AAP Common Cardiac Issues in Pediatrics 2018 PDF

Common Cardiac I ssues in Pediatrics
Common Cardiac
Issues in Pediatrics
Common
Editors
Jonathan N. Johnson, MD, FACC, FAAP, and
Cardiac Issues
in Pediatrics
Deepak M. Kamat, MD, PhD, FAAP
Learn from leading experts the latest information on cardiac

issues that present most often in a pediatric office. The
scope of focus includes signs and symptoms, management
of patients with acquired or congenital heart disease, cardiac
implications of common infectious diseases, preventive
cardiology, and other issues that are frequently managed or
evaluated by the primary care pediatrician.
Topics include
• Electrocardiography
• Heart Murmur
• Syncope
• Cardiomyopathies and Channelopathies
• Rheumatic Heart Disease
• Endocarditis
JOHNSON ∞ KAMAT
• Cardiac Pharmacology
• Transition From Pediatric to Adult-Centered
C
ardiac Care
Editors
For other pediatric resources, visit the
Jonathan N. Johnson, MD, FACC, FAAP
American Academy of Pediatrics
at shop.aap.org. Deepak M. Kamat, MD, PhD, FAAP
ISBN 978-1-61002-144-9
90000>
9 781610 021449
AAP
Common_Cardiac_issues_cover-spread_final.indd 1 3/13/18 3:31 PM

Common
Cardiac Issues
in Pediatrics
Editors
CCIP.indb 1 3/13/18 4:18 PM

American Academy of Pediatrics Publishing Staff
Mark Grimes, Vice President, Publishing
Chris Wiberg, Senior Editor, Professional/Clinical Publishing
Theresa Wiener, Production Manager, Clinical and Professional Publications
Heather Babiar, Medical Copy Editor
Peg Mulcahy, Manager, Art Direction and Production
Mary Lou White, Chief Product and Services Officer/SVP, Membership, Marketing,
and Publishing
Mary Louise Carr, MBA, Marketing Manager, Clinical Publications
345 Park Blvd
Itasca, IL 60143
Telephone: 630/626-6000
Facsimile: 847/434-8000
www.aap.org
The recommendations in this publication do not indicate an exclusive course of treatment or serve
as a standard of care. Variations, taking into account individual circumstances, may be appropriate.
Listing of resources does not imply an endorsement by the American Academy of Pediatrics (AAP).
The AAP is not responsible for the content of external resources. Information was current at the time
of publication.
Brand names are furnished for identification purposes only. No endorsement of the manufacturers or
products mentioned is implied.
Every effort has been made to ensure that the drug selection and dosages set forth in this text are
in accordance with the current recommendations and practice at the time of publication. It is the
responsibility of the health care professional to check the package insert of each drug for any change
in indications and dosages and for added warnings and precautions.
The publishers have made every effort to trace the copyright holders for borrowed material. If they
have inadvertently overlooked any, they will be pleased to make the necessary arrangements at the
first opportunity.
This publication has been developed by the American Academy of Pediatrics. The authors, editors,
and contributors are expert authorities in the field of pediatrics. No commercial involvement of
any kind has been solicited or accepted in the development of the content of this publication.
Disclosures: Dr Cannon disclosed a data safety monitoring board relationship with Medtronic.
Dr Stockton disclosed speaker’s bureau relationships with Sanofi Genzyme and Shire.
Every effort is made to keep Common Cardiac Issues in Pediatrics consistent with the most recent
advice and information available from the American Academy of Pediatrics.
Special discounts are available for bulk purchases of this publication. E-mail our Special Sales
Department at aapsales@aap.org for more information.
© 2018 American Academy of Pediatrics
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system,
or transmitted in any form or by any means—electronic, mechanical, photocopying, recording,
or otherwise—without prior written permission from the publisher (locate title at http://ebooks.
aappublications.org and click on © Get Permissions; you may also fax the permissions editor at
847/434-8780 or e-mail permissions@aap.org).
Printed in the United States of America
9-389/0418 1 2 3 4 5 6 7 8 9 10
MA0857
ISBN: 978-1-61002-144-9
eBook: 978-1-61002-145-6
EPUB: 978-1-61002-237-8
Mobi: 978-1-61002-238-5
Library of Congress Control Number: 2017940294
CCIP.indb 2 3/13/18 4:18 PM

COMMON CARDIAC ISSUES IN PEDIATRICS
Editors
Jonathan N. Johnson, MD, FACC, FAAP Deepak M. Kamat, MD, PhD, FAAP
Associate Professor of Pediatrics Professor of Pediatrics
Chair, Division of Pediatric Cardiology Vice Chair for Education
Department of Pediatric and Adolescent The Carman and Ann Adams Department
Medicine of Pediatrics
Mayo Clinic Wayne State University
Rochester, MN Designated Institutional Official
Children’s Hospital of Michigan
Detroit, MI
Contributing Authors
Sanjeev Aggarwal Heather Anderson, MD, FAAP
Professor of Pediatrics Fellow
Division of Pediatric Cardiology Division of Pediatric Cardiology
Children’s Hospital of Michigan Mayo Clinic
Wayne State University Rochester, MN
Detroit, MI Ch 19: Congenital Heart Lesions
Ch 8: Chest Pain Kristin Anton, RN, MSM, CPNP-AC
Huzaifa Ahmad, MBBS Children’s Health
MBBS Class of 2018 Dallas, TX
The Aga Khan University Ch 44: Pulmonary Hypertension
Karachi, Pakistan Neha Bansal, MD
Ch 14: Neonatal Screening for Heart Disease Fellow Pediatric Cardiology
Kiona Y. Allen, MD Children’s Hospital of Michigan
Assistant Professor of Pediatrics Detroit, MI
Northwestern University Feinberg School Ch 8: Chest Pain
of Medicine Dianna M. E. Bardo, MD, FSCCT, FNASCI
Ann and Robert H. Lurie Children’s Hospital Director, Body MRI
of Chicago Co-Director, 3D Innovation Lab
Chicago, IL Department of Medical Imaging
Ch 39: Neurodevelopmental and Psychosocial Phoenix Children’s Hospital
Outcomes in Children With Congenital Clinical Professor of Radiology and
Heart Disease Child Health
Carolyn A. Altman, MD, FAAP University of Arizona
Associate Chief, Pediatric Cardiology Phoenix, AZ
Professor, Pediatrics Ch 5: Chest Radiography
Baylor College of Medicine Sarosh P. Batlivala, MD, MSCI, FAAP
Texas Children’s Hospital Associate Professor, Pediatric Cardiology
Houston, TX Associate Program Director, Pediatric
Ch 31: Prevention of Bacterial Endocarditis Cardiology Fellowship
Ch 33: Pericardial Diseases Director, Pediatric Fellowship Training
Ahdi Amer, MD Programs
Associate Professor of Pediatrics The Children’s Heart Center
The Carman and Ann Adams Department Blair E. Batson Hospital for Children
of Pediatrics University of Mississippi Medical Center
Wayne State University School of Medicine Jackson, MS
Detroit, MI Ch 19: Congenital Heart Lesions
Ch 28: Vaccines for Patients With Cardiac
Conditions
iii
CCIP.indb 3 3/13/18 4:18 PM

Allison K. Black, MD Kanupriya Chaturvedi, MD, FAAP

Pediatric Cardiology Fellow Fellow, Pediatric Cardiology
University of Pittsburgh The Congenital Heart Collaborative
Pittsburgh, PA University Hospitals, Rainbow Babies and
Ch 38: Autonomic Dysfunction Children’s Hospital
Jessica Bowman, MD Cleveland, OH
Attending Pediatric Cardiologist Ch 36: Cardiac Screening Prior to ADHD
Nationwide Children’s Hospital Treatment
Assistant Professor of Pediatrics Sharon Chen, MD, MPH
The Ohio State University Clinical Assistant Professor
Columbus, OH Pediatric Heart Failure and Transplantation
Ch 40: Lifestyle Counseling Lucile Packard Children’s Hospital at Stanford
Harold M. Burkhart, MD University
Professor and Chief Palo Alto, CA
Department of Surgery Ch 43: Cardiac Transplantation
Division of Thoracic and Cardiovascular Surgery Devyani Chowdhury, MD, FAAP, FACC
University of Oklahoma Health Sciences Center Director, Cardiology Care for Children
Oklahoma City, OK Affiliate Faculty Children’s Hospital
Ch 16: Office Care of the Child After Cardiac of Philadelphia
Surgery Lancaster, PA
Ryan Butts, MD Ch 14: Neonatal Screening for Heart Disease
Assistant Professor of Pediatrics Jason Cole, MD
Division of Pediatric Cardiology PGY-3 Pediatric Resident
University of Texas Southwestern UN Nationwide Children’s Hospital/Ohio State
Dallas, TX University
Ch 32: Myocarditis Columbus, OH
Michael U. Callaghan, MD Ch 40: Lifestyle Counseling
Associate Professor of Pediatrics Michael Colon, MD
Children’s Hospital of Michigan Clinical Associate Professor of Pediatrics
Detroit, MI Division of Pediatric Cardiology
Ch 27: Cardiotoxicity Among Survivors of Albany Medical College
Childhood Cancer Albany, NY
Bryan Cannon, MD, FACC, FHRS, FAAP Ch 29: Lyme Carditis
Director, Pediatric Electrophysiology John Colquitt, MD, FAAP
Director, Pediatric Cardiology Fellowship Assistant Professor of Pediatrics
Program Division of Pediatric Cardiology
Associate Professor of Pediatrics Baylor College of Medicine
Mayo Clinic Texas Children’s Hospital
Rochester, MN Houston, TX
Ch 37: Cardiac Screening for Athletic Participation Ch 31: Prevention of Bacterial Endocarditis
Chesney Castleberry, MD Bibhuti B. Das, MD, FAAP, FACC
Assistant Professor, Pediatric Cardiology Pediatric Heart Failure and Transplant
School of Medicine, Washington University in Cardiologist
St Louis Joe DiMaggio Children’s Hospital
St Louis Children’s Hospital Memorial Health Care
St Louis, MO Hollywood, FL
Ch 22: Restrictive Cardiomyopathy Ch 44: Pulmonary Hypertension
iv
CCIP.indb 4 3/13/18 4:18 PM

Pirooz Eghtesady, MD, PhD, FAAP Julie Glickstein, MD, FACC, FAAP
Professor and Emerson Chair Professor of Pediatrics at Columbia University
Department of Surgery Medical Center
Chief, Pediatric Cardiac Surgery Director, Pediatric Cardiology Fellowship
Washington University in St Louis Program
Co-Director of the Heart Center Department of Pediatrics/Division of Pediatric
St Louis Children’s Hospital Cardiology
St Louis, MO Morgan Stanley Children’s Hospital of New
Ch 15: Surgical Procedures for Congenital York Presbyterian
Heart Disease New York, NY
Noelle Andrea V. Fabie, MD Ch 12: Evaluation of the Neonate With Congenital
Medical Biochemical Fellow Heart Disease
Division of Genetic, Genomic, and Metabolic David J. Goldberg, MD
Disorders Assistant Professor
Children’s Hospital of Michigan Department of Pediatrics
Detroit, MI The Perelman School of Medicine at The
Ch 17: Common Syndromes Associated With University of Pennsylvania
Cardiac Lesions Division of Cardiology
Swati Garekar, BC The Children’s Hospital of Philadelphia
Director, Pediatric Cardiology Program Philadelphia, PA
Fortis Hospital, Mulund Ch 7: Laboratory Studies
Mumbai, India Pooja Gupta, MD, FASE, FACC
Ch 26: Acute Rheumatic Fever and Rheumatic Assistant Professor of Pediatrics
Heart Disease Division of Pediatric Cardiology
Bessey Geevarghese, DO Children’s Hospital of Michigan
Assistant Professor Wayne State University
Northwestern University Feinberg School Detroit, MI
of Medicine Ch 9: Syncope
Attending Physician, Division of Infectious Caitlin Haxel, MD
Disease Chief Fellow, Pediatric Cardiology
Ann and Robert H. Lurie Children’s Hospital Division of Pediatric Cardiology
of Chicago New York Presbyterian—Morgan Stanley
Chicago, IL Children’s Hospital
Ch 25: Kawasaki Disease Columbia University College of Physicians
Miwa Geiger, MD and Surgeons
Assistant Professor of Pediatrics New York, NY
Division of Pediatric Cardiology Ch 12: Evaluation of the Neonate With Congenital
Director, Fetal Heart Program Heart Disease
Icahn School of Medicine at Mount Sinai Gurumurthy Hiremath, MD, FACC
New York, NY Assistant Professor of Pediatrics
Ch 41: Cardiac Pharmacology Division of Pediatric Cardiology
Samuel S. Gidding, MD University of Minnesota
Cardiology Division Head Minneapolis, MN
Nemours Cardiac Center Ch 1: Clinical History and Physical Examination
Professor of Pediatrics Ch 11: Heart Murmur
Sidney Kimmel Medical College of Thomas Whitnee Hogan, MD
Jefferson University Pediatric Cardiology Fellow
Wilmington, DE Department of Pediatrics
Ch 34: Dyslipidemia University of Utah
Salt Lake City, UT
Ch 20: Hypertrophic Cardiomyopathy
CCIP.indb 5 3/13/18 4:18 PM

Kelley K. Hutchins, DO, MPH Sonya Kirmani, MD

Pediatric Hematology/Oncology Fellow Instructor, Pediatric Heart Failure/Transplant
Children’s Hospital of Michigan Division of Pediatric Cardiology
Detroit, MI Duke University Medical Center
Ch 27: Cardiotoxicity Among Survivors of Durham, NC
Childhood Cancer Ch 22: Restrictive Cardiomyopathy
Anitha S. John, MD, PhD Stacie Knutson, MD
Director, Washington Adult Congenital Assistant Professor of Pediatrics
Heart Program Division of Pediatric Cardiology
Children’s National Medical Center and University of Minnesota
Washington Hospital Center Minneapolis, MN
Assistant Professor of Pediatrics Ch 1: Clinical History and Physical Examination
George Washington University Ch 11: Heart Murmur
Washington, DC William Buck Kyle, MD, FAAP
Ch 18: Adults With Congenital Heart Disease Assistant Professor of Pediatrics
Jonathan N. Johnson, MD, FACC, FAAP Division of Pediatric Cardiology
Associate Professor of Pediatrics Baylor College of Medicine/Texas Children’s
Chair, Division of Pediatric Cardiology Hospital
Department of Pediatric and Adolescent Houston, TX
Medicine Ch 19: Congenital Heart Lesions
Mayo Clinic Timothy S. Lancaster, MD
Rochester, MN Fellow in Cardiothoracic Surgery
Ch 4: Basics of Exercise Testing Barnes-Jewish/St Louis Children’s Hospitals
Joyce Johnson, MD, MS, FAAP Washington University School of Medicine
Assistant Professor, Pediatric Cardiology St Louis, MO
Ann & Robert H. Lurie Children’s Hospital Ch 15: Surgical Procedures for Congenital
of Chicago Heart Disease
Northwestern University Feinberg School of Diego Lara, MD, MPH
Medicine Pediatric and Fetal Cardiology
Chicago, IL Ochsner Hospital for Children
Ch 19: Congenital Heart Lesions Senior Lecturer
Beth D. Kaufman, MD University of Queensland-Ochsner Clinical
Clinical Associate Professor of Pediatrics School
Director, Pediatric Cardiomyopathy Program New Orleans, LA
Lucile Packard Children’s Hospital, Stanford Ch 33: Pericardial Diseases
University Shannon Lyon, DO
Palo Alto, CA University of Louisville
Ch 43: Cardiac Transplantation Department of Pediatrics
Angela M. Kelle, MD, FACC, FAAP Louisville, KY
Assistant Professor of Pediatrics Ch 21: Dilated Cardiomyopathy
Penn State Children’s Hospital Nicolas L. Madsen, MD, MPH
Hershey, PA Medical Director, Inpatient Cardiology
Ch 3: The Role of Echocardiography Assistant Professor of Pediatrics
Steven J. Kindel, MD University of Cincinnati College of Medicine
Assistant Professor of Pediatrics Cincinnati Children’s Hospital Medical Center
Medical Director of Advanced Heart Failure Cincinnati, OH
and Heart Transplantation Ch 19: Congenital Heart Lesions
Herma Heart Center
Children’s Hospital of Wisconsin
Medical College of Wisconsin
Milwaukee, WI
Ch 23: Noncompaction Cardiomyopathy
vi
CCIP.indb 6 3/13/18 4:18 PM

Bradley S. Marino, MD, MPP, MSCE, FAAP Mark D. Norris, MD, MS

Professor Pediatrics and Medical Social Sciences Medical Co-Director Adult Congenital Heart
Northwestern University Feinberg School Program
of Medicine University of Michigan
Heart Center Co-Director, Research and Ann Arbor, MI
Academic Affairs Ch 42: Transition and Transfer From Pediatric to
Divisions of Cardiology and Critical Care Adult-Centered Cardiac Care
Medicine Todd T. Nowlen, MD, FACC
Ann & Robert H. Lurie Children’s Hospital Director Ambulatory Cardiology
of Chicago Phoenix Children’s Hospital
Chicago, IL Phoenix, AZ
Ch 39: Neurodevelopmental and Psychosocial Ch 5: Chest Radiography
Outcomes in Children With Congenital
Brandon Lane Phillips, MD, FAAP
Heart Disease
Department of Pediatrics
Daniel Mauriello, MD Ochsner Health Center for Children
Assistant Professor of Pediatrics Monroe, Ochsner Clinic Foundation
Division of Pediatric Cardiology West Monroe, LA
Johns Hopkins All Children’s Hospital Ch 1: Clinical History and Physical Examination
St Petersburg, FL
Adam Putschoegl, DO, FAAP
Ch 2: Electrocardiography
Pediatric Cardiology Fellow
Shaji C. Menon, MD, FACC, FASE, FAAP Division of Pediatric Cardiology
Associate Professor of Pediatrics Mayo Clinic
Adjunct Associate Professor of Radiology Rochester, MN
Medical Director, Single Ventricle Survivorship Ch 19: Congenital Heart Lesions
Program Ch 42: Transition and Transfer From Pediatric to
University of Utah Adult-Centered Cardiac Care
Salt Lake City, UT
Muhammad Yasir Qureshi, MBBS, FASE
Ch 6: Cardiac MR Imaging and CT
Senior Associate Consultant
James H. Moller, MD, FAAP Pediatric Cardiology
Professor Emeritus and Former Head of Assistant Professor of Pediatrics
Pediatrics Mayo Clinic College of Medicine
Adjunct Professor of Pediatrics Rochester, MN
Minneapolis, MN Ch 3: The Role of Echocardiography
Ch 13: Fetal and Newborn Transitional
Hari Rajagopal, MD
Circulations
Pediatric Cardiology Advanced Imaging Fellow
Brandon Morrical, MD, FAAP Division of Pediatric Cardiology
Instructor of Pediatrics Icahn School of Medicine at Mount Sinai
Division of Pediatric Cardiology New York, NY
Mayo Clinic Ch 41: Cardiac Pharmacology
Rochester, MN
Rini Sahewalla, MD
Ch 4: Basics of Exercise Testing
Fellow, Pediatric Cardiology
Kathleen A. Mussatto, PhD, RN Children’s Hospital of Michigan
Co-Director of Cardiac Research Detroit, MI
Associate Clinical Professor of Surgery Ch 17: Common Syndromes Associated With
Children’s Hospital of Wisconsin Cardiac Lesions
Milwaukee, WI
Amy H. Schultz, MD, MSCE, FACC, FAAP
Ch 39: Neurodevelopmental and Psychosocial
Attending Cardiologist
Outcomes in Children With Congenital
Seattle Children’s Hospital
Heart Disease
Associate Professor of Pediatrics
Division of Cardiology
University of Washington School of Medicine
Seattle, WA
Ch 30: Endocarditis
vii
CCIP.indb 7 3/13/18 4:18 PM

Kristen Sexson Tejtel, MD, PhD, MPH, Joshua D. Sparks, MD

FAAP Director, Pediatric Advanced Heart Failure
Assistant Professor of Pediatrics and Transplantation
Director, Center for Preventive Cardiology University of Louisville School of Medicine
Texas Children’s Hospital Norton Children’s Hospital
Baylor College of Medicine Louisville, KY
Houston, TX Ch 21: Dilated Cardiomyopathy
Ch 35: Hypertension Ch 38: Autonomic Dysfunction
Stanford T. Shulman, MD, FAAP Rachel Steury, MSN, CNP
Virginia H. Rogers Professor of Pediatric Washington, Adult Congenital Heart Program
Infectious Diseases Children’s National Health System
Northwestern University Feinberg School Washington, DC
of Medicine Ch 18: Adults With Congenital Heart Disease
Division Head Emeritus Infectious Diseases David W. Stockton, MD, FACMG
Ann and Robert H. Lurie Children’s Hospital Professor of Pediatrics and Internal Medicine
of Chicago Chief, Division of Genetic, Genomic and
Chicago, IL Metabolic Disorders
Ch 25: Kawasaki Disease Wayne State University and Children’s Hospital
Nikki M. Singh, MD of Michigan
Pediatric Cardiology Fellow Detroit, MI
Medical College of Wisconsin Ch 17: Common Syndromes Associated With
Children’s Hospital of Wisconsin Cardiac Lesions
Milwaukee, WI Alex J. Thompson, MD, FAAP
Ch 23: Noncompaction Cardiomyopathy Department of Pediatric and Adolescent
Lalitha Sivaswamy, MD Medicine
Associate Professor of Pediatrics and Neurology Division of Pediatric Cardiology
Carmen and Ann Adams Department Mayo Clinic
of Pediatrics Rochester, MN
Wayne State University School of Medicine Ch 19: Congenital Heart Lesions
Detroit, MI Jess Thompson, MD, MSc
Ch 9: Syncope Assistant Professor of Surgery
Melissa Smith-Parrish, MD Section of Congenital Heart Surgery
Assistant Professor of Pediatrics University of Oklahoma
Northwestern University Feinberg School Oklahoma City, OK
of Medicine Ch 16: Office Care of the Child After Cardiac
Chicago, IL Surgery
Ch 39: Neurodevelopmental and Psychosocial Bhadra Trivedi, MD
Outcomes in Children With Congenital Pediatrics, Fellow, Pediatric Cardiology
Heart Disease Department of Pediatric Cardiology
Brian S. Snarr, MD, PhD Fortis Child Heart Mission
Cardiology Fellow Fortis Hospital Mulund
Division of Cardiology Mumbai, India
The Children’s Hospital of Philadelphia Ch 26: Acute Rheumatic Fever and Rheumatic
Philadelphia, PA Heart Disease
Ch 7: Laboratory Studies Juan Villafañe, MD, FAAP
Christopher Snyder, MD, FAAP Professor of Pediatrics Cardiology
Ch 36: Cardiac Screening Prior to ADHD University of Kentucky
Treatment Lexington, KY
Ch 24: Long QT Syndrome and Other
Channelopathies
viii
CCIP.indb 8 3/13/18 4:18 PM

Philip L. Wackel, MD Melissa Yamauchi, MD, MPH

Assistant Professor of Pediatrics University of Utah
Division of Pediatric Cardiology Salt Lake City, UT
Mayo Clinic College of Medicine Ch 6: Cardiac MR Imaging and CT
Rochester, MN
Ch 10: Palpitations and Arrhythmia
American Academy of
Josh Weldin, MD
Assistant Professor of Pediatrics
Pediatrics Reviewers
Division of Pediatric Cardiology Section on Cardiology and Cardiac Surgery
University of Washington School of Medicine Section on Clinical Pharmacology and
Seattle Children’s Hospital Therapeutics
Seattle, WA Section on Infectious Diseases
Ch 30: Endocarditis Section on Medicine—Pediatrics
Don P. Wilson, MD, FNLA

Diplomate, American Board of Clinical
Lipidology
Endowed Chair, Pediatric Cardiovascular
Health and Risk Prevention
Pediatric Endocrinology and Diabetes
Cook Children’s Medical Center
Fort Worth, TX
Ch 34: Dyslipidemia
ix
CCIP.indb 9 3/13/18 4:18 PM

CCIP.indb 10 3/13/18 4:18 PM
Contents
Introduction.......................................................................................... xvii
Part 1: Evaluation of the Patient

1. Clinical History and Physical Examination.......................................... 3
Brandon Lane Phillips, MD, FAAP, Stacie Knutson, MD,
and Gurumurthy Hiremath, MD, FACC
2. Electrocardiography........................................................................... 13
Daniel Mauriello, MD
3. The Role of Echocardiography............................................................ 49
Angela M. Kelle, MD, FACC, FAAP, and Muhammad Yasir Qureshi,
MBBS, FASE
4. Basics of Exercise Testing................................................................... 71
Brandon Morrical, MD, FAAP, and Jonathan N. Johnson, MD,
FACC, FAAP
5. Chest Radiography............................................................................. 79
Todd T. Nowlen, MD, FACC, and Dianna M. E. Bardo,
MD, FSCCT, FNASCI
6. Cardiac MR Imaging and CT............................................................. 95
Melissa Yamauchi, MD, MPH, and Shaji C. Menon,
MD, FACC, FASE, FAAP
7. Laboratory Studies........................................................................... 109
Brian S. Snarr, MD, PhD, and David J. Goldberg, MD
Part 2: Common Signs and Symptoms

8. Chest Pain....................................................................................... 117
Neha Bansal, MD, and Sanjeev Aggarwal, MD
9. Syncope........................................................................................... 133
Lalitha Sivaswamy, MD, and Pooja Gupta, MD, FASE, FACC
10. Palpitations and Arrhythmia............................................................. 147
Philip L. Wackel, MD
11. Heart Murmur................................................................................. 161
Gurumurthy Hiremath, MD, FACC, and Stacie Knutson, MD
12. Evaluation of the Neonate With Congenital Heart Disease................ 171
Caitlin Haxel, MD, and Julie Glickstein, MD, FACC, FAAP
xi
CCIP.indb 11 3/13/18 4:18 PM

CONTENTS
Part 3: Congenital Heart Disease

13. Fetal and Newborn Transitional Circulations..................................... 187
James H. Moller, MD, FAAP
14. Neonatal Screening for Heart Disease............................................... 197
Huzaifa Ahmad, MBBS, and Devyani Chowdhury, MD, FAAP, FACC
15. Surgical Procedures for Congenital Heart Disease............................. 205
Timothy S. Lancaster, MD, and Pirooz Eghtesady, MD, PhD, FAAP
16. Office Care of the Child After Cardiac Surgery.................................. 237
Jess Thompson, MD, MSc, and Harold M. Burkhart, MD
17. Common Syndromes Associated With Cardiac Lesions..................... 245
Noelle Andrea Fabie, MD, Rini Sahewalla, MD, and
David W. Stockton, MD, FACMG
18. Adults With Congenital Heart Disease............................................. 269
Rachel Steury, MSN, CNP, and Anitha S. John, MD, PhD
19. Congenital Heart Lesions................................................................. 287
Aortic Valve Problems, Including Bicuspid Aortic Valve
and Subaortic Membranes................................................................ 287
William Buck Kyle, MD, FAAP
Atrial Septal Defects........................................................................ 292
Alex J. Thompson, MD, FAAP, and
Nicolas L. Madsen, MD, MPH
Atrioventricular Canal Defects......................................................... 296
Sarosh P. Batlivala, MD, MSCI, FAAP
Coarctation of the Aorta................................................................... 300
“Congenitally Corrected” Transposition of the Great Arteries............ 305
Mitral Valve Anomalies.................................................................... 308
Joyce Johnson, MD, MS, FAAP
Patent Ductus Arteriosus.................................................................. 311
Patent Foramen Ovale...................................................................... 314
Pulmonary Stenosis.......................................................................... 316
Heather Anderson, MD, FAAP, and
Nicolas Madsen, MD, MPH, FAAP
xii
CCIP.indb 12 3/13/18 4:18 PM

CONTENTS
Single-Ventricle Lesions................................................................... 320

Systemic and Pulmonary Vein Anomalies.......................................... 325
Tetralogy of Fallot............................................................................ 329
Transposition of the Great Arteries................................................... 334
Tricuspid Valve Anomalies................................................................ 339
Truncus Arteriosus........................................................................... 343
Vascular Rings and Slings................................................................. 347
Ventricular Septal Defects................................................................ 353
Part 4: C
ardiomyopathies and Channelopathies
20. Hypertrophic Cardiomyopathy......................................................... 361
Whitnee Hogan, MD, and Shaji C. Menon, MD, FACC,
FASE, FAAP
21. Dilated Cardiomyopathy.................................................................. 377
Shannon Lyon, DO, and Joshua D. Sparks, MD
22. Restrictive Cardiomyopathy.............................................................. 387
Chesney Castleberry, MD, and Sonya Kirmani, MD
23. Noncompaction Cardiomyopathy...................................................... 395
Nikki M. Singh, MD, and Steven J. Kindel, MD
24. Long QT S yndrome and Other Channelopathies.............................. 411
Juan Villafañe, MD, FAAP
Part 5: Acquired Cardiac Diseases

25. Kawasaki Disease............................................................................. 423
Bessey Geevarghese, DO, and Stanford T. Shulman, MD, FAAP
26. Acute Rheumatic Fever and Rheumatic Heart Disease....................... 443
Swati Garekar, BC, and Bhadra Trivedi, MD
27. Cardiotoxicity Among Survivors of Childhood Cancer....................... 463
Kelley K. Hutchins, DO, MPH, and Michael U. Callaghan, MD
xiii
CCIP.indb 13 3/13/18 4:18 PM

CONTENTS
Part 6: Infectious Diseases

28. Vaccines for Patients With Cardiac Conditions ................................. 477
Ahdi Amer, MD
29. Lyme Carditis.................................................................................. 487
Michael Colon, MD
30. Endocarditis.................................................................................... 497
Amy H. Schultz, MD, MSCE, FAAP, FACC, and Josh Weldin, MD
31. Prevention of Bacterial Endocarditis................................................. 511
John Colquitt, MD, FAAP, and Carolyn A. Altman, MD, FAAP
32. Myocarditis...................................................................................... 517
Ryan Butts, MD
33. Pericardial Diseases.......................................................................... 529
Diego Lara, MD, MPH, and Carolyn A. Altman, MD, FAAP
Part 7: Preventive C
ardiology
34. Dyslipidemia.................................................................................... 545
Don P. Wilson, MD, FNLA, and Samuel S. Gidding, MD
35. Hypertension................................................................................... 567
S. Kristen Sexson Tejtel, MD, PhD, MPH, FAAP
36. Cardiac Screening Prior to ADHD Treatment................................... 595
Kanupriya Chaturvedi, MD, FAAP, and
Christopher Snyder, MD, FAAP
37. Cardiac Screening for Athletic Participation...................................... 603
Bryan Cannon, MD, FACC, FHRS
38. Autonomic D ysfunction................................................................... 613
Alison Black, MD, and Joshua D. Sparks, MD
Part 8: General Issues in Primary Cardiac Care

39. Neurodevelopmental and Psychosocial Outcomes in Children With
Congenital Heart Disease................................................................. 627
Kiona Y. Allen, MD, Melissa Smith-Parrish, MD, Kathleen A. Mussatto,
PhD, RN, and Bradley S. Marino, MD, MPP, MSCE, FAAP
40. Lifestyle Counseling......................................................................... 643
Jessica Bowman, MD, and Jason Cole, MD
41. Cardiac Pharmacology...................................................................... 655
Miwa Geiger, MD, and Hari Rajagopal, MD
xiv
CCIP.indb 14 3/13/18 4:18 PM

CONTENTS
42. Transition and Transfer From Pediatric to Adult-Centered

Cardiac Care.................................................................................... 685
Mark D. Norris, MD, MS, and Adam Putschoegl, DO, FAAP
Part 9: Special Conditions

43. Cardiac Transplantation................................................................... 701
Sharon Chen, MD, MPH, and Beth D. Kaufman, MD
44. Pulmonary Hypertension................................................................. 713
Kristin Anton, RN, MSN, CPNP-AC, and
Bibhuti B. Das, MD, FAAP, FACC
Index..................................................................................................... 727
xv
CCIP.indb 15 3/13/18 4:18 PM

CCIP.indb 16 3/13/18 4:18 PM
Introduction
Though heart defects in children had been studied for many years, the field
of pediatric cardiology was essentially born in the 1930s, when Robert Gross
performed the first surgical ligation of a patent ductus arteriosus. Instead of
cardiac defects being a pathologic entity seen at autopsy, they became treatable.
Helen Taussig began training pediatricians in the new field of pediatric
cardiology in the late 1940s, and pediatric cardiology became the first sub-board
of pediatrics in 1961. The Section on Cardiology of the American Academy of
Pediatrics (AAP) was formed in 1955.
The field of pediatric cardiology has seen incredible advances in its short
period of existence. Cardiopulmonary bypass, used to repair intracardiac
defects, was first successfully used in children in 1954 and 1955. The first
echocardiograms, initially 1-dimensional, were reported in 1953, but
2-dimensional images of the moving heart were not available until the early
1970s. The arterial switch procedure, now the standard of care for most patients
with transposition of the great arteries, was first performed in 1975—only
43 years ago.
As these advances in pediatric cardiac care have occurred, the scope of
pediatric primary care exposure to patients with complex cardiac anatomy has
increased. This text was created specifically for the pediatric care professional
(pediatrician, family physician, nurse practitioner, physician assistant, and all
trainees and students) who could see a patient in the inpatient or outpatient
setting with heart disease. The content starts with the fundamentals of history
and physical examination, followed by the basics of cardiac testing, including
electrocardiography, echocardiography, and chest radiography. Specific chapters
focus on common symptoms, such as chest pain, syncope, and murmurs.
Extensive guidance is provided for each type of congenital lesion a patient
may present with in your office—each easily looked up and reviewed quickly
just prior to seeing a patient. Acquired diseases such as Kawasaki disease are
discussed, as well as infectious diseases, such as rheumatic fever, Lyme disease,
endocarditis, pericarditis, and myocarditis. Common preventive cardiology issues
are presented, including dyslipidemia, hypertension, sports clearance, screening
prior to attention-deficit/hyperactivity disorder medication administration,
and adolescent autonomic dysfunction. Finally, a robust discussion of cardiac
medications is provided, focused on the pediatric care professional.
In assembling this book, we have capitalized on the rich and unique resources
of the American Academy of Pediatrics (AAP), as well as contributions from
experts from around the globe. We thank all of our authors for their time and
expertise. The contents of this book were reviewed by experts from relevant
AAP sections, committees, and councils, including non–cardiology specialty
perspectives. The editors and contributing authors are grateful for these reviewers’
expertise and generous feedback. Special thanks are due to the cardiologists
xvii
CCIP.indb 17 3/13/18 4:18 PM

INTRODUCTION
and cardiac surgeons of the Publications and Communications Workgroup

of the Section on Cardiology and Cardiac Surgery, who personally reviewed
every chapter. We want to give our sincere thanks to Chris Wiberg at the AAP,
who was the senior editor for this book. We appreciate his commitment to the
project, his editorial prowess, his constant encouragement, and his collaborative
spirit. Finally, we want to thank our families for their love, understanding, and
support while we took on this amazing endeavor.
This book is focused on the pediatric care professional for a specific reason:
You are essential partners with families and cardiology teams in the care of these
children. We hope this book will help answer questions that arise on a daily
basis and serve as an essential resource in your office, with the ultimate goal of
improving care for all children with heart disease.

Deepak Kamat, MD, PhD, FAAP
xviii
CCIP.indb 18 3/13/18 4:18 PM

PART 1
Evaluation of
the Patient
1. Clinical History and Physical Examination............................... 3
2. Electrocardiography...................................................................13
3. The Role of Echocardiography..................................................49
4. Basics of Exercise Testing..........................................................71
5. Chest Radiography....................................................................79
6. Cardiac MR Imaging and CT...................................................95
7. Laboratory Studies................................................................. 109
CCIP.indb 1 3/13/18 4:18 PM

CCIP.indb 2 3/13/18 4:18 PM
CHAPTER 1
Clinical History
and Physical
Examination
Brandon Lane Phillips, MD, FAAP, Stacie Knutson, MD,
and Gurumurthy Hiremath, MD, FACC
Introduction
The history and physical examination are the first and most important steps
in the evaluation of any child for whom there is a concern for heart disease. A
thorough history is essential when evaluating children who present with common
cardiac concerns, such as syncope and chest pain. Often, the history will contain
important clues that an astute clinician will use to guide medical decision-making
and management. A thorough physical examination can also play a role in helping
to establish the correct diagnosis without the need for expensive ancillary tests.
This chapter will address the basics of the cardiac history and physical examination
in children.
History
A thorough history—including a detailed personal history of the child, history of
the mother during pregnancy, the child’s birth history, past medical history, review
of systems, family history, and social history—should be obtained. The maternal
history should include assessment of complications during pregnancy or delivery
and assessment of any teratogenic exposures during pregnancy. In all patients, the
timing of appearance of signs and symptoms should be clearly delineated, because
CCIP.indb 3 3/13/18 4:18 PM

this can often help establish a differential diagnosis. Specific details of the
personal cardiac history can vary, depending on the age of the child.
Infants
The largest energy expenditure in infants is feeding, and infants with congenital
heart disease (CHD) or heart failure commonly present with symptoms during
feeding. Infants may ingest less breast milk or formula per feeding than usual, or
their symptoms may arise only during feeding, including sweatiness, tachypnea,
fussiness, and irritability. In infants with heart failure, the volume of feedings has
been shown to be the most sensitive variable historically associated with clinical
heart failure. Poor growth may be present, particularly in patients with large
left-to-right shunts or heart failure.
Young Children
Symptoms in young children can be subtle, because children can compensate
very well despite having clinically significant CHD or poor heart function.
Patients and their parents should be asked about any chest pain, palpitations,
or fainting spells. A chronic cough may be present if pulmonary congestion or
bronchial compression is present. Abdominal pain, nausea, or anorexia may be
present in children with heart failure because of poor cardiac output to periph-
eral tissues. Because parents often find it difficult to know what “normal” exercise
ability is for a young child, it can be helpful to ask what his or her ability level is
in comparison to other children or older siblings.
Adolescents
Although older children and adolescents may present with symptoms similar
to those of younger children, they may also complain of symptoms similar to
those of adults. Patients should be asked about any chest pain, palpitations,
dizziness or fainting spells, and changes in exercise tolerance. Patients should
also be asked about any of these symptoms occurring with exertion. Additionally,
patients should be asked about snoring and whether they have any symptoms
of orthopnea.
Past Medical History

Obtaining a thorough past medical history is important to ensure that no other
medical conditions are present that may place the patient at risk for cardiac
disease. Particular attention should be given to any history of genetic syndromes
or chromosomal abnormalities. Patients with connective tissue disorders may
report a history of pneumothorax, easy joint dislocation, or lens dislocation.
Patients should be asked about a history of Kawasaki disease and rheumatic
heart fever, particularly if they are from a geographic area or have an ethnic
background endemic to either condition. A history of previous fainting episodes
CCIP.indb 4 3/13/18 4:18 PM

Clinical History and Physical Examination
and seizures and a family history should be obtained when there is concern that
the patient’s syncopal episode may be caused by a genetic mutation, such as long
QT syndrome.
Family History
Patients and their parents should be asked about any family history of CHD,
cardiomyopathy, hyperlipidemia, hypertension, or early coronary artery disease
(manifesting before the age of 50 years). Any history of sudden, unexplained
death should be obtained, including unexplained car accidents, drownings,
seizures, or sudden infant death syndrome. It is most important to obtain this
history for first- and second-degree family members.
History Compilation Techniques

In older children, it is important to engage the patient directly in the history
compilation process, since he or she is the one experiencing the symptoms.
In a child who has undergone a prior surgical repair of CHD, history compi-
lation is an opportunity to assess the child’s knowledge about his or her own
health condition.
Precision is also important in the history compilation process. Terms such as
“heart attack” and “passing out” need to be clarified to make sure that parents
and practitioners are using the same definitions.
Physical Examination
Assessment of Vital Signs
Heart rate, respiratory rate, oxygen saturation, and blood pressure should be
assessed at each visit. An abnormal heart rate can alert the clinician to a diag-
nosis of congestive heart failure or even a noncardiac disorder, such as thyroid
dysfunction or Lyme disease with heart block. In addition to physical palpation
of the pulse in the upper and lower extremities, blood pressure measurements
should be obtained in the upper and lower extremities during the first visit to
assess the patient for coarctation of the aorta. Oxygen saturation should be
recorded in all patients. In patients who underwent a previous cardiac surgery,
oxygen saturation should be followed serially, and results should be compared to
those obtained at previous clinical encounters.
It is important to remember that blood pressure should be assessed with
the patient calm and sitting down. The use of an inappropriately sized blood
pressure cuff remains the most common cause of inaccurate hypertension
diagnoses in children. The length of the bladder of the cuff should be 80% of
the circumference of the limb being measured, and the width of the cuff should
cover two-thirds of the length of the extremity.
CCIP.indb 5 3/13/18 4:18 PM

Inspection
A considerable degree of information can be obtained with observation. The
physician should determine if the child is in any distress, is over- or under-
nourished, or has any potential genetic syndrome. Cyanosis can be indicative of
CHD but can be difficult to detect in patients with anemia or dark skin pigmen-
tation. Special attention should be given to the tongue, nail beds, and conjunc-
tiva. Acrocyanosis may be seen in healthy infants, where the hands and feet have
a blue hue but the remainder of the skin is normal. Digital clubbing can be seen
in the fingernails and toenails of a patient with prolonged desaturation.
The respiratory rate and presence of any retractions should be noted. The
chest should be inspected to look for any pectus abnormalities (excavatum or
carinatum) or asymmetry of the chest.
Palpation
Palpation of the peripheral pulse should be performed, including the pulse in
both upper and lower extremities. A weak leg pulse relative to that of the arm
suggests coarctation of the aorta.
A bounding pulse (widened pulse pressure) may be found in a patient with
patent ductus arteriosus, aortic regurgitation, or arteriovenous fistula.
Palpation of the chest should be performed to identify the apical impulse
and to look for evidence of a hyperactive precordium and thrills. After the
age of 10 years, the apical impulse is typically located at the midclavicular line
in the fifth intercostal space. An apical impulse that is displaced laterally or
downward suggests cardiomegaly. A hyperactive precordium is associated with
large left-to-right shunts. Thrills are palpable vibratory sensations associated
with harsh murmurs. Thrills may be felt on the chest wall or in the suprasternal
notch in the setting of clinically significant aortic stenosis.
Palpation of the abdomen should be performed to assess the size and texture
or consistency of the liver and spleen. With increased venous pressure or increas-
ing shunt volume, the liver will become enlarged. Percussion of the liver may be
performed in older children and adolescents.
Auscultation
To diagnose a cardiac murmur, it is necessary to understand and describe the
heart sound in the context of the cardiac cycle. The cardiac cycle can be broken
down into systole and diastole (Figure 1-1). Systole is the period of ventricular
contraction during which blood is ejected from the right ventricles (RVs) and
left ventricles (LVs) into the main pulmonary artery and aorta, respectively.
Diastole is the period of ventricular relaxation during which tricuspid and mitral
valves are open and the ventricles fill with blood from the atria. Most of the
blood enters the ventricles passively, but a small portion is ejected during atrial
contraction that occurs in late diastole. At the onset of systole, the ventricles
CCIP.indb 6 3/13/18 4:18 PM

FIGURE 1-1. The cardiac cycle. AV = atrioventricular. From https://courses.lumenlearning.com/ap2/

chapter/cardiac-cycle/.
contract, causing a rapid increase in ventricular pressure that soon exceeds the
atrial pressure. Once the pressure within the ventricles exceeds that of the atria,
the tricuspid and mitral valves are forced closed. Closure of these valves produces
the first heart sound (S1). The ventricular pressures continue to rise with
contraction during a phase called isovolumetric contraction until they exceed that
of the pulmonary artery and aorta. This results in opening of the pulmonic and
aortic valves and ejection of blood from the ventricles (ejection phase). As the
ejection of blood is completed, the ventricular pressure begins to decrease. Once
ventricular pressure falls below that of the main pulmonary artery and aorta, the
pulmonic and aortic valves are forced closed, producing the second heart sound
(S2). The ventricular pressure decreases rapidly as a result of the ventricular relax-
ation during a phase called isovolumetric relaxation. Once the ventricular pressure
falls below that of the atria, the tricuspid and mitral valves open, allowing passive
filling of blood into the ventricles, and the cycle repeats.
Being able to accurately identify the first and the second heart sounds (S1 and
S2, respectively) will allow for categorization of murmurs and extra heart sounds
on the basis of the phase of the cardiac cycle within which they occur (systole
or diastole). Both S1 and S2 are composed of 2 components, each of which can
be heard by the trained ear. The mitral valve closes slightly before the tricuspid
7
CCIP.indb 7 3/13/18 4:18 PM

valve because of normal nonsynchronous contraction of the ventricles, with the

LV beginning and ending the contraction prior to the RV. The splitting of S1
is generally not appreciated because of the minimal time difference between
when the mitral and tricuspid valves close. S2 is composed of P2 and A2, which
represent closure of the pulmonic and aortic valves, respectively. Normally, the
aortic valve closes slightly before the pulmonic valve, but because it is in close
proximity, it can be difficult to differentiate the 2 sounds. Physiological splitting
of S2 occurs throughout the respiratory cycle. With inspiration, there is increased
blood return to the right atrium and therefore the RV. This increased blood
volume results in an increase in the ejection time from the RV. Therefore, the
pulmonic valve remains open longer and accentuates the time difference between
closure of the aortic and pulmonic valves, which is heard as splitting of the S2.
During expiration, A2 and P2 occur almost simultaneously, as mentioned earlier,
and are heard as a single S2.
In addition to S1 and S2, on occasion 2 other sounds, called S3 and S4, can be
heard (audio available at www.youtube.com/watch?v=DxMnm5C5PW8&index=

1&list=PLKCIeugVenPTLW-nspw_wUkXxO2IIiesu)( ). Both of these
sounds occur during diastole. S3 occurs during early diastole as a result of rapid
filling of the ventricle after opening of the tricuspid and mitral valves. This
is generally a normal sound in children but can indicate volume overload. S4
occurs during late diastole and coincides with atrial contraction. When the atria
contract and eject blood into a stiffened ventricle, S4 is produced.
Physiology of Cardiac Murmurs

There are 4 main locations that are used for auscultation, which correspond
to the 4 cardiac valves (Figure 1-2). The aortic area is located at the second to
third intercostal space to the right of the sternum (right upper sternal border).
The pulmonic area is located at the second to third intercostal space to the
left of the sternum (left upper sternal border). The tricuspid area is at the left
lower sternal border, and the mitral area is located at the apex of the heart. As
described previously, S1 is the closure of the tricuspid and mitral valves, and it
can be best heard at the apex. S2 and splitting of the S2 are best heard at the left
upper sternal border in the pulmonic area. S3 and S4 are best heard at the apex or
the left lower sternal border, depending on whether they are originating from the
LV or the RV.
When a murmur is heard, it is important to be able to localize the sound to
a specific area of the heart and to characterize the murmur. The key components
of characterizing a murmur are timing, intensity, pitch, quality, location,
radiation, positional variation, and presence of extra heart sounds. The first step
is to identify S1 and S2. Once these are identified, the timing of the murmur
in the cardiac cycle can be defined as ejection systolic, holosystolic, diastolic,
or continuous. Systolic murmurs occur after S1, and diastolic murmurs occur
8
CCIP.indb 8 3/13/18 4:18 PM

Clinical History and Physical E
xamination
Right Infraclavicular Area Suprasternal Notch

PPS (S) AS/supravalvar AS (S)
Left Infraclavicular Area
Venoushum (C)
PPS (S)
Coarctation of the aorta
Right Upper Sternal Border (better noted left subscapular) (S)
(“aortic area”) PDA (C)
Aortic stenosis (valvar, supravalvar) (S)
PPS (S)
Left Upper Sternal Border
Left MH Sternal Border 1 (“pulmonary area”)
Innocent flow (S) PS and ejection click (S)
2 Normal pulmonary flow (S)
PS, AS, sub PS/AS (S)
Aortic pulm. Ej. click (S) PDA (C)
3
VSD (S) Apex (“mitral area”)
AR/PR (D) 4
Still’s murmur (S)
5 MR (S)
Left Lower Sternal Ejection click of AS (S)
Border (“tricuspid 6 Coarctation of the aorta (S)
area”) AR (D)
7
Still’s murmur (S) MS (D)
VSD (S) 8 MS—functional (with VSD) (D)
TR (S)
TS (D) 9
S systolic
TS—functional (with ASD) (D) 10 D dystolic
PR (D) C continuous
Lateral Chest/Axilla
PPS (also heard in midback) (S)
MR radiation (S)
FIGURE 1-2. Typical location or listening areas for murmurs. AR = aortic regurgitation,
AS = aortic stenosis, ASD = atrial septal defect, MR = mitral regurgitation, MS = mitral stenosis,
PDA = patent ductus arteriosus, PPS = peripheral pulmonic stenosis, PR = pulmonary regurgitation,
PS = pulmonary stenosis, TR = tricuspid regurgitation, TS = tricuspid stenosis, VSD = ventricular
septal defect. From Koenig P, Hijazi Z, Zimmerman F. Essential Pediatric Cardiology. New York, NY:
McGraw Hill; 2004.
after S2. Holosystolic murmurs occur at the onset of systole and result in the
obliteration of S1. The presence of a holosystolic murmur indicates that blood is
escaping from the ventricle as soon as ventricular contraction begins. This can
be caused by a ventricular septal defect or tricuspid or mitral valve regurgitation.
An ejection systolic murmur, however, begins after S1 (during the ejection phase)
and is usually caused by ventricular outflow tract obstruction. With an ejection
systolic murmur, S1 can be defined, whereas with a holosystolic murmur, S1 is
incorporated into the murmur and cannot be defined. Continuous murmurs are
present throughout systole and diastole. (See the list of Audio Recordings of
heart murmurs at the end of this chapter.)( ) 
Systolic and diastolic murmurs each have their own intensity classification.
Systolic murmurs are graded I to VI, whereas diastolic murmurs are graded I to
IV. The initial classification of systolic heart murmurs was the Levine system.
Owing to the subjective nature of this system for murmurs graded III or VI or
less, a variation may be used in which the patient’s own heart sounds are used
as an internal reference for grading.1 By using this system, grade I murmurs are
less intense than the normal heart sounds (S1 and S2). Grade II murmurs are
equal in intensity to S1 and S2, and grade III murmurs are more intense than S1
and S2. Grade IV murmurs include the presence of a thrill. Grade V murmurs
can be heard with only the edge of the stethoscope on the patient’s chest, and
grade VI murmurs can be heard with the stethoscope removed from the chest
9
CCIP.indb 9 3/13/18 4:18 PM

wall. Grading diastolic murmurs is subjective and listener dependent. Grade I

murmurs are barely audible. Grade II murmurs are faint but audible. Grade III
murmurs are easily heard, and grade IV murmurs are loud.
The next step is to describe the pitch of the murmur, which is related to
the frequency of the sound and reflects the velocity of the turbulent blood
flow; higher pitch represents higher velocity of flow. The pitch of the murmur,
therefore, provides more information about the potential cause and severity of
the lesion. High-frequency murmurs are produced when there are large (or high)
pressure gradients between 2 chambers, whereas low-frequency murmurs are
produced when there is a smaller (or low) pressure gradient.
Knowing where on the chest wall to auscultate each of the 4 valves, as
described previously, is important to localize the examination. Where on the
chest wall the murmur is heard the loudest should be specified. In addition,
where else the murmur can be heard or where it radiates to needs to be deter-
mined. Radiation of the murmur follows the course in which the blood flows.
For example, murmurs that can be heard in the back and axilla are following
the course of the pulmonary blood flow. In general, the sound of innocent mur-
murs will not radiate, so the presence of this finding should prompt the question
of a need for further evaluation.
Certain types of murmurs can be altered by positional changes, respiration,
or maneuvers. This can help to differentiate similar murmurs from each other.
In general, innocent murmurs will vary in intensity, depending on the patient’s
position during auscultation. Innocent murmurs are usually loudest when lying
supine and diminish in intensity or disappear when sitting upright or standing.
One exception to this is a venous hum, which resolves or diminishes when
lying supine. A lack of change in murmur intensity with position change should
raise suspicion for a pathologic murmur. Squatting is another positional change
that can be helpful when evaluating a murmur. In patients with hypertrophic
cardiomyopathy, the murmur intensity decreases with squatting and increases
with standing.
The Stethoscope
The bell of the stethoscope is best suited to hear low-frequency events, while
the diaphragm of the stethoscope selectively picks up higher-frequency sounds.
Using only the diaphragm of the stethoscope may result in missing some
low-pitched sounds, such as a diastolic rumble, pulmonary regurgitation, or Still
murmur (also commonly referred to as Still’s murmur). Innocent or functional
murmurs are common in children. They occur in the absence of anatomic anom-
alies. Examples include vibratory murmurs, pulmonary flow murmurs, venous
hums, and carotid bruits.
10
CCIP.indb 10 3/13/18 4:18 PM

Key Points
•• History and physical examination remain important tools in the evaluation
of children with murmurs and other common cardiac complaints.
•• A thorough history should contain a detailed personal history of the child,
maternal history during pregnancy, the child’s birth history, past medical
history, review of systems, family history, and social history.
•• In adolescent patients, it is important to obtain the history directly from them
and assess the role psychosocial stress may play in their symptoms.
•• Heart rate, respiratory rate, oxygen saturation, and blood pressure should be
assessed at each visit.
•• In addition to physical palpation of the pulse in the upper and lower
extremities, blood pressure measurements should be obtained in the upper
and lower extremities during the first visit to assess the patient for coarctation
of the aorta.
Audio Recordings ()

•• Normal Third Heart Sound (S3) (Willam Buck Kyle, MD).
www.youtube.com/watch?v=DxMnm5C5PW8&index=1&list=
PLKCIeugVenPTLW-nspw_wUkXxO2IIiesu
•• Bicuspid Aortic Valve and Systolic Click—normal speed (Willam Buck
Kyle, MD). www.youtube.com/watch?v=zsAj2xGNGs4&index=3&list=
•• Bicuspid Aortic Valve and Mild Stenosis—normal speed (Willam Buck
Kyle, MD). www.youtube.com/watch?v=opyMtEHhyLE&index=4&list=
•• Bicuspid Aortic Valve and Mild Stenosis—slow (Willam Buck Kyle, MD).
www.youtube.com/watch?v=dsoG-OX_Wv8&index=5&list=
•• Small Muscular Ventricular Septal Defect—normal speed (Willam Buck
Kyle, MD). www.youtube.com/watch?v=VLD0ao6lQ3M&index=8&list=
•• Small Muscular Ventricular Septal Defect—slow (Willam Buck
Kyle, MD). www.youtube.com/watch?v=BJ-1c4JFY9Y&index=9&list=
•• Restrictive Membranous Ventricular Septal Defect—normal speed (Willam
Buck Kyle, MD). www.youtube.com/watch?v=dnzZDGKMW5I&index=
10&list=PLKCIeugVenPTLW-nspw_wUkXxO2IIiesu
•• Restrictive Membranous Ventricular Septal Defect—slow (Willam Buck
Kyle, MD). www.youtube.com/watch?v=bpEKVgXQPhY&index=11&list=
11
CCIP.indb 11 3/13/18 4:18 PM

•• Restrictive Muscular Ventricular Septal Defect (Willam Buck Kyle,

MD). www.youtube.com/watch?v=jXvE1otbxac&index=12&list=
•• Restrictive High Muscular Ventricular Septal Defect (Willam Buck
Kyle, MD). www.youtube.com/watch?v=l-pLcHQVjQA&index=13&list=
•• Restrictive Mid Muscular Ventricular Septal Defect—slow (Willam Buck
Kyle, MD). www.youtube.com/watch?v=7YeB7wbVFNc&index=14&list=
•• Restrictive Apical Muscular Ventricular Septal Defect—slow (Willam
Buck Kyle, MD). www.youtube.com/watch?v=nKlCgY_XtjM&index=
•• Pulmonary Stenosis—mild (Willam Buck Kyle, MD). www.youtube.com/
watch?v=8uk8iKxu5HY&index=17&list=PLKCIeugVenPTLW-nspw_
wUkXxO2IIiesu
•• Aortic Regurgitation and Mild Stenosis (Willam Buck Kyle, MD).
www.youtube.com/watch?v=54BhXSnaXk4&index=19&list=
Reference
1) Keren R, Tereschuk M, Luan X. Evaluation of a novel method for grading heart murmur
intensity. Arch Pediatr Adolesc Med. 2005;159(4):329–334
12
CCIP.indb 12 3/13/18 4:18 PM

CHAPTER 2
Electrocardiography
Daniel Mauriello, MD
Introduction
Electrocardiography (ECG) provides information regarding the conduction
of electricity throughout the heart. Standard ECG in children has either 12 or
15 leads (see Figure 2-1). Each lead provides information from a particular vantage
point on the chest, like an “electrical camera.” ECG tends to be useful for deter-
mining rhythm but can also provide insights into structural or systemic disease and
cardiomyopathies. The limb leads (I, II, III, aVR, aVF, aVL) provide information
about how electricity moves in the superior-inferior and left-right directions. These
leads are useful for helping to determine rhythm, atrial enlargement, and overall
direction of net electrical force (axis). The precordial leads provide information
about the movement of electrical activity in an anterior-posterior and left-right
direction (Figure 2-1). This can be helpful for determining ventricular hypertrophy.
Both precordial and limb leads can provide information about conduction delays
and blocks, ischemia, myocardial disease, and structural abnormalities of the heart.
Standard ECG (Figure 2-2) captures 10 seconds of data. While the limb and
precordial leads can be configured to display in numerous ways, typically, the left
portion of the ECG tracing contains the limb leads, and the right portion contains
the precordial leads. Usually, 1 or more rhythm strips (RSs) of a continuous lead
tracing are recorded at the bottom, with lead II often being used because most
ventricular forces are frequently directed toward this lead. The upper portion of
the ECG tracing contains demographic data, computer-calculated intervals, and a
computer-determined analysis of the ECG tracing.
The tracing is made on a background of 1-mm × 1-mm boxes. On the x-axis,
time is typically noted, so each small box is 40 ms, and each larger box (consisting
of 5 smaller boxes) is 200 ms. The paper speed is 25 mm/s (for a 10-second ECG,
there will be 250 small boxes representing 40 ms per box); it can be changed but
13
CCIP.indb 13 3/13/18 4:18 PM

A Frontal plane leads
Frontal plane formed

by leads I, II, and III
and the three
aVR aVL
unipolar leads
-150° -30°
I
0°
III II
120° 60°
aVF
90°
B Horizontal plane leads
Horizontal plane
formed by chest
leads
V6
V1 V2 V
V3 V4 5
FIGURE 2-1. Electrocardiographic lead orientation and limb lead vectors. A. The frontal plane
leads with the negative electrodes aligned to a central point. The approximate location of the heart
is shown for reference. The leads are described relative to lead I. Counterclockwise is defined as the
negative direction, and clockwise is the positive direction. B. The horizontal or precordial plane and
the relative position of the chest leads. From Kusumoto FM. Cardiovascular Pathophysiology. Raleigh,
NC: Hayes Barton Press; 1999. Reprinted with permission from Hayes Barton Press.
14
CCIP.indb 14 3/13/18 4:18 PM

Electrocardiography
FIGURE 2-2. Standard 12-lead pediatric electrocardiogram.
typically is not. The paper speed is shown at the bottom of the ECG tracing. The
y-axis, also called the amplitude, is simply discussed in boxes or millimeters. At
the far left of the strip, the vertical standardization is conveyed by the height of
the squared-off column. Standard vertical calibration will include 10 small boxes.
Both the limb and precordial leads can have their vertical calibration changed
separately. When the ECG is “half standard,” the ECG amplitudes will display
at one-half the usual height and, as such, all amplitude measures will need to
be multiplied by 2 for making interpretive decisions. Conversely, if displayed as
“double standard,” all ECG amplitudes will be twice the usual height and should
be halved for interpretation. Change in standardization is often done when the
R and/or S waves are overlapping each other, making differentiation difficult.
By convention, electrical depolarization forces toward a lead will be displayed
as a positive deflection above the baseline, and forces away from the lead will
be displayed as a negative deflection. Each lead will show the heartbeat from
a different vantage point on the chest. The limb leads can be used to describe
the electrical direction in 360° or around a “clockface.” Information about
superior-inferior and left-right forces can be determined. Leads I, II, and III are
situated 60° apart from each other, between 0° and 120°. For most children and
adults, most electrical forces of the heart come from the ventricles. Typically,
these forces will be most directed in the range of 0° to 120°. aVF, aVL, and aVR
are augmented leads (meaning they are not directly placed on the patient but are
virtually determined via vectoral calculation). These leads are at 120° separations
15
CCIP.indb 15 3/13/18 4:18 PM

from each other and, in conjunction with leads I, II, and III, can help show a
perspective of the heart’s electrical activity from around the entire 360° clockface.
The precordial leads are situated on the chest, with V1 (V3R, V4R) starting
just to the right side of the sternum, overlying the right ventricle (RV), and
progressively moving leftward through V6 (V7), overlying the left ventricle (LV).
The quantitative measurements most often used in precordial lead interpretation
are the R and S wave heights and ratios that can be used for determination of
ventricular hypertrophy.
Interpretation Method
While there is no one correct method for ECG interpretation, essential compo-
nents must be addressed each time for complete and accurate interpretation. The
order in which they are addressed is less important than ensuring that each task
is addressed each time. Failure to address any of the following components will
result in an incomplete assessment of the ECG results.
•• Rate
•• Rhythm
•• Axis
•• Atrial enlargement
•• Ventricular hypertrophy
•• Conduction delays
•• Interval assessment
•• Segment assessment
•• Corrected QT interval (QTc) calculation and assessment
•• Repolarization (T wave assessment)
The interpretive method used here will be based on the understanding of the
physiology of a normal sinus heartbeat as it occurs through the cardiac cycle.
Understanding how the surface ECG correlates with the cardiac cycle allows
ECG interpretation to be more deeply linked to underlying cardiac physiological
processes.
The Normal Heartbeat

Each normal heartbeat (see Figure 2-3) should involve atrial depolarization
(from the sinus node), conduction to the atrioventricular (AV) node,
depolarization of the ventricles in a nearly synchronous fashion through the
His-Purkinje system, atrial repolarization, and, finally, ventricular repolarization.
Except for atrial repolarization (which gets lost in the QRS deflections), each of
these events is represented on the surface ECG (Table 2-1). Each may appear
differently, depending on which electrical vantage point or lead is viewed.
Unlike adults, the normative values for many ECG parameters will vary in
children, depending on age. Sources may differ slightly in the upper limits of
16
CCIP.indb 16 3/13/18 4:18 PM

Electrocardiography
Sinus node
impulse
Impulse passes
through AV node
Ventricular impulses
Normal heartbeat
FIGURE 2-3. The normal heartbeat: normal depolarization and conduction. AV = atrioventricular.
From Mayo Clinic. Heart Arrhythmia Web site. http://www.mayoclinic.org/diseases-conditions/
heart-arrhythmia/symptoms-causes/dxc-20188128
Table 2-1. Surface ECG Correlation to Cardiac Myocyte

Depolarization, Conduction, and Repolarization
Physiological Event ECG Correlate
Atrial depolarization P wave
Conduction to AV node PR interval
Ventricular depolarization QRS complex
Ventricular repolarization ST segment and T wave

AV, atrioventricular; ECG, electrocardiography.
normal (ULNs) and mean values. A reference range of normal pediatric values
is a required companion for ECG interpretation. In this chapter, the data of
Davignon and colleagues are provided (Table 2-2) and have been widely used for
years, but additional sets of normative data are also available.1,2
The P Wave
The normal heartbeat begins with depolarization of the sinus node, which is a
right-sided posterolateral structure situated near the junction of the superior
vena cava and the right atrium. As the right atrium depolarizes, the forces are
17
CCIP.indb 17 3/13/18 4:18 PM

CCIP.indb 18
18
Table 2-2. Age-Related Normal ECG Parameters in Children
S Wave
Heart in V1 R Wave
Rate PR Q Wave Q Wave R Wave S Wave R/S R Wave S Wave R/S plus R plus S
(beats/ QRS Axis Interval in III in V6 in V1 in V1 Ratio in V6 in V6 Ratio in Wave in Wave in
Age min) (Degrees) (ms) (mm) (mm) (mm) (mm) in V1 (mm) (mm) V6 V6 (mm) V4 (mm)
<1 d 94–155 58–168 79–160 5 2 5–27 (14) 0.5–23 0.2–9.8 0–12 (5) 0.2–10 0.5–9 2–27 (13) 12–52
(122) (+135) (107) (9) (2.3) (4) (2.5) (32)
2–3 d 91–158 65–171 81–139 5 2 5–27 (15) 0.5–21 0.2–6.0 0.1–12 0.2–10 0.5–11 2–28 (14) 17–53
(124) (+134) (108) (10) (2.0) (5) (3) (3) (33)
4–7 d 90–166 76–168 75–137 5 3 3–25 (13) 0.5–17 0.2–9.8 0.5–12 0.4–10 0.5–10 2–25 (12) 13–48
(128) (+133) (104) (7) (2.8) (5) (4) (2.5) (31)
8–30 d 106– 65–159 73–138 4 3 3–22 (11) 0.5–12 1.0–7.0 3–17 (8) 0.2–10 0.5–12 3–22 (12) 15–48
182 (110) (101) (4) (2.9) (3) (4) (31)
(148)
1–3 mo 120– 31–115 73–130 5 3 3–19 (10) 0.5–13 0.3–7.5 5–22 (12) 0.3–7 (3) 0.5–12 6–29 (17) 22–58
179 (75) (98) (5) (2.3) (4.5) (36)
(149)
3/13/18 4:18 PM
CCIP.indb 19
Table 2-2. Age-Related Normal ECG Parameters in Children, continued
4–6 mo 105– 7–105 (60) 74–145 7 3 3–20 (10) 0.5–17 0.2–6.0 6–23 (14) 0.2–10 0.5–18 7–35 (19) 21–58
185 (106) (6) (2.4) (3) (6.5) (38)
(142)
7–12 mo 107– 7–98 (54) 73–156 6 3 2–20 (9) 0.5–18 0.1–3.9 6–23 (13) 0.2–8 (2) 0.5–22 7–33 (19) 21–50
168 (156) (7) (1.8) (8) (34)
(132)
1–3 y 90–151 8–100 (55) 82–148 5 3 3–18 (9) 1–21 (9) 0.1–4.2 6–23 (14) 0.1–7 (2) 0.5–28 7–38 (22) 17–48
(119) (114) (1.4) (9.5) (33)
4–5 y 73–137 7–104 (55) 85–161 4 3 2–18 (8) 2–22 (10) 0–2.8 9–25 (15) 0.1–6 (2) 0.8–30 13–42 17–52
(108) (118) (0.9) (11) (25) (35)
6–8 y 65–133 10–140 90–164 3 5 1–13 (7) 3–24 (12) 0–2.0 9–27 (17) 0.1–4 (1) 1–30 (12) 13–47 20–53
(100) (66) (124) (0.8) (28) (36)
9–12 y 63–129 9–115 (61) 87–171 3 3 0.5–10 3–26 (12) 0–1.9 10–26 0.0–4 (1) 2–33 (14) 15–45 21–50
(92) (128) (6) (0.6) (17) (28) (35)
13–16 y 66–120 11–133 92–175 3 3 0.5–10 3–22 (11) 0–1.8 7–23 (15) 0–4 (1) 2–39 (15) 11–42 12–49
(86) (58) (135) (5) (0.5) (25) (29)
Data are electrocardiographic normal ranges (2%–98%), with mean values given in parentheses. + = positive. Data are from references 2 and 17.
Electrocardiography
19
3/13/18 4:18 PM
directed toward the feet and the left arm. As the depolarization continues to
the left atrium, this results in an upright P wave in aVF and lead I. A few quick
steps will help determine if the underlying rhythm is sinus.
Sinus rhythm, meaning each heartbeat originates from the sinus node, is
demonstrated on the ECG tracing with the following 4 criteria by using leads I
and aVF and the RS.
1. Normal P wave axis (up in I and aVF)
2. P wave precedes each QRS (RS)
3. QRS follows every P wave (RS)
4. All P waves have a similar morphologic appearance when looking at the RS
While the P wave axis provides information regarding the origin of atrial
depolarization, P wave amplitude and duration provide information about the
size of the right and left atria, respectively (Box 2-1). Normal P waves should
be less than 3 mm in height for all ages. Duration should be less than 80 ms
(2 boxes) in infants younger than 1 year, and duration should be less than 100 ms
(2.5 boxes) for children more than 1 year of age. As the right atrium depolarizes
toward lead V1, the P wave is initially upright, but as atrial depolarization
continues toward the left atrium, moving past V1, the terminal portion of the
P wave in this lead may be a negative deflection, resulting in a biphasic P wave.
The terminal (negative portion) should be less than 1 box wide.
Box 2-1. Electrocardiographic Signs of Atrial Enlargement

in Children
Right atrial enlargement
P wave ≥3 boxes tall
Left atrial enlargement
P wave ≥2 boxes (80 ms) wide for infants <1 year; ≥2.5 boxes (100 ms)
wide for children >1 year
Terminal portion of P wave (negative component of the biphasic P wave)
≥1 box wide (40 ms) in V1
There is a brief delay before the conduction continues through the AV node.
The PR interval, which includes the P wave and the PR segment (end of the
P wave to the beginning of the QRS), encompasses the time for the atria to
depolarize and for the AV delay. The appropriate range for this interval is age
dependent, with the ULN increasing as children age. A shorter-than-normal
PR interval may indicate that the P wave is originating from a spot in the
atria (ectopic focus) closer to the AV node than normal or that there is a loss
of the normal AV delay due to pre-excitation (as in Wolff-Parkinson-White
[WPW] pattern).
20
CCIP.indb 20 3/13/18 4:18 PM

Electrocardiography
The Q Wave
After conduction through the AVN, there is depolarization of the ventricles
through the His-Purkinje system. The left bundle depolarizes first, activating
the ventricular septum from the left side. Because the LV is positioned leftward
and the ventricular septum has a slight horizontal component to its plane, the
ventricular septal depolarization force is initially moving upward and to the
right. This generates a normal Q wave (the first negative depolarization below
the baseline) in the inferior (II, III, aVF) and left lateral (V5, V6) leads. Q waves
should be narrow, less than 0.5 boxes (20 ms). The ULN for age is available for
Q wave amplitude in leads III and V6 (Table 2-2). Wide or deep Q waves may
represent prior ischemia or ventricular hypertrophy (Box 2-2). Because Q waves
are the first part of ventricular depolarization, abnormalities in them can indicate
abnormal initial depolarization. Absence of Q waves in the lateral leads in the
presence of a short PR interval can be seen in WPW (the accessory pathway
bypasses the normal initial depolarization of the septum, which should create the
normal Q wave). Deep Q waves in the inferior and lateral leads can represent LV
hypertrophy (LVH) in the presence of prominent left-sided forces.
Box 2-2. Characteristics of Normal and Abnormal Q Waves

Normal Q waves
Result from septal depolarization
Narrow and less than the upper limit of normal
Seen in inferior and left lateral leads (septal depolarization is inferior to
superior and left to right)
Abnormal Q waves
Result from abnormal initial activation of the ventricles
Can be seen with ischemia and hypertrophy
Absence of normal Q waves with a short PR interval can be seen with
Wolff-Parkinson-White pattern
The QRS Complex

After septal depolarization begins, the remainder of the ventricular myocardium
will depolarize in a relatively synchronous fashion through the right and left
bundles of the His-Purkinje system. Normal QRS duration is determined by
age. While ventricular depolarization happens quickly, clinically significant
information about the ventricular myocardium can be gleaned. Initially after
birth, the RV tends to predominate the electrical forces (in fetal circulation, the
RV is responsible for most cardiac output). As children age, the LV force will
become more prominent. The net directional force of RV and LV depolarization
21
CCIP.indb 21 3/13/18 4:18 PM

are demonstrated in the limb leads. The R wave (the initial depolarization above
baseline) becomes more prominent as the electrical force is directed more toward
a particular lead. Other reasons for a more prominent (tall) R wave include
increasing ventricular mass (hypertrophy) or decreasing the distance from the
surface lead to the heart (thin chest wall). The S wave is the deflection below the
baseline that follows the R wave. The S wave represents the ventricular forces
moving away from a lead. If there is another deflection above the baseline after
the S wave, this second positive deflection is denoted R' if the R wave after the
S wave is taller than the R wave preceding the S wave. The second R wave is
denoted r' if the R wave after the S wave is smaller in amplitude than the R wave
preceding the S wave. The QRS may be annotated several ways, depending on
the composition of QRS deflections.
Just as with the P wave, the QRS complex is analyzed for direction or axis,
duration, and amplitude. The QRS axis represents the overall direction of forces
as seen in the limb leads and is described in terms of degrees (Figure 2-1). The
lead toward which the QRS forces are most directed will often have the tallest
R wave. When the R wave is of greater magnitude than the S wave in a given
lead, the QRS is said to be positive in that lead. If the S wave is of greater ampli-
tude than the R wave, the QRS is said to be negative. The limb lead in which
the R waves and the S waves are most equal is the lead to which the ventricular
depolarization is most perpendicular (the R wave is generated by the forces
traveling toward the lead, and, as the forces move past and away, the S wave is
generated). If the QRS complex is equiphasic in a limb lead, the axis should be
either more or less than 90° from that lead—that is, perpendicular. Typically, the
general direction of the QRS force can be determined by which limb lead has
the tallest R wave. A QRS axis more positive than the range of normal for age
is called right axis deviation; an axis more negative than the range of normal is
termed left axis deviation.
While the limb leads are used for describing the QRS axis, the precordial
leads (V1–V6) can be used to assess the QRS amplitude as an inference for
ventricular hypertrophy. V1 overlies the RV; therefore, RV forces are generally
represented as the R wave in V1, while the LV forces, moving away from V1,
are seen in the S wave. As the RV hypertrophies, the R wave in V1 may become
taller; similarly, as the LV thickens, the S wave amplitude in V1 increases. A
similar thought process is used when looking at lead V6, which overlies the LV.
As the LV forces increase, the R wave in V6 will grow taller, and as the RV forces
increase, the S wave in V6 increases. Age-appropriate R and S wave values are
noted in Table 2-2. The ECG criteria for ventricular hypertrophy have variable
sensitivity and specificity but are not as accurate as echocardiography for LVH
or RV hypertrophy (RVH) determination.3
The QRS duration is usually examined in the precordial leads when looking
for right bundle branch blocks (RBBBs) or left bundle branch blocks (LBBBs);
22
CCIP.indb 22 3/13/18 4:18 PM

Electrocardiography
the limb leads are also examined for QRS duration. A narrow QRS typically
indicates normal depolarization of the ventricles through the right and left
bundles of the His-Purkinje system. A wide QRS may result from aberrantly
conducted atrial or junctional beats (ie, bundle branch blocks or pre-excitation),
ventricular ectopy, conduction tissue disease, progressive ventricular hypertrophy
(taking longer to depolarize increased muscle), or myocardial disease. As children
age, the ULN for QRS duration increases. QRS duration of longer than 120 ms
at any age is typically abnormal.
The ST Segment
After rapid depolarization of the ventricles, there should be a brief return to
baseline while the ventricular myocardium is awaiting repolarization. This is
represented by the ST segment, the portion of the ECG between the end of
the QRS and the beginning of the T wave. The ST segment is examined for its
position relative to baseline (the electrically inactive part of the cardiac cycle
between the end of 1 heartbeat and the beginning of the next, seen on the ECG
tracing as the “TP segment” between the end of the T wave and the following
P wave). Because the ST segment represents the transition from depolarization
to repolarization of the ventricle, elevation or depression of the ST segment can
indicate abnormalities of the ventricular myocardium. The J point is the junction
of the QRS and the ST segment. A generally benign phenomenon known as
J point elevation is commonly seen in children and is clinically referred to as
early repolarization. Elevations or depressions of the ST segment of ≥1 box from
baseline should be noted because these can be indicators of abnormalities with
the ventricular myocardium. J point depression can be a benign entity, as well.
With benign elevations or depressions of the J point, an essential finding is an
otherwise normal ST segment and T wave. It should be as if a normal-appearing
ST segment and T wave were just moved up or down slightly.
The T Wave
While ventricular depolarization should occur rapidly, resulting in a narrow
QRS complex, the repolarization of the ventricles is much slower; therefore,
the T wave has a much longer duration. Because of this slower process, subtle
abnormalities in the ventricular myocardium may be seen in the T waves, often
before changes to the QRS complexes. A normal T wave should have a smooth
and distinctive shape. T waves that are peaked or flat or have inappropriate
polarity are abnormal. Attention should be paid to the T waves in both the
precordial and limb leads. At birth, the T waves in V1 should be upright, but they
will invert in the first week after birth. ECGs during this time will often show
the T wave in transition. T waves in V1 should remain inverted until at least 6 to
8 years of age. They may remain inverted through adolescence. Upright T waves
in lead V1 in a child between 1 week and 6 years of age are abnormal and indicate an
23
CCIP.indb 23 3/13/18 4:18 PM

abnormality in RV repolarization. When looking at the inferior and lateral leads

(II, III, aVF, V5, and V6), the T waves should always be upright. In the inferior
leads, it is not uncommon for a single lead to have a flat or inverted T wave.
Inverted or flat T waves in either of the lateral leads or in more than 1 inferior lead
indicate an abnormality in LV repolarization. Abnormal T waves can result from
structural heart abnormalities, cardiomyopathies, or conduction disturbances.
Anything that causes an alteration in how the myocardium depolarizes may
result in an alteration in how the myocardium repolarizes.
The QT Interval
The QT interval is the absolute time for the myocardium to depolarize and repo-
larize; it encompasses the beginning of the QRS to the end of the T wave. Most
normal values are derived from measurement in leads II or V5, but any leads can
be used if needed. Clinically, this interval is important as a potential marker for
being in a proarrhythmic state. As mentioned before, ventricular repolarization is
a relatively slow process, during which the myocardium is potentially vulnerable
to both ectopic and intrinsic stimulation. Increases in the QT interval are often
a result of an increased repolarization phase. For QT intervals greater than the
ULN, the risk of polymorphic ventricular tachycardia (torsades de pointes)
increases (Figure 2-4). For clinical utility, the QT is corrected for heart rate and
FIGURE 2-4. Normal corrected QT interval (QTc) distribution. QTc values are age and sex based.
LQTS = long QT syndrome, OR = odds ratio, RR = relative risk. From reference 4.
24
CCIP.indb 24 3/13/18 4:18 PM

Electrocardiography
is indicated as QTc. Normal QTc values are age and sex based. QTc intervals of
at least 500 ms are associated with increased risk of arrhythmia.4 Note that when
calculating the QTc, by using the Bazett formula, which is the most commonly
used (QTc = QT/√R-R interval), the QT interval is given in milliseconds, and
the R-R interval is given in seconds.
Rate Determination
If the rhythm is sinus, then the atrial and ventricular rates are equal. If there is
not a 1:1 relationship between P waves and QRS complexes, then both atrial
and ventricular rate determinations should be made. Recall that the standard
ECG acquisition is 10 seconds; if the P waves or QRS complexes are counted
and multiplied by 6, then a reasonable heart rate determination can be made.
Another method often used to interpret adult ECG results involves dividing the
R-R interval into 60 seconds. For example, if the distance between 2 QRS com-
plexes is 400 ms (2 large boxes), the heart rate would be 150 beats per minute
(60 seconds per minute/0.4 seconds between heartbeats). This works well if the
heart rate is constant and if an accurate measurement between 2 heartbeats can
be made. In addition to high resting heart rates, children often have prominent
physiological sinus arrhythmia (which makes beat-to-beat variability more
likely). Therefore, the former method of multiplying the total number of QRS
complexes by 6 may be more practical and accurate.
Box 2-3 summarizes this discussion, which may help ensure that all import-
ant aspects of ECG interpretation are covered.
ECG Abnormalities
This section follows the normal heartbeat through the conduction path to
examine abnormalities of structure, rhythm, and conduction that can be seen on
an ECG tracing. Treatment of specific rhythm abnormalities will be covered in
Chapter 10, Palpitations and Arrhythmia.
A Note on Arrhythmias
When analyzing arrhythmias, the particular characteristics of the abnormal
rhythm are indeed important, but equally as crucial is analyzing what occurs
with the transition into and out of the abnormal rhythm. Telemetry strips,
running 12-lead ECGs, and ambulatory ECG monitors can all be useful for
this. When assessing a suspected arrhythmia, the following should be examined.
1. How does the relationship of the P waves and the QRS complex change (does
it remain a 1:1 relationship, has the PR interval lengthened or shortened)?
2. Have the P waves changed (axis, morphologic appearance, or rate)?
3. Have the QRS complexes changed (axis, morphologic appearance, or rate)?
25
CCIP.indb 25 3/13/18 4:18 PM

Box 2-3. Fifteen-Step Electrocardiographic Evaluation

Method
1. Is the P wave sinus? (Yes/No)
a. Normal axis (up in I and aVF)
b. P before every QRS
c. QRS after every P
d. All P waves look the same in the rhythm strip
2. Atrial rate = ____ beats/min (Normal/Abnormal)
3. Is there LAE/RAE? (Yes/No)
a. RAE P wave >3 boxes tall
b. LAE P waves >2–2.5 boxes wide or terminal P wave >1 box
4. PR interval = ___ ms (Normal/Abnormal)
5. Is there PR depression or elevation? (Yes/No)
a. >1 box from baseline (TP segment)
6. QRS duration = ___ ms (Normal/Abnormal)
a. Narrow QRS indicates likely normal ventricular depolarization
through the His-Purkinje system
7. Are there abnormal Q waves? (Yes/No)
a. Q waves >½ box wide or deeper than ULN in III or V6
8. QRS axis = ___ degrees (Normal/LAD/RAD)
9. Ventricular rate = ___ beats/min (Normal/Abnormal; if sinus rhythm,
atrial = ventricular rate)
10. Are the QRS complexes related to the P waves 1:1? (Yes/No; if not,
what’s the relationship?)
11. Is there normal R wave progression through the precordial leads?
(Yes/No)
12. RVH/LVH based on voltage in V1/V6 or mid-precordial leads? (Yes/No)
13. ST segment elevation/depression? (Yes/No)
14. T waves normal in morphologic appearance and axis? (Yes/No)
15. QTc = ___ ms (Normal/Abnormal)
LAD, left axis deviation; LAE, left atrial enlargement; LVH, left ventricular hypertrophy; RAD, right axis deviation; RAE,
right atrial enlargement; RVH, right ventricular hypertrophy; ULN, upper limit of normal.
Atrial Rhythm and Conduction Abnormalities

As discussed previously, there are 4 essential criteria for sinus rhythm. When
these criteria are not met, the rhythm must be further analyzed. Abnormalities
in the atrial rhythm can come as a result of the atrial rate being tachycardic or
bradycardic or coming from an abnormal place of activation. As a quick guide,
the maximum sinus rate can be estimated by subtracting the patient’s age from
220 beats per minute. Premature neonates who present with anemia, pain, and
dehydration can have sinus heart rates into the 230s, but rates higher than 220 in
most children should raise suspicion for an abnormal mechanism of tachycardia.
Understanding normal physiological responses is crucial if we are to begin
understanding abnormal mechanisms.
26
CCIP.indb 26 3/13/18 4:18 PM

Electrocardiography
Sinus Tachycardia
Sinus tachycardia is a response of the sinus node to extracardiac stimulation.
Sinus tachycardia, like sinus bradycardia, is rarely a manifestation of primary car-
diac disease. Pain, dehydration, anemia, conditions associated with excess release
of catecholamines, and hyperthyroidism are common causes of sinus tachycardia.
It is important to recognize that the heart rate may increase quickly, over several
beats in sinus tachycardia, particularly when driven by sudden stimulation,
such as being poked by a needle, but as opposed to supraventricular tachycardia
(SVT), the change in heart rate does not occur in a single heartbeat. Similarly,
when sinus tachycardia resolves, it typically returns to baseline more gradually.
Extreme sinus tachycardia, particularly in neonates, can at times be challenging
to differentiate from abnormal mechanisms of narrow complex tachycardia.
The use of telemetry can be helpful in seeing the onset and resolution of the
tachycardia. Particular attention should be paid to changes not only in the onset
of rate, but also in P wave axis or morphologic appearance. Sinus tachycardia
should have the same appearance of P waves as the slower sinus rate but simply
at a faster rate with shorter intervals.
Supraventricular Tachycardia
Speaking grammatically, SVT would include any cause of tachycardia that
originates above the ventricles, but from a clinical perspective, SVT generally refers to
re-entrant tachycardia, of which there are 2 broad varieties, AV re-entrant tachy-
cardia (AVRT) and AV node re-entrant tachycardia. AVRT, the most common
type of SVT in neonates and small children, requires involvement of 4 compo-
nents: the atria, AV node, ventricles, and accessory pathway (see Figure 2-5).5
In this situation, there is normal sinus depolarization with activation of the AV
node and ventricles, and the accessory pathway will conduct an impulse up to
the atria, but under most circumstances, the atria are still repolarizing and are
refractory to stimulation. Any number of events (premature atrial contractions,
premature ventricular contractions [PVCs], or change in vagal tone) can change
the timing cycles of the atria, AV node, ventricles, or accessory pathway so that
when the accessory pathway stimulates the atria, the atria are repolarized. If the
timing of the 4 parts of the pathway are altered so that each can be continually
depolarized in circular succession from atria to AV node to ventricle to accessory
pathway, the re-entrant circuit can propagate until broken. SVT is essentially an
all-or-none phenomenon with patients either being in SVT or not (Figure 2-6).
Once in SVT, the atria are no longer activated by the sinus node but are rather
activated by the accessory pathway. Given the abnormal mechanism of atrial
activation in SVT, if P waves are seen, they often have an abnormal axis or
morphologic appearance. P waves are often not seen in SVT because they are
buried in QRS complexes or the T waves. Slower SVT may show the abnormal
P waves. Understanding this physiology can help differentiate SVT from
27
CCIP.indb 27 3/13/18 4:18 PM

Electrocardiogram
P P P P
AVN AP
Sinus rhythm Orthodromic atrioventricular Antidromic atrioventricular

reentrant tachycardia reentrant tachycardia
FIGURE 2-5. Mechanism of atrioventricular reentrant tachycardia. AP = accessory pathway, AVN =

atrioventricular node. From reference 5.
FIGURE 2-6. Supraventricular tachycardia (SVT, box) and premature atrial contractions (PACs)
(arrows) in a 3-week-old premature neonate. A 7-beat run of SVT is started by a PAC. About
three-quarters of the way through the electrocardiogram, another PAC is seen as the early P wave is
in the preceding T wave. SVT stops and starts suddenly in a single beat. The heart rate is over 270
beats/min, and the QRS is narrow.
28
CCIP.indb 28 3/13/18 4:18 PM

Electrocardiography
other narrow-complex tachycardias. Please see Chapter 10, Palpitations and

Arrhythmia, for the role of adenosine in both treatment and diagnosis. Table 2-3
provides comparisons between sinus tachycardia, SVT, and atrial tachycardia.
Ectopic Atrial Tachycardia
Cardiac myocytes have the property of automaticity with clusters of cells in the
sinus node; the AV node has the second fastest rates of depolarization. Ectopic
atrial tachycardia (EAT), often called simply atrial tachycardia, occurs when a
cluster of cells in the atria outside of the sinus node begins depolarizing at a
frequency greater than the sinus node. Unlike the sinus node, which exists as a
right-sided posterior structure typically near the junction of the SVC and the
right atrium, the focus of depolarization for EAT can come from anywhere
in either atrium. Like sinus tachycardia, EAT often occurs with a warm-up or
cool-down period, which may appear quick (over several heartbeats) but will
not change from baseline to a consistent higher rate in a single heartbeat as
re-entrant SVT does. When examining the ECG, one of the keys to identifying
EAT is to observe that the P wave morphologic appearance or axis will change
when compared to the P wave in sinus rhythm (Figures 2-7 and 2-8). For a left
atrial rhythm, the P wave axis will be negative in lead I, as the wave of depolar-
ization is now moving left to right, away from lead I. If the focus of cells is in the
low portion of the atrium, the P wave will be negative in aVF because the atria
are now depolarizing from the bottom to the top, and forces are moving away
from aVF. If the focus of EAT is in the low right atrium, lead I will still appear
with a positive P wave, but aVF will be negative. In addition to the location of
the tachycardia focus, types of EAT can vary in terms of how quickly the rate
increases or decreases, the peak heart rate, and the response to catecholamines.
Table 2-3. Comparison Between Sinus Tachycardia,

SVT, and Atrial Tachycardia
Sinus Tachycardia SVT Atrial Tachycardia
Heart rate (beats/ <220 >220 Variable

min)
P waves Normal Absent or Often abnormal

abnormal axis
Start and stop Gradually Single beat Gradually
Effect of P waves continue; Tachycardia Flutter waves

adenosine QRS complexes are breaks continue; QRS com-
blocked plexes are blocked
SVT, supraventricular tachycardia.
29
CCIP.indb 29 3/13/18 4:18 PM

FIGURE 2-7. Ectopic atrial tachycardia in an 18-year-old cross-country runner with racing heart-
beats at rest. This is a relatively slow example, which shows the abnormal P wave axis. The P wave is
originating from low in the atrium (negative in aVF, II, and III; most positive in aVR). The heart rate
is 102 beats/min.
FIGURE 2-8. Ectopic atrial tachycardia in a 1-week-old neonate with tachycardia. Note that the P
waves are negative in leads I and aVF and positive in aVR, indicating that the focus of the ectopic
tachycardia is in the low left atrium.
Atrial Flutter
Like SVT, atrial flutter involves a circuit, except that instead of involving the
atria, AV node, ventricles, and accessory pathway, the atrial flutter circuit is solely
contained in the atria. This results in rapid, frequent depolarization of the atria,
with rates that can exceed 300 times per minute. These frequent atrial depolar-
izations are conducted to the AV node and then to the ventricles. The appear-
ance of these abnormal flutter waves on the ECG tracing is often described as
“sawtooth.” Depending on the atrial rate, conduction to the ventricles may be
30
CCIP.indb 30 3/13/18 4:18 PM

Electrocardiography
1:1, but at higher rates, the AV node and His-Purkinje fibers may not have time
to repolarize and may therefore not conduct (referred to as blocking). If there are
2 atrial depolarizations (2 flutter P waves) for each QRS seen, this is described
as atrial flutter with 2:1 block (if there are 3 P waves for each QRS, then it is 3:1
block, and so on) (Figure 2-9). At times, the relationship between the flutter
P waves and the ventricular QRS complexes is not consistent; this is termed
variable conduction (Figure 2-10).
WPW and Pre-excitation
WPW is a particular type of abnormal conduction in the heart that may lead
to an abnormal heart rhythm, SVT. As discussed previously, for SVT known
as AVRT to occur, the 3 normal parts of the conduction pathway (atria, AV
node, and ventricles) interact with the abnormal accessory pathway to create
the obligate circuit. In the prior example, the normal conduction occurred
down the usual conduction system (orthodromic), and the accessory pathway
conducted an impulse from the ventricles to the atria. In situations in which the
accessory pathway can conduct in the direction from the atria to the ventricle,
the AV node is bypassed briefly during sinus rhythm. The normal delay of
FIGURE 2-9. Atrial flutter with 3:1 conduction: Looking only at V1, the diagnosis of atrial flutter
can be challenging, emphasizing the importance of using all the leads for electrocardiography.
FIGURE 2-10. Atrial flutter with variable conduction in a 17-year-old. The relationship of P (flutter)
waves and QRS complexes varies between 2:1 and 3:1.
31
CCIP.indb 31 3/13/18 4:18 PM

conduction through the AV node, which gives rise to the usual PR interval, is
bypassed, resulting in what is termed pre-excitation as the ventricles are initially
depolarized from the accessory pathway. Shortly after ventricular depolarization
begins from the accessory pathway, the normal AV node delay has occurred, and
the action potential is propagated down the normal pathway of the His-Purkinje
system. This results in the ECG showing a short PR interval with a slightly
wide QRS complex at the base because of the slurring of the upstroke from
the pre-excitation. The initial abnormal portion of the QRS resulting from
the accessory pathway depolarizing the ventricle is termed the delta wave. The
combination of the delta wave and the short PR interval is termed WPW pattern
(Figure 2-11).
Because patients with WPW have an accessory pathway and, as a result, have
the 4 obligate parts of a re-entrant circuit, they are at risk for SVT. Once an
individual with WPW pattern begins experiencing SVT, the diagnosis of WPW
syndrome is established. While SVT is the most common arrhythmia seen in
those with WPW, the increase of sudden death in people with WPW syndrome
is thought to be largely from patients having atrial fibrillation or flutter, which,
depending on the accessory pathway, may be conducted in a 1:1 manner to the
ventricles. If this occurs, atrial fibrillation or flutter is effectively converted into
the ventricular equivalent.6
FIGURE 2-11. Wolff-Parkinson-White (WPW) pattern in a 14-year-old with palpitations. The PR

interval is very short. The QRS complex begins almost as soon as the P wave ends, leaving virtually
no PR segment. The base of the QRS complex appears wide because of the delta wave (arrow). The
delta wave is created because the accessory pathway from the atria to the ventricle pre-excites the
ventricles, briefly bypassing the atrioventricular node. The PR interval appears shorter in V6 than in
lead I; this reflects the location of the accessory pathway and emphasizes the need to examine all
leads for the features of WPW pattern.
32
CCIP.indb 32 3/13/18 4:18 PM

Electrocardiography
Sinus Bradycardia and Escape Rhythms

Sinus bradycardia occurs when the heart rate falls below the normal range for
age. This can come from many sources, but rarely is sinus bradycardia a result
of abnormal sinus node function. As with sinus tachycardia, sinus bradycardia
almost always comes from extracardiac sources. These may include increased
vagal tone, low thyroid hormone, athletic conditioning, sepsis, increased
intracranial pressure, acidosis, and hypothermia. Sinus bradycardia is addressed
by treating the underlying condition.
As previously mentioned, all cells in the heart have automaticity. If the degree
of sinus node depolarization is less than the rate of automatic depolarization of
other cells (typically 40–60 beats/min for the AV node and <40 beats/min for
the ventricles), an escape rhythm is seen. Escape rhythms will be slower than
the baseline rhythm; ideally, telemetry will be available to view the rhythm from
before the sinus bradycardia began. The defining characteristic of an escape
rhythm is that the ventricular rate will be faster than the atrial rate (if present).
Depending on the degree of sinus bradycardia or sinus node dysfunction, P
waves may not be seen at all. It is important to identify where the escape rhythm
originates. Junctional escape will have QRS complexes that appear similar to
the sinus beats as the ventricles are being activated through the normal pathway
involving the AV node and the His-Purkinje system. Ventricular escape will
show a wider QRS complex with a different morphologic appearance from the
sinus beats because ventricular activation does not come through the normal
pathway and instead is from a focus within the ventricle (Figure 2-12).
FIGURE 2-12. Third-degree atrioventricular (complete) block with ventricular escape. The first half
of the electrocardiogram shows only P waves (stars) with no corresponding QRS complexes as a
result of complete heart block. After 5 seconds of no stimulation, the ventricles depolarize automat-
ically at an escape rate of 38 beats/min. The escape rhythm is identified as ventricular in origin from
the wide QRS complexes (arrows).
33
CCIP.indb 33 3/13/18 4:18 PM

Rhythm and Conduction Abnormalities Related to the

AV Node and the His-Purkinje System
AV Block
Commonly, 3 types of AV block (AVB) are described (also referred to as heart
block). First-degree AVB results in consistent conduction of each P wave to the
ventricles, resulting in a 1:1 relationship of P waves to QRS complexes. The
defining feature of first-degree AVB is a prolonged PR interval greater than
the ULN for age (Figure 2-13). The term block in this situation is a misnomer
because it is really a delay in conduction. Recall that the PR interval consists
of the P wave (atrial depolarization) and the PR segment (conduction through
the AV node). Any number of conditions that affect either of these can result
in first-degree AVB, including atrial enlargement (wide P waves), conduction
disease from heart surgery, infection resulting in myocarditis, rheumatic heart
disease, Lyme disease, and post-CHD repair that involves the atria or AV node.
When the PR interval is consistently prolonged, ensure that all 4 criteria
for sinus rhythm are met. Ectopic atrial tachycardia may have a prolonged PR
interval because of the normal physiology of the AV node, which can slow
conduction at faster rates of stimulation, unlike sinus tachycardia, in which the
normal intervals will shorten largely because of catecholamine effect.
Second-degree AVB occurs when some, but not all, atrial beats are conducted
to the ventricles. The forms most commonly described are Mobitz type I
(Wenckebach) and Mobitz type II. Mobitz type I AVB is from progressive
FIGURE 2-13. First-degree atrioventricular block with left ventricular hypertrophy (LVH) and
possible right ventricular hypertrophy (RVH) in a 7-month-old infant born to a mother with lupus.
The PR interval is consistently prolonged. All P waves conduct. All the criteria for sinus rhythm are
met. The R wave in V6 is higher than the upper range of normal for age (LVH), and the R wave in V1
is higher than the median (RVH). See the section on ventricular hypertrophy for more details.
34
CCIP.indb 34 3/13/18 4:18 PM

Electrocardiography
slowing of the conduction through the AV node. This results in a progressive

lengthening of the PR interval with a subsequent loss of conduction for a beat,
followed by resumption of conduction (Figure 2-14). This occurs because with
each subsequent stimulation, the AV node conducts and repolarizes more slowly
until the point is reached when the next atrial beat reaches the AV node and the
AV node is still refractory. This phenomenon of decremental conduction can be
part of normal AV node physiology. It can be exacerbated by increasing vagal
tone and should be decreased by catecholamine release. Mobitz type I AVB can
be seen normally in states of increased vagal tone and lower heart rates, such as
while sleeping or in well-conditioned athletes. It should resolve with increases in
heart rate and exercise. Mobitz type I AVB is not always a normal finding and
can also be seen in conditions that damage or result in inflammation of the AV
node or conduction tissues, such as congenital heart disease (CHD), infection,
and autoimmune disease, and after cardiac surgery.
Mobitz type II AVB occurs when the PR interval is constant but 1 or more
atrial depolarizations are blocked without PR prolongation and, as a result of the
P wave being blocked, the ventricle is not stimulated to depolarize (Figure 2-15).
This is always an abnormal finding and is not a property of normal AV node
physiology. It can be seen in conditions that damage or result in inflammation of
the AV node or conduction tissues, such as CHD and infection and after cardiac
surgery. Another variation of Mobitz type II AVB, referred to as high-grade
AVB, occurs when several P waves in a row do not conduct to the ventricles
(Figure 2-16).
Complete heart block, also known as third-degree AVB, occurs when none of
the P waves conduct to the ventricles. In this situation, the QRS complexes will
originate either from the AV node, appearing narrow (without being stimulated
by the atria), or from the ventricles, appearing wide (Figure 2-17). This is clearly
abnormal and can be seen in conditions that damage or result in inflammation
FIGURE 2-14. Second-degree atrioventricular (AV) block type I in a 12-year-old with palpitation,
seen with a Holter monitor during sleep. The PR interval increases over several beats as the refractory
period of the AV node increases until an atrial beat cannot be conducted.
35
CCIP.indb 35 3/13/18 4:18 PM

FIGURE 2-15. This complex electrocardiographic strip demonstrates some important points of
cardiac electrophysiology. Second-degree atrioventricular block type II, prolonged QT interval,
and occasional junctional beats are seen in a 2-day-old neonate with an irregular heart rate. There
is a consistent PR interval seen (P waves noted by solid arrows) with occasional nonconduction to
the ventricles (nonconducted P waves with hollow arrows). The corrected QT interval is prolonged
at more than 500 ms. This results in a prolonged period of ventricular repolarization; thus, when
some of the atrial beats reach the ventricles, the ventricles are still refractory and do not depolarize.
Occasional junctional escape beats (stars) are seen after a nonconducted atrial beat. At this time, the
ventricles have repolarized and the AV fires back up because there has been a missed beat and the
next atrial beat has not yet come. Occasionally, the P waves are buried in the T waves because of how
long the QT interval is (circles).
FIGURE 2-16. Second-degree atrioventricular block (AVB) type II with high-grade block in a
10-year-old with syncope. The top portion of this ambulatory monitor strip shows type II AVB with
a consistent PR interval for 4 beats, followed by a single dropped beat, a normally conducted beat,
a dropped beat, a normally conducted beat, and then several dropped beats. The bottom strip shows
multiple P waves in a row that are not conducted, referred to as high-grade AVB (P waves are shown
with stars). High-grade AVB is of concern and, depending on the cause, can progress to complete
(third-degree) AVB.
of the AV node or conduction tissues, such as CHD or infection, and after

surgery. Congenital complete heart block can be seen with neonatal lupus owing
to transplacental antibody transfer. Patients with CHD, such as L-transposition
of the great arteries (also known as “congenitally corrected transposition of
the great arteries”), have a risk of developing third-degree AVB over time. For
postsurgical patients with complete heart block, often 1 week to 10 days are
permitted before pacemaker placement for return of conduction as inflammation
resolves. Complete heart block falls into a category termed AV dissociation, which
36
CCIP.indb 36 3/13/18 4:18 PM

Electrocardiography
FIGURE 2-17. Third-degree atrioventricular block with ventricular escape. This electrocardiogram
(ECG) was previously used to demonstrate ventricular escape. P waves (stars), which should be able
to conduct but do not, are clearly seen. The ventricular rate of 38 beats/min is far slower than the
atrial rate of 126 beats/min. If the second QRS complex and the preceding P wave are examined in
isolation, it may appear that the QRS complex (arrows) is generated from the P wave, but when the
ECG is examined in its entirety, it is clear that the rate of the 4 ventricular beats is regular and not
related to the atrial rate.
implies that the atrial and ventricular depolarizations have no relationship with
each other.
Junctional Tachycardia
Junctional tachycardia (Figure 2-18), or junctional ectopic tachycardia ( JET), is
seen when the depolarizing rate of the AV node exceeds that of the sinus node
and other myocardial tissue. The ECG will show a narrow complex QRS with
a morphologic appearance similar to that of a sinus beat because the ventricles
are being depolarized in a similar fashion through the AV node and the His-
Purkinje system. P waves will not be seen preceding the QRS complexes because
the ventricles are being driven no longer by the atria but by the AV node. Of key
importance, in addition to identifying the lack of relationship of P waves to the
narrow QRS complexes, is recognizing that in junctional tachycardia, the rate
must be faster than the baseline rate. While this may seem elementary, junctional
FIGURE 2-18. Junctional tachycardia in a 3-year-old. Narrow complex tachycardia is seen with a
heart rate of 152 beats/min. No P waves are seen. Sinus tachycardia with first-degree heart block
can at times be difficult to differentiate from junctional tachycardia because the P waves and T wave
may overlap.
37
CCIP.indb 37 3/13/18 4:18 PM

tachycardia can at times be confused with junctional escape rhythm, the latter
being seen when the junctional rhythm is slower than the base rhythm. However,
the QRS complexes will look similar. JET is generally either congenital or seen
after cardiac surgery.
Abnormalities Related to the Ventricular Myocardium

Ventricular Hypertrophy
While limb leads are used for determining axis, the precordial leads can be used
to determine hypertrophy. As mentioned previously, lead V1 overlies the RV,
and therefore the R wave of V1 represents RV depolarization and the S wave
represents LV depolarization. Conversely, V6 overlies the LV, and the R wave of
V6 shows LV depolarization while the S wave shows the RV. When any of these
exceed the ULN for age, hypertrophy of the corresponding ventricle should be
suspected (see Table 2-2 for normal values). Normal ratios for the R/S waves
can also be used to determine hypertrophy. If the R/S ratio in V1 is higher than
the ULN, RVH should be suspected; if the R/S ratio is higher than the ULN
in V6, LVH should be suspected. If both the RV and the LV are hypertrophied,
their forces may effectively cancel each other out when observed on V1 and
V6. In that scenario, prominent voltage may be observed in the mid-precordial
leads (V3 and V4). The Katz-Wachtel criteria are used to identify biventricular
hypertrophy if the R and S waves added together are more than 60 mm in a
single precordial lead.7 By using similar logic, if criteria for either RVH or LVH
are met, the other ventricle needs to have the appropriate R or S wave in V1 or
V6 only above the mean, as opposed to above the ULN. Causes of ventricular
hypertrophy can include increased afterload (valve stenosis or hypertension),
inherited cardiomyopathies (abnormal myocyte structure), storage diseases, and
hyperinsulinemia (infants of diabetic mothers). Hypertrophy with strain is noted
when ST segment and T wave changes are seen in addition to LVH and RVH
criteria. This indicates an abnormality in how the ventricles are repolarizing
because of the hypertrophy. The ECG can have variable sensitivity and specificity
regarding hypertrophy and should be confirmed with an echocardiogram when
hypertrophy is suspected.3
PVCs and Ventricular Tachycardia
PVCs are seen when the ventricle spontaneously depolarizes before the next
sinus beat is conducted through the AV node (Figure 2-19). These are covered
in more detail in Chapter 10, Palpitations and Arrhythmia. These are wide QRS
complexes because the ventricles are activated through a wave of depolarization
rather than synchronously via the His-Purkinje system. PVCs can originate
from either ventricle or along the septum. If originating in the septum near the
conduction tissue, sometimes the QRS complexes may appear relatively narrow
because the depolarization wave may activate the His-Purkinje system. PVCs
38
CCIP.indb 38 3/13/18 4:18 PM

Electrocardiography
a.
b.
FIGURE 2-19. These tracings from 2 different patients each show 2 QRS complexes prematurely
occurring. The QRS complexes are wide, and when each premature beat is compared to the other
beat in the strip, they both have the same appearance. These are termed monomorphic or unifocal
because both premature ventricular contractions (PVCs) originate from the same location in the
ventricle. A. First-degree atrioventricular block with PVCs. B. PVCs.
that all appear similar are likely coming from a similar place in the myocardium
and are termed unifocal. PVCs are common findings that at low frequencies are
benign. When making up more than 20% of QRS complexes, PVCs can induce
a cardiomyopathy, which typically resolves with resolution of the premature
beats. Multifocal PVCs originate from multiple locations in the ventricles and
will appear on the ECG tracing to have varying morphologic appearances. These
are also termed polymorphic and are more concerning for disease. Causes of PVCs
include foci of myocardial tissue intrinsically more active than usual, electrolyte
abnormalities, ischemia, status post heart surgery, cardiomyopathy, and inherited
channelopathies. Two PVCs seen consecutively are termed a couplet, 3 are termed
a triplet, and 4 are termed ventricular tachycardia.
Ventricular tachycardia is seen when the rate of ventricular depolarization
exceeds that of atrial or AV node depolarization. A wide complex QRS is seen
on the ECG, and the rate of QRS depolarization is generally faster than the
ULN for age. The QRS is wide because the ventricles are activated through a
wave of depolarization rather than synchronously through the His-Purkinje
system. Typically, P waves are not seen because the QRS complexes obscure
them on the ECG tracing. They may be seen on occasion, but they are not
driving the ventricles. If the ventricular rate is higher than the baseline sinus rate
(within 10%–15% of baseline)8 but not so fast as to be considered tachycardic,
the rhythm is referred to as an accelerated ventricular rhythm, or sometimes an
idioventricular rhythm, and can be benign.
39
CCIP.indb 39 3/13/18 4:18 PM

Ventricular tachycardia is termed monomorphic or unifocal when the QRS

complexes, viewed in 1 lead, appear similar (Figure 2-20). Polymorphic or multi-
focal ventricular tachycardia will have multiple QRS morphologic appearances in
a given lead, as the focus of tachycardia is changing. Torsades de pointes is a par-
ticular type of polymorphic ventricular tachycardia in which the QRS complexes
appear to twist around the baseline; it is associated with long QT syndrome.
Bundle Branch Blocks
Bundle branch blocks are seen when an atrial contraction passes through the
AV node and then to the His-Purkinje system, but the His-Purkinje conduction
system of 1 or more of the branches is damaged. The result on the ECG is the
normal sequence of P wave, QRS complex, and T wave, but the QRS complex
will appear wider than normal because ventricular depolarization will use some,
but not all, of the normal ventricular conduction pathways. The appearance of
the QRS will depend on which branch of the His-Purkinje pathway is blocked.
RIGHT BUNDLE BRANCH BLOCK
If the right bundle is damaged, ventricular depolarization will occur via the
left bundle activating normally, causing the LV to depolarize quickly. The RV
will be activated from a wave of depolarization coming over from the LV. V1,
overlying the RV, will show a widening of the R wave and will often have the
classic rSR′ or “rabbit ears” pattern. The S wave representing LV depolarization
in V1 will have the usual narrow appearance (because the LV is depolarized
normally through the functional left bundle). When looking at V6, the R wave
FIGURE 2-20. Monomorphic (unifocal) ventricular tachycardia in a 15-year-old with dilated

cardiomyopathy. Wide complex tachycardia is seen with a heart rate near 300 beats/min with
occasional narrow complex beats that are likely sinus. The ventricular tachycardia beats have a
consistent morphologic appearance in a given lead, indicating that the ventricular tachycardia
comes from a consistent spot in the ventricles. Polymorphic or multifocal ventricular tachycardia
will have variable morphologic appearance of the QRS complexes.
40
CCIP.indb 40 3/13/18 4:18 PM

Electrocardiography
will appear narrow, but the S wave will appear wide and slurred; this represents
the abnormally depolarizing RV (Figure 2-21).
Note that the rSR′ pattern can be seen normally in children. For rSR′ to be a
RBBB, the R′ wave must be wide, representing the delayed RV activation. With
a narrow rSR′, if the R′ is more than 10 mm (>15 mm in infants younger than
1 year), it can be a sign of RVH.
LEFT BUNDLE BRANCH BLOCK
If the left bundle is damaged, activation of the RV will occur normally through
the functional right bundle branch, while the LV will activate in a delayed
fashion through a wave of depolarization coming from the RV instead of the
left bundle. This will show on the ECG tracing as a wide R wave in V6, with
the S wave, if present, appearing relatively narrow. In V1, if the R wave from RV
depolarization is present, it will appear narrow. V1 may only show a wide S wave,
representing the delayed LV depolarization in LBBB (Figure 2-22).
Because the ventricles are being activated abnormally with both RBBBs
and LBBBs, the QRS axis is typically deviated. RBBBs are commonly seen
after congenital heart surgery in children, particularly after ventricular septal
defect closure. Ventricular septal defect patches are sewn on the RV side of
the septum and may often interrupt the right bundle with suture placement.
LBBB can also be seen after heart surgery. Either LBBB or RBBB can be seen
with cardiomyopathy, myocarditis, drug overdose, or ischemia, and, rarely, as a
congenital finding.9,10
FIGURE 2-21. Right bundle branch block in a 13-year-old who underwent repair of tetralogy of
Fallot as an infant; rsR′ is noted in V1, with increased duration of the R′. The S wave (while small)
appears narrow, indicating normal depolarization of the left ventricle. On V6, the R wave has a nor-
mal duration and appearance while the S wave is prolonged, indicting the abnormal depolarization
of the right ventricle.
41
CCIP.indb 41 3/13/18 4:18 PM

FIGURE 2-22. Left bundle branch block (LBBB) in a 17-year-old. Note the wide S wave in V1 and
the wide R wave in V6. Often with LBBB, the right ventricular force may not be seen because of the
dominance of left ventricular forces.
ST and T Wave Abnormalities

The ST segments represent the transition from ventricular depolarization to
repolarization. Many children and adolescents will show J point elevation or
early repolarization (Figure 2-23). It is important to differentiate this from
pathologic ST elevation. With early repolarization, the entire ST and T wave
complex appears slightly elevated from baseline, but the appearance of the ST
segment and T wave are otherwise normal. In adults, early repolarization can
be associated with increased risk of arrhythmia, but risk has not been shown in
children, in whom early repolarization is a common finding.11 Pathologic ST
elevation may take on a more sloped or abrupt appearance, and the T waves
may often appear abnormal. ST elevation can be seen in ischemia, myocarditis,
pericarditis, cardiomyopathy, and channelopathies (Figure 2-24).
Because the T waves represent ventricular repolarization, it is important to
note that this process is much slower than depolarization; therefore, T waves
have a longer duration than QRS complexes. As a result, abnormalities in
the ventricular myocardium can be seen in T waves before the QRS. It is also
important to recognize that if the ventricle depolarizes abnormally, it will repo-
larize abnormally. In general, changes to the T wave morphologic appearance are
not specific for a particular disease and can be seen with hypertrophy, ischemia,
inflammation, cardiomyopathy, electrolyte abnormalities (hyperkalemia),
and inherited channelopathies (long QT syndrome and Brugada syndrome).
Normal-appearing T waves should have a gentle, hill-like appearance. They
should be neither flat nor peaked. It is important to note the direction or axis
for several leads. T wave changes can be subtle, and it can take time to develop a
sense for nonspecific T wave changes.
42
CCIP.indb 42 3/13/18 4:18 PM

Electrocardiography
FIGURE 2-23. Normal sinus rhythm with early repolarization in a 15-year-old with palpitations.
In multiple leads, the J point, where the QRS joins the ST segment, is elevated. The ST segments
and T waves appear normal.
FIGURE 2-24. Sinus rhythm with ST elevation in the inferior and lateral leads in a 1-month-old
with aortic valve stenosis. The abnormal T wave appears diffusely (flattening). Note the abnormal
appearance of the ST segment associated with the ST elevation. The T waves are flat in V6 and lead
I. There is evidence that the left ventricle is under strain because it is repolarizing abnormally. Note
that V2 shows abnormal ST depression.
T waves should always be upright in the left lateral leads V5 and V6 and in 2
of the 3 inferior leads (II, III, and aVF). Flat or inverted T waves in V5 and V6 or
in more than 1 of the inferior leads indicate abnormality with LV repolarization
(Figure 2-25).
In lead V1, at birth, the T wave is upright, and in the first week after birth, the
T wave inverts and remains inverted until at least 6 years of age. At some point
43
CCIP.indb 43 3/13/18 4:18 PM

FIGURE 2-25. T wave inversion in the left lateral (V5, V6) and inferior (II, III, aVF) leads in a
16-year-old with hypertension and left ventricular (LV) hypertrophy at echocardiography. Inverted
T waves in the inferior and left lateral leads indicate an abnormality in LV repolarization. Often,
abnormalities in the ventricular myocardium appear in the T waves before the QRS complexes.
after 6 years, the T wave becomes upright, but it can remain inverted through
adolescence. An upright T wave in V1 in a child between 1 week and 6 years of
age indicates an abnormality in the RV repolarization.
Prolonged QT Interval
Since the QT interval includes the beginning of QRS through the end of the
T wave, anything that prolongs either ventricular depolarization or repolariza
tion will increase the QT interval. This is important to recognize because the
main reason for concern with QT prolongation is an increase in the repolarization
period. With an increase in ventricular repolarization time, the ventricular myo-
cardium may be more susceptible to more spontaneous or ectopic depolarization.
This can increase the risk associated with ventricular arrhythmia, specifically
torsades de pointes. Because intervals at ECG typically decrease as the heart rate
increases, the ventricular rate must be accounted for. There are several ways to do
this, but the Bazett formula is used most commonly to derive the QTc.
QTc = QT/√R-R interval
While the math is straightforward, the equation can be problematic when
not used regularly because of the differing units used. QTc and QT interval are
in milliseconds, while the R-R interval is in seconds on the ECG printouts.
At both high and low heart rates, this equation becomes more inaccurate.12
In general, patients with QTc of longer than 500 ms are at increased risk for
arrhythmia.4 Normal postpubescent female subjects can have a slightly longer
QT interval than others (Table 2-4). Most commonly, lead II or V5 is used for
44
CCIP.indb 44 3/13/18 4:18 PM

Electrocardiography
Table 2-4. Normal Corrected QT Intervals

Patient Type Normal Corrected QT Intervals
Postpubertal female <455 ms
Male or prepubertal female <445 ms
Sinus arrhythmia present <470 ms by using the shortest R-R interval and
normal-appearing T waves
Data are from reference 5.
QTc determination, but if a clear end of the T wave cannot be seen in these
leads, others may be used.
The QT interval can be increased by a number of factors, including
medications, inherited channelopathies such as long QT syndrome, neurological
abnormalities, and occurrence after cardiac surgery (Figure 2-26).13–15 It is not
uncommon for neonates to have transient QT prolongation in the first few days
after birth. Often, these normalize in the first week after birth. Many medica-
tions can prolong the QT interval (Box 2-4); a complete list is beyond the scope
of this chapter. A commonly used online resource is www.crediblemeds.org.
It is important to recognize that increases in QRS duration also prolong the
QT interval because the QT interval starts with the QRS complex. For instance,
after ventricular septal defect surgery, many patients develop RBBB, which
prolongs the QRS duration and, as a result, the QT interval.
FIGURE 2-26. Prolonged QT interval in a 2-week-old neonate with a family history of long QT
syndrome; the T waves appear flat in multiple leads, lacking a normal “hump” appearance. Note that
the T wave ends far beyond the midpoint of the R-R interval. The corrected QT interval (QTc) is
very prolonged. The QT interval is 352 ms and the heart rate is 130 beats/min, making the R-R
interval 0.461 seconds (determined by dividing 60 seconds in a minute by 130 beats/min). By using
the Bazett formula, QTc = 352 ms/√0.461 s and QTc = 352 ms/0.679 s, so QTc =518 ms.
45
CCIP.indb 45 3/13/18 4:18 PM

Box 2-4. Common QT Interval—Prolonging Medications

Used in Children
Quinidine Hydroxyzine
Sotalol Chloral hydrate
Flecainide Methadone
Amiodarone Propofol
Chloroquine Hydrocodone
Mefloquine Albuterol
Hydroxychloroquine Levalbuterol
Primaquine Ondansetron
“Azole” antifungal medications Terbutaline
Flouroquinolone antibiotics Tricyclic antidepressants
Macrolide antibiotics (such as Selective serotonin reuptake
azithromycin and erythromycin) inhibitors
Metronidazole
Data are from references 13–16.
Myocarditis and Pericarditis

Inflammation of the myocardium and/or the surrounding pericardium can lead
to a variety of ECG changes. Inflammation of the myocardium can change how
the heart depolarizes and repolarizes. This can lead to a variety of changes in the
QRS and T waves. The classic ECG of a person with myocarditis shows diffuse
low voltages through all leads, although voltage criteria for hypertrophy may also
be present (Figure 2-27). Other changes can be seen, including the nonspecific
FIGURE 2-27. Low-voltage electrocardiogram with right bundle branch block in a 3-week-old
neonate with viral myocarditis; diffuse low-voltage R and S waves are seen in all the leads. Typically,
the total amplitude of R and S waves will be less than 5 mm.
46
CCIP.indb 46 3/13/18 4:18 PM

Electrocardiography
T wave changes of flattening or inversion. ST elevation or depression are not

uncommon in myocarditis.
The typical ECG for pericarditis shows diffuse PR segment depression, along
with ST segment elevation (Figure 2-28). As previously explained, these are
deviations when compared to the baseline segment on the ECG tracing (the TP
segment between ventricular repolarization and the next atrial depolarization).
FIGURE 2-28. Acute pericarditis in a 14-year-old with 3 days of chest pain. Diffuse ST elevation
is shown in conjunction with PR segment depression when compared to the baseline of the TP
segment. These findings evolve with development and resolution of inflammation.
Key Points
•• Successful ECG interpretation requires methodical evaluation of all lead
tracings. The most accurate interpretation will result from interpreting ECG
results in the same consistent fashion each time.
•• Understanding how the surface ECG correlates with cardiac physiology will
maximize the clinical utility of the ECG.
•• Having access to a reference for age-appropriate intervals and ECG parameters
(such as those provided in this chapter) is crucial for accurate ECG interpretation.
References
1) Rijnbeek PR, Witsenburg M, Schrama E, Hess J, Kors JA. New normal limits for the paediatric
electrocardiogram. Eur Heart J. 2001;22(8):702–711
2) Davignon A, Rautaharju P, Boisselle E, Soumis F, Mégélas M, Choquette A. Normal ECG
standards for infants and children. Pediatr Cardiol. 1980;1(2):123–131
3) Rijnbeek PR, van Herpen G, Kapusta L, Ten Harkel AD, Witsenburg M, Kors JA.
Electrocardiographic criteria for left ventricular hypertrophy in children. Pediatr Cardiol.
2008;29(5):923–928
47
CCIP.indb 47 3/13/18 4:18 PM

4) Drew BJ, Ackerman MJ, Funk M, et al; American Heart Association Acute Cardiac Care
Committee of the Council on Clinical Cardiology, the Council on Cardiovascular Nursing, and
the American College of Cardiology Foundation. Prevention of torsade de pointes in hospital
settings: a scientific statement from the American Heart Association and the American College
of Cardiology Foundation. Circulation. 2010;121(8):1047–1060
5) Ganz LI, Friedman PL. Supraventricular tachycardia. N Engl J Med. 1995;332(3):162–173
6) Pappone C, Vicedomini G, Manguso F, et al. Risk of malignant arrhythmias in initially
symptomatic patients with Wolff-Parkinson-White syndrome: results of a prospective long-term
electrophysiological follow-up study. Circulation. 2012;125(5):661–668
7) Elliott L, Anderson R, Tuna N, Adams P, Neufeld H. Complete transposition of the great
vessels II. An electrocardiographic analysis. Circulation. 1963;27(6):1118–1127
8) Rehsia SS, Pepelassis D, Buffo-Sequeira I. Accelerated ventricular rhythm in healthy neonates.
Paediatr Child Health. 2007;12(9):777–779
9) Karadeniz C, Atalay S, Demir F, et al. Erratum to: Does surgically induced right bundle branch
block really effect ventricular function in children after ventricular septal defect closure? Pediatr
Cardiol. 2015;36(5):1107–015
10) Kim JH, Baggish AL. Electrocardiographic right and left bundle branch block patterns in
athletes: prevalence, pathology, and clinical significance. J Electrocardiol. 2015;48(3):380–384
11) Safa R, Thomas R, Karpawich PP. Electrocardiographic early repolarization characteristics
and clinical presentations in the young: a benign finding or worrisome marker for arrhythmias.
Congenit Heart Dis. 2017;12(1):99–104
12) Funck-Brentano C, Jaillon P. Rate-corrected QT interval: techniques and limitations. Am J
Cardiol. 1993;72(6):17B–22B
13) Straus SM, Bleumink GS, Dieleman JP, et al. Antipsychotics and the risk of sudden cardiac
death. Arch Intern Med. 2004;164(12):1293–1297
14) Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med.
2004;350(10):1013–1022
15) Yap YG, Camm AJ. Drug induced QT prolongation and torsades de pointes. Heart. 2003;
89(11):1363–1372
16) De Ponti F, Poluzzi E, Cavalli A, Recanatini M, Montanaro N. Safety of non-antiarrhythmic
drugs that prolong the QT interval or induce torsade de pointes: an overview. Drug Saf.
2002;25(4):263–286
17) Deal B, Johnsrude C, Buck S. Pediatric ECG Interpretation: An Illustrative Guide. Malden, MA:
Blackwell; 2004
48
CCIP.indb 48 3/13/18 4:18 PM

CHAPTER 3
The Role of
chocardiography
E
Angela M. Kelle, MD, FACC, FAAP, and Muhammad Yasir
Qureshi, MBBS, FASE
Introduction
Echocardiography is the cornerstone of pediatric cardiac imaging. Transthoracic
echocardiography (TTE) is performed during the diagnostic workup and the
ongoing follow-up in virtually all children with known or suspected cardiac disease.
Echocardiography can be used to establish a timely and accurate diagnosis of struc-
tural congenital heart disease (CHD), along with hemodynamic and functional
cardiac assessment. The test is noninvasive, widely available, portable for use at the
bedside, considered to have minimal risk in all age groups, and cost-effective when
used appropriately.1-3
Basics of Echocardiography
Echocardiography is cardiac ultrasonography (US). High-velocity sound waves are
used to create real-time images of the heart. An imaging probe, or transducer, is
placed on the patient’s upper abdomen or chest wall and is angled toward cardiac
or vascular structures to obtain images. The transducer contains piezoelectric
crystals, and when electricity is applied to these crystals, ultrasonic sound waves
are produced. Pulses of sound are transmitted very rapidly for a short time, and
the transducer sends and receives these ultrasound signals.
The ultrasound wavelength is the distance from the peak of 1 sound wave to the
peak of the next sound wave. It is inversely related to frequency, which is the num-
ber of sound waves transmitted within 1 second. Both high- and low-frequency
49
CCIP.indb 49 3/13/18 4:18 PM

ultrasound transducers are available. Higher-frequency transducers have the

best image resolution. However, more sound waves are lost to the surrounding
tissues, and there is therefore less penetration (a shorter distance away from the
transducer can be imaged). The highest-frequency transducers can be used in
neonates, with the best resolution. Larger patients, such as adolescents or obese
children, require lower-frequency transducers for adequate penetration, with
resultant decreased image resolution. Overall, children have excellent subcostal
and transthoracic imaging “windows,” allowing cardiac and vascular structures
to be visualized in detail.
As ultrasound waves travel from the transducer through the patient, some
of the waves are reflected back to the transducer by the structures in the path
of the sound beam, such as the heart and blood vessels. The echocardiography
machine processes this information to generate an image. Fluids, such as blood
or effusions, reflect very little energy and appear black on the display. The air-
tissue interfaces, such as the lung or pneumothorax, reflect nearly all the sound
energy back to the transducer and are nearly white on the display. This typically
prevents visualization of any structures located beyond an air-tissue border.
The higher echogenicity of other tissues, such as heart muscle, vessel walls, and
pericardium, is dependent on the relative tissue density.
Objects in motion, such as blood and the contracting heart muscle, reflect
sound waves differently than stationary objects. This is the basis of the Doppler
principle, which states that the observed frequency of a wave depends on the
relative movement of the source of the wave and the observer. An object moving
toward an observer will have sound waves reflected more quickly than they were
sent, with a shorter wavelength and a higher frequency. The reflected waves of
an object moving away will have a longer wavelength and a lower frequency. The
frequency shift of a moving object can be measured and used to calculate the
speed and direction of the object’s motion.
In echocardiography, the transducer is the stationary observer. If blood is the
moving source being measured, the frequency shift of sound waves reflected
from moving blood (either toward or away from the transducer) can be measured
and used by the echocardiography machine to calculate an estimated blood
flow velocity. This velocity can then be used in another equation, the modified
Bernoulli equation, to estimate pressure differences across structures such as
cardiac valves or shunts. It is not necessary for the general pediatrician to know
these equations; rather, it is necessary to understand that the equations are based
on several assumptions (a parallel angle between the transducer and blood flow,
short length of any narrowed segment), and therefore, velocities and pressures
reported at echocardiography are estimations, not exact values. In most cases,
these estimations correlate reasonably well with invasive measurements obtained
via cardiac catheterization.
50
CCIP.indb 50 3/13/18 4:18 PM

The Role of Echocardiography
What Patients and Families Should Expect

During TTE
In the outpatient setting, TTE is generally performed by a trained cardiac
sonographer in a dedicated echocardiography laboratory (Figure 3-1). Echo
cardiography cannot be performed through clothing; therefore, patients are
asked to undress to the waist. Female adolescents and adults are asked to remove
their bra and wear a medical gown that opens in the front; draping is used
during the examination to maintain patient privacy. Warm blankets may be
offered for patient comfort.
Electrocardiographic (ECG) leads are placed on the patient’s chest and
remain hooked up to the echocardiography machine throughout the examina-
tion. US gel is applied on the transducer, and images of the heart and blood
vessels are obtained from multiple imaging windows (Figure 3-2): subcostal,
parasternal, apical, and suprasternal. Patients do not feel the ultrasound waves,
and echocardiography is not painful. Older adolescents or obese patients may
feel a slight pressure from the ultrasound transducer being pressed into their
upper abdomen or chest wall and can occasionally feel discomfort, particularly
in the apical window as the transducer pushes on the ribs; this is almost always
well tolerated. Older patients may be asked to breathe in or out and hold their
breath for short periods to improve visualization of the heart.
Young children (approximately 2 months to 2 years of age) may require
sedation to enable a thorough TTE examination. In this age group, distraction
techniques alone are often inadequate to ensure patient cooperation for the
duration of a complete TTE examination. Sedation protocols, including fasting
recommendations, medications, and monitoring, vary by institution. Pediatric
providers should be familiar with the protocols and recommendations of
their local echocardiography laboratory. If infants are not fasting for a sedated
FIGURE 3-1. Typical examination room in an echocardiography laboratory. The patient is positioned
on an examination table, lying supine or on the left side for various portions of the examination.
Television screens are often mounted within the patient’s line of sight for watching movies or seeing
the real-time acquisition of their own cardiac images.
51
CCIP.indb 51 3/13/18 4:18 PM

FIGURE 3-2. Standard transthoracic echocardiography imaging windows include A, subcostal,

B, parasternal, C, apical, and D, suprasternal. Used with permission of the Mayo Foundation for
Medical Education and Research. All rights reserved.
echocardiography examination, breastfeeding or bottle-feeding during an exam-

ination may in some cases provide enough infant distraction for the examination
to be performed. For toddlers and older children, age-appropriate movies often
are provided in pediatric echocardiography laboratories for distraction purposes.
Parents may consider bringing a smartphone, tablet, or laptop computer with
age-appropriate entertainment and/or other visually distracting toys. Adolescents
may prefer to watch movies or to see their own echocardiography examination
being performed, where this is available.
The time required for complete TTE can range from 30 to 90 minutes,
depending on anatomic complexity, cooperation, need for sedation, and whether
the images are reviewed by a pediatric cardiologist at that time or stored for later
review. In some laboratories, physicians may review the images after the patient
is discharged from the laboratory or even remotely via telemedicine. Parents
should expect to remain in the room with their child for the duration of the
TTE examination.
52
CCIP.indb 52 3/13/18 4:18 PM

Indications for TTE

Neonatal Indications
Pulse oximetry screening for critical congenital heart defects in newborns was
added to the United States Recommended Uniform Screening Panel in 2011,
and this screening is now performed in nearly every state.4 Prior to hospital dis-
charge, a pulse oximeter is placed on the newborn’s right hand and either foot.5
The screening result is considered positive if blood oxygen saturation in either
extremity is less than 90% or if, in 3 measures each separated by 1 hour, satu-
rations remain less than 95% in both extremities or there remains a differential
greater than 3% between extremities. Newborns with a positive screening result
for critical congenital heart defects should undergo TTE, with interpretation of
images by a pediatric cardiologist (locally or via telemedicine) prior to discharge
from the hospital.5,6
Additional indications for TTE in the newborn period include prenatally
diagnosed congenital heart defects, pathologic cardiac murmur or other physical
examination findings consistent with congenital heart defects, concerning chest
radiographic or ECG findings, central cyanosis incompletely responsive to
oxygen administration, and respiratory distress not attributable to pulmonary
causes. It is important to recognize that some newborns with congenital heart
defects and ductal-dependent lesions may “pass” pulse oximetry screening and
be discharged, then later present with severe respiratory distress, cyanosis,
shock, metabolic acidosis, and/or cardiac arrest as the ductus arteriosus closes.4,5
Echocardiography After the Newborn Period

Outside of the newborn period, it may be difficult to determine if and when
TTE is indicated. To help address this, in 2014, a group of pediatric cardiology
experts from multiple professional societies (including the American College
of Cardiology, the American Academy of Pediatrics, the American Heart
Association, and the American Society of Echocardiography) published appro-
priate use criteria for pediatric echocardiography (Table 3-1).7 The appropriate
use criteria are meant to apply to initial pediatric TTE performed in the
outpatient setting for patients without known cardiac disease. Of note, some
institutions may require a pediatric cardiology consultation prior to ordering
echocardiography.
For the purposes of the appropriate use criteria,7 appropriate (A) is defined as
benefits generally outweighing risks; the intervention is thought to be reasonable,
though not always necessary. May be appropriate (M) is defined as potentially
reasonable, depending on patient variables and physician consultation; there may
be a lack of scientific evidence or agreement regarding risks and benefits. Rarely
appropriate (R) indicates generally not reasonable, with no clear benefit to the
53
CCIP.indb 53 3/13/18 4:18 PM

Table 3-1. Appropriate Use Criteria for Outpatient

Pediatric Transthoracic Echocardiography
Indication Rating
Outpatient neonate with
Suspected cardiac abnormality at fetal echocardiography A
Maternal infection during pregnancy or delivery associated with potential A

cardiac sequelae
Maternal phenylketonuria A
Maternal autoimmune disorder, teratogen exposure, or diabetes (normal M

findings or no fetal echocardiography performed)
Isolated echogenic focus on fetal echocardiographic findings R
Cardiac murmur, which is
Pathologic (harsh, loud, or holosystolic; has a diastolic component; or is A

otherwise suspicious)
Presumptively innocent, with signs, symptoms, or findings of cardiac A

disease
Presumptively innocent, with no signs, symptoms, or findings of cardiac R

disease, benign FH
Chest pain in a patient with
Exertional chest pain A
Abnormal ECG findings and nonexertional chest pain A
FH of cardiomyopathy or SCD A
FH of premature coronary artery disease M
Recent onset of fever or recent illicit drug use M
Other symptoms or signs of cardiovascular disease with benign FH and M

normal ECG findings
No other symptoms or signs of cardiovascular disease, with benign FH R

and normal ECG findings
Normal ECG findings or no recent ECG and nonexertional chest pain R
Reproducible chest pain with palpation or deep inspiration R
ECG findings of
Supraventricular tachycardia A
Ventricular tachycardia A
Premature ventricular contractions M
Premature atrial contractions R
Sinus bradycardia or sinus arrhythmia R
54
CCIP.indb 54 3/13/18 4:18 PM


Pediatric Transthoracic Echocardiography, continued
Indication Rating
Palpitations in a patient with
Cardiomyopathy or FH of cardiomyopathy A
FH of a young age (<50 years) at SCD and/or pacemaker or ICD A
placement
Abnormal ECG findings M
Known channelopathy M
FH of channelopathy R
No other signs or symptoms of cardiac disease, benign FH, and normal R
ECG findings or no recent ECG
Syncope in a patient with
FH of a young age (<50 years) at SCD and/or pacemaker or ICD A
placement
FH of cardiomyopathy A
Abnormal ECG findings A
Exertional syncope or unexplained postexertional syncope A
Unexplained presyncope M
FH of channelopathy M
Probable neurocardiogenic (vasovagal) syncope R
Syncope or presyncope with known noncardiovascular cause R
With or without palpitations and with no recent ECG R
No other signs or symptoms of cardiac disease, benign FH, and normal R
ECG findings
Other signs or symptoms
Central cyanosis A
Signs of congestive heart failure, including respiratory distress, poor A
pulse, feeding difficulty, decreased urine output, edema, and/or
hepatomegaly
Signs or symptoms of endocarditis with negative or no available blood A
culture findings
Unexplained fever without evidence of cardiac or systemic involvement M
Scoliosis and/or chest wall deformities preoperatively M
Isolated acrocyanosis R
Fatigue with no other signs or symptoms of cardiac disease, benign FH, R
and normal ECG findings
Continued
55
CCIP.indb 55 3/13/18 4:18 PM


Indication Rating
Abnormal prior test results
Chromosomal abnormality known to be associated with cardiac disease A
Genotype positive for cardiomyopathy A
Chest radiographic findings suggestive of cardiac disease or abnormal A

ECG findings
Desaturation at pulse oximetry (<95% outside of the newborn period) A
Positive blood culture findings suggestive of endocarditis A
Abnormal cardiac biomarkers A
Abnormal barium swallow findings or bronchoscopic results suggestive A

of vascular ring
Previously normal echocardiographic findings with new signs or symp- A

toms of cardiac disease or new FH of heritable heart disease
Chromosomal abnormality with undefined risk of cardiac disease M
Known channelopathy M
Increased antistreptolysin O titers without suspicion for rheumatic fever R
Previously normal echocardiographic findings with no change in signs or R

symptoms or FH
Systemic diseases
Storage diseases, mitochondrial and metabolic disorders, or muscular A

dystrophy
Suspected syndrome or extracardiac anomaly known to be associated A

with cardiac disease
Abnormalities of cardiac or visceral situs A
Autoimmune disorders, systemic lupus erythematosus, HIV A
Suspected or confirmed Kawasaki disease, Takayasu arteritis, acute A

rheumatic fever
Suspected or known connective tissue disorder (Marfan syndrome, A

Loeys-Dietz syndrome, or other aortopathies)
Sickle cell disease or other hemoglobinopathy A
Cancer, prior to or during chemotherapy A
Renal failure A
Systemic hypertension A
Suspected pulmonary hypertension A
56
CCIP.indb 56 3/13/18 4:18 PM


Indication Rating
Stroke A
Cancer, without chemotherapy M
Failure to thrive M
Hepatic disorders M
Obesity with obstructive sleep apnea or other cardiac risk factors M
Obesity without other cardiac risk factors R
Diabetes mellitus R
Lipid disorders R
Gastrointestinal disorders not otherwise specified R
Seizures, neurological or psychiatric disorders R
Asymptomatic patients with FH of the following
Any nonischemic cardiomyopathy (hypertrophic, dilated, restrictive, A

noncompaction)
Genetic disorder at high risk for cardiovascular involvement A
Marfan syndrome or Loeys-Dietz syndrome A
Heritable pulmonary artery hypertension A
Idiopathic pulmonary artery hypertension M
Congenital heart disease (any, including bicuspid aortic valve and aortic M
coarctation)
Connective tissue disorder other than Marfan syndrome or Loeys-Dietz M

syndrome
Unexplained sudden death <50 years of age M
Premature coronary artery disease <50 years of age R
Channelopathy R
Pulmonary arterial hypertension other than idiopathic and heritable R
Disease at high risk for cardiac involvement (such as diabetes, hyperten- R

sion, obesity)
Unspecified cardiac disease R
Consanguinity R
A, appropriate; M, may be appropriate; R, rarely appropriate; ECG, electrocardiography; FH, family history; ICD,
implantable cardiac defibrillator; SCD, sudden cardiac death. Table adapted from reference 7.
57
CCIP.indb 57 3/13/18 4:18 PM

patient; if TTE is ordered for an indication designated as rarely appropriate,

clinical reasoning should be thoroughly documented in the patient chart. Family
history refers to first-degree relatives only.
Standard Echocardiographic Images and

