebral column. [170 ] With rupture
of a posterior leaflet chordae, the mitral regurgitation jet is directed anteriorly and
impinges on the atrial septum near the base of the aorta to produce a murmur
prominent in the aortic area radiating to the neck. [170 ] , [171 ] With rupture of anterior
leaflet chordae, the leakage is aimed toward the posterior left atrial wall, and the
murmur may be transmitted posteriorly. Although there is little correlation between the
intensity of the systolic murmur and the severity of the mitral regurgitation, a pansystolic
murmur is characteristic of more regurgitant flow. [170 ] , [172 ] An early diastolic
murmur may be present because of the increased volume of blood inflow across the
mitral valve. Because of the relatively noncompliant left atrium in patients with acute
mitral regurgitation, the murmur is often early and midsystolic rather than holosystolic.
[11 ] Mild regurgitation due to mitral valve prolapse or papillary muscle dysfunction is
associated with a late systolic murmur. In patients with the Barlow syndrome (severe
bileaflet mitral prolapse) and mitral regurgitation, a characteristic midsystolic click is
heard followed by a middle to late systolic murmur.
CHEST RADIOGRAPHY
In patients with chronic mitral regurgitation, cardiomegaly indicative of LV and left atrial
enlargement is commonly found on a chest radiograph [170 ] , [173 ] (Fig. 32-18) .
Acute mitral regurgitation often is not associated with an enlarged heart shadow and
may produce only mild left atrial enlargement, despite a markedly elevated left atrial
pressure. Chest x-ray findings of congestive changes in the lung fields are less
prominent in patients with mitral regurgitation compared with those with mitral stenosis,
but interstitial edema is frequently seen in individuals with acute mitral regurgitation or
those with progressive LV failure secondary to chronic mitral regurgitation.
ELECTROCARDIOGRAPHY
ECG changes are generally not reliable and depend on the etiology, severity, and
duration of the mitral regurgitation. [101 ] , [170 ] Atrial fibrillation is a common finding. In
cases of chronic mitral regurgitation, LV volume overload leads to left atrial and LV
dilatation and, eventually, some degree of LV hypertrophy. Evidence of LV enlargement
or hypertrophy occurs in one-half of patients; 15 percent have right ventricular
hypertrophy due to increased pulmonary vascular resistance, and 5 percent have
combined left and right ventricular hypertrophy. [101 ] Complex ventricular arrhythmias
may be noted on ambulatory ECG recordings, especially in patients with LV systolic
dysfunction. In acute mitral regurgitation, left atrial and/or LV dilatation may not be
evident, and the ECG may be normal or show only nonspecific findings, including sinus
tachycardia or ST-T wave alterations. [101 ] Findings of myocardial ischemia or
infarction, more commonly noted in the inferior leads, may be present when acute mitral
regurgitation is related to coronary artery disease; in these cases, first-degree AV block
is a common coexisting finding. [101 ]
In the majority of individuals with mitral valve prolapse, particularly those who are
asymptomatic, the resting ECG is normal. [101 ] , [131 ] , [174 ] In symptomatic patients,
a variety of ST-T wave changes, including T-wave inversion and sometimes
ST-segment depression, particularly in the inferior leads, can be found. [128 ] , [131 ]
QTc prolongation also may be seen. Arrhythmias may be observed on ambulatory ECG
recordings, including premature atrial contractions, supraventricular tachycardia, AV
block, bradyarrhythmias, and premature ventricular contractions. [131 ] Complex atrial
arrhythmias may be present in upwards of 14 percent of patients, and complex
ventricular arrhythmias are present in 30 percent of patients. [174 ] Age correlates with
the incidence of complex atrial arrhythmias; female gender and anterior mitral valve
thickening are predictors of complex ventricular arrhythmias. [174 ] Rarely, ventricular
arrhythmias may be potentially life-threatening, and aggressive management may be
warranted. [101 ]
ECHOCARDIOGRAPHY
In patients with chronic mitral regurgitation, progression of left atrial and LV dilatation
can be followed accurately by transthoracic echocardiography; LV systolic function
deterioration is inferred indirectly. [11 ] , [103 ] [105 ] , [175 ] , [176 ] Two-dimensional
echocardiography identifies abnormalities of leaflet morphology and function, including
myxomatous degeneration with or without leaflet prolapse, restricted leaflet motion and
lack of adequate coaptation from rheumatic valvulitis (fused leaflets), ischemic heart
disease, and leaflet destruction by endocarditis [11 ] , [104 ] , [126 ] , [177 ] (Figs. 32-19
and 32-20) . Chordal rupture causing a flail leaflet is characterized by excessive motion
of the leaflet tip beyond the normal coaptation point and mitral annular plane. Papillary
muscle rupture following myocardial infarction and annular dilatation also can be
visualized by echocardiography [104 ] (Fig. 32-21) . Pulsed-wave or continuous-wave
Doppler echocardiography tends to overestimate the severity of mitral regurgitation in
patients with depressed LV ejection fraction and low cardiac output [11 ] ; it is extremely
sensitive and specific in diagnosing mild or severe mitral regurgitation but not as
accurate in assessing moderate degrees of regurgitation. The most commonly used
method to assess the degree of regurgitation is Doppler color-flow mapping, which
permits visualization of the origin, extent, direction, duration, and velocity of disturbed
flow (regurgitant jet) within the left atrium. [104 ] , [175 ] , [176 ] Color-flow representation
of the regurgitant flow is only qualitative; however, transthoracic echocardiography with
Doppler color mapping provides reliable information that allows the cardiologist to
follow patients safely and gives the surgeon a reasonably good idea concerning the
likelihood of a successful valve repair.
Transesophageal echocardiography is superior to transthoracic echocardiography in

defining the details of the valvular pathoanatomy and the severity of acute or chronic
mitral regurgitation. [11 ] , [105 ] , [175 ] , [177 ] , [178 ] It can detect mitral vegetations, a
flail leaflet segment, ruptured chordae, leaflet perforations, calcification, and other
inflammatory changes. This modality is particularly useful in patients with annular or
leaflet calcification and those with a previously implanted aortic valve prosthesis that
can interfere with assessment of mitral regurgitation due to acoustic shadowing. This
additional morphologic information is useful in surgical decision making, i.e., whether a
valve can be repaired or is more likely to require replacement. In addition,
intraoperative transesophageal echocardiography is an excellent tool to determine the
adequacy of mitral valve reconstruction.
Cardiac catheterization and left ventriculography have been important in the

assessment of mitral regurgitation in the past, [11 ] , [100 ] , [144 ] , [173 ] , [179 ] but
today echocardiography has substantially eroded the role of catheterization. The
objectives of cardiac catheterization are to confirm the presence and estimate the
severity of the mitral regurgitation, determine LV size and systolic regional wall motion,
confirm left atrial size, assess the severity of associated valve lesions, and detect
important coronary artery stenoses. The severity of mitral regurgitation is estimated by
the degree of opacification of the left atrium and pulmonary veins following left
ventriculography [179 ] (Table 32-1) . A limitation of this semiquantitative grading
system is that left atrial size and compliance as well as LV size and contractility are not
considered. Other methods, such as calculating mitral regurgitant fraction, are similarly
limited (the regurgitant volume is determined as the difference between total LV
angiographic stroke volume and the effective forward stroke volume measured by the
Fick principle). In the past, the etiology of the mitral regurgitation was estimated by LV
angiography, [100 ] , [173 ] but echocardiography is much more precise. Currently,
left-sided heart catheterization and left ventriculography are rarely necessary, but in
older patients, coronary angiography is indicated to assess the status of the coronary
arteries. By measuring rest and (supine bicycle) exercise pulmonary artery pressures
and cardiac outputs, left- and right-sided heart catheterization can be useful in
identifying patients with primary myocardial disease who present with LV dilatation and
relatively mild degrees of mitral regurgitation (who therefore do not have a high chance
of benefiting from mitral surgery) and those with only mild mitral regurgitation under
baseline conditions.
MAGNETIC RESONANCE IMAGING
Magnetic resonance imaging (MRI) is a noninvasive modality that can be employed to

assess the cardiovascular system, including cardiac structure and function. [180 ] MRI
has been used to evaluate mitral regurgitation. The presence of valvular regurgitation
can be determined, LV volumes and mitral regurgitant fraction can be estimated, and
some information can be obtained concerning mitral anatomy. MRI findings, such as LV
end-diastolic and end-systolic volumes and regurgitant fraction, correlate well with those
determined at cardiac catheterization; however, further clinical experience with this
diagnostic modality is necessary.
Medical Therapy
The mainstay of medical management of patients with acute or chronic mitral

regurgitation historically included digoxin and diuretics, but the mainstay of therapy
today is afterload reduction. [167 ] , [181 ] [183 ] By reducing aortic ejection impedance,
the regurgitant volume into the left atrium is decreased, and thus pulmonary congestion
is ameliorated. The salutary effects of this strategy that reduces LV volume and
increases forward stroke volume result in a smaller mitral annular circumference and,
pari passu , regurgitant orifice. [141 ] , [142 ] Medical management may improve the
patient's clinical status for months or years in those with chronic mitral regurgitation. The
therapeutic goal is to decrease pulmonary capillary wedge pressure, LV end-systolic
and end-diastolic volume indexes, and mitral regurgitant fraction. While these tactics
are usually quite successful clinically, theoretical concern persists regarding whether
afterload reduction therapy may mask progressive development of irreversible degrees
of myocardial injury due to ongoing LV volume overload.
In patients with isolated mitral regurgitation (average functional class II or III) who were
treated medically, the survival estimate was 50 percent at 6 years and 27 percent at 10
years. [184 ] In a group of patients with isolated mitral regurgitation or combined mitral
regurgitation and stenosis (due to rheumatic heart disease) in a more compromised
state (more than one-third of patients were in functional class III and IV), the 5-year
survival estimate with medical management was only 46 percent. [107 ] Hickey et al.
[135 ] demonstrated similar findings in medically treated patients with moderate to
severe ischemic mitral regurgitation with an estimated 5-year survival ranging from 30
to 55 percent; the survival estimates were comparatively better for each subgroup of
surgically treated patients (Fig. 32-22) .
In asymptomatic or minimally symptomatic patients with normal LV systolic performance

and severe nonischemic mitral regurgitation due to mitral valve prolapse, each year
approximately 10 percent can be expected to progress to where surgical intervention is
clearly indicated (NYHA class III or IV). [185 ] The change in right ventricular ejection
fraction during exercise is useful in predicting the likelihood of such progression. In
patients whose right ventricular ejection fraction increased with exercise, there was a 5
percent annual risk of progressing to operation; in those without an increase in right
ventricular ejection fraction with exercise, the risk was 15 percent per year. [185 ]
The current treatment of choice in patients with acute mitral regurgitation due to
posterior papillary muscle dysfunction in the setting of an acute inferior myocardial
infarction is reperfusion therapy using thrombolysis and/or percutaneous coronary
angioplasty. [135 ] , [186 ] Successful reperfusion using these techniques usually
reestablishes valve competence. The subsequent surgical approach is based on the
extent of residual coronary artery disease, symptoms, and degree of functional
limitation. Approximately 60 percent of patients with moderate to severe ischemic mitral
regurgitation can be managed medically; however, long-term survival in these patients
is lower with medical management compared with surgical mitral repair or replacement.
[186 ]
Patients with acute mitral regurgitation resulting from papillary muscle rupture or chordal
rupture frequently present in cardiogenic shock. These patients should undergo
operation (MVR preferably or papillary muscle reimplantation coupled with mitral valve
repair) immediately. [135 ] , [186 ] , [187 ] Although surgical treatment of these high-risk
patients with acute LV failure secondary to acute myocardial infarction is associated
with high operative mortality risk (upwards of 50 percent), there really is no hope for
survival with medical therapy alone. [135 ] , [137 ] , [186 ] [188 ] Echocardiography and
coronary angiography should be performed emergently to determine the etiology of
mitral regurgitation, discern the coronary anatomy, and exclude concomitant
interventricular septal rupture.
The initial evaluation in asymptomatic patients with chronic mitral regurgitation should
include a transthoracic echocardiogram to define LV end-systolic dimension (a
surrogate for LVESVI) along with simultaneous measurement of systolic blood
pressure. [11 ] , [189 ] Stable end-systolic LV dimensions at a relatively constant
afterload in asymptomatic patients argue for continuation of medical therapy and
expectant observation with serial echocardiograms every 6 to 12 months. If signs of LV
systolic dysfunction are present or a progressive increase in LV end-systolic dimension
(at a constant afterload) is observed, further evaluation with transesophageal
echocardiography and coronary angiography in preparation for mitral valve surgery
should be carried out. [11 ] , [116 ] , [189 ]
Operation for symptomatic patients with chronic mitral regurgitation (NYHA class II or
greater) should be considered before severe irreversible LV systolic dysfunction
develops. [116 ] , [189 ] [192 ] The degree of deterioration in LV contractility
determines, for the most part, the patient's prognosis and the optimal time for operation,
but clinically, loss of contractile force is extremely difficult to measure with any precision.
Patients with severe mitral regurgitation should undergo operation if cardiac
enlargement or an elevated LVESVI is present, even in the absence of limiting
symptoms and even earlier if the valve appears to have a high chance for successful
repair.
Surgical correction of chronic mitral regurgitation can preserve LV contractility,

particularly in patients with a normal preoperative ejection fraction with minimal
ventricular dilatation; on the other hand, in patients with impaired LV contractile function
preoperatively, the expected improvement in LV function may not occur after operation.
[192 ] One predictor of persistent postoperative LV dilatation and systolic dysfunction is
a preoperative LVESVI above 89 ± 28 mL/m 2 , whereas a LVESVI of 44 ± 12 mL/m 2
correlated with a favorable clinical response. [192 ] Patients with chronic mitral
regurgitation should be referred for mitral valve surgery when the LVESVI is in the range
of 40 to 50 mL/m 2 ; when LVESVI exceeds 60 mL/m 2 , a poor outcome is likely. [158 ]
Surgical options include conventional MVR with complete excision of the subvalvular
apparatus, MVR with preservation of the chordae tendineae, or mitral valve repair. The
operative mortality rate associated with mitral valve repair is lower than that with MVR;
early mortality rate ranges from 1 to 4 percent for patients undergoing mitral valve repair
versus 4 to 12 percent for MVR. [118 ] , [124 ] , [193 ] [200 ] This apparent benefit may
result from enhanced LV systolic function due to preservation of the mitral subvalvular
apparatus. Comparing the outcome after mitral valve repair or MVR in one series
indicated that predictors of hospital death were older age, MVR (instead of repair),
higher NYHA functional class, congestive heart failure, no posterior chordal rupture, and
nonelective operation. [195 ]
Mitral valve repair for patients with myxomatous mitral regurgitation is feasible in the
large majority of patients (especially if only the posterior leaflet is involved) and offers
excellent early and late results. [119 ] , [197 ] , [201 ] , [202 ] Actuarial survival estimates
are in the range of 70 to 90 percent at 8 to 10 years and 71 percent at 15 years after
mitral valve repair. [119 ] , [193 ] , [201 ] [203 ] These survival figures are lower than
those in patients with rheumatic valve disease because of the relatively older age in the
degenerative valve disease group. The estimate of freedom from reoperation ranges
from 93 to 95 percent at 8 to 15 years. [201 ] , [202 ] Advanced myxomatous changes
with prolapse of both mitral leaflets (and particularly the anterior leaflet) are a significant
factor associated with reoperation in another large series of patients with mitral
regurgitation. [202 ] Because fewer complications and a lower operative mortality rate
are associated with mitral reconstruction compared with MVR, operation should be
considered earlier in the natural history of the disease if the pathoanatomy is judged
favorable for valve repair. [116 ] , [195 ] Unstable clinical conditions, advanced
congestive heart failure, and associated diseases are not contraindications to surgical
intervention. [116 ] When the preoperative LVESVI indicates the presence of advanced
LV systolic dysfunction, every effort should be made to perform mitral valve repair or
MVR with chordal preservation instead of conventional MVR. [116 ] , [189 ]
Mitral valve repair in younger patients with rheumatic valvulitis is followed by an

acceptable survival estimate of 70 to 95 percent at 5 years and 81 percent at 15 years.
[190 ] , [194 ] , [196 ] , [201 ] The overall rate of valve complications is higher than that
for patients with myxomatous mitral valve disease, however, and the rate of reoperation
is higher. In the rheumatic population undergoing mitral valve repair, the estimate of
freedom from valve failure at 6 years is 66 percent, and only 75 percent of patients are
free of reoperation at 5 years. [194 ] , [198 ] Alternatively, Deloche et al. [201 ] report a
reoperation-free estimate of 76 percent after 15 years in a selected cohort. In a
comparative analysis, the reoperation-free estimate at 5 years was 94 percent for
nonrheumatic patients who underwent valve repair, 77 percent for rheumatic patients
with valve repair, and 96 percent for patients who underwent MVR. [199 ] Improved
preoperative selection of patients by exclusion of those with active rheumatic carditis,
atrial fibrillation, or mixed mitral stenosis/MR may improve long-term results of mitral
valve repair in this particular patient population. [194 ] In patients with rheumatic mitral
regurgitation who have a preoperative LV end-systolic diameter greater than 50 mm, a
poor postoperative outcome is seen after MVR despite chordal preservation in
relatively young patients, and alternative strategies (such as transplantation) should be
considered. When the preoperative LV end-systolic diameter is 40 mm or less, a good
outcome is observed. [204 ]
Ischemic mitral regurgitation is associated with higher operative risk (9 to 30 percent)

than is nonischemic forms of chronic mitral regurgitation. [135 ] , [186 ] , [187 ] , [205 ] ,
[206 ] This higher mortality rate probably reflects more severe regurgitation than
suspected by routine preoperative clinical evaluation and concomitant adverse
consequences of previous myocardial infarction and ischemia. Valve repair should be
considered in these patients when feasible because it can potentially reduce early
complications and improve long-term survival. [135 ] , [186 ] , [205 ] Cohn et al., [206 ]
however, recently demonstrated that this worse postoperative outlook was no better
after mitral repair compared with after MVR. Multivariate analysis demonstrated mitral
repair to be a risk factor for decreased long-term survival; patients with ischemic mitral
regurgitation with annular dilatation or restricted leaflet motion (not chordal or papillary
muscle rupture) who underwent mitral repair had a markedly worse long-term outcome
than those who underwent MVR. [206 ] Thus the pathophysiology of the ischemic mitral
regurgitation, which is a reflection of LV function, is a major determinant (more so than
the type of valve procedure) in long-term survival. Identified incremental risk factors for a
poor outcome include emergency operation, acute myocardial infarction, congestive
heart failure, hemodynamic instability, poor LV function, pulmonary hypertension,
advanced age, and renal failure. [135 ] , [186 ] , [187 ] The long-term results appear to
be related chiefly to the severity of the preoperative LV systolic dysfunction. [187 ]
It is probably best to attempt to avoid operation in most patients with pronounced LV

dilatation and severe global systolic dysfunction who also have mitral regurgitation. [186
] , [189 ] In this patient subset, long-term survival is historically very poor after either
MVR or repair. The primary problem is LV myocardial failure, with the mitral
regurgitation being only a late manifestation of the advanced LV dysfunction. On the
other hand, Bolling et al. [207 ] have reported surprisingly favorable short-term results in
this challenging patient population (many of whom were on the cardiac transplantation
waiting list) after mitral valve reparative procedures. Unless they can be stabilized and
the secondary end-organ problems resolved, another very high risk group may be
elderly patients with advanced congestive heart failure complicated by multiorgan
failure. [186 ]
Predictors of Postoperative Outcome
Reported predictors of increased operative risk include older age, higher NHYA
functional class, associated coronary artery disease, increased LV end-diastolic
pressure, high LVESVI, low ESS/LVESVI ratio, elevated LVEDVI, elevated LV
end-systolic dimension, reduced LV ESS index, depressed resting ejection fraction,
decreased fractional shortening, reduced cardiac index, elevated capillary wedge or
right ventricular end-diastolic pressure, concomitant operative procedures, and
previous cardiac surgery. [135 ] , [158 ] , [190 ] , [192 ] , [199 ] , [204 ] , [208 ] [217 ]
Among elderly patients, these risk factors included very advanced age, MVR (versus
repair), higher NYHA functional class, ischemic etiology, and elevated pulmonary
capillary wedge pressure. [217 ]
Regarding long-term outcome, identified risk factors of cardiac deterioration include

larger LV end-diastolic dimension, increased LV end-systolic dimension, increased
LVESV, diminished fractional shortening, reduced LV ESS index, large left atrial size,
decreased LV wall thickness/cavity dimension at end-systole, and associated coronary
artery disease. [158 ] , [190 ] , [196 ] , [214 ] [216 ] , [218 ] , [219 ] Although associated
coronary artery disease portends a higher incidence of late death, simultaneous
coronary revascularization improves this prognosis. [190 ]
Successful mitral valve repair or MVR is generally associated with clinical improvement,
augmented forward stroke volume with lower total stroke volume, decreased LVEDV,
and regression of LV hypertrophy. [211 ] , [220 ] In an experimental model,
normalization of LV contractile function is associated with increased myocyte length,
augmented myocyte cross-sectional area, and significantly increased contractile protein
content. [146 ] In a fraction of patients, LV volume does not diminish, LV hypertrophy
does not regress, and the ejection fraction remains reduced. The highest-risk patients
are those with coronary artery disease complicated by ischemic mitral regurgitation;
these patients have a high early mortality and a poor long-term prognosis. [211 ] , [220 ]
Indeed, a recent investigation revealed that medium-term survival for these patients was
worse after mitral repair than following MVR, again presumably reflecting the severity of
the preoperative LV dysfunction. [206 ] This is related to the fact that LV dysfunction
may have reached an irreversible stage when these patients finally become
symptomatic.
Even after a technically satisfactory mitral valve repair or MVR, some of these patients
continue to be limited by congestive heart failure and have a suboptimal postoperative
prognosis. [191 ] In a study from the Mayo Clinic, however, the combined endpoint of
death and/or heart failure was favorably influenced by mitral repair (versus MVR), even
though repair was not an independent determinant of late death alone or postoperative
congestive heart failure. [191 ] Earlier surgical correction of the chronic mitral
regurgitation before advanced LV systolic dysfunction occurs was recommended.
Postoperative Changes in Left Ventricular Function
Since the concept was originally proposed by Lillehei et al. [221 ] in 1964, the mitral
subvalvular apparatus is recognized as an important component of LV systolic and
diastolic performance. [147 ] , [148 ] , [200 ] , [222 ] [238 ] The subvalvular apparatus,
including normal chordal and papillary muscle function, is necessary to maintain optimal
postoperative LV geometry and optimize systolic pump function. After conventional
MVR with total chordal excision, a significant decline in LV performance occurs with
depression of regional and global elastance, dysynergy of contraction, and dyskinesia
at the papillary muscle insertion sites; conversely, after MVR with chordal preservation,
LV contractile function is preserved. [164 ] , [226 ] [230 ] , [232 ] , [238 ] Differences in
LV function between mitral valve repair and MVR without chordal preservation are
attributed to disruption of the subvalvular apparatus. Severing either the anterior or the
posterior papillary muscle chordae is detrimental to global LV systolic function (reduced
maximal elastance), but function returns to normal after chordal reattachment. [229 ] The
contributions of the chordae subtending the anterior mitral leaflet are slightly greater
than (but additive to) the contributions of the posterior leaflet chordae. [228 ]
MVR with chordal division results in a decline in segmental LV systolic function not only
in the areas subtending papillary muscle insertion but also in remote LV regions. [223 ]
Clinically, Tischler et al. [237 ] showed that MVR with chordal transection produced
significant reductions in rest and exercise ejection fraction due in part to an increase in
ESS. Mitral valve repair improved rest and exercise ejection indexes, primarily due to
marked reduction in ESS and maintenance of a more ellipsoidal chamber geometry.
[237 ] Rozich et al. [236 ] found that MVR with chordal transection caused no
postoperative change in LVEDV, an increase in LVESV, an increase in ESS (89 to
111 g/m 2 ), and a decrease in ejection fraction (from 60 to 36 percent). Conversely,
patients who underwent MVR with chordal preservation had a decrease in LVEDV and
LVESV, ESS fell from 95 to 66 g/m 2 , and ejection fraction remained unchanged (63
and 61 percent). [236 ] These findings suggest that reduced chamber size, reduced
systolic load, and preservation of ventricular contractile function act in concert to
maintain ejection performance after chordal-sparing procedures. On the other hand, an
increased chamber size, increased systolic load, and probable reduction in chamber
contractile function combine to reduce ejection performance after MVR and chordal
transection. [236 ] Horskotte et al. [200 ] also showed that patients who underwent MVR
with chordal preservation were significantly better postoperatively than patients who
underwent valve replacement without chordal preservation. Parameters that improved
included pulmonary artery pressure with exercise, LVEDV index, and maximum
exercise tolerance. [200 ]
In an experimental model of chronic mitral regurgitation, Yun et al. [224 ] demonstrated

that MVR with chordal preservation optimizes postoperative LV energetics and
ventriculovascular coupling in addition to enhancing systolic performance. With chordal
interruption, global LV end-systolic elastance and the end-systolic stress-volume
relationship fell by 46 and 33 percent, respectively [148 ] (Fig. 32-23) . In terms of
myocardial energetics, the slopes of the LV stroke work-EDV and pressure-volume
area-EDV relations declined significantly by 20 and 11 percent (indicating reduced
external stroke work and mechanical energy generated at any given level of preload)
after MVR with chordal excision. Chordal interruption in dilated canine hearts
(secondary to chronic mitral regurgitation) after MVR impaired LV mechanics and
decreased LV energetics and efficiency due to an exacerbated mismatch in
ventriculovascular coupling between the left ventricle and the systemic arterial bed. [148
]
Summary
The functional competence of the mitral valve relies on the interaction of the mitral
annulus and leaflets, the subvalvular apparatus, the left atrium, and the left ventricle. The
etiology of pure mitral regurgitation is variable, including myxomatous degeneration or
floppy mitral valve in the majority of cases, rheumatic valve disease, papillary muscle
dysfunction, infective endocarditis, mitral annular calcification, idiopathic chordal
rupture, and other less common causes. In terms of cardiac energetics, reduced LV
impedance in patients with mitral regurgitation allows a greater proportion of contractile
energy to be expended in myocardial fiber shortening rather than in tension
development. Because increased shortening is a smaller determinant of myocardial
oxygen consumption than the other components, mitral regurgitation causes only small
increases in myocardial oxygen consumption. The augmented preload in mitral
regurgitation eventually leads to LV dilatation and a more spherical shape. After the
initial compensatory phase, LV systolic contractility becomes progressively more
impaired with chronic mitral regurgitation. LVESV is reflective of changes in LV systolic
function; the larger the LVESV, the worse is the systolic contractility. Correcting LVESV
for afterload and body size (LVESVI) provides an index of ventricular systolic function
that is less influenced by loading conditions and variation in patient size. Preoperative
LVESV or LVESVI is a better predictor of postoperative outcome in terms of LV
performance and cardiac death than is ejection fraction, LVEDV, or LV end-diastolic
pressure.
Patients with mild to moderate mitral regurgitation may remain asymptomatic for many
years; gradually, symptoms reflective of decreased cardiac output and/or pulmonary
congestion develop. Echocardiography is invaluable in identifying abnormalities of
mitral leaflet morphology and function. The mainstay of medical management of patients
with mitral regurgitation is afterload reduction. Patients with acute mitral regurgitation
resulting from papillary muscle rupture or chordal rupture frequently present in
cardiogenic shock and should undergo operative intervention immediately. In patients
with chronic mitral regurgitation, if signs of LV systolic dysfunction are present or a
progressive increase in LV end-systolic dimension is observed, mitral valve surgery is
considered.
Operation for symptomatic patients should be performed before severe, irreversible LV

systolic dysfunction develops. Surgical options include conventional MVR with excision
of the subvalvular apparatus, MVR with preservation of the chordae tendineae, or mitral
valve repair. The operative mortality rate associated with mitral valve repair is lower
than that with MVR, probably because of enhanced LV systolic function due to
preservation of the subvalvular apparatus. Ischemic mitral regurgitation is associated
with higher operative risk than are nonischemic forms of chronic mitral regurgitation; the
poor postoperative outlook in this patient population may be no better after mitral repair
compared with after MVR.
The mitral subvalvular apparatus is recognized as an important component of LV

performance; it is necessary to maintain optimal postoperative LV geometry and
optimize LV systolic pump function. After conventional MVR with chordal excision, a
significant decline in LV performance occurs with depression of regional and global
elastance, dysynergy of contraction, and dyskinesia at the papillary muscle insertion
sites; conversely, after MVR with chordal preservation, LV function is preserved.
Clinically, patients who undergo MVR with chordal preservation have a decrease in
LVEDV and LVESV, a decrease in ESS, and an unchanged ejection fraction. These
findings suggest that reduced chamber size, reduced systolic load, and preservation of
ventricular contractile function act in concert to maintain ejection performance after
chordal-sparing procedures.
HISTORICAL PERSPECTIVE
The concept of surgically repairing a defective mitral valve is not new. Sir Thomas
Lauder Brunton, in 1902, was the first to suggest operation for mitral stenosis. [1 ] In
1922, Allen and Graham unsuccessfully attempted to use a valvulotome with an optical
system to visualize the mitral valve. [2 ] In the same year, Cutler and Levine resected a
portion of a mitral valve, reasoning that mitral insufficiency would be better tolerated
than mitral stenosis. [3 ] After one success and six failures, the procedure was
abandoned. In 1925, Souttar dilated the mitral valve by inserting his finger through the
left atrial appendage. [4 ] The development of mitral valve surgery lay dormant for more
than 20 years, until Harken et al. and Bailey popularized the procedure and emphasized
the importance of commissurotomy with mobilization of the leaflets to avoid the creation
of mitral insufficiency. [5 ] , [6 ] The development of a mitral valve dilator by Logan and
Turner in 1955 permitted more extensive and predictable commissurotomy. [7 ] Early
surgical maneuvers to improve mitral insufficiency included a number of attempts to
block the regurgitant jet, including pedicle grafts fixed within the left ventricle and
circumferential suture of the annulus by Glover and Davila in 1938. [8 ] This latter
operation was a predecessor of modern annuloplasty. Subsequently, Bailey and Hirose
used several ingenious techniques to extend valvuloplasty to patients with mitral
insufficiency. [9 ]
The introduction by Gibbon in 1953 of the heart-lung machine permitted the first
opportunity to do mitral valve surgery under direct vision, and several techniques were
developed to treat mitral insufficiency. [10 ] Lillehei et al. were the first to attempt to
correct pure mitral insufficiency by annuloplasty. [11 ] In 1961, Starr and Edwards
performed the first mitral valve replacement and revolutionized the treatment of mitral
valve disease. [12 ] Instantly, mitral valve replacement became the procedure of choice
for mitral valve disease that did not lend itself easily to open mitral commissurotomy.
During the succeeding 20 years, several types of mechanical prostheses were
developed and in 1969, Carpentier et al. introduced a glutaraldehyde-treated porcine
heterograft that did not require long-term anticoagulation in patients who were in normal
sinus rhythm. [13 ]
A few surgeons continued to repair insufficient mitral valves, which resulted in multiple
new techniques. Wooler, Kay, and Reed and their associates performed annuloplasties
by placing sutures at the commissures to reduce the circumference of the mitral
annulus. [14 ] [16 ] These repairs converted the posterior leaflet into a buttress against
which the anterior leaflet could close. Sauvage and Wood [17 ] described a technique to
augment the posterior leaflet with pericardium to improve leaflet coaptation in patients
with restricted posterior leaflets secondary to rheumatic valvulitis. Rumel et al. [18 ]
extended the possibilities of mitral valvuloplasty for rheumatic mitral stenosis beyond
simple commissurotomy by describing a valvuloplasty in which the fibrous peel was
curetted from the anterior leaflet of the mitral valve to make the thickened, fibrotic leaflet
more mobile.
Techniques to repair the leaflets themselves soon followed. McGoon introduced a

method for repair of ruptured posterior chordae by excluding the flail segment. [19 ]
Gerbode et al. extended this technique to include plication of a portion of the annulus.
[20 ] Because this method decreased the area of the valve leaflet, annuloplasty
frequently was required. Merendino et al. modified the repair further by excising a
triangular segment and resuturing the divided valvular tissue. [21 ] In 1963, Kay et al.
proposed a method in which the leading edge of the flail segment was sutured to the
nearest underlying papillary muscle. [22 ] These techniques were used in only a few
centers as mitral valve replacement became the standard therapy for mitral
insufficiency.
In 1971, Carpentier et al. greatly advanced the techniques of valve repair by detailing
clearly the pathologic anatomic changes that occur in mitral insufficiency. [23 ] He
introduced a physiologic classification of mitral insufficiency that is the basis of our
current understanding of both the echocardiographic patterns and the anatomical
causes of mitral insufficiency. Recognition that annular dilatation occurred principally at
the attachment of the posterior leaflet led to his development of an annuloplasty ring. He
described techniques for reconstruction of various leaflet abnormalities that he
combined with an annuloplasty ring to maintain function of the anterior leaflet while
decreasing overall annular size. Subsequently, Duran et al. proposed a flexible
annuloplasty ring to allow annular motion during ventricular contraction. [24 ]
PATHOPHYSIOLOGY OF MITRAL VALVE DISEASE
When contemplating major surgery, the initial morbidity and mortality of the procedure
and its anticipated benefits on the quality and quantity of life must be weighed against
the expected survival and symptoms if only pharmacologic therapy is provided. To
make this decision, a thorough understanding of the pathophysiology and natural history
of the medically and surgically treated disease process is necessary. Mitral valve
disease imposes several unphysiologic stresses on the cardiovascular system.
Left Ventricular Volume Overload
Significant mitral regurgitation reduces the efficiency of left ventricular contraction, and
work expended produces flow that does not contribute to effective forward cardiac
output. Left ventricular preload is increased and this increases ventricular wall tension,
left ventricular diastolic volume, and stroke volume. In severe mitral regurgitation, stroke
volume may be 150 percent to 200 percent above normal.
Reduced Cardiac Output
Despite severe mitral regurgitation, patients with normal myocardial contractility

compensate by increasing stroke volume. However, with exercise, patients are unable
to augment stroke volume adequately to increase forward cardiac output. This causes
effort intolerance and is manifested as a decrease in ejection fraction with exercise.
Maintenance of adequate forward flow becomes more difficult because 50 percent of
the stroke volume is ejected into the left atrium before the aortic valve opens. [24 ] Mitral
insufficiency is severe when 60 percent or more of left ventricular stroke volume returns
to the left atrium. With decreased myocardial reserve, patients with severe mitral
regurgitation may have reduced forward cardiac output, even at rest.
Left Atrial Enlargement
The left atrium is exposed to left ventricular systolic pressure and experiences pressure
and volume overload that cause left atrial enlargement. Early in the course of the
disease, left atrial enlargement may be minimal, but as mitral regurgitation becomes
chronic and severe, the left atrium enlarges further and develops atrial arrhythmias. The
degree of left atrial enlargement is a barometer of the chronicity and severity of mitral
regurgitation.
Atrial Arrhythmias
As the left atrial myocardium becomes stretched, atrial circuits are disrupted and the
substrate for macro re-entry phenomenon is established. The atrial contribution to left
ventricular filling is lost and reduces left ventricular filling and cardiac output. Onset of
atrial fibrillation often heralds the symptomatic phase of mitral regurgitation.
Left Atrial Thrombus
Atrial fibrillation and enlargement of the left atrium causes stasis and increases the risk
of thrombus formation and embolization, even though such events are less common in
mitral regurgitation than in mitral stenosis.
Pulmonary Congestion
Symptoms of congestive heart failure are the most readily appreciated presentation of
mitral regurgitation. Increased left atrial pressure, together with decompensation of
atrial and ventricular myocardium, cause pulmonary venous and pulmonary capillary
hypertension and transudation of fluid that affects pulmonary gas transport.
Pulmonary Hypertension
Patients with mitral valve disease may have elevated pulmonary artery pressures.
Whether initially owing to arteriolar constriction, hypoxia, or lymphatic engorgement,
pulmonary artery atherosclerosis may result from longstanding, severe pressure
elevation. Pulmonary hypertension is another useful barometer of the chronicity and
severity of mitral valve disease.
Natural History
The best data on the natural history of mitral disease are derived from studies
preceding the advent of modern cardiac surgery. Ellis and Ramirez observed 42
patients with typical mitral holosystolic murmurs without opening snaps that were
presumably a result of rheumatic fever. [25 ] Asymptomatic or minimally symptomatic
patients remained in the same functional Class for 454 years. The percentage of
patients who died or who required cardiac surgery was related to functional Class:
functional Class I, 25 percent; functional Class II, 28 percent; functional Class III, 50
percent; functional Class IV, 83 percent.
Munoz et al. observed 99 medically treated patients with rheumatic mitral regurgitation
or mixed lesions. [26 ] The five-year survival rate was 45 percent. At the time of
diagnosis, 75 percent were in functional Class I or II; after 5 years, 23 percent remained
in functional Class I or II. Complications at 5 years of follow-up were endocarditis (2
percent), cerebrovascular accident (8 percent), atrial fibrillation (40 percent), and
progression of congestive heart failure (72 percent).
From 1972 to 1978, Ramanathan et al. observed 76 patients with isolated mitral
insufficiency treated medically. [27 ] At a mean follow-up of 48 months, 14 patients
improved, 20 remained the same, 12 survived with worse symptoms, and 23 died.
Mortality rates according to functional Class at the time of catheterization were 27
percent in functional Class I, 19 percent in Class II, 53 percent in Class III, and 44
percent in Class IV.
Hammermeister et al. assessed variables predictive of late survival in patients with both
medically and surgically treated mitral valve disease. [28 ] Survival of medically treated
patients was 50 percent at 5 years and 20 percent at 10 years and was associated with
age, arterial venous oxygen difference, end-diastolic volume, ejection fraction, functional
Class, left ventricular mass, pulmonary hypertension, elevation of wedge pressure, and
sex.
SURGICAL ANATOMY OF THE MITRAL VALVE
The mitral valve is a complex, finely coordinated structure that requires the functional
integrity of its anatomical subunits working in harmony for normal function. The mitral
valve includes valve leaflets, annulus, chordae tendineae, papillary muscles, and left
ventricle.
Leaflets
The mitral valve is the inlet to the left ventricle. It consists of two leaflets, the anterior
(aortic) and posterior (mural) leaflets, that are attached directly to the mitral annulus and
to the papillary muscles by primary and secondary chordae. The anterior mitral leaflet is
a semicircular structure that stretches diagonally from the posteromedial aspect of the
muscular ventricular septum anteriorly across the mitral orifice to attach to the
anterolateral wall of the left ventricle. The anterior mitral valve is in direct continuity with
the fibrous skeleton of the heart. This leaflet is contiguous with the left and noncoronary
cusps of the aortic valve, and the area beneath the intervening aortic commissure: the
fibrous subaortic curtain. Although the anterior leaflet occupies only 3545 percent of the
annular circumference, its leaflet area is almost identical to that of the posterior leaflet.
[29 ] Attachments of the leaflets to the annulus meet at the anterolateral and
posteromedial commissures. The posterior mitral valve leaflet is rectangular in shape. It
comprises all leaflet tissue posterior to the two commissural areas. The free margin of
the posterior leaflet has two variable indentations, called clefts, that divide the posterior
leaflet into three scallops: the largest or middle scallop, the posteromedial scallop, and
the anterolateral scallop. There are fan-shaped chordae that insert into and define the
clefts between the individual posterior scallops. Motion of the posterior leaflet is more
restricted than the anterior leaflet; however, both mitral leaflets contribute importantly to
effective valve closure.
The surface texture of the mitral valve leaflet is subdivided into three zones that
correspond to areas of chordal insertion and areas of leaflet coaptation during normal
valve function. The rough zone is found on the edge of both the anterior and posterior
mitral leaflets. This zone represents contact surfaces of the mitral leaflets during systole.
These two adjacent areas must abut for normal valve closure and competence. The
clear zone that is in contact with blood filling the left atrium during systole is more
peripheral to the rough zone. It is this portion of the mitral valve that billows into the
atrium during ventricular contraction. The basal zone, between the clear zone and the
annulus, receives the insertion of the basal chordae tendineae (tertiary chordae), which
originate directly from the trabeculae carneae of the left ventricle. The basal zone is
found only on the posterior leaflet.
Annulus
The mitral valve annulus represents the attachment of mitral valve leaflets to muscular
fibers of the atrium and ventricle. The annulus is flexible and decreases in diameter
during each systolic contraction by approximately 26 percent. [30 ] The orifice of the
mitral valve also changes shape from elliptical during ventricular systole to circular
during late diastole. This flexibility has the advantage of increasing the amount of
coaptation of the leaflets during systole while increasing the annular orifice area during
diastole. Changes in size and shape of the annulus result from relaxation and
contraction of the basoconstrictor muscles (bulbospiral and sinospiral bundles). [31 ] In
the horizontal plane the mitral annulus is saddle-shaped. Anteriorly, the annulus is
structurally attached to the fibrous skeleton of the heart. [32 ] This limits flexibility and the
capacity of the anterior annulus to dilate with mitral insufficiency. The posterior annulus
is more flexible and is not attached to rigid surrounding structures. This accounts for the
clinical observation that dilation of the annulus occurs posteriorly with mitral
insufficiency. [23 ]
The annulus of the mitral valve is surrounded by many important structures. The
circumflex coronary artery courses laterally around the mitral annulus in the posterior
atrioventricular groove (Fig. 33-1) . The coronary sinus runs more medially in the same
groove. The artery to the atrioventricular node, usually a branch of the right coronary
artery, runs a course parallel and close to the annulus of the anterior leaflet of the mitral
valve near the posteromedial commissure. The aortic valve is located between the
anterior and posterior fibrous trigones. The bundle of His is located near the posterior
trigone. All these structures may be injured during mitral valve repair surgery.
Chordae Tendineae
The chordae tendineae are strong chords of fibrous connective tissue that attach mitral
valve leaflets to either the papillary muscles or the left ventricular free wall. They often
subdivide and interconnect before they attach to the two leaflets. The chordae may be
divided into primary chordae, secondary chordae, and tertiary chordae. Primary
chordae attach directly to the fibrous band running along the free edge of the valve
leaflets. These chordae function to assure that the contact surfaces (rough zone) of the
leaflets coapt without leaflet prolapse or flail. Mitral valve competence improves as
ventricular systole progresses and leaflet coaptation increases. Secondary chordae
attach to the ventricular surface of the leaflets at the junction between the rough and
clear zones along the line of leaflet coaptation. These chordae are important in
maintaining ventricular function. The secondary chordae allow the ventricle to contract in
a stronger, more efficient cone-shaped fashion as opposed to the globular shape that
the left ventricular cavity assumes when secondary chordae are not present. [33 ] , [34 ]
Tertiary chordae are unique to the posterior leaflet. They arise as strands directly from
the left ventricular wall or from small trabeculae carneae to insert into the ventricular
surface of the leaflet near the annulus. An additional Class of chordae are commissural
chordae. These chords insert at the free margin of the commissural regions. The
commissural chordae arise from either the posteromedial or the anterolateral papillary
muscle and each attaches to both leaflets. This distinguishes them from other chordae.
Papillary Muscles
The anterolateral and posteromedial papillary muscles make up the muscle groups of
the left ventricle. Each supplies chordae tendineae to both leaflets. In the left ventricle,
the two groups of papillary muscles subtend the anterolateral and posteromedial
commissures and arise from the junction of the apical and middle thirds of the
ventricular wall. The anterolateral papillary muscle receives a dual blood supply from the
anterior descending coronary artery and either a diagonal branch or a marginal branch
of the left circumflex artery. [35 ] [37 ] The posteromedial papillary muscle receives its
blood supply from either the left circumflex artery or a distal branch of the right coronary
artery. Because of the singular blood supply to the posteromedial papillary muscle,
infarction of the posteromedial papillary muscle is much more common.
Left Ventricle
The posterior left ventricular wall and papillary muscles play an important part in valve
leaflet coaptation and competence. Papillary muscles are aligned parallel to the
ventricular wall and attach via chordae to the free edges of the valve leaflets. These
muscles project from the trabeculae carneae and may be single, bifid, or a row of
muscles arising from the ventricular wall. During isovolumetric contraction the mitral
leaflets are pulled downward and together by this interaction. Ventricular dilatation may
affect the alignment and tension on the papillary muscles and valve competence.
DYNAMICS OF THE NORMAL MITRAL VALVE
Normal mitral valve competence is predicated on the fact that leaflet surface area far
exceeds mitral orifice area. Chiechi et al. [38 ] demonstrated a consistent ratio of valve
leaflet surface area to mitral valve orifice area of 2:1. This difference is accentuated
during systole when the mitral valve annulus constricts. The normal cycle begins during
early diastole when the mitral leaflets begin to drift apart. Left ventricular pressure falls
during isovolumic relaxation to cause the mitral valve to open. The majority of ventricular
filling occurs early during the rapid filling phase followed by a slower late filling phase. A
second rapid filling phase occurs with atrial contraction (atrial kick). This produces the
A-wave on the left atrial pressure tracing. At slow heart rates, the atrial contribution to
ventricular filling is minimal. However, at faster rates, or with stenosis of the mitral valve,
the contribution of atrial systole to ventricular filling becomes increasingly important. In
the failing heart, the contributions of atrial systole can increase cardiac output 2030
percent. With the onset of ventricular contraction, the leaflets meet edge to edge. During
this phase of isovolumetric contraction, the mitral leaflets bulge upward, ballooning into
the atrial cavity. As the cardiac cycle progresses, the area of coaptation along the
leaflet rough zone increases and the leaflets align in an almost vertical position to
maintain valve competence.
The initial phase of ventricular contraction is isovolumetric, with the maximum rate of
pressure change (dp/dt) occurring just before ejection. The rapid ejection phase follows
opening the aortic valve and is characterized by a sharp rise in ventricular and aortic
pressure, a more abrupt decrease in ventricular volume, and greater aortic flow. This is
followed by a reduced rate of ejection, and is a longer phase that ends with closure of
the aortic valve marked by the incisura on the aortic pulse tracing. Subsequently,
ventricular pressure falls with ventricular relaxation and the mitral valve opens to begin
left ventricular filling and repetition of the entire cycle. During left ventricular ejection, the
minor (transverse) axis of the inner wall shortens by 2737 percent, whereas the major
axis (apex to base) shortens only 9 percent. [39 ]
INDICATIONS AND CONTRAINDICATIONS TO MITRAL VALVE
REPAIR
Indications for surgical intervention in patients with mitral insufficiency evolved from a
better understanding of the pathophysiology of the disease process and continued
technical advancements in mitral valve repair. [40 ] Previously, patients became
significantly symptomatic from their valvular pathology before surgical intervention was
considered. If the benefits of valve replacement outweighed the risks of medical
management and the morbidity of a valve prosthesis, patients were referred for valve
replacement. Currently, asymptomatic patients are considered for operation when left
ventricular function begins to deteriorate. Aggressive surgical intervention is justified
because symptoms correlate poorly with the degree of left ventricular dysfunction.
Asymptomatic patients may develop severe mitral regurgitation and substantial left
ventricular dysfunction. Development of clinical signs of ventricular deterioration is
variable, and depends largely on the response of the left atrium to volume overload. If
the atrium does not dilate, pulmonary venous pressure rises and symptoms occur early.
However, if the left atrium is compliant and dilates, atrial and pulmonary venous
pressures may not rise until late in the disease process. Thus, severe mitral
regurgitation may occur with normal left atrial pressures [41 ] and patients may remain
asymptomatic for long periods despite progressive left ventricular deterioration. [41 ]
Waiting for a patient to progress to functional Class III often prolongs left ventricular
volume overload, and causes permanent myocardial dysfunction, that increases
operative morbidity, mortality, and poor clinical outcomes. [42 ] Therefore, symptoms
are unreliable for determining the optimal timing of operation.
Likewise, symptoms are poor indicators of the reversibility of ventricular dysfunction.

Schuler et al. demonstrated that after a critical time period, valve replacement that
eliminates regurgitation does not decrease left ventricular size nor produce regression
of myocardial hypertrophy; instead, ventricular function progressively deteriorates and
ejection fraction falls. [42 ] Clearly, operation should precede irreversible left ventricular
dysfunction. Most surgeons use a fall in ejection fraction with exercise or left ventricular
end-systolic volume greater than 55 mm as indications of deteriorating cardiac function
and the need for surgery. Furthermore, excellent results of mitral valve repair, which
obviate the morbidity of valve replacement, foster a more aggressive approach to mitral
valve pathology. [40 ] Patients who undergo mitral valve repair maintain better left
ventricular function, have lower operative mortality rates, and superior longevity
compared to patients who have mitral valve replacement. [43 ]
Contraindications to mitral valve surgery have changed as experience with mitral repair
techniques has accelerated. Mitral regurgitation secondary to end-stage
cardiomyopathy traditionally is a contraindication to mitral valve replacement. Several
reports demonstrate extremely poor outcomes in patients who undergo mitral valve
replacement for end-stage cardiomyopathies. [44 ] [46 ] These patients develop mitral
regurgitation secondary to poor ventricular function rather than poor function owing to
long-standing mitral insufficiency. Regurgitation develops from dilatation of the left
ventricle that restricts leaflet motion. [47 ] , [48 ] Unfortunately, once mitral insufficiency
begins, it compounds ventricular dysfunction by further volume-overloading an already
dilated ventricle. [49 ] Medical therapy does not alleviate the progressive mitral
insufficiency; thus the prognosis is poor. [50 ]
Recently, encouraging results were reported in patients with severe mitral regurgitation
secondary to end-stage cardiomyopathy (mean preoperative ejection fraction 16
percent + 5 percent) who had mitral valve prolapse treated with only an annuloplasty
ring. [51 ] By preserving the annular-chordal-papillary muscle complex, left ventricular
function was maintained following repair. Preservation of the mitral valve complex
produced better left ventricular function than valve replacement with chordal removal. [52
] [55 ]
The onset of atrial fibrillation is a controversial indication for surgical intervention in

patients with mitral regurgitation. [40 ] , [43 ] The arguments favoring operation are
based on studies that demonstrate a six-fold increase in cerebrovascular accidents with
atrial fibrillation and an 18-fold increase when atrial fibrillation is associated with mitral
valve disease. [56 ] Furthermore, atrial fibrillation present for less than 1 year is likely to
convert to normal sinus rhythm in more than 90 percent of patients following mitral valve
surgery, but atrial fibrillation present for more than 1 year has less than a 10 percent
chance of converting to sinus rhythm. [57 ] Thus, earlier mitral valve repair often
alleviates atrial fibrillation and the need for long-term anticoagulation.
A study from The Mayo Clinic [58 ] confirmed that patients with recent-onset atrial
fibrillation are likely to convert to normal sinus rhythm after mitral valve repair. However,
the study did not demonstrate a survival advantage or a difference in thromboembolism
between patients in sinus rhythm undergoing mitral valve repair compared to those who
remained in atrial fibrillation. Others question the indication of recent onset atrial
fibrillation for early mitral valve repair because long-term follow-up studies of
unoperated patients demonstrate excellent outcomes. [40 ] , [59 ] Mudge et al. noted
that many patients with mild mitral regurgitation may have calcification or fibrosis within
the left atrium that predisposes atrial fibrillation and is unrelated to mitral insufficiency.
[40 ] In these patients, repair of mild asymptomatic regurgitation is not likely to influence
the natural history of the atrial dysrhythmia nor the modest hemodynamic abnormality.
However, many offer mitral valve repair surgery to patients with recent onset atrial
fibrillation when accompanied by moderate to severe mitral regurgitation. In these
patients, it is likely that atrial fibrillation is secondary to mitral insufficiency; repair
reduces the risk of systemic embolization because most patients convert to sinus
rhythm. This avoids long-term anticoagulation and late bleeding complications (1.52.5
percent per patient year). [60 ]
Mitral Stenosis
Surgical indications for mitral stenosis are more straightforward than for mitral
insufficiency. Mitral stenosis acts to protect ventricular function but impaired ventricular
filling causes symptoms of low cardiac output and congestive heart failure. Even
moderate symptoms justify surgical intervention. As with mitral insufficiency, symptoms
do not necessarily correlate with the degree of mitral stenosis. Currently, one episode of
significant paroxysmal nocturnal dyspnea or pulmonary edema associated with
moderate mitral stenosis is an indication for surgery or percutaneous balloon mitral
dilatation. Onset of atrial fibrillation strengthens the need for intervention. Not
uncommonly, a patient presents with new-onset atrial fibrillation that greatly exacerbates
symptoms by further impairing ventricular filling. Intervention also is advisable whenever
pulmonary vascular resistance increases significantly, even in the absence of
symptoms. Patients who suffer episodes of arterial embolism from demonstrated
thrombi in the left atrium also are surgical candidates. Percutaneous balloon dilatation
or open surgical commissurotomy usually is possible for early mitral stenosis and this
has led to more aggressive therapy in these patients. In a large series involving 220
surgical patients at Green Lane Hospital, only 30 percent required valve replacement.
[61 ] However, the presence of severe calcification, absence of an opening snap owing
to immobile leaflets, severe subvalvular disease, or associated mitral incompetence
usually precludes percutaneous mitral valve commissurotomy. Surgery usually is
delayed in these patients until symptoms are more pronounced because of the greater
likelihood of valve replacement. Advanced disability, tricuspid valve disease, severe
pulmonary hypertension, and coronary artery disease do not contraindicate surgery.
Absolute contraindications to mitral valve repair for mitral stenosis are still being
formulated. Incremental risk factors for premature death following mitral valve repair
currently are the same as those following mitral valve replacement. Kirklin and
Barrett-Boyes [62 ] identified older age, mitral incompetence, left ventricular
enlargement, left atrial enlargement, ischemic mitral incompetence, advanced functional
disability, and global myocardial ischemic time as incremental risk factors for
premature death following operation. None represents an absolute contraindication to
native valve repair, yet each is associated with increased surgical mortality.
Mitral annular calcification and elevated pulmonary vascular resistance following

longstanding mitral insufficiency complicate surgical repair, but are not absolute
contraindications. [63 ] Sutures do not hold if placed through annular calcium, and
annuloplasty is more difficult because the annulus is inflexible. Ventricular rupture may
occur if calcium is too aggressively debrided. However, modern repair techniques now
neutralize annular calcification as a risk factor. [64 ] [66 ]
Pulmonary hypertension may also complicate mitral valve repair. [67 ] Severe
pulmonary hypertension results from elevated left atrial pressure and reflex elevation of
pulmonary vascular resistance. The latter may have both a dynamic element,
immediately reduced by decreasing left atrial pressure, [68 ] and a fixed element that
may not regress after operation. Fortunately, severe pulmonary hypertension in most
cases regresses toward normal after mitral replacement and presumably after valve
repair. Kaul reported 30 patients who averaged preoperative pulmonary artery
pressures of 110 mmHg systolic and 74 mmHg mean. [67 ] After operation,
symptomatic improvement of these patients was impressive. Restudy at an average of
5.5 years after mitral valve replacement showed an average systolic pulmonary artery
pressure of 48 mmHg and a mean pulmonary artery pressure of 31 mmHg. These
changes occur whether the operation is for stenosis or incompetence. [69 ] Vincens et
al. demonstrated excellent long-term survival in operated patients with pulmonary
hypertension secondary to mitral stenosis. [70 ]
Functional tricuspid insufficiency secondary to longstanding pulmonary hypertension is

associated with increased operative mortality following mitral repair and decreased
long-term survival. [71 ] Pulmonary hypertension produces severe functional tricuspid
valve regurgitation in 1020 percent of patients who have mitral valve replacement. [62 ]
Despite higher hospital mortality rates, excellent long-term survival rates are reported
for patients who survive tricuspid annuloplasty combined with mitral valve repair. [72 ]
Currently, there are no absolute contraindications to mitral valve repair.
PREOPERATIVE EVALUATION OF MITRAL VALVE DISEASE
CLINICAL FINDINGS
Physical findings in patients with mitral regurgitation range from normal to infective
endocarditis. Peripheral edema may be present in patients with end-stage mitral
incompetence as a result of severe right and left heart failure; however, the physical
appearance of these patients usually is normal. Cardiac auscultation usually reveals a
normal or decreased first heart sound that may be increased if mitral stenosis is
present. With mitral valve prolapse, single or multiple systolic, pre-ejection clicks are
frequently heard. These clicks are best heard at the apex of the left sternal border, tend
to be in mid- or late-systole, and are believed to result from prolapsing leaflets and
sudden tension on elongated chordae tendineae. The auscultatory hallmark of mitral
incompetence is a holosystolic murmur. Usually, the murmur is medium to high-pitched,
blowing in quality, and of relatively stable intensity throughout systole. The intensity of the
apical murmur does not correlate with the severity of regurgitation. In most patients, the
murmur radiates to the axilla.
The most common abnormal electrocardiographic (ECG) finding in patients suffering

mitral regurgitation is atrial fibrillation. [73 ] Chest x-ray often reveals normal pulmonary
vasculature. Late in the disease after significant venous pulmonary hypertension
develops, redistribution of flow to the upper lobes and interstitial edema produces
Kerley B lines. If mitral incompetence is acute, frank pulmonary edema may be evident.
Mitral valve calcification observed at fluoroscopy is less common or prominent in mitral
incompetence than in mitral stenosis. If present, it usually represents mixed lesions.
ECHOCARDIOGRAPHIC ASSESSMENT
Echocardiography has supplanted cardiac catheterization for assessment of mitral

insufficiency. [74 ] This technology provides a noninvasive method to identify significant
insufficiency and semi-quantitates left ventricular function. Echocardiography also
accurately delineates the functional pathology of the valve and helps to determine the
feasibility of valve repair. [75 ] Nonetheless, quantitating the degree of mitral
regurgitation and proper timing of surgical intervention are two difficult tasks for cardiac
surgeons and cardiologists. Comprehensive evaluation of mitral regurgitation
addresses both the magnitude of the leak and its impact upon left ventricular function.
Several qualitative, semi-qualitative, and quantitative approaches are available to

determine the severity of regurgitation. [76 ] , [77 ] Color flow Doppler mapping provides
a rapid, semi-qualitative evaluation of the severity of the regurgitant jet and expedites
the process of spatial mapping. [78 ] The maximal area of the regurgitant jet is
expressed as a percentage of the area of the left atrium. The degree of regurgitation is
scored by the percentage of the left atrial area filled by the jet: 115 percent, mild (1+);
1635 percent, moderate (2+); 3655 percent, moderately severe (3+); and greater than
55 percent, severe (4+). The duration of the jet is also important. Pan-systolic jets
involve a greater volume of regurgitant flow than jets of equal size and brief duration.
Quantitative measurements of jet areas are limited by complex physical, geometric, and
instrument-induced factors that dictate jet size. [79 ] The size of the physical jet is
determined by jet momentum, which is the product of regurgitant flow multiplied by
velocity. Thus, a jet may appear large simply because the driving pressure across the
valve is increased, even if no change in flow rate occurs. This illustrates the importance
of measuring blood pressure at the time of echocardiography. Jet size is also
influenced by chamber size. Obviously, a jet that extends to the back wall of the atrium is
limited by that wall. [80 ] Eccentric jets close to the regurgitant valve tend to flatten out
along the chamber wall and appear much smaller than control jets of similar regurgitant
volumes (approximately 40 percent smaller). [81 ] Instrument set-up may affect the size
of displayed jets. Jets may be enlarged by increasing instrument gain, output power,
and the ensemble length (number of individual color pulses that make up each scan
line) or by decreasing pulse repetition frequency and the wall filter effect. [82 ]
Transducer frequency has a variable effect: High frequency increases sensitivity to low
velocities but also increases attenuation. Within these limitations, broad guidelines
classify jets as mild, moderate, or severe, with extra weighting given to jets that are
eccentric. [83 ]
A promising method to quantitate mitral insufficiency is called proximal flow

convergence. [84 ] As blood approaches a regurgitant orifice from the atrial
perspective, velocity increases predictably and forms concentric, hemispherical shells
of increasing velocity and decreasing surface area. Flow rate and regurgitant orifice
area (ROA) can be calculated from the converging flow of the hemispherical shells. The
functional valvular lesion can be assessed by observing changes in ROA over time in
response to therapeutic reductions in afterload or to ongoing valvular destruction from
endocarditis. Preliminary experience with ROA and mitral regurgitation indicates that
areas less than 10 mm 2 correlate with mild regurgitation; those between 10 and 25 mm
2
are moderate; those between 25 and 50 mm are moderate to severe; and ROAs
greater than 50 mm (.5 cm 2 ) signify severe valvular regurgitation. The larger the radius
of a hemispheric shell, the greater the degree of mitral insufficiency. [85 ]
Pulmonary venous flow is another index of the severity of mitral regurgitation. [86 ] As
the severity of regurgitation increases, forward velocity through the pulmonary veins
becomes increasingly turbid. In severe mitral regurgitation, flow in the pulmonary veins
actually reverses and reflects a greatly increased left atrial pressure and a mitral
V-wave.
There is no single method to quantitate the magnitude of mitral regurgitation. Several

bronze standards exist that, when taken together, provide an overall echocardiographic
assessment of regurgitant severity. This assessment is interpreted with clinical and
hemodynamic findings.
Echocardiography also accurately images the anatomy of mitral insufficiency. The

direction of the jet as determined by Doppler color flow imaging is particularly helpful for
determining mechanisms of mitral regurgitation. The direction of the jet usually is
opposite the leaflet that is flailing or prolapsing: posterior leaflet prolapse or flail causes
an anteriorly directed jet; anterior leaflet prolapse or flail causes a posteriorly directed
jet. In a series that compared preoperative echocardiographic findings with surgical
findings, jet direction accurately predicted the mechanism of regurgitation in 80 percent
of patients. [87 ] In patients with inadequate support of the middle scallop of the
posterior leaflet, short axis views show a jet in the middle of the anterior atrium. When
only the bare area of the mid-anterior leaflet is supported, the short axis views show the
systolic jet in the middle of the posterior left atrium. Some patients have flail or
elongated chordae to both leaflets; in these patients, two or more jets within the atrium
sometimes may be seen by panning the ultrasound image from side to side. Some of
these jets appear central or broad in direction. Izumi et al. described jet direction in
patients with ischemic mitral regurgitation. [54 ] When infarction was isolated to one
papillary muscle, the mitral jet emanated from the commissure served by the ischemic
papillary muscle. In the short axis view of patients with posteromedial papillary muscle
infarction, the color flow jet traversed the posteromedial commissure and coursed
anterolaterally across the left atrium. When the anterior papillary muscle infarct was
focal or isolated, chordae from the anterolateral papillary muscle ruptured and the jet
emanated from the anterolateral commissure and coursed posteromedially across the
left atrium in the short axis view.
A central mitral regurgitant jet occurs when mitral leaflets fail to coapt. This may be
owing to restricted leaflet motion from rheumatic mitral regurgitation because fibrosis
shrivels leaflet tissue and restricts motion even though the annulus is normal. A similar
central jet occurs from coronary artery disease, cardiomyopathy, or any left ventricular
dysfunction that spatially displaces the papillary muscles. In such cases, actual
leaflet-chordal length may be normal but apical displacement of the papillary muscles
displaces coapting leaflet edges into the ventricle from the annular plane. Rheumatic
mitral regurgitation may also cause anterior leaflet override that produces a jet when the
posterior leaflet is more restricted than the anterior.
Eccentric jets occur occasionally when the jet originates from the body of the leaflet
rather than at the coaptation line. These jets usually are secondary to leaflet perforations
from endocarditis. An eccentric jet also may occur in patients with congenital mitral
regurgitation owing to a cleft mitral valve or after previous mitral valve repair.
In addition to quantifying the degree of insufficiency and pathologic anatomy,

echocardiography facilitates analysis of left ventricular function. Left ventricular function
is difficult to assess in patients with chronic mitral insufficiency because standard
measures such as ejection fraction are misleading. End-systolic volume is smaller in
patients with mitral regurgitation because the left ventricle empties more completely. In
addition, left ventricular diastolic volume and preload increase because of greater
diastolic filling. Small end-systolic volume and large end-diastolic volumes increase
ejection fraction but do not reflect left ventricular contractile force. Left ventricular
ejection fractions may be normal even if myocardial contractility is substantially
depressed. [42 ] Indices of ventricular dilatation better reflect ventricular contractility than
ejection fraction. Absence of end-diastolic enlargement argue strongly against severe
ventricular dysfunction owing to mitral valvular regurgitation. However, if end-systolic
dimensions are not significantly altered, left ventricular function may still be good even if
significant end-diastolic dilatation is present in patients with severe mitral regurgitation.
End-systolic indices provide more reliable indices of ventricular dysfunction than
end-diastolic indices. End-systolic diameters over 40 mm warrant close follow-up with
frequent echocardiograms. If the ventricle continues to enlarge, particularly beyond 45
mm, surgery should be considered, even in the absence of symptoms. [88 ] [90 ]
Peak left ventricular dp/dt is another index that is used to assess left ventricular function.
Recently, Pai et al. reported that dp/dt is a good predictor of postoperative left
ventricular function. [91 ] By deriving left ventricular dp/dt from Doppler signals of mitral
regurgitation and assuming that left atrial pressure does not change significantly, they
reported that a dp/dt less than 1000 mmHg/s predicts poor postoperative left ventricular
function and higher mortality. Unfortunately, these analyses are difficult to perform, and
minimal misalignment of the continuous Doppler beam may cause substantial errors in
the estimation of dp/dt. In a recent series from the Cleveland Clinic, five of seven
patients who died following mitral valve repair had left ventricular dp/dt less than 600.
Left ventricular end-systolic volume, ejection fraction, and left ventricular dp/dt are all
load-dependent measures of ventricular function. Myocardial contractility values change
with variations in left ventricular preload and afterload and are criticized as unreliable
indices of independent myocardial function. Unfortunately, neither a truly reliable
load-independent method for determining left ventricular function nor a means of
assessing the severity of mitral insufficiency exist.
Routine cardiac catheterization is not necessary to diagnose mitral regurgitation or

determine its severity. Cardiac catheterization is used to diagnose concomitant
coronary artery disease. The presence and degree of regurgitation can be estimated by
visual inspection of the contrast ventriculogram in the right anterior oblique view. The
severity of regurgitation is graded from 1+ to 4+. One plus is present when a small
amount of dye enters the left atrium, does not fill the entire atrial cavity, and clears
completely with subsequent beats. Two plus is defined by complete filling of the atrium;
however, the degree of opacification is less than that of the ventricle. Three plus fills the
entire atrium, and the opacification is equal to that of the ventricle. With 4+, the entire
atrium and pulmonary veins fill rapidly and progressively opacify to a greater degree
than the ventricle. Grades 3+ and 4+ correlate with significant regurgitation.
Several factors affect the severity of mitral regurgitation when assessed

angiographically. The angiographic catheter may become entrapped in the mitral
apparatus and interfere with valve closure. Premature ventricular contractions and
ventricular tachycardia during contrast injection may also cause significant regurgitation.
The size of the left atrium may interfere with the subjective assessment of reflux. For a
given regurgitant volume, a severely enlarged left atrium does not opacify to the same
degree as a small atrium. In patients with large left atrial cavities the severity of mitral
regurgitation may be underestimated.
Pressure measurements at the time of cardiac catheterization assess hemodynamic

consequences of mitral regurgitation. Elevated ventricular end-diastolic and mean
pulmonary capillary wedge pressures indicate severe, decompensated mitral
regurgitation. Because of the large amount of blood injected into the atrium during
systole, wedge pressures develop large V-waves, sometimes exceeding the mean
wedge pressure by 23 fold. In very large atria the size of the V-wave may be damped.
Large V-waves may also be present in the absence of mitral regurgitation in patients
with decompensated ischemic heart disease or other pathologic states characterized
by poor ventricular compliance. [82 ] , [83 ] A normal-size mitral valve may produce a
small diastolic gradient between the wedge and left ventricular end-diastolic pressure
tracings because of increased diastolic filling. These findings, however, are not unique
to mitral regurgitation.
Mitral Stenosis
Signs and symptoms of mitral stenosis develop when the mitral valve area is reduced
significantly by any pathophysiological process. Rheumatic valve disease is the most
common etiology that narrows the valve orifice. Although rare, mitral valve stenosis can
be congenital or result from another process, such as carcinoid syndrome. Left atrial
myxoma can simulate mitral stenosis if the tumor mass obstructs the valvular orifice
during diastole.
Mitral stenosis resulting from acute rheumatic fever is a chronic, progressive disease.
Over time the valve orifice is narrowed by leaflet and chordal thickening and fusion.
When the valve area is reduced to less than 2 cm 2 a pressure gradient between the left
atrium and left ventricle develops to maintain diastolic mitral inflow sufficiently to sustain
cardiac output. Because flow across the mitral valve is proportional to the square of the
pressure gradient, cardiac output may be adequate at rest but fall with exercise. During
exercise the pressure gradient may produce high left atrial and pulmonary capillary
wedge pressures and symptoms of congestive heart failure. A four-fold increase in
pressure gradient is required to double cardiac output. When the mitral valve area is
reduced to less than 1 cm 2 a significant pressure gradient develops across the valve at
rest and resting cardiac output is reduced. The more severe stenosis increases
pulmonary capillary wedge pressure and elevates pulmonary arterial and right
ventricular pressures. Pulmonary arterial resistance and lymphatic flow increase;
pulmonary capillary permeability decreases. These compensatory mechanisms allow a
patient with severe mitral stenosis to tolerate high pulmonary wedge pressures (>2530
mmHg) without developing severe symptoms or pulmonary edema. Eventually cardiac
output is further reduced by high pulmonary arterial and capillary resistance and mitral
valvular obstruction to forward flow. Both right and left heart failure may result. Untreated,
the patient subsequently succumbs to complications of low cardiac output and
congestive heart failure.
CLINICAL FINDINGS
Patients with mitral stenosis complain of dyspnea, orthopnea, and paroxysmal nocturnal
dyspnea. One of the earliest symptoms is dyspnea on exertion. Infrequently, the
diagnosis is obvious in patients with severe pulmonary vascular disease and low
cardiac output. In these patients the arterial pulse may be reduced.
If the anterior mitral leaflet is pliable, the first heart sound is delayed. The cardinal
auscultatory features are exacerbation of the first heart sound, an early diastolic
opening snap, and a diasystolic rumble. Mild mitral stenosis is often unrecognized
unless a physician listens carefully at the apex with the patient in the left lateral
decubitus position. When the valve is calcified and immobile, the opening snap is
absent and the first heart sound is soft. With atrial fibrillation, the presystolic murmur
usually is absent. Chest x-ray is helpful in both confirming the diagnosis and assessing
the severity of stenosis. Typically, superior pulmonary vessels are prominent. A large left
atrial shadow and alveolar interstitial edema evidenced by 13 cm horizontal lines at the
costophrenic angles (Kerley B-lines) are consistent with significant mitral stenosis. With
pulmonary arterial hypertension, central pulmonary arteries are prominent and vascular
markings in peripheral lung fields are reduced. Right ventricular enlargement is best
seen in the lateral film. Valvular calcification can be identified by fluoroscopy.
The electrocardiogram often is normal except for a prolonged bifid P-wave. Atrial
fibrillation is the most common abnormal rhythm.
ECHOCARDIOGRAPHY
Two-dimensional echocardiography is an essential tool for evaluating mitral stenosis

because it allows visualization of mitral valve motion in different tomographic planes in
real time. Mitral valve area is accurately measured. The feasibility of mitral valve repair
is determined and information is obtained about chamber size, function, and about
other valvular abnormalities. The peristernal long-axis view is extremely valuable for
evaluation of mitral stenosis. A normal mitral valve demonstrates full excursion of the
leaflets during diastole and produces two well-separated, parallel, linear echo densities
representing the anterior and posterior leaflets. In mitral stenosis, valve leaflets are
thickened or calcified and produce dense echo images. Leaflet excursion during
diastole is reduced and opening of the valve is restricted. Doming of the anterior leaflet
in diastole, i.e., the body of the leaflet moving more than the edge, is a pathognomonic
feature of mitral stenosis.
There are other situations in which the mitral leaflets do not open fully and may mimic
mitral stenosis in the long-axis view. In low output, mitral valve excursion during diastole
is reduced because blood flow through the valve is reduced. The anterior leaflet does
not dome and the posterior leaflet moves posteriorly. The mitral valve area, measured
from the short-axis view, is less than 2 cm 2 during low cardiac output. Mitral valve
excursion also is reduced in severe aortic insufficiency. High left ventricular diastolic
pressures impair mitral valve opening and may reverse anterior leaflet doming toward
the left atrium.
The severity of mitral stenosis is determined by directly measuring the mitral valve
orifice in the short-axis view during diastole. This method is reliable and reproducible.
[93 ] Excellent correlation exists between mitral valve area measured by
two-dimensional echocardiogram and the area measured directly at surgery or on
pathological specimens. Area estimates calculated from pressure measurements
obtained at cardiac catheterization are not accurate.
Cardiac catheterization confirms the diagnosis of mitral stenosis, determines its

severity, and evaluates the presence of associated diseases that may influence the
surgery. The diagnosis of mitral stenosis is confirmed by demonstrating a reduced
mitral valve area. Gorlin and Gorlin developed a formula that relates valve area to valve
flow and the pressure gradient across the valve. [94 ] The normal area of an adult mitral
valve is 46 cm 2 . When this area is reduced to less than 1 cm 2 , severe mitral stenosis
is present.
Several sources of error may arise when the Gorlin formula is used to assess mitral
stenosis. Pulmonary capillary wedge and ventricular pressure tracings must not be
damped. If the pressure gradient is small, the calculated valve area may be erroneous.
Exercise during catheterization increases cardiac output and the pressure gradient, and
improves the accuracy of the area calculation.
Echocardiography has largely replaced cardiac catheterization in the diagnosis of

mitral stenosis. However, patients over the age of 50 or with chest pain or known
coronary artery disease should undergo catheterization. Significant leaflet calcification
seen by fluoroscopy or ventriculogram generally precludes open or closed
commissurotomy, and atrial thrombosis or mitral regurgitation contraindicates
percutaneous mitral commissurotomy.
A careful preoperative history and physical examination, looking for specific evidence of
right heart failure, infection, angina, bypass conduit availability, and peripheral pulses, is
an integral part of the preoperative assessment of a patient for mitral valve surgery.
Because most valve repairs and all valve replacements need implanted foreign
material, patients are required to have dental clearance to remove occult sources of
infection before surgery. The possibility that the valve will be replaced rather than
repaired and planned concomitant procedures (e.g., coronary artery bypass grafting,
tricuspid valve repair, patent foramen ovale closure) are discussed.
OPERATION
Anesthetic and Monitoring
One preferred method of monitoring patients during mitral valve repair includes routine
use of transesophageal echocardiography, a pulmonary artery catheter, and an arterial
line. Low-dose, short-acting, narcotic anesthesia is supplemented by inhalation agents
intraoperatively and short-acting intravenous sedation postoperatively to facilitate early
extubation after surgery. The bypass circuit includes bicaval cannulation and a
membrane oxygenator. Both antegrade and retrograde cardioplegia delivery systems
are used to deliver blood cardioplegia in a 4:1 mix. Retrograde cardioplegia is
extremely helpful in deairing coronary arteries and the ascending aorta to prevent air
embolism and provides myocardial protection without interrupting the surgical
procedure. [95 ]
Prior to surgery, the intraoperative transesophageal echocardiogram and pulmonary

arterial and central venous pressures are reviewed carefully. Operative strategy is
based on the pathology demonstrated by the intraoperative echocardiogram, and the
presence of significant tricuspid regurgitation and associated lesions.
Transesophageal echocardiography is very accurate in defining valve pathology. [87 ]
Methods to Expose the Mitral Valve
Excellent, consistent exposure of the mitral valve is essential for successful mitral
valvuloplasty. The mitral valve is in fibrous continuity with the aortic valve and oriented
vertically. For optimal exposure, the heart is elevated out of the chest and rotated to
allow the apex to drop posteriorly while elevating the right side of the heart. This brings
the posterior mitral valve leaflet toward the right, into a plane that faces the surgeon, and
permits an excellent view of the valve and subvalvular structures. Several maneuvers are
helpful in achieving optimal exposure. The pericardium is opened slightly to the right of
midline and the right side of the pericardium sutured under tension to the chest wall.
Pericardial edges on the left are not suspended. Adhesions over the left ventricle are
lysed sharply, to allow the apex to drop posteriorly and aid rotation. If dissection within
the pericardium is difficult, opening the left pleural space is equally effective. After
bicaval cannulation, the superior vena cava is mobilized by incising the pericardium
above it. A tourniquet is placed around the inferior vena cava with traction directed
toward the feet of the patient; this further elevates the right side of the heart.
To reduce the possibility of embolization of left atrial thrombus, the left atrium is not
manipulated until after the aortic cross-clamp is applied. The left atrium is incised
parallel to the intra-atrial groove. The incision is extended behind the superior vena
cava and a considerable distance below the inferior vena cava. A specifically designed
self-retaining retractor with three universally available retractor blades is used to
facilitate exposure. [96 ] This maximizes the size of the left atrial incision and elevates
the right side of the heart. The operating table is rotated away from the surgeon. If the
mitral valve is still difficult to see, pledgetted sutures are placed through the annulus, at
either commissure, and traction exerted to pull the valve toward the surgeon.
Exposure of the papillary muscle for chordal shortening requires additional maneuvers
to obtain exposure. Exposure of the posteromedial papillary muscle is facilitated by
sponges placed between the diaphragm and the diaphragmatic surface of the left
ventricle. Gentle pressure with a sponge stick on the right ventricular outflow tract may
facilitate exposure of the anterolateral commissure for suture placement.
Alternative Methods to Expose the Mitral Valve
There are several approaches to the heart. Alternative incisions are available for
optimum exposure of the mitral valve. A right anterolateral thoracotomy is useful in
patients with a previous sternotomy. Patients with multiple operations, recent
sternotomy, dense adhesions, or intact coronary artery bypass grafts near the midline
are particularly suitable candidates. A transatrial oblique incision may be useful in
patients who have a small left atrium. The mitral valve is exposed by incising the orifice
of the right superior pulmonary vein longitudinally across the left atrium into the right
atrium. The intra-atrial septum is then divided in line with this incision to expose the
mitral valve. An increased incidence of junctional arrhythmias, possibly owing to
transecting the sinus node artery, is reported with this incision by some authors, [97 ]
but others have not encountered long-term arrhythmias. [98 ] [101 ] Kumar et al.
prospectively compared the extended vertical transatrial approach to the standard left
atrial approach. [102 ] They found a significantly higher incidence of junctional
arrhythmias using the transeptal approach.
ASSESSMENT OF THE MITRAL VALVE FOR REPAIR
Valve analysis begins by examining the left atrium for a jet lesion caused by regurgitant
jets. The annulus is systematically evaluated for dilatation and/or deformity. Leaflets and
leaflet motion are examined next. Nerve hooks are used to assess leaflet pliability and
to assess leaflet prolapse or restricted motion. A simplified functional approach to valve
analysis has been developed by determining whether the motion of each leaflet is
normal (Type I), prolapsed (Type II), or restricted (Type III). [103 ] Lesions that produce
insufficiency with normal valve motion include annular dilatation and leaflet perforation.
Lesions that produce regurgitation with prolapsed leaflet motion include chordal rupture,
chordal elongation, papillary muscle rupture, and papillary muscle elongation. Lesions
that produce regurgitation and restricted leaflet motion include ventricular dilatation and
restricted motion of the subvalvular mechanism. The commissures are evaluated next,
looking for fusion. The chordae are examined to evaluate length, thickening, fusion, or
rupture. The papillary muscles then are assessed, looking for elongation or rupture
secondary to infarction.
TYPES OF MITRAL VALVE DISEASE
Degenerative Mitral Valve Disease
Mitral valve prolapse is a recognized pathologic entity that is also called floppy mitral
valve, myxomatous mitral valve, and degenerative mitral valve disease. [104 ] An
autosomal dominant inheritance of mitral valve prolapse has been identified and more
recently two familial abnormalities of mitral valve motion (leaflet billowing and dynamic
expansion on the mitral annulus) were recognized. [105 ] [107 ] Mitral valve prolapse
occurs in 45 percent of the general population, and is the most commonly known
abnormality of human heart valves. [108 ] An estimated 7 million people in the United
States have mitral valve prolapse, but the number who develop significant mitral
insufficiency is relatively small. Multiple reports suggest that approximately 5 percent of
patients with prolapse ultimately develop mitral insufficiency that requires surgery. [109 ]
[112 ] Assuming these estimates are correct, 4,0006,000 patients need surgery
annually for degenerative mitral insufficiency. Additionally, 11 percent of patients with
endocarditis (approximately 1,150 patients) have mitral valve prolapse. An unknown
number of these patients will require surgery for complications of endocarditis. [106 ]
Degenerative disease is the most common etiology of mitral valve disease in patients
who require mitral valve surgery in the United States and Europe. Three thousand three
hundred sixty procedures on native mitral valves were performed at The Cleveland
Clinic Foundation from 1985 through 1994. Rheumatic valvulitis was the cause in 15
percent of cases; degenerative disease in 77 percent; and the remaining operations
were for endocarditis, ischemic mitral valve disease, or miscellaneous causes (Fig.
33-2) . Rheumatic valvulitis now is less common, but degenerative mitral insufficiency
has increased in the surgical population during the last three decades. [113 ] [115 ] This
change in surgical pathology is related to the decreased incidence of rheumatic fever
and the aging of surgical patients. [116 ]
Edwards provided an excellent description of degenerative or floppy mitral valve

disease. [117 ] The classic features of floppy mitral valve result from interchordal
hooding more than 4 mm high that involves both rough and clear zones of the leaflet.
The posterior leaflet is involved more commonly than the anterior leaflet. When the
anterior leaflet is involved, the posteromedial half is affected to a greater degree than
the anterolateral half. The chordae may be elongated and thinned, ruptured, or
thickened and fused. Edwards accurately described several secondary changes of the
floppy mitral valve, including fibrous thickening of the free edge of the leaflet, fibrous
deposits on the ventricular surface of the leaflets, friction lesions on the ventricular
surface, and contact thrombosis. Contact thrombosis is the suspected source of
systemic emboli that cause transient cerebrovascular accidents. [118 ]
The pathology found in degenerative valve disease varies considerably and influences
the probability of mitral valvuloplasty and repair. Ruptured posterior chordae is the most
common finding. [43 ] The variety of pathologic findings and the likelihood of repairing
the valve in patients with degenerative mitral pathology is shown in Figure 33-3 .
Mitral valvular degenerative disease is a progressive process. Chordal involvement

must be considered as a continuum in which chordae may be normal, elongated,
attenuated, or ruptured. The location and extent to which chordae are abnormal
determine the surgical techniques used for repair. When chordae are markedly
attenuated, they should be resected and the prolapsing portion of the mitral leaflet
treated as if the chordae were ruptured.
Ruptured chordae to the middle scallop of the posterior leaflet is the most common
problem and is corrected by quadrilateral resection of the involved leaflet segment with
reapproximation of the annulus and leaflet (Fig. 33-4) . Slight variations of this pathology
may occur. When two areas with ruptured chordae are found, both sections of the
posterior leaflet are excised with closure of the defects (Fig. 33-5) .
In slightly more than one-third of patients, mitral valve incompetence is caused by

prolapse of the anterior leaflet or both the anterior and posterior leaflets. Anterior leaflet
prolapse is much more difficult to correct using repair techniques. [119 ] Results of
anterior leaflet repair therefore are less predictable. Previously, surgeons considered
anterior leaflet prolapse an indication for mitral valve replacement. However, with more
experience with posterior leaflet repair, attempts to repair anterior leaflet prolapse
increased and several techniques are now available. Chordal transfer and chordal
replacement are the most frequently used. Because the anterior leaflet is the main
closing mechanism of the mitral valve, the entire leaflet must remain. Triangular
resection of the anterior leaflet has been abandoned except for isolated cases of
endocarditis. [103 ] , [120 ] Newer techniques of chordal transfer, [70 ] , [121 ] [123 ]
chordal shortening, [120 ] , [124 ] and chordal replacement [125 ] [127 ] using expanded
polytetrafluroethylene (PTFE) have advocates, but it is not yet settled which is the best
technique.
There is little evidence that one technique is better than another. Carpentier's group
[121 ] favors chordal transfer if anterior leaflet prolapse is caused by ruptured chordae.
However, if the cause of prolapse is chordal elongation, then chordal shortening is
preferred. Chordal shortening is preferred if exposure is good and extremely thin
chordae or hypoplastic papillary muscles are not present. The Cleveland Clinic Group
favors chordal transfer when possible [123 ] and others [125 ] [127 ] prefer to treat
anterior leaflet prolapse with chordal replacement.
CHORDAL SHORTENING
Anterior leaflet prolapse most often is corrected by chordal shortening. The usual
technique buries elongated chordae into the papillary muscle. In this procedure, excess
chordal tissue is tucked into a longitudinal slit made into the tip of the papillary muscle
and is sutured securely. Approximately one-half of the excess length is tucked into the
papillary muscle (Fig. 33-6) . Deloche et al. report excellent long-term results in 89
patients who had chordal shortening using this technique. [120 ]
An alternative method attaches the shortened chord to the under surface of the mitral
leaflet by passing a suture through the chordae below the leaflet at the exact distance to
be shortened. The other end of the suture is passed midway between the first suture
and the under surface of the leaflet. Both needles are then passed through the leaflet, to
emerge close to each other on the atrial side. When tied, excessive chordal length is
drawn up beneath the leaflet and the leaflet is pulled down to the plane of the mitral
annulus to restore apposition to the other leaflet. Sutures preferably are placed through
somewhat thickened or fibrotic areas of the leaflet to avoid tears of normal, thin leaflet
tissue. Gregori et al. recently described a technique to repair elongated chordae when
papillary muscles are either thinner or shorter than usual. [128 ] A small incision is made
in a thickened portion of the mitral leaflet near the edge to which the elongated chordae
are attached. The elongated chordae are pulled up through the incision in the leaflet and
the incision is closed to secure the delivered chordae to the atrial surface of the leaflet.
This method facilitates the decision of how much length to shorten. The redundant
chordae are fastened to the atrial surface of the mitral leaflet. Long-term results for
these simple methods of chordal shortening are not yet available. Echocardiography on
22 patients followed a mean of 14 months revealed 20 patients with no or mild
regurgitation and two who required reoperation at three and four months postoperatively
for progressive rheumatic disease. No thromboembolic events were recorded.
CHORDAL TRANSFER
The second most common method used to treat anterior leaflet prolapse secondary to
chordal elongation is chordal transfer. Normal chordae from the posterior leaflet or
normal secondary chordae of the anterior leaflet may be transferred to correct a
prolapsing or flail anterior leaflet. Posterior chordal transfer is a reproducible and
durable method to repair anterior leaflet prolapse. Lessana et al. demonstrated
excellent results in 39 patients with a 97 percent freedom from reoperation at four years.
[71 ] Uva et al. and Salati et al. reported similar superb results. [121 ] , [122 ]
The technique of posterior chordal transfer involves transposing a segment of the

normal posterior leaflet to the free edge of the anterior mitral leaflet so that the
transposed leaflet (and chordae) replace the flail or ruptured primary chordae of the
anterior leaflet. The transposed leaflet tissue is attached to the anterior leaflet using
interrupted 5-0 multi-filament sutures. A quadrilateral resection of the normal posterior
leaflet is required to transfer the posterior leaflet tissue and attached chordae. The
resulting defect is repaired in standard fashion (Fig. 33-7) . When secondary chordae
are transposed from the anterior leaflet to the free edge, they are simply sutured into
place and no further repair is required (Fig. 33-8) .
Chordal transfer has recently been shown to be superior to chordal shortening. Smedira
et al. compared 31 patients undergoing chordal shortening with 77 patients undergoing
chordal transfer for repair of anterior mitral leaflet prolapse. [123 ] Five year actuarial
freedom from reoperation was 90 percent: 96 percent for the transfer group and 74
percent for the shortening group ( p = .003). Chordal shortening and New York Heart
Association functional Class III and IV were independent predictors for reoperation. The
reason for failure in six of seven patients who had reoperation after chordal shortening
was rupture of previously shortened chordae at the point of insertion to the papillary
muscle. Zussa et al. abandoned chordal shortening because of similar problems. [127 ]
Posterior chordal transfer usually includes multiple primary and secondary chordae and
may have a mechanical advantage that reduces and more evenly distributes chordal
tension. This may explain the superior long-term results of posterior chordal transfer
compared to chordal shortening.
CHORDAL REPLACEMENT
For many years, replacement of diseased chordae was used to repair anterior leaflet
prolapse. Materials used included silk, Teflon, nylon, and autologous pericardium. [22 ] ,
[129 ] , [132 ] PTFE sutures were initially used to substitute for chordae tendineae in
sheep by Vetter. [133 ] The prosthetic chordae did not calcify and became completely
covered by fibrous tissue at long-term follow-up. At reoperation the gross appearance
of these prosthetic chordae were remarkably similar to that of natural ones. David noted
that in humans, prosthetic chords may not become covered with an endothelial layer as
readily as in experimental animals. [134 ] Nonetheless, artificial chordae are associated
with low embolic and low infection rates. Although some authors prefer chordal
replacement to chordal transfer, others [126 ] prefer chordal replacement with PTFE
only when other methods of chordal transfer fail or are inappropriate. [125 ] , [126 ] Early
results using PTFE for chordal replacement are excellent. Zussa et al. reported 106
patients with artificial mitral chordae and a low reoperation rate. [126 ] Two patients
required valve replacement during the same operation because of residual
regurgitation. Despite excellent results in experienced hands, the correct length of
artificial chordae may be difficult to determine. This has limited more widespread use of
this technique. Kasegawa et al. and Frater propose several methods to minimize the
time required to determine the proper length of artificial chordae by using
echocardiographic intraoperative assessment. [135 ] , [137 ]
ANNULOPLASTY
Annular enlargement inevitably occurs with mitral insufficiency. Uniformly, annular

enlargement occurs only along the posterior annulus because the anterior annulus is
attached to the strong fibrous skeleton of the heart, the fibrous trigone. An annuloplasty
is performed to correct annular dilatation, increase leaflet coaptation, reinforce suture
lines, and prevent further annular dilatation. Accurate sizing of the annulus is critical to
allow coaptation of the anterior and posterior leaflets following repair. Selecting the
appropriate-size annuloplasty ring is done by sizing the area of the anterior leaflet of the
mitral valve. Two large nerve hooks passed behind the major chordae of the anterior
leaflet unfurl the leaflet and facilitate sizing.
Early mitral annuloplasties reduced the posterior annulus by plicating the annulus at the
commissure as described by Wooler et al., Kay et al., and Reed et al. [14 ] [16 ] These
annuloplasties were performed by taking small, anchoring suture bites of the anterior
annulus at the commissure and progressively larger bites along the adjacent posterior
annulus, to effectively decrease the length of the posterior annulus. In 1971, Carpentier
introduced the concept of using a rigid complete ring to evenly distribute tension along
the entire annulus. [23 ] Duran subsequently introduced a flexible, completely closed ring
that allowed even distribution of tension along the posterior annulus while maintaining
flexibility of the annulus during the cardiac cycle. [24 ] Completely flexible rings maintain
better left ventricular function than rigid rings. [138 ] An adjustable annulus was
developed to change the size of the annulus after implantation. [139 ]
Some surgeons only perform posterior annuloplasty because the anterior annulus does
not dilate. By eliminating that part of the repair, the procedure is simplified and
shortened. Early reports suggest that a complete ring distorts the anterior leaflet and
leads to left ventricular outflow tract obstruction and systolic anterior motion (SAM) of
the mitral valve. [140 ] It is now recognized that systolic anterior motion of the mitral
valve can occur with either a flexible or rigid ring. Last, insertion of sutures along the
anterior mitral annulus may injure the anterior leaflet or the nearby aortic valve.
Various materials are used for posterior annuloplasties including continuous sutures,
PTFE, or pericardium. [141 ] [146 ] Cooley has used a ring fashioned from a segment
of tubular Dacron. [147 ]
An annuloplasty band sutured along the posterior annulus that allows accurate,
measured plication of the posterior annulus also is available. [148 ] Measured,
consistent plication of the posterior annulus requires an annuloplasty-reinforcing band
tied over a rigid rim.
Rheumatic Valvulitis
Rheumatic valve disease is the second most common cause of mitral insufficiency. It is
a progressive process that may produce mitral insufficiency or stenosis, or both.
Patients present with a wide variety of lesions depending on the stage of disease;
leaflet and chordal fusion occur late. [149 ] Since the incidence of rheumatic mitral valve
disease has steadily declined in the United States, [116 ] patients who now present for
surgery are older and tend to have mixed mitral pathology with varying degrees of
stenosis and regurgitation caused by calcification, retraction, and fibrosis of the leaflets
and thickened or obliterated chordae.
In 1984, Inoue and colleagues introduced percutaneous balloon mitral valvuloplasty for
symptomatic mitral stenosis. [150 ] This procedure offers excellent results without
surgery and is the treatment of choice for selected patients with early mitral stenosis.
[151 ] Echocardiographic criteria are used to determine the feasibility and durability of
mitral valvuloplasty. [152 ] A grading scale developed by Wilkins and colleagues [153 ]
evaluates valve mobility, leaflet thickening, calcification, and subvalvular disease (Table
33-1) . This scale reliably predicts a patient's response to balloon valvuloplasty.
Numbers are added to calculate the splitability score that varies from mild (4) to severe
(16). Results of percutaneous balloon valvuloplasty are highly dependent upon patient
selection.
Relative contraindications to balloon valvuloplasty include other valvular disease or

coronary artery disease that requires surgical intervention, left atrial or left ventricular
thrombus, a thickened atrial septum (> 4 mm), 2+ or more mitral regurgitation,
calcification of the mitral valve, or a recent thromboembolic event. [153 ] An echo
splitability score of 48 usually is found in younger patients with a loud opening snap.
These patients are excellent candidates for balloon valvuloplasty and can expect good
long-term results. Patients with an echo score of 912, however, are less likely to achieve
lasting improvement with balloon valvuloplasty and have a greater potential for
restenosis. These patients are better suited for open surgical valve repair or
replacement. Patients with a score of 13 or greater are considered poor candidates for
successful valvuloplasty (either balloon or repair) and usually will require valve
replacement.
The best treatment for mild mitral stenosis is still controversial. Balloon mitral
valvuloplasty competes with open commissurotomy. Open mitral commissurotomy is a
well-established surgical procedure with good intermediate clinical and hemodynamic
results for pure mitral stenosis. Recent series report operative mortality rates of 03
percent. [154 ] , [155 ] The ability to inspect and separate fused chordae and papillary
muscles, remove calcium from the leaflets, remove clot from the left atrium, and oversew
the left atrial appendage are advantages of open mitral commissurotomy. [156 ]
Generally, open commissurotomy and mitral valve replacement are reserved for
patients with extensive calcification or fibrosis of the mitral leaflets or chordae (high
scores).
Many patients who present with severely damaged mitral valves undergo mitral valve
repair. Mitral valve repair represents an excellent alternative to valve replacement in
terms of longer survival rates and absence of prosthetic valve-related complications.
[157 ] , [158 ] Repair techniques address the specific pathology noted at the time of
surgery. Rheumatic valvulitis may affect the entire valve or any portion. Commissural
fusion is the most common manifestation. Commissurotomy is extremely effective for
commissural fusion, but the commissurotomy should not extend to the annulus because
insufficiency will result. Extensive subvalvular involvement poses a difficult problem for
valve reconstruction. Thickened secondary chordae that limit motion of the posterior
leaflet may be incised. In selected cases, a fibrous peel can be stripped from chordae
of rheumatic valves to reveal underlying normal chordae. In 1969, Rumel et al.
described removal of fibrous tissue from thickened, immobile anterior leaflets. [159 ]
Extensive rheumatic involvement of the leaflets causes scarring and calcification that
often can be removed. Calcification that extends into the leaflet may be excised and
defects replaced with glutaraldehyde-treated pericardial patches. Mitral valve repair for
rheumatic valves is more difficult and long-term results are not as favorable as for valves
affected by degenerative pathology (Table 33-2) .
Ischemic Mitral Insufficiency
Ischemic mitral regurgitation remains one of the most challenging management

problems in cardiac surgery. Operative morbidity and mortality rates for ischemic mitral
regurgitation are higher than for other forms of mitral valve insufficiency. [159 ] [162 ]
Over the past decade, the operative approach to moderate or severe ischemic mitral
regurgitation has evolved to include surgical revascularization combined with mitral
valvuloplasty. This approach has improved operative mortality and long-term survival in
patients suffering ischemic mitral regurgitation. [146 ] , [163 ] Kay et al. reported the
largest series, of 101 patients treated with mitral valve repair for ischemic mitral
regurgitation, and compared this group to 40 patients treated with mitral valve
replacement. [163 ] Mitral valve repair was associated with better hospital and
long-term survival.
Traditionally, ischemic mitral insufficiency is a difficult lesion to repair because many

mechanisms that have only recently been understood are involved. Ischemic mitral
insufficiency may result from rupture or elongation of the papillary muscles, distortion of
papillary muscle geometry, aneurysm formation, or ventricular dilatation (Fig. 33-9) . To
perfuse the apices of the papillary muscles, coronary arteries must extend through the
entire thickness of the myocardial free wall and ascend into the papillary muscle that is
as long as one or two thicknesses of the free wall. This makes the vascular supply of the
tip of the papillary muscle extremely tenuous. Papillary muscle infarction occurs four
times more commonly to the posterior medial muscle than to the anterior lateral
papillary muscle, because blood supply to the posterior muscle originates from a
dominant right coronary artery in 90 percent of patients. [164 ] , [165 ] In contrast, the
anterior lateral papillary muscle has a dual blood supply, that originates from the left
anterior descending and circumflex coronary arteries and provides superior collateral
perfusion. Because the anterior lateral papillary muscle is wider and shorter, it is less
prone to ischemia and rupture than is the posteromedial papillary muscle.
For clinical purposes, ischemic mitral insufficiency can be classified as acuteif it occurs
within 30 days of myocardial infarctionor chronic. From a surgical point of view,
ischemic mitral insufficiency can be classified as having either leaflet prolapse or
restricted leaflet motion. Development of large animal models of ischemic mitral
insufficiency have added to our knowledge of both acute and chronic ischemic mitral
regurgitation. [166 ] [168 ]
Acute ischemic mitral insufficiency may result from papillary muscle dysfunction that
may or may not improve when the patient is rendered non-ischemic. Papillary muscle
rupture is rare and occurs in less than 1 percent of patients with fatal acute myocardial
infarction. Rupture may involve the entire papillary muscle or one head. [169 ]
Involvement of the entire muscle is incompatible with long-term survival because the
support of half of each valve leaflet is destroyed and overwhelming mitral regurgitation
results. The ruptured papillary muscle can be sutured to the juxtaposed ventricular free
wall. Rupture involving only one head of the papillary muscle causes less severe mitral
regurgitation. Survival depends on the degree to which left ventricle function has been
impaired. Rupture of one papillary muscle head can be repaired by suturing the
ruptured head to an immediately adjacent papillary muscle (Fig. 33-10) .
Chronic ischemic mitral insufficiency may be a result of elongation of papillary muscles

secondary to infarction or marked alterations in ventricular geometry that displace the
papillary muscle away from the mitral annulus. Clinically, some patients present with
prolapsed leaflet motion that suggests chordal rupture or papillary muscle elongation.
More frequently, patients present with restricted mitral leaflet motion caused by left
ventricular remodeling.
Mitral valve repair is based on the presence of restricted leaflet motion or excessive
leaflet motion. Central regurgitation without papillary muscle disease is common in
patients with ventricular dilatation secondary to ischemic heart disease. In this situation
papillary muscles are displaced laterally to cause restricted leaflet motion. Mitral annular
dilatation sufficient to cause mitral regurgitation occurs infrequently because the surface
area of the leaflets is two times the area of the mitral orifice. The annular ring has a
sphincter-like action that constricts during systole. Pathologic examination of these
patients demonstrates no annular dilatation and no correlation between annular size
and the presence or absence of regurgitation. [170 ] However, annuloplasty alone often
reduces the size of the annulus and increases the amount of leaflet coaptation to
eliminate regurgitation.
In a series of 65 patients operated on at The Cleveland Clinic for ischemic mitral

insufficiency, 60 percent demonstrated restricted leaflet motion and 40 percent,
prolapsed leaflet motion (8 owing to papillary muscle rupture, 18 owing to infarcted
papillary muscle). [146 ] Patients who presented with restricted leaflet motion were
treated with an annuloplasty ring only. Patients with prolapse received an annuloplasty
ring and other procedures: papillary shortening in 13 patients, chordal shortening in 11,
and leaflet resection in 3. Patients presenting with restricted leaflets had a significantly
decreased midterm survival compared to patients presenting with leaflet prolapse. Only
42 percent of patients survived 3 years if they presented with restricted leaflet motion
(Fig. 33-11) .
Papillary muscle dysfunction and ventricular remodeling complicate mitral valve repair in
patients with ischemic mitral insufficiency. Ischemic mitral insufficiency is now known to
be a dynamic process related to ventricular remodeling. This may explain poor clinical
results of mitral valve repair in patients operated soon after acute myocardial infarction
or with poor left ventricular function. [160 ] , [171 ] , [172 ] Because long-term results are
suboptimal in patients with poor heart function, several authors recommend valve
replacement to avoid high reoperation rates because of progressive mitral insufficiency
in these patients. [160 ] , [171 ] , [172 ] The concern is that ventricular remodeling may
affect repaired valves at a later date. Future studies investigating the pathogenesis of
ischemic mitral insufficiency should define optimal management of these patients.
Bacterial Endocarditis
Valvuloplasty techniques have recently been used in cases of native mitral valve
endocarditis. [173 ] [174 ] Mitral valve repair has several advantages; it limits the
infective process, preserves the subvalvular apparatus, preserves left ventricular
function, and leaves native tissue that is more resistant to infection than prosthetic
material. Mitral valvuloplasty is even more appealing for acute endocarditis after
valve-related morbidity of prosthetic valves is reviewed. Prosthetic valves implanted for
acute endocarditis have high rates of reinfection, perivalvular leak, valve failure, and
thromboembolic complications. [175 ]
Mitral valve endocarditis is categorized as acute or chronic. Acute (active) endocarditis

requires either positive blood cultures, operative findings of acute inflammation, or a
positive gram stain of excised tissue. Endocarditis is considered healed or inactive if
more than 6 weeks have elapsed since diagnosis a course of antibiotics is completed,
operative blood cultures are negative, and a gram stain of excised tissue is negative.
The valve is more difficult to repair during active endocarditis because of risks of
recurrent infection and questions of repair durability. Although long-term results of mitral
valvuloplasty for endocarditis are unavailable, short-term results are excellent. [173 ] ,
[174 ] Dreyfus et al. reports 35 patients who had mitral valvuloplasty for acute native
endocarditis. [173 ] Eighty percent of all patients who presented with acute endocarditis
were repaired. The most frequent pathology included chordal rupture, leaflet perforation,
annular abscess, and vegetations. Blood cultures were positive in 75 percent of
patients and Streptococcus and Staphylococcus species were the most frequently
isolated bacteria. Similar good results were reported by Hendren et al. from The
Cleveland Clinic in patients with chronic endocarditis. [174 ] At 24-month follow-up,
patient survival was 100 percent.
One hundred forty-six patients who had surgery for complications of mitral endocarditis
were reviewed. One hundred two patients underwent repair and 44 had valve
replacement. Fifty-eight patients had evidence of acute endocarditis; 88, healed
endocarditis. Hospital mortality in the acute group was lower for valve repair (3.8 vs.
21.8 percent). Survival including freedom from late death, reoperation, major
hemorrhage, thromboembolic event, and reinfection was better in repaired patients for
both acute (74 vs. 28.9 percent; p = .02) and chronic groups (86 vs. 39 percent).
Both Dreyfus and Hendren describe several techniques that are unique to valvuloplasty
surgery for endocarditis. [173 ] , [174 ] All grossly infected tissue must be resected
without concern for repair to insure that the infection is eradicated. Annular abscesses
should be unroofed and repaired separately. Autologous pericardium is used to repair
perforations, abscesses, or to extend leaflets. Leaflet repair is performed using a
monofilament running suture to discourage bacterial sequestration and subsequent
recurrence. Most causes of acute endocarditis are not associated with annular
dilatation; this eliminates the need for an annuloplasty ring. If annuloplasty is necessary,
autologous pericardium can be used.
Frequency of Mitral Valve Repair

The etiology of mitral insufficiency significantly influences the ability to repair the mitral
valve. In a large series from The Cleveland Clinic, 79 percent of 3,208 patients with
degenerative mitral valve disease were repaired: 28 percent with ischemic disease,
and a lesser percentage with rheumatic valvulitis (Fig. 33-12) .
In the group with degenerative mitral valve disease, the likelihood of mitral valve repair
varied significantly with the pathology and the experience of the surgeon. Ninety-one
percent of patients with ruptured posterior chordae and 81 percent with elongated
chordae had valvuloplasty.
Antunes et al. report a steep learning curve for mitral valvuloplasty. [176 ] A similar
learning curve was noted at The Cleveland Clinic Foundation. The incidence of mitral
valvuloplasty climbed rapidly after 1980; in 1995 68 percent of all mitral valves were
repaired (Fig. 33-13) . Figure 33-14 demonstrates the incidence of repair for all
diseases. In 1993, 88 percent of patients with degenerative mitral valve disease
underwent mitral valvuloplasty.
Previously, mitral valve repair increased cardiac ischemic time as compared to mitral
valve replacement. [177 ] This may no longer be true, but the issue raises concerns that
risks for mitral repair may be greater than for valve replacement. These concerns have
not been substantiated in The Cleveland Clinic experience. The cumulative operative
mortality rate for the entire group of 3,208 patients undergoing repair between 1985
and 1995 was 5.6 percent. The operative mortality rate for repair was 3.7 percent and
for mitral valve replacement, 8+ percent. Operative mortality was lower for all causes of
valve disease after repair than after replacement. This lower mortality rate was most
apparent in patients had repair for degenerative mitral valve disease (2.4 percent).
COMPLEX PROBLEMS IN MITRAL VALVE REPAIR
Commissural Prolapse
Rupture of commissural chordae may cause prolapse of both anterior and posterior
mitral leaflets and represents a particularly challenging problem. [120 ] , [178 ] , [179 ]
Commissural prolapse caused by chordal rupture can be repaired by excising the flail
segment and plicating the mitral annulus at the commissure and suturing the adjacent
leaflets together (Fig. 33-15) . This technique is referred to as commissural reflection or
cusp remodeling. [173 ] , [179 ] Van Herwerden et al. introduced another technique that
avoids extensive annular plication and creates a new commissure by extending the
detachment of the posterior leaflet, rotating the leaflet across the commissure to create
a new commissure. [178 ] This extended leaflet rotation plicates the annulus over a
larger circumferential area and reattaches the posterior leaflet without undue stress on
any components of the valve, even if a large section of leaflet is excised. Extended
leaflet detachment is limited to patients with moderate to severe annular dilatation and
significant redundant leaflet tissue.
Left Ventricular Outflow Tract Obstruction and Systolic Anterior Motion (SAM)
Left ventricular outflow tract obstruction caused by abnormal systolic anterior motion
(SAM) of the anterior leaflet of the mitral valve is a complication of mitral valve repair
that occurs in 4.510 percent of patients. [180 ] [182 ] SAM only occurs in patients with
degenerative mitral valve disease. The exact mechanism of SAM of the mitral valve is
debated. Most authors feel that it is caused by the anterior displacement of the line of
leaflet coaptation. [183 ] Although other mechanisms may be involved, redundant
posterior leaflet tissue appears necessary for SAM to occur. [184 ] The point of mitral
coaptation is displaced anteriorly by excessive posterior leaflet tissue pushing into the
left ventricular outflow tract. Carpentier developed a sliding leaflet advancement
procedure that removes redundant posterior leaflet tissue and ensures a line of leaflet
coaptation away from the left ventricular outflow tract. [185 ] In a report by Jebara, [186 ]
only 2 of 84 patients (2.4 percent) with anatomic features associated with a high
incidence of postoperative SAM developed SAM after this repair. [186 ] The
postoperative obstruction was mild in both patients with gradients of 18 and 20 mmHg
[186 ] (Fig. 33-16) . Perier et al. used this technique in 48 consecutive patients with
degenerative valve disease without evidence of postoperative SAM. [187 ]
Sliding leaflet repairs require more aortic cross-clamp and cardiopulmonary bypass
time than classic plication of the posterior annulus. However, a potential additional
advantage of this procedure is that the annulus is progressively narrowed along the
posterior circumference and major changes in the geometry of the left ventricle are
avoided. Plication of the mitral annulus in a single location may adversely affect
contraction of the basoconstrictor muscle that may contribute to SAM. [188 ]
SAM of the mitral valve is reported to occur more commonly with a rigid annuloplasty
ring. [181 ] , [189 ] The mechanism may be owing to reduction of the annular
anteroposterior dimension during systole and displacement of leaflet coaptation line
anteriorly. [190 ] , [191 ] SAM also occurs with flexible rings and even without an
annuloplasty ring. [192 ] , [193 ] Thus there are probably several predisposing factors to
the development of SAM aside from a slightly redundant posterior leaflet or the use of a
rigid ring. The most susceptible period for SAM is immediately after cardiopulmonary
bypass because of hypovolemia, hypotension, a hyperdynamic state induced by
catecholamines, and a small left ventricular cavity.
Mild degrees of SAM after mitral valve repair may be treated conservatively. Grossi et
al. demonstrated that most intraoperative cases of SAM regress with time. [189 ] They
reported 28 mild to moderate degrees of SAM in 439 patients who had mitral valve
repair. Medical management of hemo-dynamically significant SAM appears to follow a
benign course and consists of stopping inotropic agents, volume loading, and
increasing afterload by pure alpha-adrenergic agents. The natural history suggests no
progression, and in most cases, resolution of the left ventricular outflow gradient. The
amount of post-repair, intraoperative gradient across the left ventricular outflow tract
gradient is controversial.
Deficient Leaflet Tissue
Patients with rheumatic heart disease or endocarditis often lack sufficient leaflet tissue
for valve repair. [120 ] In the past, various materials were used to partially replace or
extend cardiac leaflet tissue but clinical results were disappointing because of tissue
shrinkage, failure, and calcification. [194 ] , [195 ]
Recently, Chauvaud et al. reported excellent results using autologous pericardium fixed
in glutaraldehyde to replace deficient leaflet tissue (Fig. 33-17) . [196 ] Glutaraldehyde
fixation mitigates the inflammatory response that causes shrinking and calcification that
plagued former materials used for leaflet extension. Chauvaud reported 64 patients who
underwent extension of mitral leaflets. The majority of patients had rheumatic valvular
disease or endocarditis. Six patients (12 percent) required reoperation for progression
of disease but no cases of shrinkage or calcification of the pericardial patches
occurred. Mitral valve function assessed by bidirectional color flow Doppler mapping
revealed trivial or absent mitral valve insufficiency in 80 percent of patients at follow-up.
Calcified Mitral Annulus
Myxomatous mitral annular calcification is a degenerative process involving the fibrous

cardiac skeleton that results from abnormal stresses produced by mitral valve disease.
[64 ] Degenerative annular calcification typically involves the posterior annulus, but it
sometimes spreads into the posterior ventricular wall. The finding is frequently
accompanied by chordal elongation and posterior leaflet incompetence. Korn et al.
distinguished calcified myxomatous degeneration from rheumatic disease because
myxomatous calcification does not involve chordae and has non-thickened leaflets. [197
] Therefore, myxomatous valves are more amenable to repair and last longer than
repaired rheumatic valves. [198 ] Calcium must be removed carefully to avoid
atrioventricular disruption, especially if it deeply invades the ventricular wall.
Reparative experience with calcified mitral annuli has been reported. [64 ] , [65 ] , [189 ]
El Asmar et al. described end-bloc resection of posterior annular calcification using
scissors and reconstruction of the annulus with interrupted mattress sutures. [65 ] There
were no operative deaths, reoperations, or thromboembolic events in 12 patients who
underwent extensive posterior annular debridement and subsequent mitral valve repair.
All patients had minimal to no residual mitral insufficiency during postoperative
echocardiography. Bichell et al. reported no operative mortality in 14 patients
undergoing mitral valve repair for myxomatous degeneration with severe annular
calcification. [64 ] Bichell described a more conservative technique using piecemeal
resection of the calcified annulus using a rongeur. Unlike El Asmar, who sometimes
produced complete atrioventricular disassociation, Bichell favors a stepwise
debridement under direct vision. At a mean follow-up of three years, one patient in
Bichell's series required reoperation and survival was 91 percent. David's group
reported similar results reconstructing the mitral annulus with autologous pericardium.
[199 ] Carpentier described a sliding atrial technique to close the atrial ventricular
groove when calcium extends to the ventricular myocardium. In such cases, the atrial
edge is dissected to mobilize a flap that is used to cover the decalcified area. [66 ]
ASSESSMENT AFTER REPAIR BEFORE CLOSURE OF THE
ATRIUM
Following mitral valve repair, competency of the valve is tested by injecting saline into
the left ventricle under pressure. The line of leaflet closure should be parallel to the
annulus of the posterior leaflet (Fig. 33-18) . Anatomic defects should be corrected
before tying the annuloplasty device in place since the device substantially reduces
exposure. The saline test is not completely reliable because the heart is flaccid. The
aortic root should be de-aired and distended with antegrade cardioplegia during
testing.
If the repair is adequate the annuloplasty ring is tied into position and the atrium is
closed. Air is removed carefully from the aortic root to prevent perioperative myocardial
infarction [95 ] and cerebral emboli. After weaning from the heart-lung machine, the
repair is assessed under loaded conditions using transesophageal echocardiography.
Trace to 1+ mitral regurgitation is acceptable. Mitral regurgitation of 2+ or greater is
unacceptable and requires either further repair or replacement of the valve.
Approximately 8 percent of patients undergoing mitral valve repair fail intraoperative

testing. [200 ] Causes of immediate failure are left ventricular outflow tract obstruction,
incomplete correction, or suture dehiscence (Fig. 33-19) . Fix et al. reviewed the
long-term prognosis of 76 patients who had less than perfect results (1+ or 2+ mitral
regurgitation) by post-bypass intraoperative echocardiography and compared them to
76 patients matched for age, sex, left ventricular function, and concomitant surgery but
without mitral regurgitation by post-bypass echocardiography. [201 ] Hospital morbidity
and mortality were similar between groups. Patients with 1+ or 2+ mitral insufficiency
were more apt to undergo reoperation than patients without mitral regurgitation (4-year
estimates of freedom from reoperation, 83 vs 94 percent). These data provide
evidence that echo-perfect repair is not required for an adequate intermediate-term
outcome. However, the trend towards more late reoperations in patients with 1+ or 2+
mitral insufficiency by post-bypass echocardiography suggests the need for close
follow-up. Post-repair echocardiography is also helpful for recognizing other correctable
lesions before closing. Inflow tract obstruction is an uncommon problem but may occur
when a small, rigid annuloplasty ring is placed.
HIGHLIGHTS OF POSTOPERATIVE CARE, SPECIAL
CONSIDERATIONS, OR CONCERNS
Valve function should be assessed prior to discharge on approximately postoperative

day 4 when loading conditions are similar to those present before operation. Patients
do not require long-term anticoagulation with Coumadin or antiplatelet drugs after valve
repair if they remain in sinus rhythm. Patients in atrial fibrillation may require Coumadin
anticoagulation to reduce the risk of systemic embolic events.
RESULTS
Hospital Mortality
Despite the increased time required for valve repair, hospital mortality rates for mitral
valve repair are excellent. [202 ] Table 33-3 depicts hospital mortality rates between
1990 and 1994 for nine large series. Higher hospital mortality rates are recorded for
repaired patients with all types of mitral disease (including ischemic mitral insufficiency
and endocarditis) as compared to patients with only degenerative disease. The
cumulative hospital mortality of 3,066 patients was 3.4 percent. Reports comparing
mitral valve repair with mitral valve replacement at the same hospitals appear in Table
33-4 . These series total 1,025 patients who had mitral valve repair with an operative
mortality rate of 3.8 percent, and 1,064 patients who had mitral valve replacement with
an operative mortality rate of 6.9 percent. The lower operative mortality rate associated
with mitral valve repair is confirmed at The Cleveland Clinic. From 1985 to 1993, 2,066
patients underwent mitral valve repair with 83 deaths (4.0 percent) compared to 1,271
patients who had mitral valve replacement with 140 deaths (11 percent). Over the time
period of this study, despite a learning curve, the mortality rate for mitral valve repair
was consistently less than replacement. Using multivariate analyses, advancing age ( p
= .00001) and need for valve replacement p = .03) were predictors of increased
operative mortality. No differences between mortality rates for patients undergoing
repair caused by degenerative disease and rheumatic disease were found.
Patients who undergo mitral valve repair for ischemic disease have the highest
operative mortality of all groups (Table 33-5) . Oury et al. found that mitral valve repair
for ischemic mitral insufficiency (11.6 percent) is associated with a significantly lower
operative death rate than for mitral valve replacement (29 percent). [171 ] Presumably
mitral valve repairs can be performed with lower mortality because the entire mitral
valve mechanism is preserved for greater left ventricular function. Unfortunately, not all
patients are candidates for mitral valve repair.
Long-Term Results
Substantial data confirm the durability of mitral valve reconstruction after long-term
follow-up. Deloche et al. reported 206 consecutive patients followed a mean of 13.2
years. [120 ] Mitral insufficiency was caused by degenerative disease in 113 patients
(58 percent); rheumatic disease in 74 (38 percent); and ischemic and other causes in 8
(4 percent). Fifteen-year actuarial and valve-related survival rates were 72.4 and 82.8
percent, respectively. At 15 years, 93.9 percent of patients were free from
thromboembolism, 96.6 percent from endocarditis, 95.6 percent from
anticoagulant-related hemorrhage, and 87.3 percent from reoperation. Freedom from
reoperation was higher in the group with degenerative disease (92.7 percent) than in
the group with rheumatic disease (76.1 percent). Among the 157 survivors, 74 percent
were in New York Association functional Class I and II, and 66 percent were in sinus
rhythm. Doppler echocardiograms demonstrated normal ventricular function in 134
patients (84.5 percent), absence of mitral regurgitation in 112 (74 percent), trivial
regurgitation in 27 (17 percent) and significant regurgitation in 4 (2.5 percent).
These excellent results are confirmed by other surgical groups. [70 ] , [120 ] , [156 ] ,
[203 ] Lessana et al. reported on 275 patients suffering from mitral insufficiency or
stenosis who underwent repair. [71 ] The 13-year actual survival rate was 91.7 percent
with excellent but slightly lower survival rates in patients who required mitral and
tricuspid repair (88 percent) than in those undergoing isolated mitral repair (94.2
percent). Freedom from reoperation at 13 years was 72.1 percent for the overall series,
88.9 percent for isolated mitral repair, and 48.8 percent at 12 years for the
mitral/tricuspid group ( p < .01). Both Deloche et al. and Lessana et al. found a
statistically higher reoperative rate among rheumatic patients. [71 ] , [120 ] Freedom
from reoperation was 67.4 percent at 13 years in the rheumatic group and 98.2 percent
at 10 years in the degenerative group. Multivariate analyses identified younger age and
the addition of tricuspid valve disease as predictors of reoperation ( p < .01); freedom
from embolism was 94.7 percent for the entire series.
Cohn et al. and David et al. reported excellent results in North American patients
suffering only degenerative mitral valve disease. [156 ] , [203 ] Although follow-up rates
are shorter than in European studies, both groups report excellent actuarial survival,
freedom from stroke, and freedom from reoperation (Table 33-6) . Cohn's group noted
a significantly higher reoperation rate if no annuloplasty ring was used at the time of
repair. [156 ] David's group noted a significantly higher reoperation rate when both
leaflets were involved with myxomatous changes. [203 ] Doppler echocardiography at
follow-up revealed satisfactory mitral valve function in 96 percent of patients in David's
group.
Late recurrent mitral regurgitation is an infrequent complication of mitral valve repair.

The Cleveland Clinic reported 81 (3 percent) of 2,548 patients who required
reoperation for late mitral valve regurgitation between 1986 and 1994. The primary
valve pathology was degenerative in 47 patients (58 percent), rheumatic in 16 (20
percent), ischemic in 14 (17 percent), endocarditis in 3 (4 percent), and congenital in 1
(1 percent). Progression of the primary valve disease in 46 patients (57 percent) was
the most common cause of recurrent mitral regurgitation. Rupture of previously
shortened chordae was the mechanism of recurrent insufficiency in 17 of 28 patients
(61 percent) with progression of degenerative mitral valve disease. Other causes of late
failure included suture dehiscence and inadequate initial repair. Mitral valve
replacement was required in 79 percent of patient, and 21 percent underwent repeat
repair.
Much has been written about the difference between early and late survival following
mitral valve repair and mitral valve replacement for mitral regurgitation. Interestingly,
Cohn et al. reported no difference in operative mortality rates between mitral valve
replacement and mitral valve repair when the posterior leaflet and chordal structure
were maintained during valve replacement. [156 ] Preservation of the posterior leaflet
and chordae with mitral valve replacement are important not only for better immediate
left ventricular function, but also for improved late survival and reduced
thromboembolism.
Patients who undergo mitral valve repair for regurgitation have better long-term survival
rates than patients who have valve replacement with retention of the posterior leaflet. [60
] , [204 ] However, care must be taken in comparing long-term survival rates in groups of
unmatched, non-randomized patients. Some patients have leaflet and chordal
destruction that is not repairable. Patients who undergo one or more failed attempts to
repair the valve eventually receive valve replacement and presumably are at higher risk
of hospital death than patients who initially undergo valve replacement. However,
patients who are candidates for valve repair should be repaired because of better
long-term survival and reduced incidence of most valve-related complications
associated with artificial valves.
INDICATIONS FOR MITRAL VALVE REPLACEMENT
The indications for mitral valve replacement are variable and undergoing evolution.
Because of increasing use of reparative techniques, particularly for mitral regurgitation,
replacement or repair of a mitral valve often depends on the experience of the operating
surgeon. We believe that since reparative operations for many diseases of the mitral
valve are preferred, indications for valve replacement pertain to those patient subsets
that are unlikely to be repaired by most surgeons or which have been shown to have
poor long-term success after reconstruction. Indications are discussed according to (1)
pathophysiologic states for needing operation and (2) type of valve required (i.e.,
mechanical or bioprosthetic).
Mitral Stenosis
Mitral stenosis is caused by rheumatic fever. The incidence of this lesion has
decreased substantially in the United States in the last several decades. The diagnostic
workup of the symptomatic patient with mitral stenosis should include a complete
cardiac catheterization, including coronary angiography in any patient over the age of
40. Under age 40, echocardiographic findings of the mitral valve suffice in most
symptomatic patients for the definition of mitral valve pathology unless there is a history
of chest pain or coronary artery disease. Cardiac catheterization establishes the extent
of mitral valve stenosis by determining valve gradients and valve area. Pulmonary artery
pressure, which may be extremely high in long-standing cases of mitral stenosis, is also
documented. In general, operation is prescribed when the mean valve area is 1.0 cm 2
or less [35 ] ; however, with a mixed lesion of mitral stenosis and mitral regurgitation, the
valve area in symptomatic patients occasionally may be as large as 1.5 cm 2 . The
degree of pulmonary artery pressure elevation secondary to mitral stenosis continues to
be an area of concern for the mitral valve surgeon. Is there any level of pulmonary
hypertension that is too high for mitral valve replacement in the current surgical era of
improved intraoperative and postoperative care? There is still no definitive answer to
this question, but most surgeons operate on patients with severe pulmonary
hypertension (suprasystemic) with the knowledge that intensive postoperative
respiratory and diuretic therapy is necessary to maintain relatively dry lungs and to
reduce the risk of severe right ventricular failure. It has been known for over 25 years
that after mitral valve replacement for mitral stenosis, pulmonary artery pressure
decreases within hours in most patients and decreases more gradually over weeks and
months in others. [36 ] [39 ]
After the courageous mitral commissurotomy of Cutler and Levine in 1923, [1 ] after the
closed mitral commissurotomy work of Harken et al. following World War II, [2 ] and after
the development of the Starr-Edwards valve, [4 ] the incidence of mitral valve operations
for rheumatic mitral disease increased enormously for a time and then decreased as
rheumatic valve disease declined. In recent years, a small resurgence in rheumatic
valve disease has been observed in emigrés from Southeast Asia and Latin America.
In the 1990s, balloon dilation of fibrotic, stenotic mitral valve became increasingly
utilized. [40 ] , [41 ] At the present time, percutaneous mitral balloon valve dilation is
used in most cases of symptomatic noncalcified, fibrotic mitral stenosis. [42 ] , [43 ]
However, open mitral commissurotomy and valvuloplasty for such patients is a very
successful operation, especially for the long term. [44 ] Unfortunately, many patients with
chronic mitral stenosis require valve replacement because the valve has developed
significant dystrophic changes, including marked thickening and shortening of all
chordae, obliteration of the subvalvular space, agglutination of the papillary muscles,
and calcification in both annular and leaflet tissue. Aggressive decalcification and
heroic reconstructive techniques for these extremely advanced pathologic valves
generally have produced poor long-term results; nevertheless, some surgeons still
advocate aggressive repairs in this subset of patients. [45 ]
The etiology of mitral regurgitation is very diverse, and the pathologic subsets that
produce mitral regurgitation are related to a number of metabolic, functional, and
anatomic abnormalities. [46 ] These can be categorized into degenerative, rheumatic,
infectious, and ischemic diseases of the mitral valve. Most of these entities are now
amenable to mitral valve repair and reconstruction with and without the use of
annuloplasty rings, as mentioned elsewhere in this book (see Chap. 33).
For any of the preceding major pathologic subsets, indications for surgery in patients
with mitral regurgitation vary from the asymptomatic patient with an enlarging but
well-functioning left ventricle and atrium to severely depressed left ventricular function.
Any symptomatic patient with significant mitral regurgitation (3 to 4+) should be
operated on, and operation should be considered in any relatively symptom-free
individual if there is objective evidence of left ventricular deterioration and documented
and significant increases in end-systolic and end-diastolic volumes. [47 ] [49 ]
Once the valve is exposed, indications for mitral valve replacement in patients with
mitral regurgitation depend on the extent of the pathology in each patient and the
reparative experience of the operating surgeon. Thus, in regurgitation from
degenerative prolapsing myxomatous valves that have a high probability of
reconstruction, mitral valve repair is indicated if the prolapse is generalized and local
findings that decrease the probability of a successful repair are absent. [50 ] , [51 ]
Similarly, if rheumatic mitral regurgitation, calcific deposits throughout the leaflet
substance, and shortened chordae and papillary muscles are encountered, mitral valve
replacement is the most prudent operation because the probability of successful repair
is low. [52 ] In ischemic mitral regurgitation, pathology that precludes satisfactory repair
includes restrictive valve motion from shortened, scarred papillary muscles, an acutely
infarcted papillary muscle, and rupture of chordae associated with extensive
calcification of valve leaflets. [53 ] , [54 ] In endocarditis, mitral valve replacement is
often required because of destruction of the valve leaflets and subvalvular mechanisms
and annular abscess formation. Although repair of the valve and avoidance of prosthetic
material are very desirable in septic situations, the extent of the destruction may
preclude repair. Therefore, mitral valve replacement is required after careful
debridement of the infectious tissue and reconstruction of the valve annulus. [55 ]
CHOICE OF VALVE TYPE
Indications for Bioprosthetic Valves
As 15-year results have become available for various bioprostheses, it is clear that
structural valve degeneration (SVD) is the most prominent drawback of these valves.
[25 ] , [27 ] , [56 ] The durability of porcine valves is less with mitral bioprostheses than
with aortic bioprostheses. The more rapid deterioration of mitral bioprostheses may be
due to higher ventricular systolic pressures against the mitral cusps as compared with
the diastolic pressures resisted by aortic bioprosthetic leaflets. Durability of
bioprosthetic valves is directly proportional to age; deterioration occurs within months or
a few years in children and young adults and only gradually over years in
septuagenarians and octogenarians. [27 ] , [34 ] , [56 ] [59 ] Nevertheless, there are still
indications for mitral porcine bioprosthetic valves. In a young woman who desires
children, a bioprosthesis may be used to avoid warfarin anticoagulation and fetal
damage during pregnancy. [60 ] [63 ] Patients in any age group in sinus rhythm who
wish to avoid anticoagulation may prefer a porcine bioprosthetic valve. A bioprosthetic
valve is preferred in patients over age 70 and in sinus rhythm, since these valves
deteriorate more slowly in older patients. In addition, as observed by Grunkemeier et
al., [64 ] some 60-year-olds may not outlive their prosthetic valves because of comorbid
disease. Specifically, patients who require combined mitral valve replacement and
coronary bypass grafting for ischemic mitral regurgitation and coronary artery disease
have significantly reduced long-term survival as compared with patients who do not
have concomitant coronary artery disease. [58 ] , [59 ] , [65 ] [71 ] These individuals may
avoid anticoagulation with little risk of reoperation.
There is recent preliminary experience from European centers utilizing unstented

homograft [72 ] and heterograft [73 ] , [74 ] mitral valve replacements, particularly in
patients with endocarditis. The prosthetic valve is transplanted, donor papillary muscles
are reattached to recipient papillary muscles, and the annulus is sutured
circumferentially. Early results suggest that this operation may be a feasible alternative
to stented valve replacement in patients with endocarditis.
Indications for Mechanical Valves
Prosthetic (mechanical) mitral valve replacement is considerably more common today

than bioprosthetic mitral valve replacement, about 75 versus 25 percent worldwide.
Currently available prosthetic valves in the United States, in descending order of
popularity, are the bileaflet, the tilting-disk, and the ball-and-cage valve. For the young
patient, the patient in chronic atrial fibrillation who requires long-term anticoagulation, or
any patient who wants to minimize the chance of reoperation, a prosthetic valve should
be chosen if valve replacement is required. The St. Jude Medical bileaflet valve is the
most widely used prosthetic mitral valve at present because it has good hemodynamic
characteristics and is easy to insert. Indications to choose one prosthetic or another
vary primarily by surgeon preference and occasionally depending on the state of the
annulus and whether or not there have been multiple previous operations. For example,
infrequently the mitral annulus provides poor anchorage with subsequent perivalvular
leak with the bileaflet or tilting-disk valve, which requires an everting suture technique. In
this instance, the central-flow Starr-Edwards ball-and-cage valve with a bulky sewing
ring may be chosen to reduce the probability of subsequent perivalvular leak.
HEMODYNAMICS OF PROSTHETIC MITRAL VALVES
The designs of mechanical and bioprosthetic heart valves have evolved over the last
three decades in an effort to develop the ideal replacement for the pathologic mitral
valve. Biochemical and engineering advances have produced hemodynamic
improvements and reduced morbidity from valve-related complications. The ideal valve,
however, is not available, and the positive and negative characteristics of current valves
must be considered when choosing the most appropriate valve for an individual patient.
The optimal heart valve exerts minimal resistance to forward blood flow and allows only
trivial regurgitant backflow as the occluder closes. The design must cause minimal
turbulence and stasis in vivo during physiologic flow conditions. The valve must be
durable enough to last a lifetime and must be constructed of biomaterials that are
nonantigenic, nontoxic, nonimmunogenic, and noncarcinogenic. The valve also must
have a low incidence of thromboembolism.
The opening resistance to blood flow is determined by the orifice diameter; the size,
shape, and weight of the occluder; the opening angle; and the orientation of leaflet or
disk occluders with respect to the plane of the mitral annular orifice for any given annular
size. Least resistance to transvalvular blood flow during diastole for valves in the mitral
position is provided by a large ratio of orifice to total annular area. A wide opening
angle also improves the effective orifice area and results in decreased diastolic
pressure gradients. With an increasing orifice diameter, however, more energy is lost
across the valve as more backflow passes through the valve at end-diastole and early
systole. Table 34-1 shows hemodynamic assessments of each of the FDA-approved
mitral valve prostheses for the most commonly used mitral valve sizes. [75 ] [93 ] The
results of in vivo assessments at rest by invasive (catheterization) or noninvasive
(Doppler echocardiography) techniques are tabulated.
Blood turbulence flowing across mitral valve devices results from impedance to forward
or reverse flow. This impedance can be minimized by occluder design and orientation,
central flow through the orifice, and limited struts or pivots extending into flow areas (
Fig. 34-3 ). Hemolysis is the product of red blood cell destruction that is caused by
cavitation and shearing stresses of turbulence, high-velocity flow, regurgitation, and
mechanical damage during valve closure. [94 ] Areas of perivalvular blood stagnation
and turbulence increase platelet aggregation, activation of the coagulation proteins, and
thrombus formation.
Dynamic regurgitation is a feature of all prosthetic valves and is the sum of the closing
volume during occluder closure and the leakage volume that passes through the valve
while it is closed. The closing volume is a function of the effective orifice area and the
time needed for closure. Closure time is influenced by the difference between the
opening and closing angles of the occluder and valve ring. Leakage volume is inherent
to the design of the valve and depends on the amount of time the valve remains in the
closed position. [95 ] A small amount of regurgitant volume can be beneficial by
minimizing stasis and reducing platelet aggregation; this decreases the incidence of
valve thrombosis and valve-related thromboembolism. [75 ]
The Starr-Edwards Model 6120 is the only ball-and-cage mitral valve prosthesis
currently approved for use in the United States by the FDA. It was introduced with its
current design in 1965 after undergoing several engineering modifications. The
occluder is a barium-impregnated Silastic ball in a stellate alloy cage that projects into
the left ventricle. This valve has a large sewing ring that produces a relatively small
effective orifice and larger diastolic pressure gradients as compared with other
prosthetic valves of similar annular sizes. Leakage volumes are not inherent in the
ball-and-cage design, and in contrast to other mechanical valves, the presence of
regurgitation may indicate a pathologic process. The central ball occluder causes
lateralization of forward flow and results in turbulence and cavitation that increase the
risk of hemolysis and thromboembolic complications (see Fig. 34-3A ). Because the
cage projects into the left ventricle, it is unwise to implant this valve in small left
ventricles, where the cage may contact the ventricular wall or cause ventricular outflow
obstruction. [96 ]
Tilting-disk mitral valve prostheses have better hemodynamic characteristics as

compared with the ball-and-cage valve (see Fig. 34-3B ). The Medtronic Hall central
pivoting-disk valve was introduced in 1977 and is based on engineering design
modifications of the earlier Lillehei-Kaster valve. [97 ] The axis of the tilting disk was
moved more centrally to allow greater blood flow through the minor orifice and to reduce
stagnation in areas of low flow. The opening angle was originally increased to 78
degrees to decrease resistance to forward flow and later narrowed to 70 degrees when
in vitro studies revealed an unacceptable regurgitant volume. The opening angle of 70
degrees produced regurgitation volumes of less than 5 percent of left ventricular stroke
volume without significantly compromising forward flow. The disk occluder was allowed
to slide out of the housing at the end of the closing cycle to provide a gap through which
blood could flow to minimize stasis at the contact surfaces. [97 ] The large opening
angle and slim disk occluder along with a thinner sewing ring provide improved
hemodynamics with comparably larger effective orifice areas and lower mean diastolic
pressure gradients for each valve size. During implantation, the larger orifice should be
oriented posteriorly when using the larger valve sizes to minimize the potential for disk
impingement. Smaller valves (27 mm or less) should be oriented with the larger orifice
anteriorly to optimize in vivo hemodynamics. [79 ] , [98 ]
The Omniscience tilting-disk valve is a second-generation¸device also derived from

improvements to the design of the Lillehei-Kaster pivoting-disk valve. [99 ] This
low-profile device has a pyrolyte disk eccentrically located in a one-piece titanium
housing attached to a seamless Teflon sewing ring. Introduced in 1978, the
Omniscience prosthesis includes several engineering modifications from prior devices
in an effort to improve its hemodynamic function. The orifice-to-annular area ratio was
increased to minimize resistance to forward flow. The opening angle of 80 degrees is
relatively large to allow flow reserve in patients with high cardiac outputs and during
exercise. Resulting increases in regurgitant volumes are minimized by the disk design.
Turbulence is reduced by the curvature of the disk, and areas of stasis and shear stress
are reduced by the eccentric location of the pivot axis, in an effort to decrease the risk
of thrombosis, thromboembolism, and hemolysis. Retaining prongs are not utilized, and
the lower profile reduces the risk of impingement. [81 ] A potential hemodynamic
disadvantage that has been the subject of debate is the possibility of incomplete disk
opening in vivo. Clinical studies report postoperative mean opening angles of between
44.8 [79 ] and 75.9 degrees. [100 ] Implicated factors causing this variation include
valve sizing, orientation during implantation, and anticoagulation status. [100 ] , [101 ]
The unique design of the bileaflet St. Jude Medical valve was introduced in 1977. Two
separate pyrolyte carbon disks in a pyrolyte carbon housing are attached to a Dacron
sewing ring. The housing has two pivot guards that project into the left atrium. Flow is
more uniform, central, and laminar with less impedance than other designs. The bileaflet
design produces three different flow areas through the valve orifice, and this results in
less turbulence and decreased transmitral diastolic pressure gradients [95 ] , [102 ]
(see Fig. 34-3C ). The central opening angle is 85 degrees, with a closing angle of 30
to 35 degrees, which, along with a thin sewing ring, provides a large effective orifice
are¸a for each valve size at the expense of greater regurgitant volumes, especially at
low heart rates. Asynchronous closure of the valve leaflets in vivo also contributes to the
regurgitant volume. [103 ] The design of this prosthesis provides excellent
hemodynamic function even in small sizes [104 ] in any rotational plane. The
antianatomic plane, however, with the central slit between the leaflets oriented
perpendicular to the opening axis of the native valve leaflets, decreases the potential
risk of leaflet impingement by the posterior left ventricular wall. [105 ]
The prosthetic valve most recently approved by the FDA is the Carbomedics bileaflet
valve, introduced in 1986. This low-profile device is constructed of pyrolyte carbon and
has no pivot guards, struts, or orifice projections to decrease blood flow impedance and
turbulence through the valve. [95 ] The leaflet opening angle is 78 degrees, which, with
the bileaflet design, provides a relatively large effective orifice area and transvalvular
diastolic pressure differences only slightly greater than the St. Jude Medical bileaflet
valve. Rapid synchronous leaflet closure reduces closing regurgitant volumes to less
than that of the Bjork-Shiley pivoting-disk prosthesis, which has an opening angle of 60
degrees. Leakage volume, however, is greater with Carbomedics valves because of
backflow through gaps around pivots. Because of its narrow closing angle and large
leakage volume, the Carbomedics valve does not reduce the relatively large regurgitant
volume associated with the bileaflet design. Although this valve has good hemodynamic
function overall, in the mitral position, the 25-mm Carbomedics valve has a relatively
high diastolic pressure gradient and large regurgitant energy loss across the valve,
especially at high flows. Hemodynamic studies suggest that the Carbomedics valve
should be avoided in patients with a small mitral valve orifice. [95 ]
HEMODYNAMICS OF BIOPROSTHETIC VALVES
The porcine bioprosthetic mitral valves are designed to mimic the flow characteristics of
the in situ aortic valve. The Hancock I mitral valve bioprosthesis was introduced in 1970.
It has three gluteraldehyde-preserved porcine aortic valve leaflets on a polypropylene
stent attached to a Dacron-covered silicone sewing ring. The design allows for central
laminar flow through the valve, which tends to decrease diastolic pressure gradients
and minimize turbulence. [102 ] The stent, however, impedes forward flow and results in
relatively large diastolic pressure gradients across the bioprosthesis. The stent and the
large sewing ring contribute to effective orifice areas that are smaller than those of
size-matched mechanical valves (see Table 34-1 ).
The Carpentier-Edwards valve utilizes a flexible stent to decrease the stress of leaflet
flexion while maintaining its overall configuration. [96 ] Because of the relatively small
effective orifice-to-total-annulus area ratio for the Carpentier-Edwards valve, only sizes
31 or 33 mm are recommended for the mitral position. [96 ] Exercise studies show that
the effective orifice area increases significantly with increased blood flow across the
valve but that diastolic gradients also increase, although to a lesser degree. [90 ] , [92 ]
Porcine bioprostheses in the mitral position should be avoided in patients with small left
ventricles because of the possibility of ventricular rupture or left ventricular outflow
obstruction caused by the large struts. [106 ]
Structural valve deterioration is seen after long-term follow-up of patients with porcine
bioprostheses and results in mitral stenosis or regurgitation or both. Hemodynamic
studies early after operation and at 5 years reveal higher average diastolic pressure
gradients and smaller effective orifice areas when compared in the same patients at the
follow-up study. Most of these patients show hemodynamic evidence of valvular
deterioration prior to any clinical signs or symptoms. [92 ] Porcine valves have the
advantage of low thrombogenicity, which must be weighed against poor long-term
durability and subsequent hemodynamic deterioration and reoperation.
Anesthetic Preparation and Management of Cardiopulmonary Bypass for Mitral