Applications
Two-Dimensional Imaging
Two-dimensional (2D) imaging is the mainstay of anatomic diagnosis in pedi-
atric echocardiography. Images are obtained in stacks of moving clips or sweeps
in the standard imaging planes (Figure 3-2), allowing the reviewer to mentally
create a 3-dimensional (3D) image of the heart for diagnosis. Images may then
be obtained from additional (nonstandard) windows for further definition or
clarification of structures as needed. Examples of primary imaging planes are
shown in Figures 3-3, 3-4, 3-5, and 3-6.
The convention of obtaining and interpreting pediatric echocardiographic
images involves the use of a segmental approach.1,2 The goal is to assess all
cardiac and major vascular segments and connections. Subcostal views allow
determination of abdominal and cardiac situs, as well as cardiac position.
Through multiple imaging planes, venous connections to the atria, atrial sided
ness, atrioventricular connections, ventricular relationship, ventriculoarterial
connections, and great vessels are then assessed. Once cardiac segments and
their relationships are determined, further evaluation for intra- or extracardiac
shunts, cardiac valve abnormalities, cardiac chamber size, biventricular function,
and hemodynamics are assessed. Guidelines are available for both the qualitative
and quantitative performance and the interpretation of pediatric TTE.3,8
Doppler Imaging
Spectral Doppler is used to estimate blood flow velocities and pressure gradients,
as previously described. There are 2 types of spectral Doppler imaging—con-
tinuous wave (CW) and pulse wave (PW)—both of which are used during a
standard examination. CW Doppler is used to measure the maximum velocity
along the ultrasound beam. For this reason, it is prone to error via contamination
from other flows that may occur in the line of interrogation. This type of
Doppler can record very–high-velocity flows, because there is no limit of
detection scale. PW Doppler differs in that it is range gated, meaning that the
sonographer sets a point of interest for interrogation along the ultrasound beam,
and the velocities from this sample volume are displayed. The advantage of PW
Doppler is the ability to determine the flow velocity at a specific point, although
the disadvantage is that the maximum velocity that PW Doppler can display is
limited. By convention, velocities traveling toward the transducer are displayed
58
CCIP.indb 58 3/13/18 4:18 PM

FIGURE 3-3. Echocardiographic images obtained from the subcostal imaging window (see Figure
3-2 for this location). A. Transverse abdominal image is used for the determination of abdominal
situs; situs solitus (normal) is shown. B. Subcostal sagittal image shows normal connection of
the venae cavae to the right atrium (RA). The atrial septum is profiled well in this plane to detect
a defect. C. Subcostal 4-chamber view. D. Zoomed-in view of the atrial septum shows a patent
foramen ovale (PFO) with left-to-right shunt (red color flow across the septum). IVC = inferior
vena cava, LA = left atrium, LV = left ventricle, RPA = right pulmonary artery, RV = right ventricle,
SVC = superior vena cava.
above the baseline on the Doppler tracing, and velocities traveling away from the
transducer are displayed below the baseline (Figure 3-5, D, and Figure 3-6, C).
The echocardiography machine shows color Doppler images by superim-
posing a color-coded “velocity map” over a 2D image. Color Doppler imaging
displays average rather than maximum velocities. By convention, flow away from
the transducer is displayed as blue in color, whereas flow toward the transducer is
displayed as red; the acronym “BART,” for “blue away, red toward,” may be used
as a memory aid. High-velocity flows (such as through areas of stenosis) may
appear speckled in color, known as “aliasing.” An example is shown in Figure
3-3, D, where a left-to-right atrial shunt through a patent foramen ovale (PFO)
is displayed as red in color as the blood flows toward the transducer.
59
CCIP.indb 59 3/13/18 4:18 PM

FIGURE 3-4. Echocardiographic images obtained from the parasternal imaging window (see Figure
3-2 for this location). A. Parasternal long-axis view provides assessment of the mitral and aortic
valves, left ventricular (LV) function, and some types of ventricular septal defects. B. Parasternal
short-axis view at the base of the heart is used to assess aortic, tricuspid, and pulmonary valves;
right ventricular (RV) outflow tract; coronary artery origins and proximal course; and some types of
ventricular septal defects. C. Parasternal short-axis view at the midventricular level allows assessment
of ventricular function. A color sweep through the ventricular septum in this position provides
assessment of ventricular septal defects. D. An M-mode image was obtained at the same level as the
image in C; the LV cavity diameter is measured at end-diastole (d) and end-systole (s) to calculate
fractional shortening and ejection fraction, as described in the text. Ao = aorta, LA = left atrium,
RA = right atrium.
Assessment of Ventricular Systolic Function

Multiple methods are available for the assessment of ventricular systolic func-
tion.1,2,8,9 Left ventricular (LV) systolic function is typically reported as an ejec-
tion fraction (EF), representing the estimated or calculated percentage of blood
volume ejected from the ventricle during each cardiac cycle. With 1 method
of EF calculation, M-mode measurements are used (Figure 3-4, D). These are
obtained from the parasternal short-axis view of the LV, at the midventricular
level. The ultrasound beam is directed through this cross-section of the ventricle
60
CCIP.indb 60 3/13/18 4:18 PM

FIGURE 3-5. Echocardiographic images obtained from the apical imaging window (see Figure 3-2
for the location). A. Standard apical 4-chamber view allows evaluation of mitral and tricuspid valves,
cardiac chamber size, and biventricular function. B. Apical 2-chamber view allows further assessment
of left atrial (LA) and left ventricular (LV) size, LV function, and mitral valve pathologic findings.
C. Apical long-axis view allows assessment of the LV outflow tract and the aortic valve. D. Pulse
wave Doppler measurement was obtained by selecting a volume of interest in the LV outflow tract
just proximal to the aortic valve leaflets. Along with measurement of the aortic annulus diameter, the
velocity time integral from this pulse wave Doppler measurement can be used to estimate cardiac
output. Ao = aorta, RA = right atrium, RV = right ventricle.
like a virtual “ice pick” being dropped through this location. The internal LV
diameters in end-diastole and end-systole are measured. These measurements are
extrapolated to estimate ventricular volumes and yield a calculated EF. Although
M-mode measurements are used widely in clinical practice, with this method,
varied LV geometry is not taken into account, which may result in error when
estimating ventricular function.
Another common technique of measuring EF is the Simpson method, also
called the “method of disks.” The endocardial borders of the LV are traced in
both end-diastole and end-systole in the apical 4- and 2-chamber views. The
computer then divides the traced areas into disks, sums the volumes of these
61
CCIP.indb 61 3/13/18 4:18 PM

FIGURE 3-6. Echocardiographic images obtained from the suprasternal imaging window (see
Figure 3-2 for the location). A. Suprasternal coronal (“crab”) view allows visualization of pulmonary
veins entering the left atrium (LA). B. Suprasternal long-axis view of the aortic arch shows a
normal-caliber arch with no evidence of coarctation; the right pulmonary artery (RPA) is seen in
cross-section posterior to the ascending aorta (Ao). C. Continuous wave Doppler image obtained
with the ultrasound beam directed parallel to the descending aorta shows a normal maximal velocity
of 1.2 m/s, which further supports the fact that there is no evidence of coarctation in this patient.
LIV = left innominate vein, LLPV = left lower pulmonary vein, LUPV = left upper pulmonary vein,
RLPV = right lower pulmonary vein, RUPV = right upper pulmonary vein, SVC = superior vena
cava.
disks to obtain estimated ventricular volumes, and calculates an EF. This method
better accounts for LV geometry but does require good 2D images with traceable
endocardial borders. Both of these methods are preload, afterload, and heart
rate dependent.
Myocardial “Strain” Imaging

Myocardial “strain” imaging, also known as deformation imaging or speckle
tracking, is used in an increasing number of laboratories as an adjunct to the
previously discussed methods of assessing ventricular function.1,2,9 Strain analysis
requires good 2D images of the ventricular walls. The computer software
62
CCIP.indb 62 3/13/18 4:18 PM

tracks the ventricular walls (by tracking multiple “speckles” within the image)
throughout the cardiac cycle to assess wall deformation. Deformation occurs as
parts of the myocardial wall move at differing velocities, allowing the ventricle
to deform or change shape (fiber shortening, thickening, and rotation). Strain
imaging enables assessment of regional wall motion abnormalities. More
negative numbers of systolic strain indicate better function; for example, if a
patient’s global LV systolic strain is measured at −20%, which is less than the
echocardiography laboratory–defined cutoff of −18%, then the strain is normal.
Common indications for strain imaging include history of cardiotoxic chemo-
therapy medications or chest radiation therapy and screening and following up
patients with different types of cardiomyopathies, heart failure, and postcardiac
transplantation. In patients with cardiomyopathy, strain values may be abnormal
even before changes are visualized with 2D echocardiography. This is an active
area of research.
3D Imaging
Many centers are using 3D echocardiography to assist with preoperative plan-
ning, provide guidance for interventional cardiac catheterization, and assess ven-
tricular volumes and function.1,2,10 3D images of valve pathologic findings, such
as in patients with atrioventricular canal defects, are reported to be particularly
useful to the cardiac surgeon who is planning a repair. However, image resolution
at 3D echocardiography remains inferior to 2D images at the present time, and
patients without excellent 2D images
will have poor 3D images. Additional
current limitations of 3D imaging include
the availability of 3D-capable TTE and
transesophageal echocardiography (TEE)
probes for small patients (3D TEE probes
are currently only approved for patients
>30 kg), additional time for image acqui-
sition and postprocessing, and the need
for breath holds.10 These issues should
improve as 3D technology continues to
advance and as use in pediatrics becomes
FIGURE 3-7. Three-dimensional echo
more widespread. An example of 3D cardiographic image. The arrow indicates a
echocardiography is shown in Figure 3-7. mitral valve cleft.
Advanced Echocardiographic Modalities

Advanced imaging modalities, such as transesophageal, intracardiac, and stress
echocardiography, are also performed in the pediatric population. In nearly all
cases, these modalities are used after initial TTE and will be ordered under the
63
CCIP.indb 63 3/13/18 4:18 PM

guidance of a pediatric cardiologist. The following provides a brief overview of

procedures and indications for each test.
Transesophageal Echocardiography
TEE is performed by placing a TEE probe into the esophagus. The esophagus
is located directly behind the left atrium, which allows for an excellent imaging
window without the interference of chest wall structures or lungs. The probe can
be rotated and/or flexed to obtain optimal images and can be advanced into the
stomach (transgastric imaging) to look “up” at the heart, as well. Adult, pediatric,
and micro-TEE probes are available, with micro-TEE probe use reported in
neonates and infants weighing as little as 1.7 kg without complications.11

Guidelines for use of TEE in pediatrics have been published.12 The most
common indication in pediatrics is intraoperative assessment during cardiac sur-
gery. In most patients with CHD who are undergoing repair, TEE is performed
in the operating room immediately before and after surgery to confirm diagnoses
and assess surgical results, respectively. TEE can also be used in the cardiac
catheterization laboratory to guide procedures such as device closure of atrial or
ventricular septal defects, as well as aid catheter manipulation during challenging
cases. In these cases, TEE is typically performed with general anesthesia.
In the outpatient or acute inpatient setting, TEE may be performed with
sedation or general anesthesia, depending on the location of the test, patient age,
and hospital protocol. Patients should expect to have an intravenous catheter
placed for medication administration, along with ECG leads and a blood
pressure cuff for continuous monitoring of vital signs. As the patient is sedated, a
mouth guard is placed, and the probe is introduced into the mouth. The patient
may then be asked to swallow to facilitate introduction of the probe into the
esophagus, depending on the patient’s state of awareness and cooperation. The
examination usually takes 30 to 60 minutes; however, the patient needs to be
monitored until sedation wears off. A sore throat is common after the procedure.
There is a small risk of further complications, including damage to the teeth,
mouth, throat, or stomach. Esophageal rupture is a rare but serious complication,
and patients should be instructed to report to the emergency room with any
bleeding or sharp pain from this area.
Indications for TEE include a nondiagnostic TTE study, such as in a patient
with suboptimal TTE images and suspected CHD or a patient with intracardiac
baffles that are difficult to image (status post Mustard, Senning, Warden, or
Fontan procedures).12 TEE performed with agitated saline as contrast material
may be indicated to exclude a PFO in a patient who has a history of stroke or
who will be undergoing transvenous pacemaker insertion. Additional indications
include suspected endocarditis when TTE findings are negative or inconclusive,
evaluation for cardiac thrombus (such as prior to cardioversion), evaluation of
64
CCIP.indb 64 3/13/18 4:18 PM

prosthetic valve pathologic findings, and postoperative monitoring in patients

with open chest and minimal imaging windows.
Intracardiac Echocardiography
Intracardiac echocardiography (ICE) is performed in the cardiac catheterization
laboratory.1,13,14 This technique allows echocardiographic images to be obtained
from within the heart to guide interventional procedures. ICE probes are avail-
able in 8-F or 10-F sizes and are advanced through the systemic veins into the
right side of the heart. Image quality and measurements are comparable to TEE,
and ICE may be used as an alternative to TEE in the catheterization laboratory
during device closures of atrial septal defects or PFOs, cardiac biopsies, valve
procedures, and/or electrophysiology procedures.
Stress Echocardiography
Although stress echocardiography has been performed in pediatrics since the
1980s, it remains largely underused in this patient population.1 During stress
echocardiography, baseline TTE images are obtained while the child is at rest,
with further sets of images obtained after stress and during recovery. These sets
of images are compared to assess hemodynamic and functional changes, which
allows for improved understanding of cardiovascular physiology in the child’s
typical “active” state.
The applied stressor for this test is most commonly exercise, either treadmill
or cycle ergometry, though pharmacological or other stressors may be used.
Dobutamine is the most common pharmacological agent used for stress echocar-
diography in children, with atropine administered for heart rate augmentation.1
Stress echocardiography is indicated when there is suspicion for ischemic
myocardial perfusion defects—for example, in patients with anomalous coronary
artery origins, coronary artery fistulas, Kawasaki disease with giant or persistent
aneurysms, and transposition of the great arteries after an arterial switch proce-
dure.1 The test is also indicated to evaluate hemodynamic responses to stress in
some noncoronary forms of heart disease, such as in the evaluation of ventricular
function in patients with postoperative tetralogy of Fallot or Fontan circulation
or to evaluate the change in cardiac pressures with stress in some cases of valve
pathologic findings or hypertrophic cardiomyopathy.1
There are no specific contraindications to stress echocardiography in children;
however, the decision to undergo stress echocardiography must be carefully
weighed for high-risk patients, such as those with hemodynamically significant
aortic valve stenosis or hypertrophic obstructive cardiomyopathy.1 The most
common complication of dobutamine stress echocardiography is emesis in 10%
to 20% of children at peak medication dosing and typically resolves quickly on
discontinuation of the drug.1 Serious adverse events during exercise or pharma-
cological stress echocardiographic testing are rare.
65
CCIP.indb 65 3/13/18 4:18 PM

Fetal Echocardiography
Fetal echocardiography can be performed transabdominally or transvaginally,
as early as the first trimester of pregnancy (Figure 3-8). Most scans are trans-
abdominal, with the optimal time for an initial scan between 18 and 22 weeks’
gestation.1,15,16 The most common indication for fetal echocardiography is a
suspected cardiovascular abnormality at obstetric US; a diagnosis of CHD in the
fetus is confirmed with fetal echocardiography in 40% to 50% of these patients.16
The risk of CHD is approximately 1% in the general population, and fetal
echocardiography is often recommended when fetal or maternal risk factors
increase this risk to at least 2% to 3%.16 Many maternal and fetal risk factors
are associated with increased risk of fetal CHD. Not all adult providers are
aware of these indications or of family history, and, in some cases, a pediatric
care provider may provide the referral for fetal echocardiography. Common
indications for fetal echocardiographic referral are listed in Table 3-2. Prenatal
diagnosis of CHD allows time for counseling of parents and management
FIGURE 3-8. Normal 4-chamber view at fetal echocardiography. Ao = aorta, LA = left atrium,
LV = left ventricle, RA = right atrium, RV = right ventricle.
66
CCIP.indb 66 3/13/18 4:18 PM

Table 3-2. Indications for Fetal Echocardiography

Indication Rating
Maternal indications
Diabetes mellitus or phenylketonuria A
Autoantibody positive (SSA or SSB positive) A
Medications: NSAIDs in the third trimester, retinoic acid, ACE A

inhibitors
Rubella infection in the first trimester or other infection with suspicion A

of fetal myocarditis
Medications: NSAIDs in the first or second trimester, anticonvulsants, M

lithium, vitamin A, paroxetine
Medications: SSRIs (other than paroxetine), vitamin K antagonists R

(warfarin)
Infection other than rubella with seroconversion only R
Fetal indications
Suspicion of CHD or clinically significant extracardiac anomaly at A

obstetric scanning
Increased nuchal translucency at obstetric scanning (>95th percentile) A
Karyotype abnormality A
Bradycardia, tachycardia, or frequent or persistent irregular rhythm A
Hydrops or effusions A
Monochorionic twinning A
First-degree relative with CHD (mother, father, or sibling of fetus) A
First-degree relative with disorder of Mendelian inheritance associated A

with CHD
Second-degree relative with CHD M
Umbilical cord or placental abnormality M
Intra-abdominal venous abnormality M
CHD in a relative other than first or second degree R

A, appropriate (estimated >2% risk of CHD); M, may be appropriate (estimated risk of >1% but <2%); R, rarely
appropriate (estimated ≤1% risk); ACE, angiotensin-converting enzyme; CHD, congenital heart disease; NSAID,
nonsteroidal anti-inflammatory drug; SSRI, selective serotonin reuptake inhibitor. Reprinted with permission from
reference 16. ©2014 American Heart Association, Inc.
67
CCIP.indb 67 3/13/18 4:18 PM

decisions regarding location and timing of delivery. Fetal echocardiography

can also help in diagnosing and managing fetal arrhythmia, such as fetal
supraventricular tachycardia.
Key Points
•• Echocardiography is cardiac US, in which sound waves are used to image the
heart. Echocardiography does not involve radiation, and TTE is considered
minimal risk at all age levels, from fetus through adulthood.
•• TTE is the cornerstone of cardiac imaging in pediatrics and is used to accu-
rately diagnose nearly all forms of CHD, along with providing a noninvasive
hemodynamic and functional cardiac assessment.
•• Patients with suboptimal 2D imaging windows, such as those with obesity or
multiple prior operations, as well as those with indications such as suspected
endocarditis, vascular rings, or connective tissue disorders, might require other
imaging modalities in addition to TTE.
•• Appropriate use criteria are available to help guide clinicians as to when initial
outpatient TTE may or may not be appropriate.
•• Fetal echocardiography is optimally performed between weeks 18 and 22
of gestation, and clinicians should be familiar with the indications for fetal
echocardiography, including a first-degree relative of the fetus (parent or
sibling) who has CHD.
Resources for Families

•• Echocardiogram (Children’s Hospital of Pittsburgh Heart Institute).
www.chp.edu/our-services/heart/patient-procedures/echo
•• Transesophageal Echocardiogram (Children’s Hospital of Pittsburgh Heart
Institute). www.chp.edu/our-services/heart/patient-procedures/tee
•• Fetal Echocardiogram Test (American Heart Association). www.heart.org/
HEARTORG/Conditions/CongenitalHeartDefects/SymptomsDiagnosis
ofCongenitalHeartDefects/Fetal-Echocardiogram-Test_UCM_315654_
Article.jsp#
•• Transesophageal Echocardiography (American Heart Association). www.
heart.org/HEARTORG/Conditions/HeartAttack/DiagnosingaHeartAttack/
Transesophageal-Echocardiography-TEE_UCM_441655_Article.jsp
•• Echocardiogram (The Mayo Clinic). www.mayoclinic.org/tests-procedures/
echocardiogram/basics/definition/prc-20013918
68
CCIP.indb 68 3/13/18 4:18 PM

References
1) Eidem BW, O’Leary PW, Cetta F, eds. Echocardiography in Pediatric and Adult Congenital Heart
Disease. 2nd ed. Philadelphia, PA: Wolters Kluwer Health; 2015
2) Heydarian HC, Kimball TR. Echocardiography: basic principles and imaging. In: Allen HD,
Shaddy RE, Penny DJ, Feltes TF, Cetta F, eds. Moss & Adams’ Heart Disease in Infants, Children,
and Adolescents, Including the Fetus and Young Adult. 9th ed. Philadelphia, PA: Wolters Kluwer;
2016:303–337
3) Lai WW, Geva T, Shirali GS, et al; Task Force of the Pediatric Council of the American
Society of Echocardiography; Pediatric Council of the American Society of Echocardiography.
Guidelines and standards for performance of a pediatric echocardiogram: a report from the
Task Force of the Pediatric Council of the American Society of Echocardiography. J Am Soc
Echocardiogr. 2006;19(12):1413–1430
4) Oster ME, Kochilas L. Screening for critical congenital heart disease. Clin Perinatol. 2016;
43(1):73–80
5) Kemper AR, Mahle WT, Martin GR, et al. Strategies for implementing screening for critical
congenital heart disease. Pediatrics. 2011;128(5):e1259–e1267
6) Mahle WT, Newburger JW, Matherne GP, et al; American Heart Association Congenital Heart
Defects Committee of the Council on Cardiovascular Disease in the Young, Council on Cardio
vascular Nursing, and Interdisciplinary Council on Quality of Care and Outcomes Research;
American Academy of Pediatrics Section on Cardiology And Cardiac Surgery; Committee On
Fetus And Newborn. Role of pulse oximetry in examining newborns for congenital heart disease:
a scientific statement from the AHA and AAP. Pediatrics. 2009;124(2):823–836
7) Campbell RM, Douglas PS, Eidem BW, Lai WW, Lopez L, Sachdeva R. ACC/AAP/AHA/
ASE/HRS/SCAI/SCCT/SCMR/SOPE 2014 appropriate use criteria for initial transthoracic
echocardiography in outpatient pediatric cardiology: a report of the American College of
Cardiology Appropriate Use Criteria Task Force, American Academy of Pediatrics, American
Heart Association, American Society of Echocardiography, Heart Rhythm Society, Society
for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed
Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Pediatric
Echocardiography. J Am Coll Cardiol. 2014;64(19):2039–2060
8) Lopez L, Colan SD, Frommelt PC, et al. Recommendations for quantification methods during
the performance of a pediatric echocardiogram: a report from the Pediatric Measurements
Writing Group of the American Society of Echocardiography Pediatric and Congenital Heart
Disease Council. J Am Soc Echocardiogr. 2010;23(5):465–495, quiz 576–577
9) Mertens LL, Friedberg MK. Echocardiographic assessment of cardiac dimensions, cardiac
function, and valve function. In: Allen HD, Shaddy RE, Penny DJ, Feltes TF, Cetta F, eds.
Moss & Adams’ Heart Disease in Infants, Children, and Adolescents, Including the Fetus and Young
Adult. 9th ed. Philadelphia, PA: Wolters Kluwer; 2016:339–372
10) Simpson J, Lopez L, Acar P, et al. Three-dimensional echocardiography in congenital heart
disease: an expert consensus document from the European association of cardiovascular imaging
and the American society of echocardiography. J Am Soc Echocardiogr. 2017;30(1):1–27
11) Zyblewski SC, Shirali GS, Forbus GA, et al. Initial experience with a miniaturized multiplane
transesophageal probe in small infants undergoing cardiac operations. Ann Thorac Surg.
2010;89(6):1990–1994
12) Ayres NA, Miller-Hance W, Fyfe DA, et al; Pediatric Council of the American Society
of the Echocardiography. Indications and guidelines for performance of transesophageal
echocardiography in the patient with pediatric acquired or congenital heart disease: report from
the task force of the Pediatric Council of the American Society of Echocardiography. J Am Soc
Echocardiogr. 2005;18(1):91–98
69
CCIP.indb 69 3/13/18 4:18 PM

13) Liu Z, McCormick D, Dairywala I, et al. Catheter-based intracardiac echocardiography in the

interventional cardiac laboratory. Catheter Cardiovasc Interv. 2004;63(1):63–71
14) Medford BA, Taggart NW, Cabalka AK, et al. Intracardiac echocardiography during atrial septal
defect and patent foramen ovale device closure in pediatric and adolescent patients. J Am Soc
Echocardiogr. 2014;27(9):984–990
15) American Institute of Ultrasound in Medicine. AIUM practice guideline for the performance of
fetal echocardiography. J Ultrasound Med. 2013;32(6):1067–1082
16) Donofrio MT, Moon-Grady AJ, Hornberger LK, et al; American Heart Association Adults
With Congenital Heart Disease Joint Committee of the Council on Cardiovascular Disease
in the Young and Council on Clinical Cardiology, Council on Cardiovascular Surgery and
Anesthesia, and Council on Cardiovascular and Stroke Nursing. Diagnosis and treatment of
fetal cardiac disease: a scientific statement from the American Heart Association. Circulation.
2014;129(21):2183–2242
70
CCIP.indb 70 3/13/18 4:18 PM

CHAPTER 4
Basics of Exercise
Testing
Brandon Morrical, MD, FAAP, and Jonathan N. Johnson, MD,
FACC, FAAP
Introduction
Exercise testing is useful for evaluating both adults and children. The terms exercise
testing and stress testing are often used interchangeably. Exercise test is typically
preferred when exercise is being performed; stress testing can be used to describe
either exercise or pharmacological means to simulate exercise.
The goal of exercise testing is to implement physiological stress to elicit abnor-
malities or findings that are not present at rest and to measure exercise capacity.
Sometimes prognostic information can be inferred from exercise testing, as well,
or serial tests may aid in timing the intervention. Exercise testing can be used for
a variety of different indications, which are described in detail later in the chapter.
It is performed at most large centers, with a physician or exercise physiologist
present during testing.
Physiology
Exercise testing is used to assess the cardiopulmonary system at both submaximal
and maximal capacity. The cardiopulmonary system provides blood flow and
oxygen to meet the metabolic needs of the body. Identifying the limits of this
system can be useful for assessing prognosis and/or guiding therapy. General
practitioners are not expected to interpret the results of an exercise test; rather, they
will apply the interpretation of the exercise physiologist to the care of the patient.
71
CCIP.indb 71 3/13/18 4:18 PM

Multiple cardiac and respiratory variables are typically tested. In a basic

exercise electrocardiographic (ECG) test, the examiner is interested in exercise
duration, heart rate and blood pressure responses, and ECG changes. When
gas exchange analysis and pulse oximetry are added to the test, a new set of
information can be gleaned, including maximum oxygen uptake. Although it
is unnecessary for the primary care practitioner to know the minutiae of all the
different test results, it may be useful to know the background and purpose of
the most commonly reported variables measured. Normal parameters for these
variables on the basis of age, sex, and body size (weight or body surface area)1,2
are described herein.
Heart Rate
Heart rate is a good measure of the degree of effort. However, it can be affected
by other variables, such as medications, sinus node dysfunction, or arrhythmia.
The maximum expected heart rate for children and adolescents is 200 beats/min.
For subjects over 21 years of age, the maximal predicted heart rate is calculated
as 220 − age, with the result given in beats per minute.
Blood Pressure
Blood pressure is related to peripheral resistance and cardiac output and nor-
mally increases during exercise as cardiac output increases. Systemic resistance
declines with increasing exercise. The maximum systolic blood pressure can
exceed 200 mm Hg in teenagers. A lack of increase (or even a decrease) in blood
pressure during exercise can be a sign of cardiac dysfunction.3
Exercise Time
The exercise time is simply the time exercised during the test. It will vary
according to the protocol used. A longer time should indicate better exercise
tolerance and endurance. Most tests are designed to last 10 to 12 minutes for
an average patient.
Maximum Oxygen Uptake

This is the greatest amount of oxygen consumed during exercise. It is commonly
used to measure functional aerobic capacity, exercise tolerance, or endurance.
Metabolic Equivalents
Metabolic equivalents represent the energy “cost” of exercise. The average subject
uses 1 metabolic equivalent per minute at rest. Multiples of this are used to
indicate the amount of exercise performed.
72
CCIP.indb 72 3/13/18 4:18 PM

Basics of Exercise Testing
Ventilatory Anaerobic Threshold

The ventilatory anaerobic threshold is the point at which the body shifts from
aerobic to anaerobic metabolism, as the exercise demand uses up the patient’s
oxygen capacity. This parameter is determined by evaluating the graphic plot of
minute ventilation versus oxygen uptake or carbon dioxide output.
Oxygen Pulse
Oxygen pulse is the ratio of amount of oxygen consumed to heart rate. It is an
indirect estimate of stroke volume.
Types of Exercise Tests

Exercise testing most commonly requires an exercise machine. The apparatus
that measures output is called an ergometer, of which there are 2 primary types:
treadmills and cycles. Other types are available, including arm ergometers for
those with lower-extremity limitations or rowers for more full-body exercise, but
treadmills and cycles are by far the most popular. Each has advantages and dis-
advantages, and the final choice is made by the physician or exercise physiologist
who is overseeing the test. Cycles are safer than treadmills but are more difficult
to calibrate. However, higher maximum oxygen intake can be achieved by using a
treadmill because more muscle groups are used when walking and running than
when cycling.4 A typical setup for an exercise laboratory is shown in Figure 4-1.
Pharmacological stress tests can be performed for young children or patients
who are unable to exercise by using an ergometer. Multiple medications can
be used, depending on the primary indication for the test, but all have the goal
of inducing physiological stress, often by increasing heart rate and myocardial
oxygen consumption. Pharmacological stress tests may be performed concur-
rently with echocardiography or other imaging studies to examine the effects
on the heart.
Exercise Protocols
Multiple protocols exist for exercise testing, almost all of which were developed
primarily for adults and have been adapted for children. The primary goal of
most protocols is to reproducibly reach a maximum effort in a limited amount
of time, preferably around 10 to 12 minutes. There are 3 common types
of protocols4,5:
•• Multistage incremental: In these protocols, the workload increases every 2
to 3 minutes, allowing for a “steady state” at each interval. This includes the
commonly used Bruce treadmill protocol.
73
CCIP.indb 73 3/13/18 4:18 PM

FIGURE 4-1. A typical setup for an exercise laboratory. The computer on the far left displays
continuous electrocardiographic information and allows the printing of strips directly from the
console. The middle computer is for cardiopulmonary measurements such as volume of oxygen
uptake and respiratory exchange ratio. On the right is the treadmill ergometer, which changes
speed and incline at specific intervals, depending on the protocol used. On the far right is a bed
for recovery after the test.
•• Progressive: In these protocols, the workload increases every minute (progres-

sive incremental) or continuously (ramp). By using this type of protocol, one
can achieve a maximal test more quickly, though without any periods of steady
state during the test.
•• Constant work: In these protocols, there is no change in work for 5 to 10 min-
utes. This results in a submaximal test but may be useful in correlating daily
activities and stress when compared to a maximal test. This is not commonly
used for children.
Exercise testing can also be used to diagnose or evaluate pulmonary disease, such
as asthma. Certain protocols may be useful to diagnose exercise-induced asthma.
On occasion, the physician or exercise physiologist supervising the test may also
modify the protocol to answer a specific clinical question.
When traditional exercise testing is too stressful or dangerous, a 6-minute
walk test can be used. This is commonly done for patients with heart failure and
pulmonary hypertension. It entails walking for 6 minutes and recording the
distance covered in that time. While a single test is not as useful, this can be an
easy serial test for follow-up and documentation of symptom progression.
74
CCIP.indb 74 3/13/18 4:18 PM

Indications
Exercise testing is used for a wide variety of indications and clinical situations
in the pediatric population. Modified from the American Heart Association
guidelines, the following are the most common indications for pediatric exercise
testing5–7:
1. Evaluate signs and symptoms induced by exercise.
•• These can include chest pain, palpitations, or syncope when associated
with exercise.
2. Assess or identify abnormal response to exercise.
•• Typically in children with existing cardiac, respiratory, or vascular disorders
•• Can include assessment of arrhythmias or ischemia
3. Assess the effectiveness of medical or surgical treatments.
•• Including surgery for congenital heart disease (CHD) or after ablation
of arrhythmia
4. Assess functional capacity.
•• May be helpful for assessing ability for recreational, athletic, or vocational
activities
5. Determine the prognosis.
•• Baseline and serial examinations can aid in estimating the prognosis in con-
ditions such as heart failure, cardiomyopathy, and neuromuscular disorders.
6. Estimate baseline data.
•• Prior to the institution of cardiac, pulmonary, or musculoskeletal
rehabilitation
•• Prior to cardiac surgery
Exercise testing may be used differently by different providers. There are very few
clinical situations in which exercise testing is absolutely indicated, though it can
provide additional helpful information in a broad spectrum of pediatric diseases.
The age of the patient must also be considered in assessing the feasibility of
exercise testing. Typically, the lower age limit of patients able to successfully
complete a traditional exercise test on an ergometer is 5 years old. As children
get older, the compliance with the test and the reliability of the data collected
usually improve.8 Policies may vary among centers as to the ages of children they
are willing to test.
Contraindications
Previous investigators have listed multiple absolute and relative contraindications
to exercise testing in pediatrics, mostly extrapolated from adult data. However,
as testing in the pediatric population has become more common and better
understood, there are now few contraindications. Some patient populations are
clearly at higher risk for events during exercise testing and require additional
precaution and supervision, but most can still participate in testing if clinically
75
CCIP.indb 75 3/13/18 4:18 PM

indicated. For these higher-risk groups, a pediatric cardiologist or other specialist

with training in exercise physiology should be involved in the decision-making
process and potentially in the supervision of the exercise test, as well. Despite
the precautions, some of these “higher-risk” categories may include the same
patients in whom exercise testing may be most helpful. Box 4-1 lists some of the
contraindicated and higher-risk patient groups3,5:
Preparing for the Test

Patients often feel more prepared for and less anxious about a test if they have
reassuring information regarding the test prior to participation. This is especially
true in pediatrics. The following points can help prepare patients prior to sending
them for exercise testing:
•• The test is not invasive, and there are no needles.
•• The test is not dangerous.
•• The active part of the test only lasts for 10 to 15 minutes.
Box 4-1. High-Risk Patients for Exercise Testing

Contraindications High Risk
Acute myocardial or Pulmonary hypertension
pericardial inflammatory
disease
Acute ischemic disease Long QT syndrome
Severe aortic outflow Cardiomyopathy with congestive heart

obstruction failure or arrhythmia
History of hemodynamically unstable

arrhythmia
Moderate or severe obstructive airway

disease
Hypertrophic cardiomyopathy with symp-

toms, more than mild outflow obstruction,
or arrhythmia
Marfan syndrome
Unexplained syncope with exercise
Suspected myocardial ischemia with

exercise
For high-risk patients, a physician should be present, and a pediatric cardiologist or other specialist should be
involved. Adapted from reference 5.
76
CCIP.indb 76 3/13/18 4:18 PM

•• You may be asked to wear a face mask, but you can still breathe comfortably
(depending on the type of test ordered; see Figure 4-2 for an example of a
face mask).
•• Wear comfortable clothes and activity shoes (preferably no sandals or boots).
Ingest no food or caffeine for 2 to 3 hours prior to the test (specifics vary
by institution).
Key Points
•• Exercise testing is useful for a variety of indications in children with and
without CHD.
•• Exercise testing is safe, with few absolute contraindications.
•• Testing protocols vary substantially, but most can be used successfully in
children.
•• A basic understanding of exercise testing can help the primary care provider
guide the diagnostic and prognostic evaluation.
FIGURE 4-2. A patient participating in a treadmill exercise test. One technician is watching the
electrocardiographic tracings and other the data, while the other technician is watching the patient
and recording the blood pressure, as well as communicating with and encouraging the patient. The
patient is wearing a face mask to record the gas exchange, which enables measurement of oxygen
uptake, carbon dioxide output, and other ventilation variables.
77
CCIP.indb 77 3/13/18 4:18 PM


•• Pediatric Heart Care: Exercise Stress Test (American Family
Children’s Hospital/University of Wisconsin). www.uwhealthkids.org/
cardiology-cardiothoracic-surgery/exercise-stress-test/33782
•• Exercise Stress Test (Children’s Hospital of Pittsburgh). www.chp.edu/
our-services/heart/patient-procedures/stress-test
References
1) Ten Harkel AD, Takken T. Normal values for cardiopulmonary exercise testing in children.
Eur J Cardiovasc Prev Rehabil. 2011;18(4):676–677
2) Blais S, Berbari J, Counil FP, Dallaire F. A systematic review of reference values in pediatric
cardiopulmonary exercise testing. Pediatr Cardiol. 2015;36(8):1553–1564
3) Washington RL, Bricker JT, Alpert BS, et al. Guidelines for exercise testing in the pediatric
age group. From the Committee on Atherosclerosis and Hypertension in Children, Council
on Cardiovascular Disease in the Young, the American Heart Association. Circulation.
1994;90(4):2166–2179
4) Allen HD, Shaddy RE, Penny DJ, Feltes TF, Cetta F. Moss & Adams’ Heart Disease in Infants,
Children, and Adolescents, Including the Fetus and Young Adult. 9th ed. Philadelphia, PA: Wolters
Kluwer; 2016
5) Paridon SM, Alpert BS, Boas SR, et al; American Heart Association Council on Cardiovascular
Disease in the Young, Committee on Atherosclerosis, Hypertension, and Obesity in Youth.
Clinical stress testing in the pediatric age group: a statement from the American Heart
Association Council on Cardiovascular Disease in the Young, Committee on Atherosclerosis,
Hypertension, and Obesity in Youth. Circulation. 2006;113(15):1905–1920
6) Gibbons RJ, Balady GJ, Beasley JW, et al. ACC/AHA guidelines for exercise testing: executive
summary. A report of the American College of Cardiology/American Heart Association Task
Force on Practice Guidelines (Committee on Exercise Testing). Circulation. 1997;96(1):345–354
7) Balady GJ, Arena R, Sietsema K, et al; American Heart Association Exercise, Cardiac
Rehabilitation, and Prevention Committee of the Council on Clinical Cardiology; Council
on Epidemiology and Prevention; Council on Peripheral Vascular Disease; Interdisciplinary
Council on Quality of Care and Outcomes Research. Clinician’s Guide to cardiopulmonary
exercise testing in adults: a scientific statement from the American Heart Association.
Circulation. 2010;122(2):191–225
8) Rhodes J, Ubeda Tikkanen A, Jenkins KJ. Exercise testing and training in children with
congenital heart disease. Circulation. 2010;122(19):1957–1967
78
CCIP.indb 78 3/13/18 4:18 PM

CHAPTER 5
Chest Radiography
Todd T. Nowlen, MD, FACC, and Dianna M. E. Bardo,
MD, FSCCT, FNASCI
Introduction
Historically, chest radiography was integral to the evaluation of patients with con-
genital heart disease (CHD). With the improvement of other technologies, such
as echocardiography, cardiac magnetic resonance imaging, and cardiac computed
tomography, the utility of plain radiography has been diminished. In the tertiary
care setting, advanced imaging modalities are typically the primary diagnostic
tools. However, not all facilities have access to these modalities. Although chest
radiography findings are not specific enough for a definitive diagnosis of CHD,1
it is a readily accessible and inexpensive examination relative to advanced imaging
modalities. Chest radiography may therefore still be a useful diagnostic tool,
particularly in neonates or in pediatric patients when respiratory distress is present.
Historically, some advocated for screening chest radiography to be conducted
in all patients with CHD.2 In a subsequent retrospective review of 81 patients,
it was concluded that performing screening chest radiography in asymptomatic
children over 1 year of age was not useful.3 In another study of 281 patients under
12 years of age, the mean accuracy in distinguishing healthy patients from those
with CHD was 78%, and the overall accuracy in distinguishing specific cardiac
lesions was 71%. In this study, chest radiographic findings alone were not found
to be specific enough to allow diagnosis of cardiac lesions.1 On the basis of these
studies and others, chest radiography is not indicated as the primary diagnostic
imaging modality in patients with known or suspected CHD but may be useful
for the evaluation of respiratory findings or a circulatory support apparatus after
surgical palliation.1,3,4,5 However, children with myocarditis or congestive heart
failure (CHF) may present with other symptoms (most commonly respiratory
illness),6 and chest radiography should be a part of their initial evaluation in
79
CCIP.indb 79 3/13/18 4:18 PM

suspected cases.7 In a recent evaluation of pediatric chest pain guidelines using

Standardized Clinical Assessment and Management Plan methods, chest
radiography was only recommended for patients with fever (oral temperature
>101.1°F [>38.4°C]).8 Chest radiography remains very useful for the serial
evaluation of cardiac size and pulmonary vascularity in pre- and postoperative
patients. Further, chest radiography is essential in the postoperative period to
assess the placement of endotracheal tubes, chest tubes, and central lines and
to assess pulmonary health. Chest radiography is useful in any neonate with a
murmur or acute illness at presentation, anyone with a new diagnosis of cyanosis,
any patient with known CHD with a change in cardiovascular status, patients
presenting with suspected myocarditis or CHF, and anyone with chest pain
associated with a fever.
Normal Chest Radiographic Findings

Normal chest radiographic findings are presented in Figure 5-1. Chest radio
graphs must have the proper exposure and be neither overexposed (overpene-
trated) nor underexposed (underpenetrated). On an overexposed radiograph,
structures appear less radiodense or darker gray; the spine is clearly visible and
pulmonary vascularity appears decreased, while on an underexposed image, the
spine is not clearly visible and the pulmonary vasculature may appear increased.
Timing of the radiographic acquisition during the breathing cycle is important,
as this affects the visual perception of heart size. During inspiration or in an
upright position, the heart appears elongated vertically and therefore smaller; the
lungs are air filled and larger, which may be interpreted as decreased pulmonary
vasculature. During expiration or in the supine position, the cardiac silhouette is
FIGURE 5-1. Normal chest radiographic findings in a child. A. Lateral view. B. Frontal view.
Anatomic structures of the cardiovascular system are outlined.
80
CCIP.indb 80 3/13/18 4:18 PM

Chest Radiography
more horizontal or broadened and the lungs contain less air and appear denser,
which may be interpreted as cardiomegaly and increased pulmonary vasculature.
With ideal lung expansion, the diaphragm should be at the ninth or tenth
rib posteriorly.
The normal thymus is a relatively prominent superior mediastinal structure
in infancy. The apparent size and shape of the thymus gland vary normally with
the breathing cycle and may be mistaken for or contribute to an appearance
of cardiomegaly. On the lateral chest projection in an infant, the thymus fills
the retrosternal space and is often difficult to distinguish from the heart.
After infancy, the thymus is less prominent, and the retrosternal space is filled
with aerated lung, which allows one to distinguish the anterior margin of the
heart. The normal thymus may have a distinct straight or wavy margin in the
right superior mediastinum, resulting in the presence of a “sail sign” on chest
radiographs, which is a sure indication of normal thymic tissue. The thymus
may appear to be absent in infants who have experienced perinatal stress and
is absent in patients with DiGeorge syndrome.
Additional findings that need to be evaluated on chest radiographs include
the presence of pulmonary disease, abdominal visceral situs, and bone abnormali-
ties. All chest radiographs should be evaluated for heart size and position, cardiac
contour, position of the aortic arch, and pulmonary vascularity.
Heart Size
Increased volume of blood flow results in dilation of the chamber through which
it passes. Evaluating heart size may help establish clues to cardiac physiology and
diagnosis. Shallow inspiration is the most common technical cause of apparent
cardiomegaly. A clinically significant left-to-right shunt is the most common
pathologic cause of pediatric cardiomegaly. It is important to know that an
anteroposterior (AP) chest radiograph magnifies the anteriorly located cardiac
structures slightly because they are further away from the film than the posterior
structures. A normal-sized heart on a posteroanterior (PA) chest radiograph may
appear slightly enlarged on an AP image. For convenience, most neonatal radio-
graphs are obtained from an AP position. Luckily, the chest of an infant is small,
and the magnification is not typically clinically significant. Upright versus supine
positioning may also affect the appearance of cardiac size. Obesity may result in
elevation of the diaphragm or exaggerate the size of the cardiac silhouette to a
greater degree, especially on AP chest radiographs.
The size of the heart is most easily evaluated by means of the cardiothoracic
ratio. While studies demonstrate the limitations of the sensitivity and specificity
of the cardiothoracic ratio,9,10 it remains a quick and easy way to assess the
patient for cardiomegaly. Simply divide the largest transverse diameter of the
heart by the largest internal width of the thoracic cavity. The heart is considered
enlarged if the ratio is more than 0.5 in children and more than 0.6 in adults.
81
CCIP.indb 81 3/13/18 4:18 PM

The cardiothoracic ratio is more useful in the detection of left-sided chamber

enlargement than right-sided enlargement11 and is least accurate in infants. The
right ventricle (RV) does not form the right cardiac silhouette on a normal AP
chest radiograph; it is formed by the right atrium. The lateral view is the most
accurate for the evaluation of RV dilation, where the enlarged ventricle fills the
retrosternal space. The left cardiac border is formed by the left ventricle (LV),
and when enlarged, the apex is displaced downward; the distance between the
border of the LV and the left lateral chest wall is reduced. Left atrial enlarge-
ment is best assessed on the lateral view and is seen as bulging of the posterior
cardiac margin toward the spine. On the AP view, it may be implied by splaying
of the main bronchi. Cardiac chamber enlargement is summarized in Table 5-1.
Table 5-1. Optimal Views for Evaluation of the Cardiac

Chambers and Great Arteries
Enlarged
Chamber Anteroposterior View Lateral View
Left atrium With severe enlarge- Posterior protrusion of the left atrial border
ment, splaying of the with indentation and/or displacement of the
left and right main esophagus
bronchi Left main bronchus elevation
Left Leftward and inferior Lower posterior border displaced further

ventricle displacement of the posteriorly; meets the inferior vena cava
cardiac apex below the diaphragm
Right Bulging of the lower

atrium right cardiac silhouette
Right May not be obvious Filling of the retrosternal space

ventricle
Note: Enlargement of more than 1 chamber is usually seen.
Cardiac Position and Visceroatrial Situs

Cardiac and abdominal viscera malpositioning can often readily be seen on chest
radiographs. In normal visceral situs, the aortic arch, cardiac apex, and stomach
are concordant and are on the left. The left lung can be identified radiographi-
cally, since the left main bronchus is normally about twice as long as the right
main bronchus and is located below the left pulmonary artery (hyparterial bron-
chus). The right lung is identified by the right main bronchus, which is shorter
and is positioned above the right pulmonary artery (eparterial bronchus). In
situs inversus, the normally left-sided structures are concordant and on the right,
and the severity of CHD is often mild or nonexistent. In heterotaxy syndromes
(polysplenia, asplenia), structures are often discordant—a situation called situs
ambiguous—and the severity of CHD is greater. Cyanosis, a midline liver, and
decreased pulmonary vascular markings (PVMs) suggest asplenia syndrome.
82
CCIP.indb 82 3/13/18 4:18 PM

Chest Radiography
Evaluation of the Great Vessels

The size of the great vessels is optimally viewed in the AP dimension. A dilated
aorta is best seen on the AP projection as a rightward bulge of the right upper
mediastinum. This may be seen in aortic stenosis (poststenotic dilation), occa-
sionally in tetralogy of Fallot (TOF), or with connective tissue syndromes such
as Marfan syndrome. Prominence of the main pulmonary artery segment results
from poststenotic dilation (pulmonary stenosis). Increased pulmonary blood
flow from a left-to-right shunt (atrial septal defect [ASD], ventricular septal
defect [VSD], complete atrioventricular canal [CAVC], patent ductus arteriosus
[PDA]) and pulmonary hypertension also results in a prominent main pulmo-
nary artery. Hypoplasia of the main pulmonary artery results in a concave main
pulmonary artery segment along the left cardiomediastinal margin, which creates
a boot-shaped heart (TOF, tricuspid atresia). Aortic arch laterality should be
assessed on chest radiographs because a right aortic arch is much more prevalent
in cyanotic CHD. Positioning of the aortic arch can be determined by looking
for a deviation of the trachea (typically away from the aortic arch)—rightward
in a patient with a left aortic arch and leftward in a patient with a right aortic
arch. A finding of no tracheal deviation may be suggestive of an interrupted
aortic arch or a double aortic arch. A standard chest radiograph, however, does
not allow for the diagnosis of vascular rings, and further evaluation should be
pursued to establish a diagnosis.
Pulmonary Vascular Markings

For PVMs to be assessed accurately, the radiographic technique or penetration
must be optimal. Normal pulmonary vasculature is seen with compensated valvar
stenosis (pulmonary and aortic), as well as small left-to-right shunts. PVMs can
be increased by distention of the pulmonary arteries, pulmonary veins, or both.
Increased pulmonary venous markings are rare beyond the newborn period;
therefore, changes in pulmonary vasculature are most likely arterial. In 2012,
Tumkosit et al determined that chest radiography had high sensitivity in the
detection of normal and increased pulmonary vascularity but lower sensitivity in
the detection of decreased vascularity.12 In this article and others, it is stressed
that accurate diagnosis of normal and abnormal pulmonary vascularity on chest
radiographs is difficult to assign without extensive prior experience.
PVMs: Arterial (Left-to-Right Shunts)

Radiographically, it is not possible to detect increased flow through pulmonary
vessels, although one can detect an increase in the size of the vessels. With
increased flow, the vessels become enlarged, and their edges appear sharpened
against a background of aerated lung. The pulmonary arteries are typically not
83
CCIP.indb 83 3/13/18 4:18 PM

well seen in the lateral third of the lung; if readily visualized in this region, they
are likely enlarged. Prominent vessels in the lung apex and an increase in vessels
seen “on end,” or as a small nodular focus, are also consistent with vessel enlarge-
ment. Enlargement of the pulmonary trunk is also typically seen. An increase in
pulmonary blood flow of more than 50% is usually necessary before radiographic
changes are seen.13

A left-to-right shunt proximal to the atrioventricular valves, as in ASD and
partial anomalous pulmonary venous return (PAPVR), may result in increased
right-sided heart size with normal PVMs. Initially, it is easier to detect increased
vascularity when an increase is seen in both flow and pressure. This situation
occurs in lesions distal to the atrioventricular valves, VSDs, CAVC, and PDA,
which leads to increased heart size and increased PVMs.
Although a decreased pulmonary vascular pattern may be difficult to differen-
tiate on chest radiographs, images should be obtained in a cyanotic infant to help
establish a possible diagnosis.12 Decreased prominence of the hila and presence
of small-caliber or few PVMs result in a dark appearance of the lungs. In infants,
these chest radiographic findings are consistent with decreased pulmonary blood
flow, which may be found in TOF, critical pulmonary stenosis, tricuspid atresia,
and pulmonary atresia. Later in life, a normal cardiac heart size, increased caliber
of the main pulmonary artery, and decreased PVMs are suggestive of idiopathic
pulmonary hypertension.
PVMs: Venous
An increased pulmonary venous pattern is seen most often in association with
obstruction to left-sided outflow, such as mitral valve stenosis or an atretic mitral
valve with restrictive ASD in a patient with hypoplastic left heart syndrome.
With increased pulmonary venous vasculature, the heart size is typically normal
or minimally enlarged. Pulmonary venous congestion results in enlarged, hazy,
and indistinct pulmonary venous vasculature. Peribronchial cuffing may be seen.
This hazy granular pattern is often indistinguishable from hyaline membrane
disease. The simultaneous presence of pleural effusion suggests pulmonary
venous obstruction, while pulmonary consolidation with air bronchograms
suggests hyaline membrane disease. An increased venous pattern is seen with
obstructed total anomalous pulmonary venous return above or below the
diaphragm, mitral stenosis or cor triatriatum, or left-sided CHF increasing
the LV end-diastolic pressure (decompensated aortic stenosis or coarctation,
cardiomyopathy, or myocarditis). Sometimes it is not possible to differentiate
arterial from venous engorgement because both may be present simultaneously.
In PAPVR of the right-sided pulmonary veins (scimitar syndrome), a vertical
vascular shadow may be seen. This shadow represents the vessel draining the
pulmonary veins to the inferior vena cava and is associated with right pulmonary
artery and lung hypoplasia, as well as other forms of CHD.
84
CCIP.indb 84 3/13/18 4:18 PM

Chest Radiography
Classic chest radiography findings are summarized in Table 5-2.

The radiographs shown in Figures 5-1, 5-2, 5-3, 5-4, 5-5, 5-6, 5-7, 5-8, and
5-9 are examples of normal anatomy and highlights of common radiographic
findings for various forms of CHD.
Table 5-2. Classic Chest Radiographic Findings

Primary
Diagnosis Physiology Typical Radiographic Findings
Atrial septal L to R shunt Right-sided enlargement, often with normal PVMs

defect
PAPVR L to R shunt Right-sided enlargement, often with normal PVMs
Ventricular L to R shunt Left-sided dilation, increased PVMs

septal defect
CAVC L to R or R Left-sided dilation, increased PVMs, possible right

to L shunt atrial enlargement
Patent ductus L to R shunt Left-sided dilation, increased PVMs, prominent

arteriosus main pulmonary artery and ascending aorta
Scimitar L to R shunt Asymmetrical thorax with the right smaller than

syndrome the left, with elevation of the right side of the
diaphragm, scimitar vein
Pulmonary Obstructive Enlarged pulmonary trunk, decreased PVMs if

stenosis very severe
Aortic stenosis, Obstructive Prominent ascending aorta

compensated
Aortic stenosis, Obstructive, Cardiomegaly, pulmonary venous congestion

uncompensated CHF
Coarctation of Obstructive, Neonatal: Marked cardiomegaly, pulmonary

the aorta CHF venous congestion
Pediatric: Aortic knob absent, figure “3” sign, rib
notching
Tetralogy of Obstructive, Normal heart size, with decreased pulmonary

Fallot cyanotic vasculature. “Boot-shaped” heart appearance is
caused by a combination of changes: (a) absent
pulmonary artery contour of the left cardiomedi-
astinal border and (b) uplifted cardiac apex due to
RV hypertrophy
Tricuspid atresia Obstructive, Decreased pulmonary vasculature, normal cardiac

cyanotic size, or minimal cardiomegaly with rounded left-
sided heart contour due to “relative” enlargement
of the LV when compared to the RV
85
CCIP.indb 85 3/13/18 4:18 PM

Table 5-2. Classic Chest Radiographic Findings,

continued
Primary
Diagnosis Physiology Typical Radiographic Findings
Pulmonary Obstructive, Decreased pulmonary vascularity—ductal

atresia with cyanotic dependent, clinically significant cardiomegaly due
intact ventricular to marked dilation of the LV
septum
Ebstein anomaly Cyanotic Highly variable cardiac size, normal to massive

cardiomegaly with decreased pulmonary arterial
vasculature
Transposition of Cyanotic Minimal thymic tissue and great artery malpo-

the great arteries sition results in a narrow mediastinum and mild
cardiomegaly described as an “egg on a string,”
increased PVMs
Double-outlet Cyanotic, L Cardiomegaly, increased pulmonary artery trunk,

RV to R shunt increased PVMs
Truncus Cyanotic, L Cardiomegaly, increased PVMs, narrow mediasti-

arteriosus to R shunt num with absent pulmonary artery contour along
the L cardiac border
TAPVR, L to R shunt Enlarged right atrium and ventricle and enlarged

unobstructed left vertical vein (enlargement of wide, bulbous
superior mediastinal borders) result in the “snow-
man sign” (usually >1 year of age) when there is
supracardiac anomalous venous return
TAPVR, Obstructive Normal heart size, pulmonary venous congestion

obstructed
Hypoplastic left Cyanotic, L Normal to marked cardiomegaly; prominent R

heart syndrome, to R shunt atrial border and normal to increased PVMs
nonobstructed
Hypoplastic left Cyanotic, Normal heart size or mild cardiomegaly, pulmo-

heart syndrome, obstructive nary venous congestion
obstructed
Anomalous left CHF Severe cardiomegaly with pulmonary venous

coronary artery congestion, left atrial dilation
from the pulmo-
nary artery
Cardiomyopathy CHF Cardiomegaly, pulmonary venous congestion

or myocarditis
CAVC, complete atrioventricular canal; CHF, congestive heart failure; L, left; LV, left ventricle; PAPVR, partial
anomalous pulmonary venous return; PVMs, pulmonary vascular markings; R, right; RV, right ventricle; TAPVR,
total anomalous pulmonary venous return.
86
CCIP.indb 86 3/13/18 4:18 PM

Chest Radiography
FIGURE 5-2. Complete atrioventricular canal, overcirculated. A. Lateral radiograph. B. Antero

posterior (AP) radiograph. The increased caliber of sharply defined pulmonary arterial vascular
markings throughout the lungs (black arrows on B) is noted. The heart is enlarged, with prominence
of the right atrial border on the AP image (white arrows on B) and the posterior margin of the left
atrium on the lateral view (white arrows on A).
FIGURE 5-3. Tetralogy of Fallot (TOF) with pulmonary atresia. Anteroposterior radiograph
obtained in a 1-day-old shows classic findings. TOF is the most common cyanotic lesion. The cardiac
apex is uplifted (white arrow) because of enlargement of the right ventricle. The aortic arch (AA)
is on the right, and the upper left cardiac border shows absence of the pulmonary artery silhouette
(dotted circle), which contributes to the appearance of a “boot-shaped” heart. The right atrial border
(black arrows) is also enlarged. Pulmonary vascular markings are decreased as a result of undercircu-
lation. Umbilical venous (V) and arterial (A) lines are present.
87
CCIP.indb 87 3/13/18 4:18 PM

FIGURE 5-4. Partial anomalous pulmonary venous connection in a patient with scimitar syndrome,
showing overcirculation with venous congestion. A. Lateral radiograph. B. Anteroposterior radio-
graph. Increased pulmonary arterial vascular markings are seen throughout the left lung (arrows);
the combined increase of pulmonary arterial and venous markings throughout the right lung results
in greater diffuse density, which obscures the right side of the heart and the anomalously draining
scimitar vein. The cardiac silhouette is shifted to the right because of hypoplasia of the right lung; in
fact, the entire right hemithorax is smaller than the left (dotted black outline on B).
FIGURE 5-5. Anomalous left pulmonary artery from the coronary artery in a 6-month-old patient
who presented with a large pericardial effusion. A. Lateral radiograph. B. Anteroposterior (AP)
radiograph. There is marked cardiomegaly with prominence of the left (black arrowhead on B)
and right (black arrow on B) cardiac borders. The silhouette of the heart appears much larger on
both views (large white arrows) because of the large pericardial effusion. Note the difference in
tissue density between the heart and the surrounding effusion on the AP view (black arrowhead
and black arrow on B). The trachea (T) and the right main bronchus (small white arrow on B) are
displaced slightly to the right by the enlarged heart. The left hemidiaphragm is obscured on the AP
view, a finding that might raise concern for the presence of a pleural effusion; however, the normal
posterior costophrenic angle (black arrow on A) on the lateral view confirms that a pleural effusion
is not present.
88
CCIP.indb 88 3/13/18 4:18 PM

Chest Radiography
FIGURE 5-6. Dextro-transposition of the great arteries in a newborn. Anteroposterior chest radio-
graph shows the typical radiographic findings; the superior mediastinum is narrow (double-ended
arrow), and the heart has a transverse position with a prominent right atrial border and narrow left
ventricle contour (dotted white outline). This typical appearance is referred to as an “egg on a string.”
A right upper-extremity vascular catheter (black arrow) is in the superior vena cava; a nasogastric
tube (NG) is in the left side of the stomach.
FIGURE 5-7. Anteroposterior chest radiograph in a 3-week-old with Ebstein anomaly. Ebstein
anomaly, apical displacement of the septal and/or posterior leaflets of the tricuspid valve, typically
results in varied degrees of tricuspid valve regurgitation. This patient has a moderately enlarged cardiac
silhouette with marked prominence of the right atrial border (white arrows). The left ventricular apex
nearly touches the left lateral chest wall (large black arrow). Enlargement of the heart has resulted
in splaying of the carina (dotted white line). A right upper-extremity vascular catheter (small black
arrow) is in the superior vena cava, and a nasogastric tube (NG) is in the left side of the stomach.
89
CCIP.indb 89 3/13/18 4:18 PM

FIGURE 5-8. Heterotaxy. Posteroanterior radiograph demonstrates numerous abnormalities of

thoracic and abdominal visceral situs. The cardiac silhouette (black arrows) and aortic arch (AA) are
on the right; a left superior vena cava and distal aortic arch (dotted ellipse) account for the wide
appearance of the superior mediastinum and prominent left-sided area of attenuation. The umbilical
(V) and arterial (A) lines are both left of the midline. The liver is transverse, spanning the entire
upper abdomen (double-ended arrow), and the stomach is near midline (note the position of the
distal tip of the nasogastric tube [NG] ).
90
CCIP.indb 90 3/13/18 4:18 PM

Chest Radiography
FIGURE 5-9. Posteroanterior chest radiograph obtained immediately after open-heart palliation
of congenital heart disease in a 3-day-old shows the support devices. The sternum is not yet closed
(note that no sternal wires are present). The endotracheal tube (E) tip is positioned low in the trachea
and is directed at the orifice of the right main bronchus (black arrow), with subsequent collapse
of the right upper lobe of the lung (white arrow). A central venous catheter is in the right atrium
(RA), a peripheral catheter is in the right internal jugular vein (IJ), and a venous catheter (V) is in
the intrahepatic inferior vena cava. Bilateral chest tubes are positioned for pleural and mediastinal
drainage (C), and surgical clips and sutures overlie the superior mediastinum. Temporary epicardial
pacing wires (P) are projected over the right atrium and ventricle.
While chest radiography alone should not be relied on for definitive diagnosis
of CHD,1 it can be helpful in establishing a differential diagnosis. The algorithm
shown in Figure 5-10 may be useful in differentiating patients with acyanotic CHD,
while Figure 5-11 may be useful in differentiating patients with cyanotic CHD.
Key Points
•• Chest radiography is a readily accessible and inexpensive screening examina-
tion, particularly in symptomatic neonates or patients with respiratory distress.
•• Chest radiography is not useful as the primary method of diagnosis for CHD,
but it is helpful in the diagnosis of cardiac and visceral situs and for the
diagnosis of any spine or rib anomalies that may be present.
91
CCIP.indb 91 3/13/18 4:18 PM

Early: VSD,
PDA, CAVC,
ASD
Normal heart size
with normal or
increased Prominent ascenting
vascularity aorta: aortic valvar
stenosis: compensated
Prominent main
pulmonary artery:
pulmonary valvar
stenosis
Increased VSD
left side of PDA
Acyanotic the heart CAVC
Cardiomegaly
with increased
vascularity ASD
Increased
PAPVR
right side of
(above the
the heart
diaphragm)
Normal to
Ebstein
decreased
anomaly
vascularity
Severe
cardiomegaly DCM
Myocarditis
ALCAPA
Increased
CoA
vascularity
Aortic valvar
stenosis:
uncompensated
FIGURE 5-10. Possible diagnostic algorithm for chest radiography in an acyanotic patient.
ALCAPA = anomalous origin of the left coronary artery from the main pulmonary artery, ASD =
atrial septal defect, CAVC = complete atrioventricular canal, CoA = coarctation of the aorta, DCM =
dilated cardiomyopathy, PAPVR = partial anomalous pulmonary venous return, PDA = patent ductus
arteriosus, VSD = ventricular septal defect.
•• Shallow inspiration is the most common technical cause of apparent cardio-

megaly, and a left-to-right shunt is the most common pathologic cause.
•• Chest radiography is useful in any neonate with a murmur who presents
with acute illness, anyone who presents with a new diagnosis of cyanosis, any
patient with known CHD and a change in cardiovascular status, patients
who present with suspected myocarditis or CHF, and anyone with chest pain
associated with a fever.
92
CCIP.indb 92 3/13/18 4:18 PM

Chest Radiography
Normal to TOF
moderate Ebstein anomaly
cardiomegaly Pulmonary atresia with intact septum
with normal Tricuspid atresia
or decreased Critical pulmonary valve stenosis
vascularity L-TGA with VSD and pulmonary stenosis
Truncus arteriosus
D-TGA
DORV
Increased
TAPVR (above
arterial
the diaphragm)
vascularity
Normal to HLHS (nonobstructed
Cyanotic moderate atrial septum)
cardiomegaly Single ventricles
with increased
vascularity TAPVR (below
Increased the diaphragm)
venous Pulmonary vein atresia
vascularity HLHS (obstructed
atrial septum)
Severe
Ebstein anomaly
cardiomegaly
Pulmonary atresia with
with decreased intact ventricular septum
vasculature
FIGURE 5-11. Possible diagnostic algorithm for chest radiography in a cyanotic patient. DORV
= double-outlet right ventricle, D-TGA = dextro-transposition of the great arteries, HLHS =
hypoplastic left heart syndrome, L-TGA = levo-transposition of the great arteries, TAPVR = total
anomalous pulmonary venous return, TOF = tetralogy of Fallot, VSD = ventricular septal defect.

•• Chest X-Ray (Medline Plus). medlineplus.gov/ency/article/003804.htm
•• Chest X-Ray (Phoenix Children’s Hospital). bit.ly/PCHCXRform
•• Image Gently. www.imagegently.org
References
1) Laya BF, Goske MJ, Morrison S, et al. The accuracy of chest radiographs in the detection of
congenital heart disease and in the diagnosis of specific congenital cardiac lesions. Pediatr Radiol.
2006;36(7):677–681
2) Swenson JM, Fischer DR, Miller SA, Boyle GJ, Ettedgui JA, Beerman LB. Are chest
radiographs and electrocardiograms still valuable in evaluating new pediatric patients with heart
murmurs or chest pain? Pediatrics. 1997;99(1):1–3
3) Macleod C. Evaluating cardiac murmurs; are diagnostic tests helpful? Ir Med J. 2001;94(5):154–155
93
CCIP.indb 93 3/13/18 4:18 PM

4) Birkebaek NH, Hansen LK, Elle B, et al. Chest roentgenogram in the evaluation of heart defects
in asymptomatic infants and children with a cardiac murmur: reproducibility and accuracy.
Pediatrics. 1999;103(2):E15
5) Oeppen RS, Fairhurst JJ, Argent JD. Diagnostic value of the chest radiograph in asymptomatic
neonates with a cardiac murmur. Clin Radiol. 2002;57(8):736–740
6) Freedman SB, Haladyn JK, Floh A, Kirsh JA, Taylor G, Thull-Freedman J. Pediatric
myocarditis: emergency department clinical findings and diagnostic evaluation. Pediatrics.
2007;120(6):1278–1285
7) Pettit MA, Koyfman A, Foran M. Myocarditis. Pediatr Emerg Care. 2014;30(11):832–835
8) Angoff GH, Kane DA, Giddins N, et al. Regional implementation of a pediatric cardiology
chest pain guideline using SCAMPs methodology. Pediatrics. 2013;132(4):e1010–e1017
9) Satou GM, Lacro RV, Chung T, Gauvreau K, Jenkins KJ. Heart size on chest x-ray as a predictor
of cardiac enlargement by echocardiography in children. Pediatr Cardiol. 2001;22(3):218–222
10) Loomba RS, Shah PH, Nijhawan K, Aggarwal S, Arora R. Cardiothoracic ratio for
prediction of left ventricular dilation: a systematic review and pooled analysis. Future Cardiol.
2015;11(2):171–175
11) Hulett R, Ovitt T. The chest roentgenogram. In: Allen HD, Gutgesell HP, Clark EB, Driscoll
DJ, eds. Moss & Adams’ Heart Disease in Infants, Children, and Adolescents, Including the Fetus and
Young Adult. 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2001:162–170
12) Tumkosit M, Yingyong N, Mahayosnond A, Choo KS, Goo HW. Accuracy of chest radiography
for evaluating significantly abnormal pulmonary vascularity in children with congenital heart
disease. Int J Cardiovasc Imaging. 2012;28(Suppl 1):69–75
13) Amplatz K, Moeller J. Plain film diagnosis of congenital heart disease. In: Radiology of
Congenital Heart Disease. Mosby Year Book; 1993:143–155
94
CCIP.indb 94 3/13/18 4:18 PM

CHAPTER 6
Cardiac MR
Imaging and CT
Melissa Yamauchi, MD, MPH, and Shaji C. Menon,
MD, FACC, FASE, FAAP
Cardiac MR Imaging
Introduction
While echocardiography is the imaging modality used most commonly to define
cardiac anatomy and physiology in children and adults with congenital heart
disease (CHD), cardiac magnetic resonance (MR) imaging provides an excellent
adjunct modality. Cardiac MR imaging is based on the principle of nuclear MR.
In a strong magnetic field (1.5 to 3.0 Tesla), hydrogen atoms in the body are
stimulated to emit radio waves that are detected and reconstructed into images.
Unlike computed tomography (CT), MR imaging uses no ionizing radiation and
is generally a safe procedure.1 Cardiac MR imaging provides detailed information
on cardiac and extracardiac structures, cardiac function, flow, and tissue char-
acterization.2 Often, echocardiograms are sufficient for presurgical planning of
congenital heart lesions, although cardiac MR imaging can be useful for further
definition of anatomy such as the aortic arch, pulmonary arteries, and pulmonary
and systemic veins. For example, in a retrospective 10-year study in which the pre-
operative utility of cardiac MR imaging was investigated, more than 50% of infants
had clinically significant findings on cardiac MR images that altered the cardiac
surgical planning.3 Cardiac MR imaging also provides information about cardiac
structure and hemodynamics that may help prevent the need for an invasive cardiac
catheterization modality, such as quantification of valve regurgitation and the
ratio of pulmonary to systemic flow. Cardiac MR imaging can often be conducted
95
CCIP.indb 95 3/13/18 4:18 PM

without the use of general anesthesia, therefore minimizing the possible effects
of anesthesia on the developing brain.4,5
Indications
Structure
Common cardiovascular structure indications for cardiac MR imaging include
adjunctive evaluation of the aortic arch, pulmonary arteries, pulmonary or
systemic veins, septation defects, coronary artery anatomy, and valve anatomy.
Guidelines for the surveillance and evaluation of pulmonary hypertension and
the postoperative status of certain congenital heart lesions such as tetralogy
of Fallot and transposition of the great arteries also include a multimodality
approach that involves cardiac MR imaging and cardiac CT.6-8 The spin-echo
(ie, black-blood) approach shows the heart muscles as hyerintense structures
and the blood pool as hypointense structures (Figure 6-1) and can yield
high-definition images to be able to define cardiac structures. This technique
also minimizes the artifact produced by metal, such as with aortic arch stents.
Steady-state free-precession imaging (ie, the bright-blood approach) produces
cine images (ie, motion picture images) with the blood pool appearing hyper-
intense and the myocardium appearing hypointense (Figure 6-2). Cardiac MR
imaging, especially MR angiography performed with gadolinium-based contrast
material, allows aortic anomalies to be evaluated, including the diagnosis of
coarctation of the aorta or vascular rings, surveillance after coarctation repair,
and the evaluation of aortic dilation in patients with bicuspid aortic valve or
Marfan syndrome (Figure 6-3). Cardiac MR imaging can be used to evaluate
the entire aorta in exquisite detail. Parts of the cardiac and extracardiac anatomy
can be reconstructed and isolated to provide a 3-dimensional (3D) rendering of
vessels and their branches, which is invaluable for preoperative surgical planning
(Figure 6-4).1,2,9
Flow Velocity Encoding (Cine Phase Contrast Imaging)
Phase velocity mapping enables quantification of the amount and direction
of blood flow across a valve or a vessel (Figure 6-5). Aortic and pulmonary
flow assessments can be used as a noninvasive method to calculate pulmonary
(Qp) and systemic (Qs) blood flow ratios (Qp:Qs) for the surgical planning
of ventricular or atrial septal defect closure that may have borderline criteria
for repair. A Qp:Qs ratio of at least 1.5 is an indication of clinically significant
left-to-right shunt and is usually considered an indication for ventricular or
atrial septal defect closure. The regurgitant fraction (the percentage of cardiac
regurgitation across a valve) determined with flow imaging is commonly used
to determine the timing of surgical or catheter-based replacement of aortic and
pulmonary valves.1,7,9
96
CCIP.indb 96 3/13/18 4:18 PM

Cardiac MR Imaging and CT
FIGURE 6-1. The spin-echo or black-blood magnetic resonance imaging approach shows the
heart muscles as hyperintense structures and the blood pool as hypointense structures on this
coronal image.
Tissue Characterization (Perfusion and Viability)

Cardiac MR imaging has the unique ability to allow evaluation of myocardial
diseases that result from ischemia, cardiomyopathy, or storage disorders.
Cardiac MR imaging can be used to differentiate healthy myocardial tissue
and myocardial tissue with fat, edema, or fibrosis. Tissue characterization
can therefore contribute to the diagnosis of cardiomyopathies, inflammatory
processes such as myocarditis, iron overload, or cardiac sarcoidosis and cardiac
tumors. Gadolinium-based contrast material can also be used to determine late
gadolinium enhancement that shows areas of irreversible myocardial fibrosis
97
CCIP.indb 97 3/13/18 4:18 PM

FIGURE 6-2. Steady-state free-precession imaging, or the bright-blood approach, produces cine
images with the blood pool appearing hyperintense and the myocardium appearing hypointense.
Short-axis (saggital) cine images show the right ventricle (RV) and the left ventricle (LV) at
different points in the cardiac cycle. A. End-diastole. B. Start of systole. C. Mid-systole.
(Figure 6-6). This technique is used to evaluate myocardial scarring and fibrosis
after coronary injury or in cardiomyopathies such as hypertrophic cardiomyop-
athy to stratify risk for sudden cardiac death. Cardiac MR imaging can also be
used to evaluate myocardial perfusion and can be combined with dobutamine
or a vasodilator (dipyridamole, adenosine, or regadenoson) for stress myocardial
perfusion imaging in patients with suspected coronary artery disease.1,9
Contraindications
Absolute contraindications to cardiac MR imaging include intraocular and
intracochlear metal devices. Pacemakers and internal cardiac defibrillators
were also previously contraindicated, although experienced physicians may still
perform cardiac MR imaging in these patients with newer cardiac MR imaging
machines. Other smaller implanted metallic objects, such as sternal wires,
vascular clips, and septal occluders, are not contraindicated with cardiac MR
imaging because they are only weakly ferromagnetic and embedded in scar tis-
sue, although they may produce a considerable amount of imaging artifact with
98
CCIP.indb 98 3/13/18 4:18 PM

FIGURE 6-3. Sagittal cardiac magnetic resonance angiograph shows coarctation of the aorta (*).
bright-blood imaging. If contrast material is needed for cardiac MR imaging, an

allergy to gadolinium is a contraindication to the study.10 Medical monitoring
devices often contain iron or other ferromagnetic material, which may cause
harm to patients when used near the MR imaging machine. Therefore, MR-safe
medical monitoring devices should be used.
99
CCIP.indb 99 3/13/18 4:18 PM

FIGURE 6-4. Three-dimensional reconstruction of a magnetic resonance angiogram shows aortic,

pulmonary artery, and pulmonary venous anatomy in fine detail.
FIGURE 6-5. Magnitude (left) and phase (right) magnetic resonance images show flow velocity
mapping in the aorta. The magnitude image is constructed based on tissue signal intensity, and the
phase image intensity is proportional to flow velocity. AsAo = ascending aorta, DsAo = descending
aorta, SVC = superior vena cava.
100
CCIP.indb 100 3/13/18 4:18 PM

FIGURE 6-6. Magnetic resonance image shows late gadolinium-based contrast enhancement
consistent with myocardial fibrosis or ischemia in the ventricular septum of a 15-year-old with a
history of myocarditis.
Complications
Nephrogenic systemic fibrosis (NSF) is a rare disorder that can lead to mortality
and is associated with exposure to gadolinium. NSF is similar to scleroderma and
is associated with dialysis use, acute kidney injury, a low estimated glomerular
filtration rate (<30 mL/min), proinflammatory states, and high-dose gadolinium
use. Because of the association between gadolinium and NSF in patients with
decreased renal function, gadolinium use is limited in these patients.11
Other Considerations
To limit imaging artifacts and ensure optimal image quality, the acquisition
of cardiac MR images sometimes requires that the child be motionless and be
able to comply with breath holding as needed. Achieving these requirements
therefore sometimes necessitates the use of general anesthesia, so the anesthe-
siologist may perform mechanical breath holds on the ventilator. However, this
101
CCIP.indb 101 3/13/18 4:18 PM

method comes with associated risks, such as adverse reactions to anesthesia and
sedation medications.9
Key Points
•• Echocardiography continues to be the primary noninvasive imaging modality
for the diagnosis and follow-up of children with heart disease. However,
cardiac MR imaging (along with cardiac CT) is increasingly used to diagnose
CHD in infants, children, and adults with difficult echocardiographic
windows and for a more detailed evaluation of myocardial structure, function,
and flow.
•• Cardiac MR imaging provides additional information on cardiac and extra-
cardiac structures, cardiac function, flow, and tissue characterization without
using radiation.
•• Cardiac MR imaging has the unique ability to allow evaluation of myocardial
viability, perfusion, and scarring, which is used for risk stratification for
disorders such as cardiomyopathies and myocarditis.
•• Cardiac MR imaging sometimes requires anesthesia with breath holding to
prevent respiratory motion artifacts. However, evolving faster free-breathing
protocols allow the reduction of imaging time and therefore increase cardiac
MR imaging feasibility without the use of general anesthesia.
Cardiac CT
Introduction
Cardiac CT and CT angiography (CTA) are other adjunct noninvasive imaging
modalities for patients with congenital cardiovascular disorders. Cardiac CT
can provide images with high spatial and temporal resolution for an accurate
depiction of complex cardiovascular anatomic features before and after surgery.
CT and CTA are especially useful in the evaluation of complex cardiac and ext-
racardiac vasculature, including small structures, such as coronary arteries. Unlike
cardiac catheterization angiography, CTA can provide detailed 3D images of the
systemic and pulmonary vasculature without invasive catheter-based procedures,
with a lower amount of intravascular contrast material and radiation, and often
without general anesthesia.12,13
Indications
Cardiac and Extracardiac Vasculature
Cardiac CT is a supplemental imaging study that can help to define cardiac and
extracardiac vasculature (Figure 6-7). For example, cardiac CT can help to define
both pulmonary and systemic thoracic vascular abnormalities. In patients with
102
CCIP.indb 102 3/13/18 4:18 PM

FIGURE 6-7. Coronal computed tomographic angiogram shows the ascending aorta and coronary
arteries.
an aortic arch obstruction, cardiac CT can show the extent and morphologic
appearance of the anomaly. The extent and course of collateral vessels can also
be seen with great detail in patients with coarctation of the aorta before surgical
repair. For patients with a diagnosis of tetralogy of Fallot, pulmonary artery
abnormalities can be seen well with cardiac CT. Cardiac CT can also be used to
define extracardiac structures such as vascular rings (Figures 6-8, 6-9, and 6-10).
CTA is routinely used to evaluate pulmonary venous return. For example,
in patients with sinus venosus atrial septal defects, there is a high prevalence
of partial anomalous pulmonary venous return that is difficult to diagnose and
confirm with an echocardiogram (Figure 6-7). CTA-derived (a) 2-dimensional
reformatted and (b) 3D-reconstructed images are invaluable in understanding
the complex cardiovascular anomalies and are routinely used in preoperative
planning.12,13
103
CCIP.indb 103 3/13/18 4:18 PM

FIGURE 6-8. Axial CT angiogram shows a double aortic arch in a 1-year-old with recurrent
respiratory infection and stridor.
FIGURE 6-9. Axial computed tomographic angiogram demonstrates retroesophageal diverticulum

(Kommerell diverticulum) in a 10-year-old with right aortic arch and aberrant origin of left subcla-
vian artery who presented with solid food dysphagia.
104
CCIP.indb 104 3/13/18 4:18 PM

FIGURE 6-10. Computed tomographic angiogram shows the circumflex aorta.
Coronary Arteries
Echocardiography may be suboptimal in defining congenital and acquired
coronary artery anomalies, especially in older children or young adults. While
the proximal origin and course of the coronary arteries can be seen with echocar-
diography in young children with thin chest walls, cardiac CT is often required
to provide information on areas of distal narrowing, an intramural course, and
the relationship of the coronary arteries to other vessels (Figure 6-11). For
example, congenital coronary artery anomalies remain the second most common
cause of sudden death in young athletes, and structural abnormalities such as an
intramural left coronary artery can be seen well with CTA. Acquired coronary
artery anomalies, such as coronary artery aneurysms and stenosis from Kawasaki
disease, are also imaged well with CTA, which is referenced as an imaging
modality to be considered for periodic coronary artery surveillance.12,13,14
FIGURE 6-11. A. Computed tomographic angiogram of the heart. B. Digitally subtracted image
shows the coronary arteries with 3-dimensional reconstruction.
105
CCIP.indb 105 3/13/18 4:18 PM

Postoperative Anatomy
Postoperative anatomy that is difficult to differentiate with echocardiography
can often be visualized well with CT. Examples include the venous baffles for
a patient who has undergone a Mustard or Senning procedure (ie, atrial switch
procedure) for transposition of the great arteries.12,13
Cardiac Function
Although cardiac MR imaging is more commonly used for the evaluation of
cardiac function, cardiac functional information can also be determined by
using cardiac CT. For example, by using electrocardiographic gating technology,
cardiac systolic function can be calculated for both right and left ventricles.12
Contraindications and Complications

Allergy to contrast material is a contraindication to cardiac CT, because this
agent is usually required to perform the study. Poor renal function may be a
contraindication for CT contrast agents. In patients with acute or chronic kidney
disease, contrast material–induced nephropathy can aggravate or cause acute
renal dysfunction.13

One of the primary complications of CT is the relatively high dose of
radiation, which is a well-known risk factor for the development of cancer.
For children and adults with CHD, this is a particular concern because of
the need for repeat evaluations, greater sensitivity to radiation in children,
and increasing life span, which could involve exposing patients to increasing
amounts of cumulative radiation. However, recent advances in CT technology
have led to a marked radiation dose reduction, without compromising quality
or diagnostic accuracy.13,15

In response to the amount of radiation used with CT studies, the As Low As
Reasonably Achievable (ALARA) concept aims to minimize radiation exposure
by decreasing the number of radiation-producing tests as much as possible.
Other modifications include pediatric-specific protocols that may adjust radia-
tion exposure for a child’s weight. To appropriately assess the risks and benefits
of studies such as cardiac CT scans, the ordering physician should be aware of
appropriate indications and alternatives for noninvasive imaging studies.12,13,15
Sedation or, less commonly, general anesthesia is sometimes required to obtain
excellent cardiac CT images, such as in a very young patient who requires a
detailed evaluation of small cardiovascular structures. However, CT examinations
are markedly shorter than cardiac MR imaging studies, which decreases the
amount of sedation or general anesthesia required. A lower heart rate is needed
for coronary artery imaging in particular and can be achieved with medications
such as β-blockers in older children. Risks associated with sedation, anesthesia,
106
CCIP.indb 106 3/13/18 4:18 PM

and heart rate–lowering medications must be considered for each individual

patient. Table 6-1 shows the differences between cardiac CT and cardiac MR
imaging in the evaluation of cardiovascular structure and function.
Table 6-1. Indications for Cardiac MR Imaging and

Cardiac CT
Indication Cardiac MR Imaging Cardiac CT
Cardiac and extracar- Aortic arch, pulmonary artery, Aortic arch, pulmonary
diac structures that pulmonary or systemic veins, arteries, pulmonary and
are best evaluated septation defects, coronary systemic veins, coronary
with each modality artery, valve anatomy arteries, vascular rings,
pericardial disease
Cardiac function Right and left ventricular Less useful in the calcu-
ejection fractions lation of cardiac function
and flow than cardiac MR
Flow Proportion of regurgitation
imaging
across a valve
Tissue Evaluation of fibrosis, edema, Not commonly used for

characterization and fat tissues and areas tissue characterization
of decreased myocardial
perfusion
CT, computed tomography; MR, magnetic resonance.
Key Points
•• Cardiac CT is a noninvasive imaging modality that provides information on
cardiac and extracardiac vasculature, including structures such as coronary
arteries that require high-resolution imaging.
•• Cardiac CT is a brief study, therefore allowing minimization of the amount of
sedation used.
•• High-dose radiation is often required for cardiac CT, although recent
advances allow for less radiation to be used. The principles of ALARA are key
to achieving less radiation exposure.

•• Common Tests for Congenital Heart Defects (American Heart Association).
www.heart.org/HEARTORG/Conditions/CongenitalDefectsChildren
&Adults/SymptomsandDiagnosisofCongenitalHeartDefects/Common-Tests-
for-Congenital-Heart-Defects_UCM_307412_Article.jsp#.WFHhhrIrKUk
•• Cardiac MRI (National Heart, Lung, and Blood Institute). www.nhlbi.nih.
gov/health/health-topics/topics/mri
•• Cardiac CT Scan (National Heart, Lung and Blood Institute). www.nhlbi.nih.
gov/health/health-topics/topics/ct
107
CCIP.indb 107 3/13/18 4:18 PM

References
1) Driessen MM, Breur JMPJ, Budde RP, et al. Advances in cardiac magnetic resonance imaging
of congenital heart disease. Pediatr Radiol. 2015;45(1):5–19
2) Helbing WA, Ouhlous M. Cardiac magnetic resonance imaging in children. Pediatr Radiol.
2015;45(1):20–26
3) Johnson JT, Molina KM, McFadden M, Minich LL, Menon SC. Yield of cardiac magnetic
resonance imaging as an adjunct to echocardiography in young infants with congenital heart
disease. Pediatr Cardiol. 2014;35(6):1067–1071
4) Andropoulos DB, Greene MF. Anesthesia and developing brains—implications of the FDA
warning. N Engl J Med. 2017;376(10):905–907
5) Sanders RD, Hassell J, Davidson AJ, Robertson NJ, Ma D. Impact of anaesthetics and surgery
on neurodevelopment: an update. Br J Anaesth. 2013;110(Suppl 1):i53–i72
6) Cohen MS, Eidem BW, Cetta F, et al. Multimodality imaging guidelines of patients with
transposition of the great arteries: a report from the American Society of Echocardiography
developed in collaboration with the Society for Cardiovascular Magnetic Resonance and the
Society of Cardiovascular Computed Tomography. J Am Soc Echocardiogr. 2016;29(7):571–621
7) Valente AM, Cook S, Festa P, et al. Multimodality imaging guidelines for patients with repaired
tetralogy of Fallot: a report from the American Society of Echocardiography: developed in
collaboration with the Society for Cardiovascular Magnetic Resonance and the Society for
Pediatric Radiology. J Am Soc Echocardiogr. 2014;27(2):111–141
8) Latus H, Kuehne T, Beerbaum P, et al. Cardiac MR and CT imaging in children with suspected
or confirmed pulmonary hypertension/pulmonary hypertensive vascular disease. Expert
consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The
European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK.
Heart. 2016;102(Suppl 2):ii30–ii35
9) Bonnemains L, Raimondi F, Odille F. Specifics of cardiac magnetic resonance imaging in
children. Arch Cardiovasc Dis. 2016;109(2):143–149
10) Allen HD, Driscoll DJ, Shaddy RE, Feltes TF. Moss and Adams’ Heart Disease in Infants,
Children, and Adolescents, Including the Fetus and Young Adult. 8th ed. Philadelphia, PA:
Lippincott Williams & Wilkins; 2013
11) Karcaaltincaba M, Oguz B, Haliloglu M. Current status of contrast-induced nephropathy and
nephrogenic systemic fibrosis in children. Pediatr Radiol. 2009;39(Suppl 3):382–384
12) Han BK, Rigsby CK, Hlavacek A, et al; Society of Cardiovascular Computed Tomography;
Society of Pediatric Radiology; North American Society of Cardiac Imaging. Computed
tomography imaging in patients with congenital heart disease part I: rationale and utility. An
expert consensus document of the Society of Cardiovascular Computed Tomography (SCCT).
J Cardiovasc Comput Tomogr. 2015;9(6):475–492
13) Kulkarni A, Hsu HH, Ou P, Kutty S. Computed tomography in congenital heart disease: clinical
applications and technical considerations. Echocardiography. 2016;33(4):629–640
14) McCrindle BW, Rowley AH, Newburger JW, et al; American Heart Association Rheumatic
Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease
in the Young; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular
Surgery and Anesthesia; and Council on Epidemiology and Prevention. Diagnosis, treatment,
and long-term management of Kawasaki disease: a scientific statement for health professionals
from the American Heart Association. Circulation. 2017;135(17):e927–e999
15) Slovis TL. Children, computed tomography radiation dose, and the As Low As Reasonably
Achievable (ALARA) concept. Pediatrics. 2003;112(4):971–972
108
CCIP.indb 108 3/13/18 4:18 PM

CHAPTER 7
Laboratory Studies
Brian S. Snarr, MD, PhD, and David J. Goldberg, MD
Introduction
Diagnosis of congenital heart disease (CHD) in the current era has benefited
from improvements in prenatal screening, advances in fetal echocardiography,
physician education, and implementation of pulse oximeter screening. Despite
these advances, CHD may still go undiagnosed at the time of a child’s first
presentation to primary care providers. Furthermore, a patient with CHD may
be presenting for the first time with symptoms that overlap with noncardiac
conditions. As discussed in previous chapters, the history and physical examination
findings are usually the most essential components in an evaluation of a patient
with a possible CHD. In some situations, laboratory studies are needed to aid
in and support the process of correctly diagnosing the condition and triaging
the patient. This is particularly true in cases of severe forms of CHD that are
ductal dependent and in which symptoms become clinically significant after the
patent ductus arteriosus (PDA) has closed. This chapter will address the different
laboratory studies that may be helpful in the evaluation of a patient with suspected
CHD, such as blood gas analyses and biomarkers, as well as different scenarios in
which these tests may be applied.
Blood Gas Analysis

An arterial blood gas analysis is essential in the evaluation of a newborn who
presents with cyanosis, which is defined as a bluish coloration of the skin in
response to the presence of 5 g or more of reduced hemoglobin per 100 mL of
venous blood. Cyanosis is generally divided into 2 categories, central and periph-
eral. These categories are different from acrocyanosis, which is the normal bluish
coloration of the hands and feet in an infant due to decreased peripheral vascular
109
CCIP.indb 109 3/13/18 4:18 PM

tone and does not require further workup. Central cyanosis manifests as dis-
coloration of the mucous membranes, tongue, and skin and is a normal finding
until about 20 minutes after birth.1 Beyond this time, additional investigation
into the cause of cyanosis is necessary. Peripheral cyanosis may be a manifesta-
tion of differential cyanosis, in which the upper-body skin color is normal and
the lower extremities are cyanotic. This may signify conditions such as severe
coarctation of the aorta, interrupted aortic arch, or persistent pulmonary hyper-
tension of the newborn. The differential diagnosis of central cyanosis in a new-
born is broad2 and includes cyanotic CHD, heart failure, primary lung disorders,
neurological disease, and hematologic and metabolic abnormalities.1-3 An arterial
blood gas analysis, in combination with the hyperoxia test (described herein), is
useful in helping to distinguish pulmonary from CHD causes of cyanosis (see
Chapter 12, Evaluation of the Neonate With Congenital Heart Disease).
Performing an arterial blood gas analysis in the right radial artery provides
an assessment of the acid-base status of the patient and the hematocrit level, as
well as measurements of the preductal arterial oxygen tension (Pao2) and arterial
partial pressure of CO2 (Paco2). For an infant who presents to the primary care
or acute care setting with severe metabolic acidosis, this signifies shock and
requires immediate attention. This scenario should raise the provider’s suspicion
for CHD that is dependent on a patent ductus arteriosus (PDA) to maintain
systemic perfusion and should prompt an evaluation to determine if the patient
is becoming symptomatic as the PDA closes. This is most commonly seen in
patients with CHD that involve obstruction of flow from the left side of the
heart: hypoplastic left heart syndrome, critical aortic stenosis, critical coarctation
of the aorta, and interrupted aortic arch. Suspicion of ductal-dependent CHD
requires emergent care for the starting of prostaglandins to keep the PDA open.
The hematocrit level is also helpful in the evaluation of a cyanotic patient or
a patient with oxygen desaturations. As mentioned, cyanosis manifests when
reduced hemoglobin level (5 g per 100 mL) is present. A desaturated patient
who is anemic may not appear cyanotic because of the overall decreased amount
of hemoglobin and the subsequent lower amount of reduced hemoglobin present
in the blood. A patient with polycythemia without CHD may have the appear-
ance of cyanosis due to plethora from increased hematocrit level but may not
actually be hypoxemic.1

The oxygen and carbon dioxide partial pressures obtained from the arterial
blood gas analysis help further define the possible etiologic origins of cyanosis.
Decreased Pao2 confirms central cyanosis. Although low Pao2 levels may be sug-
gestive of a particular type of CHD, they do not allow complete discrimination
between causes.4 The Paco2 level is especially informative in the evaluation of the
cause of hypoxemia. An increased Paco2 level suggests alveolar hypoventilation.
Inadequate alveolar ventilation results in lower alveolar oxygen partial pressure
and limits the amount of oxygenation of blood flowing through the pulmonary
110
CCIP.indb 110 3/13/18 4:18 PM

Laboratory Studies
capillary system. Hence, alveolar hypoventilation may be the cause of hypoxemia

as opposed to CHD.3

The hyperoxia test has long been used to help discriminate between pulmo-
nary and cardiac causes of cyanosis. This test involves determining the preductal
Pao2 level from the right radial artery, while the patient is breathing room air,
and then repeating the blood gas analysis after 10 minutes of 100% fraction of
inspired oxygen (Fio2) via oxygen hood or endotracheal tube. This allows the
clinician to determine the Pao2 response after the alveolar oxygen saturation has
been maximized. In the setting of alveolar hypoventilation, 100% Fio2 adminis-
tration raises the alveolar partial pressure of oxygen and will consequently raise
the Pao2 level, usually above 100 to 150 mm Hg.3,4 In contrast, a patient with
cyanotic CHD will not show the same response. For example, in a patient with
CHD and a right-to-left shunt, the hypoxemia is caused by a mixture of venous
and arterial blood rather than inadequate oxygen transfer from the alveolus.
Thus, maximal alveolar oxygenation on 100% Fio2 will only affect the blood
passing through the pulmonary capillary bed (and not the shunted blood). This
results in only a minimal increase in arterial oxygen tension, with a total Pao2
usually less than 100 mm Hg.3,4
Biomarkers
Biomarkers across all disease spectra have received increased attention as a
potential tool to facilitate diagnosis and better estimate disease prognosis. The
2 most commonly used biomarkers in pediatric cardiovascular disease include
brain natriuretic peptide (BNP) and its prohormone N-terminal (NT) proBNP.
BNP is produced and secreted by cardiomyocytes in response to wall stress and
has been a useful tool in the diagnosis of adult heart failure.5,6
A number of studies have also demonstrated the utility of using BNP and
NT-proBNP in the evaluation of pediatric cardiovascular disease. Specifically,
BNP has been found to be increased in patients with CHD who present in the
acute care setting, compared to those without CHD.7,8 There is disagreement
about the precise BNP and NT-proBNP cutoff levels that would be diagnostic
for CHD. This is due at least in part to the natural changes in BNP and
NT-proBNP levels after birth and the need for different cutoff values in the
newborn period.9 Notwithstanding these challenges, BNP and NT-proBNP
show promise in supporting the clinical diagnosis of CHD.
BNP and NT-proBNP have also been shown to be increased in cases of
pediatric heart failure and have been useful in discriminating heart failure from
some conditions that present with similar symptoms.8,10,11 Conversely, there has
also been a study in which NT-proBNP levels could not be used to successfully
discriminate between septic patients with and those without ventricular dys-
function.10 Test results should be interpreted with caution and evaluated in the
111
CCIP.indb 111 3/13/18 4:18 PM

context of the overall clinical picture. In the most recent pediatric heart failure
guidelines from the International Society for Heart and Lung Transplantation,
a level of evidence “B” and class IIB recommendation has been issued for the
use of BNP and NT-proBNP as adjunct tests to assist in the diagnosis of new
heart failure.12
BNP and NT-proBNP may also be used as biomarkers for individual
children with known heart failure or CHD. While these markers are not always
helpful in discriminating the degree of disease between individuals, they may
be very helpful in following disease progression within a single patient. For
example, BNP and NT-proBNP may be useful markers to follow in a patient
with a known cardiomyopathy or heart failure to help determine response to
therapy and to provide a warning sign for disease progression.13 Similarly, these
biomarkers may be helpful in children with many forms of CHD who are at
risk for ventricular dysfunction over time. In children with single-ventricle heart
disease who have undergone the Fontan procedure, there is actually an inverse
relationship between serum BNP level and insulinlike growth hormone 1, which
suggests a possible relationship between heart failure burden and growth.14
Single-Ventricle CHD: A Special Case

Single-ventricle CHD is a unique form of CHD characterized by the presence
of a single cardiac pumping chamber. In the current era, survival with single-
ventricle heart disease is improved, although still far from perfect. While there
are many forms of single-ventricle CHD, most of these cardiac malformations
in children are ultimately palliated with the Fontan procedure. Survival through
the Fontan procedure is generally excellent,15 but there remain questions about
how to best monitor this cohort in the long term.
Laboratory studies play an important role in the surveillance of children
who have undergone the Fontan procedure. BNP and NT-proBNP may be
useful surrogates of heart function to complement the visual determination at
echocardiography. Similarly, an increased hemoglobin and/or hematocrit level
may be a marker of impaired cardiac output. Other laboratory studies may aid
in screening for some of the complications that can occur in children who have
undergone the Fontan procedure. Obtaining a serum albumin level, as well as
a fecal α1-antitrypsin level, can be useful screening tools to help rule out the
presence of protein-losing enteropathy, a complication characterized by protein
loss through the gastrointestinal tract. Platelet count, which may be associated
with hepatic fibrosis,16 or markers of liver function and/or injury may be useful
to follow serially, since liver congestion is inherent in those who have undergone
the Fontan procedure. As more is learned about the long-term effect of the
Fontan circulation, the utility of other organ-specific biomarkers may become
more apparent.
112
CCIP.indb 112 3/13/18 4:18 PM

Laboratory Studies
Key Points
•• The diagnosis of CHD can be challenging and sometimes difficult to
distinguish from noncardiac causes of similar symptoms.
•• History and physical examination are crucial to the successful diagnosis
of CHD.
•• Laboratory studies may be useful adjuncts in the diagnosis of CHD when
there is clinical uncertainty.
•• Arterial blood gas analysis and the hyperoxia test may help distinguish
pulmonary causes of cyanosis from CHD.
•• BNP and NT-proBNP may aid in the diagnosis of CHD and acute
heart failure.
References
1) Lees MH. Cyanosis of the newborn infant. Recognition and clinical evaluation. J Pediatr.
1970;77(3):484–498
2) Marino BS, Wernovsky G. Preoperative care. In: Chang AC, Hanley FL, Wernovsky G, Wessel
DL, eds. Pediatric Cardiac Intensive Care. Baltimore, MD: Williams & Wilkins; 1998:154–156
3) Duc G. Assessment of hypoxia in the newborn. Suggestions for a practical approach. Pediatrics.
1971;48(3):469–481
4) Jones RW, Baumer JH, Joseph MC, Shinebourne EA. Arterial oxygen tension and response to
oxygen breathing in differential diagnosis of congenital heart disease in infancy. Arch Dis Child.
1976;51(9):667–673
5) Mukoyama M, Nakao K, Hosoda K, et al. Brain natriuretic peptide as a novel cardiac hormone
in humans. Evidence for an exquisite dual natriuretic peptide system, atrial natriuretic peptide
and brain natriuretic peptide. J Clin Invest. 1991;87(4):1402–1412
6) Yancy CW, Jessup M, Bozkurt B, et al; American College of Cardiology Foundation; American
Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the man-
agement of heart failure: a report of the American College of Cardiology Foundation/American
Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62(16):e147–e239
7) Law YM, Hoyer AW, Reller MD, Silberbach M. Accuracy of plasma B-type natriuretic peptide
to diagnose significant cardiovascular disease in children: the Better Not Pout Children! Study.
J Am Coll Cardiol. 2009;54(15):1467–1475
8) Maher KO, Reed H, Cuadrado A, et al. B-type natriuretic peptide in the emergency diagnosis of
critical heart disease in children. Pediatrics. 2008;121(6):e1484–e1488
9) Cantinotti M, Storti S, Crocetti M, Assanta N, Murzi B, Clerico A. Decision levels for plasma
B-type natriuretic peptide assay to diagnose significant cardiovascular disease in children. J Am
Coll Cardiol. 2010;55(11):1166–1167, author reply 1167
10) Fried I, Bar-Oz B, Algur N, et al. Comparison of N-terminal pro-B-type natriuretic peptide
levels in critically ill children with sepsis versus acute left ventricular dysfunction. Pediatrics.
2006;118(4):e1165–e1168
11) Koulouri S, Acherman RJ, Wong PC, Chan LS, Lewis AB. Utility of B-type natriuretic peptide
in differentiating congestive heart failure from lung disease in pediatric patients with respiratory
distress. Pediatr Cardiol. 2004;25(4):341–346
12) Kirk R, Dipchand AI, Rosenthal DN, et al. The International Society for Heart and Lung
Transplantation Guidelines for the management of pediatric heart failure: executive summary.
[corrected] J Heart Lung Transplant. 2014;33(9):888–909
113
CCIP.indb 113 3/13/18 4:18 PM

13) Hall EK, Glatz AC, Quartermain MD, et al. Brain-type natriuretic peptide correlates with
right heart pressures in a cross section of pediatric heart transplant patients. Pediatr Transplant.
2011;15(1):70–74
14) Avitabile CM, Leonard MB, Brodsky JL, et al. Usefulness of insulin like growth factor 1 as a
marker of heart failure in children and young adults after the Fontan palliation procedure. Am J
Cardiol. 2015;115(6):816–820
15) Rogers LS, Glatz AC, Ravishankar C, et al. 18 years of the Fontan operation at a single institu-
tion: results from 771 consecutive patients. J Am Coll Cardiol. 2012;60(11):1018–1025
16) Schwartz MC, Sullivan LM, Glatz AC, et al. Portal and sinusoidal fibrosis are common on liver
biopsy after Fontan surgery. Pediatr Cardiol. 2013;34(1):135–142
114
CCIP.indb 114 3/13/18 4:18 PM

PART 2
Common Signs
and Symptoms
8. Chest Pain........................................................................... 117
9. Syncope................................................................................ 133
10. Palpitations and Arrhythmia................................................ 147
11. Heart Murmur..................................................................... 161
12. Evaluation of the Neonate With Congenital

Heart Disease...................................................................... 171
115
CCIP.indb 115 3/13/18 4:18 PM

CCIP.indb 116 3/13/18 4:18 PM
CHAPTER 8
Chest Pain
Neha Bansal, MD, and Sanjeev Aggarwal, MD
Introduction
The symptom of chest pain in a child is one of the most common reasons for a visit
to the primary care physician or the emergency department. Chest pain accounts
for 650,000 physician visits per year in patients 10 to 21 years of age.1 Dramatic
media reports of sudden deaths in young, healthy athletes often provoke extreme
anxiety in the patient and parent and even sometimes in the physician. Unlike
adults, most chest pain complaints in children and adolescents are benign, are
noncardiac in origin, and often improve without any intervention. Previous studies
have demonstrated a cardiac etiologic origin in only 0% to 5% of children who
present with chest pain.2 In 1 study, only 1 in 380 children (0.3%) had chest pain
related to a cardiac cause.3 Obtaining a thorough history and performing a physical
examination are the critical initial steps in the diagnosis and management of most
chest pain in children. Often, these can be followed by providing reassurance to
the patient and family about the noncardiac origin of the chest pain. However, in
practice, extensive and expensive evaluations, which are low yield and may provoke
parental anxiety, are frequently performed for chest pain in children.4 The ever-
increasing use of expensive diagnostic tests for this frequent complaint place an
unnecessary burden on the health care system.5 On the other hand, some serious
conditions may manifest with chest pain in children and adolescents, which, if not
diagnosed and treated appropriately, may lead to a fatal outcome. All of these fac-
tors in combination pose challenges and create apprehension for the pediatricians
who care for these patients. This chapter contains an overview of the common
causes of chest pain and a systematic approach to its management in children.
117
CCIP.indb 117 3/13/18 4:18 PM

Clinical Features
Pediatric chest pain can be broadly classified into 2 categories: noncardiac and
cardiac. The frequency of various causes of chest pain is listed in Table 8-1.
Table 8-1. Frequency of Causes of Chest Pain

in Children
Emergency
Department or Cardiology
Cause Pediatric Clinic Clinic
Idiopathic or unknown cause 12%–61% 37%–54%
Musculoskeletal cause or costochondritis 7%–69% 1%–89%
Respiratory cause or asthma 13%–24% 1%–12%
Gastrointestinal cause or gastroesophageal 3%–7% 3%–12%

reflux disease
Psychogenic cause 5%–9% 4%–19%
Cardiac cause 2%–5% 3%–7%

From reference 6.
Noncardiac Chest Pain

Noncardiac chest pain is significantly more common in the pediatric population
than in adults and accounts for more than 93% to 98% of all chest pain in
children.6 The noncardiac causes of chest pain are further categorized as muscu-
loskeletal, pulmonary, gastrointestinal, and miscellaneous (Box 8-1).
Musculoskeletal or Chest Wall Pain
Musculoskeletal or chest wall pain is the most common cause of chest pain in
children, ranging from 15% to 31% of all cases.7
Active children, especially teenagers, strain their chest wall muscles while
participating in sports or while carrying heavy objects. This strain is usually
associated with a localized area of pain and tenderness. In most cases, the mus-
cular strain improves with analgesics and does not require extensive evaluation.7
However, sometimes, clinically significant direct trauma to the chest wall, such
as during wrestling, causes substantial chest pain and shortness of breath, which
can indicate rib fracture or myocardial contusion and hemopericardium.
Costochondritis or costosternal syndrome is a common musculoskeletal
disorder in children.8 It is characterized by unilateral or bilateral sharp, stabbing
pain along the parasternal area at the costochondral joints, which lasts for a few
seconds and is exaggerated by deep breaths.9 This pain typically lasts for a few
minutes to a few hours and is more common in girls.10 Sometimes, the pain
can be exacerbated after excessive exercise involving the arms and shoulders.
118
CCIP.indb 118 3/13/18 4:18 PM

Chest Pain
Box 8-1. Noncardiac Causes of Chest Pain in Children

Musculoskeletal Causes
•• Costochondritis, costosternal syndrome
•• Tietze syndrome
•• Trauma and muscle strain–overuse injury
•• Sickle cell vaso-occlusive crisis
•• Nonspecific or idiopathic chest wall pain
•• Slipping rib syndrome
Pulmonary Causes
•• Bronchial asthma
•• Exercise-induced or cough-variant asthma
•• Pleurisy
•• Pneumonia
•• Pneumothorax
•• Pulmonary embolism
•• Acute chest syndrome (sickle cell patients)
Gastrointestinal Causes
•• Gastroesophageal reflux disease
•• Peptic ulcer disease
•• Drug-induced esophagitis, gastritis
•• Cholecystitis
•• Esophageal spasm
Miscellaneous Causes
•• Anxiety or panic disorder
•• Breast-related conditions
•• Herpes zoster
Diagnosis is established via reproducible chest wall tenderness on palpation

at the costochondral junctions in the absence of any signs of inflammation.
Costochondritis is self-limiting; medications such as nonsteroidal anti-inflam-
matory drugs provide relief of symptoms.9
Tietze syndrome is a rare condition caused by localized nonsuppurative
inflammation of the sternoclavicular and costochondral joints and is often seen
in adolescents and young adults.11 On physical examination, tenderness often
occurs at a single joint, commonly involving the second or third rib.11 Although
the etiologic origin of Tietze syndrome is unknown, a recent upper respiratory
tract infection with excessive coughing is believed to be a primary antecedent.12
It differs from costochondritis by having single joint involvement with the
presence of localized signs of inflammation.
119
CCIP.indb 119 3/13/18 4:18 PM

Precordial catch syndrome, or “Texidor twinge,” is a sudden onset of sharp,

stabbing, brief (lasting a few seconds) episodes of chest pain along the left lower
sternal border. A diagnostic feature of this pain is the patient suddenly holding
his breath for a few seconds while pointing to 1 localized area for the pain,
mostly below the left nipple. This pain lasts for a few seconds and worsens with
deep breathing. A poor, slouched posture and a pinched nerve are often impli-
cated, though the etiologic origin remains unknown. The diagnosis is established
by obtaining a thorough history with normal physical examination findings.
Few shallow breaths or 1 deep breath and a straightened posture often relieve
the pain. Since the pain episodes are brief, analgesics are seldom used, making
reassurance to the family extremely important.
Slipping rib syndrome, or lower rib pain syndrome,13,14 is a rare disorder
that is recognized very infrequently.15 It is characterized by severe pain in the
lower chest wall and is caused by acute trauma to the eighth, ninth, and tenth
ribs. Lower ribs are not attached to the sternum directly and are freely mobile,
which makes them prone to even minor trauma and subluxation.15,16 This
causes the periodic episodic chest pain and a clicking sound with movement
and breathing. The best way to elicit this pain is by hooking the fingers in the
inferior part of the chest and attempting to move the lower ribs out (known as
the hooking maneuver).15
Idiopathic chest wall pain is the most commonly encountered diagnosis.
The patient frequently presents with sharp pain for a short duration that occurs
with and without exercise. There are no associated symptoms, although the
patient may have anxiety because the pain is often distressing and disturbing.
The physical examination findings are completely normal, and the pain may not
be reproducible on examination. There may be temporary relief with analgesics,
although recurrence is common.
Xiphoid pain, or xiphodynia, is the pain that is referred from the xiphisternal
joint or the structures attached to the xiphoid process. First described in 1955, it
is often caused by a hypersensitive xiphoid.17 It is frequently insidious in origin
but may be precipitated by blunt trauma, coughing, acceleration-deceleration
injuries, or unaccustomed heavy lifting.18 Pain can be elicited by pressing on
the xiphoid or its surrounding structures.19 Although the course of this pain is
self-limiting and providing reassurance to the family along with analgesics and
heat application are typically enough, there are reports in the literature of com-
plete resolution with a local injection of an anesthetic-steroid combination.17,19,20
Pulmonary and Upper Airway Causes
Pulmonary and upper airway conditions are the cause of chest pain in almost
one-quarter of patients.6 The prevalence of asthma in the pediatric population
is often underestimated, and the diagnosis may be missed. Children with
asthma, severe persistent cough, or pneumonia may have pain due to the overuse
120
CCIP.indb 120 3/13/18 4:18 PM

Chest Pain
of the chest muscles or inflammation of the pleura. The diagnosis is reached

by documenting the presence of wheezing, rales, or tachypnea and relief of
symptoms with bronchodilators. Exercise-induced asthma (EIA) is a frequent
cause of chest pain during exercise.21 It is estimated that 73% of patients with
chest pain have evidence of EIA during treadmill stress testing.21 This type of
chest pain often manifests as chest tightness and is usually preceded by difficulty
breathing.21,22 The bilateral pain is in the subcostal region and is thought to be
caused by excessive muscle use. However, a sudden chest pain with respiratory
distress should alert the physician to the need to evaluate the patient for a more
serious cause, such as pneumothorax from a previously unrecognized subpleural
bleb. Patients with sickle cell anemia may present with chest pain as a symptom
of acute chest syndrome. Finally, although rare in the pediatric population, severe
hypoxia with intense chest pain, especially in the setting of a teenage girl taking
oral contraceptive pills or a patient with recent leg trauma, should raise the sus-
picion for acute pulmonary embolism. Pulmonary embolism is life-threatening,
and a prompt evaluation and management are imperative for good outcomes.
Gastrointestinal Causes
Gastrointestinal disorders such as gastroesophageal reflux disease (GERD) or
reflux esophagitis may manifest with chest pain in young children and may
account for 5% to 7% of all the causes of chest pain in children, especially
adolescents.23 The characteristic features of this pain are its burning character,
the substernal or epigastric location, and an exacerbation with a reclining
position and spicy foods. Classically, there is tenderness in the epigastric and
subxiphoid region. Histamine-2 (H2) blockers or proton pump inhibitors are
the mainstays of treatment. Rarer causes include pill esophagitis, foreign-body
ingestion (like a coin), cholecystitis, and esophageal strictures.
Anxiety or conversion disorder associated with a recent stressful event, such as a
divorce in the family, school failures, and separation from friends, may include
chest pain as a presenting symptom. It is often associated with hyperventilation,
anxious demeanor, and sleep disturbances. Conversion disorder is a diagnosis
of exclusion after an extensive history and examination findings have allowed
other common causes of chest pain to be ruled out in children. Chest pain from
breast tenderness due to the physiological changes of puberty is common during
the teenage years. Adolescent girls may report throbbing chest pain due to
mastitis, fibrocystic disease, or pregnancy. Herpes zoster, or shingles, may result
in paresthesia or burning pain in a dermatomal pattern, which can precede the
rash. Finally, idiopathic chest pain is a label given when no clear etiologic origin
is established; it constitutes about 37% to 54% of all cases.6
121
CCIP.indb 121 3/13/18 4:18 PM

Cardiac Chest Pain

A cardiac etiologic origin for chest pain in children is rare, with a prevalence of
2% to 5%.6 Some of the common causes of pediatric cardiac chest pain are listed
in Box 8-2.
Box 8-2. Cardiac Causes of Chest Pain in Children

Coronary Artery Abnormality
•• Congenital: Abnormal anatomy like ALCAPA, ALCA from right sinus,
coronary artery fistulas
•• Acquired: Kawasaki disease, hypercholesterolemia
Arrhythmia
•• Supraventricular tachycardia
•• Ventricular tachycardia
•• Intra-atrial re-entrant tachycardia or slow atrial flutter
Structural Cardiac Defects

•• Hypertrophic obstructive cardiomyopathy
•• Left ventricular outflow tract obstruction: aortic stenosis, subaortic
stenosis, coarctation of the aorta
•• Mitral valve prolapse (Barlow syndrome)
Cardiac Inflammation
•• Pericarditis
•• Myocarditis
•• Infection: viral, bacterial
•• Noninfective: SLE, Crohn disease, postpericardiotomy syndrome
•• Aortic dissection—Marfan syndrome
•• Aortic root dissection—Ehlers-Danlos syndrome, homocystinuria
•• Toxic exposure—cocaine, marijuana, methamphetamine
•• Pulmonary hypertension
ALCA, anomalous left coronary artery; ALCAPA, anomalous left coronary artery from pulmonary artery; SLE, systemic
lupus erythematosus.
Coronary Artery Abnormalities

Coronary artery abnormalities are second only to hypertrophic cardiomyopathy
as a cause of sudden cardiac death in adolescents.24 Abnormal coronary
anatomy—especially the origin of a coronary from the wrong sinus, coronary
artery origin stenosis, or coronary artery fistulas—may present as chest pain
in adolescents. These patients may present with chest pain with activity or
collapse due to myocardial ischemia with strenuous exercise. Symptoms include
122
CCIP.indb 122 3/13/18 4:18 PM

Chest Pain
squeezing chest pain radiating down the left arm. In a specific condition where
the left main coronary artery arises from the right-sided coronary cusp of the
aorta and courses intramurally between the aorta and pulmonary artery, the pre-
senting symptoms may be cardiac arrest. With exertion, the left main coronary
artery gets squeezed between the aorta and main pulmonary artery, leading to
myocardial ischemia and, often, sudden death. Thus, chest pain or syncope with
exertion merits careful consideration of a cardiac etiologic origin.
Children with a prior history of Kawasaki disease are at an increased risk of
coronary artery stenosis as a long-term complication.25 A past history of coro-
nary artery aneurysms places patients at a higher risk of rupture, thrombosis, or
stenosis of the coronary artery, causing myocardial infarction. Similarly, a history
of a past surgical repair involving reimplantation of the coronary arteries, such
as an arterial switch operation for dextro-transposition of the great arteries, also
poses an increased risk of coronary artery stenosis and myocardial ischemia.26
A family history positive for hypercholesterolemia raises concerns for coronary
artery disease in patients. It may present as early as the second decade of life. The
American Academy of Pediatrics recommends a dyslipidemia risk assessment
beginning at 2 years of age, repeated every 2 years until 10 years of age and
then annually. In case of a family history positive for hypercholesterolemia or
for myocardial infarction before 55 years of age, screening with a fasting lipid
panel is recommended. Universal screening between 9 and 11 years of age
with a nonfasting serum total cholesterol concentration is also recommended,
to be repeated after a few years, followed by a fasting lipid profile if the total
cholesterol value is abnormal.27
Arrhythmias
Arrhythmias may manifest as chest pain or chest discomfort in children. They
are often, but not always, associated with a perception of palpitations by the
patients. The parents may notice a pale look on the patient’s face with these
arrhythmias. Supraventricular tachycardia is more common, but ventricular
tachycardia also can cause brief, sharp chest pain. Patients with repaired
complex congenital heart diseases, such as Fontan palliation, are at increased
risk of arrhythmias and sudden cardiac death and may present with chest pain
with palpitations.28
Structural Cardiac Defects
Structural cardiac defects should be considered in the differential diagnosis for a
child with chest pain. A patient with hypertrophic obstructive cardiomyopathy
may present with chest pain, exercise intolerance, and fatigue. It is autosomal
dominant, and patients often have a family history of hypertrophic cardio
myopathy. On auscultation, a murmur is heard best in the standing position
or while performing a Valsalva maneuver. Left ventricular outflow obstruction
from fixed causes, such as aortic stenosis, can manifest with chest pain associated
123
CCIP.indb 123 3/13/18 4:18 PM

with fatigue, dizziness, or syncope, especially with exercise. A harsh systolic ejec-
tion murmur is best heard in the left upper parasternal area, with radiation to the
neck. An ejection click may be heard in the presence of a bicuspid aortic valve.
Finally, mitral valve prolapse (Barlow syndrome), which is rarely seen in children,
may cause chest pain associated with palpitations, dizziness, and panic attacks.
Mitral valve prolapse has the classical examination finding of a midsystolic click
and a mid-to-late systolic murmur. The click and associated murmur in MVP
get closer to the first heart sound (S1) on standing from a sitting position.
Cardiac and Pericardial Inflammation
Cardiac and pericardial inflammation is an important cause of pediatric chest
pain. Pericarditis with or without pericardial effusion often produces a sharp
stabbing retrosternal chest pain, which is worse when lying down and improves
markedly with sitting up and even more with leaning forward. Pericarditis is
mostly viral in etiologic origin in developed countries. Myocarditis can some-
times manifest with chest pain on exertion and shortness of breath. At cardiac
examination, patients with myocarditis may have a gallop rhythm and tachy
cardia or tachypnea out of proportion to the degree of fever.29,30 Cardiomegaly
may be evident on a chest radiograph. Occasionally, other systemic diseases,
such as systemic lupus erythematosus, renal failure, hypothyroidism, and Crohn
disease, may be associated with pericardial effusion and chest pain. Another
cause of pericardial effusion after a recent open-heart surgery is postpericar
diotomy syndrome. Please see Chapter 32, Myocarditis, and Chapter 33,
Pericardial Diseases, for more detailed discussions of each entity.
Miscellaneous Cardiac Causes
Patients with aortic dissection, especially with Marfan syndrome, could present
with extremely severe, tearing, midsternal chest pain that radiates to the back.
Aortic root dissection is also rarely seen in patients with Turner syndrome,
Ehlers-Danlos syndrome, and homocystinuria. Toxic exposure to cocaine,
marijuana, and methamphetamines may also cause chest pain due to myocardial
ischemia or inducing arrhythmias. Rarely, pulmonary hypertension can manifest
with chest pain associated with syncope, fatigue, or exertional dyspnea.
Evaluation
Though the etiologic origin of chest pain in most of the pediatric population
is usually benign, each child should be thoroughly evaluated to rule out any
clinically significant underlying pathologic processes. It is important to rule
out pathologic reasons for the chest pain to formulate a future management
plan for the patient.
124
CCIP.indb 124 3/13/18 4:18 PM

Chest Pain
History Compilation
There is no substitute for a detailed and meticulous history for a child with chest
pain. The history should include a thorough description of the chest pain, with
any associated symptoms, as well as identifying the aggravating and relieving
factors for the chest pain.
Onset and Duration
It is important to determine the onset and duration of the pain. An acute-onset
chest pain is more likely to have an organic etiologic origin, which may not
always be life-threatening. Pneumonia, asthma exacerbation, trauma, and
arrhythmias often present with acute pain. In a young patient with acute pain,
it is important to always rule out foreign-body ingestion (such as a coin or a
button battery). Chronic pain is more likely to have a musculoskeletal, idiopathic,
or psychogenic etiologic origin.
Character and Location of Pain
Most children poorly characterize the location of pain and describe their pain as
moderate to severe and anterior in location, often pointing to their entire chest.31
Chest wall pain, as well as pleural pain, is often sharp and is exacerbated by
taking deep breaths. Pleural pain is often superficially located and is sharp and
localized, whereas pain caused by asthma is often deep and diffuse. Psychogenic
pain is more often than not vague in character and poorly localized, with variable
locations. Cardiac pain is often described in adults as a pressure-like, crushing,
squeezing, or “elephant-sitting-on-chest” sensation, with pain radiating to
the arm and neck, although it is unclear if the presentation is the same in the
pediatric population.
Precipitating and Relieving Factors
Any chest pain that is aggravated by exercise or running is a concerning
symptom because it may indicate a cardiac etiologic origin. However, EIA and
chest wall pain may also get aggravated with physical activity. It is crucial to
differentiate whether the pain is experienced during exercise such as running
or immediately after the exercise. Ask for associated symptoms with this pain,
such as shortness of breath and wheezing, and whether there is any relief with
the use of bronchodilator therapy. Inquire about any recent chest wall trauma,
lifting weights, history of wrestling, or gymnastics training. Any temporal asso-
ciation with food intake, especially spicy food and worsening in the recumbent
position, suggests reflux as the more likely etiologic origin. The parents may have
a distinct memory of the child choking on a coin or a button battery. Any recent
stressors associated with symptoms of chest pain, especially in a teenage girl, may
be psychogenic in origin. Chest pain that is mitigated by sitting up and leaning
forward may be due to pericarditis. It is often referred to the shoulder because
of irritation of the peritoneal cavity (Kehr sign).
125
CCIP.indb 125 3/13/18 4:18 PM

Associated Complaints
Chest pain associated with palpitations or syncope is often due to cardiac
etiologic origins.6 Infectious etiologic origin of chest pain, such as pneumonia
or myopericarditis, may have associated fevers. Drooling and refusal to swallow
food indicate foreign-body ingestion. Rheumatic causes of chest pain, such as
systemic lupus erythematosus, often yield other symptoms, such as joint pains
or rash. A complete review of systems is essential in identifying other relevant
information for formulating a differential diagnosis.
Past Medical and Surgical History
A comprehensive past medical history of illnesses such as Kawasaki disease,
asthma, sickle cell disease, and connective tissue disorders should be obtained.
A past history of cardiac surgery, especially coronary artery reimplantation,
should be obtained. Complete family history should be obtained with special
focus on sudden unexplained cardiac deaths, especially during sports and swim-
ming, placement of defibrillators or pacemakers in family members, arrhythmias,
and Marfan syndrome or other genetic syndromes in the family.
Other Elements of the History
Adolescents should always be asked about the use of medications, such as oral
contraceptives or pills associated with esophagitis, including tetracyclines. They
should also be privately questioned about use of substances such as cocaine,
marijuana, or methamphetamines.
Children with chest pain generally do not present in acute distress or extremis
that requires immediate care and can frequently be evaluated in a nonemergent
setting. Vital signs should be carefully assessed for every patient, with close
attention given to the reference values for the patient’s age. The presence of
fever suggests an infectious etiologic origin of chest pain due to pneumonia or
pericarditis-myocarditis. It is important to observe the patient for any signs of
chronic illnesses, such as poor growth or pallor. A tall and thin-appearing child
could have Marfan syndrome, if the arm span exceeds the height of the patient.
Skin examination can reveal rashes like the butterfly malar rash of systemic lupus
erythematosus. A detailed chest examination should be conducted to identify
any clinically significant cardiac pathologic findings. The chest wall should be
closely observed for any deformities, such as pectus carinatum or excavatum,
breast enlargement, or any costochondral joint swelling. Chest wall tenderness
with easily reproducible chest pain points toward a musculoskeletal etiologic
origin of the pain. In a study, it was seen in almost 54% of the pediatric patients
in the emergency department who presented with chest pain.32 Breast tenderness
often indicates physiological changes of adolescence. A hooking maneuver,
which reproduces the pain, indicates the slipping rib syndrome.14 Auscultation
126
CCIP.indb 126 3/13/18 4:18 PM

Chest Pain
of the lung fields may reveal a wheeze, rales, or decreased breath sounds, which
would indicate a respiratory etiologic origin such as asthma or pneumonia.
A detailed cardiovascular examination in sitting, lying down, and standing
positions may reveal a murmur, rub, muffled heart sounds, or irregular rhythm.
However, it is important to note that an absence of any abnormal cardiac finding
does not exclude a cardiac disease. A systolic murmur, which gets louder with a
Valsalva maneuver or with standing from a squatting position, is characteristic
of hypertrophic obstructive cardiomyopathy. Every teenager who presents
with chest pain should undergo a detailed cardiac auscultation in the squatting
position, followed by transition to the standing position to elicit any increase in
the intensity of the systolic murmur or auscultation of a new murmur along the
left upper sternal border, signifying a pathologic murmur.
Investigations
For most children who present with chest pain, a comprehensive history and
thorough physical examination are enough to indicate a specific diagnosis.
Diagnostic testing in this population has limited yield, and unless specifically
indicated (Table 8-2), chest radiography or electrocardiography (ECG) should
not be ordered routinely. If the history indicates acute chest pain with specific
concerns for pulmonary or cardiac cause of the pain, chest radiographic findings
would serve to delineate the lung fields and the cardiac silhouette. Chest
radiography is indicated to look for infiltrates for a diagnosis of pneumonia in
the presence of a fever with respiratory distress and depressed breath sounds.
It may also be an adjunct to diagnosis of myocarditis or pericarditis with the
presence of cardiomegaly. Pain associated with exertion, palpitations, or syncope
warrants both chest radiography and ECG to appropriately diagnose a cardiac
cause of the pain. ECG is useful in the diagnosis of arrhythmias in the case of
chest pain with palpitations or sensed tachycardia. When chest pain is associated
with exercise, an exercise stress test is often required to assess the evolution of
arrhythmias or ischemia with exercise. In some patients with a history suggestive
of EIA, pulmonary function tests, along with the exercise stress test, may be
necessary to confirm the diagnosis. If a cardiac disease is suspected, referral to
a pediatric cardiologist is indicated. Further testing, such as echocardiography,
Holter monitoring, cardiac catheterization, or electrophysiology studies, must
be conducted at the discretion of the pediatric cardiologist.
Management
A thorough clinical history and physical examination often obviate the need for
diagnostic testing. Providing reassurance to the parents, offering analgesics to
the patient, and advising rest from substantial physical exertion in the setting
of noncardiac chest pain are often therapeutic. If the etiologic origin of the
chest pain is identified as musculoskeletal, a key point to remember and remind
127
CCIP.indb 127 3/13/18 4:18 PM

Table 8-2. Worrisome Signs and Symptoms to Prompt

Further Workup in Pediatric Patients With Chest Pain
Workup
Indicated History or Symptom Sign
Chest Fever Fever

radiography
Cough Tachypnea, rales, distress
Shortness of breath Patient ill-appearing or sick
History of trauma Clinically significant trauma
Pain that wakes the patient Extreme tachycardia

from sleep
History of drug use (eg, Pathologic auscultation of the

cocaine) heart
Symptom associated with Absent, decreased breath sounds

exercise
Acute onset of pain Palpation of subcutaneous air
Serious medical problems Tall, thin patient

(Marfan syndrome, Kawasaki
disease, lupus)
Foreign-body ingestion (coin, Drooling, gagging

button battery)
ECG Symptom associated with Pathologic auscultation of the

exercise heart
Symptom associated with Tachycardia (>180 beats/min)

syncope
History of drug use (eg, Patient ill-appearing or sick

cocaine)
Fever Fever
ECG, electrocardiography. Adapted from reference 6. The data originally appeared in reference 36.
families about is that, on most occasions, it resolves spontaneously. If the history

is suggestive of trauma, then chest radiographic findings may help to identify any
trauma to the bones. In a patient whose musculoskeletal pain is severe and/or
persists for a longer duration, advising rest, topical heat, and a week-long course
of around-the-clock analgesic therapy generally helps with symptom resolution.
A patient with any infectious etiologic origin needs appropriate treatment
of the underlying pathologic process. Any suspicion of GERD, esophagitis, or
gastritis warrants a therapeutic trial of H2 blockers, such as ranitidine, or proton
pump inhibitors, such as omeprazole. EIA requires a trial of a β-agonist, inhaled
right before the initiation of exercise. Any pain that is idiopathic or undiagnosed
can be treated with analgesics and closely monitored. Consider relaxation
128
CCIP.indb 128 3/13/18 4:18 PM

Chest Pain
techniques with referral to a psychologist or psychiatrist when appropriate, in

cases of pain related to stress or anxiety.
There are many variations in the management of these patients in an
outpatient setting, as well as in the emergency department.33 There are no set
protocols for the management of chest pain in children. However, some insti-
tutions are developing standardized protocols to evaluate and manage patients
who present with chest pain by using Standardized Clinical Assessment and
Management Plans (Figure 8-1).34 The hope is to reduce practice variation and
All patients with CP code

n = 417
All chest pain Primary complaint of

n = 406 palpitations (excluded)
n = 11
Negative exam, Concerning Abnormal Abnormal Positive

ECG, history PMHx = 4 exam ECG family history
n = 362 n = 16 n = 20 n=4
Nonexertional Exertional
Echo
chest pain chest pain
n = 145
n = 233 n = 129
Alternative No alternative
diagnosis explanation
suspected n = 119
n = 10
Chest pain at Chest pain

low level of at high level
exertion only of exertion
n = 18 n = 101
No echo
n = 261
FIGURE 8-1. The Standardized Clinical Assessment and Management Plan, or SCAMP, algorithm
to guide testing in patients with chest pain is shown. Six patients had an abnormal electrocardio-
graphic (ECG) result and an abnormal past medical history, family history, or physical examination
finding. Patients with more than 1 abnormality (ie, abnormal ECG, past medical history, family
history, and/or physical examination finding) were counted in only 1 category in this figure. CP
= chest pain, echo = echocardiogram, PMHx = past medical history. From Friedman KG, Kane
DA, Rathod RH, et al. Management of pediatric chest pain using a standardized assessment and
management plan. Pediatrics. 2011;128:239–245.
129
CCIP.indb 129 3/13/18 4:18 PM

unnecessary resource use while improving patient outcomes, reducing patient

care costs, and improving efficiency. This approach has been found to be useful
in other settings.35
When to Refer
A referral to a pediatric cardiologist is indicated when the chest pain is thought
to be caused by a cardiac disease (Box 8-3). Any chest pain with exertion, pain
associated with palpitations and syncope, abnormal cardiac auscultation with
irregular or skipped beats, or a murmur that does not sound innocent in nature
(especially one that increases with a Valsalva maneuver) requires further evalu-
ation by a cardiologist. A concerning family history that contains arrhythmias,
sudden cardiac deaths, hypercholesterolemia, or genetic abnormalities associated
with cardiac defects also necessitates referral to a cardiologist.
Box 8-3. Indications for a Referral to a Pediatric

Cardiologist
•• Chest pain with exertion
•• Associated symptoms of palpitations or syncope with pain
•• Clinically significant family history of arrhythmias, sudden cardiac deaths,
hypercholesterolemia, or genetic abnormalities associated with cardiac
defects
•• History of Kawasaki disease
•• History of previous cardiac surgeries
•• Abnormal cardiac examination: skipped beats, murmur that is not inno-
cent (especially systolic murmur accentuated with a Valsalva maneuver)
•• Electrocardiographic abnormalities
Key Points
•• In contrast to adults, chest pain in children is often noncardiac in origin.
•• Musculoskeletal chest pain is the most common cause of chest pain in children.
•• A thorough history and physical examination are often sufficient to diagnose
the cause of the pain.
•• Chest pain during exertion or pain associated with palpitations or syncope is a
red flag and requires further evaluation and referral to a pediatric cardiologist.
130
CCIP.indb 130 3/13/18 4:18 PM

Chest Pain
References
1) Feinstein RA, Daniel WA Jr. Chronic chest pain in children and adolescents. Pediatr Ann.
1986;15(10):685–686, 691–694
2) Friedman KG, Alexander ME. Chest pain and syncope in children: a practical approach to the
diagnosis of cardiac disease. J Pediatr. 2013;163(3):896–901.e1, 3
3) Sert A, Aypar E, Odabas D, Gokcen C. Clinical characteristics and causes of chest pain in
380 children referred to a paediatric cardiology unit. Cardiol Young. 2013;23(3):361–367
4) Danduran MJ, Earing MG, Sheridan DC, Ewalt LA, Frommelt PC. Chest pain: characteristics
of children/adolescents. Pediatr Cardiol. 2008;29(4):775–781
5) Borger C, Smith S, Truffer C, et al. Health spending projections through 2015: changes on the
horizon. Health Aff (Millwood). 2006;25(2):w61–w73
6) Thull-Freedman J. Evaluation of chest pain in the pediatric patient. Med Clin North Am. 2010;
94(2):327–347
7) Selbst SM. Chest pain in children. Pediatrics. 1985;75(6):1068–1070
8) Selbst SM, Ruddy RM, Clark BJ, Henretig FM, Santulli T Jr. Pediatric chest pain: a prospective
study. Pediatrics. 1988;82(3):319–323
9) Driscoll DJ, Glicklich LB, Gallen WJ. Chest pain in children: a prospective study. Pediatrics.
1976;57(5):648–651
10) Brown RT. Costochondritis in adolescents. J Adolesc Health Care. 1981;1(3):198–201
11) Mukamel M, Kornreich L, Horev G, Zeharia A, Mimouni M. Tietze’s syndrome in children and
infants. J Pediatr. 1997;131(5):774–775
12) Fam AG, Smythe HA. Musculoskeletal chest wall pain. CMAJ. 1985;133(5):379–389
13) Turcios NL. Slipping rib syndrome: an elusive diagnosis. Paediatr Respir Rev. 2017;22:44–46
14) Heinz GJ, Zavala DC. Slipping rib syndrome. JAMA. 1977;237(8):794–795
15) Porter GE. Slipping rib syndrome: an infrequently recognized entity in children: a report of
three cases and review of the literature. Pediatrics. 1985;76(5):810–813
16) Saltzman DA, Schmitz ML, Smith SD, Wagner CW, Jackson RJ, Harp S. The slipping rib
syndrome in children. Paediatr Anaesth. 2001;11(6):740–743
17) Lipkin M, Fulton LA, Wolfson EA. The syndrome of the hypersensitive xiphoid. N Engl J Med.
1955;253(14):591–597
18) Simpson JK, Hawken E. Xiphodynia: a diagnostic conundrum. Chiropr Osteopat. 2007;15:13
19) Howell JM. Xiphodynia: a report of three cases. J Emerg Med. 1992;10(4):435–438
20) Sklaroff HJ. Xiphodynia—another cause of atypical chest pain: six case reports. Mt Sinai J Med.
1979;46(6):546–548
21) Wiens L, Sabath R, Ewing L, Gowdamarajan R, Portnoy J, Scagliotti D. Chest pain in other-
wise healthy children and adolescents is frequently caused by exercise-induced asthma. Pediatrics.
1992;90(3):350–353
22) Edmondstone WM. Chest pain and non-respiratory symptoms in acute asthma. Postgrad Med J.
2000;76(897):413–414
23) Hussain MZ, Ishrat S, Salehuddin M, Mahmood M, Islam MT. Chest pain in children: an
update. Mymensingh Med J. 2011;20(1):165–170
24) Maron BJ, Doerer JJ, Haas TS, Tierney DM, Mueller FO. Sudden deaths in young
competitive athletes: analysis of 1866 deaths in the United States, 1980-2006. Circulation.
2009;119(8):1085–1092
25) Newburger JW, Takahashi M, Gerber MA, et al; Committee on Rheumatic Fever, Endocarditis
and Kawasaki Disease; Council on Cardiovascular Disease in the Young; American Heart
Association; American Academy of Pediatrics. Diagnosis, treatment, and long-term
management of Kawasaki disease: a statement for health professionals from the Committee
on Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease
in the Young, American Heart Association. Circulation. 2004;110(17):2747–2771
131
CCIP.indb 131 3/13/18 4:18 PM

26) Legendre A, Losay J, Touchot-Koné A, et al. Coronary events after arterial switch operation for
transposition of the great arteries. Circulation. 2003;108(Suppl 1):II186–II190
27) Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in
Children and Adolescents; National Heart, Lung, and Blood Institute. Expert panel on
integrated guidelines for cardiovascular health and risk reduction in children and adolescents:
summary report. Pediatrics. 2011;128(Suppl 5):S213–S256
28) Pundi KN, Pundi KN, Johnson JN, et al. Sudden cardiac death and late arrhythmias after the
Fontan operation. Congenit Heart Dis. 2017;12(1):17–23
29) Durani Y, Egan M, Baffa J, Selbst SM, Nager AL. Pediatric myocarditis: presenting clinical
characteristics. Am J Emerg Med. 2009;27(8):942–947
30) Freedman SB, Haladyn JK, Floh A, Kirsh JA, Taylor G, Thull-Freedman J. Pediatric
myocarditis: emergency department clinical findings and diagnostic evaluation. Pediatrics.
2007;120(6):1278–1285
31) Rowe BH, Dulberg CS, Peterson RG, Vlad P, Li MM. Characteristics of children presenting
with chest pain to a pediatric emergency department. CMAJ. 1990;143(5):388–394
32) Lin CH, Lin WC, Ho YJ, Chang JS. Children with chest pain visiting the emergency depart-
ment. Pediatr Neonatol. 2008;49(2):26–29
33) Hambrook JT, Kimball TR, Khoury P, Cnota J. Disparities exist in the emergency department
evaluation of pediatric chest pain. Congenit Heart Dis. 2010;5(3):285–291
34) Friedman KG, Kane DA, Rathod RH, et al. Management of pediatric chest pain using a
standardized assessment and management plan. Pediatrics. 2011;128(2):239–245
35) O’Connor GT, Plume SK, Olmstead EM, et al; The Northern New England Cardiovascular
Disease Study Group. A regional intervention to improve the hospital mortality associated with
coronary artery bypass graft surgery. JAMA. 1996;275(11):841–846
36) Gokhale J, Selbst SM. Chest pain and chest wall deformity. Pediatr Clin N Am. 2009;56:49–65
132
CCIP.indb 132 3/13/18 4:18 PM

CHAPTER 9
Syncope
Lalitha Sivaswamy, MD, and Pooja Gupta, MD, FASE, FACC
Introduction
The term syncope is derived from the Greek word synkoptein, meaning “to cut short.”
It is defined as an episode of brief loss of consciousness, with concomitant loss of
postural tone, followed by spontaneous recovery. Syncope is caused by transient
cerebral hypoperfusion. Near-syncope is the term used when the loss of conscious-
ness is not complete. In some individuals and under certain circumstances, the
phase involving complete loss of consciousness is skipped altogether, and the
prodromal symptoms followed by complete recovery constitute near-syncope.
Etiologic Origins
In most children, the cause of syncope tends to be a disorder of autonomic
imbalance or dysfunction.1 About 10% of children with syncope have an under-
lying cardiac etiologic origin.2 See Box 9-1 for common causes of syncope in the
pediatric age group.
Orthostatic hypotension is defined as sustained systolic blood pressure reduction
of more than 20 mm Hg or diastolic blood pressure reduction of more than 10 mm
Hg or an increase in heart rate of more than 30 beats per minute (postural ortho-
static tachycardia syndrome [POTS] if there is no change in blood pressure) within
3 minutes of standing up or with a head tilt of more than 60 degrees.3 Causes of
orthostatic hypotension include nonneurogenic causes, such as drugs or hypovo-
lemia, and neurogenic causes that may be preganglionic and/or postganglionic
forms of sympathetic failure or may be initiated by systemic disease states, such
as diabetes.4 Psychogenic syncope is seen in children with panic attacks, anxiety
disorders, depression, and malingering.
133
CCIP.indb 133 3/13/18 4:18 PM

Box 9-1. Common Causes of Syncope in Children

A. Autonomic Imbalance or Dysfunction That Leads to Syncope
•• Neurocardiogenic or vasovagal
•• Reflex syncope or situational syncope (also a form of neurocardio-
genic syncope)
•• Cough or defecation syncope
•• Micturition syncope
•• Postprandial syncope
•• Syncope related to a specific activity, such as swallowing or playing
a brass instrument
•• Syncope related to a blood draw or an emotional event
•• Postural orthostatic tachycardia syndrome, an autoimmune auto-
nomic neuropathy
—— From prolonged bed rest
—— From traumatic brain injury
•• Orthostatic hypotension
—— Volume depletion
—— Medications
—— Autonomic failure (eg, diabetes)
—— Prolonged standing in a hot or crowded environment
•• Breath-holding spells
•• “Fainting lark” game
B. Cardiac Causes
•• Obstructive causes: Aortic stenosis, hypertrophic cardiomyopathy,
pulmonary stenosis, sub- or supra-aortic stenosis
•• Myocardial disease or pericardial disease: Myocarditis, cardiomyop-
athy (restrictive or dilated types, arrhythmogenic right ventricular
dysplasia, related to muscular dystrophy), pericardial tamponade
•• Conduction abnormalities leading to tachy- or bradyarrhythmias,
such as supraventricular tachycardia, long QT syndrome, short QT
syndrome, catecholamine-induced polymorphic ventricular tachy-
cardia, Brugada syndrome, sinus node dysfunction, third-degree
atrioventricular block
•• Coronary causes: Anomalous origin or course of the coronary
vessels, Kawasaki disease
C. Psychogenic Causes
•• Anxiety
•• Depression
•• Conversion reactions
•• Malingering
The rest of this chapter will focus on the most common form of syncope,
which is neurocardiogenic or vasovagal; differences between cardiogenic and
neurocardiogenic syncope (NCS); and indications for referring these children
to a cardiologist. It will also address the salient features that would indicate a
neurological basis for transient alterations in level of consciousness.
134
CCIP.indb 134 3/13/18 4:18 PM

Syncope
Pathophysiology
Autonomic Imbalance
Sympathetic (adrenergic) control over the circulatory system is key to the
rapid cardiovascular changes that must occur when one assumes the standing
position, because such alterations ultimately determine the maintenance of
cerebral blood flow when upright (being upright is also referred to as orthostasis).
Normal responses to standing up consist of increases in heart rate and systolic
and diastolic blood pressures, reduced cerebral blood flow, increased peripheral
vascular resistance, and redistribution of blood volume to the lower extremities.
Children with ineffective sympathetic vasoconstriction responses develop
orthostatic symptoms. Orthostatic intolerance refers to symptoms such as
light-headedness and signs such as hypotension that occur when upright and
that are relieved with recumbence.
Neurocardiogenic Syncope
The terms NCS and vasovagal syncope are often used interchangeably. In this
chapter, the abbreviation NCS will be used to refer to this category of syncope.
The Bezold-Jarisch reflex is thought to underlie the development of NCS,
although there is no substantive evidence to support this hypothesis. This reflex
is triggered when ventricular preload is diminished by venous stasis in the
lower extremities, leading to reduced cardiac output and activation of arterial
baroreceptors in the carotid sinus. Further, mechanoreceptors in the atria and
ventricles are also activated. The net result is projection of increased signals to
the dorsal nucleus of the vagus nerve, causing bradycardia due to excitation of
the parasympathetic system. This bradycardia leads to the clinical manifestations
of syncope due to reduced cerebral perfusion. There are 3 recognized steps in
the evolution of NCS: increase in heart rate while the blood pressure stabilizes;
decline in blood pressure as the heart rate continues to increase; and precipitous
decrease in both heart rate and blood pressure.5
Breath-Holding Spells
The exact mechanism of breath-holding spells has not been elucidated.
Autonomic dysregulation that leads to reduced cardiac output and therefore
reduced cerebral blood flow is an important component of the pathogenesis.6
Iron and zinc deficiency have also been associated with breath-holding spells,
although the causal relationship remains elusive. It is speculated that iron defi-
ciency anemia leads to irritability with increased episodes of crying, which may
predispose the patient to breath-holding spells and also results in catecholamine
dysregulation, which might mediate the clinical symptoms.7 Both pallid and
cyanotic types of breath-holding spells are believed to be caused by similar
pathogenic mechanisms.
135
CCIP.indb 135 3/13/18 4:18 PM

Cardiogenic Syncope
Cardiac syncope may result from a variety of etiologic origins (Box 9-1) that
lead to reduced cardiac output, arrhythmia, or abnormal myocardial contractility
and ultimately lead to cerebral hypoperfusion. Although less common, cardiac
syncope is important to recognize because the consequences can be more severe
and can even result in sudden cardiac death and near-episodes of unexpected
sudden infant death syndrome, or SIDS.8
Clinical Features
The prevalence of syncope is higher in children than adults, with up to 15% of all
teenagers reporting at least 1 episode before the age of 18 years.9 In some studies,
a prevalence of up to 47% is estimated in adolescent girls and 24% in teenage
boys.10 At least one-half of syncopal spells are recurrent in nature. Moore and
Watemberg have correctly pointed out that syncope is frequently missed as a
diagnosis in younger children and should be considered if there is an identifiable
trigger, loss of consciousness, and rapid recovery.11
NCS typically includes 3 phases: the prodromal phase; the actual loss or alter-
ation of consciousness, which is the syncopal phase; and the recovery phase.
The prodrome can be described by individuals variably and most commonly
includes the following descriptions: feeling dizzy, “woozy,” or light headed;
headache; flushing; feeling warm; diaphoresis; nausea; muffled hearing; visual
changes, such as seeing flashes or spots or having blurry vision or tunnel vision;
and blacking out. Some individuals might experience shaking or palpitations
and may look pale during and prior to the syncopal episode.
The syncopal phase includes altered consciousness, along with loss of postural
tone that results in collapse or near-collapse on the ground. Some individuals
may experience seizure-like movements or convulsions. This phase is followed
by quick, rapid recovery of consciousness and complete recovery. After recovery,
there may be some fatigue and headache.
NCS usually occurs in the upright posture and is most likely to happen when
changing positions or standing for prolonged periods of time. Episodes may also
occur in response to pain, fear, or certain situations (eg, the sight of blood).
Breath-Holding Spells
The clinical presentation of breath-holding spells is fairly distinct from other
causes of autonomic imbalance. Breath-holding spells are unique to young
children and are of 2 types: cyanotic and pallid. Cyanotic breath-holding spells
occur in children between 6 months and 5 years of age.12 There is a loud cry,
usually in response to withdrawal of a desired object or a mild injury, followed
136
CCIP.indb 136 3/13/18 4:18 PM

Syncope
by apnea in expiration. This leads to cyanosis and, in some circumstances, loss of

consciousness, limpness or opisthotonus, and a few myoclonic jerks. The spells
tend to be short and abruptly terminated by sudden deep inspiration and return
of consciousness. The pallid variety occurs in children between 12 and 24 months
of age.12 The spells are brought on by circumstances similar to those of cyanotic
spells, but the child suddenly stops breathing, with no cry heralding the
event. The child loses consciousness and becomes pale. There is accompanying
bradycardia and, in extreme cases, even asystole during the spells. There is some
evidence that children with breath-holding spells develop NCS in adolescence.13
Fainting Lark
“Fainting Lark” is a game played by children wherein they squat with their knees
bent and take rapid, deep breaths. They quickly stand up thereafter and perform
the Valsalva maneuver. This sequence leads to transient loss of consciousness.
Postural Orthostatic Tachycardia Syndrome

POTS is a condition characterized by a heart rate increase of more than
30 beats/min that occurs within 5 to 30 minutes of standing, without orthostatic
hypotension.5 Children with POTS often have chronic symptoms, such as
light-headedness, exercise intolerance, headache, fatigue, poor temperature
regulation, and bladder symptoms, but they rarely faint. Nonetheless, the
symptoms can be fairly disabling. It has become evident that POTS can be
the manifestation of several underlying disease states, including autoimmune
autonomic neuropathy, cardiac atrophy after prolonged bed rest, traumatic
brain injury, and heightened sensitivity to catecholamines.14
Cardiac Syncope
Cardiac syncope usually manifests during exertion and may not have the
prodromal stage. However, the presence or absence of the prodromal phase
does not in itself guide one toward a cardiac or noncardiac etiologic origin.
Historical aspects and other findings that help differentiate NCS—the benign
form of syncope—from cardiac syncope, which is the more ominous form of
syncope, are discussed in the following section.
Evaluation
History
The clinical story is of utmost importance in distinguishing the benign forms of
syncope (NCS) from other serious causes, such as cardiac conditions and neuro-
logical disorders that may mimic syncope. Hurst and colleagues have shown that
specific historical features can aid in the diagnosis of cardiac causes of syncope
with a sensitivity and specificity of 100%.15
137
CCIP.indb 137 3/13/18 4:18 PM


The details of activities that preceded the syncopal episode, the patient’s exact
posture at the time, and the sequence of symptoms are helpful in the diagnosis
of NCS. Upright posture and presence of all 3 phases during the episode favors
NCS. A personal history of light-headedness (often referred to as “dizziness”),
nausea, muffled hearing, transient vision loss, clammy extremities, and pallor may
precede the actual spell, as noted in the Clinical Presentation section. A history
should be elicited from the child and parents, but every attempt must be made
to contact eye witnesses of the episode, if any, because witnesses may note the
short duration of the spell with immediate recovery of consciousness and no
sustained period of confusion or disorientation after the syncopal spell. Bladder
incontinence may occur in rare instances. Up-rolling of the eyes is not pathogno-
monic for any disease state and may be noted in children with different forms of
syncope, as well as seizures.9 The presence of focal signs, such as forcible head or
eye deviation to one side, weakness on one side of the face, or hemiparesis before
or after the collapse, may be suggestive of a neurological basis for the symptoms.
A history of brief, nonrhythmic limb movements or convulsions, which are
reminiscent of seizure-like activity, may be noted with both NCS and cardiac
syncope.16 Prolonged tiredness can be present after an episode of NCS. However,
prolonged postictal state associated with confusion will support a neurological
basis for the episode.
Syncope from serious cardiac causes may be abrupt in onset, with few or no
warning symptoms, and may skip the prodromal phase. Syncope that occurs
during physical exertion is more likely due to cardiac conditions.
Red flags in the history that should alert a clinician to investigate the
presence of a cardiac cause include the following:
•• Sudden syncopal episode with lack of prodromal symptoms
•• Syncope during exertional activity or while supine
•• Syncope preceded by palpitations and/or chest pain
•• Syncope with a personal history of cardiac disease or cardiac surgery
•• Family history of sudden cardiac death in young individuals (younger than
30 years of age) or inheritable cardiac disease or cardiomyopathy
Family history of bilateral hearing loss or seizures in immediate family members,
in addition to cardiac disease or intracardiac defibrillator placement in young
family members, may suggest long QT syndrome.
Other historical details of note include fluid and salt intake, color of the
urine (to assess hydration and fluid intake), meal schedule, caffeine intake, use
of antihypertensive and proarrhythmic medications, and use of illicit drugs.
The specific circumstances during which breath-holding spells occur make for
an easy clinical diagnosis in most instances. A family history of breath-holding
138
CCIP.indb 138 3/13/18 4:18 PM

Syncope
spells is present in up to one-third of children who experience it themselves.17

Psychogenic causes of syncope can also be delineated on the basis of history
or observation of a recorded spell by a physician and confirmed with normal
physical examination findings. Children with a history of abuse may present
with psychogenic syncope.18
A comprehensive physical examination, including a detailed cardiac and
neurological examination, is of tremendous value in management and will help
in the delivery of optimal care to the patient by preventing unnecessary testing.
Blood pressure and heart rate should be obtained after 5 minutes of being in
the supine position. These measurements should be repeated after 3 minutes of
standing up. A decrease in systolic blood pressure of more than 20 mm Hg or an
increase in heart rate of more than 30 beats per minute in the standing position
suggests orthostatic hypotension or neurally mediated hypotension. The neck
should be auscultated for carotid bruits. Physical examination for valvular heart
disease, left ventricular outflow tract obstruction, left ventricular dysfunction, and
pulmonary hypertension should be meticulously undertaken. A comprehensive
neurological examination, including fundus examination, should be performed in
all cases. The affect of the child should be noted during the history compilation
and physical examination.
Differential Diagnosis
Seizure
Syncopal spells may be accompanied by myoclonic jerks (convulsive syncope)
that onlookers often mistake for seizure activity. Seizures are not provoked
by stimuli that are often associated with syncope, tend to be associated with a
longer period of altered consciousness, and are accompanied by rhythmic move-
ments of the extremities. The eyes of a child are usually open during a seizure.
A generalized convulsive seizure is accompanied by tachycardia, unlike NCS,
wherein bradycardia is noted. Auras or premonitions that occur prior to the
episode and focal weakness after the spell are suggestive of a seizure. Children
may experience an epilepsy type known as “drop attacks,” wherein they suddenly
fall to the ground without experiencing any warning signs. In situations in which
seizure is suspected to be the cause of syncope, obtaining an electroencephalo-
graphic (EEG) recording during the event is helpful. Syncope is characterized
by slow waves or normal EEG pattern, whereas children with seizures may
show interictal spikes between spells and an ictal pattern during a seizure.
139
CCIP.indb 139 3/13/18 4:18 PM

Migraine
Migraine with a brain stem aura can be associated with altered level of
consciousness, but children also have other characteristic features, such as
bilateral paresthesia of the limbs, visual symptoms such as diplopia, slurred
speech, and a migraine-type headache that lasts for several hours after the
premonitory symptoms.
Intracranial Pathologic Processes

Children with colloid cysts of the third ventricle, moya-moya disease, and
occlusion of the carotid or basilar artery may present with spells reminiscent
of syncope. The latter may lead to transient ischemic attacks, which are caused
by momentary cerebral hypoperfusion due to intracranial vascular pathologic
processes. Headaches commonly accompany colloid cysts; the presence of a bruit
may suggest carotid occlusion, as do focal deficits such as hemiparesis and apha-
sia; and recurrent syncopal spells that occur in the setting of hyperventilation are
noted in moya-moya disease.19
Narcolepsy
Narcolepsy is a disorder characterized by intrusion of rapid eye movement
(REM) sleep into daytime activities. The core clinical features include excessive
daytime sleepiness, sleep paralysis, hallucinations prior to sleeping (hypnogogic)
or before waking up (hypnopompic), and sometimes episodes of cataplexy; the
latter may be reminiscent of syncope. Cataplexy may manifest as focal weakness
of a group of muscles, such as jaw muscles or weakness of the arms, legs, or
trunk. Children with cataplexy can collapse to the ground, usually in response
to an emotional stimulus, such as a joke or shocking news. They experience no
premonitory symptoms, unlike children who have syncope caused by autonomic
imbalance. Diagnosis may be established by ordering a sleep study and establish-
ing the short latency period from being awake to starting REM sleep.
Hypoglycemia
Hypoglycemia may cause transient loss of consciousness. However, the mech-
anism is not cerebral hypoperfusion, as it is for other causes of “true” syncope.
Symptoms such as sweating, pallor, and tachycardia often accompany the periods
of hypoglycemia, and patients may report mental “blackouts.” Children with
hyperinsulinemic states and diabetes mellitus have a greater predilection to
transient hypoglycemia. In a study in adults, it was noted that about 1% of indi-
viduals with syncope had associated hypoglycemia, defined as a blood glucose
level of less than 50 mg/dL (2.77 mmol/L).20
140
CCIP.indb 140 3/13/18 4:18 PM

Syncope
Laboratory Evaluation
Laboratory investigations such as electrolyte panels, serum glucose level, com-
plete blood counts, and blood gas analyses are rarely of benefit.20 In children with
breath-holding spells, serum iron and zinc levels may be abnormal.
Diagnostic Procedures
Electrocardiography
Twelve-lead electrocardiography (ECG) should be performed in all children
with unexplained loss of consciousness. In children with exercise-induced symp-
toms, exercise ECG should be performed. Examples of abnormalities that can be
detected with ECG are prolonged QT interval, short QT interval, axis deviation,
atrioventricular block, Wolff-Parkinson-White syndrome (in which a delta wave
is noted on the QRS complex), and Brugada syndrome.
Head-Up Tilt-Table Testing

A head-up tilt-table test is not routinely used in clinical practice because of its
poor reproducibility, low sensitivity and specificity, and, hence, poor diagnostic
value.21 It can be helpful in selective cases in which there are atypical features
but NCS is strongly suspected. During this test, the patient is kept in an upright
position (60 to 80 degrees) for 30 to 45 minutes, and along with continuous
ECG, blood pressure and heart rate are monitored. During this time, if the
patient experiences presyncopal or syncopal symptoms, it is considered to be a
positive test result.
Routine performance of Holter monitoring, event monitoring, electrophys-
iological studies, and EEG is not recommended because of the low diagnostic
yield and added cost. Holter monitoring may be considered when events occur
on a frequent basis. Video EEG monitoring and magnetic resonance (MR)
imaging of the brain are of low yield in typical cases of NCS but may be helpful
when a neurological etiologic origin is suspected for loss of consciousness.
Imaging
Echocardiography and other imaging tests should be reserved for patients with
red flags in their history, an abnormal cardiac examination finding, or abnor-
malities at ECG. Routine performance of echocardiography has poor diagnostic
yield, may add to the cost of evaluation, and may cause psychological stress to
the patient and family. A normal echocardiographic result may provide false
reassurance in cases of cardiac syncope that might involve the electrical system
of the heart. Hence, it is important to choose a diagnostic test selectively after
detailed assessment and with the knowledge of the sensitivity, specificity, and
141
CCIP.indb 141 3/13/18 4:18 PM

diagnostic value of the test being ordered. Syncope that occurs during exertion
will certainly need to be evaluated further with echocardiography and/or exercise
stress testing. In some cases, cardiac MR imaging or electrophysiology testing
may be necessary. Detailed review of the exact diagnostic testing in each individ-
ual case of cardiac syncope is beyond the scope of this review.
Computed tomography and MR imaging of the brain are unlikely to lead to
a diagnosis in most situations unless clear-cut neurological signs of disease are
noted at physical examination.
Management
Treatment Approach
Syncope is a symptom, not a disease; therefore, the foremost duty of the clinician
should be to differentiate benign origins from more ominous causes. If indeed
the symptom is believed to be caused by neurocardiogenic factors, reassurance
is the cornerstone of therapy.
Specific Treatment
Nonpharmacological and pharmacological interventions can be used to address
the symptoms. Nonpharmacological measures include simple interventions, such
as assuming a sitting or supine posture, or squatting, or crossing the legs along
with tensing of core muscles to increase venous return when the prodromal
symptoms are experienced. The European Society of Cardiology suggests the
following measures to address syncope:22
•• Tilt training—that is, standing against a wall, with the upper back pressed
against the wall for progressively longer periods of time
•• Sleeping with the head end of the bed tilted up
•• Performing isometric leg and arm maneuvers
•• Engaging in moderate aerobic and isometric exercise
Increasing fluid intake to 2 L per day and salt intake to 2 to 4 g per day is
beneficial. Paced breathing can be taught to motivated children.23
Breath-holding spells normally require only reassurance that the child will
outgrow them. However, if the serum iron level is found to be low, supplemen
tation may be helpful in reducing the recurrence.
Medications that can be useful include β-blockers, as well as α–adrenergic
agents such as midodrine and fludrocortisone. However, none of these drugs
are approved by the U.S. Food and Drug Administration for the treatment of
syncope. β-blockers are widely used in clinical practice, but studies have failed
to demonstrate superiority over placebo.24 Pacemakers are not routinely used
for NCS.
142
CCIP.indb 142 3/13/18 4:18 PM

Syncope
When to Refer
Patients should be referred to a cardiologist if they present with a sudden
syncopal episode without any prodromal symptoms, when they experience
syncope during exertional activity, when episodes are preceded by palpitations
or chest pain, when syncope occurs in the setting of known cardiac disease and/
or cardiac surgery, and in children with a family history of sudden death or
inheritable cardiac disease. Neurology consultation should be obtained if there
are focal neurological signs or a history suspicious for seizures. Patients with
recurrent and persistent NCS despite adequate hydration and other conservative
measures may be referred to a specialist who is familiar with these cases or to a
syncope clinic. In situations in which a psychogenic etiologic origin is suspected,
confrontation should be avoided. Support should be offered with counseling
and other behavioral intervention.
Athletic Participation
Athletic participation will depend on the cause of syncope. For the most
common form of syncope, which is NCS, no restrictions are necessary. Because
of active pumping of the muscles during physical activity, venous pooling is less
likely to occur; hence, syncopal episodes are very unlikely during athletic activity.
If cardiac syncope or epilepsy disorder is confirmed, restrictions will be based on
the specific diagnosis.
Prevention
Adequate hydration, avoidance of known trigger factors in children with NCS,
and nonpharmacological interventions during the prodrome can be used to avert
a spell.
Ongoing Care
Cardiac and neurological syncope will necessitate ongoing specialist care on the
basis of the specific diagnosis.
Follow-up
For NCS, follow-up should occur in 6 to 8 weeks if symptoms are not better
despite an aggressive increase in water intake and some increase in salt intake.
Further follow-up for other forms of syncope will be guided by the specific
diagnosis.
143
CCIP.indb 143 3/13/18 4:18 PM

Complications
NCS is benign and tends to get better with time. Sometimes patients may pass
out in an unsafe environment and incur serious injuries, including head trauma
and/or other fractures. State driving laws should be consulted so guidance can be
offered to teenagers who may be driving but who experience syncope. It must be
noted that syncope rarely leads to motor vehicle accidents.25
Prognosis
NCS has an excellent prognosis, and most patients experience improvement
after the teenage years, when the episodes are at their peak. The natural history
of the disease is such that children will be symptom free within 24 months in
most instances, with or without treatment.26 Children with breath-holding spells
tend to outgrow them. Prognosis for other forms of syncope will be guided by
the specific diagnosis.
Key Points
•• Syncope can occur in children of any age but is most commonly encountered
in teenagers.
•• The cause of syncope in most children is autonomic imbalance or dysfunction,
especially the type referred to as neurocardiogenic or vasovagal syncope.
•• A meticulous history and a detailed examination will help differentiate benign
from ominous causes of syncope in most instances.
•• Education, reassurance, and increased water and salt intake form the crux of
the management for neurocardiogenic or vasovagal syncope.

•• Syncope (Fainting) (American Heart Association). www.heart.org/
HEARTORG/Conditions/Arrhythmia/SymptomsDiagnosis
MonitoringofArrhythmia/Syncope-Fainting_UCM_430006_
Article.jsp#.WYM5MlGQyUm
•• Vasovagal Syncope (Mayo Clinic). www.mayoclinic.org/diseases-conditions/
vasovagal-syncope/symptoms-causes/dxc-20184778
•• STARS. www.heartrhythmalliance.org/stars/us
References
1) Kapoor WN. Syncope. N Engl J Med. 2000;1856–1862
2) Massin MM, Malekzadeh-Milani S, Benatar A. Cardiac syncope in pediatric patients. Clin
Cardiol. 2007;30(2):81–85
3) Stewart JM. Mechanisms of sympathetic regulation in orthostatic intolerance. J Appl Physiol
(1985). 2012;113(10):1659–1668
144
CCIP.indb 144 3/13/18 4:18 PM

Syncope
4) Shibao C, Okamoto L, Biaggioni I. Pharmacotherapy of autonomic failure. Pharmacol Ther.

2012;134(3):279–286
5) Dan D, Hoag JB, Ellenbogen KA, Wood MA, Eckberg DL, Gilligan DM. Cerebral blood flow
velocity declines before arterial pressure in patients with orthostatic vasovagal presyncope. J Am
Coll Cardiol. 2002;39(6):1039–1045
6) Anil BG, Nedunchezian K, Jayanthini V, Pathmanabhan M. Breath holding spells: evaluation of
autonomic nervous system function. Indian Pediatr. 2005;42(9):923–927
7) Orii KE, Kato Z, Osamu F, et al. Changes of autonomic nervous system function in patients
with breath-holding spells treated with iron. J Child Neurol. 2002;17(5):337–340
8) Ottaviani G, Buja LM. Anatomopathological changes of the cardiac conduction system in
sudden cardiac death, particularly in infants: advances over the last 25 years. Cardiovasc Pathol.
2016;25(6):489–499
9) Strickberger SA, Benson DW, Biaggioni I, et al; American Heart Association Councils on
Clinical Cardiology, Cardiovascular Nursing, Cardiovascular Disease in the Young, and Stroke;
Quality of Care and Outcomes Research Interdisciplinary Working Group; American College
of Cardiology Foundation; Heart Rhythm Society. AHA/ACCF scientific statement on the
evaluation of syncope. J Am Coll Cardiol. 2006;47(2):473–484
10) Colman N, Nahm K, Ganzeboom KS, et al. Epidemiology of reflex syncope. Clin Auton Res.
2004;14(Suppl 1):9–17
11) Moore SS, Watemberg N. Syncope is a frequently under-diagnosed condition in infants
and toddlers and has similar features to those seen in adolescents and adults. Acta Paediatr.
2016;105(9):1083–1087
12) Kanjwal K, Calkins H. Syncope in children and adolescents. Cardiol Clin. 2015;33(3):397–409
13) DiMario FJ Jr. Prospective study of children with cyanotic and pallid breath-holding spells.
Pediatrics. 2001;107(2):265–269
14) Raj SR, Robertson D. Blood volume perturbations in the postural tachycardia syndrome. Am J
Med Sci. 2007;334(1):57–60
15) Hurst D, Hirsh DA, Oster ME, et al. Syncope in the pediatric emergency department—can we
predict cardiac disease based on history alone? J Emerg Med. 2015;49(1):1–7
16) Sheldon R, Rose S, Ritchie D, et al. Historical criteria that distinguish syncope from seizures. J
Am Coll Cardiol. 2002;40(1):142–148
17) Azab SF, Siam AG, Saleh SH, et al. Novel findings in breath-holding spells: a cross-sectional
study. Medicine (Baltimore). 2015;94(28):e1150
18) Kouakam C, Lacroix D, Klug D, Baux P, Marquié C, Kacet S. Prevalence and prognostic
significance of psychiatric disorders in patients evaluated for recurrent unexplained syncope. Am
J Cardiol. 2002;89(5):530–535
19) Byard RW. Variable presentations of lethal colloid cysts. J Forensic Sci. 2016;61(6):1538–1540
20) Linzer M, Yang EH, Estes NA III, Wang P, Vorperian VR, Kapoor WN; Clinical Efficacy
Assessment Project of the American College of Physicians. Diagnosing syncope. Part 1: value of
history, physical examination, and electrocardiography. Ann Intern Med. 1997;126(12):989–996
21) Steinberg LA, Knilans TK. Syncope in children: diagnostic tests have a high cost and low yield. J
Pediatr. 2005;146(3):355–358
22) Brignole M, Alboni P, Benditt DG, et al; Task Force on Syncope, European Society of
Cardiology. Guidelines on management (diagnosis and treatment) of syncope—update 2004.
Europace. 2004;6(6):467–537
23) Jáuregui-Renaud K, Márquez MF, Hermosillo AG, et al. Paced breathing can prevent vasovagal
syncope during head-up tilt testing. Can J Cardiol. 2003;19(6):698–700
24) Madrid AH, Ortega J, Rebollo JG, et al. Lack of efficacy of atenolol for the prevention of
neurally mediated syncope in a highly symptomatic population: a prospective, double-blind,
randomized and placebo-controlled study. J Am Coll Cardiol. 2001;37(2):554–559
145
CCIP.indb 145 3/13/18 4:18 PM

25) Maas R, Ventura R, Kretzschmar C, Aydin A, Schuchert A. Syncope, driving recommendations,

and clinical reality: survey of patients. BMJ. 2003;326(7379):21
26) Biffi M, Boriani G, Bronzetti G, Frabetti L, Picchio FM, Branzi A. Neurocardiogenic syncope
in selected pediatric patients—natural history during long-term follow-up and effect of prophy-
lactic pharmacological therapy. Cardiovasc Drugs Ther. 2001;15(2):161–167
146
CCIP.indb 146 3/13/18 4:18 PM

CHAPTER 10
Palpitations and
A
rrhythmia
Philip L. Wackel, MD
Introduction
Palpitations are a common occurrence in the pediatric and adolescent population.
Often, there can be high levels of anxiety or concern over palpitations among
patients and their families because many people associate palpitations with a
serious and potentially lethal cardiac problem. Despite common preconceived
notions, most often, the cause of the palpitations in young people is not dangerous
or life-threatening. However, given that some arrhythmias can result in sudden
cardiac death, all complaints of palpitations must be taken seriously. The assessment
should be tailored to the individual to prevent overtesting but also minimize the
chance of missing a potentially clinically significant arrhythmia. This can be a dif-
ficult task because arrhythmias can have a diverse presentation, and even the same
type of arrhythmia is often perceived and described differently by different patients.
Clinical Presentation
Arrhythmias have diverse presentations, and most commonly, there will be no
persistent symptoms outside of the episodes of palpitations. Therefore, it is crucial
to get a detailed and accurate account of the palpitations because some commonly
described features can help narrow the differential diagnosis and guide the
evaluation. An arrhythmia will most commonly manifest symptomatically with
episodic increases in heart rate, although a feeling of irregular heartbeats may
also occur with some arrhythmias. The perceived sensation of an increased heart
rate is sometimes misleading, as patients often feel as if their heart is racing but
147
CCIP.indb 147 3/13/18 4:18 PM

the actual rate may not be particularly increased. Therefore, it is always helpful
if an accurate heart rate can be obtained during the events. In addition, young
children may lack the proper vocabulary to describe palpitations and often report
that their chest “hurts” or use other terms such as “beeping” to describe a racing
heart rate.
Arrhythmias that manifest in the newborn period or in patients who
are unable to communicate their symptoms can appear much differently at
presentation. In the infant, lethargy and/or signs of heart failure, such as
tachypnea, poor weight gain, and diaphoresis, may be the first presenting sign
of an arrhythmia because the increased heart rate may go unnoticed by parents.
Similarly, in an older child, an appearance of heart failure symptoms, such as
edema, shortness of breath, tachypnea, and fatigue, can also occur in the rare
patient whose arrhythmia has a rate that overlaps with the normal range for age
and has therefore gone unnoticed for a long period of time, usually weeks to
months, resulting in ventricular dysfunction. Those unaware of their tachycardia
or those who are unable to communicate are at risk for developing tachycardia-
induced cardiomyopathy secondary to prolonged episodes or incessant tachycar-
dia.1 Particular attention should be given to a possible arrhythmia that appears
as heart failure at presentation in patients with congenital heart disease (CHD)
and particularly those with a history of cardiac surgery, which can be a setup for
a slower but incessant tachycardia.
Syncope is an uncommon presentation for arrhythmia, but if an arrhythmia is
associated with syncope, this should be taken seriously. The situation surrounding
the syncopal event will largely guide the level of concern for an arrhythmia.
Syncope that is brief, requires no resuscitation, has a prodrome, and is associated
with standing or changing positions (particularly rising up to a standing posi-
tion) tends to be benign and unrelated to an arrhythmia. While the patient may
describe some increased heart rates around the time of syncope, the aforemen-
tioned characteristics are more likely to be seen in autonomic reflex-mediated
syncope.2 Often, these patients with autonomic reflex-mediated symptoms will
have additional episodes that are not true syncope, with complete loss of postural
tone and loss of complete responsiveness, but will instead have presyncope or
near-syncope that may occur on a fairly regular basis. In contrast, syncope that
requires resuscitation or that occurs during exercise, without any prodrome, while
lying flat, or in a patient with a history of heart disease, is more concerning for
an arrhythmia and warrants a thorough evaluation.
148
CCIP.indb 148 3/13/18 4:18 PM

Palpitations and A
rrhythmia
Evaluation
History and Physical Examination
As stated earlier, the history is crucial to assessing palpitations because the
patient will likely have normal physical examination findings and will be
otherwise asymptomatic when not actively experiencing the palpitations. Details
regarding the situation in which the palpitations take place, the onset and
termination, the duration, the rate, and any associated symptoms can help guide
the evaluation. Features that tend to be more characteristic of a true arrhythmia
can be found in Box 10-1, with the caveat that not all arrhythmias appear in a
typical or “classic” manner at presentation.
In addition, a history of heart disease, including congenital defects, prior
cardiac surgeries or procedures, or a history of Kawasaki disease, should heighten
awareness for a true arrhythmia. Any patient with a family history of early
arrhythmias (prior to age 50), sudden unexplained death, or cardiomyopathies
needs to be thoroughly evaluated. When inquiring about a family history of
unexplained death, it is often necessary to specifically ask about deaths in the
family that may not otherwise seem suspicious for a possible arrhythmogenic
death, such as drownings or single-car motor vehicle accidents.
Box 10-1. Features of Palpitations of Concern for

True Arrhythmia
Abnormal cardiac examination
Abnormal electrocardiographic findings
History of heart disease
Family history of sudden death, cardiomyopathy, or arrhythmia before

age 50
Rate too fast to count or >210 beats/min
Abrupt onset and termination in a single beat
Associated with syncope
Occurs with exercise
Unassociated with changing to an upright position
149
CCIP.indb 149 3/13/18 4:18 PM

Tests
Resting electrocardiography (ECG) should be performed for every patient
undergoing evaluation for an arrhythmia. Most often, the findings are normal,
because the patient may not be actively experiencing symptoms during the ECG,
but it may sometimes show baseline abnormalities that can increase suspicion
for a true arrhythmia. An exercise stress test may also be of benefit to elicit the
arrhythmia if symptoms occur around the time of exercise or if there is concern
regarding the possibility of worsening arrhythmia during exercise. Generally,
echocardiography is reserved for those with concern for underlying heart disease
prompted by a concerning history (personal or family) and an abnormal physical
examination or ECG finding, because most often, an otherwise healthy child
with palpitations will have a normal echocardiographic finding.
When evaluating palpitations, the only way to be sure of the diagnosis is to
obtain a rhythm strip or perform ECG while the patient is experiencing the
arrhythmia or symptoms. There are several devices available to aid in recording
the rhythm during symptoms, but selection of the most appropriate device
depends on the symptoms. Using a Holter monitor for 24 or 48 hours will
enable the rhythm to be continuously recorded for that period so that all the
beats can be reviewed. This type of monitoring is good if the symptoms occur
daily or multiple times per day because it is highly likely a symptomatic episode
will be recorded. Holter monitors can also be useful as a screening tool for
occult arrhythmia in select patients who may also have periods of asymptomatic
arrhythmia in addition to the episodes for which they presented. Another
potential advantage of a Holter monitor is that it will quantify the arrhythmia
burden: The total number of normal and abnormal beats is tabulated, which can
be useful to follow trends or response to treatment. In addition to a basic Holter
monitor, there is another continuous ambulatory monitor that can be worn for
up to 14 days that functions similarly to a Holter monitor.
If symptoms are less frequent, an event recorder may be more useful. There
are a number of different types of event recorders available, but a common
one is a handheld device that can be pressed against the skin over the chest
during symptoms to record a rhythm strip. That recording can then be sent via
telephone to the personnel who will interpret it. This type of event recorder
is commonly issued for 30-day intervals and is most useful for patients with
less frequent symptoms, with episodes that last long enough (approximately
>3 minutes) to allow the patient to locate and apply the event recorder. Another
advantage of this type of event recorder is that it does not need to be worn
continuously and there are no adhesive electrodes to apply and maintain.
A loop recorder is another type of monitor that can be useful when symptoms
do not occur frequently enough to record activity by other means. An external
loop recorder typically involves applying adhesive electrodes to the chest that are
150
CCIP.indb 150 3/13/18 4:18 PM

Palpitations and Arrhythmia
connected to a battery-operated recorder that continuously records the rhythm.

However, if no symptoms occur and the rate stays within the programmable
parameters, the device will then record over the old rhythm strip and will not
save that information. Alternatively, if the patient indicates that a symptom
is present or the rate falls outside the set parameters, then the rhythm strip
recorded from several seconds prior to the activation, as well as several seconds
after the activation, will be stored and can later be transmitted via the telephone
to the personnel who will interpret it. This type of device is useful for rare pal-
pitations that occur briefly, which would preclude the use of another handheld
device. The disadvantage is that it necessitates that adhesive electrodes be worn
and maintained for the duration of the use of the device, which can be difficult
in young patients or in situations where adhesion is problematic, such as with
heavy perspiration during exercise.
Advances in smartphone technology now make it possible to record a heart
rate or even a rhythm strip by using a smartphone and even transmit that tracing
via the Internet. Some applications require special equipment or attachments.
However, caution must be used when selecting a program because not all have
been validated clinically for accuracy.3

The previously mentioned event recorders and loop recorders are generally
issued in 30-day intervals, but occasionally, symptoms occur less often or are
unpredictable, which makes recording the rhythm more difficult. In those cases,
an implantable loop recorder may be necessary. An implantable loop recorder is
a recording device that is placed under the skin (generally over the left side of
the chest) that can record for approximately 2 to 3 years. It functions similarly to
external loop recorders in that there are programmable settings to automatically
record above and below certain rates, as well as record patient-activated events.
The information can be automatically downloaded by using a transmitter that is
often placed at the bedside so the events are transmitted to the personnel who
will interpret them shortly after recording. Obviously, this is a more invasive
approach to monitoring the rhythm, but it can be useful in cases in which
external monitoring has not worked or is not possible.
If these devices are unable to successfully capture the rhythm during an
event or if the suspicion for an arrhythmia is high enough, referral to a pediatric
electrophysiologist for more invasive testing may be warranted. Esophageal or
intracardiac electrophysiological studies may be needed to fully evaluate the
conduction system for arrhythmia substrate in certain circumstances. These
studies also have the added advantage of allowing a potentially curative proce-
dure (an ablation) to be performed at the same time in certain instances.
151
CCIP.indb 151 3/13/18 4:18 PM

Management
Sinus Tachycardia
Many patients who present with palpitations will undergo an evaluation only to
learn that there is no true arrhythmia. It is common to record a rhythm during
which there are perceived palpitations, only to find that the rhythm is sinus,
with a rate that either is normal or falls into the range of sinus tachycardia
for age. When this is noted, the sinus tachycardia is nearly always secondary
to another cause, which is most commonly autonomic, orthostatic, or a result
of deconditioning. Very rarely is there an underlying primary inappropriate
sinus tachycardia, hyperthyroidism, or adrenaline-secreting tumor, such as a
pheochromocytoma or neuroblastoma. If any of these are suspected on the basis
of other clinical findings, then targeted testing may be appropriate.4 Otherwise,
increased hydration, liberalization of salt intake, and regular exercise will most
often help improve symptoms.
Extrasystoles
Premature atrial contractions (PACs) and premature ventricular contractions
(PVCs) are referred to as extrasystoles. Most often, these do not cause symptoms
and appear as an incidental finding during the physical examination or are noted
during monitoring. Extrasystoles do not usually cause symptoms; however,
patients may perceive them as single “hard beats” or single “skipped beats.” The
definition of a PAC is an atrial beat that occurs before the next expected sinus
beat and originates from atrial tissue that is not the sinus node. This results in
a P wave morphologic appearance that is different from that of the sinus node.
Most commonly, the following QRS complex will look identical to a sinus beat,
but if the PAC occurs early enough, the QRS could conduct aberrantly down
the His-Purkinje system, resulting in a wide QRS complex, or the PAC may
not conduct to the ventricle at all, which is called a blocked PAC (Figure 10-1).
FIGURE 10-1. Electrocardiographic tracings show premature atrial contractions (PACs) that
conduct normally (*) or aberrantly (open arrow on the upper tracing) and have blocked conduction
to the ventricle (solid arrows on the lower tracing). Note that the PAC is occurring simultaneously
with the prior T wave.
152
CCIP.indb 152 3/13/18 4:18 PM

The key to distinguishing PACs with aberrancy from PVCs is that a PAC must
by definition have a P wave prior to it. However, some P waves are difficult
to see because they can occur during the preceding T wave; careful inspection
of the T wave is often necessary. PACs in the newborn period are particularly
common and tend to resolve without intervention in the days or weeks after
birth. Outside of the newborn period, wearing a Holter monitor may be useful
to try to correlate symptoms with PACs, quantify the PAC burden, and assess
the patient for occult atrial tachycardia, but it is not always necessary, and use
should be guided by clinical judgment.
The definition of a PVC is an early beat arising from the ventricular muscle
that is not preceded by a P wave, which results in a QRS complex that is
different from a sinus QRS. Generally, PVCs result in a wide QRS because of
slower muscle-to-muscle conduction, but on occasion, they may originate from
or very near to the His-Purkinje fibers, resulting in a QRS that is fairly narrow
(Figure 10-2). Careful inspection of the QRS complex in multiple leads is occa-
sionally required to identify a difference from a sinus QRS. Like PACs, PVCs
are most often noted incidentally and are rarely symptomatic. PVCs are common
in the pediatric population and occur in up to 40% of pediatric patients.5
Most pediatric patients with isolated PVCs have normal cardiac structure and
function. PVCs with more than 1 morphologic appearance, episodes of 3 or
more PVCs in a row that constitute ventricular tachycardia (VT), or PVCs that
increase in frequency with exercise may imply that there is an underlying cardiac
problem such as myocarditis, cardiomyopathy, or a channelopathy. Patients with
asymptomatic isolated PVCs that have 1 morphologic appearance, that are
suppressed with exercise, and that occur in the presence of a structurally normal
heart are almost always benign and rarely require any treatment. Those patients
with a high burden of ectopy (generally considered >10% PVCs with a Holter
monitor) should undergo serial follow-up by a pediatric cardiologist to watch
for the development of PVC-induced ventricular dysfunction, although this
generally doesn’t occur until the burden of ectopy is much higher.6 Treatment
FIGURE 10-2. A. ECG tracing shows the typical appearance of premature ventricular contractions
(PVCs), with a wide complex QRS and no preceding P wave (*). B. PVCs are shown on the ECG
tracing with a relatively narrow QRS complex that differs only slightly from the normal QRS, which
likely arises from within or very near the His-Purkinje system (arrows).
153
CCIP.indb 153 3/13/18 4:18 PM

for PVCs is reserved for rare cases in which patients are symptomatic from the
PVCs or develop ventricular dysfunction due to a high PVC burden. First-line
therapy can be antiarrhythmics, but some may elect to perform an ablation
procedure initially to avoid medication use and potentially provide a permanent
cure. The outcome of PVC ablation in pediatrics is favorable.7,8
Supraventricular Tachycardia
Supraventricular tachycardia (SVT) is the most common abnormal mechanism
of tachycardia in pediatric patients, with an estimated incidence from 1 in
25,000 to as high as 1 in 250.9 Most often, SVT is a sudden-onset narrow-com-
plex tachycardia in which P waves may or may not be visible between QRS
complexes (Figure 10-3). In certain scenarios, SVT will occur as a wide QRS
complex tachycardia, but this is less common. The mechanism of SVT in
pediatric patients is re-entrant in 90% of cases (either atrioventricular [AV]
re-entrant by using an accessory pathway or an AV nodal re-entrant by using 2
inputs into the AV node), but ectopic atrial tachycardia and other less common
forms of SVT are possible.10 Because of the re-entrant nature of most of these
arrhythmias, they typically have an abrupt onset and abrupt termination, as
well as some other commonly associated features (Box 10-2). In addition to the
typical clinical features of SVT, patients may also experience diaphoresis, nausea,
pale appearance, and lightheadedness, but true syncope is rare. In fact, SVT in
an otherwise healthy pediatric patient with a structurally normal heart will be
hemodynamically well tolerated for short periods of time (or even longer), even
at rates well above 200 beats per minute. While SVT can cause a great deal of
anxiety in patients and/or their family members, generally there is adequate time
to assess and treat an otherwise healthy child urgently but not emergently.
Documenting the tachycardia by recording a rhythm strip or ECG during
SVT is crucial prior to the acute treatment of an otherwise stable patient
FIGURE 10-3. ECG tracing shows supraventricular tachycardia at a heart rate of 250 beats/min.
154
CCIP.indb 154 3/13/18 4:18 PM

Box 10-2. Common Clinical Features of Supraventricular

Tachycardia in Pediatrics
Heart rate >220 beats/min or too fast to count
Abrupt onset and termination in a single beat
Abrupt termination can occur with a Valsalva maneuver
Duration of several minutes to hours
Occurs without a prodrome
because this will allow for review of the tachycardia by others at a later time.
Initial measures to acutely treat SVT include vagal maneuvers, such as ice to
the face or performing a Valsalva maneuver, which may abruptly terminate
SVT because of transient suppression of AV node conduction. Vagal maneuvers
such as gagging and ocular massage should be avoided because they can cause
physical harm when not done carefully and properly. Intravenous administration
of adenosine can usually abruptly terminate SVT when vagal maneuvers fail.
Adenosine should be administered rapidly in a push via a large-bore intravenous
catheter that is preferably placed in an upper extremity as near to the heart as
possible, followed by an immediate saline flush, because the extremely rapid
metabolism of adenosine results in a half-life of 1 to 6 seconds. Failure to prop-
erly administer adenosine is the most common reason for failure to terminate
SVT. It is important to record the rhythm during adenosine administration
because the response may yield information on the exact mechanism of SVT
when it terminates; this may have implications in both treatment and prognosis.
Before administering adenosine, one must be aware of and prepared to manage
the possible side effects, including flushing, brief anxiety or a sense of impending
doom, nausea, chest pain, bronchospasm, initiation of atrial fibrillation, transient
AV block, and transient hypotension.
Once tachycardia has terminated, a baseline ECG should be examined to
look for Wolff-Parkinson-White syndrome, which consists of a short PR inter-
val, a delta wave, and a wide QRS complex (Figure 10-4). Routine evaluation for
electrolyte disturbances and hyperthyroidism are rarely needed in the absence of
signs or predisposing factors because they rarely play a role in the development
of SVT. Referral to a pediatric cardiologist and (often) a pediatric electrophysi-
ologist is warranted. The long-term management strategy of SVT is to prevent
recurrence; this can be accomplished with either medications or an ablation
procedure. First-line medications commonly include β-blockers or calcium
channel blockers but do require lifelong compliance to be effective in most cases.
Alternatively, once a patient weighs more than 15 kg, it is a class I indication
155
CCIP.indb 155 3/13/18 4:18 PM

FIGURE 10-4. Wolff-Parkinson-White syndrome. The delta wave on the ECG tracing is identified
by the slurring of the initial QRS complex.
to pursue an ablation as a first-line treatment to obtain a permanent cure and

avoid medical therapy because the chances of success are high and the risks are
low.11 In patients who weigh less than 15 kg, medical therapy options are usually
exhausted before proceeding with an ablation because the risks of the procedure
increase below this weight. In general, ablation procedures have a high likelihood
of permanently eliminating the abnormal substrate needed for tachycardia, and
the risks are low in the modern era.12,13 This makes an ablation procedure an
attractive first-line option for many patients who wish to avoid the lifelong cost
and inconvenience of taking medications indefinitely.
Ventricular Arrhythmias
VT is defined as 3 or more consecutive beats that arise from the ventricular
myocardium, occurring at a rate faster than the expected sinus rate for a given
patient’s age. However, it is generally accepted that the rate must be at least 15%
to 20% above the expected sinus rate or more than 120 beats per minute in a
teenager to be considered VT. Runs of ventricular ectopy occurring faster than
sinus but below this cutoff rate are referred to as accelerated ventricular rhythm
(AVR). It is important to distinguish AVR from VT because AVR generally has
an excellent prognosis.14 If no underlying heart disease and/or metabolic or elec-
trolyte abnormalities are present, then AVR is almost always benign. However,
AVR does require longitudinal follow-up to assess the patient for resolution and
to monitor the patient for the development of ventricular dysfunction, similar to
the approach for frequent PVCs. Like the management of PVCs, treatment for
AVR is rarely indicated unless it produces symptoms or ventricular dysfunction.
156
CCIP.indb 156 3/13/18 4:18 PM

When there is an indication, antiarrhythmics or an ablation procedure can be

highly effective.6
True VT is rare in the pediatric population, with an estimated incidence of 1
in 100,000 and even fewer requiring treatment.15 Although pediatric VT is often
not life-threatening, particularly in the setting of an otherwise normal heart, all
VT requires a thorough cardiovascular evaluation by a pediatric cardiologist
because it can be associated with clinically significant underlying cardiac patho-
logic processes. Establishing that the heart is both structurally and electrically
normal is vital before entertaining one of the common causes of benign VT in a
child. Testing can be tailored to search for an underlying cause, including CHD,
cardiomyopathy, myocarditis, and channelopathies, which would in turn guide
the management. However, the initial testing should include echocardiography,
ECG, and Holter monitoring, with consideration for an exercise test and cardiac
magnetic resonance imaging, depending on the situation. If there is a clinical
reason to suspect a possible electrolyte abnormality, then laboratory tests should
also be performed, but most pediatric VT will occur with normal electrolyte levels.
When approaching VT, it is often useful to group VT on the basis of its char
acteristics to help guide the extent of the workup and management. VT can
be described in many ways, but commonly, it is referred to as monomorphic or
polymorphic; it can also be classified as VT occurring in the presence of a normal
heart versus that occurring in an abnormal heart. Monomorphic VT (all beats
have the same QRS morphologic appearance during VT) in the presence of a
normal heart is most likely benign, whereas polymorphic VT (changing QRS
morphologic appearance during VT) or VT in the presence of heart disease is
highly concerning for true pathologic findings and should prompt a more exten-
sive evaluation if no etiologic origin is found with initial testing (Figure 10-5).15
FIGURE 10-5. Polymorphic ventricular tachycardia. Note the beat-to-beat changing of the QRS
morphologic appearance on the ECG tracing.
157
CCIP.indb 157 3/13/18 4:18 PM

Treatment of VT depends largely on the underlying cause but could include

medical therapy with antiarrhythmics and/or an ablation procedure and possibly
implantation of a defibrillator in specific situations. However, treatment may
not be necessary in the face of a normal heart and slow VT and the absence
of symptoms, much like the management of AVR and frequent PVCs, as
previously discussed.
Key Points
•• Palpitations are common, and recording the rhythm during symptoms is the
key to confirming the diagnosis of an arrhythmia.
•• The history should guide the level of concern for true arrhythmia and the
extent of the workup.
•• Extrasystoles are common in pediatrics and most often do not require therapy.
•• SVT is often curable with an ablation procedure, which can be considered
first-line therapy in children who weigh more than 15 kg.

•• Supraventricular Tachycardia (Mayo Clinic). www.youtube.com/watch?v=
bhXpgvrRZsc
•• Irregular Heartbeat (Arrhythmia) (American Academy of Pediatrics).
healthychildren.org/English/health-issues/conditions/heart/Pages/
Irregular-Heartbeat-Arrhythmia.aspx
References
1) Moore JP, Patel PA, Shannon KM, et al. Predictors of myocardial recovery in pediatric
tachycardia-induced cardiomyopathy. Heart Rhythm. 2014;11(7):1163–1169
2) Zhang Q, Du J, Wang C, Du Z, Wang L, Tang C. The diagnostic protocol in children and
adolescents with syncope: a multi-centre prospective study. Acta Paediatr. 2009;98(5):879–884
3) Wackel P, Beerman L, West L, Arora G. Tachycardia detection using smartphone applications in
pediatric patients. J Pediatr. 2014;164(5):1133–1135
4) Sheldon RS, Grubb BP II, Olshansky B, et al. 2015 heart rhythm society expert consensus
statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus
tachycardia, and vasovagal syncope. Heart Rhythm. 2015;12(6):e41–e63
5) Massin MM, Bourguignont A, Gérard P. Study of cardiac rate and rhythm patterns in ambula-
tory and hospitalized children. Cardiology. 2005;103(4):174–179
6) Crosson JE, Callans DJ, Bradley DJ, et al. PACES/HRS expert consensus statement on the
evaluation and management of ventricular arrhythmias in the child with a structurally normal
heart. Heart Rhythm. 2014;11(9):e55–e78
7) O’Connor BK, Case CL, Sokoloski MC, Blair H, Cooper K, Gillette PC. Radiofrequency
catheter ablation of right ventricular outflow tachycardia in children and adolescents. J Am Coll
Cardiol. 1996;27(4):869–874
158
CCIP.indb 158 3/13/18 4:18 PM

8) Wackel PL, McCrary AW, Idriss SF, Asirvatham SJ, Cannon BC. Radiofrequency ablation
in the sinus of Valsalva for ventricular arrhythmia in pediatric patients. Pediatr Cardiol.
2016;37(8):1534–1538
9) Garson A Jr, Gillette PC. Electrophysiologic studies of supraventricular tachycardia in children.
II. Prediction of specific mechanism by noninvasive features. Am Heart J. 1981;102(3 Pt 1):
383–388
10) Ko JK, Deal BJ, Strasburger JF, Benson DW Jr. Supraventricular tachycardia mechanisms and
their age distribution in pediatric patients. Am J Cardiol. 1992;69(12):1028–1032
11) Philip Saul J, Kanter RJ, Abrams D, et al; Writing Committee. PACES/HRS expert consensus
statement on the use of catheter ablation in children and patients with congenital heart
disease: Developed in partnership with the Pediatric and Congenital Electrophysiology Society
(PACES) and the Heart Rhythm Society (HRS). Endorsed by the governing bodies of PACES,
HRS, the American Academy of Pediatrics (AAP), the American Heart Association (AHA),
and the Association for European Pediatric and Congenital Cardiology (AEPC). Heart Rhythm.
2016;13(6):e251–e289
12) Van Hare GF, Javitz H, Carmelli D, et al; Pediatric Electrophysiology Society. Prospective
assessment after pediatric cardiac ablation: demographics, medical profiles, and initial outcomes.
J Cardiovasc Electrophysiol. 2004;15(7):759–770
13) Van Hare GF, Javitz H, Carmelli D, et al; Participating Members of the Pediatric Electro
physiology Society. Prospective assessment after pediatric cardiac ablation: recurrence at
1 year after initially successful ablation of supraventricular tachycardia. Heart Rhythm.
2004;1(2):188–196
14) MacLellan-Tobert SG, Porter CJ. Accelerated idioventricular rhythm: a benign arrhythmia in
childhood. Pediatrics. 1995;96(1 Pt 1):122–125
15) Roggen A, Pavlovic M, Pfammatter JP. Frequency of spontaneous ventricular tachycardia in a
pediatric population. Am J Cardiol. 2008;101(6):852–854
159
CCIP.indb 159 3/13/18 4:18 PM

CCIP.indb 160 3/13/18 4:18 PM
CHAPTER 11
Heart Murmur
Gurumurthy Hiremath, MD, FACC, and Stacie Knutson, MD
Introduction
Heart murmurs are heard in up to half of all children.1 Most often they are
innocent, resulting from normal blood flow through the normal heart and blood
vessels. When confronted with a patient with a heart murmur, the pediatrician
must determine whether the murmur is innocent or indicative of a cardiac
abnormality. In general, a murmur will be innocent if the following criteria are
fulfilled: (a) There is no history suggestive of cardiac disease. (b) The patient is
asymptomatic. (c) The patient is acyanotic. (d) The murmur is systolic (with the
exception of the venous hum) and no louder than grade III. (e) The second heart
sound (S2) varies normally with respiration. (f ) The electrocardiography (ECG)
and chest radiography findings are normal.
Innocent Heart Murmurs

There are 5 innocent heart murmurs of childhood: Still murmur (also commonly
referred to as Still’s murmur), pulmonary flow murmur, peripheral pulmonary
stenosis, carotid bruit, and venous hum.
Still Murmur
Still murmur is the most common innocent murmur heard in children. It is an
early systolic, grade I–II/VI, low-frequency murmur with a vibratory or musical
quality. It is heard best at the left lower sternal border and apex. This type of mur-
mur will be loudest when the patient is supine and will diminish or disappear with
sitting or standing. The cause of a Still murmur is not completely understood but
may be due to vibrations of the chordae tendineae during systole and/or increased
flow velocity across the aortic valve. It is most commonly heard in children 2 to
161
CCIP.indb 161 3/13/18 4:18 PM

10 years of age but can also be heard in infants and adolescents. (Audio
available at www.youtube.com/watch?v=dxRx-XZ0WLg&index=2&list=
PLKCIeugVenPTLW-nspw_wUkXxO2IIiesu.) ( ) 
Pulmonary Flow Murmur
A pulmonary flow murmur or pulmonary systolic ejection murmur is caused
by normal flow across the pulmonary valve. Because of the location of the
pulmonary valve and the main pulmonary artery as the most anterior cardiac
structures, there is little distance between them and the stethoscope, so blood
flow in this location can be heard easily in a young and thin individual.
Pulmonary flow murmurs can be heard at any age and are usually grade I or II/
VI, non–harsh-sounding, mid-frequency systolic murmurs with a crescendo-
decrescendo pattern. They are heard best at the left upper sternal border in
the pulmonic area with little or no radiation. There should also be respiratory
variation with the murmur louder with inspiration. It is important to differen
tiate this from a pulmonic flow murmur caused by an atrial septal defect
(audio available at www.youtube.com/watch?v=U_xhNdf2Ggk&index=6&list=
PLKCIeugVenPTLW-nspw_wUkXxO2IIiesu and www.youtube.com/watch?v=
NFAkj9Fbfmw&index=7&list=PLKCIeugVenPTLW-nspw_wUkXxO2IIiesu)
 ( ) or valvar pulmonary stenosis (audio available at www.youtube.com/

wUkXxO2IIiesu) ( ). If an atrial septal defect is present, the intensity of
the murmur will not vary with positional changes, and there will be a widely
split and fixed S2. If valvar pulmonary stenosis is present, the murmur has a
harsher quality to it and may be associated with a click and radiation through-
out the pulmonary distribution (back and axilla).
Peripheral Pulmonary Stenosis Murmur

The peripheral pulmonary stenosis murmur is common in neonates. Because of
the normal fetal circulation, the main pulmonary artery receives a large volume
of blood when compared to the branch and distal pulmonary arteries. As a result,
the main pulmonary artery is larger in size relative to the branch and distal
pulmonary arteries. This size differential and the sudden increase in blood flow
to the lungs (about 20 times that in a fetus) result in turbulent flow and the
resultant murmur.2 In addition, the acute angles at which the pulmonary arteries
branch further contribute to flow turbulence. Peripheral pulmonary stenosis is a
grade I–II/VI, short, systolic ejection murmur heard best at the left upper sternal
border, with radiation to the back and axilla. It is a low-frequency murmur that
can sound similar to a neonate’s breath sounds. This murmur is heard in the
newborn period and should resolve over the first 6 months of life. If it persists
beyond 6 months, then further evaluation by a pediatric cardiologist for other
etiologic origins should be pursued.
162
CCIP.indb 162 3/13/18 4:18 PM

Heart Murmur
Carotid Bruit
Carotid bruits are produced by turbulent blood flow in the brachiocephalic and
carotid arteries and can be heard throughout childhood. This type of murmur
is an early systolic, grade I–II/VI ejection murmur heard over the origin of
these arteries. It is best heard in the supraclavicular region bilaterally but may
be louder on the right. The murmur intensity can be diminished with hyperex-
tension of the shoulders. This type of murmur must be differentiated from the
murmur of aortic stenosis with or without a bicuspid aortic valve, which can
have radiation to the carotid arteries. The presence of an ejection click and a
suprasternal notch thrill indicate a bicuspid aortic valve and aortic stenosis. In
addition, the murmur of aortic stenosis will not diminish with hyperextension
of the shoulders.
Venous Hum
A venous hum is a soft, blowing, grade I–II/VI, continuous, high-frequency
murmur. The murmur is caused by turbulent venous flow in the superior vena
cava. It is best heard in the right clavicular region, which is where venous blood
from the right and left arms and head enter the superior vena cava. It can also
be heard along the course of the superior vena cava at the right sternal border.
The murmur intensity increases when turning the head to the contralateral side
or sitting upright and decreases or disappears when lying supine or manually
compressing the ipsilateral internal jugular vein. Venous hums are common in
children 3 to 8 years of age. The use of positional changes and maneuvers is help-
ful in differentiating this continuous murmur from a patent ductus arteriosus.
Pathologic Murmurs
History
A personal and family history helps in identifying risk factors for pathologic
murmurs (Table 11-1).3 The presence of a chromosomal abnormality, genetic
disorder, or connective tissue disease could suggest structural heart disease. Some
examples include ventricular septal defects or atrioventricular canal defects with
trisomy 21, tetralogy of Fallot with 22q11 deletion, supravalvular aortic stenosis
with Williams syndrome, pulmonary stenosis or hypertrophic cardiomyopathy
with Noonan syndrome, bicuspid aortic valve and/or coarctation of the aorta
in Turner syndrome, and aortic root dilation with Marfan syndrome and other
connective tissue disorders.
In a newborn, poor weight gain, increased work of breathing, diaphoresis,
and fatigue with poor feeding suggest the presence of cardiac disease. Exertional
chest pain or syncope, frequent respiratory infections, or failure to thrive could
also be symptoms of unrecognized structural heart disease. Past history of
163
CCIP.indb 163 3/13/18 4:18 PM

Table 11-1. Historical Findings Suggestive of Structural

Heart Disease in Children with Heart Murmurs
Historical Finding Significance
Family history
CHD More common in children with a first-degree

relative who has CHD (three- to 10-fold
increased risk); high penetrance with ventric-
ular septal defect and mitral valve prolapse
Sudden cardiac death or hyper Increased risk of hypertrophic cardiomyo

trophic cardiomyopathy pathy (autosomal dominant pattern)
Sudden infant death syndrome Can be secondary to undiagnosed CHD

lesions
Personal history
Conditions that may coexist Certain genetic disorders (eg, DiGeorge

with CHD, such as aneuploidy syndrome, velocardiofacial syndrome) are
(eg, trisomy 21, Turner syndrome), associated with cardiac malformations
connective tissue disorder (eg, Trisomy 21 is associated with an increased
Marfan syndrome), inborn error risk of atrioventricular septal defects, atrial
of metabolism, major congenital septal defects, ventricular septal defects,
defects of other organ systems, patent ductus arteriosus, and tetralogy of
syndrome with dysmorphic features Fallot
Turner syndrome is associated with increased
risk of coarctation of the aorta, aortic valve
stenosis, and left ventricular hypertrophy
Marfan syndrome is associated with mitral
valve prolapse, aortic root dilation, and aortic
insufficiency
Frequent respiratory infections Respiratory symptoms may be attributable

to heart disease (ie, congestive heart failure);
enlarged vessels may lead to atelectasis or
difficulty clearing respiratory secretions,
thereby promoting infection
Kawasaki disease Leading cause of acquired cardiac disease

in children; can cause coronary artery
aneurysm and stenosis
Rheumatic fever Associated with development of rheumatic

heart disease
Prenatal or perinatal history
In utero exposure to alcohol or Fetal alcohol syndrome is associated with an

other toxins increased risk of atrial and ventricular septal
defects and tetralogy of Fallot
164
CCIP.indb 164 3/13/18 4:18 PM

Heart Murmur
Table 11-1. Historical Findings Suggestive of Structural

Heart Disease in Children with Heart Murmurs,
continued
Historical Finding Significance
Prenatal or perinatal history, continued
In utero exposure to selective Selective serotonin reuptake inhibitor

serotonin reuptake inhibitors exposure is associated with a small but
or other potentially teratogenic statistically significant increased risk of mild
medications heart lesions, including ventricular septal
defects and bicuspid aortic valve (although
not all studies showed an increased risk)
Lithium exposure is associated with Ebstein
anomaly of the tricuspid valve
Valproate (depacon) exposure is associated
with coarctation of the aorta and hypoplastic
left heart syndrome
Intrauterine infection Maternal infections may increase risk

of structural heart lesions (eg, maternal
rubella infection is associated with patent
ductus arteriosus and peripheral pulmonary
stenosis)
Maternal diabetes mellitus Increased risk of CHD, including transient

hypertrophic cardiomyopathy, tetralogy of
Fallot, truncus arteriosus, and double-outlet
right ventricle
Preterm delivery CHD is associated with other conditions

(eg, genetic disorders, in utero exposure to
toxins) that can result in preterm birth; 50%
of newborns weighing <3 lb 5 oz (1,500 g)
at birth have CHD (most commonly patent
ductus arteriosus)
CHD, congenital heart disease. From reference 3.
Kawasaki disease, rheumatic fever, prematurity, or intrauterine infection is

important. A family history of a first-degree relative with congenital heart
disease (CHD), sudden cardiac death, or hypertrophic cardiomyopathy increases
the risk of CHD in the index patient.
Careful review of the vital signs can demonstrate cyanosis, desaturation,
tachypnea, tachycardia, hypertension, or a widened pulse pressure. With the
implementation of pulse oximetry screening in many states, critical CHD is
being diagnosed prior to discharge from the hospital. The presence of cyanosis
165
CCIP.indb 165 3/13/18 4:18 PM

or systemic desaturation should prompt referral for further evaluation.4 The

absence of cyanosis does not exclude CHD. Cyanosis may not be apparent,
even with systemic arterial desaturation in the presence of anemia or in
darker-skinned individuals.
Tachypnea and tachycardia can be the first signs of heart failure or pulmonary
overcirculation in children because of the presence of a clinically significant
left-to-right shunt. In the setting of a patent ductus arteriosus, there can be a
widened pulse pressure and bounding pulse at examination. A diminished pulse
in the lower extremity, radiofemoral pulse delay, or clinically significant drop in
systolic blood pressure between the right upper limb and the lower limbs could
suggest coarctation of the aorta.
Children with CHD may have poor weight gain or failure to thrive because
of increased metabolic demands, fatigue with feeding, and inability to consume
adequate calories. The pulmonary examination may demonstrate tachypnea or
rales, which may be caused by a clinically significant left-to-right shunt with
pulmonary edema. Hepatomegaly occurs in children with heart failure.
In general, the cardiac examination should begin with inspection and palpation
for displaced apical impulse, heaves, and thrills, which all point to clinically
significant cardiac pathologic processes. Careful attention should be paid to the
first and second heart sounds. A wide and fixed split S2 could suggest an atrial
septal defect (audio available at www.youtube.com/watch?v=NFAkj9Fbfmw&
index=7&list=PLKCIeugVenPTLW-nspw_wUkXxO2IIiesu) ( ). A loud S2 
could indicate pulmonary hypertension or a large or anteriorly placed aorta
(transposition, tetralogy of Fallot). The change in the murmur intensity with
various physiological maneuvers provides valuable information with respect to
differential diagnosis of the most common murmurs in childhood (see Table 11-2).
Table 11-2. Change in Murmur Intensity With

Physiological Maneuvers
Atrial
Aortic Septal Flow Still
HOCM Stenosis Defect Murmur Murmur
Squatting Decrease Increase Increase No No change

(increases change or or decrease
intracardiac decrease
volume and
afterload)
Standing Increase Decrease Decrease Decrease No change
Other LV heave Suprasternal Wide, fixed Normal Normal

associated thrill and S2 exam- exam-
findings ejection ination ination
click findings findings
HOCM, hypertrophic obstructive cardiomyopathy; LV, left ventricular.
166
CCIP.indb 166 3/13/18 4:18 PM

Heart Murmur
Finally, careful evaluation for any extra heart sounds should be performed.
This includes the presence of S3 and S4, as well as any clicks. The presence of an
early systolic click should raise suspicion for a stenotic aortic or pulmonic valve,
and multiple mid-systolic clicks are heard with mitral valve prolapse.
The features of pathologic murmurs are summarized in Box 11-1.
Management
The suggested approach to a heart murmur is shown in Figure 11-1. If a child
has no red flags in the history and clinical examination, the heart murmur is
thought to be innocent or functional; no further workup is necessary. The parent
and patient can be reassured and followed up conservatively. Most innocent
murmurs in infancy or early childhood go away as the child grows older.
Once a murmur has been identified as having pathologic features, the next
step should be to refer the patient to a pediatric cardiologist. Further testing
could include ECG and echocardiography. Owing to the expense of outpatient
transthoracic echocardiography (TTE) and the frequency of its use, appropriate
use criteria for initial TTE in outpatient pediatric cardiology were released in
20145 (see Chapter 3, The Role of Echocardiography). On the basis of these
criteria, TTE is appropriate when a pathologic murmur is heard and when there
is a murmur in the setting of signs, symptoms, or findings of cardiovascular
disease. The use of TTE in the setting of an innocent murmur with a benign
family history and no signs, symptoms, or findings of cardiovascular disease
are rarely considered appropriate. Pediatric cardiologists have demonstrated an
ability to accurately distinguish between innocent and pathologic murmurs via
clinical assessment alone.6 Therefore, undergoing an evaluation by a pediatric
cardiologist prior to performing TTE in patients in whom the primary care
physician was concerned about a pathologic murmur or was uncertain of the
Box 11-1. Characteristics of Pathologic Murmurs

Diastolic, continuousa
Intensity >III/VI
Harsh quality
Abnormal S2 (Loud, widely split, fixed)
Presence of a clicks, opening snaps
Presence of S4
a
Must distinguish patent ductus arteriosus from venous hum (innocent murmur) (audio available at www.youtube.
com/watch?v=KBVNJtayzbA&index=16&list=PLKCIeugVenPTLW-nspw_wUkXxO2IIiesu) ().
167
CCIP.indb 167 3/13/18 4:18 PM

Murmur
Neonate Child/Adolescent
Cyanosis?
Respiratory distress?
?Perfusion?
No Yes
Pathologic Possible critical

murmur CHD: Urgent Abnormal family/personal history?
characteristics? cardiology Abnormal vital signs/saturation?
(see Box 11-1) evaluation Abnormal pulses?
No Yes
Systolic Yes Continuous
Clinical Possible CHD:

follow-up Cardiology Audible Diastolic: Positional
referral S1? AR change
PR present?
MS
No Yes TS No Yes
Holosystolic: PDA Venous hum

VSD Wide/fixed (disappears
MR split S2? when supine)
TR Cardiology referral
No Yes
Reassurance
ASD
Pathologic murmur
characteristics?
(see Box 11-1)
Innocent
murmur
AS
PS
MVP Reassurance
HCM
Cardiology referral
FIGURE 11-1. Suggested approach to heart murmurs. AR, aortic regurgitation; AS, aortic stenosis;
ASD, atrial septal defect; CHD, congenital heart disease; HCM, hypertrophic cardiomyopathy;
MR, mitral regurgitation; MS, mitral stenosis; MVP, mitral valve prolapse; PDA, patent ductus
arteriosus; PR, pulmonary regurgitation; PS, pulmonary stenosis; TR, tricuspid regurgitation; TS,
tricuspid stenosis; VSD, ventricular septal defect.
168
CCIP.indb 168 3/13/18 4:18 PM

Heart Murmur
diagnosis of an innocent murmur on the basis of the clinical assessment may

provide a more cost-effective approach to the use of TTE.7 Furthermore, if a
pathologic murmur is confirmed to be caused by cardiac disease, the patient
will require referral to a pediatric cardiologist for management. In this type of
situation, it may be beneficial for the patient and his or her family to have the
TTE performed, receive the results, and plan for management all in 1 visit to
reduce anxiety about the TTE results.
Key Points
•• Heart murmurs are common in children. Most heart murmurs are innocent.
•• A complete review of the history and a thorough general physical and cardiac
examination will help differentiate innocent from pathologic murmurs.
•• Once a murmur has been identified as having pathologic features, the next
step should be to refer the patient to a pediatric cardiologist.

•• Still’s (Vibratory) Murmur (Willam Buck Kyle, MD). www.youtube.com/
watch?v=dxRx-XZ0WLg&index=2&list=PLKCIeugVenPTLW-nspw_
wUkXxO2IIiesu
•• Atrial Septal Defect (Willam Buck Kyle, MD). www.youtube.com/
watch?v=U_xhNdf2Ggk&index=6&list=PLKCIeugVenPTLW-nspw_
wUkXxO2IIiesu
•• Atrial Septal Defect—large secundum (Willam Buck Kyle, MD).
www.youtube.com/watch?v=NFAkj9Fbfmw&index=7&list=
•• Pulmonary Stenosis—mild (Willam Buck Kyle, MD). www.youtube.com/
wUkXxO2IIiesu
•• Continuous Murmur with Restrictive Patent Ductus Arteriosus (Willam
Buck Kyle, MD). www.youtube.com/watch?v=KBVNJtayzbA&index=

•• Heart Murmur (American Academy of Pediatrics). www.healthychildren.org/
English/health-issues/conditions/heart/Pages/Heart-Murmur.aspx
•• Heart Murmurs (American Heart Association). www.heart.org/
HEARTORG/Conditions/More/CardiovascularConditionsofChildhood/
Heart-Murmurs_UCM_314208_Article.jsp
•• Heart Murmurs and Your Child (KidsHealth). kidshealth.org/en/parents/
murmurs.html
169
CCIP.indb 169 3/13/18 4:18 PM

References
1) McLaren MJ, Lachman AS, Pocock WA, Barlow JB. Innocent murmurs and third heart sounds
in Black schoolchildren. Br Heart J. 1980;43(1):67–73
2) Hiremath G, Kamat D. When to call the cardiologist: treatment approaches to neonatal heart
murmur. Pediatr Ann. 2013;42(8):329–333
3) Frank JE, Jacobe KM. Evaluation and management of heart murmurs in children. Am Fam
Physician. 2011;84(7):793–800
4) Mahle WT, Newburger JW, Matherne GP, et al; American Heart Association Congenital
Heart Defects Committee of the Council on Cardiovascular Disease in the Young, Council
on Cardiovascular Nursing, and Interdisciplinary Council on Quality of Care and Outcomes
Research; American Academy of Pediatrics Section on Cardiology and Cardiac Surgery, and
Committee on Fetus and Newborn. Role of pulse oximetry in examining newborns for congen-
ital heart disease: a scientific statement from the American Heart Association and American
Academy of Pediatrics. Circulation. 2009;120(5):447–458
5) Campbell RM, Douglas PS, Eidem BW, Lai WW, Lopez L, Sachdeva R. ACC/AAP/AHA/
ASE/HRS/SCAI/SCCT/SCMR/SOPE 2014 appropriate use criteria for initial transthoracic
echocardiography in outpatient pediatric cardiology: a report of the American College of
Cardiology Appropriate Use Criteria Task Force, American Academy of Pediatrics, American
Heart Association, American Society of Echocardiography, Heart Rhythm Society, Society
for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed
Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Pediatric
Echocardiography. J Am Coll Cardiol. 2014;64(19):2039–2060
6) Smythe JF, Teixeira OH, Vlad P, Demers PP, Feldman W. Initial evaluation of heart murmurs:
are laboratory tests necessary? Pediatrics. 1990;86(4):497–500
7) Danford DA, Nasir A, Gumbiner C. Cost assessment of the evaluation of heart murmurs in
children. Pediatrics. 1993;91(2):365–368
170
CCIP.indb 170 3/13/18 4:18 PM

CHAPTER 12
Evaluation of the
Neonate With
Congenital Heart
Disease
Caitlin Haxel, MD, and Julie Glickstein, MD, FACC, FAAP
Introduction
Congenital heart disease (CHD) is the most common congenital disorder in
neonates, with an incidence of 8 to 10 per 1,000 live births.1 Approximately 25%
of neonates who receive a diagnosis of CHD have critical heart disease and require
cardiac surgery or an interventional procedure during the first year after birth.2
With the advent of fetal echocardiography, many critical congenital heart lesions
are now diagnosed during pregnancy.3 However, not all infants with CHD receive
diagnoses prenatally. Up to 30% of neonates with critical CHD may appear normal
at initial physical examination.4 Delay in diagnosis of these critical lesions can lead
to increased morbidity and mortality. It is essential for primary care practitioners
to assess any neonate suspected of having heart disease in the neonatal period.
Most cardiac consultations in the newborn nursery focus on a referral for a cardiac
murmur, cyanosis, abnormal chest radiographic finding, abnormal electrocardio
graphic (ECG) finding, cardiac arrhythmia, or symptoms of congestive heart
failure (CHF). Screening guidelines for critical CHD have been endorsed by
the American Academy of Pediatrics, the American Heart Association, and the
American College of Cardiology.5 There is evidence that universal screening with
171
CCIP.indb 171 3/13/18 4:18 PM

pulse oximetry improves the identification of neonates with critical CHD when
compared to physical examination alone (see Chapter 14, Neonatal Screening
for Heart Disease).6 The spectrum of presentation of CHD in the neonate is
broad and can range from benign to catastrophic. This chapter will focus on the
evaluation and identification of both symptomatic and asymptomatic neonates
with critical and noncritical CHD.
Evaluation of the Neonate for CHD

History
The maternal history, antenatal history, and family history should be reviewed
to identify possible risk factors that increase the likelihood of CHD. Gesta
tional age must also be considered. Prematurity, with gestational age less than
37 weeks, increases the risk of CHD by two- to threefold when compared with
term neonates.7
Maternal pregestational diabetes, phenylketonuria, systemic lupus erythema-
tous (SLE), Sjogren syndrome, maternal use of certain medications, or maternal
infections can increase the incidence of CHD or cardiomyopathy. Specifically,
pregestational diabetes mellitus has been associated with an increase in the risk
of heterotaxy syndrome, single-ventricle lesions, and dextro-transposition of the
great arteries (D-TGA).8 A maternal history of phenylketonuria (if preconcep-
tion phenylalanine levels are >10 mg/dL [>605.44 mmol/L]) increases the risk
for CHD.9 A maternal history of connective tissue disorders, such as SLE or
Sjogren syndrome, is associated with cardiomyopathy and congenital heart block.
The maternal use of medications such as isotretinoin, lithium carbonate, ethanol,
phenytoin, valproic acid, carbamazepine, and angiotensin-converting enzyme
inhibitors has been associated with CHD. Finally, maternal (congenital) infec-
tions such as rubella, cytomegalovirus, coxsackievirus, parvovirus B19, h
erpes
simplex, toxoplasmosis (due to Toxoplasma gondii), and human herpesvirus 6
have also been associated with CHD.3

Family history of CHD increases the risk of CHD for the neonate, with
differing risks depending on the family member affected and the specific con-
genital heart defect. Generally, if the mother of a neonate has CHD, this confers
a 6% risk of having affected offspring, whereas a father with CHD confers a 2%
risk to his offspring. Similarly, having a sibling with CHD confers a 2% risk on
a subsequent neonate.10 A family history of syndromes associated with CHD,
such as Marfan syndrome, Ehlers-Danlos syndrome, and Noonan syndrome,
should also prompt an investigation of the neonate for similar syndromes.
It is also important to review the antenatal history, including antenatal
imaging. Routine antenatal screening for CHD was previously limited to a
4-chamber view of the heart at approximately 20 weeks’ gestation, which could
172
CCIP.indb 172 3/13/18 4:18 PM

Evaluation of the Neonate With Congenital Heart Disease
be used to detect only approximately 25% of clinically significant CHD cases.11

However, the practice guidelines of the International Society for Ultrasound
in Obstetrics and Gynecology now recommend assessment of outflow tracts,
which could be used to identify CHD lesions such as tetralogy of Fallot (TOF),
double-outlet right ventricle (RV), transposition of the great arteries (TGA),
and truncus arteriosus.12 With a higher level of suspicion, fetal echocardiography
can then be performed for more definitive diagnosis. It is important to elicit
other fetal anatomic abnormalities—such as cleft lip and palate; gastroesoph-
ageal, renal, or central nervous system anomalies; or club feet—because of the
association with CHD. Finally, it is important to review any antenatal genetic
testing to identify chromosomal abnormalities such as 22q11 deletion, 45X, and
trisomy 21, 18, and 13.
Infants who ultimately require the care of a pediatric cardiologist can have a
variety of presentations, including a murmur; cyanosis (often without a murmur);
symptoms of heart failure, which include tachypnea, tachycardia, feeding
difficulty, or failure to gain weight; or cardiovascular collapse and cardiogenic
shock. The latter 2 presentations almost always occur after discharge from the
newborn nursery.
Auscultating a heart murmur in a routine examination of an infant is not
uncommon. Not all CHD lesions are associated with murmurs, and many
infants with murmurs do not have structural heart disease. Innocent or benign
murmurs are not associated with an anatomic or physiological abnormality.
However, many infants with clinically significant CHD have no murmur
or a soft systolic murmur at birth, including neonates with large ventricular
septal defects (VSDs), single-ventricle lesions, D-TGA, and total anomalous
pulmonary venous connection. Therefore, presence or absence of a cardiac
murmur is an insensitive marker for CHD. The primary consideration in
assessing an asymptomatic neonate with or without a murmur is whether it
could be associated with a ductal-dependent lesion, in which case discharging
the neonate home without full cardiac evaluation could be life-threatening.
A full physical examination of a neonate with concern for suspected CHD
should be performed with the neonate appropriately warmed and quieted. The
examination should begin with an assessment of vital signs, including heart rate,
respiratory rate, 4-extremity blood pressure, and pre- and postductal pulse oxim-
etry (measured in the right arm and 1 lower extremity). The weight should be
obtained and plotted on an appropriate growth curve to determine if the neonate
is small, appropriate, or large for gestational age. Concerning vital signs that can
alert a physician to possible CHD in the neonate include the following:
173
CCIP.indb 173 3/13/18 4:18 PM

1. Abnormal heart rate or irregular rhythm (tachycardia >180 beats/min or

bradycardia <90 beats/min)
2. Tachypnea (respiratory rate >60 breaths/min) with or without retractions
3. Abnormal 4-extremity blood pressure (blood pressure >10 mm Hg higher in
the right upper extremity than in the lower extremities)
4. Percutaneous pulse oximetry values below 95%, or having an oxygen
saturation in the lower extremity than in the right upper extremity, are never
normal in otherwise healthy-appearing neonates measured after 24 hours
of age.13 See also Figure 14-1 in Chapter 14, Neonatal Screening for Heart
Disease, for an algorithm for pulse oximetry screening.
After measuring a full set of vital signs, the clinician should assess the neonate
overall, including the presence of dysmorphic features or other congenital
abnormalities. The clinician should evaluate the tone and activity of the neonate
and assess the neonate for any signs of birth trauma. A full assessment of the
respiratory status includes an evaluation of the airway and breathing, noting
the respiratory rate, work of breathing, and presence of retractions, nasal flaring,
grunting, hypoventilation, or apnea.
The cardiac examination includes an inspection of coloring of the mucous
membranes and nail beds to assess the neonate for cyanosis. However, cyanosis
may not be clinically apparent with mild desaturations (>80% saturation), with
anemia, or in darkly pigmented neonates.
Systemic perfusion should be assessed by palpating the pulse in the upper and
lower extremities. A discrepancy of pulse in the right and left brachial arteries
with weak or absent femoral pulse suggests a possible aortic arch abnormality
(aortic coarctation, aortic arch hypoplasia, or interrupted aortic arch). A bound
ing pulse may be present with a moderate to large patent ductus arteriosus
(PDA) or a moderate to severe aortic valve insufficiency. Palpating precordial
activity allows the clinician to determine whether the heart is located normally,
in the left side of the chest. Increased precordial activity can indicate cardiac
enlargement. A ventricular impulse that is palpable along the left parasternal
area is suggestive of RV volume or pressure overload. A thrill may be present
over the right or left upper sternal border or suprasternal notch, which can
suggest outflow tract obstruction, such as moderate to severe pulmonary or
aortic stenosis. A thrill may also represent a restrictive VSD.
Auscultation of the heart can reveal multiple abnormalities, including a
benign versus a pathologic murmur, single S2, widely or fixed split S2, clicks, or
S3 gallop. Generally, a benign murmur is soft and position dependent (occurring
while supine) and occurs during systole, with normal physiological splitting of S2
and with no associated thrill. Pathologic murmurs differ in quality and intensity.
Importantly, neonates can have CHD without having a murmur, such as in
D-TGA without a VSD. A full discussion of cardiac murmurs is included later
in this chapter.
174
CCIP.indb 174 3/13/18 4:18 PM

A complete examination also includes auscultation for bruits over the anterior
fontanelle or abdomen, indicating cerebral or hepatic arteriovenous malforma-
tions. Palpation of the abdomen is important to identify hepatomegaly, which
can be associated with heart failure or other causes of increased right-sided heart
pressure. Abnormal position of the liver in the midline or left side of the abdo-
men can also be indicative of heterotaxy syndrome and signal possible CHD.
Differential Diagnosis in Asymptomatic Versus

Symptomatic Neonates
The symptomatic neonate can present with murmur, cyanosis, heart failure, or
circulatory collapse. It is crucial to recognize that these different presentations
can overlap and reflect the myriad congenital heart lesions that are possible.
Murmur
As discussed previously, murmurs in the neonate can be benign or pathologic.
Three murmurs auscultated in the neonatal period are benign when associated
with an asymptomatic neonate with normal vital signs and cardiac testing. The
murmur of a PDA is generally a soft, higher-pitched, low-intensity systolic
murmur heard between 4 and 16 hours of age. Once outside the neonatal period,
the murmur of a PDA is typically more continuous, described as a “washing
machine–like murmur” (audio available at www.youtube.com/watch?v=
KBVNJtayzbA&index=16&list=PLKCIeugVenPTLW-nspw_wUkXxO2IIiesu)
( ). Peripheral pulmonary artery stenosis is a higher-pitched murmur heard
throughout the precordium and is heard best in the axillae or in the back. It
usually resolves in 3 to 6 months with normal growth of the pulmonary vascu
lature. Finally, a Still murmur (also commonly referred to as Still’s murmur) is
described as a lower-pitched, low-intensity systolic murmur heard best at the left
lower sternal border and apex (audio available at www.youtube.com/watch?v=
dxRx-XZ0WLg&index=2&list=PLKCIeugVenPTLW-nspw_wUkXxO2IIiesu)
( ). It is more common in children, rather than neonates, and usually resolves
with age and growth.
A murmur can also be a sign of CHD. Pathologic murmurs are generally
loud, harsh, pansystolic, diastolic, or loudest on auscultation at the left upper
sternal border, right sternal border, or apex. A loud and single S2 can be
associated with pulmonary hypertension, aortic atresia, pulmonary atresia,
severe pulmonary stenosis, truncus arteriosus, and TOF. A widely or fixed split
S2 is associated with atrial septal defects (audio available at www.youtube.com/
wUkXxO2IIiesu and www.youtube.com/watch?v=NFAkj9Fbfmw&index=

7&list=PLKCIeugVenPTLW-nspw_wUkXxO2IIiesu)( ) and other lesions
associated with RV volume overload (total or partial anomalous pulmonary
venous connection) or conduction delays. Early systolic clicks can suggest
pulmonary or aortic valve stenosis. Mid-systolic clicks can be associated with
175
CCIP.indb 175 3/13/18 4:18 PM

mitral valve prolapse or Ebstein anomaly of the tricuspid valve. An S3 gallop

is associated with ventricular dysfunction or left ventricular (LV) volume
overload. Pericardial friction rubs can be auscultated with pericardial effusions
or pericarditis.
Cyanosis
Cyanosis can be the presenting sign for neonates with suspected CHD. This
bluish skin tone is present when 5 g/dL (50 g/L) of deoxygenated hemoglobin is
present in the neonate. However, cyanosis is not clinically apparent in the setting
of mild desaturations (saturation >80%) or anemia. Additionally, cyanosis can
be difficult to assess in darkly pigmented neonates. Therefore, it is important to
obtain a pulse oximetry measurement in both upper and lower extremities. Most
commonly, 2 extremities are measured, including the right upper extremity and
either of the lower extremities.
Cyanotic congenital heart lesions result in cyanosis due to right-to-left shunt-
ing of deoxygenated blood into the oxygenated arterial system. The spectrum
of cyanotic heart lesions is varied but can be broadly categorized according to
whether there is decreased pulmonary blood flow, increased pulmonary blood
flow, or severe heart failure due to left-sided heart obstructive lesions. Many
cyanotic congenital heart defects are ductal dependent; however, the presence
of cyanosis does not imply a ductal-dependent lesion.
The 5 more common forms of cyanotic CHD include tricuspid valve anom-
alies, TOF, TGA, truncus arteriosus, and total anomalous pulmonary venous
connection (TAPVC).
Cyanotic congenital heart lesions with decreased pulmonary blood flow
include tricuspid valve anomalies and variations of pulmonary outflow tract
obstructions that range from TOF to critical pulmonary valvar stenosis and
pulmonary valve atresia. Tricuspid valve anomalies include tricuspid atresia,
tricuspid stenosis, and Ebstein anomaly, which result in varying degrees of
obstruction to blood flow across the tricuspid valve and hypoplasia of the RV
and RV outflow tract. As a result, deoxygenated blood shunts from the right
to the left side of the heart across an atrial communication and mixes in the
systemic arterial circulation, causing cyanosis. TOF can result in cyanosis,
depending on the degree of RV outflow tract obstruction. Less severe obstruc-
tion can lead to a “pink TOF” without cyanosis. More severe ventricular outflow
tract obstruction will lead to deoxygenated blood shunting from the RV into the
aorta and systemic circulation, resulting in cyanosis. Critical pulmonary valvar
stenosis and pulmonary atresia with intact ventricular septum result in severe to
complete obstruction of blood flow to the pulmonary arteries. Therefore, both
lesions are ductal dependent to provide pulmonary blood flow.
In comparison, cyanotic heart lesions with increased pulmonary blood flow
include D-TGA, truncus arteriosus, and TAPVC. Neonates with D-TGA have
parallel pulmonary and systemic circulations (oxygenated blood is pumped
176
CCIP.indb 176 3/13/18 4:18 PM

through the lungs, and deoxygenated blood is pumped through the systemic
circulation) and depend on an atrial septal communication, a PDA, and a VSD
(if present) for appropriate mixing. For those without adequate atrial commu-
nication, as the PDA closes, profound cyanosis and eventually cardiovascular
collapse develop. If a large VSD is present, neonates may have less marked
cyanosis at birth; however, heart failure may develop as a result of increased
pulmonary blood flow. In truncus arteriosus, a single great vessel arises from the
heart, from which the aorta, pulmonary arteries, and coronary arteries all arise.
This leads to mixing of oxygenated and deoxygenated blood in the systemic
arterial circulation, resulting in cyanosis and increased pulmonary blood flow,
which can cause heart failure symptoms. In TAPVC, all 4 pulmonary veins fail
to connect appropriately to the left atrium and drain into the systemic venous
circulation. To maintain cardiac output, there must be atrial communication,
ventricular communication, or PDA to allow shunting of deoxygenated blood
from the right side of the heart into the systemic arterial circulation, resulting
in cyanosis.
Critically obstructive left-sided heart lesions, such as hypoplastic left heart
syndrome and critical aortic valve stenosis, have inadequate systemic output. In
these CHD lesions, cyanosis occurs because of right-to-left shunting of deoxy-
genated blood via a PDA (from the pulmonary artery into the descending aorta).
In these patients, as the ductus begins to close, systemic output is compromised,
and cyanosis often quickly progresses to cardiovascular collapse.
Differential cyanosis is a difference in measured pulse oximetry of more than
3% between the right hand (preductal) and the foot (postductal). This occurs
in the setting of critical coarctation of the aorta and interrupted aortic arch,
in which oxygenated blood from the left side of the heart supplies the upper
body via vessels proximal to the site of arch obstruction and deoxygenated
blood shunts right to left across the PDA to supply the lower half of the body.
Differential cyanosis can also occur in neonates with structurally normal hearts
with persistent pulmonary hypertension of the newborn and a PDA. Increased
pulmonary pressure causes right-to-left shunting across the PDA, providing
deoxygenated blood to the lower extremities.
Reversed differential cyanosis occurs when the oxygen saturation in the upper
extremity is less than that in the lower extremity. This can be seen in neonates
with D-TGA with persistent pulmonary hypertension or aortic interruption
or coarctation, which causes right-to-left shunting of oxygenated blood via the
PDA to the lower extremities, with deoxygenated blood delivered from the left
side of the heart to the head and neck vessels. Reversed differential cyanosis can
also be noncardiac in etiologic origin. This includes pulmonary disorders, met-
hemoglobinemia, sepsis, hypoglycemia, dehydration, and hypoadrenalism. These
can be differentiated from cardiac lesions by means of the history, examination,
chest radiography, hyperoxia testing, and echocardiography when indicated.
177
CCIP.indb 177 3/13/18 4:18 PM

Acrocyanosis can also occur in neonates and describes the bluish discoloration
of the hands, feet, and perioral area, which is attributed to benign vasomotor
changes in diffuse venous structures in the periphery of the body.
Heart Failure
Heart failure in infants is a clinical spectrum that ranges from mild symptoms
of tachypnea to cardiovascular collapse. Clinical findings of heart failure can
include tachypnea, increased work of breathing (grunting, retractions, nasal
flaring, and head bobbing), diaphoresis, difficulty feeding, failure to thrive, gallop
rhythm, and hepatomegaly. These signs may precede the diagnosis of CHD.
Heart failure can develop at varying times throughout the neonatal period,
depending on the specific congenital heart lesion and prematurity status. At
birth, the pulmonary vascular resistance (PVR) is increased and decreases over
the first days to weeks of life. At approximately 6 weeks of life, the PVR should
have decreased to normal levels. In premature neonates, the PVR is generally
lower at birth when compared to term neonates. This can lead to heart failure
symptoms secondary to pulmonary overcirculation at any earlier age.
Heart failure symptoms secondary to excessive pulmonary blood flow can
develop shortly after birth in neonates with hypoplastic left heart, severe tri
cuspid regurgitation, or severe pulmonary regurgitation.
Within the first week of life, neonates with D-TGA or infracardiac TAPVC
or premature neonates with a large PDA will develop heart failure symptoms.
At approximately 1 to 4 weeks of age, neonates with critical aortic stenosis,
aortic coarctation, or critical pulmonary stenosis will develop heart failure as
the PDA closes and either the systemic or the pulmonary blood flow is com-
promised. The presentation of neonates with left-sided obstructive lesions will
depend on the degree of obstruction and the presence of the ductus arteriosus.
With a lesser-degree but still clinically significant obstruction, the neonate will
often exhibit heart failure symptoms over the first 2 weeks of life. With severe or
critical obstruction or with closure of the ductus, the neonate will present with
poor perfusion and cardiogenic shock because of a lack of systemic perfusion.
Infants with large VSDs, endocardial cushion defects, or large arteriovenous
malformations will generally become symptomatic at 4 to 6 weeks of life.
Certain congenital heart lesions, such as truncus arteriosus, may manifest
with a combination of cyanosis and heart failure due to mixing of oxygenated
and deoxygenated blood in the common outflow tract and excessive pulmonary
blood flow.
Cardiogenic Shock
Sudden collapse with poor systemic circulation or extreme cyanosis and
acidosis suggests a number of differential diagnoses, including sepsis, metabolic
derangement, and cardiogenic shock. Cardiomegaly and lack of response to
178
CCIP.indb 178 3/13/18 4:18 PM

volume resuscitation suggest a cardiac etiologic origin of shock. In neonates with

severe or critically obstructive left-sided heart lesions, inadequate left-sided heart
development compromises cardiac output. This can be seen in lesions such as
hypoplastic left-sided heart, critical aortic valve stenosis, and critical coarctation
of the aorta or interrupted aortic arch. In these left-sided heart lesions, the
flow from the RV into the lungs is typically unimpaired. The oxygenated blood
returning from the lungs is either completely diverted across an atrial-level
communication into the RV (in the case of hypoplastic left-sided heart) or par-
tially diverted to the right side of the heart, depending on the filling properties
of the LV. In the right atrium, pulmonary venous blood mixes with desaturated
systemic venous blood returning from the body, thereby increasing the oxygen
saturation of the right-sided heart blood. The RV maintains the systemic blood
flow by ejecting blood through the neonatal PDA. As a result, these neonates
depend primarily or entirely on patency of the ductus arteriosus for systemic
cardiac output. The relatively high saturations of the ductal blood flowing into
the aorta minimize the appearance of cyanosis, even though the RV is supplying
the entire systemic cardiac output (in hypoplastic left-sided heart or critical
aortic stenosis) or the blood flow to the lower body (in coarctation or interrupted
aortic arch). The admixture of red and blue venous returns occurs in these “left-
sided heart obstructive lesions,” just as in other cyanotic cardiac malformations,
but the potential for catastrophic deterioration caused by inadequate systemic
flow is much greater as the ductus arteriosus undergoes normal spontaneous
closure after birth.
Ductal-dependent left-sided heart lesions can appear after discharge from
the newborn nursery. Indeed, ductal patency may persist for weeks or, in rare
cases, months. The constriction and closure of the ductus arteriosus cause
decreased systemic blood flow, oliguria, acidosis, pulmonary edema, and heart
failure. As the cardiac output decreases, retrograde blood flow from the ductus
into the common coronary artery (ascending aorta) results in decreased right
and left coronary artery blood flow, leading to myocardial ischemia, ventricular
dysfunction, and death.
The clinical presentation of left-sided heart obstructive disease may mimic
sepsis; the infant exhibits tachypnea, mottled gray skin, and poor perfusion,
with decreased peripheral and central pulses. Critical clues in a 3-week-old
neonate that should lead to the consideration of a cardiac diagnosis rather than
sepsis include the presence of a gallop rhythm and marked hepatomegaly or
cardiomegaly. Profound metabolic acidosis with pH values of 7.0 or less are
characteristic. A high serum brain natriuretic peptide concentration may prove
to be a cardiac-specific marker of heart failure in this setting.
179
CCIP.indb 179 3/13/18 4:18 PM

Diagnostic Procedures and Imaging

Laboratory Evaluation
Initial laboratory evaluation, particularly in a neonate with cyanosis or cardio-
vascular collapse, should include an arterial or venous blood gas analysis and
lactate level to assess the patient for acidosis. To assess the patient for anemia, a
hemoglobin or hematocrit level can be obtained from the blood gas analysis (or
via a complete blood count). A full electrolyte panel will help rule out electrolyte
derangements that can be corrected.
Pulse Oximetry
Pulse oximetry should be used in a calm neonate to obtain simultaneous or
direct-sequence oxygen saturation measurements in the right hand (preductal)
and either foot (postductal) to assess the patient for cyanosis or differential cya-
nosis. The left subclavian artery may arise from the aortic arch before or after the
ductus arteriosus, so the left hand should not be used for pulse oximetry monitoring.
Pulse oximetry screening should be performed later than 24 hours after birth or
as late as possible prior to neonatal discharge home. See Chapter 14, Neonatal
Screening for Heart Disease, for more details on recommendations for neonatal
pulse oximetry screening.
Hyperoxia Test
With the hyperoxia test, relative changes in arterial oxygen tension (Pao2) are
used to help differentiate cardiac and noncardiac causes of neonatal cyanosis.
For this test, a neonate inspires 21% oxygen (room air); the Pao2 is measured in
the right radial artery (preductal) and an artery of a lower extremity (postductal).
The neonate is then placed on 100% oxygen for 10 minutes, after which the
preductal and postductal Pao2 measurements are repeated. In the absence of a
fixed cardiac shunt, the administration of 100% oxygen to a neonate will increase
alveolar partial pressure of oxygen and therefore increase the pulmonary venous
and systemic arterial oxygen saturation. In the presence of cyanotic congenital
heart lesions, such as D-TGA, administration of 100% oxygen will cause little or
no increase in the systemic arterial oxygen saturation.14
An exception occurs in neonates with clinically significant pulmonary
hypertension and an intracardiac (patent foramen ovale) or extracardiac (PDA)
shunt, which can allow for right-to-left shunting. Additionally, common mixing
conditions with high pulmonary blood flow, such as truncus arteriosus or single
ventricle with PDA, may have an increase in Pao2 after 100% fraction of inspired
oxygen. In comparison, respiratory conditions with severe ventilation-perfusion
mismatch may not have an increase in Pao2 after inspiration of 100% oxygen.
180
CCIP.indb 180 3/13/18 4:18 PM

Electrocardiography
ECG should be performed in all neonates with concern for CHD. An abnormal
ECG finding in a neonate can manifest as an abnormal QRS axis, abnormal
P wave axis, atrial enlargement, ventricular hypertrophy, conduction delay, or
abnormal T wave inversion. In an asymptomatic newborn, an abnormal ECG
finding can be the first indicator of possible CHD. However, asymptomatic
or symptomatic newborns with clinically significant CHD can have an ECG
finding that is normal for their age.
For example, neonates with D-TGA, TOF, or truncus arteriosus often have
ECG findings normal for their age, despite having clinically significant CHD.
The T wave in V1 should be inverted by day 5 after birth. Upright T waves after
day 5 suggest RV hypertrophy. Neonates with tricuspid atresia will classically
have ECG findings that demonstrate left-axis deviation, right atrial enlargement,
and LV hypertrophy. Newborns with pulmonary atresia will usually have a car-
diac axis between 0 and 90 degrees, which is abnormal in a neonate. Newborns
with hypoplastic left heart syndrome will have an ECG finding of normal QRS
axis for age with a paucity of LV forces.
Chest Radiography
Chest radiography is an extremely useful modality for the assessment of cardiac
size, cardiac position in the thoracic cavity, pulmonary vascular markings, and
abdominal situs. Chest radiography is an important tool for the differentiation
of cardiac and pulmonary disorders. Specifically, the size and shape of the cardiac
silhouette may yield diagnostic clues; for example, the “boot-shaped heart” in
TOF,15 the “egg on a string” in TGA, and the massive cardiomegaly associated
with Ebstein malformation of the tricuspid valve are classic patterns that suggest
specific cardiac lesions. Increased or decreased pulmonary vascular markings
may suggest excessive or restricted pulmonary blood flow. Aortic arch sidedness
can also suggest the presence of CHD. While a right-sided aortic arch may
be an isolated finding in an otherwise structurally normal heart, it can also be
associated with conotruncal malformations such as TOF, double-outlet RV, and
truncus arteriosus. Examination of the pulmonary fields may demonstrate airway
disease, pneumothorax, pleural effusion, pulmonary hypoplasia, elevation of the
hemidiaphragm, or diaphragmatic hernia.
Echocardiography
Echocardiography can assist in establishing a definitive anatomic diagnosis and
can be used to assess cardiac function when any critical or noncritical cardiac
lesion is suspected. All newborns and infants with signs or symptoms concerning
for critical CHD (shock unresponsive to volume resuscitation, cyanosis), an
abnormal ECG finding, an abnormal chest radiographic finding, a positive pulse
oximetry screening result, or a genetic disorder or extracardiac malformation
associated with a cardiovascular malformation should undergo complete
181
CCIP.indb 181 3/13/18 4:18 PM

(2-dimensional imaging, with pulsed and color Doppler imaging) high-quality

echocardiography performed by a skilled technician, with results interpreted by a
clinician with expertise in the diagnosis of CHD, such as a pediatric cardiologist.
Management
Most cardiac consultations in the newborn nursery focus on a referral for a
cardiac murmur, cyanosis, abnormal chest radiographic or ECG findings, cardiac
arrhythmias, and possible CHF. The care of the neonate with suspected CHD
varies with the presentation of the neonate. An asymptomatic neonate with a
persistent murmur who is feeding well and has an otherwise benign evaluation
finding, including normal physical examination findings, 4-extremity blood pres-
sure, and pulse oximetry screening, should undergo follow-up with a cardiology
referral and testing as indicated (ECG and/or echocardiography) but may not
require emergent evaluation. If, however, there is a symptomatic neonate with
cyanosis, signs of heart failure, abnormal 4-extremity blood pressure, positive
pulse oximetry screening, or abnormal ECG or chest radiographic finding, then
urgent cardiac evaluation is indicated, including a complete echocardiographic
examination. This neonate should not be discharged from the hospital without
excluding potentially life-threatening conditions.
If a neonate presents with worsening cyanosis, severe heart failure, or shock,
initial management should begin with an assessment of airway, breathing, and
circulation, including early intubation and ventilation if needed. Physicians
should correct acidosis, hypoglycemia, hypocalcemia, and other electrolyte
abnormalities. Sepsis and metabolic disease should be considered and appro
priately treated. For any neonate with a concern for a congenital heart defect
that is ductal dependent for pulmonary or systemic blood flow, prostaglandin
should be considered and initiated at any time. The primary physician does not
need to wait for a cardiologist consult or an echocardiographic examination to
confirm a diagnosis if there is a concern for a prostaglandin-dependent critical
congenital cardiac lesion. Prostaglandin should be considered for neonates with
profound or increasing cyanosis or neonates with acidosis and shock. Possible
side effects of prostaglandin include apnea, jitteriness, convulsions, low-grade
pyrexia, flushing, and diarrhea, which should improve with reduction in dose.
Ongoing Care
After a diagnosis of heart disease is established in a neonate, the follow-up
medical care, including a discussion about potential complications and prognosis,
depends greatly on the underlying diagnosis. The need for intervention can
include medications, cardiac catheterization, and/or cardiac surgery, either in the
neonatal period or later in life. It is important to realize that even if the diagnosis
182
CCIP.indb 182 3/13/18 4:18 PM

of CHD was established prenatally, it can be overwhelming for families to deal

with the knowledge that their child has heart disease. Families depend on the
knowledge and support of their child’s cardiologist, as well as the medical care
and support they receive from their child’s primary care physician.
Conclusion
The presentation of CHD in the neonatal period is varied and depends
on the lesion. The spectrum of disease ranges from mild to a life-threating
ductal-dependent lesion. It is through a careful history and physical examination,
along with pulse oximetry, ECG, and chest radiography, that a congenital heart
lesion can be suspected. Every neonate should have pulse oximetry performed
before discharge from the newborn nursery. This is especially important because
cyanosis in the newborn nursery can be missed. Diminished or bounding pulses
can be a presentation of CHD. Dysmorphic features or the presence of other
anatomic abnormalities can be a marker for CHD. All neonates with a heart
murmur, in whom a definitive diagnosis has not yet been established when they
leave the nursery, should be referred to a pediatric cardiologist for evaluation.
Echocardiography can be used to establish a definitive anatomic diagnosis.
Always consider CHD in a “sick neonate.” Identifying congenital heart lesions,
especially critical ones, requires a high index of suspicion by the primary
care physician.
Key Points
•• The absence of a murmur does not rule out CHD.
•• Every neonate should have pulse oximetry performed before discharge from
the newborn nursery because cyanosis in the neonate can be missed.
•• A decreased or bounding pulse is never normal and warrants evaluation.
•• Dysmorphic features or the presence of other anatomic abnormalities can be
markers for CHD.
•• Always consider CHD in a “sick neonate.”

•• Congenital Heart Defects (CHDs) (U.S. Centers for Disease Control and
Prevention). www.cdc.gov/ncbddd/heartdefects/index.html
•• Congenital Heart Defects (American Heart Association). www.heart.org/
HEARTORG/Conditions/CongenitalHeartDefects/Congenital-Heart-
Defects_UCM_001090_SubHomePage.jsp
•• Congenital Heart Defects and CCHD (March of Dimes).
www.marchofdimes.org/baby/congenital-heart-defects.aspx
183
CCIP.indb 183 3/13/18 4:18 PM

References
1) Centers for Disease Control and Prevention. Data and Statistics for Congenital Heart Disease.
www.cdc.gov/ncbddd/heartdefects/data.html. Accessed September 12, 2017
2) Oster ME, Lee KA, Honein MA, Riehle-Colarusso T, Shin M, Correa A. Temporal trends in
survival among infants with critical congenital heart defects. Pediatrics. 2013;131(5):e1502–e1508
2014;129(21):2183–2242
4) Khoshnood B, Lelong N, Houyel L, et al; EPICARD Study Group. Prevalence, timing of
diagnosis and mortality of newborns with congenital heart defects: a population-based study.
Heart. 2012;98(22):1667–1673
5) Mahle WT, Martin GR, Beekman RH III, Morrow WR; Section on Cardiology and Cardiac
Surgery Executive Committee. Endorsement of Health and Human Services recommendation
for pulse oximetry screening for critical congenital heart disease. Pediatrics. 2012;129(1):190–192
6) Valmari P. Should pulse oximetry be used to screen for congenital heart disease? Arch Dis Child
Fetal Neonatal Ed. 2007;92(3):F219–F224
7) Tanner K, Sabrine N, Wren C. Cardiovascular malformations among preterm infants. Pediatrics.
2005;116(6):e833–e838
8) Øyen N, Diaz LJ, Leirgul E, et al. Prepregnancy diabetes and offspring risk of congenital heart
disease: a nationwide cohort study. Circulation. 2016;133(23):2243–2253
9) Platt LD, Koch R, Hanley WB, et al. The international study of pregnancy outcome in
women with maternal phenylketonuria: report of a 12-year study. Am J Obstet Gynecol.
2000;182(2):326–333
10) Burn J, Brennan P, Little J, et al. Recurrence risks in offspring of adults with major heart defects:
results from first cohort of British collaborative study. Lancet. 1998;351(9099):311–316
11) Bull C; British Paediatric Cardiac Association. Current and potential impact of fetal diagnosis
on prevalence and spectrum of serious congenital heart disease at term in the UK. Lancet.
1999;354(9186):1242–1247
12) Carvalho JS, Allan LD, Chaoui R, et al; International Society of Ultrasound in Obstetrics and
Gynecology. ISUOG Practice Guidelines (updated): sonographic screening examination of the
fetal heart. Ultrasound Obstet Gynecol. 2013;41(3):348–359
13) Mahle WT, Newburger JW, Matherne GP, et al; American Heart Association Congenital
on Cardiovascular Nursing, and Interdisciplinary Council on Quality of Care and Outcomes
Research; American Academy of Pediatrics Section on Cardiology and Cardiac Surgery;
Committee on Fetus and Newborn. Role of pulse oximetry in examining newborns
for congenital heart disease: a scientific statement from the AHA and AAP. Pediatrics.
2009;124(2):823–836
14) Jones RW, Baumer JH, Joseph MC, Shinebourne EA. Arterial oxygen tension and response to
oxygen breathing in differential diagnosis of congenital heart disease in infancy. Arch Dis Child.
1976;51(9):667–673
15) Johnson C. Fallot’s tetralogy: a review of the radiological appearances in thirty-three cases. Clin
Radiol. 1965;16:199–210
184
CCIP.indb 184 3/13/18 4:18 PM

PART 3
Congenital Heart
Disease
13. Fetal and Newborn Transitional C
irculations....................... 187
14. Neonatal Screening for Heart Disease.................................. 197
15. Surgical Procedures for Congenital Heart Disease............... 205
16. Office Care of the Child After Cardiac Surgery................... 237
17. Common Syndromes Associated With Cardiac Lesions...... 245
18. Adults With Congenital Heart Disease............................... 269
19. Congenital Heart Lesions.................................................... 287

Aortic Valve Problems, Including Bicuspid Aortic
Valve and Subaortic Membranes.......................................... 287
Atrial Septal Defects............................................................ 292
Atrioventricular Canal Defects............................................. 296
Coarctation of the Aorta...................................................... 300
“Congenitally Corrected” Transposition of the
Great Arteries....................................................................... 305
Mitral Valve Anomalies........................................................ 308
Patent Ductus Arteriosus..................................................... 311
Patent Foramen Ovale.......................................................... 314
185
CCIP.indb 185 3/13/18 4:18 PM

Pulmonary Stenosis.............................................................. 316
Single-Ventricle Lesions....................................................... 320
Systemic and Pulmonary Vein Anomalies............................ 325
Tetralogy of Fallot................................................................ 329
Transposition of the Great Arteries...................................... 334
Tricuspid Valve Anomalies................................................... 339
Truncus Arteriosus............................................................... 343
Vascular Rings and Slings..................................................... 347
Ventricular Septal Defects.................................................... 353
186
CCIP.indb 186 3/13/18 4:18 PM

CHAPTER 13
Fetal and Newborn

Transitional
Circulations
James H. Moller, MD, FAAP
Introduction
Understanding of the fetal circulation and the transitions that occur with and
after birth is beneficial to pediatricians and other practitioners who care for
newborns as part of their normal practice. From their subspecialty perspectives,
neonatologists and pediatric cardiologists use this information to address the prob-
lems that their newborn patients face as they adjust to being born. For neonatol-
ogists, conditions such as persistent fetal circulation and pulmonary hypertension
represent abnormal transition to the neonatal circulation and to normal neonatal
changes in the lungs. For cardiologists, the ductus arteriosus, for example, is critical
in several anomalies, where it has helped maintain the fetal circulation, but with its
postnatal closure, cardiac manifestations quickly develop. These anomalies include
tetralogy of Fallot (TOF) with pulmonary atresia, transposition of the great
arteries (TGA), and obstructions to left ventricular (LV) outflow (eg, coarctation).
As the ductus closes in these anomalies, the sole source of pulmonary blood flow is
eliminated, an avenue for mixing disappears, or a vital source of blood to the aorta
is cut off, respectively.
Abnormalities in the pattern of fetal blood flow may also affect the formation
of the cardiac structures and major blood vessels. This maldevelopment can lead
to a cardiac malformation. These various anomalies can be identified during preg-
nancy by using fetal echocardiography. The anatomic information obtained with
187
CCIP.indb 187 3/13/18 4:18 PM

echocardiography, combined with knowledge of the malformations and their

effects on the circulation, are useful to practitioners and allow them to anticipate
which neonates will need urgent care soon after birth and plan accordingly.
Much of our knowledge about the fetal circulation and its transition has
been from the study of fetal and neonatal lambs. Rudolph and coworkers at the
University of California, San Francisco, have performed numerous sophisticated
studies of fetal lambs at various developmental stages and also in the neonatal
period.1-3 These have helped define and quantify the volume and direction
of blood flow through the heart and great vessels during this time period. In
this chapter, this information is combined with previous studies to present an
overview. Advances in fetal echocardiography4,5 are expanding our knowledge of
the human fetal circulation and its differences from circulation in fetal lambs.
Distinct Features of the Fetal Circulation

The fetal circulation functions in parallel, since both ventricles eject blood into
the aorta—the LV directly into the ascending aorta and the right ventricle
(RV) through the ductus arteriosus into the descending aorta (see Figure 13-1).
The combined fetal cardiac output from the ventricles is about 450 mL/kg/
min in both lambs and humans.4 After birth, as the patent ductus arteriosus
(PDA) closes and the lungs expand, the neonatal circulation transitions to
function as a series circulation. After this transition, the RV ejects only into
the pulmonary artery and the LV receives pulmonary venous blood, which it
ejects only into the aorta. This transition occurs as the unique features of the
fetal circulation disappear.
There are 5 distinct features of the fetal circulation that will change at or
shortly after birth as the fetal circulation transitions to the neonatal circulation:
ductus venosus, foramen ovale, PDA, placental and fetal circulation, and lungs.
Ductus Venosus
To understand the venous blood flow in the fetus below the diaphragm, it is
helpful to review each of the 5 major abdominal venous pathways. The inferior
vena cava receives blood from the lower extremities and kidneys on its path to
enter the right atrium. Just below the diaphragm, it receives the hepatic veins
carrying blood flow from the liver. The left and right hepatic veins drain blood
from the 2 hepatic lobes. The portal venous system carries blood from the intes-
tines and spleen into the liver. The well-oxygenated umbilical venous blood flows
from the placenta, and about half of its blood flows into the left and right lobes
of the liver. Finally, the ductus venosus extends on the undersurface of the liver,
receiving blood only from the umbilical vein, and passes to the inferior vena cava.
The umbilical vein as it passes from the placenta first gives rise to branches
to the left hepatic lobe, then continues rightward to the portal vein entering the
188
CCIP.indb 188 3/13/18 4:18 PM

Fetal and Newborn Transitional Circulations
Aorta
Superior
vena cava Ductus
arteriosus
Right Left
pulmonary pulmonary
artery artery
Right lung Left lung
Right
Left
pulmonary
pulmonary
vein
vein
Foramen Pulmonary
ovale trunk
Inferior
vena cava
Liver
Ductus Descending
venosus aorta
Umbilical
vein
From
placenta
Umbilical
To placenta
arteries
FIGURE 13-1. Diagram of fetal circulation. Reprinted with permission from http://www.heart.
org/HEARTORG/Conditions/CongenitalHeartDefects/SymptomsDiagnosisofCongenitalHeart
Defects/Fetal-Circulation_UCM_315674_Article.jsp#.WYSkuFGQyUk. ©2017 American Heart
Association, Inc.
right hepatic lobe.6-8 About half of umbilical venous blood passes through the
ductus venosus directly to the inferior vena cava without passing through the
hepatic vascular bed. This portion has a higher oxygen content than the other
half, which flows through the right hepatic lobe and passes through the hepatic
vascular bed. There is considerable streaming of these 2 halves. Little mixing
occurs in the inferior vena cava. The blood from the ductus venosus and the left
hepatic vein flows in the posterior and left side of the inferior vena cava and
predominantly through the foramen ovale into the left atrium.9,10 From there,
it passes through the LV to the ascending aorta and the upper part of the body,
most importantly the brain. A small portion goes through the aortic arch to the
descending aorta. As a result, the blood from the right hepatic veins, the distal
189
CCIP.indb 189 3/13/18 4:18 PM

inferior vena cava, and the superior vena cava passes almost exclusively through
the RV into the pulmonary artery. Most of this desaturated blood flows through
the PDA to the descending aorta. The oxygen saturation of this blood is lower
than that in the ascending aorta. A large portion of this transductal blood flow
is directed into the placenta, which is the fetal site of oxygenation.
Foramen Ovale
The foramen ovale provides the opening in the atrial septum, allowing blood
flow from the right to the left atrium. The atrial septum is formed by 2 embry-
ological septae. The septum primum develops and, as it completes its separation
of the left atrium from the right atrium, an opening develops in its center. This
opening is called the ostium secundum. A second septum, the septum secundum,
then develops on the right side of the septum primum. It forms on the superior
and posterior right atrial wall and progressively extends inferiorly and anteriorly
as a crescent to cover the ostium secundum. The slightly thickened edge of this
septum is called the limbus of the fossa ovalis; the atrial septum below appears as
an oval fossa, also called fossa ovalis. During fetal life, the septum primum and
septum secundum are not fused. They may or may not overlap, but they leave a
space between them or allow a small (up to 4 mm) opening between the atria.
Since right atrial pressure exceeds left atrial pressure in the fetus, blood flows
right to left through the foramen ovale. In about three-quarters of all individuals,
the foramen ovale closes anatomically during the first year of life, but in about
a quarter of individuals, it remains patent throughout life. In this instance, it is
known as a “patent foramen ovale.”
Patent Ductus Arteriosus

The ductus arteriosus is a remnant of the sixth left embryonic aortic arch. There
are both right and left sixth aortic arches, but the right regresses early during
fetal development. The sixth left arch originates from the proximal left pulmo-
nary artery at its junction with the main pulmonary artery and extends poste-
riorly and inferiorly to the dorsal aorta beyond the origin of the left subclavian
artery but proximal to the first intercostal arteries. At birth, its diameter is the
same as that of the main pulmonary artery and dorsal aorta. Its wall thickness is
the same as in these 2 major arteries. In contrast, however, its media is composed
of smooth muscle rather than elastic fibers, as in the aorta and branch pulmonary
arteries. The contraction of these smooth muscles closes the ductus normally
during the first day after birth. Three factors contribute to maintaining patency
of the ductus during fetal life: low fetal partial pressure of oxygen (Po2) levels,
circulating prostaglandins, and nitric oxide from endothelial cells.
Since the placenta, rather than the lungs, is the organ of gas exchange prior to
birth, most of the blood entering the main pulmonary artery passes from right
to left through the ductus into the descending aorta. The aortic and pulmonary
190
CCIP.indb 190 3/13/18 4:18 PM

arterial pressures are identical. The direction and magnitude of blood flows are
determined by the relative systemic and pulmonary vascular resistances. Because
the placenta is essentially an arteriovenous fistula, its resistance is low when
compared to the increased pulmonary vascular resistance. The RV ejects about
65% of the combined cardiac output (combination of LV and RV outputs). Of
this, approximately 55% flows into the aorta and 8% to 10% flows into the pul-
monary arteries to meet the metabolic requirements of the lungs.
Placental and Fetal Circulation

The placenta acts like a large arteriovenous fistula and thus has a low vascular
resistance. With progressive gestational age, the size of the placenta and its blood
flow requirements increase proportionately. About 40% of the combined fetal
cardiac output goes to the placenta. This represents about 60% of the blood flow
through the ductus arteriosus.
The placenta receives blood from 2 individuals, the mother and the fetus.
It has 2 components, the maternal placenta and the fetal placenta. These are
attached by villi. The chorionic villi provide a large area where fetal blood comes
close to the maternal blood and exchange of gases occurs. The maternal blood
flows through endometrial arteries into the intervillous space, and its venous
blood exits through endometrial veins. The umbilical arteries divide into an
extensive network of small vessels, including capillaries. It is at this level that
gas is exchanged. The adjacent venous networks coalesce into the umbilical vein,
which courses alongside the umbilical arteries toward the fetus to enter the
ductus venosus.
Lungs
During fetal life, the lungs are collapsed and airless. Because of the low-oxygen
environment in the fetus, the pulmonary vascular resistance is increased from
arteriolar vasoconstriction. The pulmonary arterioles in the fetal lung have a
thick medial coat and a narrow lumen. Therefore, the volume of pulmonary
blood flow is limited (<10% of combined cardiac output). This volume is princi-
pally to meet the metabolic needs of the lungs.
The Fetal Circulation

During fetal life, blood from the umbilical vein has the highest oxygen satura-
tion. Half of this venous blood flows through the right hepatic venous system
to the inferior vena cava, where it joins the blood flow from the superior vena
cava and enters the right atrium. This volume of blood flows predominantly into
the RV. The other half of umbilical venous blood in part flows through the left
hepatic lobe and exits into the left hepatic vein, where it joins the remainder in
the ductus venosus and passes to the inferior vena cava. This volume of blood
191
CCIP.indb 191 3/13/18 4:18 PM

enters the left posterior part of the inferior vena cava and is directed toward the
patent foramen ovale.
Since the blood with the highest oxygen content is in the LV, it passes
predominantly to the fetal brain. In contrast, blood with the lowest oxygen
content is in the RV, and most of it passes right to left through the PDA and
predominantly to the placenta.
From the ventricles, the volume and direction of flow depend on the relative
systemic and pulmonary vascular resistances. The systolic pressures in the aorta,
pulmonary artery, LV, and RV are identical. With the systolic pressures being
identical, vascular resistances govern blood flow according to the following
equation: P = R × F, where P is systolic pressure, R is vascular resistance, and
F is flow. When resistance is increased, blood flow is low, while if resistance is
low, the volume of flow is high. The blood flow into the pulmonary artery faces
(a) a high resistance to flow because of the effect of hypoxia on pulmonary
arterioles and the collapsed status of the lungs but (b) a low resistance through
the ductus arteriosus, primarily because of the low vascular resistance of the
placenta. Therefore, according to the aforementioned equation, a low volume
of blood flows into the pulmonary artery and a large volume to the descending
aorta and the placenta. Likewise, because of differences in resistance, the flow
to the ascending aorta is less than that to the descending aorta.
The Transitional Circulation

With birth, the circulatory pattern begins to change from a parallel circulation
to a series circulation. This conversion results in the RV ejecting blood solely
into the pulmonary artery. This blood flows through the lungs and returns to
the left atrium and then into the LV. LV blood is ejected into the ascending
aorta. Therefore, desaturated systemic venous blood passing through the lungs
becomes normally saturated. The saturated blood is ejected from the LV and
passes throughout the body. The human neonatal cardiac output is around
540 mL/kg/min.
The major changes that lead to this transition occur principally in the
lungs and ductus arteriosus.11 Much of this occurs during the first day of life.
Dramatic changes occur within minutes of birth. With delivery and clamping
of the umbilical cord, the organ of gaseous exchange shifts from the placenta
to the lungs. With the elimination of the low-resistance placenta, the systemic
vascular resistance nearly doubles. After birth, with expansion of the thorax,
the lungs also expand. With expansion of the lungs and inhaled atmospheric
oxygen, the pulmonary arterioles relax, and the pulmonary vascular resistance
rapidly decreases. This decrease is associated with an increase in pulmonary
blood flow and a decrease in pulmonary arterial pressure. The relative roles of
lung expansion and increased oxygen in decreasing pulmonary vascular resistance
192
CCIP.indb 192 3/13/18 4:18 PM

are uncertain. The pulmonary arterioles are sensitive to variations in oxygen

levels. After this initial change in pulmonary vascular resistance, a more gradual
decrease in both pulmonary arterial pressure and resistance to adult levels occurs
during the first couple of months of life. This later change is related to the
morphologic changes of the pulmonary arterioles. At birth, the arterioles have a
thick medial coat and narrowed lumen; during this early period, they evolve to
an adult appearance of a thin media and wide lumen.12

As a result of this change, the pulmonary vascular resistance decreases
significantly, but not to normal levels. By 1 day of age, it is still increased and
will then decrease at a slower rate during the remainder of the first year of life.13
This occurs because the number of pulmonary arterioles increases as the infant
grows. Thus, the volume of pulmonary blood flow increases to a normal level as
the ductus closes. The pulmonary blood flow increases from about 35 mL/kg/
min to 160 to 200 mL/kg/min.
At birth, the neonatal arterial Po2 increases quickly toward a normal value.
In a neonate, oxygen is a powerful vasoconstrictor of the ductus arteriosus.
Indeed, during the early neonatal period, the ductus arteriosus is sensitive to
variations in Po2, dilating in a low-oxygen environment and constricting in a
high-oxygen environment. After birth, the levels of circulating prostaglandins
decrease markedly, furthering ductal closure. In most full-term neonates, by
means of vasoconstriction, the ductus closes functionally during the first day
after birth. During the first 24 hours of life, blood flow through it is governed
by relative vascular resistances in the aorta and pulmonary artery. Thus, the direc-
tion of blood flow is initially right to left during the first few hours of life, then
bidirectional for another few hours, and finally left to right until it closes during
the first day of life. It may remain patent longer in prematurely born infants.
In these infants, the ductus may be less responsive to oxygen, and the increased
levels of circulating prostaglandins are maintained longer.
Normally, during the first month after birth, intimal hypoxia results in cell
death, which is related to the reduced ductal blood flow. This is followed by
endothelial proliferation and thickening of the ductal wall. Fibrosis occurs,
sealing the ductus. The ductus generally closes from the pulmonary arterial end
to the aortic end. At about 2 to 3 weeks, the ductus may be closed functionally
and anatomically, but a slight round depression is seen in the aortic wall where
the ductus had entered. A couple of weeks later, the aortic wall appears smooth.
Once closed in this fashion, the ductus remains as the ligamentum arteriosus
between the pulmonary artery and the proximal descending aorta.
During the first few hours after birth, while the ductus arteriosus remains
widely patent, there is flow through this vessel, and the systemic arterial pressure
influences the level of pulmonary arterial pressure. While it is widely patent, the
systemic pressure is transmitted to the pulmonary arterial pressure. As the ductus
narrows, systemic pressure gradually has less influence on the pulmonary artery
193
CCIP.indb 193 3/13/18 4:18 PM

pressure, and the intrinsic pulmonary arteriolar anatomic features become the
major determinant of the pulmonary pressure.
Because of the increased pulmonary blood flow, the volume of pulmonary
venous blood increases markedly, increasing the left atrial pressure. This displaces
the septum primum against the septum secundum, narrowing or closing the
foramen ovale. A tiny shunt may persist at the atrial level but usually disappears
during the first week after birth.
The ductus venosus closes at about 1 week of age. Its structure remains as
the ligamentum venosum on the posterior aspect of the liver. The mechanism
for its closure is unknown, but there is some evidence that prostaglandins
may maintain its patency.14 This evidence has implications for neonates with
infradiaphragmatic total anomalous pulmonary venous connection to the ductus
venosus. Administration of prostaglandin E1 (PGE1) may benefit these neonates
by maintaining patency of the ductus venosus so the pulmonary venous blood
can exit the lungs until a cardiac procedure can be performed.
Unmasking of Congenital Lesions as the Ductus

Arteriosus Closes
During the normal transition process, congenital anomalies may become
unmasked as the ductus arteriosus closes. For example, closure of the ductus
arteriosus disrupts the circulatory pattern vital for particular conditions that
appear during the first day after birth. In neonates in whom pulmonary atresia
is a component, as in TOF, during fetal life, blood flow through the ductus
arteriosus is from the aorta into the pulmonary artery (the opposite of normal).
Postnatally, as the ductus arteriosus closes, the sole source of pulmonary blood
flow is eliminated. Thus, the neonate develops progressive cyanosis during the
first day or so after birth. Administration of PGE1 will maintain ductal patency.15
The neonate can then be transferred to a cardiac center for diagnosis and man-
agement. Usually, a procedure will be performed to create a “ductus” by inserting
a tubular graft between the aorta or its branches to the pulmonary artery or 1
of its branches. This procedure is called a modified Blalock-Taussig shunt.
In neonates with obstruction to the systemic circulation, as in severe coarc-
tation of the aorta or interruption of the aortic arch, the major source of blood
flow to the descending aorta is through the ductus arteriosus. As the ductus
closes, the coarctation of the aorta is manifested by a blood pressure difference
between the ascending aorta and the descending aorta. The oxygen saturation in
the lower extremities is less than that in the upper extremities. If the obstruction
is severe, congestive heart failure develops in the first days after birth. Similarly,
in neonates with hypoplastic LV syndrome, as in infants with aortic valve
atresia or severe aortic stenosis, the major or sole source of systemic blood flow
194
CCIP.indb 194 3/13/18 4:18 PM

is right-to-left shunt through the ductus.16 The oxygen saturation is decreased

but equal in the upper and lower extremities, since the ductus is the sole source
of systemic blood. As this flow decreases, blood pressure decreases, and shock
occurs during the first days after birth as transductal volume progressively
decreases. Again, PGE1 administration is appropriate,17 and transfer of the
neonate needed.
Finally, the ductus arteriosus is critical in neonates with complete transposi-
tion of the great arteries (dextro-TGA). Before birth, mixing of blood between
the 2 sides of the heart occurs at both the atrial level and the ductus arteriosus.
Postnatally, as the ductus closes, the neonate with transposition becomes
progressively more cyanotic during the first couple of days after birth. PGE1 is
administered and maintained until an arterial switch procedure is performed.
In some neonates who are premature or have respiratory distress syndrome
or other pulmonary conditions, the ductus arteriosus may remain patent. Often
in these neonates, the pulmonary arterial pressure and resistance are increased,
as well.18 There may be a right-to-left shunt through the ductus, leading to
differential cyanosis—that is, the oxygen saturation in the lower extremities is
lower than that in the upper extremities, as in instances of coarctation of the
aorta. Chest radiography and echocardiography can help to distinguish these
2 conditions. If the ductus is patent in a premature neonate without pulmonary
disease, it can be ligated. If there is pulmonary disease, it is best if it is cleared
before treating the ductus.
Neonatal Pulse Oximetry

See Chapter 14, Neonatal Screening for Heart Disease, for details on recom-
mendations for neonatal pulse oximetry screening.
Key Points
•• The unique features of the fetal circulations support a parallel circulation,
which allows the most saturated blood to flow to the brain, while the most
desaturated blood goes to the placenta to be oxygenated.
•• Dramatic changes occur in the first minutes after birth: The process of oxy-
genation is transferred from the placenta to the lungs. With the elimination of
the placenta from the circulation, the systemic resistance nearly doubles, while
with expansion of the lungs, the pulmonary resistance decreases markedly.
•• During the first day of life, flow through the ductus decreases, and the ductus
closes. At this point, the circulation is now in series.
•• In premature infants with pulmonary disorders and some with congenital
heart disease, patency of the ductus arteriosus can play a critical role and
requires immediate attention.
195
CCIP.indb 195 3/13/18 4:18 PM

References
1) Rudolph AM. Distribution and regulation of blood flow in the fetal and neonatal lamb. Circ Res.
1985;57(6):811–821
2) Rudolph AM, Heymann MA. Circulatory changes during growth in the fetal lamb. Circ Res.
1970;26(3):289–299
3) Rudolph AM, Heymann MA. The circulation of the fetus in utero. Methods for studying
distribution of blood flow, cardiac output and organ blood flow. Circ Res. 1967;21(2):163–184
4) De Smedt MC, Visser GH, Meijboom EJ. Fetal cardiac output estimated by Doppler echo
cardiography during mid- and late gestation. Am J Cardiol. 1987;60(4):338–342
5) Eldridge MW, Berman W Jr, Greene ER. Serial echo-Doppler measurements of human fetal
abdominal aortic blood flow. J Ultrasound Med. 1985;4(9):453–458
6) Kiserud T. Fetal venous circulation—an update on hemodynamics. J Perinat Med. 2000;
28(2):90–96
7) Kiserud T. Hemodynamics of the ductus venosus. Eur J Obstet Gynecol Reprod Biol. 1999;
84(2):139–147
8) Kiserud T, Rasmussen S, Skulstad S. Blood flow and the degree of shunting through the ductus
venosus in the human fetus. Am J Obstet Gynecol. 2000;182(1 Pt 1):147–153
9) Edelstone DI, Rudolph AM. Preferential streaming of ductus venosus blood to the brain and
heart in fetal lambs. Am J Physiol. 1979;237(6):H724–H729
10) Edelstone DI, Rudolph AM, Heymann MA. Liver and ductus venosus blood flows in fetal
lambs in utero. Circ Res. 1978;42(3):426–433
11) Teitel DF, Iwamoto HS, Rudolph AM. Changes in the pulmonary circulation during birth-
related events. Pediatr Res. 1990;27(4 Pt 1):372–378
12) Wagenvoort CA, Neufeld HN, Edwards JE. The structure of the pulmonary arterial tree in
fetal and early postnatal life. Lab Invest. 1961;10:751–762
13) Fineman JR, Soifer SJ, Heymann MA. Regulation of pulmonary vascular tone in the perinatal
period. Annu Rev Physiol. 1995;57:115–134
14) Morin FC III. Prostaglandin E1 opens the ductus venosus in the newborn lamb. Pediatr Res.
1987;21(3):225–228
15) Heymann MA, Rudolph AM. Ductus arteriosus dilatation by prostaglandin E1 in infants with
pulmonary atresia. Pediatrics. 1977;59(3):325–329
16) Allan LD, Sharland G, Tynan MJ. The natural history of the hypoplastic left heart syndrome.
Int J Cardiol. 1989;25(3):341–343
17) Heymann MA, Berman W Jr, Rudolph AM, Whitman V. Dilatation of the ductus arteriosus by
prostaglandin E1 in aortic arch abnormalities. Circulation. 1979;59(1):169–173
18) Dudell GG, Gersony WM. Patent ductus arteriosus in neonates with severe respiratory disease.
J Pediatr. 1984;104(6):915–920
196
CCIP.indb 196 3/13/18 4:18 PM

CHAPTER 14
Neonatal Screening
for Heart Disease
Huzaifa Ahmad, MBBS, and Devyani Chowdhury, MD, FAAP, FACC
Introduction
As previously mentioned, congenital heart disease (CHD) is the most common
congenital abnormality in children, affecting nearly 1% of newborns each year.1
One-quarter of these patients have critical CHD (CCHD), defined as CHD
that requires surgical or catheter intervention within the first month after birth.
A missed diagnosis of CCHD can result in the death of the baby within 2 weeks
after birth.2 Timely detection improves the chances of survival and outcome.
Prenatal diagnosis with fetal echocardiography has marked variability across
geographic regions, as well as with the type of congenital defect, and many cases of
CCHD can go undetected. In the nursery, conducting only a physical examination
of the newborn can similarly lead to more than one-half of CCHD cases being
missed. Up to 30% of neonates with CCHD appear clinically normal and are
discharged with the defect undetected.3 Without access to lifesaving intervention,
these patients can rapidly decompensate and may die at home or in a hospital
emergency department. Screening for CCHD before discharge from the birth
hospitalization therefore becomes an important aspect of newborn care.
In 2011, the Secretary of the U.S. Department of Health and Human Services
recommended that CCHD be added to the recommended uniform screening
panel, a list of conditions that every newborn should be screened for. This chapter
provides an overview of pulse oximetry screening for CCHD and addresses
frequently asked questions from parents and primary care physicians.
197
CCIP.indb 197 3/13/18 4:18 PM

Definitions
CCHD: CHD that requires surgical or catheter intervention within the first
month after birth. Without early intervention in these cases, the newborn is at
high risk for developing serious complications that can lead to death.
Ductal-dependent CCHD: CCHD that requires patency of the ductus
arteriosus to continue supplying the pulmonary or systemic blood flow. The
ductus arteriosus is a vital part of the fetal circulation. It connects the pulmonary
artery to the proximal descending aorta, bypassing the fluid-filled lungs. In
ductal-dependent CCHD, newborns in the nursery may appear clinically nor-
mal because the ductus arteriosus is open, allowing blood to circulate throughout
the body. Physiological closure of the ductus arteriosus occurs within a few
days after birth. If a patient with ductal-dependent CCHD does not receive a
diagnosis before discharge, closure of the ductus arteriosus after discharge can
lead to reduced tissue perfusion and clinically significant physiological compro-
mise. Rapid clinical deterioration, characterized by metabolic acidosis, seizures,
cardiac failure, and ultimately death, can occur.4
Cyanosis: A bluish discoloration of the skin that becomes visibly apparent when
the absolute amount of deoxygenated blood exceeds 5 g/dL. Because cyanosis is
dependent on the total amount of reduced hemoglobin in the blood, the concen-
tration of hemoglobin can affect the oxygen saturation level at which cyanosis
becomes evident. A patient with a high hemoglobin concentration will look
cyanotic at a higher oxygen saturation level than an anemic patient with a lower
hemoglobin concentration. Cyanosis in a newborn can be associated with many
clinically significant and potentially life-threatening diseases. Persistent central
cyanosis in the neonate is always abnormal and requires prompt evaluation.
Principles of Pulse Oximetry

The pulse oximeter is a noninvasive, painless, and inexpensive device that is used
to measure the percentage of oxygen that is carried and bound to hemoglobin in
the blood. It consists of a probe with 2 light-emitting diodes (LEDs), a detector,
and a processor. In newborns, the probe is placed on the right hand or either
foot to measure the peripheral oxygen saturation, or Spo2. Light of 2 different
wavelengths (red and infrared) is emitted by the LEDs through the skin and
picked up on the other side by the corresponding light detector. Oxygenated
blood preferentially absorbs infrared light and allows red light to pass through,
whereas deoxygenated blood absorbs red light and allows infrared light to pass.
The microprocessor uses the differences in absorptions and light detected to
calculate the Spo2.5
198
CCIP.indb 198 3/13/18 4:18 PM

Neonatal Screening for Heart Disease
Rationale for CCHD Screening

Late Detection Increases Morbidity and Mortality
In the absence of pulse oximetry screening, approximately 30% of patients with
CCHD receive a late diagnosis, more than 3 days after birth.3 Standard practice
then dictates that detection of CCHD would rely on fetal echocardiography and
clinical examination in the nursery. However, the fetal circulation is different
than postnatal circulation because in the fetus, the placenta is the site of oxygen-
ation and the ductus is open (see Chapter 13, Fetal and Newborn Transitional
Circulations). Both fetal echocardiography and clinical examination can allow
CCHD to be missed. Studies have demonstrated that late detection of CCHD
can increase the risk of mortality to almost 30%, nearly doubling the risk when
compared to an early diagnosis. Completely missed diagnoses can lead to death
within 2 weeks.2,6 On the basis of risk calculations, screening with pulse oximetry
might prevent 20 infant deaths in the United States each year.
Cost-Effectiveness
Several studies show that screening with pulse oximetry is feasible and cost-
effective. Timely detection of CCHD through pulse oximetry screening reduces
the costs when compared to management of morbidities associated with late
detection. Late detection of CCHD has been associated with increased readmis-
sions, more days spent hospitalized, and higher inpatient costs during infancy.3
Targets of CCHD Screening

Core Conditions
The Secretary of the U.S. Department of Health and Human Services Advisory
Committee on Heritable Disorders in Newborns considers 7 primary targets
of CCHD screening with pulse oximetry: hypoplastic left heart syndrome,
pulmonary atresia, tetralogy of Fallot, total anomalous pulmonary venous return,
transposition of the great arteries, tricuspid atresia, and truncus arteriosus. These
lesions commonly manifest with hypoxia. The Centers for Disease Control and
Prevention add 5 more lesions to this list: coarctation of the aorta, double-outlet
right ventricle, Ebstein anomaly, interrupted aortic arch, and single ventricle.
These additions are less common but often manifest with hypoxia or are more
common but less often manifest with hypoxia.7
Secondary Conditions
Pulse oximetry screening is used to detect hypoxia in infants, but not all cases of
hypoxia will be caused by CCHD. These secondary targets are the non-CCHD
causes of hypoxia that in neonates may be serious medical problems that require
intervention. They include noncritical CHD, sepsis, other infection, persistent
199
CCIP.indb 199 3/13/18 4:18 PM

pulmonary hypertension, parenchymal or anatomic pulmonary disease, transient

tachypnea of the newborn, hypothermia, and hemoglobinopathies.7
The American Academy of Pediatrics

Screening Algorithm
The American Academy of Pediatrics (AAP) recommends that all newborns
be screened for CCHD, regardless of whether screening is required in the state
in which they live. The AAP screening guideline is the most commonly used
screening algorithm for the detection of CCHD in the United States. This
screening is intended for use in a well-infant nursery because of the risk of
missing CCHD cases in healthy-looking newborns. Newborns who have already
received a diagnosis of CCHD on the basis of prenatal ultrasonography findings
do not need to undergo this screening. Figure 14-1 illustrates the screening
process.8
Timing and Technique

Screening with the pulse oximeter should take place at least 24 hours after birth
to reduce the rate of false-positive findings. During the first 24 hours after birth,
the intrauterine circulation is still transitioning to an extrauterine circulation,
and this may manifest with low oxygen saturation levels during this period. The
probe is used on both the right hand (preductal) and either foot (postductal).
A measurement at both these sites is important, because some defects with a
right-to-left shunt will not be detected via a preductal (upper-extremity) mea-
surement alone. These defects manifest with differential cyanosis. In CHD with
differential cyanosis, the deoxygenated blood flows through the ductus arteriosus,
supplying the lower body, while oxygenated blood from the left side of the heart
supplies the upper body. Obtaining a preductal measurement alone would cause
the deoxygenated blood of the lower body to be missed. An absolute difference
of more than 3% in the oxygen saturation between the right upper extremity and
either of the lower extremities can be used to identify newborns with differential
cyanosis. This pattern occurs in infants with critical coarctation of the aorta,
interrupted arch, or critical aortic stenosis.
The screening should be performed by an individual who is trained in the
use of pulse oximeters and who is familiar with the AAP algorithm. Screening
should be performed by using a motion-tolerant pulse oximeter. A reusable pulse
oximeter can help to reduce costs.
Positive Screening Results

The criteria for a positive screening result (also known as “failing” the screening)
are any of the following:
200
CCIP.indb 200 3/13/18 4:18 PM

Child in well-infant nursery 24–48 h of age or

shortly before discharge if <24 h of age
Screen
<90% in RH or F 90%–<95% in RH and F ≥95% in RH or F

or >3% difference and ≤3% difference
between RH and F between RH and F
Repeat
screen
in 1 h

Repeat
screen
in 1 h

Positive Negative
Screen Screen
FIGURE 14-1. American Academy of Pediatrics pulse oximetry screening algorithm. F = foot,
RH = right hand. From reference 8.
1. Any single Spo2 measurement of less than 90%, measured at either the upper
extremity or the lower extremity. No repeat measurement is required.
2. Spo2 measurements less than 95% in both extremities with 3 measurements,
each separated by an hour.
3. An absolute difference of more than 3% in the oxygen saturations of the
upper extremity and the lower extremity, on the basis of 3 measurements,
each separated by an hour.
201
CCIP.indb 201 3/13/18 4:18 PM

The repeated pulse oximetry screening for initial results that show oxygen
saturations of less than 95% in both extremities or an absolute difference of more
than 3% between the extremities is conducted to decrease the likelihood of a
false-positive result. A test result of less than 90% oxygen saturation is a positive
screening result that does not necessitate repeated pulse oximetry testing. Any
Spo2 measurement of at least 95% in either extremity with an absolute difference
of 3% or less between the upper and lower extremities is considered a passing
result, and the screening would end for that newborn.
A cutoff of 95% Spo2 provides a sensitivity of 76.5% and a specificity of
99.9% for the detection of CCHD.9
Infants With Positive Screening Results

In a large Swedish study on pulse oximetry screening in asymptomatic newborns,
approximately 25% of babies with positive screening results received diagnoses of
CCHD.10 Thus, an infant with a positive screening result should be moved to an
appropriate setting where diagnostic resources are available to exclude CCHD or
other causes of hypoxia. Diagnostic echocardiography should be performed, with
results interpreted by a clinician who has expertise in diagnosing CHD.
False-Positive Findings
Although the primary targets of the AAP pulse oximetry screening algorithm
are CCHD, hypoxia in a newborn can still be an indicator of a clinically signifi-
cant underlying pathologic process. Studies have demonstrated that almost 50%
of false-positive findings may indicate a medical condition that requires inter-
vention. Assessment of an infant with a positive screening result should therefore
include ruling out other causes of hypoxia, such as sepsis and pneumonia.
Home Births
A growing number of Americans opt for giving birth at home. Home births
require an adapted protocol for pulse oximetry screening because community
midwives typically leave the newborn after 3 hours of birth and may return
anytime from 24 hours to 72 hours later. With no established timeline to
return, a screening performed at 72 hours may be too late for a newborn with
ductal-dependent CCHD. The ductus arteriosus may have closed by then,
leaving no viable oxygen supply for the body. A modified protocol used to screen
newborns before the midwife leaves, as tested in Europe, can be implemented to
improve safety in home births.11–13 In this protocol, the screening occurs at least
1 hour after birth and only requires 1 repeat measurement if saturations are 90%
to 94% or if there is a difference of more than 3% between the upper and lower
extremities. A measurement of less than 90% is immediately considered a
positive screening result.
202
CCIP.indb 202 3/13/18 4:18 PM

Key Points
•• Newborns with life-threatening CHD may be asymptomatic during birth
hospitalization and can rapidly decompensate after discharge if the CHD
remains undetected.
•• Pulse oximetry screening is an acceptable, painless, noninvasive tool with
higher sensitivity and specificity for the detection of CCHD than those of
physical examination and antenatal ultrasonography.
•• A baby meets the criteria for a positive screening result when the oxygen
saturation (a) is less than 90% in either extremity, (b) is less than 95% in both
the right hand and either foot in 3 measurements obtained 1 hour apart, or
(c) has an absolute difference greater than 3% between oxygen saturation of
the right hand and either foot in 3 measurements obtained 1 hour apart each.
•• Babies with positive screening results should be referred immediately for
diagnostic echocardiography, and other causes of hypoxia should be excluded.
•• False-positive findings at pulse oximetry screening may indicate underlying
noncardiac medical conditions that cause hypoxia (eg, sepsis, pneumonia,
persistent pulmonary hypertension).
•• Pulse oximetry should be performed in all babies, even if they have a normal
fetal echocardiographic or physical examination finding. Only babies with a
prior fetal diagnosis of CHD are excluded from the screening.