Valve Replacement
Preferred anesthesia for mitral valve replacement combines a narcotic and an

inhalation anesthetic to facilitate extubation. [107 ] Anesthetic management is dictated
by the wide variety of functional disabilities and hemodynamic abnormalities of patients
who undergo mitral valve replacement. For example, in a cachetic, functional class IV
mitral stenosis patient with severe pulmonary hypertension, postoperative mechanical
ventilation for 1 or 2 days is planned to remove excess pulmonary fluid by diuresis,
positive pressure, and bronchial toilet and to compensate for reduced strength for
breathing. On the other hand, healthy, young patients undergoing mitral valve
replacement usually have a short-acting anesthetic and are extubated within 6 hours
following surgery.
Monitoring should include arterial and venous lines, a urinary catheter, and a
pre-bypass-placed pulmonary artery catheter to measure pulmonary pressures and
cardiac output. Following valve replacement, a left atrial catheter directly inserted
through the left atrial incision is often used to allow measurement of pulmonary vascular
resistance. Preoperative intravenous prophylactic antibiotics are administered to all
patients and are continued for 2 postoperative days until lines are removed. Temporary
ventricular pacing wires are placed, and in many instances, temporary atrial pacing
wires are placed for possible pacing or diagnosis of various atrial arrhythmias.
Cardiopulmonary bypass is instituted by placing two right-angle cannulas into the

superior and inferior venae cavae. We place a small (22 French) plastic or metal
cannula directly into the superior vena cava, above the sinoatrial node. The inferior
caval cannula is placed at the entrance of the inferior vena cava, low in the right atrium.
These insertion sites keep the caval catheters out of the operative field and yet maintain
excellent bicaval drainage. An arterial cannula is placed in the distal ascending aorta.
Bypass flows are approximately 1.5 liters/min per m 2 , and moderate hypothermia
(30°C) is used. Myocardial protection includes antegrade and retrograde blood
cardioplegia and profound myocardial hypothermia. [108 ] [110 ] Retrograde
cardioplegia is useful for all valve surgery to protect the ischemic left ventricle and to
help remove ascending aorta bubbles. Antegrade cardioplegia, used as an initial
loading dose, is augmented by intermittent retrograde cardioplegia every 20 minutes.
When the atrium is retracted during valve replacement, the aortic valve is distorted, and
antegrade cardioplegia tends to fill the ventricle.
Exposure of the Mitral Valve
Evolution of meticulous and complicated methods of mitral valve repair and

reconstruction has required optimal exposure of the mitral valve. In primary operations,
median sternotomy, development of Sondergaard's plane, and incision of the left atrium
close to the atrial septum provide excellent exposure [111 ] , [112 ] (Fig. 34-4) . This
incision is a ubiquitous one, and we have rarely seen indications for use of other
incisions, such as the superior approach through the dome of the left atrium, [113 ] [115
] the so-called biatrial incision popularized by Guiraudon et al., [116 ] division of the
superior vena cava, [117 ] , [118 ] and the less common but occasionally useful
trans-right atrial septal incision. [115 ] , [119 ]
There is one incision, however, that is useful in reoperative mitral valve replacement
patients (see Fig. 34-4 ). This is the anterior right thoracotomy approach utilizing
femoro-femoral bypass in patients with very specific indications that make a sternotomy
difficult and hazardous. Criteria include patients in whom there is a previously placed
stented aortic prosthesis; patients who have several patent bypass grafts, particularly
an internal thoracic artery to left anterior descending artery; patients who have had
multiple previous valve replacements so that there is a virtual symphysis between the
right ventricle and sternum; and those who previously had severe, deep, infectious
mediastinitis that may make dissection extremely difficult and hazardous. Many patients
have combinations of these factors and therefore warrant exposure of the valve via right
thoracotomy [120 ] (Fig. 34-5) . A potential disadvantage of the right thoracotomy
incision is the inability to completely evacuate air from the patient's heart. Intraoperative
transesophageal echocardiography and positioning the patient so that the left atrial
incision is uppermost facilitate removal of air in the the left heart chambers.
Cannulation for right anterior thoracotomy usually involves the right femoral vein and
artery, but intrathoracic bicaval cannulation also can be used. An ascending aortic
cannula also can be placed through this incision if severe peripheral vascular disease is
present. We have used right anterior thoracotomy in about 100 patients. Myocardial
protection consists of deep systemic hypothermia (20°C), reduction of bypass flow
when anatomically critical areas need to be addressed, and maintenance of perfusion
throughout the period of cardiopulmonary bypass. The aorta is not cross-clamped, and
cardioplegia is not administered. Moderate to severe aortic regurgitation is a
contraindication to this approach.
Intracardiac Technique
Operation entails secure fixation of a valve prosthesis to the annulus by reliable suture
techniques without damage to adjacent structures or myocardium and without tissue
interference with valve function (see Fig. 34-5 ). Implantation should prevent injury to
anatomic structures surrounding the mitral valve annulus. Figure 34-6 shows the
proximity of important cardiac structures near the mitral valve annulus. These include the
circumflex coronary artery within the atrioventricular (AV) groove, the left atrial
appendage, the aortic valve in continuity with the anterior mitral curtain, and the AV
node.
An accumulation of laboratory and clinical evidence indicates that preservation of

papillary musclechordal attachments to the annulus is important for maintenance of left
ventricular function. In patients with mitral stenosis with agglutinated, fibrotic chordae
and papillary muscles, preservation of these structures probably has little effect on left
ventricular dysfunction but does protect the AV groove from rupture by preserving the
posterior leaflet. However, preservation of the posterior mitral leaflet may preclude an
adequately sized prosthesis. If fibrotic, agglutinated chordae and the posterior leaflet
are excised, placement of artificial Gore-Tex chordae to reattach the papillary muscles
to the annulus may improve early and late preservation of cardiac output. [121 ] , [122 ]
In patients with mitral regurgitation, however, it is important to preserve as much of the
papillary muscle and annular interaction as possible. This can be achieved by a variety
of techniques, as shown in Figure 34-7 . The anterior leaflet may be partially excised
and brought to the posterior leaflet [123 ] (see Fig. 34-7 ) or can be partially excised and
furled to the anterior annulus by a running Prolene suture [124 ] (see Fig. 34-7B ).
Experimental and clinical evidence suggests that preservation of the conical shape of
the ventricle is important to maintain normal cardiac output [125 ] [129 ] and that
assumption of a globular shape from cutting papillary muscles is deleterious to left
ventricular function. Furthermore, preservation of the posterior leaflet and chordae has
dramatically reduced the incidence o¸f perforation of the left ventricle and
atrioventricular separation during mitral valve replacement. [130 ] [133 ]
Suturing techniques vary according to the type of valve that is implanted. The
bioprosthetic valve is preferentially inserted with the sutures placed from ventricle to
atrium (noneverting or subannular). This has been shown to be the strongest type of
suturing technique to the mitral annulus and is used with this valve and the central-flow
Starr-Edwards ball-and-cage valve [134 ] ( Fig. 34-8A ).
To ensure adequate function of bileaflet or tilting-disk valves, everting sutures (atrium to

ventricle to sewing ring) should be used (see Fig. 34-8B ). This technique pushes the
prosthetic valve out into the center of the orifice and minimizes any tissue interference of
the prosthetic valve leaflets. This is particularly important if annular-chordal attachments
are preserved. Teflon pledgeted sutures, particularly with the thin sewing rings of the
currently available bileaflet and tilting-disk valves, should be used. If a bioprosthetic
valve is inserted, a dental mirror is used to ensure that no annular suture is wrapped
around a stent strut. A running Prolene suture for implantation of mitral valves has been
advocated by some surgeons. [135 ] [137 ] This technique makes a very clean suture
line with minimal knots but runs the risk of valve dehiscence if an infection occurs. [138 ]
During excision of a previously placed valve prosthesiseither a degenerated

bioprosthesis or a dysfunctional mechanical prosthesiscare must be taken to prevent
injury to surrounding structures. Our technique is to use dissectors to expose the sewing
ring and sutures by dissecting pannus and other material off. Knots of the previously
placed sutures are cut, and a plane is developed between the sewing ring, the annulus,
and other surrounding structures, especially the left ventricular myocardium. Using an
endarterectomy dissector, the valve prosthesis literally can be dissected away without
injury to any of the surrounding structures. Following the plane of the device as it lies
within the heart rather than trying to excise inside or outside the prosthesis prevents any
injury to adjacent structures. Once the prosthesis is removed, all residual debris,
pannus, pledgets, and unnecessary valve tissue are carefully debrided before beginning
the suturing process for the new valve.
Prior to closure, the left atrial appendage is ligated by suture or stapled to prevent clot
formation [139 ] , [140 ] in patients with chronic atrial fibrillation, enlarged left atrium, or
left atrial thrombus. The atrium is closed by a running Prolene suture, making sure that
endocardial surfaces are approximated. A left atrial catheter is inserted through the
suture line.
Weaning off Cardiopulmonary Bypass
We use transesophageal echocardiography for every valve operation and particularly

for mitral valves, where excellent images can be obtained. The echocardiograms
provide information about valve and left ventricular function, possible retained material
in the left atrium including thrombus, and removal of intracardiac air. [141 ] [143 ]
Once deairing maneuvers are completed, and after the patient is completely rewarmed,
venous return is partially occluded, and the heart is gradually volume loaded. Pulmonary
artery pressures are monitored carefully. Pharmacologic agents, such as amrinone or
dobutamine, particularly for right ventricular overload, are often used.
Postoperative Care
Postoperative care is directed toward the resumption of normal cardiac output,

respiratory function, temperature control, electrolyte management, adequate renal flow,
prophylaxis against bleeding, etc. Patients with low cardiac output are managed with a
variety of pharmacologic agents after providing adequate volume loading. The left atrial
and pulmonary arterial catheters are particularly helpful in determining optimal balancing
of volume loading and myocardial function in the first hours following operation. [144 ]
Reduction of pulmonary interstitial fluid is aggressively pursued by diuresis in the

intensive care unit in patients with severe pulmonary hypertension. Most patients with
severe pulmonary hypertension can be extubated within 48 hours following surgery.
Nutritional, respiratory, and general metabolic support is provided. Many patients with
severe, long-standing mitral disease are cachetic and, despite preoperative nutritional
support, are severely catabolic at the time of operation. These patients generally
require longer periods of ventilatory support due to lack of respiratory muscle strength.
They need aggressive nutritional support with nasogastric hyperalimentation to increase
respiratory muscle strength. In patients with severe pulmonary hypertension and cardiac
cachexia who require prolonged intubation, tracheostomy may be necessary to reduce
ventilatory dead space and facilitate faster weaning and better pulmonary toilet.
Tracheostomy is usually performed by the end of first postoperative week.
Postoperative atrial arrhythmias are so common that absence is unusual. Arrhythmias

vary from rapid supraventricular tachycardias, usually atrial fibrillation, to junctional
rhythm and heart block. These arrhythmias are treated by pharmacologic agents or
pacemakers or both. If rapid atrial fibrillation cannot be controlled pharmacologically
and is destabilizing hemodynamically, emergency cardioversion is done to improve
cardiac output. Pharmacologic management of supraventricular tachycardia is usually
required but may precipitate the need for a prophylactic transvenous pacemaker if
severe slowing of the heart rate occurs.
Anticoagulation is prescribed for all patients undergoing mitral valve replacement with
either a mechanical or a bioprosthetic valve. In the first 6 weeks following operation, the
incidence of atrial and other arrhythmias is high; thus these fluctuating rhythms mandate
anticoagulation even if the basic rhythm is sinus. In addition to rhythm concerns, the left
atrial incisions and the possibility of stasis in the left atrial appendage justify full
anticoagulation with warfarin for all patients. Some surgeons advocate immediate
intravenous heparin until therapeutic warfarin doses can be reached. [145 ] , [146 ] In
our patients who are at high risk for thromboembolism, e.g., those with a large left
atrium or an intraatrial thrombus, we use dextran 500 mL every 24 hours until the patient
is anticoagulate¸d with warfarin. We believe that this is safer than heparin in the early
postoperative period and avoids blood accumulation in the pericardium.
The therapeutic International Normalized Ratio (INR) after mitral valve replacement is
2.5 to 3.5 depending on the type of valve, cardiac rhythm, and presence or absence of
the aforementioned intraoperative risk factors for thromboembolism. [139 ] , [140 ] ,
[147 ] Anticoagulation levels are in the low range for patients with tissue valves in sinus
rhythm. Patients who have mechanical valves need lifelong anticoagulation. Patients
who have bioprosthetic valves are evaluated at 6 weeks for cardiac rhythm
abnormalities. If they are in predominately sinus rhythm, warfarin is stopped, and one
aspirin tablet is given daily indefinitely. If the patient has continuous atrial fibrillation or
fluctuating rhythms, anticoagulation with warfarin is continued.
RESULTS
Early Results
The hospital mortality for mitral valve replacement with and without coronary bypass
grafting has decreased significantly since inception of mitral valve surgery. The current
risk (1996) of elective primary mitral valve replacement with and without coronary
bypass grafting is 5 to 9 percent. [127 ] , [148 ] Operative (30-day) mortality is related to
myocardial failure, multisystem organ failure, bleeding, respiratory failure in the
chronically ill, debilitated individual, infection, stroke, and very rarely, technical
problems. [149 ] Mortality is correlated with preoperative functional class, age, and
preexisting coronary artery disease. Published results on mitral valve surgery have
improved in recent years, probably because of preservation of papillary muscles
preventing midventricular rupture [130 ] [133 ] and preservation of the normal geometry
of the left ventricle, which aids in the maintenance of early postoperative cardiac output.
[124 ] [129 ] Mitral valve replacement and coronary artery bypass surgery 15 to 20 years
ago had an associated mortality of about 10 to 20 percent. [65 ] , [150 ] , [151 ] This
mortality risk also has decreased as myocardial protection has improved with the use of
blood cardioplegia and retrograde methods of administration. [108 ] [110 ] Recent
studies have indicated that the risk of combined mitral valve replacement-coronary
artery bypass grafting is now no greater than that of mitral valve repair with an
annuloplasty ring or mitral valve replacement without coronary artery bypass grafting.
[127 ] , [152 ]
Figures from the database of the Society of Thoracic Surgeons indicate that both
reoperation and emergency operation increase operative mortality (Fig. 34-9) .
Late Results
FUNCTIONAL IMPROVEMENT
In over 90 percent of patients following mitral valve replacement, functional class

improves to at least class II. A small group of patients remain in class III or IV depending
on left ventricular function prior to surgery or other coexisting morbidity.
SURVIVAL
The causes of late death in patients following mitral valve replacement are primarily
chronic myocardial dysfunction, thromboemboli and stroke, endocarditis,
anticoagulant-related hemorrhage, and coronary artery disease. The extent of left
ventricular dysfunction and patient age, particularly if myocardial and coronary diseases
are combined, also correlates with late mortality. The probability of survival after mitral
valve replacement at 10 years is 50 to 60 percent either with a tissue or a mechanical
heart valve [6 ] , [27 ] , [34 ] , [56 ] , [77 ] , [153 ] [166 ] (Table 34-2) . Unlike patients with
severe aortic regurgitation or aortic stenosis, arrhythmias seldom cause sudden death
in patients following mitral valve replacement; however, a few die from thromboembolic
stroke due to chronic atrial fibrillation. [157 ] The fact that more than 50 percent of
patients following mitral valve replacement are in chronic atrial fibrillation increases the
propensity for thromboembolic stroke despite anticoagulation and for mechanical valve
thrombosis if the anticoagulation protocol is altered. In addition, patients with older
types of prosthetic valves who receive higher-intensity anticoagulation may develop
severe anticoagulant hemorrhage. [6 ] , [167 ]
In patients with bioprosthetic valves, one of the important determinants of mortality is

reoperation secondary to structural valve degeneration. [27 ] , [34 ] , [168 ] [171 ]
Reoperative mitral valve replacement mortality has decreased significantly in recent
years to under 10 percent even in patients who have required multiple mitral valve
reoperations. [110 ] , [172 ] , [173 ] At the Brigham and Women's Hospital, operative
mortality was less than 6 percent for reoperative mitral valve operations from 1990 to
1995. [110 ] Improved myocardial protection, earlier selection of patients for
reoperation, and better perfusion techniques including frequent femorofemoral bypass
to protect the right ventricle during incision and dissection of the heart are factors
contributing to decreased mortality. [110 ] , [120 ] , [127 ] , [170 ] , [171 ] , [174 ]
Late Morbidity
The major morbidity in patients following mitral valve replacement is structural valve
deterioration of a bioprosthetic valve and thromboembolism and anticoagulant
hemorrhage with a mechanical prosthesis. Both valve types develop perivalvular leak
and infection.
THROMBOEMBOLISM
Thromboembolism is perhaps the most common complication of either biologic or

mechanical mitral prostheses but is more frequent in patients with mechanical valves.
Chronic atrial fibrillation and local atrial factors, already discussed, increase the risk of
thromboembolism in patients with mitral prostheses. [19 ] , [25 ] , [34 ] , [159 ] , [168 ] A
number of recent studies have summarized the thromboembolic potential of various
valves [6 ] , [19 ] , [34 ] , [100 ] , [146 ] , [149 ] , [154 ] , [155 ] , [159 ] , [160 ] , [162 ] , [163
] , [169 ] , [175 ] [184 ] (Table 34-3) , and it appears that the better the valve
hemodynamics, the lower is the probability of thromboemboli. The incidence of
thromboemboli in currently available bileaflet valves and tilting-disk valves is similar to
that of bioprosthetic valvesabout 1.5 to 2.0 percent per patient-year. Thromboembolism
in patients with mitral valve replacement is lower in those with a small left atrium, sinus
rhythm, and normal cardiac output. It is much higher in patients with large left atria,
chronic atrial fibrillation, and the presence of intraatrial clot. [139 ] , [140 ] , [185 ]
Thrombosis of a mechanical valve, once a feared complication of tilting-disk valves,
[186 ] [188 ] is now relatively rare unless anticoagulation is stopped for any period of
time. Valve thrombosis can be treated with thrombolytic agents if the patient is not in
cardiogenic shock but requires surgery if the circulation is inadequate. [189 ] [192 ]
ANTICOAGULANT HEMORRHAGE
The incidence of anticoagulant-related hemorrhage has decreased markedly with

hemodynamic improvements in mitral valve prostheses. New valves do not require the
intensity of anticoagulation of older prostheses. For example, the distinctive
Starr-Edwards ball-and-cage valve requires an INR of 3.5 to 4.5. [167 ] Patients with
streamlined bileaflet or tilting-disk valves require an INR of between 2.5 and 3.5; thus
the incidence of anticoagulant hemorrhage is significantly reduced in the newer,
hemodynamically improved prostheses. [158 ] , [193 ] Table 34-3 lists the incidence of
anticoagulant hemorrhage with various bioprostheses and mechanical valves.
STRUCTURAL VALVE DEGENERATION
Structural valve degeneration (SVD) is the most important complication of the

bioprosthetic valve. The probability of structural failure with currently available porcine
valves (Hancock or Carpentier-Edwards) begins to increase 8 years after operation
and reaches over 60 percent at 15 years. [69 ] , [194 ] This finite durability is a major
impediment to long-term success of these biologic prostheses, even though the failure
rate in the elderly patient 70 years of age or older is significantly less than in younger
age groups. [66 ] [69 ] Structural valve degeneration presents as either mitral
regurgitation from leaflet tear or as calcific mitral stenosis due to calcification of valve
leaflets or as both. The appearance of a new murmur with new congestiv¸e symptoms
should prompt a noninvasive investigation of the prosthesis and elective re-replacement
if dysfunction is documented. Structural valve degeneration leading to reoperation is the
cause for at least two-thirds of the reoperations in patients with bioprostheses. [34 ] ,
[171 ] , [173 ] The probabilities of structural valve degeneration of the two commonly
used porcine biologic prostheses are shown in Tables 34-4 , 34-5, and 34-6 at 5, 10,
and 15 years. [32 ] , [34 ] , [56 ] , [164 ] , [165 ] , [169 ] , [183 ] , [195 ] , [196 ] The
incidence of reoperation is also included. With current quality controls, the incidence of
structural valve degeneration is virtually zero for bileaflet, tilting-disk, and ball-and-cage
valves.
PERIVALVULAR LEAK
Perivalvular leak is an uncommon complication because of improved surgical

techniques and the use of Teflon pledgets. The incidence of perivalvular leak for both
mechanical and biologic valves is about 0 to 1.5 percent per patient-year. [19 ] , [137 ] ,
[163 ] , [180 ] , [184 ] , [197 ] Perivalvular leak is slightly more common with the bileaflet
valve than with the porcine valve because of the need for the everting suture technique
and less bulky sewing ring. [198 ] , [199 ]
ENDOCARDITIS
Endocarditis is a feared complication after valve replacement, and prosthetic mitral

valve endocarditis often presents difficult management problems related to timing of
operation, type of operation, ability to securely fix the prosthesis, and operative and late
survival. Mitral valve endocarditis is considerably less common than aortic prosthetic
valve endocarditis, [200 ] , [201 ] but when it does appear, it may present as
septicemia, malignant burrowing infections, abscess formation, and septic emboli. With
better antibiotic prophylaxis at the time of mitral surgery and improved prophylaxis for all
patients having dental or other surgical procedures, the incidence of endocarditis is
relatively low. The probability of freedom from this morbid event is shown in Table 34-7
for both mechanical and bioprosthetic valves. [6 ] , [34 ] , [154 ] , [155 ] , [157 ] , [159 ] ,
[162 ] , [164 ] , [165 ] , [166 ] , [169 ] , [176 ] , [180 ] , [181 ] , [195 ] , [202 ] [204 ] The
diagnosis and treatment of mitral perivalvular endocarditis are related to the infecting
organism. The diagnosis is made by symptoms, appearance of a new murmur, a septic
embolus, or a large vegetation on echocardiogram. Blood cultures usually are positive,
although a small percentage of patients have culture-negative endocarditis.
Echocardiograms may show a rocking motion of the prosthesis and the presence of
vegetations. The most frequent organisms are still Streptococcus and Staphylococcus ;
the latter is usually hospital-acquired. [205 ] Antibiotic therapy depends on the sensitivity
of the organisms, but immediate high-dose intravenous therapy must begin as soon as
possible. Experience indicates that a number of patients with bioprosthetic valvular
endocarditis can be cured of low-potency organisms such as Streptococcus . However,
it is unlikely that antibiotics alone can sterilize more virulent mitral valve infections,
particularly Staphylococcus . These infections usually require urgent and sometimes
emergent surgery because of invasion of the cardiac exoskeleton.
The surgical indications for mitral valve prosthetic endocarditis are persistent sepsis,
congestive failure, perivalvular leak, large vegetations, or systemic infected emboli. [55 ]
, [206 ] , [207 ]
Operative technique is similar to other mitral procedures with respect to anesthesia,

monitoring, cardioplegia, left atrial incision, and exposure of the valve. Excision of the
valve and debridement of the annulus and abscesses must be meticulous and
extensive. All necrotic and infected tissue must be removed. After local application of an
antibacterial solution such as Betadine and local antibiotic irrigation, the annulus and
areas of tissue loss are reconstructed using autologous pericardium. Pericardium must
be used to reconstruct the mitral valve annulus, and all sutures must be placed through
the pericardial-lined annulus to obtain secure anchorage of the new prosthesis.
Autologous pericardial pledgets can be made and used instead of conventional cloth
pledgets to avoid synthetic material as much as possible. Examples of operative
techniques for closure and repair of local abscesses and infectious destruction of the
mitral valve annulus are shown on Figures 34-10 and 34-11 . [208 ]
Postoperative care should include at least 6 weeks of appropriate intravenous

antibiotics. Hospital mortality is related primarily to ongoing sepsis, multisystem organ
failure, or failure to eradicate the local infection and subsequent recurrent perivalvular
leak. Recurrence of infection depends on the type of organism and the surgeon's ability
to completely remove all areas of infection. [206 ] Recurrence of infection is the single
most important long-term complication.
CONCLUSIONS
Mitral valve replacement by mechanical or bioprosthetic valves revolutionized the care

of patients with severe mitral valve disease. Reconstructive operations of the mitral
valve have now assumed an equally important role for mitral regurgitation. A number of
advanced lesions of the mitral valve still require mitral valve replacement with reliable
devices. The bileaflet, tilting-disk, and ball-and-cage prosthetic valves are extremely
reliable in terms of durability but require long-term anticoagulation and have a high risk
of thromboembolism or thrombosis without anticoagulation. Bioprosthetic porcine
valves, conversely, in patients in sinus rhythm do not need long-term anticoagulation and
are used mainly in elderly patients who are not likely to outlive the valve and in women
who desire children and do not wish to accept the risks of warfarin or heparin during
pregnancy. The long-term durability of these valves is limited, and the probability of
valve failure at 15 years is at least 60 percent.
Improvements in mechanical valve design and biologic valve preservation of collagen

structure and resistance to calcification are ongoing and are the hopes for the future. In
addition, there is renewed interest in homograft mitral valves, which may offer better
long-term durability, as observed with cryopreserved homograft aortic valves. [209 ] ,
[210 ] Improved valve design and development of better biomaterials will eventually
improve clinical results; however, current FDA restrictions on the development and
evaluation of new prosthetic valves have an important impact on this process.
PATHOPHYSIOLOGY
The normal tricuspid valve is a tri-leaflet structure with anterior, septal, and posterior
leaflets. There are generally three papillary muscles arising from the right ventricle to
support the tricuspid valve. A large number of disease processes may affect tricuspid
valve leaflets and their supporting structures. These include rheumatic, [5 ] infective, [6 ]
traumatic, [7 ] and ischemic, [8 ] carcinoid, [9 ] myxomatous, [10 ] and collagen-vascular
diseases. [11 ] , [12 ] Pathologic involvement of the tricuspid valve may occur
concomitantly in patients who have myxomatous degeneration of the mitral valve and
mitral valve prolapse.
The most common etiology of organic tricuspid valve disease is rheumatic pancarditis.
Rheumatic tricuspid valve disease is almost always associated with severe mitral valve
disease [13 ] , [14 ] and, in the majority of patients, with aortic valve disease as well.
Pathologic changes found in patients with organic tricuspid valve disease are usually
less extensive than those affecting left-sided cardiac valves. However, the same
processes of fibrous thickening of the leaflets, [15 ] [22 ] thickening and shortening of the
chordae tendineae, and fusion at the commissures are involved. Calcification may
occur but is rarely as extensive as in mitral and aortic valves.
The most common cause of tricuspid valve regurgitation is not intrinsic or organic
involvement of the valve itself, but rather right ventricular enlargement with secondary
dilatation of the tricuspid annulus. Annular dilatation usually involves the portion of the
valve annulus that supports the posterior leaflet. Patients with functional tricuspid
regurgitation do not have the same pathologic findings as patients with organic
tricuspid valve disease. However, if severe, geometric changes affecting the right
ventricular chamber and secondary failure of the tricuspid valve may denote end-stage
cardiac dysfunction.
A wide range of lesions is associated with important functional tricuspid valve

incompetence, including left-sided valvular disease, right ventricular infarction,
congenital heart disease, various forms of right ventricular outflow tract obstruction, and
pulmonary hypertension.
Tricuspid valve incompetence also may be related to infective endocarditis and is

almost always associated with intravenous drug abuse. [23 ] , [24 ] Gram-negative
microorganisms are commonly involved, particularly Pseudomonas aeruginosa.
Staphylococcus aureus [25 ] and fungii [26 ] also may be implicated. Infective
endocarditis may produce vegetations on valve leaflets and destroy leaflet tissue.
Occasionally, right atrial tumors, collagen-vascular disease, and the carcinoid syndrome
may produce isolated tricuspid valve stenosis; however, most tricuspid stenosis is
rheumatic. Anatomic changes found in rheumatic tricuspid valve stenosis are similar to,
but usually milder than, those found in rheumatic mitral valve stenosis. Leaflets are fused
at their edges and thickened; chordae tendineae are shortened. In rheumatic tricuspid
stenosis, the subvalvular apparatus is usually only mildly involved. [27 ] [31 ]
DIAGNOSIS
Systemic venous hypertension with signs of right-sided heart failure is the hallmark of
important tricuspid valve disease, and symptoms include jugular venous distension,
peripheral edema, ascites, hepatomegaly, and in advanced cases, a pulsatile liver.
Subjective determination of the severity of these findings is an important feature of the
preoperative assessment to determine whether and which tricuspid valve intervention is
required in an individual undergoing surgery for concomitant left-sided valvular heart
lesions.
Cardiac catheterization is useful for evaluating the tricuspid valve. At catheterization, in

patients with significant tricuspid incompetence, the right atrial pressure tracing reveals
elevation of the mean right atrial pressure, absence of the x descent, and a prominent v
or c-v wave. As the severity of tricuspid regurgitation increases, the contour of the right
atrial pressure wave increasingly resembles right ventricular pulse pressure. Right atrial
and ventricular end-diastolic pressures are usually elevated in tricuspid regurgitation.
Before operation, it is often difficult to determine whether tricuspid regurgitation is a
primary abnormality of the tricuspid valve and its chordae or whether it is secondary to
left-sided disease. Pulmonary arterial systolic pressure greater than 60 mmHg
suggests left-sided valvular disease as the etiology for the tricuspid regurgitation.
Catheterization in patients with significant tricuspid stenosis reveals a diastolic

pressure gradient between the right atrium and ventricle. The gradient increases during
inspiration and decreases during expiration. A mean diastolic pressure gradient
greater than 5 mmHg often produces signs and symptoms of systemic venous
hypertension. In patients who are still in normal sinus rhythm and not in atrial fibrillation,
the right atrial a wave may be markedly exaggerated.
In addition to catheterization findings, preoperative right ventricular angiocardiography

provides a visual image of the severity of the tricuspid valve incompetence.
Angiography shows the degree of retrograde filling of the right atrium, the superior and
inferior caval veins, the hepatic veins, and the functional activity of the right ventricle. [32
] As reported previously, [33 ] 362 patients who had tricuspid valve surgery at the
Deborah Heart and Lung Center had preoperative right ventricular angiocardiography.
That analysis indicated that in patients with severe tricuspid incompetence,
preoperative angiography significantly correlated [ p < 0.001 (chi-squared)] with the
intraoperative assessment. Severity of preoperative angiographic tricuspid valve
incompetence also correlated with the need for tricuspid valve replacement as opposed
to valve repair [ p = 0.0002 (chi-squared)].
Transthoracic Doppler echocardiography is also useful in the preoperative assessment

of these patients. [34 ] [39 ] Preoperatively, echocardiography helps to establish the
anatomic basis of tricuspid valve disease. Two-dimensional echocardiography detects
tricuspid stenosis; Doppler color-flow velocity mapping quantifies tricuspid
regurgitation. Transesophageal echocardiography in the operating room assesses
tricuspid valve function before cardiopulmonary bypass. [40 ] [45 ]
Using color-flow Doppler imaging, tricuspid regurgitation is graded based on the ratio
of regurgitant jet area to right atrial area. The wider the jet area in relation to the right
atrial area, the more severe is the disease. Specifically, a ratio of 1:3 indicates mild
tricuspid regurgitation; 2:3, moderate; and ratios greater than 2:3, severe. [46 ]
During operation, right atrial and ventricular chamber sizes are noted, and the valve and
flow patterns in the right atrium are assessed by passing a finger through the right atrial
appendage. In this evaluation, the term jet is a misnomer, since even massive
regurgitant flow has a gentle, diffuse character. Multiple dynamic factors affect the
severity of tricuspid incompetence. With the induction of anesthesia, incompetence may
decrease as systemic and pulmonary vascular resistance decrease. To assess the
valve accurately, systemic arterial pressure must be raised to 120 to 140 mmHg before
clinical or echocardiographic determination of the severity of tricuspid incompetence is
made with confidence.
SURGICAL DECISION MAKING
Although a number of clinical and diagnostic tools are available for the assessment of
the severity of tricuspid valve incompetence, the final surgical decision is often difficult
and subjective. Reduction in left atrial and ventricular pressures usually decreases
pulmonary vascular resistance and right ventricular afterload. This may or may not
reduce right ventricular chamber size and tricuspid incompetence. Although others
report that up to 20 percent of patients needing mitral valve repair or replacement have
tricuspid valve intervention, [47 ] at the Deborah Heart and Lung Center, only 5 percent (
n = 530) of 9247 patients who required valvular surgery from 1961 through 1987 had
tricuspid repair ( n = 351, 66 percent) or replacement ( n = 179, 34 percent). [48 ]
Many authors contend that tricuspid surgery is indicated at the time of mitral valve
surgery in patients with functional and organic forms of tricuspid valve incompetence.
[49 ] [51 ] However, it is difficult to predict the natural history and prognosis in patients
who require mitral valve surgery and who have moderately severe tricuspid valve
incompetence ignored. [52 ] [54 ] Up to 35 percent of patients with important functional
tricuspid valve incompetence may have late valvular incompetence if the valve is not
improved at the time of mitral valve surgery. [55 ] [62 ] Unfortunately, it is not always
clear whether functional tricuspid valve incompetence, which might be expected to
improve following relief of left-sided valvular disease, will improve or whether important
residual tricuspid incompetence will remain. Expected residual elevated left atrial and
ventricular end-diastolic pressures, pulmonary hypertension, right ventricular
enlargement, and poor contractility increase the likelihood of important postoperative
tricuspid incompetence.
The risk of isolated mitral versus combined mitral and tricuspid operation also must be
considered. The surgical risk of isolated mitral valve surgery is lower than the risk of
mitral plus tricuspid valve surgery. [63 ] [65 ] It seems self-evident that if the tricuspid
valve requires repair or replacement, the surgical risk will be higher, but this higher risk
is not because of the additional operative intervention. The higher risk is usually related
to the end-stage nature of the heart disease, when the right ventricle decompensates
and dilates and important tricuspid valve incompetence develops. The presence of
pulmonary hypertension and right ventricular cardiomyopathy and the negative effects of
chronic systemic venous hypertension all contribute to poorer early and late outcomes.
[66 ] , [67 ]
Since it is difficult to identify patients who need tricuspid valvular procedures, the
Deborah Heart and Lung Center has developed an algorithm to aid the decision. If a
patient has peripheral edema and jugular venous distension and the severity of tricuspid
valve incompetence is greater than grade III/IV, tricuspid valve annuloplasty is
performed. If the patient has grade V/VI tricuspid valve incompetence and a pulsatile
liver and ascites, the valve is replaced. Also, if an annuloplasty will not produce a
competent valve because, for example, valve leaflets are markedly attenuated by
chronic severe incompetence, the valve is replaced.
Tricuspid Valve Reconstruction
Once the decision is made that the tricuspid valve needs to be addressed, a
transseptal approach to the mitral valve is utilized. [68 ] Because many patients are
predisposed to coagulopathy secondary to hepatic dysfunction and have had previous
surgery, aprotinin is used. [69 ]
A median sternotomy incision is made, and heparin is given. The ascending aorta is
cannulated, and the caval veins are cannulated directly with angled metal-tip cannulas
(DLP, Grand Rapids, Mich.). Cardiopulmonary bypass is established at a flow rate of
2.2 liters/min per m 2 at a temperature of 30°C. The heart is arrested using antegrade
cold blood cardioplegia. If a long procedure is anticipated, cold blood cardioplegia is
also infused retrograde into the coronary sinus. Caval tapes are snugged, an oblique
right atriotomy incision is made, and stay sutures are placed on the right atrial wall to
arrange exposure (Figure 35-1A) . An incision is started in the posterior portion of the
interatrial septum. The incision is extended superiorly, curving anteriorly as the superior
portion of the limbus is reached. Bimanual palpation inside and outside the roof of the
right atrium allows extension superiorly without exiting the roof of the right atrium.
Inferiorly, the incision is carried anteriorly towards and, if necessary, into the coronary
sinus. To arrange the exposure of the mitral valve, stay sutures are placed on the cut
edge of the septum (Fig. 35-1B) . Retractors are not used because the resulting trauma
to the atrioventricular node may produce heart block. Once the mitral valve portion of the
procedure has been completed, the patient is rewarmed, high suction is applied to the
aortic needle vent to remove air, the aortic cross-clamp is removed, and the septum is
closed, usually with a pericardial patch (Fig. 35-1C) . Tricuspid valve repair or
replacement is performed with the heart beating.
Tricuspid Valve Annuloplasty Repair
BICUSPIDIZATION REPAIR
Three methods of tricuspid valve annuloplasty repair, with modifications, are widely
utilized. [70 ] [86 ] The most common tricuspid annuloplasty currently performed at the
Deborah Heart and Lung Center is a bicuspidization-plication repair. For this
procedure, one or two pledgeted 0 Prolene (Ethicon, Inc., Somerville, N.J.) sutures are
used to obliterate the portion of annulus encompassing the posterior leaflet of the
tricuspid valve (Fig. 35-2A,B) . This segment of the tricuspid annulus may be importantly
dilated. It also may be useful to place the Puig-Massana-Shiley annuloplasty ring
(Shiley, Inc., Irvine, Calif.) to support the repair (Fig. 35-2C,D) . The ring is placed in a
supracoronary sinus position to avoid the area of the atrioventricular node. This
prosthesis is implanted utilizing a single continuous 3-0 Prolene suture and has the
advantage that it is flexible and adjustable. Once the ring is positioned securely, the
strings of the ring are tightened, either symmetrically or asymmetrically, to obtain a
satisfactory repair. After the device is seated, with the heart beating and the pulmonary
artery clamped, competency of the valve is tested by injecting saline into the right
ventricular chamber before the adjusting suture is tied.
DE VEGA REPAIR
The DeVega operation can be used in patients with moderately severe annular
dilatation. Many modifications of this technique have been reported. [87 ] , [88 ] The
procedure is performed utilizing a single, pledgeted 0 Prolene suture (Fig. 35-2A,B) .
The suture is started at the commissure between the anterior and septal leaflets. Using
both ends, two sequential sutures are taken clockwise through the annulus around the
anterior leaflet and down to the commissure between the septal and the posterior
leaflets. The suture is then tied so that the portion of the annulus that is plicated is
reduced in a circumferential manner. This suture is tightened until it appears that the
anterior leaflet is coapting normally. Alternatively, the Carpentier tricuspid valve
annuloplasty calibrator can be used, and the suture is tightened until the dimensions of
the chosen leaflet sizer are achieved.
CARPENTIER REPAIR
The Carpentier ring may be used for more severe degrees of incompetence. The
proper size of the ring is determined by measuring the area of the anterior leaflet with a
sizer. The ring has a gap at the segment that encompasses the area of the
atrioventricular node. The ring is implanted utilizing multiple interrupted, pledgeted 2-0
Ticron (Davis and Geck, Woodbury, Conn.) sutures. Sutures for implanting the
Carpentier ring are placed through the annulus and then passed through the
annuloplasty ring (Fig. 35-2A,B) . Note that the stitches are placed much wider apart in
the tricuspid valve annulus than in the ring. This plicates and effectively imbricates the
annulus.
INTRAOPERATIVE ASSESSMENT OF TRICUSPID VALVE REPAIR
A number of methods have been used intraoperatively to assess the adequacy of a

tricuspid valve repair. These methods include injecting saline in the right ventricular
chamber while clamping the pulmonary artery, intracavitary palpation for a tricuspid
valve jet by placing a digit through the right atrial appendage, and external palpation of
the outside of the right atrial chamber. In many cases all three methods are employed to
determine adequacy of the repair. For any annuloplasty technique, if the intraoperative
assessment indicates that the repair is not satisfactory, immediate tricuspid valve
replacement should be considered. In the Deborah series of tricuspid valve operations
described later in this chapter, tricuspid incompetence was assessed intraoperatively in
134 of 459 patients following tricuspid valve repair. Assessment indicated no
incompetence in 65 patients (49 percent), 1 + incompetence in 22 (16 percent), 2+
incompetence in 30 (22 percent), 3+ incompetence in 13 (10 percent), and 4+
incompetence in 4 (3 percent).
Since 1990, 30 patients had preoperative and postoperative assessment of tricuspid

valve repair using intraoperative transesophageal echocardiography. There was a high
correlation between the prerepair transesophageal echocardiogram and preoperative
angiographic assessment of tricuspid incompetence. This finding was useful, since
right ventricular angiocardiography remains the standard for preoperative assessment
of tricuspid valve incompetence at the Deborah Heart and Lung Center. After repair,
intraoperative transesophageal echocardiograms revealed that 15 of 30 patients had
no incompetence (50 percent), 11 had 1+ incompetence (37 percent), 1 had 2+
incompetence (3 percent), 3 had 3+ incompetence (10 percent), and none had 4+
incompetence. The transesophageal echocardiogram appears to be an accurate and
reliable method for objective documentation of the severity of residual postrepair
incompetence.
The incidence of primary tricuspid valve annuloplasty that requires immediate

secondary tricuspid valve replacement (TVR) is low. Only 4 patients (2.2 percent) in the
Deborah experience of 179 tricuspid valve replacements had immediate tricuspid valve
replacement for failed repairs. [48 ] These data imply that TVR was overutilized, but this
notion is difficult to assess, either retrospectively or prospectively.
Tricuspid Valve Replacement
In an earlier study, logistic regression analysis identified preoperative variables

associated with tricuspid valve replacement. These preoperative criteria included
increasing jugular venous distension ( p = 0.04), increasing preoperative angiographic
severity of tricuspid valve incompetence ( p = 0.008), a previous cardiac operation ( p =
0.05), and the presence of tricuspid valve stenosis ( p = 0.02). [48 ]
In addition to uncertainty and controversy regarding when TVR is required, there is also
disagreement as to which prosthesis is suitable in the tricuspid position. Isolated
reports of stent-mounted and unstented homograft valves indicate satisfactory
early-phase results. [89 ] [92 ] Although an earlier Deborah report indicated satisfactory
results in 154 patients with tricuspid bioprostheses, [93 ] we currently use a St. Jude
Medical valve (St. Jude Medical, Inc., Minneapolis, Minn.), particularly if mechanical
valves are to be implanted simultaneously in the left side of the heart. [94 ] [97 ] These
patients require anticoagulation, but in a large series of patients with multivalvular
disease, Coumadin actually conferred a survival advantage ( p < 0.001). [48 ]
For tricuspid valve replacement, the native tricuspid valve leaflets are left in situ. Multiple
interrupted, pledgeted 0 Ticron sutures are placed through the leading edge of the
tricuspid valve leaflets starting at the 9 o'clock and working posteriorly in a
counterclockwise direction to the 3 o'clock position. Sutures are placed through leaflet
tissue and then immediately through the sewing ring of the valve. This avoids injury to
the bundle of His and atrioventricular node. Once this part of the suture line has been
completed, suture ends are tagged and the needles trimmed. The anterior part of the
suture line is completed working in a clockwise direction, placing sutures from 9 o'clock
to 3 o'clock. Again, sutures are placed through the leaflet and then immediately through
the sewing ring. The St. Jude valve is implanted in an antianatomic orientation. [98 ] The
valve is seated, and the sutures are tied (Fig. 35-5A,B) .
There are advantages to leaving the tricuspid valve leaflets in place. This method
avoids trauma to the atrioventricular node and His bundle. Maintenance of subvalvular
structures may better preserve right ventricular geometry and improve mechanical
function of the right ventricle, as occurs with the left ventricle when subvalvular structures
are left in place during mitral valve replacement. [99 ]
The surgical technique for tricuspid valve replacement is modified in the presence of
Ebstein's malformation. [100 ] , [101 ] Repair may be attempted with the goal of
restoring the configuration of the atrioventricular valve orifice (Fig. 35-6AC) . However, if
the septal leaflet is attenuated or adherent to the right ventricular endocardium, the valve
should be replaced. In this situation, an interatrial communication is frequently present.
The atrial septal defect is closed using a pericardial patch, and the prosthetic valve is
implanted in the supracoronary sinus position using multiple interrupted, pledgeted 0
Ticron sutures. The inferior part of the suture line often traverses the atrial septal defect
patch. Sutures are placed in the same sequence used for straightforward tricuspid valve
replacement. Although using a bileaflet valve appears to run the risk of leaflet
impingement against the atrial free wall near the coronary sinus, once the valve has
been seated and the sutures tied, the atrial wall falls away from the area of the valve
sewing ring and the mechanical valve leaflets have free movement (Fig. 35-7A,B) .
Interventions for Endocarditis
In some patients with necrosis of a portion of the tricuspid valve due to active or chronic
infective endocarditis, it is possible to debride the necrotic portion of the valve leaflet
and perform pericardial patch reconstruction. [102 ] [105 ] However, several authors
recommend excision of infected leaflets in drug addicts to avoid early or late reinfection,
associated with resumption of intravenous drug abuse. [105 ] [109 ] Secondary valvular
replacement can be performed at a later date once the endocarditis resolves and if the
drug addict is rehabilitated. [110 ] [113 ] However, this recommendation is controversial
because some patients may not tolerate acute, massive tricuspid incompetence. [114 ]
A stented homograft valve or a bioprosthesis can be implanted primarily as an
alternative to valvectomy. [115 ] , [116 ] Implantation of a mechanical prosthesis in the
tricuspid position in a drug-addicted patient is contraindicated because of the inability
to comply with anticoagulation. The Deborah experience with isolated tricuspid
valvulectomy for tricuspid infective endocarditis is described later.
POSTOPERATIVE SURGICAL HEART BLOCK
Permanent complete atrioventricular block may occur postoperatively following tricuspid

valve surgery. The risk of heart block is low with the transatrial approach if stay sutures
are utilized to arrange exposure. Use of retractors on the atrial septum is more likely to
induce postoperative atrioventricular block. Use of a pericardial patch to close the
septum reduces tension on the atrial septum, permits less deep suturing in the area of
the anterior limbus, and may reduce the risk of both atrioventricular block and recurrent
atrial septal defect.
In a previously published report from the Deborah Heart and Lung Center, 20 of 452
patients were noted to have variable degrees of atrioventricular block in the early
postoperative period (4.4 percent) after tricuspid valve surgery. Six of these patients
(1.3 percent) required permanent pacemaker implantation. Of these 6, 2 had mitral
valve replacement plus tricuspid valve repair, 2 had aortic and mitral valve replacement
plus tricuspid valve repair, 1 had isolated tricuspid valve repair, and 1 had mitral and
tricuspid valve replacement. [48 ]
RESULTS: DEBORAH HEART AND LUNG CENTER DATA
Patient Population and Procedures
From January 1, 1995 through March 31, 1995, a retrospective assessment was made
of 659 consecutive patients who had tricuspid valve surgery at the Deborah Heart and
Lung Center between January 1, 1961 and December 31, 1994. There were only 5
patients lost to follow-up (0.8 percent).
As is usual for patients with rheumatic tricuspid valve disease and rheumatic valve
disease in general, more female patients had tricuspid valve surgery. There were 528
female patients (79 percent) and 139 male patients (20 percent) ( p < 0.0001). The
mean age at the tricuspid valve operation was 56.9 years, with a range of 4 to 79 years.
Five patients were in preoperative functional class I (1 percent), 98 were in class II (15
percent), 377 were in class III (57 percent), and 179 were in class IV (27 percent).
Of these 659 patients, 459 had repair of the tricuspid valve (69.7 percent), and 200
patients had replacement (30.3 percent). Four patients in the replacement group (2
percent) had failed primary tricuspid repair and replacement of the valve at the same
operation. These 4 failed repairs included 3 DeVega angioplasties and 1
bicuspidizationplication.
All the 659 patients had disease of the left-sided valves in addition to tricuspid disease.
On the basis of the preoperative catheterization findings, 69 (10 percent) had aortic
valve stenosis, 340 (52 percent) had aortic valvular incompetence, 429 (65 percent)
had mitral valvular stenosis, and 489 (74 percent) had mitral regurgitation. The severity
of aortic valve incompetence was 1 to 2+ in 265 patients (41 percent) and 3 to 4+ in 61
patients (10 percent). The degree of mitral regurgitation was 1 to 2+ in 2105 patients
(32 percent and 3 to 4+ in 454 patients (38 percent). In addition, coronary artery
disease was present in 90 patients (14 percent) during preoperative
angiocardiography.
Many of these patients had previous cardiac surgery. Two-hundred and thirty-eight
patients (36.1 percent) had one prior operation, 56 patients (8.5 percent) had two prior
operations, 5 patients (0.8 percent) had three prior operations, and 1 patient (0.2
percent) had four prior operations. The mean interval between the first operation and
the current procedure was 158 months, with a range of 0 to 451 months; the mean
interval from the second previous operation to the current one was 109 months, with a
range of 3 to 244 months; the mean interval from the third previous procedure to the
current operation was 83 months, with a range of 1 to 92 months; and the interval from
the fourth previous operation which was mitral and tricuspid valve replacement in one
patient was 120 months Tables 35-1 to 35-3 ).
Four hundred and eighty-six (74 percent) of the 659 patients had atrial fibrillation before
operation, 146 (22 percent) were in sinus rhythm, 11 (2 percent) were paced, 11 (2
percent) had nodal (junctional) rhythm, and 1 had supraventricular tachycardia.
Seventy-four patients (15 percent) presented with ascites, 330 (59 percent) had
palpable hepatomegaly, 172 (33 percent) had a pulsatile liver, 298 (54 percent) had
important peripheral edema, and 386 (67 percent) had evidence of jugular venous
distension. Eight hundred and forty-one concomitant procedures were performed in the
659 patients who had tricuspid valve surgery. These concomitant operations included
mitral valve replacement in 489 patients (74 percent), aortic valve replacement in 141
patients (21 percent), mitral valve repair 121 patients (18 percent), aortic valve repair in
25 patients (4 percent), and coronary arterial bypass grafting in 65 patients (10
percent).
Concomitant procedures performed in the tricuspid valve replacement group were

compared with those performed in the tricuspid valve repair group. When the mitral
valve was replaced, the tricuspid valve also was replaced. Similarly, patients
undergoing mitral valve repair also had tricuspid valve repair (Table 35-4) .
The type of tricuspid valve repair ( n = 459) is indicated in Table 35-5 . The most
frequent was simple annular plication. For tricuspid valve replacement, 105 patients had
interrupted simple or pledgeted sutures (52 percent), 55 had a simple continuous suture
(27 percent), 5 patients had interrupted plus continuous sutures (2 percent), and in 35
patients the suture method was unspecified (18 percent). One hundred and sixty-one
bioprosthetic valves (80 percent) were implanted in the tricuspid position as compared
with 39 mechanical valves (20 percent) [ p < 0.001 (chi-squared)]. The models used are
listed in Table 35-6 .
Procedures performed in 41 patients with predominantly tricuspid valve stenosis are

indicated in Table 35-7 . Twenty-five patients had tricuspid valve replacement (61
percent), and 16 had repair (39 percent).
COMPARISON OF TRICUSPID REPAIR VERSUS REPLACEMENT GROUPS
Of 200 patients who had TVR (replacement), 39 (20 percent) were male, and of 459
patients who had repair, 100 (22 percent) were male. The incidence of atrial fibrillation
was similar in both groups [ p = 0.29 (chi-squared)]. Markers of systemic hypertension
were significantly more common in TVR patients (Table 35-8) . Although differences did
not reach statistical significance, more patients in New York Heart Association classes
III and IV required TVR (180 of 200, 90 percent) than had repair (375 of 459, 81
percent) [ p = 0.064 (chi-squared)].
Comparison of preoperative catheterization data is presented in Table 35-9 . Mean

right atrial pressure was higher in the replacement group, and yet, unexpectedly, mean
right ventricular end-systolic pressure, mean pulmonary artery systolic pressure, and
mean pulmonary artery diastolic pressure were all higher in the repair group. Mean and
range of left ventricular ejection fractions were similar in both groups.
Twenty-five of 200 patients in the tricuspid valve replacement group (12.5 percent) had
tricuspid valve stenosis, and 16 of 459 patients in the tricuspid valve repair group (3.5
percent) had tricuspid stenosis [ p = 0.000003 (Fisher's exact)]. Although there was no
difference in the incidence of tricuspid valve incompetence between the two groups [ p
= 0.50 (Fisher's exact)], a statistically significant difference in the severity of tricuspid
valve regurgitation was found at right ventricular angiocardiography. More severe
degrees of tricuspid valve regurgitation were present in the tricuspid vlave replacement
group. Mean severity of tricuspid regurgitation noted at right ventricular
angiocardiography was 3.42 in the replacement groups and 3.00 repair group [ p =
0.001 (chi-squared)].
An analysis was made of the frequency of aortic valve disease in the tricuspid valve
repair versus tricuspid valve replacement groups. The incidence of aortic valve stenosis
was similar between the two groups [ p = 0.66 (Fisher's exact)], and the incidence of
aortic incompetence was the same between the two groups [ p = 0.77 (Fisher's exact)].
Further, the severity of aortic valve incompetence was similar between the two groups,
with a mean degree of aortic valve regurgitation of 1.6 in the tricuspid valve
replacement group and 1.37 in the tricuspid valve repair group [ p = 0.91 (chi-squared)].
A comparison was made of the severity of mitral valve disease between the two groups.
There was no significant difference in the incidence of mitral valve stenosis between the
two groups [ p = 0.59 (Fisher's exact)]. The incidence of mitral regurgitation tended to
be higher in the repair group but did not reach statistical significance [ p = 0.09
(Fisher's exact)]. Similarly, the severity of mitral incompetence was not different
between groups; mean mitral regurgitation was 2.39 in the replacement group and 2.44
in the repair group [ p = 0.84 (chi-squared)]. There was no difference in the incidence of
surgically treated coronary artery disease between the two groups [ p = 0.60 (Fisher's
exact)]. Mean total cardiopulmonary bypass time in the replacement group was 117
minutes (range 23 to 334 minutes) and in the repair patients was 106 minutes (range
27 to 488 minutes) [ p = 0.0003 (Wilcoxon)]. Total aortic cross-clamp time was shorter
in the repair group at 50 minutes (range 0 to 209 minutes) as compared with 60
minutes in replacement patients (range 0 to 145 minutes) [ p = 0.0001 (Wilcoxon)].
An analysis was made of the tendency to perform tricuspid valve repair as compared
with replacement in the study population. This variable was examined by computing the
number of repair patients between two adjacent replacement patients. Using this
model, the trend toward repair rather than replacement increased significantly over time
[ p = 0.024 (trend test)].
Mortality
HOSPITAL DEATH
Overall, 93 (14.1 percent) of the 659 patients who had tricuspid valve surgery suffered
hospital death (death within 30 days of operation). Hospital death occurred in 29
patients (14 percent) after valve replacement and in 64 patients (12.7 percent) after
repair [ p = 0.90 (Fisher's exact)]. The causes of hospital death ( n = 93) included acute
cardiac failure in 44 (47.3 percent), subacute cardiac failure in 17 (18.3 percent),
hemorrhage in 12 (13.0 percent), chronic cardiac failure in 5 (5.4 percent), neurologic
events in 5 (5.4 percent), sepsis in 3 (3.2 percent), arrhythmia in 2 (2.2 percent), cardiac
tamponade in 1 (1 percent), renal failure in 1 (1 percent), valve related thrombosis (due
to thrombosis (due to thrombosis of a Hufnagel valve in the tricuspid valve position) in 1
(1 percent), and infective endocarditis in 1 (1 percent), and 1 patient expired after
hospital dismissal but within 30 days of operation of unknown cause (1 percent). By
univariate analysis (Fisher's exact), risk factors associated with hospital death included
female gender ( p = 0.05), previous surgery ( p = 0.0007), hepatomegaly ( p = 0.03),
and concomitant aortic valve replacement ( p = 0.06).
LATE DEATH
By multivariate analysis (log-rank test), the following variables were associated with late
death: higher preoperative functional class ( p = 0.02), previous surgery ( p = 0.0003),
male gender ( p = 0.0001), hepatomegaly ( p = 0.0001), pulsatile liver p = 0.002),
ascites ( p = 0.0001), jugular venous distension ( p = 0.002), the presence of coronary
artery disease p = 0.0005), and the performance of coronary arterial bypass grafting ( p
= 0.01). An analysis of freedom from late death indicated no significant relationship for
the type of tricuspid repair with the incidence of late death [ p = 0.11 (log rank)]. Further,
there was no difference in late survival for tricuspid replacement or valve repair [ p =
0.33 (log rank)], as indicated by the hazard function analysis (Fig. 35-8) .
An actuarial survival analysis was performed for the hospital survivors ( n = 566). The
mean follow-up interval for these data was 82 months, with a range of 1 to 397 months.
At 12 months, survival rate was 87.3 percent (70 percent confidence limits = 85.9 to
88.8 percent). At 60 months, survival was 69.5 percent; at 120 months, survival was
45.4 percent; at 180 months, survival was 23.1 percent; and at 240 months, survival was
12.9 percent. The nomogram depicting actuarial freedom from late death is given in
Fig. 35-9 .
Morbidity
EARLY EVENTS
Early in-hospital postoperative complications were analyzed. Early paravalvular leak

occurred in three patients (0.5 percent); all three were at the mitral position, and none
occurred at the tricuspid valve position.
Prosthetic tricuspid valve endocarditis occurred in only one patient 1 month following
replacement with an Ionescu-Shiley valve (0.5 percent). At reoperation, the
bioprosthetic valve, which had prominent fungal vegetations, was replaced with another
bioprosthesis. The patient's St. Jude valve in the mitral position was free of vegetations.
This patient is alive and well 9 years later.
There were two episodes of early, intrinsic left-sided valve failure in the 659 patients.
Both events involved mechanical mitral prostheses. There was one case of early,
intrinsic tricuspid valve failure due to prosthetic valve thrombosis involving a Hufnagel
valve (0.5 percent). This patient had had open mitral valve commissurotomy at the time
that the tricuspid valve had been replaced. The patient had evidence for subacute
cardiac failure and died on postoperative day 14 from multiorgan failure. At postmortem
examination, the Hufnagel tricuspid prosthesis was thrombosed, and valve leaflet
mobility was impaired. The cause of death was attributed to the Hufnagel valvular
thrombosis.
Seven patients with tricuspid valve repair (1.5 percent) and one patient with
replacement (0.5 percent) required permanent pacemaker implantation for complete
heart block. Thirteen patients with tricuspid valve repair (2.8 percent) and none with
replacement required an intraaortic balloon pump. Overall, 13 patients required reentry
for bleeding (2.0 percent).
LATE EVENTS
Three patients developed paravalvular leaks at the tricuspid valve position (1.5
percent). One leak developed around a Beall valve. This patient did not have a
reoperation and died 6 months postoperatively with chronic cardiac failure. The
paravalvular leak, which was not diagnosed antemortem, was an incidental finding at
autopsy. One patient with an Ionescu-Shiley tricuspid valve underwent reoperation to
repair a large paravalvular leak. This operation was performed successfully, but the
patient died suddenly of unknown cause 3 years later. There was no evidence of
residual leak at the time of death. A third patient was found to have a paravalvular leak
of an Ionescu-Shiley tricuspid valve 6 years after implantation. Nine years after
implantation, the patient is alive, without reoperation.
Thirteen patients had intrinsic valve failure. Six Carpentier-Edwards valves, three Beall
valves, two Mitroflow valves, one Ionescu-Shiley valve, and one Carpentier-Edwards
porcine valve failed. Teflon disk wear, fibrous ingrowth, and improper sizing were
causes of valve failure in 3 patients. In the 10 tissue valves, stenosis, leaflet
calcification, and other degenerative changes caused valve failure. All patients with late
intrinsic valve failure had reoperation.
For the 10 failed tissue valves, 1 valve, a Carpentier-Edwards prosthesis, was simply
treated by valvuloplasty; 5 were replaced with a new tissue prosthesis, and the
remaining 4 were replaced with a mechanical prosthesis. Of these 10 patients, 1 died
on postoperative day 15, and the others survived operation. Three failed mechanical
tricuspid valves were replaced with tissue prostheses. Two of these 3 patients died
within 35 days of reoperation.
There were four late episodes of tricuspid prosthetic valve endocarditis. These included
two Carpentier-Edwards valves, one Ionescu-Shiley valve, and one Hancock porcine
valve. Hemophilus, S. aureus, Aspergillus , and Candida each caused an infection.
Three patients had reoperation and replacement of the infected valve with another
bioprosthetic valve. All three patients survived. The patient with an infected Hancock
porcine valve was not reoperated and died from multiorgan failure 10 weeks after the
original implant. At autopsy, both the tricuspid and mitral prosthetic valves were
completely obstructed with Aspergillus .
The incidence of these late events differed between tricuspid valve repair and
replacement. The incidence of intrinsic (native or prosthetic) valve failure was lower in
the valve repair group and occurred in 14 patients (3.5 percent) as compared with 20
patients (11.7 percent) who had had valve replacement [ p = 0.001 (log rank)]. Major
thromboembolic events were more common in patients with tricuspid valve repair and
occurred in 35 patients (7.6 percent) as compared with 6 patients who had replacement
(3.5 percent) [ p = 0.04 (log rank)]. Major anticoagulation-related hemorrhage occurred
in 18 patients (10.5 percent) with tricuspid valve replacement and 19 patients (5
percent) with tricuspid repair [ p = 0.01 (Fisher's exact)]. These data indicate that
avoiding anticoagulation is not an important consideration in the decision to repair or
replace the tricuspid valve. Of the late survivors, 81 percent of patients who had
undergone tricuspid valve replacement and 86 percent of patients who had undergone
tricuspid valve repair were anticoagulated with Coumadin at the time of follow-up.
REOPERATION
At least one late reoperation was required in 117 patients (17.8 percent), two
reoperations in 10 patients (1.5 percent), and three reoperations in 2 patients (0.3
percent). The mean interval from the initial operation at the Deborah Hospital to the first
reoperation was 72 months, with a range of 0 to 272 months. The mean interval to the
second reoperation was 111 months, with a range of 1 to 296 months, and the mean
interval to the third reoperation was 145 months.
Table 35-10 lists the tricuspid prostheses that were originally implanted at Deborah.
Table 35-11 indicates the prostheses implanted at reoperation. In 28 patients the
original valve was replaced (14 percent), in 1 patient a paravalvular leak was repaired
(0.5 percent), and in 1 patient a thrombectomy was performed (0.5 percent). Mean
interval to reoperation in the tricuspid valve reoperation group was 39.5 months, with a
range of 8 to 71 months.
Twelve patients who had previous surgery for tricuspid valve stenosis had reoperation.
Seven originally had valve repair, and five had replacement. Among the seven repairs,
six had tricuspid valve replacement and one had another repair. All the original valve
replacements received another prosthesis.
By univariate analysis (log-rank test), variables predictive of tricuspid valve reoperation

were ascites ( p = 0.0001), hepatomegaly p = 0.0001), peripheral edema ( p = 0.008),
jugular venous distension ( p = 0.04), higher mean right atrial pressure ( p = 0.08),
higher left ventricular end-diastolic pressure ( p = 0.001), earlier year of operation ( p =
0.001), and use of the Mitroflow prosthesis ( p = 0.0001). By multivariate analysis
(log-rank test), risk factors for tricuspid reoperation were ascites ( p < 0.001),
hepatomegaly ( p < 0.001), and peripheral edema ( p < 0.001). There was no difference
in the incidence of tricuspid reoperation between the tricuspid valve replacement ( n =
30) and the valve repair group ( n = 59) (Table 35-12) . There was no difference in
hospital death rates at the time of tricuspid valve reoperation between patients with
replacement and those with repair [ p = 0.88 (Fisher's exact)].
Freedom from reoperation in all patients at 12 months was 94.8 percent (70 percent
confidence limits = 93.8 to 95.8 percent), at 60 months was 66.8 percent, at 120
months was 67.8 percent, at 180 months was 49.1 percent, and at 240 months was
22.3 percent.
Actuarial freedom from tricuspid reoperation is shown in Fig. 35-10 . The hazard
function analysis demonstrates the hazard rate for tricuspid reoperation according to
number of years after surgery (Fig. 35-11) . The hazard rate for tricuspid repair and
replacement is shown in Fig. 35-12 .
Tricuspid Valve Excision
In this series of 659 patients, only 2 had isolated tricuspid valve excision. Both young
women were drug addicts, and both had staphylococcal endocarditis. Both survived
operation and were discharged, but one subsequently died 40 months later of chronic
heart failure and recurrent streptococcal (type A) bacteremia. The other remains alive at
10 years but refuses medical therapy.
CONCLUSION
Appropriate surgical treatment of the tricuspid valve remains an enigma despite many
years of analysis. A better understanding of the natural history of patients with tricuspid
valve disease would improve treatment protocols. Careful analysis of clinical signs and
symptoms of systemic venous hypertension, preoperative and intraoperative
transesophageal echocardiography, and prerepair right ventricular angiocardiography
provide important information for the surgeon who must devise strategies for managing
tricuspid valve disease, usually during operations that also address other valves. Early
intervention in patients with multivalvular heart disease is an important strategy to
improve results. Co-existence of tricuspid valve dysfunction in patients with left-sided
valvular heart disease is often an important indicator that end-stage right ventricular
cardiomyopathy has developed. When this happens, surgical results are significantly
compromised.
PATHOPHYSIOLOGY OF MULTIPLE VALVE DISEASE
Valvular regurgitation may result from the pathological process affecting the valve
directly or may be secondary to alterations in ventricular morphology caused by other
valve lesions; this secondary or functional regurgitation affects the atrioventricular
valves. In some patients, secondary valvular regurgitation may be expected to improve
with repair or replacement of the primarily diseased valve. In other patients, the
secondary disease process may have advanced to the stage that valve function will not
improve following correction of the primary lesion, and thus simultaneous surgical
correction should be considered.
Primary Aortic Valve Disease with Secondary Mitral Regurgitation
Isolated aortic valve lesions can cause secondary regurgitation of the mitral valve and,
rarely, of the tricuspid valve. Severe aortic valve stenosis with or without left ventricular
dilatation is frequently associated with some degree of mitral valve regurgitation. When
the mitral valve is structurally normal, its regurgitation would be expected to improve with
relief of left ventricular outflow obstruction; mild mitral valve regurgitation would be
expected to resolve almost completely following aortic valve replacement. If mitral valve
regurgitation is severe, some degree of persistent regurgitation is expected following
aortic valve replacement, and mitral valve annuloplasty may be required. In contrast, with
aortic valve stenosis and mitral valve regurgitation associated with a structurally
abnormal mitral valve, repair or replacement of the mitral valve usually is necessary.
Thus, determination of the morphology and pathophysiologic severity of each valve

lesion is critically important in planning surgical management, and preoperative
echocardiography is necessary in all patients suspected of having multiple valve
disease. Often, transthoracic echocardiography can define the etiology of mitral and
tricuspid valvular regurgitation. When valve regurgitation is entirely secondary, the mitral
valve leaflets will be thin and freely mobile. Mitral (and tricuspid valve) regurgitation
secondary to rheumatic disease is readily identified when leaflets are thickened and
chordae are shortened; fibrosis of these structures restricts leaflet mobility. Leaflet
prolapse with or without ruptured chordae tendineae may also cause atrioventricular
valve regurgitation.
Transesophageal echocardiography images the heart from a retrocardiac position,

which avoids interference from interposed ribs, lungs, and subcutaneous tissue. A high
frequency (5-MHz) transducer is employed, which yields better resolution than that of
images obtained with routine transthoracic imaging utilizing 2.25- to 3.5-MHz
transducers. [3 ] Thus, transesophageal echocardiography provides the best image of
the mitral and tricuspid valves and may be obtained preoperatively and/or
intraoperatively. In some cases, left ventriculography may help to quantify left
atrioventricular valve leakage. Right ventricular angiocardiography also can be useful in
determining the degree of tricuspid valve dysfunction, but it is rarely employed in current
practice. [4 ]
Tricuspid Valve Regurgitation Secondary to Other Valvular Disease
Secondary tricuspid valve regurgitation commonly is associated with rheumatic mitral

valve stenosis, and the exact cause is unknown. [5 ] , [6 ] Some authors believe that
secondary tricuspid valve regurgitation is a result of pulmonary artery hypertension and
right ventricular dilatation. [7 ] As with the mitral valve, tricuspid valve annular dilatation
is asymmetrical. Most enlargement occurs in the annulus subtended by the free wall of
the right ventricle, and there is little dilatation of the annulus adjacent to the septal leaflet
of the tricuspid valve. [8 ] , [9 ]
Although pulmonary artery hypertension with secondary enlargement of the right

ventricle and tricuspid valve annulus may be an important contributing factor in
secondary tricuspid regurgitation, it is not the sole mechanism. For example, congenital
heart lesions such as tetralogy of Fallot produce systemic pressure in the right ventricle,
yet severe tricuspid valve regurgitation rarely is seen in these patients. Similarly,
important tricuspid valve regurgitation is uncommon in children with ventricular septal
defects who have enlargement of the right ventricle associated with variable degrees of
Furthermore, clinical experience suggests that other mechanisms must play a role in
development of secondary tricuspid valve regurgitation. Patients who have had mitral
valve replacement for rheumatic mitral valve stenosis may develop regurgitation of their
native tricuspid valve years after initial operation, and many patients have only modest
elevation of pulmonary artery pressure. [10 ]
It is useful to classify secondary mitral and tricuspid valve regurgitation as mild,

moderate, and severe. [9 ] Usually, patients with mild tricuspid valve regurgitation do not
have clinical signs and symptoms of right heart failure. Also, mild tricuspid regurgitation
demonstrated by preoperative echocardiography may appear even less severe in the
operating room under general anesthesia. In most instances, mild secondary tricuspid
regurgitation does not require intervention.
Patients with echocardiographic evidence of significant regurgitation who do not have

symptoms or have their symptoms controlled by medical treatment can be classified as
having moderate tricuspid regurgitation. These patients usually are managed with a
deVega suture annuloplasty or a partial ring annuloplasty, as described in the following.
[11 ] Patients with severe secondary tricuspid regurgitation and clinical evidence of right
heart failure (pulsatile liver, distended neck veins, and peripheral edema with or without
ascites) are managed by concomitant ring annuloplasty or tricuspid valve replacement.
The degree of pulmonary hypertension may influence surgical management of

secondary tricuspid valve regurgitation. Kaul et al. grouped 86 patients with functional
tricuspid regurgitation in association with rheumatic mitral valve disease according to
the degree of pulmonary hypertension. One group had severe pulmonary hypertension
(mean pulmonary pressure 78), and a second group had moderate pulmonary
hypertension (mean pulmonary artery pressure 41 mmHg). Patients with moderate
pulmonary hypertension preoperatively had more advanced right heart failure and right
ventricular dilatation, and many of these patients continued to have tricuspid valve
regurgitation following mitral valve surgery without tricuspid valve surgery. The patients
with severe pulmonary hypertension all showed regression of tricuspid regurgitation,
and 28 percent had complete resolution following mitral valve surgery without operation
on the tricuspid valve. [8 ]
Excluding hospital mortality, about 40 percent of patients undergoing tricuspid valve

surgery have premature death. The usual cause is cardiac failure secondary to
cardiomyopathy, which is progressive despite adequate valve function. Risk factors for
late death in these patients are progressive increase in systemic venous pressure and
lack of warfarin therapy. [4 ]
VALVE SELECTION FOR MULTIPLE VALVE REPLACEMENT
When multiple valve replacement is confined to the left ventricle, replacement valves
should be chosen from the same class with respect to the need for anticoagulation and
projected longevity. There are no theoretical or practical advantages to use of a tissue
valve and a mechanical valve for mitral and aortic valve replacement, and studies show
no reduction in the risk of thromboembolism, valve-related morbidity, or late death. [12 ]
, [13 ] In addition, a lower reoperation rate is reported for patients with two mechanical
valves in the left ventricle compared to patients with one mechanical and one tissue
valve. [12 ]
For tricuspid valve replacement, alone or in conjunction with other valve procedures, use
of a bioprosthesis may have advantages. Although there are many reports of successful
use of mechanical valves for tricuspid valve replacement, we and others have noted a
higher rate of valve thrombosis comparing mechanical valves in the tricuspid position to
those in the mitral position. [14 ] [16 ] Furthermore, there are few hemodynamic
considerations in selecting a tricuspid prosthesis; the greater hemodynamic efficiency
of mechanical valves compared to bioprostheses rarely is an issue in atrioventricular
valve replacement, especially the tricuspid valve where the annulus diameter in adults is
often 33 mm or more. In vitro studies demonstrate only minimal hemodynamic
improvement with atrioventricular valves larger than 25 mm. [17 ]
SURGICAL METHODS
Aortic and Mitral Valve Replacement
CANNULATION
Arterial inflow is established by cannulation of the distal ascending aorta near the
pericardial reflection just to the left of the origin of the innominate artery (Fig. 36-1A) .
Venous cannulation is simplified by using a two-stage cannula in the right atrium for
venous return. Individual cannulation of the superior and inferior venae cavae is
reserved for operations that require right atrial or ventricular incisions (Fig. 36-2A) .
Cardiopulmonary bypass is commenced at 2.4 L/min/m 2 , and systemic hypothermia is

induced according to requirements of the operation. The usual level of systemic
hypothermia is 2532°C, and the lower level is preferred when longer periods of bypass
are needed (90 minutes or more) or when temporary periods of low flow are
anticipated.
Provisions for intraoperative autotransfusion are used routinely, and antifibrinolytic

drugs such as aprotinin or epsilon-aminocaproic acid (Amicar) may be useful,
especially in reoperations where pericardial adhesions may worsen bleeding. [18 ]
CARDIOPLEGIA
If the aortic valve is competent, myocardial protection during aortic cross-clamping is

achieved by initial infusion of cold (48°C) blood cardioplegia through a tack vent placed
in the aorta proximal to the clamp. The volume of cardioplegia needed to achieve
diastolic arrest and uniform hypothermia depends upon the heart size and the presence
of aortic valve regurgitation. Generally, the initial volume of cardioplegia required for
hearts with multiple valve disease is higher than that required for coronary
revascularization because of myocardial hypertrophy. For patients without cardiac
enlargement, we infuse approximately 10 mL per kg body weight, whereas 15 mL per
kg body weight are used for patients with significant degrees of myocardial hypertrophy.
Repeat infusions of 400 mL of cardioplegia are given directly into the coronary ostia at
20-minute intervals during aortic occlusion. We use custom designed soft-tipped
coronary perfusion catheters to minimize the potential for trauma to the coronary ostia
during intubation and infusion. [19 ]
If aortic valve regurgitation is moderate or severe, cardioplegia is infused directly into

the coronary ostia. Initial aortotomy is facilitated by emptying the heart, using suction on
an aortic tack vent and temporary reduction in cardiopulmonary bypass flow rate to
maximize venous return. Some surgeons prefer retrograde infusion of cardioplegia, [20
] and if this method is used, even larger volumes are necessary because of non-nutritive
flow through the coronary venous system. [21 ]
PROCEDURE
After cardioplegia, the aortic valve is inspected through an oblique aortotomy extended
into the noncoronary aortic sinus (Fig. 36-1B) . Aortic valve regurgitation caused by
cuspal perforation or prolapse of a congenitally bicuspid valve can often be repaired,
[22 ] but the decision for or against aortic valve repair should take into consideration
whether or not a mitral valve prosthesis will be needed. For example, even though aortic
valve repair might seem technically possible, prosthetic replacement may be the best
option for a patient who requires mitral valve replacement and will be maintained on
warfarin (Coumadin) for long-term anticoagulation.
Severe calcification of the valve, whether it is bicuspid or tricuspid, necessitates

replacement, [23 ] and the leaflets therefore are excised and annular calcium debrided
carefully. The aortic annulus is then calibrated; experience has shown that subsequent
replacement of the mitral valve usually reduces the aortic annular diameter by
shortening the circumference that is in continuity with the attachment of the anterior
mitral valve leaflet. Therefore, we routinely identify (but do not break the sterile
packaging of) two aortic prostheses, one prosthesis corresponding to the calibrated
dimension, and the other prosthesis is the next size smaller. Final selection of the aortic
prosthesis is made after mitral valve replacement or repair.
Although first exposed, the aortic valve usually is replaced after mitral valve repair or
insertion of the mitral valve prosthesis. Sutures placed in the portion of the aortic valve
annulus that is continuous with the anterior leaflet of the mitral valve pull the anterior
leaflet superiorly toward the left ventricular outflow area and thus hinder exposure of this
area as viewed through the left atriotomy.
If the aortic annulus is small, it can be enlarged with a patch of pericardium. [24 ] This
technique increases annular diameter by 24 mm or more, and only rarely are more
radical techniques necessary. [25 ] [27 ] Another maneuver to accommodate as large a
prosthesis as possible is to place the necessary sutures for the mitral valve repair or
replacement but not secure the mitral prosthesis until the aortic valve is implanted. This
eliminates downsizing of the aortic prosthesis but does not compromise insertion of
sutures in the superior portion of the mitral valve annulus.
After removal of the aortic valve, the right atrial cannula is repositioned, and the mitral
valve is exposed through an incision posterior to the interatrial groove (Fig. 36-1B) . The
presence or absence of thrombi in the left atrium is noted, and the mitral valve is
inspected. When there is rheumatic disease of the aortic valve, the mitral valve almost
always will be involved to some extent. If aortic valve replacement is necessary, the
surgeon should have a low threshold for replacing a diseased mitral valve because
scarring and fibrosis of the rheumatic process is progressive, and mitral valve repair
(commissurotomy for stenosis or leaflet repair and annuloplasty for regurgitation) is less
durable than repair for degenerative disease. [28 ] [30 ] In contrast, when aortic valve
replacement is necessary because of calcification of a bicuspid valve or because of
senescent calcification, repair of mitral valve regurgitation owing to degenerative
causes can be expected to give predictably good long-term results. Repair of the mitral
valve is described in a separate chapter.
In preparation for replacement, the anterior leaflet of the mitral valve is excised, and,
when possible, a portion of the posterior leaflet with its chordal attachments is
preserved to maintain left ventricular papillary muscleannular continuity. [31 ] [33 ] The
mitral prosthesis is implanted using interrupted mattress sutures of 2-0 braided
polyester reinforced with felt pledgets, which can be situated on the atrial or ventricular
side of the valve annulus (Fig. 36-1C) . The leaflets of mechanical valves should be
tested for free mobility following valve seating.
When atrial fibrillation is present preoperatively, we obliterate the left atrial appendage
by oversewing its orifice from within the left atrium or by ligating it externally. The left
atriotomy is closed from each end with running polypropylene sutures. Vent tubing is
inserted through the partially closed left atriotomy and left in place while the aortic valve
is being replaced (Fig. 36-1D) .
After appropriate exposure, the aortic prosthesis is sewn in place with interrupted 2-0
polyester mattress sutures backed with felt pledgets, and the aortotomy is closed,
usually with two layers of 4-0 polypropylene. Any remaining air is evacuated from the
heart with the usual maneuvers, and a tack vent in the ascending aorta is placed on
suction as the aortic clamp is removed. The vent is removed from the left atrium and
closure of the left atriotomy is secured.
In patients with annuloaortic ectasia, the mitral valve sometimes can be visualized and
replaced through the enlarged aortic annulus. [34 ]
Aortic Valve Replacement and Mitral Valve Repair
Intraoperative transesophageal echocardiography is useful in assessing the degree of

mitral regurgitation and, importantly, in identifying the cause of valve leakage. When
quantification of mitral valve regurgitation is judged to be unreliable (e.g., eccentric jet or
multiple jets), we may utilize double sampling dye curves as another measure of the
amount of regurgitation. In this technique, dye is injected into the left ventricle and
withdrawn simultaneously from the left atrium and aorta. Concentration-time curves from
the left atrium and aorta then are compared to measure regurgitation. When mitral valve
regurgitation is only moderate and leaflet morphology normal, we expect mitral valve
function to improve following relief of severe aortic stenosis. In all other instances, the
valve should be inspected directly to determine need for repair or replacement.
Sternotomy, cannulation, and assessment of the aortic valve proceed as previously

described. When there is no indication of tricuspid valve disease and no other right
atrial procedures are planned, venous return is obtained through a single two-staged
cannula (Fig. 36-3A) .
Specific techniques of mitral valve repair depend on operative findings. Localized

prolapse of a portion of the posterior leaflet with or without ruptured chordae usually is
managed by triangular excision of that segment and repair with continuous 4-0
polypropylene suture. Ruptured chordae to the anterior leaflet are replaced with 4-0 or
5-0 PTFE sutures inserted into papillary muscle and through the free edge of the
prolapsing leaflet. [35 ]
Almost all leaflet repairs are supplemented with a posterior annuloplasty. Interrupted 2-0
braided polyester mattress sutures are placed along the posterior circumference of the
annulus ending at the right and left fibrous trigones (Fig. 36-3A) . Sutures then are
spaced evenly through a flexible 6.06.5-cm long partial ring; this standard length can be
obtained by using a 30-mm Cosgrove-Edwards ring or two-thirds of a 27-mm Duran
ring. [36 ] Following annuloplasty, competence of the mitral valve is tested by filling the
ventricle with saline or blood; the atrium then is closed, and the aortic valve prosthesis is
sewn into place.
Mitral Valve Replacement and Tricuspid Valve Replacement or Repair
In most instances, tricuspid valve regurgitation is caused by annular dilatation. [37 ] The
severity of tricuspid valve leakage can be determined by transesophageal
echocardiography prior to bypass and by digital exploration of the right atrium just prior
to venous cannulation. Under general anesthesia, changes in blood volume and cardiac
output can cause significant changes in the amount of regurgitation, and most often, the
severity of tricuspid valve leakage is lessened in the immediate prebypass period.
The patient's clinical condition must be correlated with echocardiographic findings and
intraoperative assessment of the tricuspid valve. Patients with enlarged, pulsatile liver,
peripheral edema, and jugular venous distention are likely to require tricuspid
valvuloplasty following mitral valve replacement or repair. Those patients without the
stigmata of right heart failure usually have less-severe valve leakage, and tricuspid valve
function may improve without direct repair or replacement after left-sided valvular
lesions are corrected.
The decision for repair or replacement of functional tricuspid valve regurgitation at the
time of mitral valve replacement is important because risk of subsequent reoperation is
high. In our earlier experience, operative mortality was 25 percent in patients who
required later reoperation for tricuspid valve regurgitation; therefore, we maintained a
liberal policy for annuloplasty or prosthetic replacement at initial operation. [38 ]
PROCEDURE
For operations on the tricuspid valve, insertion of a Swan-Ganz catheter is optional; if it

is used, the catheter is withdrawn from the right heart chambers during inspection and
assessment of the tricuspid valve. We prefer direct cannulation of the inferior and
superior venae cavae. [39 ] After commencement of cardiopulmonary bypass and
cardioplegia, the cavae are snared around the venous cannulae, and the interatrial
septum and tricuspid valve are exposed through a right atriotomy (Fig. 36-2A) . A
decision for repair or replacement of the tricuspid valve is made, and the necessary
prosthesis identified.
Usually we expose the mitral valve through an incision in the interatrial septum, which
crosses the fossa ovalis and can be extended superiorly (Fig. 36-2B) . Care should be
taken during retraction to avoid tearing the septum inferiorly toward the coronary sinus
and triangle of Koch. Alternatively, the mitral valve can be exposed through a standard
left atriotomy posterior to the interatrial groove.
After repair or replacement of the mitral valve (Fig. 36-2C) , the septal or left atrial
incision is closed, and the tricuspid valve is repaired or replaced. For tricuspid valve
repair, we use either the deVega method or ring annuloplasty. [7 ] , [11 ] , [40 ] , [41 ]
Both techniques are based on the observation that the anterior and posterior valve
portions of the tricuspid valve annulus are more prone to dilation than the septal leaflet
portion of the annulus as previously described. When ring annuloplasty is indicated, we
prefer a flexible device such as the Cosgrove-Edwards prosthesis or a partial Duran
ring (Fig. 36-3B) . The use of a partial ring avoids placement of sutures in the annulus
near the penetrating bundle of His and reduces risk of injury to conduction tissue.
Tricuspid Valve Replacement and Pulmonary Valvotomy for Carcinoid Heart

Disease
The tricuspid valve is inspected after cardioplegic arrest to allow complete visualization
of right atrial structures and to prevent embolization of air if a patent foramen ovale is
present. Tricuspid valve replacement always is indicated, and it is usually necessary
only to remove the anterior leaflet. After leaflet excision, the pulmonary valvotomy can be
performed transatrially. We prefer transatrial valvectomy whenever possible, and
pulmonary valve regurgitation is well tolerated if tricuspid valve function is normal. We
replace the pulmonary valve only if there is severe right ventricular dysfunction
preoperatively.
Carcinoid disease produces fibrosis and retraction of the leaflets, so that anchoring
sutures (interrupted mattress of 2-0 braided polyester backed with felt pledgets) can be
inserted into the remaining septal and posterior leaflets. After sutures are placed in the
posterior and septal leaflets, the aortic cross-clamp is removed, and the heart is
allowed to beat rhythmically. The remaining sutures are placed, and all sutures are
secured with observation of the electrocardiogram. If atrioventricular block develops, the
sutures in the area of the penetrating bundle of His are removed and reinserted in a
more superficial location.
If pulmonary valvectomy has not been completed through the tricuspid valve orifice, a
short transannular incision is made and the fibrotic nubbins of pulmonary valve cusps
excised. The incision is closed with a pericardial patch and 4-0 polypropylene to
prevent annular narrowing. Finally, any remaining air is aspirated from right heart
chambers.
Triple Valve Replacement
Operative preparation is similar to that previously described. Usually left-sided valvular

lesions are corrected prior to tricuspid valve procedures. Again, if there is aortic valve
regurgitation, the aortotomy is performed first, and cardioplegia is administered;
simultaneously we snare the cavae and open the right atrium. After excision of the aortic
valve and calibration of the annulus, the interatrial septum is incised, and the mitral valve
is repaired or replaced. Next, the aortic valve is implanted, and after closure of the
aortotomy and septotomy, the tricuspid valvuloplasty or prosthetic replacement can be
performed without aortic cross-clamping. [42 ]
RHEUMATIC HEART DISEASE AFFECTING MULTIPLE VALVES
Introduction
As shown in Table 36-3 , rheumatic valvulitis is a common cause of multiple valve

disease; autopsy studies show that almost all patients with rheumatic heart disease
have some involvement of the mitral valve, although it is not always evident clinically. [43
] The percentages of multiple valve involvement in two autopsy studies of patients with
rheumatic heart disease are shown in Table 36-4 . Forty-seven percent of those studied
had involvement of more than one valve. Mitral and aortic valve disease was the most
common combination and was present in 34 percent of patients; the second most
common combination was mitral, aortic, and tricuspid valve disease (9 percent).
Long-term follow-up of children with rheumatic heart disease suggests that

approximately 50 percent of patients have multivalvular involvement. [44 ] , [45 ] In a
study of patients undergoing mitral valvotomy for rheumatic mitral stenosis (Table 36-5)
, 13 percent had clinical evidence of other rheumatic valve stenosis or regurgitation.
Most of these patients had associated rheumatic aortic disease. [46 ]
Rheumatic heart disease can cause valve stenosis, regurgitation, or a combination of

lesions. The percentages of 290 patients with specific valvular lesions from four studies
of multiple valve disease are shown in Table 36-6 . Mixed lesions producing stenosis
and regurgitation were encountered most commonly in both aortic and mitral valves.
Rheumatic Mitral Stenosis with Rheumatic Aortic Regurgitation
Approximately 10 percent of patients with rheumatic mitral valve stenosis also have
rheumatic aortic regurgitation. [47 ] Clinical and laboratory characteristics of patients
with mitral stenosis and aortic regurgitation are summarized in Table 36-7 .
DIAGNOSIS, SIGNS, AND SYMPTOMS
Physical findings
An early blowing diastolic murmur is present along the left sternal border in about 75
percent of patients with rheumatic mitral stenosis. [48 ] , [49 ] This murmur can mimic a
Graham Steel murmur of pulmonary valve regurgitation; however, this diastolic murmur
usually originates from the aortic valve and represents mild aortic regurgitation. [50 ] In
patients with aortic regurgitation, a late diastolic murmur can either be the murmur of
mitral stenosis or the Austin Flint murmur caused by a regurgitant jet directed toward the
anterior mitral leaflet. [51 ] Exercise or amyl nitrite inhalation intensifies the murmur of
organic mitral stenosis while diminishing the murmur of aortic regurgitation and the
Austin Flint murmur. [49 ] Doppler echocardiography differentiates mild aortic
regurgitation and pulmonic regurgitation. [52 ] Occasionally the murmur and peripheral
signs of aortic regurgitation are absent because of mitral stenosis. [48 ] , [53 ]
Electrocardiography
Electrocardiographic and roentgenographic evidence of eccentric left ventricular
hypertrophy in patients with mitral stenosis is an important clue to associated aortic
valve regurgitation. Also, atrial fibrillation early in the course of aortic regurgitation is a
clue to associated mitral stenosis. [49 ] , [54 ]
Echocardiography
Left ventricular hypertrophy and volume overload detected by echocardiography

suggest severe aortic valve regurgitation because these findings are not normally
associated with mitral stenosis. [49 ] Diastolic fluttering of the anterior leaflet of the
mitral valve and the ventricular septum is an additional finding suggesting aortic valve
regurgitation in patients with mitral stenosis. [49 ] , [55 ] In the presence of aortic valve
regurgitation, the Doppler determination of mitral valve area is overestimated when
pressure half-time measurements are used. [56 ]
Catheterization data
With current echocardiographic methods, cardiac catheterization to determine severity

of valvular heart disease is rarely indicated; however, hemodynamic profiles of such
patients have been studied thoroughly. Characteristically, the left ventricular diastolic
pressure is elevated in about 35 percent of patients with mitral stenosis and aortic
regurgitation. This can cause the transmitral gradient at rest to be small even when
significant stenosis of the mitral valve is present. [34 ] , [57 ] In patients with isolated
aortic valve regurgitation, the left ventricular diastolic pressure is elevated more
frequently than in patients with concomitant mitral stenosis and aortic regurgitation. [37 ]
Aortography may underestimate the severity of aortic regurgitation in patients with
associated mitral stenosis because low cardiac output and low stroke volume produce
a concomitant reduction in regurgitant volume. [32 ]
PATHOPHYSIOLOGY OF MITRAL STENOSIS WITH AORTIC REGURGITATION
In patients with mitral valve stenosis and aortic valve regurgitation, decreased cardiac
output minimizes the classic signs of aortic regurgitation (waterhammer pulse, head
bobbing, or visibly pulsating capillaries). Also, concomitant mitral stenosis reduces left
ventricular volume overload that is a characteristic of isolated aortic regurgitation. [57 ]
The underfilling of the left ventricle characteristic of mitral stenosis is offset by overfilling
secondary to aortic valve regurgitation. Pulmonary artery hypertension characteristic of
mitral stenosis usually is present.
OPERATIVE DECISION MAKING
Patients with rheumatic mitral stenosis and rheumatic aortic regurgitation usually
require replacement of both valves. Aortic valve repair is possible using techniques
such as cuspal extension with glutaraldehyde-treated bovine or autologous pericardium.
[58 ] Although early results with cuspal extension have been good, inexorable
progression of valve fibrosis will necessitate later prosthetic replacement for many
patients. [59 ]
Preoperative transthoracic and intraoperative transesophageal echocardiography aids

in assessing function of the aortic valve in patients requiring surgery for mitral stenosis.
At operation, the degree of ventricular fullness and amount of aortic root distention with
infusion of cardioplegia are clues to important aortic valve regurgitation. As stated
previously, if mitral valve replacement is necessary, strong consideration should be
given to replacement of the aortic valve when there is moderate or worse leakage
owing to rheumatic valvulitis.
Great care should be exercised to avoid ventricular distention if ventricular fibrillation

occurs prior to aortic clamping. If ventricular fibrillation develops, distention of the heart
can be prevented by inserting a left ventricular vent and by manually compressing the
heart. Also, even mild or moderate degrees of aortic regurgitation can complicate
cardioplegia delivery through the proximal aorta.
Rheumatic Mitral Stenosis with Rheumatic Aortic Stenosis
Physical findings
When rheumatic valve disease produces the combination of mitral valve stenosis and
aortic stenosis, the signs and symptoms of both lesions can be present; however, those
of mitral stenosis (dyspnea) tend to predominate, and the signs and symptoms of aortic
stenosis (syncope, angina) occur less frequently. Table 36-8 outlines the clinical
characteristics of patients in four studies of combined mitral and aortic stenosis.
Dyspnea, the most frequently observed symptom, was present in 95 percent of patients,
and angina and syncope were observed in 29 and 25 percent of patients, respectively.
Mitral valve stenosis may even mask the signs and symptoms of aortic stenosis,
making the clinical recognition of aortic stenosis difficult in patients with combined
disease. [60 ]
In addition, auscultatory findings may be confusing if the elevated end-diastolic pressure

caused by aortic stenosis minimizes the opening snap of mitral stenosis. [60 ] [62 ]
Clinical signs of aortic stenosis, delayed carotid upstroke, systolic thrill, and ejection
murmur may be less prominent in patients with coexisting mitral valve stenosis
compared to those with isolated aortic valve stenosis. [61 ] Some clinical features
raising suspicion of multiple valve involvement in patients with mitral stenosis or aortic
stenosis are shown in Table 36-9 and Table 36-10 .
Radiographic findings in patients with combined rheumatic mitral and aortic valve
stenosis are summarized in Table 36-11 . Left atrial enlargement is observed in 85
percent of patients, and dilatation of the proximal ascending aorta, common in patients
with congenitally bicuspid valves, is relatively infrequent (22 percent). Calcification of the
mitral or aortic valves is identified in approximately 35 percent of patients.
Electrocardiography
Atrial fibrillation is not common in patients with isolated aortic valve stenosis but is
observed in 52 percent of patients with combined disease (Table 36-12) .
Approximately one-third of patients will exhibit electrocardiographic evidence of left
ventricular hypertrophy, and right ventricular hypertrophy occurs in 18 percent of
patients. Atrial enlargement manifested by P-mitrale is observed in 32 percent of
patients.
Echocardiography
Echocardiography provides definitive information on valve structure, function, and

hemodynamics. In patients with combined mitral and aortic stenosis, estimation or
measurement of valve area may be more reliable than the pressure gradient because
cardiac output may be low, and atrial fibrillation produces variable stroke volume from
one cardiac cycle to the next. Severity of mitral valve stenosis is determined by directly
measuring the mitral valve orifice on the short-axis view of two-dimensional
echocardiography. This method is reliable and reproducible, and there is excellent
correlation between mitral valve area measured from a two-dimensional
echocardiogram and the area measured directly from a pathologic specimen. [63 ]
PATHOPHYSIOLOGY OF COMBINED MITRAL AND AORTIC STENOSIS
In contrast to isolated mitral stenosis in which ventricular function frequently is

preserved, the combination of mitral and aortic stenosis is associated with ventricular
hypertrophy and diastolic dysfunction. The pressure load from the aortic stenosis
causes a concentric hypertrophy with a small, noncompliant ventricular cavity. [54 ] Mitral
stenosis compromises the ventricle's ability to maintain cardiac output (in contrast to
isolated aortic stenosis in which cardiac output is maintained). [62 ] , [64 ] The decrease
in cardiac output minimizes the signs and symptoms of aortic stenosis and may make
the diagnosis of aortic stenosis difficult. [66 ] Other hemodynamic parameters are
similar to isolated mitral stenosis; e.g., elevation of left atrial and pulmonary arterial
pressures. [64 ] , [65 ]
Although mitral valve stenosis sometimes can be treated effectively with valvuloplasty,
commissurotomy for rheumatic aortic stenosis is rarely indicated. Thus, for patients with
both aortic and mitral valve stenosis owing to rheumatic heart disease, we favor
prosthetic replacement with mechanical prostheses if patients can manage long-term
anticoagulation.
The combination of aortic stenosis and mitral stenosis may present unique problems for
the surgeon. First, concentric hypertrophy of the left ventricle may displace the mitral
valve orifice anteriorly, producing poor exposure through a standard atriotomy; several
maneuvers and alternative incisions are described for patients in whom mitral valve
exposure is difficult. [66 ] [71 ] Also, the small left ventricular cavity may impinge upon
struts of caged-ball or stent-mounted bioprostheses. There is the potential for left
ventricular outflow obstruction from high profile prostheses in the mitral position in
patients with aortic and mitral valve stenosis and small left ventricular cavity size.
Rheumatic Mitral Regurgitation with Rheumatic Aortic Regurgitation
Physical findings
When mitral regurgitation and aortic regurgitation are both present, the cardinal signs of
either lesion may be masked by the other, [54 ] and when the clinical features of aortic
regurgitation predominate, it may be difficult to determine whether coexisting mitral
regurgitation requires surgical treatment. [54 ] The clinical characteristics of patients
with combined mitral and aortic regurgitation are summarized in Table 36-13 . Dyspnea
and congestive heart failure are most common, whereas angina, syncope, and
evidence of emboli occur less frequently.
Mitral valve regurgitation produces a characteristic systolic blowing murmur and may
also be associated with a diastolic flow murmur. Aortic valve regurgitation produces a
characteristic diastolic murmur and may also cause a systolic flow murmur. The
combination of two simultaneous murmurs during both diastole and systole may confuse
clinical diagnosis. Most patients have a long, pansystolic murmur heard best at the
apex, often with a diastolic rumble and decreased intensity of aortic closure. In general,
when aortic regurgitation is the dominant lesion, the early diastolic rumdiastolic rumble
is prominent; whereas, when mitral regurgitation prevails, the aortic diastolic murmur is
less intense. [72 ] [74 ] However, the severity of the two lesions does not always
correlate with the relative intensity of murmurs. [54 ] Additionally, a prominent S3 gallop
can be heard, whereas an S4 is unusual. [75 ]
Combined aortic and mitral regurgitation also results in significant left ventricular
enlargement, [73 ] which is evident on both electrocardiogram [54 ] , [72 ] and
roentgenogram. [54 ] , [72 ] , [74 ] , [75 ] Characteristic electrocardiographic findings are
summarized in Table 36-14 . On chest roentgenogram, nearly all patients have
cardiomegaly and left atrial enlargement. [54 ] , [72 ] Calcification of the mitral or aortic
valve is relatively uncommon. [54 ]
Echocardiography
Mitral valve motion and diastolic orifice configuration may be altered in aortic
regurgitation with a decrease in the opening amplitude of the anterior leaflet, and an
abnormal mitral orifice configuration with diastolic leaflet oscillation. [75 ] The mitral
valve orifice image is deformed because restriction in anterior leaflet excursion is most
pronounced in the center of the leaflet, where peak vertical separation normally occurs.
This restriction causes the anterior leaflet to appear flattened rather than convex
anteriorly, and in severe cases it may actually be concave toward the left ventricular
outflow tract. [75 ]
Catheterization data
Most patients have elevated right atrial and pulmonary arterial capillary wedge
pressure. There is usually a prominent v wave in pulmonary capillary wedge tracing.
Approximately 75 percent of patients have an elevated left ventricular end diastolic
pressure. [47 ] , [54 ]
PATHOPHYSIOLOGY OF MITRAL REGURGITATION WITH AORTIC

REGURGITATION
The combination of mitral and aortic valve regurgitation produces severe volume
overload of the left ventricle. The reduction of impedance to ejection allows the ventricle
to empty further, reducing ventricular wall tension with a resultant increase in the velocity
of shortening. [76 ] Chronic volume overload increases stroke volume and distention of
the left ventricle so that a larger stroke volume can be achieved with less myocardial
fiber shortening compared to normal hearts. [54 ] Patients who respond to increased
volume load by left ventricular dilation appear to tolerate surgical correction better than
patients with left ventricular hypertrophy owing to an increased pressure load. [54 ]
Patients with aortic valve regurgitation have augmented stroke volume to maintain an
adequate cardiac output, but when mitral regurgitation coexists, part of the augmented
stroke regurgitates into the left atrium and pulmonary veins. For this reason, when aortic
regurgitation is severe, concomitant mitral regurgitation greatly reduces systemic
cardiac output and can produce severe pulmonary congestion. [77 ]
As stated previously, aortic valves involved with rheumatic disease usually require
replacement. When the mitral valve also has rheumatic involvement, we replace the
mitral valve at the time of aortic valve operation. Currently, transesophageal
echocardiography is used to detect and quantify mitral regurgitation intraoperatively.
After the aortic valve is excised, the mitral valve is visually inspected if it is suspected of
being diseased or if the degree of regurgitation is severe.
MYXOMATOUS AND PROLAPSING VALVE DISEASE AFFECTING
MULTIPLE VALVES
Introduction
Myxomatous degeneration is the most common etiology of mitral regurgitation requiring

surgical correction in North America, and myxomatous aortic valve disease with annular
dilatation is, perhaps, the most common cause of aortic regurgitation. [78 ] [80 ] Most
cases of either isolated mitral or isolated aortic valve prolapse are not associated with
known connective tissue disorders. Mitral and aortic valvular prolapse coexist frequently
with connective tissue disorders such as Marfan syndrome, Ehlers-Danlos syndrome,
osteogenesis imperfecta, and others. [77 ]
Aortic valve regurgitation in patients with the Marfan syndrome is caused by

progressive enlargement of the sinus portion of the aorta and the aortic valve annulus;
i.e., annuloaortic ectasia. [81 ] , [82 ] The principal causes of mitral regurgitation in
patients with Marfan syndrome are mitral annular dilation, floppy or prolapsing leaflets,
and mitral annular calcification. [82 ] The pathological lesion in the Marfan syndrome is
cystic medial necrosis, which is characterized by degeneration of elastic fibers and
infrequent cysts. [82 ] Alterations in the synthesis and cellular secretion of fibrillin are
responsible for the phenotypic characteristics of many patients with Marfan syndrome.
[83 ] Some patients have myxomatous cardiovascular lesions and annuloaortic ectasia
without the other clinical characteristics of the Marfan syndrome.
Two-dimensional echocardiographic studies show that the frequency of aortic valve

prolapse in patients with mitral valve prolapse varies between 3 and 24 percent ( Table
36-15 ). [84 ] , [85 ] In one necropsy study, the frequency of mitral regurgitation in Marfan
patients with aortic aneurysms (most with aortic regurgitation) was 54 percent (7 of 13).
[82 ] About 17 percent of patients who undergo surgery for myxomatous aortic valve
require surgical correction of mitral regurgitation ( Table 36-16 ). Although multiple valve
involvement with myxomatous degeneration usually manifests itself as mitral
regurgitation in combination with aortic regurgitation, in some cases all four valves may
be involved. [86 ] It is not clear whether the underlying pathology of isolated mitral valve
prolapse is the same as the cardiovascular lesions that occur in the Marfan syndrome
and other multiple floppy valve syndromes. [87 ] , [88 ]
Diagnosis, Signs, and Symptoms
Signs and symptoms of aortic and mitral valve regurgitation are reviewed in the section
on rheumatic valvular disease. In addition, to complete evaluation of the aortic and
mitral valves and proximal aorta, patients with Marfan syndrome should have
assessment of the descending aorta for aneurysm or chronic dissection.
If annuloaortic ectasia is not present, patients with mitral and aortic valve regurgitation
owing to myxomatous degeneration are candidates for repair of both valves. The aortic
valve is inspected initially, and the decision for repair or prosthetic replacement is made
depending on cuspal morphology. If tissue is sturdy and there is little prolapse or
prolapse is limited to one cusp, repair can be undertaken with commissural narrowing
and cusp resuspension. Often, aortic valve regurgitation is central, and simply narrowing
the annulus by commissural plication restores valvular competence. If tissue is
attenuated or if multiple cusps have severe prolapse, the valve is replaced.
In most instances, patients with Marfan syndrome and aortic regurgitation require
composite replacement of the aortic valve and ascending aorta. [89 ] Occasionally,
moderate aortic regurgitation can be repaired at the time of aortic replacement by
suspending the aortic valve inside a tube graft or remodeling the sinus portion of the
aorta. [90 ] Even if the aortic valve is replaced with a composite graft and mechanical
valve, the surgeon should favor repair of associated mitral regurgitation. Gillinov and
associates report that valvuloplasty is possible in approximately 80 percent of patients
with mitral regurgitation and Marfan syndrome, and that 5 years postoperatively, 88
percent of patients are free of significant mitral valve insufficiency. [91 ]
Myxomatous Mitral Regurgitation with Tricuspid Regurgitation
Myxomatous degeneration may also involve the tricuspid valve, and presentation of
mitral and tricuspid valve regurgitation owing to degenerative disease is not
uncommon. In one study, 54 percent of patients with mitral valve prolapse also had
tricuspid prolapse; however, most of these patients did not have significant
regurgitation. [77 ] As with tricuspid regurgitation associated with rheumatic mitral
disease, preoperative and intraoperative echocardiography is important in evaluating
tricuspid disease in patients with myxomatous mitral regurgitation.
SENILE CALCIFIC AORTIC VALVE DISEASE WITH MULTIPLE
VALVE INVOLVEMENT
In contrast to aortic stenosis caused by rheumatic disease in which associated mitral

valve disease is common, senile calcific aortic stenosis usually presents as an isolated
lesion. Although the combination of mitral valve disease and senile calcific aortic
stenosis is uncommon, senile aortic calcification is a frequent cause of aortic valve
stenosis. [79 ] The incidence of senile calcific aortic disease has steadily increased in
the last 20 years. Therefore, although mitral valve disease associated with calcific aortic
stenosis is rare, as the incidence of calcific aortic stenosis increases, so does the
likelihood of encountering patients with disease of both valves.
Patterns of Multiple Valve Involvement with Calcific Aortic Stenosis [92 ]
CALCIFIC AORTIC STENOSIS WITH INFECTIVE ENDOCARDITIS OF THE

MITRAL VALVE
Stenotic aortic valves are frequently sites of infective endocarditis. As discussed in the
section on endocarditis, the mitral valve may become involved with infective
endocarditis by common abscess, by verrucous extension, or from a jet lesion, and
infection may cause mitral valve aneurysm, perforation, and chordae disruption. [92 ]
Management of these patients usually requires aortic valve replacement and
assessment of the mitral valve at the time of operation. Vegetations of the mitral valve
can sometimes be removed and perforations patched if the remaining tissue is sturdy
and appears healthy.
CALCIFIC AORTIC STENOSIS WITH FUNCTIONAL MITRAL VALVE DISEASE
Senile calcification of the aortic valve may lead to mixed stenosis and regurgitation, [79
] and the volume load from regurgitation may lead to left ventricular dilatation and
secondary mitral regurgitation of an otherwise normal mitral valve. [79 ] Mitral
regurgitation secondary to aortic valvular disease is discussed in the section on
Pathophysiology of Multiple Valve Disease.
CALCIFIC AORTIC STENOSIS WITH CALCIFICATION OF THE MITRAL VALVE
Degenerative calcification is an age-related process usually affecting the aortic and

mitral valves. In a study of patients over 75 years of age, one-third had degenerative
aortic or mitral calcification. [77 ] About 2550 percent of patients with calcific aortic
stenosis have calcification of the mitral valve annulus. Generally, patients with
associated mitral annular calcification are older, have more severe aortic stenosis, and
are more often female when compared with patients with aortic stenosis without mitral
annular calcification. [85 ] Mills reported 17 patients undergoing mitral valve
replacement for valvular disease related to severe annular calcification. Four of these
patients also had concomitant aortic valve replacement. [93 ] Patients with mitral
annular calcification have increased incidence of conduction defects [94 ] and aortic
outflow murmurs, and annular calcification may exist in combination with rheumatic or
myxomatous disease. [95 ]
Diagnosis, Signs, and Symptoms of Aortic Stenosis and Mitral Regurgitation
PHYSICAL FINDINGS
Auscultatory findings in aortic stenosis and mitral regurgitation consist of two systolic
murmurs that can be distinguished by location of maximum intensity and radiation.
Characteristically, aortic stenosis produces a crescendo-decrescendo murmur at the
base, and mitral regurgitation produces a holosystolic murmur at the apex.
Occasionally, a prolonged ejection murmur of aortic stenosis may simulate a
holosystolic murmur at the apex, and the murmur of severe mitral regurgitation may
radiate toward the base and may take on a crescendo-decrescendo pattern simulating
an ejection murmur. [49 ] , [52 ]
ELECTROCARDIOGRAPHY
Atrial fibrillation is uncommon in isolated aortic stenosis, and its presence is a clue to
associated mitral valve disease. [49 ] Both aortic stenosis and mitral regurgitation
produce left ventricular hypertrophy and left atrial enlargement.
ECHOCARDIOGRAPHY
Echocardiography is necessary to delineate mitral valve morphology and presence of

flail segments, and to assess the severity of aortic valve stenosis. Transesophageal
echocardiography, either preoperatively or intraoperatively, may be required to fully
evaluate the mitral valve.
INFECTIVE ENDOCARDITIS AFFECTING MULTIPLE VALVES
Introduction
As with infection of a single valve, multiple valve infective endocarditis may occur in
previously diseased valves, normal valves, and prosthetic valves. Infective endocarditis
requiring multiple valvular procedures occurs in about 1025 percent of all patients
having operationand usually involves the mitral and aortic valves ( Table 36-17 and
Table 36-18 ). [8 ] , [95 ] [101 ] Conduction defects on electrocardiogram may be a clue
to abscess involvement of both the aortic and mitral annulus. [102 ]
About 15 percent of patients who require surgery for multiple valve endocarditis have
biventricular involvement, and most instances of tricuspid valve infections are owing to
intravenous drug use. [99 ] , [103 ] Patients with multiple valve infective endocarditis
more frequently have congestive heart failure as an indication for surgery and are more
likely to have intracardiac abscess when compared to single valve infective
endocarditis. [99 ]
Aortic Regurgitant Jet Lesion of the Mitral Valve
Perforation of the anterior leaflet of the mitral valve may occur from the regurgitant jet of
aortic valve endocarditis, and the diagnosis can be made from transesophageal
echocardiography. [104 ] Often, the perforation in the mitral valve can be debrided and
repaired with a patch of pericardium or prosthetic material.
Prosthetic Valve Endocarditis
Risk of prosthetic valve endocarditis is greatest approximately 46 weeks

postoperatively and decreases to a stable rate by about one year after operation. [105 ]
, [106 ] Staphylococcus epidermidis and aureus account for 20 and 30 percent of
cases, brespectively. [107 ] Transesophageal echocardiography can identify
vegetations caused by infection as well as prosthetic valve dysfunction and associated
abscess cavities. [107 ] In general, management of patients with endocarditis affecting
multiple valves is similar to management of patients with infection of one valve. There
are, however, some special considerations. When aortic valve endocarditis is
complicated by abscess formation, infections may extend into the mitral annulus and
necessitate concomitant mitral valve replacement; this occurs in approximately 12
percent of patients with aortic root abscess [108 ] and is especially prevalent when
there is involvement of the aorticomitral junction or subannular interventricular septum.
[99 ] , [108 ]
Tricuspid Valve with Left-Sided Valve Replacement
When the tricuspid valve is excised at the time of left-sided valve replacement, there
remains a question of whether the tricuspid valve needs to be replaced. Simple
excision of the tricuspid valve seems appropriate only in the absence of pulmonary
hypertension and left-sided failure. A prosthetic left-sided valve is intrinsically stenotic,
and many patients with tricuspid valve endocarditis can have pulmonary hypertension
secondary to septic pulmonary emboli. Silverman found that patients who had tricuspid
excision alone with left-sided valve replacement required perioperative inotropic
support, and management of their postoperative congestive heart failure was more
difficult than that of the patients who had tricuspid replacement. [99 ]
Results
Early mortality following surgery for multiple valve endocarditis is in the range of 2030
percent, and Table 36-19 compares NYHA-class matched groups that had multiple
valve procedures for infective endocarditis and for other reasons.
CARCINOID HEART DISEASE AFFECTING MULTIPLE VALVES
Introduction
Valvular heart disease develops in about 50 percent of patients with carcinoid tumors;
patients with primary carcinoid tumor in the small intestine are more likely to have
carcinoid heart disease than those with carcinoid tumors in other locations. [2 ] In most
cases, the tricuspid and pulmonary valves are involved. We have offered valvular
surgery to patients with severe symptoms of right heart failure caused by carcinoid heart
disease whose systemic carcinoid symptoms are controlled by octreotide and/or
hepatic dearterialization. [109 ]
Signs and Symptoms/Diagnosis
Jugular venous distention with v waves (from tricuspid regurgitation) and a waves (from
tricuspid stenosis) can be evident. Right ventricular enlargement can produce a
pericardial lift. Most patients have murmurs from the tricuspid and pulmonary valves.
[109 ] Patients often demonstrate ascites and liver enlargement as a result of either
right-sided heart failure or hepatic metastases, or both. Therefore, these findings are
not necessarily indicative of severe tricuspid valve regurgitation.
The electrocardiogram of patients with carcinoid heart disease often shows low voltage
(85 percent), right bundle branch block (42 percent), and evidence of right atrial
enlargement (35 percent). [2 ] , [109 ] The chest roentgenogram characteristically shows
cardiomegaly (69 percent), pleural effusions (58 percent), and pleural thickening (35
percent). [109 ]
Echocardiography
Echocardiographic findings of carcinoid heart disease include thickening and reduced

motion of the tricuspid valve leaflets; the pulmonic valve cusps may be thickened and
retracted. [102 ] Fusion of the pulmonary valve commissures results in a stiff fibrotic ring
that may cause a stricture in the entire pulmonary orifice. Pulmonary regurgitation and
stenosis may both be present. [110 ]
Invasive Studies
Cardiac catheterization is not necessary unless ischemic symptoms or a history of

myocardial infarction suggest coronary artery disease. [111 ]
Pathophysiology
Carcinoid heart disease results from deposition of plaques on the endocardium of the
valves and atria; this usually occurs on the right side of the heart. However, plaques can
develop on the mitral and aortic valves when there is carcinoid tumor in the lungs, or
intracardiac shunting, which bypasses the lungs. [2 ] Valves are damaged by exposure
to circulating substances released from carcinoid tumors such as serotonin and
bradykinin. Both of these components are inactivated by the lungs and the liver; the
relationship between tumor location and the location of cardiac lesions is summarized
in Table 36-20 . [112 ] The plaques usually deposit on the downstream side of the
cardiac valves causing adherence of the leaflet to the underlying structures, producing
functional regurgitation. Carcinoid plaque deposition also may constrict the valve
annulus producing stenosis. [2 ]
The dominant functional lesion of carcinoid heart disease is tricuspid valve

regurgitation; the valve is fixed in a semi-open position, so that some degree of
stenosis is present. The pulmonary valve is fibrotic causing mixed stenosis and
regurgitation, which increases the degree of tricuspid regurgitation. [2 ]
TIMING OF OPERATION
The primary indications for surgery are increasing symptoms of congestive failure with
objective evidence of valvular disease. [111 ] Again it should be noted that some of the
signs of right heart failure such as peripheral edema, ascites, and hepatomegaly can be
caused by the primary disease. Another indication for operation may be progressive
right ventricular enlargement in the absence of symptoms. In a small series of carcinoid
patients, right ventricular size and function did not correlate with operative or late
mortality. [109 ] Currently we employ exercise testing to provide an objective
assessment of the functional status and a guideline to the timing of cardiac surgery. If
the primary cause for debilitation is right heart failure, it is reasonable to offer valve
replacement even though the prognosis may be guarded. [111 ]
TRICUSPID VALVE OPERATION
The tricuspid valve always requires replacement, and in our earlier experience, we used
mechanical prostheses because of the possibility of carcinoid plaque formation on a
bioprosthesis. However, review of our patients and those reported previously shows
little difference in patient survival with mechanical or tissue valves. [111 ] Although
involvement of a bioprosthetic cardiac valve with carcinoid plaque has been reported,
the valve was functioning normally at the time of death. [111 ] Prosthetic valve failure
secondary to carcinoid effects has not been reported. [109 ] At present, we use
bioprostheses for most patients having tricuspid valve replacement, and this may be
especially advantageous because liver dysfunction that is evident in many carcinoid
patients can add to the morbidity and difficulty of long-term anticoagulation. [109 ]
PULMONARY VALVE OPTIONS
Because pulmonary valve regurgitation is generally well tolerated if the tricuspid valve is
competent, valvectomy is all that is necessary for most patients with pulmonary stenosis
owing to carcinoid syndrome. In our most recent experience, pulmonary valvectomy has
been performed transatrially after removal of the anterior leaflet of the tricuspid valve;
this appears to adequately relieve stenosis in most patients. In other patients we use a
simple transannular incision followed by excision of pulmonary cusps and closure with a
small patch of pericardium. Pulmonary valve replacement with a homograft is reserved
for patients who have concomitant replacement of the mitral and/or aortic valves or
patients with extensive right ventricular enlargement.
Octreotide is given prior to induction of anesthesia and during operation as needed
when there is evidence of flushing and vasodilation. Octreotide may be given
subcutaneously, as a bolus or as a continuous infusion during surgery. [113 ]
Preoperative steroids and antihistamines can also be used to prevent adverse effects
from tumor-released mediators. [113 ] , [114 ] We usually give octreotide 500 µg IV
prior to induction of anesthesia with additional intravenous doses as needed at the
onset and termination of cardiopulmonary bypass. Postoperatively, octreotide is
continued at 500 µg subcutaneously each hour for the first 6 hours, and the dose is
tapered if the patient is free from carcinoid symptoms. Aprotinin, a kallikrein inhibitor,
may mitigate the effects of substances released by carcinoid tumors during anesthesia
and reduce intraoperative and postoperative bleeding. [113 ]
RARE CAUSES OF MULTIPLE VALVE DISEASE
Table 36-21 lists some rare causes of multiple heart valve disease that require surgical
correction.
AORTIC STENOSIS AND CORONARY ARTERY DISEASE
Aortic stenosis in one of the more frequently encountered valvular lesions in adult
populations. Since degenerative calcific aortic stenosis is most common in patients in
their 60s, 70s, and 80s, and since congenitally bicuspid valves that proceed to become
stenotic are more frequent in men who are susceptible to coronary artery disease at an
earlier age, it is not surprising that the combination of aortic stenosis and coronary
artery disease is encountered frequently. This disease combination is usually gratifying
to treat because the response to surgical relief of aortic stenosis and coronary artery
obstructions is significant, immediate, and relatively durable.
Patients with aortic stenosis are asymptomatic initially but eventually present with
angina pectoris, congestive heart failure, syncope, or some combination of these. When
significant coronary artery obstructions are present in addition to valvular obstruction,
angina pectoris is frequently present. However, angina pectoris can occur, as is well
known, in the absence of significant coronary artery obstructions. A complete history will
elicit relevant symptoms. It is relatively easy to identify symptoms of myocardial
ischemia or congestive heart failure in these patients. Neurologic symptoms may be
more difficult to elicit, and careful questioning regarding transient symptomatology is
required. Symptoms suggestive of carotid artery obstruction such as amaurosis fugax
or previous stroke should be sought, since specific studies of the carotid arteries may
be necessary, especially since the murmur of aortic stenosis may radiate into the
carotids and obscure the detection of bruits.
Prominent findings on physical examination include the typical crescendo/decrescendo

systolic murmur heard in the aortic area on precordial examination. The second heart
sound may be single, and signs of congestive heart failure with rales and edema may
be present. The electrocardiogram typically shows left ventricular hypertrophy because
of the increased afterload produced by aortic stenosis. If the patient suffered recent or
old myocardial infarction, electrocardiographic abnormalities typical of infarction also
may be present. The echocardiogram typically shows a hypertrophied ventricle with
calcified and immobile leaflets producing a constricted aortic orifice. All patients with
angina pectoris and all patients with aortic valve disease who are over 40 years of age
should have coronary angiography to define coronary anatomy. Right- and left-sided
heart catheterization should be performed simultaneously so that complete evaluation of
myocardial performance, including measurement of left ventricular end-diastolic
pressure and the pulmonary artery pressures, can be obtained. Transaortic valvar
gradient also can be determined at catheterization.
The preoperative evaluation of patients with aortic stenosis, coronary artery disease,
and poor ventricular function is complicated. Patients with poor ventricular function often
generate relatively low transaortic valve gradients. This renders the calculation of valve
area and the assessment of criticality of aortic stenosis less accurate. The morphology
of the valve with immobile leaflets and heavy calcification as seen on echocardiography
is often an important confirmatory sign that critical aortic stenosis is present. Even in the
presence of a small gradient, if echocardiographic signs of significant valve stenosis
are present, and if left ventricular intracavitary pressure exceeds 120 mmHg in systole,
mortality rates are acceptable, and response to valve replacement surgery is usually
good. A poorly contractile, thinned out ventricle with low transvalvular gradient and low
intracavitary systolic pressure usually suggests that operation is of high risk and of
limited benefit. A poorly contractile ventricle with normal or increased wall thickness
may recover contractile force if a substantial amount of reversibly ischemic myocardium
is present and if the degree of aortic stenosis is significant. In addition to ventricular
function, other important determinants of the risks and advisability of surgery include
patient age, presence of previous cardiac operations, and overall organ functions,
especially renal function.
Indications and contraindications for operation are implicit in the preceding discussion.
The patients least likely to benefit from this operation are those who, in fact, do not have
critical aortic stenosis and those with irreversibly poor ventricular function. As noted,
both these assessments may be difficult to make preoperatively. Patients with large,
poorly contractile left ventricles with low ejection fractions and those with low cardiac
output, a transvalvular gradient less than 30 mmHg, and an intracavitary left ventricular
systolic pressure less than 120 mmHg may have prohibitive operative risk and a less
than optimal response to surgery. Left ventricular thinning on echocardiography is a
particularly ominous sign of end-stage pump failure. Under these circumstances, the
calculation of valve area is inaccurate and therefore relatively unimportant.
Pathophysiology
Aortic stenosis produces high ventricular afterload, which ultimately is the source of all
the symptoms and signs of aortic stenosis. Most patients with aortic stenosis have
hypertrophied and thick-walled left ventricles. Contractile function is initially good, and
ejection fraction may be maintained. In later stages of the disease, the ventricle begins
to fail with enlargement and global diminution of contractile function. At any stage of the
disease, the presence of critical coronary artery obstruction can cause regional wall
motion abnormalities. Significant three-vessel coronary artery disease of long-standing
duration may itself lead to global ventricular dysfunction.
In patients with critical aortic stenosis and good ventricular function, the increased left
ventricular afterload is immediately reduced by valve replacement. Since most patients
with aortic stenosis have hypertrophied and thick-walled ventricles, intraoperative
subendocardial ischemia is more difficult to avoid during aortic cross-clamping.
Although revascularization should not decrease left ventricular contractility and may
increase it, some myocardial stunning with a temporary decrease in global and regional
left ventricular contractility inevitably results from the surgical procedure. [11 ] [14 ] This,
of course, assumes more important pathophysiologic significance in patients with poor
ventricular function preoperatively.
Postoperatively, patients may have dramatic improvement in symptoms. Relief of left

ventricular outflow obstruction immediately leads to enhanced cardiac output and
perfusion of vital organs. In addition, left ventricular function improves both immediately
and over time after relief of outflow obstruction. Correction of myocardial ischemia can
lead to recruitment of formerly hibernating ischemic myocardium [14 ] , [15 ] with
enhancement of ventricular function. [7 ] This combination of beneficial effects can lead
to a dramatic reduction in symptoms and improvement in functional capacity in patients
with reversibly poor preoperative cardiac performance.
Monitoring for surgery of the aortic valve and coronary arteries includes measurements
that have become standard for most cardiac surgical operations. All patients have
arterial lines, usually in the radial artery for continuous measurement of systemic blood
pressure and intermittent sampling of arterial blood gases. A pulmonary artery catheter
for measurement of pulmonary artery pressures is always employed. These catheters
are equipped with thermistors for determination of cardiac output by thermodilution and
optical sensors for continuous estimation of mixed venous oxygen saturation. While the
pulmonary artery catheter has a balloon at its tip, occlusion wedge pressure is rarely
measured in the perioperative period because of the danger of pulmonary artery
rupture, especially with the inevitable postoperative coagulopathy experienced by all
patients undergoing cardiopulmonary bypass. A thermistor-tipped pulmonary artery
catheter permits periodic measurement of cardiac output by thermodilution. This usually
is performed in duplicate or triplicate because of an expected 10 to 15 percent
variability in determinations using this method. Particularly useful information is
provided by continuous measurement of mixed venous oxygen saturation. Given stable
hemoglobin and oxygen consumption (which is usual on a moment-to-moment basis
postoperatively), the mixed venous oxygen saturation gives an accurate reflection of
instantaneous changes in cardiac output. Using the measurement of hemoglobin and
relatively accurate estimates of oxygen consumption, calculation of cardiac output using
the Fick method can be performed easily and compared with thermodilution
determinations. Perioperative monitoring also includes, of course, a continuous
electrocardiogram and, during anesthesia, measurement of end-tidal carbon dioxide.
The perfusion setup is standard and similar to that for isolated coronary artery bypass
(Fig. 37-2) . A single aortic cannula is ordinarily placed in the distal ascending aorta. A
single two-stage venous cannula is placed via the right atrial appendage with its tip
positioned in the inferior vena cava. After establishment of cardiopulmonary bypass, the
patient is usually cooled to 28 to 32°C, during which time a left ventricular vent is
positioned via the right superior pulmonary vein. With the heart well emptied, the aortic
cross-clamp is applied during temporary reduction in pump flow and thus aortic
pressure. Thereafter, the heart is arrested with cold (4°C) potassium blood cardioplegia
and topical irrigation with iced saline solution. After the heart is opened, the
endocardium is intermittently irrigated with iced saline solution to enhance myocardial
cooling.
A combination of antegrade and retrograde cardioplegia is optimal. The initial dose of

cardioplegia usually is given both ways, half antegrade and half retrograde.
Approximately 15 mL/kg is given as the initial dose. Subsequent doses of cardioplegia
are given retrograde throughout the operation. This is particularly convenient because
retrograde cardioplegia can be given even after the aortic root is opened and without
significantly disrupting the flow of the operation.
The left internal mammary artery is almost always used to graft the left anterior
descending artery when it has a significant obstruction. In general, reversed greater
saphenous vein is used for other bypass grafts. The reasons for choice of these
conduits are the same as the reasons to choose them in the treatment of isolated
coronary disease. The reasoning behind the choice of valve prosthesis is also similar to
that in the treatment of isolated valvular heart disease. In older patients (more than 70
years old) and those with contraindications to long-term anticoagulation, a tissue
prosthesis is used most often. Most other patients receive mechanical prostheses.
Recently, the argument has been advanced that tissue prostheses should be used in
younger patients with combined valvular and coronary artery diseases because the
coronary artery disease reduces their expected life span. [16 ] This concern may be
less important than age and suitability for anticoagulation.
The multiple steps in the combined operation follow a logical sequence (see Fig. 37-2 ).
After establishment of cardiopulmonary bypass and insertion of the left ventricular vent,
the aorta is clamped and the heart arrested with antegrade and retrograde cold blood
cardioplegia and topical hypothermia with iced saline. The first step in the operation is
performance of the distal saphenous vein bypass grafts. When these are complete, the
aorta is opened, and aortic valve replacement is carried out using the prosthesis of
choice. The aorta is closed completely at this point. The distal anastomosis of the
internal mammary artery graft is then made. Following completion of this, the aortic
cross-clamp is released and air evacuated from the heart. A partially occluding clamp is
applied to the aorta, and proximal vein grafts are performed. Alternatively, the proximal
vein graft anastomoses can be performed with the aortic cross-clamp still in place.
While this prolongs the ischemia time, it avoids application of a second clamp to the
aorta with the potential for disruption of atheromatous debris or injury to the aortic suture
line. This consideration is particularly important in patients undergoing redo operations,
especially since the presence of previous bypass grafts can make application of a
partially occluding clamp on the aorta difficult. Coordinated sinus rhythm is established,
temporary atrial and ventricular pacing wires are positioned, and the left ventricular vent
is removed. In the early minutes and hours following use of cold blood cardioplegia,
atrioventricular pacing is often required to maintain sequential atrial and ventricular
activation. Atrial/ventricular sequential activation is particularly important to optimize
hemodynamic performance in patients with aortic stenosis because as much as 30
percent of the cardiac output may be derived from atrial kick as a result of the
hypertrophied and noncompliant ventricle that is typical of the patient with aortic
stenosis.
Weaning from cardiopulmonary bypass is performed gradually with stepwise diminution

of pump flow and increased left ventricular filling. Simultaneous monitoring of the
appearance of the heart, pulmonary artery and systemic blood pressures, and mixed
venous oxygen saturation is done during weaning. In patients with hypertrophied
ventricles, it may be important to keep the left ventricle filled to prevent excessive left
ventricular outflow tract obstruction in systole and to provide adequate preload in the
noncompliant heart. In patients who are difficult to wean from cardiopulmonary bypass,
inotropic drugs may be applied. Epinephrine is usually the first choice, with dopamine,
dobutamine, and phosphodiesterase inhibitors such as milrinone available in reserve.
The usual dosage of epinephrine is 0.05 to 0.15 µg/kg per minute. Dopamine and
dobutamine are given at 5 to 10 µg/kg per minute, although these agents are rarely
required. Milrinone requires a loading dose of 50 µg/kg, followed by an infusion of 0.5
µg/kg per minute. Milrinone appears to be most efficacious when used in combination
with a catecholamine such as epinephrine. The use of milrinone is ordinarily reserved
for patients with poor ventricular function who have inadequate myocardial performance
on epinephrine alone following cardiopulmonary bypass.
In patients with high output and low systemic vascular resistance and low systemic
blood pressure, a vasoconstrictor such as Neo-Synephrine may be used. Pure
vasodilators are often not useful in patients with aortic stenosis who require more
afterload to maintain myocardial perfusion. In patients with particularly severe ventricular
dysfunction who do not wean from bypass, the intraaortic balloon pump may be used.
Two to three attempts to wean from cardiopulmonary bypass using inotropic drugs
should be made over a period of 20 to 30 minutes. If weaning from cardiopulmonary
bypass is not successful at this point, an intraaortic balloon pump should be inserted.
Persistent attempts to wean from bypass following two to three good attempts with
adequate doses of inotropic drugs and 20 to 30 minutes of elapsed time may be
counterproductive because complications from prolonged cardiopulmonary bypass may
start to occur. As the hypertrophied heart recovers following the ischemic insult,
inotropic and mechanical support often can be weaned relatively rapidly within several
hours. In patients with more impaired ventricular function, weaning, of necessity, occurs
more gradually and may take days.
Results
Early hospital mortality after aortic valve replacement and coronary bypass grafting
ranges from approximately 2 to 10 percent. [7 ] , [10 ] Higher mortality is observed in
patients with more severe symptoms of heart failure and impaired ventricular function
preoperatively. Most frequent causes of operative death are low-output cardiac failure,
myocardial infarction, and arrhythmia. Incremental risk factors for hospital death include
patient age, functional class, and several measures of ventricular function. In a number
of studies, late survival has ranged from 60 to 80 percent at 5 years and from 50 to 75
percent at 8 years postoperatively [17 ] [30 ] (Fig. 37-3) . By multivariate analysis,
variables leading to reduced late survival include older age, cardiac enlargement, and
more severe preoperative clinical symptoms. The use of a mechanical prosthesis at
valve replacement has been associated with lower long-term survival and lower
long-term event-free survival (Fig. 37-4) . Most patients with mechanical prostheses are
maintained on long-term anticoagulation. This, of course, carries with it an irreducible
risk for unwanted anticoagulant-related hemorrhage. In addition, patients with
mechanical prostheses remain at risk for thromboembolic complications even on
long-term anticoagulation.
This fact and the somewhat lower life expectancy of patients with coronary artery
disease following valve replacement have led some investigators to suggest so-called
better matching between patient and prosthesis and more liberal use of tissue valves in
patients having simultaneous bypass operations whose life expectancy may be shorter.
[16 ] While most surgeons would readily use a biologic prosthesis in patients over age
70, this reasoning argues for use of a tissue valve in patients between the ages of 60
and 70 who are also undergoing coronary artery bypass surgery. This is a decision that
cannot be made without consultation with the patient. A frank discussion of the
advantages and drawbacks of each approach continues to be an important component
of the preoperative evaluation and planning for this type of surgery.
AORTIC REGURGITATION AND CORONARY ARTERY DISEASE
Significant aortic regurgitation occurs less often in older populations and is therefore
compared with aortic stenosis, less often encountered with coronary artery disease.
Most series of patients undergoing aortic valve replacement and coronary artery bypass
surgery include a relatively small (10 to 25 percent) percentage of patients with aortic
insufficiency. [7 ] [10 ] , [17 ] [21 ] While the operative management of patients with
aortic regurgitation and coronary artery bypass surgery is similar to that previously
described, aortic insufficiency produces different pathophysiology that has implications
for perioperative management, and the presence of an incompetent aortic valve
introduces subtle nuances to the intraoperative management of these patients.
Patients with aortic regurgitation and coronary artery disease present usually in one of
three ways. The aortic regurgitation may be asymptomatic and detected incidentally
during evaluation for symptomatic coronary disease. Second, the patient may be
asymptomatic, yet a routine physical examination reveals a murmur of aortic
insufficiency that leads to cardiac evaluation and detection of coronary disease. Finally,
patients may present relatively late in the course of valvular heart disease with
congestive heart failure due to decompensation of the volume overloaded left ventricle
or ischemic damage or both. Patients therefore may present with no symptoms and
essentially normal physiology, a classic ischemic syndrome, or congestive heart failure.
The physical signs also will depend therefore on the nature of the presentation. In
general, all patients with aortic insufficiency have an audible early diastolic blowing
murmur. The exception is those with acute aortic insufficiency, but this is an extremely
rare entity except in the setting of aortic dissection. In late stages of the disease, as
noted, signs of congestive heart failure, including rales and peripheral edema, may be
present.
The preoperative evaluation of a patient with aortic insufficiency and coronary artery
disease is not different from that previously described for patients with aortic stenosis
and ischemic heart disease. As suggested earlier, the nature of the presenting
syndrome may determine how the evaluation proceeds. Patients who present with
angina pectoris will more likely have cardiac catheterization and coronary angiography
as an early diagnostic procedure. Those who present with asymptomatic or
symptomatic aortic insufficiency, in whom valve surgery is contemplated, should have
evaluation of the coronary arteries if angina pectoris is present or if they are over 40
years of age. Echocardiography is particularly useful in detecting aortic regurgitation
because the murmur is sometimes subtle and difficult to detect. In addition,
echocardiography gives important information regarding both ventricular contractile
function and ventricular size. Since many patients with aortic regurgitation are
asymptomatic, careful evaluation for changes in ventricular size or function is important
because the presence of these changes may constitute an indication to proceed with
surgical intervention.
Pathophysiology
Aortic regurgitation increases left ventricular preload and causes left ventricular
dilatation. Dilatation does not occur acutely, and patients with acute aortic insufficiency
are often severely symptomatic due to a sudden increase in left ventricular end-diastolic
pressure and decrease in net forward cardiac output. Left ventricular dysfunction due to
coronary artery disease also can produce left ventricular dilatation. Valve replacement
relieves some of the preload but does not immediately result in improved left ventricular
contractility. Revascularization may produce improved contractility by recruitment of
hibernating myocardium. [11 ] , [14 ] , [15 ] This operation does not increase left
ventricular afterload.
The indications for surgery in aortic regurgitation are somewhat controversial. Patients
can have significant amounts of aortic insufficiency for long periods of time without
developing symptoms. With improved results, there is justification for early operation in
patients with aortic insufficiency but without symptoms. The echocardiogram pays a
crucial role in making the decision to proceed with surgery. The presence of significant
(3+ or 4+) aortic regurgitation on echocardiogram is an indication for valve
replacement. Even if the patient has no symptoms and no signs of cardiac
decompensation, valve replacement should be carried out because the results are
excellent and relief of volume overload will prevent the development of irreversible
ventricular dysfunction. Obviously, if on echocardiography the patient has any ventricular
dilatation or loss of contractile function, surgery should be performed. Even with
relatively advanced ventricular dysfunction, operation is usually indicated because valve
replacement relieves the volume overload without producing an increase in ventricular
afterload. This evaluation is somewhat more difficult when coronary artery disease is
also present, because it may have an impact on ventricular function that
revascularization may or may not improve. However, except in advanced stages of
diffuse three-vessel coronary artery disease, myocardial abnormalities due to coronary
artery obstructions are usually regional and can be distinguished from global
dysfunction due to volume overload from the insufficient valve.
The operation is conducted in a fashion almost completely analogous to that described

for aortic stenosis and coronary artery disease. However, in the presence of aortic
insufficiency, antegrade cardioplegia in the aortic root cannot be given because the
cardioplegia solution leaks into the left ventricle. In general, retrograde cardioplegia
alone is used under these circumstances. Despite concerns that retrograde
cardioplegia does not provide adequate protection for the right ventricle, the use of
retrograde cardioplegia alone in patients with aortic insufficiency and coronary artery
disease appears to provide adequate protection of the right ventricle. Right ventricular
failure is an extremely unusual complication of aortic valve replacement and coronary
artery bypass surgery. Antegrade cardioplegia administered by placing cannulas in the
coronary ostia and administering cardioplegia directly into the coronary arteries also
may be performed but is usually not necessary.
Considerations in weaning from cardiopulmonary bypass are somewhat different from

those described for aortic stenosis. Patients with aortic regurgitation are more likely to
have dilated ventricles that tolerate increases in afterload poorly. Successful
perioperative management of these patients, therefore, requires careful attention to
adjustments in preload and afterload. In patients with volume overloaded ventricles due
to aortic insufficiency, vasodilators may be an important component of postoperative
management. Drugs such as milrinone and dobutamine have a role because they
provide both inotropic support and ventricular unloading. The mechanical ventricular
unloading devicethe intraaortic balloon pumpalso may be used. It is rare that
mechanical circulatory assistance with a ventricular assist device is required. Its use
should be reserved for younger patients without comorbid states in whom prompt
improvement in ventricular function is anticipated.
Results
Early results after operation for aortic regurgitation and coronary artery disease include
an expected hospital mortality of less than 10 percent. [7 ] , [10 ] Incremental risk factors
for hospital death are similar to those described previously, with advanced age and
poor ventricular function having the greatest impact. Late survival after this operation is
similar to that for aortic stenosis and coronary artery disease [17 ] [30 ] (see Fig. 37-3 ).
Despite the impression that patients with aortic insufficiency and coronary artery
disease do not do as well as those with aortic stenosis, aortic insufficiency has not
been an independent risk factor for early or late mortality. [7 ] Interestingly, recovery of
ventricular ejection fraction does have a favorable impact on late mortality. As noted
previously, when ventricular dilatation and diminution in ventricular systolic function
occur in the setting of aortic regurgitation, these often are irreversible changes. While
some improvement of function can occur with elimination of the volume overload and
with revascularization in patients with combined valvular and coronary artery diseases,
there may be less recovery of ejection fraction in patients with aortic insufficiency
compared with aortic stenosis. Failure of recovery of ventricular function in this setting
may have an impact on long-term survival but not one so great as to render aortic
insufficiency an independent risk factor for late death.
MITRAL REGURGITATION AND CORONARY ARTERY DISEASE
Successful management of patients with mitral regurgitation and coronary artery

disease remains one of the greater challenges in adult cardiac surgery. This group of
patients tends to be sicker, and their surgical care is accomplished at higher risk. [4 ] ,
[5 ] , [31 ] [33 ] This is almost certainly because of the complex interaction between the
ventricular muscle and the mitral valve. Normal valve function depends on normal
function of the entire mitral apparatus, which includes the ventricular wall and the
papillary muscles. Similarly, normal ventricular function depends on competence of the
mitral valve. Therefore, there is unique potential for coronary artery disease and mitral
valve disease to interact, making the patient sicker, the pathophysiology more
complicated, and the surgical management more difficult.
In patients with preserved ventricular function, the pathophysiology and management

strategies are not significantly different from those for treatment of isolated mitral
regurgitation or coronary artery disease. Of course, the operation is more complex and
longer, and therefore, as has been described previously, a carefully thought-out
operative plan with special attention to myocardial preservation is important. However,
the more interesting problems are in those patients with mitral insufficiency and
coronary artery disease who do not have normal hearts, and in fact, most patients with
this disease combination do not have normal ventricular function.
The spectrum of clinical presentation ranges from patients who are asymptomatic to
those who are moribund in cardiogenic shock. The patient may have no signs or
symptoms of heart disease but have a mitral murmur detected on physical examination.
Subsequent cardiac evaluation may show significant mitral insufficiency in the presence
of asymptomatic coronary artery disease. Alternatively, mitral insufficiency may have
progressed such that heart failure is the predominant symptom, and significant coronary
artery disease is detected during evaluation of valvular heart disease. In other patients,
ischemic heart disease may be prominent with angina pectoris or its equivalent. In
these patients, moderate to severe mitral insufficiency may be detected, although it
does not contribute to the clinical presentation. Finally, patients may present with acute
syndromes often related to myocardial infarction and the sudden development of mitral
insufficiency. These patients are extremely ill when they present in congestive heart
failure and cardiogenic shock. Management of these patients is the most difficult.
Findings on physical examination obviously relate to the nature of the presentation. In

almost all patients with this disease combination, a murmur of mitral insufficiency is
heard. The lone exception may be in patients who develop acute mitral regurgitation
that is so massive that sufficient turbulence to generate a murmur is not generated. As
noted, angina pectoris may or may not be present. Similarly, evidence of left ventricular
dysfunction ranging from congestive heart failure to cardiogenic shock may be
apparent.
The laboratory examination, of course, includes an electrocardiogram, which may show

evidence of ischemic heart disease. Almost all patients with murmurs of mitral
regurgitation undergo echocardiography. The echocardiogram is particularly useful
because it gives information both about the valve and about ventricular geometry and
function. Transesophageal echocardiography is especially useful in the evaluation of
mitral function. The echocardiogram provides information regarding the severity of
mitral insufficiency and its etiology. Mitral valve leaflet structure and function, chordal
anatomy, and functioning of the papillary muscles and adjacent ventricular wall are
evaluable via echocardiogram. In addition, an analysis of global and regional wall
motion can be made echocardiographically. All these data are important in planning the
operative approach to the mitral valve and assessing the risk of surgery. Cardiac
catheterization is performed in these patients for the same reasons outlined for patients
with aortic valve disease. Any patient with angina pectoris and any patient with mitral
insufficiency over the age of 40 should have coronary angiography before surgery. As
noted previously, cardiac catheterization also provides information about
hemodynamics that is important in planning the operation. Measurement of both left-
and right-sided pressures gives important information regarding left and right ventricular
function, both of which are important for management of this disease state.
Pathophysiology
Mitral regurgitation increases left ventricular preload and decreases afterload at the
expense of cardiac output. Ischemic damage causes ventricular dilatation with
decreased contractility and an increase in left ventricular filling pressures. These lesions
combined cause synergistic decompensation and can produce pulmonary hypertension
and secondary tricuspid regurgitation. Cardiac output may be very low, especially in
patients with acute mitral insufficiency. Mitral insufficiency may occur in association with
coronary artery disease, but often the coronary artery disease is the cause of mitral
insufficiency. When coronary artery disease is an incidental finding, the predominant
pathophysiology is that of primary mitral insufficiency. As has become well known, the
pathophysiology of primary mitral insufficiency can be due to involvement of the valve
leaflets, the valve annulus, the subvalvular apparatus, or some combination of all of the
above. A detailed understanding of the pathophysiology of primary mitral insufficiency is
important for planning the operative approach. In this setting, coronary artery bypass
grafting should be performed and is incidental to the pathophysiology of the disease.
When coronary artery disease is the primary cause of mitral insufficiency by its effect on
regional and global ventricular function, the pathophysiology is more complicated.
Global ventricular dysfunction from coronary artery disease can produce ventricular
dilatation with mitral annular dilatation and subsequent mitral insufficiency. The jet of
mitral regurgitation is usually central and often can be managed with annuloplasty.
Alternatively, regional wall motion abnormalities involving the papillary muscle and the
adjacent ventricular wall can produce dynamic changes that produce insufficiency of the
mitral valve. These abnormalities are just starting to become understood and are
discussed more completely in Chapter 23. Regional wall motion abnormalities may
lead to mitral insufficiency, which subsequently causes ventricular dilatation and/or
global ventricular dysfunction with subsequent annular dilatation and worsening mitral
insufficiency. As can be imagined, the interaction between mitral function and ventricular
function can be quite complex.
Operation on the mitral valve increases left ventricular afterload, which the ventricle may
have difficulty handling. Correction of mitral insufficiency either by valve repair or valve
replacement produces an instantaneous increase in left ventricular afterload. The
ventricle no longer has the low-impedance left atrial chamber in which to eject blood and
must overcome systemic afterload in systole. Contractile function of the ventricle may be
impaired by long-standing mitral insufficiency. When mitral insufficiency is combined
with coronary artery disease, ventricular function may be further impaired by ischemic
damage to the myocardium. Even when myocardial ischemia is reversible, recruitment
of hibernating myocardium may take time. These factors in combination with the sudden
increase in left ventricular afterload are responsible for the difficulty and increased risk
of management of this entity. Secondary right ventricular failure may be present or
ensue because pulmonary hypertension does not decrease immediately after mitral
valve repair or replacement, and coronary artery disease also may affect right
Symptomatic mitral insufficiency and symptomatic coronary artery disease are the usual
indicators for combined surgery. As noted, patients with acute illnesses may be in
extremis. Ventricular dysfunction is not per se a contraindication to surgery, especially if
it is due to reversible ischemia. Patients with global irreversible cardiomyopathy and
mitral insufficiency should not be operated on because the ventricle tolerates the
increase in afterload poorly and results are unsatisfactory. Estimation of the viability of
the myocardium and demonstration of reversible ischemia using thallium or PET
scanning therefore are important.
One of the important preoperative decisions in patients with mitral regurgitation and
coronary artery disease is whether there is need for any valve surgery. Since mitral
regurgitation in the presence of coronary artery disease may be functional and due to
reversible myocardial dysfunction, revascularization alone may improve mitral
regurgitation. It is important, therefore, to distinguish organic from functional mitral
insufficiency. Intraoperative transesophageal echocardiography is an important tool for
assessment of mitral valve function in this setting. [34 ] Patients with no preoperative
congestive heart failure, absent or only transient murmurs of mitral insufficiency, normal
pulmonary pressures in the operating room, and insignificant mitral insufficiency by
transesophageal echocardiography after induction of anesthesia probably do not need
mitral valve surgery at all. [35 ] Many of these patients will appear to have more mitral
regurgitation and higher pulmonary pressures at catheterization or when they are
ischemic than when they are under anesthesia. Some patients with ventricular
enlargement secondary to coronary artery disease and/or mitral insufficiency may be
managed with annuloplasty alone. Of course, patients with organic mitral valve disease
such as chordal rupture or elongation need primary repair. As noted elsewhere, results
of mitral repair and coronary artery bypass surgery are superior to those of mitral valve
replacement, which should be avoided if possible in this setting. [36 ]
Anesthetic considerations are similar to those described previously, although it must be

recognized that these patients are, in general, sicker than patients with aortic valve
disease and in some cases are among the sickest patients treated. Monitoring includes
a radial artery line and a pulmonary artery catheter. As suggested earlier,
transesophageal echocardiography is particularly important in this group of patients.
Setup for cardiopulmonary bypass is similar to that described. However, both venae
cavae are cannulated for venous return (Fig. 37-5) . This is usually accomplished by
introducing the cannulas through purse strings in the right atrium and directing them into
the superior and inferior venae cavae. After establishment of cardiopulmonary bypass,
a ventricular vent is positioned via the right superior pulmonary vein and across the
mitral valve. It is usually possible to cross the mitral valve even in the presence of
significant mitral insufficiency. After clamping the aorta, cardioplegia is administered
antegrade and retrograde as in patients with aortic stenosis. Subsequent doses of
cardioplegia are given retrograde. Choice of coronary artery grafts is in general similar.
In very sick patients, the left internal mammary artery may not be used if it is necessary
to establish cardiopulmonary bypass rapidly.
The first choice in surgery for mitral insufficiency is valve repair. When valve repair is
impossible, a mechanical prosthesis is almost always chosen because of the poor
long-term durability of tissue valves in the mitral position. However, in patients with this
disease combination and an abbreviated life expectancy, a rationale for a tissue
prosthesis may exist. [16 ] Regardless of the type of prosthesis, an effort should be
made to retain continuity between the papillary muscles and the mitral annulus. The
attachments to the posterior leaflet usually can be retained in their entirety without
interfering with either the function of a biologic or mechanical prosthesis. The anterior
leaflet must be resected either in whole or in part to avoid left ventricular outflow tract
obstruction or interference with mechanical valve function. Nevertheless, standard
practice is to retain continuity between the mitral annulus and the subvalvular apparatus
whenever the mitral valve is replaced. Short- and long-term ventricular function appears
to be better when this is done. Obviously, in this clinical setting where ventricular
function has a significant impact on short- and long-term results, all steps should be
taken to ensure optimal myocardial performance postoperatively.
Patients with papillary muscle rupture due to infarction are usually extremely sick. Valve
replacement is almost always required. Some surgeons have reported success with
reimplantation of the papillary muscle. This strategy is risky in these sick patients
because the operation must be both expeditious and effective. Multiple attempts to
achieve mitral valve competence are tolerated poorly. A re-implanted infarcted papillary
muscle does not necessarily restore mitral valve competence and also may be subject
to late breakdown.
As in combined aortic valve and coronary artery surgery, distal venous anastomoses
are performed first (see Fig. 37-5 ). Valve repair or replacement is then carried out,
followed by performance of the mammary artery graft. Proximal venous anastomoses
can be done either after release of the cross-clamp and application of a partially
occluding clamp or with the cross-clamp in place. A standard incision anterior to the
right pulmonary veins is used to expose the valve. Dissection in the interatrial plane and
mobilization of both cavae prior to performance of the incision improve exposure of the
mitral valve. This incision is usually extended behind the right atrial-inferior caval
junction, a short distance toward the mitral annulus.
In some patients, additional exposure may be needed because the left atrium is small.
A parallel incision in the right atrium just anterior to the interatrial septum followed by
division of the atrial membraneous septum toward the tricuspid annulus provides
excellent exposure. Alternatively, the left atrial incision can be extended superiorly
beneath the junction of the superior vena cava and right atrium into the superior wall of
the left atrium.
Weaning from cardiopulmonary bypass is similar to that in patients with aortic

insufficiency and coronary artery disease. Again, in this group of patients, afterload
reduction using drugs or the intraaortic balloon pump may be required. Inotropic drugs
with afterload-reducing capabilities such as dobutamine and milrinone may be
particularly indicated. The surgeon should have a low threshold for adding a drug such
as milrinone to epinephrine because this combination has some theoretical advantages
as a reselt of positive inotropic and unloading effects. Alternatively, dobutamine, which
has both central inotropic and peripheral afterload-reducing effects, may be the
first-choice drug. Since some of these patients are particularly sick, little time should be
wasted in futile attempts to wean from cardiopulmonary bypass on medications and
without the intraaortic balloon. There should be a low threshold for insertion of the
intraaortic balloon in patients whose hemodynamics may be quite tenuous for hours to
days after surgery, especially when operation is emergent.
Some attention must be paid to right ventricular function in this group of patients,
although right ventricular failure is more common in the setting of mitral stenosis. Right
ventricular failure must be anticipated and correctly diagnosed and managed. The
presence of a falling systemic blood pressure and cardiac output with falling pulmonary
artery pressure and/or pulmonary capillary wedge pressure signals a search for right
ventricular failure, as manifested by a rising central venous pressure. Failure to
recognize this and inappropriate administration of fluid can lead to irreversible right
ventricular failure.
Results
Hospital mortality for this group of patients is higher than for most other forms of
acquired heart disease. Early mortality rates range from 3 percent in good-risk patients
to 60 percent in the sickest patients. [5 ] , [6 ] , [22 ] [33 ] The higher mortality is seen in
patients with acute ischemic mitral valve disease and severe ventricular dysfunction
who require emergency operation. Incremental risk factors for early death include age,
functional class, ventricular function, pulmonary pressures, and cardiogenic shock. Late
survival in this entity is 55 to 85 percent at 5 years and 30 to 45 percent at 10 years [22 ]
[33 ] , [37 ] (Fig. 37-6) . In general, patients who survive surgery have good relief of
symptoms. Significant risk factors for late death include preoperative functional class,
left ventricular function, and an ischemic as opposed to a degenerative etiology for
mitral insufficiency (Fig 37-7) .
MITRAL STENOSIS AND CORONARY ARTERY DISEASE
Patients with mitral stenosis and coronary artery disease usually have good left
ventricular function and often are a relatively easy group of patients to take care of
because the mitral stenosis protects the left ventricle from hemodynamic loads.
Coronary artery disease may cause left ventricular dysfunction, but this is relatively rare.
A more usual concern is right ventricular dysfunction postoperatively, since in patients
with mitral stenosis pulmonary hypertension with its potential to produce right ventricular
failure and tricuspid insufficiency is often encountered.
As implied earlier, mitral stenosis is usually the dominant lesion in patients with mitral
stenosis and coronary artery disease. Therefore, symptoms usually are due to the
valvular heart disease. Patients may have congestive heart failure with shortness of
breath and orthopnea and fatigue. Atrial fibrillation is a common presenting symptom
with mitral stenosis. For some reason, patients with mitral stenosis and coronary artery
disease infrequently have angina as a presenting symptom. This may be so because
the load on the left ventricle is diminished in mitral stenosis. In the absence of major
infarction, the electrocardiogram may show evidence of right ventricular strain and
hypertrophy because the left atrial hypertension produced by mitral stenosis leads to
reactive pulmonary hypertension with increased load on the right ventricle.
Echocardiography confirms the diagnosis of mitral stenosis and usually shows a small
left ventricle with preserved contractile function. The right ventricle may be enlarged and
hypertrophied. Cardiac catheterization confirms the diagnosis by showing a gradient
across the mitral valve. Other important information gleaned from invasive
catheterization includes a measurement of the pulmonary artery pressures and central
venous pressure. The degree of pulmonary hypertension is a marker of the severity and
duration of mitral stenosis and alerts the surgeon to the potential for right ventricular
failure postoperatively. An elevated central venous pressure is a potential sign that right
ventricular decompensation has already occurred. Coronary angiography should be
done in all patients with angina pectoris and, as noted before, in any patient over age
40 in whom mitral valve surgery is anticipated.
Pathophysiology
As suggested earlier, mitral stenosis is usually the predominant lesion even when
significant coronary artery disease is present. Unlike the other entities described, mitral
stenosis and coronary artery disease do not have significantly synergistic pathologic
effects on the heart. Coronary artery disease usually has more profound effects on the
left ventricle, which remains protected in patients with mitral stenosis until late in the
disease. The right ventricle is the vulnerable ventricle to the effects of long-standing
mitral stenosis, as noted. However, even with right ventricular hypertension, the potential
impact of coronary artery disease on right ventricular function in adults is relatively
insignificant. In the rare patient with diffuse coronary artery disease and ischemic
cardiomyopathy, the risk of surgery is enhanced because of global ventricular
dysfunction.
The indications for surgery, not surprisingly, are determined usually by the severity of the
mitral stenosis. Patients with significant heart failure and low cardiac output from mitral
stenosis whose calculated valve area is less than 1 cm 2 should have a mitral valve
operation and associated bypass grafting if significant coronary artery disease is
present. As noted, it is quite uncommon for angina pectoris to be the indication for
operation. A rare patient may have significant coronary artery disease and mild mitral
stenosis detected incidentally. These patients may be managed with coronary artery
bypass surgery and mitral commissurotomy if this is technically feasible.
Monitoring, perfusion setup, and operative sequence are identical to those described
for treatment of mitral regurgitation and coronary artery disease. Transesophageal
echocardiography is useful to assess both the feasibility of mitral commissurotomy (or
more extensive mitral repair) and the results of valvuloplasty. In most patients with mitral
stenosis, valve replacement is required because irreversible damage to the leaflets and
subvalvar apparatus is usually extensive. A mechanical prosthesis is used almost
always because most patients have chronic atrial fibrillation from mitral stenosis, and
long-term anticoagulation is indicated anyway.
Transesophageal echocardiography is often important in monitoring both right and left