•• Newborn Screening for CCHD (American Academy of Pediatrics).
www.aap.org/en-us/advocacy-and-policy/aap-health-initiatives/PEHDIC/
Pages/Newborn-Screening-for-CCHD.aspx
•• Pulse Oximetry Screening for Critical Congenital Heart Defects
(U.S. Centers for Disease Control and Prevention). www.cdc.gov/features/
congenitalheartdefects
References
1) Hoffman JI, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol. 2002;
39(12):1890–1900
2) Chang RK, Gurvitz M, Rodriguez S. Missed diagnosis of critical congenital heart disease.
Arch Pediatr Adolesc Med. 2008;162(10):969–974
3) Peterson C, Ailes E, Riehle-Colarusso T, et al. Late detection of critical congenital heart disease
among US infants: estimation of the potential impact of proposed universal screening using
pulse oximetry. JAMA Pediatr. 2014;168(4):361–370
4) Schultz AH, Localio AR, Clark BJ, Ravishankar C, Videon N, Kimmel SE. Epidemiologic
features of the presentation of critical congenital heart disease: implications for screening.
Pediatrics. 2008;121(4):751–757
5) Harold JG. Cardiology patient page. Screening for critical congenital heart disease in newborns.
Circulation. 2014;130(9):e79–e81
203
CCIP.indb 203 3/13/18 4:18 PM

6) Eckersley L, Sadler L, Parry E, Finucane K, Gentles TL. Timing of diagnosis affects mortality in
critical congenital heart disease. Arch Dis Child. 2016;101(6):516–520
7) Oster ME, Aucott SW, Glidewell J, et al. Lessons learned from newborn screening for critical
congenital heart defects. Pediatrics. 2016;137(5):e20152473
8) Kemper AR, Mahle WT, Martin GR, et al. Strategies for implementing screening for critical
congenital heart disease. Pediatrics. 2011;128(5):e1259–e1267
9) Thangaratinam S, Brown K, Zamora J, Khan KS, Ewer AK. Pulse oximetry screening for critical
congenital heart defects in asymptomatic newborn babies: a systematic review and meta-analysis.
Lancet. 2012;379(9835):2459–2464
10) de-Wahl Granelli A, Wennergren M, Sandberg K, et al. Impact of pulse oximetry screening on
the detection of duct dependent congenital heart disease: a Swedish prospective screening study
in 39,821 newborns. BMJ. 2009;338:a3037
11) Smit M, Ganzeboom A, Dawson JA, et al. Feasibility of pulse oximetry for assessment of infants
born in community based midwifery care. Midwifery. 2014;30(5):539–543
12) Narayen IC, Blom NA, Verhart MS, et al. Adapted protocol for pulse oximetry screening for
congenital heart defects in a country with homebirths. Eur J Pediatr. 2015;174(1):129–132
13) Narayen IC, Blom NA, Bourgonje MS, et al. Pulse oximetry screening for critical congenital
heart disease after home birth and early discharge. J Pediatr. 2016;170:188–192
204
CCIP.indb 204 3/13/18 4:18 PM

CHAPTER 15
Surgical Procedures
for Congenital
Heart Disease
Timothy S. Lancaster, MD, and Pirooz Eghtesady, MD, PhD, FAAP
Introduction
Surgical correction or palliation is a mainstay in the management of many forms of
congenital heart disease (CHD), and a basic understanding of these surgical pro-
cedures is important for primary care providers in both the pre- and postoperative
settings. This chapter contains the most common surgical procedures performed for
CHD in children, with a focus on indications and timing for surgery, descriptions
of basic surgical details, and some important surgical complications. The most
common procedures performed for specific age groups as tabulated from the
Society of Thoracic Surgeons Congenital Heart Surgery Database1 (Tables 15-1,
15-2, and 15-3) are reviewed.
Surgical Approaches for CHD

Most of the procedures discussed in this chapter are performed via a median
sternotomy. A vertical incision is made through the skin overlying the sternum,
followed by division of the sternum itself with a bone saw or heavy scissors.
Although there is little evidence of altered outcomes, when possible, a smaller
skin incision or partial sternotomy may be performed to provide a better cosmetic
result and perhaps improved pain control or earlier hospital discharge. Through
the sternotomy, thymic tissue is often removed. Although occasionally the thymus
205
CCIP.indb 205 3/13/18 4:18 PM

Table 15-1. The 10 Most Common Congenital Heart

Procedures in Neonates
Percentage of
Primary Procedure No. All Procedures
Repair of aortic coarctation or arch 3,638 13.6%
Norwood or Damus-Kaye-Stansel procedure 2,870 10.7%
Arterial switch procedure 2,728 10.2%

Systemic to pulmonary artery shunt (MBTS, central) 2,341 8.8%
Pulmonary artery banding 1,258 4.7%
Repair of total anomalous pulmonary venous return 1,105 4.1%
Repair of truncus arteriosus 487 1.8%
Repair of interrupted aortic arch 462 1.7%
Stage 1 hybrid approach for HLHS 463 1.7%
Closure of patent ductus arteriosus, surgical 286 1.1%

HLHS, hypoplastic left heart syndrome; MBTS, modified Blalock-Taussig shunt. Data are from the Society of Thoracic
Surgeons national database from the period of January 1, 2012, to December 31, 2015.

Procedures in Infants
Percentage of
Primary Procedure No. All Procedures
Repair of ventricular septal defect 5,535 14.8%
Bidirectional Glenn procedure 4,263 11.4%
Repair of tetralogy of Fallot 4,151 11.1%
Repair of complete AV canal defect 2,916 7.8%
Repair of aortic coarctation or arch 1,370 3.7%
Closure of patent ductus arteriosus, surgical 976 2.6%
Systemic to pulmonary artery shunt (MBTS, central) 955 2.6%
Pulmonary artery banding 916 2.4%
Other RVOT procedures 620 1.6%
Repair of vascular ring 560 1.5%

AV, atrioventricular; MBTS, modified Blalock-Taussig shunt; PA, pulmonary artery; RVOT, right ventricular outflow
tract. Data are from the Society of Thoracic Surgeons national database from the period of January 1, 2012, to
December 31, 2015.
206
CCIP.indb 206 3/13/18 4:18 PM

Surgical Procedures for Congenital Heart Disease

Procedures in Children
Percentage of All
Primary Procedure No. Procedures
Repair of atrial septal defect 4,493 10.8%
Fontan procedure 4,016 9.6%
Pacemaker procedures (implant or revision) 2,864 6.9%
Repair of ventricular septal defect 1,844 4.4%
Mitral valvuloplasty 1,162 2.8%
Repair of subaortic stenosis 1,170 2.8%
Other RVOT procedures 1,177 2.8%
Heart transplant 1,144 2.7%
Pulmonary artery reconstruction 1,070 2.6%
Pulmonary valve replacement 1,020 2.4%

RVOT, right ventricular outflow tract. Data are from the Society of Thoracic Surgeons national database from the
period of January 1, 2012, to December 31, 2015.
is preserved, there is no evidence that the removal of thymic tissue causes any
untoward effects on the child, even long-term. The pericardial sac is opened
to expose the heart and proximal great vessels. In many cases, a portion of
native pericardium is removed for use as patch material during the procedure.
Autologous pericardium is usually treated with glutaraldehyde prior to implan-
tation to improve its handling and durability. Especially if additional cardiac
surgery is anticipated later in life, artificial patch materials (eg, polyethylene
terephthalate, polytetrafluoroethylene, or other biomaterials) may be substituted
to preserve the native pericardium and lessen adhesion of the heart to the
overlying sternum. The sternum is usually closed with steel wires at the end of
the procedure; relatively straight alignment of these wires on chest radiographs
is a good indication of appropriate sternal healing. The incisional scar should be
expected to lengthen proportionally as the child grows.
A left posterolateral thoracotomy is the next most common incision used
for congenital heart surgery, for repair of aortic coarctation and other aortic
procedures. An incision is made on the chest sidewall toward the back, typically
parallel with the scapula, and the thoracic cavity is accessed, usually through the
third or fourth intercostal space. This tends to be a more painful incision than a
median sternotomy, and there is a chance of intercostal nerve entrapment during
chest closure.
Cardiopulmonary bypass is used for all of the open-heart surgical proce-
dures described herein. Most procedures require the heart to be stopped via
207
CCIP.indb 207 3/13/18 4:18 PM

administration of cardioplegia solution, and some procedures require the patient

to be cooled and the entire circulation to be completely stopped for a period
of time (deep hypothermic circulatory arrest). The patient is connected to the
heart-lung machine by using venous and arterial cannulas that can be placed in a
variety of configurations, depending on the part of the heart that is to be opened.
The bypass circuit must be filled at the beginning of the procedure with a “prime”
volume of fluid or blood. It is much easier to avoid blood product exposure for
the conduct of bypass in larger patients because of their greater capacity for
hemodilution. Patients may still require blood product transfusion after bypass,
however, because of coagulation and platelet dysfunction that results from expo-
sure to the bypass circuit. There are a number of potential complications related
to cardiopulmonary bypass itself, although these have become rare as long as
the duration of the bypass is kept under about 2 hours. Most of the procedures
described herein fall into this category.
Surgery for Anomalies of the Great Vessels

Closure of Patent Ductus Arteriosus
The patent ductus arteriosus (PDA) normally closes in term infants within the
first 24 hours of life; however, persistent patency is more likely in preterm infants
in whom the ductal tissue is less responsive to increased blood oxygen levels
after birth. Patency of a large ductus arteriosus usually results in left-to-right
shunting that can impair coronary blood flow and lead to congestive heart failure
(CHF). Medical therapy with either ibuprofen or acetaminophen is successful in
many cases, and catheter-based PDA closure is becoming increasingly popular
for infants who weigh more than 1 kg. Surgical closure of a PDA is indicated
if prior therapies have failed and the patient is symptomatic or if the ductus is
wider than 1.5 to 2 mm in diameter.
Surgical PDA closure is normally performed through a limited left thora-
cotomy and without bypass. The lung is gently retracted anteriorly to expose the
descending aorta, and the ductus is carefully dissected. Care is taken to identify
and preserve the left recurrent laryngeal nerve. In preterm neonates, the ductus
can be closed with simple placement of a vascular clip (Figure 15-1). These clips
are made from titanium and are compatible with magnetic resonance (MR)
imaging, if it should be needed in the future. In the rare instance that a term
infant or older child presents for PDA closure, suture ligation is the method of
choice. Actual division of the ductus is not normally performed unless there is
concern for possible aortic coarctation, in which case repeat surgery for coarcta-
tion repair would be more challenging if the ligated ductus was left in continuity
with the pulmonary artery. On rare occasions, however, a residual shunt may
persist after PDA clipping or ligation that may be audible at examination or seen
with echocardiography.
208
CCIP.indb 208 3/13/18 4:18 PM

Surgical P
rocedures for Congenital Heart Disease
FIGURE 15-1. Closure of a patent ductus arteriosus with placement of a vascular clip, as is
performed in small neonates. Suture ligation is usually performed in term infants or children. MPA =
main pulmonary artery.
Some have reported video-assisted thoracoscopic surgical closure of the PDA

in larger infants with a small- to moderate-sized ductus, where a clip is used as
the method of closure. The size of the incision used for surgical closure, however,
is not substantially larger than that required for the video-assisted thoracoscopic
surgical closure technique (about 2 cm). The occurrence of residual PDAs may
also be higher with the video-assisted thoracoscopic surgical closure technique.
Other possible complications of PDA closure include injury to the left
recurrent laryngeal nerve, which causes hoarseness but is rare. Perhaps the most
serious complication is erroneous ligation of either the aortic arch or the left
pulmonary artery. Aortic ligation causes a presentation similar to that of aortic
coarctation (shock, lower body cyanosis, absent lower extremity pulse). Left pul-
monary artery ligation could be first recognized by the primary care pediatrician,
likely manifesting as recurrent infection of the left lung. Echocardiography is
209
CCIP.indb 209 3/13/18 4:18 PM

not always reliable for the diagnosis of this complication; findings on perfusion
images (showing absence of flow to the left lung) or alternative images (obtained
with computed tomography or MR imaging) are diagnostic. These complications
typically occur when the surgeon is not familiar with variant arch anatomy.
Repair of Aortic Coarctation

The diagnosis of aortic coarctation alone is generally an indication for treatment,
either catheter based or surgical, depending on patient age, anatomic substrate,
and expertise of the treating center. The severity of the coarctation can influence
the timing and symptoms at presentation. In the neonate, this may range from
cardiogenic shock to persistent hypertension. In the presence of additional
cardiac lesions, such as a ventricular septal defect (VSD), CHF or failure to
thrive may be the primary symptom. In the newborn period, routine examination
of the distal pulse and confirmation with blood pressure measurements obtained
in 4 extremities is key for detection. Mild lesions may not manifest until later in
childhood and may be preferentially treated with catheter-based interventions.
Coarctation repair is generally performed in early infancy. It is still debated
whether elective surgical repair should be deferred beyond the immediate
neonatal period, due to a presumed risk of recurrent coarctation after surgery.
Delay of repair in neonates with recognized coarctation requires close follow-up,
however, lest the patient develop diminished ventricular function and shock
because of progression of the coarctation. Although sometimes manifesting later
in childhood, delay of coarctation repair beyond 5 to 10 years of age increases the
risk for recurrent coarctation, as well as development of essential hypertension in
early adulthood.2
The most common technique for repair of aortic coarctation is resection and
end-to-end anastomosis, which can be performed without cardiopulmonary
bypass. Usually a left thoracotomy is used, although a median sternotomy
may be used if simultaneous repair of a concomitant VSD or other lesion is to
be performed.
In the left thoracotomy approach, the left lung is retracted, and the distal
aortic arch and descending aorta are mobilized. The ductus arteriosus is divided.
The coarctation segment is then excised, and the aortic isthmus is opened
longitudinally into the distal aortic arch. An anastomosis is created between the
2 aortic ends, and the lower body is reperfused (Figure 15-2). An “extended”
end-to-end repair may be performed in cases of extensive arch hypoplasia, in
which the incision in the aortic isthmus is extended more proximally along the
underside of the arch to allow for a longer, beveled anastomosis that augments
the aortic arch. Despite extension of the repair into the arch, some children may
be left with residual arch hypoplasia or obstruction that could require catheter
intervention. Similarly, suboptimal surgical technique can result in subsequent
arch obstruction. For these reasons, patients should undergo continued close
210
CCIP.indb 210 3/13/18 4:18 PM

FIGURE 15-2. Repair of aortic coarctation. A. The anatomy is shown, demonstrating the region of
narrowing at the level of the ductus arteriosus. Dashed lines indicate the location of the incisions
for resection of the coarctation segment. B. The anatomy is shown after the completed resection of
the coarctation segment and end-to-end aortic anastomosis. The patent ductus has been ligated and
divided. MPA = main pulmonary artery.
follow-up with a cardiologist and routine documentation of the blood pressure

measured in 4 extremities in the outpatient setting.
Potential complications of coarctation repair include chylothorax and injury
to the left recurrent laryngeal nerve. Chylothorax often requires feeding restric-
tion and can lead to a long postoperative hospital stay. This complication is more
common in patients with Turner syndrome who have lymphatic abnormalities
at baseline. Recurrent laryngeal nerve palsies are usually transient, assuming
the nerve has only been traumatized and not divided. Although additional risks
of injury to the left phrenic nerve, paraplegia, or paradoxical hypertension are
taught, these are almost never observed today. Most children can have some
duration of blood pressure increase immediately after surgery because of postop-
erative pain; this is normally self-limited and occasionally requires management
with β-blockers or angiotensin-converting enzyme inhibitors. Because these
patients are at a higher risk for systemic arterial hypertension, lifetime surveil-
lance of blood pressure is essential.
Repair of Total Anomalous Pulmonary Venous Return

Total anomalous pulmonary venous return (TAPVR), in which all of the pul
monary blood flow returns to the right atrium (RA) instead of the left, is the most
severe form of anomalous pulmonary venous connection. The diagnosis of TAPVR
alone is an indication for surgical repair, and the timing of repair is primarily
dependent on the degree of pulmonary venous obstruction. In neonates with
211
CCIP.indb 211 3/13/18 4:18 PM

severe obstruction, manifested by hypoxemia and hemodynamic compromise,

immediate repair should be undertaken. Extracorporeal membrane oxygenation
may be used for stabilization of such patients prior to definitive repair.3 In
patients without clinically significant pulmonary venous obstruction, repair is
usually recommended early in infancy but may be delayed, because the physi-
ology of nonobstructed TAPVR is essentially the same as that of a large atrial
septal defect (ASD).
In all types of TAPVR, there is an alternative pathway for pulmonary blood
return to the right side of the heart through a connecting vein, often referred to
as the “vertical vein.” Most often, the vertical vein connects to the innominate
vein (supracardiac TAPVR) or to a subdiaphragmatic vein (infracardiac
TAPVR), although the connection can occur to several other right-sided struc-
tures. Only the repair of supracardiac TAPVR is described here, but the basic
premise of all types of TAPVR repair is to reroute the anomalous pulmonary
venous blood return to the left atrium (LA).
After median sternotomy and initiation of bypass, the vertical vein is
dissected and is usually ligated or divided. An incision is made in the confluence
of the anomalous pulmonary veins, and a counter-incision is made in the LA
anterior to the confluence. The incision in the pulmonary vein confluence may
extend onto the vertical vein. The atrial incision may be started in the RA and
proceed posteriorly to cross the atrial septum and enter the LA, or the heart may
be elevated to allow an incision to be made directly onto the LA. Ultimately, the
open pulmonary confluence is anastomosed to the open LA (Figure 15-3). The
always-present ASD is then closed, usually with an autologous pericardial patch.
There is also increasing use of a “sutureless” repair technique, a term intended
to suggest that no sutures are placed directly into the pulmonary veins. In this
approach, the front wall of the pulmonary vein confluence is cut out, and the LA
opening is anastomosed to the posterior pericardium surrounding the pulmonary
vein openings. This technique may decrease the incidence of postoperative
pulmonary vein stenosis, which occurs in at least 10% of patients and can have
devastating long-term consequences.
Weaning from cardiopulmonary bypass after repair of TAPVR often requires
careful management of labile pulmonary vascular resistance. Severe pulmonary
hypertension may occasionally require postoperative support with extracorporeal
membrane oxygenation.
Surgery for Septal Defects

Repair of ASD
With the increasing use of catheter techniques for closure of ASDs, surgical
repair is now mostly reserved for primum, large secundum, and sinus venosus–
type ASDs. Primum ASDs are discussed herein, with complete atrioventricular
212
CCIP.indb 212 3/13/18 4:18 PM

FIGURE 15-3. Repair of supracardiac total anomalous pulmonary venous return. The anomalous
vertical vein is ligated and the pulmonary vein (PV) confluence opened widely. The right atrium
(RA) and left atrium (LA) are opened, and the confluence is anastomosed to the LA. The atrial
septal defect and the RA are then closed. SVC = superior vena cava.
(AV) canal defect. Secundum ASDs may be repaired either primarily or with a
patch closure technique, depending on the size of the defect and the amount of
septal tissue present. Sinus venosus ASDs may be managed with a simple patch
repair when found in isolation or with the Warden procedure or another intra-
cardiac baffling procedure when associated with partial anomalous pulmonary
venous return (PAPVR).
For the minority of ASDs that manifest early with symptoms of CHF, repair
is indicated during infancy. In asymptomatic children, repair is generally indi-
cated if there is evidence at echocardiography of right ventricular (RV) volume
overload or a color flow jet of at least 5 to 6 mm in diameter. In such cases, repair
is usually recommended before the start of grade school.
213
CCIP.indb 213 3/13/18 4:18 PM

Postpericardiotomy syndrome is an uncommon complication that can occur

after any type of cardiac surgery, but for unclear reasons occurs more frequently
with ASD repair (1% to 2%) than with any other lesion. In children, this usually
manifests with general malaise and fever a couple of weeks after surgery. A num-
ber of imaging modalities are diagnostic, and medical therapies (nonsteroidal
anti-inflammatory drugs, steroids, occasionally colchicine) are often effective.
Repair of Secundum ASD
An isolated secundum ASD is repaired through an opening in the RA. Small- to
moderate-sized defects can be closed primarily by direct suturing of the septum
primum tissue to the edge of the fossa ovalis. Larger defects are repaired by using
a circular patch, preferably of autologous pericardium harvested at the beginning
of the surgery (Figure 15-4). The patch is sutured to the margins of the defect.
The RA is then closed and the patient is weaned from cardiopulmonary bypass.
This surgery is perhaps the simplest and lowest-risk open-heart procedure.
Patients are typically discharged home within 3 to 4 days postoperatively.
Repair of Sinus Venosus ASD with PAPVR (Warden Procedure,
Scimitar Syndrome)
For repair of a sinus venosus ASD, the superior vena cava (SVC) is carefully
dissected to evaluate the presence of partial anomalous pulmonary venous
connection, most commonly from the right upper-lobe pulmonary veins. If the
FIGURE 15-4. Repair of atrial septal defect (ASD). A. A large secundum ASD is approached
through a right atriotomy. B. The defect is repaired with a patch of autologous pericardium sutured
to the margin of the ASD. Smaller ASDs can be directly repaired without a patch. RA = right
atrium, RV = right ventricle.
214
CCIP.indb 214 3/13/18 4:18 PM

pulmonary venous anatomy is normal, an isolated sinus venosus ASD is repaired

with a patch closure technique as with a secundum ASD.
With a sinus venosus ASD and partial anomalous connection to the SVC,
repair can usually still be accomplished with a single patch, because the abnormal
pulmonary vein often connects very low, near the junction of the SVC and RA.
Through an opening in the RA, the patch is sewn around the pulmonary vein
orifice and the suture line is then continued around the borders of the ASD,
creating a tunnel that routes the anomalous pulmonary venous blood through
the ASD.
When the anomalous pulmonary vein connects further away from the
SVC-RA junction, the Warden procedure is often performed. The SVC is
divided above the anomalous pulmonary vein. The RA is opened, and a baffle is
created by sewing a patch around the mouth of the SVC and continuing around
the margins of the ASD. The anomalous pulmonary venous blood is therefore
directed into the LA through the disconnected SVC and ASD (Figure 15-5, A).
The divided SVC is then reconnected to the heart by anastomosis to an opening
in the RA appendage (Figure 15-5, B). The RA is closed, and the patient is
separated from bypass.
The techniques for repair of Scimitar syndrome, in which right pulmonary
venous drainage connects to the inferior vena cava (IVC) or the IVC-RA
FIGURE 15-5. The Warden procedure for repair of sinus venosus atrial septal defect (ASD) with
anomalous connection of right pulmonary veins (PVs) to the superior vena cava (SVC). A. The SVC
is divided, and its cardiac end is oversewn. B. A patch is used to baffle the SVC internal orifice to the
ASD. The distal SVC is anastomosed to the right atrial (RA) appendage. RV = right ventricle.
215
CCIP.indb 215 3/13/18 4:18 PM

junction via a descending vertical vein (Scimitar vein), are similar to those just
discussed for anomalous connections to the SVC.
Repair of VSD
Several morphologic subtypes of VSDs exist, including membranous, conoven-
tricular, inlet, subpulmonary, and muscular VSDs. The indications and timing of
surgery for an isolated VSD can be complex, given the possibility of spontaneous
closure in a substantial fraction of VSDs (typically over the first year after birth).
In general, repair is performed for symptoms of heart failure, failure to thrive,
and, occasionally, recurrent respiratory infections. Though often discussed, the
likelihood of developing pulmonary vascular disease due to a large left-to-right
shunt is now rare because of improved recognition and treatment. The absence of
symptoms in the setting of a large VSD can be concerning, however, as it could
reflect evolving pulmonary vascular disease. In asymptomatic children, repair is
usually recommended in the first year after birth if pulmonary artery pressure
exceeds 50% of systemic pressure. Pulmonary pressures of this magnitude
indicate a large defect that is unlikely to close spontaneously. Children with
pulmonary artery pressure less than 50% of systemic pressure can be safely
followed up, although this requires regular echocardiography with assessment
of septal defect size and flow, pulmonary pressures, and particularly aortic valve
competence. New-onset aortic valve insufficiency can be another common reason
for surgical closure.
Most VSDs are approached by opening the RA and working through the tri-
cuspid valve (Figure 15-6, A), although other approaches are occasionally used,
including through the pulmonary artery for a subpulmonary VSD or through
the apical RV for an apical muscular VSD. Interrupted pledgeted sutures are
placed around the rim of the VSD, taking care to avoid the expected locations
of the conduction bundles (Figure 15-6, B). The sutures are then passed through
a patch of the chosen material and carefully tied down. Alternatively, a running
technique may be used where a single suture is woven back and forth through
the ventricular septum and the patch. Small residuals are not uncommon after
surgery but generally do not affect the patient and often close over time.
The results of VSD closure have been excellent for several decades, with low
morbidity and mortality. Transient arrhythmias, including heart block and
junctional tachycardia, may occur after surgery, for which temporary pacing
wires are routinely placed at the end of surgery. Permanent heart block, requiring
placement of a pacemaker, occurs in less than 2% to 3% of patients undergoing
repair of an isolated VSD.4
Repair of Complete AV Canal Defect

Complete AV canal defect represents a failure of endocardial cushion maturation
that results in a primum ASD, an unrestrictive inlet VSD, and a common AV
216
CCIP.indb 216 3/13/18 4:18 PM

FIGURE 15-6. Repair of ventricular septal defect (VSD). A membranous VSD is often approached
through the right atrium (RA) and tricuspid valve. Interrupted pledgeted sutures or a running suture
are used to secure a patch for closure of the defect. IVC = inferior vena cava, SVC = superior vena
cava, TV = tricuspid valve.
valve in the place of separate mitral and tricuspid valves (Figure 15-7, A). AV
canal defects span a wide range of anatomic and physiological severity, depend-
ing on the number of the aforementioned components that are present, the
position of the common AV valve, and the presence of outflow tract obstruction
or other associated anomalies. A completely balanced AV canal defect in which
the common AV valve aligns evenly with the RV and left ventricle (LV) inlets
may initially have simple ASD physiology and clearly be appropriate for a
2-ventricle AV canal repair. In contrast, a very unbalanced defect with outflow
tract obstruction, ventricular underdevelopment, or other associated anomalies
may require treatment with a single-ventricle approach. This section will focus
on 2-ventricle AV canal repair; surgical management of single-ventricle lesions
is discussed later in the chapter. Repair of complete AV canal defect should be
performed within the first year after birth, and early repair in the first 3 months
is often recommended to prevent worsening of AV valve regurgitation and
pathologic changes to the AV valve tissue. Early repair is advisable in patients
with Down syndrome, in particular, because they are at a higher risk for early
development of pulmonary hypertension.
AV canal defects are usually approached through the RA. The goal of surgery
is to close the VSD, close the ASD, and partition the common valve into
217
CCIP.indb 217 3/13/18 4:18 PM

well-functioning mitral and tricuspid valves. This can be accomplished by using

a 2-patch, single-patch, or modified single-patch technique.5 In the 2-patch
technique, the VSD is first closed with patch material that is sewn to the crest
of the ventricular septum below and to the mid-portion of the 2 common valve
leaflets above. The cleft of the anterior leaflet of the mitral valve is sewn closed.
The ASD is then closed by using a second patch, which is secured below to valve
tissue and the upper edge of the VSD patch, keeping the coronary sinus ostium
on the RA side (Figure 15-7, B). Some surgeons keep the coronary sinus to
the LA side of the ASD patch to decrease risk to the conduction tissue, which
does leave a small right-to-left shunt but does not normally cause clinically
significant cyanosis.
The single-patch technique is similar except that the inferior and superior
common AV valve leaflets are incised in their mid-portion to separate the left-
and right-sided valves. A single patch is anchored to the crest of the ventricular
septum and then brought through the divided common valve leaflets. The leaflets
are resuspended onto the pericardial patch, the mitral valve cleft is closed, and
the ASD is then closed with the remainder of the patch.
In the modified single-patch technique, several pledgeted sutures are placed
through the crest of the ventricular septum and brought up through the AV
valve tissue itself and are then brought through the bottom edge of an ASD
FIGURE 15-7. Repair of complete atrioventricular (AV) canal defect. A. Anatomy, including
primum atrial septal defect (ASD), inlet ventricular septal defect (VSD), and common AV valve.
B. Two-patch repair is performed through the right atrium (RA). A VSD patch has been placed
beneath the valve and sewn to an incision in the common leaflets. The mitral valve cleft is closed,
and an ASD patch is then secured above the VSD patch. LA = left atrium, LV = left ventricle,
RV = right ventricle.
218
CCIP.indb 218 3/13/18 4:18 PM

patch. These sutures are tied, resulting in closure of the VSD as the valve leaflets
are brought down onto the crest of the ventricular septum, resulting in primary
closure of the VSD. The remainder of the patch is then used to close the ASD.
The most clinically significant complications after repair of AV canal defect
include the need for a pacemaker (3% to 4%, which is a slightly higher incidence
rate than that for isolated VSD repair) and the need for reintervention on the
left-sided AV valve (mitral valve equivalent). This can be caused by persistent
valve regurgitation or, occasionally, stenosis. There is also risk for development
of LV outflow tract obstruction. Many infants with AV canal defects have
associated Down syndrome and may have comorbidities that require perioper-
ative management. These same infants are also at higher risk for postoperative
chylothorax for unclear reasons. The right-sided component of the AV valve
is usually much less of a problem than the left, unless the child also has an
associated RV outflow tract lesion (for example, complete AV canal defect with
tetralogy of Fallot [TOF]). These rarer lesion sets have higher complication rates
and could require specific attention to the right side during surgery.
Pulmonary Valve Replacement

Pulmonary valve replacement (PVR) is the most common surgical procedure in
adolescents and adults who have undergone a prior repair involving the RV out-
flow tract, as in TOF. The overall incidence of surgical PVR has been declining
since the introduction of a stent-mounted bioprosthetic PVR for transcatheter
implantation. Historically, about 300 PVRs were performed annually in the
United States; interestingly, more recent data suggest that nearly 600 transcath-
eter pulmonary valve implants are placed annually, and the rate appears to be
climbing. The most common indication is for clinically significant pulmonary
valve regurgitation that leads to right-sided heart dilation with symptoms of
heart failure and arrhythmias. There is ongoing discussion about the ideal timing
of intervention, considering the finite life of bioprosthetic replacement valves,
but there is unanimous agreement that the presence of symptoms warrants
intervention. In addition to the clinical history and echocardiographic findings,
cardiac MR imaging may be a useful adjunct for determining the appropriate
timing of PVR.
Surgical PVR is performed by opening the RV outflow tract, most often in
the setting of a previously placed transannular patch. The replacement valve is
implanted at the annulus in the position where the pulmonary valve normally
resides. A new patch can be sewn to the anterior portion of the valve sewing
ring and then used to close the RV outflow tract (Figure 15-8).
Bioprosthetic valves typically last about 10 years in the pulmonary position,
although duration varies on the basis of many factors, including patient age.
Postoperative stay is usually no more than 3 to 4 days, and patients rarely have
219
CCIP.indb 219 3/13/18 4:18 PM

FIGURE 15-8. Pulmonary valve replacement (PVR). A. Placement of a bioprosthetic PVR via an
incision in the right ventricular outflow tract (RVOT). B. The RVOT is closed with a new transan-
nular patch that is secured to the anterior portion of the valve sewing ring. RA = right atrium.
a complicated hospital course. Dissection of the pulmonary arteries, particularly

on the left side, can lead to possible injury to the left phrenic nerve. The greatest
morbidity (and possible mortality) of this procedure is related to repeat sternot-
omy, which is more hazardous than primary sternotomy because of scar-tissue
formation and adhesions between the sternum, heart, and other mediastinal
structures. The risk of injury during re-entry into the chest increases with each
subsequent repeat sternotomy.6
Surgery for Conotruncal Heart Defects

Arterial Switch Procedure
The arterial switch procedure is performed for the typical “dextro-” or d-loop
form of transposition of the great arteries (D-TGA), in which the ventricles
are normally related and there is ventriculoarterial discordance (morphologic
LV ejects into the pulmonary artery, morphologic RV ejects into the aorta).
Infants with D-TGA present with varying degrees of cyanosis and typically
undergo repair in the first 2 weeks after birth. Discussion of “levo-” or l-loop
transposition, known as congenitally corrected transposition of the great arteries, is
beyond the scope of this text.
Additional anomalies may be associated with D-TGA and can influence sur-
gical management, including obstruction of either ventricular outflow tract and
aortic anomalies, including coarctation, or interrupted aortic arch. The coronary
arteries most often arise from the aortic sinuses of Valsalva and maintain their
normal branching pattern; however, a variety of coronary artery anomalies are
220
CCIP.indb 220 3/13/18 4:18 PM

possible. These can influence the complexity of coronary artery transfer to the
neo-aorta (originally the main pulmonary artery [MPA]) during surgery.
The arterial switch procedure is normally performed within the first 2 weeks
after birth, with excellent outcomes. In the rare circumstance that diagnosis
is established late or a child is too ill to undergo surgery in the first 2 weeks, a
1-stage arterial switch procedure may be performed in infants between 3 and
8 weeks of age, although mechanical circulatory support may be required for a
brief period postoperatively.7 Although there are exceptions, conventional think-
ing is that beyond 8 weeks of age, the LV has likely become too deconditioned
to tolerate the systemic pressure load at the time of a 1-stage procedure, and a
2-stage arterial switch or planned mechanical support should be considered.8
During surgery, the ductus arteriosus is divided. The ascending aorta is
divided near its midpoint, and the coronary arteries are excised with a button of
aortic wall. The distal MPA is divided, and its bifurcation is brought anterior to
the ascending aorta (LeCompte maneuver). Windows are created in the neo-
aorta for implantation of the coronary buttons (Figure 15-9, A), and these are
sewn in place. The ascending aorta is then reconstructed, and the defects in the
neo-pulmonary artery (from where coronary buttons were excised) are patched
with autologous pericardium. The ASD is repaired through a right atriotomy.
The continuity of the pulmonary artery is performed last, before separation from
bypass (Figure 15-9, B).
After the arterial switch procedure, infants are for the most part considered
“cured,” although many can still go on to develop problems in later adulthood
FIGURE 15-9. Arterial switch procedure. A. Division of the aorta and main pulmonary artery
(MPA) with excision of coronary buttons and corresponding windows on the neo-aorta. B.
Completed arterial switch. LCA = left coronary artery, RA = right atrium, RCA = right coronary
artery, RV = right ventricle.
221
CCIP.indb 221 3/13/18 4:18 PM

and should continue to follow up with a cardiologist. Because the patches placed
in the neopulmonary artery do not grow with the child, there is some incidence
(5% to 10%) of pulmonary artery stenosis that can lead to further intervention
within the first couple of years after surgery. Other long-term problems can
include manifestations of occult coronary artery stenoses or development of
neoaortic valve insufficiency and enlargement or aneurysm of this root.
Repair of TOF
TOF with pulmonary stenosis is most often managed with a 1-stage complete
repair in early infancy, although in some patients a 2-stage approach with an
initial systemic to pulmonary artery shunt may be undertaken.9 Although
anatomically related, the surgical management of TOF with pulmonary atresia is
much more complex than TOF with pulmonary stenosis, owing to the severity
of pulmonary artery hypoplasia and the extent of aortopulmonary collateral
vessels.10 Only TOF with pulmonary stenosis will be considered in detail here.
Early primary repair is currently the most widely practiced approach for
TOF with pulmonary stenosis11 and is thought to provide benefits of improved
pulmonary development, decreased risk of permanent RV fibrosis and diastolic
dysfunction, and perhaps improved cognitive development.12 In stable infants,
elective repair should be undertaken in the first year after birth and is most often
performed at 3 to 6 months of age.11 Indications for more urgent surgery include
prostaglandin dependence and worsening cyanosis or cyanotic spells.
In relation to surgical repair, the most important features of TOF with
pulmonary stenosis are RV outflow tract obstruction caused by underdevelop-
ment of the subpulmonary infundibulum and an unrestrictive conoventricular
VSD, which in turn explain the coincident RV hypertrophy and rightward
displacement of the aortic valve. The infundibulum and VSD are approached
through either the RA or an incision in the RV outflow tract (ventriculotomy),
depending on the severity of obstruction. The crux of TOF repair pertains to the
management of the RV outflow tract and whether or not the pulmonary valve
must be made incompetent as a result of an incision across the pulmonary valve
annulus to relieve RV outflow tract obstruction. Typically, when the diameter
of this structure is more than 2.5 standard deviations below normal (z score less
than −2.5), placement of a transannular patch is necessary. The length of the
transannular incision and its extension onto the pulmonary artery depend on
the specific anatomy. While some have reported a “valve-sparing” incision with
limited extension across the annulus, the pulmonary valve remains at risk for
long-term insufficiency, even with very little annular disruption. Even in infants
with incisions limited to just the infundibulum, at least 25% develop long-term
pulmonary valve insufficiency because of the unique anatomy of the pulmonary
valve, in which a muscular ring supports the valve rather than a true fibrous
annular ring.
222
CCIP.indb 222 3/13/18 4:18 PM

After exposure of the infundibulum, incisions in the muscular extensions

of the conal septum are made to relieve RV outflow obstruction. Care is taken
to preserve the moderator band. Patch closure of the VSD is then performed,
usually by using a synthetic patch material (Figure 15-10). The RV outflow tract
is then patched, either with a pear-shaped transannular patch (Figure 15-11, A)
or with separate supravalvar and subvalvar patches if the valve-sparing technique
was used (Figure 15-11, B). These are intended to relieve obstruction in the
MPA and infundibulum, respectively. The patient is then weaned from bypass.
Much like in children who undergo isolated VSD closure, there is a low
risk of heart block with TOF repair. All of these infants develop some degree
of right bundle branch block because of the incisions in the septum. The child
who has undergone TOF repair should undergo continual monitoring by a
cardiologist in case of residual narrowing of the RV outflow tract or progressive
pulmonary valve insufficiency (see the “Pulmonary Valve Replacement” section
in this chapter).
FIGURE 15-10. Repair of tetralogy of Fallot through an incision in the infundibulum of the right
ventricular outflow tract. Muscular bands of the conal septum are divided, and the ventricular septal
defect (VSD) is closed with a patch. Repair can also be performed through the right atrium (RA) or
a more limited infundibular incision. MPA = main pulmonary artery.
223
CCIP.indb 223 3/13/18 4:18 PM

FIGURE 15-11. Repair of tetralogy of Fallot. Patch augmentation of the right ventricular outflow
tract, with either A. transannular patch or B. valve-sparing subvalvar and supravalvar patches. MPA
= main pulmonary artery, RA = right atrium.
Surgery for Single-Ventricle Heart Disease

Single-ventricle heart disease encompasses a wide range of congenital heart
lesions that share the common feature of 1 underdeveloped ventricle, such that
biventricular repair cannot be achieved. Such lesions are typically managed by
a 3-stage pathway that culminates in the Fontan procedure. The steps of the
3-stage Fontan pathway are a neonatal palliation procedure, the bidirectional
Glenn procedure (at approximately 3 to 6 months of age), and the Fontan pro-
cedure (beyond approximately 18 months of age). The final Fontan circulation is
characterized by 1 systemic ventricle that pumps blood to the aorta and the sys-
temic circulation, while systemic venous to pulmonary artery connections allow
passive flow to the pulmonary circulation. Either the LV or the RV may be used
as the systemic ventricle in the Fontan circulation, depending on the anatomy of
the original lesion. Specific forms of single-ventricle CHD can include tricuspid
atresia, pulmonary atresia with intact ventricular septum, double-inlet single
ventricle, unbalanced complete AV canal defects, mitral atresia, hypoplastic left
heart syndrome (HLHS), and heterotaxy syndromes.
Stage 1, Neonatal Palliation for Single Ventricle

Of the 3 stages of the typical Fontan pathway, the neonatal palliation stage
is the most variable in terms of the actual surgery performed. The type of
palliation needed is determined by the specific lesions present and the resulting
physiology, especially the presence or absence of systemic outflow obstruction,
224
CCIP.indb 224 3/13/18 4:18 PM

pulmonary outflow obstruction, or excessive pulmonary blood flow. Some of

the neonatal palliation procedures, namely systemic to pulmonary artery shunts
and pulmonary artery banding, were historically in common use for patients
with 2-ventricle CHD, as well. Today, however, their predominant use is in
single-ventricle palliation; therefore, they are discussed here.
Systemic to Pulmonary Artery Shunt
Before widespread adoption of the “early primary repair” philosophy, a variety
of systemic to pulmonary artery shunt procedures was commonly used as the
initial palliative step in the traditional 2-stage approach to many forms of CHD.
Systemic to pulmonary artery shunts were used to address inadequate pulmonary
blood flow and cyanosis in young infants, for example as in TOF, until the child
had grown to an adequate size to undertake definitive repair. Given the many
disadvantages of delayed repair, however, in most centers, systemic to pulmonary
artery shunting is now primarily used in neonates with single-ventricle lesions
and RV outflow obstruction who require maturation of the lungs prior to
progression along the Fontan pathway.13
The 2 most commonly used systemic to pulmonary artery shunts today are
the modified Blalock-Taussig shunt and the RV to pulmonary artery (Sano)
shunt. Several other shunts are rarely used in present times but deserve mention
for their historical significance. The original Blalock-Taussig shunt is a direct
end-to-side anastomosis of the transected subclavian artery to the pulmonary
artery, usually performed through a thoracotomy. The procedure does require
sacrifice of the subclavian artery, which can cause arm ischemia and can lead
to distortion of the pulmonary artery. The Waterston shunt is an anastomosis
between the ascending aorta and the right pulmonary artery, while the Potts
shunt is an anastomosis between the descending aorta and the left pulmonary
artery. Both of these shunts are prone to cause excess pulmonary blood flow if
not ideally sized and can be difficult to take down.
With the modified Blalock-Taussig shunt, a 3- to 6-mm synthetic tube graft
is used to connect the subclavian or other systemic artery to the pulmonary
artery and remedies several disadvantages of the original Blalock-Taussig shunt.
For patients with single ventricles, the shunt is most often created between the
innominate artery and the right pulmonary artery. After dissecting the vessels,
a side-biting clamp is applied to the subclavian or innominate artery, and the
arterial anastomosis is created. The opposite end of the graft is then anastomosed
to the selected location on the central right pulmonary artery (Figure 15-12).
Occasionally, a central shunt is created instead, in which the graft is sewn
between the ascending aorta and the MPA.
The RV to pulmonary artery shunt is discussed in detail as part of the
Norwood procedure, later in this section. Complications of primary concern
with systemic to pulmonary artery shunting are excessive pulmonary blood flow
due to an oversized shunt, which can lead to coronary ischemia and cardiac
225
CCIP.indb 225 3/13/18 4:18 PM

FIGURE 15-12. Modified Blalock-Taussig shunt. The subclavian artery is connected to the pulmo-
nary artery by using a synthetic tube graft, usually on the right side. MPA = main pulmonary artery,
RA = right atrium, RPA = right pulmonary artery, RV = right ventricle, SVC = superior vena cava.
arrest, as well as shunt thrombosis, which leads to recurrent cyanosis. Perhaps the
most critical element of care for these patients is the continuation of aspirin in
the postoperative period to help prevent shunt thrombosis. This simple measure
reduces mortality for these children by more than 50%.14 Aspirin should be con-
tinued even in the setting of other procedures, including cardiac catheterization
and noncardiac surgery to reduce the risk of shunt-related complications.
Pulmonary Artery Banding
Like systemic to pulmonary artery shunts, pulmonary artery banding is
a palliative procedure once widely used as initial intervention in children
undergoing delayed repair of CHD. In that era, pulmonary artery banding was
used for most congenital defects with large left-to-right shunts and excessive
pulmonary blood flow, including VSDs, atrioventricular canal defects (audio
available at www.youtube.com/watch?v=xO6mAv9eMLE&index=21&list=

PLKCIeugVenPTLW-nspw_wUkXxO2IIiesu) ( ), and truncus arteriosus.
Pulmonary artery banding is now primarily used in neonates with single-
ventricle lesions and no pulmonary obstruction who develop excessive
pulmonary blood flow and a few other lesions, such as multiple muscular
VSDs or transposition of the great arteries with delayed presentation.
226
CCIP.indb 226 3/13/18 4:18 PM

During surgery, the ductus arteriosus is divided if patent. Limited dissection

of the aorta and MPA is performed, just proximal to the bifurcation of the pul-
monary artery. A silicone band is passed around this portion of the pulmonary
artery and tightened to achieve about a 50% reduction in diameter of the MPA.
The band is then secured with sutures or clips (Figure 15-13), and the chest is
closed after a period of monitoring to verify the band tightness.
Norwood and Damus-Kaye-Stansel Procedures
Neonatal palliation for patients with single-ventricle heart disease and systemic
outflow obstruction is performed with the Norwood or Damus-Kaye-Stansel
(DKS) procedures. The 2 terms are sometimes used interchangeably, but there
is clear distinction. The DKS procedure involves division of the MPA and con-
nection of the proximal pulmonary artery to the aorta in a side-to-side fashion,
creating a “double-barrel” outflow for blood to leave the single-ventricle heart.
The term DKS is generally used to describe this procedure when performed
in patients with a single LV and transposition of the great arteries (such as
double-inlet LV or transposition of the great arteries with tricuspid atresia).
The Norwood procedure was originally described for palliation of HLHS and
involves a DKS component, as well as extensive aortic arch reconstruction,
usually with additional patch material. The description herein will focus on the
details of the Norwood procedure when performed for HLHS.
FIGURE 15-13. Pulmonary artery (PA) banding. A silicone band is secured around the main
pulmonary artery (MPA) just proximal to its bifurcation. RA = right atrium, RV = right ventricle.
227
CCIP.indb 227 3/13/18 4:18 PM

A variety of modifications have been described for the Norwood procedure,

but all have 3 common components: reconstruction of the ascending aorta and
arch (including the DKS portion described earlier), creation of a wide-open
ASD (so blood returning from the lungs can get back to the single ventricle),
and creation of a source of pulmonary blood flow (since the MPA has been
used for systemic outflow during the DKS portion). The preferred conduct
of cardiopulmonary bypass varies between centers and may include deep
hypothermic circulatory arrest, low-flow cardiopulmonary bypass, or traditional
cardiopulmonary bypass with cardioplegic arrest and alternative cannulation
sites, including the ductus arteriosus (Figure 15-14, A).
In all Norwood procedures, the proximal MPA is divided and the distal
pulmonary artery is sutured closed, either directly or with a patch. A systemic to
pulmonary artery shunt is created to establish a source of pulmonary blood flow,
either with a modified Blalock-Taussig shunt or now, more commonly, with an
RV to pulmonary artery (Sano) shunt. The latter involves a synthetic conduit
placed from the RV to the pulmonary artery, with the distal anastomosis to the
pulmonary artery performed at this point of the procedure.15,16
For the arch reconstruction, after removal of all ductal tissue, an incision is
made in the aortic arch and extended proximally all the way to the level of the
divided MPA, widely opening the hypoplastic ascending aorta and arch (Figure
15-14, B). An anastomosis is then created between the divided proximal MPA
and the opened aorta (DKS maneuver) by using a cuff of patch material to
augment the diameter of the neo-aorta and arch. A complete atrial septectomy is
FIGURE 15-14. The Norwood procedure for hypoplastic left heart syndrome (HLHS). A. Initial
anatomy of HLHS, with diminutive left ventricle, ascending aorta, and arch. Mitral and aortic valve
stenosis or atresia is present. The large patent ductus arteriosus and right atrium (RA) are cannulated
for bypass in this case. B. After division of the main pulmonary artery (MPA) and distal repair, the
ductus is ligated and the aortic arch opened proximally to the level of the MPA. C. Completion
anatomy after anastomosis of the proximal MPA to the aorta with patch augmentation to create a
neo-aorta. Atrial septectomy and creation of a right ventricular (RV) pulmonary artery (PA) (Sano)
shunt have been performed.
228
CCIP.indb 228 3/13/18 4:18 PM

Surgical P
rocedures for Congenital Heart Disease
performed next, through either the RA cannulation site or a separate right atri-
otomy. The proximal anastomosis of the Sano shunt is made to the infundibulum
of the RV to complete the reconstruction (Figure 15-14, C).
Although not discussed in detail here, an alternative to the Norwood
procedure for neonates with HLHS is a hybrid palliation procedure that involves
surgical pulmonary artery banding and transcatheter PDA stent placement with
atrial septostomy. A comprehensive stage 2 procedure is then performed at 4
to 6 months that includes removal of the ductal stent, a Norwood-type aortic
reconstruction, and bidirectional Glenn anastomosis.17 Regardless of the type of
palliation, special care should be taken during the first interstage period between
the Norwood and Glenn procedures to optimize pulmonary artery development,
maintain ventricular function, and maintain low pulmonary vascular resistance.18
Management during this interstage period remains critical, despite great
advances in the care of these infants. Residual arch obstruction (manifested as
new tricuspid regurgitation or low cardiac output syndrome) or problems related
to the shunt and pulmonary arteries (manifested as hypoxia and cyanosis) are
the 2 most common and serious post-Norwood complications that may go
unrecognized during the hospital course. Interstage weight surveillance is also
essential because many of these patients experience difficulty in gaining weight.
These infants require close monitoring and a high index of suspicion for occult
problems. Recent reports have demonstrated reduced interstage mortality in
patients treated with digoxin.19,20
Stage 2, Bidirectional Glenn Procedure

The second and third stages of the Fontan pathway are fairly generic for most
patients with single-ventricle heart disease, regardless of the specific initial
lesion. The bidirectional Glenn procedure is usually performed at 3 to 6 months
of age. Unfortunately, it cannot be performed in the immediate newborn period
because of high pulmonary vascular resistance and the relatively small size of
the SVC.
The bidirectional Glenn procedure involves taking down the existing systemic
to pulmonary artery shunt and creating a connection between the SVC and
pulmonary arteries (cavopulmonary shunt). Although the anastomosis is usually
made to the right pulmonary artery, the new connection allows systemic venous
blood to flow passively to both lungs (hence the term bidirectional) and bypass
the single ventricle, thereby reducing volume load on the ventricle and providing
some improvement in arterial oxygen saturations. A right-to-left shunt still
exists after the bidirectional Glenn procedure because of mixing of blood return
from the IVC at the atrial level, so oxygen saturations will not approach normal
until after the Fontan procedure.
The surgical approach is most often through a repeat sternotomy with
cardiopulmonary bypass, although some surgeons have performed the procedure
229
CCIP.indb 229 3/13/18 4:18 PM

without bypass. The existing systemic to pulmonary artery shunt is usually

ligated after initiating bypass, though some elect to leave the Sano shunt patent.
The right pulmonary artery and SVC are dissected free, and the azygos vein
is ligated and divided. The SVC is then clamped and divided, and its cardiac
end is oversewn. The cephalic end of the SVC is then anastomosed to the right
pulmonary artery (Figure 15-15).
Stage 3, Fontan Procedure

Arterial oxygen saturations and overall robustness and growth of the child are
usually markedly improved in the first weeks and months after the bidirectional
Glenn procedure. Progression through the second interstage period is normally
characterized, however, by gradual deterioration in oxygen saturations caused
by a relative increase in flow through the IVC when compared to the SVC with
normal growth, as well as potential development of upper-body venous collater-
als and pulmonary arteriovenous malformations. The Fontan procedure is gen-
erally undertaken after the child reaches 18 months of age and most commonly
between 2 and 5 years of age, although this may be indicated earlier in children
who have a more rapid decline in oxygen saturations to consistently less than
FIGURE 15-15. Bidirectional Glenn procedure. The right ventricle (RV) to pulmonary artery (PA)
or Sano shunt, placed at the time of the Norwood procedure, has been excised. The superior vena
cava (SVC) is divided and anastomosed to the right pulmonary artery (RPA). LPA = left pulmonary
artery, RA = right atrium.
230
CCIP.indb 230 3/13/18 4:18 PM

75%. Diagnostic cardiac catheterization is typically performed preoperatively

to confirm low pulmonary artery pressures, pulmonary vascular resistance, and
end-diastolic pressures, which help to predict success with Fontan physiology.
More recently, MR imaging is also being used in a complementary fashion to
obtain information about the child’s preoperative anatomy and physiology.
The Fontan procedure involves creation of a total cavopulmonary connection,
which requires routing of systemic venous blood return from the IVC to the
pulmonary artery, in addition to the existing SVC to pulmonary artery Glenn
shunt. The result is all systemic venous blood return (except the coronary sinus)
flowing passively to the lungs and the single ventricle being solely responsible
for pumping oxygenated blood to the systemic arterial circulation. Several
modifications to the Fontan procedure have been developed since the original
atriopulmonary anastomosis described in the 1960s, including the lateral
tunnel Fontan procedure, the extracardiac conduit Fontan procedure, and most
recently the intra- or extracardiac conduit Fontan procedure.21 The extracardiac
conduit Fontan procedure has become the most widely used technique today
because of several advantages, including low surgical mortality, lower incidence
of arrhythmias, improved hemodynamics, fewer postoperative complications,
and applicability to complex cardiac anatomy.22
Any of the modified Fontan techniques can be performed with or without a
fenestration between the cavopulmonary conduit and the LA, which provides a
small residual right-to-left shunt that can help ease the transition to the Fontan
circulation. The fenestration provides a consistent source of venous return to
the single ventricle by allowing shunting to the atrium in settings of increased
pulmonary pressure or reduced pulmonary blood flow. Potential risks of the
fenestration, however, include embolization, desaturation, and the potential
need for additional procedures to close the fenestration.
The extracardiac conduit Fontan procedure is performed through a median
sternotomy, usually with cardiopulmonary bypass. The existing Glenn anasto-
mosis, SVC, and right pulmonary artery are dissected. The IVC is clamped and
divided, and its cardiac end is oversewn. A synthetic tube graft is anastomosed
to the open end of the IVC. The right pulmonary artery is then opened some-
what opposite the area of the existing Glenn anastomosis, and the cephalic end
of the graft is anastomosed. A fenestration, if used, is created in the midpoint
of the conduit and then anastomosed to an adjacent incision made in the RA
(Figure 15-16).
The most serious complication after the Fontan procedure is low cardiac
output, which can lead to the need for Fontan takedown. Fortunately, this is
rare and is often an indication of some unrecognized underlying anatomic or
physiological problem. Acute thrombosis of the fenestration can occur, which
can be reopened in the catheterization lab. Pleural effusions are common, but
persistence beyond 7 to 10 days can be an indication to create or reopen a
231
CCIP.indb 231 3/13/18 4:18 PM

FIGURE 15-16. Extracardiac conduit Fontan procedure. The inferior vena cava (IVC) is divided and
connected to the right pulmonary artery (RPA) with a synthetic conduit. A fenestration can be made
between the conduit and the right atrium (RA). SVC = superior vena cava.
thrombosed fenestration. Many fenestrations will close spontaneously; those that

remain patent beyond about a year postoperatively can be closed with a catheter
occluder device.
Long-term follow-up of the patients in whom the first Fontan procedures
were performed in the late 1960s to early 1970s has recently begun to reveal a
number of persistent long-term problems due to Fontan physiology. Patients
with Fontan physiology are best considered as having a condition with systemic
manifestations, as well as cardiac manifestations. Exercise capacity is limited in
patients after the Fontan procedure, with maximum oxygen consumption results
at exercise testing ranging from 48% to 65% of predicted values when compared
with age- and sex-matched peers.23 Within 10 years of the Fontan procedure,
20% of patients will have arrhythmias; these may manifest as palpitations, or
the patient may describe fatigue and worsening exercise intolerance.24 Patients
may develop ventricular dysfunction and require heart failure medications. Up
to 8% of patients will develop protein-losing enteropathy, a condition where
they lose protein in their stool. A diagnosis of protein-losing enteropathy carries
an estimated 5-year mortality of 50%; thus, these patients are often referred for
cardiac transplantation.25,26 Liver disease after the Fontan procedure, including
232
CCIP.indb 232 3/13/18 4:18 PM

hepatic fibrosis, cirrhosis, and, in rare cases, hepatocellular carcinoma, has been
increasingly noted clinically and will be the focus of future investigations and
trials.27–29 Finally, presumably due to the history of multiple cardiac surgeries,
anesthesia and cardiopulmonary bypass episodes, and unknown genetic factors,
patients with Fontan physiology are more likely than their peers to have anxiety,
attention-deficit/hyperactivity disorder, and learning disabilities.30
Key Points
•• Early primary repair has become the overarching philosophy guiding the
surgical management of CHD in children.
•• A team approach with careful coordination of outpatient, inpatient, and
surgical management is key to obtaining successful outcomes for these
complex patients.

•• Congenital Heart Defects (Centers for Disease Control and Prevention).
www.cdc.gov/ncbddd/heartdefects
•• Congenital Heart Defects (American Heart Association). www.heart.org/
HEARTORG/Conditions/CongenitalHeartDefects/Congenital-Heart-
Defects_UCM_001090_SubHomePage.jsp
•• Congenital Heart Disease (Cove Point Foundation/Johns Hopkins Children’s
Heart Center). www.pted.org
•• Cardiothoracic Surgery Network. www.ctsnet.org
References
1) Executive Summary, Society of Thoracic Surgeons Congenital Heart Surgery Database, Spring.
2016. www.sts.org/national-database/database-managers/executive-summaries. Accessed
November 8, 2017
2) Brouwer RM, Erasmus ME, Ebels T, Eijgelaar A. Influence of age on survival, late hypertension,
and recoarctation in elective aortic coarctation repair. Including long-term results after elective
aortic coarctation repair with a follow-up from 25 to 44 years. J Thorac Cardiovasc Surg. 1994;
108(3):525–531
3) Ishino K, Alexi-Meskishvili V, Hetzer R. Preoperative extracorporeal membrane oxygen-
ation in newborns with total anomalous pulmonary venous connection. Cardiovasc Surg.
1999;7(4):473–475
4) Andersen HO, de Leval MR, Tsang VT, Elliott MJ, Anderson RH, Cook AC. Is complete
heart block after surgical closure of ventricular septum defects still an issue? Ann Thorac Surg.
2006;82(3):948–956
5) Backer CL, Stewart RD, Mavroudis C. What is the best technique for repair of complete
atrioventricular canal? Semin Thorac Cardiovasc Surg. 2007;19(3):249–257
6) Kirshbom PM, Myung RJ, Simsic JM, et al. One thousand repeat sternotomies for congenital
cardiac surgery: risk factors for reentry injury. Ann Thorac Surg. 2009;88(1):158–161
233
CCIP.indb 233 3/13/18 4:18 PM

7) Kirklin JW, Blackstone EH, Tchervenkov CI, Castaneda AR; Congenital Heart Surgeons
Society. Clinical outcomes after the arterial switch operation for transposition. Patient, support,
procedural, and institutional risk factors. Circulation. 1992;86(5):1501–1515
8) Bisoi AK, Ahmed T, Malankar DP, et al. Midterm outcome of primary arterial switch operation
beyond six weeks of life in children with transposition of great arteries and intact ventricular
septum. World J Pediatr Congenit Heart Surg. 2014;5(2):219–225
9) Fraser CD Jr, McKenzie ED, Cooley DA. Tetralogy of Fallot: surgical management individual-
ized to the patient. Ann Thorac Surg. 2001;71(5):1556–1561, discussion 1561–1563
10) Duncan BW, Mee RB, Prieto LR, et al. Staged repair of tetralogy of Fallot with pulmonary atre-
sia and major aortopulmonary collateral arteries. J Thorac Cardiovasc Surg. 2003;126(3):694–702
11) Al Habib HF, Jacobs JP, Mavroudis C, et al. Contemporary patterns of management of
tetralogy of Fallot: data from the Society of Thoracic Surgeons database. Ann Thorac Surg.
2010;90(3):813–819, discussion 819–820
12) Jonas RA. Early primary repair of tetralogy of Fallot. Semin Thorac Cardiovasc Surg Pediatr Card
Surg Annu. 2009;39–47
13) Jonas R. Advantages of early primary repair of congenital heart disease. World J Pediatr Congenit
Heart Surg. 2010;1(3):407–410
14) Heidari-Bateni G, Norouzi S, Hall M, Brar A, Eghtesady P. Defining the best practice patterns
for the neonatal systemic-to-pulmonary artery shunt procedure. J Thorac Cardiovasc Surg. 2014;
147(3):869–873
15) Ohye RG, Sleeper LA, Mahony L, et al; Pediatric Heart Network Investigators. Comparison
of shunt types in the Norwood procedure for single-ventricle lesions. N Engl J Med. 2010;
362(21):1980–1992
16) Sano S, Ishino K, Kawada M, et al. Right ventricle-pulmonary artery shunt in first-stage
palliation of hypoplastic left heart syndrome. J Thorac Cardiovasc Surg. 2003;126(2):504–509,
discussion 509–510
17) Galantowicz M, Cheatham JP. Lessons learned from the development of a new hybrid strategy
for the management of hypoplastic left heart syndrome. Pediatr Cardiol. 2005;26:190–199
18) Aiyagari R, Rhodes JF, Shrader P, et al; Pediatric Heart Network Investigators. Impact of
pre-stage II hemodynamics and pulmonary artery anatomy on 12-month outcomes in the
Pediatric Heart Network Single Ventricle Reconstruction trial. J Thorac Cardiovasc Surg.
2014;148(4):1467–1474
19) Brown DW, Mangeot C, Anderson JB, et al; National Pediatric Cardiology Quality Improve
ment Collaborative. Digoxin use is associated with reduced interstage mortality in patients with
no history of arrhythmia after stage I palliation for single ventricle heart disease. J Am Heart
Assoc. 2016;5(1):e002376
20) Oster ME, Kelleman M, McCracken C, Ohye RG, Mahle WT. Association of digoxin with
interstage mortality: results from the Pediatric Heart Network single ventricle reconstruction
trial public use dataset. J Am Heart Assoc. 2016;5(1):e002566
21) Jonas RA. The intra/extracardiac conduit fenestrated Fontan. Semin Thorac Cardiovasc Surg
Pediatr Card Surg Annu. 2011;14(1):11–18
22) Backer CL, Deal BJ, Kaushal S, Russell HM, Tsao S, Mavroudis C. Extracardiac versus
intra-atrial lateral tunnel Fontan: extracardiac is better. Semin Thorac Cardiovasc Surg Pediatr
Card Surg Annu. 2011;14(1):4–10
23) Durongpisitkul K, Driscoll DJ, Mahoney DW, et al. Cardiorespiratory response to exercise after
modified Fontan operation: determinants of performance. J Am Coll Cardiol. 1997;29(4):785–790
24) Lasa JJ, Glatz AC, Daga A, Shah M. Prevalence of arrhythmias late after the Fontan operation.
Am J Cardiol. 2014;113(7):1184–1188
234
CCIP.indb 234 3/13/18 4:18 PM

25) Mertens L, Hagler DJ, Sauer U, Somerville J, Gewillig M. Protein-losing enteropathy after the
Fontan operation: an international multicenter study. PLE study group. J Thorac Cardiovasc Surg.
1998;115(5):1063–1073
26) Johnson JN, Driscoll DJ, O’Leary PW. Protein-losing enteropathy and the Fontan operation.
Nutr Clin Pract. 2012;27(3):375–384
27) Asrani SK, Warnes CA, Kamath PS. Hepatocellular carcinoma after the Fontan procedure.
N Engl J Med. 2013;368(18):1756–1757
28) Pundi K, Pundi KN, Kamath PS, et al. Liver disease in patients after the Fontan operation.
Am J Cardiol. 2016;117(3):456–460
29) Rychik J, Veldtman G, Rand E, et al. The precarious state of the liver after a Fontan operation:
summary of a multidisciplinary symposium. Pediatr Cardiol. 2012;33(7):1001–1012
30) DeMaso DR, Calderon J, Taylor GA, et al. Psychiatric disorders in adolescents with single
ventricle congenital heart disease. Pediatrics. 2017;139(3):e20162241
235
CCIP.indb 235 3/13/18 4:18 PM

CCIP.indb 236 3/13/18 4:18 PM
CHAPTER 16
Office Care of
the Child After
Cardiac Surgery
Jess Thompson, MD, MSc, and Harold M. Burkhart, MD
Historical Perspective
In the 1913 edition of his monumental work, The Principles and Practice of Medicine,
William Osler summarized the entire field of congenital heart surgery in 4 simple
pages. During that era, only about 15% of all children with congenital heart disease
(CHD) survived to adulthood. The next several decades brought many surgical
advances, but all were effectively extracardiac in nature.
While the 1950s saw the emergence of the intracardiac repair, outcomes were
initially dismal. The first series of patients undergoing cardiopulmonary bypass
for the correction of intracardiac pathologic findings was reported in 1955,1 and
the surgeons from Mayo Clinic reported a morale-crushing mortality rate of
50% (the 4 deaths occurred in patients with ventricular septal defect,2 tetralogy
of Fallot, and an atrioventricular canal). Despite this inauspicious beginning, the
Mayo Clinic surgeons were able to rapidly improve their outcomes, and 2 short
years later, they reported on 245 patients who had undergone a surgery.2
The past 60 years have brought an incredible maturation of the discipline
of congenital heart surgery. Annually in the United States, approximately
11,700 children undergo a cardiac surgery.3 Owing to improved surgical technique
and perioperative care, contemporary discharge mortality rates are 0.6% for the
lowest-risk cases (eg, uncomplicated septal defects) and 19% for the highest-risk
237
CCIP.indb 237 3/13/18 4:18 PM

cases (eg, neonatal single-ventricle palliation). Today, more than 90% of children
born with a cardiac defect will reach adulthood.4
The Postoperative Office Visit

Typically, a patient discharged from the hospital will be scheduled for a routine
follow-up appointment 1 to 2 weeks after dismissal. Most patients returning
to the outpatient clinic after heart surgery report that they are doing well. A
well-structured and thoughtful postoperative visit should have the following
goals in mind: (a) determine the current health status and needs of the patient;
(b) alter the existing plan as necessary to optimize medical care; (c) determine
what follow-up is necessary; and (d) communicate with the patient, the patient’s
caregivers, and the other members of the health care team.
History
One of the most crucial aspects of a postoperative visit is to completely under
stand a patient’s preoperative anatomy and recognize how that anatomy was
altered during the recent hospital admission. Anatomic modifications may have
occurred in the operating room or in the cardiac catheterization laboratory. These
anatomic alterations will, sometimes to a large degree, dictate how closely a
patient will need to be followed up and what medications the patient may need
long-term. To increase the likelihood of accurate transmission of information,
it is useful to document the dates and outcome of each intervention.
With the traditional classification of CHD, anomalies are categorized as
either cyanotic or acyanotic conditions. A clinically more useful way to approach
a postoperative patient is to determine whether the patient has a functional
single ventricle or 2 ventricles, has persistence of an intracardiac communication,
and is anticipated to need future surgeries. Answering these key questions
will aid in the understanding of potential postoperative pitfalls, help establish
expected vital signs, determine exigent medications, and help direct planning
of future studies and interventions.
Activity
Many children behave differently after heart surgery. They may be clingy or
irritable, wet the bed, or cry. They may exhibit these behaviors after their surgery,
even if they did not before. It is important to reassure the child’s parents and
encourage them to support their child through this time. Most often, the first
few weeks after surgery should be a time to rest. It is important during the post
operative visit to start discussing what activities the child should begin to do.
Children who have had an incision through the sternum need time for the
bone to heal. For this reason, they should be careful about how they use their
238
CCIP.indb 238 3/13/18 4:18 PM

Office Care of the Child After Cardiac Surgery
arms and upper bodies for the first 6 to 8 weeks. The child should not participate
in any activity that could result in a fall or a blow to the chest. Activities such
as bicycle or skateboard riding, roller skating, swimming, and all contact sports
should be avoided. Further, the child should be discouraged from engaging in
activities that require pulling or pushing with the arms. The child should not be
pulled or lifted by the arms or from their armpit area; instead, they should be
“scooped” up.
Because of their increased risk for sudden death, patients with a functional
single ventricle or who are shunt dependent require heightened awareness. Home
monitoring enhances surveillance and promotes the early identification of
deteriorating physiology, which has been shown to significantly reduce mortality.5
Because home monitoring improves the outcomes for these patients, it is impor
tant to ascertain the patient’s compliance with a home-monitoring program.
Medications
It is important to know what medications the patient was taking preoperatively,
as well as the medications that were prescribed at the time of hospital discharge.
Many of the medications started postoperatively will only be necessary in the
immediate perioperative period. The hope is that once fully recovered, most
patients will require only a single surgery and will eventually not require any
cardiac medications. Careful assessment of the medications will be helpful
in deciding which medications need to be adjusted or discontinued. Patient
satisfaction and adherence will improve as their medication regimen is sim-
plified, if they understand the rationale for medications, and if the prescribing
instructions are clear.6
Antiplatelet agents are frequently used when there is concern for thrombo-
genic suture lines or if a large amount of foreign material has been implanted
(eg, a large intracardiac patch or baffle). To reduce the risk of thrombus forma-
tion on tissue that has been freshly operated on, the surgeon will sometimes
prescribe an antiplatelet agent until the sutures or patch material are covered by
neointimal tissue. Epithelialization typically takes around 3 months. Similarly,
patients undergoing valve replacement or repair are also placed on an abbreviated
course (usually 3 months) of either an anticoagulant and an antiplatelet agent7
or a combination of both.8 Patients receiving mechanical heart valves will need
lifelong anticoagulation therapy.
After pediatric cardiac surgery, the incidence of postoperative arrhythmias
is 15% to 48%9; arrhythmias may result in clinically significant hemodynamic
compromise. The genesis of arrhythmias postoperatively is myocardial injury
and ischemia, high catecholamine levels, and electrolyte disturbances. Should an
arrhythmia develop intraoperatively or postoperatively, pharmacological therapy
is often initiated with the aim of terminating the arrhythmia and preventing
239
CCIP.indb 239 3/13/18 4:18 PM

recurrences. Typically, antiarrhythmics begun during the hospitalization are

continued for 3 to 6 months, after which the utility of their continued adminis-
tration should be addressed.
Children undergoing heart surgery are almost always fluid overloaded, so the
administration of diuretics after surgery is ubiquitous. Preoperatively, anatomic
or physiological states predispose the patient to fluid retention. Intraoperatively,
the patient receives a large amount of extra volume from the cardiopulmonary
bypass run. Further, the intravenous administration of blood products, resus
citative inotropes and vasopressors, and parenteral nutrition can exacerbate
the amount of excess corporeal fluid. When discharged from the hospital, a
patient should be taking stable doses of oral diuretics. Patients who have been
totally corrected and no longer have cardiac dysfunction should be able to
suspend diuretic use once homeostasis and true euvolemia have been achieved.
Alternatively, patients with persistent cardiac dysfunction or volume-loading
lesions will need to maintain continued diuretic use. A careful appraisal of the
patient’s fluid balance should be conducted during the postoperative visit.
Parents are frequently astonished at how well their child tolerates a
sternotomy. At the time of hospital discharge, it is not uncommon for a patient
to be taking only acetaminophen and ibuprofen, with intermittent doses of
an opioid. To maximize analgesic coverage, it is important to instruct parents
that the administration of nonnarcotic medications can overlap if they are
administered in an alternating fashion. It is also helpful to make sure that should
opioid use still be necessary, the parents understand how to taper the dose and
that they still have sufficient quantity for the anticipated length of use. During
the postoperative visit, it is important to obtain a sense of how well the child
is continuing to tolerate the sternotomy, because worsening of pain could be a
harbinger of other concerns.
Patients whose procedure cannot be considered a total correction usually
require medications long-term. For example, patients traversing a single-
ventricle pathway may require lifelong heart failure medications and anti-
platelet agents.10,11,12 Other lifelong medications could be anticoagulants for
the thromboprophylaxis of mechanical heart valves. The goal for these patients
is to maximize adherence by minimizing the number of medications to be taken
and the difficulty of administering the medications.
Postoperative Symptoms
Most patients who return to the clinic after heart surgery report that they are
doing well. Despite the fact that most postoperative somatic symptoms are
benign, they should be taken seriously because they may indicate the presence
of potentially serious problems. Obtaining thorough information about the
symptom will assist in teasing out those that require an increased level of
240
CCIP.indb 240 3/13/18 4:18 PM

scrutiny. Three common complaints after cardiac surgery that portend the
possibility of a serious problem are chest pain, shortness of breath, and fever.
To some degree, sternal discomfort after cardiac surgery is to be expected.
Fortunately for young patients, the relative plasticity of the chest wall attenuates
much of the discomfort, and most children can be dismissed from the hospital
with little to no narcotic pain medication. For the surgeon, new-onset chest pain
is cause for concern because the pain may indicate a disruption of the surgical
repair. Although musculoskeletal pain is the most common cause of postoper-
ative chest discomfort, other etiologic origins to be considered include sternal
dehiscence, myocardial ischemia, infection, pericarditis, pneumothorax, pleural
effusion, and pulmonary embolism.
In addition to eliciting information about pain from a postoperative patient,
inquiry must also be made about the respiratory status. If the pain is poorly con-
trolled, it may lead to shortness of breath due to splinting. Clinically significant
shortness of breath could primarily be pulmonary in nature but should raise
awareness of the possibility of dysfunction of either the heart or the kidneys.
Pulmonary diagnoses to consider include atelectasis, pneumothorax, pneumonia,
pleural effusion, pleurisy, and pulmonary embolism. Cardiac diagnoses include
myocardial ischemia, cardiac tamponade, dehiscence of surgical repair, arrhyth-
mia, and reduced cardiac function.
Fever is not common in children who have undergone cardiac surgery and
are returning to the office. Because the concern is an infectious etiologic origin,
fever in this setting should be vigorously assessed. This is especially true for
patients into whom foreign material has been implanted as part of the surgical
correction. Changes to bowel or bladder habits should be queried, as well as
the onset of respiratory symptoms. All surgical and catheter sites should be
inspected for integrity, discharge, and erythema. While a 1- to 2-mm rim of
erythema is common, spreading erythema that is warm to the touch is a cause
for cellulitis. The chest should be examined for signs of pneumonia, effusion, or
new heart sounds. There should be a low threshold for obtaining blood work,
and echocardiography should be ordered if the diagnosis of endocarditis is being
considered. The clinician should be aware that patients who have poor function
after cardiac surgery may have cool extremities, so normal axillary or forehead
temperature readings may belie an underlying illness.
Vital Signs
Routine assessment of vital signs is an important step in establishing a baseline
and making certain that all is well. An abnormal heart rate could be an indica-
tion of an accelerated arrhythmia or conduction tissue disturbance. Obtaining
the blood pressure and checking the peripheral pulse are important components
of the postoperative examination. This is especially true if the aorta was involved
241
CCIP.indb 241 3/13/18 4:18 PM

in the surgical repair. If the aorta was involved, the blood pressure in the upper
and lower extremities should be obtained (to look for a residual or worsening
gradient). Suspicion of cyanosis should be confirmed via pulse oximetry. If there
are no residual lesions that allow blood to mix between the pulmonary and
systemic circulations, the oxygen saturation would be expected to be near 100%.
Oxygen saturations below this level could indicate a problem with the surgical
repair or ongoing pulmonary disease.
A residual lesion that allows for mixing of the 2 circulations may cause the
oxygen saturations to be diminished. Special care must be given to patients with
parallel circulations (ie, a functional single ventricle). An oxygen saturation of
80% in a child with a functional single ventricle indicates that the pulmonary
and systemic circulations are balanced. Higher oxygen saturations denote more
pulmonary blood flow (at the expense of systemic blood flow), while an oxygen
saturation below 80% represents the exact opposite.
Careful physical examination will often demonstrate the seriousness of
postoperative chest pain or shortness of breath. Often, it is straightforward
to ascertain whether pain is caused from a musculoskeletal source. Special atten
tion should be given to sternal stability, which can be assessed by pressing in on
both sides of the sternum. The surgeon should be notified if movement is felt.
Consultation with a cardiology service is warranted in patients with a suspected
cardiac origin of the pain. Differentiation of ST-segment elevation related to
ischemia (localized elevation) as opposed to pericarditis (diffuse elevation)
is important.
A conscientious lung examination may demonstrate diminished breath
sounds. If this is the case, a chest radiograph and electrocardiogram should be
obtained. If pleural effusions have developed or are enlarging, an echocardio
gram will help to assess the adequacy of the repair and ventricular function.
After discharge from the hospital, new onset of fever is uncommon and
should garner immediate attention. Because the patient has recently undergone
surgery, the cause for the most concern would be infection of a surgical site. Also
to be considered are anatomic sites into which a foreign object had been placed
(eg, sinusitis from a nasogastric tube, urinary tract infection from a urinary cath-
eter). The patient should be asked specifically about drainage from the wound.
While an episode of serous drainage is typically benign, odiferous or opaque
drainage could signal infection, and the surgical team should be notified. It is
common for those unfamiliar with surgical wounds to misidentify a cutaneous
reaction to suture or draining fat necrosis as an infection. Concerns for infection
should prompt early communication with the surgical team.
242
CCIP.indb 242 3/13/18 4:18 PM

Strong consideration of antibiotic therapy must be given to the postoperative

cardiac patient. This is especially true for patients into whom prosthetic material
has been implanted. Broad-spectrum antibiotics may be initially administered
and then subsequently substituted for a narrower-spectrum antibiotic once
an organism has been identified. Infected wounds can often be managed with
conservative therapy, including washing the wound directly with gentle soap and
water. In general, culturing of drainage should be discouraged because the swab
is often contaminated with skin flora.
When infection is strongly suspected, serious consideration should be given
to admitting a postoperative patient. Routine laboratory studies, including
blood cultures (preferably before the initiation of antibiotic therapy), should be
performed. If no obvious source of infection is readily demonstrable, advanced
imaging (computed tomography, echocardiography) is often required.
Wound Care
The incidence of sternal wound infection in the pediatric population is thought
to approach 1.5%.13 Each wound (eg, sternotomy, chest tube sites, temporary
pacing wire sites) should be meticulously inspected for signs of infection. Wound
closure strips that have begun to peel off can be removed completely. Often,
any remaining suture material can also be removed at this time. While it is not
uncommon for there to be a small amount of skin separation at chest tube sites,
there should not be any skin separation of the sternotomy.
While the patient should be encouraged to gently bathe the surgical wounds
with soap and water, immersing the wounds for prolonged periods can lead
to maceration of the skin edges, which could lead to their separation. For
this reason, the patient should refrain from activities such as soaking baths,
swimming, and saunas for 10 to 14 days after discharge. The routine application
of ointments, creams, or pastes to surgical wounds is not recommended and can
even be detrimental. To minimize long-term discoloration of the wound, direct
exposure to sunlight should be avoided for as long as the scar looks pink.
It is not uncommon for healing wounds to have an erythematous border.
A cause for concern, however, is erythema that is spreading. Encourage the
patient to call the surgical team in the event of an increase in redness, swelling,
tenderness, warmth, or drainage.
Key Points
•• Most children do very well postoperatively.
•• The precise postoperative anatomy must be known.
•• Convalescence includes wound care and an initial restriction of activities.
•• All wounds must be examined for integrity and signs of infection.
243
CCIP.indb 243 3/13/18 4:18 PM

•• Vital signs, especially oxygen saturation, will be affected by the postoperative

anatomy.
•• Careful assessment of new symptoms may prevent evolving problems.
•• The surgeon should be contacted immediately if questions or concerns arise.
References
1) Kirklin JW, Dushane JW, Patrick RT, et al. Intracardiac surgery with the aid of a mechanical
pump-oxygenator system (gibbon type): report of eight cases. Proc Staff Meet Mayo Clin.
1955;30(10):201–206
2) Kirklin JW, Patrick RT, et al. What is adequate perfusion. In: Allen JG, ed. Extracorporeal
Circulation. Springfield, IL: Charles C Thomas; 1958:125–138
3) Jacobs JP, O’Brien SM, Pasquali SK, et al. Variation in outcomes for risk-stratified pediatric
cardiac surgical operations: an analysis of the STS Congenital Heart Surgery Database.
Ann Thorac Surg. 2012;94(2):564–571, discussion 571–572
4) Marelli AJ, Mackie AS, Ionescu-Ittu R, Rahme E, Pilote L. Congenital heart disease in the
general population: changing prevalence and age distribution. Circulation. 2007;115(2):163–172
5) Hehir DA, Ghanayem NS. Single-ventricle infant home monitoring programs: outcomes and
impact. Curr Opin Cardiol. 2013;28(2):97–102
6) Adherence M. https://millionhearts.hhs.gov/tools-protocols/medication-adherence.html#FT.
Accessed September 20, 2017
7) Whitlock RP, Sun JC, Fremes SE, Rubens FD, Teoh KH. Antithrombotic and thrombolytic
therapy for valvular disease: antithrombotic therapy and prevention of thrombosis, 9th ed:
American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest.
2012;141(2 Suppl):e576S–e600S
8) Puskas J, Gerdisch M, Nichols D, et al; PROACT Investigators. Reduced anticoagulation after
mechanical aortic valve replacement: interim results from the prospective randomized on-X
valve anticoagulation clinical trial randomized Food and Drug Administration investigational
device exemption trial. J Thorac Cardiovasc Surg. 2014;147(4):1202–1210, discussion 1210–1211
9) Payne L, Zeigler VL, Gillette PC. Acute cardiac arrhythmias following surgery for congenital
heart disease: mechanisms, diagnostic tools, and management. Crit Care Nurs Clin North Am.
2011;23(2):255–272
10) Li JS, Yow E, Berezny KY, et al. Clinical outcomes of palliative surgery including a system-
ic-to-pulmonary artery shunt in infants with cyanotic congenital heart disease: does aspirin
make a difference? Circulation. 2007;116(3):293–297
11) Ravn HB, Hjortdal VE, Stenbog EV, et al. Increased platelet reactivity and significant changes
in coagulation markers after cavopulmonary connection. Heart. 2001;85(1):61–65
12) Jahangiri M, Kreutzer J, Zurakowski D, Bacha E, Jonas RA. Evaluation of hemostatic and
coagulation factor abnormalities in patients undergoing the Fontan operation. J Thorac Cardiovasc
Surg. 2000;120(4):778–782
13) Woodward CS, Son M, Calhoon J, Michalek J, Husain SA. Sternal wound infections in pediatric
congenital cardiac surgery: a survey of incidence and preventative practice. Ann Thorac Surg.
2011;91(3):799–804
244
CCIP.indb 244 3/13/18 4:18 PM

CHAPTER 17
Common
S
yndromes
A
ssociated With
Cardiac Lesions
Noelle Andrea Fabie, MD, Rini Sahewalla, MD, and
David W. Stockton, MD, FACMG
Down Syndrome (Trisomy 21)

Introduction
Down syndrome (trisomy 21) is the most common chromosomal aneuploidy in
the pediatric primary care setting, with an incidence estimated at about 1 in 700
live births.1 It is characterized by distinct facial features, cardiac defects, hypotonia,
and neurocognitive delay of varying severity. Risk for trisomy 21 increases with
maternal age because of higher risk of chromosomal nondisjunction.
Pathophysiology
In 90% to 95% of cases, Down syndrome is caused by meiotic nondisjunction
that leads to an extra copy of chromosome 21. The remainder of cases are caused
by Robertsonian translocations involving chromosome 21, which is functionally
equivalent to 3 copies of chromosome 21, and mosaicism for trisomy 21.
245
CCIP.indb 245 3/13/18 4:18 PM

Clinical Features
Key Clinical Findings
Characteristic facial features include upslanting palpebral fissures, epicanthal
folds, midface hypoplasia with flattening of the nasal bridge and the malar
region, and low-set ears. Other physical findings, such as the presence of single
transverse palmar creases, fifth-finger clinodactyly (medial curvature of the
fifth finger), and widened gap between the first and second toes, are common.
Down syndrome is also associated with hypotonia and joint hyperextensibility.
Congenital anomalies frequently associated with Down syndrome include
congenital heart defects, duodenal atresia, Hirschsprung disease, and tracheo-
esophageal fistula. Musculoskeletal anomalies, including polydactyly, syndactyly,
and limb-reduction defects, as well as hydrocephalus, oral clefts, and abdominal
wall defects, have also been reported.2 Cognitive impairment of varying degree
is another key feature. Other medical issues in patients with Down syndrome
include hearing and vision problems, obstructive sleep apnea, delayed dental
eruption, thyroid disease, transient myeloproliferative disorder, anemia, leuke-
mia, and atlantoaxial instability.
Associated Cardiovascular Findings
Cardiac anomalies have been reported to occur in about 40% to 50% of infants
with Down syndrome. The most commonly reported cardiac lesions are
atrioventricular (AV) septal defect (AV canal defect), atrial septal defect (ASD),
ventricular septal defect (VSD), patent ductus arteriosus (PDA), and tetralogy
of Fallot (TOF).2 Early detection and appropriate surgical repair of these cardiac
defects have contributed to increased survival of patients with Down syndrome.
There is also a reported shift in the cardiac phenotype in Down syndrome, with
complex cardiac lesions being less common. In a report published by Bergström
and colleagues in 2016, a 40% decrease in the incidence of complex congenital
heart defects was seen in 2010 to 2012, compared to 1992 to 1994.3 The cause of
this changing phenotype has not been established, and it is difficult to determine
if it is a true change in cardiac defects among patients with Down syndrome or
if it is secondary to increased prenatal diagnosis and pregnancy termination.4
•• Edwards syndrome (trisomy 18)
•• Patau syndrome (trisomy 13)
•• 1p36 deletion syndrome
Diagnostic Approach
Diagnosis is established via clinical suspicion on the basis of phenotype and is
confirmed by performing chromosome analysis. This will provide the mechanism
of the chromosomal abnormality and help determine a recurrence risk for future
246
CCIP.indb 246 3/13/18 4:18 PM

Common Syndromes Associated With Cardiac Lesions
pregnancies. Fluorescent in situ hybridization (FISH) may also be performed if

establishing a diagnosis rapidly is important; however, this must be followed by
chromosome analysis to determine the mechanism and recurrence risks.
Management
Cardiac-Specific Management
Management of the cardiac abnormalities in Down syndrome is dependent on
the specific lesion and severity. Although there are no contraindications for car-
diac surgery, it is important to keep in mind that patients with Down syndrome
are at increased risk for developing pulmonary arterial hypertension.5
Management of Other Issues
Routine health screening for patients with Down syndrome should be performed
in accordance with the American Academy of Pediatrics (AAP) Clinical Report
on the Health Supervision for Children with Down Syndrome (see the resources
at the end of this section). Baseline screening should be performed for associated
complications of Down syndrome, particularly feeding problems, hypotonia,
vision problems, constipation, thyroid dysfunction, hematologic abnormalities,
and identification of congenital heart defects.
Ongoing Care
Aside from screening per the AAP Clinical Report on the Health Supervision
for Children with Down syndrome,6 routine well-child concerns should also be
addressed. Growth should be monitored carefully by using growth curves specific
to children with trisomy 21. Early intervention for special-needs services should
be in place. Age-appropriate anticipatory guidelines should be provided, as well.
Resources
•• American Academy of Pediatrics. Health supervision for children with
Down syndrome. Pediatrics. 2011;128(2):393–406
•• National Down Syndrome Society. www.ndss.org
Trisomy 18 (Edwards Syndrome)

Introduction
Trisomy 18 (Edwards syndrome) is the second most common trisomy after
trisomy 21, affecting approximately 1 in 4,000 fetuses and 1 in 5,000 newborns.7
Because trisomy 18 pregnancies have a higher risk of stillbirth and fetal loss, the
overall pregnancy prevalence is higher than the live-birth prevalence.8
247
CCIP.indb 247 3/13/18 4:18 PM

Pathophysiology
Most cases of trisomy 18 result from presence of an extra copy of chromosome
18 because of meiotic nondisjunction. A small proportion of cases result
from mosaicism caused by postzygotic nondisjunction or anaphase lag and
translocation.9 As in other trisomies, the incidence increases with advancing
maternal age.10 A small positive association of paternal age with trisomy 18 has
also been reported.11
Clinical Features
Edwards syndrome is characterized by prenatal growth deficiency, craniofacial
features and other minor anomalies, major malformations, and marked psycho
motor and developmental delay. Typical craniofacial features include dolicho-
cephaly, short palpebral fissures, micrognathia, external anomalies of the ears,
and redundant skin at the back of the neck. Other findings include clenched fists
with overriding fingers, small fingernails, underdeveloped thumbs, short sternum,
and rocker bottom or clubfeet.
Structural anomalies of various organ systems include genitourinary
abnormalities in 25% to 75% of patients, mostly horseshoe kidney. Other
less frequently affected organ systems include the gastrointestinal tract with
omphalocele and/or tracheoesophageal fistula, central nervous system with
cerebellar hypoplasia, microphthalmia, and limb anomalies, including radial
aplasia or hypoplasia.8
Congenital heart defects are almost always present in patients with Edwards
syndrome. The frequency of heart defects reported in autopsies and echo-
cardiography studies is more than 90%.7,12 VSDs and PDA are considered
major anomalies and were originally described in the report of Edwards and
colleagues.13 Polyvalvular disease, characterized by involvement of 2 or more AV
and/or semilunar valves, has also been frequently reported.14,15 A more complex
form of cardiac malformation, such as double-outlet right ventricle, endocardial
cushion defect, or left-sided obstructive lesion, is present in about 10% of cases.16
•• Pena Shokeir syndrome type 1 or syndromes with fetal akinesia sequence
(polyhydramnios with joint contractures, including overriding fingers)
•• CHARGE syndrome (overlapping major organ malformations, including
coloboma of the eye, heart anomaly, choanal atresia, retardation, and genital
and ear anomalies)
248
CCIP.indb 248 3/13/18 4:18 PM

Diagnostic Approach
The index of suspicion for Edwards syndrome is based on the clinical presen
tation. The diagnosis of trisomy 18 is usually confirmed via chromosome analysis
that shows either partial or complete trisomy of chromosome 18. If there is
clinical urgency, FISH is available for rapid diagnosis, but results must be con-
firmed with routine chromosome analysis.17
Management
Neonatal management is based on the complexity and severity of the presen-
tation at birth. Historically, trisomy 18 was considered a condition for which
nonintervention for a newborn was indicated.18 However, the recent neonatal
resuscitation guidelines from the American Heart Association omit this con
dition from the list of conditions for which resuscitation is not indicated.19
There has always been controversy about management of cardiac lesions in
these patients. Traditionally, heart defects have been managed conservatively.
Some investigators have suggested that palliative and corrective cardiac surgeries
can be considered in selected cases.20 However, this remains a topic of dispute.
In the newborn period and thereafter, growth retardation and feeding issues
remain a major problem, and patients with Edwards syndrome usually require
nasogastric tube feeding or, in older children, gastrostomy tube placement.21
Respiratory problems, caused by either upper-airway obstruction or central
apnea, can lead to early-onset pulmonary hypertension.8 Renal and urologic
workup is needed for potential structural genitourinary tract abnormalities and
an increased risk for urinary tract infections. Functional neurological features
include hypotonia in infancy, hypertonia in older children, central apnea, and
seizures in about 25% of patients.16
Ongoing Care
After hospital discharge, there should be appropriate follow-up visits and pedi-
atric subspecialty care. The number and frequency of health supervision visits
depend on the child’s specific needs. Usually, immunization and anticipatory
guidance are similar to those for other children. However, decisions related to
specific medical treatment should be made after discussion with the parents and
medical team.
In a literature review published by Cereda and Carey, the schedule for clinical
and laboratory referrals and follow-up visits is specified in tabular form.8
249
CCIP.indb 249 3/13/18 4:18 PM

Resources
•• Trisomy 18 Foundation. www.trisomy18.org
•• Hope for Trisomy 13 and 18. www.hopefortrisomy13and18.org
•• Centre for Genetics Education. www.genetics.edu.au
Trisomy 13 (Patau Syndrome)

Introduction
Trisomy 13 (Patau syndrome) is the third most common chromosomal
aneuploidy seen in live births. It has a reported incidence of 1 in 8,000 to 1 in
15,000 live births, with a female predominance. It is characterized by severe
neurocognitive impairment and multiple congenital anomalies. As with the
other aneuploidies, advancing maternal age imparts an increased risk.
Pathophysiology
Only about three-quarters of trisomy 13 cases are caused by an extra copy of
chromosome 13 that arises from meiotic nondisjunction. Other cases are func-
tionally equivalent to trisomy 13 and are commonly caused by a translocation
between chromosome 13 and another chromosome, often chromosome 14
(Robertsonian translocation), or by trisomy 13 mosaicism. Most cases of trisomy
13 are not inherited; however, trisomy 13 caused by a translocation may recur if
either parent is found to be a balanced carrier of the translocation.
Clinical Features
Clinical features associated with trisomy 13 are highly variable. Clinically signif-
icant features include midline defects, such as variations of holoprosencephaly,
hypotelorism, and cleft lip and palate. Microphthalmia or anophthalmia can be
seen, as well as postaxial polydactyly and limb abnormalities. Kidney abnormal-
ities, such as multicystic kidney disease, horseshoe kidney, and hydronephrosis,
are often described. A characteristic scalp defect, known as cutis aplasia, may be
present. Other congenital anomalies include the presence of an omphalocele,
cryptorchidism, uterine abnormalities, and rib anomalies. Severe neurological
impairment is seen in individuals who live past their first year after birth.
Patients with mosaic trisomy 13 may have milder features of the disease.
Approximately 80% of individuals with trisomy 13 have a cardiac defect, with
the most common being atrial and ventricular defects.22 Patent ductus arteriosus
(PDA) and hypoplastic left heart syndrome are also seen.
250
CCIP.indb 250 3/13/18 4:18 PM

•• Trisomy 18, Edwards syndrome
•• Pseudotrisomy 13 syndrome
•• Meckel-Gruber syndrome
•• Smith-Lemli-Opitz syndrome
Diagnostic Approach
Given anomalies detected with prenatal ultrasonography (US) or other abnor-
mal prenatal screening findings, a diagnosis can be established by performing
chromosome analysis on a sample obtained via chorionic villus sampling or
amniocentesis. The same diagnostic test can be performed postnatally. FISH
can be performed if an urgent diagnosis is desired because this may alter the
type and extent of interventions desired for the patient. Conventional chromo-
some analysis should also be performed to determine recurrence risk.
Management
Patients with trisomy 13 are considered to have extremely poor prognosis,
and most do not survive past their first year of life. As a result, management is
complicated by a variety of ethical issues. Traditionally, management was equated
with comfort and palliative or hospice care. However, more medical interven-
tions are being performed on these patients, resulting in prolonged life spans.
Palliative and corrective cardiac surgery may be performed on some patients
after careful multidisciplinary evaluation and counseling.
Common surgical interventions may include upper gastrointestinal–related
procedures and orthopedic interventions, mostly involving tendon lengthening,
release, and transfer.23 In general, clinical decision-making should take into
account the overall clinical picture and not just the genetic diagnosis. The extent
of interventions performed should be determined in consideration of the types
of malformations present and their severity, as well as parental preferences.
Ongoing Care
Long-term management of patients with Patau syndrome is guided primarily
by comfort measures. There are no specific management guidelines, but patient-
specific interventions to improve quality of life may be indicated.
Resources
•• Unique. www.rarechromo.org
•• Support Organization for Trisomy 18, 13, and Related Disorders (SOFT).
trisomy.org
251
CCIP.indb 251 3/13/18 4:18 PM

22q11.2 Deletion Syndrome

Introduction
Chromosome 22q11.2 deletion syndrome, often referred to as DiGeorge
syndrome or velocardiofacial syndrome, is the most common contiguous gene
deletion syndrome, affecting about 1 in 2,000 to 1 in 4,000 live births.24 At
the mild end of its phenotypic spectrum, it was named for its clinical manifes-
tations. Its most severe form is named after Dr Angelo M. DiGeorge, who first
reported congenital absence of a thymus and parathyroid gland in 1965; later,
cardiac anomalies were added to the phenotype.25 When the genetic basis was
identified, it was discovered that these diagnoses represented opposite ends of
a phenotypic spectrum.
Pathophysiology
Patients with 22q11.2 deletion syndrome have heterozygous deletions in the
long arm of chromosome 22 at band 11.2. The congenital features can be related
to abnormal morphogenesis and function of pharyngeal arch system derivatives,
including craniofacial structures, thymus, parathyroid glands, aortic arch, and
cardiac outflow tracts as a result of haploinsufficiency of genes within the
deleted region.26
Clinical Features
The 22q11.2 deletion syndrome has marked clinical variability, and the clinical
presentation varies with age. In the childhood phenotype, typical features
include congenital heart defects, chronic or recurrent infections, nasal regur
gitation, hypernasal speech, hypocalcemia, feeding difficulties, developmental
delay, behavioral problems, and learning disabilities. Renal abnormalities,
laryngotracheoesophageal abnormalities, intrauterine growth retardation, short
stature, vertebral anomalies, clubfeet, scoliosis, hearing loss, microcephaly, and
hypotonia are also seen, but less frequently.26

Neonatal hypocalcemia secondary to hypoparathyroidism is found in about
50% to 65% of patients and can lead to fatigue, stridor, feeding difficulty,
seizures, and tetany.24,27 Hypoparathyroidism is often transient and resolves after
the neonatal period, but it may manifest later in life as hypocalcemic episodes
during stress, such as infections, surgery, or pregnancy. Another key feature is
immunodeficiency due to thymic aplasia. The degree of immunodeficiency is
highly variable and might include defects in T lymphocyte number and function,
as well as humoral defects. Borderline intellectual dysfunction (IQ of 70 to 75) is
common in these patients.25 Psychiatric problems have also been described, such
as attention-deficit hyperactivity disorder, anxiety disorders, depression, autism
252
CCIP.indb 252 3/13/18 4:18 PM

spectrum disorder, and psychosis.28 Palatal abnormalities are seen in almost 70%
of patients, the most common being velopharyngeal incompetence that may
manifest as a structural problem (short palate) or as a functional problem that
leads to speech abnormalities, such as hypernasal speech.25,26 Most children with
22q11.2 deletion syndrome share typical dysmorphic facial features, including a
long face, malar flattening, hypertelorism, short palpebral fissures, hooded and/
or swollen eyelids, a broad nasal bridge, a bulbous nasal tip, micrognathia, a small
mouth, and small, low-set ears.29
Congenital heart defects are found in almost 80% patients with 22q11.2 deletion
syndrome and, together with neonatal hypocalcemia, are the most frequent
features that lead to diagnosis. Most cardiac abnormalities are conotruncal
heart defects, defined as malformations of the outflow tract that include TOF
(with or without pulmonary atresia), truncus arteriosus, interrupted aortic arch
type B (in between the left carotid artery and the left subclavian artery), and
double-outlet right ventricle.25,26 TOF is the most common defect in 22q11.2
deletion syndrome, but interrupted aortic arch type B is the most specific defect.
Nonconotruncal defects, such as VSDs, ASDs, and AV septal defects, can
also be seen. Aortic arch abnormalities most frequently include a right-sided
or double aortic arch, with or without aberrant subclavian arteries. These can
form a vascular ring in about 13% of patients, who can present with feeding
difficulties or respiratory symptoms.30 Pulmonary artery abnormalities include
diffuse hypoplasia and discontinuous pulmonary arteries, with or without major
aortopulmonary collateral arteries. About 10% of patients may have aortic root
dilation of unclear clinical significance.31
•• Smith-Lemli-Opitz syndrome (polydactyly, cleft palate)
•• Alagille syndrome (butterfly vertebrae, congenital heart disease [CHD])
•• VATER (vertebral defects, anal atresia, tracheoesophageal fistula with
esophageal atresia, and radial and renal anomalies) association
•• CHARGE syndrome (CHD, palatal anomalies, coloboma, choanal atresia,
renal problems, growth deficiency, ear anomalies)
•• Isolated TBX1 mutations (typical 22q11.2 deletion syndrome cardiac defects
without full syndromic features)
Diagnostic Approach
The decision to undergo diagnostic workup for 22q11.2 deletion syndrome
depends on the index of suspicion based on the clinical features described
previously. A combination of congenital heart defects associated with neonatal
hypocalcemia often leads to the diagnosis. Other phenotypic features, such
as facial dysmorphisms, can be mild and require a high index of suspicion.
253
CCIP.indb 253 3/13/18 4:18 PM

The current method of choice for diagnosis of 22q11.2 deletion syndrome is

array comparative genomic hybridization or chromosomal microarray analysis.
This has the advantage of being able determine the specific size of the deletion
and identify other contiguous gene deletions or duplications that might be
similar phenotypically to 22q11.2 deletions.
Management
A baseline cardiac evaluation by a cardiologist includes chest radiography,
electrocardiography (ECG), and echocardiography. In cases of suspected
vascular ring, magnetic resonance (MR) imaging or computed tomography
may be needed for evaluation. The further management of specific cardiac
lesions involves surgical correction of TOF and interrupted aortic arch.
The noncardiac management of patients with 22q11.2 deletion syndrome is
highly dependent on age and phenotype and thus requires a multidisciplinary
team approach that involves various subspecialties, including immunology;
audiology; child psychology; dental specialists; endocrinology; ear, nose, and
throat specialists; gastroenterology; neurology; clinical genetics; plastic surgery;
speech therapy; and urology, depending on the patient’s specific needs.
Calcium supplementation is needed for hypocalcemia, and further referral to
an endocrinologist and nephrologist is required for management of long-term
supplementation. For feeding difficulties, a gastroenterology evaluation is
required for the possibility of structural abnormalities, such as malrotation or
diaphragmatic hernia. Immunodeficiency may require prophylactic antibiotics
and requires aggressive treatment for treating infections. The presence or absence
of a thymus when a patient undergoes cardiac surgery should be noted. This
can aid in the diagnosis and treatment of the immunosuppression. Early imple-
mentation of speech therapy should be instituted in high-risk patients. Studies
have shown that early diagnosis and intervention for psychiatric illness improves
long-term prognosis in these patients.32
Ongoing Care
Patients with 22q11.2 deletion syndrome require periodic follow-up with their
pediatrician and subspecialists. Children with immunodeficiency should not
receive live vaccines until they have undergone a thorough re-evaluation of
immune status. Irradiated blood products should be used until normalization of
immune status is confirmed. Measurement of serum ionized calcium should be
conducted every 6 months and also pre- and postoperatively to avoid hypocal-
cemia-related complications during physical stressors. Annual complete blood
254
CCIP.indb 254 3/13/18 4:18 PM

counts and thyroid studies are also indicated. Repeat ophthalmology evaluation
between 1 and 5 years of age is needed, as is repeat audiology evaluation prior to
school enrollment. Patients with 22q11.2 deletion syndrome also require routine
surveillance for development of scoliosis.
Periodic re-evaluation by a clinical geneticist can be helpful in apprising the
family of new developments and recommendations, and a high proportion of
patients with 22q11.2 deletion syndrome have inherited their deletion from an
undiagnosed parent.
The recommendations for periodic assessments of patients with 22q11.2
deletion syndrome on the basis of an extensive literature review are clearly
outlined by Bassett and colleagues.33
Resources
•• Bassett AS, McDonald-McGinn DM, Devriendt K, et al. Practical
guidelines for managing patients with 22q11.2 deletion syndrome. J Pediatr.
2011;159(2):332–339.e1
•• The International 22q11.2 Foundation. www.22q.org
•• Chromosome 22 Central. www.c22c.org
Williams Syndrome
Introduction
Williams syndrome (also known as Williams-Beuren syndrome) is a multisystemic
disorder caused by a deletion of 26 to 28 contiguous genes on a 1.5- to 1.8-Mb
segment of DNA located at chromosome band 7q11.23.34,35 This disorder was
first identified in 1961.35 Most cases of Williams syndrome are sporadic. Its
prevalence is estimated at 1 in 7,500, and it affects male and female populations
equally.22 Patients with Williams syndrome usually come for medical attention in
infancy or early childhood on the basis of recognition of clinical features.
Pathophysiology
Williams syndrome is caused by a deletion at chromosome band 7q11.23 that
includes the elastin gene (ELN). It is the haploinsufficiency of elastin that is
responsible for the cardiovascular features. There are, however, other genes within
the typical deletion that are believed to influence the other features of Williams
syndrome, such as the cognitive profile, hypercalcemia, facial features, glucose
metabolism, and hypertension.
255
CCIP.indb 255 3/13/18 4:18 PM

Clinical Features
The typical clinical features of Williams syndrome include facial dysmorphisms,
cardiovascular disease, developmental delays, a characteristic behavioral profile,
and hypercalcemia.
The facial features are characteristic and are typically described as “elfin
facies.” These include a broad forehead, bitemporal narrowing, depressed nasal
root, periorbital fullness, stellate or lacy iris pattern, malar flattening, a long
philtrum, thick vermilion of the lips, dental malocclusion, and prominent
earlobes.35 Patients with Williams syndrome are known to have an outgoing or
social personality. Other abnormalities include infantile hypercalcemia, skeletal
anomalies, renal anomalies, and cognitive deficits.22
The typical cardiovascular abnormalities are supravalvular aortic stenosis,
supravalvular pulmonary stenosis, and peripheral pulmonary stenosis. The
cardiovascular abnormalities are from haploinsufficiency of elastin, which is a
major constituent of blood vessel walls.36 Interestingly, male subjects are more
likely than female subjects to have severe cardiovascular disease.37

Among the cardiovascular abnormalities, supravalvular aortic stenosis is the
most clinically significant lesion and is present in about three-quarters of indi-
viduals with Williams syndrome.35 It can occur as a localized, hourglass-shaped
narrowing in the aortic supravalvular area at the sinotubular junction, or it may
be diffuse, extending into the aortic arch and up to the origin of the brachio-
cephalic vessels. It may occur in conjunction with supravalvular pulmonary
stenosis. It is usually a progressive lesion, leading to left ventricular outflow
obstruction, compared to supravalvular pulmonary stenosis that can improve
with time.38 Peripheral pulmonary stenosis is seen mostly in infancy and usually
improves as the child grows.
Other cardiovascular abnormalities and coronary artery abnormalities can be
seen in up to 5% of patients with Williams syndrome. These can include coronary
ostial stenosis, diffuse coronary artery stenosis, coarctation of the aorta, VSDs,
aortic valve abnormalities, and mitral valve prolapse.39 Renal artery stenosis and
systemic hypertension may also occur and worsen over time. Rhythm abnormali
ties, including prolongation of the corrected QT interval, have also been reported.40
•• Noonan syndrome
•• 22q11.2 deletion syndrome
•• Kabuki syndrome
•• Fetal alcohol syndrome
•• Isolated ELN gene mutations
256
CCIP.indb 256 3/13/18 4:18 PM

Common S
yndromes Associated With Cardiac Lesions
Diagnostic Approach
The diagnosis of Williams syndrome is indicated by the clinical presentation,
including the typical appearance and behaviors and hypercalcemia, and is
confirmed via array comparative genomic hybridization or chromosomal
microarray analysis.
Once the diagnosis of Williams syndrome is confirmed, the patient should
be referred to a pediatric cardiologist. An appropriate cardiology evaluation will
include comprehensive clinical examination, including 4-limb blood pressure
measurements, ECG, and echocardiography. Because these patients are prone to
developing hypertension, they require periodic screening. Close attention must
be paid to the presence of abdominal bruits at examination that may indicate the
presence of renal artery stenosis. Among the laboratory workup, renal function
tests, urinalysis, serum calcium determinations, and thyroid screening are
important. Referral to a clinical geneticist should be considered.40
Management
The treatment approach generally depends on the severity of the vascular lesions.
Patients with Williams syndrome who have mild arterial stenosis are less likely
to develop progressive disease and can be closely monitored. In patients who
develop systemic hypertension, angiotensin-converting enzymes should not be
used until renal artery stenosis has been ruled out. Dihydropyridine-type calcium
channel blockers are effective in treating hypertension in patients with Williams
syndrome. The use of β-blockers may serve as an additional benefit in potentially
decreasing the risk of ventricular arrhythmias in patients who have prolonged
QT intervals.41

Surgical or transcatheter management is required in about 20% of the
patients with Williams syndrome who have cardiovascular abnormalities; the
need for intervention is even higher in those who present in the first year after
birth. Most of the surgical intervention is in patients with a severe degree of
supravalvular aortic stenosis because transcatheter interventions are usually
ineffective for these patients.37
Children who receive a diagnosis of Williams syndrome require a baseline rou-
tine health examination, in addition to cardiac examination. Feeding issues that
must be addressed frequently include problems with reflux and swallowing. Early
recognition and management of constipation is also helpful. Growth evaluations
should be performed by using diagnosis-specific growth charts. Ophthalmologic
evaluation and an objective hearing assessment are essential. Baseline laboratory
testing of serum calcium level, urine, and serum creatinine level is needed. US
257
CCIP.indb 257 3/13/18 4:18 PM

of the kidneys should be ordered with a referral to nephrology if there are renal
abnormalities.
Ongoing Care
Patients with Williams syndrome need regular follow-up with periodic referrals.
Serum calcium measurements are required every 4 to 6 months until 2 years of
age. An annual comprehensive visit should include medical evaluation, vision
screening to monitor the patient for refractive errors and strabismus, hearing
evaluation, blood pressure measurements in both arms, and urinalysis with
measurement of the calcium-creatinine ratio. Other laboratory workup should
include serum calcium measurements every 2 years and thyroid function tests
every 3 years. A yearly cardiology evaluation should be conducted for the first
5 years of life and then every 2 to 3 years after that. A renal-bladder US exam-
ination should be performed every 10 years.35

The AAP published guidelines for health care supervision for children
with Williams Syndrome in 2001. These guidelines have specifically laid down
follow-up plans for different age groups.40
Resources
•• American Academy of Pediatrics Committee on Genetics. Health care super-
vision for children with Williams syndrome. Pediatrics. 2001;107:1192–1204
•• Williams Syndrome Association. www.williams-syndrome.org
•• Williams Syndrome Foundation. www.williams-syndrome.org.uk
Turner Syndrome
Introduction
Turner syndrome consists of a constellation of features, including short stature,
sexual infantilism, webbed neck, and cubitus valgus; it was originally described
by Henry Turner in 1938.42 With the advent of chromosome analysis, Turner
syndrome was found to be caused by the loss of an X chromosome. The birth
prevalence of Turner syndrome has been estimated to be from 1 in 2,000 to 1
in 5,000 female live births.43
Pathophysiology
Approximately 45% of patients with Turner syndrome have a simple 45,X
cell line, without mosaicism; 15% have an isochromosome Xq. The other
causes of Turner syndrome include a variety of chromosome abnormalities,
including mosaicism with 46,XX, 46,XY, or other chromosome compliments.
Turner syndrome features result from haploinsufficiency of multiple genes
on the X chromosome that affect embryological development, stature, and
gonadal function.42,44
258
CCIP.indb 258 3/13/18 4:18 PM

Clinical Features
The key features of Turner syndrome include a lack of breast development and
amenorrhea, with increased follicle-stimulating hormone levels by 14 years of
age and infertility.44 Other characteristics include short stature, a webbed neck, a
low posterior hair line, misshapen or rotated ears, a narrow palate with crowded
teeth, a broad chest with widely spaced nipples, cubitus valgus, hyperconvex nails,
multiple pigmented nevi, pubertal delay, and cardiac malformation.44 With the
exception of familial short stature or constitutional delay, Turner syndrome is
the most common cause of short stature in otherwise healthy girls.45 Patients
with Turner syndrome also have higher risks for hypothyroidism, diabetes, heart
disease, osteoporosis, congenital malformations, neurovascular disease, cirrhosis
of the liver, and colorectal cancers when compared to the general population.46
Cardiac abnormalities are seen in about 30% of individuals with Turner syn-
drome and represent a leading cause of mortality in these patients. The incidence
is higher in patients with 45,X monosomy than in those with mosaicism.47 The
main cardiac abnormalities are left-sided lesions, the most common of which are
bicuspid aortic valve (16%) and coarctation of the aorta (11%) or a combination
of these 2 abnormalities. Hypertension, mitral valve prolapse, and conduction
defects also occur.45,47,48

Up to 40% of girls with Turner syndrome have hypertension.49 There have
been reports of aortic root dissection in patients with Turner syndrome, and
more than 90% of these patients had a bicuspid aortic valve, coarctation of the
aorta, systemic hypertension, or a combination of these.45,49 Pulmonary and
systemic venous return abnormalities can also be seen.47
•• Noonan syndrome (these patients have normal karyotype, and cardiac lesions
are mostly right sided, the most common being pulmonic stenosis)
•• Other conditions leading to short stature, such as constitutional delay, must
also be considered
•• Gonadal dysgenesis because of other chromosome abnormalities
Diagnostic Approach
One-fifth to one-third of affected girls receive diagnoses of Turner syndrome
in the newborn period because of puffy hands and feet or redundancy of nuchal
skin, the residual effect of a cystic hygroma in utero. About one-third of girls
receive diagnoses of Turner syndrome in mid-childhood during workup for
short stature. In most other patients, Turner syndrome is diagnosed either in
adolescence because of pubertal delay or in adulthood because of infertility. The
259
CCIP.indb 259 3/13/18 4:18 PM

diagnosis should be excluded in any teenage girl with amenorrhea, especially

with short stature.45

Chromosomal analysis of at least 30 peripheral lymphocytes is the test
of choice for confirmation of a diagnosis of Turner syndrome. Chromosome
analysis usually takes about 1 week. In cases in which a result is urgently needed,
X-specific FISH can be used to identify monosomy X (45,X) in less than
24 hours; however, this must be followed by chromosome analysis to determine
the mechanism and recurrence risks.
Management
With the high incidence of cardiac involvement, patients with Turner syndrome
must undergo a baseline cardiology evaluation as part of the initial workup.
This includes an echocardiogram obtained in a pediatric cardiology center. For
patients identified in the perinatal period, this must be conducted prior to dis-
charge from the hospital because of the risk of a ductus-dependent coarctation.
Ascending aorta measurements should also be performed. MR imaging can
be conducted in cases of aortic root dilation to assess the severity. The schedule
and nature of the cardiology follow-up should be directed by the pediatric
cardiologist and be individualized to the patient’s needs. Women with Turner
syndrome often have hypertension as a result of aortic abnormality or renal
vascular disorder. Therefore, medications should be administered to control
blood pressure to minimize potentially fatal complications.
Because of the multisystemic nature of Turner syndrome, the primary care pedi-
atrician plays an important role in direct management, as well as in coordination
of multidisciplinary care.
Growth hormone therapy is the standard care for children with Turner
syndrome if their height falls below the fifth percentile for age. Growth hormone
can be started as early as 2 years of age in children with early growth failure.43
Obesity may be a problem, so diet and exercise for weight control must be
discussed.50 Diabetes mellitus type II can be well controlled with medication
and careful blood glucose monitoring. Hypothyroidism must be addressed, and
proper thyroid supplementation must be used. Spontaneous fertility is rare in
these patients. Given the sense of loss that occurs with infertility, physicians
should reassure patients about sexual function and discuss reproductive options.45
Ongoing Care
In patients with Turner syndrome who have normal cardiac evaluation findings
during childhood, the pediatrician should pay special attention to cardiovascular
examination, including blood pressure, peripheral pulses, and murmurs. At
260
CCIP.indb 260 3/13/18 4:18 PM

routine clinic visits, the pediatrician should perform weight checks, eye evalu-
ation for development of cataracts or strabismus, ear examination to check for
serous otitis media, and evaluation for hearing loss and speech delays. Growth
must be closely monitored by using diagnosis-specific growth charts for girls
with Turner syndrome. The Turner Syndrome Consensus Study Group has
guidelines endorsed by the AAP for routine supervision and ongoing care of
these patients.43
Resources
•• Turner Syndrome Society of the United States. www.turnersyndrome.org
•• Turner Syndrome Foundation. www.turnersyndromefoundation.org
•• The MAGIC Foundation. www.magicfoundation.org
Noonan Syndrome
Introduction
Noonan syndrome is a clinically and genetically heterogeneous, autosomal
dominant disorder characterized by distinct facial features, heart defects, short
stature, and developmental delay. It is the second most common cause of
syndromic CHD next to trisomy 21.51 It has a reported incidence of 1 in 1,000
to 1 in 2,500 live births. Most cases are sporadic, with no known risk factors
identified. Noonan syndrome is part of a spectrum of diseases with overlapping
features, called RASopathies.
Pathophysiology
Gene mutations in the RAS-mitogen activated protein kinase pathway cause
Noonan syndrome. This signal transduction pathway is involved in cell prolif-
eration, differentiation, and metabolism. About 10 genes have been identified
as causing Noonan syndrome, but about 50% of cases have been attributed to
mutations in the PTPN11 gene.52
Clinical Features
Distinct facial features associated with Noonan syndrome include widely spaced
and downward-slanting eyes, ptosis, epicanthal folds, and low-set ears. Facial
features typically evolve with age. Other hallmarks of the syndrome include
postnatal short stature, broad or webbed neck, chest deformities that include
a superior pectus carinatum and inferior pectus excavatum, and widely set
nipples. Patients with Noonan syndrome may also have minor renal anomalies;
cryptorchidism; hematologic abnormalities, including coagulation defects and
malignancies; musculoskeletal anomalies; eye anomalies, including strabismus,
261
CCIP.indb 261 3/13/18 4:18 PM

amblyopia, and anterior and posterior segment anomalies; lymphatic system

abnormalities, such as peripheral lymphedema and chylous effusions; skin prob-
lems, including pigmentation abnormalities and keratosis pilaris; and hearing
loss. The degree of cognitive impairment is variable but has been reported to be
in the normal to moderately impaired range.51
It is estimated that approximately 80% to 90% of individuals with Noonan
syndrome will have an identifiable heart defect.22 The most commonly associated
cardiac abnormalities are pulmonary valve stenosis and hypertrophic cardiomy-
opathy. Other structural abnormalities include AV septal defects, coarctation of
the aorta, mitral valve abnormalities, and coronary artery anomalies.51
•• Other RASopathies: cardiofaciocutaneous syndrome, Costello syndrome,
neurofibromatosis type 1, Legius syndrome, Noonan syndrome with multiple
lentigines (formerly called LEOPARD syndrome), and Noonan syndrome–like
disorder with loose anagen hair
•• Turner syndrome
Diagnostic Approach
The diagnosis of Noonan syndrome should be suspected in patients manifesting
multiple features associated with the syndrome. It is a clinical diagnosis
that should be molecularly confirmed. The diagnostic criteria for Noonan
syndrome were published in 1994 by van der Burgt and colleagues53 but have
not been widely used in the clinical setting.51,54 Confirmation of the diagnosis
is performed molecularly via multigene panel testing that contains the known
RASopathy genes.
Management
Timely referral to a cardiologist is warranted once a cardiac defect has been
identified. Management is dependent on the type and severity of the abnormal-
ity. Pulmonary valve stenosis can be managed with balloon valvuloplasty, with
more invasive open heart surgery reserved for severe cases. In most cases, mild
stenosis only requires routine follow-up. Similarly, the approach for management
of hypertrophic cardiomyopathy in Noonan syndrome is based on the severity,
which may range from mild to severe and may manifest prenatally to late in
childhood.51 Survival of patients who have Noonan syndrome with hypertrophic
cardiomyopathy is worse than those without hypertrophic cardiomyopathy and
those with isolated hypertrophic cardiomyopathy.55
262
CCIP.indb 262 3/13/18 4:18 PM


After establishing the diagnosis, complete syndromic surveillance for associated
abnormalities should be performed. Specific diagnostic tests have been presented
in various publications54,56 and have been summarized in the Noonan Syndrome
Management Guideline published in 2010 by the AAP.57

Particular to Noonan syndrome is the management of short stature and the
role of growth hormone in treatment. Diagnosis-specific growth curves are
available for individuals with Noonan syndrome.58 Use of these curves may help
identify patients who may benefit from treatment with human growth hormone.
Ongoing Care
Follow-up of patients with Noonan syndrome is important because problems
may be progressive, and associated features occur at various ages. A multidis-
ciplinary medical team is often required. Follow-up needs are also outlined in
the AAP guidelines. The prognosis is usually dependent on the existing cardiac
abnormality and other findings, such as the presence of malignancy.
Resources
•• Romano AA, Allanson JE, Dahlgren J, et al. Noonan syndrome: clinical fea-
tures, diagnosis, and management guidelines. Pediatrics. 2010;126(4):746–759
•• Noonan Syndrome Foundation. www.teamnoonan.org
•• Noonan Syndrome Association. www.noonansyndrome.org.uk
•• RASopathiesNet. rasopathiesnet.org
Pompe Disease (Glycogen Storage Disease

Type II)
Introduction
Pompe disease is a highly variable autosomal recessive lysosomal storage disorder
that causes progressive neuromuscular degeneration. Unique to its infantile
form is hypertrophic cardiomyopathy. Pompe disease has an incidence of 1 in
40,000 in the general population but approximately 1 in 14,000 in the African
American population.59 Most cases appear to be sporadic, although there is a
25% recurrence risk for the parents; there are no identified risk factors.
Pathophysiology
Pompe disease is caused by a deficiency of the lysosomal enzyme acid α-glucosidase
(GAA) that results from mutations in the GAA gene. The absence of functional
enzyme leads to the accumulation of glycogen in the lysosomes in cells of the
heart, skeletal muscle, smooth muscle, and nervous system. This accumulation in
turn causes structural and cellular dysfunction and abnormal autophagy.59
263
CCIP.indb 263 3/13/18 4:18 PM

Clinical Features
The onset of Pompe disease is extremely variable, occurring prenatally to the
fifth or sixth decade. The symptoms of Pompe disease vary on the basis of age of
onset and severity. Infantile-onset Pompe disease may manifest with hypotonia,
progressive weakness, hepatomegaly, feeding difficulties, failure to thrive, cardiac
hypertrophy, and respiratory difficulties. These symptoms may manifest within
the first few days or weeks after birth and, in the absence of early intervention,
can be rapidly progressive and lethal. In the late-onset form of the disease, there
is no cardiac hypertrophy, but patients experience progressive muscular weakness
that may also lead to respiratory failure.
The hallmark of infantile-onset Pompe disease is hypertrophic cardiomyopathy
and extremely high voltages at ECG. Other cardiac abnormalities described
include cardiomegaly, left ventricular outflow tract obstruction, and shortened
PR interval with a broad, wide QRS complex. Late-onset Pompe disease, on
the other hand, is less frequently associated with cardiac disease. However, left
ventricular hypertrophy, dilatation of the ascending aorta, and Wolff-Parkinson-
White (WPW) syndrome may be seen.59
•• Spinal muscular atrophy type 1
•• Danon disease (hypertrophic cardiomyopathy and WPW due to a
LAMP2 mutation)
•• Glycogen storage disease type IIIa (debrancher deficiency, Cori or
Forbes disease)
•• Glycogen storage disease IV (branching enzyme deficiency, Anderson disease)
•• Mitochondrial disorder, respiratory chain disorders
Diagnostic Approach
Suspicion for Pompe disease should be high in the presence of cardiomyopathy
in an infant with or without hypotonia. Obtaining a creatine kinase level may
be helpful in supporting the diagnosis, especially if it is greater than 2,000 IU/L
(33.33 mkat/L). Creatine kinase levels can, however, be within the normal range
in late-onset Pompe disease. Definitive diagnosis is obtained by measuring
GAA enzyme activity from a blood sample (dried blood spot), muscle, or skin
fibroblast. Further confirmation of the diagnosis is obtained by performing
molecular genetic testing on the GAA gene. In rare instances, a muscle biopsy
may be performed and will show periodic acid–Schiff–positive vacuolar myop-
athic abnormalities with acid phosphatase–positive vacuoles. Membrane-bound
glycogen accumulation is pathognomonic.
264
CCIP.indb 264 3/13/18 4:18 PM

Management
A high index of suspicion is important because early initiation of enzyme
replacement therapy with alglucosidase alfa is necessary to prevent primary
manifestations and limit the progression of Pompe disease.
Once a diagnosis is established, performing baseline cardiac studies, specifically
echocardiography and ECG, is essential. These studies should be performed
periodically to monitor the patient for the development of cardiomyopathy and
arrhythmias. These cardiac changes have been reported to show good response
and even resolution after starting enzyme replacement therapy.
Pulmonary function must also be monitored for any signs of insufficiency as
diaphragmatic and intercostal muscle weakness progresses. Initiation of supple-
mental oxygen therapy or noninvasive ventilator support (continuous positive
airway pressure or bilevel positive airway pressure) may be beneficial. Children
with Pompe disease have feeding issues and failure to thrive because of weakness
of facial muscles and swallowing difficulties. Tube feedings may be necessary
to provide adequate calories. It is also essential that they undergo baseline and
routine motor functional assessments to promote muscle strengthening and pre-
vent contractures and deformities. The effects of enzyme replacement therapy on
other skeletal manifestations of the disease, such as weakness, have been variable.
Ongoing Care
Aside from complications related to muscular dysfunction, ongoing care of
individuals with Pompe disease includes good infection control and routine
vaccination. Recommendations for the care of patients with Pompe disease
were published in 2006 by the American College of Medical Genetics.60

Prognosis is dependent on the extent and progression of disease. Prior to
enzyme replacement therapy, patients with infantile onset had a median survival
of less than 8 months because of cardiorespiratory failure. Since the advent of
enzyme replacement therapy, the prognosis for patients has slowly changed,
with improved cardiac and motor function.
Resources
•• ACMG Work Group on Management of Pompe Disease, Kishnani PS,
Steiner RD, et al. Pompe disease diagnosis and management guideline.
Genet Med. 2006;8(5):267–288
•• Acid Maltase Deficiency Association. www.amda-pompe.org
•• International Pompe Association (IPA). www.worldpompe.org
265
CCIP.indb 265 3/13/18 4:18 PM

References
1) Parker SE, Mai CT, Canfield MA, et al; National Birth Defects Prevention Network. Updated
National Birth Prevalence estimates for selected birth defects in the United States, 2004-2006.
Birth Defects Res A Clin Mol Teratol. 2010;88(12):1008–1016
2) Stoll C, Dott B, Alembik Y, Roth MP. Associated congenital anomalies among cases with
Down syndrome. Eur J Med Genet. 2015;58(12):674–680
3) Bergström S, Carr H, Petersson G, et al. Trends in congenital heart defects in infants with
Down syndrome. Pediatrics. 2016;138(1):e20160123
4) Riehle-Colarusso T, Oster ME. Down syndrome: changing cardiac phenotype? Pediatrics.
2016;138(1):e20161223
5) Dimopoulos K, Wort SJ, Gatzoulis MA. Pulmonary hypertension related to congenital heart
disease: a call for action. Eur Heart J. 2014;35(11):691–700
6) Bull MJ; Committee on Genetics. Health supervision for children with Down syndrome.
Pediatrics. 2011;128(2):393–406
7) Embleton ND, Wyllie JP, Wright MJ, Burn J, Hunter S. Natural history of trisomy 18. Arch Dis
Child Fetal Neonatal Ed. 1996;75(1):F38–F41
8) Cereda A, Carey JC. The trisomy 18 syndrome. Orphanet J Rare Dis. 2012;7:81
9) Carothers AD, Boyd E, Lowther G, et al. Trends in prenatal diagnosis of Down syndrome and
other autosomal trisomies in Scotland 1990 to 1994, with associated cytogenetic and epidemio-
logical findings. Genet Epidemiol. 1999;16(2):179–190
10) Savva GM, Walker K, Morris JK. The maternal age-specific live birth prevalence of trisomies 13
and 18 compared to trisomy 21 (Down syndrome). Prenat Diagn. 2010;30(1):57–64
11) De Souza E, Morris JK, Group EW; EUROCAT Working Group. Case-control analysis of
paternal age and trisomic anomalies. Arch Dis Child. 2010;95(11):893–897
12) Rasmussen SA, Wong LY, Yang Q, May KM, Friedman JM. Population-based analyses of
mortality in trisomy 13 and trisomy 18. Pediatrics. 2003;111(4 Pt 1):777–784
13) Edwards JH, Harnden DG, Cameron AH, Crosse VM, Wolff OH. A new trisomic syndrome.
Lancet. 1960;1(7128):787–790
14) Lin HY, Lin SP, Chen YJ, et al. Clinical characteristics and survival of trisomy 18 in a medical
center in Taipei, 1988-2004. Am J Med Genet A. 2006;140(9):945–951
15) Niedrist D, Riegel M, Achermann J, Schinzel A. Survival with trisomy 18—data from
Switzerland. Am J Med Genet A. 2006;140(9):952–959
16) Carey JC, Kosho T. Perspectives on the care and advances in the management of children with
trisomy 13 and 18. Am J Med Genet C Semin Med Genet. 2016;172(3):249–250
17) Rosa RF, Rosa RC, Zen PR, Graziadio C, Paskulin GA. Trisomy 18: review of the clinical,
etiologic, prognostic, and ethical aspects. Rev Paul Pediatr. 2013;31(1):111–120
18) Paris JJ, Weiss AH, Soifer S. Ethical issues in the use of life-prolonging interventions for an
infant with trisomy 18. J Perinatol. 1992;12(4):366–368
19) Association AH; American Heart Association. 2005 American Heart Association (AHA)
guidelines for cardiopulmonary resuscitation (CPR) and emergency cardiovascular care
(ECC) of pediatric and neonatal patients: pediatric basic life support. Pediatrics. 2006;117(5):
e989–e1004
20) Maeda J, Yamagishi H, Furutani Y, et al. The impact of cardiac surgery in patients with trisomy
18 and trisomy 13 in Japan. Am J Med Genet A. 2011;155A(11):2641–2646
21) Baty BJ, Blackburn BL, Carey JC. Natural history of trisomy 18 and trisomy 13: I. Growth,
physical assessment, medical histories, survival, and recurrence risk. Am J Med Genet.
1994;49(2):175–188
266
CCIP.indb 266 3/13/18 4:18 PM

22) Pierpont ME, Basson CT, Benson DW Jr, et al; American Heart Association Congenital
Cardiac Defects Committee, Council on Cardiovascular Disease in the Young. Genetic basis
for congenital heart defects: current knowledge: a scientific statement from the American Heart
Association Congenital Cardiac Defects Committee, Council on Cardiovascular Disease in the
Young: endorsed by the American Academy of Pediatrics. Circulation. 2007;115(23):3015–3038
23) Nelson KE, Rosella LC, Mahant S, Guttmann A. Survival and surgical interventions for
children with trisomy 13 and 18. JAMA. 2016;316(4):420–428
24) Swillen A, McDonald-McGinn D. Developmental trajectories in 22q11.2 deletion. Am J Med
Genet C Semin Med Genet. 2015;169(2):172–181
25) Hacıhamdioğlu B, Hacıhamdioğlu D, Delil K. 22q11 deletion syndrome: current perspective.
Appl Clin Genet. 2015;8:123–132
26) McDonald-McGinn DM, Sullivan KE, Marino B, et al. 22q11.2 deletion syndrome. Nat Rev
Dis Primers. 2015;1:15071
27) Cheung EN, George SR, Costain GA, et al. Prevalence of hypocalcaemia and its associated
features in 22q11·2 deletion syndrome. Clin Endocrinol (Oxf ). 2014;81(2):190–196
28) Schneider M, Debbané M, Bassett AS, et al; International Consortium on Brain and Behavior
in 22q11.2 Deletion Syndrome. Psychiatric disorders from childhood to adulthood in 22q11.2
deletion syndrome: results from the International Consortium on Brain and Behavior in 22q11.2
Deletion Syndrome. Am J Psychiatry. 2014;171(6):627–639
29) Hacıhamdioğlu B, Berberoğlu M, Şıklar Z, et al. Case report: two patients with partial
DiGeorge syndrome presenting with attention disorder and learning difficulties. J Clin Res
Pediatr Endocrinol. 2011;3(2):95–97
30) McElhinney DB, McDonald-McGinn D, Zackai EH, Goldmuntz E. Cardiovascular anomalies
in patients diagnosed with a chromosome 22q11 deletion beyond 6 months of age. Pediatrics.
2001;108(6):E104
31) John AS, McDonald-McGinn DM, Zackai EH, Goldmuntz E. Aortic root dilation in patients
with 22q11.2 deletion syndrome. Am J Med Genet A. 2009;149A(5):939–942
32) Clarke M, O’Callaghan E. Is earlier better? At the beginning of schizophrenia: timing and
opportunities for early intervention. Psychiatr Clin North Am. 2003;26(1):65–83
33) Bassett AS, McDonald-McGinn DM, Devriendt K, et al; International 22q11.2 Deletion
Syndrome Consortium. Practical guidelines for managing patients with 22q11.2 deletion
syndrome. J Pediatr. 2011;159(2):332–339
34) Fahed AC, Nemer GM. Genetic causes of syndromic and non-syndromic congenital heart
disease. In: Cooper DN, Chen J, eds. Mutations in Human Genetic Disease. InTech; 2012.
www.intechopen.com/books/mutations-in-human-genetic-disease/genetic-causes-of-
syndromic-and-non-syndromic-congenital-heart-disease. Accessed December 16, 2016
35) Morris CA. Introduction: Williams syndrome. Am J Med Genet C Semin Med Genet. 2010;
154C(2):203–208
36) Ewart AK, Morris CA, Atkinson D, et al. Hemizygosity at the elastin locus in a developmental
disorder, Williams syndrome. Nat Genet. 1993;5(1):11–16
37) Sadler LS, Pober BR, Grandinetti A, et al. Differences by sex in cardiovascular disease in
Williams syndrome. J Pediatr. 2001;139(6):849–853
38) Wren C, Oslizlok P, Bull C. Natural history of supravalvular aortic stenosis and pulmonary
artery stenosis. J Am Coll Cardiol. 1990;15(7):1625–1630
39) Collins RT II, Kaplan P, Somes GW, Rome JJ. Long-term outcomes of patients with cardiovas-
cular abnormalities and Williams syndrome. Am J Cardiol. 2010;105(6):874–878
40) Committee on Genetics. American Academy of Pediatrics: health care supervision for children
with Williams syndrome. Pediatrics. 2001;107(5):1192–1204
267
CCIP.indb 267 3/13/18 4:18 PM

41) Collins RT II. Cardiovascular disease in Williams syndrome. Circulation.

2013;127(21):2125–2134
42) Zhong Q, Layman LC. Genetic considerations in the patient with Turner syndrome—45,X with
or without mosaicism. Fertil Steril. 2012;98(4):775–779
43) Bondy CA; Turner Syndrome Study Group. Care of girls and women with Turner syndrome: a
guideline of the Turner Syndrome Study Group. J Clin Endocrinol Metab. 2007;92(1):10–25
44) Morgan T. Turner syndrome: diagnosis and management. Am Fam Physician.
2007;76(3):405–410
45) Sybert VP, McCauley E. Turner’s syndrome. N Engl J Med. 2004;351(12):1227–1238
46) Kesler SR. Turner syndrome. Child Adolesc Psychiatr Clin N Am. 2007;16(3):709–722
47) Dulac Y, Pienkowski C, Abadir S, Tauber M, Acar P. Cardiovascular abnormalities in Turner’s
syndrome: what prevention? Arch Cardiovasc Dis. 2008;101(7-8):485–490
48) Bondy CA, Ceniceros I, Van PL, Bakalov VK, Rosing DR. Prolonged rate-corrected QT
interval and other electrocardiogram abnormalities in girls with Turner syndrome. Pediatrics.
2006;118(4):e1220–e1225
49) Sybert VP. Cardiovascular malformations and complications in Turner syndrome. Pediatrics.
1998;101(1):E11
50) Dawson-Falk KL, Wright AM, Bakker B, Pitlick PT, Wilson DM, Rosenfeld RG.
Cardiovascular evaluation in Turner syndrome: utility of MR imaging. Australas Radiol.
1992;36(3):204–209
51) Roberts AE, Allanson JE, Tartaglia M, Gelb BD. Noonan syndrome. Lancet. 2013;381(9863):
333–342
52) Tartaglia M, Kalidas K, Shaw A, et al. PTPN11 mutations in Noonan syndrome: molecular
spectrum, genotype-phenotype correlation, and phenotypic heterogeneity. Am J Hum Genet.
2002;70(6):1555–1563
53) van der Burgt I. Noonan syndrome. Orphanet J Rare Dis. 2007;2:4
54) Hickey EJ, Mehta R, Elmi M, et al. Survival implications: hypertrophic cardiomyopathy in
Noonan syndrome. Congenit Heart Dis. 2011;6(1):41–47
55) Group DNSGD. Management of Noonan Syndrome: A Clinical Guideline. 2010
56) Romano AA, Allanson JE, Dahlgren J, et al. Noonan syndrome: clinical features, diagnosis,
and management guidelines. Pediatrics. 2010;126(4):746–759
57) Malaquias AC, Brasil AS, Pereira AC, et al. Growth standards of patients with Noonan and
Noonan-like syndromes with mutations in the RAS/MAPK pathway. Am J Med Genet A.
2012;158A(11):2700–2706
58) Dasouki M, Jawdat O, Almadhoun O, et al. Pompe disease: literature review and case series.
Neurol Clin. 2014;32(3):751–776, ix [ix]
59) Kishnani PS, Steiner RD, Bali D, et al. Pompe disease diagnosis and management guideline.
Genet Med. 2006;8(5):267–288
268
CCIP.indb 268 3/13/18 4:18 PM

CHAPTER 18
Adults With
Congenital Heart
Disease
Rachel Steury, MSN, CNP, and Anitha S. John, MD, PhD
Introduction
As surgical and noninvasive techniques have improved, there are now more adults
than children living with congenital heart disease (CHD).1 Adults with CHD
represent a diverse and often medically complex cohort of patients. In this chapter,
we will review the epidemiology of CHD in adults, physical examination features,
and common complications observed in adults with CHD, as well as the need for
follow-up and specialty referrals. We offer anticipatory guidance for those caring
for children and adolescents with CHD.
Epidemiology
Since 1985, the number of adults with CHD has outnumbered children living with
CHD.2 With continued advances in surgical and nonsurgical procedures, this dif-
ference will continue to increase. It is estimated that the birth prevalence of CHD
is 1 in 110, with some estimating 10.8 per 1,000 live births.1 It is notable that these
data reflect diagnoses established in infancy, while at least 10% of patients followed
up in adult CHD clinics receive diagnoses in adulthood.3 The mortality curve of
adults with CHD has also changed over time (Figure 18-1).4 Survival rates in
adulthood are greatly dependent on severity of disease; however, more patients
with severe disease are surviving to adulthood.3 As of 2010, 60% of individuals
269
CCIP.indb 269 3/13/18 4:18 PM

FIGURE 18-1. Distribution of age at death in patients with congenital heart disease in 1987 to 1988
and 2004 to 2005. Reprinted from reference 4.
with severe CHD were adults, leading to an increasingly older population of

patients with severe CHD and additional comorbidities.2 While survival rates
and lower mortality are influenced by many factors, the change is likely due to
improvements in diagnostic capabilities, surgical techniques, and nonsurgical,
catheter-based interventions.
Heterogeneity of CHD
It is important to recognize that there is a spectrum of complexity across
congenital cardiac defects. Even within 1 type of defect, there are variations in
clinical presentation. A patient with an atrial septal defect (ASD) diagnosed and
repaired early in life is considered to have mild disease with normal pulmonary
artery pressures. The same ASD found in adulthood may be associated with
right-sided heart enlargement and dysfunction and, in some cases, pulmonary
hypertension. This patient will now have an entirely different set of potential
complications associated with repair. A key component of tetralogy of Fallot
(TOF), one of the most common forms of cyanotic CHD, is right ventricular
(RV) outflow obstruction. The degree of obstruction determines how cyanotic
a patient is, and this has important implications on timing and type of surgical
repair. Physicians treating adult CHD need to be aware of the differences in
long-term complications among patients with variable types of repairs. Finally,
270
CCIP.indb 270 3/13/18 4:18 PM

Adults With Congenital Heart Disease
many congenital cardiac defects are associated with genetic syndromes. The pres-
ence of chromosomal anomalies may affect the clinical course of individuals with
CHD. For instance, a patient with 22q11.2 deletion (DiGeorge syndrome) may
also experience immunodeficiencies, learning disabilities, and other health issues.
Natural History and History of Interventions

Improvements in understanding the anatomy of congenital defects and the
complexity of the specialized electrical system, combined with advances in
surgical techniques, cardiopulmonary bypass, and cardiac anesthesia, have
aligned to lead to advances in congenital cardiac surgery over the past 60
years.5 Outcomes, complications, and survival depend on the era in which the
patient was born. Additionally, many defects that previously required surgery
can now be repaired by using catheter-based therapies. Hemodynamic cardiac
catheterization has been the standard of reference for hemodynamic assessment.
Advances in interventional cardiology have led to major innovations and
treatment options and in some cases allow the patient to avoid surgical risks.
Today, secundum ASDs can be safely closed by using catheter-guided devices,
coarctation of the aorta can be treated with catheter-deployed stents, and even
valve replacement can be performed by using transcatheter techniques.6 Patients
and physicians may struggle with decisions about these treatment options
because there are no comparative data on long-term outcomes.
Loss to Follow-up
With increasing numbers of children surviving into adolescence and adulthood,
the need for ongoing medical care grows. Patients and families may believe that
after an infant surgery, the patient is “cured.” It is now recognized, however, that
problems arise in adolescence or early adulthood that require evaluation and
treatment.7 Symptoms may develop gradually, and failure to recognize them may
lead to severe or irreversible changes. For example, progressive RV dilation and
severe pulmonary insufficiency after transannular patch repair of TOF may lead
to ventricular dysfunction. Continual assessment and evaluation are needed to
determine the optimal timing of pulmonary valve replacement. There are data to
suggest that loss to follow-up is more likely to happen prior to transition to adult
care.8 In a multicenter study in which the gaps and predictors in lapses in care
were examined, the first lapse commonly occurred around the age of 19 years.
While patients with mild to moderate disease complexity had higher rates of
lapses in care, the most common reason among all patients for not seeking
medical attention was “feeling well.”8 These patients had already returned to
seek care at established adult CHD centers; therefore, these results are likely
an underestimate of patients who had been lost to follow-up. Referral to adult
CHD subspecialty centers has been shown to be independently associated with
271
CCIP.indb 271 3/13/18 4:18 PM

decreased mortality in this patient population, thus emphasizing the importance

of successful transition to adult care.9
Health Care Costs

As the number of adults with CHD increases, the effect of long-term sequelae,
the need for interventions, and the occurrence of comorbidities leads to increases
in health care use.10 Adults with more severe forms of CHD are likely to have
more comorbidities and to have used health care, including outpatient cardiac
care, hospitalization, and emergency department visits.11 As adults with CHD
survive into the fourth and fifth decades of life, residua of the original CHD—
acquired heart disease and other comorbidities, such as thyroid, renal, and
hepatic issues—develop, increasing complexity of care. Between 1998 and 2005,
hospitalizations for adults with CHD more than doubled in the United States.11
History
It is important to obtain and document a thorough medical history for all
patients with CHD because this can provide clues for anticipated clinical course,
as well as therapies or interventions that may be necessary. Past records, includ-
ing all surgical reports, add essential information about potential complications.
Patients who underwent surgical repair or any procedure that required blood
transfusion prior to 1992 should be screened for hepatitis C. Patient education
should include the importance of maintaining complete records. Symptoms of
heart failure depend on the congenital lesion and patient age (Box 18-1). While
most adults with noncongenital cardiac symptoms present with signs of systemic
ventricular failure, adult patients with CHD often present with subpulmonary
ventricular failure. Assessment should include the signs and symptoms listed
in Box 18-1. Many adults with CHD also have a decline in their systemic
ventricular function, and biventricular heart failure is not uncommon. Onset
of symptoms may be gradual and subtle. Previous febrile illness should be
assessed for possible endocarditis risk.
Physical Examination Findings

Physical examination findings reflect the anatomy, type of intervention(s)
performed, complications, and other organ involvement. Because patients are
often not aware of their diagnosis and procedures, and many do not have records
of previous interventions, physical examination findings can be invaluable
diagnostic tools for the clinician who treats adults with CHD. In addition to
physical findings that result from cardiac anatomy, many individuals with CHD
have chromosomal anomalies that carry characteristic physical findings.
272
CCIP.indb 272 3/13/18 4:18 PM

Adults With C
ongenital Heart Disease
Box 18-1. Signs and Symptoms of Heart Failure in

Congenital Heart Disease
Symptoms of Systemic Signs of Systemic Ventricular Failure
Ventricular Failure
Fatigue Third or fourth heart sound (gallop)
Breathlessness Laterally displaced apical impulse
Dry cough, especially lying flat Absent breath sounds and dull percus-
sion lung bases due to pleural effusions
Orthopnea
Paroxysmal nocturnal dyspnea
Wheezing
Symptoms of Subpulmonary Signs of Subpulmonary Ventricular
Ventricular Failure Failure
Fatigue Increased jugular venous pressure
Bloating Hepatomegaly
Weight gain (>2 kg/wk) Ascites
Loss of appetite Pitting leg edema, sacral edema, scrotal

edema
Reduced exercise tolerance
Increased abdominal girth

Symptoms of Congestive Signs of Congestive (Biventricular)
(Biventricular) Failure Failure
Combined systemic and Combined systemic and subpulmonary
subpulmonary symptoms signs
Adapted from Budts W, Roos-Hesselink J, Rädle-Hurst T, et al. Treatment of heart failure in adult congenital heart
disease: a position paper of the Working Group of Grown-Up Congenital Heart Disease and the Heart Failure
Association of the European Society of Cardiology. Eur Heart J. 2016;37:1422.
Vital signs and general appearance can lend clues to diagnosis and past
interventions. With classic Blalock-Taussig shunts and subclavian flap repair
of coarctation, the subclavian artery is used to provide pulmonary flow, which
causes a decrease of the ipsilateral brachial arterial pulse. Such patients should
be instructed to avoid blood pressure measurements on those limbs because they
will result in falsely low readings. These changes are important to be aware of
because they can affect routine health screening. Collateral vessel development
allows for blood supply to the affected arm, but limb length discrepancy can
273
CCIP.indb 273 3/13/18 4:19 PM

be seen with repairs that disrupt the main arterial supply to the affected limb.
Clubbing can be seen in adults who underwent a late repair or no repair and
have been cyanotic. Differential cyanosis, lower oxygen saturations in the lower
extremities, and clubbing in the feet all are suspicious for unrepaired patent duc-
tus arteriosus (PDA), with increased pulmonary pressures leading to right-to-left
shunting at the level of the PDA (Figure 18-2). Assessing oxygen saturation in
both the hands and feet is important in this case, given the differential blood
flow. The location and types of surgical scars can provide clues to the type and
era of interventions. Early thoracotomy incisions, for example, were much larger
than those seen in the current surgical era, often circling from the torso to the
back, as with classic Blalock-Taussig shunts and coarctation repairs.
The cardiac examination of an adult with CHD is a key part of initial and
ongoing assessment. Mechanical valves have a characteristic click. Stenotic
conduits result in ejection murmurs, while insufficiency may lead to regurgitant
diastolic murmur. Single-ventricle hearts often have a single second heart
FIGURE 18-2. Differential cyanosis in a 30-year-old woman with unrepaired patent ductus
arteriosus. From Anoop TM, George KC. Differential clubbing and cyanosis. New Engl J Med.
2011;364:666.
274
CCIP.indb 274 3/13/18 4:19 PM

Adults With C
ongenital Heart Disease
sound due to absence of a semilunar valve. Signs of pulmonary edema (such

as tachypnea, rales, and increased work of breathing with exertion), as well as
changes in point of maximal impulse, presence of a gallop, hepatomegaly, jugular
venous distention, and lower-extremity edema) are important to assess for signs
of heart failure.
Other skeletal muscle and chest wall abnormalities may result from prior
surgeries. Scoliosis has been shown to develop after thoracotomy incisions
(Figure 18-3).12 Limb length discrepancy can develop, as mentioned previously.
Chest asymmetry may result from a left precordial bulge. Use of spironolactone
for heart failure therapy may lead to gynecomastia in male patients.13 Because
of nutritional challenges, underlying cardiac anatomy and function, and con
comitant genetic syndromes, adults with CHD may be of small stature.
It is important for primary care physicians to know the long-term risks
associated with underlying cardiac defects for screening and anticipatory
guidance (Table 18-1). These complications vary not only on the basis of the
anatomic subtype of CHD, but also on the type of repair. For example, an adult
patient with transposition of the great arteries who underwent an atrial switch
procedure will have a very different set of long-term complications than a
patient who underwent an arterial switch surgery.
It is essential that providers assess the patient for risk of infective endocarditis
in those with congenital cardiac defects, particularly those with mechanical
valves, shunts, or conduits, as well as residual defects, such as peripatch VSD
leaks. Poor dentition and oral infections are considered a risk factor for
endocarditis. Infected skin lesions may be a source of bacteremia, increasing the
risk for infective endocarditis. These should be promptly addressed and treated.
Nail-biting and picking of cuticles carries risk for staphylococcal infection, as
well.14 Physical evidence of these conditions warrants discussion with patients
about associated risks.
Clinical Concerns
There is great heterogeneity among patients with CHD because of anatomic
variation within diagnoses, differences in timing and type of intervention, and
individual comorbidities that affect the clinical course. There are, however,
known and anticipated consequences of CHD that are common among adults
with CHD.
Arrhythmias
There is growing understanding of the presence and effect of arrhythmias on
patients with CHD. Arrhythmias generally increase in incidence over time and
have become the leading cause of morbidity and hospital admission for adults
with CHD.15 Arrhythmias can result from inherent anatomic malformations,
275
CCIP.indb 275 3/13/18 4:19 PM

FIGURE 18-3. Frontal (left) and lateral (right) radiographs show scoliosis after sternotomy.
From Feiz HH, Afrasiabi A, Parvizi R, Safarpour A, Fouladi RF. Scoliosis after thoracotomy/
sternotomy in children with congenital heart disease. Indian J Orthop. 2012;46(1):77–80.
abnormal pressure, or volume loads caused by shunts and/or valve disease, cyano-
sis, and surgical scars.16 TOF is an instructive example of the burden and variety
of arrhythmias seen in adults with CHD, with approximately one-third of
adult survivors developing clinically significant arrhythmia 1 to 2 decades after
repair.16,17 These patients experience both atrial and ventricular arrhythmias, as
well as sinus node dysfunction and tachycardia-bradycardia syndrome. The most
common tachycardia in adults with CHD is a result of macro–re-entry within
the atria. Intra-atrial re-entrant tachycardia is different from the atrial flutter
that is seen in structurally normal hearts. It is usually slower than typical flutter,
276
CCIP.indb 276 3/13/18 4:19 PM

Table 18-1. Long-term Complications of Adults

with CHD
Diagnosis Long-Term Complications
Atrial septal defect Atrial arrhythmias (repair at >20 years of age)

Pulmonary hypertension (10% of patients)
Sinus node dysfunction (sinus venosus atrial septal defect)
Tetralogy of Fallot Pulmonary regurgitation

Right ventricular dilation and heart failure
Atrial and ventricular arrhythmias
Coarctation of the Repeat coarctation or pseudoaneurysm formation

aorta Hypertension
Berry aneurysms of the brain
Dextro-transposition Atrial or ventricular arrhythmias

of the great arteries Systemic right ventricular failure, baffle leak, or stenosis if
atrial switch repair
Coronary artery stenosis, supravalvar aortic or pulmonary
stenosis, branch pulmonary artery stenosis if arterial switch
surgery
Levo-transposition Conduction abnormalities

of the great arteries Systemic right ventricular failure
Tricuspid valve regurgitation
Eisenmenger Arrhythmias
syndrome Thromboembolic complications
Hemoptysis
Polycythemia
Right ventricular dilation and failure
Single ventricle Cyanosis

Heart failure
Arrhythmias
Liver dysfunction
with rates of 150 to 200 beats/min. Often, these rates will be conducted at
1:1 ratio and can result in hypotension, syncope, and even death. Some patients
can have lower rates (90 to 120 beats/min), which may be confused with sinus
tachycardia. This is often the case in a patient with a single ventricle after the
Fontan procedure (Figure 18-4). Despite a relatively low heart rate, symptoms
may result from loss of AV synchrony.16 Patients with atrial arrhythmias are at
higher risk for thromboembolic complications and often require some form of
anticoagulation. Treatment options include antiarrhythmic drugs, catheter abla-
tion, implanted pacemakers, internal defibrillators, and intervention with a maze
277
CCIP.indb 277 3/13/18 4:19 PM

FIGURE 18-4. Electrocardiograms of a 27-year-old man with double-inlet left ventricle status post
Fontan procedure. Atrial flutter with paced and inherent ventricular response is shown. The patient
was symptomatic, owing to loss of atrioventricular synchrony. Red arrows indicate flutter waves. Blue
arrows indicate paced ventricular beat. Green arrows indicate intrinsic ventricular beats.
procedure.18 Clinically significant arrhythmias are an indication for consultation

with a center for adults with CHD.
Heart Failure
Heart failure is a frequent problem for adults with CHD. As seen in the devel-
opment of arrhythmias, adults with CHD will often have at least 1 substrate
for the development of heart failure.19 These include anatomic abnormalities,
surgical sequelae from scar lines, or myocardial damage from long bypass times
278
CCIP.indb 278 3/13/18 4:19 PM

and progression of underlying pathologic processes. RV dilation from pulmonary

regurgitation seen after initial TOF repair often leads to heart failure symptoms.
It is not well established at what point depressed cardiac function due to RV
dilation becomes irreversible in spite of pulmonary valve replacement. Systemic
RVs, as in levo-transposition of the great arteries or dextro-transposition of the
great arteries after an atrial switch, or single RVs, demonstrate a higher incidence
of ventricular dysfunction over time.19 The current approach to management of
heart failure in adults with CHD is modeled after general heart failure guide-
lines, despite the lack of data for this specific population. Extrapolation must be
done with caution.
Anticoagulation
Anticoagulation is used in adults with CHD for a wide variety of reasons.
Guidelines are available for the use of anticoagulation for mechanical heart
valves, as well as arrhythmias.20,21 Interruption of anticoagulation is often
indicated for procedures. Guidelines are available.22 The use of warfarin requires
appreciation of medication and dietary interactions to minimize bleeding and
thrombosis risks. Appropriate anticipatory guidance should be provided to
patients and families when anticoagulation is indicated.
Noncardiac Procedures
Patients with moderate and severe CHD who require noncardiac surgery have
unique needs related to anesthesia and other surgical concerns. These patients
should undergo procedures at centers for adults with CHD, where physicians
trained in the care of adults with CHD are available. Consultation with anes-
thesia to discuss potential pitfalls during surgery is crucial to the safety of the
patient. It may be necessary to adjust settings on pacemakers and defibrillators
if the procedure will affect those devices. Anticoagulation interruption and
infective endocarditis prophylaxis are other areas where consultation with
providers who care for adults with CHD is important.
Referral for Adult CHD Care

Discussions about transition of care from pediatric cardiology to adult congenital
cardiology are addressed in Chapter 42, Transition and Transfer From Pediatric
to Adult-Centered Cardiac Care. Patients with severe and moderate disease
should be followed up at least annually in a regional center for adults with
CHD, as recommended by the 32nd Bethesda Conference.19,22 Patients with
simple congenital lesions should follow up within a regional center for adults
with CHD at least once to confirm diagnosis and develop plans for follow-up.
Clinical needs of patients living decades after an initial intervention change as
the sequelae of structural anomalies and interventions develop over time
279
CCIP.indb 279 3/13/18 4:19 PM

Health Maintenance
Mental Health and Neurocognitive Issues
Adults with CHD face not only the medical implications of their cardiac
condition but also the psychosocial implications of living with a chronic disease
that may be life shortening. There is a higher rate of mood and anxiety disorders
among adults with CHD, affecting as many as 30% of patients.23 Neurocognitive
deficits are seen in patients with CHD. This may be caused by cyanosis prior to
surgical repair, effects of cardiopulmonary bypass, and/or missing school due to
illness or hospitalization.24 It has also been shown that children who have under-
gone early cardiac surgery have deficits in fine-motor skills, visuospatial skills,
and cognition, including memory, attention, and higher-order language skills.25
Deficits in attention and executive function can manifest later in childhood or
adolescence. Growing up with CHD can involve frequent medical appointments
and hospitalizations, leading to missed school and social gatherings, body
image concerns due to scars or small stature, and even delayed progression into
adulthood because their medical condition may have led to a greater dependence
on their parents. Awareness of the psychosocial effect that surviving CHD may
have on patients is the first step in optimizing quality-of-life outcomes for this
population. Screening for mood disorders and learning disabilities should remain
a component of care of individuals with CHD and thus a component of care for
adults with CHD.
Activity and Fitness

Health promotion remains a key component of health maintenance for the
adult with CHD. In the past, exercise restrictions for children with CHD were
common, out of concern for undue stress. Most current published guidelines
regarding exercise and CHD focus on the competitive athlete.26 Physical activity
of moderate intensity has been shown to improve general health.27 The health
benefits of a physically active life, improved psychological well-being, increased
social interaction, and a positive effect on future risk of acquired heart disease
should be attainable by nearly all with CHD.28 Recommendations for an active
lifestyle should be included in all health promotion for persons with CHD.
Some diagnoses warrant specific activity restrictions. Patients with aortic dilation
are advised to avoid contact sports and exercises that elicit a Valsalva maneuver
to avoid stress on the aortic walls. Pacemakers or other implanted devices may
be damaged or cause injury to soft tissue upon impact during contact sports.
Patients should be counseled about the risks of internal bleeding with anticoag-
ulation and be cautious when engaging in activities that may involve collisions,
falls, or other types of impact.
280
CCIP.indb 280 3/13/18 4:19 PM

Cardiovascular Risk Factors

As individuals with CHD survive into adulthood, they are at risk for developing
acquired heart disease in addition to the consequences of their congenital
abnormality.29 Adults with CHD may already have issues with heart failure
due to ventricular dysfunction, valvular disease, shunts, and arrhythmias. Adult
comorbidities such as hypertension, diabetes, coronary artery disease, sleep
apnea, restrictive lung disease, and obesity may exacerbate heart failure. It has
been suggested that metabolic syndrome is more common among adults with
CHD, and there is concern that activity restrictions contribute to obesity.30
Information regarding smoking cessation, healthy diet, weight management, and
appropriate active lifestyle, as well as screening and treatment of hypertension,
diabetes, and hyperlipidemia, should remain an integral part of patient education
and health promotion counseling. Alcohol abuse has been linked to atrial
fibrillation, but the effect of social drinking on occurrence of arrhythmia has
not been well studied.31 Given that an adult with CHD may need to undergo
additional interventions over time, promotion of a healthy lifestyle is an essential
component of their ongoing care that should not be neglected.
Contraception and Pregnancy

As more and more young women with CHD survive into adolescence and
beyond, health care providers must provide counseling about contraception and
pregnancy. As with exercise, many female patients and their families were previ-
ously advised against pregnancy on the basis of concerns that the hemodynamic
changes of pregnancy would not be well tolerated by the mother and might lead
to fetal complications. As more is learned about postoperative cardiac physiology
in adults with CHD, it has been recognized that with appropriate counseling,
evaluation, risk stratification, and management, many women with CHD can
successfully carry a pregnancy to term.
Discussion about contraception, family planning, and future pregnancies
should occur early in adolescence to prevent unwanted and possibly dangerous
pregnancies for young women with CHD. Genetic counseling should be
offered to both men and women with CHD to assess patients for the risk of
transmission. The current era of contraception offers many options for women,
including those with CHD (Table 18-2). Women with increased risk for throm-
bosis, such as those with a mechanical valve, cyanosis, or arrhythmias, should
avoid estrogen-containing oral contraceptive pills because of the thrombogenic
properties of estrogen.32 Progestin-only oral contraceptive pills offer reduced
risk of thrombotic complications but must be taken reliably and at the same
time daily for maximal effectiveness. Injectable and implantable methods are
effective and appropriate for most women with CHD. Side effects, including
weight gain, headache, and mood changes, may contribute to discontinued
281
CCIP.indb 281 3/13/18 4:19 PM

Table 18-2. Combined Hormonal Contraception Use in

Women With Congenital Heart Disease
Class 1: Always Class 2: Broadly Class 3: Caution Class 4: Use
Usable Usable If Used Contraindicated
Minor valve Tissue prosthetic Thrombotic Thrombotic

disease (ie, valve lacking risk (even on risk (even on
bicuspid aortic class 3 or 4 warfarin): warfarin):
valve with nor- features Mechanical valve Mechanical valve
mal function or Uncomplicated (bileaflet) Any tricuspid valve
mild pulmonary mild aortic or Previous thrombo- Pulmonary
stenosis) mitral valve embolism hypertension of
Repaired coarc- disease
Atrial arrhythmia any cause
tation of the Most arrhythmias
aorta with no Dilated left atrium Left ventricular
other than atrial
aneurysm and >4 cm dysfunction
fibrillation or
no hypertension Risk of paradoxical (ejection
flutter
embolism: fraction <30%)
Simple lesions Uncomplicated
repaired in Potential reversal Fontan circulation
Marfan
childhood with syndrome of left-to-right Previous coronary
no residual shunt (ie, arteritis (ie,
Congenital heart
sequelae unrepaired atrial Kawasaki
disease lacking
septal defect) disease)
any class 3 or 4
features Risk of paradoxical
embolism:
Small left-to-right
shunt not Cyanotic heart
reversible with disease
physiological Pulmonary
maneuvers (ie, arteriovenous
small ventricular malformations
septal defect)
Previous cardio-
myopathy with
full recovery
Adapted from Wald RM, Sermer M, Colman JM. Pregnancy and contraception in young women with congenital heart
disease: general considerations. Pediatr Child Health. 2011;16(4):e25–e29.
use.33 Consultation with a provider who cares for adults with CHD can provide
expert-guided recommendations regarding safe and effective contraception for
women with CHD.
Risk assessment for pregnancy is an essential component of preconception
counseling for women with CHD. Factors that increase the risk of maternal
event during pregnancy include a previous cardiac event (arrhythmia, stoke,
transient ischemic attacks, pulmonary edema), New York Heart Association
282
CCIP.indb 282 3/13/18 4:19 PM

classification, pulmonary hypertension, clinically significant aortic or mitral

stenosis, mechanical valves, cyanosis, use of cardiac medications, and impaired
systemic ventricular function.32,34 Consultation with a provider who cares for
adults with CHD prior to pregnancy is strongly recommended per the 2008
American College of Cardiology and American Heart Association guidelines
for adults with CHD.19

When considering the risks of pregnancy, one must consider maternal
functional capacity, exercise tolerance, cardiac medications, arrhythmia history,
and presence of cyanosis. Manageable maternal risks during pregnancy include
transient functional deterioration, heart failure exacerbation, arrhythmias, and
complications associated with thrombi or anticoagulation. Serious events include
stroke, irreversible heart failure, and death. Review of medications is necessary to
avoid any teratogens. Anticoagulation can be a challenge during pregnancy for a
woman with a mechanical valve and should be managed by a provider with expe-
rience and expertise in this area. Prior to valve replacement, discussions should
occur regarding the risks and benefits of a bioprosthetic versus a mechanical
valve for female adolescents and women. Patients should be active participants
in the decision-making process.
End-of-Life Issues in Adults with CHD

Despite advances in care of children with CHD and increasing survival into
adolescence and adulthood, these patients often have a shorter life expectancy
than their peers. Discussions concerning end of life and patient wishes should
be an integral part of caring for adults with CHD. There is little research that
addresses the timing of such discussion, but that which is available indicates
that discussions about end of life are desired by patients earlier in their disease
progression, rather than later.35 Advance directives, living wills, and durable
power of attorney are issues that should be addressed while caring for adults with
CHD. Patients with limited cognitive understanding, such as those with trisomy
21, may need to have a parent or guardian officially designated to make medical
decisions for ongoing treatment and management, as well as at the end of life.
Conclusion
Currently, there are more adults living with CHD than children. The landscape
of caring for these patients is changing as new treatments and interventions are
developed and as the natural course of the disease progresses. Referrals to centers
for adults with CHD allow for comprehensive care, focusing on the short- and
long-term health needs of this patient population. Partnership and collaboration
with primary care pediatricians and internists are needed to facilitate smooth
transition of care and continued health management.
283
CCIP.indb 283 3/13/18 4:19 PM

Key Points
•• CHD is a lifelong medical condition. Residual pathologic manifestations can
develop in adolescence and adulthood.
•• All adults with CHD should undergo at least 1 evaluation at a center for
adults with CHD to determine appropriate follow-up.
•• Adults with CHD remain at risk for acquired heart disease. Promotion of
healthy lifestyle choices and disease-specific counseling and education should
be a part of all visits with adults with CHD.

•• A Patient’s Guide to Taking Warfarin (American Heart Association).
www.heart.org/HEARTORG/Conditions/Arrhythmia/
PreventionTreatmentofArrhythmia/A-Patients-Guide-to-Taking-Warfarin_
UCM_444996_Article.jsp#.WE2kh7IrK70
•• Adult Congenital Heart Association. www.achaheart.org
References
1) Gilboa SM, Devine OJ, Kucik JE, et al. Congenital heart defects in the United States: estimating
the magnitude of the affected population in 2010. Circulation. 2016;134(2):101–109
2) Marelli AJ, Ionescu-Ittu R, Mackie AS, Guo L, Dendukuri N, Kaouache M. Lifetime
prevalence of congenital heart disease in the general population from 2000 to 2010. Circulation.
2014;130(9):749–756
3) Warnes CA, Liberthson R, Danielson GK, et al. Task force 1: the changing profile of congenital
heart disease in adult life. J Am Coll Cardiol. 2001;37(5):1170–1175
4) Khairy P, Ionescu-Ittu R, Mackie AS, Abrahamowicz M, Pilote L, Marelli AJ. Changing
mortality in congenital heart disease. J Am Coll Cardiol. 2010;56(14):1149–1157
5) Freedom RM, Lock J, Bricker JT. Pediatric cardiology and cardiovascular surgery: 1950-2000.
Circulation. 2000;102(20 Suppl 4):IV58–IV68
6) Moore J, Hegde S, El-Said H, et al; ACC IMPACT Steering Committee. Transcatheter device
closure of atrial septal defects: a safety review. JACC Cardiovasc Interv. 2013;6(5):433–442
7) Landzberg MJ, Murphy DJ Jr, Davidson WR Jr, et al. Task force 4: organization of delivery
systems for adults with congenital heart disease. J Am Coll Cardiol. 2001;37(5):1187–1193
8) Gurvitz M, Valente AM, Broberg C, et al; Alliance for Adult Research in Congenital
Cardiology (AARCC) and Adult Congenital Heart Association. Prevalence and predictors
of gaps in care among adult congenital heart disease patients: HEART-ACHD (The Health,
Education, and Access Research Trial). J Am Coll Cardiol. 2013;61(21):2180–2184
9) Webb G, Landzberg MJ, Daniels CJ. Specialized adult congenital heart care saves lives.
Circulation. 2014;129(18):1795–1796
10) Mackie AS, Pilote L, Ionescu-Ittu R, Rahme E, Marelli AJ. Health care resource utilization in
adults with congenital heart disease. Am J Cardiol. 2007;99(6):839–843
11) Opotowsky AR, Siddiqi OK, Webb GD. Trends in hospitalizations for adults with congenital
heart disease in the U.S. J Am Coll Cardiol. 2009;54(5):460–467
12) Roclawski M, Pankowski R, Smoczynski A, et al. Secondary scoliosis after thoracotomy in
patients with aortic coarctation and patent ductus arteriosus. Stud Health Technol Inform.
2012;176:43–46
284
CCIP.indb 284 3/13/18 4:19 PM

13) Pitt B, Zannad F, Remme WJ, et al; Randomized Aldactone Evaluation Study Investigators. The
effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J
Med. 1999;341(10):709–717
14) Gatzoulis MA, Webb GD, Daubeney PEF. Diagnosis and management of adult congenital heart
disease. 2nd ed. Philadelphia, PA: Elsevier/Churchill Livingstone; 2011:xviii, 508
15) Khairy P, Balaji S. Cardiac arrhythmias in congenital heart diseases. Indian Pacing Electrophysiol
J. 2009;9(6):299–317
16) Walsh EP, Cecchin F. Arrhythmias in adult patients with congenital heart disease. Circulation.
2007;115(4):534–545
17) Khairy P, Aboulhosn J, Gurvitz MZ, et al; Alliance for Adult Research in Congenital
Cardiology (AARCC). Arrhythmia burden in adults with surgically repaired tetralogy of Fallot:
a multi-institutional study. Circulation. 2010;122(9):868–875
18) Khairy P, Van Hare GF, Balaji S, et al. PACES/HRS Expert Consensus Statement on the
Recognition and Management of Arrhythmias in Adult Congenital Heart Disease: developed
in partnership between the Pediatric and Congenital Electrophysiology Society (PACES)
and the Heart Rhythm Society (HRS). Endorsed by the governing bodies of PACES, HRS,
the American College of Cardiology (ACC), the American Heart Association (AHA), the
European Heart Rhythm Association (EHRA), the Canadian Heart Rhythm Society (CHRS),
and the International Society for Adult Congenital Heart Disease (ISACHD). Heart Rhythm.
2014;11(10):e102–e165
19) Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA 2008 Guidelines for the
Management of Adults with Congenital Heart Disease: a report of the American College of
Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee
to develop guidelines on the management of adults with congenital heart disease). Circulation.
2008;118(23):e714–e833
20) Nishimura RA, Otto CM, Bonow RO, et al; American College of Cardiology/American
Heart Association Task Force on Practice Guidelines. 2014 AHA/ACC guideline for the
management of patients with valvular heart disease: a report of the American College of
Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol.
2014;63(22):e57–e185
21) January CT, Wann LS, Alpert JS, et al; American College of Cardiology/American Heart
Association Task Force on Practice Guidelines. 2014 AHA/ACC/HRS guideline for the
management of patients with atrial fibrillation: a report of the American College of Cardiology/
American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
J Am Coll Cardiol. 2014;64(21):e1–e76
22) Webb GD, Williams RG. Care of the adult with congenital heart disease: introduction. J Am
Coll Cardiol. 2001;37(5):1166
23) Kovacs AH, Utens EM. More than just the heart: transition and psychosocial issues in adult
congenital heart disease. Cardiol Clin. 2015;33(4):625–634, ix [ix]
24) Kovacs AH, Sears SF, Saidi AS. Biopsychosocial experiences of adults with congenital heart
disease: review of the literature. Am Heart J. 2005;150(2):193–201
25) Miller SP, McQuillen PS, Hamrick S, et al. Abnormal brain development in newborns with
congenital heart disease. N Engl J Med. 2007;357(19):1928–1938
26) Pelliccia A, Fagard R, Bjørnstad HH, et al; Study Group of Sports Cardiology of the Working
Group of Cardiac Rehabilitation and Exercise Physiology; Working Group of Myocardial and
Pericardial Diseases of the European Society of Cardiology. Recommendations for competitive
sports participation in athletes with cardiovascular disease: a consensus document from the
Study Group of Sports Cardiology of the Working Group of Cardiac Rehabilitation and
Exercise Physiology and the Working Group of Myocardial and Pericardial Diseases of the
European Society of Cardiology. Eur Heart J. 2005;26(14):1422–1445
285
CCIP.indb 285 3/13/18 4:19 PM

27) Warburton DE, Nicol CW, Bredin SS. Health benefits of physical activity: the evidence. CMAJ.
2006;174(6):801–809
28) Baumgartner H, Bonhoeffer P, De Groot NM, et al; Task Force on the Management of Grown-
up Congenital Heart Disease of the European Society of Cardiology (ESC); Association for
European Paediatric Cardiology (AEPC); ESC Committee for Practice Guidelines (CPG).
ESC Guidelines for the management of grown-up congenital heart disease (new version 2010).
Eur Heart J. 2010;31(23):2915–2957
29) Moons P, Van Deyk K, Dedroog D, Troost E, Budts W. Prevalence of cardiovascular risk factors
in adults with congenital heart disease. Eur J Cardiovasc Prev Rehabil. 2006;13(4):612–616
30) Deen JF, Krieger EV, Slee AE, et al. Metabolic syndrome in adults with congenital heart disease.
J Am Heart Assoc. 2016;5(2):e001132
31) Koskinen P, Kupari M. Alcohol and cardiac arrhythmias. BMJ. 1992;304(6839):1394–1395
32) Deanfield J, Thaulow E, Warnes C, et al; Task Force on the Management of Grown
Up Congenital Heart Disease, European Society of Cardiology; ESC Committee for
Practice Guidelines. Management of grown up congenital heart disease. Eur Heart J.
2003;24(11):1035–1084
33) Archer B, Irwin D, Jensen K, Johnson ME, Rorie J. Depot medroxyprogesterone. Management
of side-effects commonly associated with its contraceptive use. J Nurse Midwifery.
1997;42(2):104–111
34) Drenthen W, Boersma E, Balci A, et al; ZAHARA Investigators. Predictors of pregnancy
complications in women with congenital heart disease. Eur Heart J. 2010;31(17):2124–2132
35) Tobler D, Greutmann M, Colman JM, Greutmann-Yantiri M, Librach LS, Kovacs AH.
End-of-life in adults with congenital heart disease: a call for early communication. Int J Cardiol.
2012;155(3):383–387
286
CCIP.indb 286 3/13/18 4:19 PM

CHAPTER 19
Congenital Heart
Lesions
Aortic Valve Problems,

Including Bicuspid Aortic Valve
and Subaortic Membranes
Anatomy
The aortic valve is positioned between the left ventricle (LV) and the aorta. It is
normally tricuspid/trileaflet, consisting of 3 thin cusps of tissue anchored to the
valve annulus. Just distal to the annulus, the aorta bulges to form the aortic root,
which then narrows at the sinotubular junction (Figure 19-1). Malformations can
lead to aortic stenosis (blockage of flow through the valve) or aortic insufficiency
(valve leakage). The most common aortic valve anomaly is a bicuspid aortic valve
(BAV). The anatomy of BAV is variable, ranging from the presence of only 2 true
cusps to fusion or partial fusion of an otherwise tricuspid valve (Figure 19-2).
One way that aortic stenosis occurs is when valve leaflet mobility is limited by
conditions like BAV. If the aortic valve annulus is undersized, stenosis can also
result. The most severe form of undersized aortic valve is aortic atresia, where
there is no opening at all. In this condition, an alternative route is required for
287
CCIP.indb 287 3/13/18 4:19 PM

FIGURE 19-1. Echocardiographic image of a normal aortic valve and its components. Image
courtesy of Josh Kailin, MD, www.pedecho.org.
FIGURE 19-2. Echocardiographic image of a bicuspid aortic valve. In this case, the right and left
coronary cusps are fused together. Image courtesy of Josh Kailin, MD, www.pedecho.org.
288
CCIP.indb 288 3/13/18 4:19 PM

Congenital Heart Lesions
blood to reach the body. Aortic insufficiency results when the coaptation of the
leaflets is compromised. This can be seen in BAV, as well as conditions in which
leaflet tissue is dysplastic. BAV is associated with dilation of the aortic root and
ascending aorta, even when stenosis and insufficiency are absent. BAV can also
be associated with coarctation of the aorta. Aortic valve problems can be a part
of more complex congenital heart disease (CHD), such as hypoplastic left heart
syndrome or certain types of ventricular septal defects.
In some patients, a fibrous ledge of tissue called a subaortic membrane can
develop beneath the aortic valve. The membrane can extend across the LV
outflow tract, or it may grow onto the aortic valve leaflets. Subaortic membranes
can cause subaortic stenosis, aortic regurgitation, or both.
The least common abnormality is supravalvar aortic stenosis, in which the
obstruction is caused by narrowing above the level of the valve. This is usually
associated with Williams syndrome.
Clinical Features
When aortic valve problems are associated with complex CHD, they are often
diagnosed at birth. “Critical” aortic stenosis is severe aortic disease in the neonate
that manifests with dyspnea, poor feeding, tachycardia, and shock as the patent
ductus arteriosus closes.1 BAV, which is present in about 1% of the population,
can be diagnosed at any time, including well into adulthood. The presenting sign
of aortic valve disease is usually a murmur (see the list of Audio Recordings at
the end of this topic).
Aortic valve disease is largely asymptomatic. When stenosis is severe,
patients may experience chest pain or syncope, particularly with exercise. These
ominous symptoms are a result of ischemia or arrhythmias and warrant urgent
consultation. Severe insufficiency can lead to angina, as well. Both stenosis and
regurgitation can cause dyspnea on exertion and limited endurance.
Aortic dissection is the feared complication of a dilated ascending aorta
(often associated with BAV), classically associated with tearing chest or back
pain. Physicians should take note of any acute-onset severe chest pain, abdom-
inal pain, neurological deficits, syncope, and reduced pulse or blood pressure in
an extremity relative to the others.
The diagnosis of aortic valve pathologic findings is established with echo-
cardiography. If aortic stenosis is significant or longstanding, LV hypertrophy
or—even worse—LV dysfunction can be seen. With insufficiency, the LV dilates
and can weaken over time. An exercise stress test is useful when considering
participation in competitive sports. LV hypertrophy at electrocardiography can
be present, but this is a nonspecific finding. Chest radiographic findings are
usually normal. Computed tomography is the most commonly used examination
if aortic dissection is a concern and should be performed emergently.
289
CCIP.indb 289 3/13/18 4:19 PM

Management
With aortic valve disease comes a wide spectrum of therapies. Aortic stenosis is
a progressive disease, but most patients will require no intervention in childhood.
Some stenosis requires an interventional cardiologist to inflate a balloon across
the valve to relieve stenosis (ie, balloon valvuloplasty). This can occur as early
as the neonatal period or even in the fetus. Sometimes the aortic valve is better
repaired surgically. The Ross procedure is one in which the patient’s own
pulmonary valve is used to replace the abnormal aortic valve. The pulmonary
valve is replaced in turn, usually by a bioprosthetic valve. Survival after aortic
valve surgery or catheter-based intervention is high, with less than 1% mortality
associated with the Ross procedure. Long-term complications after intervention
on the aortic valve include recurrence of stenosis and/or insufficiency. Abnormal
valves are at risk for endocarditis.
It is generally believed that most patients with BAV will require an inter
vention at some point in their lives, typically in adulthood.2 The most common
interventions are balloon dilation of the aortic valve by using cardiac catheter-
ization and surgical repair of the aortic valve and/or root. Guidelines exist to
assist in decision-making. When dilation of the aortic root or ascending aorta
is evident, medical therapy with β-blockers, angiotensin-converting enzyme
inhibitors, or angiotensin receptor blockers may be used to attempt to slow
progression. When present, hypertension should be aggressively controlled.
The management of subaortic membranes is particularly problematic. The
indications for surgery are not clearly established, with institutional preferences
often factoring into the decision-making process. Complicating this is that sub-
aortic membranes can and often do recur. This may repeat itself multiple times,
with some patients requiring several open-heart surgeries, which may ultimately
result in aortic valve replacement.
Ongoing Care
The long-term prognosis for patients with aortic valve abnormalities is excellent.
Any valve that requires intervention, surgical or catheter based, needs to be
monitored for the patient’s lifetime. Some require reintervention. Long-term
medications are usually not required, except in rare circumstances. Clearance for
competitive sports and amusement park rides depends on the severity of aortic
stenosis or insufficiency and requires discussion with the pediatric cardiologist.
Patients with mild disease may be cleared for all competitive sports after sur-
veillance testing by a cardiologist.3 When disease progresses, limitations become
stricter. Oxygen saturation levels will be normal. Endocarditis prophylaxis is
not recommended by the American Heart Association unless the patient has a
prosthetic valve or a history of endocarditis.
290
CCIP.indb 290 3/13/18 4:19 PM

Once BAV is diagnosed, all first-degree relatives should undergo screening

echocardiography. This includes the proband’s parents, siblings, and children.
There is an approximately 10% chance that a sibling of a person with BAV will
also have BAV.
Key Points
•• Intervention for BAV is unusual in childhood. All first-degree relatives of a
patient with BAV should undergo screening echocardiography. There is a male
predominance.
•• Symptoms of aortic stenosis and regurgitation are usually absent unless the
disease is severe, in which case a murmur should be clearly audible.
•• While prophylaxis is not routinely indicated in patients with abnormal aortic
valves, they do have an increased risk for endocarditis. Endocarditis should be
considered in such patients with prolonged fever.

•• Bicuspid Aortic Valve and Systolic Click—normal speed (Willam Buck
Kyle, MD). www.youtube.com/watch?v=zsAj2xGNGs4&index=3&list=
•• Bicuspid Aortic Valve and Mild Stenosis—normal speed (Willam Buck
Kyle, MD). www.youtube.com/watch?v=opyMtEHhyLE&index=4&list=
•• Bicuspid Aortic Valve and Mild Stenosis—slow (Willam Buck Kyle,
MD). www.youtube.com/watch?v=dsoG-OX_Wv8&index=5&list=
•• Aortic Regurgitation and Mild Stenosis (Willam Buck Kyle, MD).
www.youtube.com/watch?v=54BhXSnaXk4&index=19&list=
References
1) Friedland-Little J, Zampi J, Gajarski R. Aortic Stenosis. In: Allen H, Shaddy R, Penny D,
Feltes T, Cetta F, eds. Moss and Adams’ Heart Disease in Infants, Children, and Adolescents Including
the Fetus and Young Adult. 9th ed. Philadelphia, PA: Wolters Kluwer; 2016: 1085–1105
2) Siu SC, Silversides CK. Bicuspid aortic valve disease. J Am Coll Cardiol. 2010;55(25):2789–2800
3) Bonow RO, Nishimura RA, Thompson PD, Udelson JE; American Heart Association
Electrocardiography and Arrhythmias Committee of Council on Clinical Cardiology, Council
on Cardiovascular Disease in Young, Council on Cardiovascular and Stroke Nursing, Council
on Functional Genomics and Translational Biology, and American College of Cardiology.
Eligibility and Disqualification Recommendations for Competitive Athletes with Cardiovascular
Abnormalities: Task Force 5: Valvular Heart Disease: a Scientific Statement from the American
Heart Association and American College of Cardiology. Circulation. 2015;132(22):e292–e297
291
CCIP.indb 291 3/13/18 4:19 PM

Atrial Septal Defects

Alex J. Thompson, MD, FAAP, and
Introduction
Atrial septal defects (ASDs) are common and constitute roughly 10% of all
congenital heart disease. The incidence is thought to be around 50 to 100 per
100,000 live births.1 They occur because of failure of formation of a portion
of the atrial septum during development. There are 4 distinct types of ASDs
(Figure 19-3). By far the most common (approximately 75%) is the secundum
ASD, which occurs in the mid-portion of the septum, typically involving the
fossa ovalis. Primum ASDs are less common (approximately 20%) and are
seen in partial or complete atrioventricular canal defects. A sinus venosus ASD
PT
SVC
1
2
RV
IVC
FIGURE 19-3. Location of atrial septal defects (ASDs). 1 = Secundum ASD; 2 = primum ASD;
3 = sinus venosus ASD (superior type); and 4 = coronary sinus ASD (unroofed coronary sinus).
IVC = inferior vena cava; PT = pulmonary trunk; RV = right ventricle; SVC = superior vena cava.
292
CCIP.indb 292 3/13/18 4:19 PM

(approximately 5%) is located more posteriorly, either near the entrance of the
superior vena cava (SVC) or in the orifice of the inferior vena cava. Coronary
sinus ASDs are the most rare (<1%); if present, they are often associated with
other venous anomalies.2
Pathophysiology
ASDs result in shunting of blood across the atrial septum. The direction of blood
flow depends on the pressures in the left and right atria. In fetal life, pulmonary
vascular resistance is high, as the lungs are not inflated, which results in increased
right atrial pressures. Oxygenated blood from the umbilical vein enters the right
atrium and is shunted across the atrial septum through the foramen ovale to
the left atrium and the systemic circulation. At birth, the lungs inflate, and the
pulmonary vascular resistance drops. In a normal heart, this results in closure
of the patent foramen ovale. In patients with an ASD, the decrease in right
atrial pressure results in left-to-right shunting across the atrial septum. Larger
defects result in a greater volume of left-to-right shunting, causing right atrial
and ventricular enlargement. This can lead to tricuspid and pulmonary valve
regurgitation as the annuli dilate in response to the enlargement. In addition,
if left untreated for decades, this increased blood volume can lead to the devel-
opment of pulmonary vascular obstructive disease and Eisenmenger syndrome
(right-to-left shunt and cyanosis due to pulmonary hypertension). The effect
of increased pulmonary blood volume on the lungs is less immediate than that
seen with increased hemodynamic pressure. As a result, persons with clinically
significant ventricular septal defects are more vulnerable to Eisenmenger
syndrome in childhood, whereas ASDs do not lead to these irreversible changes
until adulthood.
Clinical Features
Signs and Symptoms
Individuals with ASDs are typically asymptomatic. Rarely, large shunts may
result in pulmonary overcirculation and failure to thrive. Recurrent respiratory
infections may also be present in children with large ASDs, particularly those
with abnormal lungs in association with other conditions (ie, premature infants).
Older children may develop fatigue and dyspnea with exertion. In addition, the
development of right atrial enlargement due to left-to-right atrial-level shunting
may predispose the patient to atrial arrhythmias. Individuals with large shunts
that go unrepaired into adulthood can develop Eisenmenger syndrome, resulting
in cyanosis from the right-to-left shunting at the atrial level. These individuals
may present with cyanosis and syncope with exertion.
293
CCIP.indb 293 3/13/18 4:19 PM

The physical examination findings, like the signs and symptoms, are dependent
on the size of the ASD and the amount of blood shunted across the septum.
Small ASDs will have little in the way of physical findings. Larger left-to-right
shunts result in right ventricular (RV) volume overload. Patients with ASDs may
have a prominent RV impulse felt along the lower left sternal border. In addition,
the increase in RV volume results in greater flow across the pulmonary valve,
yielding a crescendo-decrescendo murmur at the left upper sternal border that
begins after S1 and ends before S2. Unlike the normal physiological splitting of
S2 with respiratory variation, a child with a large ASD may have a widely “fixed”
split S2 with little or no respiratory variation. Lastly, large shunts may generate
a diastolic murmur (“rumble”) over the left lower sternal border, representing
increased inflow across the tricuspid valve (audio available at www.youtube.com/
wUkXxO2IIiesu and www.youtube.com/watch?v=NFAkj9Fbfmw&index=
7&list=PLKCIeugVenPTLW-nspw_wUkXxO2IIiesu) ( ). 
Adolescents and adults who develop pulmonary hypertension develop cyano-
sis as a result of right-to-left atrial-level shunting; if present for a long period of
time, clubbing of the digits may develop. Pulmonary hypertension will generate a
loud P2.
Diagnostic and Preconsult Testing

Chest radiography can be helpful in the identification of cardiomegaly,
increased right atrial and ventricular size, and increased pulmonary vascular
markings. In smaller ASDs, the chest radiographic findings are likely to be
normal. Electrocardiography may show right atrial enlargement or signs of RV
overload, such as right-axis deviation and an interventricular conduction delay,
but findings are often normal in those with smaller shunts. Echocardiography
is the best way to determine the presence and location of an ASD, as well as
assess right-sided chamber size and pressure. Transthoracic echocardiography
is usually sufficient for visualization of ASDs in children, but transesophageal
echocardiography can be used when the images are inconclusive. In addition,
transesophageal images may also be necessary to determine the nature of the
ASD when deciding if closure via catheter device is possible or whether surgical
closure is necessary.
Management
Management is dependent on the size and location of the shunt. The most
common indication for closure is a large shunt, typically quantified as a ratio of
pulmonary to systemic blood flow greater than 1.5 that results in right atrial and
RV enlargement at echocardiography. Most infants will be asymptomatic and
294
CCIP.indb 294 3/13/18 4:19 PM

should have repair delayed until after 2 years of age. In cases in which children
are symptomatic, their ASDs should be closed sooner. Medical management
with diuretics is rarely necessary prior to defect closure. Newborns and infants
with pulmonary disease as a result of another clinical condition (eg, chronic lung
disease) are often more sensitive to the left-to-right shunt of the ASD and may
be symptomatic earlier in life. Although secundum ASDs can be closed surgi-
cally, in many instances, percutaneous closure in the catheterization laboratory
is the preferred modality. However, to achieve a successful percutaneous closure,
the atrial septum needs to have sufficient atrial septal tissue (“rims”) surrounding
the defect to allow the device to be securely positioned. Sinus venosus, primum,
and coronary sinus ASDs all require surgical closure.
Ongoing Care
Infants who receive a diagnosis of small secundum ASDs (<5 mm) will often
have spontaneous closure in the first 2 years of life.3 An ASD larger than 8 mm
in size diagnosed in infancy is unlikely to close spontaneously.
For children who have undergone closure, the outcomes are good. Surgical
closure is associated with low morbidity and mortality; however, given the
need for a sternotomy and cardiac bypass, device closure in the catheterization
laboratory is the preferred modality when possible. Cardiac catheter compli-
cations are rare (<5% of patients) but do include device embolization, residual
shunts, femoral vessel injury, and distortion of adjacent structures (eg, SVC,
valves). A later and rare complication is erosion of the device through the wall
of the atrium anteriorly into the aorta or posteriorly into the pericardium. This
complication is unique to particular devices. In the weeks after ASD closure,
especially surgical closure, providers should be aware of symptoms consistent
with postpericardiotomy syndrome, such as fever, chest pain, nausea, and fatigue.
These symptoms are the result of a new pericardial effusion, which may be
evident by worsening cardiomegaly on chest radiographs but is best determined
by using echocardiography. All children who have undergone ASD closure of
any type require long-term surveillance with a cardiologist for conditions such as
arrhythmia and heart failure.4
Key Points
•• ASDs are common and are often asymptomatic in childhood.
•• Clinically significant shunts should be closed after 2 years of age when asymp-
tomatic (and may rarely be necessary earlier, if the child is symptomatic).
•• Clues to clinically significant shunts include cardiomegaly or increased pulmo-
nary vascular markings on chest radiographs or right-sided heart enlargement
at echocardiography.
295
CCIP.indb 295 3/13/18 4:19 PM

•• Long-standing high-volume shunts can lead to pulmonary hypertension and

Eisenmenger syndrome in adulthood.
Resource for Families

•• Atrial Septal Defect (ASD) (American Heart Association). www.heart.org/
HEARTORG/Conditions/CongenitalHeartDefects/AboutCongenitalHeart
Defects/Atrial-Septal-Defect-ASD_UCM_307021_Article.jsp#.
WWzVKWeWxaQ
References
1) Hoffman JI, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol. 2002;39(12):
1890–1900
2) Sachdeva R. Atrial septal defects. In: Allen HD, Shaddy RE, Penny DJ Feltes TF, Cetta F, eds.
Moss and Adams’ Heart Disease in Infants, Children, and Adolescents: Including the Fetus and Young
Adult. 9th ed. Philadelphia, PA: Wolters Kluwer. 2016
3) Radzik D, Davignon A, van Doesburg N, Fournier A, Marchand T, Ducharme G. Predictive
factors for spontaneous closure of atrial septal defects diagnosed in the first 3 months of life.
J Am Coll Cardiol. 1993;22(3):851–853
4) Videbæk J, Laursen HB, Olsen M, Høfsten DE, Johnsen SP. Long-term nationwide follow-up
study of simple congenital heart disease diagnosed in otherwise healthy children. Circulation.
2016;133(5):474–483
Atrioventricular Canal Defects

Introduction
Atrioventricular (AV) canal defects (AVCDs) involve abnormalities in the
endocardial cushion of the heart (AVCDs are also referred to as endocardial
cushion defects). In a very basic sense, the endocardial cushions form the center
or crux of the heart, including the lower portion of the atrial septum, the AV
valves (ie, tricuspid and mitral), and the upper portion of the ventricular septum.
AVCDs span a range of defects. The classic “complete” AVCD includes a
large atrial septal defect (ASD) and ventricular septal defect (VSD) with 1 large,
common AV valve (Figure 19-4). Other variants include a “transitional” AVCD,
in which the VSD is partially closed, and an “incomplete” or “partial” AVCD,
in which the VSD is completely closed. In rare instances, the AV valve can be
“unbalanced,” leading to functional single-ventricle physiology.
296
CCIP.indb 296 3/13/18 4:19 PM

FIGURE 19-4. Complete atrioventricular canal defect. From http://www.chop.edu/conditions-

diseases/atrioventricular-canal-defects.
AVCDs are rare, occurring in approximately 2 per 10,000 live births. Both
sexes are affected equally, but there is a strong association with trisomy 21.1,2
Pathophysiology
Like VSDs, complete AVCDs can lead to both a pressure load and volume load
on the heart. The degree of pressure transmitted to the right ventricle (RV)
depends on the size of the VSD. Complete AVCDs—with large VSDs—have
equal pressures in the left ventricle and RV. Transitional AVCDs have less
pressure transmitted to the RV, and incomplete or partial AVCDs—with no
297
CCIP.indb 297 3/13/18 4:19 PM

functional VSD—cause no pressure increase in the RV. This is important because

markedly increased right-sided heart pressures hasten symptoms and the devel-
opment of pulmonary hypertension.
In terms of volume, it is important to remember that blood flows from
areas of high resistance to low resistance. Thus, the resistance of the respective
circulations, systemic and pulmonary vascular resistance (PVR), determines the
direction and degree of shunting. Because PVR is generally lower than systemic
vascular resistance in infants, blood flows from the left side of the heart to
the right side of the heart. Given the ASD and VSD in AVCDs, there can be
clinically significant shunting. In addition to shunting through the septal defects,
many patients often have AV valve regurgitation. The result can be clinically
significant dilation, often of all cardiac chambers.
Patients with trisomy 21 often have intrinsically increased PVR. This can
limit the degree of shunting, allowing the child to tolerate the lesion without
clinically significant heart failure early on. The defect still must be repaired
because the pressure load in the pulmonary arteries can lead to permanently
increased PVR (ie, pulmonary hypertension).
Clinical Features
Signs and Symptoms
The signs and symptoms of AVCDs largely relate to excess pulmonary blood
flow. Patients may have tachypnea and increased work of breathing with activity.
Since eating is an exercise equivalent in newborns, they may have feeding
difficulties and poor growth with larger defects.1 Patients with transitional and
incomplete AVCDs may be asymptomatic early in life, presenting only with
a murmur. Some may eventually develop shortness of breath with activity, but
others may never exhibit any symptoms. Pulmonary hypertension will eventually
develop if clinically significant AVCDs are not repaired, resulting in cyanosis
and Eisenmenger syndrome.3
Physical examination findings relate to the signs and symptoms and also depend
on the size of the defect(s). Infants with complete AVCDs may have clinical
features of heart failure, with tachypnea, crackles, hepatomegaly, and failure
to thrive. A systolic murmur is often heard from either the VSD component
or AV valve regurgitation. A diastolic murmur of relative AV valve stenosis
(ie, excess shunted blood flowing across the AV valve) may be heard, as well.
The systolic murmur in these cases may be less prominent because large defects
generate less turbulence to blood flow. A hyperactive precordium with a gallop
can also often be heard.
298
CCIP.indb 298 3/13/18 4:19 PM

Older children and adults with transitional AVCDs often have a loud,
usually holosystolic murmur. A similar diastolic murmur can be heard if
pulmonary hypertension has developed with resultant pulmonary regurgitation;
the P2 component of the second heart sound will also be loud with pulmonary
hypertension.

Echocardiography is the current standard of reference for diagnosis. Most
patients do not require cardiac catheterization unless there is concern for pulmo-
nary hypertension. Thus, most referrals do not require special testing. Obtaining
a chest radiograph can be helpful in infants with symptoms or failure to thrive.
Electrocardiography commonly shows left-axis deviation.
Management
The treatment approach varies on the basis of the degree of hemodynamic
significance. In general, all AVCDs require surgical repair. Complete AVCDs
are generally repaired at about 6 months of age. Infants are managed medically,
primarily with diuretics, until the time of surgery. Pulmonary artery bands
can be placed for tiny or premature infants in whom medical management
is insufficient. Pulmonary artery bands act as fixed resistors, increasing the
resistance to pulmonary artery flow and thereby limiting shunting.4 Patients
with significantly unbalanced AVCDs may be treated with single-ventricle
palliation strategies (eg, Fontan pathway).
Pulmonary hypertension develops in response to both pressure and
volume loads to the lungs. The process occurs faster in response to pressure, so
transitional AVCDs may be repaired later, given the lower risk of developing
pulmonary hypertension. Incomplete or partial AVCDs can be repaired even
later, often somewhere between 2 and 5 years of age.
Patients generally do well after repair, with low major morbidity and mor-
tality in the current era.4 Most are able to stop taking medications after repair.
Endocarditis prophylaxis is not indicated for unrepaired AVCDs. All patients
require endocarditis prophylaxis for at least 6 months after surgical repair.
Ongoing Care
All patients born with an AVCD require lifelong follow-up. They may be at
increased risk for ventricular dysfunction, valvular stenosis and regurgitation, and
cardiac arrhythmias. These risks increase if the patient required an intervention.
These patients generally have no restrictions to athletic participation
after successful repair. Patients are expected to have relatively normal oxygen
saturation levels after repair, though the arterial saturation may be 95% or so if
299
CCIP.indb 299 3/13/18 4:19 PM

the coronary sinus is closed into the left atrium. Patients often have relatively
normal quality and length of life.
Key Points
•• Infants often develop symptoms of heart failure, given the atrial- and
ventricular-level shunting.
•• Most infants can be medically treated until surgery, often performed at about
6 months of age.
•• AVCDs are often associated with trisomy 21.

•• Complete Atrioventricular Canal Defect (American Heart Association).
www.heart.org/HEARTORG/Conditions/CongenitalHeartDefects/
AboutCongenitalHeartDefects/Complete-Atrioventricular-Canal-defect-
CAVC_UCM_307023_Article.jsp
References
1) Calabrò R, Limongelli G. Complete atrioventricular canal. Orphanet J Rare Dis. 2006;1:8
2) Cousineau AJ, Lauer RM, Pierpont ME, et al. Linkage analysis of autosomal dominant
atrioventricular canal defects: exclusion of chromosome 21. Hum Genet. 1994;93(2):103–108
3) Partin C. The evolution of Eisenmenger’s eponymic enshrinement. Am J Cardiol. 2003;92(10):
1187–1191
4) Crawford FA Jr, Stroud MR. Surgical repair of complete atrioventricular septal defect. Ann
Thorac Surg. 2001;72(5):1621–1628, discussion 1628–1629
Coarctation of the Aorta

Introduction
Coarctation of the aorta is narrowing that occurs in the proximal descending
aorta (Figure 19-5). Isolated coarctation of the aorta is fairly common, with
an incidence of approximately 0.3 per 1,000 live births; there is a slight male
predominance, with a male-to-female prevalence of 60% and 40%, respectively.1
Coarctation of the aorta is commonly associated with other cardiac conditions,
being present in up to 4% to 5% of patients with other forms of congenital heart
300
CCIP.indb 300 3/13/18 4:19 PM

Narrowed aorta
(coarctation)
AO
LA
PA
RA
LV
RV
Oxygen-rich blood
Oxygen-poor blood
AO: Aorta PA: Pulmonary artery

LA: Left atrium LV: Left ventricle
RA: Right atrium RV: Right ventricle
FIGURE 19-5. Coarctation of the aorta. From http://www.chop.edu/conditions-diseases/

coarctation-aorta.
disease (CHD). In the most extreme case, the aorta is interrupted, with the lower
segment receiving blood exclusively via a patent ductus arteriosus (PDA).
Coarctation is believed to result from extension of muscular tissue from the
PDA into the wall of the aorta. That muscular tissue constricts to close the PDA
after birth, and its extension into the aorta causes the narrowing.2 Thus, the
site of coarctation of the aorta is often referred to as “juxtaductal.” The precise
mechanism that causes this extension is incompletely understood. As an aside,
this extension of PDA tissue can occur in the pulmonary arteries and can cause
isolated branch pulmonary artery stenosis.
Pathophysiology
The narrowing in the aorta causes a pressure load on the left ventricle (LV).
The LV has to work harder to pump blood to the lower half of the body. The
LV becomes hypertrophied and, if the coarctation is significant enough, LV
301
CCIP.indb 301 3/13/18 4:19 PM

dysfunction may develop. The degree of obstruction can vary markedly. The
worst cases are critical coarctation and even interrupted aortic arch, conditions
generally defined as being “ductal dependent” (ie, the patient requires an open
PDA to survive). Some cases of interrupted aortic arch can be so severe that the
LV fails to develop sufficiently, requiring more complex repair strategies. On the
other hand, patients can have mild coarctation that causes minimal symptoms
and only trivial obstruction to blood flow. Since pressure gradients are related
to flow, exercise—which increases cardiac output—can exacerbate the degree of
obstruction and precipitate symptoms.
Because vessels proximal to the coarctation are not obstructed, they may
become hypertensive. Notably, collateral vessels can develop around the coarcta-
tion to supply blood to the lower half of the body. In some patients, the collateral
vessels can develop so extensively that there is no difference in blood pressure at
rest. Finally, bicuspid aortic valves are commonly associated with coarctation of
the aorta and will be screened for by a pediatric cardiologist.
Clinical Features
Signs and Symptoms
As discussed earlier, the signs and symptoms of coarctation of the aorta depend
on the degree of obstruction. In critical coarctation, infants present with poor
feeding, pallor, decreased urine output, and tachypnea. All of these issues are
related to cardiogenic shock with inadequate perfusion to the lower body—
including the kidneys—and subsequent metabolic acidosis. Older children most
often present with hypertension in the upper extremities. They may also have
headaches and decreasing exercise tolerance.3 The enlarged collateral arteries
can cause rib-notching on chest radiographs, which is classically associated
with coarctation of the aorta.
Physical examination findings relate to the degree of obstruction and collateral
flow. Infants with critical coarctation of the aorta present in extremis with pallor,
a murmur, bounding upper-extremity pulse, and decreased femoral pulse. Older
children and adults may present with hypertension and are found to have a
4-extremity blood pressure differential (ie, systolic arm blood pressure more than
20 mm Hg higher than the leg blood pressure is suspicious). They too may have
diminished femoral pulses and will usually have radial-to-femoral pulse delay. A
systolic murmur may be heard at the left upper sternal border or the back (ie, left
interscapular area). There may be a systolic click if the aortic valve is bicuspid.
302
CCIP.indb 302 3/13/18 4:19 PM


Echocardiography and sometimes computed tomography are key to diagnosis
currently. A chest radiograph can be helpful when evaluating the patient for
rib-notching or the “three” sign; these findings are considered “classic” in older
children and adults but are uncommon in children under the age of 5. The deci-
sion for more sophisticated imaging should be made by a pediatric cardiologist.
Management
The overall treatment approach varies on the basis of the degree of hemodynamic
significance and patient age. In general, critical coarctation in newborns requires
surgery because outcomes from primary catheterization are suboptimal. Infants
with critical coarctation of the aorta should be started on prostaglandin E
immediately, with transfer to a tertiary care facility with a complete CHD team.
For older patients, either surgery or catheterization can be the initial inter-
vention. The coarctation segment can be either dilated or undergo percutaneous
stent placement in many cases. The specific intervention depends on the patient’s
age, weight, and degree of obstruction. In general, stent implantation is reserved
for older patients, in whom larger stents can be placed with less risk of vascular
compromise.
Notably, standard medical treatments for hypertension may exacerbate or
even cause symptoms in patients with coarctation of the aorta.
Patients generally do well after repair, with low morbidity and mortality in
the current era.4,5 A substantial number (10%–20%) require a reintervention for
recurrent coarctation of the aorta. Catheterization is the treatment of choice
for recurrent coarctation of the aorta, with few requiring repeat surgery in the
current era.6 Endocarditis prophylaxis is not indicated for patients with unre-
paired coarctation of the aorta. All patients require endocarditis prophylaxis for
at least 6 months after surgical or percutaneous repair if the procedure involves
prosthetic material (ie, patch or stent).
Ongoing Care
All patients born with CHD, and especially those who have undergone an
intervention, require lifelong follow-up. Patients with residual or long-standing
coarctation of the aorta are at risk for developing hypertension and potentially
ventricular dysfunction. Patients who underwent an intervention are at increased
risk for recurrent coarctation. These patients may have restrictions to athletic
participation, depending on the degree of obstruction. Patients are expected to
have normal oxygen saturation levels after repair and a relatively normal quality
and length of life.
303
CCIP.indb 303 3/13/18 4:19 PM

Key Points
•• Coarctation can manifest with cardiogenic shock in an infant or with hyper
tension and/or decreased lower-extremity pulse in older patients.
•• Always check 4-extremity blood pressures at least once in anyone with
increased upper-extremity blood pressure.
•• Although often appearing in older children, “noncritical” coarctation can
manifest at any age.

•• Coarctation of the Aorta (American Heart Association). www.heart.org/
Defects/Coarctation-of-the-Aorta-CoA_UCM_307022_Article.jsp
References
1) Botto LD, Correa A, Erickson JD. Racial and temporal variations in the prevalence of heart
defects. Pediatrics. 2001;107(3):E32
2) Rudolph AM. Aortic arch obstruction. In: Congenital Diseases of the Heart: Clinical-Physiological
Considerations. Fully Rev. and Updated. 2nd ed. Armonk, NY: Futura Pub Co; 2001:367–412
3) Rudolph AM, Heymann MA, Spitznas U. Hemodynamic considerations in the development
of narrowing of the aorta. Am J Cardiol. 1972;30(5):514–525
4) Corno AF, Botta U, Hurni M, et al. Surgery for aortic coarctation: a 30 years experience.
Eur J Cardiothorac Surg. 2001;20(6):1202–1206
5) Hamdan MA, Maheshwari S, Fahey JT, Hellenbrand WE. Endovascular stents for
coarctation of the aorta: initial results and intermediate-term follow-up. J Am Coll Cardiol.
2001;38(5):1518–1523
6) Marshall AC, Perry SB, Keane JF, Lock JE. Early results and medium-term follow-up of
stent implantation for mild residual or recurrent aortic coarctation. Am Heart J. 2000;139(6):
1054–1060
304
CCIP.indb 304 3/13/18 4:19 PM

“Congenitally Corrected”
Transposition of the
Great Arteries
Introduction
“Congenitally corrected” transposition of the great arteries (TGA), also called
ventricular inversion or levo-TGA (L-TGA, referring to the levo-rotation of the
arteries), is a rare and complex condition in which both the ventricles and the
great artery positions are switched. The result is a normal flow of deoxygenated
blood to the lungs and oxygenated blood to the body, but with inverted ventricles
(Figure 19-6). Patients with L-TGA often have other coexisting cardiac lesions,
most commonly atrial septal defects (ASDs), ventricular septal defects (VSDs),
or pulmonary valve stenosis. L-TGA is rare, with an incidence of approximately
0.5 to 0.7 per 1,000 live births.1 The precise mechanisms that lead to L-TGA in
utero are incompletely understood.
Blue blood coming

back to heart from
Red blood being
head and upper
pumped to all parts
body (SVC)
of the body (Aorta)
Blue blood being
pumped to the
lungs (PA)
Upper chambers
are normally Left atrium
placed
Right atrium Right ventricle
Left ventricle
Pumping chambers
are the wrong way
around
FIGURE 19-6. Congenitally corrected transposition of the great arteries. PA = pulmonary artery,
SVC = superior vena cava.
305
CCIP.indb 305 3/13/18 4:19 PM

Pathophysiology
As previously noted, L-TGA has normal and physiological flow of blood, so
patients are not cyanotic. More specifically, the systemic venous blood returns
to the right atrium and then flows through a right-sided mitral valve into the
right-sided left ventricle (LV). The LV is aligned with the pulmonary artery,
so the deoxygenated blood ultimately flows to the lungs. On the other side, the
pulmonary venous blood returns to the left atrium, then flows through a left-
sided tricuspid valve into the left-sided right ventricle (RV). The RV is aligned
with the aorta, so the oxygenated blood flows normally to the body.
Although the deoxygenated and oxygenated blood flows normally, patients with
L-TGA have multiple potential issues. First, the RV is the systemic ventricle,
and it has substantial potential to fail over time. Similarly, the tricuspid valve
is under systemic conditions, so there is increased risk of developing tricuspid
regurgitation. As a corollary, the LV only pumps to the low-resistance lungs,
so it becomes “deconditioned.” Although not a major problem initially, the
deconditioning of the LV can be important prior to repair (see the next section).
The conduction system is also affected by L-TGA. Patients with L-TGA are
at substantial risk of developing complete heart block (approximately 1% chance
per year of life).
Clinical Features
Signs and Symptoms
The signs and symptoms of L-TGA can vary markedly. If there are no other
lesions, patients may have no symptoms for years or even decades. The symptoms
those patients develop are often related to RV failure or clinically significant tri-
cuspid regurgitation.2 Because the RV is the systemic ventricle, these symptoms
will be similar to what are classically considered issues with LV dysfunction.
These symptoms include fatigue, dyspnea, pallor, and peripheral edema, among
others. If other lesions (eg, an ASD, VSD, or pulmonary valve stenosis) are
present, the patient may develop symptoms related to those abnormalities.
Physical examination findings depend on the presence of other cardiac defects.
As previously discussed, some patients with isolated L-TGA may have no symp-
toms and few notable physical examination findings. Patients with RV failure
may have a gallop, respiratory findings such as wheezing and crackles, and a
systolic murmur from tricuspid regurgitation. If present, examination findings of
other defects may be noted, including a systolic murmur of a VSD or pulmonary
and/or aortic stenosis, and wide-split S2 from an ASD.
306
CCIP.indb 306 3/13/18 4:19 PM


Echocardiography is important for diagnosis. Magnetic resonance imaging can
be crucial, as well, given the additional data it can provide relating to ventricular
chamber size, mass, and fibrosis.
Management
The overall treatment approach varies and remains the subject of considerable
discussion among cardiologists and cardiac surgeons. Surgical repair is difficult
because it involves both atrial and great arterial switches, the so-called double
switch procedure.3
Given these issues, most centers take 1 of 3 approaches. The first is to repair
abnormalities early in life, before the LV becomes deconditioned.
Another approach is to perform the double switch in late childhood or early
adolescence, while the patient is still healthy and before the onset of clinically
significant ventricular or valvar dysfunction. This approach often requires 2 steps,
the first being to place a pulmonary artery band. A pulmonary artery band adds
restriction to flow, which increases workload on the LV. In a simplistic sense,
placing the band is akin to forcing the LV to “lift weights.” This technique
reconditions the LV so it can successfully pump to the higher-resistance systemic
circulation after a subsequent double switch procedure. The LV mass and
strength increase quickly, in as little as 3 to 7 days, so the second step—
the double switch—is often performed during the same hospitalization.
Finally, the third approach is to monitor the patients expectantly, treat
any morbidities, and potentially list the patient for transplantation if the RV
dysfunction becomes too severe.
Since patients with L-TGA are at risk for developing heart block, some
may require pacemaker placement. In fact, if a surgery is being performed later
in childhood, many groups opt to place permanent pacemaker wires—even
without the actual pacemaker generator—given the high likelihood of eventually
requiring a pacemaker.
Endocarditis prophylaxis is not indicated for unrepaired L-TGA. All patients
require endocarditis prophylaxis for at least 6 months after a surgery if the
procedure involves placement of prosthetic material.
Ongoing Care
All patients born with congenital heart disease, and especially those who
have undergone an intervention, require lifelong follow-up. All patients with
L-TGA that undergo a double-switch procedure are at increased risk for
numerous issues. From the atrial switch portion of the surgery, they are at risk
for developing obstruction in 1 of the segments of the repair (ie, inferior vena
cava and superior vena cava). There is also an increased long-term risk for
307
CCIP.indb 307 3/13/18 4:19 PM

atrial arrhythmias. Similarly, there is an increased risk for suprapulmonary and

supra-aortic stenosis after an arterial switch.3
Patients with L-TGA may have restrictions for athletic participation on the
basis of their overall condition and the presence of other cardiac lesions. Patients
are expected to have normal oxygen saturation levels after repair, but the quality
and length of life vary among each patient.
Key Points
•• Even after correction, patients with L-TGA will potentially have long-term
cardiac issues.
•• Surgical repair can be complex, involving both atrial and great arterial switches;
hence, there is debate about whether repair should be performed, and if so, when.
•• The RV is systemic and is at risk for developing failure.

•• L-Transposition of the Great Arteries (American Heart Association).
www.heart.org/HEARTORG/Conditions/CongenitalHeartDefects/
AboutCongenitalHeartDefects/l-Transposition-of-the-great-arteries_
UCM_307031_Article.jsp
References
2) Graham TP Jr, Bernard YD, Mellen BG, et al. Long-term outcome in congenitally corrected
transposition of the great arteries: a multi-institutional study. J Am Coll Cardiol. 2000;36(1):255–261
3) Hraska V, Duncan BW, Mayer JE Jr, Freed M, del Nido PJ, Jonas RA. Long-term outcome of
surgically treated patients with corrected transposition of the great arteries. J Thorac Cardiovasc
Surg. 2005;129(1):182–191
Mitral Valve Anomalies

Introduction
Congenital anomalies of the mitral valve are rare. Mitral valve anomalies can
result in mitral stenosis or mitral regurgitation. The male-to-female ratio of
congenital mitral valve disease is approximately 1.5 to 1.1
308
CCIP.indb 308 3/13/18 4:19 PM

Anatomy
The mitral valve consists of 2 leaflets, an anterior leaflet and a posterior leaflet.
The leaflets are normally attached to 2 papillary muscles (anterolateral and
posteromedial) by chordae. The most common anomaly that leads to mitral
regurgitation is a cleft mitral valve. In the absence of associated congenital heart
disease (CHD), the cleft typically occurs in the anterior leaflet and is directed
toward the left ventricular outflow tract.2
Mitral stenosis can result from a double-orifice mitral valve, a mitral valve
arcade, or a parachute mitral valve. In a double-orifice mitral valve, the mitral
valve leaflets open in bifid manner, creating 2 smaller orifices. In a mitral valve
arcade, the chordae are abnormal, absent, or fused, and the mitral valve leaflets
insert directly into the papillary muscles. In a parachute mitral valve, there is a
single papillary muscle. In a variation of a parachute mitral valve, there may be
2 papillary muscles, but most chordae attach to 1 of the papillary muscles, with
very few chordae attaching to the other.1,3
Clinical Features
Signs and Symptoms
Mitral regurgitation or stenosis that worsens gradually over time can manifest
with a newly noted murmur, arrhythmia, or, occasionally, evidence of pulmonary
hypertension. Acute mitral regurgitation, such as that which occurs with rheu-
matic heart disease or mitral valve endocarditis, can manifest with sudden-onset
symptoms of poor cardiac output or pulmonary hypertension. When mitral
disease occurs because of rheumatic heart disease, there is typically a history
of a preceding illness consistent with streptococcal disease. When mitral valve
disease occurs because of endocarditis, there is typically a history consistent with
endocarditis, such as indolent fevers, splenomegaly, or another septic embolic
phenomenon. The murmur of mitral regurgitation is typically a blowing systolic
murmur that is heard best at the apex. The murmur of mitral stenosis can be
more difficult to detect but is typically a rumbling diastolic murmur noted at
the apex.1

The diagnosis of mitral valve disease requires transthoracic echocardiography
(TTE). Sometimes 3-dimensional (3D) TTE can be used to help elucidate
the mechanism of the mitral valve disease. In larger patients with poor acoustic
windows, transesophageal echocardiography with or without 3D imaging may
provide improved diagnostic images. If there is concern for clinically significant
pulmonary hypertension, a chest radiograph can be useful for demonstrating
pulmonary vascular congestion.1
309
CCIP.indb 309 3/13/18 4:19 PM

Management
Surgical therapy for mitral valve disease can be difficult in infants and small
children. For this reason, surgical intervention is typically reserved for those with
symptoms such as exercise intolerance, arrhythmias, or pulmonary hypertension.
If the mechanism of mitral valve disease is such that surgical repair is deemed
likely, surgery may be attempted prior to the development of symptoms. If repair
is not possible and surgical intervention is indicated, mitral valve replacement
will be undertaken. Because of the limited sizes available for mechanical mitral
valves, as well as the lack of growth potential of a mechanical valve, this option
is delayed as long as possible. Once placed, if the mechanical valve is not adult
sized, the patient will require repeat replacement of the valve as he or she grows.1
Medical therapy for mitral regurgitation and mitral stenosis is also limited and
aimed at supportive treatment. Occasionally, low-dose diuresis may be used
to help limit pulmonary vascular congestion. The use of afterload reduction
in mitral regurgitation, such as angiotensin-converting enzyme inhibition, is
controversial, and minimal data exist in children to guide its usage.4
Ongoing Care
Mild mitral regurgitation or mild mitral stenosis can be well tolerated for some
time in children. Typically, children with mitral valve disease are encouraged to
self-limit activities. The exception would be children with mitral valve disease
caused by acute rheumatic fever. Typically, in the setting of acute rheumatic
fever, strict activity restrictions are imposed until after the inflammation has
resolved (typically 3–6 months from the time of diagnosis). Children who are
symptomatic with activity are typically referred for surgical repair or replacement
of the mitral valve.
If the mitral valve requires replacement with a mechanical valve, lifelong anti-
coagulation becomes paramount. Children who receive anticoagulation therapy
are typically restricted from contact sports to avoid bleeding complications.
There is no specific familial counseling necessary. However, families should
be counseled that there can be a risk of recurrence of CHD in subsequent
pregnancies (if the mitral valve disease is congenital and not acquired). Mothers
should be offered screening fetal echocardiography between 18 and 22 weeks of
gestation in subsequent pregnancies.
Key Points
•• Congenital mitral valve disease can worsen over time. New symptoms should
prompt re-evaluation by a pediatric cardiologist.
•• When surgical intervention is indicated, repair is preferred to replacement of
the mitral valve whenever possible.
310
CCIP.indb 310 3/13/18 4:19 PM

References
1) Mackie AS, Smallhorn JF. Anatomical and functional mitral valve abnormalities in the
pediatric population. In: Allen HD, Driscoll DJ, Shaddy RE, Feltes TF, eds. Moss and Adams’
Heart Disease in Infants, Children, and Adolescents Including the Fetus and Young Adult. 8th ed.
Philadelphia, PA: Lippincott Williams & Wilkins; 2013:1003–1022
2) Fraisse A, Massih TA, Kreitmann B, et al. Characteristics and management of cleft mitral valve.
J Am Coll Cardiol. 2003;42(11):1988–1993
3) Collins-Nakai RL, Rosenthal A, Castaneda AR, Bernhard WF, Nadas AS. Congenital mitral
stenosis. A review of 20 years’ experience. Circulation. 1977;56(6):1039–1047
4) Knirsch W, Tlach L, Stambach D, Bauersfeld U. Angiotensin-converting enzyme inhibitors in
pediatric patients with mitral valve regurgitation-case-control study and review of the literature.
Patent Ductus Arteriosus

Anatomy
The ductus arteriosus is a normal structure in every fetus in utero. It allows fetal
blood flow to bypass the lungs. Typically, the ductus arteriosus closes shortly
after birth, usually in the first 48 hours.1 If it fails to close normally, it is called a
patent ductus arteriosus (PDA). Persistence of the ductus arteriosus or a PDA is
more common in preterm infants, infants born to mothers with first-trimester
rubella infections, infants born at higher altitudes, and female infants.2–4
Clinical Features
The clinical history will vary, depending on the age of the patient and the
size of the shunt. In premature infants, the clinical history can be somewhat
nonspecific. They could demonstrate worsening respiratory status with
tachypnea, apnea, or increased ventilator requirements or could have circulatory
instability with a low diastolic blood pressure and metabolic acidosis, which
may mimic sepsis. In full-term infants and children, a small PDA may not
have any significant clinical history. A moderate or large PDA will manifest
in an infant with nonspecific symptoms, such as tachypnea, irritability, poor
feeding, diaphoresis, or failure to gain weight. Older children may present
with shortness of breath and exercise intolerance. The murmur of a PDA
is classically a “machinery-type” c ontinuous murmur that is heard best in
the second left intercostal space (audio available at www.youtube.com/
311
CCIP.indb 311 3/13/18 4:19 PM

watch?v=KBVNJtayzbA&index=16&list=PLKCIeugVenPTLW-nspw_

wUkXxO2IIiesu) ( ). However, it is important to note that in newborns,
only the systolic portion of the murmur may be heard, because of the increase
in pulmonary vascular resistance present in newborns. The murmur becomes
more continuous over time as the pulmonary vascular resistance decreases.
During blood pressure measurements, there may be a widened pulse pressure
if the PDA is large.
In general, if there is concern for a PDA on the basis of clinical findings,
chest radiography may be helpful in providing information regarding the
absence or presence of a clinically significant shunt. The definitive diagnostic
test is echocardiography, which can be used to evaluate the presence and size
of the ductus, as well as the direction of shunting. Echocardiography can also
be used to evaluate left atrial and ventricular chamber sizes to determine the
hemodynamic significance of the PDA.
Management
The main goal of treatment in premature infants is to prevent related morbidity
and mortality secondary to hemodynamic instability and comorbidities such
as respiratory distress syndrome, necrotizing enterocolitis, and intraventricular
hemorrhage. Initial treatment typically consists of medical treatment with
cyclo-oxygenase inhibitors, such as indomethacin, administered either prophy-
lactically (prior to clinically evident symptoms) or once a symptomatic ductus
is noted to be present.5 Surgical ligation is usually reserved as a second-line
treatment when medical treatment has failed or is contraindicated. Surgical
ligation of the PDA has a high success rate and low associated mortality.6
In full-term infants and children, the goal of treatment is to alleviate or
prevent heart failure and to prevent increased pulmonary pressures with a
hemodynamically significant shunt. With smaller shunts or “silent” (inaudible)
PDAs, the goal of treatment is to prevent endarteritis by intervening to close the
ductus, although this remains controversial. Any infant or child who is symp-
tomatic typically undergoes closure as soon as possible. Patients who present in
the neonatal period may not be large enough to undergo percutaneous closure at
presentation, and for these patients, medical management of their heart failure
symptoms may be instituted on a temporary basis to allow the patient to reach
a large enough size for percutaneous intervention. Catheter-based closure is the
first line of treatment in this group of patients and has been reported to have
been safely performed in patients as young as 6 months of age and as small as
5 kg.7 The procedure has a high success rate, with few complications and no
mortality.8 Surgical ligation in full-term infants and children is typically reserved
for ducts that are thought to be too large for transcatheter closure or for symp-
tomatic infants who are too small for safe transcatheter closure.
312
CCIP.indb 312 3/13/18 4:19 PM

Ongoing Care
The prognosis of most patients after catheter-based or surgical closure of a
PDA is very good. Typically, after the procedure, the patients are well, and the
procedure is considered curative. Patients with no residual cardiac disease are
frequently discharged from routine cardiology follow-up after 6 months to a
year. Patients should receive endocarditis prophlyaxis for 6 months after device
closure, but then they do not need routine endocarditis prophylaxis after that.
Patients with an untreated PDA with a normal left-sided heart size do not
require any activity restrictions. Those with a more hemodynamically significant
shunt and left-sided heart enlargement should undergo closure prior to com-
petitive athletics. Children may return to full participation 3 months after PDA
closure if they have normal cardiac examination findings with no evidence of left
ventricular enlargement or increased pulmonary pressures.
Siblings of patients with a PDA are at an increased risk (3%) of also having a
PDA,9 though no routine family screening recommendations are available.
Key Points
•• The clinical presentation of a PDA varies on the basis of the age of the patient
and the size of the PDA.
•• Prognosis of patients after catheter- or surgical-based closure of the PDA is
very good.
References
1) Kitterman JA, Edmunds LH Jr, Gregory GA, Heymann MA, Tooley WH, Rudolph AM.
Patent ducts arteriosus in premature infants. Incidence, relation to pulmonary disease and
management. N Engl J Med. 1972;287(10):473–477
2) Rothman KJ, Fyler DC. Sex, birth order, and maternal age characteristics of infants with
congenital heart defects. Am J Epidemiol. 1976;104(5):527–534
3) Gibson S, Lewis KC. Congenital heart disease following maternal rubella during pregnancy.
AMA Am J Dis Child. 1952;83(3):317–319
4) Miao CY, Zuberbuhler JS, Zuberbuhler JR. Prevalence of congenital cardiac anomalies at
high altitude. J Am Coll Cardiol. 1988;12(1):224–228
5) Dollberg S, Lusky A, Reichman B. Patent ductus arteriosus, indomethacin and necrotizing
enterocolitis in very low birth weight infants: a population-based study. J Pediatr Gastroenterol
Nutr. 2005;40(2):184–188
6) Little DC, Pratt TC, Blalock SE, Krauss DR, Cooney DR, Custer MD. Patent ductus arteriosus
in micropreemies and full-term infants: the relative merits of surgical ligation versus indometha-
cin treatment. J Pediatr Surg. 2003;38(3):492–496
7) Butera G, De Rosa G, Chessa M, et al. Transcatheter closure of persistent ductus
arteriosus with the Amplatzer duct occluder in very young symptomatic children. Heart.
2004;90(12):1467–1470
8) Masura J, Tittel P, Gavora P, Podnar T. Long-term outcome of transcatheter patent ductus
arteriosus closure using Amplatzer duct occluders. Am Heart J. 2006;151(3):755.e7–755.e10
9) Nora JJ. Multifactorial inheritance hypothesis for the etiology of congenital heart diseases. The
genetic-environmental interaction. Circulation. 1968;38(3):604–617
313
CCIP.indb 313 3/13/18 4:19 PM

Patent Foramen Ovale

Anatomy
A patent foramen ovale (PFO) is a common cardiac finding. It should be consid-
ered a normal variant, rather than an abnormality. The atrial septum is the wall
between the left and right atria. Embryologically, the foramen ovale is formed
by the overlap of 2 separate tissue flaps in the atrial septum (Figure 19-7).
The foramen ovale, which is necessary for successful gestation, usually closes
spontaneously in infancy as the 2 flaps fuse with one another.1 Failure to do so
results in a small communication between the 2 atria, a PFO. About 30% of
adults have a PFO.1
Clinical Features
Typically, a PFO is clinically silent. There are no historical findings, signs, or
symptoms that suggest its presence. Patients are fully saturated. Echocardio
graphy must be performed to identify a PFO, and even then a PFO can be
missed, particularly in older patients. As such, a PFO is usually an incidental
FIGURE 19-7. A patent foramen ovale demonstrated at echocardiography. A small amount of blood
can be seen crossing from the left to the right atrium.
314
CCIP.indb 314 3/13/18 4:19 PM

finding while testing for other pathologic processes, especially in the newborn
period. If a thrombus, typically from a deep venous thrombosis in the lower
extremities, crosses from the right atrium through the PFO into the left atrium
(ie, paradoxical embolus), there is a chance that it can compromise cerebral
circulation, resulting in a stroke. This is unusual in the pediatric population.2
There are some claims that PFOs are associated with headaches.3
Management
No medications or interventions are necessary for a PFO in most individuals.
While childhood strokes are usually caused by pathologic causes other than a
PFO, children with a stroke thought to be related to a PFO are candidates for
anticoagulant or antiplatelet therapy. The American Heart Association does
not recommend prophylactic closure of PFO in adults with a first-time stroke
and recognizes that data in children are lacking.4 Closing a PFO as a treatment
for headaches is controversial and is not recommended by the American
Headache Society.3
Ongoing Care
A PFO rarely requires therapy, cardiology consultation, or routine follow-up.
Families should be reassured that a PFO is a normal variant. Endocarditis pro-
phylaxis is not required. Individuals with a PFO are expected to have a normal
life span. Routine screening of family members is not necessary. There are no
activity restrictions of any kind, including sports and roller coasters.
Key Points
•• A PFO is a normal variant, present in approximately 30% of the adult
population. Cardiology consultation or follow-up is unnecessary for patients
with isolated PFO.
•• In the absence of a stroke thought to be related to the PFO, no therapy
is indicated.
References
1) Maleszewski J, Edwards W. Cardiac Anatomy and examination of cardiac specimens. In: Allen
H, Shaddy R, Penny D, Feltes T, Cetta F, eds. Moss and Adams’ Heart Disease in Infants, Children,
and Adolescents Including the Fetus and Young Adult. 9th ed. Philadelphia, PA: Wolters Kluwer;
2016; 188
2) Khan R, Chan AK, Mondal TK, Paes BA; Thrombosis and Hemostasis in Newborns (THIN)
Group. Patent foramen ovale and stroke in childhood: a systematic review of the literature.
Eur J Paediatr Neurol. 2016;20(4):500–511
3) Tariq N, Tepper SJ, Kriegler JS. Patent foramen ovale and migraine: closing the debate—a
review. Headache. 2016;56(3):462–478
315
CCIP.indb 315 3/13/18 4:19 PM

4) Giglia TM, Massicotte MP, Tweddell JS, et al; American Heart Association Congenital
on Cardiovascular and Stroke Nursing, Council on Epidemiology and Prevention, and Stroke
Council. Prevention and treatment of thrombosis in pediatric and congenital heart disease: a
scientific statement from the American Heart Association. Circulation. 2013;128(24):2622–2703
Pulmonary Stenosis
Heather Anderson, MD, FAAP, and
Nicolas Madsen, MD, MPH, FAAP
Introduction
Pulmonary stenosis refers to obstruction of the right ventricular outflow tract,
typically at the level of the pulmonary valve. Pulmonary stenosis often occurs
to a pulmonary valve that has a bicuspid valve or other abnormal morphologic
feature. Obstruction may also occur at the supravalvar or subvalvar levels, as well.
Supravalvar pulmonary stenosis refers to a site of narrowing just above the valve,
while subvalvar stenosis results from thickening of the muscular outflow tract
of the right ventricle (RV) below the level of the valve. Pulmonary stenosis may
occur in isolation or in association with other types of congenital heart disease
(CHD). It is commonly associated with pulmonary insufficiency in cases were
the valve is dysplastic. Approximately one-half of children with complex CHD
have some degree of pulmonary stenosis. The prevalence of pulmonary stenosis
is approximately 5 per 10,000 live births, which makes it the most common
nonseptal defect form of CHD.1
Pathophysiology
Pulmonary valve stenosis typically results from dysplasia of the pulmonary
valve, with variable degrees of commissural fusion and thickening of the valve
leaflets. The valve annulus may also be hypoplastic, resulting in further stenosis.
Pulmonary valve stenosis may be associated with Noonan syndrome.2 In these
cases, the pulmonary valve is often severely dysplastic and may be resistant to
catheter-based interventions. Pulmonary valve stenosis, as well as peripheral
pulmonary artery stenosis, can also be seen in association with congenital
rubella infection.3
316
CCIP.indb 316 3/13/18 4:19 PM

The obstruction to blood flow created by pulmonary stenosis results in an

increase in RV pressure. As a result of this afterload, the RV often becomes
hypertrophied. Severe RV hypertrophy may result in additional subvalvular
pulmonary stenosis due to increased muscle thickness in the outflow tract below
the pulmonary valve. Over time, chronically increased RV afterload may result
in dilation of the ventricle and decreased function. Mild pulmonary stenosis is
typically asymptomatic because the afterload on the RV is minimal.
Clinical Features
Signs and Symptoms
The presentation of pulmonary stenosis is variable, depending on the degree of
outflow obstruction. Critical pulmonary stenosis is rare and manifests in infancy
with cyanosis and symptoms of right-sided heart failure. These infants are
dependent on a patent ductus arteriosus to provide pulmonary blood flow. With
strenuous exercise, patients with moderate to severe pulmonary stenosis may
experience chest pain, syncope, or, rarely, sudden death. However, many children
with mild pulmonary stenosis present later in childhood with an isolated murmur
detected at routine examination (audio available at www.youtube.com/watch?v=
8uk8iKxu5HY&index=17&list=PLKCIeugVenPTLW-nspw_wUkXxO2IIiesu)

( ). These children often have normal growth and development.
Murmur is the most common clinical finding in pulmonary stenosis and is
typically distinctive. The tones are of a harsh systolic ejection quality in a cre-
scendo-decrescendo fashion best heard at the left upper sternal border. While a
case of mild pulmonary stenosis may demonstrate up to a grade III/VI murmur,
cases associated with a thrill at grade >IV/VI are more likely to be moderate to
severe stenosis. A pulmonary ejection click, which corresponds to the opening
of a dysplastic pulmonary valve, may also be present. The S1 and S2 heart tones
are both heard with pulmonary stenosis. Unless there is increasing pulmonary
hypertension, they are of normal quality.
The murmur of pulmonary stenosis should be differentiated from the benign
murmur of peripheral pulmonary stenosis. A peripheral pulmonary stenosis
murmur is typically heard in newborn infants and radiates to the axilla and
back. This murmur results from the relatively acute angle, as well as transient
hypoplasia of the branch pulmonary arteries in infancy, and should resolve
by the time the patient is 6 months old. Peripheral pulmonary stenosis is not
associated with cyanosis.
317
CCIP.indb 317 3/13/18 4:19 PM


Although the murmur of pulmonary stenosis may be believed to be diagnostic,
echocardiography is required for formal diagnosis (Figure 19-8). Echocardio
graphy is required to evaluate the level of stenosis (valvar, subvalvar, or supraval-
var), as well as the severity and the potential for associations with insufficiency or
other forms of complex CHD. Additional testing, such as exercise testing, should
be guided by a pediatric cardiologist.
Management
In most cases, patients with mild pulmonary stenosis will never require a proce-
dural intervention. However, intervention is typically required for patients with
moderate to severe stenosis. The present-day treatment of choice to relieve the
obstruction is catheter intervention consisting of balloon valvuloplasty. Children
who have a successful balloon valvuloplasty have excellent outcomes and often
FIGURE 19-8. Echocardiographic images of a normal pulmonary valve (arrow) in the A. closed and
B. open position. C. Color flow image demonstrates laminar flow through the valve. In the lower
row, D. a dysplastic pulmonary valve (arrow) is shown with thickened leaflets in the closed position
and E. doming (asterisk) during opening of the valve. F. Color flow image shows flow acceleration
through the pulmonary valve due to moderate stenosis. Ao = aorta, PA = pulmonary artery, RVOT =
right ventricular outflow tract.
318
CCIP.indb 318 3/13/18 4:19 PM

do well in long-term follow-up, with more than 75% being free of reintervention
at 15 years.4 Some children develop a variable degree of pulmonary insufficiency
after balloon valvuloplasty, which requires ongoing monitoring but is generally
well tolerated.
In children with severely dysplastic valves, balloon valvuloplasty may not
be successful in isolation; they often require surgical intervention (valvotomy).
In addition, surgical intervention is typically required for clinically significant
subvalvar or supravalvar pulmonary stenosis because these lesions do not respond
in a sustained fashion to balloon valvuloplasty.
Ongoing Care
Like other children born with CHD, children with pulmonary stenosis require
lifelong follow-up to examine for the risk of worsening RV outflow obstruction
and potential RV dysfunction. In addition, children requiring either cathe-
ter-based or surgical intervention often have resultant pulmonary insufficiency,
which requires monitoring for RV dilation and dysfunction, as well. While
usually not necessary given the success of procedural management, children
with persistent moderate to severe pulmonary stenosis should consider limiting
athletic participation to low-intensity activities, such as golf, softball, or baseball
(classified as IA and IB sports).5 Overall, pulmonary stenosis is associated with
normal oxygen saturation after intervention and normal quality and length
of life.
Key Points
•• Pulmonary stenosis is caused by abnormalities of the pulmonary valve
and may be associated with more complex cardiac defects or syndromes
(eg, Noonan syndrome).
•• A characteristic harsh crescendo-decrescendo systolic murmur at the left
upper sternal border is classic for pulmonary stenosis.
•• Most children with mild pulmonary stenosis do not require intervention,
but those with moderate or severe pulmonary stenosis may require either
catheter-based or surgical intervention.

•• Pulmonary Valve Stenosis (American Heart Association). www.heart.org/
Defects/Pulmonary-Valve-Stenosis_UCM_307034_Article.jsp
319
CCIP.indb 319 3/13/18 4:19 PM

References
1) Reller MD, Strickland MJ, Riehle-Colarusso T, Mahle WT, Correa A. Prevalence of congenital
heart defects in metropolitan Atlanta, 1998-2005. J Pediatr. 2008;153(6):807–813
2) Colquitt JL, Noonan JA. Cardiac findings in Noonan syndrome on long-term follow-up.
3) Venables AW. The syndrome of pulmonary stenosis complicating maternal rubella. Br Heart J.
1965;27:49–55
4) Garty Y, Veldtman G, Lee K, Benson L. Late outcomes after pulmonary valve balloon dilatation
in neonates, infants and children. J Invasive Cardiol. 2005;17(6):318–322
5) Van Hare GF, Ackerman MJ, Evangelista JA, et al; American Heart Association Electro
cardiography and Arrhythmias Committee of Council on Clinical Cardiology, Council
on Cardiovascular Disease in Young, Council on Cardiovascular and Stroke Nursing,
Council on Functional Genomics and Translational Biology, and American College of
Cardiology. Eligibility and Disqualification Recommendations for Competitive Athletes with
Cardiovascular Abnormalities: Task Force 4: Congenital Heart Disease: a Scientific Statement
from the American Heart Association and American College of Cardiology. Circulation.
2015;132(22):e281–e291
Single-Ventricle Lesions
Anatomy
In single-ventricle lesions, only 1 ventricle is functional. This can be due to
(a) atresia or clinically significant stenosis of either inlet (tricuspid or mitral
valve) or (b) arrest of cardiac development at an immature stage, causing the
second ventricle to not develop. Depending on the particulars of the anatomy,
infants with single ventricles will generally have a restriction to either pulmonary
blood flow or systemic blood flow. A patent ductus arteriosus is necessary
for both fetal and postnatal life to augment flow to the circulation that has
been restricted.1
Clinical Features
Many single-ventricle lesions are diagnosed prenatally, because the 4-chamber
view can appear abnormal in early gestation. Prenatal diagnosis typically allows
for immediate postnatal management at a tertiary care center. For infants to be
discharged home, they require a reliable source of both pulmonary and systemic
blood flow. Typically, surgical intervention is required in the first days of life to
provide this reliability.
320
CCIP.indb 320 3/13/18 4:19 PM

In infants who do not receive a prenatal diagnosis, the clinical presentation

will vary, depending on whether pulmonary or systemic blood flow is restricted.
When systemic blood flow is restricted, the infant will present with cardiogenic
shock upon ductal closure. When pulmonary blood flow is restricted, the infant
will present with cyanosis upon ductal closure. In all single-ventricle lesions,
deoxygenated and oxygenated blood necessarily mix and, typically, oxygen
saturation levels will be abnormally low, even prior to ductal closure. In rare
situations in which there is unobstructed pulmonary blood flow and pulmonary
vascular resistance has dropped, saturations may be in the mid to high 90s,
despite a single-ventricle lesion. Ductal closure can occur from 24 hours to
several days of age.2
Diagnosis of a single-ventricle lesion is ultimately determined with trans
thoracic echocardiography. Abnormally low saturation levels or a pre- and
postductal saturation difference can indicate a problem. A chest radiograph can
demonstrate a paucity or overabundance of pulmonary blood flow, which may
also indicate a problem.
Management
Upon suspicion of a single-ventricle lesion, prostaglandin infusion should be
strongly considered, even prior to full diagnostic testing. Single-ventricle lesions
cannot be corrected, but they can be palliated. The ultimate goal of palliation is
to allow passive pulmonary blood flow and allow the single ventricle to provide
systemic blood flow.3 Typically, achieving this goal requires 3 stages of palliation.
The first stage occurs within the first several days of life. The specifics of the first
stage depend on the anatomy but ultimately result in a reliable source of pul-
monary and systemic blood flow. When there is restriction of pulmonary blood
flow, the first stage consists of placement of a synthetic systemic to pulmonary
shunt. As an alternative to surgery, a stent can be placed in the ductus arteriosus
(Figure 19-9), keeping it open and serving the same purpose as the surgical
shunt. When there is restriction to systemic blood flow, the first stage is typically
more complicated (Norwood procedure, Figure 19-10) and requires reconstruc-
tion of the aortic arch by using the native pulmonary artery and placement of
a synthetic systemic to pulmonary shunt (such as a modified Blalock-Taussig
shunt [Figure 19-10, A] or Sano shunt [Figure 19-10, B]). Typical oxygen satu-
ration levels after the first stage are 75% to 85%, regardless of the initial anatomy.
In rare cases in which there is a single ventricle with no restriction to systemic
or pulmonary blood flow, infants will require surgical restriction to pulmonary
blood flow, called a pulmonary artery band.
The second stage (Glenn procedure, Figure 19-11) typically occurs between
4 and 7 months of age and consists of attaching the superior vena cava directly
into the right pulmonary artery to allow systemic venous return from the head,
321
CCIP.indb 321 3/13/18 4:19 PM

FIGURE 19-9. Ductal stent. PDA = patent ductus arteriosus. Image courtesy of the Department of
Surgery Medical Illustrations, Texas Children’s Hospital.
FIGURE 19-10. A. Norwood procedure with a Blalock-Taussig shunt. B. Norwood procedure with
a Sano modification. LA = left atrium, LV = left ventricle, RA = right atrium, RV = right ventricle.
Image courtesy of the Department of Surgery Medical Illustrations, Texas Children’s Hospital.
322
CCIP.indb 322 3/13/18 4:19 PM

FIGURE 19-11. Glenn procedure. Image courtesy of the Department of Surgery Medical
Illustrations, Texas Children’s Hospital.
neck, and arms to passively drain into the pulmonary arteries. The timing of the
second stage is delayed to allow for the physiological decrease in pulmonary
vascular resistance, which is necessary for passive drainage of the systemic venous
return into the pulmonary arteries. The inferior vena cava drainage remains to
the systemic circulation, and the single ventricle pumps somewhat deoxygenated
blood to the system. Typical oxygen saturations after the second stage are 80%
to 85%.4
The third stage (Fontan procedure, Figure 19-12) occurs between 2 and
4 years of age and consists of attaching the inferior vena cava into the right
pulmonary artery via an extracardiac conduit and allowing all systemic venous
return to the pulmonary arteries passively. Typical oxygen saturations after the
third stage are greater than 95%. This can vary somewhat if the extracardiac
conduit is fenestrated during the third stage, which provides a small right-to-left
shunt and can lower saturation levels into the low 90s.4,5
Ongoing Care
All infants with a single-ventricle lesion should be followed up closely by a
pediatric cardiologist. The life expectancy of a child with a single ventricle is not
normal. As advances are being made, it is difficult to determine exactly what
323
CCIP.indb 323 3/13/18 4:19 PM

FIGURE 19-12. Fontan procedure. LA = left atrium, LV = left ventricle, RA = right atrium,
RV = right ventricle. Image courtesy of the Department of Surgery Medical Illustrations, Texas
Children’s Hospital.
the expected life expectancy is for infants born today with a single ventricle.
There can be clinically significant and life-shortening complications of a sin-
gle-ventricle physiology, including protein-losing enteropathy, plastic bronchitis,
ventricular dysfunction, arrhythmias, and hepatic complications. Frequently,
children with single ventricles, particularly if complications develop, will require
cardiac transplantation. This can occur at any point in the stages of palliation.1
Children with single ventricles typically have limitations to their activity. In
general, they should be allowed to self-limit their activities. Families should be
counseled that there can be a risk of recurrence of congenital heart disease in
subsequent pregnancies. Mothers should be offered screening fetal echocardiog
raphy between 18 and 22 weeks of gestation in subsequent pregnancies.6 No rou-
tine screening of older siblings or other relatives is indicated for most patients.
324
CCIP.indb 324 3/13/18 4:19 PM

Key Points
•• Patients with single-ventricle lesions require close care by a pediatric cardiolo-
gist and will require multiple surgical procedures over their lifetime.
•• Appropriate oxygen saturation level in a patient with a single-ventricle lesion
varies on the basis of their stage of palliation but is frequently abnormal.
References
1) Earing MG, Hagler DJ, Edwards WD. Univentricular atrioventricular connection. In: Allen
HD, Driscoll DJ, Shaddy RE, Feltes TF, eds. Moss and Adams’ Heart Disease in Infants, Children,
and Adolescents Including the Fetus and Young Adult. 8th ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2013:1175–1194
2) Mahoney LT, Coryell KG, Lauer RM. The newborn transitional circulation: a two-dimensional
Doppler echocardiographic study. J Am Coll Cardiol. 1985;6(3):623–629
3) d’Udekem Y, Iyengar AJ, Galati JC, et al. Redefining expectations of long-term survival after
the Fontan procedure: twenty-five years of follow-up from the entire population of Australia
and New Zealand. Circulation. 2014;130(11 Suppl 1):S32–S38
4) Hauck A, Porta N, Lestrud S, Berger S. The pulmonary circulation in the single ventricle
patient. Children (Basel). 2017;4(8):71
5) Fiore AC, Tan C, Armbrecht E, et al. Comparison of fenestrated and nonfenestrated patients
undergoing extracardiac Fontan. Ann Thorac Surg. 2014;97(3):924–931, discussion 930–931
2014;129(21):2183–2242
Systemic and Pulmonary

Vein Anomalies
Anatomy
Systemic venous anomalies are present when 1 or more of the systemic veins
(inferior vena cava [IVC] or superior vena cava [SVC]) do not drain normally
to the right atrium. Clinical manifestations can range from none to significant
desaturation. The most common anomaly of systemic venous drainage is a left
SVC draining to the coronary sinus. This represents an embryological persistence
325
CCIP.indb 325 3/13/18 4:19 PM

of the left anterior and common cardinal vein. In approximately 8% of cases

with a left SVC, the coronary sinus is unroofed.1 Other anomalies of systemic
veins include interruption of the IVC and anomalies of hepatic vein drainage.
Interruption of the IVC occurs when there is an absence of the hepatic portion
of the IVC. This typically results in redirection of venous return from the lower
body into the azygous or hemiazygous system, with ultimate drainage into a
right- or left-sided SVC. This is particularly common in polysplenic heterotaxy,
and determination of an interrupted IVC warrants further investigation into
visceral sidedness and splenic function.2 Hepatic vein drainage anomalies are
uncommon but can be noted in asplenic heterotaxy, with hepatic vein drainage
entering the heart separately from the IVC.3
Pulmonary vein anomalies include total anomalous pulmonary venous return
(TAPVR) and partial anomalous pulmonary venous return (PAPVR). TAPVR
occurs when there is failure in the incorporation of the common pulmonary
vein into the posterior portion of the left atrium embryologically. This results in
anomalous drainage to the SVC system (supracardiac TAPVR), the coronary
sinus (cardiac TAPVR), or the hepatic–portal venous system (infracardiac
TAPVR). A combination of more than 1 drainage site can also occur.4 PAPVR
occurs when at least 1 pulmonary vein, but not all, does not return to the left
atrium. This can occur in conjunction with atrial septal defects (ASDs), as well
as deficiencies in the sinus venosus, leading to sinus venosus ASDs.5
Clinical Features
The clinical presentation and symptoms of systemic venous anomalies is
dependent on the effect on the circulation. If the coronary sinus is unroofed in
the presence of a left SVC or if the left SVC drains directly to the roof of the
left atrium, patients can present with cyanosis. If the coronary sinus remains
intact, a patient with a left SVC will demonstrate no clinical symptoms and is
considered a variant of normal. Likewise, in the absence of associated congenital
heart disease (CHD), a patient with an interrupted IVC will demonstrate no
clinical symptoms. If an interrupted IVC is noted, however, consideration should
be given to further testing of visceral sidedness and splenic function to rule out
bowel malrotation and splenic dysfunction.
Infants with TAPVR typically present in early infancy. If there is obstruction
to the pathway of pulmonary venous drainage, infants may present within the
first few hours of birth with profound cyanosis and abject respiratory distress or
failure.6 In these infants, immediate diagnosis and emergent surgical repair are
indicated. Transfer to a tertiary care center with cardiac surgical services should
be emergently initiated if TAPVR with obstruction is suspected. In infants with
TAPVR without obstruction, the clinical presentation is typically that of cyano-
sis. In rare cases, with no obstruction to pulmonary venous drainage, saturation
326
CCIP.indb 326 3/13/18 4:19 PM

levels can be near normal, and presentation may be delayed several days or weeks.
In these infants, the first clinical sign of an abnormality is typically respiratory
distress.7 PAPVR typically presents later in childhood, and if only 1 pulmonary
vein is anomalous, it may only be found incidentally. Because approximately two-
thirds of children with PAPVR will also have an atrial-level shunt, they typically
present in a manner similar to children with only an atrial-level shunt, namely a
pulmonary flow murmur.
Initial diagnostic testing for systemic or pulmonary venous anomalies is
transthoracic echocardiography. When normal drainage of systemic or pulmo-
nary veins cannot be confirmed or when abnormalities of systemic or pulmonary
venous drainage are suspected with echocardiography, cross-sectional imaging,
such as cardiac computed tomography or magnetic resonance imaging, can be
helpful. Because systemic venous anomalies are frequently associated with other
CHD, a full cardiac workup is indicated when these anomalies are suspected.
Management
A left SVC to coronary sinus represents a normal variant and requires no
ongoing cardiology follow-up or therapy. However, it can have implications for
the placement of central lines or cannulation for cardiac surgery (in conjunction
with other congenital heart defects) and should be noted in these situations.
Similarly, an interrupted IVC in isolation does not require therapy but may
have implications for other procedures.
A single anomalous pulmonary vein does not typically require surgical
correction. If more than 1 pulmonary vein drains anomalously or if there is an
atrial-level shunt, then surgical correction of the PAPVR and/or atrial-level
shunt is indicated.8 This typically occurs around age 3 or sooner, if there is
clinically significant right-sided heart enlargement.
TAPVR requires surgical correction. In the case of obstructed TAPVR,
surgical correction is typically required emergently. If there is no obstruction,
TAPVR repair can occur as soon as the first 1 to 2 weeks of life, but there is
some variability in opinion among cardiologists and cardiothoracic surgeons
as to when the optimal timing of repair is. When TAPVR is diagnosed later,
surgical correction is typically scheduled soon after diagnosis.7
Ongoing Care
Isolated systemic venous anomalies with no evident cyanosis are benign findings
and do not require ongoing cardiac follow-up once initial workup is complete.
Patients require no activity restrictions, and there is no specific familial counsel-
ing required.
327
CCIP.indb 327 3/13/18 4:19 PM

Patients with PAPVR are typically followed up as outpatients by pediatric

cardiologists, and the size of the right side of the heart is followed serially. With
1 anomalous pulmonary vein and no evidence of right-sided heart enlargement,
there is no restriction to activity. If right-sided heart enlargement is present,
activity should be self-limited and no competitive sports undertaken until the
defect is repaired. After repair, there are unlikely to be activity restrictions, but
cardiac clearance should be obtained prior to engaging in competitive sports.
Patients with TAPVR require lifelong cardiac follow-up. Prognosis is
dependent on the degree of preoperative obstruction to pulmonary venous
drainage and any residual obstruction after surgery but is typically very good.9
In patients with residual obstruction, life span can be substantially shortened,
and close monitoring by a pediatric cardiologist is indicated.7 Where there is no
obstruction, there are no specific activity restrictions, although cardiac clearance
should be obtained prior to engaging in any competitive activity. There is no
specific familial counseling indicated. However, there is an increased risk of
CHD in subsequent pregnancies, and fetal echocardiography should be offered
to the mother at 18 to 22 weeks’ gestation in subsequent pregnancies.
Key Points
•• Many common systemic venous anomalies have no clinical significance
in isolation.
•• Prognosis of total anomalous pulmonary venous return is highly dependent
on the amount of residual pulmonary venous obstruction present.
References
1) Meadows WR, Sharp JT. Persistent left superior vena cava draining into the left atrium without
arterial oxygen unsaturation. Am J Cardiol. 1965;16:273–279
2) Bengur AR, Jaggers J, Ungerleider RM. Intraoperative transesophageal echocardiography in
congenital heart disease. In: Mavroudis C, Backer CL, eds. Pediatric Cardiac Surgery. 3rd ed.
Philadelphia, PA: Mosby; 2003
3) Geva T, Van Praagh S. Abnormal systemic venous connections. In: Moss A, Allen H, eds. Moss
and Adams’ Heart Disease in Infants, Children, and Adolescents: Including the Fetus and Young Adult.
Vol. 2. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2008
4) Seale AN, Uemura H, Webber SA, et al; British Congenital Cardiac Association. Total
anomalous pulmonary venous connection: morphology and outcome from an international
population-based study. Circulation. 2010;122(25):2718–2726
5) Kafka H, Mohiaddin RH. Cardiac MRI and pulmonary MR angiography of sinus venosus
defect and partial anomalous pulmonary venous connection in cause of right undiagnosed
ventricular enlargement. AJR Am J Roentgenol. 2009;192(1):259–266
6) Herlong JR, Jaggers JJ, Ungerleider RM. Congenital Heart Surgery Nomenclature and Database
Project: pulmonary venous anomalies. Ann Thorac Surg. 2000;69(4 Suppl):S56–S69
328
CCIP.indb 328 3/13/18 4:19 PM

7) Kelle AM, Backer CL, Gossett JG, Kaushal S, Mavroudis C. Total anomalous pulmonary venous
connection: results of surgical repair of 100 patients at a single institution. J Thorac Cardiovasc
Surg. 2010;139(6):1387–1394.e3
8) Alsoufi B, Cai S, Van Arsdell GS, Williams WG, Caldarone CA, Coles JG. Outcomes after
surgical treatment of children with partial anomalous pulmonary venous connection. Ann Thorac
Surg. 2007;84(6):2020–2026, discussion 2020–2026
9) Karamlou T, Gurofsky R, Al Sukhni E, et al. Factors associated with mortality and
reoperation in 377 children with total anomalous pulmonary venous connection. Circulation.
2007;115(12):1591–1598
Tetralogy of Fallot
Introduction
Tetralogy of Fallot (TOF) is a common form of complex congenital heart
disease (CHD) with a prevalence of 1 per 2,000 live births (about 5% of all
CHD). It is estimated that 1,660 children are born with TOF in the United
States per year.1 It is characterized by 4 associated defects: an anteriorly dis-
placed overriding aorta, an anteriorly displaced ventricular septal defect (VSD),
pulmonary stenosis of variable degree, and right ventricular (RV) hypertrophy
(Figure 19-13). Most often, there are no other associated defects, although
roughly 20% of the time, there is an association with a genetic syndrome such
as DiGeorge syndrome (microdeletion of chromosome 22q11.2), trisomy 21,
or Alagille syndrome.2 The 30- to 40-year survival rate has been reported to be
85% to 90%.3
Pathophysiology
Children with TOF commonly have normal systemic and venous return to the
heart. This venous return enters the appropriate ventricle, but a variable amount
of right-to-left blood flow (“shunting”) occurs through the VSD that is typically
large and unrestrictive to flow. The ultimate volume of blood flow directed
through the pulmonary artery is dictated by the degree of pulmonary stenosis.
Roughly 20% of children with TOF will have associated coronary anomalies.2
There are various types of TOF that can be separated by the anatomy of the
pulmonary outflow tract. TOF with pulmonary atresia and TOF with absent
pulmonary valve are more uncommon types, and each is associated with unique
329
CCIP.indb 329 3/13/18 4:19 PM

Aorta
Pulmonary
artery
Narrowing of the
pulmonary valve or
area below the valve
(pulmonary stenosis)
Ventricular
septal defect
Right
ventricular
hypertrophy
FIGURE 19-13. Tetralogy of Fallot. The degree of pulmonary stenosis is related to the amount of
anterior displacement of the ventricular septal defect and the aorta. The severity of the pulmonary
stenosis will determine the amount of pulmonary blood flow and the resulting oxygen saturation.
anatomy and physiology. For instance, patients with TOF with absent pulmo-
nary valve often have massively enlarged pulmonary arteries and subsequent
airway compromise. However, this section will focus on the most common
type of TOF, with mild to severe pulmonary stenosis. Patients with this type of
TOF can be classified as “pink” or “blue,” referring to lesser or greater degrees,
respectively, of early cyanosis.
The degree of cyanosis can be dynamic; patients may have events referred to
as Tet spells. These episodes are marked by a sudden increase in hypoxia from
baseline, due to a sudden increase in subpulmonary valve (infundibular) stenosis
as a result of muscular obstruction. Tet spells can occur at random but are
commonly triggered by distress. Triggers may be difficult to prevent; they can be
as common as gastroesophageal reflux in the newborn. The sudden change to a
more hypoxic state increases pulmonary vascular resistance and further decreases
the pulmonary blood flow. When severe, these events can be life-threatening
because of the sustained hypoxia. Typical management is to eliminate the initial
distressful trigger or soothe the child. When more profound, efforts to increase
330
CCIP.indb 330 3/13/18 4:19 PM

the systemic vascular resistance to limit the right-to-left shunting are attempted,
including placement of the patients’ knees to their chest, increasing the preload
to the right side of the heart (intravenous fluid bolus), sedation with morphine
or other agents, or, finally, intubation and medical paralysis. Parents are advised
to avoid states of dehydration in the infant to prevent Tet spells.
Clinical Features
Signs and Symptoms
TOF is readily diagnosed in utero during prenatal echocardiography. If the con-
dition goes undiagnosed, the newborn will often present with cyanosis or with a
prominent pulmonary stenosis murmur in the first few weeks of life. When the
pulmonary stenosis is mild, the child will have (near) normal oxygen saturations.
The end result, however, is that all children with TOF develop cyanosis over
time. These neonates do not develop signs and symptoms of pulmonary overcir-
culation consistent with heart failure, because the pulmonary stenosis prevents
large volumes of left-to-right shunting at the level of the VSD.
Physical examination findings are primarily related to the amount of pulmonary
blood flow. The pulmonary stenosis may be of such a degree that a systolic
ejection murmur is present with a palpable systolic thrill over the left sternal
border. However, in the absence of substantial pulmonary stenosis, or if there is
near-atresia, there may not be a murmur present. The VSD is large and typically
does not contribute to a murmur. There is usually a single S2, unless the degree of
pulmonary stenosis is mild.

The diagnosis of TOF requires echocardiography. If the diagnosis is suspected
in utero, echocardiography should be performed shortly after birth to confirm.
If undiagnosed in utero, a newborn’s initial evaluation may include chest radiog-
raphy because of cyanosis, which classically shows a “boot-shaped heart,” with
the cardiac apex directed superior and to the left and the absence of the typical
pulmonary artery knob, although radiographic presentations can be variable. In
cases of severe pulmonary stenosis, there may be decreased pulmonary vascular
markings. It is unlikely that further imaging will be required to establish the
diagnosis; however, cardiac catheterization and/or magnetic resonance (MR)
imaging may be used if there is concern for aortopulmonary collateral vessels,
other irregular pulmonary artery architecture, or coronary anomalies. An electro-
cardiogram will typically demonstrate right-axis deviation and RV hypertrophy,
which can be difficult to distinguish from findings typical of a newborn.
331
CCIP.indb 331 3/13/18 4:19 PM

Management
Patients with TOF require surgical correction in the first year of life. In the
setting of less pulmonary stenosis (“pink TOF”), this is usually performed
around 4 to 6 months of age. However, when the pulmonary stenosis is more
critical (“blue TOF”) or if there is evidence of Tet spells, improving the
pulmonary blood flow in the newborn period may be necessary (less than 20%
of cases). This can be accomplished with corrective surgery as a neonate; creation
of a surgical aortic-to-pulmonary shunt, such as a Blalock-Taussig shunt; or
procedural approaches in the cardiac catheterization laboratory, including stent
placement in the RV outflow tract or the patent ductus arteriosus. The current
30-day surgical mortality rate for repair of TOF is less than 2%.3 There is little
role for medical management, since the limitation of pulmonary blood flow
is structural, except to give the patient a β-blocker when there is concern for
dynamic muscular obstruction to pulmonary blood flow.
The preferred surgical procedure is a transannular patch longitudinally across
the pulmonary valve, with the goal of minimizing the proximal and distal exten-
sion of the patch. The result of this approach is at least moderate pulmonary
insufficiency, since the competence of the pulmonary valve is sacrificed to relieve
the obstruction (more often the pulmonary insufficiency is severe or “free”).
When possible, often in the setting of mild pulmonary stenosis, the surgeon
will attempt a “valve-sparing” approach, during which the longitudinal incision
does not cross the valve annulus. The advantage of this approach is the ability
to minimize the postsurgical pulmonary insufficiency and potentially spare the
pulmonary valve function. In addition, when necessary, the surgeon will resect
infundibular muscle below the valve annulus. The VSD is closed with a patch.
Ongoing Care
Outcomes after repair are determined by the degree of pulmonary insufficiency
and the presence of a residual VSD. Unless the repair is successfully “valve
sparing,” the need for eventual pulmonary valve replacement is likely over time,
because of progressive RV enlargement and dysfunction, as well as the presence
of ventricular arrhythmias.3 The timing of pulmonary valve replacement is typ-
ically determined by RV volume and function, as measured with MR imaging.
Increasingly, these pulmonary valve replacements can be accomplished with a
percutaneous valve.
Arrhythmias are common after repair of TOF. To assess for this, serial
electrocardiography and 24-hour Holter monitoring are performed during fol-
low-up. There is a risk of sudden death associated with TOF, and if certain crite-
ria are met, especially the presence of syncope, then an implantable cardioverter
defibrillator may be necessary.4 It remains controversial whether pulmonary valve
332
CCIP.indb 332 3/13/18 4:19 PM

replacement reduces the risk of sudden death from ventricular arrhythmias.5

Lifelong serial echocardiography and regular exercise testing will be required to
monitor the need for pulmonary valve replacement and to determine the risk
for sudden cardiac death. Decisions regarding activity restriction are dependent
on these serial examinations; however, most children with TOF do not require
restriction from athletic pursuits.6 It is usually possible for women with TOF
to carry successful pregnancies to term, although obstetric expertise should be
provided by maternal-fetal medicine physicians and cardiologists specializing
in adult congenital defects.
Key Points for Providers

•• TOF is the most common cyanotic form of CHD.
•• The diagnosis is often established in utero, but if undiagnosed prior to
birth, newborns often present with cyanosis due to inadequate pulmonary
blood flow.
•• Initial surgical repair typically occurs within the first year of life, but initial
intervention may be required in the first weeks of life, depending on the
degree of cyanosis.
•• Lifelong follow-up is required, given the expectation of multiple repeat
interventions and the potential development of heart failure and arrhythmia.