ventricular function postoperatively. As suggested earlier, right ventricular failure can be
a prominent feature following surgery for mitral stenosis. The early differentiation
between left and right ventricular failure is facilitated by the use of transesophageal
echocardiography during weaning from cardiopulmonary bypass. If inotropic drugs are
required, their selection should be based in part on the consideration that pulmonary
hypertension and right ventricular failure may be an important component of the clinical
syndrome postoperatively. Drugs such as isoproterenol, dobutamine, and milrinone, the
latter usually in combination with a catecholamine, may be indicated for their combined
beneficial effects on right ventricular contractility and pulmonary vascular resistance.
Judicious use of inotropic drugs and careful administration of fluid may result in optimal
cardiac output. As noted, transesophageal echocardiography may be particularly useful
for gauging fluid and transfusion requirements by providing assessment of right and left
ventricular filling and function. The intra-aortic balloon is almost never useful in these
patients because right ventricular problems predominate and the intra-aortic balloon
has little direct effect on right ventricular function. Some surgeons have experimented
with pulmonary artery balloons with limited success. Temporary support with a right
ventricular assist device may be employed because mitral valve replacement can lead
to dramatic decreases in pulmonary artery pressures and subsequent recovery of right
Results
Early mortality after combined surgery for mitral stenosis and coronary artery disease is
approximately 8 percent. [5 ] , [6 ] , [22 ] [33 ] This is not significantly different from
results of surgery in better-risk patients with mitral regurgitation and coronary artery
disease. Long-term probability of survival is approximately 50 percent at 7 years and in
one series was not significantly different from that for patients with ischemic mitral
insufficiency. [22 ] [33 ] , [37 ] Interestingly, long-term survival of patients with myxoid
degeneration of the mitral valve and coronary artery disease (65 percent) was
significantly better than survival of the patients with rheumatic or ischemic mitral valve
disease and coronary artery disease in at least one series [31 ] (see Fig. 37-7 ). As
implied, rheumatic valve pathology is a risk factor for late death, as is poor preoperative
left ventricular function and presence of ventricular arrhythmias. Interestingly, the use of a
bioprosthesis without anticoagulants confers both a survival advantage and an
event-free survival advantage in these patients (Fig. 37-8) . Despite the reluctance of
many surgeons to use bioprostheses in the mitral position, these data lend support to
the hypothesis that biologic valves are appropriate mitral replacement devices in older
patients and in those with coronary artery disease, whose expected life span may be
shorter than the expected durability of the replacement device. [16 ]
AORTIC STENOSIS, MITRAL REGURGITATION, AND CORONARY
ARTERY DISEASE
Patients with aortic stenosis, mitral regurgitation, and coronary artery disease often
present with aortic stenosis as the predominant lesion. Of course, the extra load and
oxygen demand that aortic stenosis places on the heart combined with coronary artery
obstructions mean that angina pectoris also may be a prominent presenting symptom. It
is important to note that functional mitral regurgitation may improve after relief of aortic
stenosis with concomitant reduction in left ventricular systolic pressure. If the mitral valve
is not intrinsically diseased, it may not require operation.
Patients with these diseases often present identically to patients with aortic stenosis
and coronary artery disease. Angina, congestive heart failure, and syncope may be
presenting symptoms alone or together. It is relatively uncommon for symptoms due to
mitral insufficiency to be predominant.
The preoperative evaluation includes the usual history and physical examinations.
Murmurs of aortic stenosis and mitral insufficiency are audible. The electrocardiogram
often shows ventricular hypertrophy and may show evidence of previous ischemic
damage. Echocardiography is an extremely important tool in this disease combination.
Careful evaluation of the mitral valve, often using transesophageal echocardiography, is
necessary to determine the degree of intrinsic mitral valve disease, since improvement
in mitral insufficiency is expected after aortic valve replacement and relief of left
ventricular obstruction. It is critical to determine whether or not anatomic abnormalities
of the mitral valve are present that might not reverse with aortic surgery alone. The
transesophageal echocardiogram is the best examination to determine this. Of course,
cardiac catheterization is required, as it is for the other disease entities described.
Pathophysiology
It is important to understand the linked pathophysiology of aortic stenosis and mitral

regurgitation. Aortic stenosis increases left ventricular afterload and the potential
amount of mitral regurgitation. In this combination, symptoms often appear earlier than
with mitral regurgitation alone. Therefore, the left ventricle may be better preserved than
in patients with isolated mitral insufficiency and coronary artery disease. Also as noted,
the mitral valve may not be structurally diseased. Relief of aortic stenosis may improve
mitral insufficiency to the extent that an operation on the mitral valve is not required.
Because of the earlier presentation, pulmonary hypertension and, therefore, right
ventricular and tricuspid valve incompetence are usually not prominent features.
Because relief of outflow obstruction helps left ventricular function immediately, these
patients often do quite well.
The indications for surgery are usually the same as for aortic stenosis and coronary
artery disease. Critical aortic stenosis, when documented, requires valve replacement
with coronary artery bypass grafts done if significant coronary artery disease is present.
Mitral valve repair or replacement is performed if mitral insufficiency is severe and/or
anatomic abnormalities of the valve are detected. End-stage ventricular dysfunction with
ventricular dilatation and myocardial thinning is the only cardiac contraindication to
surgery. Except in end-stage hearts, ventricular function should improve after relief of
outflow obstruction by aortic valve replacement. With improvement of ventricular function
and reduction in ventricular size with corresponding shrinkage of the mitral annulus,
secondary mitral insufficiency should improve. Of course, this will not occur if the
ventricle is terminally dilated and dysfunctional. Coronary revascularization may further
improve both ventricular performance and mitral valve function.
Anesthesia and perfusion setup are identical to those described for mitral valve and
coronary artery surgery. In this entity, intraoperative transesophageal echocardiographic
monitoring plays an important role because the intraoperative assessment of mitral
valve function before and after bypass is critical. The choice of valves for aortic
replacement is the same as described before. Under almost all circumstances where
anatomic abnormalities of the mitral valve are detected or where mitral insufficiency is
severe, mitral valve repair should be considered. Annuloplasty may be all that is
required if the mitral insufficiency is due to mitral annular dilatation and there is a
symmetric central jet of regurgitation. More extensive disease may require replacement
of the mitral valve. If intraoperative transesophageal echocardiography suggests normal
mitral valve anatomy without severe mitral insufficiency, it is likely that no mitral valve
operation is necessary, and the mitral valve may not even be exposed during operation.
Under these circumstances, following aortic valve replacement and coronary artery
bypass surgery, transesophageal echocardiography is done to assess residual mitral
valve dysfunction. If moderate or severe mitral regurgitation remains, the valve is
repaired or replaced. This is more difficult after the aortic valve is replaced; therefore,
every effort is made to critically assess mitral valvular morphology and function before
starting cardiopulmonary bypass.
As in the other entities described, distal vein graft anastomoses are performed first
when treating patients with aortic stenosis, mitral regurgitation, and coronary artery
disease (Fig. 37-9) . After the vein grafts are completed, the aorta is opened, and the
aortic valve is resected. Replacement of the aortic valve, however, is deferred until after
the mitral valve operation because the rigid aortic prosthesis increases the difficulty and
danger of exposure of the mitral valve. However, it is important to resect the aortic valve
before replacing the mitral valve. This is so because of the contiguity of the aortic and
mitral annuli. It is preferable to resect the aortic valve before placement of the sutures for
mitral valve replacement because they may become disrupted during resection or
debridement of the aortic valve and annulus. After resection of the aortic valve, the left
atrium is opened, and the mitral operation is performed. The left atrium is closed with a
vent across the mitral valve. The aortic valve is then replaced, and the aorta is closed.
The internal mammary artery graft is done last. Proximal vein graft anastomoses can be
done with the aortic cross-clamp in place or after removal of the cross-clamp and
placement of a partially occluding clamp, as described previously.
As noted, this group of patients may have relatively preserved ventricular function, and
weaning from cardiopulmonary bypass may be relatively easy. Inotropic drugs and the
intraaortic balloon can be used as indicated. The considerations for selection of
inotropic drugs and the use of the intraaortic balloon are identical to those described for
patients with aortic stenosis and coronary artery disease. The addition of mitral valve
surgery obviously increases the length of the operation and the potential for temporary
myocardial injury. However, with careful attention to myocardial preservation, including
regular doses of retrograde blood cardioplegia during operation, weaning from
cardiopulmonary bypass in patients with reasonable ventricular function is usually
straightforward. Of course, patients with more diseased ventricles and residual mitral
insufficiency may be more difficult to wean. In these patients, an expeditious trial of
inotropic drugs and insertion of the intraaortic balloon, if necessary, are appropriate.
Since these patients may have significant mitral disease and elevated pulmonary
pressures, right-sided heart failure is a theoretical possibility after surgery for this
combination of lesions. This has not, however, turned out to be a frequent problem
Results
Early hospital mortality is about 12 to 16 percent. [38 ] , [39 ] Not surprisingly, predictors
of early death include severe mitral regurgitation, lower ejection fraction with more
severe symptoms of heart failure, and the presence of triple-vessel coronary artery
disease. Late survival is approximately 60 percent at 72 months (Fig. 37-10) .
Multivariate predictors of late mortality include advanced symptoms of heart failure and
increased severity of mitral insufficiency.
AORTIC AND MITRAL REGURGITATION AND CORONARY ARTERY
DISEASE
There are not many patients with regurgitation of both the aortic and mitral valves and
coronary artery disease. These patients usually have rheumatic heart disease and
present early in the course of the disease with minimal or incidental coronary artery
disease. Aortic regurgitation may be the primary valve pathology in a patient with
significant coronary artery disease. Patients with bad ventricular function may have
mitral disease secondary to ischemia and left ventricular dilatation from coronary artery
disease and aortic regurgitation. This group of patients is particularly difficult to evaluate
because of the complicated interaction of coronary artery disease with the two
volume-overloading valvular pathologies. An important consideration includes
assessment of the severity and pathophysiology of mitral regurgitation. Organic mitral
valve disease may not be present. Assessment of left ventricular contractility may be
difficult because of the alterations in preload and afterload produced by this
combination of lesions. In addition, the presence of reversible ischemia may obscure
accurate assessment of ventricular function. Therefore, assessment of myocardial
viability is important.
Most patients with this combination of cardiac lesions present with congestive heart
failure. It is relatively unusual to see a patient with angina as the primary symptom who
also has significant insufficiency of both the aortic and mitral valves. Typical murmurs of
aortic and mitral insufficiency are present, and the patient may have other signs of
chronic congestive heart failure, including rales and peripheral edema. If myocardial
infarction is a significant component of the pathophysiology and presentation of the
disease, evidence of it on electrocardiogram and echocardiogram may be seen. On
echocardiography, patients may have regional wall motion abnormalities if infarction
has occurred, as well as global ventricular dilatation and possibly dysfunction from the
combined valvular lesions. Cardiac catheterization defines the coronary anatomy, helps
define the severity of the valvular insufficiency, and via measurement of intracavitary
pressures gives an index of ventricular function. Accurate assessment of left ventricular
performance is difficult in this entity. Mitral insufficiency may abnormally inflate
measurements of ejection fraction because the ventricle can eject into the low-pressure
pulmonary venous circuit. The misleading ejection fraction combined with the multiple
volume overloads of leaking aortic and mitral valves and the potential contribution of
dysfunctional myocardium from ischemia make it very difficult to get an accurate
perception of preoperative left ventricular function. Thallium or PET scans may be useful
to assess what areas of dysfunctional myocardium may be viable and potentially
recruitable after revascularization.
Pathophysiology
Symptoms and signs of left ventricular failure develop as the left ventricle dilates. Since
the valve disease is often rheumatic if both valves are intrinsically damaged, ischemic
disease may be minimal. In the more common setting of patients with aortic
regurgitation and severe coronary artery disease, mitral regurgitation is likely to be
secondary to ischemia, and valve repair may be possible even if not perfect. Correction
of aortic regurgitation and reduction of mitral insufficiency improve left ventricular
volume overload. Any improved contractility from revascularization and a smaller left
ventricle should further reduce mitral regurgitation and in part offset the increase in
afterload from reducing mitral regurgitation. Because of the multiple, uncontrollable
variables in assessing preoperative ventricular function, prediction of expected
improvement from this operation is difficult.
This consideration, however, is extremely important. Patients with severe and

irreversible ischemic myocardial disease and poor ventricular function will not do well
with operative treatment of this entity. Therefore, preoperative assessments of
myocardial viability and reversible ischemia are important. It is also important to assess
whether organic mitral valve disease is present. The best results in these patients are in
those in whom no operation on the mitral valve is required.
Details of the operative technique are similar to those described previously. Because of
the presence of aortic insufficiency, retrograde cardioplegia must be used.
Transesophageal echocardiography is extremely important in the operating room for
the assessment of mitral valve function. Residual 1 to 2+ mitral regurgitation is
acceptable in these patients because relief of aortic regurgitation can be expected to
shrink the ventricle, which may lead to improvement of mitral regurgitation with time.
Similarly, myocardial revascularization also may lead to ultimate improvement in
ventricular and mitral valve function.
In weaning from cardiopulmonary bypass, afterload reduction is extremely important

because of the large preoperative volume overload of the heart. Drugs that reduce
ventricular afterload, including vasodilators and inotropic drugs such as dobutamine,
may be particularly appropriate. The intraaortic balloon pump may be needed.
Results
Early hospital mortality in this group of patients may be high, and if myocardial failure is
severe, overall mortality rates exceed the range already noted for double-valve and
coronary artery surgery. [38 ] , [39 ] Important determinants of risk in these patients are
the familiar ones. In several series, predictors of hospital death and late events included
severe mitral regurgitation, lower ejection fraction, more severe symptoms of
congestive heart failure, and severe triple-vessel coronary artery disease.
SUMMARY
This chapter has summarized the management of patients with valvular and ischemic
heart disease. The discussion has focused on management of disease of the aortic
and mitral valves, since these are the valves most frequently affected in adults and
adults are the patients who get coronary artery disease.
Rather than concentrate on the details of the technical aspects of valve implantation or
coronary artery grafting, the discussion has focused on the particular problems for
surgical management that the combined pathophysiology of valvular and ischemic heart
disease produces. As has been noted often during the discussion, there is usually an
interaction between valve function, myocardial perfusion, and ventricular performance. In
other words, dysfunction of the aortic and mitral valves has secondary effects on
ventricular function, and the addition of coronary artery disease can make this
interaction more complex. Therefore, the pathophysiology of these disease states can
be complicated. In order to manage these entities successfully, this pathophysiology
must be understood so that accurate estimates of risk and reasonable expectations for
results can be achieved.
Several recurrent themes have emerged. In almost every case, ventricular function and
severity of mitral incompetence are important short- and long-term risk factors. Second,
functional mitral insufficiency in the absence of anatomic abnormalities of the mitral
valve may improve significantly after aortic and/or coronary artery surgery, and
therefore, an operation on the mitral valve may not be required. Finally, data from
several sources suggest that patients with both coronary artery and valvular heart
disease should be considered for a tissue prosthesis because the patient may not
out-live the valve and embolic and bleeding complications may be reduced.
In addition, the complex interaction between ventricular function, valvular function, and
coronary ischemia requires that the operation be well planned and attention be paid to
expeditious surgery with short myocardial ischemia times and good myocardial
preservation. Much of the discussion in this chapter, therefore, has focused on the
operative plan and the development of a rational approach to intraoperative and
postoperative management of these patients.
Despite the complexity of the pathophysiology and the added complexity of doing
operations on both the coronary arteries and the cardiac valves, results of these
operations can be quite spectacular. Even patients with involvement of both the aortic
and mitral valves as well as the coronary arteries who may have significant degrees of
ventricular dysfunction preoperatively may do extremely well following surgery. One of
the measures of the progress that has been made in anesthetic management, the
technology of cardiopulmonary bypass, the introduction of intraoperative
transesophageal echocardiography, and the understanding of myocardial management
before, during, and after surgery is the fact that these patients with combined valvular
and coronary artery disease can be operated on routinely and do very well following
surgery.
HISTORY
In his medieval text, Sennertus first mentioned aortic dissection and described
separation of the layers of the aortic wall. [1 ] In 1756, William Hunter described an
aneurysm formed partially by a wound or rupture of some of the coats of the artery, and
partly by a dilatation of the rest. [2 ] , [3 ] In 1761, Morgagni described several cases in
which blood penetrated the layers of the aortic wall to produce an ecchymosi. [4 ] Forty
years later, Maunoir explicitly described the dissection process and termed the disease
dissection. [5 ] Rene Laennec described the aneurysmatic property of chronic aortic
dissection in 1819 (aneurisme dissequant), whereas Shekelton in 1822 observed a
double barrel aorta resulting from distal re-entry. [6 ] , [7 ]
In 1863, Peacock reported 80 cases of dissection and divided the dynamics of the
disease into three, still valid stages: rupture of the internal aortic coats, dissection and
possible external rupture, and recanalization. He also noted the high death rate within
the first 24 hours. [8 ]
The first antemortem diagnosis of aortic dissection was made by Swaine and Latham
in 1852, but the first operation to alleviate dissection-induced ischemic complications
was performed by Crowell in 1921. [9 ] , [10 ] Abbott, in 1948 and Paullin, in 1949, tried
to control aneurysmal dilatation by wrapping the aorta with cellophane. [11 ] , [12 ] In
1953, Johns sutured the site of rupture of an abdominal aortic dissection. [13 ]
DeBakey excised the dilated portion, reunited the distal dissected layers, and
re-established aortic continuity using an end-to-end anastomosis for type III dissection
in 1955. [14 ] This procedure was soon superseded by graft replacement of the
descending aorta. [14 ] [20 ] For type I dissection, Hufnagel and Morris excised the
ascending aortic entry tear, reunited the proximal and distal dissected layers and then
anastomosed the aorta end-to-end. [21 ] [23 ] Following Cooley's and DeBakey's first
successful operation, replacement of the ascending aorta with a tube graft became the
standard procedure for chronic dissecting aneurysms and was extended to acute
dissections by sandwiching thin, friable aortic layers between strips of Teflon felt. [16 ] ,
[19 ] , [24 ] [29 ]
Wheat clarified the hemodynamics of aortic dissection and established the use of
antihypertensive drugs and µ-adrenergic blockers for treating type III dissections and as
adjuncts for proximal dissections. [30 ] [36 ]
DEFINITION
Clotted blood within the damaged aortic tunica media is termed intramural hematoma,
whereas aortic dissection denotes one or more tears between the aortic lumen and a
medial cleavage plane containing active blood flow. Aortic dissection is differentiated
from spontaneous rupture of the aortic wall or laceration of the intima and media without
or with only limited separation of wall layers.
Aortic dissection may be localized to the portion of the aorta where the blood first enters
the wall (primary entry, primary tear), but usually involves most or all of the vessel. The
dissection often includes side branches, particularly supra-aortic branches and pelvic
vessels of the elastic type. The dissection rarely extends completely around the
circumference; usually a strip of aortic wall remains intact. The separation often
progresses distally from the primary entry but may propagate a variable distance
proximally (retrograde dissection). One or more fenestrations or re-entry tears often are
present to provide communication channels between the true and false lumens of the
double barrel aorta (Fig. 38-1) . The true and the false channels are separated by the
dissecting or intimal membrane or flap that contains aortic media and intima. The
dissection may stop at the most distal re-entry site or may end in a downstream blind
pocket. Blood within blind pockets, whether created by antegrade or retrograde
dissection, commonly thromboses. Blood flow in the true (intimal-lined) aortic channel or
dissected side branches may be compromised by compression by the false lumen to
cause malperfusion, or ischemia of downstream organs and extremities (Fig. 38-2) .
Because the dissection splits the outer layers of the media and weakens the external
aortic coat, the wall of the false channel may either rupture or dilate to ultimately produce
an aneurysm. The older term, dissecting aneurysm, is only justified when aneurysm
develops or if the dissection involves a pre-existing aortic aneurysm. The false channel
eventually develops an endothelial lining, but may contain extensive thrombus.
The onset of an aortic dissection almost always can be traced to an episode of severe
chest or back pain. Arbitrarily, the acute stage is terminated at 14 days. The
subsequent period that extends to 2 months after the primary event is termed subacute;
the chronic phase begins after the second month.
CLASSIFICATION
There are two accepted classifications of aortic dissection (Fig. 38-3) . DeBakey
defines a dissection beginning in the proximal aorta that involves most of or the entire
vessel as type I. Type II involves only the ascending aorta. [37 ] , [38 ] Dissection of the
descending thoracic aorta is termed type III. Type III dissections are subdivided into IIIa,
which is limited to the proximal descending portion, and subtype IIIb, which extends
beyond the diaphragmatic hiatus into the suprarenal and abdominal aorta.
At Stanford University, Daily considers any dissection involving the ascending aorta an
indication for emergency surgical intervention. [39 ] This variant is termed type A
regardless of the site of origin or the distal extent of the process. Descending thoracic
aortic dissections are labeled type B (Fig. 38-3) . Unfortunately, grouping DeBakey's
type I and II classifications together ignores very different operative and long-term
outcomes associated with these different entities.
The classification of dissection used in this text is that advocated by Kirklin. Proximal
aortic dissection involves the intrapericardial ascending aorta and may include the
aortic arch. Distal aortic dissection begins beyond the left subclavian artery but may
include a retrogradely dissected portion of the arch. However, if the retrograde
dissection extends proximally into the ascending aorta and involves a portion of the
intrapericardial segment, the dissection is labeled proximal. Thus Stanford type A and
DeBakey types I and II and type III with retrograde extension into the intrapericardial
aorta are included in the proximal dissection category. The distal dissection category
includes DeBakey type III and Stanford type B.
INCIDENCE
Dissection is the most common catastrophic event affecting the aorta and is
approximately two to three times more frequent than rupture of an abdominal aortic
aneurysm. [34 ] , [40 ] The true incidence is unknown since many clinical cases are not
correctly diagnosed. The annual incidence is estimated to be five to 10 cases per
million by Wheat and Rahbeck-Sorensen and 20 million by Pate. [34 ] , [40 ] , [41 ] In
large series of necropsies, the prevalence of aortic dissection ranges from 0.2 percent
at the Cook County Hospital in Chicago to 0.8 percent at the Massachusetts General
Hospital in Boston. [42 ] [44 ] In a Danish series of 6,480 autopsies covering 90 percent
of a regional population, dissection was discovered in 13 cases (0.2 percent). [40 ]
Aortic dissection affects males more frequently than females; the rates vary between
2:1 and 5:1. [45 ] [47 ] The fifth decade is the age-related maximum for all aortic
dissections, but there are important differences with respect to gender, race, underlying
diseases, and type of dissection. Pregnancy is a risk factor, as is Marfan syndrome.
High blood pressure is found in more than 80 percent of surgical patients treated for
aortic dissection. [47 ] Dissection before age 40 primarily affects patients with Marfan
syndrome and even includes children and infants. [48 ] , [49 ] Aortic coarctation and
congenital anomalies of the aortic valve also may facilitate aortic dissection in younger
age groups.
Aortic dissection originating beyond the origin of the left subclavian artery occurs more
frequently than the proximal variant in older patients, with a maximum incidence
between 6070 years. The age peak for patients with proximal dissection is between
5055 years. [34 ] , [49 ] In DeBakey's large surgical series, ages of peak frequencies for
types I, II, and III dissections were 53, 42, and 65 years, respectively. [47 ] The male to
female ratio in types I and II was 2:1, as compared to 3:1 in type III. Likewise, the
incidence of hypertension was considerably higher in type I and II dissection (80
percent) as compared to type III (50 percent). [50 ] , [51 ]
ETIOLOGY
The term cystic medial necrosis or medial degeneration is no longer considered the
common structural disorder of aortic dissection. Severe derangement and loss of
elastic tissue are typical of dissection in younger patients with congenital connective
tissue disorders, but correlate poorly with dissections in other patients. [52 ]
Anagnostopoulos described seven general conditions associated with damage to the

aortic media. [53 ] These include hypertension and hypervolemia, interference with the
assembly and maintenance of the media, destruction by mechanical forces, or chemical
agents, obstruction to aortic flow, and elevated cardiac output.
Several heritable disorders of elastic tissue predispose the aorta to early dissection.
These include Marfan, Turner, Noonan, and Ehlers-Danlos syndromes. [54 ] [69 ] A
fundamental genetic derangement in the assembly and deposition of a newly
discovered microfibrillar protein, fibrillin, occurs in Marfan syndrome. [59 ] , [70 ] [74 ]
Both sino-tubular ectasia and dissection may occur in non-Marfan families as a
heritable autosomal dominant defect. [75 ] [78 ] In such patients, the aortic valve annulus
may be normal or dilated and distorted. [79 ]
Unicuspid and bicuspid valve syndromes are associated with aortic dissection. [49 ] ,
[73 ] , [80 ] [86 ] In Edwards' series of 119 fatal dissections, 9 percent had congenitally
abnormal aortic valves. [85 ] Roberts confirmed this incidence. [82 ] , [83 ] The rate of
dissection in patients with congenitally deformed aortic valves is five times that of
trileaflet valves and is highest with unicuspid valves. Isolated stenosis of a three-leaflet
valve is not considered a predisposing factor for aortic dissection. [49 ] , [82 ] , [84 ] As
first noted in Abbott's series of 200 cases, coarctation of the aortic isthmus
predisposes the aorta to dissection, particularly in older patients. [87 ]
In the absence of a connective tissue disorder, arterial hypertension is the most

important predisposing factor for aortic dissection. Most large autopsy and clinical
series estimate an incidence of hypertension in patients with dissection to be at least
75 percent. [45 ] [47 ] , [85 ] , [88 ] [96 ] Hypertension causes excessive mechanical and
metabolic strain on the media, which opposes arterial pressure within the aortic wall.
The causative role of hypertension is underlined by the rare event of pulmonary artery
dissection that only occurs with pulmonary hypertension. [97 ]
Pregnancy is associated with half of the dissections that affect females below the age
of 40 and usually occurs in the last trimester or during labor. [41 ] , [46 ] , [52 ] , [95 ] , [98
] , [99 ] Contributing factors include hypercirculation during the late gestational period,
hypertension, and the loosened connective tissue owing to hormonal changes. [100 ] ,
[101 ]
Most authors believe atherosclerosis is coincidental rather than causative of aortic

dissection. [49 ] , [85 ] , [102 ] , [103 ] Severe atherosclerosis in infra-renal aneurysms
actually may impede dissection. [49 ] , [104 ] [106 ] Unfortunately, aortic dissection of an
arteriosclerotic aneurysm increases the risk of rupture. [107 ]
Extensive dissection beyond a traumatic aortic tear rarely occurs. The majority of
traumatic aortic lacerations are limited to the aortic isthmus and occasionally may
cause partial or circular prolapse of intima and media into the distal vessel to produce
pseudocoarctation.
Iatrogenic trauma occasionally causes aortic dissection. Radiological diagnostic

procedures coronary angiography, and therapeutic balloon catheter manipulation all
have produced dissections. [108 ] [116 ] Insertion of an intra-aortic balloon catheter
risks vascular injuryusually occlusion or perforation of a pelvic vessel. However,
extensive type B or even retrograde type A dissection does occur. [117 ]
Femoral arterial cannulation for retrograde extracorporeal perfusion is notorious for

producing dissection of pelvic vessels and sometimes the aorta. [118 ] [125 ] Cannula
insertion or the impact of the high-pressure blood jet emanating from the cannula may
create a false passage within the vascular wall. [26 ] Antegrade cannulation of the
ascending aorta or arch likewise may create a false passage within the medial layer or
may disrupt the aortic wall opposite the cannulation site to trigger dissection. [127 ] [132
] This risk is increased when the ascending aorta is dilated.
Local aortic trauma caused by a cross-clamp or side-biting clamp is another well-known

source of aortic dissection. [133 ] [142 ] Operations involving the ascending aorta, such
as aorto-coronary vein bypass grafting and aortic valve replacement are associated
with dissection. [141 ] , [143 ] [162 ]
Rarely, aortic dissection is associated with other conditions such as hypercortisolism,

pheochromocytoma, lupus erythmatosus, chronic nephropathic cystinosis, and
osteogenesis imperfecta. [163 ] [168 ] More recently, aortic dissection occurred after
cocaine use. [169 ] , [170 ]
HISTOLOGY AND STRUCTURE
The aortic wall is composed of three layers, the intima, the tunica media, and the
adventitia. The media is the strongest component of the aortic wall and measures on
average 1.2 mm in the ascending vessel and is the layer most affected in aortic
dissection. It is composed of elastic and collagen fibers, that each account for 2030
percent of the aortic wall by volume; smooth muscle cells represent 5 percent. [171 ]
[176 ] Smooth muscle cells produce all the constituents of the medial layer. [174 ] [176 ]
Elastic sheets are concentrically arranged fenestrated lamellae with intertwining
individual fibers. Interconnecting fibers hold the layers together. Microfibrils, recently
discovered, contain the glycoprotein fibrillin and are an important constituent of the
aortic media. Microfibrils provide a scaffold for deposition of elastin and become
completely encased with elastin to produce concentric rings of the tunica media.
Derangement of these microfibrils because of a base pair substitution is the base
deficiency responsible for Marfan syndrome. [70 ] , [71 ] , [177 ] Kainulainen in 1990 and
Dietz in 1992 mapped the genetic defect of Marfan syndrome to the long arm of
chromosome 15 (15q). [178 ] , [179 ]
ACUTE AORTIC DISSECTION
Although a small proportion of patients succumb suddenly after acute aortic dissection,
the majority stabilize for a brief but definite interval. This period can be extended with
appropriate medical intervention. As with all catastrophic surgical problems, the initial
prognosis depends on the severity and extent of the dissection, the overall physical
condition and age of the patient, the experience and expertise of the team dealing with
the problem, and the rapidity with which the problem can be addressed.
The most important factor leading to a successful early diagnosis of acute aortic
dissection is a high index of suspicion by the examining physician. Most patients with
acute aortic dissection experience sudden severe chest pain, marked anxiety, and are
aware that a catastrophic illness has occurred. A history of severe hypertension or
known thoracic aortic aneurysm, of course, should alert the examiner to the possibility of
aortic dissection. Tall stature, sternal deformity, and other characteristic stigmata of
Marfan syndrome in the presence of chest pain should particularly prompt an examiner
to rule out aortic dissection.
Severe chest pain is the cardinal feature of aortic section and occurs in more than 90
percent of patients. [46 ] , [47 ] , [105 ] , [180 ] [182 ] When the proximal aorta is
involved, symptoms are characteristically centered in the mid-substernal area; patients
with distal dissection tend to experience primarily interscapular pain. [183 ] With
DeBakey type I dissection, as the hematoma propagates from proximal to distal aorta,
the pain may move from the anterior chest to the neck, to the interscapular area, and
eventually involve much of the mid-back (Fig. 38-4) . [105 ] , [182 ] This migratory pain
pattern should arouse suspicion of aortic dissection.
Chest pain caused by acute aortic dissection must be differentiated from that caused
by coronary ischemia, myocardial infarction, and other thoracic diseases that include
aortic regurgitation without dissection, aortic aneurysm without dissection,
musculoskeletal pain, pericarditis, biliary colic, and pulmonary embolus. The pain of
dissection is usually sudden, worst at onset, severe, and not previously experienced.
Adjectives such as ripping and tearing often are used by the patient. [184 ] [186 ]
Usually the pain of dissection is constant as compared to the pain of cardiac ischemia,
which may build slowly over time to a crescendo and improve with rest. [105 ] Because
suspected acute coronary ischemia may be treated immediately with thrombolytic
agents, differentiation of the two diseases must be made promptly and conclusively.
Thrombolytics may be lethal for aortic dissection. Total or partial ostial coronary artery
occlusion by an aortic root dissecting membrane may complicate the diagnosis by
producing angina or ischemic cardiac failure.
Occlusion of the thoracoabdominal aorta by the dissecting membrane may cause

abdominal pain caused by renal or visceral ischemia. Similarly, iliac occlusion may
produce severe peripheral ischemia and painful extremities.
Rarely, painless aortic dissection occurs in patients with pre-existing, large ascending
aortic aneurysms. [185 ]
PHYSICAL FINDINGS
Patients with acute dissection may appear pale and clammy but blood pressure is
usually elevated because of essential hypertension or mechanical occlusion of a renal
artery or the aorta. [94 ] , [185 ] [187 ] Pain and anxiety usually increase circulating
catecholamines. Hypotension or profound shock associated with aortic dissection
usually indicates pericardial tamponade or manifest rupture when the proximal portion
is involved or hemorrhage into the retroperitoneum or thoracic cavity in distal dissection.
[46 ] , [105 ] , [188 ] Other sources of hypotension include obstruction of a main coronary
artery(s) and severe acute aortic insufficiency. [49 ] , [93 ] , [189 ]
A new pulse deficit is a critical finding that supports the diagnosis of acute aortic
dissection and occurs in up to 60 percent of patients with acute proximal dissection.
[105 ] , [181 ] , [187 ] A pulse deficit involving either subclavian artery usually denotes
proximal dissection, but distal dissection with retrograde extension may occlude the left
subclavian artery. [46 ] Femoral pulses may be lost because of occlusion of either the
thoracoabdominal aorta or iliac arteries from an expanding false lumen or, more
commonly, dissection into one of the pelvic vessels. A pulse deficit can change as the
hematoma dissects distally, expands, and re-enters, a finding extremely supportive of
the diagnosis of aortic dissection. [46 ] , [105 ]
The characteristic murmur of aortic regurgitation is present in most patients with acute
proximal aortic dissection and in a minority of those with distal dissection, because of
pre-existing annular dilatation without dissection. [46 ] , [105 ] , [185 ] , [190 ] A new
murmur of aortic insufficiency with chest pain and a pulse deficit strongly suggests
proximal dissection. Other auscultatory findings may include an S3 gallop owing to
severe aortic regurgitation, a pericardial friction rub, or pulmonary edema. Loss of
alveolar breath sounds in the left chest suggests hemothorax.
Signs of pericardial involvement such as jugular venous distension or a paradoxical

pulse suggest pericardial involvement and impending tamponade. [188 ]
Occasionally acute dissection causes neurologic deficits, ischemic paralysis,

paraplegia, or Horner syndrome. Syncope is particularly ominous and may indicate
rupture into the pericardium. [105 ] Stroke may be owing to acute occlusion of a carotid
artery that rarely improves with restoration of flow. [262 ] Furthermore, reperfusion may
produce severe intracerebral hemorrhage, swelling, global cerebral injury, coma, and
brain death. [192 ] , [193 ]
Obstruction of intercostal and lumbar arteries from shearing off or compression by the
dissecting membrane may result in permanent flaccid or spastic motor paraplegia. [190
] This must be differentiated from lower body and peripheral nerve ischemia owing to
occlusion of the thoracoabdominal aorta because restoration of perfusion to ischemic
lower extremity muscles and peripheral nerves usually restores function. [185 ]
Rarely expansion of the false lumen and compression of adjacent structures may cause
the superior vena caval syndrome, vocal cord paralysis and hoarseness, tracheal or
bronchial compression with attendant pulmonary collapse, massive hemoptysis from
erosion into the tracheo-bronchial tree, or hematemesis from erosion into the
esophagus. Degradation of clotting blood or release of pyrogenic substances from
ischemic tissues can produce low-grade fevers.
DIAGNOSTIC STUDIES
Severe chest pain without electrocardiographic (ECG) changes is the sine qua non of
acute aortic dissection. [105 ] In acute proximal dissection, the ECG usually shows no
ischemic changes. However, obstruction of a coronary ostium by the dissection causes
significant S-T segment changes because of severe ischemia or infarction. Underlying
coronary artery disease or hypertension also may leave evidence of previous
myocardial infarction or hypertrophy. [186 ]
Although standard chest x-rays are not diagnostic, several findings are strongly
associated with aortic dissection. [105 ] In an asymptomatic patient, the chest x-ray may
provide the first evidence of aortic pathology. Findings suggestive of aortic dissection
include slight bulging of the descending thoracic aorta, deformity of the aortic knob, a
density adjacent to the brachio-cephalic artery, enlargement of the cardiac shadow,
displacement of the esophagus after passage of a nasogastric tube, widened
mediastinum, irregular aortic contour, loss of sharpness of the aortic shadow, tracheal
or bronchial displacement, and pleural effusion. Over 80 percent of patients with aortic
dissection have one or more plain chest x-ray abnormalities, but a small number have
completely normal evaluations. Thus, a normal chest x-ray does not rule out dissection.
Serial x-rays may show enlargement of the aortic shadow or development of a pleural
effusion. Small pleural effusions, usually on the left side, are not unusual after an aortic
dissection and generally do not indicate rupture. [186 ] However, large effusions may be
associated with widening of the mediastinal shadow from mediastinal bleeding or aortic
expansion and signify rupture into the pleural space.
BLOOD TESTS
Blood tests usually are unremarkable in acute aortic dissection. A mild anemia is
common because of sequestration of blood in the false lumen even without
hemorrhage. Hemolysis of static blood may slightly increase bilirubin and lactic acid
dehydrogenase. White blood cell counts between 10,00015,000 are common. [181 ] ,
[190 ] Transaminases are normal or mildly elevated unless a malperfusion syndrome
produces hepatic ischemia. [186 ] Ischemic tissue may produce a mild metabolic
acidosis, but otherwise electrolytes usually are normal.
Initial Management
If prior information or impressions raise the possibility of acute aortic dissection, initial
management in an intensive care unit (preferably surgical) often expedites evaluation,
instrumentation, diagnosis, and preparations for operation. The history and physical
examination are done simultaneously with insertion of a large-bore intravenous catheter
and removal of a blood sample for blood typing, complete blood count and electrolytes,
creatinine, urea nitrogen, and glucose. If systolic blood pressure is over 100 mmHg,
medical therapy is started immediately (see the following) as rupture may occur during
the evaluation process.
The initial work-up focuses on the differential diagnosis of acute aortic dissection. An
electrocardiogram is obtained and the ECG is monitored continuously. A radial or
brachial arterial catheter and a Swan-Ganz catheter are inserted. A Foley catheter is
placed to monitor urine output; urine volume equal to 1 mL/kg/h indicates adequate
renal perfusion. A portable AP chest x-ray is taken.
Symptoms, neurologic status, strength of peripheral pulses, and continuously monitored

signals are checked frequently for changes during the diagnostic evaluation. A definitive
diagnostic imaging modality is selected depending on the information available and
hemodynamic stability of the patient. Often the patient is transferred to the operating
room for transesophageal echocardiography after induction of general anesthesia.
Uncomfortable procedures such as angiography or transesophageal echocardiography

increase heart rate and blood pressure and rupture has occurred during both
procedures.
PHARMACOLOGIC THERAPY
The landmark review by Wheat and colleagues described the pharmacologic reduction
of aortic wall stress in the setting of acute aortic dissection. [31 ] Initially Wheat and
associates used reserpine, trimethaphane, and guanethidine. [32 ] Later, drug
treatment was tailored to control both arterial hypertension and the force of left
ventricular ejection, dP/dt, using vasodilators and beta-adrenergic blockade.
Hypertension and the force of the pressure-pulse wave entering the aorta are the factors
responsible for propagation and rupture of the dissection.
Sodium nitroprusside, a potent and short-acting vasodilator, is the drug of first choice
for antihypertensive treatment in acute aortic dissection. The infusion is adjusted to
maintain a systolic blood pressure between 90100 mmHg. Metabolism of nitroprusside
produces thiocyanate and cyanide toxicity may develop after continuous use over
several days. Because sodium nitroprusside reduces afterload, the resultant increase in
dP/dt may propagate a dissection; therefore, beta-adrenergic blocking agents are
administered simultaneously.
Beta-adrenergic blocking drugs decrease the force of left ventricular ejection dP/dt max
in acute dissection. [31 ] Short-acting compounds are most frequently employed,
particularly if cardiopulmonary bypass is anticipated. Esmolol is a beta-1-selective
adrenergic receptor blocking agent with an ultra-short duration of action. After a loading
dose it reaches a steady state within 6 minutes; however, treatment without a loading
dose is recommended. The half-life is approximately 9 minutes. The predictable rapid
onset and short half-life of esmolol makes it ideal for acute aortic dissection. The drug is
successfully combined with sodium nitroprusside but can induce sudden heart block.
Propranolol is administered in small boluses after an initial test dose of 0.250.5 mg.
Repeat dosage, up to 12 mg, should not be administered at intervals less than 10
minutes. A reduction in pulse rate to 60 or 70 per minute indicates satisfactory beta
blockade that can be maintained by re-dosing every 46 hours. A more cardioselective
and longer acting beta-1-receptor blocker is atenolol. Intravenous dosage is
administered slowly up to 0.15 mg/kg/d.
Labetalol is an ideal drug for use in aortic dissection because it has both alpha- and
non-selective beta adrenoreceptorblocking actions. A dose-dependent decrease in
maximum dP/dt with a concomitant reduction in arterial blood pressure usually is
achieved within 5 minutes of administration. Unfortunately, the drug's half-life, which
approaches 24 hours, can complicate management of patients who require operation.
Pharmacologic therapy is started as soon as possible after the diagnosis of acute

aortic dissection is suspected. Systolic blood pressure usually is maintained between
100110 mmHg, but is reduced further if pain is not relieved as long as the patient
remains conscious and urine output is adequate.
Diagnostic Imaging
The definitive diagnosis of aortic dissection requires identification of the dissection

membrane that separates the aorta into true and false lumens. Modern imaging
technology, including aortography, computerized axial tomography (CT),
echocardiography, and magnetic resonance imaging (MRI) can demonstrate the
presence or absence of the dissection membrane. Each imaging technique has
advantages and disadvantages according to the clinical situation.
AORTOGRAPHY
In 1952, Halliday described the angiographic hallmarks of aortic dissection that are still
valid today. These include opacification of a false lumen compressing the true lumen
with a line of demarcation (the dissecting membrane) between the two channels (Fig.
38-5) . Because aortography specifies flowing blood, angiograms detect an intramural
hematoma but may fail to detect the false lumen if blood flow is brisk or if both channels
are heavily opacified.
Coronary angiography prior to emergency repair of an acute proximal aortic dissection

is not recommended. Even in the presence of moderate coronary artery disease, early
repair of the dissection has precedence over other procedures. Although involvement of
one or more of the main coronary arteries occurs in approximately 1030 percent of
patients with ascending aortic dissection, selective coronary angiography has little or no
role in the diagnosis and management of this problem. [46 ] , [50 ] The ostial coronary
anatomy and pathology is easily assessed intraoperatively.
In a personal series of 27 patients with acute dissection involving the proximal aorta, 16
had an electrocardiogram suggestive of coronary artery disease. Of these, five
underwent preoperative cardiac catheterization but none of the 16 required coronary
artery bypass surgery or died. Six of the remaining 11 patients with no clinical history of
coronary artery disease and normal electrocardiograms had cardiac catheterization,
but none had coronary artery disease. A single patient, with a history of coronary
disease, who did not undergo cardiac catheterization, suffered a perioperative
CT SCANNING
Harris reported the first diagnosis of aortic dissection using computerized axial
tomography in 1979. Definitive diagnosis requires identification of two or more
channels separated by a dissecting membrane (Fig. 38-6) . CT scans are superior to
aortography in both sensitivity and specificity, particularly if flow in both channels or flow
in the false lumen is reduced or clotted. Contrast material is needed but must not
overopacify and obscure the two lumens. Spiral scanning with 2- and 3-D reconstruction
of the aorta provides spectacular images in less than 10 minutes and rivals those
obtained from magnetic resonance imaging (Fig. 38-7) . Furthermore, CT scans are
increasingly available around the clock, and are easily interpretable.
MAGNETIC RESONANCE IMAGING (MRI)
Magnetic resonance imaging provides similar information to that obtained from CT

scanning. MRI is based primarily on the excitation of protons contained in water, and
analysis of the radiofrequency pulse emitted as the proton relaxes. [194 ] [196 ] The
emitted signal produces an image based on proton density and pulse energy. In the
aortic lumen, water and its excited protons move quickly through imaged areas with the
flow of blood. Thus, with typical spin echo, MRI intra-arterial spaces appear completely
black because excited protons have moved on prior to relaxation and pulse emission.
Conversely, the vessel wall, dissecting membrane, and surrounding tissues and organs
produce variable amounts of signal based on their water content and local chemical
environment. When blood flow is relatively slow, as in the false lumen, some
intravascular signal may be produced. The intensity varies according to flow velocity
and pulse sequences used, and thus provides a contrast between the true and false
lumens. [195 ]
The complementary modality to spin echo is gradient echo imaging, which produces
very bright images in the presence of flowing blood. [197 ] , [198 ] The combination of
both imaging modalities provides information regarding the relative flow velocities
between the fast and slow (true and false) channels and differentiates the origin of aortic
side branches between true and false lumens. Maximum intensity projection, applicable
to any structure containing flow ing blood, combines images acquired from multiple
sections into a pattern similar to that obtained from an angiogram. [199 ] , [200 ]
The definitive diagnosis of aortic dissection by magnetic resonance imaging requires

identification of an intraluminal membrane separating the two channels (Fig. 38-8) .
Using spin echo imaging, this is identified easily as a thin linear structure of moderate
intensity, contrasted by the dark void from flowing blood in the true and false lumens.
[281 ] As with other imaging modalities, when the false lumen is thrombosed, this
channel may be difficult to distinguish from concentric thrombus in an atherosclerotic
aortic aneurysm. [202 ]
MRI has not gained widespread use for evaluation of acute aortic dissection because
imaging is time-consuming and may not be available on a 24-hour basis. Magnetic
resonance imaging is most useful for follow-up of chronic dissection since it is
reproducible, reliable, and completely noninvasive. Erroneous results from MRI
scanning are extraordinarily rare; therefore this is the current gold standard for the
diagnosis of aortic dissection. [196 ] , [203 ] [206 ]
ECHOCARDIOGRAPHY
Both transthoracic (TTE) and transesophageal (TEE) echocardiography are used to

provide rapid diagnosis of aortic dissection. Given increasing availability and operator
expertise, echocardiography is the preferred diagnostic imaging method for acute
aortic dissection. Echocardiography easily identifies aortic regurgitation, pericardial
effusion, and dilation of aortic segments. Transthoracic echocardiography provides
limited views of the ascending aorta and because of body habitus may not be
applicable in all patients. Transesophageal echocardiography using new omniplane
technology provides superb imaging of the ascending aorta, but is semi-invasive and
requires sedation to prevent discomfort and hypertension. Echocardiography does not
require intravenous contrast agents or exposure to radiation.
With transthoracic echocardiography, the criteria for definitive identification of the

dissection include (1) visualization in more than one view (Fig. 38-9) ; (2) defined
motion not parallel to the motion of any other cardiac structure; (3) differentiation from
an extension or reverberation of another cardiac structure; and (4) identifiable true and
false channels separated by a repeatedly observed echogenic surface (dissection
membrane). The entire thoracic aorta must be visualized, to exclude the diagnosis. [207
] Color flow Doppler velocity mapping improves both sensitivity and specificity of the
transthoracic evaluation, quantitates the severity of aortic regurgitation, and
demonstrates communications between true and false channels. [208 ]
Nienaber reported a sensitivity of 78.3 percent for acute and 87.5 percent for subacute
proximal dissections and 40 versus 29.4 percent for acute and subacute distal
dissections in a large series comparing transthoracic echocardiography to other
modalities. [204 ] , [205 ] Although aortic regurgitation and pericardial effusions were
detected easily, transthoracic echocardiography poorly imaged the aortic arch.
The transesophageal probe, first used for diagnosis of aortic dissection by Borner in
1984, eliminates many of the limitations of transthoracic imaging, including obesity,
emphysema, mechanical ventilation, chest wall deformities, and small intercostal
spaces. [209 ] Current state-of-the-art transesophageal equipment includes omniplane
transducers that combine multifrequency two-dimensional (2-D) imaging, steerable
pulse wave, continuous wave Doppler, and color flow imaging. The probe rotates a full
180°, to provide almost unlimited viewing planes. Using current transesophageal
probes, the thoracic aorta can be examined as well as or better than with any other
imaging technique. [210 ] TEE also assesses left ventricular function, aortic and mitral
regurgitation, regional wall motion, and coronary artery involvement. [210 ] , [211 ]
Insertion of the transesophageal probe usually requires topical anesthesia and

light-to-moderate sedation at the bedside, but is easiest under general anesthesia in
the operating room. The examination can be performed in 97 percent of patients in
whom it is attempted and has relatively few contraindications. [212 ] , [213 ]
Contraindications include esophageal varices, strictures and tumors, and to a lesser
degree, a recent meal or full stomach owing to ileus. Significant complications are rare.
[213 ] Hemodynamic changes produced during transesophageal echocardiography
usually are controllable but are not trivial. [212 ] , [214 ] Several investigators, including
ourselves, have observed aortic rupture during and immediately after transesophageal
echocardiography. [213 ]
In a multicenter study, the accuracy of transesophageal echocardiography was

compared to other modalities in 164 consecutive patients suspected to have aortic
dissection. The study correctly identified all DeBakey type I and III dissections and only
one false-negative diagnosis occurred in a patient with a localized DeBakey type II
dissection. Of note, aortography also failed to identify the dissection in this case. A
false-positive echocardiographic diagnosis of DeBakey type II dissection occurred in
two patients with dilatation of the ascending aorta. The combined sensitivity and
specificity of TEE were 99 and 98 percent, respectively. When compared to
aortography, transesophageal echocardiography was superior.
TEE has the important advantage of positively identifying many of the alternative
diagnoses in patients with suspected aortic dissection. TEE reliably detects acute
myocardial infarction, pleural effusion, aortic stenosis, pericardial effusion with or
without tamponade, and aneurysm of the ascending aorta uncomplicated by dissection.
INTRAVASCULAR ULTRASOUND
Pandian and colleagues used intravascular ultrasound in 14 patients with proven

dissection, and correctly identified the entry site, extent of dissection, involvement of the
abdominal aorta and its branches, and the presence or absence of clot in the false
lumen. [215 ] Intravascular ultrasonic probes can detect minuscule aortic wall lesions
and may become important for evaluating subtle defects not visible by other techniques.
The method raises safety concerns, poorly images the aortic arch, and does not detect
aortic insufficiency or pericardial effusion.
B-MODE ULTRASOUND
B-Mode ultrasound and Doppler ultrasound can evaluate the abdominal aorta and
peripheral manifestations of aortic dissection not shown by transesophageal
echocardiography.
Diagnostic Strategy
A patient suspected of an acute aortic dissection may require one to three imaging
modalities described earlier.
The presence or absence of a dissecting membrane in the ascending aorta must be

ascertained with absolute certainty and should be differentiated from intramural
hematoma. [216 ] Demonstration of a dissection membrane is an absolute indication
for operative replacement of the ascending aorta and, in the absence of complicating
factors, no further diagnostic evaluation is necessary, as the arch and coronary ostia
can be examined during operation. The decision of which imaging modality to employ
to demonstrate a dissecting membrane in the ascending aorta depends on clinical
urgency, costs, and institutional availability.
In patients with cardiovascular collapse and a high likelihood of acute aortic dissection
(i.e., severe chest pain without ECG changes, a new murmur of aortic regurgitation, or
pulse deficit) immediate transfer to the operating room without confirmatory imaging is
recommended. After careful induction of general anesthesia, the transesophageal
echocardiography probe is inserted and an evaluation of the aorta is done at that time.
This places the patient in the safest and most useful area of the hospital for patients with
acute complicated aortic dissectionthe cardiovascular operating room. If the diagnosis
proves false, or if the ascending aorta cannot be visualized, clinical stability can be
obtained easily and rapidly in the cardiovascular operating room, invasive monitoring
lines inserted under sterile conditions, and (with the patient under the best possible
control), he or she may be transferred to the angiography suite for further evaluation.
If the patient is clinically stable, the most convenient method for confirming the diagnosis
is employed. Often a transthoracic echocardiogram quickly demonstrates an intimal flap
in the ascending aorta. If conclusive data are not obtained, the transesophageal probe
is inserted or the patient is taken to the CT scanning suite, where ultra-fast spiral CT
scanning provides a complete assessment of the aorta in 10 minutes. Magnetic
resonance scanning is reserved for occasional patients who are completely stable and
have questions regarding the precise location of the intimal tear or involvement of the
ascending aorta and aortic arch. Thus, the most common use of MRI in the acute setting
is to rule out involvement of the aortic arch in patients with acute distal dissection, since
the extent of retrograde dissection into the arch is not well-assessed by other imaging
techniques.
The use of angiography for acute aortic dissection continues to decrease for several
reasons. Most hospitals do not maintain an angiography team in the hospital on a
24-hour basis. The procedure is painful and may exacerbate hypertension to cause
extension or frank rupture. Thrombosis of the false lumen may obscure the diagnosis. If
the false lumen is less than one-half of the diameter of the true lumen, the double
channel may not be perceived. Finally, contrast material required for satisfactory
images may cause nephrotoxicity. Nevertheless, angiography remains the preferred
procedure for evaluation of possible obstructed aortic branch vessels.
Natural History
In autopsy reviews, at least 50 percent of patients with untreated acute aortic

dissections succumb within the first 48 hours; this yields a 1 percent per hour death risk
for acute aortic dissection. [45 ] , [46 ] , [217 ] This fact should be kept in mind by all
physicians evaluating patients suspected of aortic dissectiontime is paramount. In the
largest collective review of aortic dissection, comprising 963 patients with both proximal
and distal untreated dissection, 3672 percent of patients succumbed within 48 hours,
71 percent at 2 months, 89 percent at 3 months, and 91 percent at 6 months. [45 ]
Indications and Selection of Operation
PROXIMAL AORTA AND ARCH DISSECTION
Acute aortic dissection that originates in or extends to the ascending aorta is an

absolute indication for emergency operation to prevent rupture into the pericardium. A
double lumen in the intrapericardial aorta establishes the indication regardless of the
origin of the tear. The false lumen may have flow exceeding that of the true lumen,
contain partial thrombus, or be completely thrombosed. The simple presence of two
channels in the ascending aorta indicates the need for emergency repair. [216 ]
The selection of specific operations varies with the pathology. Whenever possible, the
native valve is resuspended and replacement is avoided.
The presence of stroke or acute paraplegia does not contraindicate operation, as

patients may experience significant recovery after operative repair. [85 ] , [218 ]
Obviously, in cases of brain death, operation does not proceed.
In the absence of phenotypic or historical markers for a connective tissue disorder,

patients with involvement of the ascending aorta and a normal aortic root may undergo
simple tube-graft replacement of the ascending aorta, resuspension of the aortic valve,
and an open anastomosis with reconstitution of the downstream aorta.
Patients with either historical or phenotypic markers for a connective tissue disorder or
who have dilatation of the sino-tubular portion of the aorta or aortic annulus require
composite graft replacement of the aortic valve and ascending aorta with reimplantation
of the coronary arteries. For patients with a connective tissue disorder (e.g., Marfan
syndrome) and a relatively normal aortic valve, the native aortic valve can be preserved
with prosthetic replacement of the ascending aorta, including the sinus portion. [219 ] ,
[220 ] At this time, the authors neither recommend for or against this procedure.
Regardless of whether or not the valve is replaced, it is important to use a composite
prosthesis and reimplant the coronary arteries. This avoids a high incidence of
subsequent sinus of Valsalva aneurysm that occurs after simple aortic replacement
without resection of the aortic sinuses.
Aortic dissection usually originates in the dilated portion of the ascending aorta in
patients with acquired aortic stenosis or a congenital bicuspid valve. In these patients,
the sinus portion of the aorta that contains the coronary ostia is retained, the valve is
replaced, and the dissected ascending aorta is replaced with a Dacron graft after
reuniting the two ends of the transected aorta with either resorcinol glue or Teflon felt.
In selected cases, such as female patients who wish the option of future pregnancy, use
of cryopreserved or fresh aortic homografts is advocated for composite replacement of
the aortic valve and ascending aorta for acute aortic dissection. Long-term data on the
surgical results of this procedure are not yet available.
Some surgeons recommend a tie-in prosthesis for the distal connection between graft
and dissected aorta. [221 ] [223 ] Theoretically, this technique decreases the incidence
of a perfused false lumen as compared to reuniting the dissected layers with a Teflon
felt sandwich, but this advantage has not been demonstrated in a large group of
patients from multiple centers. Furthermore, the rigid internal ring of the prosthesis
reduces intraluminal diameter and may compromise the origin of the innominate artery.
The authors prefer an open-sutured anastomosis, either with two layers of Teflon felt or
resorcinol glue for reconstitution of the distal aorta.
When the proximal dissection extends into and beyond the aortic arch (DeBakey type I),
graft replacement of the ascending aorta is extended into the lesser curvature of the
arch. [224 ] [227 ] This facilitates later repair of the arch and thoraco-abdominal aorta if
disease of these segments progresses. In patients with DeBakey type II dissections
that involve only the ascending aorta, resection removes the entire separated aorta.
The extent of ostial coronary arterial involvement is determined intraoperatively. If the

aortic root is intact and there is no intimal tear extending into the coronary artery (i.e.,
the layers are only separated), the layers of the aortic root can be repaired using either
Teflon felt or glue with rare coronary artery problems. If a tear extends into the coronary
artery or if the dissection involves either main coronary ostium, a composite graft and
repair of the coronary artery using glue is used. The coronary ostia are connected to the
graft by direct reimplantation or by the Cabrol intercoronary graft technique. The need to
oversew a dissected ostium and perform a distal coronary artery bypass graft is rare.
If the inner cylinder of the aortic arch is not torn, the arch is managed identically to
simple ascending aortic dissection. If the arch is torn, the portion containing the tear is
resected and replaced using the open anastomotic technique.
More radical operations are required when the intima of the arch is fragmented, the
arch is aneurysmal, the outer margin is ruptured, or the brachiocephalic vessels are
disrupted. In such cases one or more of the brachiocephalic vessels are directly
reimplanted into a Dacron graft after reconstitution with either Teflon felt or glue.
Unusually, dissection may originate in the arch and propagate proximally as far as the
aortic root. Even more rarely, a dissection originating in the descending thoracic aorta
may propagate retrograde as far as the ascending aorta. Operation for these two
situations is similar to dissections originating in the ascending aorta. When the tear
originates in the aortic arch, the site must be resected in conjunction with replacement
of the ascending aorta. With distal retrograde dissection separating the layers of the
ascending aorta, we replace the ascending aorta and reunite the layers of the proximal
aortic arch. This converts the retrograde dissection to a DeBakey type III.
DISTAL AORTIC DISSECTION
Patients with distal dissection tend to be older, hypertensive, and have a higher
incidence of atherosclerotic disease, which may include other vascular beds such as
the coronary and renal arteries. Currently, surgical intervention for acute distal aortic
dissection is reserved for complications of the disease and is either not involved or has
only a limited role in the management of uncomplicated patients. [228 ] [231 ]
Surgery for acute distal dissection remains controversial. Obviously, patients with
perforation of the descending thoracic or thoraco-abdominal aorta require urgent
operation. However, if the dissection stabilizes without frank rupture, patients may be
managed medically in most circumstances.
Medical treatment consists of invasive hemodynamic monitoring, beta blockade, and

arterial dilatation that is started during the initial evaluation. Once the patient is stable,
oral beta-blockers and antihypertensive medications are substituted and the patient is
allowed to return to normal activity with close follow-up. If the patient becomes
asymptomatic with medical therapy, good results without surgery are anticipated,
particularly if the diameter of the thoracic and thoraco-abdominal aorta is normal or only
slightly enlarged.
Medical management of patients with acute distal dissection can be justified because
worldwide accumulated experience shows that medical therapy is effective for
preventing death in acute distal dissections. [228 ] , [232 ] Furthermore, operative
mortality and complication rates are much higher in acute distal aortic dissections. [47 ]
, [228 ] Nevertheless, long-term complications of acute distal aortic dissection
eventually cause death in up to 84 percent of individuals treated medically. Thus, these
patients require extremely close follow-up throughout the early and late post dissection
period. Centers following large numbers of medically treated patients after acute distal
dissection report mortality rates ranging 2167 percent with an interim term survival of
3040 percent. [228 ] , [230 ] [232 ] A significant number of early deaths occur following
aortic rupture or after attempted repair of extensive aneurysmal enlargement. [47 ] , [83 ]
, [234 ] [236 ]
Indications for operation in patients with acute distal dissection generally are limited to
prevention or relief of life-threatening complications. These complications include aortic
rupture, ischemia of limbs and organ systems, persistent or recurrent intractable pain,
progression of the dissection, and uncontrolled hypertension.
Operation for acute distal aortic dissection is tailored to the indication for operation. In
cases of intractable pain, without evidence of frank rupture, we replace the proximal
portion of the descending thoracic aorta beginning above the dissection at the left
subclavian artery and extending through the proximal one-third to one-half of the
descending thoracic aorta. This procedure eliminates the most likely site of aortic
rupture and is unlikely to interfere with the blood supply to the spinal cord. When
operating for a ruptured descending thoracic or thoraco-abdominal dissection,
replacement generally begins at the distal aortic arch, hopefully to a non-dissected
proximal segment, and is carried distally to include any segment of the disrupted aorta.
Preservation of the blood supply to the spinal cord and viscera must be included, if
necessary, in this repair.
In most series, operations for acute distal aortic dissection carry a higher mortality, that
historically ranges between 3575 percent, than for acute proximal dissection. This is
primarily because these patients usually are operated on under dire circumstances
when medical therapy fails. [193 ] , [228 ] , [231 ] More recent series show some
improvement in mortality rates, but they remain elevated, particularly in patients with
preoperative visceral ischemia owing either to a malperfusion syndrome or excessive
anti-hypertensive therapy. [193 ] , [231 ] , [237 ] In the Stanford series mortality
increased from 23 to 80 percent in the presence of renal or visceral ischemia, and from
21 to 71 percent in the presence of frank rupture of the aorta. [193 ] , [231 ] Age also
played an important role in this series; 60 percent of patients over 70 died, whereas
only 10 percent of those under 40 succumbed. [231 ]
In summary, patients with acute distal aortic dissection are managed medically with
surgical intervention reserved for complications. The more common indications for
operative intervention include persistent or recurrent pain, ischemia or infarction of
major end organs, progression of the dissection during medical treatment, and frank or
contained aortic rupture. There is no absolute contraindication for operative
intervention, but expected mortality may be prohibitively high in patients with significant
co-morbidity that includes lung disease, ischemic cardiac disease, advanced age, and
renal and visceral ischemia. Acute paralysis is not a contraindication to operation,
particularly if femoral pulses are absent, as often relief of distal ischemia returns motor
and sensory functions.
CHRONIC AORTIC DISSECTION
Aortic dissection becomes chronic in survivors of asymptomatic acute dissections,

those successfully treated medically, and in unresected dissected aortic segments in
survivors of acute aortic dissections. Chronic aortic dissection usually is asymptomatic
although mild, dull chest pain from congestive failure may be present. Large
post-dissection aortic aneurysms may cause severe skeletal pain from erosion of the
bony thorax. [185 ] Most operative interventions for chronic thoraco-abdominal
dissections are prompted by aneurysmal enlargement. Probably because of distal
re-entries that decompress the false lumen, pulse deficits are unusual. [105 ]
Rarely, chronic aortic dissection causes paralysis or paraplegia following thrombosis of

a false lumen from which significant intercostal arteries originate. Embolic strokes may
occur from thrombus in proximal pockets of the false lumen.
The selection of diagnostic imaging modalities is wider in patients with chronic aortic
dissections. The primary indications for imaging include periodic surveillance (usually at
6-month intervals), onset of symptoms that may be caused by the dissection, and
preparation for operative intervention. Occasionally all four imaging techniques are
used, but usually only one or two suffice. CT scanning is a cost-effective method for
surveillance in most patients because echocardiography does not image the abdominal
aorta well. In many patients, transthoracic echocardiography provides satisfactory
surveillance of the ascending aorta. Magnetic resonance imaging often produces
spectacular images of intra- and extra-luminal aortic anatomy, and provides precise
views of complex areas for planning operative strategy. Aortography is used selectively
and may be used to demonstrate branch vessels by selective injection. Unlike acute
dissections, selective angiography is safe in patients with chronic dissections. Many
patients require coronary angiography prior to elective operations for aneurysmal
enlargement of a dissection.
Occasionally a proximal dissection may go unnoticed for weeks, months, or years.

These asymptomatic or minimally symptomatic dissections usually occur in a previously
dilated aortic root. Surgical intervention is recommended for dilatation of the aortic root
beyond 5.5 cm and/or moderate to severe aortic regurgitation.
Operation for chronic distal dissection is prescribed primarily for relief of aneurysmal
expansion, and threatened, or leaking ruptures of the dissected segment. Rarely,
patients develop chronic visceral ischemia owing to a malperfusion syndrome.
Indications for operation are similar to those of other thoraco-abdominal aneurysms, but
the risk of spinal ischemia is higher as compared to that seen with atherosclerotic
aneurysms. [238 ] The authors advocate replacement of the descending thoracic and
thoraco-abdominal aortic segments either by a single or multiple stage operation when
the affected segment reaches two times the normal aortic diameter.
Factors that increase the likelihood of rupture include eccentricity of an aneurysmal

segment and rapid expansion. In addition, several reports show that smoking may
dramatically increase the risk of rupture. Replacement of any segment of aorta that
becomes symptomatic, is tender to palpation, or productive of chronic back pain is
recommended. If the aneurysm grows more than 1 centimeter during a single 6-month
interval, operation is indicated.
OPERATION
General Considerations
The purpose of operation on the acutely or chronically dissected aorta is to eliminate

aortic segments at risk for early or late rupture. This requires obliteration of all false
channels with reconstitution of blood flow exclusively into the true lumen. Unfortunately,
this objective is rarely achieved except for DeBakey type II dissections that involve only
the ascending aorta.
Anesthesia and Monitoring
Anesthesia often is induced with midazolam, fentanyl, and pancuronium, and

maintained with inhaled isoflurane and intravenous fentanyl. The electrocardiogram,
both radial and femoral arterial pressures, and central venous pressures are displayed
continuously during operation. In addition, bladder temperature and either
nasopharyngeal or tympanic membrane temperature and capillary oxygen saturation by
pulse oximetry also are monitored. Radial and femoral arterial catheters, a Swan-Ganz
catheter, another large-bore central venous catheter, and one or more peripheral
intravenous catheters are inserted and connected to appropriate stopcocks and
transducers. A cell saver system for scavenging shed blood often is helpful. Packed
cells, fresh frozen plasma, and platelet packs generally are ordered before operation.
After induction of anesthesia, the patient is intubated and positioned for the proposed
operation.
Comparison of radial and femoral arterial pressures may allow early identification of a
malperfusion syndrome. During cardiopulmonary bypass, malperfusion may result from
retrograde flow into the false lumen without a proximal entry site; this may cause the
blind pocket phenomenon and occlude the true lumen. [239 ] , [240 ] The malperfusion is
readily identified by a pressure differential between a low right radial and elevated
femoral arterial pressures.
Bladder (or rectal) and nasopharyngeal (or tympanic membrane) temperatures are
necessary to control the depth of hypothermia. If circulatory arrest is planned, the head
is packed in ice to prevent rewarming during periods of arrest and the
electroencephalogram often is monitored to assure brain protection. We do not
routinely drain cerebrospinal fluid before or after repair of acute or chronic distal aortic
dissections.
A double-lumen endobronchial tube considerably improves surgical exposure for

procedures on the descending thoracic aorta through a left lateral thoracotomy.
Endotracheal tubes with unilateral bronchial catheter blocking devices are less
effective. After heparin is administered, manipulation of the deflated lung is kept to a
minimum to prevent serious intrapulmonary hemorrhage and loss of gas exchange.
Hemostasis
Hemostasis often is a problem, especially after prolonged periods of deep hypothermia

in patients with aortic dissections. Shed blood can be aspirated, washed, concentrated,
and returned as packed cells. Antifibrinolytic drugs (aprotinin, epsilon amino caproic
acid, and tranexamic acid) reduce bleeding significantly. Because of thrombotic
concerns aprotinin is deferred until after circulatory arrest; then three million units are
given followed by 500,000 units per hour. During cardiopulmonary bypass, one unit of
fresh frozen plasma is given every 20 minutes for complicated dissections of the aortic
arch. Platelets, fresh frozen plasma, cryoprecipitate, bovine thrombin, and homologous
blood should be available. The tendency for diffuse hemorrhage from suture lines and
raw surfaces is reduced remarkably with liberal transfusion of fresh frozen plasma and
concentrated platelets both during and early after the procedure.
Improvements in suture material, needles, collagen- or gelatin-impregnated grafts,

widespread use of Teflon felt, and both fibrin and gelatin resorcinol formalin (GRF) glue
have improved technical results considerably over the past several years. [241 ] Thus, it
is now rare for a patient to succumb to exsanguinating hemorrhage. Teflon felt is
routinely fixed within and without the aorta using a row of continuous mattress sutures
followed by a running suture prior to insertion of the graft. This provides a leak-proof
gasket at the proximal and distal suture lines. At institutions with access to GRF glue,
special clamps and dilators allow easy approximation of dissected layers, and
eliminate the need for sutures. [242 ] , [243 ] Polymerization is accelerated by warming
the glue, clamps, and Hegar dilators to 40°C. Fibrin glue, provided commercially or
made from cryoprecipitate and thrombin, rarely reunites dissected aortic layers.
Various authors use tie-in grafts equipped with a stiff, grooved ring to obviate suturing
acutely dissected aortas. [221 ] [223 ] , [244 ] Our experience with this method is not
satisfactory because available graft sizes are limited and the incidence of late
complications is substantial.
Extracorporeal Circulation and Cardioplegia
Operations on the proximal ascending aorta and arch always are performed during
extracorporeal circulation with a variety of adjunctive measures for cerebral protection.
For aortic dissection limited to the ascending aorta, cannulation of the proximal aortic
arch and right atrium is employed. When the entire aorta is involved (DeBakey type I
dissection), retrograde femoral artery cannulation for cardiopulmonary bypass is used
in conjunction with a two-stage venous cannula in the right atrium. For femoral-femoral
bypass, the right femoral vein is preferred as the cannula passes more easily from the
right-sided femoral system into the cava and right atrium. Pressures are monitored in
the femoral artery opposite the cannulation site and preferably, both the right and left
radial artery in order to promptly recognize any obstruction to retrograde flow within the
arch. [239 ] , [245 ] , [246 ]
A left ventricular (LV) vent invariably is placed through the right superior pulmonary vein.
Retrograde blood cardioplegia is administered via a cannula inserted through a
pursestring in the right atrium. If retrograde cerebral perfusion is planned, bicaval
cannulation is performed, and a bypass line from the arterial cannula to the SVC
cannula is added.
Cerebral Protection
Operations involving replacement of the distal ascending aorta or any portion of the
aortic arch require special measures to avoid brain injury. The choice of method
depends on the amount of time without cerebral circulation required to complete the
procedure.
DEEP HYPOTHERMIC CIRCULATORY ARREST
Hypothermic arrest for operative intervention on the aortic arch was first employed by
Bernard in 1963 and by Borst in 1964. [226 ] , [247 ] [251 ] The method is used widely
to provide adequate cerebral protection for aneurysms and dissection of the aortic arch.
[252 ] [257 ] Deep hypothermic circulatory arrest reduces cerebral metabolism to 23
percent of its normal value at 20°C and to 17 percent at 15°C; this allows relatively safe
periods of circulatory arrest that approach 30 minutes at 20°C and just under 1 hour
during deep hypothermia. [258 ] [260 ] Most authors do not recommend extending
hypothermia to below 15°C, as a nonischemic cerebral injury may develop. [261 ]
Svensson and coworkers found the risk of cerebral damage in patients undergoing
deep hypothermia for aortic surgery was 4 percent at 30 minutes, 7.5 percent at 45
minutes, and 10.7 percent at 60 minutes. [262 ] Ergin also noted an increased
incidence of at least temporary dysfunction after 4050 minutes of circulatory arrest, and
a rise in the stroke rate beyond this time period. [263 ] Possible new ways of extending
permissible periods of hypothermic circulatory arrest involve glutamate antagonists and
calcium channel blockers. [264 ] , [265 ]
Direct measurement of true brain temperature in humans is not possible; therefore,

nasopharyngeal or tympanic membrane temperatures are monitored to reflect brain
temperature. Unfortunately, these temperatures do not reliably correlate with the
metabolic state of the brain and electroencephalographic (EEG) silence often does not
occur at expected temperatures. [262 ] , [266 ] , [267 ] Therefore, both the EEG and a
temperature are monitored for patients who require prolonged procedures on the aortic
arch. Furthermore, cooling should continue well below the level of EEG silence and for
at least 25 minutes. It is our policy to cool to at least 20°C for brief periods of circulatory
arrest (up to 20 minutes) and to cool to approximately 15°C or 23°C below EEG silence
for longer periods.
For deep hypothermic circulatory arrest the patient is cooled on cardiopulmonary

bypass without exceeding temperature gradients over 10°C. [268 ] [272 ] The partial
pressure of carbon dioxide is not increased as the temperature drops (alpha stat
regimen). Admittedly, the choice of alpha stat management is not universally accepted
and pH stat management is preferred by others. [273 ] , [274 ]
During cooling, alpha-adrenergic blockade is instituted to allow a more even decrease

in temperature in all parts of the body. Hemodilution and hyperglycemia, which are
associated with brain injury, are avoided carefully. [269 ] , [275 ] Methylprednisolone (30
mg/kg) and sodium thiopental (15 mg/kg) are administered before circulatory arrest.
[276 ] During the period of circulatory arrest, the head is packed in ice to prevent
rewarming to room temperature. As the procedure is being completed, rewarming
begins and proceeds to a nasopharyngeal temperature of 36°C and a bladder
temperature of at least 34°C. During rewarming, the temperature gradient is not allowed
to exceed 10°C. As rewarming occurs, 20 percent mannitol (18 mg/kg) and furosemide
(10 mg/kg) are administered to encourage urine output, and sodium bicarbonate is
given to correct the pH value to normal. To eliminate possible air collection in the distal
aorta, the circulation is never completely arrested and at least 100200 mL/min of blood
flow into the femoral artery is maintained. This is interrupted if exposure is difficult.
RETROGRADE CEREBROPLEGIA
Retrograde perfusion of the superior vena cava is described elsewhere (see Chapter
10) and is helpful for maintaining a desired brain temperature and for flushing debris
from aortic arch vessels. [277 ] , [278 ] Retrograde cerebral perfusion probably provides
little nutritive flow.
On occasion, when excessively long procedures on the arch are anticipated, selective
antegrade perfusion is used. This procedure is performed easily by inserting a
right-angle cannula into the innominate artery proximal to the bifurcation. [279 ]
Atraumatic bulldog clamps are used to occlude the innominate, carotid, and subclavian
arteries. Antegrade flow is maintained to the brachiocephalic circulation at
approximately 1 L/min while both radial arterial catheters are monitored to maintain a
mean blood pressure of 70 mmHg. Monitoring the pressure in the left radial artery
assures adequate flow through the circle of Willis. An additional cannula can be inserted
into the left carotid artery if necessary.
TWO-STAGE COOLING
If arch involvement is uncertain at the outset of operation and the time required for
circulatory arrest unknown, cooling proceeds in two stages. First, temperature is
reduced to 20°C, and the circulation is interrupted. The aorta is opened in the mid
ascending portion and the interior including the arch is inspected. If the inner cylinder is
intact, the distal open reconstruction and anastomosis proceeds immediately by
suturing the graft to the proximal portion of the reconstituted arch. Antegrade circulation
usually is re-established through a cannula placed in the graft in less than 15 minutes.
However, if the inner cylinder of the arch is disrupted or if individual brachiocephalic
vessels require reconstruction, the clamp on the ascending aorta is replaced and
cooling is continued to 1517°C or 3°C below EEG silence. While cooling continues, the
proximal portion of the operation is accomplished.
Operative Techniques for Proximal Dissections
EXPOSURE
Median sternotomy is the standard incision for all procedures on the ascending thoracic
aorta and for most transverse arch procedures. The incision may be extended into one
or both of the supraclavicular spaces if arch branches require further exposure. During
re-operation for ascending aortic dissection, median sternotomy may be hazardous and
the patient should be cannulated for cardiopulmonary bypass before opening the
sternum. When the aortic arch requires replacement, the anterior wall is exposed and
the arch is retracted inferiorly to expose the origins of the arch branches. The left
phrenic and vagus nerves always are identified at the distal arch and retracted
anteriorly. A fourth rib anterolateral incision is added only when a portion of the
descending aorta is included.
REPLACEMENT OF THE AORTIC ROOT AND ASCENDING AORTA
The entire ascending aorta is replaced with a gelatin-impregnated Dacron graft and an
open anastomosis to the arch is performed in every case of acute proximal dissection.
Aortic regurgitation which is encountered in 5075 percent of patients with acute
proximal aortic dissection is most commonly managed by resuspension of the
commissures, reconstitution of the layers of the aortic root, and anastomosis to an
appropriate sized graft. [280 ] [282 ] More recently, valve-sparing procedures whereby
the valve is mounted in a Dacron graft to eliminate the sinuses of Valsalva have been
proposed, but this procedure remains controversial. [218 ] , [283 ]
The ascending aorta in acute dissection appears bluish purple and blood may seem to
seep through the aortic wall. Because the ascending aorta may rupture, manipulation is
not recommended until body temperature is substantially reduced to allow for a safe
period of cerebral protection if the aorta ruptures. Once body temperature is reduced,
the heart fibrillates and must be protected from distension.
The aorta is separated from the pulmonary artery and clamped in the mid ascending
portion using a Fogarty aortic clamp. Retrograde cardioplegia is begun. The proximal
aorta is opened and transected approximately 5 mm distal to the highest point of the
commissures. Once this is done, 4-0 Teflon pledgeted polypropylene sutures with a
finely tapered needle are passed at the apex of each commissure from inside the aortic
lumen, to outside through a second pledget (Fig. 38-10) . These are tied, to resuspend
the valve commissures. A running horizontal mattress suture is used to fasten two Teflon
felt strips inside and outside the circumference of the aorta without pursestringing. This
is followed by a running (over and over) 4-0 Prolene suture that seals the inner layer of
felt against the outer layer, with the aortic wall sandwiched between and the outer layer
of felt (thus providing a leak-proof gasket). Alternatively the root can be glued using
GRF glue. Reconstruction of the aortic root requires 1015 minutes; core cooling may
proceed during this period if the aortic arch is involved.
When the patient's core temperature reaches 2022°C, the ascending aortic clamp is
removed and the interior of the distal ascending aorta and arch is inspected. If the inner
cylinder remains intact, the layers of the dissection are reconstituted, using intimal and
adventitial layers of Teflon felt to compress the dissected walls of the aorta between
(Fig. 38-11) . Once the layers are reunited, a graft of appropriate size is beveled and
sutured to the three-layered arch using a continuous 4-0 Prolene suture. The repair is
always extended to the proximal arch to facilitate late replacement of the arch if this is
required later (Fig. 38-12) . After the distal suture line is completed, the graft is deaired,
clamped, and extracorporeal circulation is resumed after a cannula is inserted into the
graft for antegrade perfusion. This compresses dissected aortic layers together in most
patients. Rewarming proceeds while the distal graft is joined to the proximally
reconstructed aortic root. Occasionally it is useful to fold a segment of the adventitia
over either the proximal or distal suture line for additional hemostasis.
When the dissection reaches either coronary ostium without disrupting the cylinder of
the coronary vessel proper, repressurization of the root usually eliminates any potential
space between the layers. However, if the ostium is completely surrounded by the
dissection, it is preferable to excise a button with a 4-mm margin of aortic wall. The
layers are then united using GRF glue and a 5-0 Prolene suture or between donuts of
Teflon felt. The ostial button is anastomosed to a tube graft or composite graft without
torsion or tension. Partial disruption of a coronary ostium is repaired with continuous
5-0 Prolene suture leaving the ostium in continuity with the aortic wall. Aortocoronary
bypass grafting is the last resort if the ostium is very small and torn or if damage is
irreparable. [284 ]
The St. Jude valve conduit is preferred because the suturing ring is thin and minimizes
the distance between the graft and coronary ostia. Furthermore, new-generation
composite valves are packaged using an impervious ascending aortic graft. Placement
of pledgeted sutures for attachment of graft to annulus is critically important. Everting
2-0 pledgeted sutures are employed and great care is taken to place the sutures exactly
shoulder-to-shoulder along the perimeter of the annulus and corresponding valve
sewing ring (Fig. 38-13) . A minimal amount of diseased aortic wall is retained to
decrease the chance of late complications involving the coronary buttons. Once the
valve is tied to the annulus, the coronary ostia are attached to the graft by either the
side-to-side Bental technique or the preferred button technique (Fig. 38-14) .
Continuous 4-0 or 5-0 Prolene suture, usually reinforced with Teflon felt, is used. A
Cabrol interostial coronary graft (Fig. 38-15) or an ultra short (1.5-cm) graft-to-left-main
extension occasionally is employed when low-lying ostia cannot be mobilized. [285 ] ,
[286 ] The remnants of the ascending aorta are closed over the graft to protect the
prosthesis against infection or if reoperation becomes necessary. Graft inclusion should
not be used to achieve hemostasis. [287 ] , [288 ]
ACUTE DISSECTION INVOLVING THE AORTIC ARCH
Disruption of the inner arch cylinder occurs in 1030 percent of patients with acute
dissection and portends an ominous prognosis. [289 ] [291 ] The aortic arch should be
inspected during a short period of hypothermic circulatory arrest in every proximal
dissection. [292 ] Limited tears in the dissecting membrane within the arch are
managed by placing the distal anastomosis beyond the site of disruption during
circulatory arrest. Fortunately, this is the most common problem and tears tend to be
located away from the origin of the cephalic branches. [292 ]
In more severe cases, the true channels of one or more of the supra-aortic vessels are
completely separated from the arch and are supplied through secondary entry ports
(Fig. 38-16) . In the most severe circumstance, a completely separated true lumen may
prolapse distally to cause obstruction. These problems are managed by subtotal or,
more commonly, total replacement of the arch with reconnection of some or all of the
supra-aortic vessels to the prosthesis. [292 ] In acute dissections the supra-aortic
branches are anastomosed individually to separate openings in the arch graft rather
than as a unit (Fig. 38-16) . One, two, or three separate anastomoses may be required.
In addition, supra-aortic vessels themselves may require repair using GRF glue or
Teflon felt.
For subtotal or total arch replacement, the tubular portion of the arch is freed to
approximately 2 cm beyond the level of the planned distal anastomosis. Arch branches
are dissected free and the dissected layers of the aortic wallare divided near the origins
of the brachiocephalic vessels. The aortic dissecting membrane is excised and
individual arteries, usually the innominate and carotid, are divided just beyond their
origins. Next the dissected layers of the transected descending thoracic aorta are
reunited using either GRF glue or internal and external Teflon felt strips. Separate
running mattress and over-and-over prolene sutures are recommended to produce a
firm seal. When the tear extends distally into the descending thoracic aorta, after the
dissected layers are reapproximated, a short elephant trunk is added to the graft to
provide a more secure seal. Brachiocephalic vessels usually are anastomosed directly
to separate openings in the graft. Alternatively, if the anatomy is favorable, the patch of
arch vessels may be sewn to a single opening in the graft after the dissected layers of
the patch are reapproximated either with GRF glue or Teflon felt strips (Fig. 38-17) .
CHRONIC AORTIC ARCH DISSECTION
For chronic dissections or postdissection aneurysms isolated to the proximal arch, an

open distal anastomosis is made at the junction of the ascending and transverse
arches. The graft is anastomosed beyond the site of any true arch tear. When
brachiocephalic vessels are involved, flow to the true lumens is re-established with
replacement of the arch. Sometimes, individual arch grafts may be required.
Occasionally a chronic dissection membrane that involves and partially occludes the
brachiocephalic vessels or proximal descending thoracic aorta may be fenestrated. The
distal anastomosis always is made to the outer layer of the aorta.
Operative Techniques for Distal Dissections
Ischemic injury to the spinal cord and/or intra-abdominal organs is a disastrous

complication of dissected thoracic or thoraco-abdominal aortic repairs. [238 ] , [293 ]
[301 ] The risk of spinal cord damage is higher for repair of acute dissection than for
arteriosclerotic aneurysms because chronically occluded intercostal arteries in
aneurysm patients may stimulate development of spinal cord collaterals that partially
protect against ischemic injury. Moreover, the friable dissected aortic wall of an acute
dissection presents a greater technical challenge. [185 ] , [238 ] , [293 ]
Several protocols are designed to predict or prevent spinal cord ischemia, but none
have attained widespread use because of inconsistent efficacy and false-negative
and-positive results. Intraoperative monitoring of sensory or motor evoked potentials
and preoperative imaging of the great radicular artery attempt to predict cord ischemia.
[232 ] , [295 ] , [302 ] [317 ] Cooling the spinal cord by surface, intrathecal, or whole-
body hypothermia using extracorporeal circulation attempt to prevent cord ischemia.
[232 ] , [255 ] , [262 ] , [295 ] , [318 ] [333 ] Intraoperative cerebrospinal fluid withdrawal
is designed to maximize the pressure difference between the residual arterial
circulation and the cord during aortic occlusion, but clinical benefit remains undecided.
[334 ] [335 ] , [337 ] , [342 ] This method also risks intrathecal bleeding during
heparinization from a traumatic puncture. Pharmacologic agents to prevent spinal cord
damage include oxygen free radical scavengers, prostaglandin E, dextrorphan,
corticosteroids, and sodium thiopental, but none have provided reliable protection in
patients. [299 ] , [307 ] , [319 ] , [337 ] , [345 ] [354 ]
Three important principles are now recognized to reduce the risk of spinal cord and
organ ischemia. First, maintain perfusion of vessels downstream to the distal graft
anastomosis and prevent proximal hypertension. Second, promptly revascularize all
important aortic side branches. Third, reduce spinal cord and visceral organ
temperature during the period of ischemia. These principles evolved from prior
experience with simple, proximal aortic cross-clamping followed by expeditious
anastomosis of major aortic branches to the graft. This experience produced
unpredictable ischemic injuries to the spinal cord and visceral organs, and
complications owing to hypertension proximal to the clamp. [47 ] , [88 ] , [249 ] , [256 ] ,
[302 ] , [355 ] [358 ]
Our current routine for replacement of the distal aorta incorporates extracorporeal
circulation for all interventions. When only the descending thoracic aorta or
thoraco-abdominal aorta is replaced, centrifugal pump bypass from the left atrium or
pulmonary vein to the left femoral artery is used to maintain full perfusion of the distal
circulation. Cooling to 30°C is accomplished via an inline heater-cooling circuit or
surface cooling. The safety, simplicity, and lack of heparin requirement are important
advantages of left heart bypass. [359 ] [364 ]
For complex procedures on the descending thoracic aorta, cardiopulmonary bypass via
the femoro-femoral route allows cooling the patient to any desired temperature. The
ascending aorta also is cannulated and the left or main pulmonary artery also may be
cannulated to provide adequate venous drainage. These cannulations enable full
cardiopulmonary bypass, deep hypothermia, and periods of circulatory arrest. Deep
hypothermic circulatory arrest may be required for the proximal anastomosis when a
proximal aortic clamp cannot be safely placed, when brachiocephalic vessels require
repair, or when the dissection proceeds retrograde and requires reconstitution of the
dissected layers prior to graft anastomosis. [365 ] [371 ]
The patient is placed in the right lateral decubitus position with the left pelvis tilted
posteriorly for femoral vessel access. The fourth interspace usually provides adequate
access to the aortic arch for the proximal anastomosis and the mid-descending aorta
for the distal suture line. For additional exposure, the fifth or the sixth ribs may be
notched either anteriorly or posteriorly. If the distal anastomosis is made beyond the
eighth interspace, a second thoracotomy is added. If the anterior part of the incision
slants toward the costal arch, only a single skin incision is required.
A single skin incision and two thoracic incisions are used to expose extensive
dissections (Crawford type I or II). The lower thoracic incision extends across the costal
arch onto the abdominal wall. The retroperitoneum is entered just below the costal arch
and bluntly freed from the posterior muscles and abdominal wall. By carefully avoiding
tears in the peritoneum the intra-abdominal organs, especially the spleen, are protected
from injury. The diaphragm is divided radially, leaving a 2-cm margin along the chest
wall. For malperfusion syndrome involving the infradiaphragmatic aorta a tenth rib
retroperitoneal approach is useful.
When the thorax is entered, care is taken to avoid injury to either the aorta or lung.
Particularly in acute dissection, overtraction of the ribs is avoided until the patient is fully
prepared for extracorporeal circulation. Except for sites selected for cross-clamping, no
attempt is made to free the lung from aortic adhesions. When the lung is inadvertently
injured, air and blood leaks are repaired carefully and sometimes reinforced with strips
of pericardium.
DISTAL ARCH AND DESCENDING THORACIC AORTA
The most common site of aortic rupture in acute distal dissection is the proximal third of
the vessel. Because replacement of this segment comprises the majority of acute
dissections, the overall risk of spinal cord complications for distal dissections is low.
The proximal clamp is placed between the left carotid and subclavian arteries. The
vagus nerve is encircled with a Silastic band and the recurrent nerve is identified. The
left subclavian and carotid arteries are exposed by incising the overlying pleura and the
subclavian artery is encircled with umbilical tape.
The mediastinum is cleared between the subclavian and left carotid arteries down to the
trachea to free the posterior circumference of the arch. Blood pressure should be
maintained below 100 mmHg during this dissection to minimize the risk of rupture.
Ultimately, the arch is freed to the point where the index finger and thumb can squeeze
the posterior wall. If the arch ruptures during this dissection, the site of hemorrhage is
compressed and full hypothermic cardiopulmonary bypass is instituted to perform the
repair during circulatory arrest.
The proximal descending thoracic aorta is first freed for about 6 cm, by dividing visible
intercostal arteries between clips. The distal aorta is mobilized at the appropriate level,
with care to avoid important intercostal vessels and the thoracic duct. The pericardium
is incised posterior to the phrenic nerve for access to the left atrium or the upper left
pulmonary vein. An end-hole atrial cannula is advanced into the mid-atrium for left heart
bypass. The left femoral artery is cannulated. Flow rates are adjusted to maintain equal
arterial blood pressures in the upper and lower portions of the body during the
procedure. This usually requires approximately 1.52.0 L/min in adults. After establishing
left heart bypass, lidocaine is administered and the patient is cooled slowly to 30°C.
The aorta is clamped between the left carotid and subclavian arteries; the latter is
occluded with a tourniquet. A longitudinal incision is used to enter the false channel,
which is cleared of thrombus to recognize and stop any backbleeding from right-sided
intercostal and bronchial arteries. Single or multiple dissecting membranes are
identified and completely removed. The aorta then is completely divided at the junction
of the arch and descending portion, to facilitate the anastomosis and control
anastomotic bleeding. Transection also improves visualization of the recurrent laryngeal
nerve to avoid entrapment in the posterior suture line.
The aortic wall dissection usually originates at the origin of the left subclavian artery
where the primary entry tear also is located. After excising the dissection membrane,
the anastomosis is made to uninvolved aorta. A gelatin-impregnated Dacron graft is
sized to the diameter of the distal aorta and proximally beveled to the corresponding
aortic diameter. A Teflon felt strip is included in the suture line, even if a nondissected
cuff is available. Continuous 3-0 or 4-0 Prolene incorporating large bites of the aortic
wall is run from the posterior anastomosis upward. The suture line incorporates the
origin of the left subclavian artery, with full-thickness bites along the left margin. If the
subclavian artery is dissected, the false channel is closed by the anastomosis. When
the graft is anastomosed to the mid arch, a separate (8-mm) graft is placed between
the aortic prosthesis and the distal subclavian artery.
The anastomosis is tested by first releasing the subclavian artery and then unclamping
the aorta with the distal graft occluded. Any anastomotic bleeding is seen and repaired
easily.
The distal aortic wall layers always are reconstituted in an acute dissection by using
external and internal strips of Teflon felt. Approximation of the dissected layers causes
the true channel of the distal vasculature to re-expand and avoids malperfusion of vital
organs. The graft is sutured to the repaired distal aorta using 3-0 or 4-0 continuous
Prolene and generous bites of aorta. The distal aortic clamp is released first, leaks are
repaired, then the proximal clamp is released slowly.
Rewarming is begun during completion of the distal anastomosis. After termination of

extracorporeal bypass, the left atrium is decannulated, and the pericardial incision is
loosely closed. Likewise, the cannula in the femoral artery is removed, and the vessel is
repaired. The aortic remnants are firmly sutured around the graft to control diffuse
bleeding until hemostasis is achieved and to protect the graft if a pleural space infection
occurs.
When the proximal two-thirds of the descending thoracic aorta requires replacement,
the intercostal arteries arising from the excluded aortic portion are sacrificed without
fear of spinal cord complications. [342 ] , [372 ] When replacement of the entire
descending thoracic aorta is required, all sizable intercostal vessels, below the first six
pairs, are connected to the graft. For these extensive repairs moderate hypothermia is
used and the aorta is clamped sequentially after each branch anastomosis to minimize
ischemic injuries.
If the mid-arch layers are separated, they are reconstituted, either between layers of
Teflon felt or with GRF glue, under hypothermic circulatory arrest. Proximal arch
involvement must be identified prior to incising the aorta to allow for adequate cooling.
Conversion of a planned left heart bypass with moderate hypothermia to full bypass and
deep hypothermia and circulatory arrest requires addition of an oxygenator/heat
exchanger to the bypass circuit and cannulation of both the left femoral artery and
ascending aorta. The left femoral vein may be cannulated with advancement of the
catheter over a wire to the right atrium. If adequate venous drainage is not obtained, a
right-angle cannula (Polystan, Kopenhagen, Denmark) (10-mm ID) placed through the
pulmonary artery into the right ventricle improves drainage dramatically. The proximal
anastomosis then proceeds as described for proximal dissections.
In patients with chronic dissection, the distal graft-to-aorta anastomosis always is made
to the outer coat of the vessel because multiple downstream re-entries ensure perfusion
of all side branches. It is helpful to distend the graft under pressure to its final length and
configuration prior to trimming the distal end. A distal elephant trunk prosthesis
occasionally is helpful for aneurysmal chronic dissections.
THORACOABDOMINAL DISSECTION
Operative intervention for acute dissection of the thoracoabdominal aorta is indicated

for replacement of a ruptured aortic segment or for relief of distal organ malperfusion.
Total cardiopulmonary bypass with ascending aortic and left femoral arterial cannulation
and deep hypothermic circulatory arrest are used to prevent spinal cord and visceral
organ ischemia. A femoral venous catheter advanced to the right atrium and pulmonary
arterial catheter is used for venous drainage.
The aorta is exposed from the arch to its bifurcation. The proximal anastomosis is done
first (Fig. 38-18A) ; the specific technique is determined by the extent of the dissection
into the aortic arch and has been described earlier for exposure through a left
thoracotomy incision. After completion of the anastomosis, the cross-clamp is moved
distally on the graft (Fig. 38-18B) . A perfusion catheter is inserted through the proximal
graft to perfuse the upper body and, later, vessels anastomosed to the proximal graft.
The first six pairs of thoracic intercostal vessels are clipped or oversewn to prevent
backbleeding. Large lower intercostal arteries are sutured to the graft as a patch.
During circulatory arrest, a longitudinal incision is made in the left posterolateral wall of
the aorta to the aortic bifurcation (Fig. 38-18B) . After accumulated thrombus is
removed from the false lumen, the dissection membranes are excised. A small rim of
intima-media is left around the orifices of visceral, renal, and large lower intercostal and
lumbar arteries. Backbleeding from the aortic bifurcation, visceral, or renal vessels is
controlled with balloon catheters. Usually, the celiac, right renal, superior mesenteric,
and right-sided lumbar arteries originate from a nondissected strip of the aorta.
However, the left renal artery characteristically originates from the false lumen. A 4-mm
rim of aortic wall is left around the origin of the left renal artery.
The celiac, superior mesenteric, right renal, and all large intercostal and lumbar arteries
above L3 are reattached as a unit to a single opening in the graft (Fig. 38-18C) . The
lower lumbar arteries and the inferior mesenteric artery are suture-ligated. The left renal
artery and any other major vessels arising from the false lumen are attached to separate
openings in the graft. A continuous 3-0 or 4-0 Prolene suture with full-thickness aortic
bites is used for the unit anastomosis; finer sutures are used for attachment of the left
renal artery and other individual branches. Occasionally a short interposition graft is
needed to reattach the left renal artery without tension.
If visceral or renal arteries are involved in the dissection, they must be repaired to allow
perfusion of the true lumen after connection to the aortic graft. This usually is achieved
by taking deep suture bites of the vessel orifice to simultaneously reapproximate the
dissecting membrane to the outer aortic coat and connect the branch to the graft. When
the inner cylinder of visceral vessel is disrupted, the true lumen is reconstituted with a
running fine Prolene suture before it is anastomosed to the graft. In very rare cases,
individual arteries require bypass, usually because of distal occlusion or aneurysm
formation.
Once the visceral vessels are reperfused, the graft is anastomosed to the aortic
bifurcation (Fig. 38-18D) . Significant backbleeding is controlled using balloon catheters
rather than cross-clamping the aorta. Dissected layers at the aortic bifurcation are
reconstituted using Teflon felt or GRF glue prior to anastomosis to the graft.
After all anastomoses are completed, perfusion is restarted and rewarming is begun.
Leaks are controlled by separate sutures. The bowel is examined carefully for ischemia;
often a Doppler probe is helpful because of vasospasm after these long, complicated
procedures.
Malperfusion of Aortic Branches
INCIDENCE
Involvement of aortic branches in the process of dissection is not uncommon. Indeed,

branch occlusion may be prominent in the clinical presentation. In a large autopsy
series, main coronary artery involvement occurred in 7 percent of cases, dissected
supra-aortic branches in 42 percent, and visceral vessels (celiac trunk, superior
mesenteric, and renal arteries) were affected in 27 percent. Distally the iliac and
femoral vessels were involved in 26 percent (46) of patients.
Clinical series show a lower incidence of symptomatic branch ischemia. Symptomatic
dissection into the main coronary arteries occurs in 4.7 percent, into supra-aortic
branches in 9.3 percent, into visceral vessels in 8.7 percent, and into the legs in 11.7
percent. [187 ] Thus, the initial clinical presentation of aortic dissection may include
myocardial ischemia, stroke, sudden paraplegia, acute abdomen, and ischemic
extremities, and may obscure the correct diagnosis of dissection. [41 ] , [373 ] , [374 ]
Although perfusion of the lower extremities is often relieved by reuniting the true and
false lumens by repair of the aorta, malperfusion of visceral branches may persist with
disastrous consequences. [187 ] , [375 ] [379 ]
PATHOGENESIS
The dissection involves major branch arteries in several ways (Fig. 38-19) .
Compression of the true channel by overexpansion of the false is the most common
mechanism of vascular obstruction. The true channel of an individual branch vessel may
undergo complete dehiscence from the aorta if the dissection completely encircles the
origin. Intussusception of the dissected inner wall commonly occludes a branch but
reentries may cause spontaneous relief. In rare cases, the entire circumference of the
aorta may intussept distally to cause severe organ ischemia. If the entry tear is close to
the origin of a branch vessel, a mobile flap of the aortic dissecting membrane can
cause occlusion.
OPERATIVE STRATEGIES
Although malperfusion in acute dissection often disappears spontaneously, intervention

to relieve distal ischemia may be required. Fenestration of the dissecting membrane to
equalize the pressure in both vascular channels decreases the obstruction caused by
an overexpanded false channel. This was the first and still is the most commonly
performed procedure for malperfusion. Ostial reconstruction particularly is appropriate
for obstructed coronary arteries. As a last resort, formal bypass procedures, such as
aorto-mesenteric or aorto-renal grafting, occasionally are required, after an
unsuccessful membrane fenestration.
For patients at substantial operative risk with thoracoabdominal or aorto-iliac

obstruction, extra-anatomic (axillo-bifemoral) bypass can restore lower body perfusion.
In acute distal dissection, relief of a thoracoabdominal malperfusion may be the only
intervention required beyond medical management. For chronic proximal or distal
dissection, replacement of a stenotic aortic segment is a satisfactory method to
alleviate malperfusion. [229 ] , [231 ] , [375 ] , [380 ] , [380a ]
Membrane fenestration using endovascular interventional procedures is attractive in

these critically ill patients because prompt relief of vascular obstruction can be obtained
without anesthesia or the need for surgery. These procedures can precede emergency
operation on the aorta to promptly relieve potentially lethal organ ischemia. Usually, an
angioplasty balloon catheter is advanced through a small fenestration, inflated, and
withdrawn to rupture the dissecting membrane. The dissecting membrane also can be
punctured by moving a special catheter upstream and using a septostomy blade to
create a large tear in the membrane to restore flow in the distal true lumen. [375 ] , [381 ]
, [382 ] Percutaneous transluminal angioplasty can dilate a chronically narrowed
dissected aorta. [383 ] Expandable stents to reestablish blood flow in dissected branch
vessels also is possible. [231 ] , [380a ]
OPERATIONS
In acute dissection obstruction of either or both carotid arteries, usually by

overexpansion of the false lumen in the aortic arch or occasionally from a dissected
main carotid artery, is an ominous finding. When the inner cylinder is intact, as is usual,
flow improves after closing the false channel and redirecting flow into the true lumen.
When the inner cylinder of a dissected innominate or carotid artery is disrupted,
excision of that vessel from the arch, reconstitution of the dissected layers, and
reimplantation onto the arch graft is recommended. Extra-anatomic bypass operations
involving the carotid arteries rarely are performed but have been successful.
For aortic arch malperfusion in chronic dissection, fenestration of the dissecting

membrane just beyond the origin of the arch vessel usually is sufficient. Occasionally the
dissection extends peripherally into the distal main or carotid bifurcation to produce
persistent chronic malperfusion, often manifested by transient ischemic attacks (TIAs).
In this instance, the dissecting membrane is resected at the beginning of the stenotic
portion, the downstream layers are reconstructed, and the vessel is closed with a patch.
Complete collapse and obstruction of the true lumen of the arch can occur at the onset
of retrograde cardiopulmonary bypass owing to overperfusion and expansion of the
false lumen. This problem must be alleviated by rapid recannulation of the proximal true
lumen using a second arterial line kept readily available for this purpose. Either
transapical or direct aortic cannulation using a brief period of circulatory arrest can be
employed. [377 ] The transapical approach with a tourniquet surrounding the ascending
aorta is preferred.
When the entire true channel of the ascending aorta collapses during systole and
causes coronary malperfusion, repair of the root eliminates the problem. [245 ] , [377 ]
Delamination in the aortic root may extend to or encircle the main coronary ostia and
occasionally continue distally along the proximal coronary artery. This problem is
eliminated by reconstituting the layers of the aortic root either with Teflon felt or GRF
glue. After root reconstruction, the ostia may appear persistently narrowed; however,
when the inner cylinder is intact, the apparent stenosis disappears with pressurization.
Rarely, the vessel may be torn at its origin and require meticulous reconstruction with
fine sutures and glue. In the majority of these patients, the affected coronary ostium can
be salvaged and anastomosed to the aortic graft either directly or with the button
technique. When the ostium is disrupted severely and cannot be reconstructed,
ascending aortic graft-coronary bypass is required.
Relief of abdominal organ malperfusion may require a variety of interventions. These

include replacement of the aorta, membrane fenestration, and extra-anatomic bypass of
individual vessels. Even severe thoracoabdominal malperfusion often resolves with
ascending aortic repair. [223 ] , [376 ]
When simple reconstitution of the proximal aorta does not relieve visceral malperfusion,
the most frequently performed procedure is aortic membrane fenestration (Fig. 38-20) .
The infrarenal aorta is exposed at the diaphragmatic hiatus, generally using the
retroperitoneal approach. [229 ] , [365 ] , [384 ] The aorta is controlled either manually or
with a soft vascular clamp and is occluded below the renal arteries. The vessel is
incised through the nondissected portion, which usually is the right anterior wall. The
nondissected wall appears normal, whereas the freshly dissected portion appears dark
blue. This incision avoids the need to close the friable outer dissected aortic wall. The
dissection membrane is incised and partially excised, as far upstream as possible, and
well below the renal vessels exposed by briefly removing the infrarenal clamp. The
dissected layers are reconstituted below the renal arteries between layers of Teflon felt
or with GRF glue. After completion of the fenestration the aortotomy usually is closed
directly; occasionally an infrarenal tube graft is required.
Fenestration of individual vessels is sometimes needed, if the dissection membrane

extends beyond the ostium of the obstructed branch. When an individual vessel, usually
the superior mesenteric or celiac, requires fenestration, left atrio-femoral or
femoral-femoral bypass is employed with moderate cooling to 30°C. Ideally, the
membrane is completely removed but usually the downstream dissected wall layers
must be reunited by suturing or gluing the false lumen. Patch closure of the arteriotomy
is preferred to avoid narrowing the vessel.
If membrane excision does not re-establish perfusion to the ischemic organ,

extra-anatomic bypass is required. The iliac artery rather than the dissected aorta can
be utilized for inflow. [385 ]
Lower extremity ischemia from obstruction of the terminal aorta or pelvic vessels also
may spontaneously resolve after aortic repair. When unilateral malperfusion of a lower
extremity persists and percutaneous catheter-based membrane fenestration fails or is
unavailable, femoro-femoral PFTE (polyfluorotetraethylene) or Dacron bypass is the
preferred method of revascularization. [386 ] In the absence of proximal inflow,
axillo-femoral with or without a cross-femoral bypass graft is employed.
Postoperative management of patients with acute and chronic dissections is basically

similar to other complex open cardiac procedures (see Chapter 12). Invasive monitors,
placed in the operating room, are followed with special attention to the stability of vital
signs, chest tube bleeding, arterial blood gases, urine output, and temperature. Initially,
the patient remains sedated; as the patient emerges from anesthesia, a gross
neurologic assessment is made. The patient usually remains intubated until fully awake
and respiratory, hemodynamic, and bleeding concerns are resolved.
Baseline laboratory studies include an ECG, portable chest x-ray, complete blood
count, arterial blood gas, and serum electrolytes and glucose. Chest tube drainage is
replaced; persistent bleeding is managed by blood replacement products, indicated
tests and therapeutic drugs, and occasionally by surgical exploration. A cell saver that
returns washed cells to the patient is safer than one that returns filtered, anticoagulated
shed blood.
Operation rarely eliminates all dissected aorta and usually a perfused false lumen
remains in some distal segments. Postoperative management must maintain strict
control of blood pressure and dp/dt using vasoactive drugs. Adequate flow to vital
organs is maintained. Mechanical ventilation and continuous narcotics and sedatives
may facilitate control of hypertension.
Often an unstable patient with dissection undergoes operative repair without complete
evaluation; thus malperfusion of distal aortic branches may be unrecognized until
postoperatively. Close attention to peripheral pulses, urine output, and other
organ-dependent parameters is recommended. When doubt regarding perfusion of a
particular vascular bed exists, Doppler ultrasound followed by prompt angiography may
be lifesaving.
RESULTS
Acute Proximal and Arch Dissection
Since the 1960s, early results have steadily improved for repair of acute proximal aortic
dissection (Table 38-1) . By 1982, DeBakey and colleagues achieved a then
remarkable mortality of 27 percent. [417 ] A recent comprehensive review of 136
reports documented a decrease in early mortality from 40 percent in the 1960s to 15
percent (52/345 patients) in the period between 19851991. [224 ] Most large centers
continue to report perioperative mortality in the 1020 percent range. [225 ] However,
today in experienced centers, mortality is rarely caused by technical shortcomings and
uncontrollable bleeding. Currently operative deaths are largely caused by uncontrollable
complications such as malperfusion of the viscera, reperfusion hemorrhage of the brain,
myocardial infarction, and heart failure.
Acute Distal Dissection
Early mortality remains higher in surgical series of acute distal aortic dissection
primarily because operated patients largely represent failures of medical therapy (Table
38-2) . As noted earlier, operating is prescribed for irreversible ischemic and lifesaving
complications.
Chronic Dissection
Surgery for chronic proximal dissection carries lower risk than for acute dissection
because operation usually is elective and patients are stable. Furthermore, the outer
aortic wall is stronger and firmer than in acute dissection. Most experienced centers
achieve an operative mortality just under 10 percent (Table 38-3) . [226 ] , [227 ]
In general, operative mortality for chronic distal aortic dissection is similar to that of
thoraco-abdominal aortic aneurysm repair and ranges between 1020 percent. [352 ]
[355 ]
FOLLOW-UP CARE
In DeBakey's 1982 series of 527 operated survivors of aortic dissection, the

development and rupture of (subsequent) aneurysm was the most common cause of
late deaths, accounting for 29.3 percent of all late deaths. [47 ] More recent attempts to
detect and operate on these ensuing aneurysms has substantially decreased late
mortality. [237 ] , [389 ]
Aortic dissection is a generalized and chronic disease that requires lifelong

surveillance. Repair usually eliminates only a portion of the perfused false lumen. Close
follow-up is mandatory to prevent future catastrophe. Follow-up evaluation is similar to
that employed for establishing the original diagnosis. Contrast-enhanced spiral CT
scanning reliably detects expansion of both aortic and branch diameters or chronic
perfusion deficits of vital organs. Images provide precise measurements of aortic
diameter at all levels. Recent improvements in hardware now visualize the entire aorta
in continuity and new software generates 3-D images that can be rotated and viewed
from any perspective. [390 ] Furthermore, precise detail at the branch level showing
stenoses or extensions of the dissecting membrane are portrayed reliably.
Echocardiography is preferred for examining the retained aortic root because residual
or recurrent valvular regurgitation is identified and quantitated readily. Secondary
ectasia of the root is also easily recognized. Unfortunately, echocardiography is
examiner-dependent and small changes in serial examinations over time may be
difficult to detect.
The maximal aortic diameter is measured at the ascending aorta just above the sinus;
the mid-aortic arch; proximal, mid, and distal descending thoracic aorta; level of the
diaphragmatic aortic hiatus; and suprarenal and infrarenal abdominal aorta. A shorter
diameter is chosen only when an oval configuration produced by acute angulation is
present. A thrombosed false lumen is included in the determination of maximal
diameter. These measurements are compared to previous diameters to determine the
interval until the next follow-up or the need for surgery. In general, examinations at
6-month intervals are recommended after the evaluation prior to hospital discharge. The
interval is shortened if a period of rapid growth occurs or if an eccentric contour
develops.
Long-term Medical Management
Antihypertensive therapy is mandatory in patients with chronic aortic dissection.

Commonly a multi-drug regimen of both vasodilators and either calcium channel
blockers or beta-adrenergic blockers is needed to control both blood pressure and the
force of cardiac ejection. Pyeritz showed the beneficial effect of long-term beta
blockade in reducing the rate of aortic growth. [59 ] , [391 ] When composite
replacement of the ascending aorta is done, coumadin dosage is not reduced if the
false lumen is perfused persistently. Antibiotic prophylaxis for dental and endoscopic
procedures is recommended strongly.
Re-operation
After the initial operation for aortic dissection, the overall incidence of re-operations
rises from 13 percent at 5 years to 23 percent at 10 years. The incidence is unrelated to
the type and acuity of the original dissection. Independent risk factors for re-operation
include youth and intimal tear involving the arch. [235 ] , [392 ]
Complete elimination of flow in the distal false lumen during the primary repair improves
the event-free survival, whereas residual aneurysmal dilatation assures the need for
reoperation. [226 ] , [393 ] The indication for re-operation was residual aortic
aneurysmal dilatation in 87.5 percent of patients after repair of chronic dissections and
in 65 percent after repair of acute dissections. In the authors' series, local recurrence in
repaired segmental aorta accounted for 12.5 percent of patients with chronic
dissections and 35 percent in those with acute dissections. [394 ]
Valve salvage and resuspension eventually necessitates a substantial number of

re-operations for aortic regurgitation. After repair of acute dissections, actuarial
freedom from aortic valve replacement is 83.6 percent at 5 years and 79.7 percent at
10 years. [395 ] [399 ]
Mortality and morbidity rates are higher for re-operations compared to primary surgery
and emergency procedures carry a substantially higher mortality than elective
operations. [96 ] , [400 ] [402 ] Re-operation on the descending thoracic aorta is safer
with a 6.5 percent early fatality rate than the 25 percent mortality of aortic arch
re-operations. [403 ]
LATE RESULTS
The current 3-year survival rate of patients operated on by experienced groups for acute
proximal aortic dissection ranges between 4191 percent (Table 38-4) . [404 ] , [405 ]
Significant improvement of mid-term survival has occurred, however; the 10-year
survival rate remains between 5065 percent. [235 ] , [406 ] In contrast, the 5-year
survival of survivors of operated acute distal dissection averages 80 percent and
remains 65 percent at 10 years. [235 ] , [237 ] The 5-year survival for chronic distal
dissection is less favorable, varying between 6095 percent and declining to
approximately 55 percent at 10 years (Table 38-5) . [235 ] , [237 ] , [371 ] , [407 ]
HISTORY
Early Descriptions
The first recorded description of an arterial aneurysm (post-traumatic) was that of Galen
in the 2nd century. [1 ] In the 6th century, Äetius reported an arterial rupture during labor.
[1 ] Ambroise Paré noted the association between syphilis and aortic aneurysm in the
16th century, although this relationship was not widely accepted until Dohle's description
of the microscopic findings of syphilitic aortitis in 1895. [1 ] Vesalius is credited with the
first correct clinical diagnosis of an aneurysm, which he made in 1557. [2 ] In 1757,
William Hunter described a thoracic aneurysm pointing through the chest. He also first
described the pre-morbid symptom of chest pressure and made the correct distinction
between aneurysms and pseudoaneurysms. [1 ]
Early Surgical Treatment
The first excision and replacement of the thoracic aorta for any indication was
performed by Gross in May of 1948. [3 ] He used an aortic allograft to replace a
segment of the descending thoracic aorta that contained a coarctation. Surgical
treatment of ascending aortic aneurysms in the period preceding the availability of
cardiopulmonary bypass was limited to aortic wrapping or to lateral resection and
repair of discrete saccular aneurysms. [4 ] , [5 ]
Evolution of Modern Surgical Techniques
The first resection of the ascending aorta was reported by Cooley and Debakey in
1956. [6 ] The aorta was replaced with an aortic allograft. Replacement of the
supracoronary segment of the ascending aorta combined with repair of an incompetent
aortic valve was described by Mueller et al. in 1960. [7 ] Combined replacement of the
supracoronary aorta with a synthetic graft and of the aortic valve with a mechanical
prosthesis were reported by Starr et al. in 1963. [8 ] Replacement of the entire
ascending aorta except for two small segments containing the coronary arteries and
separate aortic valve replacement were performed by Wheat et al. in 1964. [9 ] In 1968,
Bentall and de Bono reported the use of a composite graft consisting of a Teflon aortic
graft attached to a Starr-Edwards ball valve prosthesis to replace the entire ascending
aorta and the aortic valve. [10 ] In 1970, Edwards and Kerr used a similar technique to
repair ascending aortic dissections associated with aortic regurgitation. [11 ] These
latter two groups utilized the inclusion-wrap technique, which involved suturing the graft
to the aortic tissue surrounding the coronary ostia and wrapping the residual aorta
around the graft in order to reduce postoperative bleeding. Subsequently, other groups
detached the coronary arteries from the aorta, implanted them into openings in the
aortic graft, and avoided tight wrapping of the aorta around the graft. These
modifications were introduced to reduce the possibility of formation of
pseudoaneurysms that were observed with the inclusion wrap technique. [12 ] , [13 ] In
1981, Cabrol et al. described a technique for complete replacement of the ascending
aorta and re-implantation of the coronary arteries using separate 8- or 10-mm Dacron
segments to attach the coronary arteries to the aortic graft. [14 ]
The first substitutes for segments of resected aorta were aortic allografts. [3 ] , [15 ]
These grafts were removed in sterile fashion from cadavers early after death, and were
preserved in a sterile, antibiotic-enriched saline and serum solution. [3 ] Problems
related to availability, preservation, structural deterioration, and long-term function of
these allografts eventually led to experimentation with synthetic substitutes that included
glass, gold, methyl methacrylate, and polyethylene plastic. [3 ] The first aortic
replacement with a fabric graft that of Vinyon N cloth was reported by Blakemore and
Voorhees in 1954. [16 ] Dacron subsequently became the most widely used synthetic
substitute. Currently, collagen- or gelatin-impregnated woven Dacron grafts, that are
highly impermeable to blood, are widely used for replacement of the thoracic aorta.
RISK FACTORS AND INCIDENCE
Hypertension, congenitally bicuspid and unicuspid aortic valves, and the Marfan
syndrome are important risk factors for the development of thoracic aortic aneurysms.
[17 ] [22 ] Generalized atherosclerosis is common in patients with aneurysms of the
thoracic aorta. [21 ] Cigarette smoking also may increase the risk of a thoracic aortic
aneurysm. [23 ]
Thoracic aortic aneurysms are estimated to develop at a rate of 5.9 new

aneurysms/100,000 person-years. [18 ] The median age at presentation is 65 years for
men and 77 years for women. [18 ] In population-based studies that are adjusted for
age, the male to female ratio ranges from 1.1:11.7:1. [18 ] , [19 ]
ETIOLOGY AND PATHOPHYSIOLOGY
Annuloaortic Ectasia and Cystic Medial Degeneration
The normal ascending aorta is a compliant artery that functions as an elastic reservoir,
storing energy during systole that is dissipated during diastole to enhance flow. Its
inherent compliance, or characteristic impedance, is essential for efficient coupling to
the left ventricle. [24 ] The ascending aorta is more compliant than the descending aorta
and has a greater concentration of elastic fibers. [24 ] , [25 ] This difference in
composition between the ascending and descending aorta is reflected in the etiology of
aneurysms that develop in these areas. The majority of ascending aortic aneurysms are
associated with degenerative changes in the elastic media. In contrast, the majority of
descending aortic aneurysms are associated with atherosclerosis. [26 ] [28 ]
The combination of ascending aortic aneurysm, dilation of the sinuses of Valsalva, and
dilation of the aortic annulus is termed annuloaortic ectasia. [29 ] Annuloaortic ectasia
may occur as an isolated condition or as part of a generalized disorder of connective
tissue such as the Marfan syndrome. As the ascending aorta and the aortic sinuses
enlarge, aortic regurgitation develops because of loss of coaption of the aortic valve
leaflets. The valve leaflets usually are normal in appearance. Histologically, the aortas of
patients with this clinical syndrome commonly exhibit the classic features of cystic
medial degeneration. [30 ] In annuloaortic ectasia, as in the Marfan syndrome, genetic
abnormalities associated with the synthesis of fibrillin, a glycoprotein that is a
component of aortic elastic fibers, are observed. [31 ] Intimal tears in the ascending
aorta are frequent in annuloaortic ectasia, and frank dissection may also occur.
The term cystic medial degeneration encompasses varying degrees of elastic fiber
fragmentation and smooth muscle loss. In the most severe form, there is complete loss
of elastic fibers and smooth muscle cells in the aortic medial layer. The accumulation of
basophilic amorphous material in the media imparts a cystic appearance. [30 ] The
term cystic medial necrosis, originally applied by Erdheim, is not completely accurate,
since no true cellular necrosis or associated inflammation is present. [30 ] , [32 ] , [33 ]
It is postulated that cystic medial degeneration is the result of repetitive aortic injury and
aging, as mild forms are commonly present in the aortas of older individuals. [34 ]
Younger individuals who have annuloaortic ectasia as an isolated condition, or as part
of the Marfan syndrome, demonstrate premature and severe cystic medial degenerative
changes. The resulting aortic dilation increases wall tension, according to the law of
Laplace; this adds to the injurious forces on the aortic wall and may accelerate the
degenerative process.
The Marfan Syndrome
The Marfan syndrome is the most common genetically determined disorder affecting
adults and occurs at a frequency of 1/10,000 births. [35 ] It is associated with a defect
on chromosome 15 that affects fibrillin synthesis. [36 ] , [37 ] Fibrillin is the core protein
of microfibrils. Fibrillin and elastin represent the major components of the elastic fiber
system. [36 ] Histopathologically, the aorta demonstrates cystic medial degeneration,
disruption of elastic fibers, and fibrosis of the media. [30 ] The abnormal elastic tissue
predisposes patients to premature and often severe cystic medial degeneration.
Seventy-five to eighty-five percent of patients with the Marfan syndrome have aortic root
dilation with or without associated aortic regurgitation, and one third have significant
mitral regurgitation. [38 ] In addition to cardiovascular disease, the Marfan syndrome is
associated with ocular, pulmonary, musculoskeletal, and central nervous system
abnormalities.
Atherosclerosis
Atherosclerosis is the second most common cause of aneurysmal degeneration of the

ascending aorta. [18 ] , [28 ] Development of invasive atheromas is associated with
extensive destruction of elastic fibers and muscle cells in the medial layer of the aortic
wall. This tissue is replaced with extracellular matrix and lipid, which weakens the aorta
and predisposes aneurysmal degeneration. [28 ] Atherosclerosis may result in irregular,
fusiform, or saccular aneurysms, as compared to the more uniformly fusiform dilation
associated with annuloaortic ectasia and cystic medial degeneration.
Aneurysms Associated with Aortic Dissection
Dilation of the ascending aorta occurs commonly in patients who survive acute
dissection of the ascending aorta. In many surgical series, this is the most common
indication for resection of the ascending aorta. These aneurysms have a more rapid
rate of expansion and a higher rate of rupture than other types of ascending aortic
aneurysms. [18 ] , [23 ] Aortic dissection is discussed in Chapter 38.
Aneurysms Associated with Aortic Valve Disease
Aneurysms of the ascending aorta commonly are associated with congenitally bicuspid
aortic valve. This phenomenon is attributed to turbulent flow (post-stenotic dilation).
However, a primary structural abnormality of the aortic wall also may exist. The
association of bicuspid valves with congenital aortic abnormalities of the aortic wall,
such as coarctation, supports this hypothesis. [39 ] , [40 ] Dilation of the aortic root
associated with a bicuspid aortic valve also is observed in a number of patients who
have minimal or no evidence of significant valvular stenosis. [41 ] Furthermore, aortic
dissection occurs at ten times the expected rate in patients with bicuspid aortic valves,
an incidence not observed with other types of aortic stenosis. [17 ] Cystic medial
degeneration occurs in the ascending aorta of patients with bicuspid valves, and may
result from the same developmental anomaly that produces a bicuspid valve. [39 ] , [40 ]
Cystic medial degeneration is associated with increased fragility of aortic tissue and
aneurysm formation. [40 ]
Infection
BACTERIAL
Aneurysms caused by primary infections of the ascending aorta are rare. Historically,
these are termed mycotic aneurysms, regardless of the infectious etiology. Organisms
most commonly isolated from patients with mycotic aneurysms are Staphylococcus
aureus, followed by Staphylococcus epidermidis, Salmonella, and Streptococcus. [42 ]
Mycotic aneurysms are believed to develop most commonly following an episode of
valvular endocarditis or from infection of an aortic jet lesion. [43 ] Infection of intraluminal
clot in an atherosclerotic aneurysm also may occur after a transient bacteremia to
produce a mycotic aneurysm. [42 ]
SYPHILITIC
Before the advent of antibiotics, syphilis was the most common cause of aneurysms of
the ascending aorta. Syphilitic infection produces aortitis and an obliterative
endarteritis. Destruction of the vasa vasorum causes degeneration of the medial elastic
fibers. [30 ] The intima in syphilitic aortas classically is described as having a tree-bark
appearance, with wrinkles, ridges, and pearly plaques. [44 ] The disease most
commonly affects the ascending aorta and aortic arch (See Fig. 39-1 ). There may be
patchy or diffuse involvement of the aorta, and both saccular and fusiform aneurysms
are observed. [44 ] , [45 ] Inflammatory changes surrounding the coronary ostia may
lead to clinically significant coronary arterial obstruction. [45 ] Anti-syphilitic drug therapy
does not reverse the vascular lesions or consequences. Patients with syphilis
commonly have other risk factors associated with aneurysm formation; thus, aneurysms
in patients who are seropositive for syphilis may not be caused by infection with
Treponema pallidum. [18 ]
Arteritis
The ascending aorta may be involved in systemic arteritis. In general, arteritis produces
obstructive symptoms, as is seen with Takayasu's arteritis. [46 ] However, giant cell or
granulomatous arteritis, which often is associated with polymyalgia rheumatica, may, on
occasion, be associated with ascending aortic aneurysm, dissection, or rupture. [47 ] ,
[48 ] Aneurysm formation is presumed to develop from medial destruction by the
inflammatory process.
Ehlers-Danlos Syndrome
Ehlers-Danlos syndrome is an inherited disorder of connective tissue. One form of this

syndrome (Type IV) is associated with life-threatening cardiovascular disease.
Spontaneous arterial rupture is the most common cause of death, and this usually
occurs in the mesentery. [49 ] Patients occasionally develop abdominal aortic
aneurysms. [50 ] , [51 ] Aneurysm formation or dissection of the ascending aorta is rare.
[52 ] Friable vascular tissue may complicate surgical treatment.
Trauma
Chronic traumatic aneurysms of the ascending aorta are rare. Although the ascending
aorta is the site of rupture in approximately 20 percent of patients with blunt traumatic
aortic injuries, only a few survive the initial injury because of acute cardiac tamponade
and associated injuries (see Chapter 42). [53 ]
Pseudoaneurysms
A pseudoaneurysm represents aneurysmal dilation that does not contain all layers of the
aortic wall. The wall usually is composed of adventitia, portions of the media, and
surrounding anatomic structures. Pseudoaneurysms may develop after trauma,
infection, or surgical procedures. In surgical patients, pseudoaneurysms arise from
sites of aortic cannulation or from aortic suture lines. They may develop from tissue
degeneration, acute dissection, technical errors, or deterioration of graft or suture
material. [54 ] , [55 ] The combination of silk sutures and low porosity Teflon grafts is
cited as a cause of pseudoaneurysms late after operation. [56 ]
NATURAL HISTORY
Cystic Medial Degeneration and Atherosclerosis
Bickerstaff and colleagues retrospectively examined the natural history of unoperated

thoracic aortic aneurysms of all types over a 30-year period. [18 ] Of 72 patients, rupture
occurred in 53 (74 percent), and the mortality rate following rupture was 94 percent. The
median interval between initial diagnosis and rupture was 2 years. Patients with aortic
dissection had a 95 percent rate of rupture, compared with a rate of 51 percent for
patients with atherosclerotic aneurysms. The 5-year actuarial survival of these patients
was 13 percent (Fig. 39-2) . Pressler et al. reported similar outcomes. [19 ] In their
series, 78 percent of patients treated non-surgically died. In patients with atherosclerotic
aneurysms of the ascending and descending aorta, 44 percent died of rupture, and 33
percent died of cardiovascular disorders. The location of the aneurysm (ascending vs.
descending) did not alter the risk of rupture for aneurysms that were not associated with
dissection.
Serial computed tomographic (CT) scans, including three-dimensional volumetric

determinations, were performed on a group of patients with thoracic and
thoracoabdominal aneurysms by Dapunt et al. [23 ] The average increase in aortic
diameter was 0.43 cm/year and in aortic volume 88 ml/year. Aneurysms larger than 5
cm in diameter at the time of the initial study increased at a rate of 0.79 cm/year versus
a rate of 0.17 cm/year for smaller aneurysms. Smokers also exhibited a faster rate of
aneurysm expansion. In this study, no correlation was noted between the rate of
aneurysm expansion and age, sex, or the presence or absence of dissection.
Hypertension was associated with larger aortic diameter at presentation and thus
accelerated expansion, but did not independently increase the rate of enlargement.
Patients who required elective operative intervention (for pain, aortic diameter greater
than 8 cm, or expansion of greater than 1 cm over 1 year) had an average increase in
diameter of 1.11 cm/year and an increase in volume of 178 ml/year. Patients who
experienced rupture of the aneurysm had an average increase of 0.7 cm/year and a
volume change of 124 ml/year. The average aortic diameter was 6.1 cm. McNamara et
al. also noted the propensity for larger aneurysms to rupture. [57 ] When serial data are
available, a recent increase in size usually precedes rupture. [23 ] , [57 ]
Marfan Syndrome
In patients with Marfan syndrome, the average age of death is approximately 32 years.
[22 ] The majority of deaths are cardiovascular; complications related to aortic root
dilation account for 6080 percent of these deaths. [22 ] , [38 ] Aortic rupture, dissection,
and heart failure from valvular disease are the most common modes of death. [22 ] The
presence of a diastolic murmur or cardiomegaly is associated with decreased survival.
[38 ]
In a cohort of patients receiving beta-adrenergic blocking drugs, the mean rate of aortic
root dilation is 1.9 mm/year; however, individual rates of aortic expansion are highly
variable and unpredictable. [58 ] Over a 4-year period, 25 percent of these patients
require surgical therapy because of increased aortic diameter. [58 ]
Acute dissection may occur in ascending aortas that are not greatly dilated. In a series
of 26 patients who experienced ascending aortic dissections, seven had aortas that
were less than 6.5 cm in greatest diameter. [59 ] The risk of aortic root complications
may be higher in individuals with a family history of aortic dissection.
Syphilitic Aneurysms
The average time from the diagnosis of advanced syphilis to the development of
cardiovascular symptoms is 1020 years. [1 ] The average survival from the onset of
symptoms is 68 months. [1 ] Saccular aneurysms, which are common in this disease,
may have a more rapid rate of expansion and greater risk of rupture than fusiform
aneurysmal dilations. [60 ]
Symptoms and Signs
The majority of ascending aortic aneurysms are detected by routine chest radiographs
or by imaging studies that are performed to evaluate other diseases. [20 ] Between
2533 percent of patients have chest pain as a presenting symptom. [20 ] , [21 ] This
pain is most commonly precordial, with radiation to the neck and jaw if the aortic arch is
involved. In contrast, 75 percent of patients with acute aortic dissections present with
severe pain, usually in the back. [19 ] , [20 ] Occasionally, signs and symptoms of
superior venal caval obstruction are present, along with dyspnea and dry cough. [21 ]
Hoarseness suggests involvement of the aortic arch or descending thoracic aorta.
The physical examination generally is unremarkable. Syphilitic aneurysms can produce

palpable pulsatile anterior chest masses that erode through the chest wall and skin. [1 ]
If aortic regurgitation is present, a widened pulse pressure, bounding pulses, and a
parasternal diastolic murmur often are present. Associated vascular disease is
common, and concomitant abdominal aortic aneurysms are present in 1020 percent of
patients with atherosclerotic thoracic aortic aneurysms. [19 ] , [26 ]
DIAGNOSTIC STUDIES
Electrocardiogram
The electrocardiogram may be normal. In cases with associated aortic regurgitation,

evidence of left ventricular hypertrophy and strain may be present. Evidence of coronary
arterial disease or previous myocardial infarction may be present in patients with
generalized atherosclerosis.
Chest Radiography
Many asymptomatic aneurysms are found on routine chest radiographs (Fig. 39-3) . A
widened mediastinum and tracheal and esophageal displacement may be observed in
the postero-anterior (PA) view. Ascending aneurysms may produce a convex contour of
the right superior mediastinum. The sternal shadow often obscures an enlarged aorta in
the PA view. Loss of the retrosternal air space is often present on lateral films.
Calcification may be seen in the arterial wall. Aneurysms limited to the aortic root and
sinuses of Valsalva may be obscured by the cardiac silhouette. [61 ]
Echocardiography
Echocardiography is increasingly important in the diagnosis and management of

ascending aortic aneurysms. A dilated aortic root or an ascending aortic aneurysm may
be first detected during echocardiographic evaluation of a regurgitant aortic valve.
Multiplanar trans-esophageal echocardiography (TEE) is a rapid and accurate imaging

technique to differentiate ascending aortic aneurysm from dissection and to detect the
presence of intramural hematoma. [62 ] Accurate imaging of the distal ascending aorta
and aortic arch with TEE is compromised by the column of air in the trachea and
mainstem bronchi. [63 ] , [64 ] Up to 40 percent of the ascending aorta is not well
visualized by TEE, and significant disease in this distal segment may not be accurately
imaged. [64 ]
Aortography
Aortography is still widely used for the diagnosis of aortic aneurysms. The relation of the
aneurysm to the arch vessels is seen clearly. Aortography also documents the presence
of aortic regurgitation, dilation of the sinuses of Valsalva, and cephalad displacement of
the coronary ostia (Fig. 39-4) .
Certain diseases have characteristic angiographic patterns. In annuloaortic ectasia, the

aortogram shows dilation of the aortic sinuses and ascending aorta. The aorta tapers to
a more normal size at the level of the innominate artery (Fig. 39-5) and often is
described as pear-shaped. A pseudoaneurysm often appears as a saccular aneurysm
with an irregular contour. [65 ]
Computed Tomography
Computed tomography (CT) with intravenous contrast enhancement permits accurate
evaluation of the extent and size of aortic aneurysms (Fig. 39-6) . CT scanning is
complementary to aortography, particularly when intra-arterial thrombus or dissection is
present. Extravasation of contrast and involvement of contiguous structures is apparent.
CT scanning is useful for serial evaluation of small asymptomatic aneurysms and
quantifies changes in size and in the rate of expansion. [23 ] However, volume
averaging in areas with rapidly changing curvature and images in planes that are not
perpendicular to the long axis of the aorta, may produce inaccurate estimates of aortic
diameter.
The utility of three-dimensional imaging techniques using CT is not established.

Theoretically, three-dimensional scanning provides more information about the
longitudinal extension of aneurysms, particularly in the descending thoracic aorta.
Saccular outpouchings are also more easily visualized and quantified with this
technique.
Magnetic resonance imaging (MRI) provides similar information to CT scanning, but

has several advantages over CT. These include avoidance of intravenous contrast and
ionizing radiation. Walls of cardiovascular structures have high natural contrast that
enhances the images (see Fig. 39-7 ). True sagittal and coronal planes can be
displayed. New technology permits assessment of direction of aortic flow and velocity
and limited imaging of coronary arteries. Theoretically, MRI potentially can image the
aorta, cardiac valves, coronary arteries, and to evaluate myocardial function. [66 ] MRI is
currently less readily available than CT, and is more expensive and uncomfortable for
the patient.
Coronary Angiography
Coronary angiography generally is performed as a part of the preoperative evaluation of

patients with ascending aortic disease who are over 40 years of age, or who have a
history of or symptoms of coronary artery disease. The abnormal aortic root
occasionally makes direct cannulation and injection of the coronary arteries difficult, and
special techniques may be required. [67 ] Ascending aortography and left
ventriculography are usually performed in conjunction with coronary arteriography.
Symptoms
Symptomatic ascending aortic aneurysms and acute aortic dissections require urgent
operative intervention. Aortic leak or rupture necessitates emergent surgical repair.
Severe or symptomatic aortic regurgitation is often the primary indication for operation
in a patient with an aneurysm of the ascending aorta.
Progressive Enlargement of the Aorta
Aneurysms that are expanding on serial chest radiographs, CT or MRI images, or

echocardiograms should be repaired. An increase in size often precedes rupture. [57 ]
Currently, a rate of expansion of >1 cm/year is an accepted indication for operation. [23
]
Size of the Aneurysm
GENERAL
Asymptomatic aneurysms greater than 5.5 to 6 cm in diameter with or without

associated aortic regurgitation should be repaired electively, since the risk of rupture is
higher for larger aneurysms, and mortality and morbidity rates for elective repair are
low. [26 ] , [55 ] , [68 ] , [69 ] In retrospective studies of unoperated thoracic aneurysms,
the average size of ruptured aneurysms ranges between 610 cm in diameter. [23 ] , [57
]
Although advanced age may be a relative contraindication to aortic replacement, Perko

et al. reported that among unoperated patients with thoracic aneurysms over 70 years
of age, 50 percent died of rupture within 1.5 years of diagnosis. [70 ] Matched patients
who survived surgical resection had a normal life expectancy.
MARFAN SYNDROME
Patients with the Marfan syndrome should undergo aortic root replacement when the
greatest diameter of the ascending aorta exceeds 5.56 cm. [38 ] , [71 ] , [72 ] Patients
with a family history of dissection or sudden death should be operated upon when the
aortic diameter reaches 5.05.5 cm. [59 ] , [71 ] Other authors suggest that progressive
increase in aortic diameter, or an aorta that is twice the diameter of a normal segment
are indications for operation. [73 ] , [74 ] Patients with severe aortic regurgitation or the
presence of symptoms of aortic dissection should undergo resection of the aneurysm
and repair or replacement of the aortic valve.
Coexisting Aortic Valve Disease with Ascending Aortic Enlargement
Aortic regurgitation or stenosis may coexist with an enlarged or aneurysmal ascending

aorta. Regurgitation may result from intrinsic disease of the valve, or from loss of
coaptation of valve leaflets. Symptoms or progression of regurgitation or stenosis may
necessitate operation before the aorta dilates sufficiently (56 cm) to require resection.
Michael observed that 25 percent of patients with aortic regurgitation who had aortic
diameters greater than 4 cm at the time of aortic valve replacement required
subsequent reoperation to replace the aorta. [75 ] The incidence of aortic dissection
after aortic valve replacement is reported as high as 27 percent in patients with aortic
diameters greater than 5 cm. [76 ] These observations suggest that patients with aortic
diameters greater than 45 cm should have replacement of the ascending aorta at the
time of valve replacement.
New or Persistent Aneurysms of the Sinus of Valsalva
Aneurysms of the sinuses of Valsalva may develop or persist after aortic valve
replacement or replacement of the ascending aorta in patients with the Marfan
syndrome or with cystic medial degeneration. [13 ] , [77 ] , [78 ] Generally repair is
advisable if progressive enlargement is documented, if intimal tears develop in the
sinuses, or if the diameter of the aorta at this level exceeds 6 cm.
Pseudoaneurysms
Generally pseudoaneurysms should be repaired as soon as they are discovered. They

have a tendency to progressively increase in size. Pseudoaneurysms may become
adherent to the undersurface of the sternum and erode into adjacent cardiac chambers
or the superior vena cava. Emergent operation is frequently required, and operative
mortality in such situations is substantial. [26 ] , [55 ]
Preoperative evaluation usually includes a chest radiograph, a CT or MRI scan,

aortography, and coronary arteriography. Echocardiography is useful to assess the
presence and severity of aortic or other valvular heart disease and to evaluate left
Carotid duplex imaging studies are obtained in patients who are 65 years of age or
older, and in younger patients who have a history of stroke or transient cerebral
ischemic events, a bruit on physical examination, peripheral vascular disease, or who
have extensive coronary artery disease, or left main coronary artery stenosis. These
patients are at a higher risk for the presence of carotid artery occlusive disease. [79 ]
Detection of severe carotid artery occlusive disease prior to operation on the
ascending aorta is important to reduce the incidence of perioperative stroke. [80 ]
Abdominal aortic aneurysms occur in 1020 percent of patients with ascending aortic
aneurysms. [19 ] , [26 ] Patients with atherosclerotic aneurysms that extend into the
aortic arch have a greater than 50 percent probability of having separate distal thoracic
or abdominal aortic aneurysms. [26 ] CT or MRI imaging of the abdominal aorta should
be performed if disease is suspected from symptoms, signs, or other information (e.g.,
x-rays or ultrasound).
Twenty to thirty percent of patients with thoracic aneurysms have severe chronic
obstructive pulmonary disease. [26 ] Preoperative pulmonary function tests and room air
arterial blood gases are obtained in patients with evidence of pulmonary disease.
Preoperative chest physiotherapy is prescribed when indicated, and cessation of
smoking prior to surgery is desirable. Renal function should be evaluated preoperatively
by appropriate testing.
CHOICE OF PROCEDURE
Ascending Aortic Aneurysm With or Without Valvular Disease
For patients with aneurysms confined to the ascending aorta who have a normal aortic
annulus and aortic sinuses, and no evidence of Marfan syndrome, the ascending aorta
is replaced with a tube graft from the level of the supravalvular ridge to the origin of the
innominate artery. Separate aortic valve replacement with a mechanical or biological
prosthesis can be performed when indicated.
Annuloaortic Ectasia
COMPOSITE GRAFT
For patients with annuloaortic ectasia, including those with the Marfan syndrome,
replacement of the ascending aorta and aortic valve with a composite graft containing a
mechanical valve and a collagen- or gelatin-impregnated Dacron graft and
reimplantation of the coronary arteries into the graft is the most commonly performed
procedure.
AORTIC ALLOGRAFT
Aortic root allografts can be used to replace the aortic valve, the aortic sinuses, and the
ascending aorta. [55 ] They are particularly valuable in the management of patients with
infective endocarditis, especially patients with annular erosion, patients with a small
aortic annulus, and patients for whom anticoagulation with warfarin derivatives is
undesirable or contraindicated. [83 ] [85 ]
PULMONARY AUTOGRAFTS
Pulmonary root autografts are also used to replace the aortic root and adjacent
ascending aorta. [81 ] , [82 ] , [86 ] The more distal ascending aorta may be replaced
with a Dacron graft if aneurysmal enlargement is present. Autografts should not be used
in patients with marked dilation of the aortic root or in patients with the Marfan
syndrome.
ALTERNATIVE PROCEDURES
Radical excision of the aorta with preservation of a rim of aorta surrounding the ostia of
the coronary arteries, replacement of the aorta with a scalloped tube graft and separate
replacement of the aortic valve is employed in some centers (see Chapter 31). [81 ]
If the aortic valve is structurally normal and aortic regurgitation is present because of
dilation of the sino-tubular junction, replacement of the enlarged ascending aorta with a
properly -sized tube graft restores competence of the valve and eliminates the need for
valve replacement in selected patients. [88 ] If one or more of the aortic sinuses is
dilated, these can also be resected and replaced by tongues of graft material extending
into the affected sinus. [88 ] If the right or left aortic sinuses are involved, the coronary
arteries are implanted into the tongue of graft that replaces the sinus.
In cases of annuloaortic ectasia in which aortic leaflets are normal, annuloplasty can be
performed by suturing an appropriately sized Dacron tube graft circumferentially to the
tissue immediately beneath the aortic annulus. The dilated aortic sinuses are excised,
the aortic valve is resuspended within the tube graft, and the coronary arteries are
reimplanted. [88 ]
MANAGEMENT OF ASSOCIATED CONDITIONS
Coronary artery disease
Approximately 25 percent of patients undergoing resection of ascending aortic

aneurysms have significant coronary artery disease in one or more vessels. [26 ]
Bypass grafting is performed at the time of aortic replacement, using the internal
thoracic artery or saphenous vein grafts. All stenoses of the major coronary arteries
greater than 50 percent should be bypassed.
Mitral valve disease
Mitral valve disease is frequently encountered in patients with aortic aneurysm. This is
particularly true for patients with the Marfan syndrome, where the incidence approaches
30 percent. [38 ] Patients who have evidence for moderate to severe mitral regurgitation
should undergo mitral valve repair or replacement at the time of aortic replacement. [55
] , [59 ] Gillinov et al. reported results of mitral valve repair in patients with Marfan's
syndrome, many of whom also had simultaneous replacement of the aortic root. [89 ]
They observed an 88 percent actuarial rate of freedom from significant mitral
regurgitation at 5 years. [89 ]
General
MONITORING AND ANESTHESIA
Venous access is obtained with a large bore central line and two large peripheral lines.
A radial arterial line is inserted for monitoring of blood pressure and for withdrawing
blood samples. Leads II and V 5 of the electrocardiogram are continuously monitored. A
Swan-Ganz catheter is placed into the pulmonary artery to measure pulmonary artery
pressures, oxygen saturation, and cardiac output. Nasopharyngeal and rectal or bladder
temperature probes are placed. Intra-operative transesophageal echocardiography is
used to evaluate the cardiac valves, the size of the aorta, the extent of aneurysmal
disease, and myocardial function. [90 ]
Anesthesia is induced with midazolam, fentanyl, and pancuronium. After intubation,

anesthesia is maintained with inhaled isoflurane and intravenous fentanyl. In patients
who are candidates for early extubation, propofol or other short-acting anesthetic
agents are used.
INCISIONS
A median sternotomy is utilized for most procedures. This incision can be extended with
a transverse (T) incision through the left third or fourth interspace if exposure of the
distal aortic arch or the descending thoracic aorta is required. Alternatively, a
transverse bilateral thoracosternotomy can be employed.
PERFUSION
Heparin 350 U/kg is administered prior to cannulation. The activated clotting time is
measured and maintained at 450 seconds or greater for the duration of
cardiopulmonary bypass. If the aneurysm does not involve the distal ascending aorta,
this area or the proximal aortic arch is cannulated. Alternatively, the common femoral or
the distal external iliac artery is exposed and is cannulated with an 18 or 22 Fr cannula.
A 21 or 24 Fr two-stage cannula is inserted into the right atrium when hypothermic
circulatory arrest is not necessary. In reoperative cases, and those requiring mitral valve
replacement or hypothermic circulatory arrest, separate cannulae are placed into the
superior and inferior venae cava.
The cannulas are attached to a perfusion circuit that contains a membrane oxygenator
with an integral heat exchanger. The circuit is primed with Ringers lactate and 25 gm of
mannitol. Glucose is not added to the prime, and administration of glucose in
intravenous solutions is minimized to avoid hyperglycemia that can exacerbate central
nervous system injury. [91 ] [93 ] A venting catheter is inserted into the left ventricle
through a purse-string suture in the right superior pulmonary vein. Alternatively, this
catheter can be inserted into the pulmonary artery. A balloon-tipped catheter is inserted
into the coronary sinus through a purse-string suture that is placed in the right atrium for
the administration of retrograde cardioplegia. A thermistor probe is placed in the
anterior ventricular septum and myocardial temperature is monitored continuously.
Cardiopulmonary bypass is established at an initial flow of 2.22.5 l/min/m 2 with
moderate systemic hypothermia (28°C) and hemodilution (hematocrit 1525 percent). A
cooling jacket is placed around the ventricles if the duration of myocardial ischemia
time is likely to exceed 60 minutes. An insulating pad is utilized to protect the left
phrenic nerve.
Cold (4°C) oxygenated hyperkalemic (30 mEq/l) blood cardioplegia is used for
myocardial protection. If the aortic valve is competent, the initial dose is given through a
large-bore needle in the aortic root for 2 minutes at a flow of 300 ml/minute. An
additional dose (200 ml/min for 2 minutes) is given retrograde into the coronary sinus to
achieve initial myocardial temperatures of 1012°C. [94 ] For hypertrophied hearts the
rate of infusion is increased to 350 ml/min (antegrade) and 250300 ml/min (retrograde).
[94 ] Additional cooling is achieved by irrigating the pericardial well with 4°C Ringers
lactate solution or a cooling jacket. Additional infusions of cardioplegic solution are
given retrogradely through the coronary sinus catheter every 2030 minutes. When
cardioplegic solution cannot be infused into the aortic root because of incompetence of
the aortic valve, arrest and cooling of the heart are achieved with retrograde
cardioplegia alone. If this does not produce adequate cooling, the aorta is opened, and
additional cardioplegic solution is administered directly into the coronary ostia. After
closure of the aorta but before removal of the cross clamp, warm blood cardioplegia is
infused through the coronary sinus (150 ml/min for 3 minutes) while gentle suction is
applied to a needle vent that is placed in the ascending aorta. [94 ] In addition to the
myocardial protective effect, this infusion facilitates the removal of air from the aorta and
coronary arteries.
CHOICE OF GRAFT AND GRAFT PREPARATION
The ideal aortic graft should be minimally porous, easy to handle, and allow firm tissue
ingrowth to minimize the risk of embolism. Scotomata and episodes of amaurosis fugax
may occur early after ascending aortic replacement and result from embolization from
the prosthetic surface. [95 ] Most currently used Dacron grafts are minimally reactive
and integrate well with biologic tissue. Knitted grafts allow the greatest tissue ingrowth
and are easy to handle, but are too porous for procedures that require full
heparinization. Woven grafts, which are more impervious, are the most commonly used
prosthetic grafts. Commercially prepared grafts that are impregnated with collagen
(Hemashield, Meadox Medical, Oakland, NJ) are used widely. These grafts are easy to
handle and are highly impervious to blood. [96 ]
Sutureless intraluminal aortic grafts that are tied into place over spools inside the
proximal and distal aorta are used in the ascending aorta by some groups with good
results. [97 ] However, these devices do not appear faster to implant than standard
grafts and are prone to migration, erosion, and significant pressure gradients. [98 ] , [99
] Compression and occlusion of the coronary arteries also may develop. [98 ]
The current graft of choice for aortic root replacement consists of a collagen- or
gelatin-impregnated, woven double velour Dacron graft that is attached to a mechanical
prosthesis. If use of a bioprosthetic valve is indicated, it can be sutured to a collagen- or
gelatin-impregnated graft.
Specific Operative Techniques
REPLACEMENT OF THE ASCENDING AORTA
After establishing cardiopulmonary bypass, the aorta is clamped proximal to the origin
of the innominate artery, and the heart is vented and arrested by infusion of a cold
cardioplegic solution. An adequate cuff of non-aneurysmal aorta should be available
proximal to the innominate artery and aortic arch to facilitate a precise distal
anastomosis to the aortic graft. If this is not possible, an open technique employing
hypothermic circulatory arrest should be used (see the following). Proximally, the aorta
is completely transected at a level just above the aortic commissures (Fig. 39-8A) . A
collagen-impregnated woven Dacron graft is sutured to the distal aorta with a
continuous 3-0 or 4-0 polypropylene suture incorporating a strip of Teflon felt (Fig.
39-8B) . If aortic valve replacement is required, it is performed at this time (Figs. 39-8C
and 39-8D) . The graft then is cut to the appropriate length and is sutured to the
proximal aorta with a continuous 3-0 or 4-0 polypropylene suture (Figs. 39-8E and
39-8F) . If the right coronary ostium is displaced cephalad, or if its origin is involved in
the aneurysmal process, the artery is detached from the aorta with a small rim of aortic
tissue and dissected free from surrounding tissue. An opening is made in the Dacron
graft opposite the coronary orifice using an ophthalmic cautery. The aortic tissue
surrounding the coronary ostium is sutured to the graft with continuous 4-0 or 5-0
polypropylene incorporating a small strip of Teflon felt. If this anastomosis is likely to be
under excessive tension, a segment of 6 or 8 mm collagen-impregnated woven Dacron
graft is interposed between the ostium of the right coronary artery and the aortic graft.
Alternatively, a segment of reversed saphenous vein is anastomosed end-to-side to the
right coronary artery and proximally to the aortic graft. The origin of the right coronary
artery is oversewn.
ALTERNATIVE TECHNIQUES
Valve preservation
Techniques for preserving the native aortic valve by resuspension inside a Dacron tube
graft or by aortic root remodeling utilizing a scalloped Dacron tube graft are described
in Chapter 31.
Lesser procedures
Rarely, focal saccular aneurysms are amenable to simple patch repair. The diseased
section of aorta is excised and the defect is replaced with a collagen-impregnated
woven Dacron patch using 3-0 or 4-0 polypropylene suture.
REPLACEMENT OF THE ASCENDING AORTA AND AORTIC ROOT
After establishing cardiopulmonary bypass, the aorta is clamped just proximal to the
innominate artery. Following venting the heart and infusing cardioplegic solution, the
aorta is incised and the aortic valve leaflets are removed. Excision of the aortic sinuses
permits optimal exposure of the aortic annulus and coronary arteries. Buttons of aortic
tissue surrounding the coronary artery are fashioned and the arteries are mobilized by
sharp dissection for 12 cm to permit a tension-free anastomosis to the Dacron graft
(Fig. 39-9A) . The aortic annulus is sized and an appropriate composite graft is
selected. The sewing ring of the graft-valve prosthesis is sutured to the aortic root with
interrupted 2-0 pledgeted braided polyester mattress sutures (Fig. 39-9B) . These
sutures are placed immediately adjacent to one another to ensure a watertight closure.
Openings in the Dacron graft are made with a cautery opposite each coronary artery
ostium (Fig. 39-9C) . Anastomosis of the left coronary artery to the graft is performed
first, with a continuous 4-0 or 5-0 polypropylene suture incorporating a thin strip of Teflon
felt (Fig. 39-9D) . The right coronary artery is attached to the graft in a similar fashion.
Tension on these suture lines must be avoided to prevent bleeding. When the coronary
arteries cannot be adequately mobilized, an 8 or 10 mm collagen-impregnated woven
Dacron graft is sutured to the aortic tissue surrounding the coronary ostium and to the
aortic graft using a 4.0 or 5.0 polypropylene suture (Fig. 39-9E) . This technique is also
used also if there is marked displacement of the coronary arteries owing to dilation of
the aortic sinuses, or if there is scarring from a previous operation.
The distal anastomosis then is completed (Fig. 39-9F) . A needle vent is placed into the
aortic graft through a purse-string suture for evacuation of air. After delivery of warm,
retrograde blood cardioplegia, the aortic cross clamp is removed and is re-applied in a
partially occlusive position. The needle vent is connected to low continuous suction.
After rewarming is complete, and the heart is contracting well, air is evacuated from the
left atrium and ventricle, the left ventricular vent is removed, and cardiopulmonary
bypass is discontinued. After decannulation and administration of protamine sulfate, all
suture lines are examined carefully. It is important that precise hemostasis be attained.
If an impermeable graft is used with the open technique of anastomosis, it is
unnecessary to wrap the graft with the remaining aorta. Any aorta that is remaining is
loosely wrapped around the graft or is excised.
ALTERNATIVE TECHNIQUES FOR AORTIC ROOT REPLACEMENT
Cabrol technique
A technique described by Cabrol involves the use of an 8- or 10-mm woven Dacron

tube graft that is anastomosed end-to-end to aortic tissue surrounding the left and right
coronary ostia. An opening is made in the mid-portion of this graft opposite a
similar-sized opening in the aortic graft ( Figs. 39-10A and 39-10B ). [14 ] This
technique facilitates performance of graft-to-coronary artery anastomoses, particularly
when the coronary ostia are located close to the aortic annulus. Care must be taken to
avoid compression or kinking this graft, particularly the right coronary artery segment.
Cabrol also described an alternative technique for inserting a composite graft. [14 ] The
aortic valve prosthesis is sutured inside an aortic graft 2 cm from the edge. The graft
then is sutured to the aortic annulus with a continuous 5-0 polypropylene suture. This
technique displaces the rigid portion of the composite graft more cephalad and
improves access to the coronary ostia.
Allografts and autografts
Aortic allografts and pulmonary autografts can be used to replace the aortic root. [81 ] ,
[82 ] , [86 ] The muscular tissue beneath the aortic allograft or pulmonic autograft valve
is sutured to the aortic annulus with a continuous or interrupted suture technique using
4-0 polypropylene or braided synthetic suture. This suture line can be reinforced with a
strip of Dacron or pericardium. Buttons of aorta or pulmonary artery are excised and the
aortic tissue surrounding the coronary ostia is sutured to the aorta or pulmonary artery
with a continuous 4-0 or 5-0 polypropylene suture. A small strip of Teflon felt may be
used to buttress these suture lines. The aorta or pulmonary artery then is sutured
end-to-end to the distal ascending aorta with a 4-0 or 5-0 polypropylene suture. The
allograft or autograft can be extended if necessary by adding a Dacron tube graft to the
distal end.
OPEN TECHNIQUE FOR DISTAL ANATOMOSES
If a clamp cannot be placed on the ascending aorta because of the large size of the
aneurysm, the presence of severe atherosclerosis or a large amount of thrombus, or
because the aneurysm also involves the aortic arch, an open technique for performing
the distal anastomosis is used during a period of hypothermic circulatory arrest. In this
situation, the common femoral artery is usually cannulated for arterial return from the
pump oxygenator. The cardiopulmonary bypass circuit utilized is illustrated in Figure
39-11A . Cardiopulmonary bypass is initiated and systemic hypothermia is induced by
gradually cooling the perfusate. Methylprednisolone (7 mg/kg) and thiopental (715
mg/kg) are administered during the period of cooling to enhance protection of the
central nervous system. Mannitol (0.30.4 g/kg) and furosemide (100 mg) are infused
prior to the period of circulatory arrest to preserve renal function. [100 ] Blood glucose is
maintained below 200 mg/dl with insulin. [101 ] Electroencephalographic (EEG)
monitoring also is used.
During cooling, an 8-mm collagen-impregnated woven Dacron graft is anastomosed to

the side of the aortic graft. At the end of the period of circulatory arrest, the arterial line
of the pump-oxygenator is inserted into the graft to reestablish antegrade flow. When
the nasopharyngeal temperature reaches 1214°C, the rectal or bladder temperature is
1820°C, and the electroencephalogram has been isoelectric for at least 5 minutes, the
circulation is arrested. The patient is put in a steep Trendelenburg (head down)
position, a tourniquet around the superior vena cava is tightened, and the superior vena
cava cannula is clamped. This raises central venous pressure in the upper half of the
body and reduces the potential for suction of air into the brachiocephalic vessels when
the aorta is opened. Circulatory arrest is established, and 2025 percent of the
calculated blood volume is withdrawn from the venous cannulas into the reservoir of the
pump-oxygenator. During cooling and circulatory arrest, cardioplegia is maintained with
intermittent infusion of cardioplegic solution.
The ascending aortic clamp is removed and the aorta is opened. The site for
anastomosis of the graft to the aorta is selected. For aneurysms that involve the
proximal and inferior portions of the aortic arch, a single anastomosis is performed
beneath the brachiocephalic vessels by beveling the graft and the aortic incision (Fig.
39-11B) . If the disease involves the entire ascending aorta and arch, the aorta is
transected beyond the origin of the left subclavian artery. The aortic graft is then
anastomosed to the descending aorta with a continuous 3-0 polypropylene suture
incorporating a strip of Teflon felt. The graft then is placed under slight tension and a
segment of graft is excised opposite the brachiocephalic vessels. The graft is sutured
to a cuff of aortic tissue surrounding these vessels with a continuous 3-0 or 4-0
polypropylene suture reinforced with a strip of Teflon felt.
As this anastomosis is being completed, cold oxygenated blood is infused from the
pump-oxygenator into the superior vena cava through a connection from the arterial line
(Fig. 39-11B) . The flow rate usually is 300500 ml/min at a central venous pressure that
does not exceed 2530 mmHg. This is done to facilitate removal of air and particulate
matter from the brachiocephalic arteries (Fig. 39-11B) . When the anastomosis is
completed, slow antegrade perfusion of the body is begun through the 8-mm graft or
through a cannula placed in the aortic graft (Fig. 39-11C) . The brachiocephalic vessels
are massaged gently to evacuate any remaining air. Then a clamp is placed on the
aortic graft just proximal to the innominate artery. Full antegrade systemic flow is
established and rewarming is begun (Fig. 39-11C) . Re-establishing flow in the
antegrade direction reduces the possibility of embolization into brachiocephalic vessels
of atherosclerotic debris or thrombus that may have fallen into the descending aorta.
During the period of rewarming, aortic valve or aortic root replacement or other
procedures (coronary artery bypass graft or mitral valve replacement or repair) are
performed. The aortic graft then is sutured to the ascending aorta or to the composite
graft with a 3-0 or 4-0 polypropylene sutures. When rewarming is completed, air is
removed from the heart and the aorta through a needle vent in the aortic graft as
previously described. Cardiopulmonary bypass is discontinued when the bladder or
rectal temperature reaches 3435°C.
OPEN VERSUS INCLUSION TECHNIQUES ON THE ASCENDING AORTA AND

AORTIC ROOT
Improved perfusion technology and the availability of pliable aortic grafts that are
impermeable to blood have eliminated the need for inclusion techniques in which the
graft is sewn to the inside of the native aorta and aortic tissue is tightly wrapped around
the grafts to control bleeding. We prefer an open technique in which all aortic and
coronary arterial anastomoses to prosthetic grafts are performed using full thickness
aortic tissue. In our early experience and that of others inclusion/wrap techniques were
associated with a substantial incidence of pseudoaneurysm formation at coronary and
aortic suture lines. [13 ] , [26 ] , [77 ] Persistent communications between the aortic
lumen and the peri-graft space can put tension on anastomotic suture lines. Not
infrequently, these suture lines separate to produce large pseudoaneurysms and
compression of the aortic graft. The open technique is associated with a low incidence
of pseudoaneurysm formation and a low incidence of reoperation. [26 ] , [55 ] , [68 ]
Special Considerations
INCLUSION OF THE AORTIC ARCH
The aortic arch may be replaced at the time of ascending aortic replacement if
aneurysmal disease extends distally. A diameter of 5.56 cm, or evidence of progressive
enlargement, are the most common indications for replacement. Resection may be
limited to the concavity (inside curve) of the aortic arch (Fig. 39-11B) or may include the
entire arch.
NEW OR PERSISTENT SINUS OF VALSALVA ANEURYSM
For patients who have aneurysms of the sinus of Valsalva after previous operations on
the ascending aorta or aortic valve, the dilated sinuses are excised and the aortic root
is replaced with a composite graft. The composite graft is sutured distally to the
previously inserted graft. Excessive fibrosis and scarring and marked dilation of the
aortic sinuses may preclude mobilization of the coronary arteries and direct attachment
to the composite graft without significant tension. In this situation, segments of 8- or
10-mm collagen-impregnated woven Dacron velour graft (Hemashield, Medox
Medicals, Oakland, NJ) are sutured to the aortic tissue surrounding the coronary ostia.
These grafts then are anastomosed to the aortic graft.
PATCH REPAIR, ELLIPTICAL INCISION, AND AORTIC WRAPPING
Patch repair and aortic wrapping were some of the earliest treatments for ascending
aortic aneurysms. [4 ] Aneurysms limited to the tubular portion of the ascending aorta
can be tailored by resecting a portion of the aneurysmal segment.
The aorta is closed primarily or is reconstructed with a Dacron or Gore-Tex patch. [102 ]
[104 ] External aortic wrapping with a Dacron graft or Vicryl mesh can be performed
with or without tailoring procedures to reduce the size of the aorta. Early results with
these techniques are satisfactory, and satisfactory long-term results are reported by
some groups. [102 ] [104 ] However, results with these techniques appear no better than
with graft replacement and long-term follow-up is limited. [55 ] , [105 ] Furthermore,
residual aortic tissue is susceptible to aneurysm formation or dissection, and high
reoperation rates are reported. [26 ]
AORTIC REPLACEMENT IN PATIENTS WITH PREVIOUS CORONARY ARTERY

BYPASS GRAFTING
In patients who have undergone previous coronary artery bypass grafting, and who
require replacement of the ascending aorta, myocardial protection is achieved by
antegrade and retrograde infusion of cold cardioplegic solution after occlusion of the
ascending aorta. Direct cannulation of bypass grafts to administer cardioplegic solution
should be avoided if the grafts have been in place for more than 23 years. The
ascending aorta and aortic arch are replaced using the techniques described in the
preceding. Previously placed vein grafts that are stenotic or have severe degenerative
changes are replaced with new grafts. Grafts without these changes usually are
re-implanted into the aortic graft using a cuff of aortic tissue that can be sutured to the
aortic graft.
CONCOMITANT PROCEDURES
Coronary artery bypass grafting
Concomitant coronary artery bypass grafting frequently is performed in combination

with graft replacement of the ascending aorta. The anastomoses of venous grafts to the
aortic graft are performed after the aortic graft is attached to the aorta, but before
removal of the aortic clamp. When circulatory arrest is required, the anastomoses of the
venous grafts or the internal thoracic artery to the coronary arteries are performed
during periods of cooling and rewarming.
Mitral valve repair or replacement
Mitral valve repair or replacement is performed during the single period of aortic
occlusion using techniques described in Chapters 33 and 34.
Management of Complications
EXCESSIVE BLEEDING
The use of pre-clotted or collagen- or gelatin-impregnated Dacron grafts has

substantially reduced the frequency and severity of postoperative bleeding. Bleeding at
anastomotic suture lines is decreased by incorporating strips of Teflon felt into the
graft-to-aorta or coronary artery-to-graft anastomoses and by the use of fibrin glue.
Avoidance of tension on these suture lines also contributes to optimal hemostasis.
Each anastomosis is examined carefully for evidence of bleeding after discontinuing
cardiopulmonary bypass. If the aorta is wrapped around the aortic graft, this should not
be done until protamine is administered and there is no evidence of bleeding. Platelets,
fresh frozen plasma, and cryoprecipitate are not used routinely. With current blood
conservation techniques, including preoperative donation of autologous blood, use of
cell-saver devices intraoperatively, and re-infusion of chest tube drainage
postoperatively, transfusion of homologous blood products is avoided in many patients
who undergo operations on the ascending aorta.
Coagulopathic bleeding should be documented by appropriate laboratory studies and

corrected by administration of fresh frozen plasma, platelet concentrates, factor VIII, and
cryoprecipitate, as indicated. A bleeding aortic anastomosis can be wrapped tightly
with a segment of Dacron graft to remove tension from the suture line and reduce
bleeding from needle holes (Fig. 39-12) . In rare circumstances, creation of a fistula
between the right atrium and perigraft space made created by wrapping the aorta or a
piece of autologous pericardium around the graft can be lifesaving. [14 ] , [106 ]
NEUROLOGIC INJURY
Neurologic injury after aortic surgery has multiple causes. In operations that require the
use of hypothermic circulatory arrest, focal deficits are generally caused by embolic clot
or atheroma. [107 ] Microemboli of air, fibrin, platelet aggregates, or other blood
elements produce diffuse injury, manifested by delirium, lethargy, or choreoathetosis.
Diffuse injury also may develop from global ischemia caused by inadequate or
non-homogenous cooling of the brain prior to establishing circulatory arrest. [107 ]
Pre-operative carotid duplex scanning identifies severe stenoses of the internal carotid
arteries that may require surgical treatment prior to an aortic procedure. Intra-operative
ultrasonographic scanning of the ascending aorta detects atherosclerotic changes that
can embolize atherosclerotic debris following aortic cannulation or clamping. [80 ] , [90 ]
, [108 ] Modifications in technique can reduce the probability of embolization of
atheromotous debris. [108 ]
When hypothermic circulatory arrest is required to manage ascending aortic disease,

resumption of flow in the antegrade direction avoids embolization of atherosclerotic
debris that may have fallen into the distal aorta (see the preceding).
PULMONARY DYSFUNCTION
Non-cardiogenic pulmonary edema and increased physiologic shunting may occur after
replacement of the ascending aorta owing to cardiopulmonary bypass mediated lung
injury. [109 ] A low hematocrit, use of fresh frozen plasma, and a heparin-protamine
reaction can exacerbate the injury. [110 ] , [111 ]
Pre-operative steroid use is advocated to reduce release of inflammatory mediators

during cardiopulmonary bypass. [112 ] , [113 ] A membrane oxygenator may decrease
complement activation and decrease lung injury. [114 ] Continuous ultrafiltration
decreases pulmonary edema and removes vasoactive substances from the circulation
in the pediatric population. [115 ] [119 ]
Lung injury produces an interstitial pattern on chest radiography, an increase in the

alveolar/arterial oxygen gradient, and a decrease in lung compliance. [120 ] Treatment
is primarily supportive, with close attention to fluid management, judicious use of
antibiotics to prevent superinfection, a minimal number of intravenous lines, and
adequate nutritional support. [120 ] [122 ]
POST OPERATIVE CORONARY INSUFFICIENCY
Patients undergoing aortic root replacement are at risk for ischemic complications
arising from technical problems of coronary artery to graft anastomoses. In our
experience and that of others, these complications are rare (<1 percent). [55 ] , [68 ] ,
[123 ] Kinking of the Dacron or vein grafts to the coronary arteries may impair coronary
flow. [68 ] Other causes of impaired coronary flow include twisting coronary buttons at
the time of the anastomoses, or compression of coronary arteries by blood in the
peri-graft space.
If myocardial ischemia is suspected in the early post-operative period, prompt

evaluation that may include transesophageal echocardiography and angiography is
indicated. Re-operation may be necessary to correct the problem.
RESULTS OF OPERATION
Perioperative Morbidity
Re-operation for bleeding in the early post-operative period is required in 211 percent
of patients. [26 ] , [27 ] , [55 ] , [124 ] [126 ] The incidence of post-operative neurologic
deficit ranges 25 percent, and depends on the definition of deficit. [26 ] , [124 ] , [125 ]
Twenty to twenty-five percent of patients require inotropic support for greater than 6
hours post-operatively. [55 ] , [124 ] Twenty-five to thirty-three percent of patients
experience significant ventricular arrythmias. [27 ] Ten percent require prolonged
ventilatory support. [124 ] The incidence of heart block, renal failure, and new
myocardial infarction in one series was 7, 6, and 3 percent, respectively. [27 ]
Perioperative Mortality
Hospital mortality rate ranges 2.210 percent and is approximately 35 percent in the
most recently reported series. [26 ] [28 ] , [55 ] , [68 ] , [123 ] [126 ] We have a 2.2
percent 30-day mortality rate for elective composite graft replacement of aneurysms
resulting from annuloaortic ectasia or chronic dissection. [55 ] Gott et al. reported no
hospital mortality among a group of 180 patients with annuloaortic ectasia without
dissection who underwent composite graft replacement of the aortic root. [68 ] The most
frequent mode of early death is cardiac failure, followed by stroke and respiratory failure
(Table 39-1) . [26 ] [28 ] , [55 ] , [123 ] [126 ]
Aortic root replacement for endocarditis is associated with a significantly higher

mortality rate (3350 percent). [125 ] , [126 ]
Risk Factors for Hospital Death
Emergent operation is the strongest risk factor for early mortality. [27 ] , [125 ] Advanced
age, prolonged duration of cardiopulmonary bypass, and depressed left ventricular
function are the strongest predictors of early mortality following elective operations. [26 ]
[28 ] , [55 ] , [124 ] [126 ] The major risk factors identified in nine surgical series are
shown in Table 39-2 .
Late Survival
Late survival ranges 6682 percent at 5 years, to 5473 percent at 10 years, and 4867
percent at 1214 years post-operatively (Fig. 39-13) . [26 ] , [27 ] , [55 ] , [68 ] , [123 ] [126
] The majority of late deaths are from cardiac causes (2440 percent); however, disease
in the remaining aorta is the second or third most common cause of death in many
series. [26 ] , [27 ] , [68 ] , [125 ] , [126 ] The presence of disease in the aortic arch or
distal aorta is a significant risk factor for late death (Fig. 39-14) . [26 ] , [124 ] Advanced
age, presence of Marfan syndrome, and advanced pre-operative New York Heart
Association functional class are also significant independent predictors of late death.
[55 ]
Reoperation on the Ascending Aorta and Aortic Valve
Reoperations for pseudoaneurysm formation, prosthetic endocarditis, technical

problems, thrombotic occlusion of the prosthetic valve, and other complications are
required in 517 percent of patients 1015 years post-operatively. [26 ] , [27 ] , [55 ] , [124
] [126 ] Crawford reports a 1-year reoperation rate of 2 percent in patients undergoing
tube graft replacement of the ascending aorta and a 4 percent rate for patients having
composite graft replacement of the ascending aorta. Freedom from reoperation on the
ascending aorta is 84 percent at 7 years. [26 ] In our series of aortic root replacement,
the probability of freedom from re-operation on the ascending aorta at 5 years for
reasons other than hemorrhage is 94 percent for the open technique and 84 percent for
the inclusion/wrap procedure (Fig. 39-15) .
In a series of patients with normal aortic sinuses who underwent tube graft replacement
of the ascending aorta, with or without associated aortic valve replacement, reoperation
on the ascending aorta was required in 6 patients (2.2 percent). Two to three percent of
patients with simple tube rafts and normal aortic valves required late reoperation for
valve replacement. [78 ]
Operations on the Remaining Aorta
Disease of remaining aorta is an important cause of late mortality. Operation on the

remaining aorta is required in 418 percent of patients undergoing repair of ascending
aortic aneurysms. [26 ] , [68 ] , [78 ] , [126 ] , [127 ] Cabrol et al. observed spontaneous
late dissection of the descending aorta in 4 of 100 patients with no history of prior aortic
dissection. [123 ] Patients with chronic dissections or the Marfan syndrome have a
higher incidence of operation on the remaining aorta. [127 ]
Thromboembolism
The actuarial probability of freedom from thromboembolic events for patients who have
undergone composite graft replacement of the aortic root is approximately 82 percent
at 1012 years (Fig. 39-16) . [55 ] , [126 ] Gott et al. report an incidence of 0.42
thromboembolic events per 100 patient years. [68 ] This is lower than the rate reported
for aortic valve replacement with a mechanical valve. They attribute this lower incidence
to the absence of pledgets and suture material in the bloodstream, and to a smaller
amount of exposed sewing ring. [68 ]
In our experience, 18 of 172 patients undergoing composite graft replacement have

transient visual disturbances including blurred vision, diploplia, scotoma, and focal blind
spots. [55 ] Generally these symptoms subside within minutes.
Anticoagulant-Related Complications
The actuarial probability of freedom from anticoagulant complications at 12 years in our

experience is 91 percent. [55 ]
Prosthetic Endocarditis
Prosthetic endocarditis is the most common late complication of composite graft
replacement and occurs in 45 percent of patients who are followed 1417 years. [55 ] ,
[68 ]
Symptomatic Status of Hospital Survivors
The vast majority of hospital survivors are NYHA functional Class I or II. [55 ] , [123 ]
Results of Operation for the Marfan Syndrome
Cardiovascular disease accounts for 6675 percent of late deaths following operations
in patients with Marfan syndrome (Table 39-3) . [71 ] , [72 ] , [128 ] Progressive disease
in the non-operated aorta and cardiac failure (often the result of longstanding aortic
and/or mitral regurgitation) account for the majority of cardiovascular deaths. Some
investigators note a higher incidence of prosthetic valve endocarditis in patients with
Marfan syndrome when compared to patients undergoing aortic root replacement for
other causes. [59 ] Risk factors for late death include advanced NYHA class,
cardiomegaly, presence of a diastolic murmur, and operation performed prior to the
1980s. [38 ] , [59 ] , [128 ] , [129 ]
Modern surgical techniques and medical therapy prolong the median survival of patients
with Marfan syndrome from 48 years, as reported by Murdoch in 1972, to 6172 years.
[22 ] , [72 ] , [128 ] Cumulative survival rates of unoperated patients, of patients from the
1972 report by Murdoch, and of a recent series of patients who received modern
surgical therapy is shown in Figure 39-17 . The 10-year cumulative probability of
survival in patients undergoing cardiovascular surgery for the Marfan syndrome is
shown in Figure 39-18 .
ETIOLOGY OF ARCH ANEURYSMS
Not surprisingly, the etiology of aortic arch aneurysms falls into the same general
categories as that of aneurysms elsewhere in the aorta. The largest number are
extensions of ascending aortic disease into the proximal arch; among these are acute
type A dissections with the site of tear either in the ascending aorta or in the arch.
These dissections occur in older individuals with degenerative aortic disease as well as
in some younger patients with Marfan syndrome and other genetic disorders of elastic
tissue. In acute type A dissections, at least part of the arch is resected if the primary
tear is in the arch, and the entire arch is resected if the tear is in the distal arch or if the
arch is extensively weakened by the dissection. [1 ] In patients with chronic dissections
followed by progressive dilatation of the aorta, there may be involvement of the arch in
either type A or type B dissections. Dissecting aneurysms are fully discussed in Chap.
38.
In patients without dissection, the largest group classified as arch aneurysms begins in
the ascending aorta but unequivocally extends into the arch or continues to show
aneurysmal dilatation so close to the origin of the innominate artery that open distal
anastomosis is the best option at the time of surgical repair. The diverse etiology of
ascending aortic aneurysms is discussed in Chapter 39.
Among patients with degenerative aortic disease presenting with fusiform aneuryms
primarily in the transverse arch, there seem to be two distinct clinical patterns, although
there is some overlap between them. The first group consists of relatively younger
patients, with a mean age between 50 and 60 years, who are frequently smokers with
chronic lung disease. These patients tend to have involvement of the entire aorta, with
symmetric expansions throughout its length, but the largest diameters are usually found
in the ascending aorta, the arch, or the proximal descending aorta.
In the other group with degenerative arch aneurysms, patients are generally older, with a
mean age between 65 and 70 years, and have evidence of severe atherosclerotic
disease elsewhere: in the iliofemoral, coronary, or carotid vessels. These patients'
aneurysms involve primarily the descending thoracic aorta, with substantial increases in
the diameter of the aortic knob and distal aortic arch and an asymmetric but fusiform
pattern. These aneurysms frequently extend to the diaphragm and beyond and contain
considerable thrombus and atheromatous debris within the aorta. Patients in this group
are almost always hypertensive and frequently have a history of cigarette smoking.
The remaining patients with arch aneurysms are comprised of several small groups with
different etiologies. A few patients present with small defects in the aortic media (1 cm
or less) giving rise to saccular aneurysms filled with thrombus. Another small group of
patients has false aneurysms following traumatic tears of the aorta, usually as a
consequence of blunt trauma sustained in vehicular accidents. Patients with various
congenital anomalies of the aortic arch, such as aberrant origin of the right subclavian
artery, double aortic arch, [2 ] or right aortic arch, [3 ] also may develop arch aneurysms;
recently, there have been several reports of arch aneurysms following patch
annuloplasty for repair of coarctation of the aorta. [4 ] , [5 ] Takayasu's arteritis, although
primarily an obstructive disease, may give rise to arch aneurysms, [6 ] as may Behçet's
disease, a vasculitis with multiple other, more characteristic manifestations, [7 ] , [8 ]
and giant cell arteritis. [9 ] Mycotic aneurysms are also seen [10 ] , [11 ] ; these are
usually asymmetric and saccular, and often the organism responsible cannot be
pinpointed preoperatively but can be cultured from the resected specimen. As
mentioned previously, individuals suffering from the Marfan syndrome or other less
common congenital abnormalities of connective tissue such as the Ehler-Danlos
syndrome also may have aneurysms of the aortic arch. [6 ] , [12 ]
NATURAL HISTORY AND INDICATIONS FOR OPERATION
It is rare for a patient with an arch aneurysm to present in such a way that operation is
scheduled urgently or immediately following the first visit to the surgeon. Most arch
aneurysms are not discovered because of symptoms but are detected in the course of
noninvasive studies done as part of a general evaluation or in the course of
investigation of an unrelated medical problem. The decision to operate is made
because of the known risk of rupture of aortic aneurysms and the recognition that
spontaneous rupture of a thoracic aortic aneurysm usually is fatal. Even if the problem is
recognized and appropriate emergency care and immediate operation are carried out
optimally, survival rate following spontaneous rupture of a thoracic aneurysm is dismal.
[13 ] Thus the indication for most aortic arch surgery, which characteristically is carried
out in an asymptomatic patient, is purely prophylactic: to prevent rupture.
Unfortunately, however, we have very little data with which to predict risk of rupture for an
aneurysm in any given patient. Furthermore, most patients are quite elderly and
frequently have chronic lung disease and other problems that make them suboptimal
surgical candidates and increase the risk of an operation that carries a relatively high
mortality even in otherwise ideal patients. Deciding whether or not to resect an arch
aneurysm involves careful assessment of both the likelihood of rupture and the
operative risk in each individual, balancing one against the other.
Risk of Rupture
The size of the arch aneurysm and of the adjacent normal distal ascending or proximal
descending aorta is probably the strongest predictor of eventual rupture. [14 ] , [15 ]
Consequently, most surgeons are reluctant to consider operation in an asymptomatic
patient with a typical fusiform aneurysm with a diameter of less than 5 cm and are
uncomfortable not recommending resection of an aneurysm that exceeds 8 cm in
diameter. However, every surgeon has seen smaller aneurysms rupture and also has
seen, in individuals for whom operation is deferred or contraindicated, that quite
significant thoracic aneurysms may enlarge minimally or not at all over a period of
years. Because the forces on the aortic wall increase linearly as aortic radius increases,
larger aneurysms are subjected to greater forces that predispose to rupture than
smaller ones. These greater forces not only make them more likely to rupture but also
encourage them to enlarge faster than smaller aneurysms. [15 ]
In a group of 67 patients with thoracic aortic aneurysms whose initial evaluation did not
prompt immediate surgery, we attempted to assess the relationship between the risk of
rupture and the initial aneurysm diameter, the rate of expansion, and a number of other
variables. [14 ] Our observations concerning aneurysm growth were similar to those of
Hirose et al., [16 ] who calculated an average rate of expansion of 0.42 cm per year for
all thoracic aortic aneurysms in 82 patients, with the most rapid expansion occurring in
patients with arch aneurysms. Our study revealed that the few patients whose
aneurysms ruptured despite careful surveillance had aneurysms with larger initial
diameters and faster rates of expansion than patients without aneurysm rupture.
Smokers also had a higher risk of rupture, and a questionably increased likelihood of
rupture was present in patients with a history of hypertension. [14 ] Serial CT scans
were compared by means of computer-generated three-dimensional reconstructions of
the aorta, and average rates of expansion for aneurysms of different sizes also were
calculated. [17 ]
Based on the data from our study, which show the rate of expansion of thoracic aortic
aneurysms to be an exponential function of diameter, as seen in Fig. 40-1 , we now
consider a rate of expansion exceeding 1 cm per year to be a clear indication for
operation and believe operation should be strongly considered if the rate exceeds 0.5
cm per year. [14 ] In addition to being influenced by size and rate of expansion of
aneurysms, we also consider operation if the aneurysm is saccular or significantly
asymmetric or if a false aneurysm is present; we think these features increase the
likelihood of rupture. Three-dimensional reconstructions of the aorta in a patient with a
typical fusiform arch aneurysm before and after surgery are shown in Fig. 40-2 ; several
views of an atypical asymmetric arch aneurysm are shown in Fig. 40-3 .
Although most patients with arch aneurysms are asymptomatic, some individuals
present with either chest pain or hoarseness and occasionally with onset of a new
cough. We consider development of symptoms to be an ominous sign of rapid
expansion and possible impending rupture; therefore, we usually operate on patients
with these symptoms, even when the arch aneurysm is of moderate size.
Operative Risk
As indicated previously, risk of rupture must be weighed against operative risk to

determine whether resection of an aortic arch aneurysm should be undertaken. The
extent of the proposed resection figures prominently in this calculation, since more
extensive aortic resections, especially in the descending thoracic aorta, carry a higher
risk of death and significant morbidity than localized resections. The patient's overall
vigor and zest are perhaps more important than chronologic age in contributing to the
decision of whether operation should be recommended. The presence of significant
other pathology that threatens to limit life expectancy or significantly reduce its quality
also must be weighed.
Chronic lung disease is very common in these patients, so its presence should not be
used as an absolute contraindication to surgery unless there is chronic oxygen
dependence and/or carbon dioxide retention. Similarly, although renal dysfunction
increases operative risk, even patients with renal failure severe enough to require
chronic dialysis but whose general health is good and whose life expectancy otherwise
is substantial can undergo successful resection of an arch aneurysm. Some degree of
systemic atherosclerosis is a frequent finding, and significant or potentially threatening
coronary artery disease may need prior or concurrent management. Only severe left
ventricular dysfunction or intractable congestive heart failure should contraindicate
surgery. Renal and iliofemoral obstructive disease may present technical problems and
may increase operative risk significantly.
APPROACH TO THE PATIENT
From the foregoing it is evident that except in patients in whom very large or
symptomatic aneurysms require immediate surgery, careful weighing of the risk of
rupture versus the operative risk for each individual is required to determine whether
operation should be recommended. In the absence of good studies to predict risk of
rupture of thoracic aneurysmsespecially in the aortic arch, where size measurements
are most problematicthere is no substitute for obtaining data with regard to the behavior
of the specific aneurysm in question before making a decision to operate.
For this reason, we routinely request that asymptomatic patients return for a second
visit, usually 6 months following the initial evaluation, but within 3 months if the aneurysm
is relatively large or if the patient is very anxious. At that time the patient brings a
second CT scan (with contrast) of the entire thoracic and abdominal aorta; comparison
of the first and second studies allows determination of how rapidly the aneurysm is
enlarging. If the situation appears stable, with minimal further enlargement of a small or
moderate-sized aneurysm, the patient continues to be followed at intervals of 6 months.
This enables periodic reexamination of expansion rate, size, and configuration of the
aneurysm, as well as factors bearing on the calculation of operative risk. This process
allows for more accurate evaluation of the need for operative intervention in borderline
situations, as well as the development of a relationship between the surgical team and
the patient. Should resection of the aneurysm eventually become necessary, it is our
experience that operative complications and suboptimal outcomes are much better
tolerated by patients and families who have gradually become convinced of the need for
operation by watching the size of an aneurysm increase and who have developed
confidence in the surgical team before operation.
We anticipate that most patients will not be operated on following their initial visit and
that many will have multiple serial evaluations. Although we do not undertake primary
responsiblity for the treatment of hypertension, we monitor its control and advise
patients to stop smoking and avoid heavy lifting. The role of beta-adrenergic blockade
is well established in ascending aortic aneurysms in patients with Marfan syndrome [18
] ; we feel that negative inotropic therapy also may be appropriate in other aneurysm
patients, particularly in those with chronic dissections. We also counsel patients
concerning their response should symptoms suggestive of accelerated expansion or
rupture occur between follow-up visits. If severe acute pain develops, patients are
instructed to go immediately to the nearest emergency room, to tell the personnel that
they have a thoracic aneurysm, and to permit emergency evaluation of the possibility of
rupture, control of hypertension, and urgent transfer if appropriate. If less severe but
persistent chest pain develops, patients are asked to return to us or to their primary
physician for reevaluation as soon as possible with a new CT scan of the entire aorta.
Our willingness to supervise the progress of individuals with aneurysmal disease who
are not immediate surgical candidates has had a decidedly positive impact on referral
patterns; internists and cardiologists appreciate that patients will not get just a rapid
one-time-only decision for or against operation but a commitment to continuing
oversight.
If, after initial screening or after serial visits, a decision is made to proceed with surgery,
more detailed evaluation of both the aneurysm and factors that affect the patient's
operative risk will be required; it is understood that some of these additional data, as
outlined below, may prompt reconsideration of the decision to operate.
A careful general medical history and routine laboratory studies are of extreme
importance in evaluating possible symptoms due to the lesion and in revealing other
medical problems in these usually elderly patients. A family history of a ruptured
aneurysm is not uncommon and aids in the decision to recommend surgery. The
discovery of other medical conditions may influence the operative approach, allow
anticipation and possibly prevention of intraoperative or postoperative complications to
which the patient is especially vulnerable, or may contraindicate operation altogether.
Evaluation of the aortic arch aneurysm itself requires a CT (computed tomographic)

scan with contrast of the entire aorta, although a complete MRI (magnetic resonance
imaging) study is preferred by some surgeons. [4 ] Angiograms are not required
routinely to visualize the lesion, but if a cardiac catheterization with coronary
arteriography is indicated (as discussed below), an aortogram can be done with very
little additional risk and is usually carried out. At present, newer technologies such as
ultrafast CT and contrast-enhanced MRI are evolving and may with time prove to be
superior to a CT study with contrast under certain circumstances both preoperatively
and during follow-up. [5 ] , [19 ] , [20 ]
Assessment of Cardiac Status and Management of Coronary Artery Disease
It is a rare individual who has not had an echocardiogram prior to referral for evaluation
of an aortic aneurysm. In young patients with no history of cardiac dysfunction or
symptoms suggestive of heart disease, no further evaluation of cardiac function is
carried out; the echocardiogram is judged adequate to rule out significant left ventricular
dysfunction or valvular disease.
In patients with aneurysms of the ascending aorta, in whom a Bentall procedure may be
required, coronary arteriography to ascertain the anatomy of the proximal coronary
arteries is carried out routinely. Patients with a low to moderate risk of coronary artery
disease, based on age, family history, serum lipids, history of smoking, or known
atheromatous disease elsewhere in the body, undergo a persantine- or
adenosine-thallium study of myocardial perfusion; if the results are abnormal, coronary
arteriography is recommended. In patients with a high risk of coronary diseasejudging
from the presence of an abnormal electrocardiogram, a history of angina, previous
angiography, or a strong family history of coronary artery diseasecoronary arteriography
is carried out routinely.
If, on the basis of preoperative evaluation, significant coronary artery disease is found
but there is no threatening lesion present, aneurysm surgery is carried out without further
ado, albeit with special concern to avoid undue cardiac stress. If significant coronary
disease is present and some of the lesions are considered potentially dangerous,
coronary artery surgery and angioplasty are considered. If the lesions are amenable to
angioplasty, this procedure is done 1 to 2 weeks before aneurysm surgery to prevent
possible coronary thrombotic sequelae that have been observed if surgeryinvolving
administration of heparin and protamineis carried out sooner. [21 ] If the aneurysm can
be resected via a median sternotomy incision, or if the coronary arteries that require
bypass are easily accessible through a left thoracotomy, coronary artery bypass grafting
can be done at the time of aneurysm repair. If the aneurysm is very extensive, or if
access to the relevant coronary arteries will be difficult through an incision that is
optimal for aneurysm resection, coronary artery bypass surgery is undertaken in a
separate procedure several weeks prior to aneurysm repair.
If severe pulmonary dysfunction is suspected on the basis of simple pulmonary function

screening tests or because of a history of severely limited exercise tolerance,
pulmonary consultation is requested. Active pulmonary infection is treated prior to
surgery. All patients are urged to stop smoking for at least 1 month before operation.
Pulmonary dysfunction increases operative risk and prolongs recovery, but chronic lung
disease is not necessarily a contraindication to operation unless oxygen dependence
or significant carbon dioxide retention is present.
Assessment of Cerebral Vessels and Prevention of Stroke
A history of transient ischemic attacks or of strokes or the presence of carotid bruits on

examination prompts noninvasive workup of extracranial cerebral vessels. Since emboli
are likely to arise from the diseased aorta in the presence of an arch aneurysm, a
history of focal cerebral insults is not a contraindication to surgery. In patients with such
a history, a CT scan of the brain is carried out preoperatively; this enables detection of
silent fresh cerebral infarcts, which necessitate postponement of surgery in most
instances. The preoperative CT scan is also invaluable for identification of new lesions
and may be helpful in prognosis if focal neurologic symptoms occur postoperatively.
Rather than attempt to identify those patients most at risk for intraoperative and
postoperative cerebral embolization because of extensive friable atherosclerotic debris
in the ascending aorta and arch, we assume that all patients with arch aneurysms have
a very high risk of embolization and take all possible steps to minimize their occurrence.
Reasonably accurate preoperative identification of those patients at highest risk is
possible using transesophageal echocardiography, and even better visualization of the
ascending aorta and arch is possible using a sterile transducer on the surface of the
aorta intraoperatively. [22 ]
Assessment of Cannulation Sites
Extensive atherosclerosis of the femoral vessels often can be identified preoperatively

because of symptoms, a history of revascularization of the lower extremities, or weak or
absent femoral pulses. If difficulty with routine cannulation for cardiopulmonary bypass
from the femoral artery is anticipated, or if such cannulation is felt to carry an excessive
risk of embolization, resection of the aneurysm can still be undertaken, but it is helpful to
give some forethought to possible alternate cannulation sites. Cannulation can be
carried out in the ascending aorta using intraoperative ultrasound to select a site free of
atheroma in a small segment of aorta adjacent to or even included in the anticipated
resection; subsequently, the perfusion cannula can be moved to the graft during the
procedure. Perfusion also can be carried out via either of the subclavian arteries.
STRATEGIES FOR CEREBRAL PROTECTION
The principal challenge involved in repair of aneurysms involving the aortic arch comes
from the requirement to preserve cerebral function despite the need to manipulate the
cerebral circulation. In addition to preventing global ischemic injury during and
immediately following aneurysm repair, early surgical experience quickly established
that preventing dislodgment of thrombus and atherosclerotic debris into the cerebral
vessels during the repair is equally if not more important. In consequence, repair of an
aortic arch aneurysm may require interruption of the cerebral circulation not only during
necessary aortic anastomoses but also during dissection and mobilization of the aortic
arch and cerebral vessels.
Strategies for protecting the brain during the interval in which its normal circulation is
interrupted have evolved into three major categories, all involving hypothermia:
complete interruption of flow or hypothermic circulatory arrest (HCA), selective cerebral
perfusion (SCP), and retrograde cerebral perfusion (RCP). Several of these techniques
can be used during the same procedure.
Hypothermic Circulatory Arrest: Historical and Theoretical Considerations
Hypothermic circulatory arrest (HCA) was first introduced in the early days of open heart
surgery as an alternative to extracorporeal circulation. In the 1960s, isolated case
reports described the use of HCA in repair of aortic aneurysms. [23 ] , [24 ] Shortly
thereafter, the merit of HCA as a technique for correction of complex congenital heart
lesions in infants was championed by Barrat-Boyes et al. [25 ] This prompted renewed
interest in its use in adults with aneurysms of the aortic arch; the first series of cases in
which HCA was used successfully in patients with aortic arch aneurysms was published
in 1975. [26 ]
Since that time, the efficacy of HCA in protecting the brain in children undergoing repair
of congenital heart lesions and in adults with aortic aneurysms has been accepted
widely. Increasing utilization of HCA also revealed some of its limitations, however, and
concern about its safety, especially when longer durations are required. Thus there is
recently renewed interest in investigation of HCA and in exploration of alternative
techniques such as selective antegrade cerebral perfusion (SCP) and retrograde
cerebral perfusion (RCP).
The basis for the initial enthusiasm for the use of hypothermia to protect the brain during
circulatory arrest was a series of investigations in adult dogs that documented profound
inhibition of cerebral metabolism with lowering of brain temperature. [2 ] Using a ratio of
normothermic metabolic rate and hypothermic metabolic rate at various temperatures,
Michenfelder and Milde originally postulated that complete arrest of the cerebral
circulation for as long as 30 minutes at 18°C would not result in any permanent injury to
the brain, and in subsequent experiments they have provided evidence indicating that
periods of HCA as long as 60 minutes should be safe. [27 ]
Although clinical results suggest that patients who have surgical correction of congenital
heart defects using HCA generally emerge from their operations without serious
neurologic sequelae, careful studies using standardized tests of behavior and learning
in young children established that some loss of cognitive function may occur following
use of HCA in infancy, especially with prolonged intervals of circulatory arrest. [28 ] , [29
] Because of the increasingly widespread trend to repair congenital heart lesions in
infancy, often using HCA, questions about possible detrimental consequences have
renewed interest in investigating clinical neurologic sequelae of HCA and in
determining the pathophysiology of the cerebral injury that may occur. [30 ] , [31 ]
Recent laboratory investigations in weanling puppies [32 ] and in young piglets [33 ]
show that depression of cerebral metabolic function by hypothermia is less complete at
the standard temperatures used for neonatal surgery than predicted by the formula
proposed by Michenfelder. In weanling puppies, cerebral metabolic rate is reduced only
to 40 percent of control levels at 18°C, and HCA for 60 minutes at 18°C results in
detectable early behavioral dysfunction following surgery and in quantitative
electroencephalographic (EEG) changes. [32 ] , [34 ] More prolonged HCA at 20°C in
young piglets produces unequivocal behavioral sequelae as well as EEG changes and
histologic evidence of cerebral damage. [35 ] In addition, these laboratory studies
consistently show a period of severe cerebral vasoconstriction lasting for several hours
following even short intervals of HCA. During this period, normal levels of cerebral
metabolism are only precariously maintained by means of increased oxygen extraction,
and the animals are especially vulnerable to hypoxic insults. [34 ] , [36 ] [38 ]
Clinically, an ongoing large prospective collaborative study of children following surgery

for repair of transposition of the great arteries in infancy using HCA has documented
subclinical EEG evidence of seizures in many children and subtle abnormalities in
neurologic examinations as late as 1 year after surgery, especially in those with
prolonged durations of circulatory arrest. [39 ] , [40 ] A disturbingly high incidence of
focal injury also has been noted in brain imaging studies carried out 1 to 4 years
postoperatively. [41 ] Another recent clinical study documented that increasing durations
of HCA during correction of congenital heart disease in infancy correlate with lower
scores on intelligence tests later in childhood. [29 ] , [42 ]
In a review of 200 adult patients who underwent HCA during operations on the thoracic
aorta, we found that 19 percent of the survivors had diffuse temporary neurologic
dysfunction consisting of prolonged postoperative obtundation, confusion, or agitation,
or transient parkinsonism, and that these symptoms correlated significantly with age
and with duration of HCA, which averaged 47 minutes in those with symptoms versus
33 minutes in those without. Duration of HCA did not correlate with mortality or with
permanent neurologic injury; permanent neurologic injury usually was focal and was
significantly more frequent in older patients and in those with obvious atheromatous
debris in the arch or descending aorta at the time of operation.
With the hope of improving cerebral outcome, a number of studies have compared
different techniques of initiation and implementation of HCA. It has been established
unequivocally that colder temperatures at the time of HCA confer a greater degree of
protection, as shown in Fig. 40-4 [33 ] , [37 ] , [43 ] , [44 ] : There is now a consensus that
a period of circulatory arrest longer than 20 minutes requires hypothermia to 12 to 15°C
to ensure adequate cerebral protection and that durations of HCA exceeding 40 or 50
minutes, even at these lower temperatures, raise concerns. Durations of circulatory
arrest exceeding 60 minutes are universally regarded as risky, although there are
reports of patients with good recovery after durations of HCA lasting considerably
longer. [45 ]
Clinical and laboratory studies also have led to conclusions regarding other aspects of
HCA; it is generally agreed that too short a period of cooling may result in damage due
to uneven and inadequate lowering of brain temperature [39 ] and that packing the head
in ice during prolonged intervals of circulatory arrest improves outcome. [35 ] , [36 ] , [39
] , [46 ]
The issue of how pH should be managed during cooling remains controversial. Some
studies suggest that pH-stat management, at least in infants, may be associated with a
better developmental outcome [30 ] , [41 ] and with a lower incidence of
choreoathetosis, a dreaded form of severe neurologic injury that occurs, albeit rarely, as
a consequence of HCA. [47 ] Cerebral perfusion is unequivocally enhanced by pH-stat
management, which abolishes cerebral autoregulation. [48 ] , [49 ] Cerebral
vasodilatation with increasing concentrations of carbon dioxide favors more thorough
cooling as hypothermia progresses but also exposes the brain to an increased embolic
load during this so-called luxury perfusion. Alpha-stat management better preserves
cerebral autoregulation, limits flow to meet metabolic requirements diminished by
hypothermia, and results in perfusion at a much higher pH. [44 ] As recently suggested,
optimal management may involve initiating cooling with pH-stat management and then
using alpha-stat principles to guide perfusion for at least several minutes prior to
instituting complete HCA. [44 ] , [50 ]
The surprising efficacy of hypothermia in protecting the brain during circulatory arrest,
which is not always adequately explained by metabolic suppression, has led to
speculation that hypothermia may provide cerebral protection via additional
mechanisms, such as suppression of release of cytotoxic amino acids or free oxygen
radicals. [51 ] The possibility that some of the cerebral injury associated with HCA may
occur during reperfusion or thereafter has prompted studies suggesting that an initial
period of cold perfusion following HCA may prevent the cerebral vasoconstriction that
results if rewarming is begun immediately after resumption of perfusion [52 ] ; the
inappropriate vasoconstriction that occurs following HCA is widely believed to be
involved in producing brain injury. The use of pharmacologic agents to try to increase
cerebral protection during HCA and reperfusion also remains an area of active
investigation. [53 ]
Clinical Implementation of HCA
In patients with aortic arch aneurysms, we monitor cerebral electrical function by means
of EEG and auditory and sensory evoked potentials. Some surgeons use EEG silence
as a sign that adequate cooling has been achieved, but we prefer to cool with perfusate
at 8 to 10°C to an esophageal temperature of 12 to 13°C for a minimum duration of ½
hour regardless of when EEG silence occurs. We find intraoperative EEG tracings
sometimes difficult to interpret, and we think that it is more prudent to rely on
disappearance of somatosensory or auditory evoked potentials, which take somewhat
longer to vanish with cooling, [54 ] and to insist on a minimum duration and temperature
for cooling.
We also monitor jugular venous bulb saturations. We have observed that mixed venous
saturations usually exceed 90 percent after 20 minutes of cooling but that jugular venous
saturations at the same time are often only 70 percent, suggesting that the brain is still
metabolically active. Since oxygen extraction is the most accurate reflection of cerebral
metabolic activity to which we have access, we continue to cool until jugular venous
saturations exceed 95 percent. An association between low preoperative cerebral
venous saturation and poor recovery of cerebral function following circulatory arrest was
noted in some of our experimental animals [32 ] and also has been observed clinically
by others. [19 ] , [55 ] Consequently, the wisdom of monitoring jugular venous saturations
to assess adequacy of cooling is gradually being acknowledged as an important
safeguard by many anesthesiologists and surgeons utilizing HCA.
Selective Cerebral Perfusion (SCP): Historical and Theoretical Considerations
The earliest attempts to repair aneurysms of the aortic arch were carried out by
DeBakey et al. [56 ] using normothermic cerebral perfusion involving several pumps and
cannulation of both subclavian and both carotid arteries. The problems associated with
controlling pressure and flow in these separate vascular beds to ensure relatively
uniform perfusion and the poor outcome of the patients led to early abandonment of this
technique. More recently, interest in selective cerebral perfusion has been reawakened
by the realization that HCA may not be safe for the long durations required for repair of
more complex and extensive aneurysms, the recognition that combining selective
perfusion with hypothermia allows use of much lower flow rates, and the unequivocal
demonstration that low-flow hypothermic antegrade perfusion provides better cerebral
protection from global ischemia than either HCA or RCP. [32 ] , [34 ] [36 ] , [46 ] , [57 ] ,
[58 ]
The recent resurgence of interest in selective cold cerebral perfusion was spearheaded
by Bachet et al. [59 ] They perfused the innominate and left carotid arteries with blood
between 6 and 12°C. In 54 patients with arch aneurysms, mortality was 13 percent, and
only one episode of severe neurologic injury occurred, with a 4 percent incidence of
transient focal lesions. [59 ] Matsuda et al. [60 ] operated on 34 patients with aortic arch
aneurysms using SCP at 16 to 20°C with an average duration of 123 minutes: they
report a mortality of 9 percent, a 3 percent incidence of stroke, and transient neurologic
symptoms in 6 percent. Kazui et al. [61 ] had a 16 percent mortality in 80 patients with
aortic arch aneurysms operated on using selective cerebral perfusion, with only one
postoperative stroke. Multivariate analysis showed lower leg ischemia, critical
cardiopulmonary dysfunction, and previous ascending aorta or arch operation to be
predictive of early mortality. Tabayashi et al. [62 ] used selective cerebral perfusion in
77 patients, with a 19 percent mortality in true aneurysms of the arch and a 7 percent
mortality in dissections; 4 patients suffered strokes, of whom 2 died. Several other
recent reports have appeared in which SCP has been used to permit open distal
anastomoses during surgery for acute dissections, with good results. [63 ] [65 ] Some
authors advocate a simplified method of SCP in which only the innominate artery is
perfused, relying on flow through an intact circle of Willis to protect the left side of the
brain. [66 ]
Clinical Implementation of SCP
Because of the enhanced risk of embolization, we are not enthusiastic about SCP,
especially if it requires multiple cannulation sites. We still do the vast majority of our
cases using HCA alone. However, we developed a simplified technique for SCP for
those patients in whom repair of an aneurysm involving the aortic arch requires a
lengthy period of circulatory arrest and use this simplified form of SCP in perhaps 10
percent of our patients.
After cooling, we isolate an island of tissue on the superior wall of the aortic arch that
includes the innominate artery, the left carotid artery, and if possible, the left subclavian
artery. If substantially displaced from other arch vessels, the left subclavian artery is
clamped and revascularized later. A beveled graft of 18-mm Dacron is sewn into this
island, and flow is established at a rate of 100 to 600 ml/ min with perfusate at 10°C.
Flow rate is adjusted to achieve a radial artery pressure of 50 mmHg. At the end of the
aortic reconstruction, the beveled graft with its attached cerebral vessels is sewn to the
rest of the aortic graft using a short interval of HCA.
Retrograde Cerebral Perfusion: Historical and Theoretical Considerations
The limitations of HCA, the success of retrograde cardioplegia, and isolated

encouraging reports of the possible efficacy of retrograde cerebral perfusion (RCP) in
mitigating the effects of massive air embolism contributed to recent widespread interest
in and enthusiasm for the technique of RCP. [67 ] , [68 ] Many of the papers have come
from the Japanese literature and report extraordinarily good clinical results with this
technique, although often with durations of RCP that are well within the limits defined as
safe for HCA alone.
Ueda et al. [69 ] first reported excellent results in 8 patients with arch aneurysms
resected using continuous RCP in 1990 and then in a total of 33 patients subsequently.
[70 ] Overall mortality was 12 percent, and circulatory arrest times were relatively short,
averaging 44 minutes; the duration of RCP exceeded 60 minutes in only 6 of the
patients. Takamoto et al. [71 ] reported 14 patients with longer durations of retrograde
perfusion, averaging 65 minutes and lasting as long as 93 minutes; 81 percent had an
uneventful neurologic recovery, and neurologic injury in the remaining 3 did not correlate
with duration of retrograde perfusion. Okamoto et al. [72 ] also reported good results in
34 patients, a minority of whom had long circulatory arrest times. Eleven patients with a
good outcome after RCP but with a mean duration of only 35 minutes were reviewed by
Safi et al. [73 ] More recently, Deeb et al. [74 ] reported 35 patients with a mean
duration of RCP of 65 minutes, with 86 percent of patients exceeding 45 minutes, 34
percent with more than 60 minutes of RCP, and 11 percent exceeding 90 minutes.
Mortality was 9 percent, and only 1 patient had a stroke. Yasuura et al. [75 ] reported a
further 5 patients with aortic arch surgery using total-body retrograde perfusion rather
than selective SVC perfusion; they had RCP for a mean duration of 57 minutes without
neurologic sequelae.
Unfortunately, RCP is very difficult to study in the laboratory. The dog, traditionally the
experimental animal of choice for cardiac surgical investigations, has a cerebral venous
system that differs significantly from that of humans, and studies of RCP have only been
possible using bilateral maxillary vein or direct sagittal sinus cannulation, quite different
techniques than are used clinically. [76 ] , [77 ] More conventional cannulation is
possible in the pig, but there are differences among species in the anatomy of the
cerebral venous circulation and in the proportion of flow going to the brain versus
extracranial structures. The use of different species as well as different techniques of
retrograde perfusion in experimental studies of RCP has yielded a confusing and often
conflicting welter of data that do not produce a clear picture of whether retrograde
perfusion is effective and, if so, why. [78 ] [80 ]
The most striking finding emerging from RCP research is how little of the retrograde
perfusate actually reaches the brain. A postmortem study in humans, using a latex
solution injected into the superior vena cava (SVC), demonstrates that most of the
retrograde flow is shunted from the SVC to the inferior vena cava, chiefly by the azygous
system. [81 ] Much of the flow bypasses the head altogether, but some retrograde
perfusion may occur via a system of collaterals surrounding the spinal cord, with flow
eventually reaching the brain via the vertebral veins. A recent clinical study showed
rapid uptake of a lipophilic tracer in the brains of three patients within several seconds
of initiation of RCP via the SVC. [82 ] Experimentally, retrograde flow to the brain can
be increased using special techniques to minimize the interference of venous valves,
e.g., by infusing directly into the sagittal sinus, but it is unclear whether data obtained by
using such techniques are relevant to the clinical situation. [77 ] Significant differences
in the percentage of flow reaching the brain may occur when selective perfusion via the
SVC is utilized compared with techniques in which the entire body is perfused
retrograde. However, even though it seems unlikely that the rate of RCP can be
manipulated clinically so that it is high enough to provide complete nutritive
maintenance during arrest of antegrade flow, RCP still has immense clinical appeal as
a possible measure to prevent or ameliorate injury from particulate emboli, which are
the major source of permanent neurologic injury following aneurysm surgery. [22 ]
Despite the confusion generated by the various experimental studies of RCP, there
does seem to be consensus with respect to a few observations. With selective superior
vena caval perfusion, less than 5 percent of retrograde flow returns via the arch vessels,
far too little to meet the ongoing metabolic demands of the brain by even the most
optimistic estimates, even in the presence of hypothermia. [35 ] Nevertheless, some
uptake of nutrients does occur, since blood returning to the arch is desaturated, and
depletion of high-energy phosphates and decline of intracellular pHas assessed by
MRIare less severe than with HCA alone. [83 ] It is also clear that retrograde perfusion
gradually leads to cerebral edema, at a rate that depends on the venous perfusion
pressure. Even at the minimum pressures required for effective retrograde flow,
development of cerebral edema clearly limits the safe duration of RCP. [76 ] , [84 ] , [85 ]
Results from a series of studies in our laboratory, begun with some skepticism about
RCP, demonstrate that RCP is more effective than HCA in preserving cerebral function
in pigs at 20°C for 90 minutes, even when the head is packed in ice. [35 ] This suggests
that effective maintenance of hypothermia is not the only mechanism at work during
RCP; theories to explain the superiority of RCP over HCA in this study include the
potential benefits of even a trickle of nutritive flow and the possible importance of
removing metabolites or other toxic substances. A subsequent study in our laboratory
suggests that RCP also may be effective in mitigating the harmful effects of particulate
emboli under some circumstances, an aspect of RCP particularly attractive when
considering its use for aortic arch surgery. [86 ] However, this study also documented
some adverse effects of RCP following embolization when high perfusion pressures
were required.
Despite the relative lack of substantive evidence proving the efficacy of RCP, a dearth
of knowledge regarding its physiologic consequences, and continuing uncertainty
regarding the best method for implementation, some surgeons have adopted the
method for routine clinical use in aneurysm surgery. [87 ] [89 ] We reserve RCP for
patients who are at the greatest risk for embolization as a consequence of thrombus or
atheroma present in the aorta at the time of aneurysm repair. Although we still see
embolization in these selected high-risk patients even with RCP, we believe RCP may
be of some benefit in minimizing these incidents. [45 ]
Clinical Implementation of RCP

Our current policy is to use short periods of retrograde perfusion in patients who have a
high risk of embolization because of clot or atheroma in the aorta, recognized either
preoperatively or intraoperatively; this includes only about 20 percent of our patients.
To initiate retrograde perfusion, we infuse blood into either one or both venae cavae at
a flow rate to maintain the SVC pressure between 15 and 20 mmHg. Given the rich
network of collaterals between the SVC and IVC, it probably makes no difference
whether inflow is into the SVC, into the IVC, or into both venae cavae. Cardiac
distension is avoided by choking both venae cavae. When whole-body retrograde
perfusion is carried out in this fashion, the initial flow rate is usually 800 to 1000 mL/min,
but once the venous capacitance vessels have been filled, a flow of 100 to 500 mL/min
is usually sufficient to maintain SVC pressure at 15 to 20 mmHg.
In general, anesthesia for repair of aortic arch aneurysms does not differ from methods
used for conventional open heart surgery, which rely primarily on the use of high doses
of narcotics. Routine hemodynamic monitoring includes a Swan-Ganz catheter, a
jugular venous bulb catheter, and right radial and femoral arterial catheters. Electrodes
are placed for EEG surveillance, and evoked potential monitoring is carried out using
auditory clicks and the median nerve, as well as the posterial tibial nerve if significant
resection of the descending thoracic aorta is planned. Transesophageal
echocardiographic monitoring of ventricular function is also carried out routinely.
We no longer administer barbiturates because, at the doses recommended to enhance

cerebral protection, they significantly depress myocardial function and because there
are conflicting laboratory data with regard to their effectiveness in the presence of
hypothermia. [51 ] We give 1 to 2 g methylprednisolone at the onset of perfusion in all
cases where the duration of HCA is anticipated to exceed 30 minutes and continue to
give steroids for another 48 hours postoperatively (125 mg q6h for 24 h; then 125 mg
q12h for 24 h).
In patients in whom a thoracotomy is utilized, use of a double-lumen tube that permits

selective ventilation of the right lung is helpful if substantial dissection and mobiliza tion
of the descending thoracic aorta are necessary before institution of cardiopulmonary
bypass.
Although some controversy still exists about whether pH during cooling should be
maintained according to alpha-stat or pH-stat principles, we continue to utilize values
corrected for temperature, the alpha-stat approach. We rely on a long duration of
cooling, a low esophageal temperature, and topical hypothermia to ensure adequate
cerebral protection during HCA.
PERFUSION
The routine protocol for perfusion used for intracardiac operations is also utilized for
repair of arch aneurysms; a membrane oxygenator is used in all cases. In all
aneurysms, a shunt is placed between the arterial and venous perfusion catheters. By
moving clamps appropriately, this setup allows rapid institution of whole-body
retrograde perfusion or placement of a second antegrade perfusion catheter if needed.
Incision
In 80 to 90 percent of aortic arch cases, an extended median sternotomy incision is

used. This incision gives access to the ascending aorta, the arch, and the proximal
descending thoracic aorta as far as 5 cm beyond the origin of the left subclavian artery.
The conventional median sternotomy is extended along the border of the left
sternocleidomastoid muscle on the left side of the neck. The strap muscles of the left
side of the neck are incised, and the left innominate vein is temporarily ligated and
divided. If the anticipated surgical procedure involves both intracardiac pathology and
resection of the aorta beyond the proximal descending thoracic aorta, some surgeons
advocate a transverse T incision perpendicular to the sternotomy to allow the entire
operation to be done in one procedure. We prefer to carry out the repair in two stages,
using the elephant trunk approach. [90 ]
In patients with a lesion primarily in the descending aorta that extends no farther
proximally than the distal ascending aorta, a left lateral thoracotomy in the fifth or sixth
intercostal space is the incision of choice; this can be extended inferiorly across the
costochondral plate, if necessary. Most frequently, we use a left lateral thoracotomy for a
descending thoracic or thoracoabdominal aneurysm in which there is not enough
normal aorta between the origin of the left subclavian artery and the proximal margin of
the aneurysm to allow safe cross-clamping for the proximal anastomosis.
On the rare occasions when aortic valve replacement is needed concurrent with repair
of a descending thoracic aortic aneurysm, a bilateral thoracotomy can be used, with an
oblique sternal incision connecting incisions in the fourth intercostal space on the left
and in the third interspace on the right. We use this approach in only 1 to 2 percent of
patients. This incision has a serious deleterious effect on pulmonary function; it puts
both phrenic nerves at risk; it is associated with more postoperative bleeding, and in
our hands it has been accompanied by a high operative mortality.
Cooling and Rewarming
We cool using perfusate at 10°C, monitoring both rectal and esophageal temperatures.
During rewarming, we never raise blood temperature above 37°C, and we avoid
creating a gradient exceeding 10°C between blood and tissues. Warming is
discontinued when the patient reaches an esophageal temperature of 35°C and a rectal
temperature of 30 to 32°C.
Graft and Suture Materials
We use collagen-impregnated grafts whenever possible; excise the aneurysmal portion

of the aorta, and do a full-thickness anastomosis to the remaining normal aorta. We use
Teflon felt on the outside of the aortic wall for reinforcement and place the graft within
the cuff of aorta. Some surgeons feel that reinforcing anastomoses with Teflon felt is not
necessary.
On rare occasions in which an extensive resection is required and a great deal of
bleeding is anticipated, we use an endoaneurysmal or inclusion technique. In these
patients we often place a shunt between the wrapped aorta and the right atrium, as
originally described by Cabrol et al. [91 ]
Most anastomoses are carred out using 3-0 Prolene, but 2-0 Prolene is used for
suturing one large graft to another because the lifetime integrity of this anastomosis is
totally dependent on the suture.
Myocardial Protection
We use only a single dose of crystalloid cardioplegia if the coronary ostia are readily
accessible. Otherwise, 60 to 100 meq potassium is infused into the pump over 1 to 2
minutes just prior to arrest of the circulation; this effectively changes ventricular
fibrillation to asystole. For the remainder of the procedure, we rely on total-body
hypothermia for myocardial protection. Other surgeons use more elaborate
cardioplegia protocols with good results.
Prevention of Paraplegia
Although the possible development of paraplegia is not a major concern with most
operations involving the aortic arch, it is a consideration in procedures involving the
descending thoracic and thoracoabdominal aorta. In these patients, some protection is
afforded by the use of total-body hypothermia, but additional safeguards are warranted
to avoid this complication.
During operations for resection of the distal arch plus a significant portion of the
descending aorta, we routinely monitor somatosensory evoked potentials (SSEPs).
Intercostal vessels are sacrificed gradually prior to institution of cardiopulmonary
bypass; each vessel is clamped initially, and a vessel is sacrificed only if no change in
SSEPs is seen for several minutes after its temporary occlusion. [92 ]
Postoperatively, SSEP monitoring is continued until the patient awakens. Function of

the lower extremities is assessed clinically on an hourly basis for a total of 72 hours of
postoperative monitoring. If a change in SSEPs or a deterioration in motor function of
the lower extremities is seen, blood pressure is increased, and intrathecal pressure is
decreased by withdrawal of cerebrospinal fluid (CSF) via an intrathecal catheter. These
maneuvers to increase spinal cord perfusion pressure have proven successful in
reversing the manifestations of late-onset paraparesis in the majority of our patients and
also have been effective in the hands of others. [93 ]
Control of Hemorrhage
Most current aortic surgery is carried out using antifibrinolytic agents of various kinds to
inhibit bleeding. We routinely use tranexamic acid, but others have reported that
epsilon-aminocaproic acid is as effective. The use of aprotinin remains controversial;
some surgeons have observed an untoward incidence of intravascular thrombosis when
using this protease inhibitor in conjunction with HCA, [94 ] , [95 ] but others feel that the
drug is safe if adequate doses of heparin are used concurrently. [96 ] Severe allergic
reactions to aprotinin have been reported. [97 ]
In simple cases involving only a short interval of hypothermia, such as a Bentall

procedure, blood and blood products are not sent routinely to the operating room, and
most patients do not require transfusion. If HCA for longer than 30 minutes or a duration
of perfusion exceeding 3 hours is anticipated, 2 to 4 units of fresh frozen plasma and 6
to 12 units of platelets are brought to the operating room at the end of perfusion. These
are infused promptly if any question arises concerning the adequacy of hemostasis
after protamine is given.
Use of Glues
European surgeons have championed strengthening the often friable aortic tissue
present in patients requiring aortic arch replacement using various cross-linking agents
and biologic glues. [98 ] Favorable results have been reported with formol resorcinol
glue, [99 ] glutaraldehyde, [100 ] and various biologic glues, which often have a
fibrinogen base. We have not found any of these agents to be necessary.
Treatment of Infected Grafts and Mycotic Aneurysms
In patients in whom a previously inserted graft has become infected, or if the patient is
supected to have a mycotic aneurysm, our initial strategy is to treat the patient for
several days with specific intravenous antibiotics when the organism is known and with
broad-spectrum antibiotics otherwise. At the time of surgery, the entire infected
aneurysm or graft is removed and replaced with a new graft; often, the organism
causing the infection can be cultured from the resected specimen. Intravenous
antibiotics are continued for 6 weeks, and if a suitable agent can be found, oral
antibiotic therapy is instituted for an additional 3 to 6 months. In cases of a frankly
purulent operating field, the omentum may be brought into the wound and tacked over
the implanted prosthetic graft. Others report the successful use of antibiotic-preserved
or cryopreserved homografts in this setting. [10 ] , [11 ]
REPRESENTATIVE PROCEDURES
Not all techniques useful in dealing with aneurysms of the aortic arch can be included
using a single representative case, so we will describe three typical patients and
procedures to illustrate different aspects of aortic arch surgery.
A Bentall Procedure, with Replacement of the Underside of the Aortic Arch
The patient is a 25-year-old man whose ascending aortic aneurysm was found during
an echocardiogram undertaken as part of an investigation of possible Marfan
syndrome. Clinical examination confirmed the diagnosis of Marfan syndrome, and CT
scan demonstrated that the aortic sinuses and the ascending aorta were dilated to
approximately 5.5 cm, with the dilatation extending up to the proximal aortic arch (Fig.
40-5A) . Cardiac catheterization revealed mild to moderate aortic insufficiency with
normal left ventricular function and normal coronary artery anatomy.
The operation was performed electively. Cannulation for cardiopulmonary bypass was
effected via catheters in the right common femoral artery and in the right atrium.
Cardiopulmonary bypass was begun gradually using cold blood perfusate, and when
the heart stopped ejecting satisfactorily, the ascending aorta was cross-clamped and
opened. Crystalloid cardioplegic solution was infused into both coronary arteries, and
the pericardium was lavaged copiously with cold saline. A vent was placed through the
right superior pulmonary vein to remove bronchial return from the left side of the heart.
Perfusate temperature was maintained at 10°C until the esophageal temperature
reached 20°C and was maintained between 15 and 20°C while the Bentall procedure
was performed.
After removing the aortic valve, a composite prosthesis was sutured to the aortic
annulus, utilizing interrupted pledgeted stitches. Buttons containing the coronary ostia,
each approximately 1 cm in diameter, were then dissected from the aorta, and the
remainder of the aorta proximal to the clamp was excised and discarded. The proximal
coronary arteries were mobilized carefully for a distance of approximately 1 cm. On the
right, this required sacrifice of some small branches passing to the right ventricular
outflow tract. Two small openings were made anteriorly and posteriorly on the graft, and
the coronary buttons were anastomosed to the graft with continuous stitches of 4-0
Prolene. Teflon felt buttressing was used to reinforce the buttons from behind. Holes in
the graft were designed to allow the aortic wall of the button to make contact with the
outer surface of the graft with the coronary artery lumen open to the bloodstream.
As the coronary anastomoses were being done, jugular venous samples were drawn
every 5 minutes and the perfusate temperature was lowered to 10°C. When jugular
oxygen saturation increased above 90 percent, the head was placed downward,
perfusion was discontinued, and the cross-clamp was removed. The distal ascending
aorta and proximal arch were mobilized and discarded, leaving a beveled aortic cuff
extending from the base of the innominate artery on the right to 1 cm proximal to the
ligamentum arteriosum and the recurrent laryngeal nerve on the left. The composite
Dacron graft was beveled and attached to the aorta with a continuous 3-0 Prolene
suture (Fig. 40-5B) . Care was taken to place a 1-cm cuff of Teflon felt outside the aorta
and to invaginate the graft within the aorta. The last few loops of the suture line were left
loose, the head was placed in a steep downward position, and perfusion through the
femoral artery catheter at a rate of 500 to 1000 ml/min was utilized to flush all air from
the aorta. The venous line was clamped during this time, and by occluding the opening
in the aorta, blood was forced through the heart to flush out all air.
Once all air was evacuated, the suture line was tightened, and perfusion with rewarming
was begun. A gradient of 10°C or less between perfusate temperature and esophageal
temperature was maintained at all times. Approximately 40 to 50 minutes of warming
was necessary to raise the esophageal temperature to 35 to 36°C and rectal
temperature to 30°C, at which time perfusion was stopped (Fig. 40-5C) .
Protamine sulfate was administered. Perfusion records showed an interval of

cardiopulmonary bypass of 150 minutes. Myocardial ischemic time was 120 minutes,
and hypothermic circulatory arrest lasted 20 minutes. Extubation was accomplished 6
hours following surgery. Hospital discharge took place on postoperative day 7, after
review of a postoperative CT scan with contrast and an angiogram that confirmed a
satisfactory repair. These studies also provide a baseline for long-term follow-up.
The patient is a 75-year-old man who had been followed for the previous 3 years with a
gradually expanding descending thoracic aortic aneurysm. Over the 6 months prior to
surgery, the maximal diameter of the aneurysm had grown from 6.5 to 7.3 cm. The
patient remained asymptomatic. The aneurysm involved the proximal descending
thoracic aorta, and its maximal dimension was just distal to the subclavian artery. The
patient had been known to be hypertensive for 30 years and also had smoked for 40
years, although he had stopped 15 years before; he was able to climb one flight of
stairs with only mild dyspnea, and a persantine-thallium scan of the heart showed no
abnormalities. CT imaging of the descending thoracic aorta suggested that there was a
substantial amount of thrombus and atheromatous debris in the aortic knob just distal to
the left subclavian artery. The aorta tapered from more than 7 cm in the proximal
descending thoracic aorta to about 3 cm at the diaphragm (Fig. 40-7A) .
Operation was carried out through a left thoracotomy in the sixth intercostal space, with
the incision extended inferiorly across the costochondral plate to improve the exposure;
the left internal mammary artery was preserved. The left femoral artery and vein were
dissected out and prepared for cannulation. The left inferior pulmonary vein also was
exposed as a potential cardiac vent site. The aorta, from approximately 3 cm distal to
the left subclavian artery down to the diaphragm, was gradually mobilized. Intercostal
arteries were serially clamped and then sacrificed when no changes in the SSEPs
developed. Care was taken not to manipulate the aorta adjacent to the left subclavian
artery.
Cannulation for cardiopulmonary bypass was carried out with a long perfusion catheter
inserted via the femoral vein and positioned in the right atrium with the aid of a
guidewire and transesophageal echo monitoring (Fig. 40-7B) . The left common femoral
artery was cannulated. Perfusion was begun gradually to avoid a rapid shift in the
perfusion patterns in the aorta that might dislodge atheromatous debris. Once perfusion
was established, care was exercised to avoid manipulating the descending thoracic
aorta at all, inasmuch as dislodged debris would be carried retrograde toward the arch
vessels and the coronary arteries. After about 10 minutes of cooling, ventricular
fibrillation occurred, pulmonary pressures rose to approximately 25 mmHg, and
transesophageal echocardiography suggested left ventricular dilatation. A vent catheter
was then introduced through the left inferior pulmonary vein into the left atrium.
After 40 minutes of cooling, the esophageal temperature had decreased to 13°C and
the rectal temperature to 18°C, and jugular venous saturations exceeded 95 percent.
Antegrade perfusion was discontinued, and infusion into the right atrial catheter was
begun at a rate to maintain the central venous pressure at approximately 10 to 12
mmHg (Fig. 40-7C) .
The left atrial vent was clamped, and the descending thoracic aorta was opened. Blood
emerging from the arch vessels and from the ascending aorta after passing through the
heart was aspirated in the aorta and returned to the reservoir for infusion into the right
atrium (Fig. 40-7C) . A cuff of the underside of the aortic arch, extending inferiorly to the
distal ascending aorta and superiorly to the margin of the left subclavian artery, was
fashioned. The recurrent laryngeal nerve was buried within the aortic tissue and
interfered substantially with proximal mobilization; accordingly, it was sacrificed, but the
vagus nerve was preserved. A 26-mm graft was brought into the field and anastomosed
to the native aorta with a running stitch of 3-0 Prolene (Fig 40-7D) ; Teflon felt was used,
and the graft was invaginated within the aorta. The arch vessels were then aspirated in
case there was any loose debris that had not been rinsed out with retrograde cerebral
perfusion. The graft was then filled with blood passing through the heart and with the
retrograde flow from the arch vessels. A perfusion catheter was placed in the graft, the
graft was clamped, and selective antegrade perfusion was begun with a blood
temperature of 10°C (Fig. 40-7E) .
Perfusion via the femoral catheter was used briefly to wash any loose debris in the
descending aorta out into the field. The distal cuff was fashioned, and the graft was
anastomosed to it, using a running stitch of 3-0 Prolene. Teflon felt was utilized (Fig.
40-7F) . The clamp on the graft was removed, and all flow in the entire body was
provided through the perfusion catheter placed in the graft. Warming was begun. The
left atrial vent was activated after the arch was closed. After about 10 minutes, left
ventricular fibrillation was present, and the heart was defibrillated. The left femoral artery
cannula was removed. The vent was clamped, and when left ventricular function was
quite satisfactory, the vent was removed.
A substantial period of warming followed. When this was completed, cardiopulmonary

bypass was discontinued, and the femoral vein and graft cannulas were removed (Fig.
40-7G) . The cooling period on cardiopulmonary bypass was 50 minutes. The period of
hypothermic circulatory arrest and intermittent retrograde perfusion was 40 minutes in
length; the period of cold selective antegrade perfusion of the upper body and heart
lasted 20 minutes, and the warming interval was 1 hour.
SSEP monitoring was continued during the first postoperative night, and arterial
pressures were maintained in the high-normal range. An intrathecal catheter had been
placed at the end of the procedure, and CSF pressure was kept below 10 mmHg for the
first 24 hours; the catheter was then removed.
The following morning the patient was awake and alert, and extubation was carried out.
Innervation to the lower extremities was intact; neurologic examinations to confirm
normal function in the lower extremities were done hourly for the next 48 hours. The
patient remained in the intensive care unit for the next 4 days for aggressive pulmonary
toilet; intermittent nasotracheal suctioning was required in part because of recurrent
nerve paralysis. Discharge occurred on postoperative day 12, after a baseline CT scan
and aortogram had been obtained.
The patient is a 75-year-old man who had been followed for the previous 3 years with a
gradually expanding descending thoracic aortic aneurysm. Over the 6 months prior to
surgery, the maximal diameter of the aneurysm had grown from 6.5 to 7.3 cm. The
patient remained asymptomatic. The aneurysm involved the proximal descending
thoracic aorta, and its maximal dimension was just distal to the subclavian artery. The
patient had been known to be hypertensive for 30 years and also had smoked for 40
years, although he had stopped 15 years before; he was able to climb one flight of
stairs with only mild dyspnea, and a persantine-thallium scan of the heart showed no
abnormalities. CT imaging of the descending thoracic aorta suggested that there was a
substantial amount of thrombus and atheromatous debris in the aortic knob just distal to
the left subclavian artery. The aorta tapered from more than 7 cm in the proximal
descending thoracic aorta to about 3 cm at the diaphragm (Fig. 40-7A) .
Operation was carried out through a left thoracotomy in the sixth intercostal space, with
the incision extended inferiorly across the costochondral plate to improve the exposure;
the left internal mammary artery was preserved. The left femoral artery and vein were
dissected out and prepared for cannulation. The left inferior pulmonary vein also was
exposed as a potential cardiac vent site. The aorta, from approximately 3 cm distal to
the left subclavian artery down to the diaphragm, was gradually mobilized. Intercostal
arteries were serially clamped and then sacrificed when no changes in the SSEPs
developed. Care was taken not to manipulate the aorta adjacent to the left subclavian
artery.
Cannulation for cardiopulmonary bypass was carried out with a long perfusion catheter
inserted via the femoral vein and positioned in the right atrium with the aid of a
guidewire and transesophageal echo monitoring (Fig. 40-7B) . The left common femoral
artery was cannulated. Perfusion was begun gradually to avoid a rapid shift in the
perfusion patterns in the aorta that might dislodge atheromatous debris. Once perfusion
was established, care was exercised to avoid manipulating the descending thoracic
aorta at all, inasmuch as dislodged debris would be carried retrograde toward the arch
vessels and the coronary arteries. After about 10 minutes of cooling, ventricular
fibrillation occurred, pulmonary pressures rose to approximately 25 mmHg, and
transesophageal echocardiography suggested left ventricular dilatation. A vent catheter
was then introduced through the left inferior pulmonary vein into the left atrium.
After 40 minutes of cooling, the esophageal temperature had decreased to 13°C and
the rectal temperature to 18°C, and jugular venous saturations exceeded 95 percent.
Antegrade perfusion was discontinued, and infusion into the right atrial catheter was
begun at a rate to maintain the central venous pressure at approximately 10 to 12
mmHg (Fig. 40-7C) .
The left atrial vent was clamped, and the descending thoracic aorta was opened. Blood
emerging from the arch vessels and from the ascending aorta after passing through the
heart was aspirated in the aorta and returned to the reservoir for infusion into the right
atrium (Fig. 40-7C) . A cuff of the underside of the aortic arch, extending inferiorly to the
distal ascending aorta and superiorly to the margin of the left subclavian artery, was
fashioned. The recurrent laryngeal nerve was buried within the aortic tissue and
interfered substantially with proximal mobilization; accordingly, it was sacrificed, but the
vagus nerve was preserved. A 26-mm graft was brought into the field and anastomosed
to the native aorta with a running stitch of 3-0 Prolene (Fig 40-7D) ; Teflon felt was used,
and the graft was invaginated within the aorta. The arch vessels were then aspirated in
case there was any loose debris that had not been rinsed out with retrograde cerebral
perfusion. The graft was then filled with blood passing through the heart and with the
retrograde flow from the arch vessels. A perfusion catheter was placed in the graft, the
graft was clamped, and selective antegrade perfusion was begun with a blood
temperature of 10°C (Fig. 40-7E) .
Perfusion via the femoral catheter was used briefly to wash any loose debris in the
descending aorta out into the field. The distal cuff was fashioned, and the graft was
anastomosed to it, using a running stitch of 3-0 Prolene. Teflon felt was utilized (Fig.
40-7F) . The clamp on the graft was removed, and all flow in the entire body was
provided through the perfusion catheter placed in the graft. Warming was begun. The
left atrial vent was activated after the arch was closed. After about 10 minutes, left
ventricular fibrillation was present, and the heart was defibrillated. The left femoral artery
cannula was removed. The vent was clamped, and when left ventricular function was
quite satisfactory, the vent was removed.
A substantial period of warming followed. When this was completed, cardiopulmonary

bypass was discontinued, and the femoral vein and graft cannulas were removed (Fig.
40-7G) . The cooling period on cardiopulmonary bypass was 50 minutes. The period of
hypothermic circulatory arrest and intermittent retrograde perfusion was 40 minutes in
length; the period of cold selective antegrade perfusion of the upper body and heart
lasted 20 minutes, and the warming interval was 1 hour.
SSEP monitoring was continued during the first postoperative night, and arterial
pressures were maintained in the high-normal range. An intrathecal catheter had been
placed at the end of the procedure, and CSF pressure was kept below 10 mmHg for the
first 24 hours; the catheter was then removed.
The following morning the patient was awake and alert, and extubation was carried out.
Innervation to the lower extremities was intact; neurologic examinations to confirm
normal function in the lower extremities were done hourly for the next 48 hours. The
patient remained in the intensive care unit for the next 4 days for aggressive pulmonary
toilet; intermittent nasotracheal suctioning was required in part because of recurrent
nerve paralysis. Discharge occurred on postoperative day 12, after a baseline CT scan
and aortogram had been obtained.
RESULTS
Over the past 10 years, we have operated on 427 patients with aneurysms involving the
aortic arch. The great majority of the lesions have begun in the ascending aorta and
have involved either an open distal anastomosis (31 percent) or replacement of the
ascending aorta and the underside of the arch (38 percent). In 15 percent, the entire
aortic arch required replacement, and in 16 percent, the aortic arch and the descending
thoracic aorta were involved. Overall mortality was 11 percent, with a mortality of 8 to 9
percent in operations primarily involving the ascending aorta and 15 to 16 percent for
operations involving the entire arch or the arch and descending aorta.
The average age of our patients was 61 years. Fifty-nine percent were males.
Twenty-eight percent were operated on as emergencies, and another 15 percent
urgently because of acute dissections or impending rupture. Fifty-seven percent had a
history of cigarette smoking.
In the majority of our patients, HCA alone was used for cerebral protection. Among the
225 patients whose operations took place since 1992, however, 21 percent underwent
RCP as well as HCA; 11 percent had supplemental use of a combination of retrograde
and selective antegrade perfusion, and 4 percent had selective antegrade perfusion in
addition to HCA.
The major morbidity following operations was neurologic. Twenty percent of patients
suffered temporary neurologic dysfunction, and 10 percent suffered strokes; 7 percent
were left with permanent focal neurologic impairment. The highest morbidity as well as
mortality was seen in the group of patients with arch and descending thoracic aortic
lesions; temporary neurologic impairment occurred in 33 percent and focal lesions in 21
percent, with permanent residua in 16 percent.
Renal failure requiring dialysis was seen in 4 percent of patients overall but in 10
percent of patients with arch and descending thoracic aneurysms.
Operation was carried out via a median sternotomy in 82 percent, using a left lateral
thoracotomy in 15 percent, and via a bilateral thoracotomy in 3 percent. Mortality in the
sternotomy group was slightly lower (9 percent) than in the left thoracotomy group (13
percent), but it was a staggering 55 percent in the bilateral thoracotomy group. The
incidence of severe respiratory insufficiency requiring tracheostomy also differed with
type of incision; 16 percent of all patients required tracheostomy, but the incidence was
32 percent in those patients with a left thoracotomy incision and 55 percent in those with
a bilateral thoractomy. The incidence of permanent neurologic sequelae was 6 percent
in the sternotomy group, 17 percent in those operated on via a left lateral thoracotomy,
and 18 percent in the bilateral thoracotomy group.
In recent years, both early and late mortality has been reduced significantly: overall
mortality fell from 16 percent in 202 patients operated on between 1985 and 1992 [101
] to 7 percent in 225 patients operated on since 1992 ( p = 0.004). The improvement is
especially marked among what we consider high-risk patients: those older than 60
years, who have evidence of clot or atheroma in the aorta, or who are undergoing total
arch or arch and descending aorta resections. In the 161 patients operated on since
1992 with one or more of these risk factors, mortality was 6 percent, compared with a
23 percent mortality in 138 comparable patients from the earlier cohort ( p = 0.001).
Unfortunately, the incidences of stroke and of permanent neurologic dysfunction have
remained essentially unchanged: 8 percent in the more recent patients versus 10
percent in the earlier group, and still 10 percent in the recent high-risk group.
Our results are similar to the outcomes in other recent large series in which aortic arch
aneurysms were repaired using HCA. Svensson et al. [102 ] report a 10 percent
mortality and a 7 percent incidence of stroke in 656 patients with arch aneurysms,
excluding patients operated on through a left thoracotomy. In a series of 130 patients
with aortic arch repairs, Laas et al. [103 ] had a 14 percent mortality and a 9 percent
incidence of serious neurologic sequelae. In an earlier series by Crawford et al., [104 ]
mortality was 9 percent; more recently, Coselli et al. [88 ] report an early mortality of 6
percent and a late mortality of 9 percent in 227 patients, with only a 3 percent incidence
of stroke, which they attribute to the use of retrograde cerebral perfusion in almost half
their patients.
In Svensson's series, there was an increased incidence of stroke after 40 minutes of

HCA and a marked increase in mortality if HCA exceeded 65 minutes. [102 ] Increased
age, the presence of disease in the descending aorta, a previous history of
cerebrovascular disease, and prolonged cardiopulmonary bypass durations were other
factors associated with an increased mortality or risk of stroke. In Crawford's earlier
series, additional factors predictive of early postoperative death following arch
replacement were severe symptoms, diabetes, a previous proximal aortic operation,
and postoperative tracheostomy or cardiac dysfunction. [104 ] In all these series,
postoperative stroke was often associated with a fatal outcome.
ETIOLOGY AND PATHOGENESIS
The etiology of thoracoabdominal aneurysms, in order of frequency, is medial

degenerative disease (myxomatous or myxoid degeneration, senile aorta), dissection,
Marfan syndrome (cystic medial necrosis), Ehlers-Danlos syndrome, infection (mycotic),
aortitis (Takayasu's disease), and trauma ( Table 41-1 ). [1 ] [3 ] Traditionally, many
thoracic aortic aneurysms were termed atherosclerotic aneurysms. Although
atherosclerosis and aortic aneurysms share common risk factors and frequently occur
concomitantly, thoracic aortic aneurysms primarily are the result of age-related changes
in elastin and collagen that lead to a loss of integrity and strength. Subsequent
enlargement and aneurysm formation provide fertile ground for superimposed intimal
atherosclerosis and further degeneration of the aortic wall.
Most etiologic conditions produce diffuse, fusiform aneurysmal dilatation. One

exception to this is infection (mycotic aneurysm), which frequently produces a saccular
aneurysm at localized areas of the aortic wall destroyed by the mycotic process.
Characteristically, for unknown reasons, such mycotic aneurysms tend to occur along
the lesser curvature of the transverse aortic arch or in the upper abdominal aorta
immediately posterior to the origin of the visceral vessels. In such cases, only a portion
of aortic circumference is affected and consequently localized weakening causes a
diverticular or saccular outpouching. Saccular aneurysms of the thoracic aorta, taken as
a whole, are more frequently secondary to atherosclerosis, although both mycotic and
degenerative saccular aneurysms may be superimposed on or combined with fusiform,
more generalized aneurysmal disease of the thoracoabdominal aorta.
In patients with Marfan syndrome, the aortic wall is weakened by fragmentation of

elastic fibers and deposition of extensive amounts of mucopolysaccharides. [4 ] Many
patients with Marfan syndrome have an abnormal mutation of the fibrillin gene located
on the long arm of the 15th chromosome. [5 ] Abnormal fibrillin in the extracellular matrix
decreases connective tissue strength in the aortic wall and produces abnormal elastic
properties that predispose the aorta to dilatation from wall tension resulting from left
ventricular ejection impulses (DP/DT). Laplace's law causes cycles of progressive
dilatation as increasing luminal diameters produce greater wall tension. The usual
histologic changes of the aging aorta include cystic medial necrosis, elastin
fragmentation, fibrosis with increased collagen, and medial necrosis. [6 ]
The diameter of the aorta remains the single most important factor in the decision to
repair a thoracic aortic aneurysm. The Ad Hoc Committee on Reporting Standards of
the Society for Vascular Surgery and the North American Chapter of the International
Society for Cardiovascular Surgery states that the definition of an aneurysm is a
permanent localized dilatation of an artery having at least 50 percent increase in
diameter compared to the expected normal diameter of the artery in question. [7 ] This
definition can be applied to the thoracic aorta, but, it is first necessary to know the
normal diameter. The average diameter of the mid-descending thoracic aorta is 28 mm
for men and 26 mm for women; at the level of the celiac axis 23 mm for men and 20 mm
for women; and the infrarenal aorta 19.5 mm for men and 15.5 mm for women. [8 ]
Normal aortic diameters, however, vary according to age, gender, and body surface
area. Aortic enlargement with advancing age is reported in a number of studies. [9 ]
Even when corrected for age and body surface area, aortic size is statistically smaller in
women than in men. On average, the aorta is 2 to 3 mm greater in diameter for men
than for women. Body surface area is a better predictor of aortic size than height or
weight and best correlates with aortic diameter in patients less than 50 years of age.
[10 ]
NATURAL HISTORY
The natural history of thoracic and thoracoabdominal aortic aneurysms is less well
defined in the literature than that for aneurysmal disease involving the infrarenal
abdominal aorta. Crawford reported 94 patients who were diagnosed with
thoracoabdominal aortic aneurysms but did not undergo operative resection and
replacement because of patient choice, age, associated co-morbidity, insufficient
dilatation to warrant replacement, or because treatment was staged with the more
proximal or distal operation performed first, and the thoracoabdominal aneurysm
deferred to a second stage. [11 ] The 2-year survival rate for this group of patients was
only 24 percent, and half of the deaths were owing to rupture of the thoracoabdominal
aortic aneurysm.
Cambria reported 57 patients with nondissecting thoracoabdominal aortic aneurysms

preselected for nonoperative management. [12 ] The overall survival rate was 39
percent, and the repair-free survival rate was only 17 percent at 5 years. They found an
expansion rate of 0.2 cm per year. Dapunt, however, reported the rate of enlargement of
thoracic and thoracoabdominal aortic aneurysms in 67 patients followed by computed
tomography scanning, and demonstrated an enlargement rate of 0.43 cm per year. [13 ]
A significantly higher rate of aneurysm expansion was found in smokers and in patients
with larger aortic diameters (greater than 5 cm) at diagnosis. No correlation was noted
between rate of enlargement and age, sex, or the presence of dissection. In a
population-based study, Bickerstaff reported the outcome of thoracic aortic aneurysms
in 72 patients. [14 ] Rupture occurred in 53 patients (74 percent) and 50 died. The
median interval between diagnosis and rupture in 16 patients with known aneurysms
was 2 years. Ninety-five percent of aortic dissections ruptured and 51 percent of
nondissecting aneurysms ruptured. The actuarial 5-year survival for all 72 patients was
13 percent; for patients with aortic dissection it was 7 percent, and for those without
dissection 19.2 percent. [14 ]
Pressler and McNamara compiled data from 176 patients with the diagnosis of thoracic
aortic aneurysm. [15 ] In their study, 90 patients (51 percent) had arteriosclerotic
fusiform aneurysms and 86 (49 percent) had dissecting aneurysms. Eighty-nine percent
of the arteriosclerotic aneurysms and 41 percent of the dissecting aneurysms were
located in the descending thoracic aorta. Seventy-eight percent of patients with
dissecting aneurysms had symptoms of pain in the back or chest, whereas only 42
percent of patients with atherosclerotic aneurysms had back or chest pain. Rupture
caused 37 of 48 deaths (77 percent) in 59 patients with dissecting aneurysms, and 25
of 57 deaths (44 percent) in 76 patients with atherosclerotic aneurysms. Concomitant
cardiovascular disease was the second leading cause of death in patients with
atherosclerotic aneurysms not treated surgically [19 deaths of 86 patients (22 percent)],
but only one of 59 patients with dissecting aneurysms not treated surgically died of heart
disease.
Aortic size at the time of diagnosis is related to the development of complications

including rupture. Pressler and McNamara reported that eight of nine ruptured
descending thoracic aortic aneurysms were larger than 10 cm. [15 ] In the report by
Dapunt on descending thoracic and thoracoabdominal aortic aneurysms, mean aortic
diameter at the time of rupture was 6.1 cm. [13 ] Crawford found a mean size of 8 cm at
the time of rupture in a series of 117 patients with descending thoracic and
thoracoabdominal aortic aneurysms. [16 ] Factors associated with increased morbidity
and mortality from rupture and related complications include aneurysm size, presence
of dissection, previous rate of expansion, and hypertension ( Table 41-2 ).
Although thoracoabdominal aortic aneurysms may remain asymptomatic for prolonged

periods of time, most ultimately produce a variety of symptoms prior to rupture and
death. When first seen, roughly 43 percent of patients are asymptomatic, [3 ] but
approximately 48 percent are symptomatic at the time of diagnosis. The most common
symptom is pain in the back, posterior chest, abdomen, or flank. This symptom is
caused by either pressure on adjacent structures, aneurysm expansion, intramural
hematoma, or contained rupture. Compression of the trachea or bronchus can produce
stridor, wheezing, or cough. Pneumonitis distal to an area of bronchial obstruction
develops if secretions cannot be cleared. Hemoptysis occurs when an aneurysm
erodes directly into the pulmonary parenchyma or bronchus. Compression of the
esophagus may produce dysphasia, whereas erosion into the esophagus causes
hematemesis. [17 ] Similarly, erosion into the duodenum causes either partial
obstruction or intermittent/massive gastrointestinal bleeding. Compression of the liver
or porta hepatis is uncommon, but when this occurs, jaundice results. Hoarseness is
owing to traction on the vagus nerve as the distal aortic arch expands, to produce
recurrent laryngeal nerve paralysis. Thoracic or lumbar vertebral body erosion causes
back pain, spinal instability, and neurological deficits from spinal cord compression.
Mycotic aneurysms have a peculiar propensity to destroy vertebral bodies. Additionally,
neurological symptoms, including paraplegia and/or paraparesis may occur with
thrombosis of intercostal and spinal arteries. This is most frequently seen with acute
aortic dissection, which may occur primarily, or become superimposed on medial
degenerative fusiform aneurysmal disease. Heart failure develops after aorto-inferior
vena caval or iliac vein fistulas. Thoracic aortic aneurysms, similar to aneurysms in other
locations, may produce distal emboli of clot or atheromatous debris that gradually
obliterates and thromboses visceral, renal, or lower extremity branches. Secondary
infection of atheromatous debris and clot within an aneurysm may produce generalized
sepsis. Nine percent of patients with thoracoabdominal aortic aneurysms present with
frank rupture at the time of diagnosis. [3 ]
DIAGNOSTIC EVALUATION
Although physical examination may detect large infrarenal abdominal aortic aneurysms,
thoracic involvement of a palpable aortic aneurysm is rarely suspected during physical
examination unless the abdominal component is so extensive that the cephalic
projection cannot be palpated because of the costal margins. Plain chest
roentgenograms may demonstrate widening of the descending thoracic aortic shadow,
which may be highlighted by a rim of calcification outlining the dilated aneurysmal aortic
wall. Aneurysmal calcium may also be seen in the upper abdomen on a standard
roentgenogram made in the anterior, posterior, or lateral projections (Fig. 41-1) .
Enough calcification may be present in the aortic wall to make the diagnosis of
aneurysms in 65 to 75 percent of cases. A negative plane chest roentgenogram does
not exclude the diagnosis of aortic aneurysm.
Ultrasonography
Ultrasonography, although useful in evaluating infrarenal abdominal aortic aneurysms, is

not useful for imaging the thoracic or suprarenal aorta primarily because of overlying
lung tissue. [18 ] The advantages of ultrasonography are wide availability, low cost,
portability, noninvasiveness, lack of ionizing radiation, and rapid examination. When the
definitive neck of an infrarenal abdominal aortic aneurysm cannot be demonstrated at
the level of the renal arteries, thoracoabdominal aortic involvement should be
suspected.
Transesophageal echocardiography provides access to the proximal aorta, and

complements transabdominal ultrasonography. [19 ] , [20 ] The technique requires
considerable technical skill both in obtaining adequate images and in interpretation.
The technique is excellent for determining the presence of dissection but has limitations
in evaluating the region of the transverse aortic arch and upper abdominal aorta.
Computed Tomography
Computed tomography scanning is widely available and provides access to the entire
thoracic and abdominal aorta. In addition to diagnosis, information regarding location
and extent is provided. [21 ] Major branch vessels including the celiac, superior
mesenteric, renal, iliac arteries, and left subclavian and virtually all adjacent organs are
imaged. Although not widely available, computer programs can construct sagittal,
coronal, and oblique images as well as three-dimensional reconstructions. [22 ] , [23 ]
Computed tomography scanning, which is contrast enhanced, provides information
regarding the aortic lumen, mural thrombus, presence of aortic dissection, intramural
hematoma, mediastinal or retroperitoneal hematoma, aortic rupture, and periaortic
fibrosis associated with inflammatory aneurysms (Fig. 41-2) . [24 ]
Magnetic resonance imaging (MRI) employs radiofrequency energy and a strong

magnetic field to produce images. Although expensive, the technology is widely
available and has the capability of accessing the entire aorta. MRI images, compared
to computed tomography scanning, more clearly distinguish arteries and veins from
viscera and other surrounding tissue. [25 ] Recent advances in computer programming
construct images that quantify blood flow and have an appearance similar to
conventional angiography; this is referred to as MRI angiography. With further
refinements, MRI imaging may become the methodology of choice and all that is
necessary for evaluation of aortic disease. [26 ]
Aortography
Classical aortography remains the mainstay for preoperative evaluation of patients with
thoracoabdominal aortic aneurysms. [18 ] It has the ability to define the extent of
aneurysm, branch vessel involvement, and branch vessel stenotic lesions. Risks of
aortography include renal toxicity from large contrast volumes required to adequately fill
large aneurysms. There is the additional risk of embolization from laminated thrombus
secondary to manipulation of intraluminal catheters. To obtain satisfactory information
regarding branch vessels, anterior, posterior, oblique, and lateral views are obtained
simultaneously. Patients with suspected renal and/or visceral ischemia, aorto-iliac
occlusive disease, horseshoe kidney, or peripheral aneurysms should be considered
for aortography prior to thoracoabdominal aortic aneurysm repair.
Aortography is performed in a well-hydrated patient who is also receiving intravenous

fluids. Routinely, 1000 mL of 5% dextrose and Ringer's lactate solution with 25 g of
mannitol is given intravenously immediately prior to the procedure and is continued at
100 cc per hour following study. If at all possible, operation is delayed for 24 hours or
longer to determine the effects of angiography on renal function and to permit diuresis
of the contrast agent. If renal insufficiency occurs or is worsened, the surgical procedure
is postponed until renal function returns to normal or is satisfactorily stabilized.
PREOPERATIVE ASSESSMENT AND PREPARATION
Preoperatively all patients undergo a thorough evaluation to estimate operative risk with
emphasis placed on cardiac, pulmonary, and renal function. [27 ]
Heart
A history of coronary artery occlusive disease is present in 30 percent of patients with

thoracoabdominal aortic aneurysms. Additionally, cardiac disease is responsible for 49
percent of early deaths and 34 percent of late deaths. [2 ] , [3 ] Transthoracic
echocardiography is a satisfactory noninvasive screening method that evaluates both
valvular and biventricular function. Dipyridamole-thallium myocardial scanning identifies
regions of myocardium that are reversibly ischemic and is more practical than exercise
testing in this generally elderly population that commonly is limited by concurrent lower
extremity peripheral vascular disease. We routinely employ preoperative screening of
all patients for coronary artery disease with cine arteriography; however, in patients with
a significant history of angina or an ejection fraction of 30 percent or less, cardiac
catheterization and coronary arteriography are performed with aortography. Patients
who have asymptomatic thoracoabdominal aortic aneurysm and severe coronary artery
occlusive disease (left main, triple vessel, and proximal left anterior descending)
undergo myocardial revascularization prior to aneurysm replacement. In appropriate
patients, percutaneous transluminal angioplasty is carried out prior to operation.
Kidney
Renal function is assessed preoperatively by serum electrolytes, blood urea nitrogen

(BUN), and creatinine measurements. Renal size may be determined from a CT scan,
by ultrasound, or from the nephrogram obtained during aortography. Renal artery
patency is confirmed by arteriography. [28 ] Patients are not rejected as surgical
candidates based on renal function. Patients with preoperative renal failure and an
established hemodialysis program do not have significantly greater morbidity than
patients with normal renal function. Patients with severely impaired renal function, not on
chronic hemodialysis, frequently require transient temporary hemodialysis early after
operation. Additionally, patients with poor renal function secondary to severe proximal
renal occlusive disease are revascularized at operation by either renal arterial
endarterectomy or bypass grafting with the expectation that renal function will stabilize
or improve.
Lung
All patients undergo pulmonary function screening with arterial blood gases and
spirometry. [29 ] [31 ] Patients with an FEV 1 greater than 1.0 and a P CO 2 less than
45 are surgical candidates. In suitable patients, borderline pulmonary function frequently
is improved by stopping smoking, progressively treating bronchitis and weight loss, and
a general exercise program for a period of 13 months before operation. However,
operation is not withheld in patients with symptomatic aortic aneurysms and poor
pulmonary function. In such patients, preservation of the left recurrent laryngeal nerve,
phrenic nerve, and diaphragmatic function is particularly important.
OPERATIVE TREATMENT
Advances in anesthetic techniques, monitoring, and perfusion technology have

contributed to improved results in the treatment of thoracoabdominal aortic aneurysms.
As a result of advanced age and concomitant prevalence of associated coronary artery
occlusive disease, anesthesia is induced with narcotic agents (fentanyl) to minimize the
risk of myocardial depression. A large-bore central venous line (a three-lumen
12-gauge catheter) and a Swan-Ganz pulmonary artery catheter are placed for access
and monitoring. A right radial and, frequently, bilateral radial intra-arterial catheters are
placed for monitoring and blood withdrawal. Muscle relaxation is achieved and
maintained with pancuronium bromide. Either a double-lumen endobronchial tube is
placed for selective ventilation of the right lung and deflation of the left lung, or
alternatively a single-lumen endotracheal tube with an intrabronchial blocker is utilized.
Deflation of the left lung reduces retraction trauma to the lung, improves exposure and
alleviates the risk of cardiac compression. The patient is turned to a right lateral
decubitus position with the shoulders placed at 6080° and the hips flexed to 3040° from
horizontal. The position is stabilized using a bean bag. Arterial blood gases,
electrolytes, and serum glucose are monitored frequently (3060 minutes).
Intraoperatively the electrocardiogram, arterial and venous blood pressures, and
temperature are monitored continuously. In patients with a significant history of cardiac
disease and/or known impaired cardiac function, a transesophageal echocardiography
probe is inserted following induction of anesthesia.
Shortly after the induction of anesthesia, 2550 g of mannitol are given intravenously to
promote a vigorous diuresis. Intravenous crystalloid solutions are begun prior to
operation. The first liter consists of lactated Ringer's solution with 5% dextrose, and the
remainder, Ringer's solution without dextrose in sufficient volumes to maintain the
central venous pressure between 7 and 10 mm h 2 o and the pulmonary capillary wedge
pressure at normal or preanesthetic levels. Proximal blood pressure, cardiac
hemodynamics, and peripheral vascular resistance are maintained at optimal levels by
administration of sodium nitroprusside and/or nitroglycerin, and replacement of fluid and
blood losses. Nitroprusside is specifically discontinued several minutes before the
release of the distal aortic cross-clamp. Sodium bicarbonate solution is administered
routinely at a rate of 23 mEq/kg/h by continuous infusion during aortic cross-clamping to
prevent acidosis.
Throughout the procedure, hemoglobin and coagulation parameters are monitored

carefully and are adjusted primarily by replacing appropriate blood components. In
general, we administer fresh frozen plasma continuously throughout the operation, and
at least one pheresis unit of platelets at the time of aortic declamping. This minimizes
problems related to coagulopathy produced by dilution of coagulation proteins.
Intraoperatively shed blood from the operative field is returned as washed red cells
utilizing an autotransfusion device. Mechanized rapid transfusion devices using large-
bore central venous catheters for access are particularly valuable in restoring blood
volume immediately prior to declamping. In all patients, intravenous heparin, 1 mg/kg, is
given prior to aortic cross-clamping or bypass.
Classification of Thoracoabdominal Aneurysms
Thoracoabdominal aneurysms can involve the entire thoracoabdominal aorta from the
origin of the left subclavian artery to the aortic bifurcation or can involve only one or
more segments. Because of the extent and conduct of operation, risk and result vary
with the location and extent of aneurysmal involvement, Crawford developed a
classification that is used widely (Fig. 41-3) . Extent I thoracoabdominal aortic
aneurysms involve most of the descending thoracic aorta from the left subclavian artery
down to vessels in the abdomen. Usually the renal arteries are not involved in extent I
aneurysms. Extent II aneurysms begin at the left subclavian artery and reach the
infrarenal abdominal aorta even as far as the inguinal area. Extent III aneurysms involve
the distal half or less of the descending thoracic aorta and substantial segments of the
abdominal aorta. Extent IV are aneurysms that involve the upper abdominal aorta and
all or none of the infrarenal aorta.
Incisions
The thoracoabdominal incision varies in length and level, depending on the anticipated
extent of aortic replacement (Fig. 41-4A) . When the aneurysm extends into the superior
aspect of the thorax (Crawford's extents I and II), the upper portion of the
thoracoabdominal incision is through the 6th intercostal space or the bed of the
resected 6th rib. When the interspace is used, the upper rib may be divided at the neck
for additional proximal exposure. With lower aneurysms (Crawford's extents III and IV),
an incision through the 7th, 8th, or 9th interspace is employed according to the desired
level of exposure. A straight transverse incision through the 10th or 11th interspace is
used in patients with aneurysms between the diaphragm and aortic bifurcation
(Crawford extent IV). In all others, a gentle curve to reduce the risk of tissue necrosis at
the apex of the lower portion of the musculoskeletal tissue flap is made as the incision
crosses the costal margin. In patients with proximal aneurysms, the posterior portion of
the incision is located between the scapula and the spinal processes. The distal extent
of the incision is carried down to a level between the umbilicus and the pubic symphysis
unless the distal extent of the aneurysm is at the level of the renal/visceral arteries
(Crawford extent I); in this case, the incision is carried down only to the umbilicus.
Exposure
After entering the chest, the left lung is deflated. The diaphragm is divided in a circular
fashion to protect the phrenic nerve and to preserve as much diaphragm as possible.
Only a 1- to 1.5-cm rim of diaphragmatic tissue is left laterally for closure at the
completion of operation.
The abdominal aortic segment is exposed using a transperitoneal approach; the

retroperitoneum is entered lateral to the left colon. [32 ] A dissection plane is developed
in the retroperitoneum anterior to the psoas muscle and posterior to the left kidney. This
is extended directly to the left posterolateral aspect of the abdominal aorta. The left
colon, spleen, left kidney, and tail of the pancreas are retracted anteriorly and to the
right. An open abdominal approach permits direct inspection of the bowel, abdominal
viscera, and visceral blood supply following completion of the aortic reconstruction. An
entirely retroperitoneal approach is used in patients with a so-called hostile abdomen,
defined by multiple prior abdominal operations, or a history of extensive adhesions
and/or peritonitis.
The crus of the diaphragm is divided and the left renal, superior mesenteric, and celiac
arteries are identified but not circumferentially dissected or encircled with tapes.
Commonly, a large lumbar branch of the left renal vein courses posteriorly around the
aorta. This may be ligated and divided as needed. If a retroaortic left renal vein is
encountered, the vessel is divided between vascular clamps if the aortic repair extends
past the vein. Direct reanastomosis or interposition grafting of this retroaortic renal vein
is necessary if the left kidney appears congested with distended testicular, ovarian, and
adrenal collaterals.
Repair
Patients with extensive thoracoabdominal aortic aneurysms (Crawford extents I and II),
and particularly those with dissection, are at greatest risk for development of
postoperative paraplegia and paraparesis. In such patients, distal aortic perfusion
during the proximal aortic portion of the repair is employed using left atrium to femoral
artery (most commonly the left) bypass, with an inline centrifugal pump (Biomedicus,
Medtronic, Inc., Eden-Prairie, Minn.) (Fig. 41-4B) . If the pericardium was previously
entered for coronary artery bypass grafting or valve replacement (Fig. 41-4C) ,
cannulation of the superior or inferior pulmonary vein is equally effective. In patients with
iliac occlusive disease, an alternative distal aortic cannulation site, such as the lower
descending thoracic or abdominal aorta, may be selected rather than the femoral artery.
Careful examination of CT or MRI scans assists selection of an appropriate site for
direct aortic cannulation to avoid intraluminal thrombus and distal embolization. Bypass
flows are adjusted to maintain distal arterial pressures of 70 mm Hg while maintaining
normal proximal arterial and venous filling pressures. Flows between 1500 and 2500
ml/min are generally required. The patient's temperature is allowed to drift down to a
rectal temperature of 32 to 33°C. After aortic repair, an inline heat exchanger may be
employed for rewarming if necessary.
Preparation of the proximal aorta for cross-clamping is difficult only when the aneurysm
encroaches on the left subclavian artery. Under these circumstances, the distal aortic
arch is mobilized gently by dividing the remnant of the ductus arteriosis. The vagus and
recurrent laryngeal nerves are identified. The vagus nerve may be divided below the
recurrent nerve to provide additional mobility. In patients with postoperative hoarseness,
vocal cord paralysis is suspected and confirmed by direct examination. Treatment is by
simple Teflon injection or direct cord medialization. Careful circumferential dissection of
the distal transverse aortic arch separates it from the pulmonary artery and esophagus.
If cross-clamping proximal to the left subclavian artery is anticipated, the left subclavian
artery is separately and circumferentially mobilized. As for all branch vessels, encircling
tapes are avoided and minimal dissection is the rule. In patients with a prior left internal
mammary arterial bypass graft, either a left common carotid to subclavian bypass or a
left subclavian to carotid transfer is necessary to avoid cardiac ischemia when the
cross-clamp is applied upstream to the left subclavian artery.
The proximal anastomosis is made between aortic clamps, with the distal clamp placed
between T4 and T7. A collagen-impregnated woven Dacron graft (Meadox Medical Inc.,
Oakland, N.J.) is used. Distal aortic perfusion provides circulation to the viscera,
kidneys, lower extremities, and lower intercostal and lumbar arteries. The aorta is
transected 1 cm distal to the proximal clamp and separated from the esophagus to
permit full thickness sutures through the aortic wall without injuring the esophagus (Fig.
41-4C) . The anastomosis and all remaining anastomoses are made with a running 3-0
polypropylene suture (Fig. 41-4D) . Teflon felt strips are avoided. In patients with Marfan
syndrome and acute dissection, 4-0 polypropylene suture is used. As the aorta is
replaced from proximal to distal, the distal aortic clamp is moved sequentially to lower
positions along the aorta in and around visceral and renal vessels and the abdominal
aorta to maintain distal perfusion (Fig. 41-4E-H) . Even reduced runoff from extreme
proximal clamping provides cardiac unloading, that may be particularly beneficial for
patients with reduced cardiac function. Because of the nature of the disease, size,
calcification, intraluminal thrombus, and tortuosity of the aorta, sequential distal
clamping is more easily described than done.
Alternatively, atrio-distal bypass may be discontinued following completion of the

proximal anastomosis. The entire aneurysm then is opened longitudinally, passing
posterior to the left renal artery to the distal extent of the aneurysm. With a chronic
dissection, the partition between the true and false lumens is completely removed.
Aorto-visceral bypass then is restarted using a Y line off the arterial perfusion line and
separate balloon perfusion catheters placed within the origin of the celiac, superior
mesenteric, and renal arteries. This provides oxygenated blood to the abdominal
viscera and kidneys (Fig. 41-5) .
All patent intercostal arteries from T7 to L2 are reattached to one or more openings
made in the graft (Fig. 41-5B) . Large intercostal arteries with little or no back bleeding
are considered particularly important. After this is done, the proximal clamp is moved
down the graft to restore flow to the intercostal arteries (Fig. 41-5C) . Subsequently,
visceral and renal artery ostia are reattached to one or more openings in the graft. The
left renal artery requires a separate opening in the graft in 30 to 40 percent of the cases.
Visceral or renal artery stenosis is encountered in at least 25 percent of cases and
requires either endarterectomy or interposition bypass grafting. [1 ] , [2 ] In patients with
lower aortic aneurysms (i.e., Crawford extents III and IV) atrio-distal aortic bypass may
be modified to provide only atrio-visceral and/or renal bypass (Fig. 41-6) . This
technique avoids distal aortic or femoral cannulation, but reduces cardiac preload,
protects the renal parenchyma, reduces post clamp acidosis, and may reduce the risk
of postoperative bacterial translocation by reducing bowel ischemia.
An alternative technique for distal arterial perfusion is employed in selected patients,

i.e., primarily those with Crawford extents I, II, or III, and in whom cross-clamping at the
diaphragm is technically feasible but is not appropriate at the mid- and upper
mid-descending thoracic aorta. Atrio-femoral bypass is used but the distal aortic
anastomosis is made first to allow for sequential graft clamping as visceral arteries and
subsequently intercostal arteries are attached to the graft from below upward (Fig.
41-7AC) .
A staged operative procedure is preferred in patients presenting with extensive

aneurysmal disease involving the ascending aorta, arch, and descending thoracic or
thoracoabdominal aorta. When the distal thoracic aorta is not disproportionately large
compared to the proximal aorta and when the distal thoracic aorta is asymptomatic,
proximal aortic repair is done first. An important benefit of initial proximal aortic repair is
that it allows treatment of valvular and coronary artery occlusive disease at the first
operation. In these patients with so-called mega aorta, the elephant trunk technique
described by Hans Borst is employed (Fig. 41-8) . [33 ] In this technique the ascending
and transverse aortic arch are replaced first, leaving a segment of graft within the
proximal descending thoracic aorta to be used at the second procedure (Fig. 41-8A) .
The technique permits access to the distal graft at the second operation without the
need to dissect in and around the distal transverse aortic arch. This reduces or
eliminates risk of injury to the left recurrent laryngeal nerve, esophagus, and pulmonary
artery.
Closure
Following completion of aortic repair, protamine sulfate is administered to reverse

heparin. It is imperative that adequate hemostasis is achieved and secured at all suture
lines. The renal, visceral, and peripheral circulation is assessed. The aneurysmal wall is
then loosely wrapped around the aortic graft using a running suture. Bleeding through
the interstices of modern collagen sealed woven Dacron grafts, even in the presence of
heparinization, is virtually nonexistent. Generally, two posteriorly located thoracic
drainage tubes and a closed suction retroperitoneal drain are placed prior to closure.
The diaphragm is closed with running nonabsorbable suture; disruption postoperatively
is exceedingly rare. To stimulate and maintain renal function, a low-dose dopamine drip
of 2 to 3 µgmg per kg per minute is initiated and continued for 2448 hours. Patients are
generally weaned from the respirator overnight and extubated the following morning. All
drains are removed and antibiotics discontinued at 3648 hours postoperatively.
Ambulation is started on the second postoperative day.
The author does not routinely use CSF (cerebrospinal fluid) drainage. In patients in
whom this is considered necessary, an 18-gauge intrathecal catheter is placed through
the second or third lumbar space. The catheter permits aspiration of cerebrospinal fluid
and pressure monitoring throughout the operation, and may be continued for several
days postoperatively. CSF is allowed to passively drain from the catheter. CSF is
aspirated as needed during the period of aortic occlusion to keep the CSF pressure at
or below 10 mm Hg using a closed collection system.
PARAPLEGIA AND SPINAL CORD PROTECTION STRATEGIES
Incidence
The incidence of paraplegia or paraparesis, as reported in the literature, following

thoracoabdominal aortic aneurysms varies substantially and ranges from 4 to 32
percent. [3 ] Generally, in large series the incidence of paraplegia and paraparesis are
equally divided. [1 ] , [2 ] Up to 30 percent of patients who develop postoperative
neurological deficits initially awake with lower extremity function but develop deficits
subsequently. [2 ] The most important factors related to the development of
postoperative paraplegia are total aortic clamp time, the presence of acute dissection
and/or rupture, and extent of aorta replaced. The risk of spinal cord injury averages,
based on the Crawford classification, 13 percent for extent I, 28 to 31 percent for extent
II, 7 percent for extent III, and 4 percent for extent IV. [3 ] Although in the past aortic
dissection was identified as a risk factor, in more recent experience, dissection is no
longer a risk factor for the development of postoperative paraplegia or paraparesis. [34
] This is primarily owing to aggressive reattachment of intercostal arteries in patients
with aortic dissection. An aggressive effort to reattach intercostal arteries has also
markedly reduced the risk of delayed paraplegia.
Vascular Anatomy of the Spinal Cord
The anatomy of the blood supply to the spinal cord is relevant to prevention of spinal
cord ischemia and its sequelae. The major arterial circulation to the spinal cord is the
anterior longitudinal spinal artery and the paired posterior longitudinal spinal arteries.
[35 ] These vessels originate from intracranial vertebral arteries, or branches thereof,
and course along the spinal cord for its entire length. The segmental spinal arteries
supplying the thoracic and lumbar regions of the cord originate from the posterior
branches of the intercostal and lumbar arteries, respectively. The anatomy is highly
variable from one individual to another. The segmental spinal arteries give rise to the
large anterior and smaller posterior radicular arteries. Each then directly supplies the
anterior and posterior longitudinal spinal arteries. Not all anterior and posterior radicular
arteries, however, reach the cord. It is this fact and the fact that the anterior spinal artery
frequently is attenuated, or entirely discontinuous, that makes the spinal cord highly
vulnerable to ischemia. The artery of Adamkiewicz is the largest of the radicular
medullary arteries. [36 ] Although it has been identified as proximal as T5 and as distal
as L4, the most common site of origin is between T9-10 and L1-2. When the vessel
reaches the anterior spinal artery, generally it bifurcates into a smaller ascending
branch and a larger descending branch. Intimal atherosclerosis, particularly in medial
degenerative fusiform aneurysms, obliterates many intercostal and lumbar arteries, and
complicates matters anatomically.
Pathophysiology of Aortic Cross-Clamping
An understanding of the pathophysiological mechanisms involved in aortic

cross-clamping and unclamping is imperative in selecting effective measures to prevent
and treat the consequences. Clamping the aorta increases impedance to aortic flow,
increases systemic vascular resistance and afterload, and redistributes blood volume
because venous vasculature distal to the aortic clamp collapses and constricts. This
effectively increases preload. The increases in afterload and preload demand an
increase in myocardial contractility, which causes an autoregulatory increase in
coronary blood flow. If coronary blood cannot increase, cardiac decompensation
follows.
Pathophysiology of Spinal Cord Ischemia
Injurious effects to the spinal cord, kidneys, lungs, and abdominal viscera are caused
primarily by ischemia and reperfusion of organs distal to the aortic clamp and to a
release of mediators from ischemic and reperfused organs. The most challenging and
troublesome complication following thoracoabdominal aortic aneurysm replacement
remains spinal cord injury and the development of paraplegia or paraparesis.
The most important reasons for spinal neurological deficits are related to reduced blood
flow to the spinal cord during aortic cross-clamping and permanent disruption of
delicate and variable arteries to the spinal cord. The duration of cross-clamping
influences the magnitude of spinal cord ischemia and reperfusion. Studies suggest that
cross-clamping for a period of less than 30 minutes is frequently safe. [37 ] [41 ]
Cross-clamping the thoracic aorta decreases anterior spinal artery pressure and
increases CSF pressure. [42 ] Reasons for increased CSF pressure include
hypertension proximal to the clamp that produces engorgement of the intracranial
compartment, volume changes in venous capacitance within the dural space, and
increased blood volume within the skull. Conceptually, reducing CSF pressure
increases anterior spinal artery flow and reduces cord ischemia. CSF drainage,
however, remains controversial as a method to reduce postoperative paraplegia and
paraparesis under clinical conditions. [43 ] , [44 ]
Sodium nitroprusside during thoracic aortic cross-clamping reduces spinal cord

perfusion pressure and increases the incidence of neurological deficits. [45 ] The
decrease in cord perfusion pressure is owing to a decrease in the distal aortic pressure
beyond the clamp and an increase in CSF pressure. The increase in CSF pressure
occurs from cerebrovasodilatation. [46 ] Pharmacological efforts to reduce proximal
aortic pressure ideally should possess minimal cerebrovasodilating properties.
Protection Strategies
Hypothermia prolongs the safe duration of ischemia for any organ, including the spinal
cord, by reducing metabolic rate and oxygen requirements. The author uses mild
passive hypothermia (3133°C) in all cases. Frank et al. report a technique using partial
bypass and moderate hypothermia for organ protection during the clamp-induced
ischemic period. [47 ] The advantages of moderate over deep hypothermia include a
stable intrinsic cardiac rhythm that eliminates the need for full cardiopulmonary bypass.
They report a series of 18 patients undergoing thoracic and thoracoabdominal aortic
aneurysm resection and replacement with moderate (30°C) hypothermia and partial
bypass (aorto-femoral or atrio-femoral). No patient developed paraplegia or significant
renal failure. There were two deaths (11 percent).
Crawford et al. reported the clinical use of cardiopulmonary bypass using hypothermic
circulatory arrest in 25 patients treated for thoracic aortic aneurysms through a
posterolateral approach. [48 ] There were 21 early survivors and cerebral protection
was entirely satisfactory. The technique was not entirely effective in eliminating
paraplegia; two (11 percent) of 18 patients at risk for ischemic spinal cord injury
developed neurological deficits. This may be explained by satisfactory cord protection
during the period of ischemia, but spinal cord injury from sacrifice of critical intercostal
arteries.
Epidural cooling for regional spinal cord hypothermia in the dog model is effective in
preventing paraplegia following aortic cross-clamping. [49 ] [51 ] Davidson et al. report
a clinical trial of epidural cooling in eight patients undergoing thoracoabdominal aortic
replacement for aneurysm. [52 ] The technique satisfactorily achieves regional spinal
cord hypothermia and adequate protection without postoperative neurological deficits.
Intuitively, sacrifice of intercostal or lumbar arteries that are critical to the direct blood
supply of the spinal cord is a significant factor in the development of postoperative
paraplegia. Maintenance of flow through such arteries during all or part of the anatomic
repair potentially keeps the period of spinal cord ischemia within the generally safe 30
minutes. [53 ] , [54 ] This concept is supported by a meta-analysis of the literature
reported by von Oppell in a review of 1742 patients treated for traumatic aortic rupture
over a 25-year period. [38 ] Simple aortic cross-clamping produces an incidence of
paraplegia of 19.2 percent, whereas shunting reduces the incidence of paraplegia to
11.1 percent. Active augmentation of distal aortic perfusion, i.e., left atrial to femoral
artery bypass or femoro-femoral bypass has the lowest incidence of new postoperative
paraplegia at 2.3 percent ( p < 0.00001). The cumulative risk of paraplegia increases
substantially if the duration of aortic cross-clamping exceeds 30 minutes, but only when
distal perfusion is not augmented ( p < 0.00001). In using left heart bypass for distal
perfusion during replacement of descending thoracic and thoracoabdominal aortic
aneurysms, Borst et al. find that the technique effectively unloads the proximal
circulation during aortic occlusion and maintains adequate perfusion of distal vital
organs to reduce early mortality and renal failure. [33 ] Further, the risk of spinal cord
damage decreases with combined distal perfusion and aggressive reattachment of
distal intercostal arteries.
Clearly, the devastating complication of paraplegia and other organ failure secondary to
ischemia is worthy of further research; however, a combination of measures including
distal aortic perfusion, aggressive reattachment of intercostal arteries, hypothermia,
avoidance of hyperglycemia, and possibly CSF drainage, have substantially reduced
this devastating complication.
RESULTS OF TREATMENT
Mortality following surgical treatment of thoracoabdominal aortic aneurysms averages