•• Tetralogy of Fallot (American Heart Association). www.heart.org/HEART
ORG/Conditions/CongenitalHeartDefects/AboutCongenitalHeartDefects/
Tetralogy-of-Fallot_UCM_307038_Article.jsp
References
2) Karl TR, Stocker C. Tetralogy of Fallot and its variants. Pediatr Crit Care Med. 2016;17
(8 Suppl 1):S330–S336
3) Downing TE, Kim YY. Tetralogy of Fallot: general principles of management. Cardiol Clin.
2015;33(4):531–541, vii–viii
4) Khairy P. Ventricular arrhythmias and sudden cardiac death in adults with congenital heart
disease. Heart. 2016;102(21):1703–1709
5) Villafañe J, Feinstein JA, Jenkins KJ, et al; Adult Congenital and Pediatric Cardiology
Section, American College of Cardiology. Hot topics in tetralogy of Fallot. J Am Coll Cardiol.
2013;62(23):2155–2166
333
CCIP.indb 333 3/13/18 4:19 PM

6) Van Hare GF, Ackerman MJ, Evangelista JA, et al; American Heart Association
Electrocardiography and Arrhythmias Committee of Council on Clinical Cardiology,
Council on Cardiovascular Disease in Young, Council on Cardiovascular and Stroke Nursing,
2015;132(22):e281–e291
Transposition of the
Great Arteries
Anatomy
The aorta and pulmonary artery (great arteries) can be reversed in a number of
forms of congenital heart disease (CHD). This discussion focuses on the most
common subset of transposition of the great arteries (TGA), in which the heart
is otherwise normally connected.
In dextro-TGA (also called ventriculoarterial discordance), the pulmonary
artery arises from the left ventricle (LV), and the aorta arises from the right
ventricle (RV) (Figure 19-14). In this arrangement, desaturated blood from
the body enters the right atrium and courses through the tricuspid valve, into
the RV, and back out to the body via the aortic valve and aorta. Conversely,
saturated blood from the lungs returns to the left atrium and goes through the
mitral valve into the LV. From there, it is pumped through the pulmonary valve
into the pulmonary artery and back to the lungs. Obviously, this circulation is
not compatible with life, so there must be a site at which the oxygenated blood
can cross over to get to the body. That site is the atrial septum. An atrial septal
defect (ASD) (or at least a patent foramen ovale [PFO]) needs to be present.
Oxygenated left atrial blood is shunted from the left to the right atrium and thus
reaches the systemic circulation. A patent ductus arteriosus (PDA) augments
this shunting because it allows extra blood to leave the aorta and go to the lungs.
With a PDA, more blood enters the lungs, becomes oxygenated, and fills the
left atrium. A greater volume of oxygenated blood filling the left atrium will
necessarily result in more of it crossing through the ASD to the right side of the
heart and out to the body. In this way, a PDA indirectly affects mixing in TGA.
334
CCIP.indb 334 3/13/18 4:19 PM

FIGURE 19-14. Transposition of the great arteries with oxygenated blood directed into the pulmo-
nary artery (PA) and deoxygenated blood directed into the aorta (Ao). A patent ductus arteriosus
(PDA) allows deoxygenated blood to reach the lungs. Mixing occurs at the atrial septal defect
(ASD). LA = left atrium, LV = left ventricle, RA = right atrium, RV = right ventricle. Image courtesy
of the Department of Surgery Medical Illustrations, Texas Children’s Hospital.
In addition to the ASD or PFO and PDA, there are several other anatomic
associations with TGA, the most common of which is a ventricular septal defect
(VSD). Other associations include LV outflow tract obstruction (pulmonary
stenosis), coarctation of the aorta, and abnormal origins of the coronary arteries.1
335
CCIP.indb 335 3/13/18 4:19 PM

Clinical Features
Some patients with TGA receive diagnoses in utero. The International Society
of Ultrasound in Obstetrics and Gynecology guidelines now recommend
that obstetricians note the arrangement of the great arteries as part of routine
prenatal ultrasonography, usually in the second trimester.2 If abnormalities are
suspected, referral for dedicated fetal echocardiography should be sought.
If there is no prenatal diagnosis of the condition, it is usually diagnosed in
the newborn period, with desaturation often being the first sign. Saturation
levels less than 90% in a newborn should raise suspicion for cyanotic CHD,
such as TGA. Some babies are hemodynamically stable, while others are ill
appearing, lethargic, tachypneic, or poorly perfused. Classically, the second
heart sound (S2) in these patients is single, instead of split. Admittedly, this is
hard to reliably detect, given the fast heart rate of a typical newborn. Other
findings that are variably present include an S1 coincident murmur if there is a

VSD (audio available at vimeo.com/137610640) ( ) or the systolic ejection
murmur of pulmonary stenosis (audio available at vimeo.com/groups/414972/

videos/137611508) ( ). Decreased lower-extremity pulse can be observed in
the setting of coarctation.
When any CHD is suspected, the baseline evaluation should include chest
radiography, electrocardiography (ECG), and 4-extremity blood pressure and
pre- and postductal oxygen saturation level. The classic chest radiographic
description is that of an “egg on a string” (Figure 19-15) appearance of the
heart. In practice, however, the radiograph often appears normal, perhaps with
increased pulmonary vascular markings if there is excessive pulmonary blood
flow from a VSD. ECG may demonstrate right atrial enlargement and RV
hypertrophy. Four-extremity blood pressure is normal unless there is coarctation,
in which case the legs would have a lower blood pressure than the arms. In
TGA with high pulmonary vascular resistance or a coarctation, a “reversed
differential” may be noted when comparing pre- and postductal saturation levels.
See Figure 19-16 for a schematic representation.
Echocardiography can be used to establish the diagnosis of TGA and any
associated pathologic findings. In the rare case that a newborn leaves the hospital
with undiagnosed TGA, the clinical picture at presentation to the pediatrician
will likely include an ill-appearing, cyanotic neonate with lethargy, respiratory
distress, and failure to thrive. With such concerns, cardiology consultation
should be sought immediately, with urgent referral to an emergency department.
Management
When TGA is diagnosed in the prenatal or neonatal period, prostaglandin E1
(PGE) will usually be used at birth as the newborn transitions. Since mixing
of oxygenated and deoxygenated blood occurs at the atrial level, an important
336
CCIP.indb 336 3/13/18 4:19 PM

FIGURE 19-15. Anteroposterior chest radiograph in a 2-day-old infant demonstrates the classic
“egg on a string” finding associated with transposition of the great arteries. The heart is the “egg,” and
the narrow mediastinum represents the “string.”
FIGURE 19-16. Mechanism of “reversed differential” in which the lower extremities have a higher
oxygen saturation level (Sat) than the upper extremities. This can occur when either increased
pulmonary pressure or coarctation of the aorta coexists with transposition of the great arteries. Image
courtesy of the Department of Surgery Medical Illustrations, Texas Children’s Hospital.
337
CCIP.indb 337 3/13/18 4:19 PM

part of echocardiography is to assess the size of the atrial septal communication.

If there is adequate mixing of blood, the PGE can be stopped. If the commu-
nication is too small, the patient will require a balloon atrial septostomy (see
Video 19-1 at https://www.aap.org/en-us/restricted/common-cardiac-issues/).
This is a catheter-based procedure in which a deflated balloon is advanced from
the umbilical or femoral vein all the way to the left atrium. Pulling the inflated
balloon back to the right atrium creates a tear in the septum to enlarge the
hole. If a newborn is ill (acidosis, clinically significant cyanosis), the septostomy
needs to be performed emergently. For this reason, it is advisable for patients
with a prenatal diagnosis of TGA to be delivered in a tertiary care center with
personnel capable of performing the intervention.
TGA is surgically corrected, usually in the first 2 weeks of life, by using the
arterial switch procedure. This involves removing the aorta and pulmonary artery
from their native positions and transposing them into a position above the
proper ventricle. The vessels are moved, but not the valves. The coronary arteries,
however, must also be moved, along with the aorta. This is a critical part of the
procedure because scarring or kinking of the coronary artery connection can
result in ischemia. VSDs and associated abnormalities are corrected at the time
of the arterial switch procedure.
Ongoing Care
In the current era, outcomes for patients with TGA are excellent. According
to the Society of Thoracic Surgery database from 2015, mortality rate with
an arterial switch procedure is 2% to 5% (according to a data analysis of the
Society of Thoracic Surgeons Congenital Heart Surgery Database, conducted
by the Duke Clinical Research Institute in June 2016, for the period ending
December 31, 2015). After clearance by their cardiologist, most patients are
allowed to participate in activities of their choosing, including competitive sports
and amusement park rides.3 Given that manipulation of the coronary arteries is
part of the procedure, in this population, one should pay attention to symptoms
that could be consistent with ischemia. These include chest pain with exercise
and syncope. Any patient with concerns that may be related to ischemia should
be evaluated immediately. Endocarditis prophylaxis is not routinely indicated
after the arterial switch procedure, except in rare circumstances. After the arterial
switch procedure, saturation levels will be normal. Medications and repeat
surgeries are not routinely required long-term. Screening of family members is
unnecessary, but fetal echocardiography is advised for subsequent pregnancies.
338
CCIP.indb 338 3/13/18 4:19 PM

Key Points
•• The size of the atrial communication (ASD, PFO) dictates the amount of
mixing of oxygenated and deoxygenated blood in the newborn.
•• Ischemic symptoms, especially chest pain with exercise and syncope, are a red
flag in the patient with repaired TGA and should be evaluated promptly.
References
1) Quereshi A, Justino H, Heinle J. Transposition of the Great Arteries. In: Allen H, Shaddy
R, Penny D, Feltes T, Cetta F, eds. Moss and Adams’ Heart Disease in Infants, Children, and
Adolescents Including the Fetus and Young Adult. 9th ed. Philadelphia, PA: Wolters Kluwer;
2016; 1163–1186
2) Carvalho JS, Allan LD, Chaoui R, et al; International Society of Ultrasound in Obstetrics and
Gynecology. ISUOG Practice Guidelines (updated): sonographic screening examination of the
fetal heart. Ultrasound Obstet Gynecol. 2013;41(3):348–359
3) Van Hare GF, Ackerman MJ, Evangelista JA, et al; American Heart Association Electro
cardiography and Arrhythmias Committee of Council on Clinical Cardiology, Council on
Cardiovascular Disease in Young, Council on Cardiovascular and Stroke Nursing, Council
Eligibility and Disqualification Recommendations for Competitive Athletes with Cardio
vascular Abnormalities: Task Force 4: Congenital Heart Disease: a Scientific Statement
2015;132(22):e281–e291
Tricuspid Valve Anomalies

Anatomy
The tricuspid valve separates the right atrium from the right ventricle (RV). The
circumferential border of the valve is called the annulus. It has 3 leaflets (anterior,
posterior, and septal) anchored to the RV myocardium by multiple small papil-
lary muscles. The defining feature of the tricuspid valve is that it has attachments
to the ventricular septum.
Pathologic changes in the tricuspid valve are variable. A common finding is
that of thickened leaflets or rolled edges. The tissue can also be redundant and
may prolapse into the right atrium. Valve abnormalities such as these can cause
tricuspid stenosis (blockage of flow) or, more commonly, regurgitation (leakage
of blood back into the right atrium). When tricuspid atresia occurs, there is no
339
CCIP.indb 339 3/13/18 4:19 PM

communication between the right atrium and the RV. This arrangement neces-
sitates a single-ventricle management strategy, discussed in Chapter 15, Surgical
Procedures for Congenital Heart Disease.
The most well-known form of tricuspid valve dysplasia is Ebstein anomaly, in
which the septal leaflet of the valve fails to delaminate or separate itself from the
ventricular septum. The usual result is an inferiorly displaced, severely dysplastic
tricuspid valve with regurgitation that can range from mild to severe. Because of
failure of delamination and inferior displacement, tissue that would otherwise
have been ventricular becomes atrial tissue. The typical result is a very large right
atrium and a relatively small RV (Figure 19-17).
Clinical Features
Most tricuspid valve abnormalities are minor and clinically silent. Regurgitation,
even when severe, is typically well tolerated, with no obvious symptoms. A
patient who is symptomatic from tricuspid regurgitation may experience
shortness of breath and fatigue. He or she may have jugular venous distention,
hepatomegaly, or swelling in the legs or abdomen. A low-pitched systolic
murmur of tricuspid regurgitation may be heard at the left lower sternal border.
If the RV dilates or enlarges, then an RV heave can be felt as an impulse on the
left sternal edge.
Tricuspid stenosis is rare and is similarly asymptomatic in its mild form.
Symptoms of tricuspid stenosis are similar to those listed for tricuspid regur
gitation. If the blood can freely flow across the atrial septum (from the right to
the left atrium), there will be no findings of venous congestion.
Tricuspid valve disease is diagnosed with echocardiography. With stenosis or
regurgitation, the right atrium can be enlarged. The RV can become dysfunc-
tional. Chest radiography can demonstrate right atrial enlargement, especially in
Ebstein anomaly, where the cardiac silhouette can be enormous in the neonate.
Electrocardiographic (ECG) findings will usually be normal with tricuspid
stenosis or regurgitation, but right atrial enlargement (tall P waves) can be
seen. Ebstein anomaly can have variable ECG findings, including right bundle
branch block or Wolff-Parkinson-White (WPW) pattern. WPW is evidenced
by a prolonged QRS duration, short PR interval, and upsloping delta wave
(Figure 19-18). Approximately 10% to 30% of patients with Ebstein anomaly
have WPW.1
Management
Isolated, non–Ebstein anomaly tricuspid valve disease does not usually require
treatment. For very dysplastic tricuspid valves, surgery can be performed to repair
(preferred) or replace the valve, but this is rare in childhood.
340
CCIP.indb 340 3/13/18 4:19 PM

FIGURE 19-17. Echocardiographic image of a heart with Ebstein anomaly. Note the septal leaflet of
the tricuspid valve (TV) tethered to the ventricular septum, creating an enlarged right atrium (RA).
LV = left ventricle, RV = right ventricle.
FIGURE 19-18. Electrocardiogram demonstrates the features of the Wolff-Parkinson-White pat-

tern, which include a delta wave (blue triangle), shortened PR interval, and widened QRS interval.
341
CCIP.indb 341 3/13/18 4:19 PM

Newborns with Ebstein anomaly can be difficult to treat. Because neonatal

surgery is associated with poor outcomes (25% mortality), one goal is to
medically treat patients with Ebstein anomaly and delay surgery until later in
life.1 One surgical option is called cone reconstruction, in which the valve tissue is
fashioned into a cone shape to improve function. In 1 report, this was performed
at a mean of 10 years of age.2 In some cases, the tricuspid valve cannot be
repaired or replaced. In these cases, usually infants with severe disease, the
tricuspid valve is closed with a fenestrated patch, committing the patient to a
single-ventricle pathway.
In children with unrepaired Ebstein anomaly, cardiologists will monitor
patients for the occurrence of arrhythmias, ventricular dilation or dysfunction,
exercise intolerance, and desaturation. These signs and symptoms are indications
that surgical repair should be considered, which should ideally occur before
the onset of ventricular dysfunction.1 Medical therapy in this cohort includes
diuretics for heart failure symptoms or medications for arrhythmias. Multiple
surgeries may be necessary over the patient’s lifetime.
Ongoing Care
Most cases of tricuspid valve dysplasia are mild, and therefore, patients will have
normal life spans, free from medications or surgery. One would expect normal
oxygen saturation levels and no exercise limitations. Any congenitally dysplastic
valve requires long-term monitoring with echocardiography to detect progres-
sion of stenosis or insufficiency. Family members do not need to be screened.
Ebstein anomaly can be asymptomatic for years. With favorable physiology
(eg, moderate or less tricuspid regurgitation), there is no restriction to compet-
itive sports. Patients with Ebstein anomaly who have severe tricuspid regur-
gitation may need to be limited to only low-intensity competitive sports.3 The
presence of arrhythmias also factors into the sports clearance decision. Saturation
levels are variable in Ebstein anomaly. If there is an atrial-level communication
(atrial septal defect or patent foramen ovale), deoxygenated blood can cross from
the right to the left atrium and proceed out to the body. Saturation levels would
be reduced to a variable extent, depending on the volume of blood crossing from
right to left. Patients with Ebstein anomaly have a 90% survival rate 10 years
after their surgery and a 76% survival rate 20 years postoperatively.4
Key Points
•• Ebstein anomaly has a highly variable presentation and will usually require
surgery at some point.
•• Oxygen saturation levels should be checked in patients with unrepaired
Ebstein anomaly because they affect the timing of surgery.
342
CCIP.indb 342 3/13/18 4:19 PM

•• Take note of concerns of palpitations or decreased endurance in patients

with Ebstein anomaly. The presence of such should be communicated to
the cardiologist.
References
1) Cetta F, Dearani J, O’Leary P, Driscoll D. Tricuspid valve disorders: atresia, dysplasia, and
ebstein anomaly. In: Allen H, Shaddy R, Penny D, Feltes T, Cetta F, eds. Moss and Adams’
Heart Disease in Infants, Children, and Adolescents Including the Fetus and Young Adult. 9th ed.
Philadelphia, PA: Wolters Kluwer; 2016:949–981
2) Anderson HN, Dearani JA, Said SM, et al. Cone reconstruction in children with Ebstein
anomaly: the Mayo Clinic experience. Congenit Heart Dis. 2014;9(3):266–271
3) Van Hare GF, Ackerman MJ, Evangelista JA, et al; American Heart Association
Electrocardiography and Arrhythmias Committee of Council on Clinical Cardiology,
Council on Cardiovascular Disease in Young, Council on Cardiovascular and Stroke Nursing,
2015;132(22):e281–e291
4) Brown ML, Dearani JA, Danielson GK, et al; Mayo Clinic Congenital Heart Center. The
outcomes of operations for 539 patients with Ebstein anomaly. J Thorac Cardiovasc Surg.
2008;135(5):1120–1136, 1136.e1–1136.e7
Truncus Arteriosus
Introduction
Truncus arteriosus is a rare form of congenital heart disease (CHD) with
an incidence of less than 1 per 10,000 live births (about 1% of all CHD).
This is equivalent to approximately 300 new cases in the United States per
year.1 Truncus arteriosus is characterized by a single arterial vessel that arises
from the base of the heart with an associated ventricular septal defect (VSD)
(Figure 19-19). This single arterial vessel gives rise to the coronary, pulmonary,
and systemic arteries. Most often, there are no other associated defects, although
there is an association with DiGeorge Syndrome (microdeletion of chromosome
22q11.2).2
343
CCIP.indb 343 3/13/18 4:19 PM

FIGURE 19-19. Truncus arteriosus. Used with permission of Mayo Foundation for Medical
Education and Research. All rights reserved.
Pathophysiology
Patients with truncus arteriosus most often have normal systemic and venous
return to the heart. This blood return mixes at the level of the ventricle through
a VSD that is typically large and unrestrictive to blood flow. Blood is then
ejected through a single arterial vessel (the “truncus”) that arises from the base
of the heart and is the embryonic result of abnormal septation of the aorta and
pulmonary arteries within the first trimester of gestation. There are various
classification systems that have been published on the basis of the pattern of
pulmonary artery branching from the truncus, including those with a main
pulmonary artery segment and those with different degrees of separation of
the pulmonary arteries. Because the pulmonary arteries arise directly from the
common trunk, a ductus arteriosus is not required to support the fetal circulation
and is often not present.
The truncal valve (the valve at the origin of the single arterial vessel) is tricus-
pid in 68% of patients with truncus arteriosus. Other common configurations
344
CCIP.indb 344 3/13/18 4:19 PM

include a quadricuspid (22%) or bicuspid (9%) valve. The truncal valve is often
dysplastic and thickened, even in the setting of a trileaflet structure. As a result,
truncal valves are commonly associated with hemodynamically significant valve
insufficiency and/or stenosis. Additionally, a right aortic arch is seen in about
one-third of patients (frequently with DiGeorge Syndrome).
Clinical Features
Signs and Symptoms
With advances in fetal echocardiography, truncus arteriosus is readily diagnosed
in utero with routine screening. If the fetus goes undiagnosed, the newborn will
often present with cyanosis due to the mixing of blood at the level of the VSD.
As pulmonary vascular resistance decreases normally after birth, the proportion
of blood flow directed to the lungs will increase. The end result is that the initial
cyanosis may lessen, but the neonate may develop signs of pulmonary overcir-
culation consistent with heart failure: tachypnea, tachycardia, excessive sweating,
and poor feeding and weight gain.
Physical examination findings are primarily related to the amount of pulmonary
blood flow and the degree of truncal valve insufficiency or stenosis. The valve
stenosis may be of such a degree that a systolic ejection murmur is present with
a palpable systolic thrill over the left sternal border. However, in the absence of
a substantial valve anomaly, there may not be a murmur present. The VSD is so
large that it does not contribute to a murmur. The peripheral pulse will become
bounding, with a wide pulse pressure due to runoff into the pulmonary vascular
bed during diastole, which may be accentuated in the setting of severe truncal
valve insufficiency. The first heart sound is normal, with a loud, single second
heart sound. An apical third heart sound may be present.

The diagnosis of truncus arteriosus requires echocardiography. If the diagnosis is
suspected in utero, echocardiography should be performed shortly after birth to
confirm the diagnosis. If the condition goes undiagnosed in utero, a newborn’s
initial evaluation may include chest radiography for symptoms of pulmonary
overcirculation. This would typically show mild cardiomegaly and increased
pulmonary vascular markings. This combination of findings would warrant fur-
ther investigation with echocardiography. It is unlikely that further imaging will
be required to establish the diagnosis; however, cardiac catheterization and/or
magnetic resonance imaging may be used in certain cases. Electrocardiography
is typically nonspecific and may only demonstrate biventricular hypertrophy.
345
CCIP.indb 345 3/13/18 4:19 PM

Management
A diagnosis of truncus arteriosus requires surgical correction for survival. Ideally,
repair is performed in the first weeks of life. Delayed surgery may cause ischemia
of the left ventricle due to persistently low diastolic blood pressure, which helps
explain the doubling of mortality when repair is performed at the age of 6 to
12 months.3 Over time, the unrepaired newborn may also develop pulmonary
vascular disease due to pulmonary overcirculation. In addition, prior to surgical
correction, there is a substantial risk of necrotizing enterocolitis caused by the
low diastolic pressures. This risk is particularly increased in the setting of severe
truncal insufficiency.
The preferred surgical approach is a complete repair, including disconnecting
the pulmonary arteries from the common arterial trunk and connecting them
to the right ventricular outflow tract, either directly or via a conduit. The VSD
is then closed, and the arterial trunk is repaired where the pulmonary arteries
were removed.
Ongoing Care
Outcomes after repair are primarily determined by the function of the truncal
valve and the need for conduit replacement. Since repair is performed in the
first weeks of life, conduit replacement is inevitable due to somatic growth and
deterioration and calcification of the conduit. Conduit dysfunction may manifest
with decreased activity, feeding difficulties, decreased saturation levels, and other
signs of right-sided heart failure.
Nearly 97% of patients with truncus arteriosus will undergo at least 1 repeat
surgery within 20 years.4 The most common reason is repair or replacement of
the conduit connecting the right ventricular outflow tract to the pulmonary
arteries. One study showed that in childhood, just over 40% of patients will have
at least 2 conduit replacements, and 15% will have 3.4 Other reasons for repeat
surgery include repair or replacement of the truncal valve and repair of the aortic
arch. In addition to surgical revision, there is also an increasingly high rate of
interventional catheterization procedures for the conduit itself, the connection
to the pulmonary arteries, and replacement of the pulmonary valve transcutane-
ously. Lifelong serial echocardiography will be required to monitor the need for
conduit replacement and to ensure the truncal valve is functioning well, without
signs of stenosis or regurgitation.
346
CCIP.indb 346 3/13/18 4:19 PM

Key Points
•• The diagnosis of truncus arteriosus is often established in utero, but if the
condition is undiagnosed prior to birth, newborns often present with signs
and symptoms of pulmonary overcirculation.
•• Complete surgical repair within the first few weeks of life is the ideal treat-
ment strategy.
•• Lifelong follow-up is required, given the expectation of multiple repeat
interventions.

•• Truncus Arteriosus (American Heart Association). www.heart.org/
HEARTORG/Conditions/CongenitalHeartDefects/AboutCongenital
HeartDefects/Truncus-Arteriosus_UCM_307040_Article.jsp
References
2) McElhinney DB, Driscoll DA, Emanuel BS, Goldmuntz E. Chromosome 22q11 deletion in
patients with truncus arteriosus. Pediatr Cardiol. 2003;24(6):569–573
3) Ebert PA, Turley K, Stanger P, Hoffman JI, Heymann MA, Rudolph AM. Surgical treatment
of truncus in the first six months. Ann Surg. 1984;200(4):451–456
4) Naimo PS, Fricke TA, Yong MS, et al. Outcomes of truncus arteriosus repair in children: 35
years of experience from a single institution. Semin Thorac Cardiovasc Surg. 2016;28(2):500–511
Vascular Rings and Slings

Introduction
A vascular ring is present when vascular structures completely encircle the
trachea and esophagus. All components of the ring do not have to be patent;
the ligamentum arteriosum (the fibrous remnant of the ductus arteriosus) is a
common component of many rings.1
A vascular sling exists when a pulmonary artery—almost always the left—
arises from the right pulmonary artery and courses between the trachea and
347
CCIP.indb 347 3/13/18 4:19 PM

esophagus. The trachea is potentially compressed by this arrangement, but not

the esophagus (Figure 19-20).1
Many types of vascular rings can develop, and complete discussion is beyond
the scope of this text. The 2 most common are a right aortic arch (RAA) with
aberrant left subclavian artery (aLSCA) and a double aortic arch (DAA). In the
case of an RAA with aLSCA, the left subclavian artery arises from the proximal
descending aorta, distal to the takeoff of the left carotid and innominate artery
(Figure 19-21). The origin of the aLSCA is often bulbous and aneurysmal and
is referred to as a diverticulum of Kommerell. The aLSCA courses behind the
trachea and esophagus to supply the left arm. A patent ductus arteriosus (PDA)
arises from this vessel, and this PDA, or the ligamentum arteriosum if it closes,
completes the ring. A DAA is exactly as the name suggests; the ascending aorta
essentially splits into 2, with a right and left arch that encircle the esophagus and
trachea, before rejoining into the descending thoracic aorta (Figure 19-22).
Anomalous
left pulmonary
artery
Right main
pulmonary
artery
FIGURE 19-20. Pulmonary artery sling.
348
CCIP.indb 348 3/13/18 4:19 PM

RCA
LCA
RSCA
LSCA
Ligamentum
Asc Ao arteriosum
LPA
MPA
FIGURE 19-21. Right aortic arch with an aberrant origin of the left subclavian artery. Asc Ao =
ascending aorta, LCA = left carotid artery, LPA = left pulmonary artery, LSCA = left subclavian
artery, MPA = main pulmonary artery, RCA = right carotid artery, RSCA = right subclavian artery.
The embryology of these lesions is well understood. The human embryo has
multiple aortic arches, some of which regress, while others persist to ultimately
form the aorta, head and neck vessels, PDA, and pulmonary arteries. Specific
combinations of arch regression and persistence lead to the specific lesions.2
Precise prevalence figures are difficult to estimate, but rings and slings are
rare, comprising only about 1% to 2% of all patients with congenital heart
disease (CHD).1
349
CCIP.indb 349 3/13/18 4:19 PM

Trachea
Double aortic
arch type
(surrounds the
trachea and
esophagus)
Oxygen-rich
blood
Oxygen-poor
blood
FIGURE 19-22. Vascular ring.
Pathophysiology
Vascular rings and slings can cause problems by compressing adjacent structures.
Not all patients with rings or slings are symptomatic. If symptomatic, most
patients have issues related to airway compression. Rarely, patients may present
with symptoms of esophageal compression.
Clinical Features
Signs and Symptoms
The presence and timing of symptoms vary markedly. Among patients with
rings, those with DAA generally have issues more often than RAA with aLSCA.
The patients with DAA often present in infancy or early childhood with cough
and stridor, usually worsened by feeding. Older children may have a chronic
cough, potentially misdiagnosed as asthma. Recurrent respiratory infections can
develop because of impaired airway clearance. Esophageal compression can cause
chronic vomiting, choking, dysphagia, and poor feeding in infants. In terms of a
pulmonary artery sling, patients often present similarly to those with DAA.
350
CCIP.indb 350 3/13/18 4:19 PM

Physical examination findings generally relate to the degree of airway compres
sion. Patients with clinically significant tracheal compression—usually infants—
can present with tachypnea, increased work of breathing, and stridor. Rales and
wheezes may be heard on auscultation. Patients with a sling may have a soft
systolic murmur related to turbulence through the tortuous pulmonary artery.
Most patients with isolated rings do not have clinically significant murmurs.

Prereferral testing can be helpful. A universal testing algorithm is impossible
to outline, but in general, strong consideration should be given to performing a
radiographic swallow study to determine the degree of esophageal compression.
Computed tomography is often helpful because it can be used to define both
the vascular and the airway structures. Given the complexity of these cases, prior
discussion with a pediatric cardiologist and a pediatric radiologist is ideal to
determine optimal testing.
Management
Surgery is currently the only definitive treatment for rings and slings. Given the
low risk of morbidity, surgery is indicated for all patients with symptoms.3 The
specific method to divide a ring depends on the patency of the ring components.
If the PDA has fibrosed into the ligamentum, then generally all that is required
is a thoracotomy with division of the ligament. On the other hand, complex
vascular repairs may be indicated if all components of the ring remain patent
or if there is a prominent diverticulum of Kommerell that directly compresses
adjacent structures. Similarly, a pulmonary artery sling requires dividing and
reattaching the pulmonary artery proximally.
Patients generally do well after repair, with very low morbidity and mortality
in the current era.4,5 Some patients may require reintervention in the catheter-
ization laboratory if any stenosis develops at the site of vascular reconstruction;
this is common for sling repairs, as well as some variants of DAA, depending on
the initial anatomy. Also, the airway may take weeks or even months to heal, so a
residual cough is not immediately concerning.
Endocarditis prophylaxis is not indicated for unrepaired rings and slings. All
patients require endocarditis prophylaxis for at least 6 months after a procedure
if it involves placement of prosthetic material.
Ongoing Care
All patients born with CHD, and especially those who have undergone an
intervention, require lifelong follow-up. In general, these patients do not have
clinically significant restrictions to athletic participation. Patients are expected
351
CCIP.indb 351 3/13/18 4:19 PM

to have normal oxygen saturation levels after repair and a relatively normal
quality and length of life.
Key Points
•• Symptoms of vascular rings and slings can develop because of airway and/or
esophageal compression.
•• Vascular rings and slings are important to rule out in patients with chronic
respiratory and/or feeding issues.
•• Repair can be straightforward once the anomaly is accurately detected.

•• Vascular Rings (Medscape). emedicine.medscape.com/article/426233-
overview
References
1) Edwards JE. Anomalies of the derivatives of the aortic arch system. Med Clin North Am. 1948;
32:925–949
2) Weinberg PM, Natarajan S, Rogers LS. Aortic arch and vascular anomalies. In: Allen HD,
Driscoll DJ, Shaddy RE, Feltes TF, eds. Moss and Adams’ Heart Disease in Infants, Children, and
Adolescents Including the Fetus and Young Adult. 8th ed. Philadelphia, PA: Lippincott Williams &
Wilkins; 2013:758–798
3) Dodge-Khatami A, Tulevski II, Hitchcock JF, de Mol BA, Bennink GB. Vascular rings and
pulmonary arterial sling: from respiratory collapse to surgical cure, with emphasis on judicious
imaging in the hi-tech era. Cardiol Young. 2002;12(2):96–104
4) Corno AF, Botta U, Hurni M, et al. Surgery for aortic coarctation: a 30 years experience. Eur J
Cardiothorac Surg. 2001;20(6):1202–1206
5) Hamdan MA, Maheshwari S, Fahey JT, Hellenbrand WE. Endovascular stents for
coarctation of the aorta: initial results and intermediate-term follow-up. J Am Coll Cardiol.
2001;38(5):1518–1523
352
CCIP.indb 352 3/13/18 4:19 PM

Ventricular Septal Defects

Introduction
A ventricular septal defect (VSD) is a congenital defect of the ventricular septum
that allows blood to flow between the left ventricle (LV) and the right ventricle
(RV). These defects are classified on the basis of their location in the septum,
with the most common types being in the muscular and perimembranous
regions (Figure 19-23).1 VSDs are the most common form of congenital heart
defect, with a reported prevalence of 2.5 per 1,000 live births and no significant
predilection based on sex.2 Although some genetic syndromes are associated
with VSDs, most occur without an identifiable genetic abnormality.3
Pathophysiology
VSDs can lead to both a pressure load and a volume load on the right side of
the heart. The degree of pressure and volume transmitted to the RV depends on
the size of the VSD. Because pressures will equalize across a large hole, the RV
and LV pressures will be the same in the setting of a large VSD. However, the
pressure transmitted between the 2 ventricles is limited when the VSD becomes
smaller. Therefore, the RV pressure may only be minimally increased, or even
normal, when the VSD is small.
In terms of volume, blood flows from areas of high resistance to areas of low
resistance. In the circulation, systemic vascular resistance (SVR) and pulmonary
vascular resistance (PVR) determine the direction and degree of blood shunting.
Since PVR is lower than SVR, in the absence of lung disease, blood flows from
the LV through the RV and into the pulmonary arteries. Most shunting occurs
during systole. Once the shunted blood flows through the RV and into the
pulmonary arteries, the extra blood returns to the left atrium and LV. Therefore,
with isolated VSDs, the pulmonary arteries and the left side of the heart receive
the extra shunted blood, and as such, the left atrium and LV may be dilated.
Two special issues are worth mentioning. First, certain VSDs are located close
to the aortic valve and can cause prolapse of an aortic valve cusp. This will result
in aortic regurgitation, which can become hemodynamically significant in some
cases. Second, another subset of VSDs can cause localized hypertrophy of muscle
in the RV. This muscle can become so thick that it creates a condition known as
“double-chambered” RV in which the muscle causes obstruction to RV outflow.
The development of either of these issues is important and factors substantially
into the method and timing of repair.
353
CCIP.indb 353 3/13/18 4:19 PM

AO
PA LA
Aortic
valve
RA Mitral
valve
Pulmonary
valve
LV
RV
Tricuspid
valve
Opening between
ventricles (VSD)
Oxygen-rich blood
Oxygen-poor blood
Mixed blood
AO: Aorta PA: Pulmonary artery
LA: Left atrium LV: Left ventricle
RA: Right atrium RV: Right ventricle
FIGURE 19-23. Ventricular septal defect (VSD). AO = aorta, LA = left atrium, LV = left ventricle,
PA = pulmonary artery, RA = right atrium, RV = right ventricle.
Clinical Features
Signs and Symptoms
The signs and symptoms of VSDs largely relate to the excess pulmonary blood
flow. Patients may have tachypnea and increased work of breathing with activity.
Since eating is an exercise-equivalent in newborns, they may have feeding
difficulties and poor growth with larger defects.4 Patients with smaller defects
may be asymptomatic early in life, presenting with only a murmur. Some may
eventually develop shortness of breath with activity, but other patients with small
or tiny VSDs may never exhibit any symptoms. If clinically significant VSDs are
354
CCIP.indb 354 3/13/18 4:19 PM

not repaired, Eisenmenger syndrome will eventually develop, and the associated
pulmonary hypertension will cause right-to-left shunting through the VSD and
resultant cyanosis.5
Physical examination findings depend on the size of the defect. Infants with
large VSDs may have clinical features of heart failure, with tachypnea, crackles,
hepatomegaly, and failure to thrive. A systolic murmur is often heard from the
VSD itself, and a diastolic murmur of relative mitral stenosis (ie, excess shunted
blood flowing across the mitral valve) may be heard, as well. The systolic murmur
may be less prominent in patients with large defects because a large defect
generates less turbulence to blood flow. A hyperactive precordium with a gallop
can also be heard. (See the list of Audio Recordings at the end of this topic.)
Older children and adults with smaller defects often have a loud systolic
murmur. The murmur may be holosystolic or may end in mid- to late systole,
depending on the VSD type (eg, muscular). An early-decrescendo diastolic
murmur may be heard if aortic regurgitation has developed. If pulmonary
hypertension develops, the P2 component of the second heart sound will
increase. A diastolic murmur may also be heard if clinically significant pul
monary valve regurgitation has developed.

Most referrals do not require special testing. A chest radiograph obtained by the
pediatrician can be a helpful first test for infants with symptoms or failure to
thrive. Echocardiography is the standard of reference for diagnosis; in general,
patients with suspected VSDs should be referred, but an experienced pediatrician
may consider ordering outpatient echocardiography for an asymptomatic child
with a “classic” VSD murmur. Most patients do not require cardiac catheter-
ization unless there is concern for irreversible pulmonary hypertension. That
decision would be made by a cardiologist.
Management
The overall treatment approach varies with the degree of hemodynamic signif-
icance. Tiny or small VSDs that are pressure restrictive with trivial shunting
and no left-sided heart dilation can be monitored. On the other hand, VSD
closure is indicated for lesions causing left-sided heart dilation or clinically
significant symptoms.
For infants, surgery is generally performed at 4 to 6 months of age. Infants
are treated medically, primarily with diuretics, until that age. Pulmonary artery
bands can also be placed for tiny or premature infants in whom medical man-
agement is insufficient. Pulmonary artery bands act as fixed resistors, increasing
355
CCIP.indb 355 3/13/18 4:19 PM

the resistance to pulmonary artery flow, thereby limiting shunting. These patients
will ultimately undergo removal of the pulmonary artery band and repair of the
VSD later in life. Recently, transcatheter devices have been developed for closure
of some defects.
Pulmonary hypertension develops in response to both pressure and volume
loads on the lungs. The process occurs faster in response to pressure, so larger
VSDs with higher RV pressure often require intervention earlier than smaller,
pressure-restrictive VSDs.
Patients generally do well after repair, with low incidence of major
morbidity and mortality.6 Most are able to stop taking medications after
repair. Endocarditis prophylaxis is not indicated for unrepaired simple VSDs.
All patients require endocarditis prophylaxis for at least 6 months after either
surgical or percutaneous VSD closure.
Ongoing Care
All patients born with congenital heart disease, and especially those who have
undergone an intervention, require lifelong follow-up. Any patients that require
an intervention are at increased risk for ventricular dysfunction, as well as cardiac
arrhythmias.
These patients generally have no restrictions for athletic participation.
Patients are expected to have normal oxygen saturation levels after repair and
relatively normal quality and length of life.
Key Points
•• The degree of shunting varies markedly, depending on the size of the defect.
•• Some VSD types (eg, muscular) are more likely to close spontaneously.
•• Small defects often have louder murmurs, but this is not always true.

•• Small Muscular Ventricular Septal Defect—normal speed (Willam Buck
Kyle, MD). www.youtube.com/watch?v=VLD0ao6lQ3M&index=8&list=
•• Small Muscular Ventricular Septal Defect—slow (Willam Buck Kyle,
MD). www.youtube.com/watch?v=BJ-1c4JFY9Y&index=9&list=
356
CCIP.indb 356 3/13/18 4:19 PM

•• Restrictive Membranous Ventricular Septal Defect—normal speed (Willam

Buck Kyle, MD). www.youtube.com/watch?v=dnzZDGKMW5I&index=
•• Restrictive Membranous Ventricular Septal Defect—slow (Willam Buck
Kyle, MD). www.youtube.com/watch?v=bpEKVgXQPhY&index=11&list=
•• Restrictive Muscular Ventricular Septal Defect (Willam Buck Kyle,
MD). www.youtube.com/watch?v=jXvE1otbxac&index=12&list=
•• Restrictive High Muscular Ventricular Septal Defect (Willam Buck
Kyle, MD). www.youtube.com/watch?v=l-pLcHQVjQA&index=13&list=
•• Restrictive Mid Muscular Ventricular Septal Defect—slow (Willam Buck
Kyle, MD). www.youtube.com/watch?v=7YeB7wbVFNc&index=14&list=
•• Restrictive Apical Muscular Ventricular Septal Defect—slow (Willam Buck
Kyle, MD). www.youtube.com/watch?v=nKlCgY_XtjM&index=15&list=

•• Ventricular Septal Defect (American Heart Association). www.heart.org/
Defects/Ventricular-Septal-Defect-VSD_UCM_307041_Article.jsp
References
1) Soto B, Becker AE, Moulaert AJ, Lie JT, Anderson RH. Classification of ventricular septal
defects. Br Heart J. 1980;43(3):332–343
3) Vaughan CJ, Basson CT. Molecular determinants of atrial and ventricular septal defects and
patent ductus arteriosus. Am J Med Genet. 2000;97(4):304–309
4) Collins G, Calder L, Rose V, Kidd L, Keith J. Ventricular septal defect: clinical and hemo
dynamic changes in the first five years of life. Am Heart J. 1972;84(5):695–705
5) Partin C. The evolution of Eisenmenger’s eponymic enshrinement. Am J Cardiol. 2003;92(10):
1187–1191
6) Kidd L, Driscoll DJ, Gersony WM, et al. Second natural history study of congenital heart
defects. Results of treatment of patients with ventricular septal defects. Circulation. 1993;87
(2 Suppl):I38–I51
357
CCIP.indb 357 3/13/18 4:19 PM

CCIP.indb 358 3/13/18 4:19 PM
PART 4
Cardiomyopathies
and
Channelopathies
20. Hypertrophic C
ardiomyopathy............................................. 361
21. Dilated Cardiomyopathy...................................................... 377
22. Restrictive Cardiomyopathy................................................. 387
23. Noncompaction Cardiomyopathy......................................... 395
24. Long QT Syndrome and Other Channelopathies............... 411
359
CCIP.indb 359 3/13/18 4:19 PM

CCIP.indb 360 3/13/18 4:19 PM
CHAPTER 20
Hypertrophic
ardiomyopathy
C
Whitnee Hogan, MD, and Shaji C. Menon, MD, FACC,
FASE, FAAP
Introduction
Definition
Hypertrophic cardiomyopathy (HCM) is a disorder in which the myocardium,
or heart muscle, becomes thickened, or hypertrophied. The ventricular cavity is
not dilated, and the hypertrophy cannot be attributed to other cardiac or systemic
diseases, such as aortic stenosis or systemic hypertension. The hypertrophy is often
asymmetrical and can occur in any region of the left ventricle (LV) but frequently
involves the ventricular septum. The hypertrophy may lead to LV outflow tract
(LVOT) obstruction. LVOT obstruction occurs in approximately 25% to 30%1 of
patients with HCM. HCM is the most common cause of sudden death in young
competitive athletes (less than 35 years of age).2–5
In the past, HCM has been defined by several different terms, including
idiopathic hypertrophic subaortic stenosis, asymmetrical septal hypertrophy,
and hypertrophic obstructive cardiomyopathy, among others. None of these
single names encompasses the heterogeneity that can be seen with this disorder.
Therefore, the term hypertrophic cardiomyopathy is regarded as the best name to
encompass the broad disease spectrum, emphasizing the hypertrophy with or
without obstruction.3,5
361
CCIP.indb 361 3/13/18 4:19 PM

Epidemiology
HCM is the most common genetic heart disease and occurs in at least 1 in
500 of the general population. As a result, approximately 700,000 Americans
are affected by this disease.6 A large proportion of patients with HCM in the
general population remain unrecognized, and symptomatic patients with HCM
who are seeking medical care constitute just the tip of the iceberg. It most
commonly manifests in adolescence, but can manifest in infancy, early childhood,
or early adulthood.5,7
Genetics
HCM is a genetic disorder caused by a mutation in cardiac sarcomere protein
genes. It is most frequently transmitted as an autosomal dominant trait and
has variable penetrance and expressivity. About 70% of the HCM mutations
are reported in the 2 most common genes, β-myosin heavy chain and myosin-
binding protein C.8,9 HCM pathogenic mutations can be identified in 60% to
70% of patients with a positive family history of HCM and in approximately
10% to 50% of patients without a family history of HCM.9,10 However, marked
genetic heterogeneity is known to exist in HCM, with more than 1,500 individ-
ual mutations identified among known genes.
Pathophysiology
The pathophysiology of HCM is complex and variable. Microscopic evaluation
demonstrates abnormal muscle orientation, or “myocardial disarray,” in which
the normal parallel alignment of the heart muscle cells has been lost and many
of the muscle cells are arranged in disorganized patterns (Figure 20-1).3,5 This
abnormal cellular organization may interfere with the normal conduction of
electrical impulses and therefore predispose the patient to arrhythmias.
The severity and location of hypertrophy are variable but are characteristically
asymmetrical, involving 1 or more segments of the LV, most commonly the
septum (Figure 20-2). The LV hypertrophy is not usually present at birth but
develops over time and may not be complete until adulthood. It has also been
noted that during adolescence, when body growth accelerates, patients often
demonstrate increases in wall thickness.7
HCM can broadly be categorized as obstructive and nonobstructive, or those
with and without LVOT obstruction. The LVOT obstruction does not occur just
as a result of septal hypertrophy but is instead caused by abnormal motion of the
mitral valve and its interaction with the thickened ventricular septum. In these
patients, the mitral valve comes into contact with the ventricular septum during
systole; this has been described as “systolic anterior motion” of the mitral valve.
The gradient across the LVOT is variable and dynamic and can be affected by
various hemodynamic changes, such as volume status and exercise. Most patients
362
CCIP.indb 362 3/13/18 4:19 PM

Hypertrophic Cardiomyopathy
FIGURE 20-1. Photomicrograph shows that, at the microscopic level, hypertrophic cardiomyopathy
is characterized by myocyte hypertrophy, myofibrillar disarray, and fibrosis.
FIGURE 20-2. Pathologic specimen demonstrates severe hypertrophy of the ventricular septum in
an infant with severe hypertrophic cardiomyopathy.
with HCM have the propensity to develop LVOT obstruction at rest or with
exercise.1 This LVOT obstruction is what leads to the murmur in those with
HCM. The systolic anterior motion of the mitral valve can also lead to mitral
regurgitation, or leaking of the mitral valve.
363
CCIP.indb 363 3/13/18 4:19 PM

LV hypertrophy is not the only clinical manifestation of the abnormal

myocardium. Myocardial ischemia, diastolic dysfunction, and arrhythmias can
also be seen in those with HCM. Potential mechanisms that lead to myocardial
ischemia include a decrease in the number of capillaries in the dense muscle
tissue, small-vessel disease characterized by abnormal intramural coronary
arteries with thickened walls and narrow lumens, and an abnormal vasodilator
response.11,12 Diastolic dysfunction, or abnormal relaxation, is also common in
HCM and can lead to some of the symptoms of heart failure. Arrhythmias,
both atrial and ventricular, are common in those with HCM and are the most
common cause of sudden death.
Clinical Features
Signs and Symptoms
Most affected individuals are asymptomatic. If symptomatic, they may present
with symptoms related to heart failure (fatigue, dyspnea, decreased exercise
tolerance), chest pain, arrhythmias (palpitations, presyncope, syncope), or
sudden death.
The cardiovascular examination findings are often normal in patients with
HCM, but there may be subtle or more concerning findings. With palpation,
a prominent or double apical impulse may be felt. In patients with LVOT
obstruction, the classic murmur is a systolic ejection murmur heard best along
the left sternal border that radiates to the right upper sternal border and the
apex. The intensity of the murmur increases with maneuvers that decrease
preload to the heart, such as standing up from a squatting position or having
the patient perform a Valsalva maneuver or bear down. A systolic murmur at
the apex may be auscultated in those with mitral regurgitation.
Electrocardiography
Electrocardiography (ECG) should be performed as part of the initial evaluation
of patients with potential HCM.9 The ECG findings are abnormal in 75%
to 95% of patients with HCM and demonstrate abnormalities such as LV
hypertrophy, ST and T wave abnormalities, and Q waves (Figure 20-3).3,13 Of
note, abnormalities may be present at ECG prior to evidence of LV hypertrophy
at echocardiography.
Echocardiography
Echocardiography is the diagnostic imaging modality of choice and is the most
common test used for screening and diagnosis of HCM. Echocardiography
364
CCIP.indb 364 3/13/18 4:19 PM

FIGURE 20-3. Electrocardiograms from 2 patients with HCM. The top image is from a 27-year-
old man with HCM and T wave inversion in the lateral leads (V4 to V6, circles). The bottom
image is from a 15-year-old male patient with HCM (myosin heavy chain mutation). The findings
demonstrate left ventricular hypertrophy (arrow) and repolarization abnormalities, with tall T waves
in the lateral leads (circle).
provides both a structural and a functional assessment. In addition to the

diagnosis being established by identifying the location, pattern, and degree of
LV hypertrophy, the LVOT and mitral valve can be evaluated, as well as both
systolic and diastolic function (Figures 20-4 and 20-5).
Cardiac Magnetic Resonance Imaging

Cardiac magnetic resonance (MR) imaging has emerged as an adjunct imaging
modality in patients with HCM. It is typically used if imaging is not adequate
with echocardiography to better define and measure wall thickness and assess
365
CCIP.indb 365 3/13/18 4:19 PM

FIGURE 20-4. An echocardiographic image from the apical plane demonstrates septal hypertrophy.
the LVOT obstruction. Late gadolinium-based contrast material enhancement

on cardiac MR images enables the identification of myocardial fibrosis, which
is associated with a high risk of sudden cardiac death. The presence of delayed
enhancement may be considered in risk stratification for implantable cardiac
defibrillator (ICD) placement in patients with HCM, especially in borderline
cases (Figure 20-6).14
Exercise Stress Testing

Exercise stress testing in patients with HCM has many roles, including
evaluating the presence of obstruction with activity, evaluating the patient for
symptoms, assessing blood pressure response to activity, and detecting myocar-
dial ischemia and arrhythmias. Only 25% to 30% of patients demonstrate LVOT
obstruction at rest, but many more have obstruction with activity, which can
be demonstrated in an exercise test.1,15 Exercise normally increases the systolic
366
CCIP.indb 366 3/13/18 4:19 PM

FIGURE 20-5. An echocardiographic image demonstrates septal hypertrophy.
FIGURE 20-6. Contrast-enhanced cardiac magnetic resonance image shows late gadolinium-based
contrast material enhancement or delayed enhancement within the ventricular septum.
367
CCIP.indb 367 3/13/18 4:19 PM

blood pressure by at least 20 mm Hg. A subset of patients with HCM either do

not increase their blood pressure appropriately or have a decrease in their blood
pressure with exercise, which is considered to be a risk factor for sudden cardiac
death.9,16 The detection of ST changes and arrhythmias during exercise stress
testing is helpful in risk stratification.
Ambulatory Monitoring
A Holter monitor, or 24-hour ambulatory monitor, is recommended in the
initial evaluation of patients with HCM to detect the presence of both atrial
and ventricular arrhythmias. Additional Holter monitoring is recommended in
patients with HCM who develop palpitations or lightheadedness.9
Sudden Cardiac Death

HCM is the most common cause of sudden cardiac death in the young and in
competitive athletes. Sudden cardiac death may occur at a wide range of ages but
most commonly occurs in adolescence and young adulthood, and rarely before
the age of 10 years.2–4 Despite the fact that most patients die while sedentary or
during normal physical exertion, death during vigorous activity is an important
aspect of HCM, which has led to the recommendation to disqualify young
patients with HCM from competitive sports.9,17 See Box 20-1 for risk factors
for sudden cardiac death and Table 20-1 for activity restrictions in patients with
HCM. The presence of multiple risk factors in a single patient increases the risk
of sudden cardiac death; however, the presence of even a single risk factor men-
tioned in Box 20-1 can be sufficient for ICD placement. The decision to place an
ICD for primary prevention should be made after detailed discussions about the
risk of sudden cardiac death and the possibility of device-associated complica-
tions, including inappropriate shocks, with the patient and family. A minority of
patients with HCM are thought to be at increased risk for sudden cardiac death,
with a rate of approximately 1% per year.9,18 ICDs offer the only effective means
of preventing sudden cardiac death and prolonging life in these patients.9,18
Box 20-1. Risk Factors for Sudden Cardiac Death

Prior cardiac arrest or sustained Family history of premature death
ventricular tachycardia related to HCM
Unexplained syncope Multiple or prolonged episodes of

ventricular tachycardia
Massive LV hypertrophy (wall thick- Hypotension or decreased blood

ness ≥30 mm) pressure response to exercise
HCM, hypertrophic cardiomyopathy; LV, left ventricular.
368
CCIP.indb 368 3/13/18 4:19 PM

Table 20-1. Recommendations for the Acceptability of

Recreational (Noncompetitive) Sports Activities and
Exercise in Patients with Hypertrophic Cardiomyopathy
Eligibility Scale for Hypertrophic
Intensity Level Cardiomyopathya
High intensity level
Basketball (full court) 0
Basketball (half court) 0
Body-building b
1
Gymnastics 2
Ice hockey b
0
Racquetball, squash 0
Rock climbing b
1
Running (sprinting) 0
Skiing (downhill) b
2
Skiing (cross-country) 2
Soccer 0
Tennis (singles) 0
Touch (flag) football 1
Windsurfing c
1
Moderate intensity level
Baseball, softball 2
Biking 4
Modest hiking 4
Motorcycling b
3
Jogging 3
Sailing c
3
Surfing c
2
Swimming (laps) c
5
Tennis (doubles) 4
Treadmill, stationary bicycle 5
Weightlifting (free weights) bd

1
Hiking 3
Continued
369
CCIP.indb 369 3/13/18 4:19 PM

Table 20-1. Recommendations for the Acceptability

of Recreational (Noncompetitive) Sports Activities
and Exercise in Patients with Hypertrophic
Cardiomyopathy, continued
Eligibility Scale for Hypertrophic
Intensity Level Cardiomyopathya
Low intensity level
Bowling 5
Golf 5
Horseback ridingb 3
Scuba divingc 0
Skatinge 5
Snorkelingc 5
Weights (non–free weights) 4
Brisk walking 5
Recreational sports are categorized according to high, moderate, and low levels of exercise and are graded on a
relative scale (from 0 to 5) for eligibility, with 0 to 1 indicating generally not advised or strongly discouraged; 4 to 5,
probably permitted; and 2 to 3, intermediate and to be assessed clinically on an individual basis. The designations of
high, moderate, and low levels of exercise are equivalent to an estimated >6, 4 to 6, and <4 metabolic equivalents,
respectively. Reprinted with permission from Gersh BJ, Maron BJ, Bonow RO, et al. 2011 ACCF/AHA guideline for
the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology
Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011;124:e783–e831.
©2011 American Heart Association, Inc.
a
Assumes absence of laboratory DNA genotyping data; therefore, limited to clinical diagnosis.
b
These sports involve the potential for traumatic injury, which should be taken into consideration for individuals
with a risk for impaired consciousness.
c
The possibility of impaired consciousness occurring during water-related activities should be taken into account
with respect to the individual patient’s clinical profile.
d
Recommendations generally differ from those for weight-training machines (non–free weights), based largely
on the potential risk of traumatic injury associated with episodes of impaired consciousness during bench-press
maneuvers; otherwise, the physiological effects of all weight-training activities are regarded as similar with respect
to the present recommendations.
e
Individual sporting activity not associated with the team sport of ice hockey.
•• Athletic heart: LV hypertrophy can be seen in elite athletes. The hypertrophy
is typically mild and symmetrical. It can be difficult to differentiate an
athletic heart from HCM. It should never be assumed that hypertrophy seen
in an athlete is due to an athletic heart without a thorough evaluation by
a specialist.19
•• Systemic hypertension with secondary ventricular hypertrophy
•• LV noncompaction cardiomyopathy can sometimes be confused with HCM.
•• Metabolic disorders: PRKAG2 genetic mutation, Fabry disease, and LAMP2
cardiomyopathy (Danon disease)
370
CCIP.indb 370 3/13/18 4:19 PM

Management
Management Approach
The management approach to HCM is geared toward heart failure management,
relief of LVOT obstruction if needed, and prevention of sudden cardiac death.
Heart failure symptom management varies and should be tailored to individual
patients, but β-blockers are most commonly used. Those who have symptoms
despite medical management, along with clinically significant outflow tract
obstruction, may undergo a surgical myectomy, or removal of a portion of the
septum. Surgical myectomy is the preferred modality for the relief of LVOT
obstruction in children who are nonresponsive to medical therapy. Alcohol septal
ablation is a treatment modality used in adults with LVOT obstruction but is
not typically recommended in children. In select, high-risk patients, placement
of an ICD is recommended for the prevention of sudden cardiac death.
When to Refer
All patients with findings suggestive of HCM should be referred to a pediatric
cardiologist for evaluation.
Evaluation of Family Members

All patients with HCM should undergo evaluation of familial inheritance and
genetic counseling. Screening is recommended for all first-degree relatives of
those with HCM, including ECG, echocardiography, cardiac MR imaging,
and possible genetic testing if the genetic abnormality is known in the family.9
Genetic testing for HCM is widely available, and numerous commercial labora-
tories and tertiary care centers now offer comprehensive genetic testing panels by
using rapid and automated DNA sequencing to identify a molecular diagnosis.
Genetic counseling by experts in cardiovascular genetics is recommended before
performing genetic testing, so that results of the genetic testing and its clinical
significance can be appropriately reviewed with the patient and families. Despite
initial enthusiasm and promise, genotype in pediatric patients with HCM has
not been shown to be of predictive value in determining the long-term progno-
sis, risk of sudden cardiac death, or responsiveness to treatment.
Patients with Genotype-Positive, Phenotype-Negative

Findings
Those individuals found through genetic screening to have a pathogenic muta-
tion of HCM but who do not demonstrate the phenotype of HCM need to be
serially followed. It is recommended that they undergo echocardiography, ECG,
and clinical assessment every 12 to 18 months in childhood and adolescence
and every 5 years in adulthood; assessment may be needed more frequently,
depending on clinical status.9
371
CCIP.indb 371 3/13/18 4:19 PM

Low-intensity aerobic exercise is reasonable as part of a healthy lifestyle in
asymptomatic patients with HCM.9 Patients should be discouraged from any
activity that provokes symptoms, such as shortness of breath. Patients with
HCM should not participate in intense competitive sports, regardless of age, sex,
race, presence or absence of LVOT obstruction, prior septal reduction therapy, or
ICD placement.9 Recommendations for physical activity need to be tailored to
individual patients. General activity guidelines are not applicable to individuals
with additional risk factors, including history of cardiac symptoms, such as
syncope or arrhythmias, prior cardiac surgery such as a myectomy, or those with
ICDs or pacemakers.9,17 Individuals who carry pathologic mutations for HCM
but who do not show any evidence of hypertrophy at echocardiography can
still have myocardial abnormalities that can be detected with advanced imaging
studies such as cardiac MR imaging. However, at present, individuals with gen-
otype-positive but phenotype-negative findings are not excluded from competi-
tive sports. See Table 20-1 for recommendations regarding activity restrictions.
Ongoing Care
Follow-up
Individuals with HCM require lifelong periodic follow-up with a cardiologist
who specializes in the management of cardiomyopathies. In many tertiary care
centers, patients with HCM are evaluated in a multidisciplinary clinic that
consists of cardiologists, electrophysiologists, and genetic counselors.
Prognosis
HCM is a heterogeneous cardiac disease with a diverse clinical presentation and
course. Most affected individuals can achieve a normal life expectancy without
major therapeutic interventions.20 Select patients have clinically significant
morbidity and risk for premature death. In these patients, the natural history can
be altered with heart failure therapies, septal myectomy, heart transplantation,
and/or ICDs for the prevention of sudden cardiac death.
Pre-Sports Participation Evaluation in Athletes

HCM is thought to be responsible for about 15 deaths per year in U.S. high
school and college students engaged in competitive sports.20 Guidelines (2010)
from the American Academy of Family Physicians, the American Academy of
Pediatrics, the American College of Sports Medicine, the American Medical
Society for Sports Medicine, the American Orthopaedic Society for Sports
372
CCIP.indb 372 3/13/18 4:19 PM

Medicine, and the American Osteopathic Academy of Sports Medicine

recommend performing a preparticipation physical evaluation that consists of
a detailed personal and family history. The history should specifically target
cardiovascular conditions that predispose patients to sudden cardiac death and
symptoms that are concerning for cardiomyopathy, including syncope, chest pain,
dizziness, and/or palpitations during exercise. Preparticipation ECG screening is
a controversial topic and has been addressed in 2014 and 2015 American Heart
Association and American College of Cardiology Scientific Statements,21,22
which do not recommend mandatory and universal mass screening with ECGs
but state that screening ECGs in association with comprehensive history com-
pilation and physical examination may be considered in select patients. Studies
have failed to demonstrate a mortality benefit from universal ECG screening.23
Key Points
•• HCM is the most common genetic heart disease, occurring in at least 1 in 500
people in the general population.
•• Most individuals with an HCM mutation are asymptomatic.
•• HCM is the most common cause of sudden death in young competitive
athletes (less than 35 years of age).
•• Although genetically heterogeneous, HCM is primarily a disease of the
sarcomeric genes. Several commercial genetic tests can be used to identify the
pathologic mutation in a high proportion of patients with HCM.
•• Screening of first-degree relatives (physical examination, ECG, echocardiog-
raphy, cardiac MR imaging, and/or genetic testing) of patients with HCM
is essential.
•• In a subset of patients with HCM at risk for sudden cardiac death, ICDs are
the optimal therapy.

•• Hypertrophic Cardiomyopathy Association. www.4hcm.org
References
1) Joshi S, Patel UK, Yao SS, et al. Standing and exercise Doppler echocardiography in obstructive
hypertrophic cardiomyopathy: the range of gradients with upright activity. J Am Soc Echocardiogr.
2011;24(1):75–82
2) Maron BJ, Haas TS, Ahluwalia A, Murphy CJ, Garberich RF. Demographics and epidemiology
of sudden deaths in young competitive athletes: from the United States national registry. Am J
Med. 2016;129(11):1170–1177
3) Maron BJ. Hypertrophic cardiomyopathy: a systematic review. JAMA. 2002;287(10):1308–1320
373
CCIP.indb 373 3/13/18 4:19 PM

4) Maron BJ, McKenna WJ, Danielson GK, et al; Task Force on Clinical Expert Consensus
Documents. American College of Cardiology; Committee for Practice Guidelines. European
Society of Cardiology. American College of Cardiology/European Society of Cardiology
clinical expert consensus document on hypertrophic cardiomyopathy. A report of the American
College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and
the European Society of Cardiology Committee for Practice Guidelines. J Am Coll Cardiol.
2003;42(9):1687–1713
5) Allen HD, Driscoll DJ, Shaddy RE, Feltes TF, eds. Moss and Adams’ Heart Disease in Infants,
Children, and Adolescents. 8th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2013
6) Maron BJ, Gardin JM, Flack JM, Gidding SS, Kurosaki TT, Bild DE. Prevalence of hypertro-
phic cardiomyopathy in a general population of young adults. Echocardiographic analysis of
4111 subjects in the CARDIA Study. Coronary Artery Risk Development in (Young) Adults.
Circulation. 1995;92(4):785–789
7) Maron BJ, Spirito P, Wesley Y, Arce J. Development and progression of left ventricular hypertro-
phy in children with hypertrophic cardiomyopathy. N Engl J Med. 1986;315(10):610–614
8) Bos JM, Towbin JA, Ackerman MJ. Diagnostic, prognostic, and therapeutic implications of
genetic testing for hypertrophic cardiomyopathy. J Am Coll Cardiol. 2009;54(3):201–211
9) Gersh BJ, Maron BJ, Bonow RO, et al; American College of Cardiology Foundation/American
Heart Association Task Force on Practice Guidelines; American Association for Thoracic
Surgery; American Society of Echocardiography; American Society of Nuclear Cardiology;
Heart Failure Society of America; Heart Rhythm Society; Society for Cardiovascular
Angiography and Interventions; Society of Thoracic Surgeons. 2011 ACCF/AHA guideline for
the diagnosis and treatment of hypertrophic cardiomyopathy: executive summary: a report of
the American College of Cardiology Foundation/American Heart Association Task Force on
Practice Guidelines. Circulation. 2011;124(24):2761–2796
10) Morita H, Rehm HL, Menesses A, et al. Shared genetic causes of cardiac hypertrophy in
children and adults. N Engl J Med. 2008;358(18):1899–1908
11) Cannon RO III, Rosing DR, Maron BJ, et al. Myocardial ischemia in patients with hypertrophic
cardiomyopathy: contribution of inadequate vasodilator reserve and elevated left ventricular
filling pressures. Circulation. 1985;71(2):234–243
12) Maron BJ, Wolfson JK, Epstein SE, Roberts WC. Morphologic evidence for “small vessel
disease” in patients with hypertrophic cardiomyopathy. Z Kardiol. 1987;76(Suppl 3):91–100
13) Maron BJ. The electrocardiogram as a diagnostic tool for hypertrophic cardiomyopathy: revisited.
Ann Noninvasive Electrocardiol. 2001;6(4):277–279
14) Rubinshtein R, Glockner JF, Ommen SR, et al. Characteristics and clinical significance of late
gadolinium enhancement by contrast-enhanced magnetic resonance imaging in patients with
hypertrophic cardiomyopathy. Circ Heart Fail. 2010;3(1):51–58
15) Argulian E, Chaudhry FA. Stress testing in patients with hypertrophic cardiomyopathy. Prog
Cardiovasc Dis. 2012;54(6):477–482
16) Sadoul N, Prasad K, Elliott PM, Bannerjee S, Frenneaux MP, McKenna WJ. Prospective
prognostic assessment of blood pressure response during exercise in patients with hypertrophic
cardiomyopathy. Circulation. 1997;96(9):2987–2991
17) Maron BJ, Chaitman BR, Ackerman MJ, et al; Working Groups of the American Heart
Association Committee on Exercise, Cardiac Rehabilitation, and Prevention; Councils on
Clinical Cardiology and Cardiovascular Disease in the Young. Recommendations for physical
activity and recreational sports participation for young patients with genetic cardiovascular
diseases. Circulation. 2004;109(22):2807–2816
18) Maron BJ, Spirito P, Shen WK, et al. Implantable cardioverter-defibrillators and prevention of
sudden cardiac death in hypertrophic cardiomyopathy. JAMA. 2007;298(4):405–412
374
CCIP.indb 374 3/13/18 4:19 PM

19) Maron BJ. Distinguishing hypertrophic cardiomyopathy from athlete’s heart physiological
remodelling: clinical significance, diagnostic strategies and implications for preparticipation
screening. Br J Sports Med. 2009;43(9):649–656
20) Maron BJ, Rowin EJ, Casey SA, et al. Hypertrophic cardiomyopathy in children, adolescents,
and young adults associated with low cardiovascular mortality with contemporary management
strategies. Circulation. 2016;133(1):62–73
21) Maron BJ, Levine BD, Washington RL, Baggish AL, Kovacs RJ, Maron MS; American
Heart Association Electrocardiography and Arrhythmias Committee of Council on Clinical
Cardiology, Council on Cardiovascular Disease in Young, Council on Cardiovascular and Stroke
Nursing, Council on Functional Genomics and Translational Biology, and American College of
Cardiovascular Abnormalities: Task Force 2: Preparticipation Screening for Cardiovascular
Disease in Competitive Athletes: a Scientific Statement from the American Heart Association
and American College of Cardiology. Circulation. 2015;132(22):e267–e272
22) Maron BJ, Friedman RA, Kligfield P, et al; American Heart Association Council on Clinical
Cardiology; Advocacy Coordinating Committee; Council on Cardiovascular Disease in the
Young; Council on Cardiovascular Surgery and Anesthesia; Council on Epidemiology and
Prevention; Council on Functional Genomics and Translational Biology; Council on Quality
of Care and Outcomes Research, and American College of Cardiology. Assessment of the
12-lead electrocardiogram as a screening test for detection of cardiovascular disease in healthy
general populations of young people (12-25 years of age): a scientific statement from the
American Heart Association and the American College of Cardiology. J Am Coll Cardiol.
2014;64(14):1479–1514
23) Maron BJ, Haas TS, Doerer JJ, Thompson PD, Hodges JS. Comparison of U.S. and Italian
experiences with sudden cardiac deaths in young competitive athletes and implications for
preparticipation screening strategies. Am J Cardiol. 2009;104(2):276–280
375
CCIP.indb 375 3/13/18 4:19 PM

CCIP.indb 376 3/13/18 4:19 PM
CHAPTER 21
Dilated
ardiomyopathy
C
Shannon Lyon, DO, and Joshua D. Sparks, MD
Introduction
Definition
Dilated cardiomyopathy (DCM) is the most common type of cardiomyopathy
in children and consists of a dilated systemic left ventricle (LV) with
systolic dysfunction.1

Over the past 15 to 20 years, along with the advancement of the field of pediat-
ric heart failure and transplantation, a substantial amount of clinical investigation
has led to a better understanding of the epidemiology, etiologic origins, clinical
manifestations, and treatment of these complex and heterogeneous diseases.
Etiologic Origins and Epidemiology

Because of the rarity and varied phenotypes and presentation of these diseases,
accurately detailing the epidemiology has presented substantial challenges. In 1994,
the Pediatric Cardiomyopathy Registry was developed and has been instrumental
in increasing knowledge and understanding of cardiomyopathy in children.1
Overall, the reported annual incidence of pediatric cardiomyopathy within this
registry was 1.13 per 100,000 children. Incidence was reportedly higher in infants
and nonwhite patients, with geographic variation across North America. Of these
patients, the annual incidence of DCM was 0.58 cases per 100,000 children per
year. The median age at diagnosis was 1.5 years, with infants under the age of
1 year representing the largest of any age group.1–3
377
CCIP.indb 377 3/13/18 4:19 PM

DCM has a myriad of etiologic origins, including myocarditis (16%), neu-

romuscular disorders (9%), familial mutations that lead to abnormal myocardial
proteins and/or support structure (5%), inborn errors of metabolism (4%), and
malformation syndromes (1%). Despite technological advances, 66% of DCM
cases are determined to be idiopathic.1

More than 20 genetic abnormalities and mutations have been identified in
patients with familial or genetic cardiomyopathies. They are most commonly
inherited in an autosomal dominant fashion but also may be inherited in an
X-linked, recessive, or mitochondrial pattern.4 Typically, onset of familial
cardiomyopathy is in adulthood, but it does sporadically occur in the pediatric
population, with variable penetrance.1,5 Children with neuromuscular disorders,
most of whom have Duchenne or Becker muscular dystrophy (dystrophin gene
mutations), typically develop DCM in mid to late adolescence; neuromuscular
disorders are the second most common etiologic origin (9%).1

Inborn errors of metabolism are one of the least common etiologic origins
and include mitochondrial disorders, amino and organic acid disorders, fatty
acid disorders, and carnitine deficiency, among others. These disorders involve
multiple organ systems, and routine echocardiograms should be obtained to
screen for the development of cardiomyopathy.1,6 Accurate diagnosis is critical
for prognostication, as well as providing disease-specific therapies that can
prevent progression or even reverse organ dysfunction in some instances.
Pathophysiology
The pathogenesis of DCM begins with an insult to the myocardium, either
inflammatory or genetic. Regardless of etiologic origin, the muscle of the heart
is weakened and abnormal, which leads to progressive dilation of the heart
chambers. Over a variable period of time, the cardiac output eventually decreases
and leads to activation of the renin-angiotensin-aldosterone, natriuretic, and
sympathetic nervous system pathways. This leads to fluid and sodium retention,
vasoconstriction, and increased heart-filling pressure. Although this is initially
compensatory, the response becomes maladaptive, worsens heart failure symp-
toms, and leads to cardiac remodeling and fibrosis.7
Clinical Manifestations and Diagnosis

Signs and Symptoms
Most children (71%) with DCM present with congestive heart failure at the
time of diagnosis.1 While adolescents tend to experience clinical syndromes sim-
ilar to those of adults (dyspnea with exertion, orthopnea, and fatigue), younger
children in heart failure will often not have obvious fluid retention or edema and
may primarily develop failure to thrive or a myriad of nonspecific symptoms.8
378
CCIP.indb 378 3/13/18 4:19 PM

Dilated Cardiomyopathy
Gastrointestinal symptoms, such as abdominal pain and vomiting, are uniquely

common in the presentation of children.9,10
History and physical examination can often be elusive and elicit signs
and symptoms that are nonspecific and/or overlap with other, more common
pediatric ailments. Findings can include tachypnea, tachycardia, hepatomegaly,
hyperactive precordium, and gallop rhythm. At times, the only symptom may
be failure to thrive. Because of these differences between infants and older
children and adults, grading and classification of heart failure can be challenging.
This challenge led to the development of the Ross classification, which is the
pediatric version of the New York Heart Association system. Although the
Ross classification can be helpful in communicating between providers, it has
demonstrated limited utility in predicting outcomes in young children with heart
failure.11,12 The American College of Cardiology (ACC) and the American Heart
Association (AHA) also have a classification system based on the presence or
absence of structural heart disease, along with historical or current symptoms,
which is useful in guiding treatment options (see Tables 21-1 and 21-2).13,14

Children typically present for evaluation of DCM because of either clinical
heart failure or an identified risk factor (eg, family history, neuromuscular
weakness, abnormal laboratory value). The diagnostic test of choice is an
echocardiogram to evaluate the heart chamber size and systolic function and to
exclude other causes or associations, such as congenital heart disease, congenital
Table 21-1. Ross Classification of Heart Failure

as Compared to the New York Heart Association
Classification
Ross Heart Failure New York Heart Association
Classification Classification
Class I Asymptomatic No limitation of physical activity;

ordinary physical activity does not
induce heart failure symptoms
Class II Mild tachypnea or diaphore- Slight limitation of physical activity;

sis with feedings in infants; comfortable at rest, but ordinary
exertional dyspnea in older physical activity induces heart failure
children symptoms
Class III Marked tachypnea or diapho- Marked limitation of physical activity;

resis with feedings in infants comfortable at rest, but less than
or prolonged feeding time ordinary activity induces heart failure
with growth failure; marked symptoms
exertional dyspnea
Class IV Tachypnea, retractions, Unable to perform any physical activity

grunting, diaphoresis at rest without symptoms of heart failure or
having heart failure symptoms at rest
From references 11 and 12.
379
CCIP.indb 379 3/13/18 4:19 PM

Table 21-2. American College of Cardiology and

American Heart Association Heart Failure Staging
Stage Description
A At risk for heart failure, on the basis of the presence of conditions with a
strong association with the development of heart failure. No structural or
functional abnormalities of the heart.
B Structural heart disease without signs or symptoms of heart failure.
C Current or prior symptoms of heart failure, with underlying structural

heart disease.
D Advanced structural heart disease and marked symptoms of heart failure

at rest, despite maximal medical therapy.
Heart failure staging was obtained from the adult literature and is based on the presence or absence of structural
heart disease and the presence or absence of symptoms of heart failure. Reprinted with permission from reference
13. ©2001 American Heart Association, Inc.
or acquired valve disease, or coronary abnormalities. Echocardiography can also

provide additional prognostic information, including mitral regurgitation, LV
size and wall thickness, and estimates of diastolic performance. Chest radio
graphy may show cardiomegaly and pulmonary edema. Electrocardiography
(ECG) can be helpful in evaluating the patient for conduction abnormalities
or classic associated findings suggestive of specific familial or metabolic
cardiomyopathies, anomalous left coronary artery from the pulmonary artery, or
myocarditis; it can also be helpful in assessing the patient for tachyarrhythmia
suggestive of tachycardia-induced heart muscle dysfunction, a very treatable form
of acute cardiomyopathy. ECG may also show LV hypertrophy and nonspecific
ST or T wave changes.15,16
Biomarkers
Blood biomarkers have been extensively studied in patients with heart failure.
They are not diagnostic for DCM but are highly sensitive for the diagnosis and
severity of clinical heart failure and may be helpful for determining the prognosis
and guiding treatment decisions. Brain natriuretic peptide (BNP) is a peptide
secreted by the heart under stress and is one of the most studied biomarkers. It
is assessed in its active and its cleaved byproduct form (prohormone N-terminal
BNP). It can be increased with normal physiology in newborns and young
infants and appears to approach normal levels after the first days to weeks of
life.17,18 For children with DCM, discharge BNP levels of more than 300 pg/mL
(300 ng/L) have been demonstrated to be predictive of adverse cardiac events.19
Additionally, serum troponin levels can be helpful in the diagnosis of ischemic or
acute injury, such as myocarditis, but are not themselves diagnostic.20
380
CCIP.indb 380 3/13/18 4:19 PM

Diagnostic Testing
As stated previously, DCM is an anatomic classification of diseased heart
muscle; however, despite the fact that only 34% of patients ultimately have a
diagnosed etiologic origin, the origin should be aggressively pursued in most
instances. The outcomes of children can vary greatly with etiologic origin.
Assessment of Genetic Cardiomyopathy

Genetic cardiomyopathies are often described as inborn errors of metabolism,
malformation syndromes, neuromuscular diseases, and familial or genetic
cardiomyopathies. Inborn errors of metabolism can include storage diseases,
disorders of energy, and disorders that produce toxic metabolites. Schwartz and
colleagues have published algorithms for evaluation of metabolic and genetic
causes of cardiomyopathy; these can be very helpful in the diagnostic evaluation
of cardiomyopathy in newborns and infants.14 Distinctive physical features may
also guide the evaluation of a genetic disorder associated with cardiomyopathy
(See Table 21-3).
Table 21-3. Physical Characteristics Associated With

Genetic Cardiomyopathies
System Feature Diagnosis
Growth Short stature Noonan syndrome

Multiple lentigines
Mucopolysaccharidosis
Macrosomia Beckwith-Wiedemann syndrome

Costello syndrome
Skeleton Joint laxity Cutis laxa
Pectus Noonan syndrome
Kyphoscoliosis Mucopolysaccharidosis
Skin and hair Wiry hair Cardiofaciocutaneous syndrome
Palmar keratosis Cardiofaciocutaneous syndrome

Palmoplantar keratosis
Lentigines Multiple lentigines
Café au lait spots Neurofibromatosis, type 1

Noonan syndrome
Neurofibromas Neurofibromatosis, type 1
Cutis laxa (loose skin) Costello syndrome
Deep plantar furrows Costello syndrome
Lipodystrophy Lipodystrophy
Insulin resistance
Continued
381
CCIP.indb 381 3/13/18 4:19 PM

Table 21-3. Physical Characteristics Associated With

Genetic Cardiomyopathies, continued
System Feature Diagnosis
Facies Distinctive Noonan syndrome

Cardiofaciocutaneous syndrome
Coarse Mucopolysaccharidosis
Pompe disease
Hypotonia Neuromuscular disease
Other Telecanthus Telecanthus

craniofacial MCA syndrome
characteristics
Cataracts Sengers syndrome
Leber congenital amaurosis
Nystagmus Leber congenital amaurosis
Macroglossia Beckwith-Wiedemann syndrome

Pompe disease
Ear creases Beckwith-Wiedemann syndrome
Neck webbing Noonan syndrome
Central ner- Microcephaly Microcephaly

vous system
Contractures Marden-Walker syndrome
External Hypogonadism MCA syndrome

genitalia Collagenoma syndrome
Cryptorchidism Noonan syndrome
Genital anomalies Genitourinary anomalies

Physical examination characteristics associated with syndromic cardiomyopathies. MCA, multiple congenital
anomalies. From reference 14.
Endomyocardial Biopsy
Endomyocardial biopsy can be performed via cardiac catheterization and is
generally conducted in the right interventricular septum or apex. It is relatively
safe, with a low reported incidence of clinically significant morbidity or mortal-
ity, but its utility remains ill-defined.21 According to the 2007 AHA, ACC, and
European Society of Cardiology scientific statement, biopsy was given a class I
recommendation for patients with new-onset heart failure of <2 weeks’ duration
with normally sized or dilated LV and hemodynamic compromise. Biopsy was
given a class IIA indication for patients with unexplained cardiomyopathy, on
the basis of limited evidence. The utility appears to be the best for those with
hypertrophic cardiomyopathy, as well as to establish the diagnosis of myocarditis,
which provides prognostic information.22
382
CCIP.indb 382 3/13/18 4:19 PM

Role of Magnetic Resonance Imaging

Cardiac magnetic resonance imaging is increasingly used in the diagnosis and
prognosis of pediatric cardiomyopathy to provide detailed information about
the myocardium, including function, thickness, and compaction. With the use
of gadolinium-based contrast material, the heart muscle can be further char-
acterized with respect to the burden of fibrosis or scar formation, with delayed
clearance of the contrast material.
Treatment and Natural History

Treatment strategies for DCM are dependent on the etiologic origin.
Considering that most patients’ DCM will prove to be idiopathic, treatment is
directed primarily at alleviating symptoms and reducing mortality risk. Decades
of research in adults with heart failure has supported therapies that target mal-
adaptive pathways, such as the renin-angiotensin-aldosterone pathway and sym-
pathetic nervous system activation. A 2014 monograph from the International
Society for Heart & Lung Transplantation provides a comprehensive review of
pediatric heart failure, along with guidelines regarding the treatment of children
with heart failure.23
Table 21-4 lists the commonly used medications for the treatment of chronic
heart failure in children.
Acute decompensated heart failure can be treated with inotropic infusions,
as well as diuretics, to improve cardiac output and reduce filling pressures.
Mechanical support as a bridge to recovery or heart transplantation has been
a hot topic in the field of pediatric heart failure since the U.S. Food and Drug
Administration approval of the first pediatric ventricular assist device in 2012.24
Heart transplantation remains the definitive treatment for refractory heart fail-
ure caused by DCM and despite the use of medications, 46% of patients having
died or received a heart transplant by 5 years after diagnosis. There is, however,
substantial variability of outcomes within specific etiologic origins. Reported
risk factors for death or transplantation include idiopathic DCM, diagnosis after
6 years of age, and congestive heart failure at the time of diagnosis.1
Key Points
•• DCM remains a rare disease with clinically significant morbidity and
mortality. The prevalence is highest in young infants, who require a thorough
evaluation for genetic, metabolic, inflammatory, and neuromuscular causes.
•• Despite improvements in the understanding of this disease, 66% of all cases
remain idiopathic.
•• Treatment is based largely on adult studies and includes β-blockers,
angiotensin-converting enzyme inhibitors, and diuretics.
383
CCIP.indb 383 3/13/18 4:19 PM

•• Despite treatment, a high proportion of patients will require advanced

therapies, including inotropic infusion, mechanical circulatory support, and
heart transplantation.
Table 21-4. Pharmacotherapy for Chronic Heart Failure

in Children With Reduced Ejection Fraction
Medication Recommendations
Diuretics Recommended for stage C heart failure with fluid retention.
Angiotensin- Recommended for routine use in stage B and C heart failure,

converting enzyme if not contraindicated. Start at a low dose and titrate up.
inhibitors
β-blockers Consider for use in stage B, C, and D heart failure, by follow-

ing adult guidelines. Start at a low dose and titrate up.
Mineralocorticoid It is reasonable to consider aldosterone antagonists in stage

receptor antagonists C heart failure, by following adult guidelines.
Angiotensin recep- Recommended for stage B and C heart failure, in children

tor antagonists who cannot tolerate angiotensin-converting enzyme
inhibitors.
Digoxin Not recommended for children with asymptomatic heart

failure. May be used for symptom relief in those with low
ejection fraction.
Hydralazine with Not recommended for children with heart failure.

isosorbide dinitrate
Antiarrhythmic Recommended in select cases of arrhythmias.

medications
Statin therapy Not indicated in children.
Renin inhibitors Not indicated in children.
Anticoagulants Heparin or warfarin may be used in the case of intracardiac

thrombus. Consider for children with history of thrombus
and ejection fraction <25%.
Nesiritide Not recommended for routine use in children.
Positive inotropic Symptomatic relief in a palliative setting or as a bridge to

agents transplantation.
Most data on the effectiveness and safety of medications are based on studies conducted in adults. Data from
reference 24.

•• The Children’s Cardiomyopathy Foundation. www.childrenscardiomyopathy.
org
384
CCIP.indb 384 3/13/18 4:19 PM

References
1) Towbin JA, Lowe AM, Colan SD, et al. Incidence, causes, and outcomes of dilated cardiomyop-
athy in children. JAMA. 2006;296(15):1867–1876
2) Lipshultz SE, Sleeper LA, Towbin JA, et al. The incidence of pediatric cardiomyopathy in two
regions of the United States. N Engl J Med. 2003;348(17):1647–1655
3) Wilkinson JD, Westphal JA, Bansal N, Czachor JD, Razoky H, Lipshultz SE. Lessons
learned from the Pediatric Cardiomyopathy Registry (PCMR) study group. Cardiol Young.
2015;25(Suppl 2):140–153
4) Hershberger RE, Cowan J, Morales A, Siegfried JD. Progress with genetic cardiomyopathies:
screening, counseling, and testing in dilated, hypertrophic, and arrhythmogenic right ventricular
dysplasia/cardiomyopathy. Circ Heart Fail. 2009;2(3):253–261
5) Michels VV, Moll PP, Miller FA, et al. The frequency of familial dilated cardiomyopathy in a
series of patients with idiopathic dilated cardiomyopathy. N Engl J Med. 1992;326(2):77–82
6) Hsu DT, Canter CE. Dilated cardiomyopathy and heart failure in children. Heart Fail Clin.
2010;6(4):415–432, vii
7) Mann DL, Bristow MR. Mechanisms and models in heart failure: the biomechanical model and
beyond. Circulation. 2005;111(21):2837–2849
8) Hsu DT, Pearson GD. Heart failure in children: part II: diagnosis, treatment, and future
directions. Circ Heart Fail. 2009;2(5):490–498
9) Macicek SM, Macias CG, Jefferies JL, Kim JJ, Price JF. Acute heart failure syndromes in the
pediatric emergency department. Pediatrics. 2009;124(5):e898–e904
10) Colan SD, Lipshultz SE, Lowe AM, et al. Epidemiology and cause-specific outcome of
hypertrophic cardiomyopathy in children: findings from the Pediatric Cardiomyopathy Registry.
Circulation. 2007;115(6):773–781
11) Hsu DT, Pearson GD. Heart failure in children: part I: history, etiology, and pathophysiology.
Circ Heart Fail. 2009;2(1):63–70
12) Yancy CW, Jessup M, Bozkurt B, et al; WRITING COMMITTEE MEMBERS; American
College of Cardiology Foundation/American Heart Association Task Force on Practice
Guidelines. 2013 ACCF/AHA guideline for the management of heart failure: a report of the
American College of Cardiology Foundation/American Heart Association Task Force on
practice guidelines. Circulation. 2013;128(16):e240–e327
13) Hunt SA, Baker DW, Chin MH, et al; American College of Cardiology/American Heart
Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for
the Evaluation and Management of Heart Failure); International Society for Heart and Lung
Transplantation; Heart Failure Society of America. ACC/AHA Guidelines for the Evaluation
and Management of Chronic Heart Failure in the Adult: executive summary. A report of
the American College of Cardiology/American Heart Association Task Force on Practice
Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management
of Heart Failure): developed in collaboration with the International Society for Heart and
Lung Transplantation; Endorsed by the Heart Failure Society of America. Circulation.
2001;104(24):2996–3007
14) Schwartz ML, Cox GF, Lin AE, et al. Clinical approach to genetic cardiomyopathy in children.
Circulation. 1996;94(8):2021–2038
15) Friedman RA, Moak JP, Garson A Jr. Clinical course of idiopathic dilated cardiomyopathy in
children. J Am Coll Cardiol. 1991;18(1):152–156
16) Durani Y, Egan M, Baffa J, Selbst SM, Nager AL. Pediatric myocarditis: presenting clinical
characteristics. Am J Emerg Med. 2009;27(8):942–947
385
CCIP.indb 385 3/13/18 4:19 PM

17) Mir TS, Laux R, Hellwege HH, et al. Plasma concentrations of aminoterminal pro atrial
natriuretic peptide and aminoterminal pro brain natriuretic peptide in healthy neonates: marked
and rapid increase after birth. Pediatrics. 2003;112(4):896–899
18) Nir A, Nasser N. Clinical value of NT-ProBNP and BNP in pediatric cardiology. J Card Fail.
2005;11(5 Suppl):S76–S80
19) Price JF, Thomas AK, Grenier M, et al. B-type natriuretic peptide predicts adverse cardiovascular
events in pediatric outpatients with chronic left ventricular systolic dysfunction. Circulation.
2006;114(10):1063–1069
20) Canter CE, Simpson KE. Diagnosis and treatment of myocarditis in children in the current era.
Circulation. 2014;129(1):115–128
21) Mills KI, Vincent JA, Zuckerman WA, et al. Is endomyocardial biopsy a safe and useful proce-
dure in children with suspected cardiomyopathy. Pediatr Cardiol. 2016;37(7):1200–1210
22) Cooper LT, Baughman KL, Feldman AM, et al; American Heart Association; American College
of Cardiology; European Society of Cardiology. The role of endomyocardial biopsy in the man-
agement of cardiovascular disease: a scientific statement from the American Heart Association,
the American College of Cardiology, and the European Society of Cardiology. Circulation.
2007;116(19):2216–2233
[Corrected] J Heart Lung Transplant. 2014;33(9):888–909
24) Fraser CD Jr, Jaquiss RD, Rosenthal DN, et al; Berlin Heart Study Investigators. Prospective
trial of a pediatric ventricular assist device. N Engl J Med. 2012;367(6):532–541
386
CCIP.indb 386 3/13/18 4:19 PM

CHAPTER 22
Restrictive
Cardiomyopathy
Chesney Castleberry, MD, and Sonya Kirmani, MD
Introduction
Definition and Pathophysiology
Restrictive cardiomyopathy (RCM) is characterized by impaired ventricular
diastolic function (or relaxation of the myocardium), with preserved systolic
function and normal ventricular wall thickness.1,2 Because of reduced compliance
and stiffness of the ventricular myocardium, the ventricles do not fill appropriately
during diastole, and blood “backs up” into the atria, as well as the systemic and
pulmonary veins. This produces the characteristic echocardiographic finding of
enlarged atria with relatively normally sized ventricles (“Mickey Mouse heart”).
Systolic function, or contractility, of the ventricles is preserved, but in studies, up
to 30% of children may present with depressed shortening or ejection fraction.2
Wall thickness is generally normal, but some patients may present with a mixed
phenotype, where characteristics of both restrictive and hypertrophic cardiology
are present.3 Restrictive physiology may also develop in patients with primary
hypertrophic cardiomyopathy as a result of myocardial scarring. As a consequence
of RCM, patients often develop progressive, potentially irreversible pulmonary
hypertension and are prone to developing dysrhythmias and thromboembolic
disease. In addition, if reduced function has developed, patients may develop
low cardiac output, at which point clinical deterioration can be rapid.4
387
CCIP.indb 387 3/13/18 4:19 PM

Epidemiology
RCM is the least common of pediatric cardiomyopathies. The prevalence of
RCM is estimated to be around 2.5% to 5% of cardiomyopathies.3,5 Worldwide,
in areas where familial endomyocardial fibrosis is common, such as Mozambique,
prevalence may reach up to 30%.2 The mean age at presentation for children is
5 to 6 years.
Etiologic Origin
The primary etiologic origin of RCM can be broadly categorized into infiltrative
or noninfiltrative processes (Box 22-1). In the pediatric population, noninfiltra-
tive disease is the most common, although evaluation for metabolic disorders,
including inborn errors of metabolism, is important. Notably, amyloidosis and
sarcoidosis primarily affect adults, while scleroderma and systemic sclerosis or
inborn errors of metabolism occur in childhood. Most cases of noninfiltrative
RCM are idiopathic, with no clear, known etiologic origin; however, sarcomere
mutations have been identified in the population, and genetic testing should be a
standard part of the evaluation.5,6 These mutations also overlap with other known
causes of cardiomyopathies, including dilated cardiomyopathy, left ventricular
noncompaction cardiomyopathy, and hypertrophic cardiomyopathy. Therefore,
a family history of any heart muscle abnormalities is important and present
in nearly 30% of cases.5,7 Other nonsarcomere mutations can occur, including
desmin mutations, and should be thought of in the presence or absence of skele-
tal myopathy.8 Other infrequent causes of RCM include anthracycline, radiation,
and drug exposure.2,5
Clinical Features
Signs and Symptoms
Children typically present with symptoms of RCM that relate to the increased
pressures transmitted to the atria and pulmonary veins from the inability of
the heart to fill adequately. The increase of these pressures leads to pulmonary
venous congestion and pulmonary edema, causing children to present with
respiratory complaints, such as dyspnea on exertion, reduced exercise tolerance,
persistent wheezing, and recurrent pneumonia. Children’s symptoms may often
be mistaken for asthma, or they may have coexisting asthma. Often, it is not
until cardiomegaly develops and is seen on chest radiographs that a referral is
made to a cardiologist. Chest pain, syncope, and sudden death can also be seen
in children with RCM, although less frequently than the other signs mentioned
earlier. At physical examination, a gallop, murmur, loud P2, hepatomegaly, ascites,
and edema may be detected. In the absence of other cardiac findings, children
may often see a gastroenterologist first for hepatomegaly and ascites.
388
CCIP.indb 388 3/13/18 4:19 PM

Restrictive Cardiomyopathy
Box 22-1. Etiologic Origins of Restrictive Cardiomyopathy

Infiltrative
•• Metabolic
—Lysosomal
— disorders
Hurler syndrome
Gaucher disease
Fabry disease
Glycogen storage disease
•• Acquired
—Sarcoidosis
—
—Amyloidosis
—
—Scleroderma
—
—Hemochromatosis
—
—Fatty
— infiltration
—Metastatic
— cancers
Noninfiltrative
•• Genetic
—Troponin
— I
—Troponin
— T
—β-myosin
— heavy chain
—Alpha
— cardiac actin
—Titin
—
—Myosin
— light chain
—Desmin
—
•• Inflammatory
—Löffler
— syndrome
—Endomyocardial
— fibrosis
•• Other
—Idiopathic
—
—Anthracycline
—
—Radiation
—
—Drugs
—
When evaluating a patient for potential RCM, constrictive pericarditis should
also be entertained because the 2 conditions can have similar echocardiographic
features and clinical symptoms. A cardiac catheterization is helpful to differ-
entiate between the 2 disease processes. Other cardiomyopathies, including
hypertrophic, dilated, and left ventricular noncompaction cardiomyopathy, also
need to be considered, given the potential for overlapping phenotypes.
389
CCIP.indb 389 3/13/18 4:19 PM

Diagnostic Approach
Once RCM is suspected on a clinical basis, referral to a pediatric cardiologist is
warranted. The evaluation includes laboratory studies for cardiomyopathy, chest
radiography, electrocardiography, echocardiography, and cardiac catheterization.
As with all cardiomyopathies, a careful family history should be obtained,
and if any familial genetic mutations are known, they should be investigated
further. Genetic testing is often pursued and is expected to have greater yield
as next-generation–based sequencing becomes more available.9
Diagnostic Tests
Brain natriuretic peptide (BNP) is a cardiac hormone secreted by cardiomyocytes
in response to stretching of the cells. Plasma BNP levels are often increased in
the setting of heart failure, and studies have shown that plasma BNP levels are
more likely to be increased in RCM than in constrictive pericarditis.10,11 Other
useful laboratory studies include evaluation for thyroid dysfunction, metabolic
disorders, and lipid disorders.5 A chest radiograph may show cardiomegaly and
pulmonary venous congestion. If pericardial calcification is present, the patient
most likely has constrictive pericarditis. Electrocardiographic findings are
typically abnormal, with signs of right and/or left atrial enlargement. Frequently,
ST segment and T wave abnormalities are seen. Arrhythmias are seen in up to
15% of pediatric patients. These include atrial flutter, second- and third-degree
atrioventricular (AV) block, Wolff-Parkinson-White syndrome, and supraven-
tricular tachycardias.2 As such, Holter monitoring is warranted for detection
and monitoring of these arrhythmias.
Imaging
The echocardiogram will frequently show the characteristic “Mickey Mouse”
appearance to the heart, with biatrial enlargement but normal ventricular sizes
and systolic function (Figure 22-1).2,5 The biatrial enlargement is generally
out of proportion to any existing mitral or tricuspid valve regurgitation.
Echocardiographic diastolic indices are often abnormal, as well. An echocar
diogram is also used to assess the patient for the presence of thrombi, which
may be apical, but also can be seen in the apex and around the AV valves,
particularly in cases of endomyocardial fibroelastosis and hypereosinophilia
syndrome. Further imaging with cardiac magnetic resonance (MR) imaging
may be useful if there is suspicion for amyloidosis, sarcoidosis, or other infiltra-
tive diseases.12 Cardiac computed tomography or MR imaging can also be used
to assess the patient for a thickened or calcified pericardium if constrictive
pericarditis has not been excluded as a primary etiologic origin.
390
CCIP.indb 390 3/13/18 4:19 PM

FIGURE 22-1. Characteristic biatrial enlargement seen on an echocardiogram, with a “Mickey

Mouse” ears appearance on the apical 4-chamber view. From reference 7.
Diagnostic Procedures
Cardiac catheterization is often the next step in diagnosis, for 2 reasons. First,
it helps distinguish RCM from constrictive pericarditis, because constrictive
pericarditis is reversible with resection of the pericardium. Second, it can
help identify the degree of pulmonary hypertension present, secondary to
the physiology of RCM.
Management
Treatment Approach
RCM is a progressive disease. The 2-year mortality rate in patients who receive
a diagnosis of RCM is nearly 50%.2,5 Therefore, listing the patient for cardiac
transplantation should be considered early.13 Antiarrhythmic therapy may also be
indicated. β-blocker therapy, which has been proven to be of benefit in dilated
and hypertrophic cardiomyopathies, has yet to be established as beneficial in
RCM.2 Because thromboembolic disease occurs secondary to atrial dilation,
anticoagulants are sometimes prescribed, including aspirin and warfarin, though
they are mostly reserved for patients with histories of thromboembolism or
391
CCIP.indb 391 3/13/18 4:19 PM

thrombi on images.14 Patients may also benefit from the addition of diuretics
for pulmonary edema. Routine Holter monitoring detection and monitoring of
clinical and subclinical arrhythmias are often performed. While some providers
have placed implantable cardiac defibrillators (ICDs) for primary prevention,
current evidence shows that, in pediatric patients awaiting heart transplantation,
the sudden cardiac death risk remains low and does not differ between patients
with and those without ICDs.15
When to Refer
In addition to concerning symptoms and signs as described earlier, patients
should be referred to a pediatric cardiologist when there is a family history of
cardiomyopathy or sudden unexplained death. A personal history of syncope,
progressive exercise intolerance, or cardiac arrest also warrants referral. Also,
if patients have risk factors, including metabolic disorders or rheumatologic
disorders like scleroderma, they should be screened for cardiomyopathy. Some
patients with a history of clinically significant radiation and anthracycline
exposure will also undergo routine screening for restrictive cardiac disease.
In general, children with RCM may continue activity as tolerated. However, the
American Heart Association and the American College of Cardiology currently
recommend that athletes with primary nonhypertrophied RCM be restricted
from participating in most competitive sports.16,17 In select cases, children with
RCM may participate in low-intensity sports (class 1A sports, such as golf and
bowling). Regular, nonstrenuous activity is recommended, along with a healthy
lifestyle for general cardiac conditioning.
Endocarditis Prophylaxis
Endocarditis prophylaxis is not required with at-risk procedures.18
Key Points
•• RCM is characterized by impaired ventricular diastolic function, with
preserved systolic function and normal ventricular wall thickness.
•• Children typically present with respiratory symptoms: reduced exercise
tolerance, dyspnea with exertion, and recurrent pneumonia. Chest pain,
syncope, and sudden death are also presenting symptoms.
•• Patients with RCM are at risk for thromboembolic disease, dysrhythmias,
and pulmonary hypertension.
•• RCM is a progressive disease with a 2-year mortality rate of nearly 50%.
Heart transplantation should be considered early.
392
CCIP.indb 392 3/13/18 4:19 PM


•• Restrictive Cardiomyopathy (American Heart Association). www.heart.
org/HEARTORG/Conditions/More/Cardiomyopathy/Restrictive-
Cardiomyopathy_UCM_444322_Article.jsp#.WDoO8_krI2w
•• Children’s Cardiomyopathy Foundation. www.childrenscardiomyopathy.org
References
1) Richardson P, McKenna W, Bristow M, et al. Report of the 1995 World Health Organization/
International Society and Federation of Cardiology Task Force on the Definition and
Classification of cardiomyopathies. Circulation. 1996;93(5):841–842
2) Denfield SW, Webber SA. Restrictive cardiomyopathy in childhood. Heart Fail Clin. 2010;
6(4):445–452, viii
3) Wilkinson JD, Westphal JA, Bansal N, Czachor JD, Razoky H, Lipshultz SE. Lessons
learned from the Pediatric Cardiomyopathy Registry (PCMR) study group. Cardiol Young.
2015;25(Suppl 2):140–153
4) Weller RJ, Weintraub R, Addonizio LJ, Chrisant MR, Gersony WM, Hsu DT. Outcome of
idiopathic restrictive cardiomyopathy in children. Am J Cardiol. 2002;90(5):501–506
5) Lipshultz SE, Cochran TR, Briston DA, et al. Pediatric cardiomyopathies: causes, epidemiology,
clinical course, preventive strategies and therapies. Future Cardiol. 2013;9(6):817–848
6) Kaski JP, Syrris P, Burch M, et al. Idiopathic restrictive cardiomyopathy in children is caused by
mutations in cardiac sarcomere protein genes. Heart. 2008;94(11):1478–1484
7) Zangwill S, Hamilton R. Restrictive cardiomyopathy. Pacing Clin Electrophysiol. 2009;32(Suppl
2):S41–S43
8) Dalakas MC, Park KY, Semino-Mora C, Lee HS, Sivakumar K, Goldfarb LG. Desmin
myopathy, a skeletal myopathy with cardiomyopathy caused by mutations in the desmin gene.
N Engl J Med. 2000;342(11):770–780
9) Tariq M, Ware SM. Importance of genetic evaluation and testing in pediatric cardiomyopathy.
World J Cardiol. 2014;6(11):1156–1165
10) de Lemos JA, McGuire DK, Drazner MH. B-type natriuretic peptide in cardiovascular disease.
Lancet. 2003;362(9380):316–322
11) Leya FS, Arab D, Joyal D, et al. The efficacy of brain natriuretic peptide levels in
differentiating constrictive pericarditis from restrictive cardiomyopathy. J Am Coll Cardiol.
2005;45(11):1900–1902
12) Gupta A, Singh Gulati G, Seth S, Sharma S. Cardiac MRI in restrictive cardiomyopathy. Clin
Radiol. 2012;67(2):95–105
13) Zangwill SD, Naftel D, L’Ecuyer T, et al; Pediatric Heart Transplant Study Investigators.
Outcomes of children with restrictive cardiomyopathy listed for heart transplant: a multi-
institutional study. J Heart Lung Transplant. 2009;28(12):1335–1340
14) Chen K, Williams S, Chan AKC, Mondal TK. Thrombosis and embolism in pediatric
cardiomyopathy. Blood Coagul Fibrinolysis. 2013;24(3):221–230
15) El-Assaad I, Al-Kindi SG, Oliveira GH, Boyle GJ, Aziz PF. Implantable cardioverter-
defibrillator and wait-list outcomes in pediatric patients awaiting heart transplantation. Heart
Rhythm. 2015;12(12):2443–2448
393
CCIP.indb 393 3/13/18 4:19 PM

16) Maron BJ, Udelson JE, Bonow RO, et al; American Heart Association Electrocardiography and
Arrhythmias Committee of Council on Clinical Cardiology, Council on Cardiovascular Disease
in Young, Council on Cardiovascular and Stroke Nursing, Council on Functional Genomics
and Translational Biology, and American College of Cardiology. Eligibility and disqualification
recommendations for competitive athletes with cardiovascular abnormalities: Task Force 3:
hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and other
cardiomyopathies, and myocarditis: a scientific statement from the American Heart Association
and American College of Cardiology. Circulation. 2015;132(22):e273–e280
17) Longmuir PE, Brothers JA, de Ferranti SD, et al; American Heart Association Atherosclerosis,
Hypertension and Obesity in Youth Committee of the Council on Cardiovascular Disease in
the Young. Promotion of physical activity for children and adults with congenital heart disease: a
18) Wilson W, Taubert KA, Gewitz M, et al; American Heart Association Rheumatic Fever,
Endocarditis, and Kawasaki Disease Committee; American Heart Association Council on
Cardiovascular Disease in the Young; American Heart Association Council on Clinical
Cardiology; American Heart Association Council on Cardiovascular Surgery and Anesthesia;
Quality of Care and Outcomes Research Interdisciplinary Working Group. Prevention
of infective endocarditis: guidelines of the American Heart Association. Circulation.
2007;116(15):1736–1754
394
CCIP.indb 394 3/13/18 4:19 PM

CHAPTER 23
Noncompaction
Cardiomyopathy
Nikki M. Singh, MD, and Steven J. Kindel, MD
Introduction
Definition
Left ventricular (LV) noncompaction (LVNC) is a relatively newly recognized
entity. While initially described in the 1930s, it was not defined as a disease
until the 1980s. One of the earliest published case series of isolated LVNC was
described in 1990, which included 8 cases in patients ranging from 11 months
to 22.5 years of age.1 LVNC is a rare form of cardiomyopathy morphologically
characterized by deep trabeculations within the muscle of the LV walls,
which may have features of dilated or hypertrophic cardiomyopathy, or both.
Pathologically, the LV is characterized by a spongy morphologic appearance of
the myocardium, in which sinusoids communicate with the LV cavity.2,3,4

The exact cause of these persistent trabeculations is unknown, but several
genetic associations have been found. LVNC was initially described in association
with other congenital heart diseases (CHDs), but not in isolation. With increased
screening and improved imaging techniques, LVNC is now more commonly found
in isolation.5,6
Epidemiology
The prevalence of LVNC is unknown but is likely underestimated. Current preva-
lence estimates in the general population range from 0.02% to 0.25%, with a male
predominance.4,7–10 LVNC is relatively rare in white populations. A review of 1,146
echocardiograms from adolescent athletes yielded a higher prevalence among
395
CCIP.indb 395 3/13/18 4:19 PM

African and Afro-Caribbean athletes than among white and Asian athletes, with
Asian athletes having the lowest prevalence.4,11
Etiologic Origin
During normal intrauterine cardiac development and morphogenesis, the
myocardium is initially trabeculated to allow blood supply to the myocardium
via the LV cavity prior to coronary artery development. Between 5 and 8 weeks
of embryogenic gestation, coronary artery development occurs, which will
ultimately be the sole source of blood supply to the cardiac muscle. Shortly after
establishment of coronary flow, the myocardium starts to lose its trabeculation
and gradually becomes more compact, with organized muscle bundles.12–14

There are 2 main theories on the etiologic origin of LVNC, an embryogenic
hypothesis and a nonembryogenic hypothesis. The embryogenic hypothesis is
founded on the idea that during embryogenesis, the ventricular myocardium
becomes compacted after development of the coronary tree.9,10,14 When there
is a disturbance or arrest in this process, ventricular trabeculations persist,
producing LVNC morphologic changes. This theory, while useful and consistent
with early LVNC, fails to explain development of LVNC later in life. It also
does not reconcile with the often-described undulating phenotype of LVNC,
where findings of this cardiomyopathy have been shown to wax and wane.12

With the nonembryogenic hypothesis, it is argued that LVNC occurs over
time as a unique form of cardiac remodeling that leads to enhanced trabecular
development in the LV cavity. This hypothesis would explain the LVNC some-
times seen to develop over time in individuals, such as in pregnant women and
those with sickle cell anemia, in which certain physiological changes occur—for
instance, increased ventricular preload. This viewpoint would also potentially
explain the LVNC and prominent LV trabeculations seen in some young
athletes and the development of LVNC after the newborn period in familial
cases of the disease.9 Ultimately, these 2 theories need not be exclusive; both
may contribute to specific presentations of LVNC (Figure 23-1).
Genetics
LVNC occurs in both familial and sporadic forms and is a genetically
heterogeneous disorder. Most reported cases are sporadic, while the familial
cases may manifest with autosomal dominant, autosomal recessive, X-linked, or
mitochondrial inheritance.3,4,15
It is estimated that 24% to 40% of patients with LVNC who have undergone
genetic testing have genetic variants. Sarcomere-encoding genes, including
TNNT2, MYH7, TPM1, and MYBPC3, and cytoskeletal variants in TTN,
LDB3, and DTNA have all been described.16–18 Many of the genes associated
with LVNC are also associated with other disease processes, such as other
cardiomyopathies and congenital heart defects.3,13 Overlap with genes found
396
CCIP.indb 396 3/13/18 4:19 PM

Noncompaction Cardiomyopathy
FIGURE 23-1. The spectrum of left ventricular (LV) noncompaction (LVNC). C, compacted
muscle; NC, trabeculae. From reference 13.
in dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), or

restrictive cardiomyopathy (RCM) is common. This fact may explain cases of
mixed phenotype seen with combination of DCM, HCM, or RCM, along with
LVNC.3,10 There is variable penetrance and phenotypic expression of these genes,
which results in variable expression, even among family members carrying the
same mutation.19 While isolated clinical genetic testing has been less effective for
the discovery of gene mutations in LVNC than in other cardiomyopathies (such
as HCM), when combined with a thorough history, examination, and pedigree
creation, an etiologic origin can be found in up to 40% of patients.18
Risk Factors
Characteristics of LVNC have been reported in almost all types of congenital
heart lesions; when present, they are thought to potentially contribute to abnor-
mal myocardial function and worse global outcomes.15 Right-sided congenital
heart lesions, including Ebstein anomaly, tricuspid atresia, pulmonic stenosis, and
variants of tetralogy of Fallot, are more frequently associated with LVNC.16,20
397
CCIP.indb 397 3/13/18 4:19 PM

Left-sided lesions, such as unicuspid or bicuspid aortic valve, coarctation of the

aorta, and subaortic obstruction, have also been described.20 Certain genetic
syndromes, such as Barth syndrome, neuromuscular diseases, and mitochondrial
myopathies, can place one at increased risk of developing LVNC.12,16,21–23
Furthermore, LVNC can present as a mixed phenotype or in isolation in
families with other forms of cardiomyopathy.12
Pathophysiology
In patients with LVNC, there is a notable abnormality of the myocardium
with deep recesses, which communicate with the LV cavity. These segments
of noncompaction can have abnormal contractility.24 Depressed LV ejection
fraction, diastolic dysfunction, abnormal mitral valve papillary musculature, and
LV thrombi have all been described.15,25 It is generally believed that chronic
hypoperfusion of the myocardium due to LVNC leads to myocardial dysfunc-
tion, which precipitates symptoms of heart failure, arrhythmia, or thrombosis.4,14
Clinical Features
Signs and Symptoms
The clinical presentation of children with LVNC has a spectrum, from incidental
discovery to acute symptomatic heart failure symptoms. These patients can have
underlying CHD, dysmorphic features, neuromuscular findings, or other genetic
abnormalities. Some groups have reported worse outcomes in patients who
present in infancy, although this has been debated.2 Patients who are clinically
asymptomatic are often referred for other reasons, such as screening for family
history of LVNC, other structural heart disease, a heart murmur, an abnormal
electrocardiographic (ECG) finding, or abnormal chest radiography findings.
Symptoms, when present and attributable to LVNC, are generally related
to ventricular systolic and/or diastolic dysfunction, ventricular arrhythmias,
thromboembolic events, or any combination of the three.10,14,16,17 Generally, the
degree of LV dysfunction is thought to be related to the extent and distribution
of noncompacted cardiac segments. Symptoms of heart failure in children
with LVNC are indistinguishable from other forms of pediatric heart failure,
including tachypnea, pulmonary vascular congestion, exercise intolerance, and
gastrointestinal symptoms such as anorexia, feeding intolerance, vomiting, and
diarrhea. Thromboembolic events, including stroke, transient ischemic events,
and pulmonary embolism, are thought to be secondary to extensive trabecula-
tions, decreased ventricular function, and atrial fibrillation.15 Thromboembolic
events in children can occur and are more common in those with poor systolic
function, but the true incidence is unclear.4
398
CCIP.indb 398 3/13/18 4:19 PM

The differential diagnosis of LVNC is fairly broad. More benign differential
diagnoses include prominent trabeculations, isolated persistent sinusoids, abnor-
mal mitral valve chords, changes from chronic hypertension, and other causes of
cardiac hypertrophy. Noncompaction differs from isolated persistent sinusoids,
in which the deep recesses do not communicate with the coronary circulation.14
More clinically significant (and likely symptomatic) diseases to consider include
DCM, HCM, RCM, and arrhythmogenic right ventricular cardiomyopathy.
Diagnostic Approach
Development of diagnostic criteria for LVNC has been challenging. Previously,
LVNC was a frequently missed diagnosis because prominent trabeculations can
be seen in healthy individuals and also in combination with other pathologic
disease processes of the heart. The advancement of imaging modalities, such as
echocardiography and cardiac magnetic resonance (MR) imaging, have made
LVNC easier to identify; however, lack of consensus on strict diagnostic criteria
remains. Diagnostic accuracy is challenged by the competing needs to prevent
overdiagnosis in healthy individuals with prominent trabeculations while not
underrecognizing LVNC when it is truly present.
Echocardiography
The diagnosis of LVNC is established from imaging of the heart and assessment
of the myocardium. Echocardiography is the first-line imaging modality for the
diagnosis of LVNC because it is widely available at relatively low cost.17 There
are no set criteria agreed upon by experts, but several key features are generally
used to aid in diagnosis.
The 3 main diagnostic criteria currently used are (a) noncompacted to
compacted ratio of more than 2.0, measured in diastole from parasternal short-
axis and apical views, where noncompacted length is measured as the distance
between epicardial surface and peak trabeculations;1 (b) ratio of noncompacted
to compacted myocardium of more than 2.0 measured in systole, predominantly
localized in the lateral, apical, or inferior walls in association with evidence of
color Doppler flow within deep intertrabecular recesses, in communication
with the LV in the absence of coexisting cardiac disorders;26 and (c) more than
3 trabeculations, apical to the papillary muscles, with the same echogenicity of
the myocardium and perfusion of the intertrabecular spaces from the LV cavity,
with a ratio of noncompacted to compacted myocardium of more than 2.0
(Figures 23-2 and 23-3).27
399
CCIP.indb 399 3/13/18 4:19 PM

LV cavity
Trabeculations
Recesses
Noncompacted
layer ‘X’
Compacted
layer ‘Y’
FIGURE 23-2. Left ventricular (LV) noncompaction (LVNC). By using the apical view of the LV,
the ratio of noncompacted (X) to compacted (Y) myocardium can be measured to help establish the
diagnosis of LVNC.
Cardiac MR Imaging
Cardiac MR imaging is frequently used for the diagnosis and assessment of
LVNC, although there have been few studies in the pediatric population to
validate its use. Cardiac MR imaging can be beneficial in patients with suspected
LVNC in whom the diagnosis could not be confirmed with echocardiography
because of either poor acoustic images or incomplete imaging data. It can also be
used to further evaluate myocardial characteristics and to assess the patient for
myocardial fibrosis with late gadolinium-based contrast material enhancement
(Figure 23-4).
In 2005, Petersen and colleagues28 used cardiac MR imaging to assess the
patient for LVNC by assessing the ratio of noncompacted to compacted myocar-
dium in diastole, similar to the method described by Jenni and colleagues26 with
echocardiograms. Results from this study showed low specificity, suggesting the
need for continued development of appropriate guidelines and diagnostic criteria
for LVNC. Jacquier and colleagues have proposed a trabeculated LV mass of
at least 20% of the global LV mass during end-diastole as more precise cardiac
MR imaging criteria for LVNC. Further study is needed to determine the best
cardiac MR imaging diagnostic criteria for LVNC in children.29
400
CCIP.indb 400 3/13/18 4:19 PM

FIGURE 23-3. A. Apical and B. short-axis views of the left ventricle (LV) of a 3-month-old boy
with isolated LV noncompaction show noncompaction of the myocardium along the LV free wall
and apex by means of echocardiographic assessment.
401
CCIP.indb 401 3/13/18 4:19 PM

FIGURE 23-4. Sagittal magnetic resonance image obtained in the left ventricle (LV) of a patient
with LV noncompaction shows a cross-section of noncompacted trabeculations along the free wall
of the LV.
Electrocardiography
Although no specific ECG finding is diagnostic for LVNC, ECG changes can
be seen in up to 90% of patients.6,15,19 One common ECG pattern is the presence
of abnormally high voltages, especially in the midprecordial leads.2 Additional
ECG changes can include intraventricular conduction delay (especially in a left
bundle branch block pattern), LV hypertrophy and abnormal repolarization,
atrial enlargement, and axis deviation.19 Ventricular pre-excitation is seen in as
many as 8% to 15% of children with LVNC.15,19
Although repolarization abnormalities or ECG changes, such as high-voltage
R waves, are not specific for LVNC, those with abnormal ECG findings, with
either symptoms or strong family history of cardiomyopathy, should undergo
additional screening with echocardiography or cardiac MR imaging.
402
CCIP.indb 402 3/13/18 4:19 PM

Additional Workup
Generally, laboratory evaluation results are normal in asymptomatic patients;
however, if there are concerns for compensated heart failure, they may be helpful.
Assessment of brain natriuretic peptide (BNP) or N-terminal proBNP levels can
be valuable to assess the patient for evidence of volume overload or cardiac con-
gestion. In addition, consideration should be given to assessment of a complete
metabolic profile with liver function testing, complete blood count, and, if there
are worries about neuromuscular disease, creatinine kinase testing. Troponin I
testing can be helpful if there is concern for acute or subacute ischemic cardiac
injury. Of note, troponin T may be less specific for cardiac injury because levels
can be increased without cardiac injury in the setting of skeletal muscle injury or
neuromuscular disease. In the asymptomatic patient, chest radiography findings
will generally be normal, but assessment of heart size and pulmonary vascular
congestion in the symptomatic patient is reasonable. Evaluation for metabolic
or syndromic disease is important, as is the investigation of family history and
development of a 3-generation pedigree.18,30 If there is suspicion for metabolic
disease, especially in a symptomatic infant, consideration of metabolic laboratory
assessment or formal consultation with a local specialist in genetics or metabolic
disease is warranted. Testing may include urine organic acid analysis, serum
amino acid assessment, acylcarnitine profile, free carnitine level, and lactate
testing. Genetic testing can be valuable in a patient with family history, evidence
of a global syndrome, or neuromuscular disease or in sporadic cases where
identification of a gene variant could help direct further family screening.3 As
in the evaluation of any pediatric cardiomyopathy, consideration of collaborative
assessment with a medical geneticist and genetic counselor is recommended to
help direct genetic testing and interpret the results.18,31
Despite attempts to use strict criteria for LVNC, the challenge of overdiagno-
sis remains. Hypertrabeculation of the LV can occur in healthy individuals with-
out risk factors or complications associated with LVNC. It has been proposed
that these criteria continue to be revised, given that they might be too sensitive
and result in overdiagnosis.21,32
Management
There is no specific therapy to treat LVNC to induce disease remission or to
“cure” the morphologic structures of the heart. As such, therapies are largely
focused on treatment or prevention of potential complications of LVNC,
including heart failure, thromboembolism, and arrhythmia.21 Those with a
history of arrhythmias or myocardial dysfunction have a worse prognosis than
those with isolated hypertrabeculations and should be managed closely by a
pediatric cardiologist.6
403
CCIP.indb 403 3/13/18 4:19 PM


Generally, those patients with LVNC, preserved cardiac function, and no
symptoms at the time of diagnosis are at low risk of having a clinically signifi
cant cardiovascular event.32 Treatment approach should be based on symptoms—
specifically heart failure, arrhythmias, and thromboembolic events.
Heart Failure
For patients who present with heart failure symptoms, the International Society
for Heart & Lung Transplantation recommends that medical management
for heart failure be initiated.33 Patients who present with New York Heart
Association or Ross classification III–IV or IV (see Chapter 21, Dilated Cardio
myopathy) have a greater risk of morbidity and mortality.32 Adult patients with
LVNC who are symptomatic with congestive heart failure due to abnormal
systolic function are treated with standard heart failure medications, including
angiotensin-converting enzyme (ACE) inhibitors and β-blockers, as recom-
mended by heart failure guidelines.33,34
The standard approach outlined in adult heart failure guidelines is often used
in pediatrics as well, despite a lack of large randomized, controlled trial data.
Children with LVNC and systolic dysfunction may benefit from the use of
ACE inhibitors and β-blockers. Diuretics are frequently added for symptomatic
patients with edema or other evidence of cardiac congestion. In patients with
decompensated heart failure, use of inotropic drips, such as epinephrine, dopa-
mine, or milrinone, may be required for initial stabilization or even to support
the patient while awaiting more definitive therapy via heart transplantation.33

Mechanical circulatory support is an option for some patients who have
more recalcitrant cardiogenic shock.33,35 Mechanical circulatory support may be
challenging in these patients because of restrictive hemodynamics or lack of clin-
ically significant LV dilation and presence of prominent trabeculations, which
may interfere with inflow placement and flow. Within the spectrum of disease,
it is rare for patients with LVNC to need heart transplantation, unless their
cardiac function is markedly depressed or does not improve with heart failure
management or if they have restrictive hemodynamics. Heart transplantation
for this group of patients is addressed more specifically later in this section.
Arrhythmias
LVNC subtypes that manifest with arrhythmias have a higher risk of sudden
cardiac death than the healthy population. Although the exact mechanism for
arrhythmia development in unknown, it is postulated that the abnormal trabec-
ulations can alter the normal conduction system in the ventricles and also allow
for re-entrant circuits to develop. The development of endomyocardial fibrosis
could also present a substrate for the development of ventricular tachycardia, and
atrial dilation with restrictive disease may create an environment conducive to
the development of atrial tachycardias and fibrillation.
404
CCIP.indb 404 3/13/18 4:19 PM

Czosek and investigators studied 72 patients, with a mean age of 13 years,

who received diagnoses of LVNC with ejection fraction of more than 45%
and a prior Holter monitor analysis.36 They found that 58% of them had rare
or occasional premature atrial contractions, and 28% had rare or occasional
premature ventricular contractions. Ectopy was more common in patients with
mild cardiac dysfunction than those with normal function. Only 2% had non-
sustained ventricular tachycardia or ventricular couplets. The authors concluded
that for asymptomatic patients with normal function, the placement of a single
Holter monitor may not be beneficial, but serial monitoring could be helpful
for assessment of disease progression. Further, it is likely valuable to consider
intermittent rhythm monitoring in patients with depressed systolic function
and to educate families and patients about concerning symptoms of dizziness,
syncope, tachycardia, or palpitations, especially if related to exercise.
LVNC has been associated with ventricular pre-excitation and development
of supraventricular tachycardia. In patients with pre-excitation at ECG, an elec-
trophysiology study should be considered for risk assessment and ablation, espe-
cially in children with prior tachycardia or other concerning features. Routine
Holter monitors should be considered every 6 to 12 months in children with
pre-excitation and history of arrhythmia that cannot be managed with ablation;
consultation with a pediatric electrophysiologist should strongly be considered.
Thromboembolic Events
In adults with LVNC, an increased risk of thromboembolic events is an accepted
concern. The hypothesis is that a clot can form in the deep intertrabecular
recesses and then be ejected to the systemic circulation. In adults, administering
anticoagulation therapy to all patients with LVNC has been recommended by
some, even if the patients have no evidence of intracardiac thrombus.21 Others
use anticoagulation therapy for patients with impaired systolic function or if
there are sustained arrhythmias, such as atrial fibrillation or ventricular tachy-
cardia.37 There are currently no guidelines for the prevention of thromboembolic
events in children with LVNC.
Heart Transplantation
There are limited studies of heart transplantation in patients with LVNC.
However, in patients who have LVNC cardiomyopathy with severely diminished
systolic function and/or severe restrictive physiology with end-stage heart failure,
heart transplantation listing can be considered.
A 2015 review of the United Network of Organ Sharing registry, which
encompasses 45,289 patients (adult and pediatric), showed that LVNC
accounted for a total of 0.3% of all patients listed for orthotopic heart trans-
plants (113 patients), including both children and adults, from 2000 to 2013.
Of those, 60% were pediatric patients, with a mean age of 16.9 years.38 Review
405
CCIP.indb 405 3/13/18 4:19 PM

of the Pediatric Heart Transplant Study data set from 2005 to 2013 showed that
of the 1,342 children registered who were listed for heart transplantation with a
diagnosis of cardiomyopathy, 4% had LVNC.39 In both analyses, outcomes after
heart transplantation for LVNC were similar to those in patients who received
transplants for DCM.38,39
If LVNC is suspected or diagnosed in a patient, the primary concerns are heart
failure, thrombosis, and arrhythmia, as outlined earlier. These considerations
can be challenging for the practitioner in consideration of athletic participation
because sudden cardiac death has been reported in this patient population.6
These concerns are only heightened in competitive pediatric athletes.
In general, patients who receive diagnoses of LVNC and who are asymptom-
atic with normal cardiac function should be able to participate in sports without
restriction. These patients should still be monitored closely for development
of abnormal systolic or diastolic cardiac function, which may develop over
time. Further, some counseling is recommended for both the family and the
young athlete to ensure that they are aware of concerning new symptoms that
would require assessment, including palpitations, frequent dizziness, syncope,
exertional chest pain, and worsening exercise tolerance. If symptoms do develop,
further testing, such as Holter monitoring, cardiopulmonary exercise testing, or
cardiac MR imaging with or without stress may be helpful for risk stratification.
Exercise stress testing has not been routinely conducted in these patients but
may be beneficial if there are concerns for decreased cardiac function, exercise
intolerance, unexplained syncope with exercise, or compromised myocardial
perfusion or for risk assessment in highly competitive athletes.
Further challenges arise in the assessment of pediatric athletes who compete
in high-intensity sports. This subset of patients can have myocardial changes
because of high preload and afterload related to intense exercise and training. In
a large study performed in the United Kingdom and France, athletes 14–35 years
of age who participated at a regional or national level underwent evaluation with
ECG and echocardiography. These participants were compared to those with
a more sedentary lifestyle. Investigators found that the athletes had a higher
incidence of LV hypertrabeculation, and a subset of these patients also met the
criteria for LVNC when compared to the sedentary group. Further workup of
these patients demonstrated negative Holter monitor results, and cardiac MR
imaging demonstrated no evidence of fibrosis or ischemia. The authors con-
cluded that a subpopulation of athletes exist with LVNC morphologic structures
but without clear disease, at least in this cross-sectional assessment.11 This study
would indicate that a cautious diagnosis and minimal restriction are required
in the asymptomatic patient with LVNC. If there are concerns over whether
406
CCIP.indb 406 3/13/18 4:19 PM

to restrict a patient from sports or not, then the patient should be referred to a
pediatric cardiologist.
Screening of Relatives
Given the variable phenotypes and reported genetic abnormalities, genetic test-
ing for etiologic origins is not universally performed unless there is concerning
evidence for a syndrome with known risk of developing cardiomyopathy or
LVNC, such as Barth syndrome, neuromuscular disease, or family history of
cardiomyopathy. If genetic testing is performed in the proband and a variant
is found that is believed to be causative of LVNC, then genetic screening of
family members would be appropriate. It would be valuable to include a genetic
counselor and/or a clinical geneticist in this process because determination
of the causative nature of genetic variants and the best screening algorithm
for families is challenging. If no genetic diagnosis is pursued or if one is not
obtained via genetic testing, then first-degree relatives of children with cardio-
myopathy (including HCM, DCM, and RCM) should undergo screening echo-
cardiography ideally serially through 20 to 30 years of age.30
Ongoing Care
All pediatric patients with suspected LVNC should be referred to a pediatric
cardiologist for complete evaluation. This is mainly so that precise echocar-
diographic images can be obtained, along with additional diagnostic testing, if
needed. The results of this evaluation and their implications for the patient’s
management should then be carefully reviewed with the family. If a patient ulti-
mately receives a diagnosis of LVNC, there will be a need for routine follow-up
and evaluation, as outlined in the Clinical Features and Management sections
in this chapter. This would include periodic follow-up echocardiography, ECG,
and Holter monitoring to assess the patient for the progression of disease.
The heterogeneity of this rare phenotype makes outcomes challenging
to predict. In those with more severe disease who present with heart failure,
arrhythmia, or thromboembolic events, especially in infancy, a guarded prognosis
with close follow-up is appropriate because this group has the highest risk for
early mortality. If the disease progresses to a more severe phenotype, options for
mechanical circulatory support and heart transplantation are available. However,
in asymptomatic patients with normal systolic function, one would anticipate
a normal life span without restrictions, albeit with ongoing monitoring for
development of more serious disease.
407
CCIP.indb 407 3/13/18 4:19 PM

Key Points
•• LVNC is a rare but increasingly recognized form of cardiomyopathy.
•• LVNC can occur in isolation, in combination with other forms of cardiomy-
opathy, or with CHD.
•• Genetic etiologic origins of LVNC are diverse; therefore, application of
genetic testing and interpretation of the results can be challenging.
•• Family history, family screening, and evaluation for global syndromic,
metabolic, and neuromuscular conditions are warranted in the evaluation
of children with LVNC.
•• In isolated LVNC without cardiac dysfunction, hypertrophy, or associated
CHD, observation without therapy is appropriate for many patients.