13 percent for elective procedures and 47 percent for emergent operations. [2 ] , [3 ] ,
[34 ] Intraoperative mortality is 45 percent, 30-day mortality 1012 percent, and
in-hospital mortality 1215 percent. [2 ] , [3 ] , [34 ] The etiology of early mortality is
primarily multiple organ failure, pulmonary complications, renal failure, myocardial
infarction, hemorrhage, and rupture of other aneurysms ( Table 41-3) .
The incidence of postoperative renal dysfunction defined as a significant increase in

postoperative creatinine averages 20 percent in reported series and ranges from 4 to
37 percent. [3 ] , [34 ] Seven to nine percent of patients required postoperative new
onset hemodialysis. Prolonged ischemic times, extent of aorta replaced, and
preoperative renal dysfunction with elevated creatinine are the primary variables
associated with an increased risk of postoperative renal failure.
During the period between January 11, 1986, and March 19, 1996, the author operated
on a consecutive series of 723 patients for treatment of aneurysm of the
thoracoabdominal aorta (Table 41-4) . There were 420 male patients (58.1 percent)
and 303 female patients (41.9 percent). Mean age was 65.2 years (median 66 years)
with a range of 21 to 88 years. Five hundred sixty-five patients (75 percent) were
treated for medial degenerative fusiform aneurysms or others of nondissection etiology.
Acute dissection was present in 25 patients (3.5 percent) and chronic dissection
occurred in 156 patients (21.6 percent). There were 46 patients (6.4 percent) with
Marfan syndrome, and 55 patients (7.6 percent) presented with rupture. The extent of
aortic replacement based on the Crawford classification included 254 with extent I (35.1
percent), 209 patients with extent II (28.9 percent), 120 patients with extent III (16.6
percent), and 140 patients with extent IV (19.4 percent). The 30-day overall survival was
94.9 percent and in-hospital survival was 92.4 percent. Mean total aortic clamp time
was 43.5 minutes (median 41 minutes) with a range of 6127 minutes. There were three
(0.4 percent) intraoperative deaths. The overall incidence of paraplegia or paraparesis
was 5.5 percent (40 patients). CSF drainage was not used in this series of patients.
The incidence of paraplegia and paraparesis was evenly divided. Postoperative renal
failure requiring hemodialysis occurred in 48 patients (6.6 percent); in 14 (29.2
percent), failure was temporary. Twelve patients (1.7 percent) were returned to the
operating room for postoperative bleeding, and 12 patients (1.7 percent) suffered
perioperative stroke.
Five hundred seventy-four patients (79.4 percent) were operated on without the use of
distal aortic perfusion, i.e., atrio-femoral bypass or femoro-femoral bypass (Table 41-5)
. Of these, paraplegia or paraparesis developed in 32 (5.6 percent) and renal failure in
33 (5.7 percent). In 119 patients with extent II aneurysms, the incidence of neurological
deficit was 14.3 percent (17 patients). Atrio-distal aortic bypass for distal aortic
perfusion using a centrifugal pump was utilized as a protective operative strategy in 149
patients (20.6 percent) (Table 41-6) . Of these, paraplegia or paraparesis developed in
eight patients (5.4 percent) and renal failure in 15 (10.1 percent). In 90 patients with
extent II aneurysms in whom distal perfusion was used, only five patients (5.6 percent)
developed postoperative neurological deficits.
In patients with chronic aortic dissection, paraplegia and paraparesis developed in 3.3
percent versus 5.5 percent for patients with chronic fusiform medial degenerative
disease. Consequently the presence of chronic dissection is no longer a variable
associated with the development of postoperative neurological deficits. However, in
patients with acute dissection the incidence of spinal cord ischemic sequela remains
high (4/25, 16.0 percent).
A significant reduction in neurological deficits was found in patients with extent I and
extent II aneurysms in whom intercostal arterial reattachment was accomplished: 12.6
percent versus 5.6 percent ( p < 0.0001). This reduction occurred despite the fact that
mean total clamp time was 60 minutes for those with atrio-distal bypass and 38.4
minutes for those without ( p = 0.0001). Reattachment of intercostal arteries was
accomplished in 59.6 percent of the entire group of patients, but, as a result of anatomic
availability, was achieved as part of the repair in 81.2 percent of patients with extent I
and II aneurysms. Intercostal ischemic time in extents I and II was significantly less ( p =
0.0001) for patients with atrio-distal bypass versus those without atrio-distal bypass.
Preoperative, operative, and postoperative variables for this series were analyzed for
development of postoperative neurological deficits and early (30-day) mortality.
Multivariate analysis revealed that age, rupture, and total clamp time were variables
predictive of early mortality, whereas rupture and extent II were variables predictive of
paraplegia or paraparesis.
In this series of 723 patients, atrio-distal aortic bypass and aggressive reattachment of
lower intercostal and upper lumbar arteries substantially reduced postoperative
paraplegia and paraparesis. Crawford et al. reported a 60 percent 5-year survival
following thoracoabdominal aortic aneurysm replacement. Survival was reduced to 25
percent in patients with rupture, 40 percent with renal dysfunction, and 49 percent with
coronary artery disease. The most common causes of late mortality were cardiac,
pulmonary, and renal failure, sepsis, and aneurysm rupture of unoperated segments. In
addition to the severe impact on lifestyle, the devastating complication of postoperative
paraplegia or paraparesis decreased late survival to 44 percent versus 62 percent at 5
years.
The evaluation and treatment of patients with thoracoabdominal aortic aneurysms

remains a significant challenge and requires a great deal of investigative and clinical
work to bring about the multifactorial approach necessary to solve the remaining
complex problems.
INCIDENCE
Traumatic aortic rupture occurs in 1223 percent of deaths from blunt trauma, but not all
deaths are caused by aortic rupture. [2 ] , [3 ] , [5 ] , [7 ] Parmley estimates that
approximately half of victims with ruptured aorta would die of associated injuries even if
the aorta was not injured. [1 ] Traumatic ruptured aorta is primarily caused by motor
vehicle accidents and falls; thus in the past half century the incidence has increased in
direct proportion to the number of high-speed motor vehicle accidents. [3 ] , [5 ] , [6 ]
Seventy-three to ninety-two percent of all cases involve motor vehicle drivers,
passengers, or pedestrians. [1 ] , [2 ] , [5 ] , [8 ] Most of the motor vehicle accidents are
high-speed and up to 43 percent of the dead drivers have evidence of alcohol or other
substance abuse. [2 ] , [5 ] , [9 ] Ejection from the vehicle doubles the risk of aortic
rupture; seat belts reduce the chance of a fatal accident by a factor of four. [2 ] , [4 ]
Accidental or suicidal falls, crush injuries, airplane accidents, and rare cave-ins are
other causes of traumatic aortic rupture. [1 ] , [2 ] , [5 ] Seventy to eighty percent of the
victims are male, and the average age is 3537 years, with a range of 388 years. [3 ] , [5
]
Because of the high incidence of death at the scene or shortly afterwards (8493
percent), the population of living patients who reach hospitals differs from that reported
in autopsy series. Forty to ninety-two percent of patients reported from trauma centers
are transferred from another hospital. [10 ] [12 ] Apriori these patients survive longer
following the accident; they also have fewer severe associated injuries. [10 ] , [13 ]
Crowley noted that the mean Injury Severity Score (ISS), excluding the aortic rupture,
was 17.4 for transferred patients and 19.3 for victims brought directly from the accident.
[10 ]
Table 42-1 lists the frequency of various associated injuries in patients with traumatic
ruptured aorta treated at trauma or surgical centers. These lesions must be ruled out or
diagnosed and treated in patients who present with ruptured aorta. Although the
frequency of severe head, cardiac, and other lethal injuries is less than in autopsy
series, 2034 percent of initial survivors have central nervous system deficits. [1 ] , [2 ]
The most frequent injury is concussion, but a significant number have intracranial
bleeding that requires operation. [11 ] [13 ] Cardiac contusion is the most frequent
cardiac lesion; rare patients suffer a cardiac laceration. Over 33 percent of patients
have lung injury, usually contusion, but approximately 25 percent have lacerated
abdominal or retroperitoneal organs. Sixty-six percent of the patients have one and
usually more fractures. Approximately 5 percent of patients do not have serious
associated injuries other than ruptured aorta. [14 ]
PATHOLOGY
Acute Ruptured Aorta
Blunt trauma produces a transverse laceration of the aorta with smooth edges that
always involves the intima and part of the media and often involves all three layers (Fig.
42-1) . In autopsy series the laceration usually extends around the entire circumference
to completely transect the aorta and separate the lacerated edges by serveral
centimeters. [1 ] , [2 ] , [6 ] Noncircumferential lacerations vary from only a few
millimeters to nearly the entire circumference. [1 ] Spiral lacerations, longitudinal
extensions, or ragged edges are uncommon. [1 ] Small intramural hematomas and
minidissections may be seen with some small partial (not full thickness) lacerations. [1 ]
Rarely, longer dissections extending several inches develop. [15 ] Immediate death
occurs in the majority of complete lacerations, but a surprising number of patients
survive for a time if extravasated blood is contained by mediastinal tissues. [1 ] Wall
structure of the lacerated aorta does not differ microscopically from uninvolved aorta,
and atherosclerosis is almost never involved. [1 ] , [2 ] , [5 ] The role of possible
differences in tensile strength [16 ] in the location of the laceration has not been
established; the adventitial layer provides most of the tensile strength of the aorta. [16 ] ,
[17 ]
Occasional patients, some even with complete circumferential aneurysms, survive

without operation to form chronic false aneurysms. [1 ] Initially a false aneurysm
containing pulsating clotted and fluid blood forms, and over time the thrombus organizes
to form a fibrous wall that may eventually calcify. Depending on the circumferential
extent of the initial laceration, these chronic aneurysms are fusiform or saccular. Late
expansion and rupture may occur years after the initial injury, but little is known of the
natural history of chronic, traumatic aortic aneurysms.
In autopsy series lacerations occur in all aortic segments and occasionally in the
abdominal aorta. [1 ] Thirty-six to fifty-four percent occur at the aortic isthmus, and this is
the most common location (Fig. 42-2) . [1 ] , [4 ] , [5 ] , [18 ] Eight to twenty-seven
percent involve the ascending aorta, and 818 percent occur in the aortic arch. [1 ] , [4 ] ,
[5 ] , [18 ] Eleven to twenty-one percent involve the distal descending thoracic aorta.
Abdominal aortic lacerations occur in approximately 5 percent of patients; multiple
lacerations develop in 618 percent of cases. [1 ] , [5 ] Occasional lacerations also occur
at the base of the innominate and rarely subclavian arteries. [12 ] , [19 ]
The mix is different in surgical series because patients with highly lethal ascending
aortic ruptures and those with severe associated injuries seldom reach the hospital
alive. In surgical series 84100 percent of aortic ruptures are at the aortic isthmus or
proximal descending thoracic aorta; only 3.710.2 percent involve the arch, descending
thoracic, or ascending aorta. [11 ] [14 ] , [18 ] , [20 ] [23 ] Essentially all lacerations are
circumferential (transverse), and many are complete with the aortic edges separated
1.55.0 cm. [12 ] Thirty-five to sixty percent of lacerations are posterior, partial (media
and intima only) transverse tears. [12 ] , [24 ]
Blunt trauma can also produce lacerations of the thoracic great vessels, and these
lesions may represent up to one-third of thoracic arterial injuries reaching surgeons. [19
] , [22 ] The majority involve the left subclavian; a few involve the base of the innominate
artery; the left carotid is injured least. [20 ] , [22 ] , [25 ]
Approximately 25 percent of patients with acute aortic rupture survive without operation
to form chronic false aneurysms. [1 ] , [26 ] Chronic traumatic aortic aneurysm is defined
as aneurysms that have partial or complete disruption of at least the intima and media
and that exist 3 or more months after a major deceleration or chest impact injury. [26 ] ,
[27 ] After the aorta ruptures, a false aneurysm containing pulsating, clotted, and fluid
blood initially forms, and over time the thrombus organizes to form a fibrous wall that
matures over a period of 3 months. Eventually the aneurysmal wall may calcify. [26 ] [28 ]
Over 90 percent of these aneurysms occur at the aortic isthmus but have been reported
in the ascending, arch, and descending thoracic aorta. [29 ] [31 ] Depending on the
circumferential extent of the initial laceration, these chronic aneurysms are fusiform or
saccular. Late expansion and rupture may occur years after the initial injury.
The number and severity of associated injuries at the time of accident are less than for
patients found to have aortic rupture immediately after the injury. Fifty percent of the
patients have only one associated injury, and 35 percent have none. [27 ]
PATHOGENESIS
The preferred sites of traumatic aortic rupture; the transverse, inside-outside

lacerations; the forces that produce the lesion; and the anatomy of the heart and great
vessels are clues to a puzzle that has aroused the curiosity of many investigators over
many years; yet despite extensive study, experiment, analysis, and debate, no
consensus or unified understanding of the pathogenesis of the injury has emerged. [2 ] ,
[5 ] , [16 ] , [17 ] , [32 ] [39 ] Deceleration and direct chest impact are the most frequent
forces that cause traumatic aortic rupture, although other forces are sometimes involved
(e.g., acceleration when a pedestrian is hit). [37 ] Symbas suggests that these forces
produce four different major stresses: torsion, shear, bending, and bursting in various
combinations. [38 ] Others doubt the importance of torsion and bursting stresses and
champion the role of traction stresses, particularly at the relatively fixed aortic isthmus
and ascending aorta. [5 ] , [37 ]
The ligamentum arteriosum, left main bronchus, and paired intercostal arteries limit the
mobility of the aortic isthmus and proximal descending thoracic aorta. The anterior
location of the ascending aorta and the weight and ease of displacement of the heart
downward and to the left in response to impact chest injuries are anatomic features that
appear related to linear tears just above the aortic valve and in the ascending aorta. [1 ]
, [37 ] Experiments show that the aorta can be displaced in a longitudinal (cranial or
caudal) direction sufficiently to cause traction tears at the isthmus. [35 ] Hyperextension
and vertebral and spinal injuries appear related to lacerations of the distal descending
thoracic and abdominal aorta. [37 ] Although the normal aorta can withstand pressures
of 2000 mmHg or more before bursting, dynamic factors such as rate of blood pressure
rise and secondary pressure waves and the tensile strength of various segments of the
aorta may also be relevant to the pathogenesis of traumatic aortic rupture. [16 ] , [32 ] ,
[40 ]
Deceleration forces that sometimes reach several hundred times the force of gravity
can produce the injury without any direct impact on the chest. [33 ] , [34 ] , [37 ] However,
direct blows to the chest produced by impact, blast, cave-in, or a crushing injury also
can produce the lesion without deceleration. [37 ] Most probably the majority of victims
of motor vehicle accidents experience some combination of deceleration and direct
chest impact. Sevitt explains the pathogenesis of isthmic aortic ruptures as caused by
cranially or caudally directed deceleration after impact, producing traction stress on the
aorta at the isthmus. A shovelling mechanism is postulated to explain cranially directed
traction stresses in drivers and front seat passengers in motor vehicle accidents, but
Sevitt does not rule out the possibility of horizontal (stress perpendicular to the aorta)
deceleration as an etiologic factor. [41 ] Ascending aortic tears are explained by
cardiac displacement and traction stress after direct chest wall impact, and distal
descending thoracic aortic lacerations are thought to be caused by hyperextension and
shear and bending stresses.
NATURAL HISTORY
Acute Aortic Rupture
Containment of hemorrhage by adventitial remnants, mediastinal tissue, parietal pleura,

and formation of clot permits survival for varying intervals in a few patients. Although 86
percent of patients with aortic rupture die at the scene, Parmley observed that 30 of 275
(11 percent) patients survived longer than 6 hours (Fig. 42-3) . [1 ] Since all patients
died, except two who had operations, these data underestimate the rate of long-term
survival.
Akins et al. and Hilgenberg et al. report 14 and 6 patients with acute lacerations of the
aorta who could not have immediate operation because of other injuries and were
treated with beta blockade and vasodilators for 2 days to 4 months. [11 ] , [42 ] Systolic
blood pressure was maintained between 100 and 120 mmHg, whereas other injuries
were stabilized. None died before the delayed surgery. Akins also reports five patients
who did not have surgery at all because of the severity of associated injuries. [42 ] None
of these patients died in an average follow-up of 51 months. [42 ] These data
emphasize the need to carefully assess the severity of associated injuries and to
diagnose the aortic laceration before deciding on treatment sequences.
Numerous anecdotal reports confirm long-term survival in self-selected patients who

were not diagnosed at the time of injury. [28 ] , [31 ] , [43 ] [47 ] Bennett and Cherry and
Finkelmeier et al. reviewed the literature for reports of chronic traumatic aortic
aneurysms and from these data plotted the natural history of the untreated injury beyond
3 months after the accident. [26 ] , [27 ] Of 60 patients who did not have operation for
chronic traumatic aortic aneurysm, 71 percent survived 5 years, 66 percent survived 10
years, and 62 percent lived 20 years, but one-third died of late rupture. [27 ] When a
cohort of operated and unoperated patients were evaluated for development of
aneurysmal-related symptoms, 22 percent became symptomatic within 1 year, 42
percent by 5 years, and 58 percent by 10 years (Fig. 42-4) . [27 ]
Ninety-four percent of chronic traumatic aortic aneurysms are located at the aortic
isthmus; the remainder are equally divided between the arch and ascending aorta. [27 ]
Others have also reported patients with chronic ruptured aneurysms in the ascending
thoracic aorta and other locations. [30 ] , [48 ]
The diagnosis of traumatic ruptured aorta is only made if it is suspected. If speeds and
distances suggest severe impact or high deceleration forces, the possibility of ruptured
aorta is invariably raised. However, less violent accidents including broadside crashes
may also produce sufficient force to lacerate the aorta; therefore, the diagnosis should
be ruled out in all except minor trauma. A definitive diagnosis is made by one of several
diagnostic tests; clues that prompt the diagnosis are listed in Table 42-2 . About 30
percent of patients have dyspnea, back pain, or higher blood pressure in the arms as
compared to the legs. [49 ] , [50 ] About 20 percent of patients have a midscapular
systolic murmur. [50 ]
The initial management of a patient after violent trauma follows well-accepted trauma
protocols that emphasize resuscitation and include immediate attention to ventilation,
control of visible bleeding, and maintenance of a circulation. [38 ] A history (if possible)
of other disease and allergy and an expeditious, but reasonably thorough, physical
examination with inventory of abnormalities and possible injuries and insertion of two or
more venous catheters are done promptly. X-rays in situ are ordered as indicated and
should include a chest x-ray that may provide the first clues of lacerated aorta (Table
42-2) . A list of associated lesions (proven or suspected) must be made before the
patient is moved for diagnostic tests or to the operating room (Table 42-1) .The vast
majority of patients have one or more fractures that should be temporarily stabilized
before the patient is moved. Usually the definitive diagnosis of ruptured aorta is made in
the emergency room.
DIAGNOSTIC STUDIES
Plain Chest X-ray
A standard PA chest x-ray often shows a widened mediastinum (> 8 cm) in patients with
rupture at the aortic isthmus, and this site is involved in 84100 percent of patients who
reach the hospital alive. [49 ] , [52 ] The definition of widened mediastinum is quite
variable and depends on the projection of the plain chest x-ray. Supine anteroposterior
films show the normal mediastinum to be wider than upright postero-anterior chest
x-rays. Eighty to ninety percent of patients with ruptured aorta have widened
mediastinum and loss of the aortic arch contour, but the specificity of these findings is
low. [49 ] , [50 ] , [53 ] Tracheal deviation associated with widened mediastinum
suggests an aortic injury; widened mediastinum without tracheal deviation suggests
venous bleeding. Gundry finds the sensitivity of mediastinal widening in patients with
ruptured aorta is 80 percent overall and is least sensitive in patients over 65 years. [54 ]
Mediastinal widening in an accident victim is a definite indication for further
investigation. [49 ] , [50 ] , [53 ]
An average of seven abnormalities are present on chest films of patients with lacerated
aortas, but approximately 25 percent have a normal mediastinum on admission and
develop positive findings on later x-rays. [50 ] , [55 ] Loss of the aortic knob, obliteration
of the aortic window, an apical cap, and deviation of an esophageal nasogastric tube
are other clues to the diagnosis of lacerated aorta on plain chest films. [49 ] [52 ] , [56 ]
Specificity and sensitivity of these findings vary considerably among reports, but all are
prompts for further investigation of the possibility of aortic laceration. [49 ] Chest x-rays
also indicate injuries to bony structures, hemothorax, lung contusions, and positions of
central catheters. Suggestive findings on a plain chest x-ray with or without a supportive
history and physical examination initiate attempts to definitely rule in or rule out the
diagnosis of aortic rupture.
Aortography
Traditionally angiography of the thoracic aorta is the definitive imaging technique for
ruling in or ruling out lacerations of the thoracic aorta (Fig. 42-5) . The procedure is
expensive and time-consuming, occasionally is associated with exsanguination and
death in the angiography suite and has a complication rate up to 10 percent. [51 ] , [57 ]
[59 ] Eighty-five to ninety percent of aortograms taken to diagnose traumatic ruptured
aorta are negative. [53 ] , [57 ] Contrast material may contribute to renal failure in
patients in shock. Aortography has a low false negative rate, but occasionally patients
with negative aortograms are found at autopsy to have aortic lacerations. [18 ] , [24 ] ,
[60 ] [62 ] The causes of these false negative exams are believed due to thrombosis of
the laceration, inadequate views, or inadequate contrast material. [18 ] , [57 ] , [63 ] , [64
] The false positive rate of 6 to 17 percent is caused by atheromata or a ductal
diverticula. [53 ] , [57 ] , [61 ] , [65 ] , [66 ] These data indicate that aortograms for acute
traumatic ruptured aorta are not infallible, even though the examination is considered
the reference standard. Increasingly, angiography is used selectively, usually to resolve
nondefinitive findings obtained by other imaging techniques.
Computerized Axial Tomography
Computerized axial tomography with contrast (CAT scan) is noninvasive, less

expensive than aortography, and widely available and is frequently used to exclude the
diagnosis of ruptured aorta in patients with positive plain chest x-rays. [67 ] Since
approximately 85 percent of angiograms for suspected traumatic ruptured aorta are
negative, CAT scans are useful for screening patients with possible ruptured aorta. [49 ]
, [51 ] , [54 ] , [56 ] , [68 ] [71 ] In most series, but not all, the sensitivity of CAT scans is
100 percent, but the specificity is low. [9 ] , [67 ] , [68 ] , [72 ] , [73 ] For the diagnosis of
ruptured aorta the poor specificity, unclear sensitivity, need to transport badly injured
patients to a separate facility, and the time required for study limit the use of CAT scans
to facilities in which other imaging techniques are not readily available. However, CAT
scans are invaluable for managing symptomatic closed head injuries and for assessing
damage to intraabdominal, pelvic, and retroperitoneal structures.
Magnetic resonance imaging provides excellent images of the thoracic aorta, but the
risks of confining badly injured patients in an inaccessible magnet, the time required for
the study, and the accuracy and utility of transesophageal echocardiography have
preempted its use in acutely traumatized patients. [74 ] , [75 ] The technique is suitable
for the rare patient who is suspected of missed aortic rupture days or weeks after the
accident.
Transesophageal echocardiography (TEE) reliably images the entire thoracic aorta

except for the distal 35 cm of the ascending aorta and arch because of the intervening
trachea and left main bronchus. [19 ] , [53 ] TEE is more sensitive and more specific
than transthoracic echocardiography and more reliably detects coexistent myocardial
contusion, pericardial fluid, and valvular insufficiency. [51 ] , [75 ] TEE can be used in the
emergency room in most patients and in the operating room in nearly all; it requires
1030 minutes for an examination that minimally interferes with simultaneous procedures
and care. [53 ] The procedure can be done with topical anesthesia but requires an
experienced operator. The risk of physical injury from probe insertion is low unless the
esophagus or pharynx contains lesions that may impede passage. The procedure is
contraindicated in patients who are suspected to have cervical spine, oropharyngeal, or
severe maxillofacial injuries or esophageal disease.
TEE may miss very small, partial lacerations, but these are not likely to require surgery.
[60 ] The sensitivity and specificity of the method approach 100 percent with some
operators but has a sensitivity as low as 63 percent and a specificity of 84 percent with
others. [53 ] , [57 ] , [69 ] , [76 ] [79 ] TEE and aortography images are highly correlated
in patients with lacerations of the aorta, and discrepancies between the two imaging
methods raise questions about the accuracy of aortography as the reference standard.
[53 ] , [57 ] The major limitation of TEE is that diagnostic accuracy and speed are
dependent on the experience and expertise of the physician performing the study. [79 ]
Multiplane TEE probes permit acquisition of cross-sectional tomographic images at

different angles along a single rotational axis. A 5-mmHz ultrasound transducer permits
resolution of anatomic structures as small as 12 mm. Time-resolved imaging permits
evaluation of the movement of anatomic structures and enhances the ability to
determine the physiological consequences of structural abnormalities. Doppler
echocardiography improves diagnostic accuracy by demonstrating patterns of blood
flow in different aortic segments. Although intravascular ultrasound has been used for
the diagnosis of aortic rupture, thoracoscopy in the operating room is probably safer
and equally reliable to confirm the diagnosis in the event that TEE is equivocal. [80 ]
ECHOCARDIOGRAPHIC FEATURES OF TRAUMATIC AORTIC RUPTURE
A mural flap within the aortic lumen extending several centimeters longitudinally is the
most common echocardiographic feature of aortic intimal disruption (Fig. 42-6) . [53 ] ,
[76 ] , [81 ] [84 ] Mural flaps caused by traumatic aortic rupture viewed in short axis
closely resemble intimal flaps produced by aortic dissections (Fig. 42-7A) , but are
confined to relatively short longitudinal distances (Fig. 42-7B) . Thickening or increased
echogenicity within the vessel wall may indicate a contained rupture with intramural
hematoma. Intraluminal thrombus appears as a homogeneous, irregularly shaped,
echogenic mass, usually attached to the mural flap within the vessel lumen. Color
Doppler flow mapping (Fig. 42-8) detects interruption of blood flow at the site of injury.
Interruption of intraluminal blood flow produces a sharp demarcation or border in the
color Doppler map of blood flow velocities (Fig. 42-8) . Turbulent flow within the vessel
lumen caused by acceleration of blood across the site of disruption appears as a
downstream mosaic of colors. Although TEE provides high-resolution images, it does
not distinguish tissue characteristics. [53 ] Chronic atherosclerotic changes may
produce falsely positive intimal defects that are difficult to distinguish from those caused
by acute trauma. [53 ] In older patients mediastinal hematoma should be present with
aortic rupture, and other areas of the aorta should be examined for evidence of
atherosclerosis.
MANAGEMENT PLAN
Initial Management
A comprehensive management plan is necessary before a lacerated aorta is treated

definitively because 95 percent of patients with traumatic aortic rupture who reach a
hospital alive have associated injuries. Kodali et al. report that 26 (34 percent) of 76
patients with lacerated aortas who arrived alive died before surgery was started. [14 ]
Eight died during treatment of associated injuries; 12 died before the diagnosis of
rupture; and 6 died after diagnosis before operation. [14 ] Others report similar figures.
[10 ] , [13 ] , [24 ] , [85 ] Clearly, some of these patients cannot be saved from lethal
associated injuries or exploding aortic lacerations. However, these data emphasize the
need for a coordinated, carefully planned, expeditious team effort for patients with
nonlethal associated injuries that are hemodynamically stable and for unstable patients
for whom short-cuts are necessary for any hope of survival. Because of the high
sensitivity and specificity of TEE, this examination is strongly recommended early after
arrival in patients with clinical and plain chest x-ray clues of ruptured aorta.
In all patients certain associated injuries must be addressed promptly even before
treatment of ruptured aorta. These include patients with compromised ventilation,
hemodynamically unstable patients with or without active bleeding, unconscious
patients with closed head injuries, and conscious patients with worsening neurologic
deficits. In the emergency room ventilation must be established, and the circulation must
be stabilized as first priorities. Reestablishing ventilation and circulation may require
intubation, insertion of chest tubes, resuscitation from cardiac arrest, laparotomy, and
even thoracotomy to control massive bleeding; unfortunately few of these patients
recover. [10 ] , [14 ] , [70 ] If at all possible, unstable patients should be transferred
promptly to the operating room, where both diagnosis and therapy of life-threatening
injuries can proceed simultaneously.
Preoperative Imaging
Once ventilation and circulation are adequate, a CAT scan of the head is indicated prior
to an aortic operation for all patients with clinical evidence of closed head injury. Relief
of intracranial space occupying lesions takes priority over nonbleeding aortic
lacerations if recovery of the brain injury is a reasonable possibility.
The role of truncal CAT scans in patients with ruptured aorta who do not have a closed
head injury is murky. Truncal CAT scans provide an excellent inventory of associated
lesions, particularly abdominal and retroperitoneal lesions (Fig.42-9) and the presence
of pelvic fractures. A truncal CAT scan is not necessary for the diagnosis of ruptured
aorta; TEE is more sensitive and more specific and is at least as reliable as
aortography in the hands of skilled, experienced operators.
We recommend expeditious truncal CAT scans in stable patients since 25 percent of

patients with ruptured aorta have intraabdominal or retroperitoneal lacerations. Often
truncal CAT scans are obtained at referring hospitals that do not have the facilities and
personnel for TEE, aortography, or aortic surgery. The scans suggest the diagnosis of
ruptured aorta and provide information relevant to the decision to transfer. The time
required for the test is a drawback if the patient has an aortic laceration, but the test is
necessary for patients with closed head injuries and is desirable, but risky, to survey
abdominal, retroperitoneal, and pelvic injuries in stable patients. [24 ]
Although aortography may be available, this study is not needed if the TEE
unequivocally indicates ruptured aorta. [12 ] If the TEE is equivocal, aortography adds
additional information that affects the decision to operate and is indicated if the patient
is stable without symptomatic closed head injury. Thoracoscopy is an alternative
diagnostic test that can be used to confirm the presence of an aortic rupture in patients
with equivocal TEE and avoids the delay needed for aortography. Laparoscopy can be
used to diagnose intra-abdominal bleeding but is not helpful for ruling out
retroperitoneal bleeding or pelvic injuries.
During emergency room and diagnostic imaging, blood pressure should be carefully
monitored and controlled to maintain systolic pressures between 100 and 120 mmHg.
[42 ] Blood pressure control and beta blockade (if cardiac output is adequate) reduces
the chance of rupture prior to operation.
Timing of Operation
Immediate thoracotomy is recommended in stable patients without the need for prior
laparotomy or craniotomy. In patients with closed head injuries caused by space filling
lesions or those with evidence of intraabdominal or retroperitoneal bleeding,
thoracotomy is delayed until these associated injuries are addressed. A double-lumen
endotracheal tube is passed, or, if time is a concern, an endotracheal tube with left
bronchial blocker may be used. The patient is positioned so that immediate
thoracotomy can be done if evidence of significant bleeding from the laceration occurs
during the craniotomy or laparotomy. During the delay the rupture site is monitored by
TEE, and blood pressure is controlled by appropriate drugs. Nonthreatening associated
lesions are addressed by surgical specialists after the aortic lesion is repaired, but
procedures that require extensive surgery or those that can be treated later are
deferred.
Unstable patients who are considered salvageable are removed to the operating room
as soon as possible, and all diagnostic tests are bypassed and replaced by
appropriate surgical procedures to locate and control bleeding. The surgical
procedures chosen depend on the adequacy of the circulation. Immediate thoracotomy
and/or laparotomy based on available, albeit inadequate, clinical evidence may be
needed since there is no time to obtain more information. If time allows, thoracoscopy is
used to confirm the presence, exact location, and bleeding status of the aortic
laceration. Similarly, laparoscopy may be used to locate intraabdominal bleeding. In
these patients, the operating room is utilized as a diagnostic and therapeutic suite for
all truncal life-threatening injuries.
OPERATION
There are many different methods to resect or repair the lacerated aortic isthmus, and
to date no method has proven superior, but standardized protocols are developing. The
choice of procedure is influenced by the urgency to control bleeding, associated
injuries, and surgeon preference.
Blood for lab work is sent from the emergency room shortly after admission for
hematocrit, white blood cell count, platelet count, electrolytes, glucose, liver chemistries,
and blood urea nitrogen (BUN) and creatinine. At least 10 units of blood are typed and
cross-matched. [86 ] A nasogastric tube is passed to aspirate the stomach but is
removed for the TEE probe.
Preparations
If hemodynamics are stable, the patient is placed supine on the operating table, and a
double lumen endotracheal tube is inserted. Recently, some centers have placed a
single lumen, bronchial blocker tube if the patient is intubated before operation, since
this tube is easily inserted and allows bilateral ventilation during transport and
preoperative preparation and single right lung ventilation during operation. Although it is
possible to repair a transsected aorta while the left lung is ventilated, it is much easier
and safer to perform this operation with single right lung ventilation.
The electrocardiogram, rectal or bladder temperature, urine output, and peripheral

arterial oxygen saturation are monitored continuously. A right radial arterial catheter, a
Swan-Ganz catheter, and appropriate large bore intravenous catheters for volume
replacement are inserted. Once invasive monitoring catheters are placed, anesthesia is
induced, usually with a synthetic narcotic drug such as fentanyl. Full stomach
precautions are observed during induction. The patient is turned to a right lateral
decubitus position with a slight thoracoabdominal tilt if the left femoral artery and vein
are cannulated. A cell saver system is prepared.
Adjuncts to prevent paraplegia
The need to cross-clamp the aorta just distal or proximal to the left subclavian artery
risks ischemia of the spinal cord. The spinal cord is supplied by anterior and posterior
spinal arteries that consist of anatomic vascular chains that run the length of the cord
(Fig. 42-10) . [87 ] In the upper thorax the anterior spinal artery, which supplies the
anterior two-thirds of the spinal cord, usually is well developed, but in the lower chest
and upper abdomen the artery is smaller, less well developed, with segments
dependent upon specific, but variable, segmental branches from intercostal or lumbar
arteries (Fig. 42-11) . The anterior spinal artery is supplied by 710 unpaired, anterior
medullary branches that vary in location along the spinal canal (Fig. 42-10) . Usually at
least two anterior medullary vessels supply the cervical cord, and either two or three
medullary vessels join the anterior spinal artery in the thoracic region. Loss of one of
these medullary arteries rarely causes cord ischemia because the anterior spinal artery
is well developed in this location. At the level of the first or second lumbar vertebra
(variations T12 to L4) the tenuous anterior spinal artery receives the artery of
Adamkiewicz (arteria radicularis magna); in over 25 percent of patients this vessel is
essential for the blood supply of the lower spinal cord. [88 ] Because collateral blood
supply between normal intercostal arteries is poor, occlusion of an intercostal vessel at
the aorta profoundly decreases blood pressure in the distal vessel. [89 ]
Prolonged hypotension produced by aortic cross-clamping near the aortic isthmus

produces profound hypotension in the lower body and spinal cord segments supplied by
vital intercostal or lumbar arteries. Clamping the left subclavian artery or upstream to
this artery increases the risk of paraplegia since some branch vessels, such as the
internal thoracic artery and branches of the vertebral and subscapular arteries, are
sources of collateral vessels. [90 ] , [91 ] Paraplegia has occurred after only nine
minutes of aortic cross-clamping without extracorporeal perfusion of the lower body
(Bavaria, personal case). Perfusion of the lower body at pressures of 60 mmHg or
higher during aortic cross-clamping reduces the likelihood of spinal cord ischemia, but
this catastrophic complication still occurs in a disturbing number of patients with
traumatic aortic rupture despite lower body perfusion.
Several adjuncts are proposed to reduce the likelihood of paraplegia and paraparesis
in patients who have elective resection of descending thoracic and thoracoabdominal
aneurysms, but most of these adjuncts are not practical for the management of patients
with acute traumatic ruptured aorta. Hypothermia using cardiopulmonary bypass is not
feasible because heparin is too dangerous. Somatosensory evoked potentials permit
early detection of spinal cord ischemia and could prompt an increase in lower body
blood flow in patients perfused with partial left heart bypass or right atrial to femoral
arterial bypass. [92 ] , [93 ] Insertion of a spinal intrathecal catheter is a means to
prevent increases in spinal fluid pressure but requires extra time before operation for
insertion. [94 ] Experience with pharmacologic adjuncts and selective spinal cord
hypothermia has not been reported in these patients.
Incision
A standard left posterolateral incision is used with either resection of the fifth rib or
entrance through the fourth interspace. The incision should be long enough to permit
dissection of the descending thoracic aorta and clamping between the left carotid and
subclavian arteries. Often the trans-section process extends into the orifice of the left
subclavian artery. Any dissection near the tear in the isthmus is avoided until both the
proximal and distal aortae are dissected sufficiently to place proximal and distal
clamps. The aorta is first encircled in the midthoracic descending aorta for distal
control. The proximal aorta is approached only after distal control is obtained and
cannulations for perfusing the lower body during aortic clamping are complete.
Occasionally, during dissection of the proximal aorta, the mediastinal hematoma is
entered, and torrential bleeding ensues. [95 ] Obviously, if the patient is already
bleeding, rapid proximal control is gained first.
Once the aorta is adequately exposed, a decision regarding circulatory management of

the lower body and distal aorta must be made.
Management of Lower Body Circulation
Controversy currently exists regarding the best management of the lower body
circulation system during repair of an acute aortic transsection. Most recent reports and
a general consensus recommend using a method to provide distal aortic perfusion
rather than the traditional clamp-and-run technique. [10 ] , [13 ] , [14 ] Available collateral
circulation from the proximal aorta to distal intercostal vessels is insufficient to
adequately perfuse the spinal cord and distal aorta. [88 ] , [89 ] , [91 ] Nevertheless,
there are circumstances (e.g., active aortic bleeding) that require a straight
clamp-and-repair approach without distal aortic perfusion.
SIMPLE AORTIC CROSS-CLAMPING
There are many advantages of simple aortic cross-clamping. It is the easiest method
and can be used by any experienced surgeon in any hospital in the United States. The
method is especially useful in unstable patients who are actively bleeding from the
aortic laceration; in these patients there is no time to implement a distal aortic perfusion
system. The clamp-and-run technique can be utilized by general surgeons, vascular
surgeons, and trauma surgeons who may not have experience in setting up complex
extracorporeal circuits and cannulating cardiac chambers and great vessels.
If cross-clamp times remain under 2530 minutes, the paraplegia rate is low. [10 ] [12 ]
The average cross-clamp time reported in the literature for repair of aortic rupture is
41.0 minutes. [96 ] Many cases of aortic transection require more than 30 minutes to
repair because of extravasated blood, friability of the aorta, and difficulty in identifying
local anatomy. [97 ] This is especially true if the tear extends to the orifice of the left
subclavian artery. These patients require clamps between the left carotid and left
subclavian arteries and a separate clamp on the subclavian. Occlusion of the left
subclavian increases the incidence of paraplegia.
LOWER BODY PERFUSION SYSTEMS
General considerations
Several important considerations are relevant to all systems that are presently used to
provide blood flow to the lower body during peri-isthmic aortic clamping. Distal
perfusion pressure should be monitored and maintained above 60 mmHg. [91 ] , [93 ]
The system should be simply applied, generally available, and reliable. Extracorporeal
circuits that require full heparinization are contraindicated in patients with multiple
injuries and potential bleeding sites, are associated with increased mortality and lung
injury, and are no longer used for isthmic aortic tears. [11 ] , [42 ] , [65 ] The least amount
of heparin that can be safely used is best. [65 ] Hess et al. recently concluded that
partial left heart bypass without heparin is associated with the least paraplegia and
overall mortality as compared to other operative protocols. [98 ] In addition trauma
patients are often hypothermic; therefore, a heat exchanger is an important component
of the perfusion system in patients with core temperatures below 35°C.
Partial left heart bypass
A popular lower body perfusion technique used in repair of aortic transsection involves
placement of a cannula (20-20 mm double stage pediatric) into the left atrium either
directly or via the left pulmonary vein. [65 ] , [98 ] The arterial outflow cannula is placed
into the left femoral artery or, preferably, into the distal aorta (Fig. 42-12) . Cannulation
of the distal aorta allows the entire operation to be done through the thoracotomy and is
convenient and fast. Partial left heart bypass unloads the left heart and facilitates control
of proximal hypertension during aortic clamping. The atrial cannula minimizes ventricular
arrhythmias, and the extracorporeal perfusion circuit facilitates control of intravascular
volume and provides a method to rapidly reinfuse volume if needed. The lower body is
well perfused; flow rates can be monitored and adjusted.
Disadvantages include the need for heparin, but with surface-coated heparin circuits,
systemic heparin can be omitted with little incremental risk of thrombosis or emboli. [65
] , [98 ] The small surface area of the perfusion circuit substantially reduces the
thrombotic stimulus; however, until more experience is gained, antifibrinolytic drugs
(aprotinin, tranexamic acid, or epsilon amino caproic acid) should probably not be given
before or during bypass. The major risk is ventricular arrhythymias since the native heart
must perfuse the upper body. Single lung ventilation does not increase postoperative
lung problems after left heart bypass. The system is often used without a heat
exchanger (because of the greater surface area); therefore, great care must be taken to
reduce heat losses and maintain near-normal temperatures.
Right atrial to femoral artery
Recently, an alternative technique using a long catheter placed via the right femoral vein
into the right atrium and a right femoral artery catheter has been used with and without
an oxygenator (Fig. 42-13) . [86 ] The advantages of this technique over left atrial to
femoral artery bypass are that cannulation can be done peripherally prior to the thoracic
incision and that the left atrium and pulmonary veins near the mediastinal hematoma
need not be dissected out. When an oxygenator is used, systemic heparin is not given,
but the entire perfusion circuit is coated with heparin, and a closed system is
maintained. [86 ] All field blood is returned to a cell saver system and washed before it
is returned to the perfusate.
If the system lacks an oxygenator, no heparin or a low dose of heparin may be used as
with partial left heart bypass. The lower body is perfused at adequate flows (23 l/min),
but arterial pao 2 is approximately 40 mmHg (saturation 4560 percent), which is
adequate for tissue oxygen needs if the hemoglobin concentration remains above 10
gm. Highly desaturated inferior venal caval blood mixes with better-oxygenated superior
caval blood to maintain differential oxygen saturations in the upper and lower body. The
technique is simple and safe but requires left groin cannulation that may be desirable or
undesirable for individual patients. Young et al. ventilate the lungs with 100 percent
oxygen to increase mixed venous oxygen saturation. [99 ] Although concerns that
reduced oxygen saturation may injure the spinal cord have been expressed, this has not
occurred. [92 ]
Passive proximal to distal aortic shunts (Gott shunt)
The Gott shunt is a tapered, heparin-coated, polyvinyl tube made so that both ends can
serve as cannulas. The proximal end is usually placed in the ascending or arch aorta;
ventricular cannulation is rarely used because of reduced flow, arrhythmias, bleeding,
and a higher incidence of paraplegia. [12 ] , [100 ] [104 ] Because of low pressure the
left atrium cannot be used for the inflow cannula. The distal end is placed in the
descending thoracic aorta or the left femoral or external iliac artery (Fig. 42-14) . The
diameter of the shunt is fixed; therefore, flow is passive, unmonitored, and completely
dependent on pressure differences. There is no guarantee of a specific flow rate to
distal organs; femoral arterial pressure monitoring is recommended. [100 ] The
technique requires exposure and cannulation of the aortic arch or ascending aorta and
may require anterior extension of the incision. The Gott shunt is simple and easy to use
and is probably the most commonly used method to provide lower body perfusion in the
world at large, since it can be stocked in any hospital and does not require
cardiopulmonary bypass. [105 ]
Management of the Ruptured Aorta
Once the incision is made and exposure is adequate, the decision of how to manage
the lower body circulation is finalized. This decision may be made before thoracotomy if
percutaneous catheters are planned, but unless heparin is given, vessels cannot be
cannulated without initiating extracorporeal circulation. Guide wires, however, can be
inserted in preparation for expeditious cannulation if right atrial to femoral bypass is
chosen.
Distal control of the aorta is obtained shortly after the chest is entered, but care is taken
to avoid the mediastinal hematoma. [95 ] , [106 ] The descending aorta in the midchest
is dissected out and encircled with a traction tape. A purse string suture is placed
downstream to this level for cannulation if partial left heart bypass or a shunt is used. If a
Gott shunt is used, another purse string suture is placed in the distal ascending aorta or
medial arch for cannulation before control of the proximal aorta is obtained. Often the
shunt is actually placed and opened before dissecting out the aorta between the left
carotid and subclavian arteries. The left atrium or left superior pulmonary vein usually is
within the mediastinal hematoma; therefore, we prefer to dissect the site for the
proximal clamp prior to preparing to cannulate the left atrium.
The mediastinal pleura is incised along the anterior surface of the left subclavian artery,
and the vagus nerve is identified and protected. The dissection continues medially on or
near the aortic arch to the left carotid artery. The anterior aortic arch between these two
vessels is dissected behind the trachea and superior to the left main bronchus. The
posterior arch is dissected with scissors initially and then with gentle finger dissection
until a clamp and traction tape can be passed around the arch at this level. A bulldog
clamp is placed on the left subclavian artery 23 cm from its origin. Percutaneous groin
catheters are inserted, and perfusion is started if right to left bypass is used, and
similarly the shunt catheter is opened at this time. The inflow catheter for left atrial to
arterial bypass is inserted before the mediastinal hematoma is entered and the left
inferior pulmonary vein is identified. For the left inferior pulmonary vein we use a 20-20
mm double stage pediatric catheter inserted through a purse string suture and
advanced into the atrium. Lower body perfusion begins (if it is used), and large Fogarty
clamps are placed first on the distal aorta and then on the proximal aorta before the
rupture site is approached. The lower body perfusion system permits control of
systemic blood pressure so that sudden rupture of the aorta does not occur with
application of clamps. Pressures and hemodynamics of both patient and perfusion
system are checked, and the field is prepared for aortic repair.
If the aorta is already ruptured with bleeding into the hemothorax, proximal dissection of
the aortic arch above the hematoma and usually between the left carotid and subclavian
arteries is obtained rapidly first, and a clamp is applied. The descending thoracic aorta
is clamped in the midchest, and the hematoma is entered. No attempt is made to
provide circulation to the lower body, but every effort is made to maintain normal or
slightly elevated systemic blood pressure to reduce the possibility of spinal cord
ischemia. The aortic repair by direct suture or interposition graft is done as
expeditiously as possible.
If the aorta is not actively bleeding, perfusion of the lower body begins before the
hematoma over the rupture site is opened. The edges of the transected aorta are
identified. Many times the transection is complete, and edges of the aortic intima are
separated 24 cm. At other times the aorta is partially transected. Some authors
advocate direct suture repair of aortic transection, especially in partial transections. [12
] Most surgeons use a short interposition graft to reduce tension on the anastomosis
and to avoid dissection and possible sacrifice of intercostal arteries. [10 ] [14 ]
Collagen-coated woven Dacron grafts or gelatin-impregnated grafts are most
commonly used; PTFE (polytetrafluoroethylene) grafts are also suitable (needle holes
bleed more).
An intraluminal prosthesis is rarely used for three reasons. [107 ] , [108 ] Often the tear
is near the origin or the left subclavian artery or extends into the origin of this vessel so
that insertion of the proximal cuffed ring occludes the artery. Secondly, the normal aorta
is small in diameter so that only a 14 or 16 intraluminal graft can be inserted without
stretching and perhaps tearing the friable, transected aorta. This produces a slight
obstruction to descending aortic flow and a pressure drop across the graft. Lastly,
unless a small intraluminal graft is used, it is just about as fast to sew in an interposition
graft or do a primary repair if exposure is good. We do not recommend or use
intraluminal grafts for ruptured aorta except in rare circumstances (e.g., an elderly lady
with a calcified aorta that may be difficult to suture).
Running over and over anastomoses with 3-0 or 4-0 prolene are used usually without
teflon felt reinforcement, but with generous bites of adventitial and mediastinal tissue for
the outer layer. The suture line begins on the aortic wall opposite the surgeon, and the
posterior wall is done first. The anastomosis is facilitated if the two ends of the aorta are
sufficiently exposed and gently approximated with the clamps as the suture is drawn up.
Rarely a running horizontal mattress suture everting the cut edges may be used if the
aorta is very friable and separated by several centimeters. A running suture is always
used for interposition grafts. The anterior suture line uses the opposite needle and
moves toward the surgeon to be tied to the posterior suture. First the distal and then the
proximal clamp is released; when leaks are controlled, lower body perfusion is stopped,
and the cannulas are removed. The chest is closed in standard fashion; no attempt is
made to close the mediastinal pleura. Usually one chest tube is left for drainage.
Special Problems
PREVIOUS LEFT THORACOTOMY
If a left thoracotomy at a lower level is made in the emergency room by other surgeons,
a decision is needed to use or not use that incision. It is almost always best to enter the
chest through the fourth interspace or through the bed of the resected fourth rib, even if a
second skin incision is required.
Adhesions between lung and mediastinum help contain the rupture but make dissection
in the area more difficult even with the left lung collapsed. Consideration is given to
perfusing the lower body through femoral catheters without either heparin or an
oxygenator. If this is done, the amount of dissection is reduced, and the operation
proceeds as planned.
EXTENSION OF THE TEAR INTO THE LEFT SUBCLAVIAN ARTERY
If the tear extends proximally, the proximal clamp may have to be moved to partially
occlude the left carotid artery while the proximal anastomosis of an interposition graft is
performed. The left subclavian is completely detached from the aorta and prepared for
reanastomosis, and a properly sized interposition graft is brought up before the clamp
is moved. Good exposure somewhat deep in the mediastinum must be achieved before
the clamp is moved so that the suture line can be finished expeditiously. Occlusion of
the left carotid artery for 10 or 15 minutes usually is tolerated without cerebral damage;
therefore, the clamp is moved again as soon as the anastomosis is completed. The
distal anastomosis is made next. The distal subclavian is anastomosed to the graft
end-to-side or with a short synthetic or saphenous vein graft interposed.
Nonisthmic Lacerations
Lacerations at the base of the left subclavian artery can be managed through the left
posterior lateral incision in the fourth interspace or from a median sternotomy using a
vein or synthetic interposition graft from the aorta to the distal artery. [20 ] Some of
these lacerations can be repaired primarily; others involve extensive vessel damage
and thrombotic occulsion of the vessel and require a graft. [20 ]
Lacerations in the descending thoracic aorta above T-8 usually can be exposed through
a posterior lateral thoracotomy in thin individuals, but lower lacerations and
mid-descending thoracic lacerations in obese individuals need a thoracoabdominal
incision. We prefer the retroperitoneal approach for nontraumatic thoracoabdominal
aneurysms; in trauma patients, entering the abdomen has the important advantage of
also addressing intraabdominal injuries. The decisions can be made preoperatively;
transesophageal echocardiography is very reliable for locating aortic abnormalities in
the descending thoracic aorta.
A rare patient with an acute traumatic rupture in the ascending aorta or arch who
survives to reach a hospital probably should be managed with blood pressure control
and beta blockade until the number and severity of associated injuries are known. A
decision to operate requires full cardiopulmonary bypass with full heparin and may
require deep hypothermia if the head vessels must be clamped. [14 ] , [20 ] , [25 ] Kirsh
reports two survivors of ascending aortic lacerations. [20 ]
Lacerations at the base of the innominate artery or at the base of the left carotid artery
are best approached from a midline sternotomy incision. [14 ] , [20 ] , [109 ] An
extension into the right or left neck with detachment of the anterior portion of the
sternocleidomastoid muscle facilitates exposure. Mattox recommends that innominate
tears be treated with a bypass Dacron graft from ascending aorta to the distal
innominate artery with suture closure of the proximal innominate arterial stump. [109 ]
This operation is done without cardiopulmonary bypass.
In patients with multiple lacerations all must be repaired or resected if at all possible.
[110 ] The incidence in surgical series is approximately 1 percent. [18 ] Only a few
patients with multiple aortic lacerations survive long enough to receive successful
treatment. [14 ] , [20 ] , [25 ] , [110 ]
ASSOCIATED INJURIES
Briskly bleeding abdominal and retroperitoneal lacerations, intracranial bleeding, and

symptomatic depressed skull fractures should be addressed before repair of the aortic
laceration, with the aortic repair following as soon as the life-threatening associated
injury is controlled. In the Duke series, 5 percent of patients had craniotomy, and 15
percent had laprotomy. [13 ] The delay may be risky; Kirsh lost 5 of 12 patients during
laprotomy prior to aortic rupture repair. [24 ] Following repair, other associated injuries
are addressed. Laproscopy is rational as a postoperative screening examination to
detect slowly bleeding liver and spleen injuries, ruptured bowel, and other abdominal
injuries that are easily repaired while the patient is in the operating room. The
procedure adds little morbidity.
Orthopedic work and repair of initial stabilization of maxillo-facial injuries are done after
the thoracotomy is closed as part of the same anesthetic. The additional time required
adds little morbidity and can profoundly improve the final outcome. The patient
continues to be carefully monitored with judicious fluid replacement (avoiding fluid
overload) and optimizing respiratory, circulatory, and renal function. These patients tend
to cool; it is wise to warm the operating room to help maintain normal body temperature.
POSTOPERATIVE CARE
Postoperative care for the lacerated aorta with or without associated cardiac or lung
contusion is not different from that given elective patients who have major cardiac or
lung surgery. Vital signs, filling, and systemic blood pressures, cardiac output,
electrocardiogram, urine output, chest tube output, nasogastric tube drainage,
temperature, arterial blood gases, and usually coagulation function are monitored.
Packed cells, fresh frozen plasma, and platelets are given as indicated; rarely the chest
must be reopened to control surgical bleeding at the repair site. Appropriate x-rays,
including a chest x-ray, are obtained from the bedside as indicated. Intravenous broad
spectrum antibiotics, started in the emergency room, are continued during and after
operation for at least 5 days and often longer for associated injuries. The patient
remains intubated, sedated if necessary, and mechanically ventilated for the first
several hours after operation.
COMPLICATIONS
Table 42-3 lists complications reported following repair of traumatic aortic ruptures.
Approximately 41 percent of patients suffer major postoperative complications. [10 ] [12
] Aside from death, paraplegia and paraparesis and residual complications of
intracranial injuries are the most devastating, lasting residua. An average of 2.6 patients
has paraplegia owing to the accident prior to operation. [96 ]
RESULTS
Paraplegia or paraparesis occurs in an average of 9.9 percent of 1,492 patients

reviewed by von Opell. [96 ] The range varies from 2.3 percent when the lower body
circulation is actively perfused, to 11.1 percent when passive shunts were used, and
19.2 percent when no provision for lower body circulation was made (Table 42-4) . In a
subset of 32 recent patients with aortic cross-clamp times averaging 16 minutes (range
645 minutes) Schmidt reports one case of postoperative paraplegia. [12 ] The
preponderance of data indicates that the incidence of postoperative new paraplegia
increases with duration of aortic clamping and with the nonuse of lower body perfusion
(Fig. 42-15) . [10 ] , [14 ] , [96 ] , [111 ] [113 ]
Fourteen percent of patients admitted alive die before reaching the operating room, but
as previously noted this figure reflects whether the patient arrives directly from the
accident scene or is transferred from another hospital. [96 ] A few patients die before
thoracotomy is made. [20 ] Von Opell reports that an average of 7.8 percent of patients
die during operation (usually of exsanguination or cardiac arrest), and 13.5 percent die
in the postoperative period. [96 ] Mortality rates among individual series vary
considerably largely because of differences in the lapsed time between accident and
admission and the severity of associated injuries. Both age and injury severity score
(ISS) are significant risk factors for hospital death. [10 ] , [21 ] , [114 ]
The quality of life of survivors is related to associated injuries, particularly neurologic

injuries. [11 ] , [42 ] Late complications from the aortic repair are rare. [115 ]
CHRONIC TRAUMATIC AORTIC ANEURYSM
Patients who develop chronic traumatic aortic aneurysms are often asymptomatic and
unaware that the aorta was injured in a long-ago accident. The false aneurysm may
remain stable for years, but eventually symptoms of aneurysm expansion develop.
When a cohort of operated and unoperated patients was evaluated for development of
aneurysmal-related symptoms, 22 percent became symptomatic within 1 year, 42
percent by 5 years, and 58 percent by 10 years after the accident (Fig. 42-16) . [27 ]
Pain, usually in the back and probably due to local stretching of nerve fibers, is the most
common symptom. [26 ] , [27 ] Dyspnea and/or cough occurs presumably from pressure
on the left main bronchus. Hoarseness may develop from stretching the left recurrent
nerve. Other symptoms include decreased lower body pulses from thrombosis,
paraplegia, wheezing, hemoptysis, dysphagia, syncope, and rupture. [26 ] , [27 ] , [29 ] ,
[31 ] Hemoptysis may be caused by an aortic-bronchial fistula. [46 ] , [115 ] Sudden
rupture does occur, but usually the patient has symptoms for at least a brief period
before that catastrophe. [27 ]
An isthmic bulge or calcified wall is visible on plain chest x-rays. [116 ] Most of the
reported aneurysms were imaged by aortogram because other imaging methods were
not available. Magnetic resonance imaging is applicable for these patients and
provides excellent detail. Other methods are also satisfactory. [116 ] Serial images may
show expansion of the aneurysm. [27 ]
Operation
Operation is clearly indicated for symptomatic chronic traumatic aortic aneurysm and
can be justified for most asymptomatic aneurysms that are discovered by screening
chest x-rays. About half of operations for chronic traumatic aortic aneurysm are done
within 5 years of the injury. [27 ]
Isthmic aneurysms are approached through a left posterolateral thoracotomy through the
fourth interspace or the bed of the fifth rib. In most instances provision is made to
perfuse the lower body during aortic clamping using partial left heart bypass, right atrial
to femoral bypass, or a passive shunt. [29 ] , [116 ] We prefer partial left heart bypass
because of its effectiveness and simplicity. The aorta downstream is dissected for
placement of a clamp; then the aorta between the left carotid and subclavian arteries is
encircled. The vagus and recurrent nerves are dissected off the aneurysmal wall and
retracted medially. An interposition graft of synthetic material is placed after the
aneurysm is excised in most patients. [27 ] , [29 ] , [31 ] , [116 ] Prat prefers not to excise
the aneurysm but to insert a Dacron graft within the opened aneurysm. [31 ] Small
aneurysms with normal adjacent aorta can be excised with primary anastomosis of the
aortic cuffs. [27 ] , [29 ]
Results
Operative mortality ranges between 0 and 4.6 percent. [27 ] , [29 ] , [31 ] The major
causes of operative deaths are bleeding, myocardial infarction, and renal failure. [27 ] ,
[29 ]
Approximately 11 percent of patients develop major complications. The incidence of

paraplegia is 1.4 percent. [27 ] , [31 ] Bleeding, myocardial infarction, renal failure,
recurrent nerve palsy, phrenic nerve palsy, stroke, and superficial wound infection are
the most common complications. [27 ] , [29 ] , [31 ] , [116 ]
Long-term survival for operated patients is 7991 percent at 5 years and 7785 percent at
10 years. [27 ] , [29 ]
BLUNT TRAUMA TO THE HEART
Demographics
Blunt trauma to the heart occurs commonly in motor vehicle accidents and along with
central nervous system injury accounts for the preponderance of deaths. [11 ] Cardiac
injuries have been implicated in from 10 to 76 percent of deaths related to such
accidents, and Liedtke and DeMuth [16 ] noted that cardiac injuries are the most
common unsuspected injuries found in fatal accidents. [12 ] [17 ]
Parmley et al., [18 ] in a review of autopsy findings, classified cardiac injuries produced
by blunt trauma and noted that rupture of the heart, often in combination with rupture of
the aorta, was the usual cause of death (Table 43-1) . More important to this discussion
is the clinical series from the Maryland Institute for Emergency Medical Services
Systems (MIEMSS). [19 ] This facility serves a large population with multiple system
injury; 75 percent of the patients arrive by helicopter. During the 3 years from January
1982 through December 1984, 5378 patients were admitted, 515 of whom suffered
blunt trauma to the chest. The mean age was 37 years, and there was a 2.7:1
male-female ratio. The causes of injury were automobile accidents (70.9 percent),
pedestrian accidents (9.5 percent), motorcycle accidents (7.8 percent), falls (7.6
percent), and miscellaneous causes, including plane crashes and farm accidents. Three
hundred and thirty-nine (66.2 percent) patients arrived with stable vital signs, defined as
a systolic pressure of 90 mmHg or greater. Using this criterion, 143 (27.5 percent)
patients were hypotensive and 30 (5.7 percent) had no pulse or blood pressure and
cardiopulmonary resuscitation was in progress. Of the 515 patients, only 84 (16.3
percent) had isolated thoracic injuries. Nearly half (245 patients, or 47.5 percent) had
two or more systems injured in addition to their thoracic injury. Most common were head
injuries (222 patients), extremity fractures (202 patients), and intraabdominal trauma
(147 patients). An array of injuries, including facial and soft tissue trauma and pelvic and
spinal injuries, was present in 181 patients.
Fractures of the bony thorax were the most common injury; 451 fractures of ribs,
scapulae, sternum, and clavicles were noted. Rib fractures were the most prevalent
(368 patients), with nearly half involving three or more ribs. One hundred and
twenty-seven patients had no radiographic or clinical evidence of bony injury despite
documented thoracic injury. Nine of 19 patients with ruptured aortas and 10 of 23
patients with ruptured diaphragms had no thoracic bony injury. Cardiac contusion was
diagnosed in 33 patients by a variety of methodologies. Twenty (60.6 percent) of these
patients had no bony thoracic injury. Cardiac rupture was present in 14 patients, 4 of
whom had no bony thoracic injury. It is apparent that significant cardiac injury can occur
without bone injury to the thorax.
Mechanics of Injury
The heart is suspended in the middle mediastinum, where it is protected by the bony
thorax and surrounded by soft tissue. Despite these structures, injury may occur
following blunt forces transmitted through or by these structures. [20 ] Penetration of the
heart by fractured ribs is a well-known entity. De Muth et al., [21 ] in the dog model, have
shown that the extent of injury is related to the magnitude of the force, the duration over
which the force is applied, and the rate of change over time. Compression of the heart
by the sternum or between the sternum and the vertebral column is most common. The
classic example is steering wheel injury, but similar mechanisms are at play in athletic
injuries such as falling on a football or being struck by a hockey puck. [22 ] , [23 ]
Furthermore, since the heart is suspended superiorly and posteriorly by the great
vessels, it is susceptible to acceleration-deceleration injury through rotation along these
axes. [24 ] Laskey et al. [25 ] have described transmission of forces through the
diaphragm, the hydraulic ram effect seen with lap seat belt injury of the abdominal
structures and the heart. Commotio cordis, the occurrence of sudden death following a
blow to the chest (often from athletic injuries), continues to be reported. [26 ] This event
is thought to be due to ventricular fibrillation.
Myocardial Contusion
Myocardial contusion, probably first recognized by Akenside [27 ] in 1764, is the most
common injury of the heart from blunt trauma. It represents a spectrum of injury ranging
from mild epicardial and myocardial hemorrhage and cellular edema of little or no
physiologic or functional consequence to myocardial infarction. Accordingly, the
incidence of such injury is difficult to quantitate. In the autopsy series of Parmley et al.
[18 ] and Siegler [14 ] it ranges from 3 to 78 percent. Clinically, the incidence is equally
variable. In patients with a history of blunt chest trauma, the incidence of myocardial
contusion varied from 5 to 75 percent depending in great part on the criteria and
methodology used to determine its presence. [28 ] [34 ] Wisner et al. [35 ] noted an
incidence of 3 percent in 3010 blunt trauma admissions, with a 14 percent incidence at
autopsy. Fabian et al. [36 ] reported a 5 percent incidence, 56 of 1110 blunt trauma
patients.
In 1929, Kahn and Kahn [37 ] recognized that fatal injury to the heart could occur
following chest trauma despite the lack of external evidence of damage. Bright and
Beck [12 ] in 1935 reviewed all reported cases of nonpenetrating trauma to the heart
and for the first time called attention to this clinical problem. The study by Mortiz and
Atlans [38 ] in 1938 described the pathologic changes of contusions produced in canine
hearts struck by a wooden mallet.
There have been a number of studies describing the injury of contusion. [39 ] [42 ]
Grossly, the heart may reveal little damage, or there may be demonstrable epicardial
edema and hemorrhage. With more severe injury, hemorrhage may extend into the
underlying muscle. Microscopically, there may be evidence of hemorrhage, leukocyte
infiltration, cellular edema, and injury and patchy necrosis. Giant capillary sinuoids
develop along the distribution of the terminal arteriole that are responsible for local
arteriovenous shunting of blood within the myocardium. [39 ] , [43 ] This results in
decreased coronary artery perfusion and myocardial ischemia. Others have
documented a redistribution of blood away from the endocardium favoring the
epicardium, much as occurs in myocardial infarction and in low-flow states.[44 ]
Localized areas of ischemia presumably produce the wide variety of arrhythmias seen
with this condition. Healing occurs by scar formation and contraction. Since the
coronary arteries usually escape demonstrable injury, the zone of transition between
normal and contused myocardium is sharper than the usual gradual transition seen in
hearts suffering from coronary artery occlusion. This is an important distinction clinically
and provides the rational for treating hemodynamically significant myocardial contusion
with inotropic agents without the risk of extending myocardial damage, as may occur
with coronary artery disease. The result of injury is a decrease in cardiac function that
may range from mild to severe. Liedke et al. [41 ] and Doty et al. [40 ] measured
decreases in cardiac output of 30 to 40 percent in humans and in experimental animals,
decrements that may persist for several weeks.
DIAGNOSTIC STUDIES
Radionuclide angiography (RNA) is a technique widely used to determine right and left
ventricular function. Both first pass and multigated acquisition (MUGA) have been
utilized to measure ventricular function following blunt trauma. Sutherland et al.[45 ]
studied myocardial function by gated cardiac scintigraphy in 43 patients who had
suffered blunt chest trauma. Twenty-eight had wall motion abnormalities and were
classified as having myocardial contusion. Fifteen patients had normal wall motion and
were used as controls. The right ventricle was by far the most commonly affected
chamber, demonstrating abnormal motion in 18 patients. Combined ventricular
dysfunction was identified in 6 patients and isolated left ventricular dysfunction in 4
patients. Systemic oxygen transport was not statistically different in those patients with
isolated right ventricular dysfunction and the control group, although right ventricular wall
motion was severely compromised. Right ventricular volume was greatly increased and
worked at a higher end-diastolic volume, as defined by the Frank-Starling mechanism.
Rosenbaum and Johnston [46 ] studied 54 patients with multiple system trauma by the
use of first-pass and electrocardiographically gated radionuclide ventriculography.
Twenty-six patients (48 percent) had abnormalities of ventricular wall motion, 92 percent
of which were right ventricular. No correlation was found with electrocardiographic
(ECG) findings. Waxman et al. [47 ] evaluated thallous chloride thallium-201
singlephoton-emission computed tomography (CT) in a series of 48 patients following
blunt chest trauma. Twenty-three had normal scans; none developed serious
arrhythmias during 3 days of continuous monitoring. Of the 25 with abnormal or
ambiguous studies, 5 (20 percent) developed serious arrhythmias requiring treatment.
Schamp et al. [48 ] reported the use of combined first-pass and equilibrium-gated RNA
in 111 patients with blunt chest trauma admitted to MEIMSS. Criteria for an abnormal
RNA scan included a right ventricular (RV) ejection fraction of less than 40 percent, a
left ventricular (LV) ejection fraction of less than 44 percent, and/or segmental wall
motion abnormality of the right or left ventricle. An abnormal RNA scan was present in
40 patients (35 percent of those studied). The majority of abnormalities (33 of 40) were
confined to the right ventricle. Isolated abnormality of the left ventricle was seen in only 1
patient, while 6 patients had abnormalities of both ventricles. In these studies, RNA was
much more sensitive in detecting myocardial contusion than were clinical findings,
ECGs, or CK-MB isoenzymes. Despite the high prevalence of abnormalities, the
prognosis was good. Three of the 40 patients with abnormal RNA died compared with
2 of the 71 patients with normal RNA. These studies were repeated at the time of
discharge. Only 15 percent of originally abnormal scans remained abnormal. These
authors note that resolution of 85 percent of initially abnormal scans is similar to the
results found in the literature. Sturaitis et al. [49 ] reported a 1-year follow-up of
traumatized patients and found that patients originally classified as having myocardial
contusion based on RNA findings had a similar clinical course and RNA values as
those originally classified as free of myocardial contusion. These findings suggest that
RNA abnormalities obtained 24 to 48 hours after admission may be of minimal clinical
importance in the absence of obvious hemodynamic compromise.
Electrocardiographic changes invariably are present with contusion. [49 ] Nonspecific

ST-T wave changes are most common. Arrhythmia is the hallmark of experimental
contusion. Clinically, arrhythmias are present in from 15 to 85 percent of patients with
blunt chest trauma and are manifest on admission or within 24 hours. [50 ] , [51 ] They
are usually transient, and most resolve during hospitalization. Sinus tachycardia, atrial
fibrillation, and atrial flutter are common. Premature atrial and ventricular complexes are
often present, but ventricular tachycardia and fibrillation are unusual. Tenzer [52 ]
pointed out that the ECG is more influenced by the much greater muscle mass of the left
ventricle but the right ventricle is the more commonly injured structure. A normal ECG
does not rule out myocardial damage. The presence of significant change in usual
patterns may not be indicative of myocardial damage but may be the result of
mediastinal shift due to pneumothorax or on the basis of head or neck injury. [53 ]
Classic Q-wave patterns are the hallmarks of cellular death, and their presence, if new,
is diagnostic. It is apparent that a wide range of ECG findings may occur with
myocardial contusion. The appreciation of these changes and their correlation with the
clinical state and other studies are useful but in and of themselves are not diagnostic.
Creatine kinase (CK) is present in the brain, kidney, and cardiac muscle, and serial
measurements of CK and its myocardial band (MB) fraction are the most sensitive
determinants of myocardial damage. [54 ] [58 ] Elevations of the MB fraction above 5 to
6 percent have been correlated with myocardial cell death. Massive tissue injury
reduces this specificity because the CK MB fraction is present in lesser concentrations
in other tissues, including the gut, the diaphragm, skeletal muscle, and the liver. [59 ] [61
] The correlation of the CK MB fraction with myocardial contusion has been unreliable.
Potkin et al., [56 ] in a retrospective study of suspected myocardial contusion, found no
statistical significance in correlation with isolated elevation of these values.
Echocardiography (ECHO) has been studied extensively in the diagnosis of myocardial

contusion. Two-dimensional ECHO is ideal for detecting the abnormalities that may
occur, including global dysfunction, regional wall motion akinesis, hypokinesis and
dyskinesis, and abnormal changes in wall thickness and density. Unfortunately, the
study is difficult to do in the chest-injured patient and cannot be performed satisfactorily
in 20 percent or more of these situations. Further, while ECHO is very effective in
visualizing the left ventricle, it is not nearly so reliable in visualizing the right ventricle. [53
]
Reid et al. [62 ] used two-dimensional ECHO to study 39 patients with suspected
cardiac injury from blunt trauma. Pericardial effusion was identified in 6 patients and
wall abnormalities in 2. No abnormality was identified in 19 patients; the study was
unsatisfactory in 6 patients because of technical inadequacy. Beggs et al. [63 ] used
two-dimensional ECHO, serial ECGs, and isoenzyme assays to analyze cardiac
damage in 40 patients who sustained blunt chest trauma. Twenty patients were found to
have abnormal findings in one or more of these determinations. ECHO identified
pericardial effusion in 4 patients, chamber enlargement in 3, and ECHO-dense areas of
the right ventricle in 2. No correlation was found with isoenzyme assays or ECG
changes.
Frazee et al. [64 ] studied 291 victims of blunt thoracic trauma by isoenzyme screening
and two-dimensional ECHO. Fifty-eight patients (20 percent) demonstrated an MB
fraction within 24 hours of injury. Of these patients, 60 percent had normal
two-dimensional ECHO and were classified as having cardiac concussion. Forty
percent (23 of 58 patients) had abnormal findings on two-dimensional ECHO, usually in
right ventricle function. One instance (3 percent) of arrhythmia was noted in the 35
patients in the concussion group, but 9 patients (39 percent) with abnormal
two-dimensional ECHO findings developed cardiac arrhythmias within 72 hours of
injury. These studies suggest that in those in whom two-dimensional ECHO can be
obtained, 7 to 29 percent may have abnormal findings. In most studies, the correlation
between ECG or the CK MB fraction and two-dimensional ECHO is poor, and 2-D
ECHO abnormalities may be found in patients with normal ECGs or CK MB fractions.
Most, but not all, studies suggest that two-dimensional ECHO, when adequate, may be
more sensitive in predicting complications or need for intervention than the ECG or CK
MB enzymes.
Transesophageal echocardiography (TEE) is a semi-invasive technique that may be

performed rapidly and with minimal risk even in seriously injured patients on ventilators.
These devices incorporate biplane M-mode, two-dimensional, and Doppler ECHO in a
transducer mounted on the end of a flexible esophagoscope. The images are not
degraded by the chest wall or lungs, and because of the proximity to the heart, a
high-frequency transducer can be used. Much greater anatomic detail and resolution
are possible than with transthoracic ECHO. In addition, structures not well seen from the
precordium, such as the left atrial appendage and descending aorta, can be visualized.
Shapiro et al., [65 ] from St. Louis University Medical Center, reported their experience
with TEE in 19 patients who sustained severe blunt trauma and had mediastinal
widening on chest x-ray. Excellent images of the heart and aorta were obtained on all
patients. There were no complications of the procedure. Abnormalities were found in 12
(63 percent) of the 19 patients and included aortic wall hematomas in 2 patients,
regional wall motion abnormalities compatible with contusion in 5 patients, tricuspid
regurgitation in 3 patients, mitral and aortic regurgitation in 1 patient, and pericardial
effusion in 1 patient. These authors indicate that TEE can be performed safely in
patients sustaining severe blunt or penetrating chest trauma and that this study yields
useful information concerning the aorta and cardiovascular function.
CLINICAL MANAGEMENT
The diagnosis of myocardial contusion should be considered in any patient who suffers
blunt chest trauma. A careful history, including those facts learned from observers of the
accident or its aftermath, is essential. Chest pain is common, but the differentiation of
cardiac from bony and soft tissue pain is not exact. Anginal pain or pain similar to that
experienced in myocardial infarction may be present and is more reliable. [66 ] Nitrates
are not helpful in diagnosis because they may not relieve pain produced by myocardial
necrosis. The chest wall should be examined for contusion and steering wheel tatoo,
which is present in about 30 percent of patients, and for sternal and rib cage fracture or
instability. Heart sounds, while often difficult to assess adequately in the acute setting,
should be listened for and noted. Murmurs from unsuspected damage may occur later.
Adventitious sounds should be documented, as should auscultated arrhythmias. A
standard 12-lead ECG should be obtained, and the addition of a V 3 R-lead tracing may
be helpful in diagnosing right ventricular injury.
If the patient is stable or stabilizes after treatment of concurrent injury, significant

contusion is unlikely, and expectant observation is indicated. Most patients will progress
satisfactorily. If the patient is unstable, and especially if operative intervention is
required for associated injury, echocardiography is indicated. Transthoracic
two-dimensional ECHO is widely available and useful, but the transesophageal
technique is more revealing and, if not contraindicated by cervical or other injury, is the
diagnostic measure of choice. While CK MB fraction determination and radionuclide
angiography are still carried out in some trauma centers, their utility is questionable. [67
]
If significant contusion is suspected or proven, careful observation and monitoring are

indicated. The major concern is cardiac arrhythmia, although the clinical significance of
such monitoring on outcome is questionable. In a prospective study at the regional
trauma center in Stonybrook, McLean et al. [68 ] carefully monitored 312 patients with
blunt chest trauma. Twenty-seven patients were found to have significant ventricular
arrhythmias, 18 with ventricular tachycardia and 9 with over 100 ventricular systoles per
hour. There were no serious consequences. The most significant dysrhythmia
correlating with outcome was atrial fibrillation. Nine patients suffered atrial fibrillation,
and 5 diedbut none from cardiac injury.
The proper treatment of arrthymia is in doubt. [69 ] , [70 ] Potassium and magnesium
levels should be normalized. Nonsustained asymptomatic ventricular arrhythmias
probably are best not treated, although intravenous xylocaine has been suggested and
utilized. Xylocaine has been used effectively for sustained ventricular tachycardia for 30
years and is a standard in cardiopulmonary resuscitation. Prophylactic treatment has
proven helpful in preventing ventricular tachycardia and fibrillation in myocardial
infarction, but hospital mortality is unchanged. [71 ] No similar studies exist for trauma,
but prophylactic treatment may be more effective in the contused heart, which has great
potential for recovery. Atrial fibrillation with rapid response should be treated, but care
must be exercised because most antiarrhythmia drugs except digoxin reduce
ventricular function to some degree. The calcium-channel blocker diltiazem, of all drugs
currently available, has the least myocardial depressive effect, is widely used, and can
be recommended in acute situations where tachycardia is associated with
hemodynamic compromise. Its vasodilating effect is salutary in reducing the work of the
heart, but it may produce an undesirable fall in blood pressure.
In those instances where cardiac output is reduced to unacceptable levels on the basis
of ventricular dysfunction, inotropes are indicated and have proven effective. Degroot
and Prewitt, [72 ] using a captive bolt pistol to produce cardiac contusion in dogs,
demonstrated that dobutamine was superior to volume loading to increase cardiac
output. Flancbaum et al. [73 ] showed significant improvements in the cardiac output of
patients with myocardial contusions treated with inotropes. These authors described a
group of 19 patients who underwent general anesthesia and operative treatment, 15 (79
percent) on the day of admission. These patients were monitored carefully. Eleven
required inotropic support, and 1 required intraaortic balloon counterpulsation. No
patient died, and none suffered significant cardiac complications.
Severe dysfunction is unusual, but its occurrence is well documented. It should be

suspected in those patients who continue to exhibit low cardiac output despite
adequate volume resuscitation and inotropic support. Aggressive invasive monitoring
and additional inotropic and pressor support are indicated. In patients who do not
respond, use of the intraaortic balloon pump (IABP) has been lifesaving. [74 ] [80 ]
Permanent sequelae from cardiac contusion are rare. Of the more than 2500 patients
treated for blunt chest trauma over a 15-year period at the Maryland Institute for
Emergency Medicine, no one has been identified with lasting abnormality. [81 ] Other
large series report a low incidence of sequelae. Most arrhythmias resolve early on, and
decreased ventricular function usually normalizes within a few days or, when severe,
within 4 weeks. [82 ]
Despite the statistically favorable outcome, there are reports of lasting damage and
death. Progressive heart pump failure from myocardial fibrosis represents the other end
of what appears to be a bell-shaped curve representing the severity of myocardial
contusion. There is at least one report of heart failure so severe that transplantation was
carried out. [23 ]
Myocardial Laceration
The occurrence of cardiac rupture in autopsy and clinical series of blunt trauma patients
is very low. Rodriguez and Turney [81 ] surveyed a 10-year period at MIEMSS during
which 16,000 patients were admitted for blunt trauma; only 59 patients (0.3 percent) had
cardiac or pericardial rupture. On the other hand, rupture of the heart is the most
common cause of death in autopsy series of blunt trauma of the chest. Bright and Beck
[12 ] in 1935 reported 168 people who died following blunt trauma, of whom 152 had
suffered myocardial laceration or rupture. All four chambers were ruptured with equal
frequency. Parmley et al. [18 ] classified cardiac injuries produced by blunt trauma and
noted that rupture of the heart, often in combination with aortic rupture, was usually the
cause of death. Of 546 victims, 353 had suffered cardiac rupture. Eighty had
associated aortic rupture. Ventricular rupture was twice as common as atrial rupture,
with right ventricular rupture being the most common, followed by the left ventricle, the
left atrium, and the right atrium. One hundred and six victims suffered multiple-chamber
rupture, and atrial and ventricular septal rupture was found in 43, with 5 isolated
ventricular and 8 isolated atrial septal ruptures. A recent series from India by
Kulshrestha et al. [83 ] in 1990 reported on 3657 autopsies for trauma. Forty-four
victims had died from blunt cardiac trauma, with 36 having either one or both ventricles
ruptured.
The mechanism of rupture is speculative, and a number of explanations have been

offered. Atrial rupture is postulated to occur secondary to compressive force transmitted
directly to the heart at the end of ventricular systole. At this point in the cardiac cycle, the
atria are filled and the ventricles contracted. Concomitant compression of the abdomen
and chest can markedly elevate vena cavae and pulmonary vascular pressures. [84 ]
The sum total is sudden rapid elevation of atrial pressure against closed atrioventricular
valves, with bursting of the thin atrial wall. A second explanation is based on torsion of
the auricular appendage on the fixed atrium. This would account for tears commonly
seen in this area. Torsion may be similarly responsible for tears seen at the atrial-caval
junction, lesions that have been uniformly fatal. Ventricular rupture probably occurs as a
result of sudden compressive forces on the full heart in end-diastole. [85 ] Free wall
rupture is usual, but there are reports of septal rupture. [86 ] Delayed rupture,
presumably from myocardial necrosis and partial laceration, has been documented. [87
]
Most patients with cardiac rupture die at the scene of the accident, but both Bright and
Beck [12 ] and Parmley et al. [18 ] noted that from 10 to 20 percent of patients were
alive sufficiently long to have undergone operation if they had been transported
expeditiously. Bright and Beck noted that 30 of 152 patients with ventricular rupture
survived for 30 minutes or longer after the initial trauma. Calhoon et al. [88 ] confirmed
this and described 10 patients who arrived at their emergency center alive following
blunt trauma and cardiac laceration. Six presented wtih cardiac tampanode, 3 with
hemorrhagic shock, and 1 with combined symptoms. Associated injuries averaged
2.25 organ systems. Nine were operated on within 90 minutes of admission. Primary
repair of the laceration without cardiopulmonary bypass was accomplished in all, and 7
patients survived.
In the MIEMSS series of 56 patients with ruptured hearts transported from all over
Maryland by helicopter, 50 percent were lifeless on arrival. [89 ] Death occurs from
massive exsanguination or from cardiac tamponade or both. Patients with atrial tears
survive longer, probably related to the higher pressures generated by the ventricle.
Leavitt et al. [90 ] reviewed a total of 40 survivors of blunt cardiac rupture from the world
literature and found that 74 percent had atrial rupture. In the review by Patton et al. [91 ]
of 24 patients with atrial tears, operation was delayed for more than an hour in 16. This
delay occurred despite the finding that all 24 were hypotensive and 21 had neck vein
distension or elevated central venous pressure.
DIAGNOSIS
The diagnosis of cardiac rupture usually has been made fortuitously when the patient, in
extremis, has been submitted to thoracotomy. The clinical presentation is tamponade or
shock, either from controlled hemorrhage with an intact pericardium or from a partially
disrupted pericardium that allows bleeding into the pleural cavity. Beck's triad of shock,
muffled heart sounds, and distension of the cervical veins may be present but is
unreliable. Hemothorax may be present. Cyanosis of the upper body, the etiology of
which is not clear but probably relates to the nondistensibility of the veins in the upper
caval system, has been observed frequently. Central venous and pulmonary artery
determinations vary widely; they may be markedly elevated if the presentation is
tamponade or low if the presentation is hemorrhage. Volume replacement may produce
an increase in intervascular volume followed by an increase in central venous,
pulmonary artery, and systemic pressures that results in increased bleeding and a
secondary fall in both arterial and venous pressures. Associated injury may further
confuse the issue.
In the small group of patients who are stable or who become stable with treatment,
various diagnostic maneuvers have been described, including ECG, chest x-ray, CT
scanning, echocardiography, and pericardial lavage. The chest x-ray or CT scan may
reveal a dislocated heart from pericardial rupture or other indirect evidence of heart
damage, including a fractured sternum, fractured ribs, and hemopneumothorax.
Echocardiography may reveal pericardial effusion, myocardial disruption, dyskinesia, or
later a psuedoaneurysm. Subxyphoid pericardial window is advocated for those
patients whose diagnosis is in doubt. Pericardiocentesis is mentioned only to be
abandoned; Borja and Lansing [92 ] note a 25 percent incidence of false-negative
results.
The performance of a subxyphoid window should be carried out in the operating room
(Fig. 43-1) . This procedure is more difficult and time consuming than generally
recognized. The whole chest and upper abdomen should be prepped for possible
anterior thoracotomy or sternotomy. If possible, the patient should be placed in a slight
semi-Fowler's position. Local or general anesthesia may be used. A vertical incision 6
cm in length is centered over the xyphoid process in the midline. The linea alba fascia is
divided, and the xyphoid process is freed or removed. The sternum is retracted
superiorly, and the fibrofatty tissue on the diaphragm and pericardium is dissected until
the fibrous pericardium is identified. The pericardium is opened with a knife between
long Kelly or Allis clamps. The presence of blood should result in immediate exploration.
TREATMENT
Initial resuscitation should follow the standard principles used in the care of all trauma
patients, with airway control, adequate ventilation and oxygenation, and volume
replacement. Definitive treatment, including placement of chest tubes based on clinical
findings and rapid x-ray examination, should be commenced simultaneously. Most
patients will deteriorate rapidly. Under these circumstances, a left anterolateral
thoracotomy is performed in the admitting area. [93 ] In those rare instances when the
patient is stable and the diagnosis is suspected by diagnostic examination, sternotomy,
rapidly and efficiently performed, is a more familiar and better incision for dealing with
the injured heart and pericardium.
Repair of the lacerated heart should be carried out with standard nonabsorbable,
pledgeted sutures of the type generally used for aortic and atrial cannulation. Obvious
bleeding should be controlled by gentle finger pressure. Foley catheters blown up within
the heart have been recommended, but some bleeding is inevitable, and as pressure is
exerted on the heart wall to control this bleeding, extension of the laceration is a distinct
hazard. [94 ] A torn atrium may be grasped and bleeding controlled with Babcock
clamps or an appropriate vascular clamp. Repair is accomplished with running or
purse-string sutures as indicated. Right ventricular tears are most common, and if
bleeding cannot be controlled by finger pressure, it usually can be controlled by laterally
placed holding sutures until repair is accomplished. The first repair suture should be
placed in the middle of the tear, well away from the edge of the defect. This suture and
the normal contraction of the heart during systole generally will greatly reduce bleeding
and allow repair to be carried out. Left ventricular rents are best repaired without
resorting to clamping maneuvers. Ventricular repairs are best accomplished by
interrupted sutures tied over pledgets because it is difficult and dangerous to adjust
tension on a running suture in a traumatized beating heart. For posterior wall or
atrioventricular groove injuries cardiopulmonary bypass may be necessary.
Two events are common during repair: hypotension from hypovolumia and ventricular
fibrillation, which can be exacerbated by hypothermia and acidosis. Once bleeding is
controlled or significantly reduced, one should pause to allow the anesthesiologist the
opportunity to reestablish volume deficiencies, correct acidosis, and adjust
medications. If ventricular fibrillation occurs, bleeding is markedly reduced, and 30
seconds of this event can be justified for placing definitive sutures before beginning
electrical defibrillation and manual compression.
When one reviews the literature on blunt trauma injuries of the myocardium, certain
findings are apparent. Emergency thoracotomy is not successful for blunt trauma victims
who are lifeless at the scene of the accident and rarely is successful for those who are
lifeless on arrival at the trauma unit. [95 ] [99 ] Harnar et al. [100 ] in Seattle performed
emergency thoracotomy on 65 patients who had suffered blunt trauma and were
undergoing cardiopulmonary resuscitation. Eight patients (12 percent) survived, but
details of injury and what was accomplished by thoracotomy were not stated. Fifty
percent of the patients in the series of Fulva et al. [89 ] were undergoing
cardiopulmonary resuscitation upon arrival, and all died. Fifty percent more suffered
arrest after arrival, and 50 percent of these patients survived. The overall survival rate
was 24 percent. Pevec et al. [94 ] reviewed the literature and found 60 cases of survival
following blunt rupture of the heart, and other, more recent series have added additional
survivors. Thus vigilance for this lesion is indicated because cure is possible.
Ventricular Aneurysm
There are rare reports of ventricular aneurysm and pseudoaneurysm following blunt
trauma. [101 ] , [102 ] Normal coronary arteries suggest that a contained disruption of
the myocardial wall occurred followed by aneurysm formation. Repair is indicated, but
the final decision is on an individual basis.
Septal Defects
Ventricular septal defects have been reported following blunt trauma but less frequently
than free-wall rupture. [103 ] [107 ] They usually are located in the muscular septum near
the apex. Atrial defects are rare. Parmley et al. [18 ] noted 25, but only 8 were isolated.
Jenson et al. [108 ] reviewed the literature and reported a total of 5 operated cases.
There are anecdotal reports of multiple ventricular septal defects, sinus of
Valsalva-atrial fistulas, and torn septa leading to heart block. [109 ] [112 ] The
mechanism of injury probably is the same as that for free-wall rupture.
Ventricular septal defects may present early or late. They are heralded by a new systolic
murmur and by heart failure if the defect is hemodynamically significant. Diagnosis can
be confirmed by two-dimensional echocardiography performed transthoracically or
transesophageally and by demonstrating an oxygen step-up with catheterization. [103 ] ,
[106 ] Repair usually is indicated unless the shunt is small (less than 1.5 to 1) and
asymptomatic. There is at least one report of a small defect closing. [113 ] Generally, it
is recommended that repair be delayed for some months if possible to allow fibrosis of
the adjacent myocardium to occur.
Larger shunts producing uncontrollable heart failure require early and at times
immediate repair. The situation is not unlike a ventricular septal defect due to
myocardial infarction. A loud systolic murmur is present, and the patient experiences
chest pain, severe dyspnea, and a low cardiac output state with cyanosis and acidosis.
In these circumstances, hemodynamically significant myocardial contusion may be
present and may severely compromise cardiac function in the pre- and postrepair
period. Use of the intraaortic balloon pump is indicated. [114 ] This device is highly
effective in reducing the shunt and in increasing effective cardiac output and coronary
flow. A delay of 1 to 2 weeks should be sufficient to allow the contusion to heal. Repair
using cardiopulmonary bypass usually requires Dacron patch closure, and sutures
should be buttressed with Teflon pledgets. Small defects with firm edges have been
closed primarily. [115 ]
Valvular and Valvular Apparatus Injury
Valvular injury following blunt trauma has been recognized for over 100 years. [116 ] The
aortic valve is injured most commonly. In our clinical experience, the injury takes the
form of commissural avulsion or dissection resulting in aortic regurgitation. More severe
injuries, including leaflet disruption and laceration, may produce early and severe heart
failure. These injuries have been repaired successfully in the immediate postinjury
period. Mitral valve injury also presents with an array of clinical symptoms and signs,
ranging from a new murmur (with few symptoms from chordal rupture) to angina and
mild shortness of breath to fulminating pulmonary edema on the basis of acute massive
mitral regurgitation. Tricuspid injury is rare, and the reported patients have ranged from
having few symptoms to showing significant edema and ascites.
AORTIC VALVE INJURY
Aortic valve injury probably represents a lesser form of aortic rupture, which is a major
cause of death from blunt trauma. Tremendous pressure is needed to burst the aorta.
Commack et al. [117 ] have estimated that the occupants of cars involved in a 60-mi/h
head-on collision develop a sudden elevation in aortic pressure to about 2250 mmHg,
which is about 250 mmHg more than is necessary to rupture the aorta. Zehuder [118 ]
estimated that it requires 2000 mmHg to rupture the aorta. Equally important is the
shearing stress that develops in the aortic root, particularly with vertical deceleration.
[119 ] The adventitia and external elastic lamella have a higher elastic limit than the
intima, which presumably accounts for the occurrence of intimal tears with intact outer
walls seen with rapid deceleration injury. One may postulate that these mechanics
produce leaflet rupture and/ or intimal disruptions in the valve area, particularly if the
valve is closed during diastole. This lesion, while unusual, is by no means rare. Symbus
[120 ] has indicated that a major trauma center may see 2 to 10 of these injuries in a
10-year period. One of the authors (McLaughlin) has treated at least 4 such lesions in
the past decade, but 3 were chronic.
The signs and symptoms of aortic valve injury are those of aortic valve regurgitation and
its consequences. These may occur early or late, depending on the severity of the injury
and the occurrence of heart failure. [121 ] A systolic murmur from turbulence around the
disrupted valve or intimal flap is usually present. A prolonged diastolic murmur of aortic
regurgitation is invariably present and may mimic a seagull's cry. In severe injury,
particularly with tachycardia, this murmur may be harsh and blend in with the systolic
component, mimicking the croaking of a frog. Dyspnea, pulmonary congestion, and
increasing heart size are classic findings that may be mild or dramatic. Diagnosis can
be confirmed by two-dimensional echocardiography and by catheterization and
aortography.
Treatment depends on the magnitude of the injury and the circumstances existing at the
time of repair. A commissural disruption may only require resuspension of the valve.
This is accomplished by placing pledgeted nonabsorbable sutures through the wall of
the aorta and repairing the associated intimal tear in a like manner to protect from later
dissection. Leaflet repair may be possible but often is undependable. Aortic valve
replacement is usually necessary. Of interest are reports of bioprosthetic valves being
disrupted by blunt trauma and being replaced successfully. [122 ] Those injuries
associated with dissection of the ascending aorta may require composite valve graft
interposition and coronary artery implantation.
MITRAL VALVE INJURY
Isolated mitral valve injury is rare. Parmley et al. [18 ] found none in their review of 546
autopsy cases of blunt trauma victims, although there was mitral valve injury in
association with other fatal injury in 5 percent of these patients. Mitral and tricuspid
injuries probably result from a sudden compressive force transmitted to the heart during
late diastole or beginning systole when the heart is full and the valves are closed. Lyan
et al. [123 ] have shown in isolated hearts that a pressure of 320 mmHg is necessary to
produce ventricular wall and valve rupture. The type and magnitude of injury may vary
widely. In the 20 or so reported operated cases, the most common injury was papillary
muscle rupture. Both anterior and posterior muscles have been affected, and disruption
may occur at some time following the actual trauma (presumably from necrosis or from
completion of a partial tear). [124 ] Chordae tendineae rupture is much less common,
and valve leaflet tears are few. There are reported combined mitral and tricuspid valve
injuries and at least two cases of mitral prosthetic valve dysfunction following blunt
trauma. [125 ] [127 ]
Symptoms may be immediate or delayed and vary from minimal to severe. Initially,
cardiac contusion compounds the problem, and there is at least one anecdotal report of
significant combined mitral and tricuspid insufficiency improving with time. [128 ]
Symptoms of heart failure predominate, with dyspnea, pulmonary edema, and evidence
of low cardiac output. A loud systolic murmur, at times with the typical seagull pitch of
ruptured chordae or papillary muscle, is present at the base and radiates to the axilla. In
the acute injury state, this murmur may be difficult to hear, and transthoracic
echocardiography may not be diagnostic. Transesophageal echocardiography usually
is definitive for visualization of the mitral valve. [129 ] Right-sided heart catheterization
reveals pulmonary hypertension, and left-sided heart ventriculography is diagnostic for
mitral valve regurgitation. Operative treatment of traumatic mitral valve regurgitation
depends on the type of damage encountered. Unlike chronic regurgitation, where the
process is one of progressive deterioration and failure, traumatic regurgitation is acute
and demands urgent attention. Severe failure is best treated initially by the intra-aortic
balloon pump. The situation is not unlike papillary muscle rupture from myocardial
infarction, but in the case of trauma, the associated contusion is self-limiting, and early
operation is indicated. Most patients have required replacement of the valve, but
various valve repairs have been carried out since 1964, when a valvuloplasty was
performed on a 7-year-old boy 8 months following an anterior leaflet and chordae tear
by one of the authors. [130 ] The prognosis for repair is good, and results depend in
great part on associated injury.
TRICUSPID VALVE INJURY
In clinical series, tricuspid valve injury is reported more commonly than mitral valve
injury. This may relate to its anterior location in the right ventricle and to the less serious
nature of tricuspid regurgitation as compared with mitral regurgitation. Perlroth et al.
[131 ] in 1986 collected 30 cases of posttraumatic tricuspid regurgitation.
Characteristic findings described were a history of trauma, right bundle branch block,
and cardiomegaly without signs of left ventricular failure. The authors also noted that
atrial hypertension of long standing may produce right-to-left shunting through a patent
foramen ovale with resulting cyanosis.
Van Son et al. [132 ] described the Mayo Clinic experience with 13 such cases treated
surgically over a 30-year period (19641993). All patients were male and ranged in age
from 17 to 64 years (mean 39 years). The etiology of injury was motor vehicle accidents
in 12 and the explosion of a compressed air tank in 1. Six patients were in sinus rhythm,
and 7 were in atrial fibrillation. Right ventricular function was decreased in 12. The
specific injury was chordae rupture in 9, rupture of the anterior papillary muscle in 3, and
tear of the anterior leaflet in 1. The septal leaflet was missing in 1 patient and retracted
and adherent to the septum in another.
The majority of patients reported have had chronic and often progressive symptoms, but
there is at least one report of acute deterioration requiring immediate surgery. [133 ]
This young woman presented in shock following a riding accident. Echocardiography
demonstrated complete disruption of the posterior papillary muscle. Other reports
describe annular tears [134 ] and rupture of the tricuspid valve in association with the
development of a septal aneurysm and a ventricular septal defect documented by serial
echocardiography. [135 ] Diagnosis of triscupid injury depends on the recognition of
right-sided heart failure, a systolic murmur, evidence of a right-sided heart abnormality
by electrocardiography, and demonstration of the injury by echocardiography. [136 ]
Treatment depends on the hemodynamic consequences of the lesion. Many patients

will do well for many years with conservative therapy, but there appears to be relentless
deterioration of right-sided heart function. [132 ] In older persons with mild damage and
symptoms, repair probably is not indicated. In younger patients, a more aggressive
approach is in order, recognizing that most will require valve replacement with its
intrinsic problems. In the Mayo Clinic series, valve repair was accomplished in 5
patients, and valve replacement was necessary in 8. In 7 of the latter group, the
chordae, papillary muscles, and tricuspid valve leaflets were in a contracted and
atrophic state. There were no deaths, and in follow-up extending to 26 years (median 12
years), 12 patients were in New York Heart Association class I and 1 patient was in
class II. Nine patients were in sinus rhythm, and 4 were in atrial fibrillation. These
authors suggest that earlier operation increases the possibility of repair and decreases
the consequences of prolonged right-sided heart dysfunction, including atrial fibrillation.
Pericardial Injury
Pericardial effusion of no physiologic consequence has been identified by

echocardiography in the posttraumatic state. This finding is common in patients in
whom myocardial contusion is suspected. Posttraumatic pericarditis frequently is
overlooked in the multiple injury patient. Friction rubs are difficult to hear in the intensive
care unit environment and are fleeting in duration. Fortunately, this condition rarely
progresses to pericardial tamponade. Tamponade, however, can occur and is heralded
by deterioration of the patient's hemodynamic status. Although nonspecific to the
condition, a rapid pulse rate, lowered blood pressure, and oliguria should alert a
physician to the possibility of tamponade. The ECG is frequently nonspecific, and chest
x-ray studies are not reliable. Intracardiac pressure measurement and
echocardiography are diagnostic.
In the series of Parmley et al., [18 ] pericardial laceration or rupture was found in 249 of
546 autopsy cases of blunt chest trauma. While not commonly reported, DeMuth et al.
[137 ] suggested that isolated pericardial laceration occurs and may be present more
often than is generally appreciated in survivors of blunt chest injury. Moer and Solheim
[138 ] reviewed the literature on pericardial rupture and noted an improved survival rate
resulting from, they contend, a heightened awareness of the condition.
In a review of the literature from 1939 to 1983, Clark et al. [139 ] identified 142 patients
with pericardial rupture. A later consideration of the subject from MIEMSS in 1990
identified 22 patients with pericardial rupture out of 20,000 trauma admissions over the
10-year period 1979 to 1989. [140 ] Sixteen patients were injured in vehicular accidents
(72 percent), 3 (13.6 percent) in motorcycle crashes, 2 in falls (9.1 percent), and 1 was
crushed (4.5 percent). Eighteen patients (81.8 percent) were diagnosed intraoperatively
during resuscitation or surgery for associated injuries, and 4 (18.1 percent) were
diagnosed preoperatively by pericardial window. Eighteen were males, and 4 were
females. The ages ranged from 17 to 68 years (median 40.1 years). The tears were
found at the following sites: left pleuropericardial, 14 (64 percent); diaphragmatic, 4 (18
percent); right pleuro-pericardial, 2 (9 percent); and superior mediastinal, 2 (9 percent).
Five patients (23 percent) with associated cardiac injury died. Herniation of the heart
usually to the left side occurred in 6 patients. The overall mortality was 64 percent (14 of
22 patients).
Rupture of the diaphragmatic surface of the pericardium was reviewed by Van

Loenhout et al., [141 ] who found 58 cases and added 1 of their own. The majority of
patients had been involved in traffic accidents and presented with both abdominal and
cardiopulmonary symptoms. Most associated skeletal lesions were on the left side of
the body. A number of studies, including chest x-rays, CT scans, and echocardiography,
were helpful in making the diagnosis, while pneumoperitoneum was not. These authors
suggest an abdominal approach in the acute phase so that the entire diaphragm and
the abdominal organs can be inspected.
The discovery of a pericardial tear may be fortuitous at the time of emergency

thoracotomy. Small tears may be asymptomatic. Larger tears are often associated with
herniation of the heart, an often fatal complication that has been reported in both adults
and children. [142 ] , [143 ] Herniation may occur at any time, and there are reports of
intermittent dislocation brought on by change of position [144 ] ( Figs. 43-2 and 43-3 ).
There is a recent report of dislocation occurring 6 months after the original injury. [145 ]
Classically, dislocation produces electrical-mechanical dissociation. This event may
occur from torsion of the heart on the venae cavae or by actual compression of the heart
by the edges of the tear.
Physical examination may be helpful if herniation occurs but usually is not revealing. The
bruit de moulin (the splashing wheel) was described by Morel-Lavallee [146 ] in 1866
but is rarely heard. A pericardial rub may be present but often is obscured by ventilatory
sounds. A chest x-ray may reveal pericardial air and cardiac dislocation. Turney and
Rodriguez [144 ] recommend the use of a pericardial window in those patients in whom
the diagnosis is suspected. If blood is present in the pericardium, they proceed with
sternotomy.
Pericardial tears demand inspection to control bleeding, to assess concurrent injury,

and to prevent cardiac herniation. Diaphragmatic tears found during laparotomy or
sternotomy should be repaired. Moderate-sized defects through which the heart can
herniate should be repaired, with the proviso that cardiac edema and swelling may
occur and that the pericardium should be left open anteriorly. Smaller defects can be left
alone once hemostasis is ensured.
Postpericardial injury syndrome is common following trauma, but its etiology is obscure.
The clinical findings are similar to those seen following myocardial infarction or open
heart surgery. A pericardial friction rub usually is present in early stages but is heard
less often with the formation of pericardial fluid and its lubricating effect. Chest pain,
fever, and an elevated white blood cell count usually are present. Diagnosis is one of
exclusion. Treatment with anti-inflammatory agents such as indomethocin, ibuprofen, or
aspirin usually is effective. On occasion, particularly if anticoagulants are being used,
pericardial tamponade may ensue. Echocardiography has great utility in dealing with
pericardial problems. This examination should be performed as soon as possible
following injury or operation to provide a baseline. Repeat study should be performed at
approximately 1 week, or sooner if indicated by clinical findings, and should be
repeated periodically until the effusion subsides. This condition rarely leads to
constrictive pericarditis. [147 ]
Coronary Artery Injury
Myocardial infarction following blunt trauma has been documented, and coronary artery
injury following penetrating trauma is well known. Not so well documented is coronary
artery occlusion from blunt trauma. Parmley et al. [18 ] identified 10 coronary artery
lesions among 546 autopsies. Subsequently, a number of coronary artery lesions have
been reported anecdotally and include coronary artery disruption and laceration,
thrombosis, intimal dissection, and anteriovenous and cameral fistulas. [148 ] [151 ]
Autopsy studies have been insufficiently detailed, and only recently has coronary
angiography been performed on these patients. The left anterior descending artery is
the most frequently injured, followed by the right coronary artery; the circumflex artery is
rarely injured. It is often difficult to determine how much of the mechanism of injury is
because of preexisting coronary arteriosclerosis and how much is on the basis of acute
coronary damage. Nonetheless, there are a few well-documented reports of isolated
coronary artery occlusion following blunt trauma in patients whose other coronary
arteries were normal. [152 ] , [153 ] Treatment of these patients has been limited to
general medical therapy of the resulting myocardial infarction.
Surgical treatment should be tailored to the lesion. If a small or distal artery is lacerated,
control of bleeding by ligation is sufficient. Larger arteries may require bypass. In
chronic fistulas, ligation above and below the fistula and distal bypass are the
procedures of choice.
PENETRATING INJURY OF THE HEART
Penetrating injury of the heart continues to increase in frequency. Twenty years ago,
most thoracic wounds in civilian practice were from knives. Less than 15 percent were
from gunshots, and these wounds usually were from small-caliber, low-velocity
weapons. This scenario has changed dramatically (Table 43-2) . Today, most wounds
are from gunshots, and the percentage of wounds caused by high-velocity weapons is
increasing. Urban police wear protective Kevlar vests, a practice that has been adopted
by some drug dealers. The wounds closely resemble those seen in battle. There has
been a progressive change in the treatment of these wounds to earlier and more
frequent thoracotomy. Grover [154 ] noted that in civilian practice, thoracotomy may be
required in 15 to 30 percent of patients with penetrating thoracic injuries (Table 43-3) ,
which is in marked contrast to the 5 to 10 percent incidence of two decades ago.
Further, one must be impressed by the percentage of patientsoften with cardiac
woundsmandating immediate thoracotomy in emergency departments (Table 43-4) .
[155 ]
Incidence and Demographics
In the past, most victims of cardiac penetration died at the scene, often with an injury
that could be corrected. [156 ] With the development of rapid transport systems and
facilities devoted to emergency care, many such patients arrive in the hospital alive, are
treated immediately, and survive. Parenthetically, this trend has been counterbalanced
by the increase in firearm injury. In a 1979 report from Louisville, the authors noted a
tenfold increase in gunshot wounds and stated that these accounted for 60 percent of
the wounds of the heart in their series. [157 ] The prehospital mortality from cardiac
wounds in the 1960s and 1970s was at least 50 percent and probably closer to 85
percent. [158 ] [163 ] Data are difficult to interpret because most series report patient
status at the time of hospital arrival with varying definitions of life and lifelessness.
Steichen et al. [164 ] in 1971 classified a series of patients with cardiac wounds into
three groups depending on their status on arrival: group I, lifeless; group II, shock from
hemorrhage or progressive tamponade or both; and group III, stable tamponade. This
classification has been modified by Ivatury et al. [165 ] at the same institution to include
quantifying anatomic as well as physiologic severity. Many authors now use variations of
these classifications, but uniformity is lacking. [166 ]
The frequency of wounds to the heart chambers depends on anatomic location. The
right ventricle, because of its anterior position, is wounded most commonly. Karrell et
al., [167 ] in a collective review of 1802 patients, found right ventricular injury in 765
(42.5 percent), left ventricular injury in 594 (33 percent), and right and left atrial injury in
277 (15.4 percent) and 105 (5.8 percent), respectively. Sixty-one had injury of the great
vessels. In our series of 109 patients collated by Attar et al., [168 ] the right ventricle was
injured in 51, the left ventricle in 30, the right atrium in 11, the left atrium in 4, and the
superior vena cava in 3. Thirteen patients had multiple-chamber injury, with 7 having
both right and left ventricle involvement and 3 having right atrial and ventricular injury.
Mechanics of Injury
Penetrating wounds can be classified as those from low-velocity agents such as stab
wounds from knives and some handguns and those which strike with high velocity. In the
former, the severity of injury depends upon the organ penetrated and the extent of direct
damage. High-velocity missiles add the factor of concurrent damage. Amato et al. [169
] studied the events that occur within various times after high-velocity bullet wounding.
The major forces consist of the velocity, the mass, and the change in shape of the
projectile when it penetrates the tissue. The most important force is velocity. The initial
velocity on impact is the striking velocity . If the bullet leaves the tissue, the remaining
velocity is the residual velocity . The effective velocity of injury is the difference
between the two velocities ( V 1- V 2). The kinetic energy KE imparted to the tissues is
expressed in footpounds:
where M equal mass and g equals gravity. In low-velocity wounds, destruction is

confined to the pathway of the projectile. High-velocity missiles generate shock waves
with pressure up to 100 to 200 atm that produce severe tissue destruction. A
medium-velocity 22-caliber magnum is capable of eight times the energy release of a
relatively low-velocity 38-caliber revolver. [3 ] High-velocity assault weapons are
capable of producing missile velocities greater than 2000 ft/s.
Presentation and Pathophysiology
Basically, there are two results of cardiac wounding: hemorrhage and pericardial
tamponade. Valve injury and other structural injury, including septal defects and
coronary artery injury and laceration, may add to the insult. Hemorrhage and tamponade
may range from minimal to profound.
Pericardial tamponade is the dominant presentation in 80 to 90 percent of patients with

stab wounds. [159 ] , [170 ] , [171 ] In these patients, the formation of clot and the
adjacent pericardial fat seal the tear in the pericardium and may seal the heart wound
as well. Demetriades and Vander Veen [161 ] reported that 92.7 percent of their
patients with right ventricular wounds presented with tamponade as opposed to 42.9
percent of patients with left ventricle lacerations. Moreno et al. [72 ] observed improved
survival for patients presenting with tamponade with injuries of both the right and left
ventricles from both stab and gunshot wounds. They reported a survival rate of 73
percent (24 of 33) in patients with tamponade compared with 11 percent (5 of 44)
without its protective effect. Our studies do not confirm this observation. One thing is
clear, pericardial tamponade may present a clinical picture out of proportion to the
degree of injury producing it, and its relief profoundly alters this condition.
Cardiac tamponade may have severely deleterious effects on the heart and circulation.
Wechsler et al. [173 ] have shown experimentally that this condition produces
endocardial and epicardial ischemia. Compression of the right ventricle reduces its
filling volume and output and subsequently the left ventricular output with resulting shock
and decreased coronary artery and cerebral blood flow. Low levels of tamponade can
be compensated readily by volume infusion, but the concurrent increase in ventricular
pressure leads to additional bleeding and worsening tamponade as the limits of
pericardial distensibility are reached. Decreased perfusion leads to death.
Gunshot wounds are characterized by bleeding, but approximately 20 percent will

present with cardiac tamponade. [174 ] , [175 ] Once again, tamponade has been
suggested as a protective mechanism for both gunshot and fragment injury, which
probably relates to low-velocity missile penetration and minimal disruption of the
pericardial and myocardial tissues. Hemorrhage may vary from obscure and clinically
not apparent to massive and characterized by profound shock.
Diagnosis
Cardiac injury must be suspected in anyone who has a history of penetrating trauma to
the chest. Fifty percent of patients who reach the hospital with potentially fatal wounds
are temporarily stable on admission. [170 ] An anterior wound and hemodynamic
instability greatly increase the likelihood of such injury. The danger zone includes the
area of the precordium, epigastrium, and superior mediastinum. [168 ] , [176 ] However,
cardiac injury can occur with penetrating wounds anywhere in the chest, neck, back, or
abdomen. DeGennaro et al. [177 ] analyzed 53 patients with penetrating wounds within
the cardiac shadow and found that 85 percent had thoracic injuries that required
operative control, including 42 percent with cardiac injury. Seimans et al. [178 ] noted
that 65 percent of their patients who required cardiac repair had upper mediastinal
wounds.
Echocardiography has been used with increasing frequency to diagnose cardiac injury.
Whye et al. [179 ] used two-dimensional ECHO to identify pericardial tamponade
resulting from a stab wound in a patient who was hemodynamically stable. Bolton et al.
[180 ] performed two-dimensional ECHO on 5 patients with penetrating trauma whose
vital signs stabilized following fluid administration and who had minimal clinical findings.
A small effusion was identified in 3, but the other 2 had no obvious abnormalities.
Surgical exploration was carried out, and all 5 were found to have intrapericardial injury.
These authors concluded that a normal echocardiographic study does not rule out
significant intrapericardial injury.
Plummer et al. [181 ] reviewed the records of penetrating cardiac trauma at the
Hennepin County Hospital over a 10-year period. Forty-nine patients were evaluated.
Twenty-eight were studied immediately by two-dimensional ECHO (ECHO group), and
21 were not studied immediately (non-ECHO group). The time from emergency room
admission to diagnosis and disposition for surgical intervention was 15.5 ± 11.4
minutes for the ECHO group and 42.4 ± 21.7 minutes for the non-ECHO group. The
actual survival was 100 percent for the ECHO group and 57 percent for the non-ECHO
group. These authors conclude that since the introduction of immediate
echocardiographic study, survival has increased. These are interesting findings, but
other factors, including increased awareness of the possibility of cardiac injury, may
play a role.
Transesophageal echocardiography (TEE) also has been utilized for diagnosis. [182 ]
[184 ] It has value in localizing fragments in the heart and is effective in cases where
transthoracic ECHO is not. Its utility in acute situations has not been established.
SUBXIPHOID PERICARDIAL WINDOW

Subxiphoid pericardial window is clearly established as the most effective way of
confirming a diagnosis of cardiac or pericardial injury short of formal thoracotomy or
sternotomy when the issue is in doubt. [185 ] The results are very consistent, if not 100
percent certain.
Brewster et al. [186 ] reported 108 patients with penetrating wounds in proximity to the
heart who had no obvious signs of cardiac injury and who underwent subxiphoid window
procedures. Thirty procedures were positive, 2 of which were false-positive studies.
Twenty-eight patients had injuries (20 ventricle, 3 atrium, and 5 pericardial), and 21 of
these patients required suture repair. Eleven patients with cardiac injuries were not
hypotensive and did not have signs of tamponade. The procedure caused no significant
morbidity and was used in conjunction with laparotomy on 39 occasions.
Andrade-Alegre and Mon [187 ] at the Santo Tomas Hospital in the Republic of
Panama performed pericardial windows on 76 patients with penetrating wounds near
the heart. Patients with shock and an obvious diagnosis were not included in their
series. The procedure was carried out under general anesthesia. Sixteen patients were
found to have positive studies. There were no false-positive or false-negative studies,
and all patients survived, with a morbidity rate of 1.3 percent.
Management of Penetrating Wounds
Most potential cardiac wounds are obvious (Fig. 43-4) . If the patient has suffered a
penetrating injury to the anterior chest and is in shock from blood loss or tamponade,
immediate action is indicated. The guidelines established by the American College of
Surgeons in the Advanced Trauma Life Support Management Protocols provide a
basis for action. [188 ] An airway must be established. In the patients under discussion,
this generally means an orally inserted endotracheal tube, ideally one with an internal
diameter of 8 mm. Sellick's maneuver (cricoid pressure) to prevent regurgitation and
aspiration is useful. [189 ] If ventilation is impaired, hemopneumothorax should be
entertained clinically, and chest tubes should be inserted on clinical grounds and
physical findings without waiting for radiologic studies. Simultaneously, venous access
is obtained above and below the diaphragm, with one access being a large-bore
14-gauge catheter in the anticubital fossa on the side opposite the injury. For the patient
in shock, rapid volume infusion is indicated.
Throughout the time that the preceding maneuvers are being carried out, an
assessment of the patient is performed. A brief history of injury is sought from the
patient or the emergency crew. The level of consciousness and the extent of
spontaneous movement are determined. Additional injury and exit wounds are sought.
The heart sounds are listened for, and the cervical venous status is noted. Both lungs
are auscultated in the axillary area of the chest away from the bronchial and tracheal
sounds. The abdomen is evaluated. Pulses are palpated in all four extremities.
A course of action is determined. Time is of the essence.
THE LIFELESS PATIENT
A distinction must be made between those patients who are lifeless at the scene and
those who are lifeless on arrival but who exhibited signs of life during transport. The
survival rate of the former group is virtually zero. [163 ] , [190 ] The survival rate in the
second category is as much as 30 percent with immediate thoracotomy. Stab wounds
have a much better prognosis than gunshot wounds. [170 ] Multiple-chamber injury,
coronary artery injury, and significant associated injury worsen the prognosis.
Mattox and Feliciano [191 ] found no survivors among 100 trauma patients who had
external cardiac compression for more than 3 minutes in the field. Ivatury et al. [192 ]
reported 100 consecutive patients with penetrating thoracic injuries who were in
extremis and required emergency room thoracotomy (ERT). Fifty-one patients had
attempted stabilization in the field, compared with 49 patients who had immediate
transportation. The anatomic injury, the severity, and the mode of injury in the two groups
were similar. There was a significant incidence of cardiac trauma. The overall survival
rate was 10 percent. None of the patients who had attempts at stabilization at the scene
showed improvement in clinical status. There were a higher number of patients arriving
at the emergency room with signs of life in the rapid-transport group, and survival was
much improved. These data suggest that rapid transport of the patient with penetrating
thoracic trauma is critical, particularly considering the high percentage of cardiac
injuries associated with cardiac tamponade.
Steichen et al. [164 ] were among the first to suggest and champion emergency room
thoracotomy (ERT). Mattox et al. [155 ] , [193 ] , [194 ] strongly endorsed this concept.
Subsequently, a number of authors have proven the utility of this procedure. Ivatury et al.
[163 ] reviewed a 20-year experience at the Lincoln Hospital of 228 patients with
penetrating cardiac wounds. Twenty-seven were classified as dead on arrival; i.e., they
had no vital signs during transport nor on arrival in the emergency unit. None of these
patients survived. Eighty-nine patients arrived in extremis. ERT resulted in 45 patients
(62 percent) being resuscitated sufficiently for their transfer to the operating room for
definitive operations; 26 (29 percent) were eventually discharged. One hundred and
twelve patients arrived with vital signs; 82 (73 percent) survived, including 70 of 89 (78
percent) with knife wounds and 12 of 23 (52 percent) with gunshot wounds. Overall
survival was 50 percent. In analyzing their data, the authors noted a yearly increase in
gunshot wounds and a decrease in survival in those patients arriving in extremis.
THE PATIENT WITH SIGNS OF LIFE
As many as 50 percent of patients with cardiac injury arrive with some signs of life, a
tribute to modern emergency transport services. Some will deteriorate rapidly and
require immediate thoracotomy. No time should be wasted in transporting these
patients to the operating room. Ivatury et al. [163 ] comment on 5 patients who
presented in a semiconscious state with no palpable blood pressure who were
transported to the operating room for thoracotomy; all died despite having tamponade
that could have been decompressed by emergency room thoracotomy. Some patients
will be relatively stable and require diagnostic procedures to confirm the diagnosis. This
is a relatively small group of patients, usually but not always these are knife wound or
small-caliber hand gun victims with minimal external evidence of cardiac wounding.
Two-dimensional ECHO, if immediately and expertly available, may be of value, but the
safest course is to transfer these patients to the operating room for pericardial window.
Between these extremes are a group of patients with suspected heart wounds who are
stable or who respond immediately to resuscitative efforts. These patients are best
served by being transferred rapidly to the operating room for definitive care.
INCISION DECISION
Emergency room thoracotomy is best performed by the left anterolateral approach (

Figs. 43-5 and 43-6 ). In males the incision line follows the subpectoral crease; in
females the breast is retracted upward, and the incision line follows the lower border of
the breast. The intercostal space just beneath the skin incision is entered, and the
intercostal muscles from the sternal margin to the midaxillary line are divided. A large
thoracotomy retractor is inserted and opened, usually disarticulating the upper rib costal
cartilage-sternal junction and not infrequently fracturing the lower rib. The lung is
retracted laterally. The pericardium is incised in a vertical manner anterior to the phrenic
nerve. Clots are removed manually, and free blood is suctioned. Finger pressure is
used to control the wound. Most cardiac wounds can be controlled and sutured by this
exposure. At times, it is necessary to cross the sternum for right atrial injuries and more
rarely because of posterior bleeding, which requires lifting the heart. Some authors
recommend aortic clamping to improve coronary and cerebral blood flow. We have
used this maneuver rarely, preferring to compress the aorta against the spine to
achieve the same result without the danger of additional injury from hasty and frequently
blind application of clamps. Since bleeding is not a problem in the severely hypotensive
patient, no effort is made to achieve hemostasis during entry. If one is rewarded with
re-establishment of the circulation, bleeding from the mammary and intercostal vessels
becomes apparent and should be controlled before proceeding to the operating room
for more definitive care, cleansing, and closure.
OPERATING ROOM CARE
The operating room staff should be prepared for emergency cardiac procedures by
clearly defined protocols. A cardiac surgery alert system should be in place to summon
essential personnel, including cardiac specialty nurses, cardiopulmonary perfusionists,
and Cell Saver technicians. The blood bank should be alerted so that appropriate blood
products including fresh frozen plasma and platelet concentrate are available. Most
important, the physician surgical team should be experienced cardiothoracic surgeons.
There is evidence that outcome is dependent on the experience of the team. [195 ]
There is controversy concerning the proper incision for cardiac wounds managed in the
operating room. Traditionally, a left anterior or anterolateral thoracotomy was used. As
indicated, most wounds can be cared for by this approach. Deep infections and
dehiscence are rare, and superficial wound infections, while not uncommon, usually heal
by secondary intention. On the other hand, a median sternotomy gives superb exposure
of the heart and anterior great vessels, allows inspection and repair of the lungs and
pulmonary vessel injury, and is ideal if cardiopulmonary bypass is required. Sternotomy
infection and dehiscence can be formidable problems but, fortunately, are rare.
Sternotomy is being utilized increasingly and now is the incision of choice. [196 ]
CONDUCT OF OPERATION
Following sternal division, the pericardium is incised in the midline initially from the
edge of the diaphragm to the base of the aorta just below the innominate vein area.
Lateral incision of the pericardium 1 cm above the diaphragmatic base is carried out to
enhance exposure. Clot is removed manually and by suction. The injury is identified and
controlled by gentle finger pressure. Foley catheters are not advised because sufficient
tension to stop bleeding is often adequate to extend the defect. With relief of
tamponade and control of bleeding, hemodynamics should improve. The anesthesia
team should be given time to optimize the situation. A slow response probably indicates
volume depletion and myocardial depression. A poor response may indicate
intracardiac injury.
Ventricular repair usually can be accomplished with mattress sutures of 3-0

polyprophylene tied over Teflon pledgets ( Figs. 43-7 and 43-8 ). As the myocardium
contracts, the defect tends to close, and little tension is needed. With larger stab
wounds, the first mattress suture should be placed in the middle of the wound. Gunshot
wounds may be surrounded by an area of damaged myocardium. As a general rule,
myocardium that appears normal probably will hold sutures. One centimeter into
normal-appearing myocardium is sufficient for secure closure. Wounds adjacent to
coronary arteries usually can be closed by placing the sutures beneath the artery.
Atrial wounds usually can be controlled by placing a finger into the defect ( Figs. 43-9
and 43-10 ). Subsequent repair can be accomplished by a mattress suture of 4-0
polyprophylene placed in a purse-string manner. Larger wound edges can be grasped
by Allis or Babcock clamps and held together to allow application of a vascular clamp.
Closure is accomplished with running 4-0 polyprophylene. Superior vena caval injuries
are handled in a similar manner. Pulmonary artery wounds usually can be controlled with
gentle finger pressure or by Allis or Babcock clamps and are repaired by mattress
sutures placed beneath the finger or clamps. At times the application of a partially
occluding clamp is necessary. Patients who survive aortic wounding usually do so
because the wound is small and sealed off by contiguous pericardium and clot.
Exposure may result in vigorous bleeding that may be difficult to control. Finger
pressure, followed by careful exposure and the application of a partial occlusion clamp,
is required (Fig. 43-11) . Gunshot wounds theoretically produce collateral damage to the
aortic wall, but experience has shown that normal-appearing aorta will hold sutures.
Sutures should be placed 0.5 cm from the wound and tied over pledgets. Once bleeding
is controlled and the patient stabilized, the surgeon should search for collateral damage.
The most obvious of these are exit wounds, which may produce continued and serious
bleeding and require early attention. Valves may be damaged, septal defects
produced, and foreign objects buried in the myocardium. Decisions must be made
concerning these conditions.
CARDIOPULMONARY BYPASS
The majority of heart wounds can be treated without cardiopulmonary bypass. Reports
from Croatia and Iraq describe the successful treatment of fragment and bullet wounds
of the heart without the aid of cardiopulmonary bypass. [198 ] , [199 ] Knott-Craig et al.
[199 ] at the University of Stellenbosch treated 129 patients with stab wounds of the
heart by early thoracotomy without delay for other diagnostic tests. Multiple entrance
wounds were present in 12 patients, and entrance and exit stab wounds were present in
10. The overall mortality rate was 8.5 percent, including a 54 percent mortality in 13
patients undergoing emergency room thoracotomy. Cardiopulmonary bypass was not
used initially, but 7 patients underwent subsequent intracardiac repair without mortality.
There are situations where cardiopulmonary bypass is required acutely and without
which the victim will not survive. The two most pressing indications are coronary artery
injury and wounds in areas of the heart that cannot be reached without intolerable lifting,
i.e., the left atrium, the high ventricular area near the coronary sinus, and the inferior
vena cava.
Coronary artery injury is fairly common. As a general rule, small branches and terminal
segments of major arteries may be ligated. Proximal and middle injury of major arteries,
particularly the left anterior descending and right coronary arteries, require coronary
artery bypass grafting. Espada et al. [47 ] described 9 such injuries in 76 patients with
heart wounds. The right coronary artery was injured in 2 patients, the left anterior
descending artery in 6, and the circumflex artery in 1. One patient with a proximal left
anterior descending artery injury was treated by saphenous vein bypass. The others
were treated by ligation of the artery. One patient with right coronary artery injury treated
by ligation died. In our series, 3 patients were treated by saphenous vein grafts; all
survived. [168 ]
Symbus et al. [201 ] in 1973 described a series of 56 patients wounded by knives or

bullets, 14 of whom had 16 instances of delayed sequelae: intracardiac shunts in 5,
valvular lesions in 3, ventricular aneurysms in 5, and retained foreign bodies in 3. Asfaw
et al. [202 ] reported 12 patients with interventricular septal defects among 227 stab
wounds of the heart. None required immediate repair of the defect, and only 4 eventually
required repair. Our experience indicates that laceration of the septum may not be
apparent clinically in the acute phase and that left-to-right shunting develops over a
period of time. [168 ] However, if sought for, a systolic thrill frequently is present in these
patients' hearts at the time of operation. Before the use of Swan Ganz catheters and
intraoperative Doppler echocardiographic techniques, the diagnosis was in doubt as to
whether the lesion was valvular or septal. If the patient's heart did not enlarge, the lungs
did not congest, and the vital signs remained normal, the procedure was terminated and
specific diagnosis and therapy left to a later date. Fortunately, most patients did well
with this scenario.
In present-day practice, intracardiac lesions can and are being identified at the time of
initial operation. Questions exist as to whether lesions of the valve and septum should
be repaired at that time. Certainly, the technology is available, but many of these lesions
produce minimal physiologic dysfunction, and one must weigh the risk-benefit
relationship in each circumstance. Results from later elective repair, when criteria for
repair are more clearly defined, have been excellent. [204 ] , [205 ]
A number of residual lesions have been reported, including aortic, pulmonary, and
coronary artery heart chamber fistulas. [206 ] These usually are heralded by
high-pitched, prolonged systolic and diastolic murmurs depending on the structures
involved. Cardiac catheterization and coronary angiography are required for diagnosis.
Pseudo-aneurysms may reach significant size before producing symptoms and often
are discovered surreptitiously. These should be repaired [184 ] (Figs. 43-12 and 43-13)
.
FOREIGN BODIES
Symbus et al. [206 ] reviewed the English-language literature on cardiac foreign bodies
and found reports of 222 missiles in the hearts of 201 patients. They added the
experience from Emory University Medical School with 24 additional patients. The
retained missiles were 45 bullets in 45 patients, 109 shrapnel fragments in 99 patients,
18 pellets in 7 patients, and 50 unidentified missiles in 50 patients. Thirteen of the
missiles were completely embedded intramyocardially, 122 were partially embedded
intramyocardially, 47 were free in a cardiac chamber, and 40 were intrapericardial. One
hundred and four were removed, with 6 deaths. Twenty-seven patients had symptoms,
all but 2 having had no attempt or an unsuccessful attempt at removal. In the Emory
group, there were 24 missiles-18 bullets, 1 bullet fragment, and 5 pellets-in the hearts of
24 patients. Ten missiles were removed, 1 could not be removed, and no attempt was
made at removal in the remaining 13 patients. All did well and have no symptoms
related to the missile.
Bland and Beebe [207 ] reported a 20-year follow-up on 40 patients with missiles left in
the heart from World War II. Pericarditis was common, and significant effusion occurred
in 25 percent. Elective removal was successful in 3 of 8 patients in whom the procedure
was attempted. There was significant anxiety in those patients with retained foreign
bodies, but no infection, embolization, or erosion occurred.
Foreign bodies in the pericardium should be removed at the time of original exploration.
Foreign bodies seen embedded in the heart wall usually can be removed without undue
difficulty, and while many of the smaller bullets can be removed by passing pledgeted
mattress sutures beneath the anticipated defect prior to removal, cardiopulmonary
bypass is a desirable adjunct. For those missiles deep in the myocardium, in the
septum, or free within a heart chamber, bypass is mandatory. It is generally
recommended that foreign bodies with jagged edges and those 2 to 3 cm in size be
removed. Yet many myocardial missiles are well tolerated, and if significant damage is
required for their removal, they are probably best left alone. Missiles free within a
chamber should be removed because of the potential for embolization. [208 ] , [209 ]
Since many of these are removed electively, localization of the missile by
two-dimensional echocardiography should be carried out preoperatively.
Transesophageal echocardiography and/or portable echocardiography and fluoroscopy
or portable x-ray capability are necessary. Minimal manipulation of the heart during
cannulation is vital. The aorta and pulmonary artery should be cross-clamped and
cardioplegia administered before removal is attempted.
THE STUNNED HEART
Most victims of penetrating trauma are young men without underlying heart disease.
Despite this, some will demonstrate suboptimal hemodynamics postoperatively. While
stab wounds produce little collateral damage unless a coronary artery is disrupted or a
valve or septum is lacerated, studies indicate decreased right and left ventricular
ejection fractions that may not be manifest clinically. [210 ] These abnormal values
generally return to normal in a few weeks. In our series, two patients with right ventricular
stab wounds who presented in shock continued to have cardiogenic shock after repair.
The intraaortic balloon was used successfully in one of these patients. Horowitz [211 ]
reports a similar situation with shock following right ventricular repair and salvage with
intraaortic balloon counterpulsation. While initial results with prolonged cardiopulmonary
bypass in postinjury cardiogenic shock were disappointing, newer methods of
circulatory support including cardiac assist devices that do not require heparin and
which can be inserted percutaneously offer hope for the future. [212 ]
Postoperative Evaluation
Since up to 50 percent of followed patients will have some sort of residual problem, a
follow-up plan is indicated. [200 ] , [205 ] , [213 ] Mattox et al. [214 ] follow their patients
with penetrating heart trauma by physical examination, electrocardiogram, and chest
x-ray. Patients with signs and symptoms of heart problems are examined by
echocardiography and cardiac catheterization. Of interest is the finding of an abnormal
echocardiogram in 30 of 37 symptomatic patients.
CENTRAL VASCULAR INJURY
Injury of the vascular structures of the chest is unusual but is increasing in frequency.
Because of their location, the vascular structures are difficult to diagnose and to treat.
The majority of such injuries are from gunshot wounds, but the mechanism of injury may
be blunt trauma. A systematic approach is necessary for dealing with all injuries but is
particularly vital when dealing with injuries of the vessels of the central chest and the
thoracic outlet.
In civilian practice, thoracic vascular injury accounts for 11.5 percent of all vascular
injury. Blunt trauma accounts for only 15 percent of these, with most injuries involving the
descending aorta. Mattox et al., [215 ] in their report of 5760 cardiovascular injuries,
noted 597 injuries of the thoracic vasculature; 326 (54.4 percent) of these involved the
central vessels. The incidence of injury of the vessels of the thoracic outlet (zone I of the
neck) is difficult to quantitate. The region is compact, and vascular injuries frequently are
associated with multiorgan injury. In the original report by Brawley et al. [216 ] from
Johns Hopkins Hospital, only 20 patients were identified with thoracic outlet injury, and
only 20 more were added over the next 5 years. Clark et al. [217 ] in 1991 described
100 patients with cervical thoracic injury treated at San Francisco General Hospital; only
8 had vascular injury in the thoracic outlet. The experience from Parkland Hospital over
an 11-year period is one of the largest. Flint et al. [218 ] treated 206 major vascular
injuries of the thoracic outlet equally distributed between arterial and venous injury in
146 patients. The mortality was 7.8 percent.
Mechanics of Injury
The majority of these wounds are the result of firearms. In one large series, gunshot
wounds comprised 57 percent of the injuries, compared with a 25 percent incidence
from stab wounds. [219 ] The mechanism of injury carried a significant clinical effect.
Gunshot wounds lead to neurologic deficit in 75 percent of patients, whereas neurologic
findings occurred in only 29 percent of patients with stab wounds.
Blunt injuries of the vessels of the thoracic outlet are even less common and occurred in
less than 8 percent of the 510 patients with aortic arch injury reviewed by Fischer et al.
[220 ] Castagna and Nelson, [221 ] in an extensive literature review, found 36 cases of
blunt thoracic outlet vascular injuries. Twenty-two of these involved the innominate artery.
Symbas [222 ] described only 4 cases of rupture of the thoracic outlet vessels in his
extensive experience reported in 1989. The mechanism of injury is felt to be a
combination of deceleration, chest compression, and neck extension. [223 ] , [224 ]
Anatomy
Exposure is the key to dealing with thoracic vascular injury. Exposure depends on a
complete knowledge of the anatomy of the region and choice of the proper incision to
expose this anatomy ( Figs. 43-14 through 43-18 ).
The thoracic outlet extends from the cricothyroid membrane to the manubrium and
includes the axilla and the superior mediastinum. The great vessels of the chest, the
esophagus, the trachea, the thoracic duct, and many neural structures, including the
vagus and phrenic nerves, are compacted in this relatively small area. The vertebral
column, the clavicles, the manubrium sternum, and the first and second ribs surround
this area and, along with the neck and shoulder girdle muscles, protect it from injury.
Because of these barriers, physical examination, clinical evaluation, and surgical
exposure are difficult.
The first branch of the aortic arch is the innominate artery, which passes posterior to the
innominate vein and anterior to the trachea. It divides into the right subclavian artery and
the right common carotid artery at the level of the sternoclavicular joint. The subclavian
artery gives rise to the vertebral and internal mammary arteries and the thyrocervical
trunk and then passes posterior to the scalenus anticus muscle. The phrenic nerve runs
along the anterior surface of this muscle, and care must be taken to avoid injury to this
nerve when the muscle is divided for exposure. The vagus nerve passes anterior to the
subclavian artery and medial to the vertebral artery. The right common carotid artery
ascends into the neck and is without branches until it birfurcates into the internal and
external carotid arteries.
The left common carotid and left subclavian arteries are the next two major branches of
the aortic arch. The left common carotid artery ascends into the neck until it bifurcates at
the upper border of the thyroid cartilage. The subclavian artery from its more posterior
origin ascends as the most lateral structure in the superior mediastinum. Its location
makes it difficult to expose from an anterior approach. The vagus nerve runs arterior
and medial to the subclavian artery until it crosses anterior to the artery just above its
origin from the aorta. The vertebral artery arises as the first superior branch of the
subclavian artery, but in approximately 8 percent of persons it takes its origin from the
aortic arch on the left between the carotid and subclavian arteries and rarely on the right
between the innominate and carotid arteries. At times, a thyroidea ima artery takes
origin from the arch and ascends to the inferior pole of the thyroid gland.
The major venous structures of the superior mediastinum and thoracic outlet include the
internal jugular, axillary, subclavian, and innominate veins and the superior vena cava.
The axillary veins course medially anterior to their matched arteries and become the
subclavian veins to pass anterior to the scalenus anticus muscle and anterior and
inferior to the subclavian arteries. The innominate veins are formed by the junction of the
jugular and subclavian veins just posterior to the medial aspect of the clavicle. The
thoracic duct joins the left subclavian vein posteriorly at its junction with the jugular vein.
The right innominate vein courses vertically and is joined by the left coursing inferiorly
and to the right anterior to the innominate artery. The union of these two veins forms the
superior vena cava at the level of the first costal cartilage on the right. This courses
inferiorly, entering the pericardium at the level of the third right costal cartilage. The
azygous vein drains into the midportion of the superior vena cava posterolaterally.
Management Strategy
The early management of a trauma victim with suggestive evidence of a great vessel
injury is critical. Studies have shown that an orderly anatomic approach to evaluation
and treatment can lead to improved survival and decreased morbidity. [215 ] , [225 ]
The standard approach to airway, breathing, and circulation should be applied, with
particular attention to examination of the airway. Many of these patients will have an
enlarging hematoma in the lower neck or mediastinum that may rapidly compromise the
airway. If there are signs of airway compression, rapid endotracheal intubation is
mandatory. Robbs et al. [226 ] reported 4 deaths in their series due to cardiac arrest
during attempted intubation after delayed recognition of stridor. If intubation is difficult, a
cricothyroidotomy should be performed without delay and prior to any other intervention.
Cricothyroidotomy may inhibit exposure if operative therapy is required, but this should
not influence one to persist in continued attempts at difficult endotracheal intubation. If
ventilation is impaired, hemopneumothorax should be suspected clinically, and chest
tubes should be inserted based on physical examination without waiting for
radiographic studies.
The standard trauma venous access of two large-bore catheters in the upper
extremities may be inadequate, since central venous injury may make these sites
unreliable. Vascular access above and below the diaphragm is mandatory whenever a
thoracic vascular injury is suspected. For the patient in shock, rapid volume infusion is
indicated.
Concomitant with the initial measures at stabilization, a history of injury should be

obtained, if possible, and a rapid physical examination carried out. All four extremities
should be examined for the presence of pulses and for any indications of neurologic
deficit. A decreased distal pulse is found in only 50 percent of great vessel injuries due
to extensive collateral circulation and persistent vessel patency. [227 ] Central as well as
peripheral neurologic examination is essential, and any neurologic deficit should be
documented. The neck should be examined for the presence of hematoma, and the
carotid arteries should be palpated and auscultated. Jugular venous distension may
indicate venous obstruction from mediastinal hematoma as well as concurrent heart
injury and cardiac tamponade. Chest examination should include auscultation of the
supraclavicular and infraclavicular areas as well as the upper and lower precordium.
Bruits may be present with great vessel injury but are difficult to hear in the emergency
room environment.
A portable chest x-ray examination should be part of the initial evaluation. Vascular
injury may present as a hemo-or pneumothorax. An apical cap, mediastinal widening,
and soft tissue fullness in the upper mediastinum are suggestive evidence of vascular
injury (Fig. 43-19) .
If the patient arrives in stable condition or responds to resuscitation measures,

emergent aortography should be performed. [228 ] , [229 ] Arteriography is the best
guide to diagnosis and operating strategy. The indications for arteriography include all
penetrating injuries below the level of the cricoid cartilage (zone I neck injury); a clinically
detectable and expanding hematoma of the mediastinum, supraclavicular, or cervical
regions; a widened mediastinum on plain chest x-ray examination; transmediastinal
passage of a missile; and a decreased peripheral pulse, bruit, or suggestion of
arteriovenous fistula. Arteriographic findings include false aneurysm, a filling defect, or
complete obstruction. Evidence of avulsion or tear near the origin of the great vessels
from the aortic arch is the usual finding in blunt trauma injuries. [230 ] [232 ]
Arteriography is warranted in asymptomatic, stable patients with injury near the great
vessels. Occult injuries, including vascular thrombosis and intimal flaps, can be
identified and are more readily dealt with in the acute setting. [233 ]
Patients with hemodynamic instability who have a poor response to volume

resuscitation and those who are hemorrhaging rapidly should be taken to the operating
room for emergent operation. Once the injured vessel is identified, manual compression
is used to stop the hemorrhage and allow time for intravascular volume to be restored.
Once the patient's condition is stabilized, the injury may be repaired through the
thoracotomy. If exposure is inadequate, the incision can be tailored for better exposure.
Incision Decision
The choice of exposure and the placement of the incisions are the most critical aspects
of the management of these injuries. [234 ] The patient should be prepped from the
mandible to the knees to allow for possible saphenous vein harvest and for laparotomy
and neck incisions. When arteriography is available, the operative approach can be
planned based on the injured vessel and location of injury. [235 ] In the absence of
arteriography, the location of bleeding, hematoma, or a pulse deficit may guide the
surgeon to the site of injury; however, although reasonable, this is not necessarily a
reliable course of action. [219 ]
When the injury site is in doubt, median sternotomy is the incision of choice. This
exposes the heart and provides access for proximal control of the innominate and left
carotid arteries. The incision can be extended superiorly into the neck for more
exposure of the carotid arteries or laterally above the clavicle for exposure of the
subclavian vessels. An anterolateral thoracotomy in combination with the sternotomy
and supraclavicular incision results in the trapdoor or open book thoracotomy (Fig.
43-20) . This approach allows proximal and distal vascular control and exposure for
complete repair without the need to reposition the patient but is highly morbid.
Exposure of Specific Vessels
The innominate artery is exposed by median sternotomy. Mobilization of the innominate

vein allows proximal exposure of the right subclavian artery and right common carotid
artery. The innominate vein may be divided, if necessary, to facilitate exposure and
avoid a venous traction injury. As a general rule, any injury to the right subclavian artery
proximal to the vertebral artery and any right common carotid artery injury within 2 cm of
its origin require median sternotomy for proximal control. Extension of the incision into
the neck or along the clavicle may be needed for distal control. A supraclavicular
approach should be used to visualize the subclavian artery at the level of the vertebral
artery. An infraclavicular approach should be used to expose the more distal vessel.
The left common carotid artery is well exposed via median sternotomy, with extension
as needed along the medial border of the sternocleidomastoid for distal exposure.
The left subclavian artery is poorly exposed through a median sternotomy due to its
posterior origin from the aortic arch and its posterolateral course. In an emergency
situation, a left anterior third interspace incision provides adequate exposure for
proximal control of the vessel. In a more elective setting, a posterolateral thoracotomy is
the approach of choice. The patient should be positioned in the right lateral decubitus
position, angled at 45 to 60 degrees to allow access to the clavicular area if another
incision is necessary. Any injury distal to the left vertebral artery can be repaired through
a local nonthoracic approach.
The vertebral arteries can be exposed through a supraclavicular incision. The more
proximal the injury, the more likely it is that repair of the subclavian artery will be
required. In these circumstances, proximal control through the chest is necessary.
Because of the fragile nature of the vertebral artery, this injury is best treated by ligation,
a procedure that usually is well tolerated.
Technique of Repair
The technique of repair of arterial injuries depends on the location, extent, and
mechanism of injury. [236 ] Simple stab wounds can be repaired primarily with
nonabsorbable monofilament suture. [237 ] More extensive injuries result in a loss of
vessel length. The subclavian artery may be mobilized by ligating some of its branches;
this usually provides adequate length for primary anastomosis. The other great vessels
do not lend themselves to lengthening and require interpositional or bypass grafting.
Normally, the saphenous vein is too small in caliber to use as an interpositional graft in
the subclavian, innominate, or proximal common carotid arteries. The use of a
polytetrafluoroethylene tube prosthesis, 8 to 10 mm in size, is suitable in most
circumstances. [238 ] Vessels injured at their origin from the aortic arch are best treated
by bypass grafts from the ascending aorta and proximal ligation. The innominate and
carotid arteries may be occluded temporarily to control hemorrhage, but some type of
shunt is recommended to reestablish cerebral perfusion during repair. [239 ] The
presence of a carotid or innominate artery injury with a central neurologic deficit is a
therapeutic dilemma. If a fixed neurologic deficit is noted on admission, particularly if it
is several hours old, some recommend vessel ligation because of the possibility of
producing a hemorrhagic infarction with reinstitution of blood flow. [240 ] If neurologic
evaluation is not possible due to the patient's mental status, or if the neurologic deficit
waxes and wanes, reestablishment of arterial flow is the treatment of choice.
Cardiopulmonary bypass may be required to repair injuries of the aortic arch and its
branches, the ascending aorta, or the main pulmonary artery. [241 ] , [242 ] These
repairs may include the need for circulatory arrest and its attendant hazards. [243 ]
Furthermore, heparinization may lead to bleeding from occult injury. The lifesaving
potential of repair of an intrapericardial or aortic arch injury usually supersedes these
concerns.
Most venous structures in the thoracic outlet, including the jugular, subclavian, and
innominate veins, can be ligated with little consequence. [225 ] There are, however,
anecdotal reports of deterioration of neurologic function in patients with neurologic
deficit after innominate vein ligation, presumably due to an increase in cerebral venous
pressure. Under these circumstances, repair of the venous injury should be pursued
aggressively before resorting to ligation.
ANATOMY
The purpose of this section is to relate pericardial anatomy to clinical events associated
with the pathophysiology of pericardial disease. The pericardium, pleura, and
peritoneum each consist of visceral and parietal tissue layers lined with mesothelial
cells. The visceral pericardium is also the epicardium. Except in disease, the visceral
pericardium has little clinical significance. The parietal pericardium is a thin, tough,
fibrous tissue. The two pericardial layers are separated, in patients free of cardiac and
pericardial disease, by approximately 15 ml of lubricating fluid. [1 ] This pericardial fluid
is an ultrafiltrate of circulating blood [2 ] and therefore reflects the concentrations of all
permeable substances. Thus the heart beats freely in the pericardial space.
Although superior and inferior pericardiosternal ligaments are frequently described,

pericardial attachments to the sternum are not obvious to the surgeon. The parietal
pericardium attaches to the ascending aorta superiorly, just below the innominate vein
(Fig. 44-1) . It fixes across the superior vena cava (SVC) several centimeters above the
sinoatrial (SA) node and then courses down over the right superior and inferior
pulmonary veins to encircle the inferior vena cava (IVC). Thus the surgeon is able to
pass a clamp completely round the IVC inside the pericardial space by cutting only a
thin bit of coapted pericardial tissue posterior to the IVC. From the IVC, the pericardial
attachment attaches to the left atrium near the entrances of the pulmonary veins superior
to the atrioventricular (AV) groove. This anatomy is important when explanting a
diseased heart prior to cardiac transplantation. The surgeon can easily leave a 1-cm
rim of left atrium inside the pericardial attachment for anastomosis to the donor heart.
Thus the posterior wall of the left atrium is really an extrapericardial chamber. This
explains why posterior pericardial effusions are frequently detected
echocardiographically behind the left ventricle but cannot be seen behind the left atrium.
The volume of the pericardial space exceeds the cardiac volume by 10 to 20 percent.
Thus small alterations in cardiac or pericardial fluid volumes elicit negligible
hemodynamic sequelae. The tough parietal pericardium is formidably non-compliant,
however. Should fluid accumulate in the pericardial space, it can push in against the
compliant right atrium and right ventricle much more easily than it can push out against
the stiff pericardium (Fig. 44-2) . Initially, a small elevation in pericardial fluid increases
the intrapericardial pressure minimally (Fig. 44-3) . However, as soon as the elastic limit
of the pericardium is exceeded, pressure shoots up dramatically. Thus a relatively small
amount of pericardial fluid may produce a large increase in pressure compressing the
heart.
Conversely, the slow development of a large chronic pericardial effusion may produce
negligible hemodynamic consequences (see Fig. 44-3 ). It is important to recognize that
pericardial fluid volume and pericardial pressure are not linearly related .
For practical purposes, we define pericardial effusion as an abnormal accumulation of

pericardial fluid with hemodynamic sequelae that are not clinically important. Pericardial
tamponade is defined as fluid (either a lot or a little) under sufficient pressure to
produce hemodynamic consequences. Obviously, the spectrum between an effusion
and tamponade is a continuum. However, pericardial effusion is an anatomic diagnosis,
whereas pericardial tamponade is a physiologic one. The echocardiographic
identification of pericardial fluid cannot be escalated to a diagnosis of pericardial
tamponade without confirmatory clinical findings.
The phrenic nerves are adherent to and course bilaterally down the lateral sides of the
pericardium anterior to the pulmonary vessels. Phrenic nerve injury can result in
diaphragmatic paralysis with serious respiratory compromise. Although occasionally
tempting, the surgeon should not attempt to peel the phrenic nerves off the pericardium.
When pericardial resection is indicated, it is safest to leave a 1- to 2-cm-wide bridge of
pericardium underneath the phrenic nerves.
Ultrastructure
The parietal pericardium is composed of abundant collagen bundles interspersed with

occasional elastin fibers covered by a single layer of mesothelial cells. The surfaces of
the mesothelial cells contain exuberant microvilli 1 µm wide and 3 µm high. [3 ] The
dynamic orientation of parietal pericardial fibroelastic elements reduces friction, and the
serosal cell microvilli facilitate fluid and ion exchange. [4 ] Cardiopericardial lymphatics
drain fluid from the subepicardium into mediastinal nodes and ultimately via the thoracic
duct back into the venous system. [5 ]
The membrane characteristics of the pericardial mesothelial cells and microvilli favor
clearance of fluid. [6 ] Utilizing radioisotopically tagged albumin and red cells in
patients, protein appeared in the peripheral circulation in minutes, while blood was
cleared in hours. [7 ] In patients with clinically apparent pericardial effusions, mean
albumin turnover is reported as 1.86 g/day. [7 ]
PATHOPHYSIOLOGY OF PERICARDIAL COMPRESSION
Pulsus Paradoxus
Pulsus paradoxus is defined as a decrease in arterial systolic pressure of 10 mmHg or

more with inspiration. An explanation of this clinical sign, which occurs because of the
dynamic relationship between pericardium and heart requires simultaneous and
accurate delineation of cardiac chamber pressures and volumes throughout the cardiac
cycle. Pressures are easy. Volumes are hard. Recently, thermodilution volume detection
measurements have been refined for clinical use [8 ] and validated with contrast
angiography [9 ] , [10 ] and radionuclide imaging. [11 ] , [12 ] Rapid thermodilution
measurements have enabled precise examination of clinical pulsus paradoxus.
If you watch the continuous arterial pressure tracing of a patient in a surgical intensive
care unit, you note fluctuation in the systolic pressure concurrent with respiration.
Although this association has been observed for 100 years, the mechanism causing the
fluctuation continues to stimulate consternation.
Only two mechanisms seem to be involved. Under normal circumstances, pleural and
pericardial pressures are both negative and essentially identical. Indeed, all
intrathoracic organs are subject to comparable pressure changes associated with
respiration/ventilation. Where veins and arteries enter or leave the thorax, however,
breathing produces a pressure gradient. During spontaneous inspiration, negative
intrathoracic pressure pulls venous blood into the chest, augmenting right atrial and right
ventricular filling. Thus one anticipates the dominant influence of breathing/ventilation to
be on right-sided heart function. [8 ] Equally important, however, negative intrathoracic
pressure is transmitted to the distensible left ventricle. This increases the force the
ventricle must exert (relative to extrathoracic arteries) to maintain a stable systemic
arterial pressure. This mechanism increases the relative afterload, and the left ventricle
empties incompletely during spontaneous inhalation. Both systolic pressure and pulse
pressure decrease. [13 ]
The second mechanism relates to the fact that the right and left ventricles are separated
by a pliable, mobile inter-ventricular septum. Thus distension of the right ventricle during
spontaneous inspiration displaces the septum left-ward, compromising left ventricular
diastolic filling. Decreased left ventricular filling translates into decreased stroke volume
with resulting reduced systolic and pulse pressures. These two mechanisms conspire to
reduce blood pressure during negative-pressure inhalation (breathing) and reciprocally
augment blood pressure during positive-pressure inhalation (ventilation). As a logical
extrapolation, this phenomenon is exacerbated by an increase in pericardial pressure
(tamponade). It is possible to reproduce this process in animals [14 ] [16 ] and
document it in patients. [8 ] , [17 ]
Routine echocardiography reveals the surprising frequency of clinically silent and

irrelevant pericardial effusions [18 ] (Fig. 44-4) , especially in dialysis patients. [19 ]
Rankin et al. [20 ] have provided elegant explanations of the physiology of paradoxical
pulse and cardiac tamponade in conscious dogs. During tamponade at peak
spontaneous inspiration (breathing), right ventricular filling increases while the
interventricular septum shifts leftward and the septal arc decreases. In control animals
without tamponade, inspiration decreases left ventricular end-diastolic volume (LVEDV)
by 10 percent, but during graded tamponade, LVEDV decreases by up to one-third. As
predicted, reduced LVEDV is associated with both pulsus paradoxus and a decreased
cardiac output. Several groups [11 ] , [21 ] also have produced acute tamponade in
spontaneously breathing dogs. With inspiration, right ventricular filling occurs at the
expense of left ventricular filling. Right ventricular dimensions increase, provoking a
decrease in LVEDV. Mean pericardial pressure increases from 1.2 to 10.5 mmHg. This
increased pericardial pressure decreases systolic blood pressure from 126 to 82
mmHg, while pulsus paradoxus increases from a normal 4.3 to an abnormal 10.5
mmHg. [21 ] For purposes of clinical relevance, it is important to emphasize that an
effusion is pericardial fluid without hemodynamic consequences , whereas pericardial
tamponade exacerbates pulsus paradoxus, compromises left ventricular filling, and
decreases cardiac output. Pericardial fluid volume does not relate to pericardial
pressure in a linear fashion (see Fig. 44-3 ).
Pericardial Effusion without Tamponade
The physiology of this part of the spectrum of pericardial fluid accumulation has been
elucidated in a group of 56 medical patients with large pericardial effusions. [24 ]
During inspiration, right ventricular dimensions increased and left ventricular
dimensions decreased, but 36 of 56 patients maintained a systolic blood pressure of
greater than 100 mmHg, and 27 of 56 had a pulse pressure of more than 40 mmHg.
These patients obviously did not have pericardial tamponade. Yet 52 of the 56 patients
had an enlarged cardiac silhouette. Thus pericardial fluid is not synonymous with
tamponade. Forty-three of the 56 patients required a heart rate higher than 100 beats
per minute to maintain adequate peripheral perfusion, but 13 did not. These
observations clarify the spectrum. When a patient has sufficient time to simultaneously
expand intravascular volume and enlarge pericardial space, a huge effusion produces
minimal hemodynamic impairment. However, if the elastic limits of the pericardial
space are exceeded acutely, tamponade may snuff out forward flow with only subtle
clinical clues.
Constrictive Pericarditis
During cardiac catheterization, constrictive physiology traditionally has been defined by

the following parameters [23 ] , [24 ] :
1. Equalization of pressures . When pericardial compression becomes a dominant

determinant of hemodynamic status, end-diastolic ventricular pressures are within 5
mmHg of each other.
Elevation of mean atrial pressures . This is a sine qua non of both acute and
chronic pericardial tamponade. Jugular venous distension and measured mean
atrial pressures above 10 mmHg are diagnostic requirements of tamponade.
Square root sign . A dip-plateau pattern of the ventricular filling pressure curves
reflects normal ventricular filling that abruptly (as opposed to gradually) reaches the
elastic limits of the fused ventricular and constrictive pericardial chambers (Fig.
44-5) . Conceptually, blood slams up against the constrictive
pericardium/myocardium at end diastole, producing an abrupt pressure overshoot
(square root sign).
Prominent y descent in the right atrial pressure tracing . Neither the a nor the v
waves are typically prominent; however, both the x and y descents may be
exaggerated.
Elevated right ventricular end-diastolic pressure . Right ventricular end-diastolic

pressure (RVEDP) is typically more than a third of the RV systolic pressure. Thus
stroke volume is decreased and pulse pressure is reduced both by elevating the
floor (RVEDP) and lowering the ceiling right ventricular end-systolic pressure
(RVESP).
Left ventricular ejection fraction (EF) . Left ventricular EF must be above 40 percent
for a diagnosis of tamponade or constriction. With tamponade, systolic function is
typically well preserved. Conversely, all the preceding indicators may reflect
ventricular muscle dysfunction instead of pericardial compression. Thus EF must
exceed 40 percent.
PERICARDIAL CONSTRICTION VERSUS RESTRICTIVE
CARDIOMYOPATHY
Decreased diastolic compliance or an apparent increase in ventricular stiffness may

result from intrinsic cardiac muscle disease or from pericardial compression. The
relatively recent distinction between systolic and diastolic dysfunction and the
recognition of diastolic cardiomyopathy [25 ] as a discrete entity have focused clinical
attention on the diagnostic features of primary pericardial disease. Although still
challenging, the distinction is pivotal because patients with constrictive pericarditis may
be denied operation. [26 ]
Congestive heart failure may develop from systolic dysfunction, diastolic dysfunction, or
more typically, both. The most visible manifestation of systolic dysfunction is a decrease
in cardiac output. Diastolic dysfunction leads to impaired cardiac filling and pulmonary
and hepatic congestion. Severe left ventricular overloading (aortic stenosis or systemic
hypertension) results in left ventricular hypertrophy with a consequent decreased
ventricular compliance and diastolic function. Conversely, mitral stenosis and
pericardial constriction maximally unload the left ventricle. These differences in
ventricular systolic and diastolic function should permit diagnostic discrimination of
primary muscle versus primary pericardial disease. However, in practice, this
distinction is very difficult but also is very important.
The criteria for the diagnosis of restrictive cardiomyopathy have been delineated. [30 ]
Unfortunately, each of these criteria (Table 44-1) are or can be true of pericardial
constriction.
Numbers attached to the clinical criteria listed in Table 44-1 are admittedly risky but are
helpful in distinguishing restrictive cardiomyopathy and constrictive pericarditis from
other causes of failure and, to a much lesser extent, from each other. [26 ]
None of the criteria listed in Tables 44-1 and 44-2 are pathognomonic for either
constrictive pericarditis or restrictive cardiomyopathy. Other information may or may not
help to distinguish these two entities. Endomyocardial biopsy may identify muscle
disease, and even suggest therapy, but when it exhibits myocyte hypertrophy or
interstitial fibrosis, it does not exclude concurrent pericardial constriction. [27 ]
Echocardiography may qualitatively distinguish normal from thickened pericardium.
Much like the presence of pericardial fluid, however, the existence of a thick
pericardium does not mandate hemodynamic significance. [23 ] Characteristic
echocardiographic features of abnormal septal motion, flattening of left ventricular
posterior wall diastolic motion, and left ventricular wall thickness have each been
proposed as indicative of restrictive versus constrictive disease. [23 ]
In medical patients who have not had thoracotomy, the distinction between constrictive
pericarditis and restrictive cardiomyopathy is typically easier because the disease is
usually either myocardial or pericardial but not both. With pericardial constriction,
systolic function is preserved. Echocardiography reveals no impairment of ventricular or
atrial filling during early diastole. Pericardial compression is ubiquitous, and mean atrial
and ventricular end-diastolic pressures are similar. Restrictive muscle disease,
however, compromises both systolic and diastolic function. Ejection fraction may be
reduced. Ventricular muscle is stiffer, and echocardiography can sometimes identify
even early diastolic filling problems. Unlike the global pericardial compression of
constrictive pericarditis, however, myocardial restrictive disease tends to be
heterogeneous. Thus although the end-diastolic pressures may be fortuitously
comparable in both ventricles in restrictive disease, these pressures often splay out at
differing intravascular volumes (filling pressures). However, with global cardiac
compression associated with constrictive pericarditis, end-diastolic pressures of both
ventricles track each other in response to a volume challenge.
In surgical patients , the issue is more complex because it is almost never isolated.
This is illustrated by the not uncommon postoperative cardiac surgical patient whose
mediastinal tubes are draining 100 mL/hour. Blood pressure is 85/65 mmHg (reduced
blood pressure and pulse pressure), heart rate is 125 beats per minute, pulmonary
artery diastolic and right atrial mean pressures are both 20 mmHg, cardiac index is 1.8
liters/min per m 2 , and with ventilation, pulsus paradoxus is 20 mmHg. This patient had
an ejection fraction of 35 percent prior to cardiac surgery. We assume and confirm by
echocardiography that this patient has some mediastinal thrombus. The critical
question is whether or not to reexplore this patient to evacuate pericardiac compressive
clot.
This frequent and important clinical question has been examined exhaustively. In the
vast majority of instances, chest x-ray, echocardiography, computed tomography (CT),
nuclear magnetic resonance imaging (MRI), radionuclide angiography, and physical
examination are all useless . This patient almost certainly has both restrictive and
constrictive disease. The essential need is to determine the magnitude of the
constrictive component. With a fluid challenge, [29 ] the contribution of the constriction
can be assessed by the degree to which the end-diastolic pressures of the two
ventricles track each other. If the pressures splay out with infused fluid, the patient's
problem is likely primary muscle disease, and reoperation will not be helpful.
Conversely, if the right atrial mean and both ventricular end-diastolic pressures respond
similarly to infused volume, the patient may benefit by a return to the operating room.
Table 44-3 summarizes useful criteria for distinguishing restrictive cardiomyopathy (RC)
from constrictive pericarditis (PC). This distinction is often tremendously important. Not
only does stiff, fibrotic, inflamed heart muscle have no surgical therapy (short of
transplantation), but such patients also tolerate surgical stress very poorly. [23 ]
Conversely, the only effective therapy for hemodynamically significant pericardial
constriction is surgical excision.
PERICARDIAL DEFECTS AND CYSTS
Congenital Defects
These entities are rare, with less than 200 cases reported in the world's literature. [30 ]
The vast majority of pericardial defects occur on the left side and result from premature
atrophy of the left common cardinal vein or duct of Cuvier. [31 ] The left duct of Cuvier
should atrophy to form a portion of the left superior intercostal vein. The right duct of
Cuvier becomes the superior vena cava and ensures closure of the right
pleuropericardial membrane. Thus pericardial defects are more common on the left.
Unilateral complete absence of the pericardium may occur as frequently as 1 in 14,000
births, with a male predominance, but is rarely clinically significant. [30 ] In 30 percent of
instances, congenital pericardial absence is associated with other congenital
anomalies. [30 ] Resulting displacement of the heart into the pleural space also has
been associated with incarceration [32 ] and surgically correctable tricuspid
insufficiency. [31 ] Total absence of the pericardium is rarely symptomatic, so treatment
of a symptomatic partial defect paradoxically may dictate pericardial resection. [30 ]
Pericardial resection may be accomplished thorascopically, [30 ] or absent pericardium
may be replaced with patch material at thoracotomy. Although the latter is more
appealing intuitively, experience suggests that both therapies work.
Pericardial Cysts
Most pericardial cysts are appreciated initially on routine chest x-ray (Fig. 44-6) .
Although they have been associated with nonspecific chest pain, there is little evidence
to suggest that pericardial cysts cause pain. Cysts contain clear yellow fluid and
uncommonly communicate with the pericardial space. The majority of these cysts are
located at the pericardiophrenic angle (right more common than left), but they can be
located anywhere contiguous with the pericardium. If a pericardial cyst is asymptomatic
and can be identified reliably as a fluid-filled cyst by CT scan, they can be watched. In
symptomatic patients or patients in whom the cystic nature of the mass cannot be
confirmed, surgical excision is warranted. Recently, thoracoscopic resection has been
described. [33 ]
PERICARDITIS
As will soon be examined, dialysis, radiation, and some drugs each affect the
pericardium and the efflux of pericardial fluid. Procainamide (with or without
drug-induced lupus) and hydralazine can lead to pericarditis but do not commonly
produce constriction. The mechanical irritation of cardiac surgical procedures irritates
the pericardium and typically is associated with mediastinal thrombus. More patients
now survive massive myocardial infarction (the mortality of an acute myocardial
infarction has halved in the past two decades), and more patients are seen with
myopericardial inflammation (Dressler's syndrome), which may cause
pericardial-epicardial fibrosis. Infectious pericarditis from an extremely wide variety of
organisms remains an important cause of pericarditis. With each decade the most
frequent causes of pericarditis seem to change, but the frequency and importance of
the disease do not diminish.
Infectious Pericardial Disease
Microorganisms may invade the pericardial space from contiguous infections in the
heart, lung, subdiaphragmatic space, or the wound of postoperative patients. Bacterial
pericarditis associated with endocarditis is particularly serious. Septicemia also may
seed the pericardial space, especially in immunosuppressed patients, patients with HIV
infections, and those with concurrent burns or neoplastic disease. [34 ]
Pericarditis, resulting in fluid accumulation, typically results from inflammation of both

the pericardium and the underlying myocardium. As cardiopericardial lymphatics
become progressively clogged with inflammatory debris, fluid accumulates. The
concurrent myocardial inflammation explains the electrocardiographic (ECG) features
distinguishing pericarditis from ischemia/coronary artery spasm. The ECG in acute
pericarditis typically exhibits tachycardia and reciprocal ST-segment depression in lead
V 1 . [35 ]
Only one-third of patients with purulent pericarditis exhibit tamponade physiology;

however, purulent pericardial tamponade is lethal. Aggressive surgical drainage and
treatment with a cidal antibiotic may avert mortality, which is generally high. [34 ] The
most common organisms cultured from the pericardium include Staphylococcus,
Pneumococcus, Streptococcus, Hemophilus , and other gram-negative bacilli and less
commonly fungi ( Histoplasma, Candida, Coccidioides ). A large number of organisms
produce pericarditis in immunosuppressed patients.
Purulent bacterial pericarditis requires both antibiotics and surgical drainage.