•• Pediatric Cardiomyopathies (American Heart Association). www.heart.org/
HEARTORG/Conditions/More/CardiovascularConditionsofChildhood/
Pediatric-Cardiomyopathies_UCM_312219_Article.jsp
•• Understanding Left Ventricular Non-Compaction Cardiomyopathy
(Children’s Cardiomyopathy Foundation). www.childrenscardiomyopathy.org/
site/images/publications/LVNC-Q-A-insert-final.pdf
•• Left Ventricular Non-Compaction Cardiomyopathy (Cincinnati
Children’s). www.cincinnatichildrens.org/service/c/cardiomyopathy/types/
left-ventricular-non-compaction-cardiomyopathy
References
1) Chin TK, Perloff JK, Williams RG, Jue K, Mohrmann R. Isolated noncompaction of left
ventricular myocardium. A study of eight cases. Circulation. 1990;82(2):507–513
2) Towbin JA. Left ventricular noncompaction: a new form of heart failure. In: Baliga R, Young J,
eds. Heart Failure Clinics. Vol 6, no. 4. Philadelphia, PA: Elsevier; 2010: 453–469
3) Dellefave LM, Pytel P, Mewborn S, et al. Sarcomere mutations in cardiomyopathy with left
ventricular hypertrabeculation. Circ Cardiovasc Genet. 2009;2(5):442–449
4) Udeoji DU, Philip KJ, Morrissey RP, Phan A, Schwarz ER. Left ventricular noncompaction
cardiomyopathy: updated review. Ther Adv Cardiovasc Dis. 2013;7(5):260–273
5) Jefferies JL, Wilkinson JD, Sleeper LA, et al; Pediatric Cardiomyopathy Registry
Investigators. Cardiomyopathy phenotypes and outcomes for children with left ventricular
myocardial noncompaction: results from the pediatric cardiomyopathy registry. J Card Fail.
2015;21(11):877–884
6) Brescia ST, Rossano JW, Pignatelli R, et al. Mortality and sudden death in pediatric left ventric-
ular noncompaction in a tertiary referral center. Circulation. 2013;127(22):2202–2208
7) Stanton C, Bruce C, Connolly H, et al. Isolated left ventricular noncompaction syndrome. Am J
Cardiol. 2009;104(8):1135–1138
8) Ting TW, Jamuar SS, Brett MS, et al. Left ventricular non-compaction: is it genetic? Pediatr
Cardiol. 2015;36(8):1565–1572
408
CCIP.indb 408 3/13/18 4:19 PM

9) Arbustini E, Weidemann F, Hall JL. Left ventricular noncompaction: a distinct cardiomyopathy

or a trait shared by different cardiac diseases? J Am Coll Cardiol. 2014;64(17):1840–1850
10) Sarma RJ, Chana A, Elkayam U. Left ventricular noncompaction. Prog Cardiovasc Dis.
2010;52(4):264–273
11) Gati S, Chandra N, Bennett RL, et al. Increased left ventricular trabeculation in highly trained
athletes: do we need more stringent criteria for the diagnosis of left ventricular non-compaction
in athletes? Heart. 2013;99(6):401–408
12) Pignatelli RH, McMahon CJ, Dreyer WJ, et al. Clinical characterization of left ventricular
noncompaction in children: a relatively common form of cardiomyopathy. Circulation.
2003;108(21):2672–2678
13) Arbustini E, Favalli V, Narula N, Serio A, Grasso M. Left ventricular noncompaction: A distinct
genetic cardiomyopathy? J Am Coll Cardiol. 2016;68(9):949–966
14) Ichida F. Left ventricular noncompaction. Circ J. 2009;73(1):19–26
15) Carrilho-Ferreira P, Almeida AG, Pinto FJ. Non-compaction cardiomyopathy: prevalence,
prognosis, pathoetiology, genetics, and risk of cardioembolism. Curr Heart Fail Rep.
2014;11(4):393–403
16) Towbin JA, Lorts A, Jefferies JL. Left ventricular non-compaction cardiomyopathy. Lancet.
2015;386(9995):813–825
17) Caselli S, Attenhofer Jost CH, Jenni R, Pelliccia A. Left ventricular noncompaction
diagnosis and management relevant to pre-participation screening of athletes. Am J Cardiol.
2015;116(5):801–808
18) Kindel SJ, Miller EM, Gupta R, et al. Pediatric cardiomyopathy: importance of genetic and
metabolic evaluation. J Card Fail. 2012;18(5):396–403
19) Miyake CY, Kim JJ. Arrhythmias in left ventricular noncompaction. Card Electrophysiol Clin.
2015;7(2):319–330
20) Stähli BE, Gebhard C, Biaggi P, et al. Left ventricular non-compaction: prevalence in congenital
heart disease. Int J Cardiol. 2013;167(6):2477–2481
21) Oechslin E, Jenni R. Left ventricular non-compaction revisited: a distinct phenotype with
genetic heterogeneity? Eur Heart J. 2011;32(12):1446–1456
22) Statile CJ, Taylor MD, Mazur W, et al. Left ventricular noncompaction in Duchenne muscular
dystrophy. J Cardiovasc Magn Reson. 2013;15:67
23) Scaglia F, Towbin JA, Craigen WJ, et al. Clinical spectrum, morbidity, and mortality in 113
pediatric patients with mitochondrial disease. Pediatrics. 2004;114(4):925–931
24) Bennett CE, Freudenberger R. The current approach to diagnosis and management of
left ventricular noncompaction cardiomyopathy: review of the literature. Cardiol Res Pract.
2016;2016:5172308
25) Eidem BW. Noninvasive evaluation of left ventricular noncompaction: what’s new in 2009?
Pediatr Cardiol. 2009;30(5):682–689
26) Jenni R, Oechslin E, Schneider J, Attenhofer Jost C, Kaufmann PA. Echocardiographic and
pathoanatomical characteristics of isolated left ventricular non-compaction: a step towards
classification as a distinct cardiomyopathy. Heart. 2001;86(6):666–671
27) Stöllberger C, Finsterer J. Left ventricular hypertrabeculation/noncompaction. J Am Soc
Echocardiogr. 2004;17(1):91–100
28) Petersen SE, Selvanayagam JB, Wiesmann F, et al. Left ventricular non-compaction: insights
from cardiovascular magnetic resonance imaging. J Am Coll Cardiol. 2005;46(1):101–105
29) Jacquier A, Thuny F, Jop B, et al. Measurement of trabeculated left ventricular mass using cardiac
magnetic resonance imaging in the diagnosis of left ventricular non-compaction. Eur Heart J.
2010;31(9):1098–1104
409
CCIP.indb 409 3/13/18 4:19 PM

30) Hershberger RE, Lindenfeld J, Mestroni L, Seidman CE, Taylor MR, Towbin JA; Heart Failure
Society of America. Genetic evaluation of cardiomyopathy—a Heart Failure Society of America
practice guideline. J Card Fail. 2009;15(2):83–97
31) Fitzgerald-Butt SM, Byrne L, Gerhardt CA, Vannatta K, Hoffman TM, McBride KL. Parental
knowledge and attitudes toward hypertrophic cardiomyopathy genetic testing. Pediatr Cardiol.
2010;31(2):195–202
32) Greutmann M, Mah ML, Silversides CK, et al. Predictors of adverse outcome in adolescents and
adults with isolated left ventricular noncompaction. Am J Cardiol. 2012;109(2):276–281
[Corrected]. J Heart Lung Transplant. 2014;33(9):888–909
34) Yancy CW, Jessup M, Bozkurt B, et al; American College of Cardiology Foundation; American
Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the man-
agement of heart failure: a report of the American college of cardiology Foundation/American
heart association task force on practice guidelines. J Am Coll Cardiol. 2013;62(16):e147–e239
35) Blume ED, Duncan BW. Pediatric Mechanical Circulatory Support. In: Frazier OH, Kirklin
JK, eds. ISHLT Monograph Series Mechanical Circulatory Support. Vol 1. New York, NY: Elsevier;
2006:127–135
36) Czosek RJ, Spar DS, Khoury PR, et al. Outcomes, arrhythmic burden and ambulatory moni-
toring of pediatric patients with left ventricular non-compaction and preserved left ventricular
function. Am J Cardiol. 2015;115(7):962–966
37) Stöllberger C, Finsterer J. Left ventricular hypertrabeculation/noncompaction and stroke or
embolism. Cardiology. 2005;103(2):68–72
38) Al-Kindi SG, El-Amm C, Ginwalla M, Hoit BD, Park SJ, Oliveira GH. Heart transplant
outcomes in patients with left ventricular non-compaction cardiomyopathy. J Heart Lung
Transplant. 2015;34(6):761–765
39) Lal AK, Pruitt E, Hong BJ, Lin KY, Feingold B. Left ventricular non-compaction cardiomyop-
athy in children listed for heart transplant: analysis from the Pediatric Heart Transplant Study
Group. J Heart Lung Transplant. 2016;35(4):540–542
410
CCIP.indb 410 3/13/18 4:19 PM

CHAPTER 24
Long QT Syndrome
and Other
Channelopathies
Juan Villafañe, MD, FAAP
Introduction
The cardiac channelopathies are a heterogenous group of arrhythmia syndromes
associated with sudden cardiac death. They are caused by gain or loss of function
of ion channel subunits, located in the myocardial cell membranes or at an
intracellular organelle. Genetic abnormalities affect these specialized channels,
producing an arrhythmogenic substrate. Most of the channelopathies show auto-
somal dominant inheritance with incomplete penetrance and variable expressivity
of the specific gene mutation. This may result in a concealed channelopathy
and underestimation of the true prevalence of the arrhythmia syndromes. Most
diagnosed channelopathies involve abnormal function of channels for potassium,
sodium, and calcium ions. Clinically, cardiac channelopathies can manifest as long
QT syndrome (LQTS), Brugada syndrome (BrS), catecholeminergic polymorphic
ventricular tachycardia (CPVT), short QT syndrome (SQTS),1,2 cardiac conduc-
tion disorder, and pathologic early repolarization. Rarely, there can be overlap
among these syndromes (eg, BrS, SQTS, pathologic early repolarization).
General Evaluation and Management

Clinical symptoms usually include palpitations and syncope. There is a higher
incidence of epilepsy in some of the channelopathies.3 Additionally, sudden,
unexplained infant deaths have been linked to cardiac channelopathies.
411
CCIP.indb 411 3/13/18 4:19 PM

Therapy
Although most of these channelopathies are potentially lethal, they are highly
treatable. β-blockers are the mainstay treatment in most, although these are gen-
erally contraindicated in BrS. Cardiac events may manifest in the setting of non-
adherence to medical treatment. An automatic implantable cardiac defibrillator
(ICD) is effective in preventing sudden cardiac death. Unfortunately, there can
be many device-related complications, and therapeutic shocks can trigger what
is called an “electrical storm,” especially in patients with CPVT. The benefits and
risks of this therapy need to be taken into consideration.
Evaluation
Event recorders or an implantable loop recorder may be useful in evaluating
the patient for medical noncompliance and to determine the level of sports
participation that is safe for a patient. In symptomatic patients, it may help to
show whether or not clinical symptoms are associated with a benign arrhythmia.
Stress tests may be useful in most patients, especially those with LQTS, SQTS,
and CPVT. Electrophysiology testing is usually not helpful.
Cardiopulmonary resuscitation training for caregivers should be part of the
management, as well as availability of an automatic external defibrillator. Patients
who receive an ICD or who had aborted sudden cardiac death should be referred
for psychological counseling. There is a higher incidence of anxiety and depres-
sion in these patients. Family screening and genetic counseling are also advisable.
Unfortunately, it is not clear what to do with variances of questionable clinical
significance or with a positive genetic mutation result with a negative phenotypic
expression. A family history of juvenile sudden cardiac death or a channelopathy
should be investigated. Medical management should be arranged in conjunction
with a cardiac electrophysiologist or genetic cardiologist.
Long QT Syndrome
LQTS is the most common cardiac channelopathy, with a prevalence of 1 in
2,000 children.4–7 Most cases are linked to 3 LQTS subtypes—LQT1 (due
to mutation in the KCNQ1 gene), followed by LQT2 (due to mutation in the
KCNH2 gene), and, less frequently, LQT3 (due to mutation in the SCN5A
gene)—although many rarer subtypes also exist. The subtypes are classified
according to the ion channel involved (potassium, sodium, or calcium) and the
specific gene mutation (affected protein). The most common clinical presentation
of LQTS is abrupt syncope, usually upon exertion. Less common symptoms
are presyncope, seizures, and palpitations. Sudden cardiac arrest may be the first
clinical presentation in LQTS. It is usually associated with torsades de pointes, a
412
CCIP.indb 412 3/13/18 4:19 PM

Long QT S
yndrome and Other Channelopathies
potentially lethal form of ventricular tachycardia. Fetal and neonatal arrhythmias

consist of sinus bradycardia (in LQT1) or 2:1 atrioventricular (AV) block (in
LQT2 or LQT3).8,9 Family history is positive for LQTS in more than one-third
of patients. Genetic and electrocardiographic (ECG) screening of the immediate
family is recommended by the Heart Rhythm Society and the European Heart
Rhythm Association.10

Triggering events for torsades de pointes include exercise and swimming (in
LQT1) or loud sounds and emotional stress, especially in the early morning
(in LQT2).11 Postpartum surveillance of patients with LQT2 can be lifesaving
because they are more vulnerable to development of torsades de pointes. LQTS
is a potentially lethal arrhythmia syndrome, but it is treatable. Lack of compli-
ance with β-blocker therapy is considered a risk factor in these patients. Other
risk factors for sudden cardiac death include a corrected QT interval longer
than 0.5 seconds (500 ms), aborted cardiac arrest, recurrent syncope (despite
β-blocker therapy), T wave alternans, double-hit (more than 1 gene) mutation,
LQT1 in younger male patients, LQT2 in postpubertal female patients, and
certain LQTS subtypes.5,12,13 An ICD may be indicated in the high-risk
subtypes, such as patients with autosomal recessive LQTS, LQT3, and Timothy
syndrome (LQT8). Some of the subtypes, like LQT8, have associated cardiac
(congenital defects, hypertrophic cardiomyopathy) and noncardiac abnormalities
(musculoskeletal abnormalities, cognitive impairment, syndactyly, hypoglycemia)
and congenital deafness ( Jervell and Lange-Nielsen syndrome, LQT7, LQT8).
β-blockers are the mainstay therapy for most of the LQTS subtypes. Nadolol
therapy has been shown to be the most effective and atenolol the least effective.
Effectiveness of a medical therapy is not dependent on changes of QT interval
duration. Some advocate for the use of potassium chloride and spironolactone in
LQT2. Patients with LQT3 may require other antiarrhythmic agents. There is a
high mortality rate in symptomatic patients with LQT3, especially male patients.
Symptoms may occur during sleep.
Prevalence of sudden cardiac death decreases markedly with β-blocker
therapy, especially in LQT114,15 and in aging patients. Caffeine, decongestants,
certain antibiotics, and medications such as cardiac, gastrointestinal (prokinetic
agents), antifungal, potassium-loss, and psychotropic (antidepressant, anti-
psychotic) agents can prolong the QT interval or trigger torsades de pointes.
(For more information, please refer to www.qtdrugs.org. See also Box 2-4 in
Chapter 2, Electrocardiography.)
Stimulant therapy for children with LQTS and ADHD has been controver-
sial. Rohatgi and colleagues studied outcomes and frequency of cardiac events in
patients with LQTS with concomitant attention-deficit/hyperactivity disorder
(ADHD) stimulant therapy. Patients with LQTS, with mild to moderate risk,
had a low adverse event rate. Arrhythmia risk in these patients was insignif-
icant.16 QT duration and rhythm surveillance is advisable for patients with
413
CCIP.indb 413 3/13/18 4:19 PM

LQTS who are receiving cardioeffective medications, especially those taking

stimulant therapy for ADHD.
Eligibility and disqualification recommendations for competitive sports in
patients with LQTS and other cardiac channelopathies have been redefined in
recent years.17 Any sports participation should be approved by a heart rhythm
specialist or genetic cardiologist. Stress testing should be performed in cases of
concealed LQTS (approximately one-quarter of patients with LQTS), but with
suspicion of the syndrome.
Healthy newborns may have transitory prolongation of the QT interval,
especially in the first 48 hours after birth. Performing follow-up ECG at 1 to
4 weeks of age is advisable in newborns whose corrected QT interval is more
than 440 ms.
Brugada Syndrome
BrS is an autosomal-dominant channelopathy with variable penetrance.17,18
Prevalence is not well established because many cases are concealed. More than
one-third of patients with BrS have a normal resting ECG finding. As in most
channelopathies, the physical examination findings are usually unremarkable.
Typical presentation is abrupt syncope, nocturnal agonal respirations, and cardiac
arrest, which usually occurs during sleep or in the early morning, especially
after a large meal.19 A febrile illness, vaccination-related fever, or even increased
temperature due to heavy exertion may trigger symptoms. Patients with
BrS should avoid the use of recreational drugs, such as cocaine and alcohol.
Electrolyte imbalance, bradycardia, vagotonic agents or events, antidepressants,
and β-blockers can trigger ventricular fibrillation.20–22 (For more information
regarding safe drug use and which medications to avoid, please consult www.
brugadadrugs.org.)
BrS is more common in Asian patients, especially male subjects. ECG find-
ings include a coved ST segment with J-point elevation and inverted T waves in
the anterior precordial leads. A right bundle branch block pattern may be pres-
ent. BrS may manifest with atrial or ventricular fibrillation and/or a polymorphic
ventricular tachycardia. Just like with CPVT, stress testing may be helpful in the
diagnosis of “concealed” cases. Nearly 40% of patients with BrS have a mutation,
which usually involves the SCN5A gene.23 Besides the sodium channel, the
potassium and calcium channels may also be affected by a gene mutation.
Most patients with BrS develop symptoms after puberty. However, children
may present with supraventricular or ventricular tachyarrhythmias, sinus node
dysfunction, abrupt syncope, and sudden death.24 Unlike with other channelop-
athies, propranolol should generally be avoided. An ICD is advisable in patients
with BrS who have cardiac symptoms or spontaneous sustained ventricular
tachycardia.25 Quinidine is useful in children as a bridge or as an alternative to
ICD. BrS may overlap with other channelopathies.
414
CCIP.indb 414 3/13/18 4:19 PM

Long QT Syndrome and Other Channelopathies
Catecholeminergic Polymorphic Ventricular

Tachycardia
CPVT is a highly malignant inherited arrhythmia that may manifest during
emotional stress or moderate exertion,26,27 resulting in abrupt syncope, drowning,
or sudden death. It was first described by Berg in 1960.28 Prevalence is estimated
at 1 in 10,000 people,29 but this may be an underestimation. Age of presentation
ranges from infancy to adulthood. CPVT may remain concealed at heart rates
below 110 to 130 beats per minute. Worsening ventricular ectopy (premature
ventricular contractions to bigeminy to polymorphic couplets to ventricular
tachycardia to ventricular fibrillation) usually manifests at progressively faster
heart rates. Cardiac arrest may be the first symptom.27 The resting ECG finding
is usually normal, except for occasional sinus bradycardia. In young children,
supraventricular arrhythmias include atrial fibrillation, ectopic atrial tachycardia,
and sinus node dysfunction.26,30–32 Most patients with CPVT present with
exercise-induced syncope and seizures, usually within the first decade after birth.
CPVT may be associated with sudden infant death syndrome. Two-thirds of
patients with CPVT have a positive result for genetic mutation, which usually
involves a defect in ryanodine receptors (ryanodine receptor 2). It is mostly an
autosomal-dominant inheritance, although rarely, it can be autosomal recessive.33
Cardiac arrest is seen in about three-quarters of patients who are untreated.
The first line of treatment is β-blockers, such as nadolol.34 Unfortunately,
β-blockers are less protective in CPVT35 than in LQTS. Therefore, concomitant
treatment with flecainide, calcium-channel blockers, and/or left cardiac sympa-
thetic nerve denervation should be entertained, especially in children with recur-
rent syncope or polymorphic ventricular tachycardia.34,36–41 Patients who remain
symptomatic despite treatment are candidates for an ICD.34 Unfortunately, ICD
therapeutic shocks can trigger recurrent ventricular tachyarrhythmias, so-called
electrical storm.42,43 Therefore, concomitant use of a β-blocker is essential in
these patients.
Stress testing is most helpful for the diagnosis of CPVT44 and for evaluation
of medical treatment, because increased heart rates during stress bring out the
characteristic arrhythmias. Holter monitoring is also useful.30 Patients with
CPVT should limit their exposure to emotional stress, strenuous exercise, and
most competitive sports.34
There is a family history of juvenile sudden death in one-third of patients
with CPVT.45 Genetic testing46 and family counseling are indicated. A specialist
in this type of channelopathy should be part of the management team. Incidence
of sudden cardiac death is 5% per year while taking β-blocker therapy. There
may be overlap of CPVT with LQTS, ERP,47 or arrhythmogenic right ventric-
ular dysplasia,48 in which the use of cardiac magnetic resonance imaging may
be diagnostic.
415
CCIP.indb 415 3/13/18 4:19 PM

Early Repolarization Syndrome

Early repolarization pattern, with an upsloping ST segment pattern, is common
in young athletes. There is a J point elevation in 2 contiguous leads, followed
by ST segment elevation. Most patients with early repolarization pattern are
asymptomatic. The pathologic type, early repolarization syndrome (ERP), is
associated with sudden cardiac death, polymorphic ventricular tachycardia, or
ventricular fibrillation.
QRS notching and/or horizontal (or downsloping) ST segment is usually
present, especially in the inferior and/or lateral leads. ERP has been found in
about one-third of patients with idiopathic ventricular fibrillation. ERP may
overlap with other channelopathies, including BrS, with anterior J elevation in
V1 to V3, idiopathic ventricular fibrillation, and CPVT.47
Short QT Syndrome
SQTS is a rare, primary electrical disease that affects mainly males (4:1 male-to-
female ratio). The underlying pathophysiological feature involves shortening of
cardiac repolarization. Typical ECG findings include a short QT interval and tall
T waves. The corrected QT interval is usually less than 330 ms, although in some
affected patients, it is greater.49 The QT interval fails to adapt to changes in heart
rates. The prevalence of SQTS is not well defined. Symptoms may manifest very
early in life. Almost two-thirds of patients are symptomatic. Cardiac arrest is
seen in one-fourth to one-third of patients, usually as a first presentation. Other
symptoms include palpitations and unheralded syncope. Atrial and ventricular
fibrillation is commonly seen. There is a unique SQTS clinical manifestation
in the neonate, with atrial fibrillation and marked bradycardia that require
implantation of a pacemaker.50,51 It should be noted that there is a high incidence
of sudden cardiac death during infancy, which may be associated with ventricular
fibrillation. The therapeutic approach to SQTS is not well defined. Quinidine
may prolong the QT interval and may be effective in preventing syncope and
sudden cardiac death, but not atrial fibrillation—especially in children.52 An
ICD is the treatment of choice for symptomatic individuals with SQTS,53
although there is a high rate of inappropriate ICD shocks, especially in pediatric
patients.50 Propafenone and sotalol have been used for atrial fibrillation. SQTS
may show phenotypic overlap with BrS.54
Cardiac Conduction Disorder

Cardiac conduction disorder encompasses a variety of usually progressive
conduction disorders, including AV block, right bundle branch block, and left
bundle branch block; it may be associated with bradycardia. Syncope and sudden
cardiac deaths are common manifestations. Cardiac conduction disorder can be
associated with dilated or restrictive cardiomyopathies.
416
CCIP.indb 416 3/13/18 4:19 PM

References
1) Gussak I, Brugada P, Brugada J, et al. Idiopathic short QT interval: a new clinical syndrome?
Cardiology. 2000;94(2):99–102
2) Villafañe J, Young ML, Maury P, et al. Short QT syndrome in a pediatric patient. Pediatr
Cardiol. 2009;30(6):846–850
3) Parisi P, Oliva A, Coll Vidal M, et al. Coexistence of epilepsy and Brugada syndrome in a family
with SCN5A mutation. Epilepsy Res. 2013;105(3):415–418
4) Schwartz PJ, Stramba-Badiale M, Crotti L, et al. Prevalence of the congenital long-QT
syndrome. Circulation. 2009;120(18):1761–1767
5) Goldenberg I, Moss AJ. Long QT syndrome. J Am Coll Cardiol. 2008;51(24):2291–2300
6) Sarquella-Brugada G, Campuzano O, Iglesias A, et al. Genetics of sudden cardiac death in
children and young athletes. Cardiol Young. 2013;23(2):159–173
7) Tester DJ, Ackerman MJ. The molecular autopsy: should the evaluation continue after the
funeral? Pediatr Cardiol. 2012;33(3):461–470
8) Lupoglazoff JM, Denjoy I, Villain E, et al. Long QT syndrome in neonates: conduction
disorders associated with HERG mutations and sinus bradycardia with KCNQ1 mutations. J Am
Coll Cardiol. 2004;43(5):826–830
9) Lupoglazoff JM, Cheav T, Baroudi G, et al. Homozygous SCN5A mutation in long-QT
syndrome with functional two-to-one atrioventricular block. Circ Res. 2001;89(2):E16–E21
10) Ackerman MJ, Priori SG, Willems S, et al. HRS/EHRA expert consensus statement on the state
of genetic testing for the channelopathies and cardiomyopathies this document was developed
as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm
Association (EHRA). Heart Rhythm. 2011;8(8):1308–1339
11) Tester DJ, Ackerman MJ. The molecular autopsy: should the evaluation continue after the
funeral? Pediatr Cardiol. 2012;33(3):461–470
12) Priori SG, Napolitano C, Diehl L, Schwartz PJ. Dispersion of the QT interval. A marker of
therapeutic efficacy in the idiopathic long QT syndrome. Circulation. 1994;89(4):1681–1689
13) Hobbs JB, Peterson DR, Moss AJ, et al. Risk of aborted cardiac arrest or sudden cardiac death
during adolescence in the long-QT syndrome. JAMA. 2006;296(10):1249–1254
14) Schwartz PJ. The congenital long QT syndromes from genotype to phenotype: clinical implica-
tions. J Intern Med. 2006;259(1):39–47
15) Moss AJ, Robinson J. Clinical features of the idiopathic long QT syndrome. Circulation.
1992;85(1 Suppl):I140–I144
16) Rohatgi RK, Bos JM, Ackerman MJ. Stimulant therapy in children with attention-deficit/
hyperactivity disorder and concomitant long QT syndrome: a safe combination? Heart Rhythm.
2015;12(8):1807–1812
17) Ackerman MJ, Zipes DP, Kovacs RJ, Maron BJ; American Heart Association Electro
cardiography and Arrhythmias Committee of Council on Clinical Cardiology, Council on
Cardiovascular Disease in Young, Council on Cardiovascular and Stroke Nursing, Council
Eligibility and Disqualification Recommendations for Competitive Athletes with Cardiovascular
Abnormalities: Task Force 10: the Cardiac Channelopathies: a Scientific Statement
2015;132(22):e326–e329
18) Brugada P, Brugada J. Right bundle branch block, persistent ST segment elevation and sudden
cardiac death: a distinct clinical and electrocardiographic syndrome. A multicenter report. J Am
Coll Cardiol. 1992;20(6):1391–1396
19) Take Y, Morita H, Toh N, et al. Identification of high-risk syncope related to ventricular
fibrillation in patients with Brugada syndrome. Heart Rhythm. 2012;9(5):752–759
417
CCIP.indb 417 3/13/18 4:19 PM

20) Antzelevitch C, Brugada P, Brugada J, Brugada R. Brugada syndrome: from cell to bedside. Curr
Probl Cardiol. 2005;30(1):9–54
21) Antzelevitch C. Brugada syndrome. Pacing Clin Electrophysiol. 2006;29(10):1130–1159
22) Skinner JR, Chung SK, Nel CA, et al. Brugada syndrome masquerading as febrile seizures.
Pediatrics. 2007;119(5):e1206–e1211
23) Kapplinger JD, Tester DJ, Alders M, et al. An international compendium of mutations in the
SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic
testing. Heart Rhythm. 2010;7(1):33–46
24) Gonzalez Corcia MC, de Asmundis C, Chierchia GB, Brugada P. Brugada syndrome in the
paediatric population: a comprehensive approach to clinical manifestations, diagnosis, and
management. Cardiol Young. 2016;26(6):1044–1055
25) Harris BU, Miyake CY, Motonaga KS, Dubin AM. Diagnosis and management of pediatric
brugada syndrome: a survey of pediatric electrophysiologists. Pacing Clin Electrophysiol.
2014;37(5):638–642
26) Leenhardt A, Lucet V, Denjoy I, Grau F, Ngoc DD, Coumel P. Catecholaminergic poly-
morphic ventricular tachycardia in children. A 7-year follow-up of 21 patients. Circulation.
1995;91(5):1512–1519
27) Roston TM, Vinocur JM, Maginot KR, et al. Catecholaminergic polymorphic ventricular
tachycardia in children: analysis of therapeutic strategies and outcomes from an international
multicenter registry. Circ Arrhythm Electrophysiol. 2015;8(3):633–642
28) Berg KJ. Multifocal ventricular extrasystoles with Adams-Stokes syndrome in siblings. Am Heart
J. 1960;965–970
29) Liu N, Ruan Y, Priori SG. Catecholaminergic polymorphic ventricular tachycardia. Prog
Cardiovasc Dis. 2008;51(1):23–30
30) Sy RW, Gollob MH, Klein GJ, et al. Arrhythmia characterization and long-term outcomes in
catecholaminergic polymorphic ventricular tachycardia. Heart Rhythm. 2011;8(6):864–871
31) van der Werf C, Nederend I, Hofman N, et al. Familial evaluation in catecholaminergic poly-
morphic ventricular tachycardia: disease penetrance and expression in cardiac ryanodine receptor
mutation-carrying relatives. Circ Arrhythm Electrophysiol. 2012;5(4):748–756
32) Di Pino A, Caruso E. Costanzo L, Guccione P. A novel RyR2 mutation in a 2-year-old baby
presenting with atrial fibrillation, atrial flutter, and atrial ectopic tachycardia. Heart Rhythm.
2014;11:1480–1483
33) Lahat H, Eldar M, Levy-Nissenbaum E, et al. Autosomal recessive catecholamine- or exer-
cise-induced polymorphic ventricular tachycardia: clinical features and assignment of the disease
gene to chromosome 1p13-21. Circulation. 2001;103(23):2822–2827
34) Priori SG, Wilde AA, Horie M, et al. HRS/EHRA/APHRS expert consensus statement on the
diagnosis and management of patients with inherited primary arrhythmia syndromes: document
endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC
in June 2013. Heart Rhythm. 2013;10(12):1932–1963
35) van der Werf C, Zwinderman AH, Wilde AA. Therapeutic approach for patients with
catecholaminergic polymorphic ventricular tachycardia: state of the art and future developments.
Europace. 2012;14(2):175–183
36) Collura CA, Johnson JN, Moir C, Ackerman MJ. Left cardiac sympathetic denervation for the
treatment of long QT syndrome and catecholaminergic polymorphic ventricular tachycardia
using video-assisted thoracic surgery. Heart Rhythm. 2009;6(6):752–759
37) Wilde AA, Bhuiyan ZA, Crotti L, et al. Left cardiac sympathetic denervation for catecholamin-
ergic polymorphic ventricular tachycardia. N Engl J Med. 2008;358(19):2024–2029
418
CCIP.indb 418 3/13/18 4:19 PM

38) Rosso R, Kalman JM, Rogowski O, et al. Calcium channel blockers and beta-blockers versus
beta-blockers alone for preventing exercise-induced arrhythmias in catecholaminergic polymor-
phic ventricular tachycardia. Heart Rhythm. 2007;4(9):1149–1154
39) Watanabe H, Chopra N, Laver D, et al. Flecainide prevents catecholaminergic polymorphic
ventricular tachycardia in mice and humans. Nat Med. 2009;15(4):380–383
40) van der Werf C, Kannankeril PJ, Sacher F, et al. Flecainide therapy reduces exercise-induced
ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia.
J Am Coll Cardiol. 2011;57(22):2244–2254
41) Imberti JF, Underwood K, Mazzanti A, Priori SG. Clinical challenges in catecholaminergic
polymorphic ventricular tachycardia. Heart Lung Circ. 2016;25(8):777–783
42) Mohamed U, Gollob MH, Gow RM, Krahn AD. Sudden cardiac death despite an implantable
cardioverter-defibrillator in a young female with catecholaminergic ventricular tachycardia.
Heart Rhythm. 2006;3(12):1486–1489
43) Palanca V, Quesada A, Trigo A, Jiménez J. Arrhythmic storm induced by AICD discharge
in a patient with catecholaminergic polymorphic ventricular tachycardia. Rev Esp Cardiol.
2006;59(10):1079–1080 [in Spanish]
44) Hayashi M, Denjoy I, Hayashi M, et al. The role of stress test for predicting genetic mutations
and future cardiac events in asymptomatic relatives of catecholaminergic polymorphic ventricular
tachycardia probands. Europace. 2012;14(9):1344–1351
45) Priori SG, Napolitano C, Memmi M, et al. Clinical and molecular characterization of patients
with catecholaminergic polymorphic ventricular tachycardia. Circulation. 2002;106(1):69–74
46) Hofman N, Tan HL, Alders M, et al. Yield of molecular and clinical testing for arrhythmia
syndromes: report of 15 years’ experience. Circulation. 2013;128(14):1513–1521
47) Tülümen E, Schulze-Bahr E, Zumhagen S, et al. Early repolarization pattern: a marker of
increased risk in patients with catecholaminergic polymorphic ventricular tachycardia. Europace.
2016;18(10):1587–1592
48) Patel H, Shah P, Rampal U, Shamoon F, Tiyyagura S. Arrythmogenic right ventricular dysplasia/
cardiomyopathy (ARVD/C) and cathecholaminergic polymorphic ventricular tachycardia
(CPVT): A phenotypic spectrum seen in same patient. J Electrocardiol. 2015;48(5):874–878
49) Bjerregaard P, Collier JL, Gussak I. Upper limit of QT/QTc intervals in the short QT syndrome.
Review of the world-wide short QT syndrome population and 3 new USA families. Heart
Rhythm. 2008;5:91
50) Villafañe J, Atallah J, Gollob MH, et al. Long-term follow-up of a pediatric cohort with short
QT syndrome. J Am Coll Cardiol. 2013;61(11):1183–1191
51) Villafañe J, Fischbach P, Gebauer R. Short QT syndrome manifesting with neonatal atrial
fibrillation and bradycardia. Cardiology. 2014;128(3):236–240
52) Gaita F, Giustetto C, Bianchi F, et al. Short QT syndrome: pharmacological treatment. J Am Coll
Cardiol. 2004;43(8):1494–1499
53) Gaita F, Giustetto C, Bianchi F, et al. Short QT syndrome: a familial cause of sudden death.
Circulation. 2003;108(8):965–970
54) Antzelevitch C, Pollevick GD, Cordeiro JM, et al. Loss-of-function mutations in the cardiac
calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT
intervals, and sudden cardiac death. Circulation. 2007;115(4):442–449
419
CCIP.indb 419 3/13/18 4:19 PM

CCIP.indb 420 3/13/18 4:19 PM
PART 5
Acquired Cardiac
Diseases
25. Kawasaki Disease.................................................................. 423
26. Acute Rheumatic Fever and Rheumatic Heart Disease........ 443
27. Cardiotoxicity Among Survivors of Childhood Cancer....... 463
421
CCIP.indb 421 3/13/18 4:19 PM

CCIP.indb 422 3/13/18 4:19 PM
CHAPTER 25
Kawasaki Disease
Bessey Geevarghese, DO, and Stanford T. Shulman, MD, FAAP
Introduction
Kawasaki disease (KD) is an acute, self-limited vasculitis of small- and medi-
um-sized blood vessels with a predilection for the coronary arteries that typically
occurs in young children. It was first described by Japanese pediatrician Tomisaku
Kawasaki in 1967, after he started seeing unusual cases of children presenting
with fever and rash.1 KD was independently recognized as a novel disease in the
1970s by Melish et al at the University of Hawaii.2 Originally thought to be a rare
condition, KD is now recognized as the most common cause of acquired heart
disease in children in the developed world.3 The etiologic origin of KD remains
unknown, and there is no diagnostic test. However, it is currently believed that the
disease represents an abnormal inflammatory and immune-mediated host response
to 1 or more as-yet unidentified pathogen(s) in genetically susceptible individuals.4
Fevers usually last for 10 to 12 days, if not treated. However, echocardiographic
and cardiac angiographic data indicate that 20% to 25% of untreated patients
develop coronary artery abnormalities, which can lead to myocardial infarctions,
ischemic heart disease, and, rarely, sudden deaths.5 Treatment with high-dose
intravenous immunoglobulin (IVIg) plus aspirin within 10 days of fever onset
resolves inflammation and reduces the occurrence of coronary artery abnormalities
to less than 5%.
The clinical features in classic KD include fever of at least 5 days’ duration and
4 of the following 5 features: oral mucosal inflammation, nonpurulent conjunctival
injection, lymphadenopathy, edema of the distal extremities, and a polymorphous
rash. In the absence of a diagnostic test and with marked similarities to various
infectious and noninfectious processes, diagnosis remains a challenge. In addition,
many children present with incomplete criteria and atypical symptoms. Clinicians
must rely on the presence of specific clinical criteria and certain laboratory data
423
CCIP.indb 423 3/13/18 4:19 PM

that support KD. In almost all patients, imaging with echocardiography can be
used to detect whether coronary artery dilatation and aneurysms have developed.
Early and accurate diagnosis is imperative in these children to prevent morbidity
and mortality associated with this illness.
Epidemiology and Etiologic Origins

KD has been reported in more than 60 countries on all continents and increas-
ingly in many resource-limited countries. In North America and Europe, the
current annual incidence is 4 to 25 in 100,000 children under 5 years of age.6
In contrast, the annual incidence of KD in Japanese children, as well as other
Asian countries (Korea, Taiwan), is 10 to 20 times higher, with the incidence
rate continuing to rise.7 Asian children who reside in non-Asian countries also
continue to have high rates of KD.
In temperate climates such as the United States, KD is more common during
the winter and early spring, with boys much more commonly affected than girls
at a ratio of 1.5:1.6 Although most children with KD are between the ages of
1 and 8 years, with 80% younger than 5 years of age, infants under 6 months
of age have an especially high risk for coronary lesions. In this younger group,
the diagnosis is frequently delayed because signs and symptoms of KD may be
subtle or absent. Children older than 8 years also appear to be at higher risk for
coronary aneurysms.
Epidemiological features suggest a ubiquitous infectious microbe as the
causative agent. However, the specific agent and the pathogenesis of KD are
poorly understood. The rarity of KD in infants younger than 3 months is com-
patible with protection from passive maternal antibodies, and the near lack of
KD in adults suggests widespread immunity. The presence of a winter-to-spring
predominance of cases in temperate climates, epidemics of illness, occurrence of
community outbreaks with wavelike geographic spread, and the age distribution
support an infectious cause.8 A recent study from Japan showed protective
effects of breastfeeding on the development of KD in the first 6 to 30 months
after birth, which indicates that breastfeeding provides maternal immunologic
memory and contributes to immune system maturation.9 Many infectious
etiologic origins have been suggested, but none have been confirmed. It has
been hypothesized that KD is triggered by a bacterial superantigen similar to
those produced in staphylococcal toxic shock syndrome (TSS) or scarlet fever.10
However, this remains controversial, without substantial supporting data.
In acute KD, inflammatory cells (including macrophages, monocytes, and
CD8+ T lymphocytes) infiltrate the vascular wall, mainly the coronary artery.11
There has been promising evidence for an oligoclonal antibody response,
particularly immunoglobulin A (IgA) plasma cell infiltration of the vascular wall,
as well as nonvascular tissues, including the myocardium, upper respiratory tract,
424
CCIP.indb 424 3/13/18 4:19 PM

Kawasaki Disease
pancreas, and kidney.12 This IgA response suggests a mucosal portal of entry of
the etiologic agent of KD. Subsequent research has led to the identification of
viral-like cytoplasmic inclusion bodies in acute KD bronchial epithelium, which
supports a viral pathogen.13
In 1 report, it was suggested that seasonal changes in tropospheric wind
patterns from northeast China and the northern Pacific temporally correlate
with KD cases in Hawaii, Southern California, and Japan, indicating that the
environmental trigger for KD could be wind-borne.14 However, similar associa-
tions with wind patterns have not been observed or independently confirmed in
other parts of the world. Observational attempts to associate KD with exposure
to environmental pollutants and toxins, such as pesticides, heavy metals, and
chemicals, have been unsuccessful.
Despite clinical, epidemiological, and laboratory markers being suggestive
of an infectious cause, current efforts with viral and bacterial cultures, highly
sensitive polymerase chain reaction (PCR) testing, and biomarkers have not
yet resulted in identifying a definitive agent.
Pathologic Changes
The low mortality rate of KD and its predilection for mainly coronary arteries
has limited a thorough understanding of how pathologic changes in the coronary
arteries evolve over time. In early autopsy studies, KD was considered a panar-
teritis without fibrinoid necrosis. In these early studies, it was proposed that an
initial neutrophilic infiltration of the coronary arteries occurred in the first 1 to
2 weeks of illness, followed by displacement of the neutrophils by mononuclear
cells and then resolution of the inflammation within 2 months from onset of
illness.15,16 Infiltration of inflammatory cells leads to destruction of the media
and internal elastic lamina, with eventual thrombus formation on the inflamed
arterial luminal surfaces.16
More recent detailed observations indicate 3 specific linked processes—
necrotizing arteritis, subacute chronic vasculitis, and luminal myofibroblastic
proliferation (LMP)—all of which occur within the first 2 weeks after fever
onset.17,18 Necrotizing arteritis, which is described as neutrophilic infiltration
of the arterial wall, begins early in KD, with the process complete in the
first 2 weeks of illness. This initial process can lead to the formation of giant
aneurysms, which may thrombose, resulting in risk of myocardial ischemia and
infarction.17 The second process, subacute chronic vasculitis, begins in the first
2 weeks after fever onset and can affect all blood vessels but mainly involves
segments of medium-sized muscular arteries, such as the coronary arteries.17,18
The last process, LMP, involves proliferation of medial smooth muscle
cell–derived myofibroblasts, which can obstruct the arterial lumen over time.
Both chronic vasculitis and LMP can persist for months to years after initial
425
CCIP.indb 425 3/13/18 4:19 PM

illness. This model could explain why death can occur months to years after KD
in patients who, at autopsy, are found to have ongoing coronary artery inflam-
mation and obliteration of the coronary artery lumen by cellular proliferation by
persistent subacute chronic vasculitis and luminal myofibroblastic proliferation.18
However, it is unknown why there is persistent coronary artery inflammation
and myofibroblastic proliferation in many of these patients.
Some propose that clinical features of KD may be the result of a common
pathway of immune-mediated vascular inflammation involving genetic factors
after an infection(s), rather than being triggered by a specific pathogen.19
Specific immune cell types involved in KD have been identified; however, the
mechanisms that result in such abnormal immune function or overexpression
of inflammatory cytokines are not well understood. Genetically determined
dysregulation of the immune response plays an integral factor in KD pathogen-
esis. This is supported by several observations, mainly the higher rates of KD
among the Japanese population and, to a lesser extent, the Korean and Taiwanese
populations. Also noted is an increased incidence of KD among siblings and
parents of affected children.20,21 Current research on the investigation of the
transcriptional profile of coronary arteritis in patients with KD showed marked
activation of T lymphocytes and dendritic cells with upregulation of type 1
interferon responses.22 Ongoing research into understanding the genetic basis
of susceptibility to KD could help identify individuals at increased risk, as well
as provide insights into pathogenesis and pathways, which could reveal new
targets for treatment.
Clinical Features
Signs and Symptoms
The diagnostic criteria for classic KD were established by Dr Kawasaki from
his personal evaluation of 50 patients in Japan.1 These original criteria require
the presence of at least 5 days of fever, in addition to at least 4 of the following
5 signs of mucocutaneous inflammation: (a) bilateral conjunctival injection, most
often without discharge and described as limbic sparing; (b) mucosal changes,
including cracked lips and strawberry tongue; (c) extremity changes, including
redness of the palms and/or soles and swelling of the dorsal surfaces of the hands
and feet, with periungual desquamation in the convalescent stage; (d) polymor-
phous rash; and (e) cervical lymphadenopathy, usually unilateral, with 1 node
1.5 cm or more in diameter.11 Patients may not present with all features at once
and require close follow-up to ensure the correct diagnosis.
Fever, typically high and spiking, is usually the initial sign of KD in most
patients and can last for a mean duration of 11 days, although fever that lasts
several weeks has been reported. It is important to ask parents how temperatures
426
CCIP.indb 426 3/13/18 4:19 PM

Kawasaki Disease
are obtained, because oral or rectal temperatures are most accurate. Bulbar con-
junctival injection is usually bilateral, and pain and photophobia are infrequent.
Mild anterior uveitis can be seen at slit lamp examination. Changes in the lips
and oral cavity can develop in various degrees but do not include oral erosions
or ulcers. The typical skin rash is a polymorphous exanthema; however, KD rash
can have many forms, including maculopapular, scarlatiniform, erythroderma,
and typical erythema multiforme. Vesicular and bullous rashes have not been
described and should prompt a search for an alternative diagnosis, if present.
Rash can involve the trunk, extremities, and perineal region. Desquamation of
the fingers and toes, beginning in the periungual area, is usually not seen until 2
to 3 weeks after onset of symptoms. Of the classic features, cervical lymphade-
nopathy is the least commonly described (approximately 50%). In some patients,
however, fever and large, painful unilateral cervical node(s) are the only 2 initial
symptoms that persist for several days. In KD, cervical adenopathy can also be
associated with retropharyngeal and/or parapharyngeal phlegmon.23,24
At least 10% to 20% of children who develop coronary aneurysms do not
meet the classic diagnostic criteria. The difficulty in diagnosing these cases with
incomplete symptom sets has highlighted the importance of imaging and using
supplemental laboratory criteria for identifying and treating these children.
Incomplete or atypical KD should be considered in children who have fever for
at least 5 days, with fewer than 4 of the 5 principal findings. An unexplained
high fever and marked irritability or lethargy may be the only initial findings
in infants (<12 months of age). Diagnosis of incomplete KD is facilitated by
use of the algorithm developed by the American Heart Association (AHA)
(Figure 25-1).25

In the acute phase of KD, clinically significant cardiovascular findings include
gallop rhythm, tachycardia out of proportion to the degree of fever, and hyper-
dynamic precordium, as well as innocent flow murmurs.11 The pericardium, myo-
cardium, endocardium, valves, and arteries can all be affected by inflammation
with presenting symptoms of myocarditis, valvular regurgitation, and pericarditis.
Because KD is a systemic vasculitis, evidence of inflammation and com-
plications can be seen in many organ systems. Gastrointestinal involvement is
common, with abdominal pain being the most common symptom. Other fre-
quent findings include hepatomegaly, hydrops of the gallbladder, increased liver
enzyme levels, and cholestasis. Children with KD often present with extreme
irritability, most likely as a result of aseptic meningitis, with rapid improvement
seen after starting treatment. Arthritis and arthralgia are often seen with patients
who refuse to walk. In countries that offer bacillus Calmette-Guérin (BCG)
inoculation, erythema and induration at the BCG site develop in children within
the first year. Some of these nonspecific symptoms, such as irritability, arthralgia,
vomiting, diarrhea, abdominal pain, rhinorrhea, and cough, have been reported in
the days before the onset of fever.
427
CCIP.indb 427 3/13/18 4:19 PM

Kawasaki shock syndrome (KSS) is a relatively rare manifestation in

which patients with KD present with systolic hypotension or clinical signs of
poor perfusion related to cardiogenic and/or distributive shock, myocardial
dysfunction, or relative volume overload.26 The etiologic origin is unknown but
may be secondary to severe vasculitis with cytokine dysregulation, myocardial
dysfunction, or systemic capillary leak syndrome.26,27 Patients with KSS have
been found to have higher inflammatory marker levels, increased risk of IVIg
resistance, clinically significant anemia, thrombocytopenia, and more frequent
hypoalbuminemia and hyponatremia than those of patients with typical KD.
Diagnostic Approach
KD is self-limited. Without treatment, signs and symptoms typically evolve over
the first 10 days and then gradually resolve. For best outcomes, treatment should
be instituted by the tenth day of illness. A comprehensive history and physical
examination are the most critical components of timely diagnosis and manage-
ment of KD. Diagnostic criteria for complete and incomplete KD are detailed
in the 2017 AHA and American Academy of Pediatrics (AAP) guidelines.25
Because the clinical diagnosis remains challenging, laboratory testing can
help the clinician evaluate the degree of inflammation and aid in the diagnosis
of KD (Box 25-1). Supplemental laboratory criteria that support a diagnosis
of acute KD include leukocytosis with predominance of immature and mature
granulocytes; normocytic, normochromic anemia; increased levels of inflamma-
tory markers (sedimentation rate and/or C-reactive protein [CRP] level); hypo-
albuminemia; increase in alanine aminotransferase level; thrombocytosis after
7 days; and sterile pyuria. Mild to moderate increases in serum transaminase
levels (≤40%), increased γ-glutamyl transpeptidase level, (approximately 67%),
and mild hyperbilirubinemia (approximately 10%) have been reported.11 Studies
Box 25-1. Useful Laboratory and Diagnostic Tests to Assist

in KD Diagnosis
Complete blood cell count with differential
Erythrocyte sedimentation rate and C-reactive protein level
Comprehensive metabolic panel, including γ-glutamyl transpeptidase
Antistreptolysin O titer and anti-DNase B
Respiratory viral panel, respiratory adenovirus polymerase chain reaction
Urinalysis
Blood culture
Chest radiography, echocardiography
428
CCIP.indb 428 3/13/18 4:19 PM

Kawasaki Disease
have also shown that the percentage of eosinophils and absolute eosinophil

count may be increased in acute KD.28 Thrombocytosis is seen in the subacute
phase of KD. Abnormalities such as increased levels inflammatory markers, high
platelet count, and low hemoglobin level generally resolve over 2 to 6 weeks.
Transthoracic echocardiography has been shown to be a reliable method for
detecting coronary aneurysms in acute and subacute stages of KD and should
be performed as soon as the patient’s symptoms indicate the diagnosis. Starting
treatment for KD should not be delayed by the timing of the echocardiogram.
The most commonly involved sites of coronary artery abnormalities include the
proximal left anterior descending artery (LAD) and the proximal right coronary
artery (RCA), followed by the left main coronary artery, the left circumflex
artery, and the distal RCA.11 In the United States, definition and classification
of coronary artery abnormalities is a dual system with both absolute coronary
artery measurements and body surface area–adjusted coronary artery z scores
(measurements of the internal dimension of the proximal coronary segments
normalized on the basis of body surface area and expressed in standard deviation
units from the mean). Coronary artery aneurysms are described as small if the
z score is at least 2.5 to less than 5, medium with z scores of 5 to less than 10,
and large or giant if larger than 8 mm in internal diameter or with a z score of
at least 10.11,29 Of note, z scores are available for only the left main coronary
artery (LMCA), the proximal LAD, and the proximal RCA. The presence of
3 of the following echocardiographic findings should also increase the clinical
suspicion of KD: pericardial effusion, lack of tapering of the coronary arteries,
a coronary z score of 2 to 2.5 of the right or left anterior descending coronary
arteries, decreased left ventricular function, and mitral regurgitation.11 LMCA
measurements may not be as reliable as others because the LMCA is short and
branches very quickly.
Risk factors for coronary artery aneurysms include both demographic
variables and severity of vasculitis at initial presentation. Even after adjusting for
higher incidence of KD, boys are more likely than girls to develop aneurysms.
Infants younger than 6 months and children older than 8 years remain at
higher risk. Clinical and laboratory indications of persistent and/or worsening
inflammation (fever, increased CRP level, progressive anemia, hyponatremia,
hypoalbuminemia, thrombocytopenia, and higher percentage of neutrophils) are
also predictors of coronary artery abnormalities. Additionally, longer interval
from disease onset to treatment and IVIg resistance increase the risk of coronary
artery abnormalities.
There are multiple infectious and noninfectious illnesses with clinical features
that overlap with and mimic KD, making it challenging to diagnose incomplete
cases. Childhood illnesses that should be differentiated from KD include viral
429
CCIP.indb 429 3/13/18 4:19 PM

infections (particularly adenovirus, enterovirus, and measles), scarlet fever,

staphylococcal scalded skin syndrome, TSS, Stevens-Johnson syndrome, bacterial
cervical lymphadenitis, and juvenile idiopathic arthritis ( JIA) (Box 25-2).
Primary adenovirus infections are common and share a peak incidence of
disease in the same age range as KD (<5 years), as well as common features of
prolonged fever, conjunctivitis, and increased levels of inflammatory markers.
The presence of adenovirus can be detected though polymerase chain reaction
(PCR) testing of the nasopharynx in about 10% of healthy children. Adenoviral
pharyngoconjunctival fever most closely mimics KD; however, adenoviral con-
junctivitis often manifests with unilateral onset, increased tearing, and follicular
hyperplasia. In a recent retrospective study, clinical and laboratory findings were
compared between children with acute adenoviral infection with KD-like symp-
toms and children with KD who have incidental adenovirus shedding from the
respiratory tract.30 Most children with primary adenovirus infection have fewer
than 4 KD-like clinical features, with the least common findings being extremity
changes and unilateral neck swelling. Laboratory features in patients with
primary adenovirus disease showed a lack of 3 or more supplementary laboratory
criteria to support a diagnosis of incomplete KD.30 With the widespread use of
PCR testing for respiratory viruses, it is common to find 1 or multiple pathogens
in children. Careful differentiation between the incidental finding of 1 or more
viruses in patients and a primary viral infection is critical to avoid misdiagnosis
and subsequent morbidity of untreated KD.
Box 25-2. Illnesses Commonly Confused with KD

Streptococcal scarlet fever
Stevens-Johnson syndrome
Drug eruption
Toxic shock syndrome
Adenovirus
Epstein-Barr virus
Parvovirus
Measles
Juvenile idiopathic
arthritis
Leptospirosis
Enterovirus
Rickettsial exanthems
430
CCIP.indb 430 3/13/18 4:19 PM

Kawasaki Disease
TSS is a toxin-mediated disease caused by either Staphylococcus aureus or

Streptococcus pyogenes. Symptoms include high fever, rash, hypotension, and
desquamation, which can rapidly progress to multiple organ failure. Patients
with KD at presentation are typically found to be younger than those with TSS.
Other features seen more often in patients with KD include anemia, thrombocy-
tosis, and, of course, cardiac abnormalities.
Children with systemic-onset JIA generally lack the conjunctival and oral
findings of KD. Lymphadenopathy is also generalized, and it may be accompa-
nied by hepatomegaly and splenomegaly. Some patients only receive diagnoses
of JIA when they fail to respond to treatment for KD and continue to have
persistent fever and arthritis.
Management
Treatment Approach
Standard Therapy for Acute KD
The goals of therapy in KD are to suppress inflammation as soon as possible
and to prevent thrombosis in developing coronary aneurysms. Even though the
etiologic origin and pathogenesis of KD remain to be clearly understood, current
standard management is based on prospective, controlled, multicenter treatment
trials that unmistakably prove the effectiveness of IVIg and high-dose acetyl-
salicylic acid (ASA) to reduce inflammation and decrease the risk of developing
coronary aneurysms.31 IVIg consists of a pooled preparation of normal human
immunoglobulin G purified from the plasma of several thousand healthy donors.
Guidelines of the AHA and the AAP are available for the treatment of patients
who fulfill the diagnostic criteria for KD and for those who are classified as
having incomplete cases (Figure 25-1).
Since the publication of the second IVIg trial by the U.S. Multicenter
Kawasaki Disease Study Group in 1991, it has been the standard of care in
the United States to treat patients with 2 g/kg of IVIg as a single infusion.32
The mechanism by which IVIg controls the vascular inflammation of KD is
unknown, but effects may be secondary to controlling cytokine production,
modulating T cell activity, and suppressing antibody synthesis. Ideally, it should
be administered within the first 7 to 10 days of the illness. Treatment with high-
dose IVIg within the first 10 days of illness not only decreases inflammation
(fever, clinical signs, inflammatory markers), but also reduces the risk of coronary
artery aneurysms to less than 5%. Treatment should still be administered after
the tenth day of illness in most circumstances, with persistent fever, evidence
of ongoing inflammation, and/or presence of coronary artery abnormalities.
IVIg administered before day 5 has been reported by some to result in poorer
outcomes; however, this is most likely due to more severe KD illnesses in those
431
CCIP.indb 431 3/13/18 4:19 PM

Evaluation of Suspected Incomplete Kawasaki Disease1
Children with fever ≥5 days and 2 or 3 compatible clinical criteria2 OR

Infants with fever for ≥7 days without other explanation3
Assess Laboratory Tests
CRP <3.0 mg/dL and ESR <40 mm/hr CRP ≥3.0 mg/dL and/or ESR ≥40 mm/hr
Serial clinical and 3 or more Laboratory Findings:

laboratory re-evaluation 1) Anemia for age
if fevers persist No 2) Platelet count of ≥450,000
Echocardiogram if after the 7th day of fever
typical peeling6 develops 3) Albumin ≤3.0 g/dL
4) Elevated ALT level
5) WBC count of ≥15,000/mm3
Treat5 Yes 6) Urine ≥10 WBC/hpf
OR
Positive echocardiogram4
FIGURE 25-1. Evaluation of suspected, incomplete Kawasaki disease (KD). (1) In the absence of a
standard of reference for diagnosis, this algorithm cannot be evidence based but rather represented
the informed opinion of the expert committee. (2) Clinical findings of KD are listed in the 2017
American Heart Association guidelines. (3) Infants ≤6 months of age are the most likely to develop
prolonged fever without other clinical criteria for KD and are at high risk for developing coronary
artery abnormalities. (4) Echocardiography findings are considered positive for the purposes of
this algorithm if any of 3 conditions are met: z score of at least 2.5 for the left anterior descending
coronary artery or right coronary artery; coronary artery aneurysm is observed; or at least 3 other
suggestive features exist, including decreased left ventricular function, mitral regurgitation, pericardial
effusion, or z scores of 2 to 2.5 in the left anterior descending coronary artery or right coronary
artery. (5) If the echocardiographic finding is positive, treatment should be given within 10 days of
fever onset or after the tenth day of fever in the presence of clinical and laboratory signs. (6) Typical
peeling begins under the nail beds of the fingers and toes. ALT = alanine aminotransferase, CRP
= C-reactive protein, ESR = erythrocyte sedimentation rate, hpf = high-power field, WBC = white
blood cell. To convert albumin level to grams per liter, multiply by 10. Reprinted with permission
from McCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis, treatment, and long-term
management of Kawasaki disease: a scientific statement for health professionals from the American
Heart Association. Circulation. 2017;135:e927–e999. ©2017 American Heart Association, Inc.
432
CCIP.indb 432 3/13/18 4:19 PM

Kawasaki Disease
who receive diagnosis and treatment earlier.33,34 Even though IVIg is a safe and
reliable treatment for KD, adverse effects may occur and can vary with the spe-
cific infusion product. These include fever, chills, hypotension, severe hemolytic
anemia, and aseptic meningitis.
ASA has been used in KD to decrease inflammation (at higher doses) and
to inhibit platelet aggregation (at lower doses). However, it has no effect on
development of coronary aneurysms.11 A meta-analysis of North American and
Japanese studies indicated that the rate of coronary artery abnormalities was
inversely related to the total IVIg dose but was independent of the aspirin
dose.35 Duration of high-dose ASA varies across institutions, with many
centers now eliminating high-dose ASA altogether and using low-dose ASA
(3–5 mg/kg once daily) from the onset of therapy. Patients should remain in
the hospital until they have been afebrile for at least 24 hours, with decreasing
inflammatory marker levels to make sure retreatment is not needed. Of note,
IVIg increases the erythrocyte sedimentation rate, which is not useful in assess-
ing ongoing inflammation after IVIg administration. Therefore, the CRP level is
much more accurate and useful after IVIg therapy.
All patients being evaluated for KD should undergo baseline echocardi-
ography early in their hospitalization. Repeat echocardiography is generally
performed at 2 weeks and again 6 to 8 weeks after onset of illness. In children at
higher risk for coronary artery aneurysms (persistent fever and/or inflammation)
or with evidence of large or giant coronary artery abnormalities, more frequent
echocardiograms are required to guide therapy. If no coronary abnormalities are
seen at the 6- to 8-week echocardiography examination, ASA can be discon-
tinued. Some centers also perform 6- to 12-month follow-up echocardiography.
In patients with clinically significant coronary artery abnormalities, computed
tomographic (CT) angiography and magnetic resonance (MR) angiography are
used to detect distal lesions and evidence of coronary artery stenosis.
Children receiving high-dose ASA are at risk for developing Reye syndrome,
particularly with influenza and varicella. During the winter months and influ-
enza season, all children and families should receive an influenza vaccine. Any
child with symptoms concerning for varicella or influenza should be evaluated
promptly. Clopidogrel can be substituted for ASA in those who have varicella
or influenza and in children who may be allergic to aspirin. In patients who
have received IVIg, live vaccines should be deferred for 11 months secondary to
decreased immunogenicity of the vaccines related to passive antibodies in the
IVIg preparation.
Aggressive systemic anticoagulation and antiplatelet therapy have been
associated with improved outcomes in patients with severe inflammation and
large or giant aneurysms (>8 mm in diameter) who are at high risk for coronary
artery thrombosis. The intensity of antithrombotic therapy increases with the
433
CCIP.indb 433 3/13/18 4:19 PM

severity of coronary artery dilatation on the basis of z scores. Current AHA rec-
ommendations are to continue ASA in all children who have persistent coronary
dilatation. In patients with severe coronary artery abnormalities, clopidogrel and/
or anticoagulation therapy with warfarin or low–molecular weight heparin may
be indicated. Expert advice is recommended by the AHA.11,25
Recurrent and Refractory KD
Approximately 85% to 95% of patients treated with IVIg and aspirin defervesce
had improved clinical signs and inflammatory markers within 36 hours after the
conclusion of an initial IVIg infusion.32 Approximately 5% to 15% of patients
who received IVIg and aspirin had persistent fever or recurrence of fever after
an initial period of being afebrile at least 36 hours after completion of the IVIg
infusion.36 A persistently increased or rising CRP level is also an indication
of poor response. These children are at increased risk for developing coronary
artery aneurysms. No data from randomized controlled trials exist to guide the
treatment of these patients. In most institutions, patients who do not defervesce
within 36 to 48 hours or who have recurrent fever and increased CRP level after
initial IVIg treatment are given a second dose of IVIg at 2 g/kg. A thorough
assessment to confirm the diagnosis of KD should be performed because some
children may not have had KD.
The 2% to 4% of patients with KD who do not respond to a second dose of
IVIg are considered IVIg refractory. Several treatment options for this subgroup
are available; however, optimal therapy is unknown. The major options include
a third dose of IVIg (2 g/kg), intravenous pulsed methylprednisolone (usually
30 mg/kg daily for 3 days), and infliximab (5 mg/kg). All 3 of these options
have been associated with some treatment response in case reports and small
series of IVIg-resistant patients.18 Recent studies with infliximab have shown
shorter duration of fever, shorter time to normalization of inflammatory markers,
and reversal of progression of coronary artery dilation. However, there was no
decrease in refractory KD when used as adjunctive initial treatment or in the
incidence of coronary artery abnormalities in IVIg-resistant KD.37–39
The effectiveness of cyclosporine has been suggested in a small case series
(4–8 mg/kg daily for 14 to 21 days, with adjustment of dosing on the basis of
serum levels) with the theory that therapy directed at the calcium-signaling
pathway may prevent T cell destruction of the coronary artery wall.40 Other
agents used in rare cases include the cytotoxic agent cyclophosphamide and
interleukin-1 receptor antagonist anakinra. Several of these agents are currently
being studied in larger prospective, randomized trials.
434
CCIP.indb 434 3/13/18 4:19 PM

Kawasaki Disease
Adjunctive Primary Therapy

Corticosteroids
Combination immunomodulator treatments have been studied as adjunctive
therapy with IVIg in patients who do not respond to an initial dose of IVIg and/
or are considered to be at high risk for coronary complications. Previous studies
showed that steroids could improve the patient’s clinical condition and degree of
inflammation, lowering the risk and incidence of coronary artery abnormalities.41
However, these results were challenged by the 2007 U.S. Pediatric Heart
Network study, which showed no difference in the duration of hospitalization
and fever with the use of steroids.42 The dose used in this study was a single
pulsed dose of intravenous methylprednisolone administered in conjunction
with IVIg and aspirin, and all patients with KD were included.
In 2012, a randomized trial in Japan, known as the “RAISE” study
(Randomized Controlled Trial to Assess Immunoglobulin Plus Steroid Efficacy
for Kawasaki Disease), showed that combination treatment with IVIg plus pred-
nisolone was superior to IVIg alone in preventing coronary artery abnormalities
in patients identified as being high risk, thus reducing the need for additional
treatment and achieving more rapid resolution of fever and inflammatory
markers in patients with severe KD.43 This has been the most comprehensive
and best-powered study of corticosteroids in patients with KD. Patients were
enrolled by using a risk-stratification scoring system whereby those with high-
risk scores were identified as potential nonresponders to primary IVIg. These
patients were randomized to standard IVIg and aspirin therapy, with or without
intravenous prednisolone (2 mg/kg daily for 5 days). After defervescence, the
steroid-treated group was switched to oral prednisolone at 2 mg/kg daily for 5
days, which was then tapered to 0 over 15 days after the CRP level had normal-
ized. The striking benefits observed were not at the cost of increasing the risk of
adverse events. Possible explanations for the varying results between the earlier
studies and the RAISE study include differences in dose and timing of steroids,
as well as patient selection between the different studies.
A recent systematic review and meta-analysis of 16 clinical studies in which
corticosteroids plus IVIg therapy were compared with IVIg therapy alone again
demonstrated that adjunctive steroid therapy was associated with a significantly
lower rate of coronary artery complication when compared with IVIg alone,
especially among high-risk patients.44 Almost all of the included studies were
conducted in Japan, where higher prevalence and awareness of KD may lead
to earlier treatment. Unfortunately, scoring systems used in Japan to identify
high-risk patients do not seem to be effective in identifying high-risk children
in multiethnic populations such as those in North America.45 Current recom-
mendations from the AHA and AAP are to use IVIg and ASA without steroids
as first-line therapy. Exceptions include high-risk patients, where a steroid taper
435
CCIP.indb 435 3/13/18 4:19 PM

with IVIg and ASA can be considered. Consultation with an expert should be
sought in such cases.
Infliximab
In addition to steroids, other immune-modulatory agents have been proposed
and used in KD. Currently, the most commonly used agent besides steroids
is infliximab, a human monoclonal antibody against tumor necrosis factor
(TNF-α). TNF-α levels are increased during the acute phase of KD and may
be correlated with the development of coronary artery abnormalities.46 However,
Rowley and colleagues did not find the TNF-α pathway to be upregulated in
KD arteritis when analyzing the transcriptional profile of fatal KD tissues.22 In a
recent double-blinded, placebo-controlled randomized trial of adjunctive therapy,
patients with KD were treated with IVIg and aspirin, plus either a dose of inflix-
imab (5 mg/kg) or placebo. There was no difference between the groups in the
rate of resistance to treatment, nor in the proportion of patients with coronary
artery abnormalities.39 However, it was noted to be safe and well tolerated, with
no directly attributable adverse effects.
At this time, outside of Japan, there is no standard method to identify high-
risk children (except young infants) or to recommend therapy for children with
KD who are thought to be at high risk. Further research is needed to develop a
reliable scoring system to identify high-risk children outside Japan.
Ongoing Care
Complications
The major complication of KD is coronary artery aneurysms, which may result
in myocardial ischemia, myocardial infarction, heart failure, and sudden death.
Infarcts most often occur in the first year after disease onset, with the highest
risk in the first 2 months. Undiagnosed and untreated KD in children can
manifest with myocardial infarction in later childhood or in adulthood.
Other cardiovascular complications include decreased myocardial function in
the acute phase, valvular regurgitation, pericardial effusion, and, rarely, peripheral
artery aneurysms. Patients with giant coronary aneurysms can also have periph-
eral aneurysms in medium-sized peripheral arteries, such as axillary, brachial, or
femoral arteries.
In rare cases, persistent fever after IVIg treatment has been associated with
macrophage activation syndrome. Characterized by activation and proliferation
of macrophages and T cells, it can lead to severe complications, including dis-
seminated intravascular coagulopathy, cytopenias, and thrombosis. Sensorineural
hearing loss, usually transient and asymptomatic, has been reported after KD.
436
CCIP.indb 436 3/13/18 4:19 PM

Kawasaki Disease
Prognosis
Long-term prognosis in children with coronary aneurysms depends on the
size and shape of the aneurysms, as well as the number of coronary arteries
involved. Aneurysms may increase in size over the first few months after illness
onset. Angiographic resolution 1 to 2 years after onset of KD has been observed
in 50% to 75% of vessels with coronary aneurysms, with smaller aneurysms
having a higher chance of regression.5,11 A longitudinal study over 10 to 21
years in almost 600 Japanese children with KD and aneurysms in the pre-IVIg
era showed regression of aneurysms in about 50% of patients, development of
coronary stenosis in 20%, and persistence of aneurysms without stenosis in 40%.
In patients with giant coronary artery aneurysms (>8 mm absolute dimension),
about one-half developed stenosis or complete obstruction over about 20 years,
resulting in myocardial infarction in some.5 Coronary artery dilatation less than
8 mm generally improves over time, and most aneurysms smaller than 6 mm in
diameter fully resolve, as assessed with echocardiography.47 In younger children,
aneurysms are more likely to regress if they are in a more distal location or if
they are fusiform rather than saccular in shape.11 Children with aneurysms
should be followed up indefinitely because they remain at risk for persistent
myofibroblastic proliferation, resulting in encroachment on the lumen and
thrombus formation.
In a retrospective study of 546 patients with KD, in which 79% were treated
with IVIg, 5% were noted to have persistent aneurysms. Overall, there were low
rates of long-term cardiovascular complications over a mean follow-up period of
approximately 15 years after initial illness, and complications were restricted to
the subgroup with aneurysms.48 In the largest cohort outcomes study to date of
U.S. patients with KD who had coronary artery aneurysms, an overall regression
rate of 75% was found. Major cardiac adverse events occurred in approximately
5% of patients with coronary artery abnormalities, almost all in those with giant
coronary artery abnormalities (z score >10) at diagnosis.49
Generally, patients without known cardiac sequelae during the first 6 weeks of
their illness have been shown to return to their baseline state of health without
signs or symptoms of cardiac impairment.5 However, questions still remain as
to whether these patients may possibly be at some increased risk for premature
atherosclerosis and cardiovascular disease, although this has not been observed
to date.
Long-term Management
The AHA recommendations for the frequency of follow-up and testing, duration
of medical therapy (anticoagulation therapy), and physical activity restrictions
are based on the coronary artery status of the patient (Table 25-1).11 As children
grow, a more accurate way to study vascular structures and detect thrombosis or
stenosis may be with CT angiography or MR angiography if echocardiographic
437
CCIP.indb 437 3/13/18 4:19 PM

CCIP.indb 438
438
Table 25-1. Risk Stratification and Long-term Care of Patients with KD
Pharmacological Follow-up and
z Score Risk Level Therapy Physical Activity Diagnostic Testing Invasive Testing
<2 I: No coronary artery None beyond the first No restrictions beyond General CV risk assess- None
changes at any stage 6–8 wk first 6–8 wk ment and counseling
of illness
2 to <2.5 II: Dilatation only None beyond the first No restrictions beyond General CV risk assess- None
6–8 wk first 6–8 wk ment and counseling
≥2.5 to <5 III: Small aneurysm Low-dose aspirin, at Lifelong surveillance tailored to coronary artery status and age:
least until aneurysm • Echocardiography (serial)
regression is • Angiography (CT, MR imaging)
documented • Stress testing for inducible myocardial ischemia
With or without statin • Coronary intervention (catheter, surgical)
• Counseling
≥5 to <10 IV: Medium aneurysm Long-term antiplatelet
——Exercise recommendation
and absolute therapy and warfarin
——No contact or high-impact sports, given the risk of bleeding
dimension or low–molecular
——CV risk management
<8 mm weight heparin
With or without statin
≥10 or absolute V: Large and giant Long-term antiplatelet

dimension aneurysm therapy plus anticoag-
≥8 mm ulation therapy
With or without
β-blockers
With or without statin
CT, computed tomography; CV, cardiovascular; MR, magnetic resonance. Adapted from Newburger JW, Takahashi M, Burns JC. Kawasaki disease. J Am Coll Cardiol. 2016;67(14):1738–1749.
Additional data from McCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals
from the American Heart Association. Circulation. 2017;135:e927–e999
3/13/18 4:19 PM
Kawasaki Disease
evaluation is limited. Exercise stress testing is used in older children, in addition

to cardiac imaging. Recommendations for participation in competitive sports are
based on coronary involvement, stress test results, and anticoagulation therapy.
All patients who have a history of coronary aneurysms should undergo life-
long surveillance, with the primary goal of preventing coronary thrombosis and
associated complications. Even in patients without coronary artery involvement,
it is recommended that all undergo careful assessment of cardiovascular risk
factors and behaviors, including family history, weight, presence of dyslipidemia,
hypertension, smoking, obesity, diabetes mellitus, and sedentary lifestyle.
Key Points
•• Epidemiological data strongly suggest an infectious etiologic origin for
KD, which is the leading cause of acquired heart disease among children in
developed countries.
•• Whenever possible, patients should be treated within the first 10 days of fever
with IVIg (2 g/kg) and aspirin. Patients who received diagnoses after 10 days
should receive IVIg if they are still febrile, have increased inflammatory
marker levels, or have evidence of coronary artery abnormalities.
•• KD should be considered in the differential diagnosis of all infants with
persistent fever of unclear etiologic origin because they are at higher risk for
coronary aneurysm formation.
•• Approximately 10% to 20% of patients with KD do not respond to a single
dose of IVIg and often need a second dose of IVIg and, rarely, additional
treatment. These patients are at increased risk of developing coronary
artery abnormalities.
•• Patients with more severe coronary disease generally require long-term
follow-up into adulthood.

•• Kawasaki Disease Foundation. www.kdfoundation.org
•• Genetics Home Reference: Kawasaki Disease (U.S. National Library of
Medicine). ghr.nlm.nih.gov/condition/kawasaki-disease#genes
References
1) Kawasaki T, Kosaki F, Okawa S, Shigematsu I, Yanagawa H. A new infantile acute febrile muco-
cutaneous lymph node syndrome (MLNS) prevailing in Japan. Pediatrics. 1974;54(3):271–276
2) Melish ME, Hicks RM, Larson EJ. Mucocutaneous lymph node syndrome in the United States.
Am J Dis Child. 1976;130(6):599–607
3) Taubert KA, Rowley AH, Shulman ST. Seven-year national survey of Kawasaki disease and
acute rheumatic fever. Pediatr Infect Dis J. 1994;13(8):704–708
439
CCIP.indb 439 3/13/18 4:19 PM

4) Rowley AH. Kawasaki disease: novel insights into etiology and genetic susceptibility. Annu Rev
Med. 2011;62:69–77
5) Kato H, Sugimura T, Akagi T, et al. Long-term consequences of Kawasaki disease. A 10- to
21-year follow-up study of 594 patients. Circulation. 1996;94(6):1379–1385
6) Uehara R, Belay ED. Epidemiology of Kawasaki disease in Asia, Europe, and the United States.
J Epidemiol. 2012;22(2):79–85
7) Makino N, Nakamura Y, Yashiro M, et al. Descriptive epidemiology of Kawasaki
disease in Japan, 2011-2012: from the results of the 22nd nationwide survey. J Epidemiol.
2015;25(3):239–245
8) Fulton DR. Kawasaki disease. In: Long S, Pickering L, Prober C, eds. Principles and Practices of
Infectious Disease. 4th ed. Churchill Livingstone; 2007:988–993
9) Yorifuji T, Tsukahara H, Doi H. Breastfeeding and risk of Kawasaki disease: a nationwide
longitudinal survey in Japan. Pediatrics. 2016;137(6):e20153919
10) Leung DY, Giorno RC, Kazemi LV, Flynn PA, Busse JB. Evidence for superantigen involve-
ment in cardiovascular injury due to Kawasaki syndrome. J Immunol. 1995;155(10):5018–5021
management of Kawasaki disease: a statement for health professionals from the Committee on
Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease in the
Young, American Heart Association. Circulation. 2004;110(17):2747–2771
12) Rowley AH, Shulman ST, Mask CA, et al. IgA plasma cell infiltration of proximal
respiratory tract, pancreas, kidney, and coronary artery in acute Kawasaki disease. J Infect Dis.
2000;182(4):1183–1191
13) Rowley AH, Baker SC, Shulman ST, et al. RNA-containing cytoplasmic inclusion bodies
in ciliated bronchial epithelium months to years after acute Kawasaki disease. PLoS One.
2008;3(2):e1582
14) Rodó X, Curcoll R, Robinson M, et al. Tropospheric winds from northeastern China carry
the etiologic agent of Kawasaki disease from its source to Japan. Proc Natl Acad Sci USA.
2014;111(22):7952–7957
15) Amano S, Hazama F, Hamashima Y. Pathology of Kawasaki disease: I. Pathology and morpho-
genesis of the vascular changes. Jpn Circ J. 1979;43(7):633–643
16) Fujiwara H, Hamashima Y. Pathology of the heart in Kawasaki disease. Pediatrics.
1978;61(1):100–107
17) Orenstein JM, Shulman ST, Fox LM, et al. Three linked vasculopathic processes charac-
terize Kawasaki disease: a light and transmission electron microscopic study. PLoS One.
2012;7(6):e38998
18) Shulman ST, Rowley AH. Kawasaki disease: insights into pathogenesis and approaches to
treatment. Nat Rev Rheumatol. 2015;11(8):475–482
19) Takahashi K, Oharaseki T, Yokouchi Y. Update on etio and immunopathogenesis of Kawasaki
disease. Curr Opin Rheumatol. 2014;26(1):31–36
20) Uehara R, Yashiro M, Nakamura Y, Yanagawa H. Kawasaki disease in parents and children. Acta
Paediatr. 2003;92(6):694–697
21) Fujita Y, Nakamura Y, Sakata K, et al. Kawasaki disease in families. Pediatrics.
1989;84(4):666–669
22) Rowley AH, Wylie KM, Kim K-YA, et al. The transcriptional profile of coronary arteritis in
Kawasaki disease. BMC Genomics. 2015;16:1076
440
CCIP.indb 440 3/13/18 4:19 PM

Kawasaki Disease
23) Kanegaye JT, Van Cott E, Tremoulet AH, et al. Lymph-node-first presentation of Kawasaki
disease compared with bacterial cervical adenitis and typical Kawasaki disease. J Pediatr.
2013;162(6):1259–1263, 1263.e1–1263.e2
24) Kato H, Kanematsu M, Kato Z, Teramoto T, Kondo N, Hoshi H. Computed tomographic
findings of Kawasaki disease with cervical lymphadenopathy. J Comput Assist Tomogr.
2012;36(1):138–142
25) McCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis, Treatment, and Long-Term
Management of Kawasaki Disease: A Scientific Statement for Health Professionals from the
American Heart Association. Circulation. 2017;135(17):e927–e999
26) Kanegaye JT, Wilder MS, Molkara D, et al. Recognition of a Kawasaki disease shock syndrome.
Pediatrics. 2009;123(5):e783–e789
27) Dominguez SR, Friedman K, Seewald R, Anderson MS, Willis L, Glodé MP. Kawasaki disease
in a pediatric intensive care unit: a case-control study. Pediatrics. 2008;122(4):e786–e790
28) Tremoulet AH, Jain S, Chandrasekar D, Sun X, Sato Y, Burns JC. Evolution of laboratory values
in patients with Kawasaki disease. Pediatr Infect Dis J. 2011;30(12):1022–1026
29) Manlhiot C, Millar K, Golding F, McCrindle BW. Improved classification of coronary artery
abnormalities based only on coronary artery z-scores after Kawasaki disease. Pediatr Cardiol.
2010;31(2):242–249
30) Song E, Kajon AE, Wang H, et al. Clinical and virologic characteristics may aid distinction of
acute adenovirus disease from kawasaki disease with incidental adenovirus detection. J Pediatr.
2016;170:325–330
31) Newburger JW, Takahashi M, Burns JC, et al. The treatment of Kawasaki syndrome with
intravenous gamma globulin. N Engl J Med. 1986;315(6):341–347
32) Newburger JW, Takahashi M, Beiser AS, et al. A single intravenous infusion of gamma globulin
as compared with four infusions in the treatment of acute Kawasaki syndrome. N Engl J Med.
1991;324(23):1633–1639
33) Tse SML, Silverman ED, McCrindle BW, Yeung RSM. Early treatment with intravenous
immunoglobulin in patients with Kawasaki disease. J Pediatr. 2002;140(4):450–455
34) Muta H, Ishii M, Egami K, et al. Early intravenous gamma-globulin treatment for Kawasaki
disease: the nationwide surveys in Japan. J Pediatr. 2004;144(4):496–499
35) Terai M, Shulman ST. Prevalence of coronary artery abnormalities in Kawasaki disease is
highly dependent on gamma globulin dose but independent of salicylate dose. J Pediatr.
1997;131(6):888–893
36) Burns JC, Capparelli EV, Brown JA, Newburger JW, Glode MP; US/Canadian Kawasaki
Syndrome Study Group. Intravenous gamma-globulin treatment and retreatment in Kawasaki
disease. Pediatr Infect Dis J. 1998;17(12):1144–1148
37) Burns JC, Best BM, Mejias A, et al. Infliximab treatment of intravenous immunoglobulin-resis-
tant Kawasaki disease. J Pediatr. 2008;153(6):833–838
38) Youn Y, Kim J, Hong YM, Sohn S. Infliximab as the first retreatment in patients with kawasaki
disease resistant to initial intravenous immunoglobulin. Pediatr Infect Dis J. 2016;35(4):457–459
39) Tremoulet AH, Jain S, Jaggi P, et al. Infliximab for intensification of primary therapy for
Kawasaki disease: a phase 3 randomised, double-blind, placebo-controlled trial. Lancet.
2014;383(9930):1731–1738
40) Tremoulet AH, Pancoast P, Franco A, et al. Calcineurin inhibitor treatment of intravenous
immunoglobulin-resistant Kawasaki disease. J Pediatr. 2012;161(3):506–512
41) Inoue Y, Okada Y, Shinohara M, et al. A multicenter prospective randomized trial of cortico-
steroids in primary therapy for Kawasaki disease: clinical course and coronary artery outcome. J
Pediatr. 2006;149(3):336–341
441
CCIP.indb 441 3/13/18 4:19 PM

42) Newburger JW, Sleeper LA, McCrindle BW, et al; Pediatric Heart Network Investigators.
Randomized trial of pulsed corticosteroid therapy for primary treatment of Kawasaki disease. N
Engl J Med. 2007;356(7):663–675
43) Kobayashi T, Saji T, Otani T, et al; RAISE study group investigators. Efficacy of immu-
noglobulin plus prednisolone for prevention of coronary artery abnormalities in severe
Kawasaki disease (RAISE study): a randomised, open-label, blinded-endpoints trial. Lancet.
2012;379(9826):1613–1620
44) Chen S, Dong Y, Kiuchi MG, et al. Coronary artery complication in Kawasaki disease and
the importance of early intervention: a systematic review and meta-analysis. JAMA Pediatr.
2016;170(12):1156–1163
45) Sleeper LA, Minich LL, McCrindle BM, et al; Pediatric Heart Network Investigators.
Evaluation of Kawasaki disease risk-scoring systems for intravenous immunoglobulin resistance.
J Pediatr. 2011;158(5):831–835
46) Matsubara T, Furukawa S, Yabuta K. Serum levels of tumor necrosis factor, interleukin 2 recep-
tor, and interferon-gamma in Kawasaki disease involved coronary-artery lesions. Clin Immunol
Immunopathol. 1990;56(1):29–36
47) Fukushige J, Takahashi N, Ueda K, Hijii T, Igarashi H, Ohshima A. Long-term outcome of
coronary abnormalities in patients after Kawasaki disease. Pediatr Cardiol. 1996;17(2):71–76
48) Holve TJ, Patel A, Chau Q, Marks AR, Meadows A, Zaroff JG. Long-term cardiovascular
outcomes in survivors of Kawasaki disease. Pediatrics. 2014;133(2):e305–e311
49) Friedman KG, Gauvreau K, Hamaoka-Okamoto A, et al. Coronary artery aneurysms in
Kawasaki disease: risk factors for progressive disease and adverse cardiac events in the US
population. J Am Heart Assoc. 2016;5(9):e003289
442
CCIP.indb 442 3/13/18 4:19 PM

CHAPTER 26
Acute Rheumatic
Fever and
Rheumatic Heart
Disease
Swati Garekar, BC, and Bhadra Trivedi, MD
Introduction
The literal meaning of the Latin word rheum is “flow or movement;” the term
rheumatic is used with diseases that affect joints, which make movements difficult.
Rheumatic heart disease (RHD) is the chronic manifestation of acute rheumatic
fever (ARF). ARF is caused by an autoimmune response to certain streptococcal
strains in susceptible people and affects multiple organs, most severely the heart.
RHD is an important cause of heart failure in the developing world. This chapter
will cover ARF, with an emphasis on its carditis aspects and RHD.
Epidemiology
The epidemiology of RHD largely depends on factors that influence the epidemi-
ology of ARF. There is no RHD without a prior episode of ARF, whether ARF
has been diagnosed or not.
ARF is most common in the age group of 5 to 15 years and is rare before the
age of 2 years or after 35 years. There are approximately 4 to 5 million new cases
of ARF every year, of which 3 to 4 million are seen in children aged 5 to 14 years.1
There is no sex predilection, although RHD is more severe in female patients.
443
CCIP.indb 443 3/13/18 4:19 PM

ARF (and hence RHD) is prevalent in areas of the world that struggle with
overcrowded homes, maintaining sanitation, malnourishment, and poor access
to medical facilities and education. The causative Streptococcus organism is spread
via droplet transmission and is more likely to cross-infect in these conditions,
and the patient is less likely to receive timely treatment. Developed countries see
sporadic epidemics.
It is estimated that there are 15 to 20 million people living with RHD in the
world currently, of which 10% are children aged 5 to 14 years.1 RHD prevalence
varies widely, with very low rates in the United States2 to the highest rates in
South Central Asia, sub-Saharan Africa, and the indigenous population of
Australia (see Figure 26-1). A study from the 1990s showed a prevalence of 4
to 22.2 per 1,000 school children.3 However, in more recent studies, such as one
from Nicaragua,4 a much higher prevalence of up to 40 in 1,000 was reported in
children going to school. This change may be attributed to improved detection
methods and a rise in the global awareness of RHD. In endemic areas of the
world, more than 15% of heart failure is caused by RHD.
Etiologic Origins
Certain strains of group A β-hemolytic Streptococcus (GABHS) that cause
pharyngitis induce an autoimmune response in 0.3% to 3.0% of infected people.
Rheumatic strains of GABHS are described in terms of M protein types. Of
more than 130 M protein types, 15 lead to ARF.
The initial streptococcal pharyngitis may be asymptomatic or indistinguish-
able from viral pharyngitis. There is no correlation between severity of sore
throat symptoms and occurrence of ARF. Carriers of GABHS are not more
susceptible to getting ARF.5
FIGURE 26-1. Worldwide prevalence of rheumatic heart disease (RHD). From Seckeler MD,
Hoke TR. The worldwide epidemiology of acute rheumatic fever and rheumatic heart disease. Clin
Epidemiol. 2011;3(1):67–84.
444
CCIP.indb 444 3/13/18 4:19 PM

Acute R
heumatic F
ever and Rheumatic Heart Disease
Pathophysiology of Acute Rheumatic Fever

The molecular mechanism behind ARF is explained by the shared similarities
between streptococcal cell wall antigens and human heart cells and other
connective tissue. Several human leukocyte antigen alleles have been implicated
in the T and B cell response to streptococcal cell wall antigens and subsequent
production of autoantibodies against cardiac valvar tissue (endothelial cells).
The hemodynamic alterations associated with the damaged valves leads to the
typical clinical presentation of affected individuals. Mitral regurgitation occurs
in 95% of cases of ARF-associated carditis, while aortic regurgitation is seen in
20% to 25% of cases. See Box 26-1 for anatomic changes in ARF valvulitis.
The autoimmune phenomenon affects the pericardium and myocardium
too, but there are no chronic effects. Constrictive pericarditis is extremely rare.
The myocardium gets inflamed (edematous), but there is no cell damage. The
Box 26-1. Morphologic Findings at Echocardiography in

Rheumatic Valvulitis
Acute mitral valve changes
Annular dilation
Chordal elongation
Chordal rupture resulting in flail leaflet with severe mitral regurgitation
Anterior (or less commonly posterior) leaflet tip prolapse
Beading, nodularity of leaflet tips

Chronic mitral valve changes not seen in acute carditis
Leaflet thickening
Chordal thickening and fusion
Restricted leaflet motion
Calcification
Aortic valve changes seen in either acute or chronic carditis
Irregular or focal leaflet thickening
Coaptation defect
Restricted leaflet motion
Leaflet prolapse
Reprinted with permission from Gewitz MH, Baltimore RS, Tani LY, et al. Revision of the Jones Criteria for the
diagnosis of acute rheumatic fever in the era of doppler echocardiography. A scientific statement from the American
Heart Association. Circulation. 2015;131(20):1806–1818. ©2015 American Heart Association, Inc.
445
CCIP.indb 445 3/13/18 4:19 PM

heart failure in ARF (or RHD) is not caused by myocarditis but is secondary to
valvar damage.
The musculoskeletal and central nervous systems and the kidneys may also be
affected in ARF.
Pathophysiology of RHD
The initial injury inflicted to cardiac valves is followed by activation of an inflam-
matory cascade that takes a chronic form. Aschoff bodies, which are considered
pathognomonic of RHD, are aggregates of T cells, plasma cells, and activated
macrophages found in the cardiac perivascular interstitium 12 to 16 weeks after
onset of inflammation. Valvar damage results in a combination of regurgitation
and stenosis in 45%, pure regurgitation in 20%, and pure stenosis in 34%.5
Mitral Regurgitation
Mitral regurgitation is the most commonly found lesion. See Box 26-1 for the
rheumatic changes in the mitral valve. With progression of mitral regurgitation,
the left ventricle (LV) dilates and is hypercontractile because it can empty
into the left atrium easily. The LV function is maintained until late into the
disease process.
Aortic Regurgitation
See Box 26-1 for morphologic changes in the aortic valve that are brought about
by RHD. The regurgitant volume also overloads the LV and causes it to dilate.
Over time, the compensatory mechanisms are overcome, resulting in LV failure.
Mitral Stenosis
See Box 26-1 for morphologic changes in mitral stenosis. Mitral stenosis is
likely to be preceded by mitral regurgitation in most cases but rarely is the only
lesion. Mitral stenosis develops over time in mitral leaflets repeatedly damaged
by recurrent ARF carditis in cases where the initial ARF was associated with
severe carditis. Mitral stenosis is not seen in the initial ARF carditis. Patients
with a combination of mitral regurgitation and mitral stenosis have the most
deformed valves.
Aortic Stenosis
See Box 26-1 for morphologic changes in aortic stenosis. The aortic cusps
become thickened with progression of disease and calcification. The calcified
cusps have poor excursion, leading to a restricted orifice. The LV hypertrophies
in response, eventually leading to failure.
446
CCIP.indb 446 3/13/18 4:19 PM

Acute Rheumatic Fever and Rheumatic Heart Disease
Tricuspid and Pulmonary Regurgitation or Stenosis

The tricuspid and pulmonary valves are uncommonly involved, although micro-
scopic evidence is prevalent.
Natural History of ARF and RHD

Clinical manifestations of ARF are evident after 2 to 4 weeks of the GABHS
pharyngitis. All organ systems other than the heart are only transiently affected.
Approximately 30% to 70% of patients with ARF develop carditis, of whom 15%
to 50% have severe associated heart failure.6,7 The afflicted valves are most likely
to show improvement in the first 6 months after an episode of ARF.
RHD occurs insidiously over the years after the attack of ARF.
Approximately 35% to 65% of patients with ARF develop RHD.8,9 Each repeat
attack of ARF on an already injured valve leads to further damage. A person
with a history of ARF is more likely to have recurrent attacks. An initially mild
carditis is likely to resolve without clinical manifestations, in contrast to a case of
severe initial carditis, with recurrent superimposed attacks. When compared to
the natural history in developed countries, chronic RHD in developing countries
occurs early on, evolves more rapidly with greater severity, and is more likely
to lead to heart failure. Untreated RHD also predisposes the patient to atrial
fibrillation, stroke, infective endocarditis, and high-risk pregnancy. Symptomatic
heart failure secondary to mitral stenosis especially has a high mortality rate if
left untreated, with a 0% to 15% 10-year survival rate.10
Noncardiac Clinical Features of ARF

Polyarthritis and polyarthalgia are the most common clinical findings and are
best described as a migratory involvement of large joints. Chorea is characterized
by involuntary movements of the face and extremities that increase with exci-
tation and decrease with sleep. The erythema marginatum of ARF is a macule
with serpiginous margins and central clearing seen on the trunk or arms and
thighs. Subcutaneous nodules are rare and occur on the elbows, wrists, knees,
ankles, scalp, and back, with the size ranging from 5 mm to 20 mm. Arthritis,
carditis, and erythema marginatum are indicative of ARF, while chorea and
subcutaneous nodules are associated with ARF in the past. There is a female
predominance for chorea.
Cardiac Clinical Features of ARF

Cardiac symptoms are most likely to appear within the first 2 weeks of ARF.
Mild carditis may be asymptomatic or may manifest with a murmur. Patients
with moderate or severe mitral or aortic regurgitation typically present with
dyspnea of all degrees and cough. The clinical features are also affected by the
447
CCIP.indb 447 3/13/18 4:19 PM

severity of the lesion. Sudden-onset mitral regurgitation due to mitral leaflet

chordal rupture may manifest with flash pulmonary edema by coughing with
frothy sputum and air hunger.
Tachycardia is a consistent finding in the presence of clinically significant mitral
regurgitation and aortic regurgitation. There is accompanying tachypnea and
increased precordial activity.
Patients with mitral regurgitation have a high-pitched holosystolic
murmur best heard at the apex. There is poor correlation of severity of mitral
regurgitation with intensity of the murmur. Carey Coombs murmur is a
mid-diastolic murmur caused by increased flow across the mitral valve secondary
to mitral regurgitation.
Patients with acute aortic regurgitation have a normal pulse pressure. Aortic
regurgitation produces a soft, short, early diastolic murmur at the aortic area.
Clinical Features of RHD

Mitral regurgitation and aortic regurgitation may remain asymptomatic for years
because they may be well compensated. They manifest with dyspnea of varying
degrees when decompensation starts. Severe aortic stenosis manifests with chest
pain, poor exercise tolerance, and syncope as the cardiac output is fixed.
In chronic mitral regurgitation, the precordial activity is increased, and the apex
beat is shifted outward as the LV is dilated. S2 is clearly split because the A2
component occurs early (LV ejection time is less as part of the stroke volume
is pushed to the left atrium). The high-pitched holosystolic murmur of chronic
mitral regurgitation is best heard at the apex. Its intensity correlates with the
severity. The S2 may be loud if there is associated pulmonary hypertension
secondary to increased LV diastolic pressure with dysfunction.
Patients with chronic aortic regurgitation have a wide pulse pressure. A high-
pitched diastolic murmur is audible at the upper sternal border. See Figure 26-2
for manifestations of aortic regurgitation.
Mitral stenosis is a late presentation in RHD, although it has been described
in children younger than 5 years in the South Asian population. Usual
presenting symptoms are dyspnea on exertion, cough, wheeze, and orthopnea.
On examination, there is a low-pitched diastolic murmur best heard at the apex,
along with a characteristic early diastolic opening snap.
Aortic stenosis manifests with angina, syncope, and dyspnea on exertion.
Physical examination findings are clinically significant for low-volume pulses
448
CCIP.indb 448 3/13/18 4:19 PM

Acute R
heumatic F
FIGURE 26-2. Manifestations of chronic aortic regurgitation. L = left, R = right. From Runge MS,
Patterson C, Stouffer GA. Netter’s Cardiology. 2nd ed. Philadelphia, PA: Saunders, 2010: 301.
and a systolic ejection murmur at the upper sternal border. An ejection click
is uncommon.
Diagnostic Approach
The approach to the patient with suspected ARF is governed by the need to
recognize carditis, treat it, and initiate antibiotic prophylaxis to prevent valve
damage. The need for early and accurate diagnosis of ARF and RHD is also
justified by the cost incurred to treat them. A rough estimate of the cost of
rheumatic valve repair and replacement in the United States is around $25,000.11
In the past, carditis was diagnosed purely on the basis of clinical examination
findings. However, knowing that approximately 65% of patients with ARF
(as diagnosed via conventional criteria) develop RHD, it is possible that the
remaining 35% of cases have subclinical carditis, which can be detected through
echocardiography. An important modification in the current update of the
American Heart Association (AHA) and American College of Cardiology
(ACC) guideline for diagnosis of ARF is that subclinical carditis diagnosed via
echocardiography is now a major criterion.12 As noted previously, the advantage
of identifying a case of subclinical carditis is that the individual could be admin-
istered penicillin prophylaxis for future GABHS pharyngitis and thus prevent
subsequent ARF episodes.
In many instances, in parts of the world with a high prevalence of ARF,
physicians prefer to label patients as having “presumptive RHD” and follow
449
CCIP.indb 449 3/13/18 4:19 PM

them for 1 to 2 years to monitor the evolution of the disease; the label of RHD
may be withdrawn later, if appropriate.
Diagnosis of ARF
Jones first developed diagnostic criteria for ARF in 1944. The criteria have been
revised multiple times, most recently in 2015 (see Box 26-2).6 The 2015 revision
states that echocardiography with Doppler imaging is indicated in all cases of
suspected or confirmed ARF. It adds that subclinical carditis may be diagnosed
if criteria as outlined in Box 26-1 and Box 26-3 are met in a patient with no
cardiac symptoms.
In brief, for the diagnosis of ARF, evidence of a preceding GABHS infection
is a requirement. The laboratory test results indicative of GABHS include
antistreptolysin O, anti-DNAase B, positive throat culture result for GABHS,
or positive rapid antigen test result (in cases with high pretest probability of
GABHS pharyngitis). A rising titer is preferred over just a single increased
number and should be evaluated in the acute setting and again 14 to 28 days
later. The combination of antistreptolysin O and anti-DNAase B titers increases
the specificity of diagnosis to 90%.
In addition, 2 major or 1 major and 2 minor Jones criteria must be met. There
are 2 exceptions to the rule of having evidence of preceding GABHS infection:
isolated chorea and patients who present with RHD and no prior recallable
history of ARF.12
The AHA has provided further clarification in cases that manifest with
chorea, nodules, and carditis in the 2015 revision of the Jones criteria.12
Diagnosis of RHD
RHD is easily diagnosed when echocardiography shows findings of damaged
valves in a patient with a history of ARF. However, in a large proportion of cases,
there is echocardiographic evidence of RHD, but no history of ARF is elicited.
The 2015 revision of the Jones criteria12 has a provision to diagnose ARF and
RHD in such instances. It recommends the use of stringent echocardiographic
criteria (Boxes 26-1 and 26-3) to diagnose rheumatic carditis (acute or chronic).
The World Heart Federation guidelines for echocardiographic diagnosis of
rheumatic heart disease mention using Doppler echocardiography alone for
diagnosis,13 while the ACC and AHA guidelines for the diagnosis of ARF
endorse Doppler and 2-dimensional echocardiography to diagnose RHD.12
The differential diagnosis of ARF includes arthritis, murmurs, heart failure, and
rash. Migratory polyarthritis is the most common manifestation of ARF and has
a long differential diagnosis outside the scope of this chapter. However, it must
be mentioned that poststreptococcal reactive arthritis (which is not associated
450
CCIP.indb 450 3/13/18 4:19 PM

Box 26-2. Revised Jones Criteria for Rheumatic Fever

For all patient populations with evidence of preceding GAS infection
Diagnosis: Initial ARF: 2 major manifestations or 1 major
plus 2 minor manifestations
Recurrent ARF: 2 major manifestations or 1 major

and 2 minor manifestations or 3
minor manifestations
Low-risk populationsa Moderate and high-risk
populations
Major Criteria
Carditisb—clinical and/or subclinical Carditis—clinical and/or
subclinical
Arthritis—polyarthritis only Arthritis—monoarthritis or

polyarthritis
Chorea Polyarthralgiac
Erythema marginatum Chorea
Subcutaneous nodules Erythema marginatum
Subcutaneous nodules
Minor Criteria
Polyarthralgia Monoarthralgia
Fever (≥38.5°C [≥101.3°F]) Fever (≥38°C [≥100.4°F])
ESR ≥60 mm in the first hour and/or ESR ≥30 mm in the first hour
CRP level ≥3.0 mg/L (≥28.58 nmol/L)d and/or CRP level ≥3.0 mg/L
(≥28.58 nmol/L)
Prolonged PR interval Prolonged PR interval

ARF, acute rheumatic fever; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; GAS, group A
Streptococcus. Reprinted with permission from Gewitz MH, Baltimore RS, Tani LY, et al. Revision of the Jones
Criteria for the diagnosis of acute rheumatic fever in the era of doppler echocardiography. A scientific statement
from the American Heart Association. Circulation. 2015;131(20):1806–1818. ©2015 American Heart Association, Inc.
a
Low-risk populations are those with ARF incidence ≤2 per 100,000 school-aged children or all-age rheumatic heart
disease prevalence of ≤1 per 1,000 population per year.
b
Subclinical carditis indicates echocardiographic valvulitis.
c
Should only be considered as a major manifestation in moderate- to high-risk populations after exclusion of other
causes. Additionally, joint manifestations can only be considered in either the major or minor categories, but not
both in the same patient.
d
The CRP value must be greater than the upper limit of normal. Also, because ESR may evolve during the course of
ARF, peak ESR values should be used.
451
CCIP.indb 451 3/13/18 4:19 PM

Box 26-3. Doppler Findings in Rheumatic Valvulitis

Pathologic mitral regurgitation (all 4 criteria must be met)
Seen in at least 2 views
Jet length ≥2 cm in at least 1 view
Peak velocity >3 m/s
Pansystolic jet in at least 1 envelope

Pathologic aortic regurgitation (all 4 criteria must be met)
Seen in at least 2 views
Jet length ≥1 cm in at least 1 view
Peak velocity >3 m/s
Pandiastolic jet in at least 1 envelope

Reprinted with permission from Gewitz MH, Baltimore RS, Tani LY, et al. Revision of the Jones Criteria for the
diagnosis of acute rheumatic fever in the era of doppler echocardiography. A scientific statement from the American
Heart Association. Circulation. 2015;131(20):1806–1818. ©2015 American Heart Association, Inc.
with valvulitis) has a shorter latent period (7–10 days), involves small joints
at the same time, and is not migratory. In such cases, in high-risk areas of the
world, clinicians may choose to perform an echocardiogram for detection of
subclinical rheumatic carditis.
Table 26-1 lists the common differential diagnoses of pediatric heart failure.
Table 26-1. Differential Diagnosis of Heart Failure

Disease Cardiac Involvement
Mitral valve prolapse Severe mitral regurgitation
Autoimmune disease (systemic Mitral regurgitation

lupus erythematosus, juvenile
idiopathic arthritis)
Infective endocarditis Severe valvar affliction
Anemia Increased circulating blood volume
Myocarditis Depressed contractility of the

ventricles
Congenital valvar disease (mitral Severe valvar affliction

arcade, dysplastic aortic valve)
452
CCIP.indb 452 3/13/18 4:19 PM

Isolated mitral valve prolapse with mitral regurgitation is a common

condition that superficially may mimic the prolapse seen in rheumatic carditis.
Close inspection of the rheumatic valve on echocardiograms will show that the
anterior leaflet is not redundant or myxomatous. In addition, the tip of the leaflet
prolapses in rheumatic carditis (leaving the central portion normal), in contrast
to isolated mitral valve prolapse, where the whole leaflet prolapses.
Management
Management can be broadly divided into 2 categories. The first deals with
prevention of ARF and RHD. The second is treatment for ARF and the diseased
rheumatic valves.
Primordial Prevention
Primordial prevention is aimed at preventing occurrence of GABHS pharyngitis
to eliminate future episodes of ARF. Efforts are directed by national govern-
ments to improve living conditions of the poor by reducing overcrowding,
improving hygiene, eliminating malnourishment, enabling easy access to medical
facilities, and educating the populace.
Primary Prevention
Primary prevention aims to treat GABHS pharyngitis promptly to prevent
progression to ARF. Two separate meta-analyses showed that treatment of
streptococcal pharyngitis decreased the risk of ARF by 60% to 80%.14,15
The penicillin group of drugs is the mainstay of antibiotic treatment for
GABHS because there is no evidence of resistance developing against this
group of drugs to date (see Table 26-2). It is proven that antibiotic treatment
started within 9 days of the onset of infection is protective against ARF and
RHD.16 Challenges to primary prevention are that a large proportion17,18 of
GABHS pharyngitis is subclinical (no symptoms implies no treatment) and that
patients and their caretakers may not be aware of the importance of starting and
completing the antibiotic course after proven GABHS pharyngitis. In addition,
diagnostic tests are expensive for mass use, as is the mass treatment of all sore
throats without establishing the diagnosis of GABHS pharyngitis to circumvent
diagnostic tests.19
A vaccine against group A Streptococcus would also be a form of primary
prevention. Vaccines based on the C terminal end of the M protein of group A
Streptococcus have been showing encouraging results in animal studies.20
Treatment of ARF
The goal of treatment is to reduce inflammation, which typically lasts for
12 weeks. The first line of anti-inflammatory medicine is aspirin. See
453
CCIP.indb 453 3/13/18 4:19 PM

Table 26-2. Treatment Regimens for Group A

Streptococcal Infection
Drug Dosage Duration
Patients without penicillin allergy
Penicillin V, oral Children: 250 mg 2 or 3 times daily 10 d
Amoxicillin, oral 50 mg/kg once daily (maximum, 1,000 mg) 10 d

OR 25 mg/kg twice daily (maximum, 500
mg)
Penicillin G benzathine, <27 kg: 600,000 U

intramuscular
≥27 kg: 1,200,000 U Single dose
Patients with penicillin allergy
Clindamycin, orala 30 mg/kg per day in 3 divided doses (maxi- 10 d

mum, 900 mg per day)
Azithromycin, oralb 12 mg per kg once daily (maximum, 500 mg) 5d

Adapted from Shulman ST, Bisno AL, Clegg HW, et al. Clinical practice guideline for the diagnosis and management
of group a streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. Clin Infect Dis.
2012;55(10):e86–e102.
a
Dose guidance updated from original guidelines to reflect current recommendations in the American Academy of
Pediatrics Red Book.
b
Resistance of group A Streptococcus to this agent is well known and varies geographically and temporally.
Table 26-3 for dosage regime.21 Aspirin brings resolution of joint symptoms
within 24 to 48 hours; this also helps differentiate arthritis of rheumatic fever
from other forms of arthritis.
With severe carditis causing florid heart failure, steroids are additionally used
in many protocols, including Indian, Australian, and World Health Organization
guidelines.22 Chorea resolves spontaneously, although sedatives and haloperidol
are commonly used.
Treatment of Florid Heart Failure in ARF

Florid heart failure in ARF is caused by uncontrolled mitral regurgitation in
most cases. It requires anti–heart failure therapy. Intensive use of diuretics,
digoxin, and afterload reducers, such as angiotensin-converting enzyme (ACE)
inhibitors (enalapril, lisinopril) is required.23 ACE inhibitors also remodel the
LV and delay the progression of mitral regurgitation.
If the patient continues to deteriorate despite intensive medical management,
surgical intervention is indicated, even in the presence of active carditis.
Accepted markers of active carditis are high ESR and CRP levels. Mitral or
aortic valve repair or replacement, as indicated, is lifesaving.
454
CCIP.indb 454 3/13/18 4:19 PM

Table 26-3. Use of Aspirin and Steroids for Control

of Inflammation
Drug Dose
Arthritis with or without mild carditis
Aspirin Regime 1. Starting doses: Children, 100 mg/kg/day for

2–3 weeks; adults, 6–8 g/day (divide into 4–5 doses).
Tapering doses: Once symptoms have resolved, taper to
60–70 mg/kg/day. For older children, administer 50 mg/kg/
day for a total of 12 weeks.
Regime 2. 50–60 mg/kg /day for a total of 12 weeks.
Naproxen (aspirin 10–20 mg/kg/day

intolerance detected)
If no response to Switch to steroids

aspirin after 4 d
Moderate to severe carditis
Steroids Regime 1. Prednisolone: 2 mg/kg/day, maximum of 80

mg/day, until ESR normalizes—usually 2 weeks. Taper over
2–4 weeks by reducing the dose by 2.5–5.0 mg every
third day. Start aspirin 50–75 mg/kg/day simultaneously to
complete a total of 12 weeks of treatment.
Regime 2. Prednisolone: Administer the same doses

for 3–4 weeks. Taper slowly to cover a total period of
10–12 weeks.
Nonresponders
Methylprednisolone If there is no response to oral steroid therapy, then start

(intravenous) intravenous methylprednisolone at 30 mg/kg/day for
3 days.
ESR, erythrocyte sedimentation rate. From reference 21.
Treatment of RHD
Chronic Mitral Regurgitation
Asymptomatic patients with normal LV function can be serially followed up
for years. Medical treatment for chronic mitral regurgitation involves the use
of ACE inhibitors, diuretics, and digoxin.24 Some studies show limited or no
role for ACE inhibitors;24 however, they are widely used. Surgical outcome is
suboptimal once LV dysfunction sets in.
Mitral Stenosis
The medical management of mitral stenosis is primarily aimed at controlling
symptoms and arrhythmias, as well as preventing thrombus formation until
455
CCIP.indb 455 3/13/18 4:19 PM

intervention. β-blockers are the drug of choice for controlling atrial fibrillation
caused by clinically significant dilatation of the left atrium. Digitalis and
amiodarone are second-line drugs for rate control. Diuretics reduce preload, as
well as pulmonary congestion, and help relieve symptoms. An individual may
receive warfarin to prevent thrombus formation due to atrial fibrillation. A
severely enlarged left atrium will also justify the use of anticoagulation.
Surgical treatment for mitral stenosis is by commissurotomy or valve replace-
ment. However, transcatheter balloon mitral valvotomy is the treatment of
choice if the valve leaflets are pliable and noncalcified and there is absence of
the subvalvar component of stenosis.
Aortic Regurgitation
Diuretics and ACE inhibitors help by reducing preload and afterload.
Angiotensin receptor blocking agents are specifically indicated when the aortic
root is dilated. Medical therapy has only a limited role in aortic regurgitation.
Surgical Interventions
Available surgical options are aortic valve repair, aortic valve replacement,
and using the patient’s own pulmonary valve as an aortic autograft (Ross
procedure).25 Aortic valve replacement with mechanical valves requires
lifelong anticoagulant therapy, while the Ross procedure does not require
anticoagulation therapy.
Aortic Stenosis
Medical management has a limited role in aortic stenosis. All symptomatic
patients require intervention. Transcatheter balloon aortic valvuloplasty is not
suitable for the rheumatic aortic valve. A limited temporizing indication is
when surgical risk is too high in the presence of severe LV dysfunction. The
Ross procedure is an alternative to mechanical aortic valve replacement with
a comparable long-term outcome to valve replacement, without the need for
anticoagulation therapy.
A Note on Bioprosthetic Replacement Valves
Bioprosthetic valves provide a substantial benefit over metallic valves because
they do not require anticoagulation therapy. The implication is more profound
when it comes to replacing valves in female patients of childbearing age, where
the benefit of not requiring warfarin is obvious. The currently available biopros-
thetic valves usually last for 10 years. This is in comparison to the almost lifelong
durability of the metallic valve.
Secondary Prophylaxis for ARF and RHD

Secondary prophylaxis is aimed at preventing carditis among those who have
had a prior episode of ARF. Each new attack of GABHS damages the valve
even more, so all patients who have had an episode of ARF or who have received
456
CCIP.indb 456 3/13/18 4:19 PM

a diagnosis of RHD should receive secondary prophylaxis. See Table 26-4 for
antibiotic options with doses for secondary prophylaxis and Table 26-5 for
duration of secondary prophylaxis.
For patients who are taking warfarin, deep intramuscular penicillin should be
avoided, and another alternative should be considered.
The consensus is toward no restriction for mild valvar lesions without any
chamber dilatation or hypertrophy. Individuals with moderate lesions should
restrict themselves to low to moderate dynamic and static sports. Those with
severe lesions should be prohibited from participating in any competitive sports.
The available guidelines are provided in the resources at the end of this chapter.
According to AHA guidelines, infective endocarditis prophylaxis is limited to
patients with RHD who have undergone valve replacement surgeries.26 However,
the recent National Institute of Health and Care Institute guidelines and
Australian guidelines suggest infective endocarditis prophylaxis for patients with
all acquired valvar lesions.27 These guidelines are followed in most endemic areas
of RHD in the world. Because patients with RHD will have been taking long-
term penicillin prophylaxis (at a lower dose than what is used for endocarditis
prophylaxis), they are more likely to have colonization by resistant organisms.
Therefore, they should be given azithromycin, clarithromycin, or clindamycin
instead of penicillin prophylaxis for infective endocarditis.
Ongoing Care
Follow-up
Children with clinically significant valvar lesions should be followed up every
6 months by a pediatric cardiologist. This is an opportunity to adjust medica-
tions, check for clinical or echocardiographic indications for invasive interven-
tion, and remind the family about the importance of penicillin prophylaxis.
Complications
Uncontrolled RHD may be complicated by florid heart failure, as detailed pre-
viously. Atrial fibrillation, stroke, infective endocarditis, and high-risk pregnancy
are also potential complications.
457
CCIP.indb 457 3/13/18 4:19 PM

Table 26-4. Secondary Prevention of Rheumatic Fever

(Prevention of Recurrent Attacks)
Agent Dose Mode
Benzathine penicillin G 0.6 million units for children ≤27 kg, 1.2 Intramuscular
million units for those >27 kg every 4 wka
Penicillin V 250 mg twice daily Oral
Sulfadiazine 0.5 g once daily for patients ≤27 kg, 1.0 g Oral
once daily for patients >27 kg
For individuals who are allergic to penicillin and sulfadiazine
Macrolide or azalide Variable Oral

From Gerber MA, Baltimore R, Eaton C, et al. Prevention of rheumatic fever and diagnosis and treatment of
acute streptococcal pharyngitis. A scientific statement from the American Heart Association, Rheumatic Fever,
Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Quality of
Care and Outcomes Research Interdisciplinary Working Group. Circulation. 2009;119(11):1541–1551.
a
In high-risk populations, administration every 3 weeks is justified and recommended.
Table 26-5. Duration of Secondary Prophylaxis

Patient Duration
Patients without proven carditis For 5 years after the last attack or until 18 years of
age (whichever is longer)
Patients with carditis For 10 years after the last attack or at least until
25 years of age (whichever is longer)
More severe valvar disease For life
After valve surgery For life

Reprinted from World Health Organization. WHO Expert Consultation on Rheumatic Fever and Rheumatic Heart
Disease. Geneva, Switzerland: World Health Organization; 2004. Copyright 2004.
Key Points
•• ARF results from an autoimmune response to acute group A β-hemolytic
streptococcal pharyngitis; RHD is the only chronic manifestation of ARF.
•• ARF and RHD are endemic in parts of the world with poverty, malnourish-
ment, and illiteracy and are responsible for 15% of cases of heart failure there.
•• ARF and RHD are diagnosed on the basis of the modified Jones criteria.
•• RHD commonly afflicts the mitral and aortic valves, with regurgitation being
a common pathologic finding.
•• A patient with ARF is likely to experience repeated attacks of GABHS-
induced ARF, each time damaging the valves even more; therefore, prophylac-
tic penicillin is indicated for patients with ARF and RHD to prevent further
episodes of ARF.
458
CCIP.indb 458 3/13/18 4:19 PM

Acute R
heumatic F
•• RHD necessitates careful long-term follow-up, medical therapy, and catheter-

ization or surgical intervention in patients with severely affected valves.

•• RHD Australia. www.rhdaustralia.org.au
•• Rheumatic Fever and Heart Disease (National Heart Foundation of New
Zealand). www.heartfoundation.org.nz/your-heart/heart-conditions/
rheumatic-heart-disease
•• Rheumatic Fever Helpline (American Heart Association). 800/242-8721
•• What About My Child and Rheumatic Fever? (American Heart Association).
www.heart.org/idc/groups/heart-public/@wcm/@hcm/documents/
downloadable/ucm_300321.pdf
•• RHD Action Alliance. rhdaction.org
Resources for Sports Participation

•• Maron BJ, Zipes DP, Kovacs RJ. Eligibility and disqualification recommen-
dations for competitive athletes with cardiovascular abnormalities: a scientific
statement from the American Heart Association and American College of
Cardiology. J Am Coll Cardiol. 2015;Nov 2:[Epub ahead of print]
•• Recommendations for competitive sports participation in athletes with car-
diovascular disease. A consensus document from the Study Group of Sports
Cardiology of the Working Group of Cardiac Rehabilitation and Exercise
Physiology and the Working Group of Myocardial and Pericardial Diseases of
the European Society of Cardiology. Eur Heart J. 2005;26(14):1422–1445
•• Dean PN, Gillespie CW, Greene EA, et al. Sports participation and quality
of life in adolescents and young adults with congenital heart disease. Congenit
Heart Dis. 2015; 10:169–179
•• Hirth A, Reybrouck T, Bjarnason-Wehrens B, Lawrenz W, Hoffmann A.
Recommendations for participation in competitive and leisure sports in
patients with congenital heart disease: a consensus document. Eur J Cardiovasc
Prev Rehab. 2006;13(3):293–299
References
1) Carapetis JR, Steer AC, Mulholland EK, Weber M. The global burden of group A streptococcal
diseases. Lancet Infect Dis. 2005;5(11):685–694
2) Stockmann C, Ampofo K, Hersh AL, et al. Evolving epidemiologic characteristics of invasive
group a streptococcal disease in Utah, 2002-2010. Clin Infect Dis. 2012;55(4):479–487
3) Longo-Mbenza B, Bayekula M, Ngiyulu R, et al. Survey of rheumatic heart disease in school
children of Kinshasa town. Int J Cardiol. 1998;63(3):287–294
4) Paar JA, Berrios NM, Rose JD, et al. Prevalence of rheumatic heart disease in children and
young adults in Nicaragua. Am J Cardiol. 2010;105(12):1809–1814
459
CCIP.indb 459 3/13/18 4:19 PM

5) Shulman ST, Bisno AL, Clegg HW, et al. Clinical Practice Guideline for the Diagnosis and
Management of Group A Streptococcal Pharyngitis: 2012 Update by the Infectious Diseases
Society of America. Clin Infect Dis. 2012
6) Chockalingam A, Gnanavelu G, Elangovan S, Chockalingam V. Current profile of acute
rheumatic fever and valvulitis in southern India. J Heart Valve Dis. 2003;12(5):573–576
7) Sanyal SK, Thapar MK, Ahmed SH, Hooja V, Tewari P. The initial attack of acute rheumatic
fever during childhood in North India; a prospective study of the clinical profile. Circulation.
1974;49(1):7–12
8) Bland EF, Duckett Jones T. Rheumatic fever and rheumatic heart disease; a twenty year report
on 1000 patients followed since childhood. Circulation. 1951;4(6):836–843
9) Majeed HA, Batnager S, Yousof AM, Khuffash F, Yusuf AR. Acute rheumatic fever and the
evolution of rheumatic heart disease: a prospective 12 year follow-up report. J Clin Epidemiol.
1992;45(8):871–875
10) WHO Technical Report, Series. Rheumatic Fever and Rheumatic Heart Disease: Report
of a WHO Expert Panel. Geneva, Switzerland: October 29 to November 1, 2001. Geneva,
Switzerland: WHO; 2004
11) Colquhoun SM, Carapetis JR, Kado JH, Steer AC. Rheumatic heart disease and its control in
the Pacific. Expert Rev Cardiovasc Ther. 2009;7(12):1517–1524
12) Gewitz MH, Baltimore RS, Tani LY, et al; American Heart Association Committee on
Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease
in the Young. Revision of the Jones Criteria for the diagnosis of acute rheumatic fever in the
era of Doppler echocardiography: a scientific statement from the American Heart Association.
Circulation. 2015;131(20):1806–1818
13) Reményi B, Wilson N, Steer A, et al. World Heart Federation criteria for echocardiographic
diagnosis of rheumatic heart disease—an evidence-based guideline. Nat Rev Cardiol.
2012;9(5):297–309
14) Lennon D, Kerdemelidis M, Arroll B. Meta-analysis of trials of streptococcal throat treatment
programs to prevent rheumatic fever. Pediatr Infect Dis J. 2009;28(7):e259–e264
15) Robertson KA, Volmink JA, Mayosi BM. Antibiotics for the primary prevention of acute
rheumatic fever: a meta-analysis. BMC Cardiovasc Disord. 2005;5(1):11
16) American Academy of Pediatrics. Group A streptococcal infections. In: Kimberlin DW, Brady
MT, Jackson MA, Long SS, eds. Red Book: 2015 Report of the Committee on Infectious Diseases.
30th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2015:732–744
17) Veasy LG. Lessons learned from the resurgence of rheumatic fever in the United States. In:
Narula J, Virmani R, Reddy KS, Tandon R, eds. Rheumatic Fever. Washington, DC: American
Registry of Pathology. Armed Forces Institute of Pathology; 1999:69–78
18) Veasy LG, Wiedmeier SE, Orsmond GS, et al. Resurgence of acute rheumatic fever in the
intermountain area of the United States. N Engl J Med. 1987;316(8):421–427
19) Kumar RK, Tandon R. Rheumatic fever & rheumatic heart disease: the last 50 years. Indian J
Med Res. 2013;137(4):643–658
20) McNeilly C, Cosh S, Vu T, et al. Predicted coverage and immuno-safety of a recombinant
C-repeat region based Streptococcus pyogenes vaccine candidate. PLoS One. 2016;11(6):
e0156639
21) Mishra S, Saxena A, Kumar RK et al. Consensus guidelines on pediatric acute rheumatic fever
and rheumatic heart disease. Indian Pediatr. 2008;45
22) Carapetis JR, Brown A, Wilson NJ, Edwards KN; Rheumatic Fever Guidelines Writing Group.
An Australian guideline for rheumatic fever and rheumatic heart disease: an abridged outline.
Med J Aust. 2007;186(11):581–586
23) Boon NA, Bloomfield P. The medical management of valvar heart disease. Heart. 2002;87(4):
395–400
460
CCIP.indb 460 3/13/18 4:19 PM

24) Borer JS, Bonow RO. Contemporary approach to aortic and mitral regurgitation. Circulation.
2003;108(20):2432–2438
25) Kalfa D, Mohammadi S, Kalavrouziotis D, et al. Long-term outcomes of the Ross procedure
in adults with severe aortic stenosis: single-centre experience with 20 years of follow-up. Eur J
Cardiothorac Surg. 2015;47(1):159–167, discussion 167
26) Wilson W, Taubert KA, Gewitz M, et al. Prevention of Infective Endocarditis. Guidelines from
the American Heart Association: a Guideline from the American Heart Association Rheumatic
Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in
the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and
Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group.
Circulation. 2007;116(15):1736–1754
27) Centre for Clinical Practice at NICE (UK). Prophylaxis against infective endocarditis:
antimicrobial prophylaxis against infective endocarditis in adults and children undergoing
interventional procedures. 2008. Updated in 2016.
461
CCIP.indb 461 3/13/18 4:19 PM

CCIP.indb 462 3/13/18 4:19 PM
CHAPTER 27
Cardiotoxicity
Among Survivors of
Childhood Cancer
Kelley K. Hutchins, DO, MPH, and Michael U. Callaghan, MD
Introduction
Survival rates among patients with childhood cancers have increased substantially
over the past 5 decades. Thanks to advancements in detection and treatment, there
are more survivors of childhood cancer living today than ever before. With this
advancement, however, comes the need for improvement in long-term follow-up
care to improve the morbidity and early mortality that exists once these patients
are in remission and eventually cured of cancer, as well as to improve their quality
of life.
It is imperative that the primary care practitioner realizes that there are impor
tant implications after cancer treatment for survivors of childhood cancer and
that the size of this population is growing. It is in the best interest of not only the
survivor but also the provider to have knowledge of patients’ cancer history. It is
not uncommon for patients to be unaware of when they received therapy, what
type of therapies they received, or even what kind of cancer they had. Additionally,
many may not be aware that they are at increased risk of having long-term effects.
Among the most pronounced adverse late effects is increased morbidity and
early mortality from cardiotoxicity. Several key factors have been identified that
put certain patients at particularly increased risk. Multiple preventive strategies
and interventions have been studied, but unfortunately, few have shown success at
ameliorating these adverse effects. Guidelines have been developed that provide
463
CCIP.indb 463 3/13/18 4:19 PM

screening recommendations after completion of therapy, which should be

considered when continuing to care for these patients. Treatment options for
cardiotoxicity once it develops have not been standardized and are lacking.
Cardiotoxicity is a clinically significant concern for survivors of childhood
cancer, and additional research is needed to gain more insight into optimal
preventive, screening, and treatment options for this vulnerable population.
The Health Effects of Cardiotoxcity Among

Survivors of Childhood Cancer
Approximately two-thirds of survivors of childhood cancer will develop 1 or
more chronic health conditions, with an estimated 40% developing a severe
and even life-threatening condition within 30 years after cancer diagnosis.1
A systematic medical assessment of patients enrolled in the St Jude Lifetime
Cohort Study indicates that the prevalence of adverse health outcomes among
adult survivors of childhood cancer may be even higher.2 Survivors of childhood
cancer are at a particularly increased risk of excess morbidity and early mortality
from cardiotoxicity when compared to healthy control subjects.3,4 In comparison
to healthy siblings, survivors are significantly more likely to develop congestive
heart failure (CHF), myocardial infarction, pericardial disease, and valvular
abnormalities.4 A large retrospective review of more than 20,000 patients
enrolled in the Childhood Cancer Survivor Study showed that after relapse of
their primary malignancy and subsequent secondary neoplasms, cardiotoxicity is
the leading cause of premature death among this patient population.3 Addressing
this growing concern is necessary to improve outcomes for these patients.
Risk Factors for Cardiotoxicity

A multitude of risk factors have been found to be related to the development of
cardiotoxicity (Box 27-1). These include not only those that are related to cancer
therapy, but also factors inherent to the patient and factors that are modifiable.
Therapy-Related Risk Factors

Some modalities used to treat and cure patients with childhood cancer have the
potential to cause acute, subacute, chronic, and long-term adverse cardiac effects.
Such effects may include but are not limited to arrhythmias, valvular disease,
coronary artery disease, pericardial disease, and CHF.4–9 Physicians’ recognition
of these serious potential complications is critical to the health and well-being
of this patient population.
464
CCIP.indb 464 3/13/18 4:19 PM

Cardiotoxicity Among Survivors of Childhood Cancer
Box 27-1. Risk Factors for Cardiotoxicity Among Survivors

of Childhood Cancer
Therapy-related risk factors
•• Anthracycline agentsa
—Daunorubicin
—
—Doxorubicin
—
—Epirubicin
—
•• Radiation exposure
—Increased
— risk with increased dose
•• Alkylating agents
—Cyclophosphamide
—
—Ifosfamide
—
•• Targeted therapy
—Trastuzumab
— (monoclonal antibody against human epidermal
receptor-2)
—Bortezomib
— (proteasome inhibitor)
Patient-related risk factors
•• Female sex
•• Younger age at diagnosis
•• African Americans
•• Trisomy 21
•• C282Y gene mutation
•• Tobacco use
•• Illicit drug use
a
Risk is based on lifetime cumulative dose, with increased risk >300 mg/m2 doxorubicin equivalent.
Anthracyclines That Cause Cardiotoxicity

Some chemotherapy medications have been shown to cause adverse cardiac
effects.10 Anthracyclines, such as daunorubicin and doxorubicin, are vital to
the treatment of many childhood cancers; unfortunately, they are notorious
for their cardiotoxic profile. Anthracyclines can adversely affect the heart at all
stages of therapy, from (a) an acute or subacute onset that may occur within
hours to days of treatment and is usually reversible to (b) late onset, in which
irreversible adverse effects may not be noted until years or even decades after
completion of therapy.10,11 Anthracyclines damage cardiomyocytes, leading to
thinning of the left ventricular (LV) wall and, ultimately, decreased LV function
and cardiomyopathy.11

Anthracyclines are used to treat both hematologic malignancies, such as
acute lymphoblastic leukemia, and solid tumors, such as osteosarcoma.12 This
class of chemotherapy is limited by its cumulative dose; the greater the lifetime
anthracycline dose received, the greater the risk of developing cardiotoxicity.13,14
465
CCIP.indb 465 3/13/18 4:19 PM

Despite the increased risk with higher cumulative dosages, cardiac damage has
also been shown to occur at relatively low cumulative dosages.15,16 Therefore, any
exposure to doxorubicin or other anthracyclines should be considered as a risk
factor for the development of cardiotoxicity.
Radiation Therapy
Radiation therapy has been used for decades in the treatment of many types of
cancers among children and adolescents. This form of therapy is notorious for
subjecting patients to cardiotoxicity, such as pericardial disease, coronary artery
disease, myocardial fibrosis, and valvular disease.9 Radiation therapy has been a
substantial problem, particularly for patients previously treated for Hodgkin dis-
ease in whom extensive thoracic radiation has been used.17–19 The risk of toxicity
among patients and survivors is dependent on the cumulative radiation dosage,
daily fractionation, and radiation field involvement during therapy. Radiation
exposure has also been shown to cause cumulative cardiotoxicity when used in
combination with anthracyclines.20
Additional Cancer Agents Associated With Cardiotoxicity

In addition to the anthracyclines, a number of other medications used to treat
childhood malignancies have been shown to be associated with cardiotoxicity.
Groups of chemotherapy agents, including (a) alkylating agents such as
cyclophosphamide and ifosfamide and (b) taxanes such as paclitaxel and
docetaxel, have been associated with adverse cardiac effects.10,21 Adverse cardiac
events have also been noted in adult patients treated with many newer targeted
therapies. For example, trastuzumab, a monoclonal antibody against human
epidermal receptor 2 used in patients with breast cancer, as well as bortezomib,
a proteasome inhibitor used in patients with mantle cell lymphoma, have
been associated with LV dysfunction.9,21 These findings are important as new
therapies continue to be studied and developed among children and adolescents
with cancer to understand the potential adverse effects that may come as a cost
of treatment.
Patient-Related Risk Factors

A number of inherent patient risk factors have been associated with particularly
increased risk from anthracycline-associated cardiotoxicity. For example, female
sex, younger age at diagnosis, African American race, and trisomy 21 have been
associated with increased risk of cardiac damage from anthracyclines among
survivors of childhood cancer.4,11,22,23 Studies have also demonstrated specific
genetic variations to be associated with increased risk of cardiotoxicity. Lipshultz
and colleagues found that doxorubicin-associated myocardial injury is associated
with patients who are carriers for the C282Y hemochromatosis gene mutation,
466
CCIP.indb 466 3/13/18 4:19 PM

the same mutation found in patients with hereditary hemochromatosis.24

Additionally, just as behaviors such as tobacco and illicit drug use and physical
inactivity are associated with the development of cardiac disease among the
general population, these behaviors can also potentiate cardiac disease among
survivors of childhood cancer.25,26
Prevention
Preventing cardiotoxicity among survivors of childhood cancer is of utmost
importance, as these patients are now living decades beyond their cancer diag
nosis.10 Prevention must be carefully weighed against ensuring continued opti-
mal oncological effectiveness and success for overall and event-free survival.12
Currently, most treatment regimens for childhood cancer are standardized and
do not take individual patient risk factors into account. Various techniques and
medications have been studied in attempts to improve treatment strategies
to reduce cardiotoxicity, particularly from anthracyclines, without adversely
affecting antineoplastic effects. Prolonging the infusion times of anthracyclines
has been shown to decrease cardiotoxicity among adults but unfortunately has
not led to a clinically significant improvement among children.27–29 Angioten
sin-converting enzyme inhibitors have been shown to delay the development of
cardiac dysfunction among children with acute lymphoblastic leukemia but have
not prevented its development.30
A number of additional medications and nutritional supplements have been
studied as potential cardioprotectants against anthracycline-mediated cardiotox-
icity. One medication that has been studied extensively is dexrazoxane. Believed
to act through its iron chelation properties and as a DNA type II topoisomerase
inhibitor, dexrazoxane has been studied as a cardioprotectant in several random-
ized clinical trials among adult and pediatric patients with cancer treated with
anthracyclines.31–34 This medication has been shown to be effective at preventing
cardiotoxicity while retaining the antineoplastic effects of anthracycline ther-
apy.25,34 Dexrazoxane is currently approved for use among patients with advanced
breast cancer to prevent doxorubicin-induced cardiomyopathy and is included
in a number of clinical trials for pediatric patients with cancer (see clinicaltrials.
gov/ct2/results?term=dexrazoxane+children&Search=Search).35

Substantial changes and developments over the years have helped to diminish
the cardiotoxic effects of radiation therapy. Given the increased toxicity with
higher dosages and with more tissue exposure, therapies have been designed to
limit the cumulative dose to 25 Gy when possible among children, as well as to
deliver radiation directly to the tumor, known as conformal radiation, to avoid
the healthy surrounding tissues.18,19 Results from recent clinical trials suggest
that certain patients with Hodgkin disease may be able to avoid radiation
exposure altogether, depending on their stage at diagnosis and their response
to initial therapy.36
467
CCIP.indb 467 3/13/18 4:19 PM


For most childhood cancers, there are standards of care regarding treatment
regimens with cure as the primary goal when possible. These treatments,
however, do not take into account specific risk factors that may place particular
patients at higher risk of adverse effects, such as cardiotoxicity. As survival
rates continue to improve, increased focus should be on survivorship and the
prevention of late effects, when feasible. In addition to cure, the goal should be
to provide therapies tailored to individual patients that account for specific risk
factors to prevent adverse late effects when possible—particularly cardiotoxicity.
Screening and Follow-up

Being able to recognize the many risk factors that exist for developing cardio-
toxicity and then screening for cardiac disease among survivors of childhood
cancer who are at increased risk is important to allow for early detection and
intervention. The first step to ensure adequate screening is for these patients to
continue receiving necessary follow-up with a health care provider. Guidelines
have been established by multiple organizations, such as the Children’s Oncology
Group (COG), as to how often and in what fashion survivors should be screened
for cardiotoxicity and followed up after completion of therapy.37 These guidelines
and screening recommendations are based on specific risk factors, such as
whether patients received radiation and/or anthracycline therapy. The COG
long-term follow-up guidelines were developed in response to the Institute of
Medicine (IOM) report “Childhood Cancer Survivorship: Improving Care
and Quality of Life” in 2003.37–39 The IOM report described particular health
needs of survivors of childhood cancer and recommended the development of
evidence-based clinical practice guidelines for survivor care, improved awareness
of late effects, and their implications on long-term health outcomes, as well as
improved education regarding late effects and their management.37,39 The COG
long-term follow-up guidelines for survivors of childhood, adolescent, and young
adult cancer may be found at www.survivorshipguidelines.org.40 These guidelines
are helpful not only for oncologists but also as a reference tool for general prac-
titioners and other clinicians who care for survivors of childhood cancer. These
guidelines provide specific information on the basis of exactly what therapy the
patient has received.
An initial and important screening tool is compiling a thorough history.
Patients should be asked questions regarding their cardiac health status that
reflect upon possible symptoms associated with cardiac disease. General ques-
tions may include whether they have increased shortness of breath with activity,
chest pain relieved with rest, or lower-extremity edema. Performing a thorough
physical examination, including routine evaluation of vital signs to assess the
patient for signs of cardiac disease, is also a pertinent first step in screening. For
example, rales that are discovered in a respiratory examination, jugular venous
distention, or hepatomegaly would be signs concerning for CHF.
468
CCIP.indb 468 3/13/18 4:19 PM

Depending on the patient’s specific risk factors, imaging and/or laboratory

evaluations may be warranted.37,40 Echocardiography is the imaging modality
used most commonly to screen the patient for early signs of heart failure and
cardiac dysfunction among survivors of cancer and is currently recommended
for patients who received anthracyclines.9,40,41 The echocardiogram is easy to
perform, safe, and noninvasive. Assessing the patient for dyslipidemia with
cholesterol laboratory evaluation may be warranted in those at risk for develop-
ing a metabolic syndrome, such as patients who underwent radiation therapy at
specific sites on their bodies.40
Although the recommendations presented in the COG long-term follow-up
guidelines were developed to increase awareness of potential late effects for
survivors of childhood, adolescent, and young adult cancers and to standardize
follow-up care,37 clinicians must be aware that limitations exist. For example,
echocardiography may be limited by the fact that these tests are operator
dependent and may not be able to demonstrate subclinical changes before
clinical signs and symptoms develop.9,41 Additionally, evidence-based guidelines
for therapeutic interventions, if and when abnormal results are discovered,
are lacking. Nonetheless, these guidelines are an impressive compilation of
both evidence-based information and clinical expertise.37 Expert screening
recommendations were developed on the basis of evidence-based established
associations between therapeutic intervention and late effects. Therefore, these
screening recommendations should be considered as tools to use when caring
for survivors of childhood, adolescent, and young adult cancers.
Markers of cardiac disease have also been studied during and after therapy
and have been shown to correlate with late cardiac dysfunction.10 For example,
increased cardiac troponin T levels, a well-known marker of cardiac injury, have
been shown to be associated with abnormally reduced LV mass and end-diastolic
posterior wall thickness among patients with high-risk acute lymphoblastic
leukemia who had been treated with doxorubicin.42 These markers, however, are
not routinely used to guide management decisions among children with cancer.
Treatment
Numerous medications are considered as standard of care for various types of
cardiac disease; however, treatment options for cancer therapy–related cardiac
dysfunction are limited. Angiotensin-converting enzyme inhibitors and
β-blockers, medications routinely used for CHF and hypertension, have not
been decisively shown to improve outcome or quality of life among survivors of
childhood cancer.43 Unfortunately, no standardized formulation exists for the
treatment of cardiac dysfunction that develops as a result of childhood cancer
therapy. The best treatment for these patients at the present time is to, when
feasible, prevent adverse cardiac effects from developing.
469
CCIP.indb 469 3/13/18 4:19 PM

The Future for Survivors of Childhood Cancer

The number of survivors of childhood cancer will undoubtedly continue to
increase, given the successful treatment modalities that exist and continue to be
developed. Further research, however, is needed to improve the morbidity and
early mortality associated with cardiotoxicity among this population, as well as
to improve the overall quality of life. Development of less cardiotoxic therapies
is warranted to decrease the late effects that currently exist. It is vitally important
to continue monitoring these patients throughout their lifetime because late
effects from cardiotoxic therapies may develop decades after therapy. Physicians
play a critical role in identifying patients at greatest risk for cardiotoxicity, and
screening and early intervention will be essential to ensure the best chance of a
healthy future.
Key Points
•• Survivors of childhood cancer are at significantly increased risk of excess
morbidity and early mortality when compared to the general population,
owing to their treatment.
•• Cardiotoxicity is among the leading causes of excess morbidity and early
mortality among survivors of childhood and adolescent cancer.
•• Long-term follow-up care is essential for survivors of childhood and adoles-
cent cancer after completion of their cancer treatment.
•• It is important for physicians to have a thorough understanding of a patient’s
cancer history (eg, type of malignancy, age at diagnosis, therapeutic modalities
used during treatment).
•• Screening guidelines developed by COG to assist health care providers in
caring for survivors of childhood, adolescent, and young adult cancer can be
found at www.survivorshipguidelines.org.