Pericardiocentesis provides the diagnosis, but tube drainage with irrigation and
breakdown of fibrinous adhesions is often needed to remove loculated pus. Early and
complete drainage of the pericardial space also decreases the likelihood of late
constrictive pericarditis in survivors.
Although tuberculous pericarditis was formerly uncommon, it has experienced a

resurgence (Fig. 44-7) . Like other pericardial infections, tuberculous pericarditis
begins with an effusion and requires aggressive surgical drainage and antituberculous
chemotherapy to avoid development of thickened, constrictive pericarditis. [36 ]
Diagnosis is best made by culture and biopsy. Fortunately, triple-drug therapy is
typically very effective. Nine months of pharmacologic therapy is recommended, with at
least 6 months of therapy following culture conversion. Quale et al. [37 ] advocate early
surgical intervention for patients with tuberculous pericarditis. This group proposes a
pericardial window for both diagnosis and therapy in patients with suspected
tuberculous pericarditis. Because tuberculous pericarditis is prone to develop
constrictive pericarditis, they also propose complete pericardiectomy for pericardial
thickening even in the absence of tamponade.
Viral and Idiopathic Pericarditis
Pericarditis due to viral infection and idiopathic (unknown) causes rarely requires
surgical intervention. These infections, which are usually associated with other
manifestations of viral infection, often produce myocarditis and may produce pericardial
tamponade. In uncommon patients, viral or idiopathic pericarditis may produce fibrinous
exudates and progress to constrictive pericarditis.
Uremic Pericarditis
The etiology of uremic pericarditis is not known. Although initially recognized by Bright
[38 ] in 1836, uremic toxins, fluid overload, anticoagulation, infection, and too much or
too little dialysis have been incriminated. [39 ] The attendant pericardial inflammation
may lead to chest pain, fever, and a pericardial friction rub. Initial therapy includes
nonsteroidal anti-inflammatory agents and more aggressive dialysis. [40 ] The timing of
pericardiocentesis and/or pericardial excision is controversial. [41 ] , [42 ] Drainage is
advocated if a pericardial effusion persists following a 2-week course of aggressive
dialysis. [42 ] For practical purposes, a pericardial effusion is innocuous, even in uremic
patients. However, any evidence of hemodynamic compromise warrants
pericardiocentesis, especially in uremic patients undergoing dialysis. Similarly,
recurrent pericardial effusion with hemodynamic embarrassment mandates a
pericardial window with drainage either into the pleural or peritoneal space. Uremic
pericardial constriction is rare, and its etiology is also unclear. Surgical pericardial
resection is contemplated only when evidence of hemodynamically significant
constrictive physiology is clear.
Drug-Induced Pericarditis
Procainamide (with or without an associated lupus syndrome), hydralazine, emetine,

and methysergide have each been associated with pericardial inflammation, while
minoxidil has been reported to induce pericardial effusion. [43 ] The principles of
diagnosis and surgical intervention are identical to other etiologies of pericardial
effusion, tamponade, and constriction.
Radiation Pericarditis
Until the 1960s, the heart was considered relatively resistant to ionizing radiation.
Indeed, single cardiac doses up to 10,000 rads are well tolerated in rats. [44 ] In the
1960s and 1970s, a large number of patients received gratifyingly successful
mediastinal radiation at Stanford for lymphomas (primarily Hodgkin's disease). Many of
these patients survived for years and continue to present for cardiac evaluation. A clear
dose-response effect is now apparent relating radiation to cardiac and pericardial
disease. [44 ] Both an acute pericarditis and pancarditis are produced. Indeed,
acceleration of coronary arterial disease also has been reported. [45 ]
From the surgical vantage point, radiation pericarditis is a complex problem. Patients
characteristically present with combined pericardial constriction, restrictive
radiation-induced myocardial fibrosis, and a superimposed ischemic cardiomyopathy
years to decades following radiation therapy. In the large series from Stanford, [46 ] 20
percent of patients who exhibited radiation-induced delayed pericarditis progressed to
symptomatic constriction that required pericardiectomy.
Post-Myocardial Infarction and Cardiac Surgery
The myopericardial inflammation associated with an acute myocardial infarction was

first described by Dressler. [47 ] This pericardial inflammation, secondary either to
cardiac muscle damage or postoperative cardiotomy, can lead to pain, a friction rub,
and ECG changes suggestive of ischemia. This process is important for two reasons.
First, when the pericardium is opened in any patient who has had a myocardial
infarction, the surgeon should anticipate potentially dense pericardial adhesions.
Second, if a patient suffers postinfarction cardiac rupture into a zone of dense
pericardial adhesions, bleeding may be contained with development of a cardiac false
aneurysm as opposed to rapid demise from free intrapericardial rupture and
tamponade.
Pericardial friction rubs are heard frequently after open heart surgery, and some
patients develop fever and chest pain consistent with Dressler's syndrome. [48 ] Usually
symptoms and rub respond to a course of a nonsteroidal anti-inflammatory drug;
occasional patients require a course of steroids. Pericardial effusions may develop;
sometimes one causes hemodynamic compromise and must be tapped (usually only
once). However, despite the obligate irritation of pericardial surfaces and production of
mediastinal thrombus, postoperative constrictive pericarditis is uncommon and
reported primarily as case reports. When this occurs, operation is required to relieve
the constriction.
CHRONIC CONSTRICTIVE PERICARDITIS
In recent years, constrictive pericarditis has become a less frequent surgical problem,
but almost any of the multiple causes of acute pericarditis may progress to fibrinous
pericarditis and eventually chronic constrictive pericarditis. The forces that determine
whether or not fibrinous pericarditis develops into adhesive pericarditis and constriction
are not yet clear. Interestingly, pericardial mesothelial cells harbor a plasminogen
inhibitor, [50 ] produce adenosine [51 ] (which is rapidly depleted by inflammation), but
do not express tissue factor to activate the extrinsic coagulation pathway. [52 ]
Nevertheless, all forms of pericarditis can on occasion produce a fibrinous, suppurative
exudate that eventually produces adhesion between the visceral and parietal layers and
thickened, calcific constrictive pericarditis.
The resurgence of tuberculosis, postradiation pericarditis, and occasional patients with

postoperative or postinfarction pericarditis indicates that constrictive pericarditis has
not disappeared. The constricting envelope surrounds the entire heart and interferes
with diastolic filling. The disease affects filling of all cardiac chambers, and as the
constriction progresses, only early diastolic filling is possible. The diagnosis is usually
easy because of the physical signs or right-sided heart failure, echocardiographic
evidence of a thickened, fused pericardium, and characteristic catheterization findings.
Computed tomography and magnetic resonance imaging may be very helpful in
patients with suspected constrictive pericarditis. In patients with compromise of cardiac
function, operation to remove the constricting envelope is the only effective long-term
treatment.
MALIGNANT PERICARDIAL DISEASE
Malignant tumors of breast and lung are common tumors that metastasize to the
pericardium relatively frequently. Primary or contiguous pericardial malignancies
include lymphomas, leukemias, thymomas, malignant mesotheliomas, teratomas,
angiosarcomas, and rhabdomyosarcomas. In the therapy of these formidable clinical
problems, the surgeon primarily has a diagnostic role. However, with localized giant
lymph node hyperplasia, surgical excision has been reported as uniformly curative. [53 ]
The multicentric form of this process (Castleman's disease) can cause cardiac
tamponade [54 ] with a more ominous prognosis despite surgical therapy.
When malignant tumor fills the pericardial space (with either solid tumor or malignant
effusion), surgical debulking and decompression are both gratifyingly effective and
astonishingly transient. It is important to remove sufficient tumor cells to define the
diagnosis and to delineate potential adjunctive therapy. Without effective adjunctive
chemo/radiation therapy, surgical pericardial decompression is frustratingly
evanescent. Instillation of nonspecific chemotherapy (5-fluorouracil) rarely provides
more than psychological benefit. Furthermore, an aggressive pericardial window is
typically completely invisible at autopsy 6 weeks later.
OPERATIONS
Postoperative Pericardial Tamponade
Following cardiac surgery, drainage tubes routinely are left inside the pericardium. It is
disappointing that clinically significant pericardial compression can occur despite a
wide open pericardium and patent pericardial tubes, but it can. The clinical situation that
must automatically trigger suspicion is the postoperative patient who has been bleeding
150 to 200 mL/h from his or her pericardial tubes and abruptly cuts back to 20 mL/h.
When this apparently favorable observation is coupled with (1) decreasing cardiac
index, (2) progressive tachycardia, (3) decreasing pulse pressure, and (4) increasing
filling pressures (central venous, pulmonary artery diastolic, and pulmonary capillary
wedge pressures), then pericardial compression must be suspected. Unlike measles or
pregnancy, patients can exhibit some tamponade physiology. It is a spectrum. Some
pericardial compression can exacerbate compromised postoperative cardiac muscle
function. Thus it is very, very important to detect and reverse any compressive
tamponade physiology in patients with poor cardiac function. It is inconvenient to
reoperate on patients but gratifying to watch them improve hemodynamically when you
peel clots off their hearts.
When clinically significant pericardial compression is suspected, echocardiography

often is helpful. Transthoracic echocardiography usually reveals an inspiratory increase
in right ventricular diastolic diameter and a reciprocal decrease in left ventricular
dimensions. [21 ] Similarly, peak early tricuspid flow velocity is increased, and mitral
flow is reduced. [55 ] , [56 ] These are subtle echocardiographic findings, however.
A decrease in cardiac output triggers a formidable array of neuroendocrine

compensatory systems. With a decrease in stroke volume, the early line of defense is a
tachycardia. A more chronic decrease in cardiac output prompts a
mineralocorticoid-mediated increase in intravascular blood volume that augments
preload.
Pericardiocentesis
Pericardial tamponade is not uncomfortable. With progressive tamponade, the cardiac

output falls, and the patient may become somnolent. Patients do not thrash about, but
you should be certain that your patient is comfortably supine with surface ECG and
blood pressure monitoring (depending on the hemodynamic status of the patient and
urgency of the procedure). Systemic analgesia is typically not necessary. A skin weal is
made over the left xiphoid-costal junction with 1% lidocaine. A 25-mL syringe containing
10 mL of lidocaine is affixed to a three-way stopcock and then to an 18-gauge spinal
needle. The needle is inserted (45 degrees down and 45 degrees to the left) toward the
patient's left shoulder (Fig. 44-8) . For a free pericardial effusion, the needle should be
directed toward the left shoulder. Attaching this metal needle to a precordial ECG lead
is not recommended because the data are both confusing and unnecessary. The
needle is advanced until blood, air, or serous fluid is returned. If air is encountered, the
needle should be withdrawn and reinserted with a more medial trajectory. When blood
is withdrawn, 5 ml should be placed on a bed sheet to see if it clots. Defibrinated blood
that has remained in the pericardial space for even a short time should not clot. [50 ] By
manipulating the three-way stopcock, nonclotting blood and fluid are removed from the
pericardial space without disengaging the syringe.
Pericardial Window
When fluid reaccumulates following pericardiocentesis, to cause the recurrent

symptoms and signs of tamponade, a pericardial window is indicated. The purpose of a
partial pericardial resection (window) is to drain fluid into the pleural or peritoneal
compartment lined by a larger area of absorptive mesothelial cells. Should fluid already
exist in either of these spaces (ascites or pleural effusion), then pericardial drainage will
be suboptimal.
Drainage into the pleural space may be accomplished either thoracoscopically or via an
anterior thoracotomy. Peritoneal drainage also can be produced through a subxiphoid
incision (Fig. 44-9) . General anesthesia is required for all these procedures, but
anesthesia is poorly tolerated with concurrent pericardial compression. With induction
of anesthesia, a precipitous fall in blood pressure typically ensues. Preanesthetic
pericardiocentesis or administration of a volume load is needed to prevent this event.
With the patient safely anesthesized and monitored, the distended pericardium is
identified through either the subxiphoid or anterolateral thoracotomy incision. To
minimize excitement, it is wise to delineate the pericardial space initially with an
18-gauge needle. Typically, fluid will exit under pressure. Even minimal decompression
produces dramatic hemodynamic improvement (see Fig. 44-3 ). Once the thickness of
the pericardium is appreciated, it is safely incised and then excised. Through a
subxiphoid incision, excise as much diaphragmatic pericardium as is technically
feasible. Through the left anterolateral thoracotomy incision, excise all accessible
pericardium ventral to the phrenic nerve. Pericardium anterior and posterior to the
phrenic nerve can be removed at thoracoscopy, and the procedure can be done through
either the right or the left hemithorax.[57 ] When a generous pericardial window has
been made, it is not necessary to leave a drainage tube within the pericardium.
Pericardial Stripping
Some pericardial diseases (typically radiation-induced or tuberculosis) produce

epicardial inflammation that fuses the pericardium directly to the epicardium to produce
visceroparietal constriction. Sometimes, particularly with tuberculosis, calcification
dives deep into the myocardium. In patients with constriction of only the parietal
pericardium, the pericardial space may be discernible, but in patients with
visceroparietal constriction, pericardiectomy is a formidable challenge (Fig. 44-10) .
We and others [29 ] , [37 ] recommend median sternotomy with full cardiopulmonary
bypass in all patients with constrictive pericarditis. In the past, pericardial stripping has
been done through a left thoracotomy incision without cardiopulmonary bypass, [58 ] but
this approach limits options the surgeon may need. The goal is to release the
straightjacket on the left and right ventricles. Absence of an epicardial-pericardial plane
can make this an exciting and very bloody procedure with a frightening potential
mortality. [37 ] For this reason, we encourage the use of full heparinization, aprotinin,
Cell Saver techniques, and cardiopulmonary bypass so that blood losses may be
immediately salvaged and reinfused.
The pericardium should be removed from phrenic to phrenic nerve anteriorly but also
should be removed posterior to the left phrenic nerve, as shown in Fig. 44-11 .
Complete removal of the constricting pericardium restores the left ventricular
pressure-volume loop to normal or near normal. [59 ]
The results of pericardial stripping vary with the etiology of the pericarditis and with the
severity of heart failure and myocardial disease preoperatively. [58 ] , [60 ] , [61 ]
Operative mortality ranges between 10 and 20 percent and is adversely influenced by
the severity of heart failure, elevation of right atrial pressure, and co-morbid disease. [58
] , [60 ] , [61 ] Long-term results are poorest in patients with radiation pericarditis, [61 ]
and in all patients results vary primarily in proportion to the preoperative severity of heart
failure. With better methods available to detect thickened pericardium and early signs of
constriction after pericarditis of any etiology, early pericardial stripping is strongly
recommended before the onset of severe heart failure. [37 ]
DEEP VENOUS THROMBOSIS (DVT)
Deep venous thrombosis primarily affects the veins of the lower extremity or pelvis and
rarely affects the venous system elsewhere. The process may involve superficial as well
as deep veins, but superficial venous thrombosis does not generally propagate beyond
the saphenousfemoral vein junction and therefore rarely causes PE. [7 ] , [16 ] Venous
thrombosis of the upper extremity almost always is associated with trauma, indwelling
catheters, or other pathologic states and is an uncommon cause of PE but can be fatal.
[17 ] Pulmonary emboli that do not originate from the deep venous system of the legs
and pelvis are thought to come from a diseased right atrium or ventricle or from
retroperitoneal and hepatic systems. [16 ] , [18 ]
DVT is most common in hospitalized patients but may occur in ambulatory patients
outside the hospital. [19 ] In recent years improved understanding of the pathogenesis
of the disease and better diagnostic tests have identified patients at risk, improved
prophylaxis, and increased the percentages of patients who are diagnosed and treated.
Pathology
In careful autopsy studies microscopic thrombi may be found in the pockets of venous
valve cusps, in vein saccules, and at vein junctions of pelvic, thigh, and calf veins. [16 ] ,
[20 ] Calf vein thrombi are most common, [11 ] , [21 ] , [22 ] and multiple and bilateral
thrombi at independent sites within the lower body venous system can occur
simultaneously. [16 ] The initial thrombus grows by accretion of platelets, fibrin, and
emeshed red cells [23 ] and may detach at any time. Six primary sites of origin of DVT
are described: external iliac, common femoral, termination of either the superficial or
deep femoral, popliteal, posterior tibial, and intramuscular calf veins. [16 ] Most calf vein
thrombi either do not embolize or produce small, often asymptomatic emboli of little
clinical significance. [18 ] However, somewhere between 20 and 30 percent of calf vein
thrombi propagate proximally into upper thigh veins. [7 ] , [21 ] The majority of PE
originate in thigh and pelvic veins. [24 ] , [25 ]
Thrombi are composed of fibrin, platelets, and usually large numbers of red cells that
may form lakes within the clot. In clots that do not embolize, the fibrinolytic system
usually dissolves the thrombus. Incomplete dissolution results in the formation of
granulation tissue at sites where the thrombus attaches to the vein wall. The organizing
thrombus becomes incorporated into the vein wall, but usually destroys the adjacent
valve as proliferating vascular channels and fibroblasts invade the site. [20 ]
Pathogenesis
In 1856 Rudolf Virchow made the association between DVT and PE and suggested
that the causes of DVT were related to venous stasis, vein wall injury, and
procoagulants in the blood. This triad of etiologic factors remains relevant today and is
supported by an ever-growing body of evidence.
Injections of contrast material in foot veins require up to 1 hour to clear from venous
valves in the soleus muscle of immobilized patients. [26 ] Venous stasis is also
produced by mechanical obstruction of proximal veins, by low cardiac output, by venous
dilatation, and by increased blood viscosity. [19 ] Some pelvic tumors, bulky inguinal
adenopathy, the gravid uterus, previous caval or iliac venous disease, and elevated
central venous pressures from cardiac causes also enhance venous stasis.
Tourniquets, anesthetic agents, pregnancy, high dose estrogens, [7 ] , [27 ] and
increasing age produce venous dilatation; polycythemia, hyperfibrinogenemia, and
some abnormal protein diseases increase the viscosity of blood. [19 ] It is not clear
whether or not superficial varicosities increase the likelihood of DVT in deep veins.
However, immobilization is by far the most important cause of venous stasis in
hospitalized patients.
The role of vein wall injury is less clear since DVT often begins in the absence of
mechanical trauma. Direct venous injury, for example, during hip surgery or by catheter
denudation of endothelial cells, exposes the subendothelium, which activates both the
intrinsic and extrinsic coagulation pathways and causes adherence of circulating
platelets, [28 ] [30 ] leukocytes, and monocytes. [31 ] In these circumstances the role of
vein wall injury is clear, but most DVT is not associated with overt vein wall injury. [16 ] ,
[27 ] However, recent work shows that subtle vein wall injuries may occur during
operation in veins remote from the operative field. [32 ] , [33 ] In animals, endothelial cell
tears have been found at junctions of small veins with larger veins at remote sites during
hip replacement (Fig. 45-1) . The mechanism is thought to be venous dilatation
mediated by the production of circulating vasoactive substances, including histamine,
bradykinin, activated complement, and the leukotrienes during operation. [27 ] Exposure
of subendothelial tissue factor provides a powerful procoagulant stimulus by activating
factor VII and the extrinsic coagulation pathway. [29 ]
The cytokines, interleukin-1 (IL-1), and tumor necrosis factor (TNF), produced by
macrophages and other cells in various pathologic conditions, stimulate procoagulant
activity of endothelial cells. Cytokines activate endothelial cells to express tissue factor,
[34 ] which initiates the extrinsic coagulation pathway [35 ] ; to produce plasminogen
activator inhibitor-1 (PAI-1), [36 ] which inhibits fibrinolysis; to suppress protein C
activation [34 ] ; and to reduce production of thrombomodulin, which inactivates
thrombin. IL-1 also induces adhesion of monocytes and rolling neutrophils. [34 ] , [37 ] ,
[38 ] In ways that are still not clear, these processes may combine with venous stasis,
microscopic endothelial tears, and blood procoagulant activity to localize the formation
of the initial thrombus to venous saccules and valve pockets of the deep leg veins.
Simultaneous maintenance of the fluidity of blood and the integrity of the vascular
system requires a balance between blood pro- and anticoagulants. Some patients with
DVT have deficiencies in natural anticoagulants. Three uncommon familial deficiencies
associated with venous thrombosis are in antithrombin, protein C, and protein S. [39 ]
[42 ] Antithrombin is a natural plasma protease that inhibits thrombin after it is formed
and to a lesser extent before it is formed. Antithrombin is also the cofactor that is
accelerated 1,000-fold by heparin. Antithrombin deficiency may be congenital in
approximately 0.3 percent of the population or may be acquired in patients with severe
liver disease, the nephrotic syndrome, severe cachexia, newborns, and severely
polycythemic patients. [43 ] Protein C is a potent inhibitor of factor V and platelet-bound
factor VII and requires protein S as a cofactor for anticoagulant activity. Both protein C
and S are vitamin-K-dependent zymogens that are activated by thrombin and
accelerated by thrombomodulin produced by endothelial cells. The incidences of both
protein C and S deficiencies are similar to that of antithrombin. [40 ]
A much more common coagulation deficiency, resulting from a mutation of factor V

(factor V Leiden) that prevents its degradation by protein C, has been described
recently and is present in approximately 67 percent of study populations of Swedes and
North American males. [44 ] [46 ] Both the homozygous and heterozygous mutants are
strongly associated with venous thrombosis and pulmonary embolism but are not
associated with stroke, myocardial infarction, and other manifestations of arterial
thrombosis. [45 ] , [46 ] The Ridker study observed that the factor V mutation is
particularly prevalent among men over age 60 who have had their first episode of
venous thrombosis.
Presence of the lupus anticoagulant, which is an acquired IgG or IgM antibody against
prothrombinase, increases the likelihood of venous thrombosis by poorly understood
mechanisms. [47 ] The disease may be associated with lupus-like syndromes,
immunosuppression, or intake of specific drugs, such as procaine amide.
Decreased fibrinolytic activity in blood may also contribute to the development of DVT.
Fibrinolytic activity is less in leg veins than in arm veins, particularly in older patients. [48
] Decreased fibrinolytic activity may be owing to decreased production of tissue
plasminogen activator (t-PA) or increased concentrations of plasminogen activator
inhibitor-1. [49 ] Patients with decreased fibrinolytic activity are more likely to develop
postoperative venous thrombosis and recurrent DVT. [49 ] [51 ]
Risk Factors for DVT
The presence of major risk factors increases the likelihood of venous thromboembolism
in proportion to the number of risk factors present. In patients with clinically suspected
DVT, 50 percent of patients with three risk factors have DVT proven; however, without
any risk factors DVT is proven in only 11 percent. [52 ] The rationale for aggressive
prophylactic therapy against the disease is based on the strong association between
major risk factors and venous thromboembolism.
Table 45-1 presents a list of major risk factors for development of DVT or PE. Previous
thromboembolism, older age, immobilization over 1 week, orthopedic surgery of the hip
or knee, recent surgery, multiple trauma, and cancer are strong risk factors. In patients
with a history of venous thromboembolism the risk of developing a new episode during
hospitalization is nearly eight times that of someone without a history. [7 ] , [53 ] Up to 10
percent of patients with a first episode of DVT or PE and up to 20 percent of those with
a recurrent event develop a new episode of venous thromboembolism within 6 months.
[54 ]
The incidence of DVT and PE increases exponentially with age (Fig. 45-2) . Patients in
the seventh and eighth decades of life are 200 times more likely to develop venous
thromboembolism than patients below age 40. Males are at greater risk than females.
Immobility from any cause and prolonged bed rest are major risk factors. Although
usually other risk factors are present, the incidence of autopsy-proven venous
thrombosis rises from 15 to 80 percent in patients at bed rest for more than 1 week. [55
]
Orthopedic surgery involving the hip or knee has an incidence of DVT of 50 percent and
of PE between 5 and 18 percent. [1 ] , [7 ] , [56 ] , [57 ] After knee or hip surgery, over 90
percent of proximal thrombi occur in veins of the operated leg. [7 ] Proximal DVT is
more common after knee arthroplasty than after hip arthroplasty (36 vs. 16 percent). [57
] Patients with pelvic femoral and tibial fractures are also at high risk for DVT and PE. [7
]
Without prophylaxis the risk of DVT and PE after major abdominal surgery is
approximately 25 and 2 percent, respectively. [1 ] , [11 ] , [56 ] The risk of venous
embolism also is increased following urologic surgery and operations for gynecologic
cancer. [7 ] After multiple trauma the risk of DVT and PE is over 50 percent in patients
with pelvic, thigh, or leg injuries. More surprisingly, approximately 40 percent of patients
with face, chest, and abdominal injuries also had DVT and PE. [58 ]
The incidence of venous thromboembolism increases threefold in patients who have

operations for cancer. [7 ] The incidence is highest in patients with advanced or
metastatic disease and may be related to production of procoagulant material or
suppression of fibrinolytic activity by some tumors. [7 ] Patients with congestive heart
failure are at higher risk of venous thromboembolism because of venous stasis and
higher venous pressures and, if PE occurs, are more likely to die because of reduced
cardiac reserve. Acute myocardial infarction may be an independent risk factor for PE,
but this is not clear because other risk factors usually are present. [7 ]
Although the risk of PE is low, women who have just given birth are at higher risk of PE
than during pregnancy, and PE remains a major cause of maternal mortality. [19 ]
High-dose estrogen given to treat some malignancies is associated with an increased
risk of venous thromboembolism. It is not clear whether or not oral estrogen
contraceptives increase the risk of thromboembolism. Low-dose estrogens, obesity,
and varicose veins are probably not independent risk factors for DVT or PE but may be
additive. [7 ]
Of particular interest to cardiac surgeons and cardiologists is the recent observation

that clinically silent DVT develops during hospitalization in nearly 50 percent of patients
after myocardial revascularization. [59 ] Nearly all of the thrombi occur in calf veins and
are distributed equally between the saphenous vein donor leg and the opposite
extremity. [59 ] Patients are asymptomatic for DVT, there are no physical clues, but all
thrombi in this small series were proven by duplex scanning. [59 ]
A follow-up study [60 ] found that the incidence of PE in hospital after coronary arterial
bypass operations was 3.2 percent; risk factors included prolonged postoperative
recovery, previous venous thromboembolism, obesity, and hyperlipidemia. Hospital
mortality in patients with PE was 18.7 percent. [60 ] Interestingly, valvular surgery was
not associated with development of PE. [60 ] In a retrospective study of 5694 patients
who had open heart surgery, Gillinov and colleagues found the risk of PE proven by V/Q
scan (20 patients), angiography (4 patients), or autopsy (8 patients) was 0.56 percent
within 60 days. However, mortality was 34 percent in patients with PE. [61 ]
Diagnosis
Approximately two-thirds of patients with DVT do not have clinical symptoms [7 ] ;

therefore, the diagnosis depends on a high degree of clinical suspicion and a variety of
objective diagnostic tests. Venography remains the most reliable test for detecting
thrombus in calf veins but competes with noninvasive tests for detecting DVT in thigh
and pelvic veins. Venography, however, is invasive, not suitable for serial studies, and
the contrast material may be thrombogenic if allowed to remain within the deep venous
system. [14 ] Direct injection is needed to reliably demonstrate clot in iliofemoral veins
by venography, but this technique is seldom used. [62 ]
The most popular noninvasive test, which can be done at the bedside, is a combination
of ultrasound and color flow Doppler mapping, widely referred to as duplex scanning .
The method does not detect fresh thrombi directly but infers the presence of clot by flow
patterns and inability to compress the vessel in specific locations. [14 ] , [62 ] In the
hands of skilled examiners duplex scanning is highly accurate for detection of thrombus
in popliteal, deep femoral, and superficial femoral veins and has a sensitivity between
89 and 100 percent against venography in symptomatic patients. Diagnostic accuracy
is much less in asymptomatic patients for thrombi in these locations. [14 ] , [62 ] , [63 ]
Specificity is nearly 100 percent in both symptomatic and asymptomatic patients. [62 ]
Against magnetic resonance imaging (MRI) duplex scanning has a sensitivity of 70
percent for pelvic veins and a specificity of nearly 100 percent. [62 ] The test is less
accurate in the calf and also in patients suspected of recurrent DVT.
Magnetic resonance imaging is a noninvasive method that can image the entire venous
system, including upper extremity veins and mediastinum. [64 ] Thrombi can be imaged
with either spin echo or gradient echo techniques; however, gradient echo may be more
specific. [62 ] The method detects flow within the venous system and reliably separates
flowing blood from stagnant blood or thrombus. Compared to venography, the sensitivity
and specificity of MRI for the detection of DVT is greater in the pelvis, equal in the thigh,
and worse in the calf. [64 ] , [65 ] For pelvic DVT the sensitivity of MRI against direct
injection venography is 100 percent, and the specificity is 95 percent. In the thigh MRI is
100 percent sensitive and specific. [62 ] MRI is somewhat less sensitive in the calf at 87
percent but nearly 100 percent specific. MRI is better than other methods for
differentiation of acute and chronic DVT. Disadvantages include cost, availability, and
occasional patients with claustrophobia.
Impedance plethysmography assesses volume changes in the leg after occlusion of the
vein with calf electrodes and a thigh cuff. It is clinically useful in symptomatic patients but
has relatively low sensitivity and specificity in asymptomatic patients and calf
thrombosis. [62 ] Injection of iodine-125-labeled fibrinogen with subsequent leg
scanning is a sensitive test for detecting calf vein thrombus but does not detect
iliofemoral vein thrombosis. The combination of these two tests improves sensitivity and
specificity, but in most hospitals both tests have been superseded by duplex scanning,
venography, and MRI.
Prophylaxis
The prevalence of DVT, its strong association with PE, and identification of risk factors
in the pathogenesis of the disease provide the basis and rationale for prophylactic
measures that are recommended in patients with two or more major risk factors, such
as age over 40 years and major surgery. [7 ] Innocuous measures such as compression
stockings probably should be prescribed more often and be used in most
nonambulating patients in the hospital. Intermittant pneumatic compression is more
expensive and more cumbersome but is also effective. Both methods reduce the
incidence of DVT after general surgery to approximately 40 percent of control patients.
[7 ] Low-dose subcutaneous heparin or low-molecular-weight heparin given once per
day reduce the incidence of DVT to approximately 35 percent and 18 percent of
controls, respectively. [7 ] , [56 ] , [66 ] The reduction in PE with subcutaneous standard
heparin or low-molecular-weight heparin is similar. [56 ] , [66 ]
Calf vein DVT that does not propagate has low risk of PE, and controversy exists
whether or not these patients should be anticoagulated. [18 ] Of patients who have DVT
diagnosed in hospital without PE, the probability of clinically diagnosed PE within the
next 12 months is 1.7 percent. [8 ] If PE occurs, the probability of recurrent PE is 8.0
percent. [8 ] Six months of warfarin anticoagulation are recommended for patients who
have DVT with or without PE as prophylaxis against recurrent disease. [67 ]
PULMONARY EMBOLISM
Pathology and Pathogenesis
Partial or complete occlusion of calf or thigh veins reduces velocity of flow in the more
proximal femoral and iliac veins and enhances propagation of thrombus toward the
heart. The thrombus is attached to the vein wall at the site of origin, [12 ] usually does
not develop other sites of attachment immediately, [16 ] and may grow to fill most of the
lumen of the vein and extend into the vena cava. The only firm attachment is at the site of
origin, usually a venous saccule or venous valve pocket. The degree of organization
within the thrombus varies, but recent clots are more likely to migrate than older thrombi
that are more firmly attached to the vessel wall.
Detached venous thrombi float in the moving bloodstream through the right heart into
the pulmonary circulation. Large thrombi may float as a single embolus or fragment into
smaller clots along the way. Some seemingly recurrent emboli may actually be
fragments of the original embolus that have been delayed in transit through the right
atrium or ventricle. [18 ] In autopsy series the percentage of emboli that obstruct two or
more lobar arteries (major) ranges between 25 and 67 percent of all emboli [68 ] ;
however, this percentage varies with the thoroughness of the examination. In clinical
trials based on angiographic data the percentage of major emboli is similar and ranges
from 30 to 64 percent. [69 ] The majority of pulmonary emboli lodge in the lower lobes
[16 ] and are slightly more common in the right lung than in the left. Soon after reaching
the lungs emboli become coated with a layer of platelets and fibrin. [16 ]
Simple mechanical obstruction of one or more pulmonary arteries does not entirely
explain the often devastating hemodynamic consequences of major or massive emboli.
Humoral factors, specifically serotonin, adenosine diphosphate (ADP), platelet-derived
growth factor (PDGF), thromboxane from platelets coating the thrombus,
platelet-activating factor (PAF), and leukotrienes from neutrophils are also involved. [70
] In animal and early clinical studies serotonin inhibitors, cyprohepitadine and
ketanserin, partially block constriction of both pulmonary arteries and bronchi
associated with pulmonary embolism. [71 ] Anoxia and tissue ischemia downstream to
emboli inhibit endothelium-derived relaxing factor (EDRF) production and enhance
release of superoxide anions by activated neutrophils. The combination of these effects
contributes to enhanced pulmonary vasoconstriction. [70 ]
Natural History
The mortality of untreated PE is 1833 percent, but with therapy overall mortality is under
8 percent. [10 ] , [72 ] , [73 ] Seventy-five to 90 percent of patients who die of pulmonary
emboli do so within the first few hours of the primary event. [4 ] , [74 ] It is possible that
those who die later do so of recurrent PE. [10 ] , [18 ] In patients who have sufficient
cardiopulmonary reserve and right ventricular strength to survive the initial few hours,
autolysis of emboli occurs over the next few days and weeks. [75 ] On average,
approximately 20 percent of the clot disappears by 7 days, and complete resolution
may occur by 14 days. [73 ] , [76 ] For many patients, up to 30 days are needed to
dissolve small emboli and up to 60 days for massive clots. [4 ] As the natural fibrinolytic
system dissolves the embolic mass, the available cross-sectional area of the pulmonary
arterial tree progressively increases, and pulmonary vascular resistance and right
ventricular afterload decrease. In the vast majority of patients, pulmonary emboli
significantly resolve [77 ] ; thus interventional therapy, particularly surgical embolectomy,
is not necessary for survival except in the minority of patients who cannot survive the first
few hours.
In a very small minority of patients, perhaps only 0.1 percent, PE do not lyse, and
chronic thromboembolic obstruction of the pulmonary vasculature develops. [18 ] The
reasons for failure of emboli to dissolve are unknown. Patients often are asymptomatic
until symptoms of dyspnea, exercise intolerance, or right heart failure develop.
Asymptomatic patients may have partial or complete chronic thrombotic occlusion of
one or more segmental or lobar arteries. Symptomatic patients usually have over 40
percent of their pulmonary vasculature obstructed by organized and fresh thrombi.
ACUTE PULMONARY EMBOLISM
Acute pulmonary embolism usually presents suddenly. Symptoms and signs vary with
the extent of blockage, the magnitude of the humoral response, and the pre-embolus
reserve of the cardiac and pulmonary systems of the patient. [78 ] Symptoms and signs
vary widely, but the clinical diagnosis often is missed or falsely made. Most pulmonary
emboli occur without sufficient clinical findings to suggest the diagnosis. [78 ] In autopsy
series of proven emboli only 1638 percent of patients were diagnosed during life. [68 ]
On the other hand, angiographic studies have found that only 2529 percent of patients
suspected of PE actually had PE. [79 ] , [80 ]
The acute disease is conveniently stratified into minor, submassive (major), or massive
embolism on the basis of hemodynamic stability, arterial blood gases, and lung scan or
angiographic assessment of the percentage of blocked pulmonary arteries. [69 ] , [78 ] ,
[81 ] Most pulmonary emboli are minor or submassive. These patients present with
sudden, unexplained anxiety, tachypnea or dyspnea, pleuritic chest pain, cough, and
occasionally streak hemoptysis. [68 ] , [74 ] , [77 ] , [81 ] , [82 ] Examination may reveal
tachycardia, rales, low grade fever, and sometimes a pleural rub. Heart sounds and
systemic blood pressure are often normal; sometimes the pulmonary second sound is
increased [68 ] ; less than a third have clinical DVT. [68 ] Room air arterial blood gases
indicate a Pa o 2 between 65 and 80 torr and a normal Pa co 2 around 35 torr. [81 ]
Pulmonary angiograms show less than 30 percent occlusion of the pulmonary arterial
vasculature or less.
Major pulmonary embolism is associated with dyspnea, tachypnea, dull chest pain, and
some degree of hemodynamic instability manifested by tachycardia, mild to moderate
hypotension, and elevation of the central venous pressure. [81 ] , [83 ] Some patients
may present with syncope rather than dyspnea or chest pain. In contrast to massive
pulmonary embolism, patients with major embolism (at least two lobar pulmonary
arteries obstructed) are hemodynamically stable, and cardiac output is adequate. [69 ]
Room air blood gases reveal moderate hypoxia (Pa o 2 < 65, > 50 torr) and mild
hypocarbia (Pa co 2 < 30 torr). [81 ] Echocardiograms may show right ventricular
dilatation. Pulmonary angiograms indicate that 3050 percent of the pulmonary
vasculature is blocked; however, in patients with preexisting cardiopulmonary disorders,
lesser degrees of vascular obstruction may produce similarly alarming symptoms.
Massive pulmonary embolism is truly life-threatening and is defined as a PE that

causes hemodynamic instability. [69 ] It is sometimes associated with occlusion of more
than 50 percent of the pulmonary vasculature, but may occur with much smaller
occlusions, particularly in patients with preexisting cardiac or pulmonary disease. The
diagnosis is clinical, not anatomical. Patients develop acute dyspnea, tachypnea,
tachycardia, and diaphoresis and sometimes lose consciousness. Both hypotension
and low cardiac output (< 1.8 l/m [2 ] /min) are present. Cardiac arrest may occur. Neck
veins are distended; central venous pressure is elevated; a right ventricular impulse
may be present. Room air blood gases show severe hypoxia (Pa o 2 < 50 torr), [84 ]
hypocabia(Pa co 2 < 30 torr), and sometimes acidosis. Urine output falls; peripheral
pulses and perfusion are poor.
Diagnosis
The clinical diagnosis of acute major or massive pulmonary embolism is unreliable and
is wrong in 7080 percent of patients who have angiography subsequently. [78 ] , [79 ] ,
[84 ] , [85 ] Even in postoperative patients and those with additional major risk factors
for DVT, differentiation of major or massive pulmonary embolism from acute myocardial
infarction, aortic dissection, septic shock, and other catastrophic states is difficult and
uncertain. A plain chest x-ray, an electrocardiogram (ECG), and insertion of a bedside
Swan-Ganz catheter may add confirmatory information, but absence of ECG evidence
of an acute infarction does not rule out that diagnosis. Usually, the ECG shows
nonspecific T-wave or RS-T segment changes with PE. A minority of patients with
massive embolism (26 percent) may show evidence of cor pulmonale, right axis
deviation, or right bundle branch block by ECG. [68 ] The chest film may be normal but
usually shows some combination of parenchymal infiltrate, atelectasis, and pleural
effusion. A zone of hypovascularity or a wedged-shaped pleural-based density raise the
possibility of PE, but the diagnosis cannot be made with certainty on the basis of a
chest film. A normal chest film in the presence of sudden hypoxia and collapse is
suggestive of massive PE. [78 ] An echocardiogram showing right heart dilatation
raises the possibility of major or massive PE. A Swan-Ganz catheter generally shows
pulmonary arterial desaturation (Pa o 2 < 25 torr) but usually does not show pulmonary
hypertension over 40 mmHg because of low cardiac output and cor pulmonale. To date,
no circulating markers of pulmonary embolism have been discovered. [78 ]
Pulmonary angiograms provide the most definitive diagnosis, [68 ] , [81 ] but collapse of
the circulation may not allow time for this procedure. Pulmonary angiograms cannot be
performed during closed chest massage and are unwise if the patient's circulation
cannot be stabilized by pharmacologic or mechanical means. In stable patients,
angiograms are associated with a mortality of 0.2 percent and are not recommended if
the right atrial pressure is over 20 mmHg. [87 ] A negative angiogram excludes clinically
significant PE. [88 ] In hemodynamically unstable patients, the volume of contrast only
should be enough to show the presence of major pulmonary emboli; it is not necessary
and may be risky to document details with large contrast media injections.
Ventilation-perfusion (V/Q) scans may provide confirmatory evidence, but these studies
are less reliable, since pneumonia, atelectasis, previous pulmonary emboli, and other
conditions may cause a mismatch in ventilation and perfusion and mimic positive
results. [76 ] , [89 ] A negative V/Q scan essentially rules out the diagnosis of clinically
significant PE. [68 ] V/Q scans usually are interpreted as high, intermediate, or low
probability of PE to emphasize the lack of specificity but high sensitivity of the test (Fig.
45-3) . Magnetic resonance imaging (MRI) is a better noninvasive method for the
diagnosis of pulmonary emboli and provides specific information regarding flow within
the pulmonary vasculature. [90 ] Unfortunately, the method is expensive,
time-consuming, and not widely available and is not suitable for hemodynamically
unstable patients. Transthoracic (TTE) or transesophageal (TEE) echocardiography
with color flow Doppler mapping can provide reliable information about the presence or
absence of major thrombi obstructing the main pulmonary artery. More than 80 percent
of patients with clinically significant PE have abnormalities of right ventricular volume or
contractility or acute tricuspid regurgitation by TTE [84 ] , [91 ] (Fig. 45-4) . In some
patients abnormal flow patterns can be discerned in major pulmonary arteries during
TEE. Intravascular ultrasound imaging is a new diagnostic method that requires venous
access but that can be done at the bedside and may prove useful in the diagnosis of
PE. [91 ]
Management of Major Pulmonary Embolism
For purposes of this chapter major or submassive pulmonary embolism is defined as

an acute episode that causes hypoxia and mild hypotension (systolic arterial pressure >
90 mmHg), but that does not cause cardiac arrest or sustained low cardiac output and
cardiogenic shock. Management of these patients is nearly always done after definitive
diagnosis by internists. By definition there is sufficient time in these patients to definitely
establish the diagnosis and to attempt pharmacologic therapy and possibly removal of
embolic material by catheter suction. However, even though a satisfactory circulation is
established, a few patients may become unstable and require management as outlined
in the following under the diagnosis of massive pulmonary embolism. [92 ] This
subgroup of patients may be those with echocardiographic evidence of significant and
progressive right ventricular failure.
The first priority after sudden collapse of any patient is to establish adequate ventilation
and a survival circulation. This may require intubation and mechanical ventilation and
always requires added oxygen. [69 ] , [84 ] The initial treatment of low cardiac output
includes calcium, epinephrine, and sodium bicarbonate. Later if enough blood reaches
the left ventricle to sustain the circulation, dobutamine, dopamine, or norepinephrine
may be added or substituted for epinephrine. In some patients phosphodiesterase
inhibitors also may be useful to sustain an adequate cardiac output. [84 ] Once the
circulation has been stabilized, both arterial and central venous catheters are placed for
access and for continuous pressure monitoring. Usually a Swan-Ganz catheter also is
placed to monitor cardiac output and pulmonary arterial oxygen saturation. The ECG is
monitored, a Foley catheter is placed for recording urine output, and blood gases are
obtained.
If the patient's circulation can be stabilized, intravenous heparin is started with an initial
bolus dose of 70 U/kg followed by 18 U/kg/h if there are no contraindications to heparin.
Heparin prevents propagation (as opposed to movement) of existing clots but does not
dissolve thrombus. In most instances the patient's own fibrinolytic system lyses fresh
thrombi over a period of days or weeks. [75 ] Without heparin up to 16 percent of
patients with documented DVT developed PE, and 2.3 percent had fatal PE. [9 ] When
heparin was used in patients with PE, mortality was 4 percent, and the recurrence rate
was 9 percent. [93 ] Heparin is monitored by measurement of activated partial
thromboplastin times, which are maintained between 51 and 68 seconds (twice
control), every 68 hours. Platelet counts should be obtained at the beginning of heparin
and every 23 days to detect the presence or appearance of heparin-induced
thrombocytopenia. Prothrombin times also are obtained at baseline to prepare for
long-term anticoagulation with warfarin later.
The addition of streptokinase, urokinase, or recombinant tissue plasminogen activator

(rt-PA) increases the rate of lysis of fresh thrombi and is recommended in patients with
stable circulations and no contraindications. Thrombolytic therapy increases the rate of
lysis of fresh pulmonary clots [94 ] , [95 ] over that of heparin alone during treatment, [96 ]
but there is little difference in the amount of residual thrombus between the two
treatments at 5 days or thereafter. [77 ] , [93 ] , [97 ] [99 ] There is also no statistical
difference in mortality or in the incidence of recurrent PE, [93 ] , [98 ] , [99 ] but more
recent experience shows a trend toward better results with thrombolytic therapy
because of more rapid reduction in right ventricular afterload and dysfunction. [96 ]
There are no data that indicate that thrombolysis reduces the subsequent development
of chronic pulmonary thromboembolism. [18 ] , [96 ] Thrombolytics also accelerate lysis
of propagated clots in the iliofemoral system. [82 ] , [95 ] As compared to heparin,
streptokinase, urokinase, and rt-PA are associated with two or three times higher rates
of major bleeding (1427 percent vs. 614 percent). [77 ] , [98 ] [100 ] T-PA is usually
given in 2-hour infusions as opposed to 12- and 24-hour infusions for other agents. [96 ]
Despite precautions, bleeding complications occur in approximately 20 percent of
patients. [95 ] , [99 ] , [101 ] Contraindications to the use of fibrinolytic agents include
patients with fresh surgical wounds, recent stroke, peptic ulcer, or bleeding disorders.
[82 ] , [95 ] These drugs are also contraindicated in severely anemic patients and
patients with potential sources of catastrophic intracranial, retroperitoneal, or
gastrointestinal bleeding. [96 ]
Mechanical removal of pulmonary thrombi is possible by a catheter device inserted

under local anesthesia into the femoral (preferred) or jugular vein. [81 ] , [102 ] The
catheter, which has a small, terminal cup, is steered into the pulmonary artery using
fluoroscopy for guidance. Syringe suction is applied to the cup as a thrombus is
engaged, and the whole assembly is removed through the venotomy. The procedure
may be repeated. Successful extraction of clot with meaningful reduction in pulmonary
arterial pressure varies between 61 and 84 percent. [102 ] Sixty to 70 percent of
patients with major, massive, or chronic PE survive.
Management of Massive Pulmonary Embolism
Time becomes paramount if the circulation cannot be stabilized at survival levels within
several minutes or if cardiac arrest occurs after a massive PE. Most deaths from acute
pulmonary embolism occur before effective treatment is instituted or are not diagnosed
in life. Eleven percent of patients with fatal PE die within the first hour, 4380 percent
within two hours, and 85 percent within 6 hours. [84 ] To a great extent, circumstances
and the timely availability of necessary equipment and personnel determine therapeutic
options. [103 ] Mitigating factors such as advanced age, irreversible underlying health
problems, and likelihood of brain damage also enter decisions. A decision to treat
medically in an effort to stabilize the circulation at a survival level may preempt
life-saving surgery but also may make surgery unnecessary. For many reasons
retrospective studies are of limited relevance for this decision. Sometimes surgical
treatment is not available immediately [103 ] ; at other times deteriorating patients are
referred to surgery too late after failing medical therapy. The relative infrequency of
treatment opportunities in massive pulmonary embolism, mitigating factors, and the lack
of clear criteria for prescribing medical or surgical therapy leave the management of
massive PE unsettled.
Newer understanding and new technology offer a reasonable, if untried, algorithm for
dealing with probable massive pulmonary embolism with life-threatening hemodynamic
instability in hospitalized patients. In otherwise healthy patients in whom a thoracotomy
poses little risk or morbidity, emergency thromboembolectomy with preoperative
confirmation of the diagnosis in the operating room by transesophageal
echocardiography offers the surest chance of survival. Although the patient may
undergo an unnecessary operation, the patient is highly likely to survive. When surgery
is not immediately available or in patients who are older, who may have suffered
irreversible organ damage, or in whom an alternate diagnosis seems more likely,
emergency extracorporeal life support (ECLS) using peripheral cannulation is an
attractive alternative. [104 ] , [105 ] In prepared institutions ECLS can be instituted
rapidly outside the operating room, [104 ] , [106 ] and the morbidity is much less than
thoracotomy. ECLS compensates for acute cor pulmonale [107 ] and hypoxia and
sustains the circulation until the clot partially lyses, pulmonary vascular resistance falls,
and pulmonary blood flow becomes adequate.
Emergency Pulmonary Thromboembolectomy
Emergency pulmonary thromboembolectomy is indicated for suitable patients with

life-threatening circulatory insufficiency as discussed earlier but should not be done
without a definitive diagnosis. A clinical diagnosis of PE is often wrong. [79 ] , [86 ] , [93
] , [104 ] If a patient has been taken directly to the operating room without a definitive
diagnosis, transesophageal echocardiography and color flow Doppler mapping can
confirm or refute the diagnosis in the operating room. [81 ] , [108 ] Transesophageal
echocardiography permits good assessment of right ventricular volume, contractility,
and tricuspid regurgitation, which are strongly associated with massive pulmonary
embolism and acute cor pulmonale. [93 ]
Echocardiographic detection of a large clot trapped within the right atrium or ventricle is
another indication for emergency pulmonary thromboembolectomy. [84 ] , [109 ]
A midline sternotomy incision is used for acute pulmonary thromboembolectomy. [110 ]

The ascending aorta and both cavae are cannulated after 3 mgm/kg of heparin. With full
cardiopulmonary bypass the heart may be electrically fibrillated or arrested with cold
cardioplegic solution after the aorta is clamped. Hypothermia is not necessary since
only a short period of complete bypass is needed. The main pulmonary artery is opened
several centimeters downstream to the valve, and the incision is extended into the
proximal left pulmonary artery and into the proximal right pulmonary artery behind the
ascending aorta. Clot is removed manually by forceps and suction catheters. If a sterile,
pediatric bronchoscope is available, the surgeon can use this instrument to locate and
remove thrombi in tertiary and quartenary pulmonary vessels. Alternatively pleural
spaces are entered, and each lung is gently compressed to dislodge small clots into
larger vessels and the suction cannula. The arteriotomy is closed with a fine running
suture (e.g., 5-0 prolene). After restarting the heart, the patient is weaned from bypass,
decannulated, and closed.
Greenfield recommends placement of an inferior vena caval filter before closing the
chest. [14 ] , [111 ] A variety of filters are available and are effective in preventing
recurrent PE. [112 ] European surgeons generally clip the intrapericardial vena cava at
the end of pulmonary thromboembolectomy to prevent migration of large clots into the
pulmonary circulation. [84 ] This clip increases venous pressure and stagnant flow in the
lower half of the body and causes considerable morbidity in over 60 percent of patients.
[85 ]
Although recurrent PE is always a threat, the likelihood during the immediate

postoperative period is statistically small. Modern diagnosis of proximal DVT,
knowledge of risk factors, and efficacy of anticoagulant therapy permit brief deferral of
the decision to place a filter. Anticoagulation for 6 months is recommended for most
patients with PE, but an inferior vena caval filter is recommended for patients with
contraindications to anticoagulation or with recurrent PE, or those who require
pulmonary thrombendarterectomy. The cone-shaped Greenfield filter is most widely
used and is associated with a lifetime recurrent embolism rate of 5 percent and has 97
percent patency rate. [113 ]
Wider availability of long-term extracorporeal perfusion (termed extracorporeal life

support, ECLS) using peripheral vessel cannulation to stabilize the circulation offers a
compromise position since most massive pulmonary emboli will dissolve in time. ECLS
can be implemented outside the operating room, but extensive preparations must be
made before ECLS is available for emergency therapy. An emergency team must be
assembled and trained, and needed equipment and supplies must be collected. ECLS
can be implemented within 1530 minutes by an equipped team of trained personnel.
[106 ] Once the circulation is stabilized on ECLS, the patient may be conveniently
transferred to a critical care unit, a diagnostic unit, the operating room, or another
hospital if necessary.
The femoral vein and artery are rapidly cannulated under sterile conditions using local
anesthesia. If the circulation is reasonably stable, both vessels can be cannulated over
guide wires inserted via No. 16 angiographic needle punctures. A small skin incision is
made to accommodate the cannulas, and after giving a bolus of heparin (1 mgm/kg)
first dilatators and then cannulas are inserted. Alternatively, both femoral vessels can be
exposed by surgical cutdown and then cannulated using guide wires under direct vision.
If pulses are absent or weak, a cutdown is usually faster; however, since patients need
heparin and possibly fibrinolytic drugs, a minimal wound is preferred. The tip of the
venous catheter is advanced into the right atrium to obtain flow rates of 2.54 l/min using
an emergency pump-oxygenator circuit primed with crystalloid. [114 ] The perfusion
circuit consists of a small venous reservoir with intravenous access tubes, a centrifugal
pump, and membrane oxygenator (Fig. 45-5) . An arterial filter is not needed; an
electromagnetic flowmeter is usually placed on the arterial line. The extracorporeal
tubing is wrapped with insulation to conserve heat, and heating blankets and ceiling
infrared lights are used to maintain normal temperature. During ECLS, heparin is
infused to maintain activated clotting times between 140 and 160 seconds. Activated
clotting times are measured every 30 minutes initially and every hour thereafter.
Although the groin wound is minimal, some bleeding occurs. [106 ] , [115 ] Usually the
amount of bleeding is small, but it is often persistent. Theoretically, the addition of
thrombolytic drugs accelerates clot lysis and may decrease the duration of ECLS;
however, these drugs are likely to increase bleeding complications and are not needed
once the circulation is stabilized. An alternative is to give low-dose fibrinolytic therapy
directly into the thrombus via a pulmonary arterial catheter. ECLS should not be needed
beyond a few hours or 12 days since clot lysis proceeds rapidly. Once pulmonary
vascular resistance is adequately reduced, femoral cannulation sites should be closed
surgically because of the need for heparin and long-term anticoagulation. ECLS should
be discontinued in the operating room because vessels should be sutured closed
because of the need for heparin and long-term anticoagulation.
Postoperative Care
Postoperative care is not different from care for other patients who require open
cardiac surgery. Cardiac output is maintained by pharmacologic means and is usually
adequate if the patient can be weaned from cardiopulmonary bypass and has not
suffered irreversible myocardial damage. Reperfusion pulmonary edema is not a
problem, but renal failure and ischemic brain damage from preoperative periods of
inadequate circulation may become apparent. Antibiotics are required, particularly if
sterile conditions were compromised in the resuscitation effort.
Results
Survival mortality rates for emergency pulmonary thromboembolectomy vary widely

between 40 and 92 percent. [83 ] , [85 ] , [92 ] , [103 ] , [104 ] , [116 ] , [117 ] Results are
best if cardiopulmonary bypass is used to support the circulation during pulmonary
arteriotomy. [92 ] The eventual outcome largely depends upon the preoperative
circulation of the patient. [83 ] , [85 ] If cardiac arrest occurs and external massage
cannot be stopped without ECLS, mortality ranges between 45 and 75 percent. [83 ] ,
[85 ] , [116 ] Without cardiac arrest mortality ranges between 8 and 36 percent. [83 ] ,
[85 ] , [103 ] , [116 ] ECLS instituted during cardiac resuscitation is associated with
survival rates between 43 and 56 percent. [85 ] , [104 ] Primary causes of death include
brain damage, cardiac failure, and sepsis. [83 ] , [85 ] , [104 ] Recurrent embolism is
uncommon, [85 ] and approximately 80 percent of survivors maintain normal pulmonary
arterial pressures and exercise tolerance. [118 ] In these patients postoperative
angiograms are normal or show less than 10 percent obstructed vessels. A minority of
patients have 4050 percent of pulmonary vessels obstructed and have significantly
reduced exercise tolerance and pulmonary function. [118 ]
CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION
Pathogenesis and Pathology
The strong association between DVT and PE supports the assumption that chronic
thromboembolic pulmonary hypertension (CTEPH) develops when acute PE fail to
resolve [119 ] , [120 ] ; however, studies of known, single, large pulmonary emboli or
repeated thromboembolic events uniformly fail to document progression to CTEPH.
[121 ] , [122 ] The majority of patients with CTEPH present with symptoms of dyspnea
and fatigue, are discovered to have pulmonary hypertension at the time of presentation,
and lack a clear history of either DVT or PE. [119 ] , [121 ] [123 ] Furthermore, it is
estimated that only 0.10.2 percent of patients with clinical PE develop CTEPH. [119 ]
The occult presentation of CTEPH; questions of hypercoagulable and deficient
fibrinolytic states; the role of cytokines and thrombin in endothelial cell expression of
tissue factor [34 ] and platelet adhesion [124 ] ; and the distribution of lesions within the
pulmonary vasculature, while not negating the importance of DVT and PE, strongly
suggest a more complex pathogenesis. Furthermore, a dynamic component of the
disease [125 ] cannot be totally excluded although pulmonary vascular resistance is
generally unresponsive to known vasodilators. [119 ] , [121 ] , [122 ]
Progression of pulmonary hypertension and increased right heart afterload are

secondary to occlusions of the pulmonary vasculature that decrease the cross-sectional
area of the vascular bed and the compliance of central pulmonary vessels. As
pulmonary hypertension progressively develops, damage to the microvascular bed of
the remaining patent portions of the pulmonary circulation ensues. These microvascular
changes are similar to those that occur from most other causes of pulmonary
hypertension. [126 ] Surgical removal of obstructing lesions and reopening occluded
pulmonary vessels preempts development of irreversible changes in the small vessels
of the pulmonary circulation. [123 ]
Occlusion of substantial portions of the pulmonary vascular bed and reduced

compliance of central pulmonary arteries are considered prerequisites for the
development of pulmonary hypertension. Pulmonary vascular compliance is normally
large and can accommodate three to four times the resting cardiac output before
pulmonary arterial pressure doubles. Thrombotic material in various stages of
organization often partially or completely obstructs lobar and segmental and
occasionally main pulmonary arteries. When thrombi are fibrotic, organized, and
endothelialized, they no longer respond to standard anticoagulation or thrombolytic
therapy. [121 ] , [123 ] Sometimes fresh clot attached to occluding, organized thrombus
is also found (Fig. 45-6) , but it is not always clear whether or not the new clot
represents propagation of thrombosis or a new embolus. Occasionally spotty eccentric,
yellowish lesions, suggestive of early atherosclerosis, appear within the thrombotic
material. Microscopically the obstructing thrombotic material shows intimal and medial
fibroplasia with well-organized fibrous tissue, penetrating blood vessels, and concentric
ribbons of elastic fibers. No endothelial cells are visible (Fig. 45-7) . Infarction of lung
tissue rarely occurs unless the ischemic segment also becomes atelectatic. [127 ]
Thrombotic occlusion of the pulmonary microvasculature also occurs. [123 ] , [126 ] ,

[128 ] Lung biopsies show variable medial hypertrophy, but severe eccentric intimal
fibroplasia. Thrombotic material at different stages of organization with eccentric intimal
lesions, fibrous septa, and recanalized passages is recognized and differs from the
concentric microvascular occlusions associated with plexogenic arteriopathy. [123 ] ,
[126 ] The appearance of these thrombotic lesions, which may extend into any number
of higher order branches and involve main and lobar arteries, suggests thrombosis in
situ rather than embolism. [123 ] At operation or autopsy affected vessels seem
covered by a very thin, transparent membrane that may be contiguous with and part of
more bulky material. This membrane often extends as a thin fibrous sleeve far into
segmental vessels. When removed, a shiny, inner wall of the artery remains.
Microscopically this material consists of intimal fibroplasia with one or two strands of
elastic fibers and no endothelial cells (Fig. 45-8) .
Chronic thrombembolic pulmonary hypertension is an uncommon and frequently

under-recognized but treatable cause of pulmonary hypertension. [129 ] , [130 ] There
are no signs or symptoms specific for chronic thromboembolism. The most common
symptom associated with thromboembolic pulmonary hypertension, as with all other
causes of pulmonary hypertension, is exertional dyspnea. [131 ] Like complaints of easy
fatigability, dyspnea that initially occurs only with exertion is often attributed to anxiety or
being out of shape.
Syncope, or presyncope (light-headedness during exertion) is another common

symptom in pulmonary hypertension. Generally, it occurs in patients with more
advanced disease and higher pulmonary arterial pressures.
Anginalike chest pains occur in approximately 50 percent of patients with more severe
pulmonary hypertension; the pain is similar to that typical of left ventricular ischemia and
is generally felt to represent right ventricular ischemia. Hemoptysis can occur in all
forms of pulmonary hypertension and probably results from abnormally dilated vessels
distended by increased intravascular pressures. Peripheral edema, early satiety, and
epigastric or right upper quadrant fullness or discomfort may develop as the right heart
fails (cor pulmonale).
Some patients with chronic pulmonary thromboembolic disease present after a small
acute pulmonary embolus that may produce acute symptoms of right heart failure.
Sometimes hemoptysis occurs. A careful history brings out symptoms of dyspnea on
minimal exertion, easy fatigability, diminishing activities, and episodes of anginalike
pain or light-headedness. Further examination reveals the signs of pulmonary
hypertension.
The physical signs of pulmonary hypertension are the same no matter what the
underlying pathophysiology. [131 ] [133 ] Initially the jugular venous pulse is
characterized by a large A-wave. As the right heart fails, the V-wave becomes
predominant. The right ventricle is usually palpable near the lower left sternal border,
and pulmonary valve closure may be palpable in the second left intercostal space.
Occasional patients with advanced disease are hypoxic and slightly cyanotic. Clubbing
is an uncommon finding.
The second heart sound is often narrowly split and varies normally with respiration; P2
is accentuated. [134 ] A sharp systolic ejection click may be heard over the pulmonary
artery. As the right heart fails, a right atrial gallop usually is present, and tricuspid
insufficiency develops. Because of the large pressure gradient across the tricuspid
valve in pulmonary hypertension, the murmur is high pitched and may not exhibit
respiratory variation. These findings are quite different from those usually observed in
tricuspid valvular disease. A murmur of pulmonic regurgitation also is frequently
detected.
Pulmonary function tests reveal minimal changes in lung volume and ventilation [135 ] ;
patients generally have normal or slightly restricted pulmonary mechanics. Diffusing
capacity (D1CO) is often reduced and may be the only abnormality of pulmonary
function testing. Pulmonary arterial pressures are elevated and in one series averaged
45 mmHg mean with an average pulmonary vascular resistance of 1000 dyne-sec-cm -5
. [135 ] Resting cardiac outputs and pulmonary capillary wedge pressures are in the
normal range, but pulmonary arterial oxygen saturations are reduced. Most patients are
hypoxic; room air arterial oxygen tension ranges between 50 and 83 torr, average 65
torr. [135 ] co 2 tension is slightly reduced and is compensated by reduced bicarbonate.
Dead space ventilation is increased. Ventilation-perfusion studies show moderate
mismatch with some heterogeneity among various respiratory units within the lung and
correlate poorly with the degree of pulmonary obstruction. [135 ]
Diagnosis
To ensure diagnosis in patients with chronic pulmonary thromboembolism, a

standardized evaluation is recommended for all patients who present with unexplained
pulmonary hypertension. [123 ] , [131 ] , [132 ] , [136 ] This workup includes a chest
radiograph, which may show either apparent vessel cutoffs of the lobar or segmental
pulmonary arteries or regions of oligemia suggesting vascular occlusion. Central
pulmonary arteries are enlarged, and the right ventricle may also be enlarged without
enlargement of the left ventricle (Fig. 45-9) . The electrocardiogram demonstrates
findings of right ventricular hypertrophy (right axis deviation, dominant R-wave in V 1 ).
Pulmonary function tests are necessary to exclude obstructive or restrictive intrinsic
pulmonary parenchymal disease as the cause of the hypertension.
The ventilation-perfusion lung scan is the essential test for establishing the diagnosis of
unresolved pulmonary thromboembolism. A normal lung scan excludes the diagnosis of
both acute or chronic, unresolved thromboembolism. The usual lung scan pattern in
most patients with pulmonary hypertension either is relatively normal or shows diffuse
nonuniform perfusion. [120 ] , [129 ] , [130 ] , [137 ] When subsegmental or larger
perfusion defects are noted on the scan, even when matched with ventilatory defects,
pulmonary angiography is appropriate to confirm or rule out thromboembolic disease.
Organized thromboembolic lesions do not appear like intravascular filling defects seen
with acute pulmonary emboli, and experience is essential for proper interpretation of
pulmonary angiograms in patients with unresolved, chronic embolic disease. Organized
thrombi appear as unusual filling defects, webs, or bands, or completely thrombosed
vessels that may resemble congenital absence of the vessel [138 ] (Fig. 45-10) (Table
45-2) . Organized material along a vascular wall of a recanalized vessel produces a
scalloped or serrated lumenal edge. Because of both vessel-wall thickening and
dilatation of proximal vessels, the contrast-filled lumen may appear relatively normal in
diameter. Distal vessels demonstrate the rapid tapering and pruning characteristic of
pulmonary hypertension (Fig. 45-10) .
Although there was once reluctance to perform angiography in patients with pulmonary
hypertension, use of selective and subselective injections with small amounts of contrast
material have significantly reduced the risks of pulmonary angiography. [139 ] Although
some risk remains, the benefit of establishing the presence of a treatable cause of the
hypertension far outweighs the small risk; pulmonary angiography should be performed
whenever there is a possibility that chronic thromboembolism is the etiology of
In recent years computed tomographic scanning (Fig. 45-11) , two-dimensional

echocardiography (Fig. 45-12) , magnetic resonance imaging (Fig. 45-13) , and
ultrafast computed tomographic scanning have all been actively investigated as
noninvasive imaging modalities for diagnosing the presence of organized thrombotic
material in the pulmonary vasculature. [140 ] , [141 ] Pulmonary angioscopy has also
been proposed as a means for confirming the diagnosis and for determining the
proximal extent of the organized clot as an aid in planning surgery. [142 ] Although
computed tomographic scanning may show the presence of proximal clot (Fig. 45-11) ,
it is less sensitive than magnetic resonance imaging (Fig. 45-13) for showing more
peripheral obstructions, vessel wall lesions, and abnormal vessel flow patterns. The
most definitive information and the best for planning operation remain the pulmonary
angiogram.
Medical Management
Standard anticoagulants and thrombolytic agents have not proven successful in treating
these patients; clots are organized and fibrotic and are no longer amenable to
pharmacologic therapy. [119 ] , [121 ] , [123 ] Once the diagnosis is established,
evaluation for surgical thromboendarterectomy should proceed. Placement of an inferior
vena caval filter is advised to prevent recurrent emboli and is recommended in most
patients prior to thromboendarterectomy. Operation relieves the vascular obstructions,
increases pulmonary blood flow, improves the distribution of blood flow, and reduces
pulmonary arterial pressure and right heart sequelae.
Natural History
The natural history of chronic thromboembolic pulmonary hypertension is dismal, and

nearly all patients die of progressive right heart failure. [122 ] Because of insidious
onset the diagnosis is usually made relatively late in the progression of the disease
when dyspnea and/or early symptoms of right heart failure develop and pulmonary
hypertension is severe (> 40 mmHg mean). In Riedel's series of 13 patients 9 died a
mean of 2.8 years after diagnosis of right heart failure. [122 ] Seven of the 13 had
recurrent episodes of fresh emboli demonstrated by new perfusion defects or by
autopsy. In Sutton's series of 8 patients 4 died, 3 of right heart failure and one after
surgery. [121 ] The severity of pulmonary hypertension at the time of diagnosis inversely
correlates with duration of survival. [121 ] , [122 ]
Pulmonary Thrombendarterectomy
Although there were previous attempts, the first successful pulmonary

thromboendarterectomy was done by Allison [143 ] through a sternotomy using surface
hypothermia. Only fresh clots were removed; operation was 12 days after a thigh injury
that led to PE. In 1978 Cabrol reported a series of 16 patients with six deaths; 14
patients were operated through a lateral thoracotomy and two through a median
sternotomy with cardiopulmonary bypass. [144 ] Cabrol condemned sternotomy (both
patients died), but others revived the operation with reports of 12 successful cases
using cardiopulmonary bypass in 14 patients. [145 ] , [146 ] This operation, using deep
hypothermia and intermittent circulatory arrest, became the standard procedure
thereafter. [147 ]
INDICATIONS
Patients should be considered for thromboendarterectomy when they are found to have
chronic thromboembolic disease with functional consequences. Since there is
significant reserve in the pulmonary vascular bed, [148 ] the presence of an unresolving
embolus per se does not indicate the need for surgical intervention. We consider
surgery for those patients with evidence of unresolved thromboemboli (unchanging
ventilation-perfusion lung scans over 8 to 12 weeks with adequate anticoagulation) who
have functional limitations and evidence of compromise of the pulmonary vascular bed
who are in either New York Heart Association Functional Class III or IV. Patients must
not have significant comorbid conditions that cannot be addressed at operation.
Comorbid conditions usually add operative risk, but the increased risk is sometimes
justified because of patient insistence and the potential for benefit. Resting mean
pulmonary arterial pressure should be greater than 30 mmHg or resting pulmonary
vascular resistance more than 300 dynes-sec-cm [6 ] , [119 ] Rarely a patient with
predominantly unilateral disease is considered for surgery because of respiratory
symptoms and elevated dead-space ventilation (VD/VT) in the absence of significant
hemodynamic effects.
In all cases, our absolute prerequisite for considering a patient for surgery is the
documentation by any of the techniques detailed earlier that the proximal extent of the
organized thrombotic material is at least at the level of the lobar pulmonary arteries so
that a plane of dissection can be established and the obstructing thrombotic material
can be removed.
OPERATION
Median sternotomy
Under lorazepam sedation catheters are placed in a radial artery, jugular vein, and
antecubital space for venous access. The jugular Swan-Ganz catheter is advanced into
the proximal pulmonary artery for monitoring during induction and later before stopping
cardiopulmonary bypass. It is then withdrawn into the right ventricle. The
electrocardiogram and both nasopharyngeal and bladder or rectal temperature are
monitored. Transesophageal echocardiography is useful for the diagnosis of patent
foramen ovale and for assessment of right ventricular function following operation.
Anesthesia is induced with midazolam and maintained with isofluorane. Other
medications include epsilon aminocaproic acid (57.5 gm load; 1 gm/h infusion),
ce-fazolin (1 gm), and vancomycin (1 gm). Prostaglandin E1 (up to 1 ug/min) may be
helpful during induction if cor pulmonale is present. If so, phenylephrine or
norepinephrine may be needed to sustain systemic blood pressure. The patient is
intubated with a cuffed endotracheal tube and positioned supine. The chest and both
groins and thighs are prepped into the sterile field.
The operation is done with deep hypothermia and circulatory arrest, but a choice must
be made regarding protection of the brain during periods of circulatory arrest. Until
recently the brain was protected by alternating 10-to-20-minute periods of hypothermic
circulatory arrest with equal periods of systemic perfusion. [149 ] , [150 ] More recently
retrograde cerebroplegia has been used for up to one hour of continuous circulatory
arrest and repeated for up to 30 minutes after 15 minutes of systemic perfusion. [151 ]
[153 ]
The chest is entered through a midline sternotomy; the edges are spread widely to
facilitate exposure of lobar pulmonary arteries. If hypothermic circulatory arrest is
planned, the aorta, coronary sinus, and right atrium are cannulated after heparin (3
mgm/kg). A two-stage cannula is used. With the activated clotting time over 400
seconds, cardiopulmonary bypass is started, and the patient is cooled for at least 30
minutes to a nasopharyngeal temperature of 15°C. The pericardial attachments of the
superior cava and right pulmonary veins and arteries are divided and dissected back;
the right pulmonary artery is dissected free 12 cm beyond the origin of the upper lobar
branch. The superior cava and aorta are dissected completely off the right main
pulmonary artery and encircled with umbilical tape to facilitate retraction (Fig. 45-14) .
Before the heart arrests, a catheter is inserted into the right superior pulmonary vein-1
left atrial junction to vent the left heart; the aorta is clamped, and the heart is arrested
with cold blood retrograde cardioplegia. Myocardial temperature is monitored, and the
flaccid heart is kept between 10 and 15°C with intermittent cardioplegia every 30
minutes.
The left pulmonary artery is dissected out, and its pericardial attachments and the
superior attachments of the left superior pulmonary vein are divided (Fig. 45-15) . The
ligamentum arteriosum is not divided, but the upper lobar branch and main left
pulmonary artery to the lingular branches are separated from the pericardium, pleura,
and overlying phrenic nerve. The pleural space is not entered. The main pulmonary
artery is separated from the aorta sufficiently to place a large bulldog clamp just above
the pulmonary valve during circulatory arrest.
After reaching 15°C, the circulation is arrested, and venous blood is drained into the
bypass circuit. The venous line is clamped by the perfusionist, but the arterial line is not
in order to minimize aortic pressure and bronchial blood flow without introducing air.
The main and left pulmonary arteries are opened beyond the bulldog clamp to a point
between the upper and lingular branches. The right main pulmonary arterial incision
begins at its origin from the main and extends past the upper and middle lobar
branches to a point just proximal to the lower lobar branches of the dissected artery.
The dissection of the fibro-thrombotic sleeve usually begins in the main or right main
pulmonary artery at a spot where a thin membranous layer with or without some
yellowish, atherosclerotic discoloration is seen. Using a periosteal elevator, this
membrane is separated from the arterial wall usually at the arteriotomy incision but
sometimes where a fine edge is visible (Fig. 45-16) . It is imperative that the proper
plane in the inner media is established; the underlying wall is shiny and light gray in
color and will strip very easily if the wrong plane in the outer media is entered.
Endothelium and intima are very delicate and are removed with the fibrous sleeve, but a
deeper plane into the media risks leaving only adventitia and exposed tissue factor,
which is thrombogenic. Once the proper plane between inner media and fibrous sleeve
is found, the friable and easily torn sleeve is separated by gently pushing the arterial
wall away from the sleeve. The separation usually proceeds fairly quickly and easily if
the sleeve remains intact. The sleeve often thickens in places, and there may be
deposits of recent or old thrombus layered on top. The dissection proceeds
circumferentially and into the upper lobar artery. Depending upon the mass of the
specimen, portions may be removed to improve exposure as the dissection proceeds.
Within lobar branches the specimen is firmly held as the walls of the lobar and
segmental branches are gently teased away. In the process smaller vessels are partially
turned inside out. Eventually the fibrous sleeve becomes so thin that it breaks away
cleanly leaving the branch vessel completely clean and fully patent. This process
continues until all of the lobar and segmental arteries and even some tertiary branches
are opened (Fig. 45-17) . The fibro-thrombotic sleeve is removed from the left lung and
distal main pulmonary artery in a similar manner.
Exposure is facilitated by using a pediatric Yankauer sucker tip for aspirating passive
bronchial blood flow and run-down and long firm gripping forceps. After every 1020
minutes the dissection is interrupted by restarting cardiopulmonary bypass after first
carefully checking for air in the arterial line and catheter. Usually three to five periods of
circulatory arrest or a total of 4060 minutes are needed to clear both lungs. It is usually
not necessary to inspect lobar arteries for residual material with a pediatric
bronchoscope since all of the material that can be reached is removed.
If the intima tears or if the wrong plane is entered, the reddish brown adventitial layer is
visible. A 7-0 prolene suture is used to reapproximate the media edges to prevent
extravasation of blood into the lung parenchyma.
The arteriotomy of the first dissected lung may be closed during the alternate periods of
perfusion using the cardiotomy suction system to expose the vessel walls. A 5-0 prolene
suture is used as a doubled running suture. The arteriotomies in the second lung are
closed after rewarming begins.
Rewarming takes about 1 to 1.5 hours. The aortic cross clamp is removed, and the
cardioplegic catheter is removed. The heart is kept decompressed until coordinated
contractions are maintained. Temporary atrial and ventricular pacing wires are placed;
suture lines are carefully inspected for bleeding; obvious bleeding points are stopped.
The lungs are gently inflated once the heart begins to beat. An infusion of PGE 1 is
started at 0.51.0 ug/min. This infusion is continued without interruption for the first 4896
hours after operation. When rewarming is complete (bladder temperature 34°C;
nasopharyngeal > 36.5°C), cardiopulmonary bypass is stopped. Dobutamine is used
for inotropic support if needed. The pulmonary artery pressures off bypass usually are
still elevated, but approximately half of prebypass values and cardiac output is
significantly increased.
If the alternative method of retrograde cerebroplegia is used, work need not be

interrupted unless longer than 1 hour is needed to clear all of the segmental arteries.
The right atrium is cannulated with a separate superior vena cava catheter and a
two-stage catheter extending into the inferior vena cava. The perfusion setup is
reconfigured in the surgical field (Fig. 45-18) . A spur off the arterial line is constructed
to the catheter in the superior vena cava. A purse string suture is placed in the
ascending aorta downstream to the planned site of the aortic clamp for a second
suction catheter to decompress the aorta during retrograde brain perfusion. During
systemic perfusion the spur between the arterial line and superior caval catheter is
clamped; during cerebroplegia both the arterial line downstream to the spur connection
and the superior caval line upstream to the spur are clamped. The aortic venting
catheter is advanced into the proximal descending thoracic aorta to keep the aorta
decompressed during cerebroplegia and to reduce bronchial arterial flow. The brain is
perfused at 15°C and 25 mmHg pressure; this generally amounts to about 200 ml/min.
The advantages of this method are that it allows uninterrupted work and may provide
superior protection of the brain. [146 ] [148 ] After 60 minutes, if the dissection is not
complete, systemic perfusion is resumed for 15 minutes to prevent ischemic damage of
the spinal cord and other organs before resuming a second period of circulatory arrest.
After rewarming, bypass is discontinued in the usual manner. Attention is paid to the
ratio of pulmonary and systemic arterial pressures, to cardiac output, and to arterial
oxygen tension. Right heart failure is usually not a problem if the myocardium has been
adequately protected. In difficult cases transesophageal echocardiography may be
useful to assess right ventricular volume and contractility and left ventricular filling. PGE
1 is invaluable for reducing pulmonary arterial vasoconstriction, and inhalation of 2040
parts/million of nitric oxide may also be helpful in avoiding pulmonary arterial
vasoconstriction. [154 ] The arterial Pa co 2 is kept below 35 mmHg. After cannulas are
removed, protamine is given, and the chest is closed over two mediastinal drainage
tubes.
Lateral thoracotomy
The first operations were performed through lateral thoracotomy incisions without
cardiopulmonary bypass. [92 ] , [141 ] , [144 ] , [155 ] This approach has largely been
abandoned because the use of cardiopulmonary bypass permits simultaneous
treatment of both lungs, simultaneous closure of atrial septal defects, myocardial
revascularization, and other procedures and generally is less painful. Unilateral
thoracotomy occasionally is used for predominantly unilateral disease but is not
recommended except for extraordinary circumstances.
POSTOPERATIVE CARE
The electrocardiogram, systemic and pulmonary arterial pressures and central venous
pressure, temperature, urine output, arterial oxygen saturation, chest tube drainage, and
fluid balance are monitored. A pulse oximeter is used to continuously monitor peripheral
oxygen saturation. Management of cardiac arrhythmias and output and treatment of
wound bleeding are identical to other open heart operations. Patients are mechanically
ventilated at inspired oxygen tensions sufficient to maintain arterial oxygen saturations
over 95 torr and carbon dioxide tensions below 35 torr. Early after operation 80100
percent inspired oxygen tensions are often needed, and in addition 510 cm of positive
end-expiratory pressure are used to improve the distribution of ventilation and to
attenuate reperfusion pulmonary edema. The chest x-ray usually shows increased hilar
markings and prominent central pulmonary vessels. The lowest pulmonary end diastolic
pressure needed to maintain adequate cardiac output is preferred.
PGE 1 is infused at 0.51.0 ug/min continuously; systemic arterial blood pressure is

increased, if necessary, by phenylephrine. Dobutamine, dopamine in low doses, and
amrinone or milrinone are used to increase myocardial contractility if needed to achieve
a diuresis. Hemoglobin is maintained at 10 gm or above.
Some patients may be extubated the following morning after meeting usual criteria.
Most require more time, and some require 1 or 2 weeks of mechanical ventilation and
positive end-expiratory pressure (PEEP) for hypoxemia and/ or hypercarbia from right
to left shunting and reduced pulmonary compliance. Diuretics are used to reduce
interstitial edema to improve both the shunt and compliance. Efforts are made to
prevent pneumonia by positioning, antibiotics, and chest physical therapy; chest x-rays,
cultures, and gram stains are taken as indicated for surveillance. Antibiotics, often a
cephalosporin and vancomycin beginning just before operation, are continued three
days afterwards or as long as the patient remains intubated. With prolonged intubations
periodic surveillance cultures and grams stains are obtained every three days or with
clinical indications of infection and antibiotics are changed. The patient is extubated as
soon as the usual criteria for extubation are met. Supplemental oxygen is continued until
the patient is able to maintain peripheral oxygen saturations > 90 percent.
Heparin is restarted as soon as wound bleeding has stopped. Partial thromboplastin

times are maintained initially between 50 and 60 seconds. When extubated, coumadin
is started with low-dose (80 mgm) aspirin every other day; heparin is stopped when the
prothrombin time reaches an INR of 2.53.5 units. Compression stockings are used until
the patient is ambulatory. [156 ] The patient is discharged when peripheral oxygen
saturation is 90 percent or greater on room air or appropriate supplemental oxygen,
blood is anticoagulated with coumadin, the patient is ambulatory and self-sufficient for
personal care, and all operative and postoperative complications are controlled or
resolved.
COMPLICATIONS
Patients are subject to all complications associated with open heart and major lung
surgery (arrhythmias, atelectasis, wound infection, pneumonia, mediastinal bleeding,
etc.) but also may develop complications specific to this operation. These include
reperfusion pulmonary edema, malignant pulmonary hypertension, hemorrhagic lung,
and neurologic disorders related to deep hypothermia and cerebral ischemia.
Reperfusion pulmonary edema may appear immediately after operation or 2 or 3 days

later. [145 ] Pulmonary secretions become proteinaceous and even blood tinged; chest
films show increased interstitial markings; pulmonary compliance decreases. Infiltrates
are often patchy and, although Moser and colleagues report otherwise, [18 ] , [119 ] in
our experience bear only remote relationships to areas of recently unblocked pulmonary
arteries. Reperfusion pulmonary edema increases the physiologic shunt (often over 30
percent), increases the need for high inspired oxygen tensions, and decreases
pulmonary compliance. The process also reduces alveolar surfactant in affected areas,
enhances atelectasis and pneumonia, and increases the work of breathing. Invariably
extubation must be postponed until the process resolves spontaneously and shunt
fraction and pulmonary compliance return to more acceptable levels. The process is
similar to acute respiratory distress syndrome (ARDS) and is best treated by
aggressive diuresis, ventilatory support with PEEP, prophylaxis against infection, and
time. Hemorrhagic lung (which we have not encountered) may be a severe
manifestation of reperfusion edema or possibly owing to extravasation of blood into the
perivascular parenchyma of some pulmonary segments.
Malignant pulmonary arterial constriction is a devastating complication that is largely

controlled by the prophylactic administration of PGE 1 (suggested by Dr. K.M. Moser).
Typically patients have pulmonary arterial pressures that are 5060 percent of systemic
following cardiopulmonary bypass in the operating room and increased cardiac outputs
as compared to prebypass. However, over the ensuing several days pulmonary arterial
pressure and pulmonary vascular resistance progressively increase despite
nitroglycerine, hypocarbia, anticholinesterase inhibitors, dobutamine, isoproterenol, and
even PGE 1 . These patients may eventually develop severe right heart failure and low
cardiac output without any relaxation of the pulmonary arterial constriction. Autopsy
does not show residual thrombi or new clots.
The mechanism of malignant pulmonary hypertension is unknown but may be related to

vasoconstriction of the uninvolved pulmonary arteries first noted by Utley and colleagues
on postoperative ventilation-perfusion scans. [146 ] Moser and colleagues term this
phenomenon vascular steal owing to overperfusion of newly opened pulmonary vessels.
[157 ] PGE 1 prophylaxis seems to prevent malignant pulmonary arterial constriction,
and it is possible that the process may respond to adenosine (we have no experience).
However, recently we observed that inhaled nitric oxide (2040 parts/million) reduces
postoperative pulmonary arterial pressures and simultaneously increases arterial
oxygen tension in some but not all patients. In view of our experience with malignant
pulmonary vasoconstriction (see the following), the benefits of prophylactic infusion of
PGE 1 and newer knowledge of potent endothelial cell vasoconstrictors, we suspect that
vasoconstriction of uninvolved pulmonary arteries is the primary cause of blood flow
redistribution to previously occluded vessels.
Transient neurologic abnormalities are associated with the duration of hypothermic

circulatory arrest [150 ] , [158 ] and with careful postoperative neurologic examination
occur in the majority of patients. Symptoms of cognitive and psycho-motor behavior
peak 23 days after operation and usually disappear by the time of discharge.
Exceptional patients recover fully after several weeks. Permanent neurologic deficits
are related to longer circulatory arrest times (> 60 minutes) and are more common in
older patients. [159 ] Although not proven, transient neurologic abnormalities appear to
be less common when retrograde cerebroplegia is used.
RESULTS
Operative (30 day or death before discharge) mortality ranges between 5.4 and 27
percent but is primarily related to date of operation (before 1990) and experience of the
operating surgeon. Prior to 1990 operative mortality ranged from 12.6 to 37.5 percent,
[144 ] , [149 ] , [155 ] , [160 ] [163 ] but more recent experience and better patient
selection has reduced operative mortality to 5.420 percent. [150 ] , [160 ] , [163 ] Our
operative mortality in 34 patients since 1985 is 17.6 percent, but none of 10
consecutive patients treated in the past 2 years with prophylactic PGE 1 has died. Of
the 6 patients who died, 4 had malignant pulmonary hypertension that progressed after
satisfactory postoperative reductions in pulmonary arterial pressures and increases in
cardiac output despite intense efforts, including extracorporeal perfusion, to relieve the
vasoconstriction. One patient died of bleeding; the sixth had both malignant pulmonary
hypertension and infection. Fedullo et al. report that unrelieved pulmonary hypertension
caused half of the 12 deaths in 222 patients in their series. Other causes of death were
intraoperative cardiac arrest, aortic dissection, cerebral vascular accident, and
bleeding, with one death from reperfusion pulmonary edema. [150 ]
Risk factors for operative death include preoperative pulmonary vascular resistance
greater than 1100 dyne-sec-cm-5 [161 ] , [162 ] and postoperative ventilator
dependency (> 5 days) that was partially related to prolonged cardiopulmonary bypass,
presence of ascites, and need for four or more blood transfusions. [162 ]
Patients are anticoagulated with coumadin and low-dose aspirin (80 mgm every other
day) for life. The target prothrombin time is an INR of 2.83.5. Patients are discharged
when arterial oxygen saturation is 90 percent or above on room air, but some patients
need supplemental oxygen for a few weeks for activity. Improvement in right ventricular
pressures and volumes occurs early [164 ] (Fig. 45-19) ; pulmonary arterial pressures
usually decrease to 5060 percent of preoperative values to normal or slightly higher than
normal. [164 ] , [165 ] In a series of 128 patients Fedullo reports that mean preoperative
pulmonary arterial pressure decreased from 46 to 28 mmHg; that pulmonary vascular
resistance decreased from 901 to 261 dyne-sec-cm-5 and that cardiac output increased
from 3.7 to 5.7 l/min. [150 ] Tricuspid regurgitation improves or disappears. [165 ]
Pulmonary capillary wedge pressure does not change; however, there is considerable
improvement in left ventricular diastolic function with increased diastolic and stroke
volume. [165 ]
LATE FOLLOWUP
One year following operation 76 percent of patients are in Class I (New York Heart
Association), and another 20 percent are in Class II. The remainder are in Class III. [166
] All signs of severe right heart failure resolve, and even severe stasis changes of the
legs improve dramatically. Hypoxemia, which sometimes persists in the immediate
postoperative period, progressively improves in the first few months after operation and
eventually disappears. [166 ] , [167 ] Ventilation-perfusion lung scans are well matched
and are normal or show only small areas of inequality. Repeat angiograms appear
normal or show minimal distal obstructions in occasional segmental arteries. Cardiac
catheterization studies indicate that the reduction in pulmonary vascular resistance and
increase in cardiac output present at the time of discharge are maintained. Recurrent
pulmonary embolism or thrombosis is rare and related to lapses in coumadin
anticoagulation. [166 ] However, in occasional patients the recovery of right heart
function and functional capacity appears to relate to the extent to which the secondary
microvascular changes in the previously unoccluded pulmonary vascular bed regress
after operation.
Primary cardiac neoplasms have been described in medical writings since the 16th
century. [6 ] A left atrial myxoma was described in 1845. [7 ] In 1931 Yater reported nine
cases of primary cardiac tumors and established a classification system that is similar
to that used today. [8 ] The first antemortem diagnosis of a cardiac tumor, a sarcoma,
was accomplished in 1934 using the electrocardiogram and a lymph node biopsy. [9 ]
The first echocardiographic diagnosis of an intracardiac primary tumor was made in
1959. [10 ]
In 1934 Beck partially excised an intrapericardial teratoma. [11 ] Bahnson, in 1952,

removed a right atrial myxoma using bicaval inflow occlusion, but the patient died shortly
after surgery. [12 ] Using cardiopulmonary bypass, Crafoord, in 1954, successfully
excised a left atrial myxoma, and in 1959 Kay removed a left ventricular myxoma. [13 ] ,
[14 ] By 1964 only 60 atrial myxomas had been removed successfully, but increasing
numbers were diagnosed in life using angiocardiography, and later, echocardiography.
[15 ]
CLASSIFICATION
Cardiac tumors are classified into primary benign or malignant tumors that arise from
the heart or into secondary, metastatic tumors that invade the heart. Secondary tumors
are 20 times more common than primary cardiac lesions. [2 ] , [4 ] , [5 ] , [15 ] Of 444
primary tumors examined at the Armed Forces Institute of Pathology, 72 percent were
benign, and 28 percent were malignant. Myxoma is the most common benign cardiac
tumor in adults by far; angiosarcoma and rhabdomyosarcoma are the most common
primary malignant lesions. [2 ]
PRIMARY BENIGN TUMORS
Myxoma
INCIDENCE
Myxoma comprises 50 percent of all benign cardiac tumors in adults but only 15 percent
of such tumors in children. Occurrence during infancy is rare. The vast majority of
myxomas occur sporadically and tend to be more common in women than in men. [4 ]
The peak incidence is between the third and sixth decades of life, and 94 percent of the
tumors are solitary. [17 ] Approximately 75 percent occur in the left atrium. The
chromosomal pattern of deoxyribonucleic acid (DNA) of sporadic myxomas is normal in
80 percent of patients. [18 ] These tumors are unlikely to be associated with other
abnormal conditions and have a low reccurrence rate. [4 ] , [17 ]
About 5 percent of myxoma patients show a familial pattern of tumor development

based on autosomal dominant inheritance. [20 ] , [21 ] These patients and 20 percent of
those with sporadic myxoma have an abnormal (deoxyribonucleic acid tetraploid)
chromosomal pattern. [18 ] In contrast to the typical sporadic myxoma profile of a
middle-aged, frequently female patient with a single left-atrial myxoma, familial myxoma
patients are more likely to be younger, equally likely to be male or female, and more
often (22 percent) have multicentric tumors originating from either atrium or ventricle. [16
] , [19 ] , [22 ] [25 ] Although familial myxomas have the same histology as sporadic
tumors, familial myxoma has a higher recurrence rate after surgical resection (2167
percent). [19 ] , [26 ] , [27 ] Approximately 20 percent of familial patients have
associated conditions, such as adrenocortical nodular dysplasia, Sertoli cell tumors of
the testes, pituitary tumors, multiple myxoid breast fibroadenomas, cutaneous
myxomas, and facial or labial pigmented spots. [17 ] These patients often are
described as complex myxomas within the group of familial myxoma. [18 ]
PATHOLOGY
Myxomas occur in any chamber of the heart but have a special predilection for the left
atrium, from which approximately 75 percent originate. The next most frequent site is
the right atrium, where 1520 percent are found; 68 percent are equally distributed
between the left and right ventricles. [2 ] Both biatrial and multicentric tumors are more
common in the familial disease. Biatrial tumors probably arise from bidirectional growth
of a tumor originating from within the atrial septum. [28 ] Atrial myxomas generally arise
from the interatrial septum at the border of the fossa ovalis but can originate anywhere
within the atrium including the appendage [4 ] ( Figs. 46-1 and 46-2 ). In addition,
isolated reports confirm that myxomas arise from the cardiac valves, pulmonary artery
and vein, and vena cava. [20 ] , [21 ] , [29 ] , [30 ] Right atrial myxomas are more likely to
have broad-based attachments than left atrial tumors and also are more likely to be
calcified [22 ] , [23 ] and, if so, are visible on chest radiographs ( Fig. 46-3 ). Ventricular
myxomas occur more often in women and children and may be multicentric. [2 ] , [31 ]
Right ventricular tumors typically arise from the free wall, and left ventricular tumors tend
to originate in proximity to the posterior papillary muscle.
Grossly, myxomas are round or oval tumors with a smooth or slightly lobulated surface.
Most are polypoid, relatively compact, pedunculated, mobile, and not likely to fragment
spontaneously. [2 ] , [4 ] Mobility depends on the length of the stalk, extent of attachment
to the heart, and amount of collagen in the tumor. [4 ] Most tumors are pedunculated with
a short, broad base and, although sessile forms occur, they are unusual. [2 ] , [32 ]
Less-common villous or papillary myxomas are gelatinous and fragile and are prone to
fragmentation and embolization. [33 ] Myxomas are white, yellowish, or brownish in
color and frequently covered with thrombus. [2 ] Focal areas of hemorrhage, cyst
formation, or necrosis may be seen on cut section. The average size is about 5 cm in
diameter, but growth to 15 cm in diameter and larger has been reported. [4 ] Growth
rates vary, but most tumors appear to grow rapidly, although a few seem to stop
growing. [4 ] Weights range from 8 to 175 grams, with a mean between 50 and 60
grams. [34 ]
Histologically, myxomas are composed of polygonal-shaped cells and capillary

channels within an acid mucopolysaccharide matrix (Fig. 46-4) . [4 ] The cells appear
singly or in small clusters throughout the matrix. Mitosis is rare. [35 ] The matrix also
contains a smattering of smooth muscle cells, reticulocytes, collagen, elastin fibers, and
a few blood cells. Cysts, areas of hemorrhage, and foci of extramedullary hematopoesis
are present throughout the matrix. [33 ] , [36 ] , [37 ] Ten percent of tumors have
microscopic deposits of calcium and metastatic bone deposits [37 ] and sometimes
glandularlike structures. [33 ] The base of the tumor contains large arteries and veins
that connect with the subendocardium but do not extend deeply beyond the
subendocardium. [37 ] Myxomas tend to grow into the overlying cardiac cavity rather
than into the surrounding myocardium. The tumor surface is covered by a monolayer of
polygonal cells with interspersed primitive blood vessels.
Myxomas arise from the endocardium and are considered a derivative of the
subendocardial multipotential mesenchymal cell, [38 ] , [39 ] although origin from
endocardial nervous tissue also has been suggested. [40 ] The multipotential
mesenchymal cells are thought to be embryonic cells left behind during septation of the
heart and are capable of differentiating into endothelial cells, smooth muscle cells,
angioblasts, fibroblasts, myoblasts, and cartilage. This accounts for the occasional
presence of hematopoietic tissue and bone in these tumors. There is no evidence that
these tumors are of thrombotic origin as was formerly speculated. [41 ]
Interestingly, myxomas have developed after cardiac trauma, including atrial septal
defect closure and transseptal puncture for percutaneous dilation of the mitral valve. [42
] , [43 ] We recently excised a left ventricular myxoma that was detected by
echocardiography 3 months after aortic valve replacement. We speculate that it was
induced by trauma from a left ventricular venting catheter.
PRESENTATION
The major consequences of a cardiac myxoma are the development of constitutional

symptoms, the obstruction of blood flow through the heart, cardiac arrhythmia, systemic
embolization, and rarely, infection. Symptoms that develop as a result of all but the first
of these implicate the heart as the source of illness and often lead to an
echocardiogram, which is diagnostic.
Constitutional symptoms
Nearly all myxoma patients, on careful questioning, admit to a variety of constitutional
symptoms that may include weight loss, fever, and lethargy. These complaints may be
accompanied by laboratory abnormalities, including leukocytosis, elevated erythrocyte
sedimentation rate, hemolytic anemia, thrombocytopenia, and elevated C-reactive
protein. Immunoelectrophoresis may reveal abnormal immunoglobulin levels with
increased circulating IgG levels. [44 ] These symptoms often suggest an inflammatory or
autoimmune disease and are unrelated to the location and size of the tumor. [4 ]
The recent discovery of elevated levels of interleukin-6 in patients with myxoma [31 ] ,
[45 ] , [46 ] has been linked to a variety of associated conditions, including
lymphadenopathy, tumor metastases, ventricular hypertrophy, and the development of
constitutional symptoms. [31 ] , [45 ] , [49 ] Other less frequent complaints include
Raynaud's phenomenon, arthralgias, myalgias, erythematous rash, and clubbing of the
digits. [4 ] , [50 ] , [51 ]
Possible etiologies for such varied complaints and symptoms include tumor
embolization with secondary myalgias and arthralgias and an elevated immunoglobulin
response. [52 ] Circulating antibody-tumor antigen complexes with complement
activation also may play a role in the constitutional symptom complex. [53 ] More
important, such symptom complexes tend to resolve following surgical resection of the
tumor. [36 ] , [54 ] , [55 ]
Obstruction
Obstruction to blood flow through the heart is the most common cause for acute
presenting symptoms. The nature of these symptoms is determined by which of the
chambers is involved and by the size of the tumor.
Left atrial myxomas tend to mimic mitral valve disease. They produce dyspnea, which
may be positional, [56 ] and other signs and symptoms of heart failure associated with
elevated left atrial and pulmonary venous pressure. Clinically, mitral stenosis is often
suspected and leads to echocardiography and the diagnosis of myxoma. On occasion,
large myxomas may interfere with mitral leaflet closure and produce mitral regurgitation,
but this is uncommon. [4 ] Syncopal episodes occur in some patients and are thought to
result from temporary occlusion of the mitral orifice. [23 ] , [56 ] [58 ]
Right atrial myxomas can produce a clinical picture of right heart failure with signs of
systemic venous hypertension including hepatomegaly, ascites, and dependent edema.
The tumor simulates tricuspid valvular stenosis by partially obstructing the valve orifice.
[23 ] , [56 ] , [57 ] If a patent foramen ovale is present, right-to-left atrial shunting may
occur with central cyanosis; paradoxical embolism also has been reported. [57 ] , [59 ] ,
[60 ] Tricuspid regurgitation is less common and occurs because of leaflet or chordal
damage or failure of leaflet opposition.
Large ventricular myxomas may mimic outflow obstruction. Left ventricular myxomas
can produce the equivalent of subaortic or aortic valvular stenosis, [61 ] , [62 ] whereas
right ventricular myxomas can simulate right ventricular outflow tract or pulmonic valvular
obstruction.
Embolization
Systemic embolization is the second most common mode of presentation for patients
with myxoma and occurs in 3040 percent of patients. [2 ] , [4 ] , [23 ] , [56 ] , [57 ]
Because the majority of myxomas are left-sided, approximately 50 percent of embolic
episodes affect the central nervous system, owing to both intracranial and extracranial
vascular obstruction. The neurologic deficits following embolization range from transient
to permanent, but a high proportion do not resolve. [63 ] Specific central nervous system
consequences include intracranial aneurysms, seizures and hemiparesis, and brain
necrosis. [64 ] [67 ] Retinal artery embolization with visual loss has occurred in some
patients. [68 ] , [69 ]
Embolic material from cardiac myxoma has been found in the iliac and femoral vessels,
causing acute lower extremity ischemia. [70 ] [72 ] Other sites of tumor embolization
include the abdominal viscera and the renal and coronary arteries. [73 ] Histologic
examination of surgically removed peripheral myxomatous emboli establishes the
diagnosis of an otherwise unsuspected tumor. [23 ] , [56 ] , [57 ]
Right-sided myxomatous emboli usually do not cause clinical manifestations but do

obstruct pulmonary arteries and cause pulmonary hypertension and even death from
acute obstruction. [4 ] , [60 ]
Infection
Infection arising in a myxoma is a rare complication and produces a clinical picture of

infectious endocarditis. [74 ] [78 ] A variety of bacterial pathogens has been isolated [79
] as well as fungus forms. [80 ] Infection increases the likelihood of systemic
embolization. [4 ] An infected myxoma warrants urgent surgical resection.
CLINICAL EXAMINATION
Auscultation
Findings at the time of clinical assessment of patients with cardiac myxoma vary
according to the size, location, and mobility of the tumor. Left atrial myxomas may
produce auscultatory findings similar to mitral stenosis just as these tumors may mimic
the symptoms of mitral disease. The well-described tumor plop is an early diastolic
sound, frequently heard and confused with a third heart sound. The diastolic tumor plop
occurs just after the opening snap of the mitral valve and is believed to be secondary to
contact between the tumor and the endocardial wall. [81 ] , [82 ] Of note, the murmur of
cardiac myxoma may be dependent on position, and this may aid in the auscultatory
diagnosis. Left atrial myxomas that cause partial obstruction of left ventricular filling may
result in elevation of pulmonary vascular pressures with augmentation of the pulmonary
component of the second heart sound. [83 ]
Right atrial myxomas may produce the same auscultatory findings as left atrial
myxomas with the exception that they are best heard along the lower right sternal border
rather than the cardiac apex. These include both systolic and diastolic murmurs and a
tumor plop. In addition, right atrial hypertension can produce a large A wave in the
jugular venous pulse and, when severe, can mimic superior vena caval obstruction.
Similarly, elevated right atrial pressure can lead to right-to-left shunting across a patent
foramen ovale. This may produce polycythemia, cyanosis, and clubbing of the digits.
Lower body manifestations of venous hypertension are hepatomegaly, ascites, and
peripheral edema.
Chest radiograph and electrocardiogram
The findings on chest roentgenogram, although nonspecific, may include generalized

cardiomegaly, individual cardiac chamber enlargement, and pulmonary venous
congestion. A more specific occasional finding is a density within the cardiac silhouette
caused by calcification within the tumor (Fig. 46-3) . This finding occurs more often with
right-sided atrial myxomas. [4 ]
Electrocardiographic findings similarly are nonspecific. Abnormalities reflecting

chamber enlargement, cardiomegaly, or bundle branch block and axis deviation are all
seen. [84 ] Fewer than 20 percent of patients have atrial fibrillation. [25 ] Evaluation of
nonspecific electrocardiographic abnormalities occasionally leads to an incidental
diagnosis of myxoma.
Echocardiography
Cross-sectional echocardiography is the most useful test employed for the diagnosis
and evaluation of myxomas. The sensitivity of 2-D echocardiography for myxoma is 100
percent, and this imaging technique has largely supplanted angiocardiography. [85 ]
However, coronary angiography usually is prescribed in patients over 40 years old to
rule out asymptomatic coronary arterial disease in a patient who has another indication
for cardiac surgery. A transthoracic echocardiogram usually provides all the information
necessary for surgical resection, but transesophageal echocardiography provides the
best information concerning tumor size, location, mobility, and attachment. [86 ] , [87 ]
Transesophageal echocardiograms detect tumors as small as 13 mm in diameter. [88 ]
Our practice is to obtain a transesophageal echocardiogram in the operating room
before commencing the operation (Fig. 46-5) . We particularly evaluate the posterior left
atrial wall, atrial septum, and right atrium, which often are not well displayed on
transthoracic examination, to exclude the possibility of biatrial or multiple tumors.
Computed tomography and magnetic resonance imaging
Although myxomas have been identified using computed tomography (CAT scan), [84 ] ,
[90 ] this modality is most useful in the evaluation of malignant tumors of the heart
because of its ability to demonstrate myocardial invasion and tumor involvement of
adjacent structures. [84 ] Similarly, magnetic resonance imaging (MRI) has been
employed in the diagnosis of myxomas and may yield a clear picture of tumor size,
shape, and surface characteristics. [84 ] , [87 ] , [89 ] , [90 ] MRI is particularly useful for
detecting intracardiac and pericardial extension and invasion of malignant secondary
tumors and also is useful for the evaluation of ventricular masses that occasionally turn
out to be myxomas. Both CAT scan and MRI detect tumors as small as 0.51.0 cm and
provide information regarding the composition of the tumor. [4 ] Neither CAT scan nor
MRI are needed for atrial myxomas, since the information is not likely to alter the
surgical approach. An exception is the occasional right atrial myxoma that extends into
one or both cavae or the tricuspid orifice. CAT scan and MRI should be reserved for
situations where the diagnosis or characterization of the tumor is unclear after complete
echocardiographic evaluation.
SURGICAL MANAGEMENT
Surgical resection is the only effective therapeutic option for patients with cardiac
myxoma and should not be delayed, because death from obstruction to flow within the
heart or from embolism may occur in as many as 8 percent of patients awaiting
operation. [91 ] , [92 ]
A median sternotomy approach with ascending aortic cannulation usually is employed

and is recommended. Manipulation of the heart before initiation of cardiopulmonary
bypass is minimized in deference to the known friability and embolic tendency of
myxomas. Both vena cavae are cannulated directly, and caval snares are used for right
atrial myxomas. For typical left atrial tumors caval catheters are inserted near the
atrial-caval junctions. Body temperature is allowed to drift down, but there is no attempt
to induce systemic hypothermia unless the need for reduced perfusion flow is
anticipated. Modern cardioplegia techniques yield a quiet operative field and protect
the myocardium from ischemic injury during aortic cross-clamping. Cardiopulmonary
bypass is started, and the aorta is clamped prior to manipulation of the heart.
Left atrial myxomas can be approached by incision through the anterior wall of the left
atrium ventral to the right pulmonary veins (Fig. 46-6) . This incision can be extended
behind both cavae for greater exposure (Fig. 46-7) . Exposure of large tumors is
improved by a second incision parallel to the first in the right atrium (Fig. 46-8) . This
biatrial incision allows easy removal of tumors attached to the fossa ovalis with en bloc
excision of the site of attachment.
Our preferred biatrial incision, however, is the superior-septal incision, which is initiated
in the right atrial free wall, carried along the medial aspect of the appendage and thence
down the superior wall, between the aorta and vena cava, into the superior wall of the
left atrium, and then continued caudally through the interatrial septum through and to the
base of the fossa ovalis (Fig. 46-9) . This incision provides excellent exposure, avoids
the tumor stalk before it is adequately exposed, and facilitates removal of even large
tumors. The interatrial septum is closed easily with a pericardial patch.
Right atrial myxomas pose special venous cannulation problems, and intraoperative
echocardiography may be of benefit in allowing safe cannula placement. Often both
vena cavae can be cannulated directly. When a low- or high-lying tumor precludes safe
trans-atrial-caval cannulation, cannulation of a jugular or femoral or iliac vein can
partially drain the upper or lower body. If the tumor is large or attached near both caval
orifices, peripheral cannulation of both the jugular and femoral or iliac vein may be used
to initiate cardiopulmonary bypass and deep hypothermia. After the aorta is clamped
and the heart is arrested with antegrade cardioplegia, the right atrium can be opened
widely for resection of the tumor and reconstruction of the atrium, using pericardium or
polyfluorotetraethylene during a period of circulatory arrest, if this is needed for a dry
field. Resection of large or critically placed right atrial myxomas often requires careful
preoperative planning, intraoperative transesophageal echocardiography, and special
extracorporeal perfusion techniques to insure complete removal of the tumor, protection
of vital right atrial structures, and reconstruction of the atrium. Because myxomas rarely
extend deep into the endocardium, it is not necessary to resect deeply around the
conduction system. The tricuspid valve and right atrium as well as the left atrium and
ventricle should be inspected carefully for multicentric tumors in patients with right atrial,
with or without familial, myxoma.
Regardless of the surgical approach, the ideal resection encompasses the tumor and a
portion of the cardiac wall or interatrial septum to which it is attached. Whether excision
of full thickness wall is necessary or excision of only the endocardial attachment is
sufficient to prevent recurrence is controversial. Our policy is to resect full thickness
whenever possible. However, when only partial thickness resection of the area of tumor
attachment has been done, neither we, nor others, have noted an increased recurrence
rate. [93 ] , [94 ]
Ventricular myxomas usually are approached through the A-V valves, [95 ] but
occasional small tumors in either outflow tract can be removed through the outflow valve.
[95 ] , [96 ] If necessary, the tumor is excised through a direct incision into the ventricle. It
is not necessary to remove the full thickness of the ventricular wall since no recurrences
have been reported with partial thickness excisions. As with right atrial myxoma, the
presence of a ventricular myxoma prompts inspection for other tumors because of the
high incidence of multiple tumors.
Every care should be taken to remove the tumor without fragmentation. Following tumor
removal from the field, the area should be liberally irrigated, suctioned, and inspected
for loose fragments. Whether blood removed from the field during tumor manipulation
should be discarded or returned to the pump circuit is also controversial. There are rare
instances of distant metastasis from myxoma appearing many years after tumor
resection, and these reports raise the issue of potential intraoperative dissemination of
tumor cells. [97 ] , [98 ] We use the cardiotomy suction during operation, but use the
discard suction during the brief time that the tumor actually is excised. We reason that
macro tumor emboli entering the perfusion circuit will be filtered out in the cardiotomy
reservoir. Microembolization, considering the growth of the tumor within the
bloodstream and its friable character, would seem to pose no greater threat for distant
metastasis during tumor removal than it did during tumor development. The low
malignant potential of the vast majority of myxomas and the rarity of metastasis further
support this policy of retaining rather than discarding blood.
RESULTS
Removal of atrial myxoma carries an operative mortality rate of 5 percent or less.

Results of 202 resections indicate that operative mortality is related to advanced age or
disability and comorbid conditions. [99 ] Excision of ventricular myxomas carries a
higher risk (approximately 10 percent), but the experience is small.
Recurrence of nonfamilial, sporadic myxoma is approximately 14.7 percent [4 ] , [93 ] ,

[94 ] and probably is even lower in patients with normal DNA chromosomal patterns.
Many large series report no recurrent tumors. [93 ] , [95 ] , [100 ] [102 ] A total of 35
recurrent myxomas have been reported since 1967. [4 ] The 20 percent of patients with
sporadic myxoma and abnormal DNA have a recurrence rate estimated between 12
and 40 percent. [4 ] , [17 ] The recurrence rate is highest in patients with familial,
complex myxomas, all of whom have abnormal DNA, and this is estimated to be about
22 percent. [4 ] Tumors recurred in three of four patients who had surgical resection,
and in one a second recurrence developed.
Overall, recurrences are more common in younger patients (perhaps those patients all
have abnormal DNA); the interval averages about 4 years but can be as soon as 6
months. [93 ] Most recurrent myxomas occur within the heart but in the same or different
cardiac chamber, and many are multiple. [23 ] , [103 ] [105 ] Recurrence after resection,
tumor embolization with subsequent tumor growth, and local invasion all have been
observed. [106 ] [108 ] , [111 ] The relationship of local recurrence to the adequacy of
the original resection remains unsettled because sporadic tumors rarely recur even if full
thickness excision of the base is not done and because recurrent tumors do not often
recur at the site of the original tumor. [93 ] , [100 ] The biology of the tumor, which cannot
be predicted by histologic examination, probably is most important and may be the only
risk factor for recurrence. DNA testing of all patients with cardiac myxoma may prove to
be the best predictor of the likelihood of recurrence. [112 ]
Uncertainty concerning the true malignant potential of myxomas is increased by reports

that myxomas originally classified as malignant are found on subsequent review to be
sarcomas with myxoid degeneration. [113 ] However, this issue also remains unsettled
because of reports of metastatic growth of embolic myxoma fragments in brain,
arteries, soft tissues, and bone. [63 ] , [98 ] , [111 ] [120 ] Symptomatic lesions of
possible metastatic myxoma should be excised if possible. [63 ] , [118 ]
The extent to which patients should be subjected to long-term echocardiographic

surveillance after myxoma resection is not standardized. However, it would seem
prudent to closely follow patients who are treated initially for multicentric tumors, those
whose tumors are removed from unusual locations in the heart, all whose tumors are
believed to have been incompletely resected, and patients found to have the abnormal
DNA chromosomal pattern. In addition, patients whose apparent myxoma is deemed to
have malignant characteristics on careful pathologic examination should have long-term
follow-up.
Nonmyxomatous Benign Cardiac Tumors
As shown in Table 46-1 , myxomas comprise approximately 41 percent of benign

cardiac tumors with three other tumors, lipoma, papillary fibroelastoma, and
rhabdomyoma, together contributing a similar proportion. A variety of rarely
encountered tumors accounts for the remainder (Table 46-2) .
LIPOMA
Lipomas are well-encapsulated tumors of mature fat cells that may occur anywhere in
the heart but usually are found in the pericardium, subendocardium, subepicardium, or
interatrial septum. [2 ] They may occur at any age and have no sex predilection.
Lipomas are slow growing and may attain considerable size before producing
obstructive or arrhythmic symptoms. Many are asymptomatic and are discovered
incidentally on a routine chest roentgenogram, echocardiogram, or at surgery or
autopsy. [121 ] , [122 ] Subepicardial and parietal lipomas tend to compress the heart
and may be associated with pericardial effusion. Subendocardial tumors may produce
chamber obstruction. The right atrium and left ventricle are sites most often affected.
Lipomas lying within the myocardium or septum can produce arrhythmias or conduction
disturbances. [123 ] , [124 ] Large tumors that produce severe symptoms should be
resected. Smaller asymptomatic tumors encountered unexpectedly during other cardiac
operations should be removed if excision can be performed without adding risk to the
primary procedure. These tumors are not known to recur. [125 ]
LIPOMATOUS HYPERTROPHY OF THE INTERATRIAL SEPTUM
Nonencapsulated hypertrophy of fat within the atrial septum is known as lipomatous

hypertrophy. [2 ] This abnormality is more common than cardiac lipoma and usually is
encountered in elderly, obese, or female patients as an incidental finding during a
variety of cardiac imaging procedures. [126 ] Various arrhythmias and conduction
disturbances have been attributed to its presence. [127 ] [129 ] The main problem
posed is differentiation from a cardiac neoplasm when the lesion is discovered by
echocardiography. [130 ] There is no evidence that surgical extirpation is indicated.
PAPILLARY FIBROBLASTOMA OF HEART VALVES
Papillary fibroelastomas are tumors that arise characteristically from the cardiac valves
or adjacent endocardium. [131 ] Grossly the tumors are described as resembling sea
anemones, with frondlike projections. The A-V and semilunar valves are affected with
equal frequency. Formerly thought to be innocuous, because they were incidental
findings at autopsy, it is now known that they are capable of producing obstruction to
flow, particularly coronary ostial flow, and may embolize to the brain and produce stroke.
[131 ] [138 ] They usually are asymptomatic until a critical event occurs but now are
found more often because of the more frequent use of echocardiography. Papillary
fibroelastomas of the cardiac valves should be resected whenever diagnosed because
of their known tendency to produce life-threatening complications. Valve repair, rather
than replacement, should follow resection of these benign tumors whenever technically
feasible.
RHABDOMYOMA
Rhabdomyoma is the most frequently occurring cardiac tumor in children and usually
presents during the first few days after birth. It is thought to be a myocardial hamartoma
rather than a true neoplasm. [139 ] Although rhabdomyoma appears sporadically, it is
associated strongly with tuberous sclerosis, a hereditary disorder characterized by
hamartomas in various organs, epilepsy, mental deficiency, and sebaceous adenomas.
Fifty percent of patients with tuberous sclerosis have rhabdomyoma, but more than 50
percent of patients with rhabdomyoma have or will develop tuberous sclerosis. [140 ] ,
[141 ] The exceptional patient is one with a solitary, single rhabdomyoma who does not
have or develop tuberous sclerosis.
Over 90 percent of rhabdomyomas are multiple and occur with approximate equal
frequency in both ventricles. [142 ] The atria are involved in fewer than 30 percent of
patients. Pathologically these tumors are firm, gray, and nodular and tend to project into
the ventricular cavity. Micrographs show double normal-sized myocytes, filled with
glycogen and containing hyperchromatic nuclei and eosinophilic staining, cytoplasmic
granules. [2 ] , [143 ] Scattered bundles of myofibrils can be seen within cells by electron
microscopy. [142 ]
The most common presentation is heart failure caused by tumor obstruction of cardiac
chambers or valvular orifice flow. Clinical findings often mimic valvular or subvalvular
stenosis. Arrhythmias, particularly ventricular tachycardia and sudden death, may be a
presenting symptom. [143 ] Atrial tumors may produce atrial arrhythmias. [143 ] The
diagnosis is suggested by clinical features of tuberous sclerosis and is made by
echocardiography. Cardiac catheterization usually is needed to assess the location and
severity of circulatory obstruction. Rarely, no intramyocardial tumor is found in a patient
with ventricular arrhythmias, and the site of rhabdomyoma is located by
electrophysiologic study. [143 ]
Early operation is recommended in patients who do not have tuberous sclerosis before
one year of age. [125 ] The tumor usually is removed easily in early infancy, and some
can be enucleated. [125 ] Unfortunately, symptomatic tumors often are both multiple and
extensive, particularly in patients with tuberous sclerosis, who, unfortunately, have a
dismal long-term outlook. In such circumstances surgery offers little if any benefit.
FIBROMA
Fibromas are the second most common benign cardiac tumor; over 83 percent occur in
children. These tumors are solitary, occur exclusively within the ventricle or
interventricular septum, and affect the sexes equally. Fewer than 100 tumors have been
reported, and most are diagnosed by age 2 years. These tumors are not associated
with other disease, nor are they inherited.
Fibromas are nonencapsulated, firm, nodular, gray-white tumors that can become bulky.
They are composed of elongated fibroblasts in broad spiral bands and whorls mixed
with collagen and elastin fibers. Calcium deposits or bone may occur within the tumor
and occasionally are seen on roentgenography.
The majority of fibromas produce symptoms through chamber obstruction, interference

with contraction, or arrhythmias. Depending on location and size, such a tumor may
interfere with valve function, obstruct flow paths, or cause sudden death from conduction
disturbances in up to 25 percent of patients. [125 ] Intracardiac calcification on chest
roentgenogram suggests the diagnosis, which is confirmed by echocardiogram.
Surgical excision is successful in some patients, particularly if the tumor is localized,

does not involve vital structures, and can be enucleated. [125 ] , [144 ] [146 ] However, it
is not possible always to completely remove the tumor; partial removal is only palliative,
although some patients have survived for many years. [125 ] , [145 ] , [146 ] Operative
mortality may be high in infants; most successful cases are in adolescents and adults.
[125 ] , [144 ] [146 ] Successful, complete excision is curative. [144 ] [146 ] Children with
extensive fibromas have been treated by cardiac transplantation. [147 ] , [148 ]
MESOTHELIOMA OF THE A-V NODE
Mesothelioma of the atrioventricular node, also termed polycystic tumor, Purkinje tumor,
or conduction tumor, is a relatively small multicystic tumor that arises in proximity to the
atrioventricular node and may extend upward into the interatrial septum and downward
along the bundle of His. [2 ] Mesothelioma is associated with heart block, ventricular
fibrillation, and sudden death. Cardiac pacing alone does not prevent subsequent
ventricular fibrillation. There are no reports of antemortem diagnosis or surgical
excision. [149 ]
PHEOCHROMOCYTOMA
Cardiac pheochromocytomas arise from chromaffin cells of the sympathetic nervous

system and produce excess amounts of catecholamines, particularly norepinephrine.
Approximately 90 percent of pheochromocytomas are in the adrenal glands; fewer than
2 percent arise in the chest; only 32 cardiac pheochromocytomas have been reported.
[150 ] The tumor predominantly affects young and middle-aged adults, with an equal
distribution between the sexes. Approximately 60 percent occur in the roof of the left
atrium; the remainder involve the interatrial septum or anterior surface of the heart. The
tumor is reddish-brown, soft, and lobular and contains nests of chromaffin cells.
Patients usually present with symptoms of uncontrolled hypertension and are found to
have elevated urinary catecholamines. The tumor usually is located by scintigraphy
using 131-1-metaiodobenzylguanidine [151 ] , [152 ] and CAT-scan or MRI. [151 ] , [152
] Occasionally, cardiac catheterization with differential chamber blood sampling is
necessary. [150 ] Because these tumors are vascular and may be near major coronary
arteries, coronary angiograms are advisable.
After the tumor is located, it should be removed using cardiopulmonary bypass with
cardioplegic arrest. Patients require preanesthetic alpha- and beta-blockade and
careful intra- and immediate postoperative monitoring. Most tumors are extremely
vascular, and uncontrollable intraoperative hemorrhage has occurred. [152 ] Resection
may require removal of atrial or ventricular wall or a segment of a major coronary artery.
[150 ] Transplantation has been done for an irresectable tumor. Complete excision
produces cure. [150 ] , [152 ]
HEMANGIOMA
Hemangiomas of the heart are rare tumors (24 clinical cases reported) affecting all
ages and may occur anywhere within the heart. [153 ] , [154 ] These are vascular tumors
composed of capillaries or cavernous vascular channels. Patients usually develop
dyspnea, occasionally arrhythmias or signs of right heart failure. [155 ] Diagnosis is
difficult; the chest roentgenogram may be abnormal but is nonspecific.
Echocardiography or cardiac catheterization usually, but not always, establishes the
diagnosis of cardiac tumor by showing an intracavitary filling defect. [156 ] CAT scan
and MRI should be done and are likely to be helpful, but there is little experience.
Coronary angiography typically shows a tumor blush and maps the blood supply of the
tumor.
These tumors can be resected in symptomatic patients, but cardiopulmonary bypass is

recommended. Meticulous ligation of feeding vessels is required to prevent
postoperative residual arterial-venous fistulas or intracavitary communications. Partial
resections have produced long-term benefits. [153 ] Rarely, the tumor resolves
spontaneously. [157 ]
TERATOMA
Cardiac teratoma is a rare tumor that usually presents in infancy or young children but
has occurred in adults. [158 ] About 80 percent of tumors are benign; the remainder
have microscopic and clinically malignant cells. [159 ] These tumors are discovered by
echocardiography after a variety of symptoms prompts cardiac or mediastinal
evaluation. There is little experience with surgical removal, which should be possible
with modern imaging and surgical technology.
PRIMARY MALIGNANT NEOPLASMS
Fortunately, primary malignant tumors of the heart are rare because nearly all are
incurable. Slightly more than 25 percent of primary cardiac tumors are malignant, and
nearly all are sarcomas. According to the survey made by McAllister and Fenoglio, the
most common are angiosarcoma (31 percent), rhabdomyosarcoma (21 percent),
malignant mesothelioma (15 percent), and fibrosarcoma (11 percent). [2 ]
Primary malignant cardiac tumors show no familial preference and usually arise in
adults over age 40 years. Patients often present with symptoms of heart failure, pleuritic
chest pain, and constitutional symptoms of fever, malaise, anorexia, and weight loss.
[160 ] , [161 ] A few develop refractory arrhythmias, syncope, pericardial effusion, or
pericardial tamponade. [162 ] The chest roentgenogram may be abnormal and even
show a mass lesion; the diagnosis of cardiac tumor is made by echocardiography [163
] , [164 ] (Fig. 46-10) . If confirmation is needed or if surgical resection is contemplated,
CAT scan and/or MRI provide detailed anatomic information and may suggest the
actual histology. Cardiac catheterization seldom is necessary, although angiosarcomas
may show a tumor blush on coronary angiogram.
A tissue diagnosis may be obtained by cardiac catheterization, and this should be

attempted if one is needed. A tissue diagnosis may be needed to differentiate the
tumor from metastatic malignancies for which effective radiation or chemotherapy is
available. Surgery for tissue diagnosis is a last resort and can be justified only by a
reasonable expectation that the primary or secondary tumor can be meaningfully
palliated by radiation or chemotherapy. Whether primary or secondary, a decision to
resect is made on the basis of tumor size and location and absence of evidence of
distant spread after a thorough work-up to detect metastasis. Modern imaging
technology with a history and physical examination reliably provides this information.
Radiation and chemotherapy are largely ineffective for primary cardiac sarcomas,
although if a resection is carried out postoperative radiation is recommended and is
associated with slightly improved survival. [161 ] , [164 ] [166 ] Resection for local tumor
control must be carefully considered in that operation generally only changes the modus
of the terminal event and rarely postpones it.
Angiosarcoma
Angiosarcomas are two to three times more common in men than in women and have a
predilection for the right heart. Eighty percent arise from the right atrium. [160 ] , [169 ] ,
[170 ] These bulky tumors aggressively invade adjacent structures, including the great
veins, tricuspid valve, and wall of the heart, and cause obstruction [169 ] (Fig. 46-11) .
Microscopic sections show anastomosing vascular channels lined with atypical,
anaplastic endothelial cells. Unfortunately, the majority of these patients have distant
metastasis, usually to lung, liver, and brain, at the time of diagnosis. [160 ] Resection is
seldom justified; 90 percent of patients are dead in 912 months after diagnosis despite
radiation or chemotherapy. [168 ] , [171 ]
Rhabdomyosarcoma
Rhabdomyosarcomas do not evolve from rhabdomyoma and occur equally in the sexes.
The tumors are multicentric in 60 percent of patients, arise from either ventricle, and
frequently invade cardiac valves or interfere with valve function because of their
intracavitary bulk. Microscopically the tumor cells have pleomorphic nuclei and spidery,
wispy, streaming eosinophilic cytoplasm, usually in a musclelike pattern (Fig. 46-12) .
The tumors are aggressive and may invade pericardium. Surgical excision of small
tumors may be rational, but local and distant metastases and poor response to
radiation or chemotherapy limit survival to less than 1 year in the majority of patients.
[161 ] , [163 ] , [164 ] , [166 ] , [172 ] , [173 ]
Other Sarcomas
McAllister and Fenoglio found that malignant mesotheliomas arising from the heart or
pericardium and not from the surrounding pleura are the third most common primary
malignant cardiac tumors and that fibrosarcomas are the fourth. [2 ] However, in the two
decades since their work clinicians have rarely encountered or reported these tumors,
probably because the histologic criteria for classifying primary malignant cardiac
neoplasms have changed since their study. [125 ] , [160 ] [164 ] , [166 ] [168 ] , [172 ]
[175 ]
The histology of these tumors can be ambiguous and difficult and resemble several
different sarcomas, and some might be called fibrous histiocytomas today. The
behavior of the tumors is more important; as with other cardiac sarcomas, resection of
small tumors in the absence of known metastases perhaps is justified, but data are
scarce. [162 ] , [164 ] , [168 ] , [173 ]
Leiomyosarcoma, liposarcoma, osteosarcoma, chrondomyxosarcoma, plasmacytoma,

carcinosarcoma, and malignant fibroblastic histiocytoma arising from the heart have
been reported. [125 ] , [176 ] [180 ] By the time the diagnosis is made, only palliative
therapy can be offered, and this rarely includes surgery. With reportable exceptions
these patients are dead within 1 year.
Lymphomas may arise from the heart, although that is rare. [181 ] These tumors are
sensitive to radiation therapy, and even though only incomplete resection can be
accomplished to relieve acute obstructive symptoms, radiation and chemotherapy have
prolonged survival for nearly 3 years in the author's experience.
HEART TRANSPLANTATION
Malignant tumors of the heart typically are discovered when symptoms arise secondary
to extensive tumor growth, with local invasion, intracardiac chamber obstruction, or both.
Local resection, even if feasible, often is unsuccessful because of the presence of
residual tumor at the resection margins. The frequent failure of local resection has led to
the treatment of some patients by means of total cardiectomy and orthotopic heart
transplantation. Reports of transplantation for a number of cardiac tumors, including
sarcoma, [182 ] [184 ] pheochromocytoma, [185 ] lymphoma, [186 ] fibroma, [148 ] and
myxoma, [187 ] have appeared. However, long-term results are uncertain because
some patients die from recurrent or metastatic disease despite cardiac transplantation.
[184 ] , [186 ] , [188 ] Given the shortage of donor hearts relative to need, treatment of
patients with malignant sarcoma by orthotopic heart transplantation is highly
controversial. Perhaps transplantation would best be suited for patients with
unresectable benign tumors of the heart such as cardiac fibroma.
SECONDARY METASTATIC TUMORS
Approximately 10 percent of metastatic tumors eventually reach the heart or

pericardium, and almost every type of malignant tumor has been known to do so. [2 ] ,
[5 ] , [175 ] , [189 ] Secondary neoplasms are 2040 times more common than primary
cardiac malignancies. [4 ] , [190 ] Up to 50 percent of patients with leukemia develop
cardiac lesions. [175 ] Other cancers that commonly involve the heart include breast,
lung, lymphoma, melanoma, and various sarcomas. [2 ] , [191 ] , [192 ] Metastases
involve the pericardium, epicardium, myocardium, and endocardium in roughly that
order of frequency. [2 ] , [5 ]
The most common means of spread, particularly for melanoma, sarcoma, and
bronchiogenic carcinoma, is via the blood stream and coronary arteries. Metastases
can also reach the heart through lymphatic channels, through direct extension from
adjacent lung, breast, esophageal, and thymic tumors, and from the subdiaphragmatic
vena cava. The pericardium most often is involved by direct extension of thoracic
cancer; the heart is the target of hematogenous and/or retrograde lymphatic
metastases. [175 ] Cardiac metastases rarely are solitary and nearly always produce
multiple microscopic nests and discrete nodules of tumor cells (Fig. 46-13) . [2 ] , [5 ] ,
[175 ]
Cardiac metastases produce clinical symptoms in only about 10 percent of afflicted

patients. [175 ] , [193 ] , [194 ] The most common symptom is pericardial effusion or
cardiac tamponade; occasionally patients develop refractory arrhythmias or congestive
heart failure. Chest radiographs and electrocardiograms tend to show nonspecific
changes, but echocardiography is particularly useful for diagnosis of pericardial effusion
or intracavitary masses interfering with blood flow.
Surgical therapy is limited to relief of recurrent pericardial effusions or occasionally

cardiac tamponade. In most instances these patients have widespread disease with
limited life expectancies. Surgical therapy is directed at providing symptomatic relief
with minimal patient discomfort and hospital stay. This is most readily accomplished via
subxyphoid pericardiotomy, which can be accomplished under local anesthesia with
reliable relief of symptoms, a recurrence rate around 3 percent, and little mortality. [192 ]
Alternatively, a large pericardial window into the left pleural space can be created using
thoracoscopy. [195 ] This can be accomplished with minimal patient discomfort but
does require general anesthesia with single lung ventilation and may be poorly tolerated
by patients with hemodynamic deterioration secondary to large effusions.
RIGHT ATRIAL EXTENSION OF SUBDIAPHRAGMATIC TUMORS
Abdominal and pelvic tumors on occasion may grow in a cephalad direction via the
inferior vena cava to reach the right atrium. Such tumors most frequently are renal cell
carcinomas, although hepatic, adrenal, and uterine tumors occasionally have exhibited
this behavior. Up to 10 percent of renal cell carcinomas invade the inferior vena cava,
and nearly 40 percent of these reach the right atrium. [196 ] Radiation and
chemotherapy are not effective in relieving the obstruction to blood flow. [197 ]
Renal cell tumors with atrial extension typically are resected in a procedure combined
with abdominal dissection to ensure resectability followed by median sternotomy and
aortic and superior vena caval cannulation. The operation is most frequently performed
under hypothermic circulatory arrest or with low flow cardiopulmonary bypass and
moderate hypothermia. The right atrium is opened obliquely with the incision carried in
the direction of the inferior vena cava. The tumor is dissected free from any atrial or
caval attachments and subsequently extracted with gentle traction. After the atrium and
cava are inspected for residual tumor fragments, the atrium is closed and the patient
warmed.
Five-year survival of 75 percent has been achieved following nephrectomy and

resection of right atrial tumor extension. [198 ] , [199 ] Other subdiaphragmatic tumors
with atrial extension that have been resected successfully include hepatic and adrenal
carcinoma as well as gynecologic tumors. [200 ] [204 ]
MANAGEMENT CONSIDERATIONS
Preoperative Considerations
The natural history of the congenital defect, the sequelae of previous surgical
interventions, and possible development of newly acquired cardiovascular disease
must all be evaluated and planned for. Long-standing cyanosis, or pressure or volume
overloads, may result in right or left ventricular dysfunction or secondary valvular
regurgitation that may require repair. Additionally, cyanosis and underperfusion of the
lungs may cause aortopulmonary collateral development that may require coil
embolization prior to reoperation. Pulmonary vascular resistance may be affected by
long-standing excessive flow or by severe underperfusion and, in older patients, by
pulmonary thromboembolism. Older patients may have developed coronary artery
disease that requires concomitant revascularization.
Perioperative Management
Adults with congenital heart disease undergoing operation or reoperation pose special
problems that may increase operative risk. Redo median sternotomy can produce
catastrophic hemorrhage. Previous use of a polyfluorotetraethylene (Gore-Tex)
pericardial substitute facilitates safe redo sternotomy and is used in all patients in
whom reoperation is expected, as in those with tissue valves. The femoral artery and
vein are exposed, ready for cannulation prior to sternotomy. In some high-risk patients,
such as those with a homograft or a dilated right atrium, right ventricle, or aorta
immediately beneath the sternum, the femoral vessels are cannulated with thin-walled
cannulas, and bypass is instituted prior to sternotomy. In the presence of aortic
regurgitation or where hypothermia is used, the left ventricle (LV) can be decompressed
with a vent inserted via a small lateral thoracotomy placed over the LV apex. Bleeding
may be a problem during chest opening due to the presence of numerous large
thin-walled vessels throughout the mediastinum that are commonly found in chronically
cyanotic patients. Chronic cyanosis and polycythemia are associated with a
coagulopathy due to platelet dysfunction. Chronic hepatic congestion also contributes to
this coagulopathy. The use of antifibrinolytic agents such as aprotinin, aminocaproic
acid, and tranexamic acid should be considered in high-risk patients except when
circulatory arrest is used. Autologous blood donation (when not contraindicated) and the
use of cell-saving devices are routine. Because right or left ventricular dysfunction may
be present, meticulous myocardial protection is critical to the outcome of these patients.
Noncoronary collateral flow is usually well developed, and there is often excessive
bronchial return to the left atrium. For these reasons, we use both antegrade and
retrograde cardioplegia with a purse-string around the coronary sinus administered
every 10 minutes as well as deeper levels of systemic hypothermia.
Postoperative Care
The adult with congenital heart disease may present a far more complex postoperative
course than the usual adult with acquired heart disease. Both right and left ventricular
function may be compromised and require support. Both the pulmonary and systemic
vascular resistance may require manipulation. For this reason, right-atrial (RA),
pulmonary-artery (PA), and left-atrial (LA) pressure-monitoring lines should be used
when indicated. Left-atrial lines should be used rather than attempting to obtain PA
wedge pressures because of the danger of PA rupture and possible discrepancy
between PA diastolic pressures and LA pressure. Transesophageal echocardiography
may be required postoperatively to assess left and right ventricular function and to
evaluate left- and right-sided valve function.
Long-Term Follow-Up
Because of the complexities of the pathophysiology of many adults with congenital heart
disease, long-term follow-up is important to identify possible future sequelae and to
attempt to prevent them. In addition, many patients require reoperative or a catheter
type of intervention for tissue-valve failure or recurrent stenoses. The long-term
prognosis of the young adult depends on preserving myocardial function, which requires
timely intervention to relieve pressure or volume overload.
Antibiotic prophylaxis against endocarditis is recommended for all patients with

prosthetic material (e.g., Gore-Tex conduit or valves), especially if there is a residual
lesion with abnormal flow such as a ventricular septal defect or a systemic to pulmonary
artery shunt. The American Heart Association guidelines are usually followed. [3 ] , [4 ]
Pregnancy
Young women present a special problem because of the risks posed by future
pregnancy. If a complete correction is achieved, pregnancy is usually feasible, provided
there is no serious concern regarding myocardial function. Repair and reoperation may
require valve replacement, which could have a serious impact on a future pregnancy. It
is known that the use of warfarin is associated with an increased incidence of
congenital malformations and stillbirths. Although the most recent report from
Hammersmith describes a fairly good experience with the use of warfarin and heparin
in patients with mechanical valves, most centers prefer the use of a tissue valve if repair
is not possible to avoid the use of warfarin. [5 ] Where feasible, a homograft or a
porcine valve is used. For the aortic position, the Ross procedure (pulmonary autograft
in the aortic position and homograft in a pulmonary position) is the operation of choice
for a young woman planning pregnancy.
The Hammersmith study showed that there was a 35 percent incidence of accelerated
bioprosthetic valve deterioration presumably due to changes in calcium metabolism in
the pregnant woman. The authors therefore recommend the use of mechanical valves.
They experienced a successful outcome in 83 percent of pregnancies with bioprosthetic
valves and 73 percent of pregnancies with mechanical valves. There was a 10 percent
incidence of thrombosis or bleeding in the warfarin group, but no embryopathies were
found.
Women with persistent cyanotic defects also have been studied. Presbitero et al. [6 ]
reported a 43 percent rate of live births in 44 patents who had a total of 96 pregnancies.
The best success rate (86 percent) was for patients with Ebstein's anomaly and atrial
septal defect, and the worst rate (31 percent) was for single-ventricle physiology. There
was a 32 percent incidence of maternal cardiovascular complications and one death
from endocarditis 2 months after delivery. The most important predictions of fetal
outcome were hemoglobin and arterial oxygen saturation.
SPECIFIC CONGENITAL MALFORMATIONS
Table 47-2 summarizes the UCLA experience with surgery in adults with congenital
heart disease during the last 5 years. This section discusses guidelines for treating
various specific defects.
Atrial Septal Defects
Atrial septal defects (ASD) of the secundum type are the most common lesions, but we
see sinus venosus defects of both the superior and inferior vena caval types, as well as
primum atrial septal defects in adults.
The amount of left-to-right shunting is variable. In older patients, as right ventricular

dysfunction and tricuspid regurgitation develop, the degree of left-to-right shunting may
decrease. [7 ] In other patients, due to hypertension and reduced LV compliance, the
left-to-right shunt may increase. About 15 to 20 percent of children with an ASD
eventually develop pulmonary vascular disease. [8 ] [10 ] If it does not occur by the end
of the second decade, it is very unlikely to occur. Pulmonary vascular disease eventually
causes reversal of the shunt and development of hypoxia that may be intermittent and
severe depending on RV function and tricuspid regurgitation. As long as the Q P /Q S
ratio (pulmonary flow to systemic flow) is greater than 1.5:1 and the calculated
pulmonary vascular resistance (PVR) is less than 68 units/m 2 (or Wood units/m 2 ),
depending on systemic vascular resistance at the time of measurement, closure is
usually indicated. Although most adolescents with an ASD are asymptomatic through
the second decade, by the third or fourth decade adults commonly develop atrial
fibrillation or a reduction in exercise tolerance, and eventually heart failure. It is
preferable to close the defect when the diagnosis is made, prior to the development of
these sequelae.
The operation is performed using cardiopulmonary bypass and moderate hypothermia.

For cosmetic purposes in young women, a submammary skin incision with median
sternotomy is used. More recently, we have used a small right anterolateral thoracotomy
with femoral cannulation (Fig. 47-1) . Extensive deairing is performed prior to releasing
the cross-clamp. Maneuvers to reduce the risk of air embolism include clamping or
snaring the right pulmonary veins prior to opening the right atrium. The ASD is closed
either primarily or with a pericardial patch. The right-sided pulmonary veins must all be
identified, and if they are draining anomalously, they are baffled to the left side with the
pericardial patch. It is also important to identify the inferior vena caval orifice so that it is
not inadvertently baffled into the left atrium by sewing the patch to a well-developed
eustachian valve. In adults, the redundant right atrial wall is excised, and if present, a
regurgitant tricuspid valve should be repaired with an annuloplasty. After closure of the
defect and right atrium, extensive deairing is performed prior to releasing the
cross-clamp. This includes syringe and large-bore needles, deairing of the left atrium,
and venting of the aorta. If air has entered the left ventricle during the procedure, a small
submammary left-sided thoracotomy is made, and a small left ventricular apical vent is
also inserted to assist in deairing. In patients with chronic atrial fibrillation, consideration
should be given to performing a Maze procedure at the time of repair (see Chap. 26).
Long-term follow-up after repair of isolated ASDs is well documented. [11 ] , [12 ] When
patients are operated on at or before 25 years of age, normal life expectancy may be
anticipated, but this may not be the case when patients are corrected after 25 years,
when both right and left ventricular reserve are diminished in the presence of a
long-standing ASD. However, patients with ASD closure after 40 years of age may still
realize improvement of symptoms. At the University of Alabama, it was found that age
and New York Heart Association (NYHA) class were fairly well correlated, thus
suggesting that ASD closure is indicated when the defect is hemodynamically
significant (Q P /Q S µg1 1.5:1). [7 ] Older age per se is not a risk factor for operative
mortality.
Occasionally, surgical treatment of a patent foramen ovale is indicated if patients

present with paradoxical emboli.
Ostium primum defects are unusual in adults; however, survival similar to that of a large
ASD can be expected for partial AV canals with minimal valvular incompetence. [13 ]
There is also a group of previously operated patients that may present because of left
AV valve malfunction following repair at an earlier age. These patients can often be
treated with a rerepair of their mitral valves, particularly if a residual defect such as a
cleft is present in the anterior leaflet. Some will require valve replacement.
Recently, there has been an interest in the use of intravascular devices to close ASDs.
[14 ] , [15 ] These techniques are currently experimental, and long-term follow-up is
needed before adopting widespread use of such an approach.
Ventricular Septal Defects
Small restrictive ventricular septal defects (VSDs) may allow survival to adulthood
without surgical treatment. Such defects are likely to result from partial spontaneous
closure or from residual patch leaks following earlier surgical closure. [16 ] , [17 ] Use of
the term restrictive implies a pressure gradient between the ventricles. Generally, if the
Q P /Q S is greater than 1.5:1 and the calculated pulmonary vascular resistance is
under 6 units/m 2 , closure is recommended. In patients with large VSDs, the probability
of developing severe pulmonary vascular disease is about 50 percent by the third
decade of life. Consequently, patients eventually die of complications of Eisenmenger's
syndrome if they remain unoperated. These patients ultimately will become cyanotic as
a result of right-to-left shunting, and the only surgical options available are either
heart-lung transplantation or lung transplantation with repair of the VSD. Generally, if
desaturation occurs during exercise testing, the long-term survival is poor. A pulmonary
vascular resistance greater than 6 units/m 2 is considered a high risk for isolated VSD
closure.
VSDs are categorized into four anatomic types. The perimembranous type represents
the majority of VSDs presenting later in life. This defect is located beneath the septal
leaflet of the tricuspid valve between the divisions of the septal band. Rarely, such
VSDs cause aortic regurgitation, particularly if immediately subjacent to the
noncoronary or right coronary aortic-valve cusps. The aortic valve may require repair at
the time of VSD closure [18 ] (Fig. 47-2) .
The subarterial VSD is located in the supracristal area and lies directly beneath the
pulmonary valve. The right coronary cusp of the aortic valve and sometimes the
noncoronary cusp may prolapse into the defect, which may therefore be restrictive. The
aortic valve may require repair with suspension of a prolapsing cusp.
It is unusual for the endocardial cushion type of VSD to be associated with adult
survival. These are located in the inlet of the right ventricle and are directly adjacent to
the tricuspid valve, central fibrous body, and mitral valve. These may have associated
mitral-valve defects and therefore require mitral-valve repair at the time of surgery. This
usually involves closure of the cleft and correction of the dilated annulus with
annuloplasty.
Muscular VSDs occur anywhere within the muscular septum. They may be anterior, in
the inlet septum (separated from the tricuspid valve by the moderator band of muscle),
midmuscular, or apical. These are very unlikely to be present in adulthood because they
have a tendency to close in the first year of life.
The surgery for VSD closure is done on cardiopulmonary bypass with moderate
hypothermia and blood cardioplegic arrest. The VSD usually can be closed via an
incision in the right atrium through the tricuspid valve. Postoperatively, pulmonary artery
pressure must be monitored. If acute pulmonary hypertension exists, this can be treated
with intravenous nitroglycerin, prostaglandin E1, or nitric oxide. Transcatheter closure of
VSDs remains experimental. [19 ] , [20 ]
Long-term follow-up is required to monitor pulmonary artery pressure in patients with

large VSDs closed late in life. [21 ] , [22 ] This can be done echocardiographically if
there is a small tricuspid-valve jet to calculate the RV pressure or by measuring the
pulmonary-valve opening time. The pulmonary vascular resistance (PVR) may continue
to rise after VSD closure, resulting in systemic or suprasystemic RV pressures. This
may result in angina, sudden death, or RV failure with tricuspid-valve regurgitation.
Lung or heart-lung transplantation may be required for adults with VSD and
Eisenmenger's syndrome, in whom closure of the defect would produce suprasystemic
RV pressures. These patients may be offered heart-lung transplantation particularly if
there is significant ventricular dysfunction. If ventricular function is good, consideration
should be given to VSD closure combined with single or, more often, double lung
transplantation. [23 ] [25 ] The mortality for this procedure is about 20 percent, and the
5-year survival is expected to be approximately 60 percent. [26 ] , [27 ]
Patent Ductus Arteriosus
Isolated patent ductus arteriosus (PDA) may present with congestive heart failure by the
third or fourth decade of life. [28 ] Occasionally, the ductus may become aneurysmal
secondary to flow characteristics. The aortic aspect of the PDA is usually calcified in the
older adult patient. Pulmonary vascular disease also may be present as a result of this
longstanding left-to-right shunt. While mortality in the first year of life is about 30 percent,
thereafter the cumulative death rate is about 0.5 percent per year. This doubles to 1
percent by adulthood and increases to 24 percent by midlife. There is always a risk of
endocarditis (regardless of the size of the PDA) that is dependent on the presence of
abnormal flow. Adults with large PDAs may develop Eisenmenger's syndrome and the
classic finding of differential cyanosis in the lower body. Preoperatively, pulmonary
vascular resistance should be measured. If the resistance is greater than 68 units/m 2 ,
the ductus should not be closed, and the patient may be considered for transplantation.
[23 ] [27 ]
Surgical closure of a PDA is usually carried out via a small posterior thoracotomy.
Thoracoscopic procedures are probably not appropriate for the older adult because of
the greater risk of rupture while tying the ductus. In patients over 40 years of age, or if
calcification of the ductus is demonstrated, the procedure should be conducted via a
median sternotomy on bypass. During cooling, the ductus is occluded by finger
pressure on the PA. The ductus is exposed via an incision made in the PA. Using low
flow, the ductus is closed on the PA side with horizontal pledgeted mattress sutures, or
the PA defect may be patched with glutaraldehyde-treated pericardium or a Gore-Tex
patch.
More recently, use of a prosthesis for catheter closure has been reported. [29 ] [31 ]
This is, however, dependent on institutional experience, and most of the patients are
quite young. Additionally, 510 percent of patients have a small persistent residual shunt,
and the risk of endocarditis in such patients is unknown. PDAs with a neck or a
narrowing on entering the aorta are considered most amenable to this approach.
Patients with Eisenmenger's syndrome may be candidates for either single or double
lung transplantation combined with PDA closure or for heart-lung transplantation if there
is significant ventricular dysfunction.
Aortic Coarctation
Aortic coarctation in adults usually presents with upper-body hypertension typically in the
second or third decade of life. Although these patients comprise a selected group that
have survived free of complications beyond childhood, long-term complications include
aneurysm formation of the aorta and also aneurysmal dilatation of the intercostal
arteries, which may rupture. [32 ] This latter anomaly is important because the initial
portion of these arteries must be resected with the coarctation at the time of surgery if
they appear disproportionately enlarged. Other complications include premature
coronary artery disease, left ventricular hypertrophy, aortic dissection and rupture,
endocarditis, and intracranial hemorrhage. Late in life, beyond 40 years, congestive
heart failure may develop due to a cardiomyopathy. Up to 40 percent of patients have
associated bicuspid aortic valves that also may become stenotic and/or incompetent. If
coarctation is left untreated, 90 percent of patients eventually die by the age of 50 due
to the preceding causes. The oldest patient in our series was 81 years old. Repair also
may be required for patients who have had previous coarctation repairs with recurrence
or for patients who have developed recurrence after previous balloon aortoplasty. [32 ] ,
[33 ] Residual coarctation following repair in childhood is usually due to failure of growth
of the anastomosis or because of technical factors such as a short subclavian flap
aortoplasty. In these patients, aneurysm formation also may have occurred and should
be looked for and repaired at the time of surgery.
In adults with coarctation, there is usually an extensive collateral circulation. The source
is mainly from the branches of the subclavian artery, the internal mammary artery, and
the intercostal chest-wall circulation. Collateral flow into the descending aorta is
dependent on enlarged intercostals at the level of the third and fourth ribs beyond the
coarctation.
Surgical repair is indicated when the gradient across the coarctation is greater than or
equal to 30 mmHg at rest. If the gradient is less and the anatomic obstruction severe, an
exercise test will reveal a more severe gradient, which is an indication for repair. The
preferred method is resection with end-to-end anastomosis (Fig. 47-3) , although patch
repair may be used for reoperations or where the collaterals are particularly enlarged
and difficult to mobilize. Tube-graft interposition is rarely used. Special precautions are
taken to prevent spinal-cord ischemia, which is a major risk. Arterial lines are placed in
the upper and lower extremities for monitoring blood pressure during aortic clamping.
The distal pressure should be maintained above 50 mmHg throughout the procedure.
Cerebrospinal fluid pressure is monitored by catheter, and the fluid is allowed to drain if
pressure exceeds 10 cm h 2 o (essentially central venous pressure). This is monitored
for 24 hours postoperatively. The goal is to aid in perioperative perfusion of the spinal
cord by increasing the pressure gradient during and after aortic clamping.
The patient is also placed on a temperature-regulated blanket and cooled to 33°C. Cold
saline is used to bathe the left chest cavity to aid in cooling, and the room is cooled.
Positioning for the left thoracotomy is important in that one must prep and drape the
groins to have access to the femoral arteries if left atrial-to-femoral artery (or
descending aorta) bypass becomes necessary during the operation. One must carefully
identify chest-wall collaterals, which can bleed massively and which must be ligated
individually during the thoracotomy.
Somatosensory evoked potentials (SSEPs) can be monitored intraoperatively to aid in

the decision to use extracorporeal circulation to help prevent spinal-cord ischemia
during aortic cross-clamping. The aorta is mobilized extensively, and the ligamentum
arteriosum is divided and oversewn. Large intercostal branches are identified and
encircled in preparation for snaring. Prior to clamping the aorta, 30 mg/kg of
methylprednisolone sodium succinate and 100 mg of lidocaine are administered
intravenously as well as 8 g of mannitol. The patient is anticoagulated with 1 mg/kg of
heparin. Once the aorta is clamped proximally and distally if the distal pressure is below
50 mmHg, distal aortic bypass is instituted. The distal pressure is maintained above 60
mmHg. This can consist of left atrial-to-femoral artery bypass using a centrifugal pump,
or alternatively, one can use a heparin-bonded shunt from the aortic arch to the
descending thoracic aorta or femoral artery. Upper extremity pressure is maintained at
about 120 mmHg systolic. Once the aortic coarctation is resected, reconstruction with a
tube graft or end-to-end anastomosis is carried out with 4-0 polypropylene suture
mounted on a small needle.
For patients undergoing reoperation for recurrent coarctation, mobilization of the aorta
for end-to-end anastomosis may be difficult and cause excessive blood loss. In these
patients, the aorta is clamped proximal to the left subclavian artery, and a
glutaraldehyde-treated pericardial patch is used to enlarge the aorta from the base of
the subclavian artery to the distal aorta. There should be no gradient between upper and
lower extremities upon release of the clamps. During closure, special care is taken to
control intrathoracic bleeding and to check chest-tube and pericostal suture sites.
Hypertension is controlled and is treated aggressively in the intensive-care unit.

Abdominal pain and distension may be present in 5 percent of patients postoperatively.
Management is usually conservative. The patient is given nothing by mouth (NPO) for at
least 24 hours postoperatively until bowel sounds return.
In older patients who have a coarctation and also require coronary revascularization, we
prefer a median sternotomy approach with cannulation of both the ascending aorta and
the femoral artery. After completing the coronary revascularization, an adequately sized
Dacron graft is placed between the ascending aorta and the proximal abdominal aorta
through the diaphragm.
Outcome following repair is generally good, and follow-up may be assisted with
transesophageal echocardiogram, computed tomographic (CT) scan, or magnetic
resonance imaging (MRI). [34 ] , [35 ] The latter is useful to detect aneurysm formation or
recoarctation. Recoarctation is defined as a gradient greater than 20 to 30 mmHg at
rest. Balloon angioplasty can be an alternative to surgery for this situation. Results in
children and young adults are good, with about 80 percent success and 2.5 percent
mortality. These results are likely to improve as experience with this technique grows.
The possibility of coronary disease and systemic hypertension requires lifelong
monitoring.
Tetralogy of Fallot
Tetralogy of Fallot is the most common cyanotic heart lesion to reach adulthood. It
basically consists of stenosis of the right ventricular outflow tract (RVOT) and pulmonary
valve in association with a ventricular septal defect. In the current era, repair is carried
out in infancy or childhood, and long-term results are excellent, although reoperations in
adulthood may become more common.
Palliated patients usually require correction either because of progressive cyanosis as

they outgrow the shunt or because of the effects of volume overload from a large
systemic-to-pulmonary artery shunt such as a Waterston or Potts shunt. Additionally, a
small number of patients with classic Blalock-Taussig (B-T) shunts may have adequate
palliation until adulthood. Stewart et al. [36 ] reviewed long-term results with the classic
B-T shunt. Two of 85 patients had either upper-extremity ischemia or claudication.
Treatment for this consisted of a carotid-to-distal subclavian bypass graft. At 2-year
follow-up, 97 percent of the patients palliated when they were older than 1 month of age
remained well, while only 87 percent of patients palliated before 1 month of age
remained well. At 4-year follow-up, these numbers fell to 87 and 54 percent,
respectively.
Definitive procedures in adults require takedown of previously placed shunts. On the

right side, the shunt is dissected out behind the superior vena cava. On the left side,
care must be take to avoid injury to the phrenic nerve.
Takedown of a Waterston shunt is done from within the pericardium. The right
pulmonary artery is mobilized. The aortic cannulation site for cardiopulmonary bypass is
placed distally. When cardiopulmonary bypass is initiated, shunt flow is controlled with a
clamp flush with the aorta, and the patient is cooled to 20°C. Cardioplegia is
administered after aortic clamping. With the heart arrested and at low flow, the shunt
clamp is released, and the anastomosis is excised from the aorta. This mobilizes the
right pulmonary artery. The aorta is closed primarily. The incision in the right pulmonary
artery is extended proximally and distally to relieve any stenoses. The right pulmonary
artery is reconstructed with a pericardial or Gore-Tex patch.
Takedown of a Potts anastomosis usually requires a period of low flow or circulatory

arrest. [37 ] The shunt is occluded by pressure on the left pulmonary artery while blood is
cooled to under 20°C. With the head down, the left pulmonary artery is incised and
opened under low flow so that the opening to the aorta can be occluded with a Hegar
dilator. Under low flow or circulatory arrest, the aortic side is closed primarily, and the
pulmonary artery is repaired with a Gore-Tex or pericardial patch (Fig. 47-4) .
Long-term results are documented in patients who had complete repair of tetralogy of
Fallot in the late 1950s and early 1960s. [38 ] [41 ] Actuarial survival ranges from 77 to
90 percent at between 20 and 30 years of follow-up. Late mortality from cardiac causes
accounts for about two-thirds of all late deaths. Between 40 and 60 percent of these are
sudden and presumed to be due to arrhythmias or to heart block. Other causes include
right ventricular outflow abnormalities (obstruction, pulmonary incompetence, aneurysm)
and congestive heart failure partly related to residual VSDs, which are reported in 18
percent of all operated patients in these early series. In the current era, residual VSDs
are expected after less than 5 percent of tetralogy repairs. [42 ]
Residual VSDs are reoperated if the QP/QS ratio is greater than 1.5:1 or if there are
associated residual abnormalities such as RVOT stenosis or regurgitation or
tricuspid-valve regurgitation.
Pulmonary-valve regurgitation is very common after repair of tetralogy of Fallot, since

approximately 70 to 80 percent were repaired in the past with a transannular patch.
Even though exercise capacity may be decreased, the vast majority of patients tolerate
this well unless they have an additional residual VSD or pulmonary-artery stenosis or
enlargement. In addition, we see patients without these associated residual defects
who slowly develop right ventricular dilatation and eventually tricuspid regurgitation. This
may progress over 20 years, and patients increasingly present late as they become
symptomatic from combined pulmonary and tricuspid valve regurgitation. [43 ] In view of
the risks of sudden death and the progressive nature of the RV dilatation, we prefer to
operate on these patients. The tricuspid valve can almost always be repaired with a
pericardial strip annuloplasty. The right ventricle is remodeled by resection of redundant
scar and the outflow tract patch. The pulmonary valve is replaced either with a
cryopreserved homograft valve if the distance between outflow and pulmonary artery
bifurcation is adequate (Fig. 47-5) or with an outsized porcine valve placed within the
RV outflow tract just below the annulus where there is more room for the valve. An adult
patient can accomodate a 27- or 29-mm valve placed in this position.
Aneurysm of the RVOT occurs with the use of an excessively large transannular patch,
particularly when it is a pericardial patch. Such dilatation can be further aggravated by
the presence of residual RVOT obstruction. [42 ] Although risk of rupture is low, the
patch tends to expand and should be treated with resection and usually with valve
insertion.
Residual RVOT obstruction may occur at the infundibular level, at the valve, or more
distally. If it is an isolated lesion, it is usually operated on if the RV-to-LV pressure ratio
is greater than 0.75. If it is associated with other residual lesions, particularly with
progressive RV dilatation, it is operated on earlier. The obstruction is relieved, and in
the adult, we generally prefer pulmonary valve insertion.
Sudden death after tetralogy repair accounts for a significant number of the late deaths.
[44 ] , [45 ] , [239 ] It usually occurs in patients who have had a right ventricular incision
and have right ventricular dilatation combined with an elevated RV pressure above 60
mmHg. Nonsustained ventricular arrhythmia is difficult to interpret. Electrophysiologic
studies may show a focal area that can be treated by catheter ablation. If there are
associated significant hemodynamic abnormalities, they should be corrected.
Pacemakers are required in less than 4 percent of patients late after tetralogy repair.
[42 ] They may be indicated for late sick-sinus syndrome or late block. If there is right
bundle branch block combined with left anterior hemiblock, a pacemaker should be
considered. Electrophysiologic studies are used to assess conduction in the posterior
bundle, and if this is abnormal, a permanent pacemaker is implanted.
Patients who have had tetralogy repair in late childhood may have other sequelae that
may have an impact on late reoperative surgery. The long-term volume load from a
large shunt may produce permanent left ventricular dysfunction. The pulmonary vascular
resistance may be elevated. Mild or even moderate aortic valve regurgitation is not
uncommon due to dilatation of the aorta and should be repaired at the time of
reoperation.
Older patients and particularly those with risk factors for coronary artery disease should
undergo coronary angiography preoperatively and may require concomitant
revascularization. Our oldest tetralogy-repair patient is a 65-year-old man who also
required bypass to five vessels.
Bicaval cannulation is used, and myocardial protection comprises antegrade and

retrograde cold-blood cardioplegia followed by warm-blood cardioplegia and
warm-blood reperfusion. Mediastinal bleeding is usually increased, and the use of
antifibrinolytic agents should be considered. Aorta-to-pulmonary artery type shunts must
be controlled as soon as cardiopulmonary bypass is instituted. Ventricular distension is
avoided with venting of the left ventricle. The VSDs may be approached through the
right atrium or through the right ventricular scar or patch. A Gore-Tex or
glutaraldehyde-treated pericardial patch may be used. The repair should include a
competent pulmonary valve, which may require valve insertion.
The results of primary repair of tetralogy in adults are good. Presbitero et al. [46 ]
reported an operative mortality of 2.8 percent in a series of 40 adults. There were two
residual VSDs and two patients with residual RVOT obstruction. The results of
reoperative surgery in adults are also generally good. [47 ] , [48 ] Mortality ranges from 7
to 20 percent. This includes results from all previous eras, and one anticipates
improved results for the current era. In the series from the Mayo Clinic reported by
Uretzky et al., [47 ] 5 patients (12 percent) had a second reoperation. Pome et al. [48 ]
reported an actuarial survival of 87 percent for 22 patients at 20-year follow-up for this
particular cohort. Eighty-nine percent of patients were NYHA class I, and only 1 patient
(5.5 percent) was in class III. Two women experienced normal pregnancy. Forty-four
percent had persistent cardiac enlargement on chest x-ray, and 3 patients eventually
needed a permanent pacemaker.
Pulmonary Atresia and Ventricular Septal Defect
The anatomy of this lesion is very variable. True pulmonary arteries may be absent, or if
present, they may be hypoplastic, discontinuous, or supply only a portion of the lungs.
Collaterals usually develop stenoses by about 6 months of age. Collaterals may be
either dominant, supplying most of the lungs, or nondominant, with true pulmonary
arteries supplying most of the lungs. Collaterals also may overlap the true pulmonary
arteries in their distribution.
Most patients with this lesion die in childhood if they are unoperated. There is a group,
however, with pulmonary blood flow from collaterals that is adequate for oxygenation but
not excessive enough to cause severe heart failure.
When these patients present as adults, the pulmonary atresia with ventricular septal
defect (PA-VSD) may be unoperated, as was the case in 62 percent of our adult
patients, or they may have had prior palliative procedures such as shunts or
unifocalization procedures. Approximately two thirds of adult patients can be offered
surgical treatment.
Others are excluded because of advanced ventricular dysfunction and/or pulmonary

hypertension. [49 ] The preoperative evaluation includes angiography to delineate the
true pulmonary arteries as well as all collaterals. Pressures are measured distal to
stenoses in all vessels. Lung scans are helpful in assessing pulmonary vascular
resistance on each side. Electron-beam CT scans are useful to assess collaterals. Left
ventricular function and aortic-valve competence must be assessed. About one half of
adults with this condition have mild or moderate aortic-valve regurgitation.
Many adults with PA-VSD are symptomatic and limited in exercise capacity. Even if
they have minimal symptoms, their long-term outlook is poor due to volume overload
that produces left ventricular dysfunction and heart failure.
Early or staged biventricular repair requires adequately sized pulmonary arteries,

including true pulmonary arteries and collaterals, and acceptable pulmonary vascular
resistance.
If true pulmonary arteries are dominant and adequate in size, immediate complete
repair may be possible. This involves coil embolization or ligation of redundant
(nonessential) collaterals and anastomosis of essential collaterals to the true pulmonary
artery if they can be reached from the front. [50 ] The VSD is closed, and the RV is
connected to the pulmonary artries by a conduit using an aortic homograft.
If the collaterals are dominant, we prefer a staged approach. [51 ] The side requiring
more immediate attention or with reduced flow is chosen first. If there is only a single
large collateral posterior to the hilum of the lung, it can be disconnected from the aorta
and connected to the ascending aorta or subclavian artry by an adult-sized Gore-Tex
graft or pericardial tube. If multiple collaterals are present, they are disconnected from
the descending thoracic aorta and connected to a pericardial tube using the technique
shown in Fig. 47-6 . The pericardial tube is brought to the anterior mediastinum where a
shunt from either the subclavian artery or the ascending aorta is constructed to provide
controlled pulmonary blood flow. It is important not to oversize the shunt and to target a
pressure about one-third systemic, depending on the pulmonary vascular resistance.
About 6 months is allowed between the right and left lung stages (Fig. 47-7) . After each
stage, the patient is studied by angiography and with a lung scan to evaluate the
distribution and resistance of the circulation. If these are acceptable, the definitive
procedure is carried out.
At the time of complete correction, the VSD is closed. The right and left unifocalization
grafts are connected to each other by an adult-size transverse Gore-Tex graft placed
either anterior or posterior to the aorta. The RV is connected to the transverse graft
using an aortic homograft (Fig. 47-8) .
At UCLA, we have performed 90 unifocalization procedures in 66 patients, of whom 16

were adults aged 17 to 35 years old. The early mortality is 10 percent, with no deaths in
the adults.
We have performed biventricular repairs in 23 patients, of whom 11 were adults aged

19 to 34. There were 2 deaths, with no deaths occurring in the adult group.
In view of these results, we believe that adults with this lesion should be fully evaluated
as soon as diagnosed. If they have anatomy and physiology amenable to a complete
repair, they should undergo staged unifocalization procedures. Because of the
ultimately poor results of nonsurgical management, this is indicated even in patients
who are not severely symptomatic.
Transposition of the Great Arteries
In the current era, atrioventricular concordance with associated ventriculoarterial

discordance is treated with the arterial switch procedure in early life. [52 ] , [53 ]
The majority of adults with this defect are those who previously underwent an arterial
switch with a Mustard or Senning procedure. Such patients have the morphologic right
ventricle acting as the systemic ventricle, and the natural history of such anatomy is well
documented. [54 ] There is about 7080 percent survival at 20 years; 10 percent of
patients have symptomatic right ventricular dysfunction, and about 60 percent have
dysfunction that becomes evident at exercise testing. Additionally, atrial arrhythmias are
common, and many patients are in junctional rhythm at 10 years of follow-up. Baffle
obstruction can lead to vena caval or pulmonary venous obstruction. [55 ]
Webb et al. [56 ] documented late complications after Mustard's operation. Ongoing
late mortality was 0.5 percent per year. Causes of late death for isolated transposition
were arrhythmia (12 percent), sudden death (20 percent), pulmonary-vein stenoses (12
percent), pulmonary vascular disease (6 percent), and myocardial dysfunction (18
percent). An additional 30 percent of deaths had a combination of these causes, and in
10 percent of patients, cause of death was unknown. Fifteen percent of surviving
patients required a pacemaker at 20 years of follow-up. In many cases there also was a
need to suppress supraventricular arrhythmias.
Reoperation following Mustard's procedure was necessary in 22 percent of patients.

Causes included baffle leak, baffle obstruction (vena caval or pulmonary-vein stenosis),
tricuspid regurgitation, and left ventricular outflow-tract obstruction. Superior vena caval
(SVC) obstruction occurs in about 10 percent of patients with the Mustard procedure,
especially if there is inadequate resection of the superior part of the interatrial septum.
The Senning operation has had similar results. [52 ] Although initially abandoned, it was
revived in the 1970s because there was more potential for growth with less foreign
material. [57 ] Other advantages postulated were less risk for stenosis of the venae
cavae. Turina et al. [58 ] reviewed long-term follow-up in 220 patients surviving an
average of 10 years. Actuarial survival was 89 percent at 10 years and 82 percent at 20
years. Survival rate was improved for patients operated on after 1978. There were 22
late deaths, with sudden death and heart failure accounting for 14 of these. There was a
tendency for these two events to occur in patients with complex transposition. Eighteen
patients underwent 23 reoperative procedures, two thirds of which took place in the first
2 years postoperatively. Causes were stenosis of the SVC and inferior vena cava (IVC)
(8), residual atrial and ventricular defects (11), and stenosis of the pulmonary venous
obstruction (4). The cumulative incidence of pacemaker insertions was 10 percent at 20
years.
Reoperation for obstruction of either systemic veins or pulmonary veins almost always
can be accomplished by incision of the site of obstruction and patching using a
pericardial patch when it is available. Usually, with repair of the caval part of the baffle,
the functional left atrium is also enlarged.
For patients who present with right ventricular (RV) dysfunction and tricuspid-valve
regurgitation, the choice of therapy is more complex. If the major problem is
tricuspid-valve regurgitation in the presence of relatively well-preserved RV function, we
prefer to repair or replace the tricuspid valve. If RV function is significantly depressed,
the LV function and the left ventricular outflow tract (LVOT) and pulmonic valve are
evaluated. If LV function is good and there is no fixed LVOT obstruction or pulmonic
stenosis, the patient is a candidate for LV preparation and the arterial switch
procedure. [59 ] If there is LV dysfunction, however, and/or fixed LVOT obstruction, this
will not be possible, and the patient is a candidate for either a high-risk tricuspid-valve
repair or replacement or heart transplantation when symptoms warrant.
The results of tricuspid valve repair or replacement in suitable patients are generally
good. Care must be taken to avoid conduction tissue that is very vulnerable at the
junction of septal and posterior leaflets.
Preparation of the LV requires PA banding to a pressure of 6070 percent of systemic

pressures initially and then delayed rebanding to systemic pressures. Six months to a
year may be required to achieve this and to obtain a normal LV wall thickness. Once
this is achieved, the arterial switch is performed. The atrial baffle is also removed, and a
new atrial septum is constructed in the anatomic position (Fig. 47-9) .
Results of staged conversion to arterial switch for the failing right ventricle (RV) are
reported by Cochrane et al. [60 ] Twenty-four patients were entered into a program an
average of 7 years after atrial switch. Twenty of the 24 patients underwent staged
conversion with interim pulmonary artery banding to prepare the left ventricle (LV), while
4 patients had direct conversion. Early mortality was 12.5 percent, and 1-year actuarial
survival was 80 percent. Seven patients had late aortic valve dysfunction. The authors
point out that retraining the left ventricle in the mature heart is a longer process than in
the neonate and that there is less margin for error when placing a band in a fully
septated heart.
The band is placed and adjusted so that the final LV pressure is 70 percent of maximal
LV pressure when the band is fully tightened for 23 seconds. The authors also comment
on the need to occasionally loosen the band after the first 24 hours of observation in the
intensive-care unit and on the use of orotic acid to augment the hypertrophic response.
After 1 week, patients are taken to the catheterization laboratory to consider the need
for further tightening the band. When such reoperations are necessary, the training
period generally lasts about 1 year, after which time the LV peak pressure is greater
than 0.75 systemic, the LV wall thickening is normal (indexed), and a rise in peak LV
pressure to suprasystemic levels is observed in response to isoproterenol.
Single-Ventricle and Tricuspid Atresia: The Glenn Operation and Modified

Fontan
Single-ventricle and tricuspid atresia are currently treated by bypass of the right side of
the heart with direct connection of systemic veins to the pulmonary arteries using either
the Glenn procedure for partial bypass or the Fontan procedure for complete bypass of
the heart. [61 ]
These procedures are usually done in childhood, but there are patients who have been
well-balanced or who have been palliated until adulthood and present for definitive
repair.
The hemodynamic criteria are shown in Table 47-3 . These procedures require
sufficiently low pulmonary artery (PA) pressure to ensure that the systemic venous
hypertension that ensues is tolerated.
THE GLENN SHUNT
On the basis of hemodynamics and ventricular function, patients are stratified into low-
and high-risk categories. Patients considered to be borderline for a Fontan procedure
because of risk factors are usually better treated by a bidirectional Glenn shunt. [62 ] As
long as the PA pressure after the Glenn is less than 20 mmHg, it is usually tolerated and
comes down with time.
The Glenn shunt has the advantage of directing desaturated venous blood to the lungs
and is therefore more efficient than a systemic artery-to-PA shunt, which imposes a
volume load on the left ventricle.
If additional lesions are present, such as subaortic obstruction or AV valve regurgitation,

the Glenn shunt is done on cardiopulmonary bypass. If intracardiac repair is not
necessary, the Glenn shunt is performed without bypass, using a temporary SVC-to-RA
shunt while the SVC is clamped, divided, and anastomosed to the pulmonary artery
(Fig. 47-10) .
In the adult, the SVC accounts for only 35 percent of the systemic venous return. We
therefore prefer to leave an additional small source of pulmonary blood flow, such as a
banded pulmonary artery or a small systemic arterial shunt. The total estimated Q p /Q s
for all sources of pulmonary blood flow should be about 1.
In the long term, the Glenn shunt loses its effectiveness due to development of venous
collaterals. [63 ] These can be coil-embolized by catheter technique. In addition, the late
development of pulmonary AV fistulas may reduce oxygenation. If the systemic source
of pulmonary blood flow decreases due to closure of a systemic artery-to-PA shunt and
a Fontan procedure is not possible, an axillary artery-to-vein fistula is effective in
increasing pulmonary blood flow without thoracotomy. [64 ]
THE MODIFIED FONTAN PROCEDURE
If the hemodynamics in adult patients indicate a relatively low risk for the Fontan
procedure, they can proceed without a preliminary Glenn shunt. Other adult patients are
candidates after a preliminary Glenn shunt that may provide prolonged palliation. The
procedure is similar to that in younger children and has been well described. [61 ] , [65 ]
In these chronically cyanotic patients, bleeding is a common problem, and

antifibrinolytic agents such as aprotinin should be considered. Systemic artery-to-PA
shunts are controlled prior to bypass. The SVC is anastomosed to the PA, and a lateral
tunnel is constructed with a Gore-Tex patch. We routinely use a snare-controlled
adjustable ASD, which may be essential to reduce venous pressure early
postoperatively (Fig. 47-11) . In adults, consideration also may be given to the use of an
extracardiac conduit, such as a Gore-Tex graft, or the use of a pericardial tube. [66 ]
The snare is tightened in the catheterization category within twelve months
postoperatively depending on measured pressures.
The UCLA experience with 21 adults (aged 19 to 40 years) undergoing the Fontan
procedure was reviewed recently by Gates et al. [67 ] Operative mortality was 5 percent.
Actuarial freedom from reoperation at 12 years was 69 percent. There was one late
death due to an arrhythmia. Among three reoperations, one was for atrial fibrillation 11
years after an RV-to-PA conduit that was converted to a lateral tunnel. Another
developed obstruction of a Dacron RV-to-PA valved conduit 1 year postoperatively and
required replacement with a Gore-Tex conduit. A third patient developed an atrial baffle
leak 4 years after a RA-to-PA Fontan procedure. This patient was revised to a lateral
tunnel Fontan with a snare-adjustable ASD.
LATE REOPERATIONS AFTER THE FONTAN PROCEDURE
The long-term results after the Fontan procedure have shown that a significant number
of patients require late reoperation. [61 ] , [68 ] Most of these are for patching
obstruction. It is important to keep in mind that with the newer lateral tunnel modification
using Gore-Tex, it is likely that this will become less frequent. The highest incidence (13
percent) was for patients in whom a valved conduit was used. Obstructions are
aggravated by the use of Dacron, in which pseudointimal build-up leads to obstruction
or dissection. Older age at operation remains a risk factor for late death after the
Fontan procedure. Revision of the AV valve closure in double-inlet ventricles or repair of
the AV valve in tricuspid atresia is needed in more than 5 percent of patients.
Protein-losing enteropathy can occur in about 10 percent of patients. This complication

is sometimes difficult to diagnose. [61 ] , [68 ] It is characterized by a low serum albumin
level and peripheral edema with or without diarrhea. It is associated with a 20 percent
mortality. This seems to occur more frequently in patients with heterotaxia, polysplenic
syndromes, as well as in those with elevated pulmonary vascular resistance or
abnormal systemic venous drainage. Conversion to a lateral tunnel or transplantation
should be considered for these patients.
Arrhythmias are common after the Fontan procedure. [69 ] Approximately 1020 percent
require pacemaker insertion for sick-sinus syndrome. Supraventricular arrhythmias,
including atrial flutter and fibrillation, are more common after the RA-to-PA type of
Fontan procedure, which was the most common modification until 1982. Progressive
RA dilatation results in atrial arrhythmias and thromboembolism. When the RA is
enlarged, warfarin anticoagulation is indicated. Such patients are now considered for
reoperation with conversion to either a lateral tunnel Fontan or to an extracardiac
conduit with resection of the enlarged RA. [70 ] If additional surgery is required for a
Fontan patient with an RA-to-PA conversion, simultaneous conversion to a lateral tunnel
is recommended if the RA is enlarged.
We have had no deaths in 8 patients (aged 7 to 36 years) who have undergone lateral
tunnel conversions. Particular to this procedure is that cyanosis from the adjustable
fenestration is poorly tolerated after the first few postoperative days. Five patients have
required permanent pacemaker insertion for sick-sinus syndrome or AV-node
dysfunction. One patient required amiodarone, and another patient underwent
radiofrequency ablation of the AV node because of development of
pacemaker-induced tachycardia.
Ebstein's Anomaly
Ebstein's anomaly refers to a condition with downward displacement of the septal and
posterior leaflets of the tricuspid valve into the right ventricle, leaving an atrialized
portion of the right ventricle. [71 ] It usually occurs in the pulmonary ventricle but can
occur in the systemic RV in corrected transposition. It is associated with varying
degrees of tricuspid-valve regurgitation, and the valve may cause obstruction due to
extensive RV muscular attachments. There may be an associated ASD in about 50
percent of patients or pulmonary stenosis. Aberrant conduction pathways are present in
5 percent of patients. [72 ] , [73 ]
Patients may present with cyanosis due to the ASD and tricuspid regurgitation.
Arrhythmias are the presenting symptom in 40 percent of adolescents and adults. [74 ] ,
[75 ] They also may present with heart failure due to tricuspid regurgitation that usually
results in massive enlargement of the RA.
Arrhythmias due to an aberrant tract may be treated by catheter ablation. Atrial flutter or
fibrillation due to massive RA enlargement requires surgical repair.
The indications for surgery are symptoms unresponsive to medical therapy. With
improved results of valve repair, we recommend treatment before massive
cardiomegaly develops. If severe tricuspid regurgitation or progressive cardiac
enlargement is present, surgery should be considered.
The preoperative echocardiogram is helpful in predicting the ability to repair the valve. If
the anterior leaflet is adequate in size and is not extensively bound down by muscular
attachments, repair is almost always possible.
Two main techniques of repair have been described. Danielson was the first to
demonstrate the ability to repair these valves and avoid replacement. [76 ] Repair
includes plication of the atrialized RV back to the true annulus and an annuloplasty.
Carpentier et al. [77 ] described a technique in which the atrialized RV is plicated
perpendicular to the valve annulus toward the apex of the heart. The displaced leaflets
are detached from the RV at their base and resutured to the true annulus (Fig. 47-12) .
Both techniques are effective, and we use both of them selectively, depending on the
anatomy. We perform an annuloplasty using a glutaraldehyde-treated strip of
pericardium. The redundant RA wall and appendage are excised, and the ASD is
closed.
Repair is rarely possible with Ebstein's anomaly in the systemic ventricle, as occurs in
corrected transposition. Valve replacement is usually required in this condition.
The results of repair of Ebstein's valve are excellent. The early mortality is 714 percent,
and the incidence of late tricuspid valve incompetence is low (<10 percent). At UCLA,
24 children and adults with Ebstein's anomaly were operated on between 1982 and
1994 with no deaths. Fourteen patients had tricuspid valve repair, and seven had
replacement. In three patients, the anomaly was in the systemic ventricle, and two of
these required valve replacement.
TRICUSPID VALVE REPLACEMENT
Repair of the tricuspid valve may not be possible in up to one third of patients. The
tricuspid valve tissue is excised, leaving a remnant of the anterior and septal leaflets in
the area adjacent to the conduction tissues to avoid placing sutures in the AV node. If
this is not possible, we use a glutaraldehyde-treated pericardial patch to bridge the
triangle of Koch to avoid placing sutures in the area of the bundle of His [78 ] (Fig.
47-13) . The patch is fashioned in a triangular shape and is sutured to the RA behind the
anterior lip of the coronary sinus and posterior to the tendon of Todaro, coming back to
a point anterior to the anteroseptal commissure. The patch is then sutured to the
remaining sewing ring.
We prefer to use a porcine xenograft valve. In the absence of atrial arrhythmias or

severe atrial wall thickening, this allows anticoagulation with aspirin only. Generally,
tissue valves are preferred in the tricuspid position because of the risk of thrombosis of
a right-sided mechanical valve. There is, however, a recent report of good results with
the St. Jude valve in the tricuspid position. [79 ]
In corrected transposition, the systemic AV valve is usually replaced with a mechanical

valve.
Transplantation
Adults with congenital heart disease may not be amenable to palliation or repair due to
severe ventricular dysfunction or pulmonary vascular disease. They may be candidates
for heart, lung, or heart-lung transplantation. In addition, patients previously repaired
may deteriorate and may have no other options.
HEART AND HEART-LUNG TRANSPLANTATION
In symptomatic patients who are NYHA class III or IV and who have an acceptable
pulmonary vascular resistance, heart transplantation is usually feasible. Anomalies of
systemic and pulmonary venous return can be corrected. Deformities of the pulmonary
artery can be repaired. This may require quite extensive repair, particularly in some
patients after the Fontan procedure (Fig. 47-14) . Dextrocardia and transposition may
be challenging, but with reconstruction of the left atrium and the use of cava-caval
anastomoses, transplantation is almost always possible [80 ] , [81 ] (Fig. 47-15) .
Patients with pulmonary vascular disease, good biventricular function, and relatively
simple congenital anomalies such as ASD, VSD, or PDA are candidates for
intracardiac repair and single- or double-lung transplantation. [23 ] [25 ] The mortality for
these procedures is relatively high (up to 20 percent), but in view of the scarcity of
heart-lung donors, this may be the only option (see also Chap. 50).
When pulmonary vascular disease is combined with complex cardiac disease or poor
ventricular function, heart-lung transplantation may be the only option. [26 ] , [27 ]
Because of the frequency of previous thoracotomy or median sternotomy for previous
surgery in these patients, the risk of massive bleeding is high. This has been particularly
true in patients with multiple aorta-to-pulmonary artery collaterals.
There is a large experience in heart and lung transplantation from both Stanford
University and the National Heart and Lung Institute in the United Kingdom (Harefield
Hospital). Fifty-one of 109 patients at Stanford had Eisenmenger's syndrome or
complex congenital heart disease (19811994). [26 ] Operative mortality was 12 percent
overall, and actuarial survival at 1 year was 68 percent. Five-year actuarial survival was
43 percent. In the experience from Harefield Hospital, 303 patients underwent heart and
lung transplantation between 1983 and 1991. [27 ] Of these, 93 patients had
Eisenmenger's syndrome. Early mortality was 30 percent, and 2-year actuarial survival
was 51 percent. Long-term survival was limited mainly by obliterative bronchiolitis,
which is estimated to occur in up to 40 percent of patients after 4 years.
THE MAJOR HISTOCOMPATIBILITY COMPLEX
An allogeneic organ is one that is transferred from one individual to another of the same
species but with differing genetic repertoire. A donor heart or lung is immunologically
incompatible with the host tissues, and an immunologic reaction or alloresponse is
directed against donor proteins or antigens located on the surface of the endothelial,
mesenchymal, and epithelial cells of the allograft.
The major histocompatibility locus (MHC) is a complex of polymorphic genes whose

glycoprotein MHC molecule products are expressed on the surface of cells. The protein
products are the principle determinants of whether an organ is deemed self or non-self
and the primary targets of the immune response to allografts. The MHC likely has
evolved to guide the development of T-lymphocytes that, when mature, would have a low
affinity to self and to use the reaction to self as a way in which foreign peptides are
recognized (MHC restriction). In humans, because the MHC molecules were first noted
on the surface of white blood cells, they have become known as human leukocyte
antigens (HLA). Immune responses to organs with different HLA gene types define the
alloresponse in humans. The HLA molecules arise from a 3500 kKb area on the short
arm of chromosome 6 that represents approximately 0.1 percent of the human genome.
The telemetric end of the HLA region contains genes that encode HLA molecules A, B,
and C, which have been described as class I, as they stimulate cytotoxic T-lymphocytes
(CD8). The central area of the HLA complex (centromere) contains genes that encode
HLA class II molecules DP, DQ, and DR that bind foreign antigen that is recognized by
the pro-inflammatory CD4 T-lymphocytes. There is a third region within the HLA
complex termed class III that falls between the telemetric class I and the centromeric
class II regions. The class III area does not produce MHC molecules but encodes for
complement protein C4, C2, BF, and tumor necrosis factor (TNF). [1 ]
The class I molecule consists of an immunoglobulin-like heavy chain (Fig.48-1) . Its

proximal or membrane-bound portion that is nearest the cell's surface provides for a
transmembrane anchor and consists of an alpha-3 domain that combines with a
polypeptide, termed beta microglobulin, which is encoded on chromosome 15. The
distal portion of the class I molecule is formed by alpha-1 and alpha-2 domains, which
combine to form a grooved site for binding of the antigenic peptides. The class II
molecule consists of heterodimers of immunoglobulin-like alpha and beta chains
(Fig.48-1) . The proximal domains support the distal alpha-1 and beta-1 regions that
form the peptide binding site.
Tissue compatibility requires the determination of HLA A, B, and DR types. Variations

in each HLA protein are extensive and are termed polymorphisms. There are at least
20 definable antigens at HLA A, 40 at HLA B, and 10 at HLA DR. [2 ] The inheritable
differences at each of the HLA A, B, and DR loci are called alleles . Each individual has
two alleles, one maternal and one paternal, at each MHC locus (i.e., two HLA A, two
HLA B, and two HLA DR) that direct expression of one glycoprotein product each.
These proteins are co-expressed on the cell's surface. Because class I and class II
genes are closely linked, this group of loci is inherited as a continuous unit or haplotype.
The antigen present in the donor but not in the recipient is a potential target for
alloreactivity and is thus termed a mismatch . The single DR locus can have 0, 1, or 2
mismatches, and the combination of HLA A, B, and DR loci can be mismatched for 0
through 6 antigens. [2 ]
There are several large single-institution studies that examine the effect of HLA
matching on outcome in cardiac transplantation. Smith et al. recently reported results
from 1,135 heart transplants performed between 1980 and 1994. [3 ] Of them, 826 had
valuable typing data, and among these patients the authors showed an association
between HLA DR mismatching and the number of episodes of rejection in the first 3
months after transplant. Rates of rejection during this time period were 0.80, 1.22, and
1.44 for 0, 1, and 2 mismatches, respectively. A similar association was not present for
HLA A and B matching. They also showed a significant association between the
degree of HLA DR matching and actuarial graft survival at 1, 5, and 10 years. At 1 year
patients with two DR mismatches had a 14 percent lower survival compared to those
with none. This gap widened to 24 percent at 10 years. These authors advocate
prospective DR matching and have been successful in applying this policy to a
substantial number of recipients at their institutions.
Sheldon et al. analyzed 157 consecutive cardiac transplants and also showed an
important effect of HLA-matching at the DR locus (only) on the frequency of rejection
post-transplant. [4 ] The frequency of rejection in the first year dropped from 33 to 30 to
15 percent as the number of mismatches decreased from 2 to 0. In a report from the
Texas Heart Institute, Kerman and colleagues reviewed 448 heart transplants. [5 ] As is
the case with other single-center reports, there were few well-matched patients: One
had no mismatches, 19 had one, and 101 had two HLA A/B (class I) mismatches. No
difference in survival was seen when well and poorly matched patients were compared
either at the class I loci or the class II loci. HLA DR mismatch grade was found to be a
significant predictor of early rejection occurring within 30 days of transplant.
Interestingly, an inverse relationship between HLA A and B mismatches and death from
cardiac allograft vasculopathy was noted. Zerbe et al. analyzed 349 recipients from the
University of Pittsburgh with respect to acute cellular rejection in the first 3 months after
transplant. [6 ] These authors included HLA A, B, and DQ loci: There were 12 patients
with 0-2 mismatches (combined), 60 with 34, 124 with 56, and 41 with 78. There was a
lower incidence of rejection and longer time to onset of rejection as the degree of
mismatching decreased.
Clearly the most important study to date examining the relationship between HLA
matching and outcome in cardiac transplantation is the Collaborative Transplant Study,
published in 1992. [7 ] The large size of this study resulted in an adequate pool of
well-matched recipients who could be compared to less-well-matched patients. This
study evaluated the effect of HLA matching on graft survival in 8,331 recipients. One
hundred twenty-eight patients (1.5 percent) with either 0 or 1 combined HLA A, B, or DR
mismatches were compared to those with 12 mismatches and 36 mismatches. Mean
rates of survival at three years were a striking 83, 76, and 71 percent, respectively.
Multifactorial regression analysis further established that HLA matching had a strong
independent effect on graft survival. The effect on graft survival was most pronounced in
the 6 months after transplant. These investigators did not report the effect of HLA
matching on rejection rates.
Data demonstrating the effect of HLA matching on outcomes in heart-lung and lung
transplantation are sparse. In one study from the University of Pittsburgh, 74 single and
double lung transplant recipients were analyzed, and a strong effect of HLA DR
matching on graft survival was evident (100 vs. 75 vs. 56 percent for 0, 1, and 2 DR
mismatches, respectively). [8 ] Combining HLA A, B, and DR mismatches showed 100
percent survival at 6 months for 0-2 mismatches, 78 percent for 34, and 58 percent for 5
or 6. A recent update from the Collaborative Transplant Study showed a trend toward
improved survival for well matched grafts in both heart-lung and lung recipients, but this
did not reach statistical significance (1,176 patients enrolled in the lung transplant group
and 640 in the heart-lung group). [9 ]
Taken together, the data strongly support the conclusion that HLA matching confers an
important benefit after heart and probably after heart-lung and lung transplantation.
Conventional wisdom deems prospective HLA matching to be unfeasible in thoracic
organ transplantation, but technologic advances may bolster more prospective
matching efforts. PCR techniques now permit typing of lymphocytes obtained from
peripheral blood and allow HLA typing before removal of donor organs. Some groups
have reported impressive advances in achieving prospective HLA matching. One is the
Harefield group, which recently reported that within their donor allocation zone, HLA
typing was available before organ retrieval in 69 percent of cases performed in 1994. [3
] Based on outcome data from their institution, this group has focused on HLA DR
matching only and has seen an increase in prospective matching from 5 to 25 percent
of transplants in a recent 1-year time period and a reduction in acute rejection in those
matched. [10 ] Further advances, particularly in allograft preservation, may allow us to
fully exploit HLA compatibility for the maximal benefit of the patient.
ANTIGEN PROCESSING
HLA class I and class II molecules are not uniformly expressed on the same cells. Donor
hearts and lungs rarely express much HLA protein until after transplantation when
organs can be found to stain prominently for both classes. HLA expression is increased
by the cytokine product interferon (INF) produced by lymphocytes as part of an
inflammatory response (Fig. 48-2) . Class I molecules can be found on the surfaces of
almost all nucleated cells, whereas class II expression is uniquely found on the surfaces
of dendritic cells, B lymphocytes, macrophages, and thymic epithelium. Cells found
expressing HLA molecules are termed antigen presenting cells (APC), and those
specializing in class II are also referred to as professional APCs.
Professional APCs that express class II HLA process and bind fragmented donor MHC
protein shed from the cell membranes and other parts of the allograft (Fig. 48-3) .
Professional APCs can be transplanted with the donor organ, that is, passenger cells,
or can be of host origin. These fragments are known as soluble antigens or exogenous
peptides and are internalized in the APC by endocytosis. They are fixed in cytoplasm to
specific binding on class II molecules before being transported as a unit to the cell
surface. The class II molecule and bound peptide exclusively react with the CD4 subset
of circulating T-lymphocytes. Unlike class II presentation, myocytes from donor hearts
and lung mesenchymal cells present MHC class I molecules bound to protein products
produced from the endogenous breakdown of its own MHC protein (Fig. 48-3) . The
wall-bound MHC molecule with its specific protein then is exposed to CD8 cells that
have become active cytotoxic lymphocytes (CTL) owing to earlier binding to a class I on
a professional APC. The CTL proliferates and kills its target when influenced by IL-2
from active CD4 cells and when co-stimulated by membrane ligands between target
(APC) and the CTL.
The T cell response to allogeneic MHC antigen differs from most other immunologic
reactions because these antigens can be recognized directly by T cell receptors without
the need for the foreign peptide to be processed and presented by the host MHC
molecule. [11 ] , [12 ] In the direct or allorestricted pathway, donor cells are APCs, and
the host T cells respond to their presentation of a donor class I or II MHC molecule that
binds endogenous protein derived from its own MHC family (Fig. 48-4) . [13 ] , [14 ] The
capacity for direct recognition is based on the similarity of allo-MHC antigen and the
host self MHC antigen. This pathway is known to stimulate large numbers of T cells
(perhaps 1 percent), and direct recognition of donor class II and I MHC by host CD4 and
CD8 cells leads to prompt cell-mediated rejection. The indirect or self-restricted
pathway relies on the host-derived APCs that process exogenous foreign MHC
fragments and bind them to host class II and I MHC on their surfaces for presentation to
host T cells. The exact role for the indirect alloresponse is not well characterized, but it
is believed to be a significant contributor to late and chronic rejection when donor APCs
are eventually replaced by those of the host. [10 ] It may be especially important in
xenograft responses where recipient T cells and donor APC cannot make efficient
contact with each other. Also, direct and indirect pathways likely have differential
sensitivities to immunosuppressive drugs.
CD4 cells elaborate various cytokines that amplify the generalized inflammatory
response. Two different phenotypes of the CD4 cells have been characterized and
include TH1 cells, which secrete cytokines INF, and interleukin 2 (IL-2), which stimulates
cell-mediated defense and TH2 cells that secrete interleukins 4 and 10, which stimulate
B-lymphocytes to produce antibodies. [15 ] While mechanisms are evolving, it appears
that the TH1 cells are more likely to arise from class II presentation on macrophages
and TH2 cells from class II presentation by B-lymphocytes. Unlike the donor organ class
I APC, professional class II APCs are rarely killed by their reacting lymphocytes. This
provides for amplification of the response by the limited number of APCs available.
ALLORESPONSE
When a heart or lung allograft is recognized as foreign, the immune system unleashes
cellular and humoral (antibody) attack (Fig. 48-5) . The response usually begins when
host CD4 and CD8 cells bind to donor protein MHC molecules presented by host
(indirect) or donor (direct). The CD8 cells become activated cytotoxic lymphocytes
(CTL), and the activated CD4 cells secrete various cytokines that drive the inflammatory
response. [16 ] IL-2 increases the expression of IL-2R on CD4 cells, driving proliferation
and further differentiation of CD4 cells. The activated CD4 cells secrete additional
lymphokines, including INF, that with IL-2 stimulate the activated CTL cells to bind to the
allograft cells presenting donor MHC protein molecules (direct). The CTL proliferate and
specifically kill the allotarget. A mix of INF and lymphotoxin tumor necrosis factor (TNFB)
acts as macrophage activity factor (MAF). Macrophages release IL-1, which amplifies
the response by driving cells to produce more IL-2. Cytokines also increase class I and
II expressions on donor cells. The humoral response begins as host and B cells are
drawn into the alloresponse by the lymphokines and by their own class I and II cell
receptor engagement with the donor cells. The activated B cells evolve into plasma cells
that produce allospecific antibodies against the donor class I and II HLA molecules and
engage the complement cascade.
There appears to be at least two ways a CTL can kill its target cells. Most NK cells,
activated CD8 (CTL), and most cytotoxic CD4 cells release the protein perforin. [17 ] In
the presence of Ca 2+ perforin polymerizes onto the target cell and causes 1620 nm
pores to open this membrane. These pores are nonselective and result in osmotic
collapse of the affected cell. The other likely method for CTL-mediated cytolysis is by
stimulation of apoptosis or programmed cell death. It is believed that the CTL interacts
with the APO-1/Fas receptor of the target cell, which transmits a signal into the cell that
activates endonucleases and proteases to cause fragmentation of DNA to cause the
cell to dissolve. [18 ]
T-CELL LYMPHOCYTE MATURATION AND ALLOACTIVATION
T cells form receptors (TCR) in the thymus that bind to MHC molecules expressed on
APCs. The TCR is bound to the cell membrane and is joined by five invariant
polyproteins collectively called the CD3 complex . Together the TCR and CD3 form the
TCR complex. [19 ] Genes responsible for the TCR randomly rearrange within the
thymus to provide an astonishing array of potential binding sites (10 [16 ] ) necessary for
diversity. Immature T cells are selected to survive in the thymus based upon whether
and how strongly their TCR binds the HLA class I and II molecules expressed on the
thymic epithelium (Fig. 48-6) . T cells have been said to be restricted by the HLA
molecule with which they have interacted. [20 ] A compatible interaction results in T cell
survival and its ultimate differentiation into either CD8 or CD4, depending on whether it
is bound with class I or class II. It is believed that when T cells react too strongly or too
weakly to HLA molecules in the thymus, they are negatively selected and die of apotosis
DNA fragmentation, presumably to prevent the establishment of clones autoreactive
and impotent cells. In fact, 95 percent of the thymocytes do not survive this selection.
Until the T cells encounter specific antigens in the periphery to which an individual has
been exposed, T cells are said to be naive.
When the TCR expressed on a lymphocyte engages its specific membrane-bound

MHC molecule on an APC, a series of reactions occur in the cell that result in a rise of
intracellular calcium (Fig. 48-7) . [21 ] [23 ] The Cal2+ influx results in the accumulation
of calcineurine, which in turn removes a phosphate from nuclear factor for activating T
cells (NFAT-P). [24 ] NFAT can then enter the nucleus where it promotes transcription of
the cytokine IL-2. IL-2 prompts the appearance of IL-2 receptors (IL-2R) on the surface
of T cells with which it reacts, prompting proliferation and differentiation of the
lymphocyte. Whereas the TCR/CD3 dependent signal is necessary, it alone cannot
completely activate quiescent T cells. Full activation requires a second or co-stimulatory
signal provided by physical contact between various T cell surface proteins known as
integrins and their ligands on the APC surface. [25 ] The accessory molecules
contribute to T cell recognition and activation by functioning as adhesion molecules.
Immunoglobulin super gene molecules CD4 and CD8 are found on the surfaces of CD4
and CD8 T cells, respectively (Fig. 48-7) . They assist in the binding of the T cell to its
MHC peptide of class I or class II specificity and modify the TCR signal. Other
participants include CD2 and lymphocyte function associated (LFA-1) antigens on the T
cell that interact with the APC's LFA-3 and intracellular adhesion molecule (ICAM-1)
(Fig. 48-8) . These react to provide for further and lasting Ca 2+ influx necessary for the
transcription of cytokine. The T cell surface protein CD28/CTLA4 associates with the
B7/B7-2 APC ligands to stabilize the cytokine mRNA. Other T cell integrins combine
with matrix molecules of the allograft. The matrix molecules include fibronectin, lamenin,
fibrinogen, and vitronectin, which can become exposed during inflammation and
provide for co-stimulatory binding sites, linking the immune response to the organizing
framework of all tissues. Another family of cell adhesion molecules called selectins has
been identified on the endothelium and assists in the first contact leukocytes,
macrophages, and platelets to the donor organ by inducing a rolling, sticking, and finally
transepithelial migration. The selectins are up-regulated by the inflammatory cytokine
IL-1, INF, and TNF that are elaborated from immune cells during the alloresponse.
REJECTION OF HEART AND LUNGS
Hyperacute rejection (HAR), which is pathologically associated with edema,

hemorrhage, and thrombosis, occurs when antibodies exist that can immediately bind
to endothelial antigens on the heart or lung. Examples of these antibodies include those
directed against blood group antigens, those reactive with MHC antigens in hosts
previously exposed to allogeneic tissue from blood transfusions and pregnancies, and
finally those xenoreactive antibodies responsible for the reaction against cross species.
Although this topic is detailed in the xenograft portion of this chapter, in essence the
antibodies stimulate the endothelial cells toward several destructive pathways. They
activate the complement cascade that destroys the cell, disrupts the heparin sulfatelike
molecules on the endothelium, and also causes release of vasorestrictive substances
like bradykinin and kallikrein. [26 ] , [27 ] The endothelial cells also express adhesion
molecules and release cytokines that attract various phagocytes and platelets, causing
them to adhere and agglutinate further, leading to thrombosis. This is an extremely rare
process in heart and lung transplantation because patients with preexisting antibodies
to HLA antigens are found during evaluation by exposing their serum to panels of donor
cells that expose most HLA types. If a candidate is determined to react to more than 10
percent of the panel, specific pretransplant crossmatching is recommended between
the donor lymphocytes and candidate's serum.
Acute Rejection
Acute rejection is most common within weeks to months after transplantation. Although
late acute episodes can occur, they often do so in the setting of a change in the balance
of immunosuppression versus host immunity. A decrease in the blood level of
immunosuppressant either by prescription or drug interaction or an upregulation in
alloreactivity owing to viral infection can cause a late allorejection. As discussed in the
alloresponse section of this chapter, acute rejection is both cellular and humoral but
generally is weighted toward the former. Myocardial and pulmonary cytolysis is the
major finding, and disrupted cells tend to localize with CTL CD8 cells. When CD4 and
CD8 cells recognize MHC class II and I alloantigen, a very complicated and
self-enhancing process of cytotoxicity and inflammation disables the allograft. The
histopathology of acute rejection of the heart and lung has been described and graded
for purposes of uniformity (Table 48-1) .
Acute vascular rejection has been primarily used after cardiac transplantation to refer to
depositions of immunoglobulin and complement within the walls of the coronary artery.
[28 ] Although it has been proposed that this is a common form of acute rejection that
can lead to allograft ischemia and dysfunction, many believe that the deposits are
nonspecific and more related to endothelial injury from ischemia or reaction to the use
of mouse anti-CD3 antibody. [29 ] Although some physicians advocate aggressive
therapy when there is a suspicion, most will not treat with increased immunotherapy and
plasma pheresis to mouse antibody unless there is significant allograft dysfunction.
Chronic Rejection of the Heart

Chronic, persistent cell-mediated rejection causes progressive myocardial fibrosis and
dysfunction, but most physicians consider allograft vasculopathy (AV) as the more
troubling and more common form of chronic rejection. AV is known to occur in at least
50 percent of patients within five years of transplantation. [30 ] The obstructive process
can result in near-complete occlusion of the epicardial coronary arteries and causes
micro- and macro-infarction ( Figs. 48-9 and 48-10 ). It has become the leading cause
of death 1 year following cardiac transplantation. The histologic findings demonstrate a
uniform pattern of near-luminal occlusion by intimal proliferation. [31 ] The pattern's
concentric nature differs from that seen in typical atherosclerosis, and the histology
shows fewer accumulations of extracellular lipid. Although both naturally occurring
atherosclerosis and AV demonstrate inflammatory cells within the artery unlike those
observed in the natural process, the T cells in AV encircle the entire vessels (Fig. 48-10)
. Endothelial cells generally remain intact but are known to be dysfunctional based on a
paradoxical response to acetylcholine that releases endothelial-derived relaxation
factor. [32 ]
A number of potential explanations have been offered for the process. Earlier belief that
AV might be due to an arterial injury that occurs during cardiac harvest and implantation
is not tenable as animal models of syngeneic transplants do not develop the lesion. It
has been difficult to correlate any of the usual factors associated with natural
atherosclerosis including hypertension, hyperlipidemia, history of smoking, or prior
atherosclerosis with an increased risk of allograft vasculopathy. Some studies have
suggested that cytomegalovirus (CMV) infection might prompt the atherosclerotic
process and, although there appears to be some association, it has been clearly
demonstrated that cytomegalic infection is not required for the process to occur and the
association may be more an association than cause and effect. [33 ] , [34 ] Immune
staining of these lesions suggests near equal numbers of CD4 and CD8 subtypes and
the endothelium stains briskly for MHC class II antigen after transplantation. [35 ] , [36 ]
Animal data have shown that rodents with MHC mismatches at class I, II and non-HMC
antigens demonstrate variable amounts of AV. Recently, Russell has shown that mice
can develop cardiac AV because of cellular humoral effectors either in isolation or
together. [37 ] Our work with rodent tolerance has shown an absence of AV in animals
with variable chimerism induced by transfusion of bone marrow (Fig. 48-11) . Murase
and Madsen, working with miniature swine, have demonstrated that MHC class I
mismatch is necessary and that anti-CD8 antibody can prevent porcine cardiac AV.
[37a ] , [38 ] Evidence suggests that there is an immune injury that may or may not
persist, and the response of the arterial wall follows a common pathway but is
accelerated with endothelial-derived growth factors prompting physical changes and
relocation of smooth muscle cells. Immunologists are readdressing the relative
importance of the direct antigen presentation pathway in which the donor endothelial
and donor mesenchymal cells present antigen versus the indirect path in which host
APCs present fragments of injured donor endothelial cells. [10 ] It is now believed that
CD4 cells respond to the MHC class II antigen expressed on the endothelium, which
results in an elaboration of the cytokine IL-2. [39 ] The growth factors TNF and IFN are
also elaborated from the CD4 cells that affect mesenchymal cells and macrophages.
INF released activates macrophages to produce other cytokines and growth factors that
promote the proliferation and synthesis of matrix by vascular smooth muscle cells. It is
likely that some of the intimal smooth muscle cells migrate from the media.
Experimental and clinical studies also implicate humoral immunity. Rose showed 16
percent of HLA antibody producers developed angiographic AV compared to only 2.0
percent of nonproducers. [40 ] It has recently been shown that increased levels of
expressions of ICAM-1 and vascular cell adhesion molecule (VCAM-1) are noted in
coronary arteries from transplanted human hearts. [41 ] [43 ] These adhesion molecules
among others serve an important role in the recruitment, adherence, and
transendothelial migration of leukocytes important for the development of AV.
Treatment strategies will remain elusive unless more-complete control of the

alloresponse can be maintained by the newer xenobiotics and monoclonal antibodies
or induction of tolerance. Clinicians are anxious to explore the potential for new
xenobiotics that have demonstrated striking reduction in experimental AV based on
their suppression of the smooth muscle response to the growth factors.
Chronic Rejection of Lung Allografts
It is fascinating that the lung allograft, too, appears to be affected by a chronic process
that limits usefulness of the organ and can affect 3050 percent of recipients within 3
years of pulmonary transplantation. [44 ] The chronic process in the lung leads to
obliteration and fibrotic scarring of the terminal bronchioles, and the histologic features
have been described as obliterative bronchiolitis (OB). Burke first recognized clinical
and histologic features of OB as a long-term complication after heart-lung
transplantation 2 years after the Stanford group initiated successful trials of heart and
lung transplantation. [45 ] Whereas the clinical features describe progressive airway
disease and most notably are detected by a fall in forced expired velocities, the
histologic changes like those of cardiac AV are most interesting and provide insight
into the etiology of the process, including potential therapy. [46 ]
The histological diagnosis of OB requires presence of dense fibrous scarring in the

membranous and respiratory bronchioles that may partially or completely obliterate the
lumen of the airway (Fig. 48-12) . [47 ] Secondary effects include distention of distal
airways and frequent association of secondary acute infection usually with
pseudomonas organisms. Linking cardiac AV and pulmonary OB is the finding of
progressive myo-intimal thickening of the pulmonary arteries and veins associated with
OB. [48 ] As in cardiac AV, in addition to an allogenic response various etiologies have
been proposed for OB and include a response to immune injury and viral injury of the
graft. The lungs and specifically the airways appear to be quite susceptible to ischemic
injury during harvest and perhaps thereafter because the arterial supply to the bronchus
is not directly reestablished. It has been proposed that ischemia to the epithelium
causes an exaggerated and chronic inflammatory response resulting in airway scarring.
OB has accompanied graft versus host disease following bone marrow transplantation
and other autoimmune diseases. [49 ] , [50 ] This, of course, is interesting in an area of
intense investigation as it has been determined that donor macrophages and other
immune cells can be identified for long periods in the donor organ following
transplantation. [51 ] CMV infection can increase donor specific and nonspecific
immune responses. [52 ] There is an increase in the activity of APCs in renal allografts
following CMV infection. [53 ] An increase in INF has been noted in bronchoalveolar
lavage (BAL) cells during infections with CMV, and MHC class II antigens are noted to
have increased expression during the viral infection as well. [54 ] Most transplant
centers believe in this association, although a precise relationship is far from uniformly
accepted. [55 ]
As with cardiac AV, although there may be other facilitating factors, OB is primarily
owing to an alloresponse. Acute rejection appears to be the leading risk factor for the
eventual development of OB. [55 ] [57 ] It has been proposed that acute episodes of
rejection can cause direct injury or prompt a delayed hypersensitivity response. [54 ] An
increased number of cytotoxic natural killer (NK) cells have been found within the
submucosa and epithelium of the airways during acute episodes of rejection. Bronchial
epithelium can increase this expression when immunologically stimulated, and there is
class II-specific lymphocytotoxic activity in the bronchial lavages from OB patients (Fig.
48-13) . [59 ] , [60 ] In a human bronchial epithelial cell line, INF pretreatment induced
adhesion molecules ICAM-1, MHC class I, and II, induced proliferation of lymphocytes.
[61 ] Bronchial and epithelial cells expressed mRNA for growth factors known to
stimulate smooth muscle proliferation and migration. Autopsy studies have
demonstrated an increased number of MHC class II antigen positive dendritic cells in
patients with OB (Fig. 48-14) . [58 ] MHC class I antigen-specific lymphocyte activity
was noted in patients with progressive OB and class II reactivity in transplant recipients
who had a more stable course. [62 ] Along the same lines, patients with OB tend to have
lymphocytes in BAL specimens that express donor-specific alloreactivity. If this
alloreactivity persists in spite of augmented immunosuppressive therapy, patients
appear to be at risk for continued OB. [54 ] As previously demonstrated in cardiac AV,
cytokine mRNA profiles in bronchoalveolar lavage (BAL) cells show increases in IL-2
and IL-6 in patients with acute rejection and in those with OB, and it has been noted that
transcription for IL-1 and IFN is increased in patients with OB. [63 ] The humoral arm of
the immune system has also been implicated in OB in a recent study in which anti-HLA
antibodies were increased. [64 ] Finally, one of the more-compelling links between an
alloresponse and OB has been its resolution in cases following augmented
immunosuppression. [52 ] , [65 ] , [66 ] Of interest has been reduction in the MHC class II
staining on bronchial epithelium following corticosteroid treatment. In the Pittsburgh
study of microchimerism, it appeared that those patients with OB had less evidence of
microchimerism in blood, lymph nodes, and skin, which again follows the general
concept of less immune reactivity for those patients with a generalized chimeric state.
[67 ]
Until recently, experimental models of OB have not been available, and thus treatment
strategies for the process have been slow in development. Now with the use of rodent
subcutaneous and intra-abdominal tracheal implants as close approximations of OB
seen in humans after whole lung transplantation, investigators have begun to better
understand the process and possible drug strategies to limit it. [68 ] , [69 ] As in cardiac
AV, the focus is on the newer immune drugs that might reduce not only the initial
allogeneic response but the secondary effects that result in mesenchymal cell
recruitment for luminal scarring. [70 ]
NEW IMMUNOSUPPRESSIVE DRUGS
The improved outlook for transplant recipients has followed the introduction of
xenobiotic immunosuppressants, that is, those drugs produced by organic synthesis or
micro organisms that suppress the immune system. Between 1960 and 1985 only
steroids, azathioprine (AZA), and CsA had been adopted for use in clinical
transplantation. These were joined by early polyclonal and of late monoclonal anti-T cell
antibodies. In the last few years, however, our astonishing progress in understanding
the molecular events of the alloresponse has not only made new discoveries possible
but also has been in part owing to the xenobiotics and antibodies whose actions help to
piece together mechanistic paradigms. With the better knowledge agents have been
classified by mechanism of molecular action (Fig. 48-8) (Table 48-2) . [71 ]
Corticosteroids
Transplant physicians have recognized the benefits of steroids from the very early days
of clinical transplantation. These molecules have protean effects. It has been
determined that much of their benefit is due to their inhibition, which increases signals
for activation of lymphocytes and include but are not limited to IL-1, IL-3, IL-6, and
ICAM-1.
Cytokine Synthesis Inhibitors
CsA inhibits the gene activation necessary for IL-2 production that prevents IL-2R
binding and all consequent proliferative events. [72 ] The likely explanation for the CsA
effect is that it complexes with its binding intracellular protein cyclophilin and inhibits the
function of Ca 2+ calcineurin phosphatase. [73 ] As discussed in the events describing
the activation of T cells, when calcineurin is not bound to cyclophilin, it cannot function as
a serine-thereonine phosphatase to cleave a phosphorous from the DNA binding
protein (NFAT), leaving this molecule inactive. Inactive NFAT-P cannot engage the
promoter sequence of the IL-2 gene. CsA was widely embraced as the central
component for effective multidrug immunosuppression until FK 506 (tacrolimus) was
introduced to patients in Pittsburgh in 1988. Tacrolimus, like CsA, combines with a
cytosolic protein (FK binding protein) and complexes with Ca 2+ activated calcineurin to
prevent its phosphatase function. [73 ] , [74 ] Tacrolimus has proven to be of at least
equal clinical potency in heart and lung transplant patients and is very useful as a switch
from CsA-based immunosuppression when rejection on the latter regimen is refractory.
[75 ] , [76 ] The reason for the effectiveness of tacrolimus over CsA for a few patients
with refractory rejection is interesting and must relate to the pharmacokinetics of the
drug rather than to mechanism of action as both drugs are similar in that regard. [77 ] It
would appear that tacrolimus is associated with less facial disfigurement and hirsutism
common in those recipients receiving CsA but tends to have equal nephrotoxicity and
perhaps a greater neurotoxicity than observed in patients receiving CsA.
Rapamycin (serolimus) (RPM) is a microbial by-product of the actinomyces

Streptomyces hygroscopicus that was first found on Easter Island. [78 ] Although
serolimus is structurally similar to tacrolimus and also must bind with FK binding protein
to be effective, it does not inhibit the calcium-activated calcineurin. [74 ] , [79 ] In fact by
competing for FK binding protein, serolimus is theoretically antagonistic to tacrolimus in
the inhibition of IL-2. [80 ] , [81 ] The system is obviously more complex because
success has occurred with combinations of tacrolimus and serolimus. [79 ] Whereas the
biochemical events responsible for the inhibition of the cytokine action by the
serolimus-FK binding protein combination are not well understood, it appears that the
likely target is a lipid kinase. [82 ] Elimination of this kinase results in blocking of T cell
proliferation that is facilitated through the CD28 pathway or an effect on the interaction
between IL-2 with its IL-2R. Serolimus appears to be effective with B cells as well. Its
possible benefits in mitigating chronic rejection are likely not only owing to its B cell
effect but also owing to its limiting effect on growth factors that stimulate smooth muscle
proliferation. [83 ] It has been recently observed that RPM potently inhibits the
stimulation of vascular smooth muscle cell DNA synthesis derived from platelet-derived
growth factor and basic fibroblast factor in all cultures. [84 ]
RPM is joined by LEFLUNOMIDE (LFM) as an inhibitor of cytokine action. [85 ] Current

investigations suggest that its mechanism is related to its blocking activity on tyrosine
kinases associated with cell surface growth factor receptors. [86 ] Although this drug
has been used in patients with rheumatoid arthritis, much less is known about its
potential usefulness in humans. [87 ] Both serolimus and LFM represent potential
targets for use with the cytokine inhibitors CsA or tacrolimus. Combinations of these
potential drugs that act in both Ca 2+ -dependent and independent fashion in limiting the
activation sequence of T and B cells likely will present additive immunosuppressive
effects. This will not only effectively reduce the alloresponse but also potentially do so
with lower doses of each.
Inhibitors of DNA Synthesis
Antimetabolites are immunosuppressive because they inhibit the synthesis of

nucleotides necessary for DNA's rapidly dividing cells. The classic drug for the
postcytokine active antimetabolites has been AZA, which inhibits purine synthesis
throughout all bone marrow lineages. Three new inhibitors of DNA synthesis have
undergone evaluation and are at various stages of clinical investigation. The first two,
mycophenolate mofetil (MMF) and mazorabine (MZR), appear to be more selective for
T and B cells than classic antimetabolite AZA. [88 ] [90 ] Their selectivity is based on
their ability to block the activity of enzyme inosine monophosphate dehydrogenase,
which is responsible for the synthesis of purines in the de novo pathway. Unlike other
parenchymal and other peripheral blood cells, T cells and B cells cannot use the
alternative or salvage pathway for purine synthesis. Panneutropenia has not been a
limiting factor with these drugs as it has been with AZA. Brequinar sodium (BQR) is the
third new addition to the antimetabolite group. [91 ] , [92 ] Unlike the others, its action
appears to be directed against an enzyme in the pathway leading to synthesis of
pyrimidines. Less selective than MZR or MMF, BQR has been shown to be myelotoxic,
and its rationale for use as an immunosuppressant is dependent on the assumption that
immune cells are more sensitive to its antimetabolic effects than nonimmune cells. It is
similar to AZA in this regard. Although clinical development currently is on hold, this drug
likely will emerge should the previous two in this category fail current expectations.
Inhibition of T- and B-Cell Maturation
The last of the new xenobiotics is deoxyspergualin (DSG). [93 ] Because DSG is not an
effective inhibitor of cytokine synthesis or of their actions or of DNA synthesis, its
immunosuppressant mechanism likely is linked to its inhibition of cell maturation of T
and B cells. [94 ] , [95 ] It also acts on APC function. Clinical trials are being conducted
in the United States in high-risk renal allograft recipients who previously have
undergone one or two allografts within the year. DSG is limited because it must be
administered intravenously and is being used as an induction course in conjunction with
conventional immunosuppression. Broadened use will depend on the early trials.
Receptor Antagonists and Monoclonal Antibodies
Throughout the last 25 years various preparations have been used as anti-T cell serum.
In fact, in Pittsburgh, in support of our first cardiac transplant in 1968,
equine-antibody-to-human-thymus was made on Dr. Henry T. Bahnson's small farm.
Commercially available serum has standardized the product to some extent. These
polyclonal anti-T cell preparations recognize T-cell surface structures and kill these
targets by inducing FC-receptor mediated cell lysis or by complement-dependent cell
lysis. When the monoclonal antibody preparations were first made available in the
mid-1980s, transplant physicians were given a standardized product with which to treat
the alloresponse. [96 ] The most commonly used monoclonal antibody has been the
anti-CD3 antibody (OKT3) that recognizes the epsilon protein of the CD3 complex.
Although it was assumed initially that the binding of the antibody would expose its
then-activated FC piece to cytotoxic cells that in turn would remove the coated T cell
from the circulation, further evaluation has demonstrated that this is likely to be only a
minor component of the effectiveness of the antibodies. It has been learned that the
major mechanism of anti-CD3 action is to coat the surface TCRCD3 complex with
antibody, causing it to be internalized or shed from the cell surface. The lymphocyte
without a TCRCD3 complex, although present, no longer is active in the alloresponse.
Experience in heart and lung transplantation has shown that the commercially available
anti-CD3 antibody is effective in eliminating acute rejection, but its role as a
prophylactic agent to improve long-term survival has been challenged. Multiple other
monoclonal antibodies, including those to CD4, ICAM-1, TCR, LFA-1, and IL-2
receptors, are in various stages of clinical development. It can be assumed that a few of
these, if not all of them, will have a specific role in therapy, but hopes for a magic bullet
likely will not be realized, as the immune response is far from simple and is based on
redundancy by way of alternative pathways. Research will focus on antibodies that could
selectively eliminate or activate alloreactive T cells without enabling the host defense
against usual pathogens.
TOLERANCE
Immunosuppressive agents have permitted the replacement of heart and lungs to

become realities. However, their toxic side effects and inability to prevent more chronic
forms of rejection have caused investigators to search for alternative strategies.
Because the only clinically transplanted graft that does not require any type of
immunosuppression is the immune system itself, for example, bone marrow, it seems
reasonable that the marrow be used as a probe to study mechanisms for the induction
of tolerance. In 1953, Billingham et al. demonstrated that immunologic tolerance to
donor-specific skin grafts could be acquired by the inoculation of hematopoietic cells
into newborn mice. [97 ] The engraftment of donor bone marrow putatively induces
tolerance to antigens of the donor by clonal deletion and clonal anergy. [98 ] In a
process as central to survival as the recognition of self, it is very likely that each of the
possible mechanisms plays a role. The clonal deletion paradigm, also known as the
production of central tolerance, derives from the observation that one of the most
reliable approaches to induce donor-specific tolerance has been through engraftment of
the allogenic stem cell. In mixed chimeras bone marrowderived elements of both host
and donor appear in the thymus and present ligands for negative selection of newly
developing T cells that are either donor or host reactive. [99 ]
The second mechanism for the induction and maintenance of tolerance is anergy, also
known as peripheral tolerance. [100 ] Anergy describes the functional inactivation of
antigen reactive T-lymphocytes. The interaction of the T-cell receptor with its antigen
can result in either activation and clonal expansion or unresponsiveness. It would
appear that for the latter necessary second signaling events that occur in the
surrounding environment are absent. [101 ]
Engagement of the T-cell receptor alone will induce unresponsiveness or a lack of T-cell
proliferation on antigen stimulation. If however the TCR is engaged with an APC and
receives a second signal from either another cell type or as the result of surface
molecule ligand-association, there is an effective alloresponse. As previously
described, different second signals, such as those subsequent to the engagement of
the CD28, LFA, or CD2 ligand, are necessary for the proliferation of T cells. The
two-signal model of T-cell activation has been suggested as the mechanism for
induction and maintenance of T-cell anergy both in-vivo and in-vitro. It has long been
recognized that passenger leukocytes, that is, cells derived from the organ transplant
most commonly dendritic in nature, can escape the organ and home to peripheral host
lymphoid tissues. It is possible that the donor-derived cells mediate the form of anergy
by limiting the second signal response necessary for T-cell proliferation.
Previous attempts to use donor bone marrow infusion to prolong allograft survival have
incorporated various conditioning regimens with mixed results. The first report of
combined bone marrow transplantation and solid organ grafting was by Monaco et al.,
who gave donor marrow to a renal transplant recipient 25 days after operation. [102 ]
The recipient was conditioned with ALS in addition to standard immunosuppression.
Although the patient survived 8 months without evidence of rejection before succumbing
to a perforated sigmoid diverticulum, there was no evidence of durable hematopoietic
cell engraftment. Barber et al., in a series of renal transplant recipients preconditioned
with ALS, CsA, AZA, and prednisone, showed that donor bone marrow infusion was
associated with better graft survival and a lower incidence of rejection. [103 ] Low levels
of donor cell chimerism were present in 5056 percent of patients 312 months after
transplantation. [104 ] Using a similar regimen, Rolles et al. were unable to show any
advantage to adjuvant bone marrow infusion in liver allograft recipients. [105 ] Kahn et
al. preconditioned six patients with high-dose total lymphoid irradiation (TLI), similar to
that used to treat Hodgkin disease, before heart transplantation and intraperitoneal
injection of donor bone marrow. In addition, these patients also received standard
immunosuppression (high-dose steroids, AZA, CsA, and lympholytic induction with
antithymocyte globulin). [106 ] Two patients died of infection in the perioperative period
(likely a result of the profound immunosuppressive effects of combined TLI and
standard immunosuppression), and a third died of acute right heart failure shortly after
transplantation. A fourth died of chronic rejection at 7 months, and two patients were
long-term survivors. In the one patient tested, in-vitro measurements of donor-specific
immune reactivity did show donor-specific hyporeactivity. Levels of chimerism were not
determined.
MICROCHIMERISM AND SOLID ORGAN TRANSPLANTATION
It was first observed in 1969 that liver transplant recipients enjoying long-term survival
had virtually complete replacement of donor hepatic macrophages with recipient-type
macrophages. [107 ] Recent work has shown that the converse also is true: Donor-type
lymphoid and dendritic cells migrate from the graft and establish themselves in the
recipient's periphery. [108 ] The establishment of low levels of donor cells in the
periphery of the recipient is referred to as microchimerism and has been shown to
occur in heart, lung, kidney, and liver transplant recipients. [109 ] [113 ] The term
microchimerism has been applied where donor-derived cells have been detected with
polymerase chain (PCR) techniques at levels less than cytometric detection in the
periphery of solid organ transplant recipients (1 in 105 cells).
We have reported microchimerism in lung transplant recipients. Autopsy evaluation of

nine female recipients of male lung allografts using a PCR technique and a
Y-chromosome-specified probe showed the presence of male (donor) leukocytes at low
levels in the native lung, liver, skin, kidneys, and lymph nodes of all recipients at intervals
of 34501 days after transplantation. [110 ] We have also shown an association between
microchimerism, donor-specific hyporeactivity, and lower incidence of OB. [113 ]
The observation that microchimerism is a common event after solid organ

transplantation, and the belief that migration of graft lymphoid and dendritic cells into the
unconditioned recipient is associated with long-term graft acceptance, have stimulated
attempts to augment microchimerism with perioperative bone marrow transfusion.
Prospective clinical trials at the University of Pittsburgh Medical Center to evaluate the
safety and efficacy of perioperative infusion of unmodified bone marrow concurrent with
heart, lung, liver, kidney, and islet transplantation are in progress. [114 ] [116 ] Three
hundred million bone marrow cells per kilogram of recipient's body weight are infused
within 68 hours of organ transplantation. Patients are maintained on standard
immunosuppression regimens and evaluated for the presence of microchimerism at
regular intervals after transplantation. There were no complications associated with
bone marrow infusion and no evidence of GVHD. Survival and incidence of acute
rejection was similar in the two groups. With a mean follow-up of 175 ± 102 days,
chimerism detectable either by flow cytometry or PCR was present in 73 percent of
bone marrowaugmented patients and 20 percent of controlpatients. The use of
unmodified bone marrow without a conditioning regimen (radiation or antilymphocyte
serum) appears to be safe and is associated with increased levels of donor cell
chimerism. However, a significant association between the development of chimerism
and decreased incidence of target events such as rejection or graft survival has yet to
be detected. [117 ] Microchimerism is far from a universal finding among long-term
survivors after solid-organ grafting under conventional immunosuppression. A study of
15 long-surviving (> 20 years) kidney transplant recipients showed microchimerism in
only 33 percent. [118 ] A similar study of heart recipients was able to detect
microchimerism in 58 percent three or more years after transplant. [119 ] The presence
of microchimerism has not consistently conferred a lower incidence of episodes of
rejection or improved survival. Studies underway in which the development of chimerism
after transplantation is evaluated prospectively should clarify the importance of
microchimerism in solid organ transplantation. Mixed allogeneic chimerism technically
includes all levels of chimerism between these two extremes but perhaps should refer to
levels of chimerism detectable by flow cytometry; that is, > 0.5 percent donor cells of
multilineage origin present in the recipient's peripheral blood. To date, only mixed
allogeneic chimerism has been shown in animal models to induce systemic, stable
donor-specific transplantation tolerance (DSTT) to a variety of solid organ grafts with
preservation of recipient immunocompetence. [120 ] , [121 ]
XENOTRANSPLANTATION
Animal-to-human transplantation, known as xenotransplantation as opposed to

allotransplantation performed between the same species, has been proposed to
alleviate the critical shortage of human donor organs. Approximately 30 percent of the
patients waiting for hearts and lungs will die without receiving a transplant. In 1964, 4
years before the first human allotransplant, Hardy attempted replacing a 68-year-old
man's failing heart with one obtained from a chimpanzee. [122 ] Since then, there have
been only six additional attempts of xenotransplantation reported using either pig,
sheep, baboon, or chimpanzee donors. [123 ] [126 ] Two of the most recent cases,
although unsuccessful, have provided insight and promise to the field. In 1984, Bailey
and colleagues placed an ABO-incompatible baboon heart into a child with a
hypoplastic left heart syndrome. [125 ] Baby Faye, as the child was known, made
remarkable progress for 20 days when rather suddenly the xenograft stopped
functioning. Examination of the heart gave evidence consistent with a humoral rejection,
perhaps related to the blood group incompatibility. Although some special
circumstances, such as pediatric transplantation, might lend themselves towards the
limited use of small subhuman primate hearts and lungs for concordant cross-species
transplantation, broad use of these generally precious animals would not gain societal
acceptance. Accordingly, the pig has been the focus as a source of phylogenetically
disparate or discordant donor organs. In the most recent xenograft cardiac transplant
reported, Czaplicki et al. reported a 24-hour survival of a pig-to-human heart transplant
recipient in 1992. [126 ] The extended survival was the longest recorded for a
discordant cardiac transplant, and the relative success may have been related to a
preoperative regimen of anti-pig antibody depletion.
The first major obstacle to discordant cross-species transplantation is generally

believed to be the process described as hyperacute rejection (HAR). Hyperacute
rejection is mediated largely by xenoreactive antibodies and the relative incompatibility
of xenograft complement regulatory proteins with the human complement system. If HAR
is prevented by disrupting antibody binding by depletion or by inhibition of complement,
xenografts might then be subjected to a similar but distinctly different acute vascular
rejection (AVR). Most believe that if HAR and AVR can be prevented initially, then the
xenograft may accommodate in a manner in which the xenograft endothelium will
become resistant to the effects of human antibody and complement. [127 ] This has
been noted to occur in some ABO incompatible kidney allotransplants. Ultimately,
however, discordant xenografts will need to be protected from cell-mediated rejection
that may be more intense than that which occurs following allotransplantation.
Xenograft Hyperacute Rejection
It has been determined that the primary human xenoreactive antibodies that initiate
HAR against pig hearts are IgM class specific for the membrane-associated sugar
galactose- (1-3-galactose). [128 ] This sugar (Gal[(13 Gal]) is catalyzed by 13 galactosyl
transferase that is not present in humans, apes, and old world monkeys. [129 ] Although
some discordant animal combinations utilize an alternative pathway of complement
activation that does not depend on the binding of antibody, pig-to-primate xenografts
utilize the classical pathway, and activation follows the binding of xenoreactive
antibodies. [130 ] The porcine xenograft has demonstrated considerable susceptibility
to injury by complement owing to inadequate function of swine regulatory proteins for
human complement. This leads to uncontrolled deposition of the terminal complement
complexes (C5b67) on the swine endothelial cells, resulting in the loss of endothelial
cell barrier function as they retract and generate intracellular gaps. Platelets then are
attracted to exposed extracellular matrix and release vasoactive substances, including
thromboxane A2, that stimulate vasoconstriction. The procoagulant state is intensified
because of the loss of heparinsulfate protoglycans from their surface. [127 ]
These findings have led White, Pedor, and Platt to develop swine that are transgenic for
human DAF and CD-59. [130 ] , [132 ] , [133 ] It has been determined that these
animals overexpress human DAF and CD-59, and it has been reported that this has
resulted in the transgenic organs successfully averting hyperacute rejection in most
circumstances. [134 ] An alternative strategy also has been pursued that has attempted
to down-regulate the -1,3 galactosyl transferase gene or to delete it. [135 ] This is
proving difficult and perhaps beyond reach at present. [136 ] Another potential for
transgenic therapy is focused on an intracellular competition between -1,3 galactosyl
transferase and -1,2 fucosytransferase, the enzyme responsible for O blood groups
H-antigen. [137 ] Mice have been produced that express human -1,2 fucosytransferase
that results in reduced expression of -1,3 galactosyl transferase. If transgenic swine can
similarly be produced, this might lead to a significant advance.
Acute Vascular Xenograft Reaction
If HAR can be avoided, it would appear that it will be at risk for an acute vascular
xenograft reaction (AVR). Although the histologic picture of AVR with its hemorrhage
and thrombosis is very characteristic of HAR, it appears to be a distinct process not
dependent on complement nor appearing in concordant transplant combinations. It
would appear that the pathophysiology begins with naturally occurring anti-pig
antibodies binding to the surface. This leads to levels of complement activation through
the membrane attack complex (MAC) that are below lytic levels but that lead to the
induction of IL-1, which mediates other changes on the surface of the endothelial cell
that, by and large, create a strongly procoagulant state. These changes include the
induction of procoagulant tissue factor, release of plasminogen activator inhibitor,
decrease in tissue plasminogen activator, and a loss in thrombomodulin activity.
Thrombomodulin is expressed on the surface of vascular endothelial cells and reduces
thrombotic process by thrombin-dependent activation of protein C, which in turn
degrades the procoagulant co-factor's factors Va and VIIIa. It has been noted also that
E-selectin, responsible for leukocyte rolling on the endothelium, is also expressed
during AVR. Platt and Lawson have speculated that endothelial cells may be stimulated
to the phenotypic changes described directly by the binding of antiporcine antibodies to
cell surface receptors that express the Gal- (13 Gal.) empitope. This alternative or
complementary pathway once again is evidence of the exquisite backup systems
seemingly ever-present throughout the immune system.
Cell-Mediated Xenograft Rejection
Although cell-mediated rejection has not been studied extensively in the xenograft
model because of difficulties in overcoming HAR and AVR, recent investigations have
suggested that xenografts will be susceptible to cell-mediated injury and also to attack
by NK cells. [138 ] NK cells normally are inhibited by class I MHC receptors, yet when
added to xenografic tissue culture, NK cells have been demonstrated to cause
cytotoxicity and phenotypic changes in a disruptive endothelial cell monolayer
consistent with retraction and gap formation typical of the activated endothelium
described in HAR. [139 ] , [140 ] It was hoped that thymic selection, which permits
T-lymphocytes to recognize allogeneic cells directly, might be less effective in producing
T-lymphocytes that might recognize the porcine xenogenic cells. However, it has been
determined that human T cells can recognize porcine cells directly through MHC class II
antigen. [141 ]
It would appear that although progress has been made with the discordant
porcine-to-primate model, opportunities for discordant xenografting to significantly
impact human transplantation must await additional studies that promote a further
understanding of the effects of the inhibition of early HAR, methods to persistently
reduce AVR, and finally a way of dealing with cell-mediated rejection. It is likely that a
combination of immunosuppressants, transgenic animals, and even tolerance-induction
protocols may provide a suitable therapeutic cocktail. Chief clinical investigators in the
field of xenotransplantation have stressed the need to look for intermediate endpoints
as means of understanding processes, since the long-term goal of routinely successful
discordant xenografting will require solving multiple complex processes. It is likely then
that well-prepared surgical groups will soon initiate bridge trials in which short-term
survival of the xenograft might be predicted, and information gained will be invaluable to
the science.
HISTORY OF HEART TRANSPLANTATION
The birth of cardiac transplantation can be traced back to the innovative French surgeon
Alexis Carrel (Fig. 49-1) who performed the first heterotopic canine heart transplant with
Charles Guthrie in 1905. [1 ] , [2 ] Twenty years later, the concept of cardiac allograft
rejection was proposed by Frank Mann at the Mayo Clinic to explain the eventual failure
of heterotopic canine allografts. [3 ] He described the rejection process as a biologic
incompatibility between donor and recipient manifested by an impressive leukocytic
infiltration of the rejecting myocardium. In 1946, Vladimir Demikhov of the Soviet Union
successfully implanted the first intrathoracic heterotopic heart allograft. [4 ] He later
demonstrated that heart-lung and isolated lung transplantation were also technically
feasible. The use of moderate hypothermia, cardiopulmonary bypass, and an atrial cuff
anastomotic technique permitted Norman Shumway and Richard Lower at Stanford
University to surmount the formidable barriers of orthotopic heart transplantation using
the canine model in 1960 (Fig. 49-2) . [5 ] The first human cardiac transplant was a
chimpanzee xenograft performed at the University of Mississippi by James Hardy in
1964. [6 ] Although the procedure using Shumway's technique was technically
satisfactory, the primate heart was unable to maintain the recipient's circulatory load
and the patient succumbed several hours postoperatively. Despite great skepticism that
cardiac transplantation would ever be successfully performed in humans, South African
Christiaan Barnard surprised the world when he performed the first human-to-human
heart transplant on December 3, 1967. [7 ] Over the next several years, poor early
clinical results led to a moratorium on heart transplantation, with only the most dedicated
centers continuing experimental and clinical work in the field. The pioneering efforts of
Shumway and his colleagues at Stanford eventually paved the way for the
re-emergence of cardiac transplantation in the late 1970s. The introduction of
transvenous endomyocardial biopsy by Philip Caves in 1973 finally provided a reliable
means for monitoring allograft rejection. [8 ] The advent of the immuno-suppressive
agent cyclosporine dramatically increased patient survival and marked the beginning of
the modern era of successful cardiac transplantation in 1981. [9 ] Heart transplantation
is now a widely accepted therapeutic option for end-stage cardiac failure, with more
than 2,700 procedures performed annually. [10 ]
ECONOMICS OF HEART TRANSPLANTATION
Organ transplantation is under close scrutiny as future strategies for the allocation of
health care dollars are investigated in the United States. [11 ] , [12 ] In an effort to
optimize outcomes while curbing escalating costs, recent managed care proposals
have focused on establishing global pricing systems that will provide a fixed
reimbursement for transplantation and other costly procedures to a limited number of
well-experienced institutions (i.e., centers of excellence). Through case management
and preventive care, designated centers will be forced to seek the most cost-effective
means to perform transplantation in an effort to match the contracted fee negotiated
with the third-party payer. Attempts to control costs will be complicated further by current
recipient prioritization that favors selection of the sickest patients for cardiac
transplantation, a trend that will nearly double hospital charges. [13 ]
THE CARDIAC TRANSPLANT RECIPIENT
Recipient Selection
The evaluation of patients with end-stage heart disease and the selection of potential
candidates for cardiac transplantation is undertaken by a multidisciplinary committee to
ensure an equitable, objective, and medically justified allocation of the limited donor
organs to patients with the greatest chance of postoperative survival and rehabilitation.
Because of the current excellent results of transplantation and the introduction of
cyclosporine-based immunosuppression, eligibility criteria have been significantly
expanded contributing to the escalating donor shortage, complicating the selection
process, and perhaps jeopardizing the results of future procedures. Indications and
potential contraindications are outlined in Table 49-1 . These inclusion and exclusion
criteria are evolving guidelines, and variations exist between transplantation centers.
The basic objective of the selection process is to identify those relatively healthy
patients with irreversible cardiac disease not amenable to other therapy who will
resume a normal active life and be compliant with the rigorous medical regimen
postoperatively. Accumulating transplant experience will facilitate optimal donor organ
allocation through improved risk stratification of potential recipients and prediction of
successful outcomes for cardiac transplantation.
ETIOLOGY OF END-STAGE CARDIAC FAILURE
Determination of the etiology and potential reversibility of end-stage cardiac failure is

critical for the selection of transplant candidates. The vast majority of patients are
referred with New York Heart Association (NYHA) Class III or IV symptoms caused by
ischemic heart disease or idiopathic dilated cardiomyopathy. [10 ] The spectrum of
known causes of dilated cardiomyopathy include infectious (viral), inflammatory, toxic,
metabolic, and familial etiologies. [14 ] Infrequent indications for transplantation include
intractable angina, refractory malignant ventricular arrhythmias, allograft occlusive
coronary artery disease, and cardiac failure caused by valvular or congenital heart
disease. The perception of the irreversibility of advanced cardiac failure is changing
with the growing popularity of tailored medical therapy, high-risk revascularization
procedures, and newer anti-arrhythmic pharmacologic agents and devices.
EVALUATION OF THE POTENTIAL CARDIAC RECIPIENT
The initial evaluation involves a comprehensive history and physical examination, chest
roentgenogram, routine hematologic and biochemical laboratories, a limited panel of
infectious disease serologies, and an exercise test with maximal oxygen consumption
(vo 2 ) measurement. Although the majority of referred patients have already undergone
right heart cardiac catheterization and coronary angiography, the former study should
be repeated at the transplantation center to rule out irreversible pulmonary hypertension.
Cine coronary angiography should be reviewed to confirm the inoperability of coronary
artery lesions in ischemic cardiomyopathy. Endomyocardial biopsy should be
performed on all patients with non-ischemic cardiomyopathies symptomatic for <6
months to assist in therapeutic decision making.
The complete routine preoperative evaluation in patients selected for transplantation

includes thyroid function studies, fasting and postprandial blood sugar, creatinine
clearance, lipoprotein electrophoresis, viral titers, fungal serologies, 12-lead
electrocardiogram, Holter monitor, echocardiogram, pulmonary function tests, panel
reactive antibody screen, and HLA typing. Abdominal ultrasound, carotid and lower
extremity Doppler flow studies, esophagogastroduodenoscopy, and screening studies
for malignancy are indicated in selected patients.
INDICATIONS FOR CARDIAC TRANSPLANTATION
Cardiac transplantation is reserved for a select group of patients with end-stage heart
disease not amenable to optimal medical therapy or other surgical procedures (i.e.,
re-vascularization, balloon angioplasty, catheter ablation techniques). [15 ] Prognosis
for 1-year survival without transplantation should be 75 percent. Prediction of patient
survival involves considerable subjective clinical judgment by the transplant committee
as no reliable objective prognostic criteria are currently available. Low ejection fraction
(<20 percent), reduced serum sodium (<135 mEq/dL), high pulmonary capillary wedge
pressure (>25 mmHg), elevated plasma norepinephrine (>600 pg/ml), increased
cardiothoracic ratio, and reduced maximal vo 2 (10 ml/kg/min) have all been proposed
as predictors of poor prognosis and potential indications for transplantation in patients
receiving optimal medical therapy. [16 ] [22 ] A vo 2 value between 1015 ml/kg/min may
be an indication if a steady decline has been noted. Left ventricular ejection fraction and
maximal oxygen consumption are the strongest independent predictors of survival.
CONTRAINDICATIONS FOR CARDIAC TRANSPLANTATION
Age is one of the most controversial exclusionary criteria for transplantation. The upper
age limit for recipients is between 5565 years, but emphasis is placed on the patient's
physiologic rather than chronologic age. [23 ] , [24 ] Survival and quality of life in carefully
selected older patients is comparable to that of younger recipients. [25 ] , [26 ] Although
the elderly have a greater potential of occult systemic disease that may complicate their
postoperative course, they have fewer rejection episodes than younger patients. [25 ] ,
[27 ]
Elevated pulmonary vascular resistance (PVR) is one of the few absolute

contraindications for orthotopic cardiac transplantation. A fixed PVR greater than 6
Wood units or a transpulmonary gradient greater than 15 mmHg are accepted criteria
for rejection of a candidate. [28 ] [31 ] Preoperative assessment of these patients
should include evaluation of the reversibility of the pulmonary hypertension with
vasodilators (oxygen, sodium nitroprusside, dobutamine, amrinone, or prostaglandin
E1) in the cardiac catheterization laboratory. If this hemodynamic maneuver does not
reduce PVR by 50 percent, a trial of parenteral inotropes or vasodilators is initiated and
after 4872 hours repeat catheterization is performed. A fixed elevated PVR is defined
as one that cannot be significantly reduced with the aforementioned interventions and
predicts fatal right heart failure in the immediate postoperative period. [32 ] , [33 ] These
patients may be candidates for heterotopic heart or heart-lung transplantation. [34 ] , [35
] For a recipient with moderate pulmonary hypertension (36 Wood units), a larger donor
heart often is selected to provide additional right ventricular reserve.
Transplantation in patients with diabetes mellitus is only contraindicated in the presence

of significant end-organ damage (diabetic nephropathy, retinopathy, or neuropathy). [36
] , [37 ] Control of blood sugar is possible with the reduction (or elimination) of
corticosteriods in the cyclosporine era. [38 ] , [39 ] The high risk of cavitation and
subsequent pulmonary abscess associated with recent (<6 weeks) pulmonary infarction
precludes transplantation in these patients. [40 ] Active infection (including human
immunodeficiency virus), irreversible renal or hepatic dysfunction, active peptic ulcer
disease, chronic lung disease, severe noncardiac arteriosclerotic vascular disease,
malignancy, and diverticulitis are contraindications for transplantation owing to potential
exacerbations with corticosteroids and other immunosuppressive agents. Poor
nutritional status as manifested by cachexia increases risk of infection and may limit
early postoperative rehabilitation.
The ultimate success of transplantation is intimately dependent on the psychosocial

stability and compliance of the recipient. [41 ] The rigorous postoperative regimen of
multidrug therapy, frequent clinic visits, and routine endomyocardial biopsies demands
commitment on the part of the patient. A history of psychiatric illness, substance abuse,
or previous noncompliance (particularly with medical therapy for end-stage heart failure)
may be sufficient cause to reject the candidacy of a patient. [42 ] , [43 ] Lack of
supportive family members or companions is an additional relative contraindication.
Standards for the psychological evaluation of potential cardiac recipients have been
proposed but not yet validated. [44 ] [46 ]
Management of the Potential Cardiac Recipient
TAILORED MEDICAL THERAPY FOR END-STAGE CARDIAC FAILURE
Conventional outpatient management of congestive heart failure includes digoxin,

diuretics, and vasodilators (in particular, angiotensin-converting enzyme inhibitors). [47 ]
[50 ] Eighty to ninety percent of patients referred for cardiac failure refractory to this
pharmacologic regimen usually can be stabilized for initial discharge after the institution
of tailored medical therapy. [51 ] One technique involving establishment of invasive
monitoring followed by therapy tailored for the individual patient is achieved by
optimizing hemodynamic parameters with intravenous sodium nitroprusside, high-dose
diuretics, and occasionally dobutamine. [52 ] , [53 ] While the patient's cardiac function
is closely monitored, the parenteral agents are then tapered as oral diuretics and
vasodilators (captopril, nitrates, and if necessary, hydralazine) are added. Compliant
patients who fail this outpatient regimen are considered for transplantation.
PHARMACOLOGIC BRIDGE TO TRANSPLANTATION
Critically compromised patients require admission to the intensive care unit for
intravenous inotropic therapy. Dopamine, dobutamine, and amrinone (or milrinone) are
the agents of choice. [54 ] , [55 ] Placement of an intra-aortic balloon pump (IABP) and
afterload reduction with sodium nitroprusside or nitroglycerin also may be necessary.
The percentage of recipients requiring inotropic support or IABP while on the waiting list
has increased to 5272 percent. [56 ] , [57 ] However, if these critical patients can be
stabilized, their outcomes following transplantation are comparable to patients who do
not require inotropic drugs and/or IABP. [58 ] , [59 ]
To avoid extended periods in the intensive care unit, intermittent outpatient dobutamine
administration is gaining popularity. [60 ] [62 ] A previous multicenter randomized trial
was abandoned because of the increased mortality in the outpatient group. [63 ] The
use of low-dose dobutamine (5 µg/ /kg/min), frequent follow-up with screening of serum
electrolytes, and the addition of amiodarone to the regimen results in a low incidence of
sudden death in more recent studies. Some patients demonstrate prolonged intervals
of improvement after these intermittent short-term sympathomimetic infusions. [64 ] , [65
] Revision of current status criteria is necessary to take into account outpatient inotropic
support in the prioritization for donor allografts.
MECHANICAL BRIDGE TO TRANSPLANTATION
A ventricular assist device (VAD) or total artificial heart (TAH), the mechanical bridges
to transplantation, may be indicated in potential cardiac recipients who remain unstable
after 2448 hours of maximal pharmacologic support (Table 49-2) . [66 ] , [67 ] In the
setting of chronic cardiac failure, it is imperative that the patient's candidacy for
transplantation be scrutinized closely prior to placement of a VAD or TAH, since these
devices are rarely weaned. If contraindications to transplantation exist, they must be
potentially reversible with the improved hemodynamics of assisted circulation. Patient
selection for a mechanical bridge is a complex, evolving field closely followed by the
U.S. Food and Drug Administration. [68 ] The use of mechanical assist devices remains
controversial in light of the current donor organ shortage and some conflicting
preliminary evidence exists regarding survival in recipients requiring mechanical
circulatory support. [57 ] , [69 ] , [70 ] Most large series suggest an improvement in
survival because the patients are rehabilitated while on the device.
HIGH-RISK REVASCULARIZATION PROCEDURES
Occasional patients with end-stage heart disease caused by ischemic cardiomyopathy

may be candidates for revascularization procedures. [71 ] Few series are available in
the literature, but preliminary long-term results in carefully selected patients are relatively
good despite the increased risk of intraoperative and early postoperative death in most
cohorts (perioperative mortality between 2.620 percent). [72 ] , [73 ] Three-year survival
is reported between 7283 percent, and five-year survival is 80 percent. [74 ] , [75 ] The
presence of more than one region of reversible myocardial dysfunction (by Thallium
scan or positron emission tomography) and a left ventricular end-diastolic diameter less
than 70 mm are predictors of a favorable outcome. [76 ] [78 ] While long-term survival
and function are still uncertain, high-risk revascularization procedures appear to be a
viable alternative for some patients referred for transplantation. Furthermore, previous
coronary artery bypass grafting does not preclude the possibility for future
transplantation should heart failure persist after revascularization. It is unclear if the risk
of transplantation is increased in patients with previous cardiac surgery. [79 ]
LIFE-THREATENING VENTRICULAR ARRHYTHMIAS
Symptomatic ventricular tachycardia or fibrillation and a history of sudden cardiac death

(SCD) are indications for placement of an automatic implantable
cardioverter-defibrillator (AICD), long-term amiodarone therapy, or occasionally,
radiofrequency catheter ablation. [80 ] , [81 ] SCD is the most common cause of death
in patients awaiting heart transplantation. [82 ] Mortality is greatest in the first 3 months
after referral for transplantation. [83 ] Randomized clinical trials are underway to explore
the potential benefits of prophylactic placement of an AICD in these high-risk patients.
Recipient Prioritization for Transplantation

Organ allocation is based on recipient priority status, duration on the waiting list, and
distance between donor and potential recipient. Highest priority is given to local status I
patients possessing the earliest listing dates. The recipient status criteria established
by the United Network for Organ Sharing (UNOS) in 1992 are outlined in Table 49-3 .
Although only 25 percent of patients are classified as status I at time of listing, 48
percent progress to status I by the time of transplantation owing to the lengthy waiting
periods. [84 ] By the year 2000, it is predicted that transplantation will be performed only
on status I patients. [85 ] , [86 ] The mean waiting period for a recipient is currently over
8 months with >50 percent of patients waiting more than 1 year.
Patients considered for transplantation should be examined at least every 3 months for
re-evaluation of recipient status. Yearly right heart catheterization is indicated for all
candidates on the waiting list, and in selected cases, for patients rejected because of
pulmonary hypertension. Presently, there is no established method to de-list patients
who have stabilized on medical therapy without loss of their previously accrued waiting
time.
THE CARDIAC DONOR
Donor Availability
The availability of donor organs remains the major limiting factor to heart
transplantation. Of the estimated 7,000 to 14,000 potential donor candidates in the
United States, less than 2,500 patients actually become heart donors annually. [87 ] [89
] As a result, 2040 percent of patients on the waiting list for a cardiac allograft die prior
to transplantation. [90 ] [92 ] The Uniform Anatomic Gift Act of 1968 states that all
competent individuals over the age of 18 (may) donate all or part of their bodies and
established the current voluntary basis of organ donation practiced in the United States.
[93 ] To accommodate the increasing demand for organs, the original stringent criteria
for donor eligibility have been relaxed and educational campaigns have increased
awareness of the need for a larger donor pool. Interestingly, several reports indicate that
the most important reason for the organ shortage is not the indifference of the public,
but rather a failure of health care providers to discuss the option of organ donation with
families of dying patients. [94 ] In 1986, the Required Request Law based on Medicare
and Medicaid funding was passed to encourage physician compliance in the donor
request process. [95 ] Several European countries have implemented controversial
Presumed Consent legislation whereby organ procurement may automatically proceed
in brain dead individuals if wishes to the contrary are not made by the patient prior to
death. [96 ] Even in the presence of documentation of the patient's wishes to donate,
consent for organ donation in the United States usually is verified with the family. The
adoption of Presumed Consent legislation, the use of anencephalic newborns as
donors, and financial incentives for the donor family have all stimulated considerable
controversy. [97 ] , [98 ] Future reforms will be molded by the evolving public attitude
towards transplantation and will likely focus on continued public and physician education
as well as enforcement and expansion of Required Request legislation. [99 ]
Allocation of Donor Organs
In an effort to increase organ donation and to coordinate an equitable allocation of

allografts, Congress passed the National Organ Transplant Act in 1984. [100 ] This act
resulted in the drafting of the aforementioned Required Request Law as well as the
awarding of a federal contract to the United Network of Organ Sharing (UNOS) for the
development of a national organ procurement and allocation network. [101 ] Eleven
regions were created that are locally managed by transplant coordinators of individual
Organ Procurement Organizations (OPOs). Allocation of organs is based on three
criteria: recipient's urgency status (I or II), proximity of the donor to the potential
recipient, and duration on the waiting list. Admission to the intensive care unit for
inotropic and/or mechanical support (intra-aortic balloon pump, ventricular assist
device) to maintain cardiac output classifies the patient as status I. Providing the most
critically ill patient with a heart while minimizing allograft ischemic time are the primary
goals of this allocation system.
Brain Death
Establishment of criteria for brain death was imperative with the advent of heart
transplantation so that the organ could be procured while still functioning to minimize
ischemic injury. After early attempts to define brain death by the Harvard Committee,
the University of Minnesota, and the National Institutes of Health, the Uniform Brain
Death Act (1978) and later the Uniform Determination of Death Act (1980) were passed
to provide national guidelines for state legislators to adopt. [102 ] [105 ] The basic
criteria used for the diagnosis of brain death include loss of cortical function, apnea,
absence of brain stem reflexes, and irreversibility over a 1224 hour observation period.
Furthermore, any potentially reversible cause for the patient's neurologic status,
including metabolic disturbances, pharmacologic agents, and hypothermia must be
ruled out. [106 ] , [107 ] The vast majority of donors are victims of blunt head trauma
(motor vehicle accident), penetrating head trauma (gunshot wound), or cerebrovascular
accident. The diagnosis of brain death may be made on clinical grounds alone by the
patient's physician; however, if uncertainty exists or the observation period must be
abbreviated because of patient instability, ancillary confirmatory tests, including
electroencephalogram, cerebral angiography, or radionuclide cortical blood flow
studies, should be performed. [108 ] Declaration of brain death and confirmation of
written informed consent must be documented in the patient's chart.
Donor Selection
Once a brain dead individual has been identified as a potential cardiac donor, the
patient undergoes a rigorous three-phase screening regimen. The primary screening is
undertaken by the organ procurement agency. Information regarding the patient's age,
height and weight, gender, ABO blood type, hospital course, cause of death, and
routine laboratory data including CMV, HIV, HBV, and HCV serologies are collected.
Cardiac surgeons or cardiologists perform the secondary screening, which involves
further investigation in search of potential contraindications (Table 49-4) , determination
of the hemodynamic support necessary to sustain the donor, review of the
electrocardiogram, chest roentgenogram, arterial blood gas, and echocardiogram.
Although adverse donor criteria may be reported, a team is often dispatched to the
hospital to evaluate the donor on-site. Echocardiography has been extremely useful for
detection of wall motion abnormalities, decreased ventricular function, and unsuspected
congenital heart lesions. [104 ] Coronary angiogram is indicated in the presence of
advanced donor age (male donors >45 years of age, female donors >50 years of age)
or risk factors for atherosclerotic coronary artery disease (tobacco abuse, diabetes,
significant family history). The use of small amounts of non-ionic contrast medium for
this study will not endanger renal allografts in patients considered for multiple organ
donation. The final and often most important screening of the donor occurs
intraoperatively at the time of organ procurement by the cardiac surgical team. Direct
visualization of the heart is performed for evidence of ventricular or valvular dysfunction,
previous infarction, or myocardial contusion secondary to closed-chest compressions
or blunt chest trauma. The coronary arterial tree is palpated for gross calcifications
indicative of atheromatous disease. If direct examination of the heart is unremarkable,
the recipient hospital is notified and the procurement surgeons proceed with donor
cardiectomy, usually in conjunction with multiorgan procurement.
In light of continued attempts to liberalize the criteria for donor eligibility, [109 ] the
screening process continues to evolve and intensify to predict early allograft failure
because of latent cardiac disease. Promising early studies have been performed using
serial myocardial biopsies and left ventricular end-systolic pressure volume
measurements for cardiac viability and functional assessment. Considerable
experimental work is still necessary for the development of a simple, reproducible test
for detecting cardiac allograft injury prior to explantation.
Management of the Cardiac Donor
Medical management of cardiac donors, an integral part of organ preservation, is

complicated by the complex physiologic phenomenon of brain death and the need to
coordinate procurement with other organ donor teams. Optimal care requires that the
donor be treated as any other intensive care unit patient with invasive hemodynamic
monitoring, ventilatory support, and meticulous attention to intravascular volume status
and electrolyte Table 49-5 . [110 ] , [111 ] . Continuous monitoring of arterial pressure,
central venous pressure, and urinary output is mandatory. As the number of marginal
donors increases with the acceptance of more lenient eligibility criteria, some transplant
centers have established mobile intensive care teams that are dispatched to ensure
appropriate management of these highly labile patients. [112 ]
Hemodynamic instability in the donor may result from vasomotor dysfunction,

hypovolemia, hypothermia, and dysrhythmias. Increased intracranial pressure may lead
to massive sympathetic discharge with elevated levels of circulating endogenous
catecholamines. The resultant episodes of systemic hypertension and coronary
vasospasm place the allograft at significant risk of ischemic injury. [113 ] Rapid
afterload reduction may be achieved with sodium nitroprusside, whereas volatile
anesthetics assist in reducing the intensity of sympathetic bursts. To minimize cerebral
edema prior to the declaration of brain death, potential donors have been
intravascularly volume depleted via strict fluid restriction and osmotic diuresis.
Aggressive volume resuscitation is central to the initial hemodynamic stabilization of the
donor [114 ] and should begin with a bolus of 12 liters of lactated Ringer's (LR) followed
by a maintenance regimen of 100 ml/h plus the previous hour's urine output. Additional
crystalloid boluses may be required to maintain central venous pressure between 512
mmHg to ensure adequate preload. Use of a Swan-Ganz catheter can be extremely
helpful in determining adequate filling pressures, cardiac output, and systemic vascular
resistance. Fluid overload should be avoided to prevent postoperative allograft
dysfunction caused by chamber distention and myocardial edema. Blood transfusions
are indicated to optimize oxygen delivery if the hemoglobin falls below 10 gm/dl. Mean
arterial pressure should be maintained between 8090 mmHg. If fluid resuscitation is
inadequate to restore blood pressure in the hypotensive donor, a dopamine infusion is
initiated for inotropic support. [115 ] , [116 ] Phenylephrine occasionally may be
indicated for hypotension caused by loss of systemic vasomotor tone. Prolonged
administration of high-dose catecholamine therapy (dopamine >015 µg/kg/min) has
been associated with poor cardiac function in the post-transplant period because of
depletion of myocardial norepinephrine stores. [117 ] , [118 ] Traditionally, these
patients were rejected for use as cardiac donors, but high-dose inotropic support is no
longer an absolute contraindication for donation. [119 ] Loss of central thermoregulatory
mechanisms results in transient initial hyperthermia followed by persistent hypothermia.
To reduce risk of hypothermia-induced ventricular dysrhythmias, core temperature is
maintained >35°C with infrared lamps and warming blankets. Maintenance of normal
electrolyte levels, osmolarity, acid-base balance, and oxygenation is critical for optimal
allograft preservation. Common electrolyte disturbances include hypernatremia,
hypokalemia, hypomagnesemia, and hypophosphatemia. [120 ] Central diabetes
insipitus develops in more than 50 percent of donors because of pituitary dysfunction,
and the massive diuresis complicates fluid and electrolyte management. [121 ] A
low-dose aqueous vasopressin (Pitressin) infusion is initiated at 0.81.0 U/h and titrated
to keep urinary output <100200 ml/h. [122 ] Alternatively, vasopressin may be
administered periodically subcutaneously or intramuscularly (10 U every 4 hours).
Ongoing fluid loss should be replaced hourly with a balanced crystalloid solution.
Mechanical ventilatory dependence results from the absence of respiratory effort, adult
respiratory syndrome, and neurogenic pulmonary edema. [123 ] Frequent blood gas
analysis, positive end-expiratory pressure, and diligent endotracheal suctioning are
essential in these vulnerable patients. [124 ]
Broad spectrum antibiotic therapy with a cephalosporin is initiated following collection

of blood, urine, and tracheal aspirate for culture. Brain death is associated with the
depletion of a variety of hormones, including free triiodothyronine (T3), cortisol, and
insulin. [125 ] , [126 ] Although evidence suggests that reduced T3 may contribute to
allograft dysfunction, donor pretreatment with hormone replacement therapy remains
controversial. [127 ] [129 ]
Donor Heart Procurement
The prolonged intraoperative manipulation of the donor associated with routine

multiorgan procurement necessitates that the anesthesiologist continue the meticulous
management provided in the intensive care unit. Following stabilization of the donor, the
multiorgan procurement and procedure begins (Table 49-6) . Donor cardiectomy
proceeds as follows. Median sternotomy is performed and the pericardium incised
longitudinally. The heart is inspected and palpated for evidence of cardiac disease or
injury. The superior and inferior vena cava are circumferentially mobilized and encircled
with ties. The aorta is dissected from the pulmonary artery and isolated with umbilical
tape. To facilitate access to the epigastrium by the liver procurement team, the cardiac
team often then temporarily retires from the operating room table or assists with
retraction. Once preparation for liver, pancreas, lung, and kidney explantation is
completed, the patient is administered 30,000 U of heparin intravenously. The superior
vena cava is doubly ligated (or stapled) and divided proximal to the azygous vein but at
least 1 cm cephalad to the ligature to avoid sinoatrial node injury (Fig. 49-3) . The
inferior vena cava is clamped at the level of the diaphragm (if the abdominal IVC is
vented) and then divided proximal to the clamp to permit efflux of the cardioplegia.
Additional venting is achieved with transection of the right superior pulmonary vein. The
aortic cross-clamp is applied at the takeoff of the innominate artery and the heart is
arrested with a single flush (500 ml) of cardioplegic solution infused through a 14-gauge
needle inserted proximal to the crossclamp. Rapid cooling of the heart is achieved with
copious amounts of cold saline (4°C) poured into the pericardial well. Following several
minutes of cardioplegia, cardiectomy proceeds as the apex of the heart is elevated
cephalad and any remaining intact pulmonary veins are divided. This maneuver is
appropriately modified to retain adequate left atrial cuffs for both lungs and the heart if
the lungs also are being procured. While applying caudal traction to the heart with the
nondominant hand, the ascending aorta is transected proximal to the innominate artery
and the pulmonary arteries are divided distal to bifurcation (again, modification is
necessary if the lungs are being procured). More generous segments of the great
vessels and superior vena cava may be required for recipients with congenital heart
disease.
Once explantation is complete, the allograft is placed in a basin of cold saline on the
back table for final preparation. The heart is examined for evidence of a patent foramen
ovale, which should be closed at that time, or any valvular anomalies. Left atrial cuff is
formed by joining the pulmonary vein orifices. The allograft is then sequentially placed in
two sterile bowel bags each filled with cold saline, a sterile saline-filled air-tight
container, and finally a standard cooler of ice for transport.
Organ Preservation
Current clinical preservation techniques of the cardiac allograft generally permit a safe
ischemic period of 46 hours. The donor heart is vulnerable to injury at all stages of the
transplantation procedure. Factors contributing to the severity of postoperative
myocardial dysfunction include insults associated with suboptimal donor management,
hypothermia, ischemia-reperfusion, and depletion of energy stores. A single flush of a
cardioplegic solution followed by static hypothermic storage is the preservation method
employed by more than 90 percent of transplant centers. [130 ] Cold saline is the most
frequently used storage media. Despite two decades of investigation, no single
preservation regimen has demonstrated consistent, clinically significant superior
myocardial protection when used within the current safe limits of ischemia. [8 ] , [131 ]
Controversy abounds in the literature regarding optimal storage temperature,
composition of cardioplegic and storage solutions, techniques of solution delivery,
additives, and reperfusion modification. Hypothermia remains the cornerstone of
current organ preservation. Target storage temperature is institutional-dependent and
generally ranges between 07°C. [132 ] Experimental evidence suggests that 4°C, the
temperature of melting ice, provides the best protection. Perfusion of the donor heart
with a cardioplegic solution to achieve electromechanical arrest is an invaluable adjunct
to topical hypothermia. Crystalloid solutions of widely different compositions are
available and the debate over them speaks for the fact that no ideal solution currently
exists. Depending on their ionic composition, solutions are classified as intracellular or
extracellular [133 ] [135 ] Intracellular solutions, characterized by moderate to high
concentrations of potassium and low concentrations of sodium, purportedly reduce
hypothermia-induced cellular edema by mimicking the intracellular milieu. Commonly
used examples of these solutions include University of Wisconsin, Euro-Collins, and in
Europe, Bretschneider (HTK) solutions. Extracellular solutions, characterized by low to
moderate potassium and high sodium concentrations, avoid the theoretic potential for
cellular damage and increased vascular resistance associated with hyperkalemic
solutions. Stanford, Hopkins, and St. Thomas Hospital solutions are representative
extracellular cardioplegic solutions. Although a plethora of pharmacologic additives
have been included in cardioplegic-storage solutions, the greatest potential for future
routine use may lie with impermeants, substrates, and antioxidants. Currently used
impermeants (mannitol, lactobionate, raffinose, and histidine) counteract intracellular
osmotic pressure to reduce hypothermia-induced cellular edema in the allograft. The
preservation of myocardial high energy phosphates during ischemia (to prevent
contracture bands) and their rapid regeneration at reperfusion (to fuel the newly
contracting heart) are the primary objectives for the use of substrate-enhanced media.
Adenosine, L-pyruvate, and L-glutamate have been studied most intensely. [136 ]
Recognizing that oxygen-derived free radicals and neutrophils likely are critical
mediators of myocardial reperfusion injury, considerable investigative effort has been
undertaken to modify the untoward effects of ischemia-reperfusion with antioxidant
additives including allopurinol, glutathione, superoxide dismutase, catalase, mannitol,
and histidine. A variety of pharmacologic and mechanical strategies for leukocyte
inhibition and depletion are also being explored. [137 ] , [138 ] Potential benefits of
continuous perfusion preservation techniques are currently overshadowed by
exacerbation of extracellular cardiac edema and logistical problems inherent to a
complex perfusion apparatus. [139 ] Experimental low pressure (microperfusion) and
intermittent flush techniques theoretically provide sufficient oxygen and substrates for
basal metabolic demands without causing significant edema. [140 ] Continued
research will be necessary to resolve these ongoing debates over the various aspects
of cardiac allograft preservation, since the heart transplant registry continues to report
that 20 percent of perioperative deaths are caused by cardiac dysfunction.
Donor-Recipient Matching
Criteria for matching potential recipients with the appropriate donor are based primarily
on ABO blood group compatibility and patient size. ABO barriers should not be crossed
in heart transplantation, as incompatibility frequently results in fatal hyperacute rejection.
Donor weight should be within 30 percent of recipient weight except in pediatric
patients, where closer size matching is required. In cases of elevated pulmonary
vascular resistance in the recipient (>6 Wood units), a larger donor is preferred to
reduce the risk of right ventricular failure in the early postoperative period. Previous
catheter-documented reversibility of PVR more adequately determines post-transplant
right ventricular dysfunction. A random panel of pooled lymphocytes representing the
major histocompatibility antigens in the community is used to screen the recipient for
anti-human lymphocyte antigen antibodies that may also mediate hyperacute rejection.
If the percent (or panel) reactive antibody (PRA) is 1015 percent, indicating recipient
cytoxicity against several lymphocytes, a prospective negative T-cell crossmatch
between the recipient and donor sera is mandatory prior to transplantation. [141 ] , [142
] A positive crossmatch is an absolute contraindication to transplantation. A crossmatch
is always performed retrospectively, even if the PRA is absent or low. Retrospective
studies have also demonstrated that better matching at the HLA-DR locus results in
fewer episodes of rejection and infection with an overall improved survival. [143 ]
Because of current allocation criteria and limits on ischemic time of the cardiac
allograft, prospective HLA matching is not possible logistically.
Hyperacute rejection results from preformed, donor-specific antibodies in the recipient.

[144 ] ABO blood group and panel reactive antibody screening have made this
condition a rare complication. The onset of hyperacute rejection occurs within minutes
to several hours after transplantation and the results are catastrophic. Gross inspection
reveals a mottled or dark red, flaccid allograft, [145 ] and histologic examination
confirms the characteristic global interstitial hemorrhage and edema without
lymphocytic infiltrate. Immunofluorescence techniques reveal deposits of
immunoglobulins and complement on the vascular endothelium. [146 ] No treatment is
effective except retransplantation, and even this aggressive strategy frequently is
unsuccessful.
OPERATIVE TECHNIQUES IN HEART TRANSPLANTATION
Orthotopic cardiac transplantation, the surgical technique of choice, involves the

replacement of part (or occasionally all) of the recipient's heart with a healthy donor
allograft. Heterotopic cardiac transplantation, the piggy-backing of an allograft onto the
patient's heart, is rarely performed today. It may be indicated if orthotopic
transplantation is not possible because of elevated pulmonary vascular resistance or
when a donor heart is too small to sustain the recipient. [147 ] , [148 ] Even in these
selected cases, results have been disappointing. [35 ] , [149 ]
Orthotopic Heart Transplantation
ANESTHETIC MANAGEMENT
Once the organ procurement team has confirmed the acceptability of the donor allograft
at time of operation, recipient induction may commence. High-dose narcotics (e.g.,
fentanyl) usually are employed for induction and maintenance anesthesia. [150 ] , [151 ]
In light of the poor ventricular function of the recipient, all anesthetic agents should be
titrated carefully with inotropic and vasoactive agents readily accessible for the rapid
management of induction-induced hypotension. Inhaled agents may be added if
necessary, but their potential myocardial depressant effects limit widespread use in this
patient population. Prior to skin incision, some centers initiate aprotinin or
aminocaproic acid therapy to minimize perioperative blood loss. [152 ]
OPERATIVE PREPARATION OF THE RECIPIENT
The surgical technique of orthotopic cardiac transplantation has changed little from the
original description reported by Shumway and Lower. [5 ] Following median sternotomy
and vertical pericardiotomy, the patient is heparinized and prepared for
cardiopulmonary bypass. Bicaval cannulation of the right atrium is achieved with venous
cannulae placed posterolaterally near the caval-atrial junctions. [153 ] The aortic cannula
is inserted just proximal to the origin of the innominate artery. Umbilical tape snares are
passed around the superior and inferior vena cava. Bypass is initiated, the patient is
cooled to 30°C, caval snares are tightened, and the ascending aorta is cross-clamped.
The great vessels are transected above the semilunar commissures, whereas the atria
are incised along the atrioventricular grooves leaving cuffs for allograft implantation.
Removal of the atrial appendages reduces the risk of postoperative thrombus
formation. [154 ] Following cardiectomy, the proximal 12 cm of aorta and pulmonary
artery are separated from one another with electrocautery, taking care to avoid injuring
the right pulmonary artery. Continuous aspiration of pulmonary venous return from
bronchial collaterals is achieved by insertion of a vent into the left atrial remnant, either
directly or via the right superior pulmonary vein.
Timing of donor and recipient cardiectomies is critical to minimize allograft ischemic

time and recipient bypass time. Frequent communication between the procurement and
transplant teams permits optimal coordination of the procedures. Ideally, the recipient
cardiectomy is completed just prior to the arrival of the cardiac allograft. [87 ] , [155 ]
IMPLANTATION
The donor heart is removed from the transport cooler and placed in a basin of cold
saline. If not previously performed, preparation of the donor heart is accomplished.
Electrocautery and sharp dissection are used to separate carefully the aorta and
pulmonary artery. The left atrium is incised by connecting the pulmonary vein orifices
and excess atrial tissue is trimmed forming a circular cuff tailored to the size of the
recipient left atrial remnant (Fig. 49-4) . Implantation begins with placement of a
double-armed 3-0 Prolene through the recipient left atrial cuff at the level of the left
superior pulmonary vein and then through the donor left atrial cuff near the base of the
atrial appendage (Fig. 49-5) . The allograft is lowered into the recipient mediastinum
atop a cold sponge to insulate it from direct thermal transfer from adjacent thoracic
structures. The suture is continued in a running fashion caudally and then medially to the
inferior aspect of the interatrial septum (Fig. 49-6) . Upon completion of the posterior
left atrial suture line, continuous topical cold saline (24°C) is initiated, and the patient is
oriented in a left side down-head up position to allow drainage of the saline away from
the operative field and maximal cold saline exposure of the left and right ventricles. The
second arm of the suture is run along the roof of the left atrium and down the interatrial
septum. It is important to continually assess size discrepancy between donor and
recipient atria so that appropriate plication of excess tissue may be performed. The left
atrium is filled with saline and the two arms of suture are tied together on the outside of
the heart. Some centers introduce a line into the left atrial appendage for continuous
hypothermic saline lavage of the allograft (5075 ml/min) and evacuation of intracardiac
air.
Once the left atrial anastomosis is complete, a curvilinear incision is made from the
inferior vena caval orifice toward the right atrial appendage of the allograft. This
modification in the right atriotomy initially introduced by Barnard reduces the risk of
injury to the sinoatrial node and accounts for the preservation of sinus rhythm observed
in most recipients. [156 ] The tricuspid apparatus and interatrial septum are inspected.
Recipients are predisposed to increased right-sided heart pressures in the early
postoperative period owing to pre-existing pulmonary hypertension and volume
overload. Both conditions are poorly tolerated by the recovering right ventricle. To avoid
refractory arterial desaturation associated with right-to-left shunting, patent foramen
ovale are oversewn. [157 ] The right atrial anastomosis is performed in a running
fashion similar to the left with the initial anchor suture placed either at the most superior
or inferior aspect of the interatrial septum so that the ends of the suture meet in the
middle of the anterolateral wall (Fig. 49-7) .
The end-to-end pulmonary artery anastomosis is next performed using a 4-0 Prolene
suture beginning with the posterior wall from inside of the vessel and then completing
the anterior wall from the outside. It is crucial that the pulmonary artery ends be trimmed
to eliminate any redundancy in the vessel that might cause kinking. [158 ] Rewarming is
initiated at this time. Finally, the aortic anastomosis is performed using a technique
similar to the pulmonary artery except that some redundancy is desirable in the aorta as
it facilitates visualization of the posterior suture line (Fig. 49-8) . Beveling the aorta may
be necessary to accommodate the size discrepancy between donor and recipient.
Caval tapes then are released to permit displacement of any residual intracardiac air
with blood. Prior to securing the aortic anastomosis, the lungs are ventilated and the
heart is manually agitated for additional deairing. [159 ] Cold saline lavage is
discontinued, lidocaine (100200 mg IV) is administered, and the aortic cross-clamp is
removed. Half of patients require electrical defibrillation. A needle vent is inserted in the
ascending aorta for final deairing with the patient in steep Trendelenberg. Suture lines
are carefully inspected for hemostasis. Isoproterenol infusion is initiated and titrated to
achieve a heart rate between 90110 bpm. [160 ] The patient is weaned from
cardiopulmonary bypass and the cannulae are removed. Temporary epicardial pacing
wires are placed in the donor right atrium and ventricle. Following insertion of
mediastinal and pleural tubes, the median sternotomy is closed in standard fashion.
ALTERNATIVE TECHNIQUES FOR ORTHOTOPIC HEART TRANSPLANTATION
Two alternative techniques for orthotopic heart transplantation have been gaining
popularity over the past several years. Total heart transplantation involves complete
excision of the recipient heart with bicaval end-to-end anastomoses and bilateral
pulmonary venous anastomoses (Fig. 49-9) . [161 ] [163 ] The Wythenshawe bicaval
technique is performed in a similar fashion except that the recipient left atrium is
prepared as a single cuff with all four pulmonary vein orifices (Fig. 49-10) . [164 ]
Although these procedures are more technically difficult than standard orthotopic
transplantation, preliminary series using these techniques have reported shorter
hospital stays, reduced postoperative dependence on diuretics, in addition to lower
incidences of atrial dysrhythmias, conduction disturbances, mitral and tricuspid valve
incompetence, and right ventricular failure. [164 ] [167 ] The efficacy of these alternative
techniques still remains to be determined.
RECIPIENTS WITH CONGENITAL ANOMALIES
Unlike children and infants, transplantation in adults with previous palliative procedures
for congenital anomalies is uncommon. It is critical that a generous donor cardiectomy
be performed so that sufficient tissue is available for optimal reconstruction (Fig. 49-11)
. There are a variety of anomaly-specific implantation techniques. [168 ] [170 ]
Heterotopic Heart Transplantation
DONOR ALLOGRAFT PREPARATION
Like the cardiectomy for patients with congenital disease, the maximal length of aorta,
superior vena cava, and pulmonary arteries is procured. The inferior vena cava and the
right pulmonary veins are oversewn, and a common left pulmonary vein orifice is
created (Fig. 49-12) . A linear incision is made along the long axis of the posterior right
atrium extending 34 centimeters into the superior vena cava.
IMPLANTATION
The details of the technique are well described in the literature [171 ] [173 ] and are
beyond the scope of this chapter. Briefly, the sequence of anastomoses is as follows:
donor left pulmonary vein orifice to recipient left atrium, donor superior vena cava-right
atrial orifice to recipient right atrium, end-to-side aortic-aortic anastomosis, and finally
an end-to-side anastomosis joining the pulmonary arteries of donor and recipient (Fig.
49-13) . The pulmonary artery anastomosis often requires the use of an aortic homograft
or synthetic graft conduit permitting the donor heart to reside within the right pleural
space.
Domino Donor Procedure
To avoid wasting relatively healthy hearts from selected heart-lung transplant recipients,
these organs may be transplanted into another recipient using standard orthotopic or
heterotopic techniques. [174 ] , [175 ] There is some controversy as to whether these
heart-lung recipients would be better served with a double lung transplant. [176 ]
Proponents of the domino donor procedure assert that hearts conditioned to the
elevated pulmonary vascular resistance associated with end-stage lung disease
theoretically are ideal for cardiac recipients with moderate pulmonary hypertension.
Today, similar success in lung transplantation can be attained with either the domino
donor procedure or bilateral sequential lung transplantation.
POSTOPERATIVE MANAGEMENT
Intensive Care Unit
ISOLATION AND MONITORING
Postoperatively, the transplant recipient is usually admitted to a private room in the

intensive care unit (ICU). Traditional protective isolation with elaborate
positive-pressure air filtration systems has been abandoned by most centers, as recent
studies demonstrate no benefit over mask and handwashing regimens. [177 ] , [178 ]
Contact with individuals with communicable diseases should be avoided.
Intensive care monitoring is analogous to that of any patient who has undergone cardiac
surgery. A radial artery catheter, left internal jugular venous catheter, continuous
telemetry, pulse oximeter, capnography, and Foley catheter are essential components
for optimal postoperative care. Occasionally, a Swan-Ganz catheter is indicated in
patients with increased pulmonary vascular resistance or if donor allograft dysfunction is
anticipated. If the patient remains hemodynamically stable, all invasive monitoring lines
and Foley catheter should be removed by 4872 hours to minimize the risk of
nosocomial infection. Chest tubes are removed on the first postoperative day if
drainage is <25 ml/h.
HEMODYNAMIC MANAGEMENT
Heart allograft physiology
The intact heart is innervated by antagonistic sympathetic and parasympathetic fibers of

the autonomic nervous system. Transplantation necessitates transection of these fibers,
yielding a denervated heart with altered physiology. Devoid of autonomic input, the
sinoatrial (SA) node of the transplanted heart fires at its increased intrinsic resting rate
of 90110 beats/min. [179 ] , [180 ] The allograft relies on distant noncardiac sites as its
source for catecholamines; thus, its response to stress (e.g., hypovolemia, hypoxia,
anemia) is delayed until circulating catecholamines can exert their positive chronotropic
effect on the heart. [181 ] [183 ] Careful examination of the electrocardiogram
occasionally may reveal a distinct P-wave originating from the innervated atrial remnant
of the recipient, and an increase in its rate may be used as an early indicator of stress.
The absence of a normal reflex tachycardia in response to venous pooling accounts for
the frequency of orthostatic hypotension in transplant patients.
Denervation alters the heart's response to therapeutic interventions that act directly
through the cardiac autonomic nervous system. Carotid sinus massage, Valsalva
maneuver, and atropine have no effect on sinoatrial node firing or atrioventricular
conduction. [179 ] Because of depletion of myocardial catecholamine stores associated
with prolonged inotropic support of the donor, the allograft is very sensitive to
exogenous catecholamines, and therefore, these agents must be titrated carefully in
cardiac recipients. Finally, since afferent sensory fibers are absent, transplant
recipients classically do not experience the characteristic chest discomfort associated
with myocardial ischemia. [184 ] However, there have been reports of sporadic cases of
angina-like pain believed to be secondary to late reinnervation of allograft in a few
patients.
Routine hemodynamic management
Donor myocardial performance is transiently depressed in the immediate postoperative

period. Allograft injury associated with donor hemodynamic instability and the
hypothermic, ischemic insult of preservation contributes to the reduced ventricular
compliance and contractility characteristic of the newly transplanted heart. [185 ] [187 ]
Abnormal atrial dynamics owing to the midatrial anastomosis exacerbate the reduction
in ventricular diastolic loading. [166 ] An infusion of isoproterenol or dobutamine is
initiated routinely in the operating room to provide temporary inotropic support. [187 ] ,
[188 ] The positive chronotropic effect of isoproterenol also is therapeutic for the
bradyarrhythmias that frequently complicate the early post-transplant period. [189 ]
Restoration of normal myocardial function usually permits the cautious weaning of
inotropic support within 24 days. [160 ]
Early allograft failure
Early cardiac failure accounts for up to 25 percent of perioperative deaths of transplant

recipients. [190 ] [192 ] The cause may be multifactorial, but the most important
etiologies are pulmonary hypertension, ischemic injury during preservation, and acute
rejection. Hypotension, urine output < 0.5 ml/kg/h, and cool, clammy extremities are the
best clinical indicators of inadequate cardiac output. Inability to wean routine
postoperative inotropic support after several days is another common presentation. A
Swan-Ganz catheter should be placed to optimize aggressive hemodynamic
management with inotropes and vasopressors. An emergent endomyocardial biopsy
should be performed to avoid empiric increases in immunosuppression for graft
salvage. Ventricular function is monitored with daily echocardiogram. Mechanical
support with an intra-aortic balloon pump or ventricular assist device is indicated in
cases refractory to pharmacologic interventions. [193 ] Retransplantation in this setting
is associated with very high mortality. [194 ] , [195 ]
Chronic left ventricular failure frequently is associated with elevated pulmonary vascular
resistance, and the unprepared donor right ventricle may be unable to overcome this
increased afterload. Although recipients are screened to ensure that those with
irreversible pulmonary hypertension are not considered for transplantation, right heart
failure remains a leading cause of early mortality. [196 ] [198 ] Central venous pressures
should be monitored perioperatively in all recipients for early detection of right
ventricular failure. [199 ] Initial management involves placement of a Swan-Ganz
catheter, optimization of oxygenation, and first-line pulmonary vasodilators
(isoproterenol, nitroglycerin, or sodium nitroprusside). Pulmonary hypertension
refractory to these vasodilators will often respond to prostaglandin E1. (PGE 1 ) [200 ]
[202 ] To counteract the profound systemic hypotension associated with PGE 1 ,
norepinephrine is concurrently infused through a left atrial catheter. Inhalation nitric oxide
may be a therapeutic alternative in the future. Intra-aortic or pulmonary artery balloon
counterpulsation and right ventricular assist devices have been utilized in patients
unresponsive to medical therapy. [203 ] Our perioperative mortality during the initial
hospitalization is 5 percent.
Dysrhythmias
Sinus or junctional bradycardia occurs in more than half of transplant recipients. [204 ]
The primary risk factor for sinus node dysfunction is prolonged organ ischemia.
Adequate heart rate is achieved with isoproterenol infusion and/or temporary epicardial
pacing. Most bradyarrhythmias resolve over 12 weeks, although recovery may be further
delayed in patients who received preoperative amiodarone therapy. [205 ]
Aminophylline has been effective in some patients with prolonged bradycardia. [206 ]
Although placement of a permanent pacemaker is necessary in 225 percent of patients,
few are still pacer-dependent at 6 months. [207 ] , [208 ] Ventricular arrhythmias,
primarily premature ventricular beats (PVCs) and nonsustained ventricular tachycardia,
have been reported in up to 60 percent of recipients when monitored continuously. [209
] [211 ] Atrial fibrillation-flutter is treated with digoxin, but at a higher dose than used in
the setting of an innervated heart. [131 ] , [212 ] Arrhythmias occasionally are markers
for acute rejection.
Systemic hypertension
Mean arterial pressures > 80 mmHg should be treated to prevent unnecessary afterload
stress on the allograft. In the early postoperative period, intravenous sodium
nitroprusside or nitroglycerin is administered. [213 ] , [214 ] Nitroglycerin is associated
with less pulmonary shunting because of a relative preservation of the pulmonary
hypoxic vasoconstrictor reflex. [215 ] If hypertension persists, an oral antihypertensive
(nifedipine, hydralazine, or prazosin) can be added to permit weaning of the parenteral
agents.
RESPIRATORY MANAGEMENT
Upon admission to the ICU, endotracheal tube placement is confirmed by auscultation

and chest roentgenogram. Baseline arterial blood gas is obtained and fractional
inspired oxygen is weaned to maintain an arterial oxygen 75 mmHg. Once the patient is
awake, warm, hemodynamically stable, and without significant mediastinal bleeding,
ventilatory support is rapidly weaned. Most patients can be extubated within 812 hours
following transplantation. Frequent suctioning of the endotracheal tube and chest
physical therapy are important components of early postoperative care if extubation is
delayed. After extubation, the orogastric tube should be removed to facilitate clearance
of secretions. Humidified supplemental oxygen by face mask or nasal cannula is
continued for several days. Aggressive pulmonary toilet with incentive spirometry,
coughing and deep breathing exercises, and early ambulation help reduce the risk of
pulmonary infection. Chest roentgenograms are obtained daily in the intensive care unit
and thereafter as indicated by the clinical course. To optimize ventilation and to
eliminate a potential nidus for infection, postoperative pleural effusions should be
drained by thoracentesis.
RENAL FUNCTION
Preoperative renal insufficiency owing to chronic heart failure and the nephrotoxic
effects of cyclosporine place the recipient at increased risk of renal insufficiency. The
tendency toward extravascular water retention exhibited by these patients is
exacerbated by the effects of cardiopulmonary bypass and corticosteroids. Fluid
balance is monitored closely in the early postoperative period with an indwelling urinary
catheter. Low urinary output (<0.5 ml/kg/h) is managed with optimization of
hemodynamic status, diuretics, and dopamine. Chronic preoperative diuretic
dependence often necessitates the use of high-dose furosemide therapy or more
potent diuretics (ethacrynic acid, bumetanide). Care must be taken to avoid the
ototoxicity associated with excessive use of loop diuretics. Dopamine may be
administered at 23 µg/kg/min to augment renal blood flow. [216 ] Acute
cyclosporine-induced renal insufficiency usually will resolve with the reduction in
cyclosporine dose and thus frequent measurements of cyclosporine levels are
imperative for timely dose adjustments. Concurrent administration of mannitol with
cyclosporine may reduce its nephrotoxicity. Patients at risk for renal failure initially may
receive cyclosporine as a continuous intravenous infusion to eliminate the wide
fluctuations in levels associated with oral dosing. Alternatively, some centers administer
a cytolytic agent in the immediate postoperative period and delay the initiation of
cyclosporine therapy. If persistent fluid overload, acidosis, or hyperkalemia develop, a
brief course of dialysis may be necessary until the renal dysfunction resolves.
NUTRITION AND ACTIVITY
Patients are moved out of bed into a chair within 24 hours of surgery. Ambulation with
assistance and physical therapy with upper and lower extremity exercises can be
initiated on the second postoperative day. A clear liquid diet (µ1,000 ml/24 h) is started
on the first postoperative day and advanced as tolerated to a no-added-salt, low-fat,
low-cholesterol diet.
Intermediate Care Unit and Convalescent Ward
Following 2472 hours in the ICU, patients are transferred to the intermediate care unit
and shortly thereafter to a cardiac surgery convalescent ward. Physical therapy is
continued with a stationary bike and extremity exercises. Cyclosporine levels and
routine hematology and chemistry laboratories are drawn daily. Echocardiogram and
the first endomyocardial biopsy are performed 710 days post-transplantation. Unless a
bradyarrhythmia persists, pacer wires should be removed after approximately 57 days.
Repeat serum titers and cultures for opportunistic infections are collected. Baseline
renal function is assessed with a 24-h urine determination of creatinine clearance.
Chest roentgenograms and electrocardiograms are obtained twice a week.
Because of the rising cost of health care and the risk of nosocomial infection with
resistant bacteria, the cardiac recipient is no longer subjected to a lengthy hospital
convalescence. Most patients are discharged 714 days following transplantation. [217 ]
Patient education is performed by the cardiac nursing staff. Topics include medications
(regimens and potential side effects), diet, exercise (routines and restrictions), and
infection recognition. Patients are discharged on an immunosuppressive protocol
(cyclosporine, prednisone, azathioprine), antimicrobial prophylaxis
(trimethoprim-sulfamethoxazole, acyclovir), H2 blocker (ranitidine), and analgesic
medication.
Outpatient Follow-up
Close follow-up by an experienced transplant team is the cornerstone for successful

long-term survival after cardiac transplantation by facilitating the early detection of
rejection, opportunistic infections, patient noncompliance, and adverse sequelae of
immunosuppression. Clinic visits routinely are scheduled concurrently with
endomyocardial biopsies and include physical examination, a variety of laboratory
studies, chest roentgenogram, and electrocardiogram.
IMMUNOSUPPRESSIVE THERAPY
An organism's ability to distinguish self from nonself is critical for its survival in a hostile
environment. In transplantation, the recipient's host defense mechanisms recognize the
human leukocyte antigens (HLA) on allograft cells as being nonself, and if permitted, will
respond to eradicate the foreign cells. [218 ] The ultimate goal of immunosuppressive
therapy is the selective modulation of the recipient's immune response to prevent
rejection, while concurrently sparing immune defenses against infections or neoplasia
and minimizing the toxicity associated with immunosuppressive agents (Table 49-7) .
Pharmacologic Immunosuppressive Strategies
Immunosuppression following transplantation consists of an early induction phase

followed by a long-term maintenance phase. This basic strategy essentially is universal,
although the choice of immunosuppressive agents, dosages, and combination
protocols vary widely between transplantation centers. [219 ] Since the tendency for
allograft rejection is greatest in the early postoperative period, the most intense
immunosuppression is administered during this phase. Increased doses of
corticosteroids and cyclosporine are administered routinely during this period, and
some centers provide additional induction prophylaxis with potent polyclonal or
monoclonal lympholytic antibodies. After several months, immunosuppression is
gradually reduced to chronic maintenance levels while endomyocardial biopsies,
performed to monitor for rejection, are also reduced in frequency.
Azathioprine and prednisone comprised the conventional maintenance regimen of early

cardiac transplantation. Following the introduction of cyclosporine, [220 ] trials
substituting azathioprine with cyclosporine (double drug therapy) were briefly
undertaken [9 ] ; however, the high dose of cyclosporine necessary to control rejection
episodes resulted in an unacceptable incidence of severe nephrotoxicity and
hypertension. The vast majority of centers abandoned this regimen in favor of triple drug
therapy, which re-incorporated azathioprine to permit a 3040 percent reduction in
cyclosporine doses. [221 ] , [222 ] The addition of induction cytolytic therapy (OKT3,
ATG) to triple drug therapy characterizes quadruple drug therapy. The use of a
multi-drug regimen permits adequate immunosuppression with reduced doses of
individual agents to minimize their toxicity. Today, the majority of centers report using a
variation of a triple drug protocol. A few centers continue to employ two-drug therapy
consisting of cyclosporine and azathioprine. The immunosuppressive regimen currently
used at the Johns Hopkins Hospital is outlined in Table 49-8 .
To avoid the multiple untoward sequelae associated with chronic corticosteroid therapy,
several protocols have been proposed for steroid-free maintenance
immunosuppression (cyclosporine, azathioprine). [223 ] , [224 ] Timing of postoperative
withdrawal of prednisone is controversial. Some clinicians discontinue prednisone
within several weeks of transplantation, [223 ] , [225 ] , [226 ] whereas late withdrawal
strategists delay the taper until 612 months post-transplantation. [224 ] , [227 ] , [228 ]
Early corticosteroid withdrawal requires a course of induction cytolytic therapy.
Aggressive rejection surveillance is recommended for all patients during the
corticosteriod taper. Preliminary trials suggests that 5080 percent of patients can be
weaned from corticosteroids without an increased incidence of rejection. Attempts at
corticosteroid withdrawal in female recipients or patients with history of rejection in the
preceding 3 months have been usually unsuccessful. [229 ] , [230 ]
Individual Immunosuppressive Agents
CORTICOSTEROIDS
Corticosteroids have played an integral role in immunosuppression since the beginning

of cardiac transplantation. These nonselective agents influence essentially all limbs of
the immune response. [231 ] [233 ] Conventional immunosuppression in the
pre-cyclosporine era was achieved with corticosteroids and azathioprine. [234 ] , [235 ]
Currently, methylprednisolone is used during induction, and prednisone is usually part of
maintenance immunosuppressive regimens. Corticosteroids are also the first-line
therapy for acute rejection in most centers. The numerous untoward sequelae
associated with long-term corticosteroid therapy have driven clinicians to significantly
reduce doses of or even eliminate these drugs from maintenance regimens particularly
in diabetic patients and the elderly. [38 ] , [236 ]
AZATHIOPRINE
An imidazole derivative from 6-mercaptopurine, azathioprine inhibits antigen-stimulated

proliferation of lymphocytes. [237 ] Dosage adjustments are made to maintain the
leukocyte count between 4,0005,000/mm3. Azathioprine causes a dose-related bone
marrow suppression which can be profound if administered concurrently with allopurinol.
[238 ] If severe leukopenia or hepatotoxicity develop, azathioprine may be replaced with
cyclophosphamide. [239 ] Preliminary experience with mycophenolate mofetil suggests
this drug may be an important substitute for azathioprine.
CYCLOSPORINE
Cyclosporine (cyclosporin A), a cyclic undecapeptide fungal metabolite, [240 ] inhibits

the production of the lymphokine interleukin-2 (IL-2) by helper T-lymphocytes,
attenuating cytotoxic T-lymphocyte proliferation. [241 ] By sparing macrophages,
neutrophils, suppressor T-lymphocytes, and some B-lymphocytes, cyclosporine
provides more selective immunosuppression than azathioprine and corticosteroids.
[242 ] , [243 ] It has also permitted the reduction in corticosteroid doses in maintenance
immunosuppression. [244 ] , [245 ] Indeed, the improved survival of cardiac recipients in
the cyclosporine era is primarily secondary to a reduction in infection-related mortality
likely associated with a relative preservation of host defense against microbials.
Although the introduction of cyclosporine has not altered the incidence of acute
rejection, it has dramatically attenuated the severity and associated morbidity of
rejection episodes. [246 ] Doses of cyclosporine are adjusted to achieve trough serum
levels between 150300 ng/ml. [247 ] , [248 ] The low therapeutic index of cyclosporine
and the wide variation in pharmacokinetics between individuals mandates close
monitoring of levels to maximize immunosuppression while minimizing nephrotoxicity.
[249 ] [251 ] In light of the frequency of cyclosporine drug interactions, the initiation or
discontinuation of drugs should prompt frequent measurements of levels. For patients
who develop renal insufficiency, cyclosporine temporarily may be administered as a
continuous infusion to prevent wide fluctuations in serum levels. A new formulation of the
drug, Neoral (cyclosporin G), appears to have more predictable intestinal absorption
and improved pharmacokinetics compared with the original formulation. [252 ] , [253 ]
Nephrotoxicity and hypertension are the primary complications associated with
cyclosporine. [254 ]
POLYCLONAL ANTIBODIES
Polyclonal antibodies (antithymocyte, antilymphocyte) are produced by animals

following immunization with human lymphocytes. By attaching to circulating lymphocytes
and thus promoting cytolysis or opsonization by the reticuloendothelial system, these
antibodies can decrease the level of circulating T-cells to <10 percent of normal. The
precise mechanism by which polyclonal antibodies provide their immunosuppressive
effect is still under investigation. Antithymocyte globulin (ATG) and sera (ATS) have
been used as part of induction therapy protocols and for rescue therapy for acute
rejection refractory to corticosteroids. [255 ] [257 ] Use in the immediate postoperative
period permits a reduction in early corticosteroid doses and a delay in initiating
cyclosporine therapy in the patient at risk of perioperative renal failure. [258 ] , [259 ]
OKT3
OKT3 is a murine monoclonal antibody that binds and modulates the CD3 receptor site
on cytotoxic T-lymphocytes interfering with antigen recognition and preventing cellular
proliferation. [260 ] , [261 ] Like polyclonal preparations, administration of OKT3 can
also eliminate almost all circulating T-lymphocytes, though its monoclonal specificity
prevents it from having a cytolytic effect on other circulating cells. [262 ] Monitoring of T3
subpopulation cell counts can be used to determine adequacy of therapy. While it has
been used for induction therapy, OKT3 has demonstrated its greatest benefit on rescue
therapy. [263 ] [266 ] Thirty percent of patients develop antibodies against OKT3, but
few patients develop high enough titers to preclude reuse of the drug in the future. [267 ]
, [268 ] Studies comparing efficacy of OKT3 and ATG have yielded conflicting results.
[269 ] , [270 ] Controversy exists concerning the long-term side effects of both
monoclonal and polyclonal antibody therapy (i.e., increased risk of viral infections and
malignancy).
INVESTIGATIONAL AGENTS
FK-506 and rapamycin are potent, novel immunosuppressive agents derived from the
fungus Streptomyces . The mechanism and toxicities of FK-506 resemble those of
cyclosporine, and early experience in cardiac transplantation has yielded encouraging
results. [271 ] , [272 ] Rapamycin directly inhibits IL-2- (and IL-4)-driven proliferation
T-lymphocytes instead of blocking IL-2 production. [273 ] Lymphocyte-specific inhibition
of de novo purine synthesis by mycophenolate mofetil, an agent possessing properties
similar to azathioprine, currently provides the most promise for the induction of
allograft-specific unresponsiveness. [274 ] , [275 ] Clinical trials are ongoing to evaluate
the efficacy and toxicity of these agents, whereas the search for more selective, less
toxic immunosuppressive drugs continues. [276 ] Preliminary studies have found
FK-506 to be most effective in reversing recalcitrant rejection.
Nonpharmacologic Immunosuppressive Strategies
TOTAL LYMPHOID IRRADIATION (TLI)
Fractionated delivery of radiation to lymphatic tissues using an inverted Y-mantle field

provides several weeks of generalized, nonspecific immunosuppression. Experimental
indications for TLI include recurrent rejection unresponsive to pharmacologic
intervention and treatment-limiting toxicity associated with standard
immunosuppressive agents. [277 ] [279 ] Because of the potential for life-threatening
bone marrow suppression, azathioprine is discontinued during TLI therapy.
PHOTOPHERESIS
Peripheral mononuclear blood cells are obtained via leukopheresis from recipients who
have received a photoactivatable agent (e.g., 8-methoxypsoralen). Following ex vivo
activation with ultraviolet A light, the mononuclear cells are reinfused into the recipient
where they have a suppressor effect on T-lymphocytes (mechanism unclear).
Preliminary studies have demonstrated that this non-toxic immunomodulating technique
can reverse acute rejection (including recalcitrant cases). [280 ] , [281 ]
APHERESIS
Apheresis procedures (e.g., therapeutic plasma exchange) permit the removal of

circulating antibodies and cytokines. In the future, selective immunoabsorption filtration
techniques may allow the reduction of antibodies to HLA antigens in sensitized patients
as well as the removal of specific cellular subsets. Controversy exists regarding current
indications for the use of apheresis.
ACUTE REJECTION
Cardiac allograft rejection is the normal host response to cells recognized as nonself.
The vast majority of cases are mediated by the cellular limb of the immune response
through an elegant cascade of events involving macrophages, cytokines, and
T-lymphocytes. Humoral-mediated rejection (also called vascular rejection) is less
common. More than 80 percent of episodes of acute rejection occur in the first 3 months
after transplantation, and most recipients will have at least one episode of rejection
during this period. [282 ] , [283 ] The highest risk factors are female gender, human
leukocyte antigen (HLA) mismatches, and allografts from younger or female donors.
[284 ] Although 8096 percent of episodes can be reversed with corticosteroid therapy
alone, [285 ] [287 ] rejection is still a major cause of mortality in cardiac recipients. [288
] , [289 ]
Diagnosis of Acute Rejection
Classic clinical manifestations of acute rejection include low-grade fever, malaise,

leukocytosis, pericardial friction rub, supraventricular arrhythmias, low cardiac output,
reduced exercise tolerance, and signs of congestive heart failure. Unfortunately, in the
cyclosporine era, most episodes of rejection are characteristically insidious and
patients remain asymptomatic until late. Thus, routine surveillance studies for early
detection are crucial to minimize cumulative injury to the allograft.
Right ventricular endomyocardial biopsy remains the gold standard for the diagnosis of
acute rejection. [290 ] , [291 ] The most frequently utilized technique for orthotopic
allografts is a percutaneous approach through the right internal jugular vein (Fig. 49-14) .
Fluoroscopic (or echocardiographic) guidance of the bioptome ensures that the jaws
engage the interventricular septum. [292 ] , [293 ] Specimens are fixed in formalin for
permanent section although frozen sections occasionally are performed if urgent
diagnosis is necessary. Hemodynamic parameters may also be obtained with a
pulmonary artery catheter. Complications are infrequent (12 percent), but include
venous hematoma, carotid puncture, pneumothorax, arrhythmias, heart block, and right
ventricular perforation. The exact schedule for endomyocardial biopsies varies among
institutions but reflects the greater risk of rejection during the first 6 months following
transplantation. Biopsies are initially performed every 710 days in the early
postoperative period and eventually tapered to 3- to 6-month intervals after the first
year. Suspicion of rejection warrants additional biopsies. The benefit of routine,
long-term rejection surveillance in cardiac transplantation currently is being challenged
since few rejections occur during maintenance immunosuppression and they are rarely
asymptomatic. Several centers recommend that after 6 months endomyocardial
biopsies only be performed if there is a suspicion of rejection, but most feel that chronic
unrecognized rejection (even if asymptomatic) may jeopardize long-term survival. [294 ]
, [295 ]
The pattern and density of lymphocyte infiltration in addition to the presence or absence
of myocyte necrosis in the endomyocardial biopsy determine the severity grade of
cellular rejection (Table 49-9) . [296 ] Interpretation of histology may be complicated by
the lymphocyte infiltration and perimyocytic fibrosis associated with cyclosporine
therapy. [297 ] , [298 ] Inflammatory infiltrates associated with organ preservation injury
or infection may also mimic rejection. [299 ] Etiologies of biopsy-negative allograft
dysfunction include focal rejection, accelerated coronary artery disease, and
occasionally, vascular (humoral-mediated) rejection.
Noninvasive studies for the diagnosis of acute rejection have been unreliable.
Electrocardiographic voltage summation and E-rosette assay techniques were useful
adjuncts in the early cardiac transplant experience [300 ] ; however, they are now of no
value in patients receiving cyclosporine. [301 ] More recent attempts with
signal-averaged electrocardiography, [302 ] , [303 ] echocardiography, [304 ] , [305 ]
magnetic resonance imaging, [306 ] Technetium ventriculography, [307 ] and a variety
of immunologic markers [308 ] , [309 ] have not provided sufficient sensitivity to warrant
widespread use. [310 ]
Treatment of Acute Rejection
Corticosteroids are the cornerstone for antirejection therapy (Fig. 49-15) . [286 ] The
treatment of choice for any rejection episode occurring during the first 13 months
postoperatively or for an episode considered to be severe is a short course (3 days) of
intravenous methylprednisolone (1,000 mg/d). [286 ] Virtually all other episodes are
initially treated with increased doses of oral prednisone (100 mg/d) followed by a taper
to baseline over several weeks. [285 ] , [311 ] Although not yet universally accepted,
many centers successfully reduce the doses of these corticosteroids with reversal rates
of rejection similar to traditional dosing. [287 ] , [312 ]
Repeat endomyocardial biopsy should be performed 710 days after the cessation of
antirejection therapy to assess adequacy of treatment. If biopsy does not show
significant improvement, a second trial of pulse-steroid therapy is recommended; if
rejection has progressed (or if the patient becomes hemodynamically unstable), rescue
therapy is indicated. Rescue protocols for recurring or refractory rejection include
methylprednisolone plus OKT3 polyclonal antibody therapy (ATS, ATG, ALG), or
methotrexate. [255 ] , [263 ] , [313 ] [315 ] Methotrexate has been particularly successful
in eradicating chronic low-grade rejection. Trials using the investigational drugs
FK-506, [271 ] rapamycin, [273 ] and mycophenolate mofetil [274 ] are ongoing. Total
lymphoid irradiation and photopheresis also demonstrate success in some cases of
refractory rejection. [277 ] , [281 ] Cardiac retransplantation is the ultimate therapeutic
option for patients who do not respond to the aforementioned interventions. However,
the results of retransplantation for rejection are dismal and in most centers, it is no
longer performed for this indication.
Except in the occasional case of rejection associated with significant symptoms or

hemodynamic instability, the decision to treat acute rejection is complex. The risk of
infection associated with increased immunosuppression must be carefully weighed
against the potential sequelae of untreated rejection. Asymptomatic mild rejection
(grade 1) is usually not treated but are monitored with repeat endomyocardial biopsies,
because only 2040 percent of mild cases progress to moderate rejection. [316 ] , [317 ]
On the other hand, presence of myocyte necrosis (grades 3B and 4) represents a
definite threat to allograft viability and is a universally-accepted indication for therapy.
Management of moderate rejection (grade 3A) is the most controversial and requires
consideration of multiple variables. [318 ] , [319 ] Regardless of the biopsy results,
allograft dysfunction is an indication for hospitaliza tion, antirejection therapy, and if
severe, invasive hemodynamic monitoring and inotropic support. Interestingly, biopsy
results of up to 60 percent of patients presenting with hemodynamically significant
rejection reveals only mild or moderate rejection. [320 ]
Acute Vascular Rejection
Vascular rejection is mediated by the humoral limb of the immune response. [321 ] [323
] There is growing interest in antibody-mediated mechanisms of acute rejection
particularly in patients with a history of treatment with cytolytic agents, an elevated panel
of reactive antibodies, or multiparity. [324 ] , [325 ] Unlike cellular rejection,
hemodynamic instability often necessitating inotropic support is common in cases of
vascular rejection. [326 ] Diagnosis requires evidence of endothelial cell swelling on
light microscopy and immunoglobulin-complement deposition by immunofluorescence
techniques. [327 ] , [328 ] Aggressive treatment of patients with allograft dysfunction
consists of plasmapheresis, high-dose corticosteroids, heparin, and
cyclophosphamide. [329 ] [331 ] Despite these interventions, symptomatic acute
vascular rejection is associated with a high mortality. [332 ] It is theorized that repeated
episodes of acute vascular rejection or chronic low-grade vascular rejection play a
dominant role in the development of allograft coronary artery disease. [333 ] [335 ]
INFECTIOUS COMPLICATIONS IN HEART TRANSPLANTATION
Infection is a leading cause of morbidity and mortality in the cardiac transplant

population. [336 ] , [337 ] Impaired host defense secondary to chronic
immunosuppression is the primary predisposing factor for the increased susceptibility
to microbial pathogens. The introduction of cyclosporine (CYA), coincident with a more
aggressive approach to diagnosis and treatment, has resulted in a dramatic reduction
in the frequency and severity of transplant-related infections over the past decade. [338
] [340 ] The incidence of infection is 0.06 episodes per patient-month. The Registry of
the International Society of Heart and Lung Transplantation reports that the mortality due
to infectious complications currently accounts for approximately 15 percent of early and
40 percent of late deaths in cardiac recipients. Patients are at greatest risk of
life-threatening infections in the first 3 months after transplantation and following
increases in immunosuppression for acute rejection episodes or retransplantation. [336
] , [341 ]
Organisms and Timing of Infections
The source of post-transplant infection may be exogenous (nosocomial, latent infection

in the donor organ, and community-acquired) or endogenous (reactivation of a latent
recipient infection). Table 49-10 illustrates the most common organisms causing
infections in the cardiac recipient. The types of infections often follow a predictable
temporal sequence following transplantation. [342 ] , [343 ] During the first postoperative
month, nosocomial bacterial pathogens common to any patient undergoing surgery and
requiring intensive care unit admission account for the majority of early infections. [344 ]
Opportunistic pathogens (e.g., microorganisms that almost never cause severe illness
in healthy individuals with normal cellular immunity) are responsible for the majority of
infections between 16 months. [345 ] Thereafter, infections in the immunosuppressed
recipient are caused by a mixture of community-acquired bacterial and opportunistic
organisms. [346 ] , [347 ] Major infections are rare after the first year in the absence of
recurrent acute rejection episodes.
Diagnosis and Treatment of Infection
Attenuation of the normal host response to microbial invasion by immunosuppressive

agents and the indolent early presentation of many opportunistic infections demands a
high index of suspicion for the timely diagnosis of transplant-related infections.
Diagnosis may be complicated further by concurrent episodes of acute rejection or
coexistent infections. A multidisciplinary approach involving consultation with specialists
in infectious disease, pulmonology, neurology, and gastroenterology is essential.
Any fever >38.0°C should be aggressively evaluated for an infectious source. Initial
work-up consists of a thorough history and physical examination, complete blood count
with differential, cultures (blood, sputum, urine), and chest roentgenogram. Indwelling
catheters should be replaced and cultured. Attention should be initially focused on ruling
out a pulmonary process since the lung is the most common site of infection in cardiac
transplant recipients. [348 ] , [349 ] Because of the fulminant nature of many
opportunistic lung infections in immunosuppressed hosts, new pulmonary symptoms or
suspicious radiographic findings warrant prompt diagnostic evaluation by fiberoptic
bronchoscopy with transbronchial biopsy and bronchoalveolar lavage or CT-guided
transthoracic needle aspiration. [350 ] , [351 ] Persistent headache, change in mental
status, seizures, or nuchal rigidity should be evaluated with a CT scan of the brain, and if
negative, a lumbar puncture to rule out a central nervous system infection. [352 ]
Additional diagnostic studies are guided by the clinical presentation and include chest
or abdominal CT scan, endoscopy, and serologic studies.
If the patient's condition is deteriorating, empiric antibiotics are initiated after

appropriate cultures have been obtained. To reduce the risk of bacterial resistance,
specific antimicrobial therapy is initiated as soon as the pathogen has been identified.
Immunosuppression may be reduced cautiously to aid host defenses in combating
infection. Cyclosporine-antimicrobial drug interactions mandate that CYA levels and
serum creatinine be closely monitored to avoid acute rejection or nephrotoxicity. [353 ] ,
[354 ]
Preventive Measures and Prophylaxis against Infection
PREOPERATIVE SCREENING
Prevention of postoperative infection begins with pretransplant screening of the donor

and recipient. [355 ] Current suggested guidelines are outlined in Table 49-11 .
Potential donors or recipients with active systemic infection or positive serologies for
human immunodeficiency virus (HIV) or hepatitis B virus (HBV) are not candidates for
transplantation. [356 ] Controversy exists regarding cardiac transplantation in patients
seropositive for hepatitis C virus (HCV). [357 ] , [358 ] Recipient prophylaxis is
indicated for donors seropositive for cytomegalovirus (CMV) or Toxoplasma gondii if
the recipient is seronegative. [359 ] , [360 ]
PERIOPERATIVE INFECTION PREVENTION
A first-generation cephalosporin (e.g., cefazolin) should be initiated prior to induction of

anesthesia and continued for 48 hours postoperatively or until all intravascular catheters
are removed for routine anti-staphylococcal coverage. [361 ] In patients with
documented beta-lactam allergy, vancomycin is the antibiotic of choice. Agents against
opportunistic pathogens are not indicated in the perioperative period since the relatively
immunocompetent transplant recipient is at risk of common nosocomial infections
during this period. Meticulous aseptic technique must be practiced during preoperative
intravascular catheter insertion and during the transplant procedure. Postoperatively, the
patient is generally is admitted to a private room. Although elaborate protective
isolation procedures are no longer used, [362 ] all individuals who come in contact with
the recipient must perform handwashing and those with communicable diseases are
not permitted to enter patient's room. [363 ] Endotracheal tubes, intravascular catheters,
and indwelling urinary catheters should be removed as soon as possible. Patients
requiring prolonged intubation for ventilatory support may benefit from selective
oropharyngeal and bowel decontamination. [364 ]
POSTOPERATIVE ANTIMICROBIAL PROPHYLAXIS
Trimethoprim-sulfamethoxazole (TMP/SMX) or aerosolized pentamidine (if TMP/SMX

not tolerated) provide effective prophylaxis against Pneumocystis carinii pneumonia.
[365 ] , [366 ] TMP/SMX also reduces the incidence of Toxoplasma gondii , Listeria,
Legionella, and possibly Nocardia infections. Nystatin or clotrimazole is routinely given
to prevent mucocutaneous candidiasis. [367 ] The frequency and severity of
recurrences of herpes simplex and varicella-zoster infections can be reduced with
low-dose oral acyclovir although routine prophylaxis is not universally accepted. [368 ]
Standard endocarditis antibiotic prophylaxis is indicated prior to bacteremia-producing
procedures. Recipients with a positive PPD skin test should be considered for
prophylactic isoniazid (±rifampin) therapy. [369 ]
POSTOPERATIVE IMMUNIZATIONS
Recommended postoperative vaccinations are listed in Table 49-11 . [370 ] , [371 ]

Live, attenuated virus vaccines should be avoided in the immunocompromised
transplant patient. Immunization for influenza A virus is controversial as this pathogen is
not responsible for significant morbidity in cardiac transplantation. [372 ] Exposure to
measles, varicella, tetanus, or hepatitis B by a nonimmunized recipient often warrants
specific immunoglobulin therapy (e.g., Varicella-Zoster Immune Globulin, VZIG). [373 ]
POSTOPERATIVE INFECTION SURVEILLANCE
At discharge from the hospital, patients should be instructed to promptly report any
signs of infection (fever, malaise, cough, shortness of breath, diarrhea) or suspicion of
infectious exposure. Postoperative infection surveillance includes periodic
examinations, bacterial cultures, viral titers and serologies, and chest roentgenograms.
Management of infections in recipients should generally be undertaken in centers
experienced in transplant medicine.
Donor-Transmitted Infection
CMV, Toxoplasma gondii , HBV, HCV, and HIV may be transmitted to the recipient via
the donor allograft. [374 ] , [375 ] Ideally, recipients seronegative (SN) for CMV or
Toxoplasma would receive appropriately SN organs to prevent the development of a
life-threatening primary infection postoperatively. [376 ] Because of the scarcity of
donors, CMV and Toxoplasma serologic mismatches are sometimes unavoidable.
Both SN and seropositive (SP) recipients receiving a heart from a CMV-SP donor are
routinely administered intravenous ganciclovir, while the subsequent administration of
high-dose oral acyclovir and/or CMV hyperimmune globulin therapy is more
center-specific. [377 ] , [378 ] Patients SN for CMV should only receive CMV-SN blood
products. This can be accomplished with CMVblood or the use of a leukocyte filter if
CMV+ blood must be administered. [379 ] Toxoplasma serologic mismatches are
prophylactically treated with a pyrimethamine. [360 ]
Specific Organisms Causing Infection Following Heart Transplantation
BACTERIA
Gram-negative bacilli are the most common cause of early postoperative pneumonia.
Pneumonia owing to Nocardia asteroides usually occurs 12 years after transplantation
and requires a prolonged course of sulfa drugs. [380 ] Legionella pneumophila and
Mycobacterim sp., uncommon causes of pneumonia in cardiac recipients, are treated
with high-dose intravenous erythromycin and isoniazid/rifampin, respectively. Listeria
monocytes meningoencephalitis is associated with a high mortality. [381 ]
VIRUS
CMV, the most common pathogen following cardiac transplantation, occurs in >75
percent of recipients. [382 ] , [383 ] Infections develop because of donor-transmission,
reactivation of latent recipient infection, or reinfection of a CMV-sero-positive patient
with a different viral strain. [384 ] Mortality from serious CMV infections has been
dramatically reduced with ganciclovir. The reduction in leukocytes associated with CMV
infection predisposes the patient to superinfection with other pathogens (e.g., CMV
Pneumocystis carinii pneumonia). [385 ] Although not a cure for herpes simplex or
zoster viruses, acyclovir can reduce recurrences and the discomfort associated with the
vesicular lesions. Epstein-Barr virus infection may be associated with post-transplant
lymphoproliferative disorders in immunocompromised hosts. [386 ]
FUNGUS
Mucocutaneous candidiasis is common and usually can be treated with topical

antifungal agents (nystatin or clotrimazole). Fluconazole is indicated for candidiasis
refractory to this therapy or involving the esophagus. [387 ] Aspergillus causes a serious
pneumonia in 510 percent of recipients during the first 3 months after transplantation
and requires intravenous amphotericin B (or oral itraconazole). [388 ] Dissemination of
aspergillus to the central nervous system is almost uniformly fatal. [389 ] Cryptococcus
usually presents as a meningitis after an asymptomatic primary infection of the lungs.
PROTOZOA
Pneumocystis carinii is the most common cause of late pneumonia. [390 ] Since the
organism resides in the alveoli, bronchoalveolar lavage usually is necessary for
diagnosis. TMP-SMX or pentamidine are the agents of choice for treatment of this
protozoa. [365 ] , [366 ] In addition to donor-transmission, Toxoplasma gondii infection
may be acquired from under-cooked meat and cat feces. It usually causes CNS
infections and is effectively treated with pyrimethamine and sulfonamides for 6 months.
[391 ]
Even before the landmark Surgical Forum presentation of orthotopic cardiac

transplantation by Shumway and Lower in 1960, [1 ] Demikhov [2 ] developed numerous
anatomic variants of intrathoracic heterotopic cardiac transplantation and the first
successful method of en bloc heart-lung transplantation in the mid-1940s, establishing
the technical feasibility of these operations. In the West, several groups undertook
experimental heart-lung transplantation. In 1953, Marcus et al. [3 ] at the Chicago
Medical School described heterotopic heart-lung grafting to the intraabdominal aorta
and vena cava in canines (Fig. 50-1) . In addition to developing the operative technique
for total heart-lung replacement, early studies characterized the physiologic effects of
total cardiopulmonary denervation. Heart-lung denervation in canines consistently
resulted in adverse alterations in respiratory patterns and cast doubt on the functionality
of such operations. [4 ] , [5 ] Fortunately, studies by Haglin et al. [6 ] that were later
confirmed by Nakae et al. [7 ] showed that denervation of both lungs did not prevent a
return of adequate spontaneous respiration in primates as it did in dogs. Further work
reported by Castaneda et al. [8 ] , [9 ] in 1972 at the University of Minnesota revealed
that pulmonary ventilation and perfusion and circulatory hemodynamics were preserved
after heart-lung autotransplants in baboons. In 1972, Reitz et al. [10 ] at Stanford
University began a series of heart-lung auto- and allotransplants in primates resulting in
survival well over 5 years. Reitz et al. [11 ] also described a major modification to the
standard technique in the use of a retained portion of the right atrium for a single inflow
anastomosis instead of separate caval anastomoses (Fig. 50-2) . This technique
preserved the donor sinoatrial node, eliminated potential caval anastomotic stenosis,
and facilitated the operation in humans, where the intrathoracic inferior vena cava is
short. Use of the immunosuppressant cyclosporin A by the Stanford group also proved
to be a key factor in their successes. These remarkable results in primates led directly
to a clinical trial of heart-lung transplantation at Stanford. On March 9, 1981, Reitz et al.
[12 ] performed the first successful human heart-lung transplantation in a 45-year-old
woman with end-stage primary pulmonary hypertension. Further advances in
perioperative management accompanied subsequent successful heart-lung transplants
at Stanford, giving rise to a new therapeutic modality for terminal cardiopulmonary
disease.
INDICATIONS FOR HEART-LUNG TRANSPLANTATION
Heart-lung transplantation was developed initially for patients suffering from severe
pulmonary vascular disease, specifically primary pulmonary hypertension (PPH) and
Eisenmenger's syndrome secondary to congenital heart disease. Over time, the
indications for this procedure have broadened to include patients with intercurrent
end-stage lung disease and cardiac dysfunction as well as patients with septic lung
disease. The diagnostic profile of heart-lung transplant recipients reported to the
Registry of the International Society for Heart and Lung Transplantation (ISHLT) in 1994
[13 ] is shown in Fig. 50-3 .
Primary pulmonary hypertension with severe right-sided heart failure is the most
common indication for heart-lung transplantation and was the diagnosis in 31.5 percent
of the heart-lung transplants reported to the ISHLT Registry. The past several years
have seen a shift away from heart-lung transplantation to single and bilateral lung
transplantation for pulmonary hypertension without right-sided heart decompensation.
This shift resulted from the relative shortage of heart-lung blocs and the recognition that
right-sided heart function could recover if pulmonary vascular resistance was
decreased. However, the long-term outcome of patients with pulmonary hypertension
treated with single and bilateral lung transplantation is unknown. Bando et al. [14 ] at the
University of Pittsburgh reported that graft-related mortality is significantly greater and
overall functional recovery is significantly lower at 1 year in single versus bilateral lung
and heart-lung recipients transplanted for pulmonary hypertension.
Uncorrectable congenital heart disease with severe Eisenmenger's syndrome is the

second most frequent diagnosis encountered in heart-lung transplantation. Congenital
cardiac lesions that may lead to severe Eisenmenger's syndrome include atrial and
ventricular septal defects, patent ductus arteriosus, and truncus arteriosus. Other
complex congenital defects that have been treated successfully with heart-lung
transplantation include univentricular heart with pulmonary atresia and aortic
atresiahypoplastic left heart syndrome.
The balance of heart-lung transplants are performed for a variety of cardiac and
pulmonary disease processes. Septic lung disease, particularly cystic fibrosis and
bronchiectasis, and severe emphysema have been treated successfully with heart-lung
transplantation. Other situations include simultaneous end-stage coronary disease with
severe emphysema, primary parenchymal lung disease with right-sided heart
decompensation (e.g., idiopathic pulmonary fibrosis, lymphangioleiomyomatosis,
sarcoidosis, and desquamative interstitial pneumonitis), and cardiomyopathy with
pulmonary hypertension. In patients in whom right ventricular function is relatively
preserved, single or bilateral lung transplantation should be considered.
Recipient Selection Criteria
The overriding objective in recipient evaluation is to select individuals with progressively

disabling cardiopulmonary or pulmonary disease, yet possessing the capacity for full
rehabilitation after transplantation. Disabling symptoms prompting consideration for
transplantation typically include dyspnea, cyanosis, syncope, and hemoptysis. Most
recipients fall within New York Heart Association functional classes III or IV. [15 ] In the
heart-lung transplant program at Stanford, suitability for transplantation is determined in
an outpatient pretransplant clinic where data from routine screening and selected
specialized studies are reviewed ( Table 50-1 ).
Adherence to strict recipient selection criteria has played an important role in achieving
the excellent results observed in heart-lung transplantation today. However, recent
advances in the management of these patients both before and after transplantation
have been accompanied by a relaxation of certain criteria, including upper age limits,
concomitant disease, and level of disability. Although a wider range of patients has
benefited from this expansion of eligibility, the perennial problem of donor organ
shortage has been exacerbated. Consequently, current efforts are directed toward
refining recipient evaluation methods and selection criteria to channel grafts to those
patients who are in most immediate need while maintaining good short- and long-term
outcomes.
Among most heart-lung transplant programs, the upper recipient age limit is 50 years,
with projected life expectancies limited to less than 12 to 18 months despite the use of
appropriate medical or alternative surgical strategies. Mortality while on the waiting list
remains considerable, ranging from 10 to 30 percent at most institutions performing
heart-lung transplantation.
There are several well-established general contraindications to heart-lung

transplantation ( Table 50-2 ).Patients suffering from systemic disease with significant
renal or hepatic dysfunction, acute illness, unresolved malignancy, or psychiatric illness
are not offered transplantation. Relative contraindications include cachexia or obesity
and a recent history of active peptic ulcer disease. Patients requiring systemic
corticosteroids are tapered to the lowest tolerable level, preferably below 10 mg/day or
off completely, before transplantation. Cigarette smokers must quit smoking and remain
abstinent for at least several months before transplantation. During the early years of
heart-lung transplantation, previous cardiothoracic surgery and pleurodesis were
considered absolute contraindications due to bleeding from chest wall adhesions and
difficulty preserving the vagus, recurrent laryngeal, and phrenic nerves. With improved
surgical technique, however, these patients are now being considered selectively for
transplantation. Of course, a stable, supportive socioeconomic environment is an
important requirement.
Patients with cystic fibrosis or a significant smoking history are held to additional
requirements at Stanford. All prospective cystic fibrosis recipients should have an
otolaryngologic evaluation before being placed on the active waiting list. Most of these
patients will require endoscopic maxillary antrostomies for sinus access and periodic
antibiotic irrigation to decrease bacterial colonization in the upper respiratory tract. This
measure has decreased the incidence of serious posttransplant bacterial infections in
this group of patients. Previous smokers must undergo extensive screening to exclude
smoking-related illnesses, specifically peripheral vascular disease and malignancy. A
negative sputum cytology, thoracic computed tomographic (CT) scan, bronchoscopy,
otolaryngologic evaluation, carotid duplex scan, and flexible
sigmoidoscopy/colonoscopy are required prior to listing.
Clinical and Laboratory Criteria for Listing
Patients deemed suitable for heart-lung transplantation enter a second phase of testing
(see Table 50-1 ),are categorized, and are listed on the basis of clinical status, time on
the waiting list, ABO blood group, and thoracic cage dimensions. Pagers are issued
and travel arrangements are completed with social worker assistance. Each potential
recipient is usually required to reside within 2 hours of the transplant center by
automobile or air charter. The average time from listing to transplantation ranges from 1
to 2 years at Stanford. Listed candidates are seen in clinic every 3 to 6 months prior to
transplantation to maintain them in optimal medical condition.
Currently, donor-recipient matching parameters include ABO compatibility and body

size. ABO compatibilities are strictly adhered to because isolated episodes of
hyperacute rejection have been observed in cardiac transplants performed across ABO
barriers. Donor-to-recipient lung volume matching is based on the vertical (apex to
diaphragm along the midclavicular line) and transverse (level of the diaphragmatic
dome) radiologic dimensions on chest roentgenogram as well as body weight, height,
and chest circumference. In practice, matching donor and recipient height seems to be
the most reproducible method of selecting the appropriate donor lung size. In general,
the dimensions of the donor lungs should not be greater than 4 cm over similar
measurements in the potential recipient and preferably should be smaller than those of
the recipient. In a series of 82 heart-lung transplants at Papworth Hospital, Tamm et al.
[16 ] recorded recipient lung volumes after transplantation and compared them with
preoperative and predicted volumes to evaluate the influence of donor lung size and
recipient underlying lung disease. The investigators showed that by 1 year after surgery,
total lung capacity (TLC) and dynamic lung volume returned to values predicted by the
patient's sex, age, and height. They proposed that the simplest method of matching
donor lung size to that of the recipient is to use their respective predicted TLC values.
Moreover, they concluded that the recipient's predicted lung volumes should be attained
by 1 year after transplantation and that failure to do so suggests possible complications
within the transplanted lungs.
Once an appropriate donor-recipient pairing is made, the recipient is screened for

preformed antibodies against a panel of random donors. A percent reactive antibody
(PRA) level greater than 50 percent prompts a prospective specific crossmatch
between the donor and recipient. The relationship of heart-lung allograft-related death
and chronic rejection to human leukocyte antigen (HLA) matching was studied in 40
consecutive heart-lung transplant recipients operated on between 1981 and 1986 at
Stanford. [17 ] This study revealed a significant increase in graded obliterative
bronchiolitis with total mismatch at the HLA-A locus. Furthermore, there was a tendency
toward increased frequency, severity, and mortality with respect to obliterative
bronchiolitis in these mismatched patients. Unfortunately, HLA matching is currently not
feasible on a prospective basis in cardiopulmonary transplantation.
RECIPIENT MANAGEMENT AFTER LISTING
Some patients awaiting heart-lung transplantation are in some degree of heart failure.
All standard therapeutic measures are applied in these patients, namely, dietary
restrictions, diuretics, and vasodilators. Intravascular fluid management for patients in
heart failure consists of dietary water and salt restriction and diuretic therapy. Loop
diuretics effectively reduce intravascular volume. Particularly in patients with underlying
pulmonary disease, care must be exercised in their use, because the metabolic
alkalosis associated with this class of potent diuretics aggravates ventilatory
insufficiency by depressing the effectiveness of carbon dioxide as a stimulus to
breathing. Afterload reduction in the form of vasodilators, particularly nitrates,
hydralazine, and angiotensin-converting enzyme inhibitors, has proven to effectively
improve functional capacity and prolong survival in patients suffering from severe
cardiac failure. [18 ]
Despite the clinical heterogeneity among patients with primary pulmonary hypertension,
conventional medical therapy targets the sequelae of the pulmonary vascular
derangements associated with this disease process. Supplemental oxygen therapy is
generally recommended for any patient exhibiting arterial hypoxemia, defined as either
an arterial So 2 less than 90 percent or an arterial Po 2 less than 60 mmHg at rest,
during exertion, or while asleep. [19 ] Oxygen supplementation is intended to eliminate
the stimuli for hypoxic pulmonary vasoconstriction and secondary erythropoiesis,
lessening the burden placed on the right side of the heart and diminishing the
contribution of myocardial hypoxia to cardiac arrythmogenesis. Pulmonary vasodilator
therapy is based on the notion that pulmonary vasoconstriction is an important
component of PPH. [19 ] Reeves et al. [20 ] , [21 ] have shown that patients in whom a
reduction in pulmonary vascular resistance of greater than 30 percent is achieved
during an acute vasodilator trial are more likely to demonstrate sustained clinical
improvement than those who do not respond. Unfortunately, most standard vasodilators
have potent systemic effects and require careful dosing and follow-up. Severely ill
patients with PPH awaiting heart-lung or lung transplantation who were unresponsive to
oral vasodilator therapy have received continuous infusions of prostacyclin or
prostacyclin analogues to obtain reductions in pulmonary arterial pressure and
pulmonary vascular resistance. [22 ] , [23 ] Despite the favorable response to
prostacyclin seen in most of these patients, many become resistant to the drug's
effects. Therefore, patients placed on hold for heart-lung transplantation following
dramatic improvements with prostacyclin therapy should be followed closely and
reactivated early if deterioration is noted.
Interstitial lung disease in patients awaiting transplantation results from a wide variety of
diffuse inflammatory processes such as sarcoidosis, asbestosis, and collagen-vascular
diseases. Increases in pulmonary vascular resistance leading to right-sided heart failure
are thought to result from interstitial inflammatory infiltrates that entrap and eventually
destroy septal arterioles, reducing the distensibility of the remaining pulmonary vessels.
[19 ] This process, coupled with closure of peripheral bronchioles, results in arterial
hypoxemia, which further aggravates pulmonary hypertension. Corticosteroids are used
commonly in treating this class of diseases. Unfortunately, the adverse effects of
steroids on tracheal healing mandate significant dose reductions (prednisone to less
than 0.1 mg/kg per day) in anticipation of heart-lung transplantation.
Patients with dilated cardiomyopathy, congestive heart failure, and primary pulmonary
hypertension are predisposed to pulmonary and systemic thrombosis and embolization.
[19 ] Most centers employ routine prophylactic anticoagulation in the form of heparin,
warfarin, or antiplatelet agents in these patients.
The multisystem manifestations of cystic fibrosis, particularly chronic bronchopulmonary

infection, malabsorption, and diabetes mellitus, pose difficult management problems in
potential heart-lung recipients. [24 ] Aggressive chest physiotherapy, antibiotics, enteral
or parenteral nutritional supplementation, and tight serum glucose control require
meticulous medical management while awaiting transplantation.
ORGAN PROCUREMENT AND PRESERVATION
Donor Selection
Donors must have sustained irreversible brain death, usually as a result of blunt and
penetrating head trauma or intracranial hemorrhage. Due to the susceptibility of the
lungs to infection and edema, particularly in the settings of brain death and trauma,
suitable heart-lung blocs are more difficult to obtain than other organs. Less than 20
percent of nonthoracic organ donors possess lungs suitable for donation. [25 ]
Donor evaluation consists of a directed history and physical examination, chest film,
12-lead electrocardiogram, arterial blood gases, echocardiogram, serologic screening
[i.e., human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg),
hepatitis C antibodies, herpes simplex virus, cytomegalovirus (CMV), and Toxoplasma
], and direct inspection and palpation of the heart and lungs at explantation.
Echocardiographic evidence of normal cardiac function and the absence of a
significant cardiac history and significant coronary atherosclerosis must be established.
A donor age of less than 40 years is preferred, although potential donors aged 40 to 50
years are considered at most centers with a more detailed evaluation, including
coronary angiography to rule out significant coronary artery disease. A donor chest film
must be entirely clear, and the arterial PO 2 should exceed 100 mmHg on an FIO 2 of 30
percent and 400 mmHgn FIO 2 of 100 percent. Lung compliance can be estimated by
measuring peak inspiratory pressures, which should be less than 30 cmh 2 o.
Bronchoscopy should ensure the absence of purulent secretions or signs of aspiration.
Donors should receive broad-spectrum antibiotics prior to explantation for infection
prophylaxis.
Absolute contraindications for donation include severe coronary or structural heart

disease, prolonged cardiac arrest, prior myocardial infarction, a carbon monoxide
hemoglobin level greater than 20 percent, arterial oxygen saturation less than 100
percent, active malignancy (sometimes excluding primary brain and skin cancers), a
significant smoking history (greater than 5 pack-years or 1 pack per day over the past
year), and positive HIV status. Relative contraindications include thoracic trauma,
sepsis, prolonged severe hypotension (i.e., less than 60 mmHg for more than 6 hours),
noncritical coronary artery stenosis, HBsAg or hepatitis C antibodies, multiple
resuscitations, severe left ventricular hypertrophy, and a prolonged high inotropic
requirement (e.g., dopamine in excess of 15 µg/kg per min for 24 hours). It is important
to rule out correctable metabolic or physiologic causes of cardiac rhythm disturbances
and electrocardiographic anomalies (e.g., brain herniation, hypothermia, hypokalemia).
Donor Management
The overriding goal in managing the heart-lung donor is the maintenance of

hemodynamic stability and pulmonary function. Patients suffering from acute brain injury
are often hemodynamically unstable due to neurogenic shock, excessive fluid losses,
and bradycardia. Donor lungs are subject to neurogenic pulmonary edema, aspiration,
nosocomial infection, and contusion. Continuous arterial and central venous pressure
monitoring, judicious fluid resuscitation, vasopressors, and inotropes are usually
required.
Meticulous fluid management serves to prevent intraoperative blood pressure instability

and minimize the need for inotropes and vasopressors that stress the myocardium.
Intravascular volume should be given to maintain the central venous pressure between 5
and 8 mmHg without administering fluids at rates far in excess of the hourly urine output.
Crystalloid fluid boluses should be avoided. Diabetes insipidus is common in organ
donors and requires the use of intravenous vasopressin (0.8 to 1.0 unit/h) to reduce
excessive urine losses.
To maintain adequate perfusion pressures, dopamine is the standard inotropic agent

used, although alpha agonists (e.g., phenylephrine) are often appropriate. Blood
transfusions should be used sparingly to maintain the hemoglobin concentration at
around 10 g/dL to ensure adequate myocardial oxygen delivery. CMV-negative and
leukocyte-filtered blood should be used whenever possible. Hypothermia should be
avoided because it predisposes to ventricular arrhythmias and metabolic acidosis.
Regarding mechanical ventilation, FIO 2 values in excess of 40 percent, especially

100% oxygen challenges, should be avoided, since these oxygen levels may be toxic to
the denervated lung. Ventilator settings should include positive end-expiratory
pressures (PEEP) between 3 and 5 cmh 2 o to prevent atelectasis.
Donor Operation
The donor operation is performed via a median sternotomy (Fig. 50-4A) . After the
sternum is divided, a standard chest retractor is placed, and both pleural spaces are
opened immediately with inspection of the lungs and pleural spaces, particularly in
cases of trauma. The lungs are briefly deflated, and the pulmonary ligaments are
divided inferiorly using electrocautery. After completely excising the thymic remnant, the
pericardium is opened vertically and laterally on the diaphragm and cradled during
dissection of the great vessels and trachea. The ascending aorta, pulmonary artery, and
venae cavae are dissected. Umbilical tapes are placed around the ascending aorta
and venae cavae (Fig. 50-4B) . The pericardium overlying the trachea is incised
vertically, and the trachea is encircled with an umbilical tape between the aorta and
superior vena cava at the highest point possible and at least four rings above the carina
(Fig. 50-4C) . The entire anterior pericardium is excised back to each hilum (Fig.
50-4D) .
Approximately 15 minutes prior to applying the aortic cross-clamp, prostaglandin E1

(PGE 1 ) is infused intravenously initially at a rate of 20 ng/kg per min, followed by
incremental increases of 10 ng/kg per min to a target rate of 100 ng/kg per min (Fig.
50-4E) . During PGE 1 infusion, the mean arterial blood pressure should be maintained
at or above 55 mmHg. Ventilation is continued with an FIO 2 of 40 percent and a PEEP
of 3 to 5 cmh 2 o. The superior vena cava is ligated, and a straight Potts clamp is
placed across the inferior vena cava. After the heart is allowed to empty, the aortic
cross-clamp is applied, and 10 mL/kg of cold crystalloid cardioplegia, commonly the
Stanford formulation, is rapidly infused into the aortic root. The inferior vena cava is
incised, and the left atrial appendage is amputated immediately after starting the
cardioplegic infusion to avoid cardiac distension. Simultaneously with the cardioplegic
infusion, pulmonoplegia, most commonly Euro-Collins solution at 2 to 4°C, is rapidly
flushed into the main pulmonary artery at a rate of 15 mL/kg per min for 4 minutes.
Ice-cold saline or Physiosol solution (Abbott Laboratories, North Chicago, Ill.) is
immediately poured over the heart and lungs. During the cardioplegic and
pulmonoplegic infusions, ventilation is maintained with half-normal tidal volumes of room
air.
Upon completion of plegic infusions and topical cold application, all solutions are
aspirated from the thoracic cavity, and the lungs are fully deflated. The heart-lung bloc is
dissected free from the esophagus commencing at the level of the diaphragm and
continuing cephalad to the level of the carina. The dissection keeps close to the
esophagus and avoids injury to the trachea, lung, or great vessels. The posterior hilar
attachments are divided. The lungs are inflated to a full normal tidal volume, and the
trachea is stapled at the highest point possible with a TA-55 stapler (U.S. Surgical,
Norwalk, Conn.) at least four rings above the carina (Fig. 50-4) . The trachea is then
divided above the staple line, and the entire heart-lung bloc is removed from the chest.
The graft is wrapped in sterile gauze pads and immersed in ice-cold saline at 2 to 4°C
in several plastic bags placed within a sterile plastic container. This, in turn, is placed in
an ice-filled chest and transported to the transplant center.
Organ Preservation and Transport
On-site lung procurement was considered essential between 1981 and 1984 due to
inadequate lung preservation techniques. [26 ] , [27 ] Since then, active research and
clinical experience have produced several different preservation protocols that have
permitted distant procurement. [28 ] Nevertheless, current techniques are far from ideal,
since inadequate lung preservation still remains a significant cause of early graft
dysfunction following lung and heart-lung transplantation.
Heart-lung blocs are typically preserved with a modified Euro-Collins pulmonary artery
flush in conjunction with standard crystalloid cardioplegic arrest. The pulmonary artery is
flushed with a modified Euro-Collins cold crystalloid solution. Euro-Collins solution is of
essentially intracellular composition and is the most commonly used lung perfusate.
PGE 1 is also given intravenously to counteract reflex pulmonary vasoconstriction
resulting from the cold flush and to permit uniform distribution of the perfusate
throughout the lung. The Stanford formulation is a commonly used cardioplegic
formulation comprised of potassium chloride 30 meq/liter, sodium bicarbonate 44.6
meq/liter, and mannitol 12.5 g/liter in 5% dextrose in water. Generally, with proper
preservation technique, cold ischemia times of up to 6 hours appear to be consistently
well tolerated. Longer ischemic times increase the risk of significant posttransplant
pulmonary edema, alveolar damage, and early graft dysfunction.
Experimental studies suggest improved graft function when the lung is inflated, when
100% oxygen is used, when the lung is transported at 10°C, and when PGE 1 is
administered before perfusion of the modified Euro-Collins solution. [28 ] The
development of improved lung preservation has focused recently on reducing injurious
oxygen free radicals with scavengers, [29 ] leukocyte depletion techniques, [30 ] and
colloid-based perfusates. [31 ] Based on experimental evidence that donor lymphocytes
play a role in ischemic lung graft injury, [32 ] methylprednisolone is given intravenously to
the donor (Stanford) to inactivate them.
These preservation techniques coupled with streamlined donor and recipient protocols
have permitted procurements as far as 1000 miles from the transplant center. Extensive
communication and coordination must be maintained between the organ procurement
agency, donor and recipient operative teams, medical centers, and abdominal organ
procurement teams. The major procurement agencies in existence are the United
Network for Organ Sharing (UNOS) in the United States, Multiple Organ Retrieval
(MORE) in Canada, and The EURO Transplant Organization in Europe.
RECIPIENT OPERATION
After the chest is entered through a median sternotomy, a sternal retractor is placed,
and both pleural spaces are opened anteriorly from the level of the diaphragm to the
level of the great vessels (Fig. 50-5A) . At this point, any pleural adhesions should be
divided using electrocautery. In patients in whom dense pleural adhesions are
anticipated, as in those with previous thoracotomies or cystic fibrosis, a bilateral
clamshell thoracotomy with the use of perioperative antifibrinolytic therapy (e.g.,
aprotinin) and an argon beam coagulator considerably facilitate lysis of adhesions and
hemostasis. The anterior surface of the pericardial surface is excised, and the lateral
segments are preserved to support the heart and protect the phrenic nerves. A 3-cm
border of pericardium should be left both anteriorly and posteriorly to each phrenic
nerve extending from the level of the diaphragm to the level of the great vessels (Fig.
50-5B) .
After fully heparinizing the recipient, the ascending aorta is cannulated near the base of
the innominate artery, and the venae cavae are individually cannulated laterally and
snared. Cardiopulmonary bypass with systemic cooling to 28 to 30°C is instituted, and
the heart is excised at the midatrial level. The aorta is divided just above the aortic
valve, and the pulmonary artery is divided at its bifurcation (Fig. 50-5C) . The left atrial
remnant is then divided vertically at a point halfway between the right and left pulmonary
veins. At Stanford we have gravitated toward the use of bicaval venous anastomoses in
most heart-lung transplants. This technique is mandatory for domino procedures and
requires excision of most atrial tissue.
The posterior edge of the left atrial and pulmonary venous remnant is developed in a
manner that allows the left inferior and superior pulmonary veins to be displaced over
into the left chest. Following division of the pulmonary ligament, the left lung is then
moved into the field, allowing full dissection of the posterior aspect of the left hilum,
being careful to avoid the vagus nerve posteriorly. Once this is completed, the left main
pulmonary artery is divided (Fig. 50-5D) , and the left main bronchus is stapled with a
TA-30 stapler and divided. The same technique of hilar dissection and division is
repeated on the right side (Fig. 50-5E) , and both lungs are removed from the chest.
The native main pulmonary artery remnant is removed, leaving a portion of the
pulmonary artery intact adjacent to the underside of the aorta near the ligamentum
arteriosus to preserve the left recurrent laryngeal nerve. Attention is then turned to
preparing the distal trachea for anastomosis. The stapled ends of the right and left
bronchi are grasped, and dissection is carried up to level of the distal trachea.
Bronchial vessels are individually identified and carefully ligated. Patients with
congenital heart disease and pulmonary atresia or severe cyanosis secondary to
Eisenmenger's syndrome may have large mediastinal bronchial collaterals that must be
meticulously ligated. Perfect hemostasis is necessary during this area of dissection
because it is obscured once graft implantation is completed. Once absolute
hemostasis is achieved, the trachea is divided at the carina with a no. 15 blade. The
chest is now prepared to receive the graft (Fig. 50-5F) .
The donor heart-lung graft is removed from its transport container and prepared by
irrigating, aspirating, and culturing the tracheobronchial tree and by trimming the
trachea to leave one cartilaginous ring above the carina. The heart-lung graft is then
lowered into the chest, passing the right lung beneath the right phrenic nerve pedicle.
The left lung is then gently manipulated under the left phrenic nerve pedicle. The tracheal
anastomosis is performed using a continuous 3-0 polypropylene suture (Fig. 50-5G) .
The posterior membranous portion of the anastomosis is performed first, followed by
completion of the anastomosis anteriorly. Upon completion of the anastomosis, the
lungs are ventilated with room air at half-normal tidal volume to inflate the lungs and
reduce atelectasis. Topical cooling with a continuous infusion of cold Physiosol into
both thoraces is begun. To augment endomyocardial cooling and to exclude air from the
graft, a third cold bubble free line is placed directly in the left atrial appendage.
Next, the recipient inferior vena cava is anastomosed to the donor inferior vena
cava-right atrial junction with a continuous 4-0 polypropylene suture. At this point, the
patient is rewarmed toward 37°C, and the superior vena caval and aortic anastomoses
are performed end-to-end with continuous 4-0 polypropylene sutures (Fig. 50-5H) . After
the ascending aorta and pulmonary artery are cleared of air, the aortic cross-clamp and
caval tapes are removed. The left atrial catheter is removed, and the atrium is allowed
to drain. The amputated left atrial stump is oversewn, and the pulmonoplegia infusion
site on the pulmonary artery is closed. The heart is defibrillated, and the patient is
gradually weaned from cardiopulmonary bypass in the standard fashion.
Methylprednisolone (500 mg) is administered to the recipient following heparin reversal
with protamine sulfate.
PEEP at 3 to 5 cmh 2 o and an F IO 2 of 40 percent is maintained. As in cardiac

transplantation, isoproterenol (0.005 to 0.01 µg/kg per min) is usually initiated on graft
reperfusion to increase the heart rate to about 100 to 110 beats per minute and to lower
pulmonary vascular resistance. Temporary right atrial and ventricular pacing wires are
placed. Right and left pleural chest tubes (right angle) are placed along each
diaphragm, as well as one mediastinal tube. The chest is closed in standard fashion.
Finally, the tracheal anastomosis is checked endoscopically before transporting the
patient to the intensive care unit.
Lick et al. [33 ] at the University of Texas and University of Arizona have recently
described an interesting alternative to the standard technique in which the pulmonary
hila are placed anterior to the phrenic nerves and direct caval anastomoses are used
whenever feasible. This modification obviates extensive dissection of the phrenic
nerves and posterior mediastinum, decreasing the likelihood of phrenic and vagus
nerve injury. Furthermore, the posterior mediastinum can be inspected more easily for
bleeding after implantation by rotating the heart-lung bloc anteriorly and medially while
still on bypass.
EARLY POSTOPERATIVE MANAGEMENT
Heart-Lung Graft Physiology
Interesting corollaries to the clinical benefits of heart-lung transplantation are the

structural and functional aspects of the transplanted heart-lung bloc (Table 50-3) .
During procurement, the heart is separated from sympathetic and parasympathetic
pathways. The denervated heart is no longer subject to normal autonomic regulation of
rate, contractility, or coronary arterial caliber. The resting heart rate in heart-lung
recipients is generally higher due to the absence of vagal tone. Respiratory sinus
arrhythmia and carotid reflex bradycardia are absent. Interestingly, the denervated heart
develops an increased sensitivity to catecholamines apparently due to an increase in
beta-adrenergic receptor density and a loss of norepinephrine uptake in postganglionic
sympathetic neurons. [34 ] , [35 ] This augmented sensitivity plays an important role in
maintaining an adequate cardiac response to exercise and stress. During exercise, the
recipient experiences a steady but delayed increase in heart rate due primarily to a rise
in circulating catecholamines. This initial rise in heart rate is subsequently accompanied
by an immediate increase in filling pressures resulting from augmented venous return.
These changes lead to an augmentation of stroke volume and cardiac output sufficient
to sustain an increase in activity. The ability of the coronary circulation to dilate and
increase blood flow in response to increased myocardial oxygen demand is normal in
cardiac transplant recipients and would likewise be expected to be so in recipients of
heart-lung grafts. Conversely, graft coronary vasodilator reserve is abnormal in the
presence of rejection, hypertrophy, or regional wall motion abnormalities.
Ischemia and reperfusion injury in the transplanted lung as well as disrupted pulmonary
lymphatics result in increased vascular permeability and varying degrees of interstitial
edema. Moreover, the diminished cough reflex, as well as impaired mucociliary
clearance mechanisms in the denervated lungs, predisposes recipients to pulmonary
infections and necessitates aggressive postoperative pulmonary toilet. [36 ]
The Early Postoperative Period
The acute postoperative management of the heart-lung transplant patient resembles

that of other cardiac patients. Upon completion of the transplant, the intubated transplant
patient is transported immediately to the intensive care unit (ICU), where cardiac rhythm
and arterial and central venous pressures are monitored. Strict isolation precautions,
previously enforced to reduce the incidence of infection in these immunocompromised
patients, are no longer required; simple handwashing and face masks are now
considered sufficient.
Simply put, the primary objective in the immediate postoperative period is to maintain
adequate perfusion and gas exchange in the recipient while minimizing intravenous fluid
administration, cardiac work, and barotrauma. Approximately 10 to 20 percent of
transplant recipients experience some degree of transient sinus node dysfunction in the
immediate perioperative period, often manifested as sinus bradycardia that usually
resolves within a week. The use of bicaval venous anastomoses has been reported to
lower the incidence of sinus node dysfunction and improve tricuspid valve function. [37 ]
Because cardiac output is primarily rate-dependent after transplantation, the heart rate
should be maintained between 90 and 110 beats per minute during the first few
postoperative days using temporary pacing or isoproterenol (0.005 to 0.01 µg/kg per
min) as needed. Although rarely seen, persistent sinus node dysfunction and
bradycardia may require a permanent transvenous pacemaker. The systolic blood
pressure should be maintained between 90 and 110 mmHg using afterload reduction in
the form of nitroglycerin or nitroprusside if necessary. Renal-dose dopamine (3 to 5
µg/kg per min) is used frequently to augment renal blood flow and urine output. The
adequacy of cardiac output is indicated by warm extremities and a urine output greater
than 0.5 mL/kg per hour without diuretics. Cardiac function generally returns to normal
within 3 to 4 days, during which parenteral inotropes and vasodilators can be weaned.
Several factors may contribute to some form of depressed global myocardial

performance in the acute postoperative setting. The myocardium is potentially subject to
prolonged ischemia, inadequate preservation, or catecholamine depletion prior to
implantation. Hypovolemia, cardiac tamponade, sepsis, and bradycardia also should
be considered and treated expeditiously in the event of reduced cardiac output and
hypotension. A Swan-Ganz pulmonary artery catheter should be used in cases of
persistently abnormal hemodynamics.
Proper ventilator management is important during this period, since barotrauma and
high airway pressures that might compromise bronchial mucosal flow must be avoided.
Lower tidal volumes and flow rates may be necessary to limit peak airway pressures to
less than 40 cmh 2 o. Upon arrival in the ICU, an anteroposterior chest film is obtained,
and the ventilator is typically set to an F IO 2 of 50 percent, tidal volume of 10 to 15
mL/kg, an assist-control rate of 10 to 14 breaths per minute, and positive end-expiratory
pressure (PEEP) of 3 to 5 cmh 2 o. These settings are adjusted every 30 minutes to
achieve an arterial PO 2 greater than 75 mmHg on an F IO 2 of 40 percent, an arterial
carbon dioxide pressure (paco 2 ) between 30 and 40 mmHg, and pH between 7.35
and 7.45. Pulmonary toilet with endotracheal suctioning is an effective means of
reducing mucus plugging and atelectasis. Ventilatory weaning is initiated after the
patient is deemed stable, awake, and alert. Usually, weaning is accomplished through
successive decrements in intermittent mandatory ventilation rate followed by a trial of
continuous positive airway pressure. Once ventilatory mechanics and arterial blood
gases are deemed acceptable, the patient is extubated, usually within the first 24 hours
after operation. Subsequent pulmonary care consists of vigorous diuresis and
supplemental oxygen for several days, aggressive pulmonary toilet, and serial chest
roentgenograms.
A diffuse interstitial infiltrate is often found on early postoperative chest films. Previously
referred to as a reimplantation response , [38 ] this finding is better defined as graft
edema due to inadequate preservation, reperfusion injury, or early rejection. [25 ] It
appears that the degree of pulmonary edema is inversely related to the quality of
preservation. [39 ] Judicious administration of fluids and loop diuretics is required to
maintain fluid balance and minimize this edema.
Early lung graft dysfunction manifested by persistent marginal gas exchange without
evidence of infection or rejection occurs in less than 10 percent of transplants.
Histologic analysis revealing diffuse alveolar damage suggests that this phenomenon is
a result of ischemia or reperfusion injury. Of course, technical causes of graft failure
always must be considered. In cases of persistent, severe pulmonary graft dysfunction
refractory to mechanical ventilatory maneuvers, extracorporeal membrane oxygenation
(ECMO) has been used successfully to stabilize gas exchange in several patients. [40 ]
Expedient removal of vascular lines has been shown to reduce the incidence of line
sepsis. Pleural and mediastinal chest tubes are removed when drainage has fallen off
to less than 25 mL/h, and atrial pacing wires are removed between 7 and 10 days after
operation provided pacing is not required. After several days, barring significant
complications, the patient is transferred from the ICU to a standard cardiac surgical
ward for the remainder of the hospital stay.
Immunosuppression
Currently, conventional immunosuppression in heart-lung transplant recipients consists

of the triple-drug combination of cyclosporine, azathioprine, and prednisone. Initially,
high doses of these drugs are given with eventual tapering for chronic administration. A
typical dosing protocol employed at the Stanford University Hospital is outlined in Table
50-4 . Cyclosporine is begun in the early postoperative period, initially intravenously
(0.05 to 0.1 mg/kg per h) and subsequently orally when oral intake is well established (5
to 10 mg/kg per day in two divided doses). Dosing is titrated to maintain a trough serum
concentration between 150 and 250 ng/mL in the first few weeks after transplantation
and from 100 to 150 ng/mL thereafter. Azathioprine is administered intravenously at 4
mg/kg preoperatively and subsequently maintained at approximately 2 mg/kg per day.
Azathioprine dosages are adjusted to maintain the white blood cell count greater than
5000 cells/mm [3 ] . Methylprednisolone is administered intraoperatively (500 mg
intravenously at the conclusion of cardiopulmonary bypass) and postoperatively for 24
hours (125 mg intravenously for three doses every 8 hours). Steroids are then
suspended for 2 weeks, after which prednisone is started at a daily oral dose of 0.6
mg/kg and gradually tapered over the next 3 to 4 weeks to 0.1 to 0.2 mg/kg per day.
From 1987 to 1993, the Stanford transplant program added prophylactic induction
therapy with OKT3 (Ortho Biotech, Raritan, N.J.) monoclonal antibodies (0.1 mg/kg per
day for 14 days) to its standard triple-drug regimen. Directed against the T-cell (CD3)
receptor, OKT3 antibodies rapidly remove circulating T-lymphocytes without affecting
erythrocytes, granulocytes, or platelets. At Stanford, OKT3 therapy is dosed to maintain
a T-cell count below 5 percent. OKT3 induction therapy has delayed the time to first
rejection and has reduced early rejection rates. From 1993 to the present, rabbit
antithymocyte globulin (RATG) has been used as an induction agent in heart-lung and
lung transplant recipients at Stanford. Reichenspurner et al. [41 ] found that the
incidences of acute pulmonary rejection and postoperative infections were significantly
lower in recipients induced with RATG compared with those induced with OKT3.
ATGAM (The Upjohn Company, Kalamazoo, Mich.) is a polyclonal antithymocyte
preparation used by some transplant programs.
Judicious doses of these drugs are usually well tolerated by patients; however, each is
associated with side effects. Cyclosporine is commonly associated with nephrotoxicity,
hypertension, hepatotoxicity, hirsutism, and an increased incidence of lymphoma. The
primary toxicity of azathioprine is generalized bone marrow depression manifested as
leukopenia, anemia, and thrombocytopenia. Steroids are associated with a myriad of
side effects, including the appearance of cushingoid features, hypertension, diabetes,
osteoporosis, and peptic ulcer disease. Initial doses of OKT3 or RATG may cause
significant hypotension, bronchospasm, or fever, presumably due to T-cell-mediated
release of lymphokines. Therefore, patients receiving OKT3 or RATG are monitored
closely and premedicated with acetaminophen, antihistamines, and corticosteroids.
Most of these adverse effects are readily manageable or reversible with dosage
reduction; however, their prevalence emphasizes the inadequacies of pharmacologic
immunosuppression. Active experimental and clinical research is directed toward
developing more potent, less toxic immunosuppressive agents. FK506 and
mycophenolate mofetil are two promising drugs recently approved for use in organ
transplantation by the Food and Drug Administration.
Patient Follow-Up
At Stanford, clinical follow-up of heart-lung transplant recipients typically consists of

serial pulmonary function tests, arterial blood gases, and bronchoscopic evaluation at 1,
2, 3, 4, 8, and 12 weeks after transplantation and every 3 months thereafter or as
clinically indicated. Transbronchial biopsies are obtained from the left and right lower
lobes, and lavage specimens are submitted for staining (i.e., Gram, fungal, acid-fast
bacillus, and silver), culture, and cytology.
POSTOPERATIVE COMPLICATIONS
Early morbidity and mortality after heart-lung transplantation (within 30 days of operation
or before initial discharge from hospital) is caused most commonly by infection and
graft failure. Late mortality after 1 year is caused most commonly by obliterative
bronchiolitis, infection, and malignancy. Causes of death among heart-lung transplant
recipients at Stanford from 1981 to 1994 are shown in Figure 50-6 .
Acute Rejection
As in cardiac transplantation, the majority of acute rejection episodes in heart-lung

transplant recipients occur within the first year after transplant. From 1981 through 1994
at Stanford, acute lung rejection (either isolated or simultaneous with heart rejection)
occurred in more than 67 percent of heart-lung patients within the first year. [42 ] Death
is very rarely a direct consequence of acute rejection, however. In the early
posttransplant period, the diagnosis of acute rejection is usually based on clinical
parameters. Signs of rejection include fever, dyspnea, impaired gas exchange
manifested by a decrease in arterial PO 2 , a diminished forced expiratory volume
during 1 second (FEV 1 , a measure of airway flow), a fall in vital capacity (VC), and the
development of a characteristic bilateral interstitial infiltrate on chest film (Fig. 50-7A) .
After the first postoperative month, the chest film is frequently normal during episodes of
acute rejection; this places greater emphasis on the other clinical parameters of
rejection. Unfortunately, it is difficult to distinguish between graft rejection and infection
using chest radiography alone. Fiberoptic bronchoscopy with transbronchial
parenchymal lung biopsy and bronchoalveolar lavage is the gold standard in the
diagnosis of acute lung rejection and pulmonary infection. At Stanford, postoperative
lung biopsies are performed on a routine schedule, initially on a weekly basis, later by
gradual lengthening to 1-year intervals. Clinical indications for transbronchial biopsies
include fever, tachypnea, dyspnea, hypoxemia, and pulmonary infiltrates. Starnes et al.
[43 ] reported that when transbronchial biopsies were performed for clinical indications,
72.5 percent were positive for rejection or infection compared with a diagnostic yield of
16.7 percent from routine surveillance biopsies. In most cases, positive biopsies
directly guided successful treatment of rejection or infection.
Acute lung rejection is characterized histologically by lymphocytic perivascular infiltrates

(Fig. 50-8) . Clelland and Colin [44 ] at Papworth Hospital describe a histologic grading
scheme for acute lung rejection in heart-lung transplant recipients based on the amount
and extent of inflammatory infiltration of the lung (Table 50-5) .
In heart-lung transplantation, experimental and clinical evidence suggests that

pulmonary and cardiac rejections occur independently of each other. [43 ] , [44 ]
Higenbottam et al. [45 ] at Papworth Hospital reported a surprisingly low diagnostic
yield from routine endomyocardial biopsies in heart-lung recipients compared with
functional or histologic tests of pulmonary rejection. The authors advanced that because
of this, transbronchial biopsy eliminated the need for routine endomyocardial biopsies
in heart-lung transplant recipients. Likewise, the results of simultaneous surveillance
endomyocardial and transbronchial biopsies were compared recently at Stanford.
Pulmonary and cardiac rejection presented asynchronously in most patients.
Transbronchial lung biopsy produced a sensitivity of 89 percent in predicting cardiac
rejection, while endomyocardial biopsy yielded a sensitivity of only 34 percent in
predicting lung rejection. Based on these findings, surveillance endomyocardial
biopsies have been abandoned in heart-lung transplant recipients at Stanford, in whom
transbronchial biopsies can be performed reliably.
As in cardiac transplantation, efforts are being made to develop noninvasive ways of

diagnosing early acute lung rejection. Loubeyre et al. [46 ] at the Hôpital
Cardiovasculaire et Pneumologique report an association between ground-glass
density areas seen on high-resolution computed tomography (HRCT) and histologically
diagnosed acute lung rejection in heart-lung transplant recipients. They found that
ground-glass opacities on HRCT had a sensitivity of 65 percent in detecting lung
rejection and a specificity of 85 percent for detecting an acute lung complication.
At Stanford, the timing and severity of rejection episodes dictate therapy according to
an algorithm illustrated in Figure 50-F . Rejection episodes occurring within the first 3
months or that are graded moderate or severe are treated with intravenous
methylprednisolone at a dose of 1000 mg/ day for 3 consecutive days, followed by
augmentation of the oral maintenance dose to 0.6 mg/kg per day that is tapered to 0.2
mg/kg per day over 3 to 4 weeks. Clinical and radiographic improvement (see Fig. 50-7
) following steroid therapy is often rapid and dramatic and is considered confirmatory of
rejection. Episodes occurring after the first 3 months or those which are mild are treated
initially with an increased oral prednisone dose, followed by a gradual taper over 3 to 4
weeks. Acute rejection refractory to steroid therapy is treated with antilymphocyte
preparations in the form of RATG or OKT3 monoclonal antibody. Potent second-line
therapies that are used in especially difficult, persistent cases of rejection include
methotrexate and total lymphoid irradiation (TLI). Transbronchial biopsies are repeated
10 to 14 days following antirejection therapy to assess efficacy.
Chronic Rejection
Chronic lung allograft rejection poses the greatest limitation to the long-term benefits of
lung and heart-lung transplantation. Chronic lung rejection most commonly presents as
obliterative bronchiolitis (OB), a pulmonic corollary to cardiac graft atherosclerosis
originally described by Burke et al. [47 ] at Stanford as an unexpected complication
following heart-lung transplantation. Recent data demonstrate that 70 percent of
heart-lung and bilateral single-lung transplant recipients are diagnosed with OB by the
fifth postoperative year. [48 ] Transbronchial biopsies and pulmonary function tests are
the gold standards for diagnosing OB.
OB is histologically characterized by dense eosinophilic submucosal scar tissue that

partially or totally obliterates the lumen of small (2 mm) airways, specifically the terminal
and respiratory bronchioles (Fig. 50-10) . Physiologically, OB decreases arterial PO 2 ,
FEV 1 , FEF 2575 [forced expiratory flow at 25 to 75 percent (midrange) of lung
volumes], and FEF 50 /FVC (ratio of FEF 50 to forced vital capacity). A characteristic
concave bowing of the expiratory limb of the flow-volume loop also has been associated
with OB. A standardized working formulation for the clinical staging of chronic lung graft
dysfunction based on the ratio of the current FEV1 (forced expiratory volume at 1
minute) to the best posttransplant FEV 1 has been developed by an ISHLT working
group [49 ] (Table 50-6) . The term bronchiolitis obliterans syndrome was agreed on
for those patients with a 20 percent or greater decline in FEV 1 irrespective of
pathologic evidence of bronchiolitis obliterans. Although it would seem that structural
changes precede functional changes with respect to OB, there is often no correlation
between histologic and physiologic manifestations of OB. [39 ]
Valentine and the Stanford group [48 ] have recently reported that measurements of
small airway function (i.e., FEF 2575> , FEF 50 /FVC) are more sensitive indicators of
physiologic OB than the FEV 1 in heart-lung and bilateral single-lung transplant
recipients. An FEF 50 /FVC persistently below 0.7 for 6 consecutive weeks was
selected as the most sensitive predictor of OB. Approximately 50 percent of heart-lung
and bilateral single-lung recipients with biopsy-proven OB developed a fall in their FEF
50 /FVC nearly 4 months prior to fulfilling the working group critieria for bronchiolitis
obliterans syndrome.
With regard to the etiologies of OB, experimental and clinical evidence points to injury
of the bronchial epithelium by one or more mechanisms. These include infection
(particularly by CMV), toxic fume inhalation, chronic foreign-body exposure stemming
from impaired mucociliary clearance, and immunologic mechanisms. [39 ] Keller et al.
[50 ] at St. Louis University and the Baylor College of Medicine retrospectively reviewed
32 recipients of single- and double-lung and heart-lung transplants to assess the
frequency, predictors, and risk factors associated with development of OB. They found
that 50 percent of the reviewed patients developed OB and that this was associated
with a 56 percent mortality. More than three episodes of histologically documented
acute rejections in any 12-month period were eventually associated with a 100 percent
incidence of OB. Interestingly, CMV pneumonitis occurred with greater frequency in
patients with OB and generally preceded or occurred concomitantly with the diagnosis
of acute rejection or OB.
The current management of OB hinges on prevention, close surveillance, and

immediate therapeutic intervention when patients are symptomatic or when
asymptomatic physiologic changes occur. Heart-lung recipients at Stanford are
encouraged to perform 5 sets of 15 repetitions per day of incentive spirometry to
prevent microatelectasis of lungs deprived of native innervation, bronchial circulation,
and normal mucociliary clearance mechanisms. Moreover, all recipients are instructed
to contact the transplant center or primary physician when respiratory tract symptoms
develop so that pulmonary function tests can be performed. Any alteration in FEF 2575
or FEF 50 /FVC or specific changes in the flow-volume loop are an indication for
bronchoscopy with bronchoalveolar lavage and transbronchial biopsy, especially in the
absence of infectious bronchitis or pulmonary edema. Stanford reports a specificity of
78.4 percent for the diagnosis of OB by transbronchial biopsy.
Augmentation of immunosuppression constitutes current therapy. The prednisone dose

is increased to 0.6 to 1.0 mg/kg per day and slowly tapered to 0.2 mg/kg per day while
concomitantly optimizing cyclosporine and azathioprine dosing. DHPG is reinstituted
during treatment for those patients at risk of reactivation CMV infection, and
antimicrobial therapy is directed against any organims isolated from bronchoalveolar
lavage. Follow-up pulmonary function tests are performed. Pulmonary function can be
stabilized in most patients, but significant improvement is uncommon. Unfortunately,
relapse rates are greater than 50 percent and progressive pulmonary failure or infection
due to increased immunosuppression are the most common causes of death in lung
transplant patients after the second year. Among 89 heart-lung and 13 bilateral
single-lung recipients who underwent transplantation at Stanford between 1981 and
1995, a 5-year survival rate of 49 percent among recipients diagnosed with OB ( n =
59) was noted compared with 74 percent among recipients without OB ( n = 43). [48 ]
The 1-, 3-, 5-, 8-, and 10-year actuarial survival rates following the diagnosis of OB were
74, 50, 43, 23, and 11 percent, respectively, with a median survival of 3 years following
diagnosis.
Retransplantation is the only option for terminal respiratory failure secondary to OB.
Retransplantation in patients who have developed end-stage OB generally has yielded
poor results. Adams et al. [51 ] at Harefield Hospital describe their experience with
repeat heart-lung transplantation in 25 heart-lung recipients suffering from terminal OB.
Survival rates at 1, 6, 12, and 24 months after retransplantation were 52, 33, 25, and 25
percent, respectively. Postoperative complications included bleeding, multisystem
organ failure, and infection. OB resulted in death or graft failure in 3 patients between
12 and 36 months after retransplantation. Interestingly, encouraging results were
obtained with single-lung retransplantation in 9 heart-lung recipients. Survival rates at 1,
6, 12, and 24 months were 89, 67, 67, and 50 percent, respectively, with significantly
less postoperative morbidity than experienced with heart-lung retransplantation. The
absence of preformed antibodies, retransplantation at least 18 months after original
transplantation, and negative preoperative sputum cultures were associated with
improved survival after retransplantation. Efforts at preventing the development of OB
focus on improved immunosuppression, aggressive treatment of acute rejection
episodes, and improved infection prophylaxis.
Accelerated graft coronary artery disease (CAD) or graft atherosclerosis is another

major obstacle to long-term survival in heart-lung transplant recipients. Significant graft
CAD resulting in diminished coronary artery blood flow may lead to arrhythmias,
myocardial infarction, sudden death, or impaired left ventricular function with congestive
heart failure. Classic angina due to myocardial ischemia is usually not noted in
transplant patients because the cardiac graft is essentially denervated. Multiple
etiologies for graft CAD have been proposed, but they all focus on chronic,
immunologically mediated damage to the coronary vascular endothelium. In fact,
elevated levels of antiendothelial antibodies have been correlated with graft CAD.
Unlike coronary artery occlusive disease in the native heart, which tends to be focal in
nature, transplant atherosclerosis represents a more diffuse vascular narrowing
extending symmetrically into distal branches. Histologically, transplant arteriopathy is
characterized by concentric intimal proliferation with smooth muscle hyperplasia (Fig.
50-11) .
Coronary angiograms are performed on a yearly basis to identify recipients with

accelerated CAD. Because graft CAD manifests as diffuse coronary intimal thickening,
intracoronary ultrasound has been advanced as a more sensitive means to detect graft
atherosclerosis due to its ability to assess vascular wall morphology in addition to
lumenal diameter. Interestingly, graft CAD occurs at a reduced incidence compared
with the cardiac transplantation population. [52 ] In a recent retrospective survey at
Stanford, 89 percent of heart-lung recipients were free from graft CAD at 5 years
compared with 73 percent of heart transplant recipients. Clinically observed risk factors
for developing this condition in heart transplant recipients include donor age greater
than 35 years, incompatibility at the HLA-A1, A2, and DR loci, hypertriglyceridemia
(serum concentration greater than 280 mg/dl), frequent acute rejection episodes, and
documented recipient CMV infection. It is not clear whether these risk factors can be
extended to the heart-lung transplant population.
Percutaneous transluminal coronary angioplasty and coronary artery bypass grafting

have been used to treat discrete proximal lesions in some cases of graft CAD;
however, the only definitive therapy for diffuse disease is retransplantation. Effective
prevention of graft CAD will rely on developments in improved immunosuppression,
recipient tolerance induction, improved CMV prophylaxis, and inhibition of vascular
intimal proliferation.
Infection
Bacterial, viral, and fungal infections are the leading causes of morbidity and mortality in
heart-lung recipients. The risk of infection and infection-related death peaks early during
the first few months after transplantation and declines rapidly to a low persistent rate
thereafter. Between 1981 and 1994 at Stanford, only 20 percent of heart-lung recipients
were free from infection 3 months after transplantation. In a retrospective analysis of
200 episodes of serious infections occurring in 73 heart-lung recipients at Stanford
between 1981 and 1990, Kramer et al. [53 ] found that bacterial infections accounted for
half of all infections, with the highest incidence in the first month after transplantation.
Fungal infections (14 percent) also were common in the first month. CMV was the most
common viral agent (15 percent), occurring primarily in the second month after
transplantation, followed by other viruses (i.e., herpes simplex, adenovirus, and
respiratory syncitial virus). Pneumocystis carinii infections (5 percent) were most
common 4 to 6 months after transplantation, and Nocardia infections (2 percent)
generally appeared after 1 year. Surprisingly, there was no significant difference in the
incidence of infections between patients receiving triple-drug or double-drug
(cyclosporine and prednisone) immunosuppression. Infectious mortality comprised 40
percent of all deaths.
Posttransplant infections can be classified broadly into those which occur early and late
after transplantation ( Table 50-7 ). Early infections, occurring during the first month after
transplantation, are commonly bacterial (especially gram-negative bacilli) and manifest
as pneumonia, mediastinitis, catheter sepsis, and urinary tract and skin infections. In the
late posttransplant period, opportunistic viral, fungal, and protozoan pathogens become
more prevalent. The lungs, central nervous system, gastrointestinal tract, and skin are
the usual sites of invasion.
Bacterial infections, particularly caused by gram-negative bacteria, predominate during

the early postoperative period, although the risk of bacterial pneumonia persists
throughout the recipient's course. Most common are pulmonary bacterial infections. The
diminished cough reflex in the denervated lung, abnormal mucociliary clearance
mechanisms, and deficiencies in lymphatic drainage predispose grafted lungs to
infection. Between 75 and 97 percent of bronchial washings obtained from donor lungs
before organ retrieval culture at least one organism. [39 ] Posttransplant invasive
infections frequently are caused by organisms cultured from the donor. Conversely,
bacterial infections developing in patients with septic lung disease, particularly cystic
fibrosis, most commonly originate from the recipient's airways and sinuses. Heart-lung
transplantation does not appear to alter the radiographic characteristics of opportunistic
lung infections. Treatment of bacterial infections generally involves characterization of
the infective agent (e.g., cultures, antibiotic sensitivities), source control (e.g., catheter
removal, debridement), and appropriate antibiotic regimens.
As in heart transplant recipients, CMV is the most common and clinically significant viral
pathogen in heart-lung recipients. CMV presents either as a primary infection or
reactivation of a latent infection, most commonly 1 to 3 months after transplantation. By
definition, primary infection results when a previously seronegative recipient is infected
via contact with tissue or blood from a seropositive individual. The donor organ itself is
thought to be the most common vector of primary CMV infections. Reactivation infection
occurs when a recipient who is seropositive prior to transplant develops clinical CMV
infection during immunosuppressive therapy. Seropositive recipients are also subject to
infection by new strains of CMV. Primary infection in previously seronegative recipients
is generally more serious than reactivation or reinfection in seropositive patients.
Clinically, CMV infection has protean manifestations, including leukopenia with fever,
pneumonia, gastroenteritis, hepatitis, and retinitis. CMV pneumonitis is the most lethal
of these, with a 13 percent mortality, while retinitis is the most refractory to treatment,
requiring indefinite treatment. The significance of CMV as an infective agent becomes
clear when one realizes that it is implicated as a trigger for accelerated graft CAD [54 ]
and OB [55 ] as well as an inhibitor of cell-mediated immunity. Because of organ
scarcity, most transplant centers perform transplants across CMV serologic barriers
using ganciclovir (DHPG) and/or hyperimmune globulin prophylactic protocols in cases
of CMV-positive donors and/or recipients. [56 ]
Diagnosis of CMV infection is made by direct culture of the virus from blood, urine, or
tissue specimens, by a fourfold increase in antibody titers from baseline, or by
characteristic histologic changes (i.e., markedly enlarged cells and nuclei containing
basophilic inclusion bodies). Most cases respond to DHPG and hyperimmune globulin.
CMV prophylaxis includes DHPG, acyclovir, and polyvalent immune globulin.
Fungal infections, the most infrequent but most deadly of infectious complications in
transplant patients, peak in frequency between 10 days and 2 months after
transplantation. Fungal species encountered in these patients include Candida
albicans and Aspergillus . Treatment consists of fluconazole, itraconazole, or
amphotericin B. Reichenspurner et al. [57 ] recently reported that the actuarial incidence
and linearized rate of fungal infections after heart, lung, and heart-lung transplants
performed at Stanford were significantly reduced in recipients who received inhaled
amphotericin prophylaxis.
Pneumocystis carinii pneumonia has been prevented effectively in lung and heart-lung
transplant patients since the institution of prophylaxis, specifically oral
trimethoprim-sulfamethoxazole or inhalational pentamidine for sulfa-allergic patients.
The highest risk of infection with Pneumocystis occurs during the first transplant year;
however, infections do occur late after transplant, prompting most transplant programs
to continue prophylaxis indefinitely.
Infection prophylaxis in heart-lung transplant patients is comprised of vaccinations,

perioperative broad-spectrum antibiotics, and long-term prophylactic antibiotics.
Pretransplant inoculations with pneumococcal and hepatitis B vaccines as well as DPT
boosters are recommended. All transplant recipients also should receive annual
influenza vaccinations. Perioperative antibiotic regimens vary widely between transplant
centers; however, first-generation cephalosporins (e.g., cefazolin) or vancomycin is
commonly used. Long-term prophylaxis typically includes nystatin mouthwash for
Candida thrush, trimethoprim-sulfamethoxazole for opportunistic bacterial and P. carinii
infections, aerosolized amphotericin B for Aspergillus colonization, and antivirals such
as acyclovir or DHPG.
Neoplasm
Heart-lung transplant recipients, as with nonthoracic organ recipients, possess a

significantly greater risk for developing cancer, undoubtedly due to chronic
immunosuppression. Tumors to which recipients are predisposed include skin cancer,
B-cell lymphoproliferative disorders, carcinoma in situ of the cervix, carcinoma of the
vulva and anus, and Kaposi's sarcoma. On the other hand, neoplasms of the breast,
lung, prostate, and colon do not appear to be increased in these patients. On average,
tumors appear approximately 5 years after transplantation.
The incidence of B-cell lymphoproliferative disorders in transplant patients is a

staggering 350 times greater than that seen in the normal age-matched population. [25 ]
Diagnosis is established by lymph node biopsy. Lymphomas are frequently observed in
younger recipients (younger than 20 years) within a year after transplantation and carry
an 80 percent mortality over the 3 months following diagnosis. Older recipients (older
than 45 years) diagnosed with lymphoma tend to present several years after transplant
with an average survival of 9 months following diagnosis. Thought to be caused by
unchecked Epstein-Barr virus infection in the setting of T-cell suppression, B-cell
lymphoproliferative disorders generally are treated with a reduction in
immunosuppression and administration of an antiviral agent such as acyclovir or
DHPG. A response rate of 30 to 40 percent can be expected, with recurrence being
uncommon. Chemotherapy and radiotherapy have been used successfully in some
cases. Of course, close monitoring of the graft along with clinical assessment of tumor
status is important during therapy.
Airway Complications
Improvements in surgical technique and posttransplant management have resulted in a

relatively low incidence of airway complications after heart-lung transplantation.
Shumway et al. [58 ] at the University of Minnesota report an airway complication rate of
3.8 percent. The avoidance of perioperative steroids has long been considered
important in preventing airway complications; however, recent experimental and clinical
evidence suggests that the detrimental effects of steroids may be overestimated. [59 ]
The most common airway complications are partial anastomotic dehiscence and
stricture. Such complications are usually diagnosed during bronchoscopic examination.
Airway dehiscence is treated by reoperation or close observation and supportive care.
Strictures are treated with laser ablation or dilation with rigid bronchoscopy and balloon
or bougie dilators. Most strictures are stented after dilation. Cystic fibrosis patients
appear to be at higher risk for developing airway complications after transplantation.
Hemorrhage
Perioperative hemorrhage is an infrequent but significant cause of early death in

heart-lung transplantation. Much of this stems from operating in the midst of dense
adhesions from previous operations or the inflammatory response to chronic lung
infections. Between 1981 and 1994, hemorrhage accounted for approximately 8
percent of all deaths among heart-lung recipients at Stanford. As mentioned previously,
meticulous attention to hemostasis is mandatory, and all available means should be
used to achieve a dry field on completing the operation.
THE DOMINO PROCEDURE
To address the severe shortage of thoracic organs for transplantation, the so-called
domino operation has been developed. This approach involves the use of explanted
hearts from patients undergoing heart-lung transplantation for primary lung disease for a
second recipient in need of a heart transplant. Over 50 percent of heart-lung transplant
recipients possess hearts with normal or near-normal left ventricular function and some
degree of right ventricular hypertrophy resulting from elevated pulmonary artery
pressures. The use of hearts explanted from patients with pulmonary hypertension has
theoretical appeal in that the right ventricle is already adapted to elevated pulmonary
vascular resistances, thereby decreasing the likelihood of acute donor right-sided heart
failure in recipients with preexisting pulmonary hypertension. Kells et al. [60 ] report
preservation or improvement of right ventricular function among 7 domino heart
transplant recipients at Stanford. Oaks et al. [61 ] at Papworth Hospital described their
experience with 32 domino heart transplants performed from 1988 to 1992. No
difference was observed in the 3-month and 1-year survival rates between domino and
nondomino cardiac transplant recipients. Yacoub et al. [62 ] at Harefield Hospital report
an actuarial 1-year survival of 75 percent among recipients of domino hearts from cystic
fibrosis patients who underwent heart-lung transplantation.
The domino donor cardiectomy differs slightly from the standard technique described by
Lower and Shumway [1 ] in 1960. In preparing the heart-lung recipient for
cardiopulmonary bypass, the venous cannulas are placed into the inferior vena cava
extrapericardially close to the diaphragm and the high superior vena cava at least 4 to 5
cm above the sinoatrial node. This modification enables the excision of the domino
heart high on the superior vena cava to preserve the sinoatrial node for the domino
recipient.
RESULTS OF HEART-LUNG TRANSPLANTATION
At Stanford, the 1-, 5-, and 10-year actuarial survival rates after heart-lung
transplantation performed between 1981 and 1994 are 68, 43, and 23 percent,
respectively [42 ] (Fig. 50-12) . Theodore et al. [63 ] at Stanford demonstrated that the
integrated functions of the transplanted heart and lungs are well maintained with
exercise. Most recipients are able to resume active lifestyles without supplemental
oxygen and demonstrate significant increases in posttransplant exercise capacity.
Pulmonary function measured by spirometry and arterial blood gases is markedly
improved in patients within several months after transplantation (Table 50-8) , with a
normalization of ventilation and gas exchange after 1 to 2 years.
Sharples et al. [64 ] at Papworth Hospital retrospectively assessed potential risk factors
for mortality among 100 patients who received heart-lung grafts between 1984 and
1991. Recipient age, sex, and preoperative diagnosis did not have a significant effect
on early (within 3 months) or late death. Positive CMV serologic status of donor or
recipient conferred a greater risk of death within the first 90 days. Blood loss in excess
of 2 liters within the first 24 postoperative hours and ventilation for greater than 24 hours
were significant prognostic indicators of early death. After the first 3 months, the primary
risk factor for death was early acute rejection within the first 3 months after
transplantation.
CONCLUSION
The evolution of combined heart and lung transplantation from rudimentary laboratory
experimentation to its current prominence as an accepted therapy for end-stage
cardiopulmonary disease is a product of ingenuity, perseverance, skill, and courage.
Many debilitated patients, both adult and pediatric, now have an opportunity to resume
full and active lifestyles after heart-lung transplantation. Nevertheless, significant hurdles
have yet to be overcome, particularly graft rejection, infection, and a limited donor pool.
Important advances on the horizon include cross-species transplantation, improved
immunosuppression, the induction of immunologic tolerance to foreign tissue, and
improved organ preservation techniques.
DESCRIPTION OF AVAILABLE LONG-TERM CIRCULATORY
SUPPORT SYSTEMS
Three devices that are currently used to support patients in need of long-term
mechanical assistance are the Thoratec ventricular assist system (VAS), the Novacor
left ventricular assist system (LVAS), and the HeartMate LVAS. Each of these devices
has unique characteristics that offer specific advantages and disadvantages and was
developed with the assistance of the NHLBI.
Thoratec VAS
The Thoratec VAS (Thoratec Corporation, Berkeley, CA) is a pneumatically powered,

pulsatile assist device with a stroke volume of 65 mL and a maximum output of 7 L/min
(Fig. 51-3) . [14 ] [16 ] Under an investigational device exemption from the United States
Food and Drug Administration (FDA), the Thoratec VAS has been used clinically since
1976. It was approved for general use recently. The system is used both for bridging to
transplantation and for postcardiotomy weaning. The Thoratec pump consists of a
ridged polycarbonate housing that encloses a flexible, seam-free, segmented sac. The
inlet and outlet portions of the pump contain Bjork-Shiley concavo-convex tilting disc
valves to ensure unidirectional blood flow. The drive console uses negative and positive
pressures to fill and empty the pump. The pump can be used to provide either partial or
total circulatory support; either 1 or 2 blood pumps may be used to provide left, right, or
biventricular support.
The system can operate in three different modes: volume, fixed-rate, and
external-synchronous mode. In the volume mode, pump filling (as measured by a Hall
sensor) determines the pumping rate; in the fixed-rate mode, pump rate is set by the
operator and functions independently of the patient's natural heart rate; in the
external-synchronous mode, the pump empties when triggered by the patient's R-wave.
Generally, the Thoratec is operated in the volume mode; if, however, a pump rate of 80
beats/min cannot be achieved, the fixed-rate mode should be used. When biventricular
support is implemented, right pump flow is adjusted so that it is less than left pump flow
to prevent pulmonary injury and congestion.
The Thoratec control console continuously displays the ejection pressure, percent
ejection time, pump rate, pump flow, and vacuum pressure. To provide adequate pump
ejection, the Thoratec control console must provide a driveline pressure of 200 mmHg
(or at least 75 mmHg more than the patient's systolic pressure) and an ejection time of
300 msec. To optimize pump filling, an adjustable vacuum is used.
Because the Thoratec is an extracorporeal system, patients supported by this device

have limited mobility. Nevertheless, this system is widely used because of its versatility
and demonstrated safety and effectiveness in supporting critically ill patients.
Novacor LVAS
The Novacor LVAS (Baxter Healthcare Corporation, Novacor Division, Oakland, CA) is
a pulsatile device with an implantable blood pump consisting of a seamless
polyurethane pump sac compressed by dual pusher plates (Fig. 51-4) . [17 ] , [18 ] The
Novacor currently is used solely as a bridge to transplantation. This system is monitored
by an external drive console and can produce a stroke volume up to 70 mL. An internal
solenoid powers the pump by converting the electrical energy from the console to
mechanical energy. This energy is utilized to compress the pusher plates and
pressurize the pump sac for blood ejection. In both the inflow and outflow conduits, a
21-mm bioprosthetic valve is used to maintain unidirectional flow.
The drive console is connected to the pump with a 20-foot drive cable. This console is
the power and control center of the pump. Transducers within the pump transmit
information on pump parameters to the console. The console displays this information,
as well as electrocardiographic signals and blood pressure. The Novacor can operate
in three different modes: the synchronized mode, the fill-to-empty mode, and the
fixed-rate mode. The synchronized mode maximizes cardiac unloading. In this mode, an
electrocardiographic signal causes the pump to fill with cardiac systole and eject with
cardiac diastole. The fill-to-empty mode, in contrast, maximizes pump output. The pump
rate is adjusted automatically and depends on the pump's filling rate. Finally, in the
fixed-rate mode, the operator sets the pump at a constant rate. In this rarely used mode,
the device pumps asynchronously to the heart.
Limitations of the Novacor LVAS include the audibility of the drive mechanism and the
nonportability of the drive console. Testing a wearable version of the Novacor LVAS
recently began. [19 ] This system operates on battery power without the console
necessary for the other model. A monitor is available for LVAS patients to use during
rest. Battery power lasts for up to 12 hours to allow increased patient mobility.
HeartMate LVAS
The HeartMate Implantable Pneumatic (IP) and Vented Electric (VE) LVASs (Thermo
Cardiosystems, Inc., Woburn, MA) are pulsatile blood pumps used to promote
hemodynamic recovery in patients waiting for transplant. [17 ] These devices have
identical blood pumps, are both portable, and have similar operating modes, which
differ mainly in their method of pump actuation: The IP-LVAS is powered pneumatically
through a portable external drive console, whereas the VE-LVAS is powered through a
percutaneous electric lead attached to a light-weight, rechargeable battery pack.
Because this battery pack is worn by the patient in a shoulder holster, it offers almost
unlimited mobility. Both the IP- and VE-LVAS have a maximum stroke volume of 85 mL,
with maximum blood flows of 12 L/min for the IP-LVAS and 10 L/min for the VE-LVAS.
Support by either of these devices can improve hemodynamic parameters and
end-organ function in patients waiting for transplantation, and enables these patients to
remain mobile.
The HeartMate blood pump consists of a flexible polyurethane diaphragm enclosed

within a ridged outer housing constructed of a titanium alloy (titanium, 90%; aluminum,
6%; vanadium, 4%). The IP-LVAS pump weighs 570 g, whereas the VE-LVAS pump
weighs 1150 g. The blood-contacting surfaces are textured to reduce the risk of
hemolysis and thromboembolic complications (Fig. 51-5A) . The housing is covered by
sintered titanium spheres and the diaphragm is textured with polyurethane fibrils. This
surface interfaces with fibrin and cellular components in the blood, to create a
pseudoneointimal lining and to eliminate the need for antithrombolytic agents.
IMPLANTABLE PNEUMATIC LVAS
The IP-LVAS is powered and controlled by a microprocessor-based drive console. This

console weighs 33 kg and is transported on a cart. Internal batteries provide about 40
minutes of use independent of the console. The console is connected to the pump with
a 6-foot cable and pressurizes the blood chamber by sending out programmed
pneumatic pulses to move the diaphragm upward. The position of the diaphragm is
monitored by a position sensor within the pump housing and determines the stroke
volume of the system. The stroke volume is displayed by the console, along with the
pump rate and total pump flow. Audible and visual alarms are activated if pump flow or
battery level is low.
The IP-LVAS can be operated in fixed-rate, automatic, and external synchronous

modes. In the fixed-rate mode, the pump rate is set by the operator. This mode is
generally used in the operating room when the system is first started or when a patient
is at rest. The automatic mode is used to maximize pump flow. The microprocessor in
the console adjusts the rate of flow according to the filling status of the pump and
maintains an average stroke volume of about 75 mL. In the external synchronous mode,
pump systole occurs in conjunction with the patient's R-wave.
Recently, a new portable, pneumatic console was introduced. Whereas patients

supported by a pneumatic system were previously unable to leave the hospital while
awaiting transplantation, this new console allows these patients to return home to await
transplantation. Conventional lead acid-gel cell batteries provide up to 8 hours of
continuous operation. The new driver weighs only 8.5 kg and can be pulled on wheels or
carried with a shoulder strap, to permit the patient far greater mobility than was allowed
by the previous model.
VENTED ELECTRIC LVAS
In contrast to the IP-LVAS, the VE-LVAS is powered by an internal motor (Fig. 51-5B) .
This motor is located inside the pump and is connected to an external console and
battery pack by an electrical line. The system is actuated by either a stationary console
or two lead-acid batteries worn in a shoulder holster. The batteries can be charged by
the control console. The internal motor rotates a pair of ball bearings against helical
face cams on the pusher plate and diaphragm. Each rotation of the rotor and ball
bearings produces an ejection. Because the motor is detached from the pusher plate
and diaphragm, the pump fills passively at the end of ejection. The electric lead and vent
tube of the new VE-LVAS are combined into one percutaneous lead. Implantation is
thus similar to that of the pneumatic pump.
The VE-LVAS can be operated in either the fixed-rate or automatic mode (but not the
external synchronous mode). Patients are generally required to wear a system controller
and two batteries. The system controller allows the patient to control the mode of the
LVAS. Three indicator lights and an audible beeper alert the patient to any abnormal
operating condition. For home use, the patient is also given a battery charger with a
20-foot power cable. To assess pump function or change various operating
parameters, the system controller can be accessed with a personal computer or display
monitoring unit. Equipment is generally run and maintained by the patient or a family
member.
PATIENT SELECTION
Patient selection criteria for device implantation are similar among the Novacor,
Thoratec, and HeartMate. [17 ] , [20 ] However, although the Novacor and HeartMate
are primarily used for bridging patients to transplantation, the Thoratec may be used for
both bridging patients to transplantation and for postcardiotomy weaning. To receive
mechanical circulatory support, patients generally must be considered in imminent
danger of death or irreversible end-organ dysfunction. Patients are eligible for
mechanical support if they have heart failure that persists after maximal treatment with
inotropic drugs and (if possible) support with an intraaortic balloon pump (Table 51-1) .
Patients with severe right heart failure, irreversible renal and/or hepatic dysfunction, or a
systemic life-threatening illness other than heart disease are generally ineligible for
mechanical support. Other contraindications include age greater than 70 years,
unresolved pulmonary emboli, respiratory insufficiency requiring intubation, renal failure
requiring hemodialysis, irreversible cerebrovascular accident, unacceptable
psychosocial history, and severe coagulation disorders.
End-organ dysfunction is a major cause of death in patients supported by mechanical

assist systems. Delaying implantation until the onset of irreversible end-organ
dysfunction may result in complications that contraindicate transplantation or cause
death. [16 ] Although it is sometimes difficult to determine conclusively whether
end-organ dysfunction is irreversible, or whether function can recover with use of an
assist device, Burnett and colleagues report that mechanical circulatory support can
improve severe end-organ dysfunction if the device is implanted before irreversible
organ failure occurs. [20 ] , [21 ]
The Novacor and HeartMate generally are less effective in patients with acute
biventricular or right heart failure because these patients have low left ventricular
volume, high pulmonary vascular resistance, and unconditioned right ventricles.
However, the Thoratec VAS can be used for either univentricular or biventricular
support. [22 ] In addition, because the pump is placed extracorporeally, it can be used
to support all sizes of patients, including smaller patients.
Before implantation of a mechanical circulatory assist device, the patient may require
treatment with prostaglandin E-1 to reduce pulmonary vascular resistance. Although
prostaglandin can lower systemic blood pressure, reducing the rate of infusion usually
restores systemic pressure. In addition, a transesophageal or transthoracic
echocardiogram is taken to determine if a patent foramen is present. If this defect is
detected, it must be repaired or high right-sided pressures may produce right-to-left
shunting.
General anesthesia and cardiopulmonary bypass are used during implantation of each
device.
INSERTION OF DEVICE
Thoratec
The pump inflow cannula may be inserted into the left atrial appendage or through the
reflected interatrial groove adjacent to the right superior pulmonary vein or the left
ventricular apex. [23 ] The left atrial appendage may be used, but is friable. If the
reflected interatrial groove is used, the device may be inserted without cardiopulmonary
bypass. This site also allows easy access to the left atrium. Insertion of the cannula
through the left ventricular apex provides the best filling for the device, but may be
difficult to remove safely. The left ventricular apex is the preferred site of insertion for
bridge-to-transplant patients (Fig. 51-6) . A 12-mm preclotted woven Dacron graft,
located at the distal end of each outflow cannula, is anastomosed to either the
ascending aorta or the pulmonary artery. The cannulas are exteriorized below the costal
margin and are connected to the blood pumps, which rest on the abdomen. Often, left
ventricular function of the pump is monitored, and if pump filling is not adequate, right
ventricular support is begun. Before weaning from cardiopulmonary bypass is initiated,
the pumps are deaired.
Novacor
The pump is placed in the abdominal wall, just anterior to the posterior rectus sheath,
between the left iliac crest and the costal margin. [24 ] , [25 ] General anesthesia is
administered and an extended median sternotomy is performed. The midline
abdominal incision is extended 2 cm past the umbilicus. The pocket for the LVAS is
created posterior to the left rectus abdominus (Fig. 51-7) . The pocket should extend
superiorly to the diaphragm, and should be large enough to accommodate the device
without tension after the abdominal wall is closed. In smaller patients, the pocket may be
extended below the oblique muscles of the lateral abdominal wall. It is important to
avoid opening the peritoneum. Before insertion of the device, hemostasis should be
achieved with electrocautery and suture ligation. A suprapubic incision is made through
which the control cable will pass. The control cable is pulled through its exit (usually on
the right side of the abdominal wall) and connected to the console, at which time
function of the device is checked.
After the graft has been preclotted, the ascending aorta is clamped and anastomosed
end-to-side with 4-0 polypropylene sutures. The left ventricular cannula is tunneled
through the diaphragm. The pump is primed with saline and placed in the prepared
pocket. With a trocar, the cable is tunneled across the abdomen to exit from the right
upper abdominal quadrant (Fig. 51-8) .
Cardiopulmonary bypass is instituted and the apex of the heart is exposed. Buttressed
sutures (2-0 Ethibond, Ethicon, Inc., Somerville, NJ) are sewn around the apical dimple
and through the apical sewing ring (Fig. 51-9) . The sutures are tied and a stab incision
is made in the center of the ring. A Foley catheter with a 30-mL balloon is placed into
the left ventricle. The balloon is inflated and the apical core is excised and removed.
After the apical cannula is inserted, the pursestring suture of the apical ring is tied, the
skirt of the cannula is sutured circumferentially to the apical ring. The device is activated
and air is vented through the graft.
HeartMate
To implant the HeartMate LVAS, a median sternotomy is performed with an extended

midline abdominal incision to the umbilicus. [26 ] Cardiopulmonary bypass is routinely
utilized for implantation with full-dose heparin (3 mg/kg). A centrifugal pump and
membrane oxygenator can be used to reduce the risk of damage to platelets and other
clotting factors in these severely ill patients. The coronary sinus is cannulated for
retrograde infusion of cardioplegic solution and protection of cardiac function.
The outflow graft of the HeartMate is anastomosed to the ascending aorta either with
partial cross-clamping before cardiopulmonary bypass is instituted, or with total
cross-clamping and cardioplegic arrest. The outflow graft is trimmed so that it lies to the
right of the mediastinum; this protects the outflow graft from damage when sternotomy is
performed at the time of heart transplantation. A protective membrane of Gortex or
bovine pericardium also may be laid over the graft. The HeartMate pump is placed in
either a intra-abdominal or extraperitoneal position (Fig. 51-10) . If the device is placed
extraperitoneally, a pocket is created similar to that of the Novacor.
Cold cardioplegia and mild systemic hypothermia are used to institute cardiac arrest.
The left ventricular apex is cored with a circular knife in the anterior apical aspect of the
left ventricle. A Teflon-covered Silastic sewing ring is sewn to the apex with interrupted
pledgeted sutures. A suitable opening is made in the diaphragm for the inlet tube. After
the pump is in position, the inlet tube is passed through the diaphragmatic opening and
placed in the left ventricle. If the system is pneumatic, a Dacron-covered driveline is
tunneled through a stab incision in the left lateral abdominal wall, just above the iliac
crest; if the system is electric, the combined electric and vent lead is tunneled through
the abdominal wall at the same position. The pump is secured to the anterior abdominal
wall, and the outflow graft is connected to the outflow valve assembly by a screw-ring
connector.
WEANING FROM CARDIOPULMONARY BYPASS
Weaning patients from cardiopulmonary bypass after left ventricular device implantation
requires caution and patience. Because these patients are in advanced heart failure,
care must be taken to reduce pulmonary vascular resistance and avoid right ventricular
failure. In patients supported by the Thoratec, however, right ventricular failure is less of
a concern because right-sided support is easily instituted. If a patient with a Novacor or
HeartMate requires a right ventricular assist device, he or she can be temporarily
supported with an Abiomed BVS 5000 (Abiomed Inc., Danvers, MA) or a Biomedicus
pump until weaning is achieved.
POSTOPERATIVE CARE
After LVAS implantation, patients are cared for in the intensive care unit. [15 ] To avoid
infection, patients receive antibiotics for 5 days after implantation. After that, antibiotics
are administered only with evidence of infection.
The patient can be weaned from mechanical ventilator support when hemodynamically
stable, usually within 48 hours of operation. After implantation of a mechanical assist
device, emphasis is placed on physical rehabilitation of the patient through nutrition and
exercise. [27 ] Patients begin this rehabilitation by taking short walks, and eventually
build up to vigorous treadmill exercise. As they recover physically, their need for
medical care becomes minimal and most patients can care for themselves by the time
of transplantation.
After postoperative bleeding is controlled, anticoagulation is initiated. Because the

HeartMate allows a biological lining to form on blood-contacting surfaces, patients
supported by this device require only limited use of anticoagulants. [28 ] At the Texas
Heart Institute, low molecular weight dextran is infused at 10 mL/hr until patients are
able to tolerate a regular diet, usually 7 days after operation. Patients are then given
aspirin (80 mg/day) and dipyridamole (75 mg, three times per day) until the heart is
transplanted.
Because of the danger of thrombus formation, patients supported with the Thoratec and
Novacor systems must receive continuous anticoagulation therapy. Once operative
bleeding is controlled, the patient receives a combination of dextran, dipyridamole, and
heparin or warfarin to modify platelet function or prolong the coagulation time. [29 ] [31 ]
COMPLICATIONS
Bleeding
Bleeding occurs frequently as an early complication in patients supported by

mechanical assist devices and remains the most common complication for patients
bridged to transplantation with a mechanical assist device. [32 ] [35 ] Risk factors for
bleeding include preoperative hepatic congestion and failure, prolonged
cardiopulmonary bypass times, extensive surgical dissection, multiple cannulation sites,
and platelet interaction with the biomaterial surfaces. [18 ] , [36 ] Between 2273 percent
of reported cases of bleeding require reoperation. [37 ] , [38 ] Thus, hematological
status must be closely monitored. When the patient arrives at the intensive care unit
after operation, complete blood count, partial thromboplastin time, prothrombin time,
platelet count, and fibrinogen and fibrin split products should be measured. Depending
on the findings of these tests, plasma, blood, and platelets are given.
Right Ventricular Failure
In the early postoperative period, a common cause of death of patients supported with a
left ventricular assist device is right ventricular failure. [32 ] [35 ] Right ventricular failure
is diagnosed when right atrial pressure rises and output of the device drops. [16 ] In
some cases, patients with right ventricular failure can be treated with pulmonary
vasodilators; often, however, temporary mechanical support may be necessary. [39 ]
Need for right ventricular support after LVAS implantation usually cannot be predicted
before implantation; however, support of the left ventricle generally promotes recovery of
the congested right ventricle. [40 ] , [41 ] In multicenter trials of the Thoratec, Novacor,
and HeartMate assist systems, patients who required only left ventricular assistance
had a greater survival rate than those who required both left and right ventricular
assistance. [22 ] , [42 ] , [43 ]
Infection
Infection is another frequently reported complication during mechanical support. Most

incidences of infection in the LVAS patient occur at the site of the driveline and are
easily managed. [44 ] Mechanical devices that are placed orthotopically (like artificial
hearts) leave the patient at risk for mediastinal infection. The incidence of infection in
devices like the HeartMate, Novacor, and Thoratec is much lower. When infections do
occur, successful transplantation can be achieved. We theorize that this reduction in the
rate of infection is owing to extrathoracic placement of the pump. [21 ] In the HeartMate,
the risk of infection is reduced further by the tissue capsule that forms around the pump.
Nevertheless, infection remains a concern during mechanical support, and must be
treated aggressively.
Thromboembolic Complications
In the past, the risk of thromboembolic complications prevented long-term mechanical

support from being a viable therapeutic option. The textured, blood-contacting surfaces
of the HeartMate reduce the risk of such complications. These biocompatible surfaces
promote the formation of a stable lining of smooth, well-adherent neointimal tissue,
consisting of a meshwork of fibrin and collagen that includes a variety of cell types. [45 ]
[48 ] The textured surfaces of the HeartMate eliminate the need for warfarin, even during
extended support. Anticoagulation therapy in patients supported by the HeartMate is
limited to aspirin and dipyridamole.
The risk of thromboembolic complications in HeartMate patients is further reduced by

the length of the inflow graft. In early calf studies with a prototype of the HeartMate, we
observed pannus formation on the inlet graft. Although the calf is a thrombogenic model,
we eliminated excess length in the graft for longer-term clinical studies. To date, no
pannus formation has occurred on inlet grafts that have been correctly placed.
End-organ Failure
Long-term mechanical circulatory support can improve end-organ function in patients

awaiting transplantation. [21 ] Any recovery of end-organ function takes several weeks.
After this period, renal and hepatic function generally normalize in patients who have not
experienced irreversible end-organ failure. Because the general condition of these
patients has improved, they become better candidates for transplantation. A clinical trial
is warranted to determine whether a period of mechanical circulatory support for
marginal candidates for cardiac transplantation can promote some long-term recovery
of native heart function.
RESULTS
Early survival rates after transplantation for patients supported by mechanical assist
systems are as good or better than those of patients who undergo transplantation
without such support. [49 ] [52 ] After 1 year, 89 percent of patients bridged to
transplantation with a ventricular assist system are alive versus the 82.5 percent of
patients who receive a heart without circulatory support. These results are similar for
each device.
Thoratec
As of 1993, over 214 patients had undergone implantation with a Thoratec VAS as a
bridge to transplantation. [15 ] In one multicenter study, 73 percent of patients supported
by the Thoratec VAS required biventricular support; the remaining 26 percent required
only left ventricular support. Overall, 64 percent of the Thoratec patients underwent
transplantation. The most frequent complications associated with Thoratec use were
bleeding (44 percent) and infection (40 percent). Of the patients who underwent
transplantation, 83 percent survived, a rate comparable to that of the overall heart
transplantation population. In a clinical study involving postcardiotomy patients, 37
percent were weaned from the VAS, and 57 percent of these survived. In these patients,
perioperative myocardial infarction and renal failure were the primary causes of
adverse morbidity and mortality. [53 ] , [54 ]
Novacor
Since clinical trials of the Novacor LVAS began in 1984, 129 patients have been
bridged to transplantation. Sixty percent of these patients had successful
transplantation. Of the patients who underwent transplantation, 89 percent were
discharged from the hospital; 82 percent of patients supported by the Novacor for over
30 days were long-term survivors. [55 ] The most common complications were infection
and bleeding. While being supported by the Novacor LVAS, many patients are
ambulatory and undergo physical rehabilitation. These results are comparable to those
obtained in patients supported by other devices and with those who underwent heart
transplantation without mechanical assistance.
HeartMate
Clinical trials of the HeartMate IP-LVAS began in 1986, and trials of the VE-LVAS
began in 1991. Results of trials with the VE-LVAS and the IP-LVAS are similar.
Between January 1986 and July 1995, the IP-LVAS was implanted in 422 patients
worldwide. [56 ] The FDA trial included 108 heart transplantation candidates, but 33
were control patients and did not receive an LVAS. [34 ] Seventy-one percent of the
LVAS patients underwent transplantation, while only 36 percent of the control patients
had transplantation. After transplantation, patients who had been supported with the
IP-LVAS had a 60-day survival rate of 65 percent; patients in the control group,
however, had a 60-day survival rate of only 30 percent. The improved survival rates of
patients bridged to transplantation with an LVAS are largely due to physical
rehabilitation produced by prolonged support by the LVAS. In many patients, end-organ
and ventricular function had returned to near normal by the time of transplantation.
Based on these positive findings, the FDA approved the HeartMate IP-LVAS for
general use in October, 1994.
Clinical trials of the VE-LVAS are ongoing. Like patients supported by the IP-LVAS,
VE-LVAS patients who survive beyond the immediate postoperative period experience
improvements in end-organ and ventricular function. [56 ] , [57 ] Patients supported by
the VE-LVAS who meet all the requirements of a patient release protocol are allowed to
leave the hospital while waiting for transplantation. Many of these patients have been
able to return to work (Fig. 51-11) . The minor technical problems that occur during
patient release programs have been resolved either by the patient or by hospital
personnel.
PERMANENT LVAS
Clinical trials of the HeartMate VE-LVAS recently began in three U.S. centers
(Columbia-Presbyterian Medical Center, Texas Heart Institute, and Cleveland Clinic
Foundation) for patients who are not eligible for cardiac transplantation. The primary
objective of this randomized, prospective trial of 6575 patients in each group is to
evaluate the safety and efficacy (survival and quality of life) of LVASs implanted for
indefinite use. Eligible patients must be less than 72 years of age and if less than 65
years must also have either insulin-dependent diabetes or chronic renal insufficiency
(creatinine > - 2.5 mg/dl). All patients must have NYHA Class IV heart failure for more
than 90 days with a left ventricular ejection fraction < -25 percent, pulmonary capillary
wedge pressure over 18 mmHg, and a cardiac index of 2.2 L/min after over 30 days of
maximal medical therapy. A long list of exclusionary criteria serves to reduce the
number of confounding variables to focus the study on the treatment of heart failure.
The impetus of this trial and a forthcoming trial of the Novacor N120 LVAS is the
magnitude of the heart failure problem. Population-based studies estimate that between
three and four million Americans have heart failure and that approximately 400,000 new
patients are added each year. [58 ] Five-year survival rates after diagnosis range 3040
percent. For patients with NYHA Class IV heart failure 1-year survival rates are 4050
percent. [59 ] Cardiac transplantation is donor-limited and only approximately 2,000
donor hearts are harvested each year, although approximately 16,500 patients per year
are eligible candidates. [60 ] Mortality rates for patients on transplant waiting lists are
rising. [61 ]
The availability of totally implantable electrical LVASs, the pressing need to improve
therapy for Class IV heart failure, the ability of some bridged patients to live at home
and even work with only a single transcutaneous cable, and the high costs of
conventional therapy for severe heart failure are compelling facts that support these
trials. All patients enrolled in the trials will be followed for at least 2 years.
THE FUTURE OF MECHANICAL CIRCULATORY SUPPORT
Since Gibbon first introduced the heart-lung machine in 1953, mechanical circulatory
support has evolved significantly. Materials used in mechanical systems have become
more durable and more biocompatible. Progress also has been made in patient
selection and management. As a result, the 1-year survival rate for patients bridged to
transplantation is comparable to or better than that of patients undergoing
transplantation alone. Thus, long-term mechanical circulatory support now is a widely
used and accepted method of supporting the circulation of patients awaiting heart
transplantation.
There are further developments to come. In the future, pulsatile assist devices will be
completely implantable, with batteries and control systems placed within the body.
Transcutaneous energy systems will power and control these devices by transmitting
signals across intact skin. A long-term compliance chamber, a necessary component of
a completely implantable system, will be developed. Advances in new biomaterials,
plastics, metals, ceramics, and composite materials will markedly increase the life of
bearings, seals, connectors, and other assist-device components. Other anticipated
advances include longer-lasting batteries; smaller, faster microprocessors; and genetic
modification of blood-contacting surfaces. In addition, fully implantable, non-pulsatile
pumps are being developed that will obviate the need for a compliance chamber. The
effects of long-term support with a continuous-flow pump, however, are yet to be
investigated.
Cardiac transplantation is expensive. Patients awaiting transplantation must often be

cared for in the intensive care unit and supported with medical therapy and an
intra-aortic balloon pump. Patients supported with the LVAS, however, usually are
transferred to a general care unit. In time, some of these patients can wait for
transplantation at home, with a reduction in costs and improvement in quality of life. One
recent study reported that daily charges for patients awaiting transplant in an intensive
care unit is $5,150/day, for patients supported by an LVAS in a general care unit,
$3,178/day, and for an LVAS patient waiting at home, $27/day. [62 ] Patients also may
return to work and become economically productive. In addition, patients supported with
a mechanical assist device often experience physical rehabilitation. This rehabilitation
improves their prognosis after transplantation, and makes efficient use of scarce donor
organs.
In its short history, the mechanical circulatory assist system has become more than just
a means for survival. Experience demonstrates that these systems produce real
recovery. The HeartMate originally was designed to provide long-term mechanical
support. Since we began using the HeartMate to bridge patients to transplantation, we
have noticed significant improvements in left ventricular function of patients supported
by this device. In a recent study, we examined the clinical, histological, and biochemical
changes that occur after prolonged support with an LVAS. [63 ] All clinical indices of left
ventricular function improved significantly. Interestingly, the ventricle also showed signs
of recovery on the cellular and sub-cellular levels. These data indicate that some
patients may experience enough recovery that the device could be removed without
transplantation. Already, investigators from Germany and Japan have removed the
LVAS from heart failure patients with good initial results. Studies are warranted to
assess the safety and effectiveness of using the device as both a permanent implant
and a bridge to recovery.
HISTORICAL DEVELOPMENT
Skeletal muscle has been used both clinically and experimentally since the 1930s [1 ] ,
[2 ] to repair or reinforce cardiac trauma or ventricular aneurysms [1 ] [10 ] (Table 52-1) .
Some of the earliest attempts to revascularize myocardium included a skeletal muscle
graft that served as a source of extracoronary blood supply for ischemic myocardium. [3
] By the late 1950s, with the advent of early cardiac pacemakers, the idea of artificially
stimulating skeletal muscle in synchrony with the cardiac cycle to achieve cardiac assist
became plausible. [4 ] In the 1960s and 1970s, a number of investigators explored the
concept of biomechanical cardiac assistance using stimulated skeletal muscle to
provide direct cardiac assist or to power a mechanical ventricular assist device. These
attempts had limited success until two fundamental issues were addressed. The first
was the problem of muscle fatigue that occurs when skeletal muscle is repeatedly
stimulated for a prolonged period of time. This issue was not resolved until the early
1980s, when the technique of transforming skeletal muscle fiber types, which had been
discovered earlier, was adopted. [9 ]
The second problem was the inherent difference in the electrophysiologic responses
between cardiac and skeletal muscles (Table 52-2) . Since cardiac muscle is a
syncytium, once the strength of the stimulating electrical impulse exceeds a threshold,
myocardium undergoes an all or none contraction. In contrast, skeletal muscle is
composed of individual motor units, which can be recruited to increase the force of
muscle contraction. Advances in pacemaker technology made it possible to develop a
burst stimulator, which recruits motor units in skeletal muscle to enhance contractile
force while synchronizing the contraction precisely with the cardiac cycle. [8 ] With the
development of an implantable cardiomyostimulator, it became possible to carry out
long-term experiments as well as clinical trials. Convergence of these two solutions led
to the first clinical application in 1985 of dynamic cardiomyoplasty, wherein stimulated
skeletal muscle wrapped around the ventricles was used to assist a failing heart. [10 ]
BIOLOGIC BASIS OF SKELETAL MUSCLE-POWERED CARDIAC
ASSIST
Skeletal Muscle Transformation
Skeletal muscle is normally composed of two main fiber types: type I slow-twitch,
aerobic, and fatigue-resistant fibers and type II fast-twitch, anaerobic, and more
powerful but also more fatigue-prone fibers. These two skeletal muscle fiber
phenotypes can be altered by a number of interventions, including cross-innervation,
administration of T3 (tri-iodothyrodine) hormone, and electrical stimulation [11 ] (Fig.
52-1) . Low-frequency electrical stimulation of a mixed-fiber-type skeletal muscle, such
as the latissimus dorsi muscle, for 4 to 6 weeks induces sequential changes in
phenotype expression for various cellular structures and functions [12 ] and produces
predominantly type I highly fatigue-resistant skeletal muscle [13 ] (Fig. 52-2) . This
phenomenon, known as skeletal muscle transformation , provides the basis for
preparing skeletal muscle for cardiac assist (Table 52-3) . Such transformation of the
skeletal muscle fiber types is, however, reversible upon cessation of electrical
stimulation. It is now known that a wide variety of stimulation protocols can induce
transformation. Thus continuous 10-Hz stimulation and 30-Hz short-burst stimuli during
the systolic phase of every second heart beat each transform skeletal muscle into
fatigue-resistant type I fibers. In current clinical protocols for transforming skeletal
muscle, [14 ] electrical stimulation is usually initiated after a vascular delay period, since
the dissection to raise the muscle flap often interrupts collateral vessels. [15 ] As
discussed later, vascular delay of 1 week to 10 days avoids overstimulating relatively
ischemic distal portions of the pedicle graft and causing damage. Thereafter, gradual
increases in the strength and frequency of the stimulation transform the muscle in 4 to 6
weeks and prepare it for the full stimulation protocol required for cardiac assistance.
Conformational Changes in Skeletal Muscle Geometry and Fiber Length
The ability of skeletal muscle, displaced from its normal anatomic site, to adapt to a
new geometric configuration and resting tension is among the biologic changes
required for cardiac assistance. After skeletal muscle is wrapped around the heart,
within weeks the muscle flap takes on the geometric shape of epicardium, even when it
is dissected away from the heart underneath. [16 ] Presumably, this property is due to
the adaptation of connective tissue within the muscle pedicle and causes skeletal
muscle fibers to assume a curvilinear orientation rather than the original linear direction.
Furthermore, it is known that skeletal muscle can delete or add sarcomeres when
resting tension chronically is altered. [17 ] The lengths of skeletal muscle fibers adjust to
optimize resting tension but maintain the physiologic lengths of individual sarcomeres
(see Table 52-2 ) to preserve normal interaction of myosin and actin molecular chains.
Thus, after cardiomyoplasty, the initial resting tension created following transposition of
a skeletal muscle graft may change over time in a conformational adaptive process. [18
]
Skeletal Muscle Power Output and Blood Flow
A reduction in the contractile force of up to 50 percent is one of the consequences of

transforming skeletal muscle to enhance fatigue resistance. Nevertheless, calculations
based on data obtained from physiologic studies indicate that skeletal muscle power
output during sustainable effort is in the range of 10 W/kg. Therefore, even if
transformation significantly reduces contractile force, theoretically, the muscle should be
capable of generating the power produced by the resting heart, which is about 2 W/kg.
Specific tension generated by cardiac muscle is 0.2 to 0.5 kg/cm 2 , while in skeletal
muscle this reaches 1 to 2 kg/cm 2 . At least in theory, skeletal muscle is capable of
generating power comparable with that of myocardium. [19 ] Transformation protocols
that may induce fatigue resistance without sacrificing contractile force are being
explored experimentally.
All striated muscles, both cardiac and skeletal, follow Frank-Starling's law; greater
contractile force develops as resting tension of the muscle fiber increases until the peak
of the Frank-Starling curve is reached. However, as depicted in Table 52-2 , there is a
difference in the normal operating range of cardiac muscle as compared with skeletal
muscle. Myocardium normally operates in the rising line of the force/length curve, but
skeletal muscle uses the peak of the force/length curve. In contrast to a normal cardiac
ventricle, which has an end-diastolic pressure of 5 to 15 mmHg, a ventricle made of
skeletal muscle, either transformed or nontransformed, functions optimally at resting
cavitary pressures of 25 to 30 mmHg. [20 ] This characteristic has important
implications for the optimal configuration of skeletal muscle ventricles used for
circulatory assistance.
Another physiologic difference between cardiac and skeletal muscle is that blood
perfusion through the muscle occurs predominantly during diastole in myocardium and
during systole in skeletal muscles. When skeletal muscle undergoes forceful
contraction, during either cardiac systole or diastole, blood perfusion through the
muscle is significantly reduced but is followed by reactive hyperemia. [21 ] This is an
important consideration for determining how long and how often skeletal muscle can be
stimulated to contract without causing ischemic damage.
Selection of Skeletal Muscle for Cardiac Assist
Many different skeletal muscles have been used in experimental studies to provide
cardiac assistance. These include the rectus abdominis muscle, the serratus anterior
muscle, the pectoralis major muscle, and the psoas muscle. The most commonly used
skeletal muscle, both experimentally [6 ] and clinically, [9 ] is the latissimus dorsi muscle.
The rationale for selecting this muscle is based on a number of anatomic
characteristics. The latissimus dorsi is a large, powerful mixed-fiber muscle that can be
transformed into almost pure type I fatigue-resistant fibers. Its extensive use as a
pedicle graft for reconstructive surgery demonstrates that no significant motor functional
impairment results from transposition. The thoracodorsal neurovascular bundle provides
the dominant nerve and blood supplies. This makes preservation of blood perfusion and
electrical stimulation of the muscle graft technically easier. For the latter, a single pair of
electrodes on or near the thoracodorsal nerve recruits motor units throughout the entire
muscle graft, in contrast to other muscles that have motor nerve fibers that require many
electrodes. Because of its anatomic proximity to the heart, the latissimus dorsi muscle
can be raised as a pedicle graft with an intact neurovascular bundle and still allow its
middle and distal portions to reach the heart to provide direct cardiac assist. For
cardiomyoplasty, the most commonly used muscle is the left latissimus dorsi muscle,
but the right latissimus dorsi muscle also may be used when necessary. [22 ]
CARDIOMYOSTIMULATORS
A cardiomyostimulator is a burst electrical stimulator for skeletal muscle that enables it

to contract in synchrony with the cardiac cycle [8 ] (Fig. 52-3) . Current
cardiomyostimulators sense the R wave of the electrocardiogram and, after a
programmed delay, deliver a train of electrical impulses to the skeletal muscle. The
frequency of the burst, its duration, and its strength (voltage) are also programmable [23
] (Fig. 52-4) . Based on experimental studies, a burst frequency of approximately 30 Hz
appears to recruit a maximum number of skeletal muscle motor units. This frequency
generates a strong contractile force but also minimizes energy consumption of the
stimulator. [24 ] Sensing of the R wave is obtained from either an epicardial or an
endocardial pacemaker electrode. The voltage required to recruit skeletal muscle
contractile force depends in part on the type of skeletal muscle electrodes used. For
nerve cuff electrodes, stimulation voltages of less than 2 V are adequate; for the
neuromuscular electrodes depicted in Fig. 52-5 , 4 to 8 V are commonly used in
patients.
In a more advanced type of cardiomyostimulator, both synchronization delay and burst

duration can be programmed as a percentage of the preceding RR interval to permit
the stimulator to adapt automatically to changing heart rates. [25 ] Since the RR interval
is based on the preceding cardiac cycle, irregular cardiac rhythms, such as those
associated with atrial fibrillation, make this adaptative feature ineffective.
The life expectancy of cardiomyostimulator batteries depends on the stimulation

parameters set. Currently, for most patients, batteries last for 5 years or more.
EXPERIMENTAL STUDIES
Methods to Couple Transformed Skeletal Muscle to the Circulation
A transformed fatigue-resistant skeletal muscle needs to be coupled with the

cardiovascular system to achieve circulatory assist. A number of coupling strategies are
under investigation. Depending on the way they are coupled, skeletal muscles may be
stimulated in synchrony with cardiac cycles or independent of them. In a surgical
procedure known as dynamic cardiomyoplasty , skeletal muscle is wrapped around
native ventricles and stimulated in synchrony with cardiac systole to squeeze the heart.
This is the most widely studied mode of coupling and the only one that has been applied
clinically. [10 ] Skeletal muscle also may be wrapped around either the ascending aorta
[26 ] or descending thoracic aorta [27 ] and stimulated to contract during cardiac
diastole to produce diastolic augmentation analogous to an intraaortic balloon pump. In
ascending aortomyoplasty , an elliptical patch to enlarge the diameter of the ascending
aorta has been suggested to increase the vascular volume that can be displaced during
diastolic aortic compression. In the descending thoracic aortomyoplasty , a perceived
risk is spinal cord injury produced by interruption of pairs of intercostal arteries during
wrapping of the aorta. Unlike the intraaortic balloon pump, aortomyoplasty achieves
limited systolic unloading but produces long-term diastolic augmentation in
experimental animals.
Skeletal muscle also can be used to compress an artificial chamber to function as an

auxiliary skeletal muscle ventricle. [28 ] Such a ventricle can be connected to the
cardiovascular system to achieve right [29 ] or left [30 ] ventricular bypass or
counterpulsation. [31 ] In a ventricular bypass configuration, one-way valves are usually
required to direct blood from the right ventricle to the pulmonary artery or from the left
ventricle to the aorta. Atrial inlet of the blood to the skeletal muscle ventricle
compromises function because of low filling pressures. As described earlier, [20 ]
skeletal muscle requires greater resting tensions than myocardium. When a skeletal
muscle ventricle is connected in series to the descending thoracic aorta and stimulated
to contract during cardiac diastole, diastolic augmentation lasting for more than 2 years
has been achieved in some canine experiments. To prevent thrombosis in skeletal
muscle ventricular cavities, blood-compatible materials, such as autologous
pericardium, [32 ] have been used to replace polymer surfaces. Attempts are also being
made to endothelialize these interfaces with cell seeding.
A dual-chamber concept of muscle-powered mechanical cardiac assistance uses a

hydraulic pouch placed beneath the muscle or wrapped around with the muscle. The
pouch is designed to increase the power generated by contracting skeletal muscle. [33 ]
This augmented power is transmitted by hydraulic conduits to a blood chamber that is
connected to the cardiovascular system. This concept may be applied to design a
device which allows skeletal muscle fibers to contract linearly [34 ] to move a piston to
convert muscle shortening to hydrostatic pressure. Alternately, piezoelectric crystals
may be used to convert skeletal muscle power to electricity that powers an electric
pump for cardiac assist. Thus numerous strategies to convert skeletal muscle power for
cardiac assistance are possible. Successful development of such devices will eliminate
the need for an external power source and avoid the need for frequent battery
recharging as required for contemporary electric cardiac assist devices. However,
except for dynamic cardiomyoplasty, all these coupling strategies are still in the design
and experimental animal stage of development.
Dynamic Cardiomyoplasty: Experimental Studies and Mechanisms of Action
For more than a decade, dynamic cardiomyoplasty has undergone extensive animal
studies to develop and refine surgical techniques, to evaluate skeletal muscle
transformation protocols, to develop a synchronizable burst stimulator, and to
demonstrate efficacy. The effects of various skeletal muscle fiber orientations when
wrapped around the ventricle have been investigated, and the use of left, right, or
combined bilateral latissimus dorsi muscles to wrap the heart has been explored. [22 ] If
the wrap is too tight, the muscle may constrict the heart during diastole and reduce
venous return. Conformational adaptive changes in resting tension [17 ] reduce the
need to precisely stretch the muscle at the time of operation. These experimental
studies led to the most commonly used technique for clinical application, which is
described below. [35 ]
A vascular delay period to allow the ischemic distal portion of the muscle graft to
recover prior to beginning skeletal muscle transformation [15 ] is common practice.
Despite vascular delay, fibrosis and fat infiltration of wrapped skeletal muscle may
occur. [36 ] , [37 ] Risk factors for skeletal muscle damage [38 ] include muscle
ischemia due to interruption of collateral circulation when the pedicle is raised, loss of
resting tension, and excessive electrical stimulation and contraction. Since some
patients who are candidates for cardiomyoplasty have severe heart failure, low cardiac
output and cardiac cachexia may compromise the quality of the skeletal muscle pedicle.
Preventive measures include vascular delay to prevent ischemic damage and muscle
stimulation at less than 1:1 synchronization with the cardiac cycle. For patients who
suffer from cardiac cachexia, use of anabolic steroids and exercise regimens to
strengthen the latissimus dorsi muscle have been proposed.
Dynamic cardiomyoplasty was thought originally to enhance systolic function by

squeezing the native, failing heart during systole. Experimentally, systolic assist occurs
in both normal and failing hearts. [39 ] However, in clinical series, hemodynamic
evidence of systolic assist is often modest, although most patients have significant
improvement in functional status [40 ] and quality of life. [41 ] In many patients, subjective
improvements develop gradually, even though stimulator on-off studies show
inconsistent hemodynamic improvement. These observations have led to exploration of
other mechanisms to explain the effects of cardiomyoplasty in failing hearts in both
animals and patients.
Pressure/volume loop studies combined with ultrasonography [42 ] , [43 ] and direct
measurements of transmyocardial pressure [44 ] indicate that dynamic cardiomyoplasty
reduces systolic myocardial stress, which is a major determinant of myocardial oxygen
consumption. Other studies in animals [45 ] and in humans [43 ] with unstimulated or
stimulated cardiomyoplasties show reduced progression of ventricular dilatation and
modulation of the ventricular remodeling process. Potentially, these changes could
improve the clinical course of patients with dilated cardiomyopathy. In animal studies,
contracting skeletal muscle wrapped around the ventricle can provide extracoronary
blood to underlying ischemic myocardium. Microsphere studies confirm a significant
increase in myocardial perfusion from this source, [46 ] and in clinical postmortem
specimens, vascularity is sometimes seen in the interface between the skeletal muscle
wrap and underlying ischemic myocardium. Lastly, the possibility that stimulation of the
thoracodorsal nerve may affect heart failure thorough neurohormonal pathways is also
being investigated. Thus dynamic cardiomyoplasty may produce observed salutary
clinical effects by a variety of integrated mechanisms other than systolic augmentation
[47 ] (Fig. 52-6) .
CLINICAL EXPERIENCE
Dynamic cardiomyoplasty is a surgical procedure in which a skeletal muscle pedicle

graft is wrapped around failing ventricles, electrically transformed into fatigue-resistant
type I fibers, and then stimulated to contract in synchrony with cardiac systole to provide
cardiac assist. This surgical procedure is proposed for selected patients who suffer
from dilated cardiomyopathy and heart failure. [48 ] Patient age and etiology of the
cardiomyopathy are not as important as in heart transplantation, since the procedure
does not require a donor organ, is an autologous tissue, and does not require
immunosuppression. In addition to common idiopathic and ischemic cardiomyopathies,
patients who suffer from Chagas' disease can also be candidates for cardiomyoplasty.
[49 ] .
Dynamic cardiomyoplasty should be considered one of several therapeutic options for

patients with heart failure. Patients should be selected for operation by comparing
benefits and risks of cardiomyoplasty with alternate therapies, which include medical
therapy and cardiac transplantation. [50 ] Currently, investigative restrictions exclude
patients with comorbid cardiac disease such as left ventricular aneurysm, symptomatic
coronary arterial disease, valvular disease, and sustained ventricular arrhythmias from
cardiomyoplasty; however, the procedure does not exclude concomitant cardiac
procedures. An ideal candidate is a New York Heart Association functional class III
patient who is unsatisfied with symptom progression despite appropriate medical
therapy and not eligible or unwilling to undergo heart transplantation.
There are a number of absolute and relative contraindications for cardiomyoplasty.

Patients who do not have an intact latissimus dorsi muscle, such as those who have had
previous posterolateral thoracotomy, require the contralateral latissimus dorsi or
another muscle for the wrap. Patients who have had previous thoracic or cardiac
surgery may require extensive lysis of adhesions, which may increase the technical
difficulty and risk. Since the muscle flap occupies part of the pleural space, patients with
poor pulmonary function may experience some reduction in respiratory reserve.
Patients in terminal heart failure, such as those in New York Heart Association
functional class IV, have a higher operative mortality because the procedure requires
several weeks for muscle transformation. [51 ] Although absolute physiologic
contraindications are still being determined, experience so far suggests that patients
with maximal exercise oxygen consumptions (vo 2 ) of less than 10 mL/kg per min,
patients with high pulmonary vascular resistance, and those with very low ejection
fractions tend to have higher risks, even though some patients with ejection fractions as
low as 10 percent have survived and benefited. [52 ]
Skeletal muscle grafts have been used to either replace or reinforce diseased
myocardium. In the former operation, the muscle is used to replace a segment of
ventricular wall after resection of a ventricular aneurysm or to enlarge a small ventricular
cavity. For reinforcement, the skeletal muscle graft is wrapped over the heart and
contracts in synchrony to augment contractile force. [26 ] So far, hemodynamic
improvement after dynamic replacement cardiomyoplasty has not been well
demonstrated, but clinical experience is small. Reinforcement dynamic cardiomyoplasty
constitutes most of the clinical experience [53 ] , [54 ] (Fig. 52-7) .
General anesthesia is induced using a double-lumen endotracheal tube; the patient is

placed in the right lateral position with the left arm elevated. The incision for raising the
latissimus dorsi muscle flap is made at the lateral border of the muscle and extends
from axilla to iliac crest. The muscle is detached from all surrounding tissues, except for
the thoracodorsal neurovascular bundle. This bundle is easily seen from the costal
(deep) surface of the muscle [23 ] (see Fig. 52-5) . Test stimulation of the nerve is done
to ensure proper placement of the permanent electrodes. For such testing, muscle
relaxants administered during anesthesia must be reversed. Approximately 6 cm of the
second or third rib at the anterior axillary line is resected. After detaching the origin of
the latissimus dorsi muscle from the humerus, the muscle and electrode leads are
introduced into the left pleural cavity through the bed of the resected rib, taking care not
to kink or overstretch the neurovascular bundle. The detached tendinous origin of the
latissimus muscle is then sutured to the periosteum of the resected rib using pledgeted
mattress sutures. The bed of the latissimus dorsi is drained using a closed draining
system, the incision is closed, and dressings are applied.
The patient is then turned supine and reprepped and draped. A standard midline sternal
incision is made. A reversed C-shaped pericardial incision is made to fashion a
pericardial flap, which may be used to anchor or supplement the muscle wrap later.
Epicardial sensing electrodes are placed, and sensing thresholds are measured as
done for a demand cardiac pacemaker. The latissimus dorsi muscle flap and nerve
electrodes are retrieved from the pleural cavity, and the muscle is wrapped around both
ventricles. It does not appear to make any difference which surface of the muscle flap is
applied to the epicardium, but it is important to avoid twisting the muscle flap. The entire
muscle graft is inspected and palpated for evidence of twist. It is possible to wrap the
muscle around both ventricles without placing sutures directly in the diseased and often
friable myocardium. Two sutures in the posterior pericardium, one to the left of the
pulmonary valve and the other at the medial junction of the inferior vena cava and right
atrium, together define the location of the posterior atrioventricular groove. When these
two pericardial sutures are sewn to corresponding points on the posterior border of the
muscle flap, the muscle flap is secured behind the heart. The maneuver requires briefly
lifting the cardiac apex, sliding the posterior border of the muscle flap beneath, and
tying the two sutures. Arrhythmias associated with manipulation of the heart are
controlled by intravenous xylocaine prior to the maneuver. [55 ] Following this, the rest of
the muscle is folded over the right border and apex of the heart and pulled up snugly but
not tightly to the lateral border of the muscle flap to complete the wrap. The pericardial
flap fashioned earlier is used either to anchor the wrap cephalad or to cover the outflow
tract of the right ventricle when the length of the muscle flap is not sufficient to cover both
ventricles.
The sensing and stimulating electrodes are then connected to a cardiomyostimulator

that is placed into a subcutaneous pocket, usually made in the left upper quadrant of the
abdomen. The mediastinum is drained, the sternum is approximated, and all wounds
are closed. Cardiopulmonary bypass is on standby throughout the operation; an
intraaortic balloon pump may be inserted if necessary.
Postoperative Management
The patient is monitored and supported in the intensive care unit, and then allowed to
recover for 1 week with the cardiomyostimulator turned off. This is the vascular delay
period designed to avoid stimulating the ischemic distal portion of the muscle graft
caused by division of some collaterals when the muscle graft is raised. [15 ] Following
the delay, the patient undergoes a graded protocol of skeletal muscle transformation by
incrementally increasing the frequency and strength of stimulation for the following 4 to 6
weeks prior to full-burst stimulation used for cardiac assist. [14 ]
Although the burst stimulation may be delivered during every systole, less frequent
muscle stimulation such as a 1:2 ratio to heart rate may prevent skeletal muscle
damage, particularly during high heart rates. Stimulation voltage is adjusted either by
palpating the muscle contraction of the extrathoracic portion of the muscle graft in the
left axilla or by observing contraction of the muscle under fluoroscopy or
ultrasonography. The synchronizing delay is best determined using two-dimensional
echocardiography. Many patients with dilated cardiomyopathy have mild to moderate
mitral insufficiency, and premature initiation of the muscle wrap contraction can
increase mitral regurgitation. Therefore, the onset of burst stimulation is synchronized
with mitral valve closure, as determined by ultrasound. This is particularly important for
patients with cardiac conduction abnormalities. In many patients, synchronization delay
can be further optimized by measuring aortic flow of stimulated beats with Doppler
echocardiography and selecting the delay period that maximizes observed aortic flow
velocity. [47 ] Burst frequency is usually started at about 30 Hz, which has been shown
experimentally to produce near-maximal recruitment of skeletal muscle motor units with
minimal stimulator battery consumption. [24 ] Burst duration also must be programmed
to avoid impairment of diastolic filling by the muscle wrap if it fails to relax in time. [56 ]
The patient is monitored long term in a manner similar to patients who have cardiac
pacemakers and heart failure. Medical therapy is optimized according to the patient's
condition, and arrhythmias are controlled carefully by medication and electrical
conversion if necessary. The cardiomyo-stimulator is replaced as required; prophylactic
replacement is predicted by the selected stimulation parameters chosen for each
individual patient.
Results
Since the first clinical application of dynamic cardiomyoplasty a decade ago, more than
500 patients worldwide have undergone this operation. Results reported by various
centers [22 ] , [36 ] , [37 ] are largely consistent with those obtained in the recently
completed phase II clinical trial under a protocol approved by the Food and Drug
Administration of the United States. [57 ] At present, a phase III prospective,
randomized clinical trial to compare dynamic cardiomyoplasty with medical therapy is
under way in North America. This study, in itself, pioneers rigorous scientific evaluation
of new surgical procedures. [47 ]
In the phase II trial, a prospective study was carried out in approximately 50 patients
who had dynamic cardiomyoplasty. Outcomes were compared with those of a reference
group of medically treated patients with matched demographic, etiologic, clinical, and
hemodynamic parameters. [58 ] Entry criteria and pre- and postoperative evaluations
were clearly defined. Both in cardiomyoplasty and in the reference group, most patients
were in New York Heart Association functional class III heart failure, suffered from either
idiopathic or ischemic cardiomyopathies, and received well-supervised medical
therapy. Operative mortality for cardiomyoplasty was about 10 percent, and 6 months
after operation more than 80 percent of patients showed functional improvement that
was significantly better than that of the reference group (Fig. 52-8) . These results were
consistent with improved quality of life measurements observed in cardiomyoplasty
patients (Fig. 52-9) . Hemodynamically, systolic functions such as left ventricular
ejection fraction showed statistically significant but clinically modest improvement (Fig.
52-10) . There also was a trend toward less utilization of intensive care services by
cardiomyoplasty patients. Actuarial survival data at 1 year were similar in the two
groups (Fig. 52-11) . However, nearly 20 percent of patients in the reference group
received heart transplants during this period; thus this survival comparison may not be
valid because so many patients were not on medical therapy alone.
Dynamic cardiomyoplasty can be considered a bridge to transplantation in selected

patients. Successful heart transplantation has been carried out in a number of patients
after cardiomyoplasty. One of the important findings obtained so far is that few patients
who survived the early postoperative period died from pump failure; more than 70
percent succumbed to sudden death, presumably due to arrhythmias. A new generation
of cardiomyostimulators that also have the capacity to function as an implantable
defibrillator is being developed. This may further improve the survival of patients
following dynamic cardiomyoplasty.
CONCLUSIONS AND FUTURE PERSPECTIVES
The ability to transform a patient's own skeletal muscle into a highly fatigue-resistant
fiber type introduces a unique power source to assist the failing heart. The best
methods to couple this power source to the circulatory system to achieve cardiac assist
and to maximize power output without damaging the muscle need further exploration.
Dynamic cardiomyoplasty, which applies the transformed skeletal muscle directly to the
heart to augment myocardial function, also may affect the remodeling process of a
failing heart, reduce myocardial stress, and provide an additional source of blood
supply. These mechanisms may explain the consistent findings of clinical improvement
following cardiomyoplasty despite relatively modest enhancement of systolic function.
Although the survival advantage of dynamic cardiomyoplasty has not been shown, this
procedure is still evolving. A new generation of cardiomyostimulator-defibrillators soon
will be available. Additional data regarding clinical outcomes following dynamic
cardiomyoplasty and a greater understanding of the underlying physiology and
morphology of the wrapped heart will improve our ability to select appropriate patients
for this procedure. The operation is particularly suited for those who are not eligible for
heart transplantation or who do not respond satisfactorily to alternate therapy.
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Cardiac Surgery in Adults

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Dedication

Cary W. Akins, M.D. [20] Robert B. Karp, M.D. [30]

Robert C. Ashton, M.D. [21] Steven A. Leyland [5]

James M. Bailey, M.D. [8] James E. Lowe, M.D. [14, 24]

Hendrick B. Barner, M.D. [17] Joren C. Madsen, M.D. [22]

Davis C. Drinkwater, Jr. M.D. [47] Vivek Rao, M.D. [10]

M. Arisan Ergin, M.D. [40] Ross M. Reul, M.D. [34]

James I. Farm, M.D. [32] Robert C. Robbins, M.D. [50]

Carl C. Hug, Jr., M.D. [8] James T. Willerson, M.D. [16]

W. R. Eric Jamieson, M.D. [29]

W. R. Eric Jamieson, M.D. [29]

Ellis L. Jones, M.D. [18]

Mark E. Josephson, M.D. [25]

All that we know is that it is a superb text. Is anything else important?

September 9Worsening status. Pulse weaker, increasing cardiac dullness on

September 15Irregular pulse worsening after camphor injections. Morphine helps.

Frederic Trendelenburg was first to attempt a pulmonary embolectomy. [16 ] In his

The clinical picture is characteristic: rapid collapse, frequently accompanied by substernal

. . . Regarding surgical technique, I reported my animal studies in 1907: following rapid

Trendelenburg goes on to say, In contrast to the failure in my patient, I wish to present a

Although cardiac catheterization is not considered heart surgery, it is an invasive

He goes on to say, I confirmed these facts by studies on a cadaver, catheterizing any

Dear Dr. Harken:

With very kind regards.

In the early 1950s, Charles Hufnagel, in Washington, D.C., and J. M. Campbell, in

Combined mitral and tricuspid commissurotomy was performed by Brofman in 1953.

Muller [62 ] reported successful surgical treatment of transposition of the pulmonary

Another of Gross's pioneering surgical procedures was the surgical closure of an

The cavopulmonary anastomosis has had several variations by different designers.

The development of the heart-lung machine made repair of intracardiac lesions

McLean described his finding in February 1916 at a medical society meeting in

Extracorporeal life support is an extension of cardiopulmonary bypass.

As the safety of cardiopulmonary bypass steadily improved, surgeons addressed more

In 1958, Lowell Edwards presented himself in my office with a proposal to develop an

I began to investigate numerous cross-linking inducing factors and found that

With the development of cardiopulmonary bypass, valves could be approached under

Alexis Carrel remarked in 1910 [115 ] :

Arthur Vineberg, a Canadian surgeon, in 1946 reported implanting the internal

At that time we were doing the coronary thromboendarterectomy procedure, we also, I

As early as 1952, Vladimir Demikhov, the renowned Soviet surgeon, was

My own contributions (F.C.S.) to coronary bypass were principally experimental studies

After 25 minutes of intermittent stimulation, however, the spontaneous ventricular

Early implantable pacemakers were fixed-rate, asynchronous devices that delivered an

On January 2, 1968, Barnard performed a second heart transplant on Phillip Blaiberg,

A clinical trial of heart-lung transplantation was commenced at Stanford University in

We were greatly impressed with the report of Voorhees on the use of a

Another advance in aortic surgery appeared in 1955 when DeBakey et al.

In 1968, Bentall and De Bono [266 ] introduced replacement of the

Location of the Heart Relative to Surrounding Structures

The Pericardium and Its Reflections

Mediastinal Nerves and Their Relationships to the Heart

Bilateral Transverse Thoracosternotomy (Clam Shell Incision)

The bilateral transverse thoracosternotomy (clam shell incision) is an alternative incision

Morphology of the Right Atrium and Tricuspid Valve

APPENDAGE, VESTIBULE, AND VENOUS COMPONENT

ATRIOVENTRICULAR SEPTUM AND NODE: TRIANGLE OF KOCH

Morphology of the Left Atrium and Mitral Valve

APPENDAGE, VESTIBULE, AND VENOUS COMPONENT

Morphology of the Right Ventricle and Pulmonary Valve

INLET AND APICAL TRABECULAR PORTIONS

OUTLET PORTION AND PULMONARY VALVE

SUPRAVENTRICULAR CREST AND PULMONARY INFUNDIBULUM

A distinguishing feature of the right ventricle is a prominent muscular shelf, the