•• Keeping your Heart Healthy After Treatment for Childhood Cancer
(Children’s Oncology Group). www.survivorshipguidelines.org/pdf/
healthlinks/English/heart_health_Eng.pdf
•• Preventing Cardiovascular Complications After Treatment for Childhood
Cancer (Children’s Oncology Group). www.survivorshipguidelines.org/pdf/
healthlinks/English/cardiovascular_risk_factors_Eng.pdf
•• Staying Healthy Through Diet and Physical Activity (Children’s Oncology
Group). www.survivorshipguidelines.org/pdf/healthlinks/English/
diet_and_physical_activity_Eng.pdf
•• Late Effects of Treatment for Childhood Cancer (PDQ)—Patient Version,
Cardiovascular System (National Cancer Institute). www.cancer.gov/types/
childhood-cancers/late-effects-pdq#section/_44
470
CCIP.indb 470 3/13/18 4:19 PM

References
1) Oeffinger KC, Mertens AC, Sklar CA, et al; Childhood Cancer Survivor Study. Chronic health
conditions in adult survivors of childhood cancer. N Engl J Med. 2006;355(15):1572–1582
2) Hudson MM, Ness KK, Gurney JG, et al. Clinical ascertainment of health outcomes among
adults treated for childhood cancer. JAMA. 2013;309(22):2371–2381
3) Mertens AC, Liu Q, Neglia JP, et al. Cause-specific late mortality among 5-year
survivors of childhood cancer: the Childhood Cancer Survivor Study. J Natl Cancer Inst.
2008;100(19):1368–1379
4) Mulrooney DA, Yeazel MW, Kawashima T, et al. Cardiac outcomes in a cohort of adult survivors
of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor
Study cohort. BMJ. 2009;339:b4606
5) Goorin AM, Chauvenet AR, Perez-Atayde AR, Cruz J, McKone R, Lipshultz SE. Initial
congestive heart failure, six to ten years after doxorubicin chemotherapy for childhood cancer.
J Pediatr. 1990;116(1):144–147
6) Lipshultz SE, Lipsitz SR, Sallan SE, et al. Chronic progressive cardiac dysfunction years
after doxorubicin therapy for childhood acute lymphoblastic leukemia. J Clin Oncol. 2005a;
23(12):2629–2636
7) Shankar SM, Marina N, Hudson MM, et al; Cardiovascular Disease Task Force of the
Children’s Oncology Group. Monitoring for cardiovascular disease in survivors of childhood
cancer: report from the Cardiovascular Disease Task Force of the Children’s Oncology Group.
Pediatrics. 2008;121(2):e387–e396
8) Lipshultz SE, Cochran TR, Franco VI, Miller TL. Treatment-related cardiotoxicity in survivors
of childhood cancer. Nat Rev Clin Oncol. 2013a;10(12):697–710
9) Curigliano G, Cardinale D, Dent S, et al. Cardiotoxicity of anticancer treatments: Epidemiology,
detection, and management. CA Cancer J Clin. 2016;66(4):309–325
10) Dolci A, Dominici R, Cardinale D, Sandri MT, Panteghini M. Biochemical markers for
prediction of chemotherapy-induced cardiotoxicity: systematic review of the literature and
recommendations for use. Am J Clin Pathol. 2008;130(5):688–695
11) Lipshultz SE, Colan SD, Gelber RD, Perez-Atayde AR, Sallan SE, Sanders SP. Late cardiac
effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood. N Engl J Med.
1991;324(12):808–815
12) Wouters KA, Kremer LC, Miller TL, Herman EH, Lipshultz SE. Protecting against anthra-
cycline-induced myocardial damage: a review of the most promising strategies. Br J Haematol.
2005;131(5):561–578
13) Steinherz LJ, Steinherz PG, Tan CTC, Heller G, Murphy ML. Cardiac toxicity 4 to 20 years
after completing anthracycline therapy. JAMA. 1991;266(12):1672–1677
14) Kremer LCM, van Dalen EC, Offringa M, Ottenkamp J, Voûte PA. Anthracycline-induced
clinical heart failure in a cohort of 607 children: long-term follow-up study. J Clin Oncol.
2001;19(1):191–196
15) Trachtenberg BH, Landy DC, Franco VI, et al. Anthracycline-associated cardiotoxicity in
survivors of childhood cancer. Pediatr Cardiol. 2011;32(3):342–353
16) Lipshultz SE, Franco VI, Miller TL, Colan SD, Sallan SE. Cardiovascular disease in adult
survivors of childhood cancer. Annu Rev Med. 2015;66:161–176
17) Hancock SL, Donaldson SS, Hoppe RT. Cardiac disease following treatment of Hodgkin’s
disease in children and adolescents. J Clin Oncol. 1993;11(7):1208–1215
18) Adams MJ, Lipsitz SR, Colan SD, et al. Cardiovascular status in long-term survivors of
Hodgkin’s disease treated with chest radiotherapy. J Clin Oncol. 2004;22(15):3139–3148
19) Galper SL, Yu JB, Mauch PM, et al. Clinically significant cardiac disease in patients with
Hodgkin lymphoma treated with mediastinal irradiation. Blood. 2011;117(2):412–418
471
CCIP.indb 471 3/13/18 4:19 PM

20) Pihkala J, Saarinen UM, Lundström U, et al. Myocardial function in children and adolescents
after therapy with anthracyclines and chest irradiation. Eur J Cancer. 1996;32A(1):97–103
21) Yeh ETH, Bickford CL. Cardiovascular complications of cancer therapy: incidence, patho
genesis, diagnosis, and management. J Am Coll Cardiol. 2009;53(24):2231–2247
22) Lipshultz SE, Lipsitz SR, Mone SM, et al. Female sex and higher drug dose as risk factors
for late cardiotoxic effects of doxorubicin therapy for childhood cancer. N Engl J Med. 1995;
332(26):1738–1743
23) Krischer JP, Epstein S, Cuthbertson DD, Goorin AM, Epstein ML, Lipshultz SE. Clinical
cardiotoxicity following anthracycline treatment for childhood cancer: the Pediatric Oncology
Group experience. J Clin Oncol. 1997;15(4):1544–1552
24) Lipshultz SE, Lipsitz SR, Kutok JL, et al. Impact of hemochromatosis gene mutations on
cardiac status in doxorubicin-treated survivors of childhood high-risk leukemia. Cancer.
2013B;119(19):3555–3562
25) Lipshultz SE, Adams MJ. Cardiotoxicity after childhood cancer: beginning with the end in
mind. J Clin Oncol. 2010;28(8):1276–1281
26) Steiner R. Increasing exercise in long-term survivors of pediatric cancer and their siblings:
should treatment be a family affair? Pediatr Blood Cancer. 2013;60(4):529–530
27) Legha SS, Benjamin RS, Mackay B, et al. Reduction of doxorubicin cardiotoxicity by prolonged
continuous intravenous infusion. Ann Intern Med. 1982;96(2):133–139
28) Lipshultz SE, Giantris AL, Lipsitz SR, et al. Doxorubicin administration by continuous infusion
is not cardioprotective: the Dana-Farber 91-01 Acute Lymphoblastic Leukemia protocol. J Clin
Oncol. 2002a;20(6):1677–1682
29) Lipshultz SE, Miller TL, Lipsitz SR, et al; Dana-Farber Cancer Institute Acute Lymphoblastic
Leukemia Consortium. Continuous versus bolus infusion of doxorubicin in children with ALL:
long-term cardiac outcomes. Pediatrics. 2012a;130(6):1003–1011
30) Lipshultz SE, Lipsitz SR, Sallan SE, et al. Long-term enalapril therapy for left ventricular
dysfunction in doxorubicin-treated survivors of childhood cancer. J Clin Oncol. 2002b;20(23):
4517–4522
31) Speyer JL, Green MD, Zeleniuch-Jacquotte A, et al. ICRF-187 permits longer treatment with
doxorubicin in women with breast cancer. J Clin Oncol. 1992;10(1):117–127
32) Wexler LH, Andrich MP, Venzon D, et al. Randomized trial of the cardioprotective agent
ICRF-187 in pediatric sarcoma patients treated with doxorubicin. J Clin Oncol. 1996;
14(2):362–372
33) Swain SM, Whaley FS, Gerber MC, Ewer MS, Bianchine JR, Gams RA. Delayed administra-
tion of dexrazoxane provides cardioprotection for patients with advanced breast cancer treated
with doxorubicin-containing therapy. J Clin Oncol. 1997;15(4):1333–1340
34) Lipshultz SE, Rifai N, Dalton VM, et al. The effect of dexrazoxane on myocardial injury in
doxorubicin-treated children with acute lymphoblastic leukemia. N Engl J Med. 2004;
351(2):145–153
35) Hutchins KK, Siddeek H, Franco VI, Lipshultz SE. Prevention of cardiotoxicity among
survivors of childhood cancer. Br J Clin Pharmacol. 2017;83(3):455–465
36) Radford J, Illidge T, Counsell N, et al. Results of a trial of PET-directed therapy for early-stage
Hodgkin’s lymphoma. N Engl J Med. 2015;372(17):1598–1607
37) Landier W, Bhatia S, Eshelman DA, et al. Development of risk-based guidelines for pediatric
cancer survivors: the Children’s Oncology Group Long-Term Follow-Up Guidelines from the
Children’s Oncology Group Late Effects Committee and Nursing Discipline. J Clin Oncol.
2004;22(24):4979–4990
38) Hewitt M, Weiner SL, Simone JV, eds. Childhood Cancer Survivorship: Improving Care and
Quality of Life. Washington, DC: National Cancer Policy Board; 2003
472
CCIP.indb 472 3/13/18 4:19 PM

39) Eshelman D, Landier W, Sweeney T, et al. Facilitating care for childhood cancer survivors:
integrating children’s oncology group long-term follow-up guidelines and health links in clinical
practice. J Pediatr Oncol Nurs. 2004;21(5):271–280
40) Children’s Oncology Group (COG). (2013). Long-Term Follow-up Guidelines for Survivors
of Childhood, Adolescent, and Young Adult Cancer. www.survivorshipguidelines.org. Accessed
November 8, 2017
41) Plana JC, Galderisi M, Barac A, et al. Expert consensus for multimodality imaging evaluation
of adult patients during and after cancer therapy: a report from the American Society of
Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc
Echocardiogr. 2014;27(9):911–939
42) Lipshultz SE, Miller TL, Scully RE, et al. Changes in cardiac biomarkers during doxorubicin
treatment of pediatric patients with high-risk acute lymphoblastic leukemia: associations with
long-term echocardiographic outcomes. J Clin Oncol. 2012b;30(10):1042–1049
43) Lipshultz SE, Adams MJ, Colan SD, et al; American Heart Association Congenital Heart
Defects Committee of the Council on Cardiovascular Disease in the Young, Council on
Basic Cardiovascular Sciences, Council on Cardiovascular and Stroke Nursing, Council
on Cardiovascular Radiolo. Long-term cardiovascular toxicity in children, adolescents, and
young adults who receive cancer therapy: pathophysiology, course, monitoring, management,
prevention, and research directions: a scientific statement from the American Heart Association.
Circulation. 2013c;128(17):1927–1995
473
CCIP.indb 473 3/13/18 4:19 PM

CCIP.indb 474 3/13/18 4:19 PM
PART 6
Infectious Diseases
28. Vaccines for Patients With C
ardiac Conditions .................. 477
29. Lyme Carditis....................................................................... 487
30. Endocarditis......................................................................... 497
31. Prevention of Bacterial Endocarditis.................................... 511
32. Myocarditis........................................................................... 517
33. Pericardial Diseases.............................................................. 529
475
CCIP.indb 475 3/13/18 4:19 PM

CCIP.indb 476 3/13/18 4:19 PM
CHAPTER 28
Vaccines for
Patients With
C
ardiac Conditions
Ahdi Amer, MD
Introduction
It is not uncommon for a pediatrician to be faced with the decision of whether
or not to vaccinate a child who has a cardiac disorder. Patients who have cardiac
conditions may have primary immunodeficiency, such as DiGeorge syndrome, or a
secondary immunodeficiency due to immunosuppression after cardiac transplant.
The issue of immunizations for the immunocompromised child depends to
great extent on the degree and nature of impairment of the immune system and
whether the deficiency is a primary or secondary immunodeficiency.1 This chapter
provides guidance to pediatricians and other primary care clinicians on how to
safely and effectively vaccinate children and adolescents with certain cardiac
conditions associated with alterations in the immune system. This chapter also
provides general principles for ensuring appropriate vaccinations for household
members of these individuals.
Live Versus Inactivated Vaccines in the

Immunocompromised Child
Generally, children and adolescents who are severely immunocompromised should
not receive live vaccines. However, inactivated vaccines and immunoglobulin (Ig)
preparations should be used when indicated because the immune response to
477
CCIP.indb 477 3/13/18 4:19 PM

inactivated vaccines is not affected by circulating antibody, and safety is usually

not a concern.
The American Academy of Pediatrics recommends annual seasonal influenza
vaccination with inactivated influenza vaccine for immunocompromised patients
aged 6 months and older.2 Patients who are unlikely to respond, such as those
who received anti–B-lymphocyte antibody therapy within 6 months, are not
advised to receive the vaccination.2
Timing of Vaccination
Guidelines published by the Infectious Diseases Society of America (IDSA)3
recommend that generally, every effort should be made to administer all required
vaccines prior to a planned immunosuppression. Live vaccines should be avoided
within 2 weeks of the planned date of immunosuppression, and a minimum
of 4 weeks should be allowed prior to the initiation of immunosuppression.
In the case of cardiac transplant, one cannot always control when a heart will
become available, so this should not necessarily pre-empt acceptance of a heart.
However, in other cases that do not involve an immediate transplant, planned
immunosuppression can be delayed to allow for the recommended time interval
after vaccination.
For all inactivated vaccines, a minimum of 2 weeks should be allowed prior
to the initiation of immunosuppression.
The timing to resume vaccine administration after the reduction or cessation
of immunosuppression therapy will vary according to the vaccine, the underlying
disorder, and the specific immunosuppressive therapy.3
Vaccines for Household Members Living With

the Immunocompromised Patient
According to IDSA guidelines, household members living with immunocom-
promised patients can receive inactivated vaccines on the basis of the Centers
for Disease Control and Prevention (CDC) annual vaccination schedules for
children and adults, and all household members living with immunocompro-
mised patients 6 months of age and older should receive inactivated influenza
vaccine annually.3
On the basis of the annual CDC schedule, healthy household members living
with immunocompromised patients may safely receive the measles, mumps, and
rubella vaccines; the varicella and zoster vaccines; and the rotavirus vaccine in
infants 2 to 7 months of age. Also, those who are traveling can safely receive
the yellow fever and oral typhoid vaccines.3
Household members living with immunocompromised patients cannot
receive oral polio vaccine, which is no longer in use in the United States.
478
CCIP.indb 478 3/13/18 4:19 PM

Vaccines for Patients With Cardiac Conditions
Household members who develop skin lesions after varicella or zoster vacci-
nation should avoid contact with immunocompromised patients until the lesions
are cleared.
Individuals who are significantly immunocompromised should avoid
handling diapers of infants who have received rotavirus vaccine for 4 weeks
after vaccination.
Immunization in Certain Cardiac Conditions

That Alter the Immune System
DiGeorge Syndrome
DiGeorge syndrome, one of the primary immunodeficiency disorders, is charac-
terized by cellular (T cell) deficiency, congenital heart disease, and hypocalcemia
(see Chapter 17, Common Syndromes Associated With Cardiac Lesions). Most
individuals with DiGeorge syndrome have a microdeletion at 22.q11.2 that
results in a developmental field defect, which in turn leads to hypocalcemia and
variable T cell deficiency. A combined T and B cell deficiency can result from
lack of T helper cell function, as in cases of complete DiGeorge syndrome.4
Incomplete DiGeorge syndrome is characterized by immunodeficiency due
to a mild to moderate defect in T cell lineage caused by thymic hypoplasia.
A small fraction of patients (those with complete DiGeorge syndrome) may
present with marked impairment of T cell function associated with a complete
absence of thymus T cells and severe systemic infections.5
For the few children and adolescents with complete DiGeorge syndrome, all
live vaccines are contraindicated, and inactivated vaccines are probably ineffec-
tive. The only vaccine that should be given if the patient is receiving intravenous
Ig is annual inactivated influenza vaccine. For most patients with DiGeorge
syndrome, all live vaccines are also contraindicated, and the effectiveness of
any inactivated vaccine depends on the degree of immune deficiency. However,
routine inactivated vaccines should generally be given (see Table 28-1). Live
vaccines may be administered after the T-cell function improves. A clinical
immunologist should be consulted to see if live vaccines can be administered
to these patients.
Cardiac Transplantation
The population of cardiac transplant recipients is increasing, and preventing
infection among these patients is critical. Many immunocompromised patients
are unable to mount protective immune responses, and vaccine-preventable
infections in these patients can lead to serious morbidity and mortality because
antimicrobial therapy is usually less effective.6
479
CCIP.indb 479 3/13/18 4:19 PM

CCIP.indb 480
480
Table 28-1. Immunization of Children and Adolescents With Primary and Secondary
Immune Deficiencies
Example of a Specific Effectiveness and Comments, Including Risk-Specific
Category Immunodeficiency Vaccine Contraindications Vaccinesa
Primary Immune Deficiencyb
B lymphocyte Severe antibody OPV,c BCG, smallpox, LAIV, YF, Effectiveness of any vaccine is uncertain if dependent
(humoral) deficiencies (eg, X-linked and live-bacteria vaccinesd; no only on humoral response (eg, PPSV23 or MPSV4); IVIg
agammaglobulinemia data for rotavirus vaccines therapy interferes with response to all vaccines, therefore,
and common variable annual IIV is the only vaccine given to patients receiving
immunodeficiency) IVIg therapy; routine inactivated vaccines can be given if
not receiving IVIg.
Less severe antibody OPV,c BCG, YF vaccines; other All vaccines are probably effective; immune response may
deficiencies (eg, selective live vaccinese appear to be safe be attenuated; vaccines should be given as on the annual
IgA deficiency and IgG immunization schedule for immunocompetent people.

subclass deficiencies)
T lymphocyte Complete defects (eg, All live vaccinesd,e,f All inactivated vaccines are probably ineffective. The only
(cell-mediated severe combined immu- vaccine that should be given if the patient is receiving IVIg is
and humoral) nodeficiency, complete annual IIV if there is some residual antibody production.
DiGeorge syndrome)
Partial defects (eg, most All live vaccinesd,e Effectiveness of any inactivated vaccine depends on the
patients with DiGeorge degree of immune suppression. Routine inactivated vaccines
syndrome, hyper-IgM should be given. Those with ≥500 CD3+ T lymphocytes/
syndrome, Wiskott- mm3, ≥200 CD8+ T lymphocytes/mm3, and normal mitogen
Aldrich syndrome, ataxia response should receive MMR and VAR vaccine (but not
telangiectasia) MMRV). PPSV23 in addition to PCV13 is indicated in ataxia
telangiectasia.
3/13/18 4:19 PM
CCIP.indb 481
Immune Deficiencies, continued
Primary Immune Deficiencyb, continued
Complement Persistent complement None All inactivated and live-virus vaccines on the annual immuni-
component, properdin, zation schedule are safe and are probably effective; PPSV23
or mannan-binding lectin at 2 years and older and an MCV4 vaccine are recommended,
deficiency in addition to standard vaccines.
Phagocytic Chronic granulomatous Live-bacteria vaccinesd, OPV,c All inactivated vaccines are safe and are probably effectiveg;
function disease, leukocyte smallpox, BCG, combined live-virus vaccines are probably safe and effective.
adhesion defects, myelop- MMRV, LAIVe; withhold MMR and
eroxidase deficiency varicella in highly immunocom-
promised children; YF vaccine
may have a contraindication
or precaution depending on
indicators of immune functionh
Secondary Immune Deficiencya
HIV, AIDS Rotavirus vaccine is recommended on a standard schedule;

MMR and VAR are recommended for HIV-infected children
who are asymptomatic and are not highly immunocompro-
misedi,j; all inactivated vaccines, including IIV, may be effec-
tive; PPSV23 is recommended in addition to the standard
PCV13 vaccine; consider the Hib vaccine if not administered
Vaccines for Patients With Cardiac Conditions
during infancy and MCV4 at 2 through 10 years of age.
481
Continued
3/13/18 4:19 PM
CCIP.indb 482

482
Secondary Immune Deficiencya, continued
Malignant neoplasm, Live-virus and live-bacteria Effectiveness of any vaccine depends on the degree of
transplantation, vaccines, depending on immune immune suppression; annual IIV is recommended unless
autoimmune disease, statusd,e receiving intensive chemotherapy or on anti-B cell antibod-
immunosuppressive or ies; inactivated standard; PPSV23 is recommended at least 8
radiation therapy weeks after the last dose of PCV13. Vaccines are indicated if
not highly immunosuppressed, but doses should be repeated
after chemotherapy ends.
Asplenia (functional, None All standard vaccines are safe and are likely effective; PPSV23
congenital anatomic, should be given at 24 months and older; MCV4-D (Menactra
surgical) [Sanofi Pasteur, Swiftwater, PA]) should not be used before
4 weeks after completion of the 4-dose series of PCV13 (eg,
22 months of age and older) because of interference with
antibody response to PCV13 when vaccines are administered
concurrently; other MCV4 vaccines are used in infants and
toddlers as licensed by age, without concern for interference
with PCV13. In addition to standard vaccines, consider Hib
vaccine if not administered during infancy.
Chronic renal disease LAIV All standard vaccines are indicated; PPSV23 is recommended
at 24 months and older, in addition to standard PCV13.
3/13/18 4:19 PM
CCIP.indb 483
Secondary Immune Deficiencya, continued
CNS anatomic barrier None All standard vaccines are indicated; PCV13 if not received as
defect (cochlear implant, standard; PPSV23 at 2 years and older (≥8 weeks after receipt
congenital dysplasia of of PCV13).
the inner ear, persistent
CSF communication with
naso- and oropharynx)
BCG, bacillus Calmette-Guérin; CD3+, cluster of differentiation 3; CD8+, cluster of differentiation 8; CNS, central nervous system; CSF, cerebrospinal fluid; Hib, Haemophilus influenzae type b; IgA,
immunoglobulin A; IgG, immunoglobulin G; IgM, immunoglobulin M; IIV, inactivated influenza vaccine; IVIg, intravenous immunoglobulin; LAIV, live-attenuated influenza vaccine; MCV4, quadrivalent
Vaccines for P
meningococcal conjugate vaccine; MMR, measles-mumps-rubella; MMRV, measles-mumps-rubella-varicella; MPSV4, quadrivalent meningococcal polysaccharide vaccine; OPV, oral poliovirus;
PPSV23, 23-valent pneumococcal polysaccharide vaccine; PCV13, 13-valent pneumococcal conjugate vaccine; VAR, varicella vaccine; YF, yellow fever. From American Academy of Pediatrics.
Immunization in special clinical circumstances. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2015 Report of the Committee on Infectious Diseases. 30th ed. Elk Grove Village, IL:
American Academy of Pediatrics; 2015:68–107.
a
Other vaccines that are recommended universally or routinely should be administered if not contraindicated.
b
All children and adolescents should receive an annual age-appropriate inactivated influenza vaccine. LAIV is indicated only for healthy people 2 through 49 years of age.
c
OPV vaccine is no longer available in the United States.
d
Live-bacteria vaccines: BCG and Ty21a Salmonella typhi vaccine.
atients With C
e
Live virus vaccines: LAIV, MMR, VAR, MMRV, herpes zoster, OPV, YF, vaccinia (smallpox), and rotavirus.
f
Regarding T-lymphocyte immunodeficiency as a contraindication to rotavirus vaccine, data only exist for severe combined immunodeficiency syndrome.
g
Additional pneumococcal vaccine is not indicated for children with chronic granulomatous disease beyond age-based standard recommendations for PCV13, because these children are not at
increased risk for pneumococcal disease.
h
YF vaccine is contraindicated in HIV-infected children younger than 6 years who are highly immunosuppressed. There is precaution for use of YF vaccine in asymptomatic HIV-infected children
younger than 6 years with total lymphocyte percentage of 15% to 24% and children older than 6 years with cluster of differentiation 4 (CD4+) T-lymphocyte counts of 200–499 cells/mm3. From
Centers for Disease Control and Prevention. Yellow fever vaccine: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR Recomm Rep. 2010;59[RR-07]:1–27.
i
HIV-infected children should receive immunoglobulin after exposure to measles and may receive VAR if the CD4+ T-lymphocyte count is ≥15% of expected values for age for those younger than
5 years or if the CD4+ T-lymphocyte count is ≥200 cells/mm3 for those 5 years and older.
j
People with perinatal HIV infection who were vaccinated with a measles, rubella, or mumps-containing vaccine prior to the establishment of combination antiretroviral therapy (cART) should be
ardiac Conditions
considered unvaccinated and should receive 2 appropriately spaced doses of MMR vaccine once effective cART has been established (at least 6 months with CD4+ T-lymphocyte percentage of
483
≥15% for children younger than 5 years or CD4+ T-lymphocyte count ≥200 cells/mm3 for children 5 years or older).
3/13/18 4:19 PM
Vaccination with live virus vaccines may result in the unmeasured proliferation
of the live attenuated vaccine strains; therefore, live vaccines are generally
avoided in cardiac transplant recipients.
Children and adolescents who are candidates for cardiac transplant should
receive all vaccinations as appropriate for age, immune status, and exposure
history on the basis of the annual immunization schedule for immunocompetent
people. Routinely recommended live-virus vaccines should be administered as
long as the patient is not already immunosuppressed and the interval to the start
of the immunosuppression is at least 4 weeks.2 All household members of these
patients should be counseled about risks of infection and should have vaccination
status made current.
A Canadian study showed that a substantial proportion of children with
cardiac transplant lacked posttransplantation serologic evidence of immunity
against vaccine-preventable diseases.7 This was especially true for children who
received the transplant at a young age. Therefore, passive immunization may be
considered for cardiac transplant patients on the basis of their immunization
status and the immunosuppression they are receiving. It is important to consult
a clinical immunologist or infectious diseases specialist for guidance. In general,
passive immunization with the respective immunoglobulin should be considered
for cardiac transplant patients exposed to either chickenpox or measles. Also,
palivizumab, a humanized monoclonal antibody against respiratory syncytial
virus (RSV), should be administered monthly to infants and children younger
than 24 months who are undergoing cardiac transplantation during RSV season.
Patients Recently Treated With Immunoglobulin and

Other Blood Products
The use of Ig and other blood products or the receipt of specific antibodies
to protect immunocompromised cardiac patients after exposure to certain
infections can diminish the immunogenicity to live-virus vaccines when given
within 2 weeks before and up to 11 months after the time of administration.
The immune response to the measles vaccine, in particular, can be affected for
up to 11 months.8
Usually, the appropriate minimal intervals needed after Ig administration and
measles immunization vary, depending on the dose of Ig and the specific product
used (see Table 28-2). Similar to the case of measles vaccine, other live-virus
vaccines such as varicella, mumps, and rubella should be delayed because of the
same risk of potential interference with the immune response. When Ig needs to
be given within 14 days after administration of measles or varicella-containing
vaccines, these vaccines should be repeated after the interval specified in Table
28-2, unless serologic testing at the appropriate interval after Ig administration
can be used to document seroconversion.
484
CCIP.indb 484 3/13/18 4:19 PM

Vaccines for P
atients With Cardiac Conditions
Patients with Kawasaki disease (KD) who have received IVIg therapy have a
high risk of possible interference with the immune response; therefore, measles
and varicella-containing vaccines should be delayed for 11 months after receipt
of high-dose IVIg. However, if the child is at a high risk of exposure to measles
or varicella within this period, the child should be immunized immediately
but then reimmunized at least 11 months after the administration of IVIg
(see Table 28-2).
Patients with KD frequently receive aspirin therapy; live-attenuated vari-
cella-containing vaccines should be avoided during this therapy because of the
potential risk of Reye syndrome. Generally, the schedule for administration of
inactivated childhood vaccines should not be interrupted.
Table 28-2. Suggested Intervals Between Immunoglobulin

Administration and Measles Immunization (MMR or MMRV)
Dose Interval,
Indications or Product Route U or mL mg IgG/kg moa
RSV prophylaxis (palivizumab IM … 15 (mono- None
monoclonal antibody)b clonal)
Tetanus prophylaxis (as TIg) IM 250 U 10 3
Hepatitis A prophylaxis (as Ig)

Contact prophylaxis IM 0.02 mL/kg 3.3 3
International travel IM 0.06 mL/kg 10 3
Hepatitis B prophylaxis (as HBIg) IM 0.06 mL/kg 10 3
Rabies prophylaxis (as RIg) IM 20 IU/kg 22 4
Varicella prophylaxis (as VariZIg) IM 125 U/10 kg 20–40 5
(maximum
625 U)
Measles prophylaxis (as Ig)
Standard IM 0.25 mL/kg 40 5
Immunocompromised host IM 0.50 mL/kg 80 6
Intravenous botulinum immuno- IV 1.5 mL/kg 75 6
globulin (human)
Blood transfusion
Washed RBCs IV 10 mL/kg Negligible 0
RBCs, adenine-saline added IV 10 mL/kg 10 3
Packed RBCs IV 10 mL/kg 20–60 5
Whole blood IV 10 mL/kg 80–100 6
Plasma or platelet products IV 10 mL/kg 160 7
Continued
485
CCIP.indb 485 3/13/18 4:19 PM

Table 28-2. Suggested Intervals Between Immunoglobulin

Administration and Measles Immunization (MMR or MMRV),
continued
Dose
Interval,
Indications or Product Route U or mL mg IgG/kg moa
Replacement (or therapy) of IV … 300–400 8

immune deficiencies (as IVIg)
Therapy for ITP (as IVIg) IV … 400 8
Varicella prophylaxis (as IVIg) IV 400 8
Therapy for ITP (as IVIg) IV … 1000 10
Therapy for ITP or Kawasaki IV … 1600–2000 11

disease (as IVIg)
HBIg, hepatitis B immunoglobulin; Ig, immunoglobulin; IM, intramuscular; ITP, immune (formerly termed “idiopathic”)
thrombocytopenic purpura; IV, intravenous; IVIg, intravenous immunoglobulin; MMR, measles-mumps-rubella;
MMRV, measles-mumps-rubella-varicella; RBCs, red blood cells; RIg, rabies immunoglobulin; RSV, respiratory
syncytial virus; TIG, tetanus immunoglobulin; VariZIg, varicella-zoster immunoglobulin. From American Academy of
Pediatrics. Active immunization. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2015 Report of
the Committee on Infectious Diseases. 30th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2015:13–56.
a
These intervals should provide sufficient time for decreases in passive antibodies in all children to allow for an
adequate response to measles vaccine. Physicians should not assume that children are protected fully against measles
during these intervals. Additional doses of Ig or measles vaccine may be indicated after exposure to measles.
b
RSV monoclonal antibody (palivizumab) does not interfere with the immune response to vaccines.
References
1) Lindegren ML, Kobrynski L, Rasmussen SA, et al; Centers for Disease Control and
Prevention. Applying public health strategies to primary immunodeficiency diseases: a poten-
tial approach to genetic disorders. MMWR Recomm Rep. 2004;53(RR-1):1–29
2) American Academy of Pediatrics. Immunization in immunocompromised children. In:
Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2015 Report of the Committee
on Infectious Diseases. 30th ed. Elk Grove Village, IL: American Academy of Pediatrics;
2015:74–89
3) Rubin LG, Levin MJ, Ljungman P, et al; Infectious Diseases Society of America. 2013 IDSA
clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis.
2014;58(3):309–318
4) Nugent N, McGillivary A, Earley MJ. 22q11 chromosome abnormalities and the cleft service.
J Plast Reconstr Aesthet Surg. 2010;63(4):598–602
5) Patel K, Akhter J, Kobrynski L, Benjamin Gathmann MA, Davis O, Sullivan KE; International
DiGeorge Syndrome Immunodeficiency Consortium. Immunoglobulin deficiencies: the
B-lymphocyte side of DiGeorge syndrome. J Pediatr. 2012;161(5):950–953
6) Hibberd PL, Rubin RH. Approach to immunization in the immunosuppressed host. Infect Dis
Clin North Am. 1990;4(1):123–142
7) Urschel S, Cremer S, Birnbaum J, et al. Lack of serologic immunity against vaccine-preventable
diseases in children after thoracic transplantation. Transpl Int. 2010;23(6):619–627
8) American Academy of Pediatrics. Active and passive immunization. In: Kimberlin DW, Brady
MT, Jackson MA, Long SS, eds. Red Book: 2015 Report of the Committee on Infectious Diseases.
30th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2015:39–41
486
CCIP.indb 486 3/13/18 4:19 PM

CHAPTER 29
Lyme Carditis
Michael Colon, MD
Introduction
Etiologic Origins and Epidemiology
Lyme disease is caused by the gram-negative bacteria Borrelia burgdorferi, a
spirochete. It is the most common tick-borne illness in the United States. More
than 30,000 cases are reported by the Centers for Disease Control and Prevention
(CDC) each year. Most cases occur in New England and the Atlantic and North
Central United States.1 There is a slight male predominance, with the incidence
highest in children 5 to 10 years of age. Lyme disease is most commonly diagnosed
during the summer months.2
In the United States, B burgdorferi is transmitted primarily by Ixodes scapularis,
a deer tick.3 The tick is infected by feeding on the host, which is commonly the
white-footed mouse. The tick is most likely to transmit the infection to humans
during the nymphal stage, which emerges in the spring.4 There is then a delay
from infection to presentation in the human, which explains the summer being
the most common time of year for patients to present with Lyme disease. Of
note, the infected tick must feed for about 48 to 72 hours or longer to transmit
B burgdorferi.5 Lyme disease has the potential to affect multiple organ systems,
including the heart.
Risk of Carditis
Lyme carditis is a rare occurrence in adults and children with Lyme disease. It
is estimated that 4% to 10% of adult patients in the United States who have
untreated Lyme disease develop carditis.6 However, when only accounting for
higher-grade atrioventricular (AV) block (second degree or greater), only 1.1% of
adults develop Lyme carditis.7 In a prospective study of 201 children with Lyme
487
CCIP.indb 487 3/13/18 4:19 PM

disease, only 0.5% of patients presented with carditis.8 Of hospitalized children

with Lyme disease, 16% had carditis. Seven percent of patients had either
second- or third-degree AV block, and only 2% had complete heart block.9
Woolf and colleagues found a 7% incidence of electrocardiographic (ECG)
changes common to Lyme carditis in asymptomatic children with definite or
probable Lyme disease.10 Up to 50% of adult patients with Lyme carditis develop
complete heart block,11 and 42% of hospitalized children with Lyme carditis
were found to have advanced block.9 Lyme carditis is more likely to affect male
subjects, with a 3:1 male-to-female predominance.11
Pathogenesis
The injury in Lyme carditis is caused by direct invasion of all layers of the heart
by spirochetes, as well as the resultant inflammatory response. Murine models
have demonstrated spirochetes in the cardiac conduction tissue, myocardium,
and epicardium. In addition, macrophages predominate the inflammatory
response in the cardiac tissue.12,13 However, in the small number of reported
human patients who have undergone myocardial biopsy or autopsy, there has
been a predominantly lymphocytic infiltration of the endocardium, myocardium,
and pericardium.9,14
Clinical Features
Signs and Symptoms
The clinical manifestations of Lyme disease are classically divided into 3 stages.15
Stage 1, early localized disease, presents several days to a month after the tick
bite. Symptoms include flulike symptoms, such as fever, malaise, myalgia, and
headaches, along with the classic erythema migrans rash (Figure 29-1). This is
an expanding red macule or papule. It can have central clearing (“target lesion”)
or be uniformly erythematous. It may be pruritic or cause minor pain. Stage 2,
FIGURE 29-1. Two examples of the erythema migrans rash.

488
CCIP.indb 488 3/13/18 4:19 PM

Lyme Carditis
the early disseminated form of the disease, occurs weeks to months after the tick
bite. It most commonly manifests with multiple annular secondary erythema
migrans lesions, as well as neurological symptoms, such as facial palsy and
meningitis. The least commonly encountered manifestation during this stage is
Lyme carditis, which most commonly manifests with conduction abnormalities.
Stage 3 or late disseminated disease, which occurs weeks to months after the
initial infection, is not associated with cardiac abnormalities. This stage presents
with mono- or oligoarthritis that affects the large joints, especially the knee, or
neurological sequelae.
Symptoms of Lyme carditis include those of early disseminated disease, such
as fever, malaise, headaches, and myalgia; single or multiple erythema migrans
rashes; and meningitis. Specific cardiac symptoms include palpitations, chest
pain, syncope, near syncope, and dyspnea. In a study of 207 hospitalized children
with early disseminated Lyme disease, absence of these 5 cardiac symptoms had
99% specificity for identifying patients without carditis. However, the presence
of cardiac symptoms had only a 42% sensitivity for identifying Lyme carditis.9
The most common clinical feature of Lyme carditis is AV block, which can
occur in varying degrees and may fluctuate rapidly. There can be first-degree
AV block with a PR interval above the normal limit for age but an otherwise
normal heart rate (Figure 29-2). Symptoms in these patients are unusual.
Patients may have a second-degree AV block with intermittent loss of atrio
ventricular conduction, with or without a preceding lengthening of the PR
interval (Figure 29-3). Lastly, they may exhibit third-degree AV block, also
known as complete AV block, with absence of atrial impulse conduction to the
ventricles (Figure 29-4). This can be associated with a slow escape rhythm (30
or 40 beats per minute) with wide complex QRS. There can also be long pauses.
FIGURE 29-2. Electrocardiogram shows first-degree atrioventricular block.
489
CCIP.indb 489 3/13/18 4:19 PM

FIGURE 29-3. Electrocardiogram shows second-degree, type 1 atrioventricular block.
FIGURE 29-4. Electrocardiogram shows complete atrioventricular block.
In the initial description of Lyme carditis by Steere et al, 90% of patients pre-
sented with first-degree AV block, and 44% had complete AV block. Progression
from first-degree AV block was more likely when the PR interval was above
300 milliseconds. ST segment depression and T wave inversions were also seen
at ECG in 60% of patients.16 Other ECG findings are less frequent but include
tachyarrhythmias and corrected QT interval prolongation.17
Although spirochete invasion and myocardial inflammation are seen through-
out the heart, myocarditis and pericarditis are rare findings in Lyme carditis. A
490
CCIP.indb 490 3/13/18 4:19 PM

Lyme Carditis
report of 84 cases of Lyme carditis showed that 10% had associated myocarditis,
and only 2% had pericarditis.18 Rare cases of pericardial effusion and congestive
heart failure have been reported.19 In these rare cases, myocardial dysfunction is
often mild and self-limited. Mortality is extremely rare but has been reported.20
In addition to Lyme carditis, the differential diagnosis for children who present
with heart block should include the congenital heart defect of levo-transposition
of the great arteries. This is also known as congenitally corrected transposition or
ventricular inversion. Transthoracic echocardiography is therefore important to
rule out structural abnormalities. Congenital heart block, most often related to
maternal autoimmune disease, or heterotaxy syndrome (specifically left atrial
isomerism), are more common causes of heart block in newborns. In rare cases,
heart block can also be seen in myocarditis, after ingestion of certain medications
or supplements, and with myotonic dystrophy.
Diagnosis
The diagnosis of early localized disease is established clinically because
antibodies to B burgdorferi are not detectable in the first weeks after infection.
Diagnosis of early disseminated and late disease is established clinically and
serologically. Lyme carditis is diagnosed most accurately by means of historical
evidence of Lyme infection (tick bite, erythema migrans, etc) as well as cardiac
symptoms, such as palpitations, chest pain, syncope, near syncope, or dyspnea
with variable AV block at ECG. The final requirement for diagnosis is positive
serological test results for B burgdorferi antibodies. Two-step antibody testing is
recommended by the CDC.21 The first test is a sensitive screening test such as
an enzyme-linked immunosorbent assay, which is used to measure the overall
antibody response of a patient to whole-cell sonicate preparation of B burgdorferi
as antigens. However, because it can be cross-reactive with antigens from the
host or other pathogens, the specificity is poor. Therefore, if this first test result is
positive or equivocal, a Western immunoblot is recommended by the CDC as a
confirmatory test. The Western blot is also a serological test that can be used to
detect antibodies produced against B burgdorferi, but it uses preselected protein
antigens for B burgdorferi. A positive immunoglobulin M (IgM) result is 2 or
more of the 3 bands (21–24, 39, and 41 kDa), and a positive immunoglobulin G
(IgG) result is the presence of 5 or more of the 10 bands (18, 21–24, 28, 30, 39,
41, 45, 58, 66, and 93 kDa).21 It is important to note that IgM and IgG against
B burgdorferi can persist for many years after the initial infection, despite ade-
quate treatment.22
491
CCIP.indb 491 3/13/18 4:19 PM

Management
Treatment
No study has shown that antibiotics for Lyme disease prevent Lyme carditis.
However, in a study of 118 adults with confirmed Lyme disease with erythema
migrans, none developed cardiac symptoms after antibiotic treatment.23
Therefore, early disease should be treated orally with doxycycline, amoxicillin, or
cefuroxime (if allergic to penicillin) for 14 to 21 days. Children under 8 years of
age should not be treated with doxycycline because it may permanently discolor
their teeth. In patients with Lyme carditis with minor cardiac involvement,
specifically those without cardiac symptoms and first-degree AV block with
a PR interval less than 300 ms, outpatient management with oral antibiotics
is appropriate, as outlined earlier. If the patient is symptomatic, a PR interval
is greater than 300 ms, or there is more advanced AV block, then the patient
should be hospitalized with continuous telemetry monitoring for the initiation
of intravenous (IV) antibiotic therapy. In this situation, treatment with ceftriax-
one or penicillin for 14 to 28 days is appropriate15; see Table 29-1 for appropriate
dosages. As the symptoms improve, therapy can be completed with an oral agent
after discharge from the hospital.
In patients with advanced heart block with hemodynamic instability or
clinically significant symptoms, infusion of isoproterenol and temporary pacing
may be required. A transthoracic echocardiogram should be performed to
evaluate the patient for the possibility of myocarditis. A permanent pacemaker
is not indicated because complete heart block generally resolves within 1 week,
and lesser conduction blocks resolve within 6 weeks.24 While corticosteroids are
occasionally used, there is no evidence that they are beneficial to patients with
Lyme carditis and advanced heart block (see Figure 29-5).24,25
Prevention
The prevention of Lyme carditis is similar to that of Lyme disease in general.
The risk of tick bites can be reduced by avoiding tick-infested wooded and tall
grassy areas, using diethylmetatoluamide (“DEET”) repellents, and performing
daily tick checks. Of note, most individuals who recognize having been bitten by
a tick remove the tick within 48 hours. Because the tick must feed and become
engorged for 48 to 72 hours or longer to transmit B burgdorferi, the risk of
Lyme disease from a recognized tick bite is low (1%–3%), even in areas of high
incidence.26 It is therefore important that clinicians be aware of the clinical
features of early localized and disseminated Lyme disease, even in the absence of
a known history of tick bite.
492
CCIP.indb 492 3/13/18 4:19 PM

Lyme Carditis
Table 29-1. Pharmacological Treatment of Patients with

Lyme Disease
Disease Dosage for Dosage for Length of
Category Medication Route Children Adults Treatment
Early Amoxicillin PO 50 mg/ 500 mg 3 14–21 days

Localized kg per day times per
divided into day
3 doses
Doxycycline PO If >8 y of age 100 mg 2 14–21 days

then 4 mg/ times per
kg per day day
divided into
2 doses
Cefuroxime PO 30 mg/ 500 mg 2 14–21 days

kg per day times per
divided into day
2 doses
Carditis Ceftriaxone IV 50–75 mg/ 2 g daily 14–28 days

kg daily
Penicillin G IV 200,000– 18–24 14–28 days

400,000 million
U/kg per units per
day divided day, divided
into doses into doses
administered adminis-
every 4 h tered every
4h
Cefotaxime IV 150–200 2 g every 8 14–28 days

mg/kg per hours
day divided
into 3–4
doses
Symptomatic Isoproterenol IV Bolus 0.01 Bolus As needed

complete mg/kg then 0.02–0.06 to maintain
heart block 0.05–2.00 mg then hemody-
mg/kg/min 2–20 mg/ namics
min
IV, intravenous; PO, per os (“by mouth”).
493
CCIP.indb 493 3/13/18 4:19 PM

Suspected Lyme carditis
Suspected on the basis Patient has Patient is

of history and physical cardiac hemodynamically
examination findings symptoms unstable due
but no cardiac symptoms to heart block
1. Order 2-tier Lyme antibody testing

2. Order electrocardiography (ECG)
Antibody test results ECG shows PR interval Initiate isoproterenol

are positive and greater than 300 ms and consider temporary
the PR interval is or higher-degree pacing (transcutaneousor
less than 300 ms atrioventricular block transvenous)
1. Initiate oral antibiotics 1. Consult a pediatric cardiologist

2. Repeat ECG in 1–2 days 2. Admit the patient to the hospital with continuous
telemetry monitoring
3. Initiate intravenous (IV) antibiotics
4. Order transthoracic echocardiography
FIGURE 29-5. Management of lyme carditis
Ongoing Care
The long-term prognosis of Lyme carditis is excellent. After the resolution of
symptoms and ECG changes, which typically occurs within 6 weeks, there
is no need for further treatment or follow-up. There is no such entity as late
disseminated Lyme carditis.
Key Points
•• Lyme carditis is rare (incidence ranging from 0.5% to 16%) in children with
Lyme disease.
•• Symptoms include palpitations, dyspnea, chest pain, syncope, and near
syncope, along with other potential symptoms and signs of early disseminated
Lyme disease.
•• The most common manifestation is transient AV block, with asymptomatic
first-degree AV block being most common. However, it can be variable
and fluctuate.
494
CCIP.indb 494 3/13/18 4:19 PM

Lyme Carditis
•• Clinically significant myocardial dysfunction is rare.

•• Diagnostic testing includes 2-tier antibody testing and ECG.
•• Treatment includes antibiotics for 14 to 28 days (IV while hospitalized) and
supportive care, with temporary pacing as needed.
•• Prognosis is excellent, with nearly all conduction abnormalities resolving
within 6 weeks. There are no late cardiac findings or follow-up necessary.

•• Lyme Disease (American Academy of Pediatrics). www.healthychildren.org/
English/health-issues/conditions/from-insects-animals/Pages/Lyme-Disease.
aspx
•• Lyme Disease (Centers for Disease Control and Prevention). www.cdc.gov/
lyme
References
1) Centers for Disease Control and Prevention. Notice to readers: final 2014 reports of nationally
notifiable infectious diseases. MMWR Morb Mortal Wkly Rep. 2015;64(36):1019–1033
2) Centers for Disease Control and Prevention (CDC). Lyme disease—United States, 2003-2005.
MMWR Morb Mortal Wkly Rep. 2007;56(23):573–576
3) Shapiro ED, Gerber MA. Lyme disease. Clin Infect Dis. 2000;31(2):533–542
4) Nadelman RB, Nowakowski J, Fish D, et al; Tick Bite Study Group. Prophylaxis with
single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite.
N Engl J Med. 2001;345(2):79–84
5) Piesman J, Mather TN, Sinsky RJ, Spielman A. Duration of tick attachment and Borrelia
burgdorferi transmission. J Clin Microbiol. 1987;25(3):557–558
6) Cox J, Krajden M. Cardiovascular manifestations of Lyme disease. Am Heart J. 1991;122(5):
1449–1455
7) Forrester JD, Meiman J, Mullins J, et al; Centers for Disease Control and Prevention (CDC).
Notes from the field: update on Lyme carditis, groups at high risk, and frequency of associated
sudden cardiac death—United States. MMWR Morb Mortal Wkly Rep. 2014;63(43):982–983
8) Gerber MA, Shapiro ED, Burke GS, Parcells VJ, Bell GL; Pediatric Lyme Disease Study Group.
Lyme disease in children in southeastern Connecticut. N Engl J Med. 1996;335(17):1270–1274
9) Costello JM, Alexander ME, Greco KM, Perez-Atayde AR, Laussen PC. Lyme carditis in
children: presentation, predictive factors, and clinical course. Pediatrics. 2009;123(5):e835–e841
10) Woolf PK, Lorsung EM, Edwards KS, et al. Electrocardiographic findings in children with
Lyme disease. Pediatr Emerg Care. 1991;7(6):334–336
11) van der Linde MR. Lyme carditis: clinical characteristics of 105 cases. Scand J Infect Dis Suppl.
1991;77:81–84
12) Fish AE, Pride YB, Pinto DS. Lyme carditis. Infect Dis Clin North Am. 2008;22(2):275–288, vi
13) Ruderman EM, Kerr JS, Telford SR III, Spielman A, Glimcher LH, Gravallese EM. Early
murine Lyme carditis has a macrophage predominance and is independent of major histocom-
patibility complex class II-CD4+ T cell interactions. J Infect Dis. 1995;171(2):362–370
14) Duray PH. Histopathology of clinical phases of human Lyme disease. Rheum Dis Clin North
Am. 1989;15(4):691–710
495
CCIP.indb 495 3/13/18 4:19 PM

15) Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and
prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice
guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43(9):1089–1134
16) Steere AC, Batsford WP, Weinberg M, et al. Lyme carditis: cardiac abnormalities of Lyme
disease. Ann Intern Med. 1980;93(1):8–16
17) Seslar SP, Berul CI, Burklow TR, Cecchin F, Alexander ME. Transient prolonged corrected QT
interval in Lyme disease. J Pediatr. 2006;148(5):692–697
18) Ciesielski CA, Markowitz LE, Horsley R, Hightower AW, Russell H, Broome CV. Lyme disease
surveillance in the United States, 1983-1986. Rev Infect Dis. 1989;11(Suppl 6):S1435–S1441
19) Koene R, Boulware DR, Kemperman M, et al. Acute heart failure from lyme carditis. Circ Heart
Fail. 2012;5(2):e24–e26
20) Deresinski S. Sudden unexpected cardiac death from Lyme disease. J Infect Dis. 2014;33:37–39
21) Centers for Disease Control and Prevention (CDC). Recommendations for test performance
and interpretation from the Second National Conference on serologic diagnosis of Lyme disease.
MMWR Morb Mortal Wkly Rep. 1995;44(31):590–591
22) Kalish RA, McHugh G, Granquist J, Shea B, Ruthazer R, Steere AC. Persistence of immuno-
globulin M or immunoglobulin G antibody responses to Borrelia burgdorferi 10-20 years after
active Lyme disease. Clin Infect Dis. 2001;33(6):780–785
23) Smith RP, Schoen RT, Rahn DW, et al. Clinical characteristics and treatment outcome of early
Lyme disease in patients with microbiologically confirmed erythema migrans. Ann Intern Med.
2002;136(6):421–428
24) McAlister HF, Klementowicz PT, Andrews C, Fisher JD, Feld M, Furman S. Lyme carditis: an
important cause of reversible heart block. Ann Intern Med. 1989;110(5):339–345
25) Silver E, Pass RH, Kaufman S, Hordof AJ, Liberman L. Complete heart block due to
Lyme carditis in two pediatric patients and a review of the literature. Congenit Heart Dis.
2007;2(5):338–341
26) Murray TS, Shapiro ED. Lyme disease. Clin Lab Med. 2010;30(1):311–328
496
CCIP.indb 496 3/13/18 4:19 PM

CHAPTER 30
Endocarditis
Amy H. Schultz, MD, MSCE, FAAP, FACC, and Josh Weldin, MD
Introduction
Endocarditis is an inflammatory and usually infectious disorder of the endocardial
lining of the heart, characterized by the development of vegetations. This disease
process can result in local destruction of cardiac structures, embolic complications,
and systemic manifestations related to bacteremia (or fungemia) and immunologic
phenomena. Most clinically manifest endocarditis is infective in nature.
Pathogenesis of Infective Endocarditis

Experimental models and histopathologic studies have led to the conclusion
that the following sequence of events leads to infective endocarditis (IE).1 First,
cardiac endothelium is damaged. Damage can be caused by high-velocity jets of
blood flow through high-pressure shunts (such as a ventricular septal defect or
surgically constructed shunt) or stenotic or regurgitant valves. Alternatively, direct
trauma to the endocardium can be caused by an indwelling central line or device,
such as a pacemaker lead. Second, deposition of platelets and fibrin occurs at the
site of endocardial damage; such deposits are referred to as nonbacterial thrombotic
endocarditis (NBTE). Third, NBTE is colonized by bacteria or fungi at times of
bacteremia or fungemia. The organisms typically express multiple adhesins that
allow attachment to the NBTE substrate. Highly virulent organisms such as
Streptococcus pyogenes, Streptococcus pneumoniae, and Staphylococcus aureus are capable
of causing endocarditis in a previously structurally normal heart. Direct infection
of intracardiac devices can also occur at the time of implantation and should be
considered a deep surgical site infection.
497
CCIP.indb 497 3/13/18 4:19 PM

Pathogenesis of Noninfective Endocarditis

Noninfective endocarditis, which progresses through the first 2 steps described
earlier to NBTE, can be clinically symptomatic in a variety of other serious
diseases, including systemic lupus erythematosus (SLE; Libman-Sacks endocar-
ditis), disseminated malignancy, sepsis, extensive burns, trauma, and persistent
pulmonary hypertension of the newborn.2–4 Clinical manifestations are typically
related to embolic phenomena, rather than valve destruction, although valvular
dysfunction can be progressive in SLE. In these instances, endothelial damage is
thought to result from cytokines or immunologic factors, and procoagulant states
(such as disseminated intravascular coagulation or antiphospholipid antibody
syndrome) frequently coexist.
Epidemiology of IE in Children
The epidemiology of IE in children in developed countries has shifted over the
last 50 years (Figure 30-1).5-10 Before the 1970s, approximately 70% of children
with IE had underlying congenital heart disease (CHD), while the remaining
30% had underlying rheumatic heart disease. With the decline in acute
rheumatic fever, by the 1970s and 1980s, rheumatic heart disease accounted for
only approximately 5% of cases. By the 1990s and 2000s, pediatric medicine
had advanced such that many children with complex medical conditions were
alive and hospitalized for prolonged periods. Treatment, including chronic
central venous lines and other implanted devices, as well as immunosuppression,
predisposes this population to IE. Studies of IE from administrative data sets
and single-institution reviews differ with respect to the frequency of various
underlying conditions but clearly present a different picture than earlier eras
(Figure 30-2). While CHD remains the single most common underlying
condition (ranging from 35% to 80% of cases, depending on the study),
children with complex medical conditions but no underlying cardiac disease
Congenital 70% Congenital 65%–85%

Rheumatic 30% Rheumatic 5% Complex medical care
Before 1970s 1970s–1980s 1990s–2000s

• Complex medical conditions
with prolonged hospitalizations
• Chronic central venous lines
• Immunosuppression
FIGURE 30-1. The underlying conditions that predispose the patient to pediatric infective
endocarditis in developed countries have shifted over time.
498
CCIP.indb 498 3/13/18 4:19 PM

Endocarditis
Underlying Conditions
5–20%
10–30%
35–80%
5%
5%
Any underlying heart

disease 42–85%
CHD
Rheumatic
Other heart disease
Complex non-cardiac
Previously healthy
FIGURE 30-2. Frequency range of underlying conditions in clinical series of pediatric infective
endocarditis. Data from references 5–10. CHD = congenital heart disease.
account for the second largest fraction of the cases, ranging from 10% to 30%.
Rheumatic heart disease remains an uncommon underlying etiologic origin at
approximately 5%. Consistent in every series is a small percentage of patients
(5%–20%) who were previously entirely healthy. Typically, these children are
infected with virulent organisms and have a fulminant course characterized by
a sepsis-type presentation.
With respect to the age distribution of IE within the pediatric population,
there are 2 peaks—1 in the first year of life, and another in the teenage years.8
The risk of IE appears to be lower between the ages of 1 and 11 years (Figure
30-3). The 2 most common causative organisms are S aureus and viridans group
streptococci. Viridans group streptococci account for 20% to 30% of cases
499
CCIP.indb 499 3/13/18 4:19 PM

Age Distribution (n = 1480)

600
500 485
437
Number of Patients
400
304
300
200
108 93
100
53
0
≤30 days 31 days– 1–4 5–11 12–16 17–20
11 months years years years years
Age
FIGURE 30-3. Age distribution of pediatric patients admitted with infective endocarditis in the
Kids’ Inpatient Database from 2000 and 2003. Reproduced with permission from Day MD, Gavreau
K, Shulman S, et al. Characteristics of children hospitalized with infective endocarditis. Circulation.
2009;119:865-870.
in most series and are more common among children with underlying heart
disease.5-10 S aureus seems to have become a more common pathogen since 2000,
particularly among children without underlying cardiac disease. In 2 recent series
derived from administrative data sets, S aureus accounted for 37% to 57% of
cases in which an organism was recorded.8,10
Clinical Features
Clinical Features and Microbiology of IE
The presentation of IE is generally classified as either an acute or a subacute
process. These distinctions are informed by the microbiology of the causative
organism and the epidemiology of the disorder.10 Broadly speaking, acute IE
is rapidly progressive, fulminant, and associated with highly virulent organisms
(S aureus, most commonly). High spiking fevers, hemodynamic instability, and
higher mortality rate characterize acute endocarditis. Longer hospital stays and
multiorgan involvement are also more common in staphylococcal endocarditis.
Subacute IE, in contrast, tends to have a more indolent course, with nonspecific
500
CCIP.indb 500 3/13/18 4:19 PM

Endocarditis
signs and symptoms of low-grade fevers, fatigue, arthralgias, myalgias, weight

loss, and exercise intolerance. These symptoms are often subtle and retrospec-
tively present—most commonly in children with underlying CHD who even-
tually receive a diagnosis of IE. The organisms associated with subacute IE tend
to be less virulent; Streptococcus viridans and coagulase-negative staphylococci are
identified most commonly. Gram-negative IE is relatively rare, even in patients
with gram-negative sepsis.
Other clinical features may include a new murmur secondary to cardiac
valvulitis and septic emboli to either the lungs or the systemic circulation. Septic
emboli are relatively common in children with IE. Glomerulonephritis can
develop in patients with subacute IE, while the other immunologic sequelae of
IE that often lead to physical examination findings are less common in children
than in adults. Nonetheless, these findings are still included in the diagnostic
criteria for IE (see the next section).
Neonates who present with IE often do not have the same constellation of
symptoms as older children and adults. Fever may not be present. Poor feeding,
tachycardia, and a new heart murmur may be observed.
Diagnostic Approach and Laboratory Tests

Accurate diagnosis of IE occurs as the result of a progressive, stepwise approach.
The Duke Criteria for the diagnosis of IE have classically been taught and
used by generations of physicians in establishing the diagnosis of IE. The Duke
Criteria have been modified over time to reflect uncertainty in the diagnosis and
advancements in cardiac imaging.11 The definitions used in the modified Duke
Criteria and the criteria themselves are shown in Boxes 30-1 and 30-2.
While useful, the Duke criteria can only be fully applied after microbiological
and imaging results are available; the criteria are of questionable utility early in
the consideration of the diagnosis of IE. Individual patients may fail to meet the
definitions of “definite” or “possible” IE in the Duke criteria; thus, these criteria
cannot be used alone in diagnostic and treatment decisions made for every
patient. As noted earlier, neonates may fail to have many of the clinical features
of IE, and children in general often do not have many of the immune-mediated
findings commonly seen in adults (Osler nodes and Roth spots). Children who
have been pretreated with antibiotics may not have interpretable blood culture
results. Many children also may not have positive blood culture results, even
when drawn appropriately. This is referred to as culture-negative IE.
Three blood cultures should be obtained from separate venipunctures in the
first 24 hours.1 Obtaining an additional 2 blood cultures in the next 24 hours is
reasonable if there is no growth in the initial cultures. In patients who are not
severely ill, it is reasonable to withhold antibiotic therapy for at least 48 hours.
Bacteremia is generally continuous, and blood cultures do not have to be drawn
at a particular time in the fever cycle. Adjunctive blood test results, such as an
501
CCIP.indb 501 3/13/18 4:19 PM

Box 30-1. Definitions of Terms Used in the Modified Duke

Criteria for the Diagnosis of Infective Endocarditis
Major Criteria
1. Positive blood culture result for IE
A. Typical microorganism consistent with IE from ≥2 blood cultures, as
noted herein
i. Viridans streptococci,a Streptococcus bovis, or HACEK group
or
ii Community-acquired Staphylococcus aureus or enterococci, in the
absence of a primary focus
or
B. Microorganisms consistent with IE from persistently positive blood
culture results, defined as:
i. ≥2 Positive culture results for blood samples drawn >2 h apart
or
ii. All of 3 or a majority of ≥4 blood cultures, irrespective of the timing
iii. One positive blood culture result for Coxiella burnetii or anti-
phase-I immunoglobulin G antibody titer >1:800
2. Evidence of endocardial involvement

A. Positive echocardiographic findings (TEE recommended in prosthetic
valves, rated at least possible IE with clinical criteria or complicated
IE; TTE as the first test in other patients) for IE, defined as
i. Oscillating intracardiac mass on a valve or supporting structures,
in the path of regurgitant jets, or on implanted material in the
absence of an alternative anatomic explanation
or
ii. Abscess
or
iii. New partial dehiscence of prosthetic valve
or
B. New valvular regurgitation (worsening or changing of pre-existing
murmur not sufficient)
Minor Criteria
1. Predisposition: having a predisposing heart condition or intravenous
drug use
2. Fever: temperature ≥38.0°C (≥100.4°F)
3. Vascular phenomena: major arterial emboli, septic pulmonary infarcts,
mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages,
and Janeway lesions
4. Immunologic phenomena: glomerulonephritis, Osler nodes, Roth spots,
and rheumatoid factor
502
CCIP.indb 502 3/13/18 4:19 PM

Endocarditis
Box 30-1. Definitions of Terms Used in the Modified

Duke Criteria for the Diagnosis of Infective Endocarditis,
continued
Minor Criteria, continued
5. Microbiological evidence: positive blood culture result but does not
meet a major criterion as noted earlier or serological evidence of active
infection with organism consistent with IE
HACEK, Haemophilus species, Aggregatibacter species, Cardiobacterium hominis, Eikenella corrodens, and Kingella
species; IE, infective endocarditis; TEE, transesophageal echocardiography; TTE, transthoracic echocardiography.
Source: Baltimore RS, Gewitz M, Baddour LM, et al. Infective endocarditis in childhood: 2015 update: a scientific
statement from the American Heart Association. Circulation. 2015; 132:1487. Original credit: modified from
Durack et al (copyright 1994 Elsevier) and Li et al (copyright 2000 Oxford University Press), with permission
from the publishers.
a
Includes nutritionally variant strains (Abiotrophia species). Excludes single positive cultures for coagulase-negative
staphylococci and organisms that do not cause endocarditis.
Box 30-2. Duke Clinical Criteria for the Diagnosis of

Infective Endocarditis
•• Definite IE
—Pathologic
— criteria
Microorganisms: demonstrated via culture or histologic evaluation
in a vegetation, a vegetation that has embolized, or an intracardiac
abscess
or
Pathologic lesions: vegetation or intracardiac abscess present,
confirmed by histologic findings that show active endocarditis
—Clinical
— criteria as defined in Box 30-1
2 Major criteria
or
1 Major criterion and 3 minor criteria
or
5 Minor criteria
—Possible
— IE
Findings consistent with infective endocarditis that fall short of
“definite” but not “rejected”
—Rejected
—
Firm alternative diagnosis for manifestations of endocarditis
or
Resolution of manifestations of endocarditis with antibiotic therapy
for ≤4 days
or
No pathologic evidence of infective endocarditis at surgery or
autopsy, after antibiotic therapy for ≤4 days
Source: Baltimore RS, Gewitz M, Baddour LM, et al. Infective endocarditis in childhood: 2015 update: a scientific
statement from the American Heart Association. Circulation. 2015;132:1487. Original credit: Modified from Durack et
al (copyright 1994 Elsevier) and Li et al (copyright 2000 Oxford University Press) with permission from the publishers.
503
CCIP.indb 503 3/13/18 4:19 PM

increased white blood cell count and increased markers of inflammation, may
support the diagnosis but are not included in the diagnostic criteria.
A careful history and physical examination, appropriate blood cultures, and
appropriate cardiac and noncardiac imaging performed by a multidisciplinary
pediatric team are generally required to establish the diagnosis. This team may
include but is not limited to primary care providers, pediatric cardiologists, and
infectious disease specialists. Electrocardiography (ECG) is recommended in the
evaluation of IE. Its chief utility is in the setting of aortic valve endocarditis, in
which a perivalvular abscess can invade the crux of the heart, causing atrioven-
tricular (AV) block. The ECG results should be inspected for prolongation of the
PR interval or any higher grades of AV block.
Imaging
Echocardiography is an essential study in the diagnosis and management of
IE. It is the primary modality used to assess the second major criterion of the
modified Duke Criteria for diagnosis of IE (Box 30-1), specifically evidence of
endocardial involvement. This criterion is satisfied by echocardiographic evidence
of an oscillating intracardiac mass (vegetation), an intracardiac abscess, new
partial dehiscence of a prosthetic valve, or new valvular regurgitation.1
Transthoracic echocardiography (TTE) is usually the first imaging study. Two
pediatric series support the use of TTE in patients weighing less than 60 kg to
detect vegetations reliably, with a sensitivity of 92% to 97%.12,13 Transesophageal
echocardiography (TEE), which requires sedation, is superior and indicated in
the following circumstances: (a) the echocardiographer interpreting the images
determines that the transthoracic windows are poor, resulting in suboptimal
image quality at TTE; (b) a prosthetic valve is present; or (c) there is a high risk
for abscess, typically in the setting of aortic valve endocarditis.1 For pediatric
patients who weigh more than 60 kg, it is reasonable to use adult guideline
recommendations for imaging, which recommend the use of TEE in all cases in
which there is moderate to high clinical suspicion for IE.14
Serial echocardiography also plays an important role in the diagnosis and
management of IE. Repeat echocardiography is indicated if the initial study
findings are negative, but there remains a high clinical suspicion for IE. In
established cases of IE, serial echocardiography is used to document changes
in valvular and ventricular function; detect other complications, such as the
development of an abscess or prosthetic valve dehiscence; and document the
resolution of vegetations.
504
CCIP.indb 504 3/13/18 4:19 PM

Endocarditis
Management
Medical
Treatment of IE is similar for adults and children and is guided by the causative
organism (if identified). Empirical therapy for patients who are acutely ill—after
appropriate blood cultures have been drawn—should be directed toward the
most likely pathogens. This drug regimen should cover staphylococci (including
methicillin-resistant S aureus), streptococci, and enterococci. Vancomycin is
generally an acceptable empirical choice for most patients, although many
clinicians choose to empirically add gram-negative coverage (such as ceftriaxone)
while culture results are pending. If a causative organism is identified, the drug
regimen should be appropriately altered to the narrowest effective treatment
regimen possible. Treatment is entirely parenteral, and the duration is typically
between 4 and 6 weeks. The details of antibiotic regimens used in the treatment
of IE are beyond the scope of this chapter but are readily available in the peri-
odically updated American Heart Association Scientific Statement on Infective
Endocarditis in Childhood.1 Longer treatment regimens are indicated for highly
virulent or resistant organisms and for patients with secondary cardiac (eg, valvu-
litis) or noncardiac complications (eg, septic emboli). In general, uncomplicated
right-sided endocarditis with highly susceptible organisms may be adequately
treated with a 4-week course of parenteral antibiotics. Additional decisions about
hospital-based treatment versus outpatient parenteral treatment are based on the
clinical scenario, the family’s ability to provide in-home medical care, and the
adherence to follow-up.
Surgical
Indications for surgical intervention for IE are controversial. For the adult
population, American14 and European15 guidelines differ, with the European
guidelines generally advising more aggressive intervention. The American
pediatric IE guideline published in 2015 emphasizes individualized decision
making and has no strong categorical recommendations for surgery.1 The
guideline does, however, state, “In general, for patients with IE, we recommend
that the degree of illness not be considered a limitation to surgical intervention,
because the alternative, to delay or defer surgery, can have dire consequences.”1
Thus, surgery can have a life-saving role in certain circumstances, which should
be determined by the team caring for an individual patient. Such circumstances
generally include (a) heart failure induced by severe, acute valvular dysfunction;
(b) infection that cannot be controlled by antimicrobial therapy alone, such as
the development of an abscess or a prosthetic valve infection; and (c) prevention
of recurrent embolism. The guidelines recommend not using routine prophylactic
surgery to prevent a primary embolic event, “given the lack of proven benefit and
long-term risks of valve replacement in childhood.”
505
CCIP.indb 505 3/13/18 4:19 PM

Prevention
The cornerstone of prevention of IE is risk reduction. The American Heart
Association, in the 2015 update to its scientific statement on IE in childhood,
stated, “It is reasonable to shift the disproportionately large focus on antibiotic
prophylaxis to an emphasis on oral hygiene and prevention of oral disease.”1 In
terms of the role of the primary care provider, ensuring that the patient has a
reliable dental home is paramount in reducing the burden of pediatric dental
disease and preventing the most common source of bacteremia that leads to IE.
The importance of oral health in children’s well-being has been a broad focus of
the American Academy of Pediatrics. An excellent dental home for all children
would undoubtedly prevent some cases of IE.16
Prophylaxis
See Chapter 31, Prevention of Bacterial Endocarditis, for details on prophylaxis.
The Role of Primary Care

Prevention and Prophylaxis
As alluded to in the previous sections, the primary care provider has an import-
ant role in the prevention of IE. The primary care provider should pay particular
attention to dental health screening and ensuring that patients with underlying
cardiac disease have a dental home. In addition, primary care providers should be
aware of the most current IE prophylaxis recommendations, reinforce the need
for prophylaxis for eligible patients, and prescribe antibiotics when necessary.
When to Consider IE in Primary Care

Understanding the epidemiology of IE is helpful in establishing the diagnosis.
The bimodal distribution in ages shown in Figure 30-3 illustrates the increased
incidence in infants and is especially relevant in high-risk subsets of neonates,
such as preterm neonates and/or newborns who have central venous lines.
Patients who present with shock and sepsis-like symptoms should have acute
IE considered as a potential cause. As previously mentioned, this is the typical
presentation for patients who develop IE who do not have underlying cardiac
heart disease or invasive devices. This consideration is especially relevant to
physicians who provide emergency, inpatient, and critical care. The diagnostic
consideration in this type of patient must be made concurrently with appropriate
cardiorespiratory support and initially may not differ a great deal from other
patients who present with septic shock. However, certain features should raise
the suspicion early in the course of acute IE. The presence of septic emboli
resulting in extracardiac infections such as septic pneumonia, osteomyelitis, or
506
CCIP.indb 506 3/13/18 4:19 PM

Endocarditis
neurological findings from central nervous system septic emboli such as new
seizures, stroke, or altered mental status should raise suspicion. Isolation of
highly virulent organisms from the bloodstream (S aureus, S pyogenes) should
prompt consideration of IE and echocardiography. Consultation with a pediat-
ric cardiologist is advisable when this diagnosis is being considered.
The symptoms of subacute IE tend to be less specific and more indolent.
Low-grade fever and fatigue are common symptoms in a busy primary care
office setting, while IE is an uncommon disorder in outpatients. Thus, the
challenge to the primary care provider is to remember to consider the diagnosis
of subacute IE in the appropriate clinical context. Patients who receive diagnoses
of subacute IE are most commonly those who have underlying cardiac disease.
For patients with even a distant history of repaired CHD or those who may have
a history of intravenous drug use, the diagnosis should be considered earlier than
it would be in the general population.
Additionally, primary care providers have an important role in avoiding
antimicrobial therapy without good rationale. Such therapy, in addition to
promoting antimicrobial resistance, can obscure the diagnosis of IE and result
in an inability to obtain a definitive microbiological diagnosis. Pretreatment
with antibiotics increases the incidence of culture-negative IE and may lead
to treatment regimens that are longer and broader in spectrum than would be
necessary if a specific organism could be isolated.
Ongoing Care
Follow-up
Follow-up after completion of treatment for endocarditis is the shared respon-
sibility of the pediatric cardiologist and the primary care team. Development of
new symptoms after completing treatment for IE should prompt collaboration
between providers to assess the patient for relapse or structural causes of new
symptoms (eg, new valvar insufficiency).
Complications
IE is a destructive process, especially if the infecting organism is an aggressive
one. While vegetations can regress with appropriate antimicrobial therapy, the
patient can be left with permanent valvular dysfunction. In the case of native
valves, typically, regurgitation develops. In the case of previously placed bio-
prosthetic valves or conduits, progressive stenosis can be observed. Mechanical
prosthetic valves can also become unstable and dehisce. Infection of foreign
material can be hard to clear, requiring removal and replacement. Intracardiac
abscesses can develop, particularly in the setting of aortic valve endocarditis or
prosthetic valve endocarditis. AV block can develop because of destruction of
the conduction system by an extending intracardiac abscess.
507
CCIP.indb 507 3/13/18 4:19 PM

Embolic phenomena are another major complication of IE. If IE is confined

to the right side of the heart, septic pulmonary emboli result and can lead to
multiple lung abscesses. Vegetations on the left side of the heart can embolize
systemically, leading to stroke, myocardial infarction, or other systemic ischemic
phenomena. Abscesses, particularly of the spleen, and mycotic aneurysms can
develop at sites where septic emboli lodge.
The musculoskeletal symptoms of arthralgia and myalgia each occur in 10%
to 15% of patients with IE. Osteomyelitis can be a secondary complication of
IE. Acute renal failure is a potential complication of IE and may be related to
sepsis-associated hemodynamic instability, immune complex–related phenom-
ena, embolic phenomena, and/or antibiotic toxicity.
Prognosis
IE is a life-threatening infection that requires aggressive management and
follow-up until resolved. Individuals who have had 1 episode of IE are known
to be at higher risk for recurrent IE. Thus, a history of IE is an indication for
lifetime endocarditis prophylaxis for indicated procedures. In addition, if the
predisposing cardiac lesion can be eliminated with surgery, such as a ventricular
septal defect, surgery is indicated after recovery. Otherwise, the patient’s
prognosis will be determined by any residua from the infection, which can
include valvular dysfunction, ventricular dysfunction, need for valve repair or
replacement, and mycotic aneurysms caused by embolization of vegetations.
Key Points
•• IE is an uncommon but potentially life-threatening condition that requires
aggressive treatment from a multidisciplinary team.
•• The primary care provider’s most important contributions to the prevention
of IE are dental health screening and ensuring that the patient has an
adequate dental home. This role is particularly important in caring for
children with underlying heart disease.
•• Primary care providers should consider the diagnosis of IE in the appropriate
clinical context—namely, in patients with underlying heart disease who
present with intermittent fever and malaise and in any patient who presents
with an acutely ill appearance.
•• Avoidance of antibiotics prior to obtaining blood cultures is crucial when
diagnosing and treating IE.
508
CCIP.indb 508 3/13/18 4:19 PM

Endocarditis

•• Infective Endocarditis (American Heart Association). www.heart.org/
HEARTORG/Conditions/CongenitalHeartDefects/TheImpactof
CongenitalHeartDefects/Infective-Endocarditis_UCM_307108_Article.
jsp#.V_03DnLrvGg
•• What Is Infective Endocarditis? (American Heart Association) www.heart.
org/idc/groups/heart-public/@wcm/@hcm/documents/downloadable/
ucm_300297.pdf
•• Heart Valves and Infective Endocarditis (American Heart Association).
www.heart.org/HEARTORG/Conditions/More/HeartValveProblemsand
Disease/Heart-Valves-and-Infective-Endocarditis_UCM_450448_Article.
jsp#.V_04E3LrvGg
References
1) Baltimore RS, Gewitz M, Baddour LM, et al; American Heart Association Rheumatic Fever,
Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease
in the Young and the Council on Cardiovascular and Stroke Nursing. Infective endocarditis
in childhood: 2015 update: a scientific statement from the American Heart Association.
Circulation. 2015;132(15):1487–1515
2) Young RSK, Zalneraitis EL. Marantic endocarditis in children and young adults: clinical and
pathological findings. Stroke. 1981;12(5):635–639
3) Morrow WR, Haas JE, Benjamin DR. Nonbacterial endocardial thrombosis in neonates:
relationship to persistent fetal circulation. J Pediatr. 1982;100(1):117–122
4) Bouma W, Klinkenberg TJ, van der Horst ICC, et al. Mitral valve surgery for mitral regurgita-
tion caused by Libman-Sacks endocarditis: a report of four cases and a systematic review of the
literature. J Cardiothorac Surg. 2010;5:13
5) Rosenthal LB, Feja KN, Levasseur SM, Alba LR, Gersony W, Saiman L. The changing
epidemiology of pediatric endocarditis at a children’s hospital over seven decades. Pediatr Cardiol.
2010;31(6):813–820
6) Coward K, Tucker N, Darville T. Infective endocarditis in Arkansan children from 1990 through
2002. Pediatr Infect Dis J. 2003;22(12):1048–1052
7) Marom D, Levy I, Gutwein O, Birk E, Ashkenazi S. Healthcare-associated versus communi-
ty-associated infective endocarditis in children. Pediatr Infect Dis J. 2011;30(7):585–588
8) Day MD, Gauvreau K, Shulman S, Newburger JW. Characteristics of children hospitalized with
infective endocarditis. Circulation. 2009;119(6):865–870
9) Pasquali SK, He X, Mohamad Z, et al. Trends in endocarditis hospitalizations at US children’s
hospitals: impact of the 2007 American Heart Association Antibiotic Prophylaxis Guidelines.
Am Heart J. 2012;163(5):894–899
10) Gupta S, Sakhuja A, McGrath E, Asmar B. Trends, microbiology, and outcomes of infective
endocarditis in children during 2000-2010 in the United States. Congenit Heart Dis.
2017;12(2):196–201
11) Li JS, Sexton DJ, Mick N, et al. Proposed modifications to the Duke criteria for the diagnosis of
infective endocarditis. Clin Infect Dis. 2000;30(4):633–638
12) Humpl T, McCrindle BW, Smallhorn JF. The relative roles of transthoracic compared with
transesophageal echocardiography in children with suspected infective endocarditis. J Am Coll
Cardiol. 2003;41(11):2068–2071
509
CCIP.indb 509 3/13/18 4:19 PM

13) Penk JS, Webb CL, Shulman ST, Anderson EJ. Echocardiography in pediatric infective endocar-
ditis. Pediatr Infect Dis J. 2011;30(12):1109–1111
14) Baddour LM, Wilson WR, Bayer AS, et al; American Heart Association Committee on
Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular
Disease in the Young, Council on Clinical Cardiology, Council on Cardiovascular Surgery and
Anesthesia, and Stroke Council. Infective endocarditis in adults: diagnosis, antimicrobial therapy,
and management of complications: a scientific statement for healthcare professionals from the
American Heart Association. Circulation. 2015;132(15):1435–1486
15) Habib G, Lancellotti P, Antunes MJ, et al. 2015 European Society of Cardiology guidelines for
the management of infective endocarditis. Eur Heart J. 2015;36:3075–3128
16) Segura A, Boulter S; Section on Oral Health. Maintaining and improving the oral health of
young children. Pediatrics. 2014;134(6):1224–1229
510
CCIP.indb 510 3/13/18 4:19 PM

CHAPTER 31
Prevention
of Bacterial
Endocarditis
John Colquitt, MD, FAAP, and Carolyn A. Altman, MD, FAAP
Introduction
The American Heart Association (AHA) first published recommendations for the
prevention of infective endocarditis (IE) in 1955. These guidelines have undergone
periodic revisions, with the tenth and most recent published in 2007.1
The fundamental principles behind prophylaxis are as follows: (a) Prevention is
preferable to treatment of established infection, (b) certain cardiac conditions pre-
dispose the patient to IE, and (c) bacteria known to cause IE are part of the normal
oral and respiratory tract flora. Because the occurrence of bacteremia is c rucial to
the initiation of IE, and bacteremia may occur during invasive procedures, it has
been postulated that preventing or promptly treating transient bacteremia can
prevent IE.
Despite sound theory, however, the evidence to support antimicrobial prophy-
laxis for the prevention of procedure-related bacteremia is weak. The data used in
support of the 2007 revision of the AHA guidelines include the following.
•• Dental procedure bacteremias are short-lived and of low magnitude, similar to
those that result from routine daily activities.2–4
•• The frequency and cumulative exposure of random bacteremia from chewing
food and brushing teeth (every day) are far greater than those from dental
procedures (the average person has <2 dentist visits per year).5,6
511
CCIP.indb 511 3/13/18 4:19 PM

•• Most patients who develop IE have not had a dental procedure within 2 weeks
prior to the onset of IE.7–9
•• The estimated risk of developing IE from a single dental procedure in adults
with predisposing cardiac conditions is low, both with and without the use of
prophylaxis (1:150,000 vs 1:46,000, respectively). A large number of prophy-
laxis doses would be necessary to prevent a very small number of IE cases.10
•• Even if administered, prophylaxis is not 100% effective.9,11
•• Antibiotic exposure and use are not risk free. The risks of antibiotic-associated
adverse reactions likely far exceed the benefits for many patients, and the
indiscriminate use of antibiotics may contribute to an increase in resistant
organisms.12,13
In response to these findings, the 2007 AHA recommendations narrowed the
groups of both patients and procedures for which prophylaxis is reasonable.
Prophylaxis is restricted to patients with the highest risk of adverse outcome
from IE who would derive the greatest benefit from prevention of IE. Moreover,
the 2007 guidelines emphasize the maintenance of oral health and hygiene to
reduce daily bacteremia and underscore that this is more important than any
dental antibiotic prophylaxis.
AHA Recommendations
Patient Groups
According to the 2007 AHA guidelines, patients with the highest-risk
conditions, for whom prophylaxis is reasonable, are those with
•• Prosthetic heart valves, including bioprosthetic and homograft valves
•• A prior history of IE
•• Unrepaired cyanotic congenital heart disease (CHD), including palliative
shunts and conduits
•• Completely repaired congenital heart defects with a prosthetic material or
device, whether placed via surgery or catheter intervention, during the first
6 months after the procedure (prophylaxis is reasonable because endotheliali-
zation of prosthetic material occurs within 6 months after the procedure)
•• Repaired CHD with residual defects at the site or adjacent to the site of the
prosthetic patch or prosthetic device (which inhibits endothelialization)
•• Valve regurgitation due to a structurally abnormal valve in a transplanted heart
Except for these conditions, antibiotic prophylaxis is no longer recommended
by the AHA for any other form of CHD.
512
CCIP.indb 512 3/13/18 4:19 PM

Prevention of Bacterial Endocarditis
Dental Procedures
Prophylaxis is considered reasonable in all procedures that involve manipulation
of gingival tissue or the periapical region of teeth or perforation of the oral
mucosa, such as tooth extractions, drainage of a dental abscess, and routine
dental cleaning.
The following procedures and events do not require prophylaxis: routine
anesthetic injections through noninfected tissue, obtaining dental radiographs,
placement of removable prosthodontic or orthodontic appliances, adjustment
of orthodontic appliances, placement of orthodontic brackets, shedding of
deciduous teeth, and bleeding from trauma to the lips or oral mucosa.
Respiratory Tract Procedures

Only those procedures that involve incision or biopsy of the respiratory mucosa,
such as tonsillectomy, adenoidectomy, or bronchoscopy with biopsy, should be
considered for antimicrobial IE prophylaxis.
Treatment Regimens
Table 31-1 shows the AHA-recommended regimens for antimicrobial prophy-
laxis prior to dental and respiratory procedures. Table 31-2 provides information
on specific procedure sites.
Table 31-1. Regimens for Antimicrobial Prophylaxis

Prior to Dental and Respiratory Procedures
Regimen: Single Dose 30 to 60 min Before
Procedurea
Situation Agent Children Adults
Oral Amoxicillin 50 mg/kg 2g
Unable to take oral Ampicillin 50 mg/kg, IM or IV 2 g, IM or IV

medication OR 30 mg/kg, IM or IV 1 g, IM or IV
Cefazolin or (cefazolin); 50 mg/kg, IM
ceftriaxone or IV (ceftriaxone)
Allergic to penicil- Cephalexinb,c 50 mg/kg 2g

lins, oral OR 10 mg/kg 900 mg
Clindamycin 15 mg/kg 500 mg
OR
Azithromycin
or
clarithromycin
Allergic to Cefazolin or 30 mg/kg, IM or IV 1 g, IM or IV

penicillins and ceftriaxonec (cefazolin); 50 mg/kg, IM 900 mg, IM or IV
unable to take oral OR or IV (ceftriaxone)
medication Clindamycin 10 mg/kg, IM or IV
Continued
513
CCIP.indb 513 3/13/18 4:19 PM

Table 31-1. Regimens for Antimicrobial Prophylaxis

Prior to Dental and Respiratory Procedures, continued
Regimen: Single Dose 30 to 60 min Before
Procedurea
Situation Agent Children Adults
Already on Choose an antibiotic of a different class, or if possible, delay

antibiotics for the procedure until 10 days after the completion of antibiotics
other indications
at the time a
relevant procedure
is undertaken
IM, intramuscular; IV, intravenous. From reference 1.
a
If inadvertently not administered before the procedure, the dose may be given up to 2 hours after the procedure.
b
Or other first- or second-generation oral cephalosporin in equivalent pediatric or adult dosage.
c
Cephalosporins should not be used in a person with a history of anaphylaxis, angioedema, or urticaria with
penicillins or ampicillin.
Table 31-2. Guidance for Specific Procedure Sites

High-Risk Patient Undergoing an Invasive The Therapeutic Regimen Should
Procedure in the Area of or to Treat an Include an Agent Active Against the
Established Infection in the Following: Following:
Skin, skin structure, musculoskeletal tissue Staphylococci and β-hemolytic

streptococci
Respiratory tract Viridans group streptococci; S aureus

(if known or suspected cause)
Gastrointestinal or genitourinary tract Enterococci

Data from reference 1.
Procedures Excluded From Prophylaxis

In the absence of active infection, the AHA does not recommend prophylaxis for
gastrointestinal or genitourinary procedures. This is a major departure from pre-
vious guidelines. There is no evidence to support a link between these procedures
and the development of IE, nor is there proof of effectiveness of prophylaxis,
although some have argued that the absence of proof of effectiveness and safety
cannot be used as proof of absence of effectiveness and safety.13
Prophylaxis is also not recommended for vaginal or cesarean delivery. The
2008 American College of Cardiology and AHA adult CHD guidelines14 note
that it is reasonable to consider antibiotic prophylaxis before vaginal delivery
at the time of membrane rupture in select patients with the highest risk of
adverse outcome: those with prosthetic cardiac valve or unrepaired or palliated
cyanotic heart disease (with the caveat that there is no proof of effectiveness of
prophylaxis).
514
CCIP.indb 514 3/13/18 4:19 PM

Prevention of Bacterial Endocarditis
Key Points
•• Use of antimicrobial prophylaxis for prevention of bacterial endocarditis is
based on theoretical advantage, rather than data from clinical trials.
•• IE is much more likely to result from frequent random bacteremias from daily
activities, such as brushing teeth, flossing, and chewing, than from a dental,
gastrointestinal tract, or genitourinary tract procedure.
•• Maintenance of optimal oral health and hygiene and access to routine dental
care are more important than prophylactic antibiotics in reducing IE risk.
•• Antimicrobial prophylaxis is restricted to cardiac patients with the highest
risk of adverse outcome from IE.
References
1) Wilson W, Taubert KA, Gewitz M, et al; American Heart Association Rheumatic Fever,
Endocarditis, and Kawasaki Disease Committee; American Heart Association Council on
Cardiovascular Disease in the Young; American Heart Association Council on Clinical
Cardiology; American Heart Association Council on Cardiovascular Surgery and Anesthesia;
Quality of Care and Outcomes Research Interdisciplinary Working Group. Prevention of
infective endocarditis: guidelines from the American Heart Association: a guideline from the
American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee,
Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology,
Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes
Research Interdisciplinary Working Group. Circulation. 2007;116(15):1736–1754
2) Roberts GJ, Jaffray EC, Spratt DA, et al. Duration, prevalence and intensity of bacteraemia after
dental extractions in children. Heart. 2006;92(9):1274–1277
3) Lucas VS, Lytra V, Hassan T, Tatham H, Wilson M, Roberts GJ. Comparison of lysis filtration
and an automated blood culture system (BACTEC) for detection, quantification, and identifica-
tion of odontogenic bacteremia in children. J Clin Microbiol. 2002;40(9):3416–3420
4) Durack DT, Beeson PB. Experimental bacterial endocarditis. II. Survival of a bacteria in
endocardial vegetations. Br J Exp Pathol. 1972;53(1):50–53
5) Guntheroth WG. How important are dental procedures as a cause of infective endocarditis?
Am J Cardiol. 1984;54(7):797–801
6) Roberts GJ. Dentists are innocent! “Everyday” bacteremia is the real culprit: a review and
assessment of the evidence that dental surgical procedures are a principal cause of bacterial
endocarditis in children. Pediatr Cardiol. 1999;20(5):317–325
7) Strom BL, Abrutyn E, Berlin JA, et al. Dental and cardiac risk factors for infective endocarditis.
A population-based, case-control study. Ann Intern Med. 1998;129(10):761–769
8) Durack DT. Antibiotics for prevention of endocarditis during dentistry: time to scale back?
Ann Intern Med. 1998;129(10):829–831
9) van der Meer JT, Thompson J, Valkenburg HA, Michel MF. Epidemiology of bacterial endo-
carditis in the Netherlands. II. Antecedent procedures and use of prophylaxis. Arch Intern Med.
1992;152(9):1869–1873
10) Duval X, Alla F, Hoen B, et al. Estimated risk of endocarditis in adults with predisposing cardiac
conditions undergoing dental procedures with or without antibiotic prophylaxis. Clin Infect Dis.
2006;42(12):e102–e107
11) Durack DT, Kaplan EL, Bisno AL. Apparent failures of endocarditis prophylaxis. Analysis of
52 cases submitted to a national registry. JAMA. 1983;250(17):2318–2322
515
CCIP.indb 515 3/13/18 4:19 PM

12) Groppo FC, Castro FM, Pacheco AB, et al. Antimicrobial resistance of Staphylococcus aureus
and oral streptococci strains from high-risk endocarditis patients. Gen Dent. 2005;53(6):410–413
13) Ashrafian H, Bogle RG. Antimicrobial prophylaxis for endocarditis: emotion or science? Heart.
2007;93(1):5–6
14) Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA 2008 Guidelines for the
Management of Adults with Congenital Heart Disease: a report of the American College of
Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee
to develop guidelines on the management of adults with congenital heart disease). Circulation.
2008;118(23):e714–e833
516
CCIP.indb 516 3/13/18 4:19 PM

CHAPTER 32
Myocarditis
Ryan Butts, MD
Introduction
Definition
Myocarditis is defined as an inflammatory and infiltrative process that involves cell
damage and necrosis of the myocardium and is not caused by coronary perfusion
abnormalities. Typically, myocarditis is an acute process. However, myocarditis can
have clinically significant long-term sequelae.
Etiologic Origins
Most pediatric acute myocarditis is likely of viral etiologic origin. However,
identifying the causative virus is often difficult. In a recent review of pediatric
patients admitted for acute myocarditis, only approximately 30% had an identified
viral etiologic origin.1 Studies performed in the 1970s and 1980s showed that
the coxsackievirus was the most common etiologic origin for myocarditis.2,3 In
subsequent decades, adenovirus became the most commonly identified virus.4,5
Most recently, parvovirus B19 has been identified as a leading cause of pediatric
viral myocarditis. However, the viral pathogens associated with myocarditis are
many, including enterovirus, influenza, Epstein-Barr virus, cytomegalovirus, herpes
simplex virus, hepatitis C, rubella, varicella, HIV, and respiratory syncytial virus
(RSV).6–15 Less commonly, various other nonviral pathogens have been associated
with myocarditis, including Streptococcus, Mycoplasma, Rickettsia, Trypanosoma cruzi,
Histoplasma, and Candida.16–18 Rheumatic disorders, such as mixed connective
tissue disorder, systemic lupus erythematosus, and rheumatic arthritis, have been
associated with myocarditis.19 Kawasaki disease can cause pericarditis, as well
as myocarditis.20 Other possible etiologic origins include autoimmune diseases,
environmental toxins, and adverse reactions to medications.
517
CCIP.indb 517 3/13/18 4:19 PM

Epidemiology
The exact incidence of myocarditis is unknown. Reviews of large hospitalization
databases show that myocarditis is not a common reason for admission, account-
ing for less than 1% of pediatric hospitalizations.21,22 However, myocarditis
is 1 of the leading causes of sudden unexplained death in pediatric patients.
A single-center autopsy review showed that 36% of patients who presented
with sudden unexplained death had evidence of myocarditis.23 In the adult
Myocarditis Treatment Trial, approximately 10% of patients who presented
with new-onset heart failure without coronary artery disease had biopsy results
positive for myocarditis.24 The prevalence of myocarditis among pediatric cases
of new-onset acute heart failure is not known.
Myocarditis has a bimodal age distribution.25 There is a significantly increased
incidence in the first 2 years of life, after which the curve sharply drops.
However, around the age of 13 years, the frequency of myocarditis increases
again (Figure 32-1). This has been demonstrated in multiple studies.1,21
FIGURE 32-1. Histogram demonstrates the age of admission for a multicenter database of 171
patients with myocarditis. The histogram demonstrates a bimodal age distribution with the highest
percentage of patients admitted with myocarditis in the first 2 years of life and in adolescence.26
518
CCIP.indb 518 3/13/18 4:19 PM

Myocarditis
Clinical Features
Signs and Symptoms
The clinical presentation of myocarditis varies with the age of the patient. Often
in the emergency department, the first sign is a nonspecific tachycardia that does
not improve with reduction of fever or with fluid resuscitation and is often out of
proportion to the degree of fever. A viral prodrome may precede the illness but is
only reported in less than half of patients who are hospitalized. Given the rarity
of myocarditis, pediatricians must have a high index of clinical suspicion to be
able to diagnosis myocarditis.
Infants
Newborns and infants often present with nonspecific signs of acute heart failure
that mimic more common pediatric disorders. In a recent review of inpatient
admissions for myocarditis, the most common presenting symptom was respira-
tory distress (68%), followed by poor feeding (24%) and malaise and/or fatigue
(22%).1 Despite the frequency of viral illness in this age group, only 37% of
patients had a viral prodrome. At physical examination, a little more than half of
infants had respiratory distress, 40% had hepatomegaly, and 30% had diminished
pulses and gallop.1 These data highlight the fact that the presentation of infant
myocarditis is incredibly subtle and nonspecific and is therefore easily missed.
Children
Toddlers and school-aged children, excluding adolescents, are most likely to
present with malaise and/or fatigue (34%) and chest pain (40%).1 Approximately
one-half will have a viral prodrome. At physical examination, hepatomegaly,
respiratory distress, and gallop are the most common findings; however, approxi-
mately one-half of patients had normal physical examination findings.
Adolescents
Adolescents (aged 13–18 years) are more likely to present with chest pain
and dyspnea. A viral prodrome is present in fewer than one-half of patients.
Adolescents are less likely than younger age groups to have physical examination
findings of congestive heart failure (CHF). This may be due to earlier recogni-
tion of symptoms in this age group, as well as an overlap between myocarditis,
pericarditis, and myopericarditis syndromes.
Any disease state that manifests with cardiogenic shock and acute CHF should
be considered in the differential diagnosis of myocarditis. However, the most
challenging situation is determining whether a patient has acute viral myocardi-
tis rather than dilated cardiomyopathy with an intercurrent illness that led to the
519
CCIP.indb 519 3/13/18 4:19 PM

patient’s presentation. The differential diagnosis for newly detected ventricular

dysfunction on the basis of age is outlined in Box 32-1.
Box 32-1. Differential Diagnosis for Ventricular Dysfunction

on the Basis of Age
Infant Child Adolescent
Dilated cardiomyopathy Dilated Dilated
cardiomyopathy cardiomyopathy
Anomalous left coronary Coarctation of the Pericarditis

from pulmonary artery aorta
Coarctation of the aorta Tachycardia- Tachycardia-induced

induced cardiomyopathy
cardiomyopathy
Sepsis
Tachycardia-induced
cardiomyopathy
Laboratory Findings
Laboratory results in myocarditis are highly variable. Because myocarditis is a
disease process that involves an inflammatory process that leads to myocardial
cell damage, it is often thought that inflammatory markers, such as erythrocyte
sedimentation rate (ESR) and C-reactive protein (CRP) level, should be
increased and that findings should include markers of myocardial cell damage
(ie, troponin). A recent report showed that CRP levels and ESR were often
within normal ranges for patients with myocarditis, especially in patients under
2 years of age.1 Also, while troponin level was increased for the entire group, up
to 1 in 8 patients had a troponin level less than 0.1 ng/mL. Overall, troponin
level was lower in the younger age group (age <2 years) than in the older age
groups (age 2–18 years). Brain natriuretic peptide (BNP), a marker of heart
failure, was markedly increased in all age groups. Table 32-1 summarizes the
breakdown seen in laboratory findings on the basis of age group.
Diagnostic Tests and Imaging

First-line diagnostic testing and imaging usually consists of chest radiography
and electrocardiography (ECG). Chest radiographs can show signs of heart
failure, which include pulmonary edema, increased pulmonary vasculature
markings, and cardiomegaly. The presence of high left atrial pressure and left
atrial dilation may lead to widening of the carina. Unfortunately, it is common to
have no remarkable findings on chest radiographs. The classic findings at ECG
520
CCIP.indb 520 3/13/18 4:19 PM

Myocarditis
Table 32-1. Comparison of Laboratory and

Echocardiography Values Between Age Groups
13–18 y
<2 y (n = 41) 2–12 y (n = 44) (n = 86) P Value
Laboratory Values
Brain natriuretic peptide 3,562 1,637 194 <.01

(pg/mL) (1,601–4,229) (721–2,800) (55.4–728)
Troponin (ng/mL) 0.8 0.4 (0.12–8.5) 8.6 <.01

(0.09–4.3) (1.5–49)
Creatine kinase (IU/L) 79 (49–219) 204 (24–521) 300 .23

(41–635)
ESR (mm/h) 8 (1.9–29) 10.5 (2–40.7) 11 (6–33) .44
CRP (mg/dL) 0.87 (0.5–1.7) 3.3 (0.5–12.6) 4.6 <.01

(1.1–10.5)
Echocardiography Values
Ejection fraction (%) 30 (20–43) 33 (23–45) 54 <.01

(35–62)
Shortening fraction 16 (11–22) 18 (12–26) 30 <.01

(22–37)
Diastolic z score 1.63 (-0.55 to 1.7 (0.11–2.8) 0.55 .05

4.1) (-0.35 to
1.66)
Systolic z score 2.9 (1.2–6.9) 3.8 (0.7–6.8) 1.4 (-0.09 <.01

to 2.7)
Data shown are medians, with interquartile ranges in parentheses. Patients <2 years of age were more likely to
present with increased brain natriuretic peptide levels, lower troponin levels, and worse ventricular function on
echocardiograms. P values were generated with the Kruskal-Wallis test for nonparametric data. To convert pico-
grams per milliliter to nanograms per liter for brain natriuretic peptide level, multiply by 1.0. To convert nanograms
per milliliter to micrograms per liter for troponin level, multiply by 1.0. To convert international units per liter to
microkatals per liter for creatine kinase level, multiply by 0.0167. CRP = C-reactive protein, ESR = erythrocyte
sedimentation rate. From reference 1.
include sinus tachycardia, low-voltage QRS, and prominent Q waves. Changes

in ST segments may also be seen. However, the most common finding is sinus
tachycardia alone. Other findings include frequent atrial or ventricular ectopy,
ventricular tachycardia, and atrial tachycardia. Atrioventricular (AV) nodal block
has also been well described in myocarditis.
Echocardiography is used early in the evaluation of suspected myocarditis.
Typical findings include depressed ventricular function, with mild or no
ventricular dilation. Other findings include mitral regurgitation, pericardial
effusion, and wall-motion abnormalities. Echocardiographic findings of acute
myocarditis may overlap with tachycardia-induced cardiomyopathy and newly
521
CCIP.indb 521 3/13/18 4:19 PM

diagnosed dilated cardiomyopathy. The degree of ventricular dilation may help

the cardiologist distinguish between myocarditis and dilated cardiomyopathy.
Especially in the younger age group, it is important to ensure that coronary
artery anatomy is normal at echocardiography when considering myocarditis
(to rule out anomalous left coronary artery arising from the pulmonary artery).
Echocardiographic findings in myocarditis broken down according to age group
are summarized in Table 32-1.
Identifying the viral etiologic origin is often difficult in acute viral myocar-
ditis. Myocardial polymerase chain reaction (PCR) is considered the standard
of reference for diagnosing specific viral etiologic origins; however, this requires
invasive endomyocardial biopsy and is not available at all institutions. Frequently,
viral PCRs from the serum, respiratory secretions, and/or urine are performed.
Only 25% to 30% of patients with clinically diagnosed myocarditis have a
positive PCR result from a site other than the myocardium.1
Magnetic resonance (MR) imaging and endomyocardial biopsy are currently
considered the standard of reference methods for diagnosing myocarditis. On
MR images, T2-weighted imaging may demonstrate areas of myocardial edema
in myocarditis, and late gadolinium-based contrast material enhancement can
help identify areas of myocardial injury. At endomyocardial biopsy, routine his-
tologic findings will usually show a mononuclear inflammatory infiltrate within
the myocardium, with possible myocardial cell damage. While biopsy is the
standard of reference, it is invasive and has associated procedural risks. Biopsies
may be of use in adolescent patients, who have a lower procedural risk, when
rare causes of myocarditis, such as giant cell myocarditis, are being considered.
MR imaging is the newer technique and has been compared to biopsy in adult
myocarditis with excellent results.27 When determining between dilated cardio-
myopathy and myocarditis, the presence of inflammation on MR images has
been associated with recovery of ventricular function.28 Given the insensitivity
of biopsy combined with the ability of MR imaging to demonstrate all parts
of the myocardium, the use of MR imaging in the diagnosis of myocarditis has
grown in pediatrics.21
Inpatient Management
Supportive Treatment
The degree of supportive treatment depends on the degree of ventricular
dysfunction and the presence of cardiogenic shock. For patients with cardiogenic
shock, admission to the intensive care unit is required. These patients often
require mechanical ventilation. Inotropes are often needed to increase cardiac
output; however, the patient should be monitored closely for the development of
arrhythmias. The development of arrhythmias should be recognized quickly and
treated immediately. Atrial and ventricular tachyarrhythmias should be treated
522
CCIP.indb 522 3/13/18 4:19 PM

Myocarditis
with antiarrhythmics. AV block, especially complete heart block, would likely

require a temporary pacemaker. Volume overload, evidenced by pleural effusions,
pulmonary edema, or ascites, should be treated with diuretics. For refractory
cardiogenic shock, invasive mechanical circulatory support via extracorporeal
membrane oxygenation or ventricular-assist device (VAD) are often used.29–31
These therapies provide the added benefit of reducing myocardial stress during
the inflammatory phase but have substantial associated morbidities (thrombo-
embolism, stroke, hemorrhage). Pediatric VADs have been used with increasing
frequency for heart failure over the past decade, and VADs will likely have a
more prominent role in the stabilization and treatment of fulminant myocarditis
in the future.
Traditional heart failure medications are often used in pediatric myocarditis
once the patient is no longer in cardiogenic shock. Angiotensin-converting
enzyme inhibitors or angiotensin receptor blockers are often used to help the
myocardial remodeling process, especially in patients with persistent left ven-
tricular dysfunction or dilation. β-blockers and aldosterone antagonists have also
been shown to be safe and likely aid in myocardial recovery after myocarditis.
Intravenous Immunoglobulin and Steroids

In the mid-1990s, Drucker and colleagues reported an improvement in ventricu-
lar function in pediatric patients with myocarditis who were treated with intrave-
nous immunoglobulin (IVIg) when compared with historical control subjects.32
This led to rapid adoption of IVIg in pediatric myocarditis; however, subsequent
single-center reviews and multicenter database analyses have not reproduced a
benefit of IVIg.7,15–18 Because of the study by Drucker and colleagues, IVIg use
continues to be popular, with approximately two-thirds of patients admitted
for myocarditis receiving IVIg. In a multi-institutional observational study of
patients admitted from 2008 to 2012, patients who received IVIg and/or steroids
showed no improvement in hospital mortality, ejection fraction at discharge,
or cardiac readmission within 1 year.1 In multivariable analysis, IVIg and/or
steroids were not independently associated with worse outcomes. Given the
design of this study and previous studies, the role that IVIg and/or steroids play
in pediatric myocarditis remains controversial. This question will likely require a
prospective clinical trial to answer definitively. However, attempts to create such
a study have been frustrated by lack of clinical equipoise, consensus definition of
myocarditis, low patient volumes, and appropriate study primary end points.
Outcomes
Despite the fact that a large portion of patients with myocarditis present in
severe cardiogenic shock, approximately 80% to 90% have transplant-free sur-
vival to discharge. Currently, known risk factors for death and/or transplantation
include younger age, severely depressed left ventricular systolic function at
523
CCIP.indb 523 3/13/18 4:19 PM

presentation, increased BNP level, and presence of gastrointestinal symptoms.1,33

Approximately 10% to 20% of patients discharged will have a cardiac readmis-
sion within 1 year of discharge.
Outpatient Follow-up
Immediately after discharge, the patient with myocarditis requires close mon-
itoring, typically with a cardiologist. The cardiologist should frequently assess
ventricular function by using echocardiography, as well as assess the patient for
arrhythmias via long-term ECG monitoring. As described in the next section,
a full evaluation by a cardiologist should be performed between 3 and 6 months
after initial presentation before the patient returns to competitive sports.
While myocarditis is often thought of as an acute process, there has been
increasing recognition of long-term sequalae, mainly the return of myocardial
dysfunction and heart failure. The exact reason for the recurrence of heart failure
remains unclear, but interactions between viral and host genomes have been
implicated.34,35 Therefore, patients with myocarditis should undergo long-term
follow-up to evaluate them for the return of ventricular dysfunction and
heart failure.
The American Heart Association and the American College of Cardiology
published guidelines for participation in competitive sports in 2015.36 While
not specific to pediatric myocarditis, the guidelines provide a useful matrix for
allowing participation in athletics after a diagnosis of myocarditis. On the basis
of animal models, a period of 3 to 6 months of rest from competitive sports is
recommended. Prior to returning to training, the guidelines recommend that
all athletes undergo echocardiography that shows normal ventricular function;
serum markers of myocardial injury, inflammation, and heart failure should all
be within normal ranges; and Holter monitoring and stress testing should show
no arrhythmias or frequent ectopy. It is still unknown if evidence of myocardial
injury or fibrosis on MR images should be resolved prior to returning to
competitive sports.
Key Points
•• Myocarditis is rare disease in pediatrics that is characterized by myocardial
inflammation and necrosis, not from coronary-related ischemia.
•• Pediatric patients with acute myocarditis present with the nonspecific signs of
tachycardia, poor feeding, chest pain, and emesis.
•• The signs and symptoms at presentation differ with age.
524
CCIP.indb 524 3/13/18 4:19 PM

Myocarditis
•• First-line diagnostic studies include chest radiography, serum troponin levels,

ECG, and echocardiography.
•• Standard of reference tests are MR imaging and endomyocardial biopsy.
However, standard of reference tests may not be clinically feasible and should
not delay treatment.
•• Treatment is intended to support cardiac output in the acute phase.
•• The role of IVIg and steroids remains controversial.
•• Most patients are discharged and have ventricular function return to normal.
References
1) Butts RBG, Deshpande S, Gambetta K, et al. Pediatric Myocarditis in a Contemporary Multi-
Center Cohort. 2016 ISHLT Meeting. 2016
2) Berkovich S, Rodriguez-Torres R, Lin JS. Virologic studies in children with acute myocarditis.
Am J Dis Child. 1968;115(2):207–212
3) Dec GW Jr, Palacios IF, Fallon JT, et al. Active myocarditis in the spectrum of acute dilated
cardiomyopathies. Clinical features, histologic correlates, and clinical outcome. N Engl J Med.
1985;312(14):885–890
4) Bowles NE, Bowles KR, Towbin JA. Viral genomic detection and outcome in myocarditis. Heart
Fail Clin. 2005;1(3):407–417
5) Bowles NE, Ni J, Kearney DL, et al. Detection of viruses in myocardial tissues by polymerase
chain reaction. evidence of adenovirus as a common cause of myocarditis in children and adults.
J Am Coll Cardiol. 2003;42(3):466–472
6) Morriss FH Jr, Lindower JB, Bartlett HL, et al. Neonatal enterovirus infection: case series of
clinical sepsis and positive cerebrospinal fluid polymerase chain reaction test with myocarditis
and cerebral white matter injury complications. AJP Rep. 2016;6(3):e344–e351
7) Gross ER, Gander JW, Reichstein A, Cowles RA, Stolar CJ, Middlesworth W. Fulminant
pH1N1-09 influenza-associated myocarditis in pediatric patients. Pediatr Crit Care Med.
2011;12(2):e99–e101
8) Reitman MJ, Zirin HJ, DeAngelis CJ. Complete heart block in Epstein-Barr myocarditis.
Pediatrics. 1978;62(5):847–849
9) Dehtiar N, Eherlichman M, Picard E, et al. Cytomegalovirus myocarditis in a healthy infant:
complete recovery after ganciclovir treatment. Pediatr Crit Care Med. 2001;2(3):271–273
10) Koga M, Fujiwara M, Ariga S, et al. CD8+ T-lymphocytes infiltrate the myocardium in
fulminant herpes virus myocarditis. Pediatr Pathol Mol Med. 2001;20(3):189–195
11) Pepe A, Meloni A, Borsellino Z, et al. Myocardial fibrosis by late gadolinium enhancement
cardiac magnetic resonance and hepatitis C virus infection in thalassemia major patients.
J Cardiovasc Med (Hagerstown). 2015;16(10):689–695
12) Moriuchi H, Yamasaki S, Mori K, Sakai M, Tsuji Y. A rubella epidemic in Sasebo, Japan in
1987, with various complications. Acta Paediatr Jpn. 1990;32(1):67–75
13) Kao KL, Yeh SJ, Chen CC. Myopericarditis associated with varicella zoster virus infection.
Pediatr Cardiol. 2010;31(5):703–706
14) Bowles NE, Kearney DL, Ni J, et al. The detection of viral genomes by polymerase chain
reaction in the myocardium of pediatric patients with advanced HIV disease. J Am Coll Cardiol.
1999;34(3):857–865
15) Menchise A. Myocarditis in the setting of RSV bronchiolitis. Fetal Pediatr Pathol.
2011;30(1):64–68
525
CCIP.indb 525 3/13/18 4:19 PM

16) Mattoo TK, al-Mutair A, al-Khatib Y, Ali A, al-Sohaibani MO. Group A beta-haemolytic
streptococcal infection and Henoch-Schonlein purpura with cardiac, renal and neurological
complications. Ann Trop Paediatr. 1997;17(4):381–386
17) Hartleif S, Wiegand G, Kumpf M, Eberhard M, Hofbeck M. Severe chest pain caused by
Mycoplasma myocarditis in an adolescent patient. Klin Padiatr. 2013;225(7):423–425
18) Montalvo-Hicks LD, Trevenen CL, Briggs JN. American trypanosomiasis (Chagas’ disease)
in a Canadian immigrant infant. Pediatrics. 1980;66(2):266–268
19) Vogel T, Kitcharoensakkul M, Fotis L, Baszis K. The heart and pediatric rheumatology. Rheum
Dis Clin North Am. 2014;40(1):61–85
20) Newburger JW, Burns JC. Kawasaki syndrome. Cardiol Clin. 1989;7(2):453–465
21) Ghelani SJ, Spaeder MC, Pastor W, Spurney CF, Klugman D. Demographics, trends, and
outcomes in pediatric acute myocarditis in the United States, 2006 to 2011. Circ Cardiovasc
Qual Outcomes. 2012;5(5):622–627
22) Klugman D, Berger JT, Sable CA, He J, Khandelwal SG, Slonim AD. Pediatric patients hospi-
talized with myocarditis: a multi-institutional analysis. Pediatr Cardiol. 2010;31(2):222–228
23) Ilina MV, Kepron CA, Taylor GP, Perrin DG, Kantor PF, Somers GR. Undiagnosed heart
disease leading to sudden unexpected death in childhood: a retrospective study. Pediatrics.
2011;128(3):e513–e520
24) Mason JW, O’Connell JB, Herskowitz A, et al; The Myocarditis Treatment Trial Investigators.
A clinical trial of immunosuppressive therapy for myocarditis. N Engl J Med. 1995;333(5):
269–275
25) Messroghli DR, Pickardt T, Fischer M, et al; MYKKE Consortium. Toward evidence-based
diagnosis of myocarditis in children and adolescents: rationale, design, and first baseline data of
MYKKE, a multicenter registry and study platform. Am Heart J. 2017;187:133–144
26) Butts RJ, Boyle GJ, Deshpande SR, et al. Characteristics of clinically diagnosed pediatric
myocarditis in a contemporary multi-center cohort. Pediatr Cardiol. 2017;38(6):1175–1182
27) Friedrich MG, Sechtem U, Schulz-Menger J, et al; International Consensus Group on
Cardiovascular Magnetic Resonance in Myocarditis. Cardiovascular magnetic resonance in
myocarditis: a JACC white paper. J Am Coll Cardiol. 2009;53(17):1475–1487
28) Raimondi F, Iserin F, Raisky O, et al. Myocardial inflammation on cardiovascular magnetic
resonance predicts left ventricular function recovery in children with recent dilated cardio
myopathy. Eur Heart J Cardiovasc Imaging. 2015;16(7):756–762
29) Dimas VV, Morray BH, Kim DW, et al. A multicenter study of the impella device for mechan-
ical support of the systemic circulation in pediatric and adolescent patients. Catheter Cardiovasc
Interv. 2017;90(1):124–129
30) Wilmot I, Morales DL, Price JF, et al. Effectiveness of mechanical circulatory support in
children with acute fulminant and persistent myocarditis. J Card Fail. 2011;17(6):487–494
31) Lin KM, Li MH, Hsieh KS, et al. Impact of extracorporeal membrane oxygenation on acute
fulminant myocarditis-related hemodynamic compromise arrhythmia in children. Pediatr
Neonatol. 2016;57(6):480–487
32) Drucker NA, Colan SD, Lewis AB, et al. Gamma-globulin treatment of acute myocarditis in
the pediatric population. Circulation. 1994;89(1):252–257
33) Sachdeva S, Song X, Dham N, Heath DM, DeBiasi RL. Analysis of clinical parameters and
cardiac magnetic resonance imaging as predictors of outcome in pediatric myocarditis. Am J
Cardiol. 2015;115(4):499–504
34) Bergelson JM, Cunningham JA, Droguett G, et al. Isolation of a common receptor for Coxsackie
B viruses and adenoviruses 2 and 5. Science. 1997;275(5304):1320–1323
35) Badorff C, Lee GH, Lamphear BJ, et al. Enteroviral protease 2A cleaves dystrophin: evidence of
cytoskeletal disruption in an acquired cardiomyopathy. Nat Med. 1999;5(3):320–326
526
CCIP.indb 526 3/13/18 4:19 PM

Myocarditis
36) Maron BJ, Udelson JE, Bonow RO, et al. Eligibility and Disqualification Recommendations
for Competitive Athletes with Cardiovascular Abnormalities: Task Force 3: Hypertrophic
Cardiomyopathy, Arrhythmogenic Right Ventricular Cardiomyopathy and Other
Cardiomyopathies, and Myocarditis: a Scientific Statement from the American Heart
Association and American College of Cardiology. J Am Coll Cardiol. 2015;66(21):2362–2371
527
CCIP.indb 527 3/13/18 4:19 PM

CCIP.indb 528 3/13/18 4:19 PM
CHAPTER 33
Pericardial Diseases
Diego Lara, MD, MPH, and Carolyn A. Altman, MD, FAAP
Introduction
The pericardium is a tough, fibrous sac that encloses the heart. This sac has 2 layers,
a serous layer called the parietal pericardium and the reflected cardiac portion on
the surface of the heart, which is called the epicardium.1 There is normally 10 to
50 mL of pericardial fluid in the space between the epicardium and pericardium.
When demonstrable with echocardiography, this should be a small rim visible only
during systole.2,3

The most common disorders of the pericardium include acute pericarditis,
recurrent pericarditis, myopericarditis, pericardial effusion and cardiac tamponade,
and constrictive pericarditis.
Acute Pericarditis
Acute pericarditis is a new, rapidly developing inflammation of the pericardium. It
is the most common form of pericardial disease. Epidemiological data for pediatric
acute pericarditis are limited, but a large Italian study showed an incidence of 27.7
per 100,000 for the general population (including children and adults).4 Acute
pericarditis can be an isolated problem, a component of systemic disease, or a
response to trauma or medication (Box 33-1). In developed countries, the etiologic
origin of isolated pericarditis is usually a viral infection; in the developing world,
tuberculosis is the most common cause.5
529
CCIP.indb 529 3/13/18 4:19 PM

Box 33-1. Etiologic Origins of Acute Pericarditis

Infectious
Viral (common)
Enteroviruses
Herpesviruses (cytomegalovirus, Epstein-Barr virus)
Adenovirus
Parvovirus
Bacterial
Mycobacterium tuberculosis (common; other bacterial causes are rare)
Fungal (very rare; generally found in an immunocompromised host)
Histoplasma
Blastomyces
Noninfectious
Autoimmune (common)
Systemic lupus erythematosus
Sjögren syndrome
Systemic idiopathic arthritis
Systemic vasculitides (polyarteritis nodosa, Takayasu disease)
Inflammatory bowel disease
Neoplastic disorders
Metabolic disorders
Uremia
Anorexia nervosa
Trauma related
Drug related
Drugs involved in lupus-like syndromes (procainamide, hydralazine,
methyldopa, isoniazid, phenytoin)
Antineoplastic drugs (doxorubicin, daunorubicin)
Amiodarone
Thiazides
Cyclosporine
Data are from reference 9.
Clinical Features and Diagnostic Criteria

The diagnosis of acute pericarditis is established with 2 or more of the following
criteria6:
•• Chest pain (>85% to 90% of cases), which classically improves when the
patient sits forward and worsens in the supine position.7 This pain typically
worsens on inspiration or during a cough and is often described as sharp.
•• Pericardial friction rub (<33% of cases) is a scratchy or squeaky tripartite sound
(1 systolic and 2 diastolic sounds) heard best over the left sternal border. This is
distinguished from a pleural rub, which changes more directly with inspiration.8
530
CCIP.indb 530 3/13/18 4:19 PM

•• Widespread electrocardiographic (ECG) changes (60% of cases): Diffuse ST

segment elevation (concave upward) in all leads except aVR and V1, where
there is usually ST depression. PR segment depression may be present. The
ECG may also show diffusely low voltages. ECG changes correlate with the
onset of chest pain (Figure 33-1).
•• Pericardial effusion (60% of cases), often small and not hemodynamically
significant.
Important supportive findings for the diagnosis of acute pericarditis are
increased markers of inflammation such as C-reactive protein (CRP) level,
erythrocyte sedimentation rate (ESR), and white blood cell count.
Management
Diagnostic evaluation for all patients with suspected pericarditis should include
ECG, transthoracic echocardiography, chest radiography, CRP level, complete
blood count, ESR, and troponin levels.9
A triage system for pericarditis has been developed by the European Society
of Cardiology to separate high- and low-risk patients (Figure 33-2); this system
was not developed specifically for infants and children, however. Per this triage
strategy, high-risk patients with concern for a systemic disease or those with a
predictor of poor prognosis warrant inpatient admission. Low-risk cases may be
considered for treatment on an outpatient basis.
Pediatric cardiology consultation should be sought for all patients with
suspected acute pericarditis.
Activity Restrictions
All patients should be restricted from exercising, generally for a 3-month
period.10 Nonathletes can return to physical activity (such as physical education
class) after resolution of symptoms and normalization of CRP level.11 The
FIGURE 33-1. Typical electrocardiogram for acute pericarditis. Courtesy of C. de la Uz, MD, Texas
Children’s Hospital.
531
CCIP.indb 531 3/13/18 4:19 PM

Pericarditis?
(physical examination, ECG,
chest x-ray, echocardiogram,
CRP, troponin)
No Yes
Diagnostic criteria not statisfied. Specific etiology highly suspected
Search for alternative diagnoses or any predictor of poor prognosis
Yes No
Empiric trial with NSAID
Predictors of poor prognosis: High Risk Cases Non-High Risk Cases

Major Admission and No admission and
• Fever >38ºC etiology search etiology search.
• Subacute onset (major or minor Response to NSAID?
• Large pericardial effusion prognostic predictor)
• Cardiac tamponade
• Lack of response to
aspirin or NSAIDs after
No Yes
at least 1 week of therapy
Minor
• Myopericarditis
• Immunosuppression Moderate Risk Cases Low Risk Cases
• Trauma Admission and Outpatient
• Oral anticoagulant therapy etiology search follow-up
FIGURE 33-2. Proposed triage of acute pericarditis according to epidemiological background and
predictors of poor prognosis at presentation. At least 1 predictor of poor prognosis is sufficient to
identify a high-risk case. Major criteria have been validated with multivariate analysis. Minor criteria
are based on expert opinion and literature review. Cases with moderate risk are defined as cases
without negative prognostic predictors but incomplete or lacking response to nonsteroidal anti-
inflammatory drug therapy. Low-risk cases include those without negative prognostic predictors and
good response to anti-inflammatory therapy. Specific etiologic origin is intended as nonidiopathic
etiologic origin. CRP = C-reactive protein, ECG = electrocardiography, NSAID = nonsteroidal
anti-inflammatory drug. From reference 9.
European Society of Cardiology recommends that athletes return to competition

only after resolution of symptoms and normalization of CRP, ECG, and
echocardiographic findings.10
Nonsteroidal Anti-inflammatory Drugs
Although there is not a strong body of evidence for their use, standard practice
for treatment of acute pericarditis is an anti-inflammatory dose of aspirin or
532
CCIP.indb 532 3/13/18 4:19 PM

other nonsteroidal anti-inflammatory drugs (NSAIDs).12 Ibuprofen adminis-

tered at 10 mg/kg per dose (up to 600 mg) by mouth every 8 hours for 2 weeks
is a typical regimen, followed by a slow taper over another 2 weeks to prevent
rebound recurrence of symptoms. It is important to remember to provide gastric
protection to patients taking scheduled ibuprofen in the form of a proton pump
inhibitor or H2 blocker.
Colchicine
Low-dose colchicine has become the drug of choice in adults for prevention
of incessant (persistent symptoms lasting more than 4–6 weeks but less than 3
months) and recurrent pericarditis (in which symptoms recur after a 4–6-week
asymptomatic phase).13,14 Approximately 15% to 30% of patients not treated
with colchicine will develop incessant or recurrent symptoms; colchicine reduces
this rate by about half.13 The dose for patients who weigh less than 70 kg is 0.5
mg once daily, and for those who weigh more than 70 kg, it is 0.5 mg twice daily
by mouth for 3 months. A recent meta-analysis showed insufficient evidence to
support or discourage the use of colchicine in children;15 however, some practices
continue to use it.
Corticosteroids
Corticosteroids are not considered primary therapy for pericarditis because
they have been found to increase the risk of recurrence.12 However, they can be
used in cases where NSAIDs have failed or are contraindicated, where steroids
should be a secondary therapy. A large meta-analysis demonstrated that a low-
dose course of prednisone (0.2–0.5 mg/kg per day) was superior to high-dose
(1.0 mg/kg per day) therapy.12 Given the questionable effectiveness and high
incidence of adverse reactions associated with steroid use, a short 5- to 7-day
course may be advisable. Steroids should be avoided in patients with suspected
or known tuberculosis or bacterial or fungal pericarditis.
Follow-up
Uncomplicated cases of acute pericarditis require follow-up at least at 1 week
and 1 month after diagnosis to assess the effectiveness of therapy.16 A further
visit at 3 months is indicated to determine readiness to return to competitive
sports or physical education class. Complicated or persistent pericarditis
follow-up will be undertaken according to the advice of the rheumatologist or
pediatric cardiologist treating the patient.
Prognosis
Most patients with isolated acute pericarditis treated on an outpatient basis
experience resolution of symptoms with no long-term complications.17 Rarely,
patients may go on to develop progressive effusions that result in tamponade.
There is a small risk of developing constrictive pericarditis, about 1% over a time
533
CCIP.indb 533 3/13/18 4:19 PM

frame of 3 months to several years. Therefore, patients should be counseled to

return for urgent evaluation promptly with the onset of worsened chest pain,
dyspnea, orthopnea, or fever. Given the vague symptoms that can accompany
pericarditis, it is important to not limit the reasons to return to a small set of
symptoms but rather to instruct the family to look for substantial changes or
ill appearance.
Myopericarditis
Patients with a clinical diagnosis of pericarditis but with markers of myocardial
injury, such as increased troponin I or creatine kinase–MB levels, are thought to
have myopericarditis.18
Patients with myopericarditis are considered higher risk and should be
hospitalized. The choice of therapy has some controversy, and consultation
with pediatric cardiology and/or rheumatology is warranted. While some
authors recommend traditional therapy with aspirin or NSAIDs, animal studies
have showed increased mortality with these traditional anti-inflammatory
treatments.19 Colchicine therapy is not used in myopericarditis because there is
insufficient evidence for its use.20 Another distinction in therapy is that patients
with myopericarditis should have activity restrictions for at least 6 months, not
the usual 3 months for pericarditis.10
Recurrent Pericarditis
Recurrent pericarditis is diagnosed with recurrence of symptoms and signs after
a 4- to 6-week symptom-free period.13 It is diagnosed on the basis of the same
criteria as acute pericarditis and shares the same etiologic origins. It is often
attributable to inadequate initial treatment of acute pericarditis.9
Recurrent pericarditis is treated in the same manner as acute pericarditis, with
standard NSAIDs and the addition of colchicine.21 If corticosteroids are added
to therapy, an extended taper should be used to prevent recurrence.22
Pericardial Effusion and Cardiac Tamponade

A pericardial effusion is a pathologic amount of fluid in the pericardial space
(usually exceeding 15 mm in diameter at end-diastole by echocardiography) that
has a transudative or exudative source.
It can be classified on the basis of several different distinguishing
characteristics9:
•• Onset: acute or chronic (>3 months)
•• Distribution: circumferential or loculated
•• Hemodynamic effects: range of effects, from none to tachycardia to tampon-
ade physiology
534
CCIP.indb 534 3/13/18 4:19 PM

•• Composition: exudate, transudate, or blood

•• Size: small, medium, or large
Etiologic Origins
The etiologic origins of pericardial effusions mirror those of pericarditis. Most
are idiopathic (50%); the remaining 50% are divided almost evenly between neo-
plasia (10%–25%), infection (15%–30%), and connective tissue or rheumatologic
diseases (5%–15%).23,24 It is important to note that large effusions are more likely
to be associated with neoplasia or infection.2
Clinical Features
An important predictor of the clinical presentation of a pericardial effusion is the
time course of its development. If it is rapid, the acute stretch of the pericardium
by even a small volume of fluid can cause significant hemodynamic effects, while
a slowly accumulating effusion can become very large before any hemodynamic
effects are noted.25

The symptoms associated with a pericardial effusion can range from a com-
plete absence of symptoms to the shock state associated with cardiac tamponade.
The most common symptoms include chest pain, dyspnea, orthopnea, tachy-
cardia, fever, palpitations, and/or cough.26 Nausea, dysphagia, hoarseness, and
hiccups from the pericardial sac pressing on adjacent structures can also occur.26

The physical examination findings may be normal in those with small
to moderate effusions, although a pericardial rub may be detected in 40%.27
Tachycardia is also a frequent finding. In hemodynamically significant effusions,
muffled heart sounds and jugular venous distention are the classic findings. In
patients with tamponade physiology, pulsus paradoxus may be demonstrated
with manual cuff blood pressure. This is defined as a decrease in systolic
blood pressure of more than 10 mm Hg during inspiration. Pulsus paradoxus
results from an exaggeration of the normal phenomenon of interventricular
dependence. During inspiration, there is increased right ventricular filling
from the increased systemic venous return. With tamponade, the fluid in the
pericardial sac constrains the overall space available for ventricular filling.
During inspiration, then, right ventricular filling occurs at the expense of left
ventricular filling. Thus, the pressure of the effusion exaggerates the normal
“ventricular interdependence” and causes the decrease in systemic blood pressure
by limiting left ventricular filling. The loss of a palpable pulse during inspiration
is a more severe manifestation of this finding and explains the etiologic origin
of the nomenclature. Pulsus paradoxus demonstrable with pulse usually reflects
impending cardiovascular collapse.
535
CCIP.indb 535 3/13/18 4:19 PM

Diagnosis
Investigations that assist in the diagnosis of a pericardial effusion are the same
as those of pericarditis: ECG, chest radiography, transthoracic echocardiography,
and markers of inflammation. ECG may display diffusely decreased voltages. In
the setting of a large pericardial effusion, ECG may demonstrate an alternans
pattern, with changing of the QRS/T wave axis as the heart swings in the large
effusion. The chest radiograph will often show an enlarged cardiac silhouette.
However, chest radiography cannot be relied on to exclude a hemodynamically
significant effusion, because even a small effusion may cause clinically significant
symptoms if rapidly accumulating. The diagnostic modality of choice is the
echocardiogram, which directly demonstrates the presence, size, and distribution
of the effusion. Echocardiography can indicate but not confirm the composition
of the effusion (ie, an echogenic effusion may suggest purulent effusion).
Echocardiography may further provide evidence of impending or blatant tam-
ponade physiology. However, it is important to recognize that cardiac tamponade
is a clinical diagnosis and not solely an echocardiographic one. Some of the
important echocardiographic signs of impending tamponade physiology include
right atrial collapse, early diastolic septal bounce, enlarged inferior vena cava,
and exaggerated respiratory changes of the tricuspid and mitral valve inflows.3
Ventricular diastolic collapse is a more severe and even more concerning finding.
Therapy
If there are signs of systemic inflammation in a patient with a pericardial
effusion, the treatment should be the same as that for acute pericarditis.9
In patients with no signs of inflammation, a specific diagnosis should be
determined via inpatient admission. In these patients, there is no role for the use
of anti-inflammatory medications.26 In patients with symptomatic pericardial
effusions who have failed anti-inflammatory therapy or in those who are not
candidates for therapy, pericardiocentesis and possibly drain placement are
indicated for treatment and to aid in achieving diagnosis; in recurrent cases,
surgical options such as a pericardial window or pericardiectomy are considered.2
Echocardiographically guided pericardiocentesis is the treatment of choice for
cardiac tamponade. Prior to drainage of the effusion, the main therapeutic goal
should be fluid resuscitation to provide enough preload to maintain cardiac
filling. As a corollary, diuretics should be avoided in this situation. In patients
who are asymptomatic and hemodynamically stable, a trial of low-dose diuretic
therapy with furosemide can be attempted with careful monitoring to ensure
that the diuresis does not impair cardiac filling.
536
CCIP.indb 536 3/13/18 4:19 PM

Follow-up and Prognosis

Mild effusions generally have good prognoses.2 However, up to one-third of
moderate to large effusions may worsen to develop tamponade.28 Therefore,
patients with moderate and large effusions should be followed up frequently by
using echocardiography until they are believed to be stable.9
Constrictive Pericarditis
Constrictive pericarditis is caused by a loss of the elastic qualities of the pericar-
dium, resulting in impairment of diastolic filling.9
Incidence and Etiologic Origins

For patients with idiopathic pericarditis, the risk of developing constrictive
pericarditis is low (<1%). For patients with autoimmune or neoplastic etiologic
origins, the risk is higher at 2% to 5%. The risk is substantial at 20% to 30% for
those with bacterial pericarditis.17 A transient constrictive pericarditis can occur
over the first 3 months after diagnosis; the more severe, chronic form can con-
tinue until treated.17 In the developing world, tuberculosis is the most common
cause of constrictive pericarditis, especially in patients with HIV.29
Clinical Features
The presenting signs and symptoms of constrictive pericarditis are those of right-
sided heart failure: fatigue, peripheral edema, dyspnea, and abdominal swelling.
Physical examination findings will often show tachycardia, jugular venous
distention, hepatomegaly, and a pericardial knock.9 A history of resolved acute
pericarditis in a patient with these new symptoms should prompt an urgent
referral to a pediatric cardiologist.
Diagnosis
Appropriate investigations include chest radiography and transthoracic
echocardiography initially. Cardiac magnetic resonance images frequently
demonstrate the thickened pericardium better than echocardiography. Cardiac
catheterization may be necessary if noninvasive measures are nondiagnostic or
if the hemodynamics of constrictive pericarditis need to be distinguished from
restrictive cardiomyopathy.
There are generally 3 therapeutic strategies, depending on the type of
constrictive pericarditis. If the etiologic origin is tuberculous, therapy should
be targeted at treating the infection.30 If the finding of constrictive pericarditis
is new, it may be due to a transient constriction during the healing process,
and typical pericarditis therapy may be helpful.31 In symptomatic constrictive
pericarditis, the treatment of choice is surgical pericardiectomy.9
537
CCIP.indb 537 3/13/18 4:19 PM

Postcardiac Injury Syndrome

Postcardiac injury syndrome (PCIS) is an overarching term that encompasses sev-
eral disorders, including postpericardiotomy syndrome (associated with cardiac
surgery), posttraumatic pericarditis (associated with cardiac interventions such as
radiofrequency ablation or pacemaker lead insertion or with accidental trauma),
and postmyocardial infarction pericarditis.32
Incidence and Etiologic Origins

The incidence of PCIS is not known, but PCIS is a common cause of pericar-
ditis; in 1 study, it was found to be the etiologic origin in 21% of patients with
acute pericarditis.33 It is estimated that 10% to 40% of patients who undergo
cardiac surgery are affected by postpericardiotomy syndrome.34 The current
understanding of the pathogenesis of PCIS is that it is an autoimmune response
triggered by damage to myocardial or pleural mesothelial cells.32
Clinical Features and Diagnosis

PCIS clinically looks very much like acute pericarditis but is distinguished by the
fact that it can be associated with pleuropericardial involvement and pulmonary
infiltrates. Therefore, a special set of diagnostic criteria has been proposed for
PCIS, with the presence of 2 criteria being diagnostic in the setting of a cardiac
injury: fever without alternative causes, pericarditic or pleuritic chest pain, peri-
cardial or pleural rubs, or evidence of pericardial effusion and/or pleural effusion
with increased CRP level.9
Therapy
The same regimen of nonsteroidal drugs and colchicine used in acute pericarditis
is the therapy of choice for PCIS in adults.35,36
Key Points
•• Acute pericarditis is a new, rapidly developing inflammation of the
pericardium.
•• Acute pericarditis is diagnosed on the basis of the presence of 2 or more of
the following: chest pain, pericardial friction rub, widespread ECG changes
(diffuse ST segment elevation), and pericardial effusion.
•• Therapy for acute pericarditis is a combination of colchicine (0.5 mg once
daily for patients who weigh less than 70 kg; 0.5 mg twice daily for those
who weigh more than 70 kg for 3 months) and an NSAID medication such
as ibuprofen (2 weeks with a slow taper), along with activity restriction for
3 months. Steroid therapy is rarely indicated.
538
CCIP.indb 538 3/13/18 4:19 PM

•• Patients with a clinical diagnosis of pericarditis but with markers of myo-

cardial injury, such as increased troponin I or creatine kinase–MB levels, are
thought to have myopericarditis and should be treated similarly to patients
with myocarditis; NSAIDs and colchicine are not used.
•• Recurrent pericarditis is diagnosed with recurrence of symptoms and signs of
acute pericarditis after a 4- to 6-week symptom-free period; it is generally due
to undertreatment of the initial episode of acute pericarditis.
•• A pericardial effusion is a pathologic amount of fluid in the pericardial space
(usually exceeding 15 mm in diameter at end-diastole by echocardiography)
that has a transudative or exudative source. Large or rapidly evolving effusions
can have significant hemodynamic consequences, the most serious of which is
shock elicited by cardiac tamponade.
•• Constrictive pericarditis is a rare, late consequence of acute or recurrent
pericarditis most frequently associated with purulent pericarditis. The loss of
the elastic qualities of the pericardium results in impairment of diastolic filling,
causing signs and symptoms of right-sided heart failure.
•• PCIS is a form of pericardial disease that occurs after an insult or injury to
the pericardium and is thought to be autoimmune mediated. It is treated in a
similar manner to acute pericarditis.

•• Pericarditis (American College of Cardiology). www.cardiosmart.org/
Heart-Conditions/Pericarditis
•• Pediatric Infective Pericarditis (Medscape). emedicine.medscape.com/
article/897899-overview
•• Pericardial Disease (Cleveland Clinic). www.clevelandclinicmeded.com/
medicalpubs/diseasemanagement/cardiology/pericardial-disease
References
1) Anderson RH. Paediatric Cardiology. 3rd ed. London, United Kingdom: Churchill Livingstone;
2009
2) Imazio M, Adler Y. Management of pericardial effusion. Eur Heart J. 2013;34(16):1186–1197
3) Klein AL, Abbara S, Agler DA, et al. American Society of Echocardiography clinical
recommendations for multimodality cardiovascular imaging of patients with pericardial disease:
endorsed by the Society for Cardiovascular Magnetic Resonance and Society of Cardiovascular
Computed Tomography. J Am Soc Echocardiogr. 2013;26(9):965–1012.e15
4) Imazio M, Cecchi E, Demichelis B, et al. Myopericarditis versus viral or idiopathic acute
pericarditis. Heart. 2008;94(4):498–501
5) Imazio M, Gaita F. Diagnosis and treatment of pericarditis. Heart. 2015;101(14):1159–1168
6) Troughton RW, Asher CR, Klein AL. Pericarditis. Lancet. 2004;363(9410):717–727
7) Lange RA, Hillis LD. Clinical practice. Acute pericarditis. N Engl J Med.
2004;351(21):2195–2202
539
CCIP.indb 539 3/13/18 4:19 PM

8) Pinsky LE, Wipf JE. Techniques: Heart Sounds & Murmurs Web site. http://depts.washington.
edu/physdx/heart/tech5.html#pp. Accessed December 14, 2017
9) Adler Y, Charron P, Imazio M, et al; European Society of Cardiology (ESC). 2015 ESC
Guidelines for the diagnosis and management of pericardial diseases:the Task Force for the
Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology
(ESC) endorsed by: the European Association for Cardio-Thoracic Surgery (EACTS). Eur
Heart J. 2015;36(42):2921–2964
10) Pelliccia A, Corrado D, Bjornstad HH, et al. Recommendations for participation in competitive
sport and leisure-time physical activity in individuals with cardiomyopathies, myocarditis and
pericarditis. Eur J Cardiovasc Prevent Rehab. 2006;13(6):876–885
11) Seidenberg PH, Haynes J. Pericarditis: diagnosis, management, and return to play. Curr Sports
Med Rep. 2006;5(2):74–79
12) Lotrionte M, Biondi-Zoccai G, Imazio M, et al. International collaborative systematic review of
controlled clinical trials on pharmacologic treatments for acute pericarditis and its recurrences.
Am Heart J. 2010;160(4):662–670
13) Imazio M, Brucato A, Cemin R, et al; ICAP Investigators. A randomized trial of colchicine for
acute pericarditis. N Engl J Med. 2013;369(16):1522–1528
14) Imazio M, Bobbio M, Cecchi E, et al. Colchicine in addition to conventional therapy for
acute pericarditis: results of the colchicine for acute pericarditis (COPE) trial. Circulation.
2005;112(13):2012–2016
15) Alabed S, Pérez-Gaxiola G, Burls A. Colchicine for children with pericarditis: systematic review
of clinical studies. Arch Dis Child. 2016;101(10):953–956
16) Imazio M, Spodick DH, Brucato A, Trinchero R, Adler Y. Controversial issues in the manage-
ment of pericardial diseases. Circulation. 2010;121(7):916–928
17) Imazio M, Brucato A, Maestroni S, et al. Risk of constrictive pericarditis after acute pericarditis.
Circulation. 2011;124(11):1270–1275
18) Imazio M, Brucato A, Barbieri A, et al. Good prognosis for pericarditis with and without
myocardial involvement: results from a multicenter, prospective cohort study. Circulation.
2013;128(1):42–49
19) Khatib R, Reyes MP, Smith F, Khatib G, Rezkalla S. Enhancement of coxsackievirus B4
virulence by indomethacin. J Lab Clin Med. 1990;116(1):116–120
20) Imazio M, Brucato A, Belli R, et al. Colchicine for the prevention of pericarditis: what we know
and what we do not know in 2014—systematic review and meta-analysis. J Cardiovasc Med
(Hagerstown). 2014;15(12):840–846
21) Imazio M, Belli R, Brucato A, et al. Efficacy and safety of colchicine for treatment of multiple
recurrences of pericarditis (CORP-2): a multicentre, double-blind, placebo-controlled,
randomised trial. Lancet. 2014;383(9936):2232–2237
22) Imazio M, Brucato A, Cumetti D, et al. Corticosteroids for recurrent pericarditis: high versus
low doses: a nonrandomized observation. Circulation. 2008;118(6):667–671
23) Corey GR, Campbell PT, Van Trigt P, et al. Etiology of large pericardial effusions. Am J Med.
1993;95(2):209–213
24) Levy PY, Corey R, Berger P, et al. Etiologic diagnosis of 204 pericardial effusions. Medicine
(Baltimore). 2003;82(6):385–391
25) Shabetai R. Pericardial effusion: haemodynamic spectrum. Heart. 2004;90(3):255–256
26) Imazio M, Mayosi BM, Brucato A, et al. Triage and management of pericardial effusion.
J Cardiovasc Med (Hagerstown). 2010;11(12):928–935
27) Sagristà-Sauleda J, Mercé AS, Soler-Soler J. Diagnosis and management of pericardial effusion.
World J Cardiol. 2011;3(5):135–143
28) Sagristà-Sauleda J, Angel J, Permanyer-Miralda G, Soler-Soler J. Long-term follow-up of
idiopathic chronic pericardial effusion. N Engl J Med. 1999;341(27):2054–2059
540
CCIP.indb 540 3/13/18 4:19 PM

29) Mutyaba AK, Balkaran S, Cloete R, et al. Constrictive pericarditis requiring pericardiectomy
at Groote Schuur Hospital, Cape Town, South Africa: causes and perioperative outcomes in
the HIV era (1990-2012). J Thorac Cardiovasc Surg. 2014;148(6):3058–65.e1
30) Mayosi BM, Burgess LJ, Doubell AF. Tuberculous pericarditis. Circulation.
2005;112(23):3608–3616
31) Syed FF, Schaff HV, Oh JK. Constrictive pericarditis—a curable diastolic heart failure. Nat Rev
Cardiol. 2014;11(9):530–544
32) Imazio M, Hoit BD. Post-cardiac injury syndromes. An emerging cause of pericardial diseases.
Int J Cardiol. 2013;168(2):648–652
33) Gouriet F, Levy PY, Casalta JP, et al. Etiology of pericarditis in a prospective cohort of 1162
cases. Am J Med. 2015;128(7):784.e1–784.e8
34) Imazio M, Brucato A, Ferrazzi P, Spodick DH, Adler Y. Postpericardiotomy syndrome: a
proposal for diagnostic criteria. J Cardiovasc Med (Hagerstown). 2013;14(5):351–353
35) Imazio M, Brucato A, Ferrazzi P, et al; COPPS-2 Investigators. Colchicine for prevention of
postpericardiotomy syndrome and postoperative atrial fibrillation: the COPPS-2 randomized
clinical trial. JAMA. 2014;312(10):1016–1023
36) Horneffer PJ, Miller RH, Pearson TA, Rykiel MF, Reitz BA, Gardner TJ. The effective treatment
of postpericardiotomy syndrome after cardiac operations. A randomized placebo-controlled trial.
J Thorac Cardiovasc Surg. 1990;100(2):292–296
541
CCIP.indb 541 3/13/18 4:19 PM

CCIP.indb 542 3/13/18 4:19 PM
PART 7
Preventive
Cardiology
34. Dyslipidemia........................................................................ 545
35. Hypertension........................................................................ 567
36. Cardiac Screening Prior to ADHD Treatment.................... 595
37. Cardiac Screening for Athletic Participation........................ 603
38. Autonomic D ysfunction....................................................... 613
543
CCIP.indb 543 3/13/18 4:19 PM

CCIP.indb 544 3/13/18 4:19 PM
CHAPTER 34
Dyslipidemia
Don P. Wilson, MD, FNLA, and Samuel S. Gidding, MD
Introduction
While myocardial infarction as a manifestation of atherosclerotic cardiovascular
disease (ASCVD) typically occurs in the fifth decade of life, the development of
atherosclerosis begins as early as fetal life. Several major risk factors are known
to be strongly related to atherosclerosis development and ASCVD, including
dyslipidemia, hypertension, tobacco use, diabetes, physical inactivity, and obesity.
Autopsy studies of adolescents and young adults demonstrate that the earliest
atherosclerotic lesions, called fatty streaks, are present in late adolescence and are
strongly related to these known risk factors.1,2 By young adulthood, these early
lesions have progressed to more advanced lesions, including fibrous plaques, which,
when ruptured, cause acute events. The presence of early atherosclerosis in young
individuals, combined with the knowledge that risk factors measured in youth can
be used to predict both subclinical atherosclerosis and future risk in adulthood,
provide the rationale for early recognition of risk to prevent future disease.3

Increases of cholesterol and triglyceride levels in the blood, or dyslipidemia,
are measurable in childhood. Lipid levels provide a sum of the total amount of
cholesterol and triglycerides being actively transported through the body on lipo-
protein particles for metabolic purposes. These particles are principally low-density
lipoprotein (LDL), high-density lipoprotein (HDL), very low-density lipoprotein
(VLDL), and chylomicrons. LDL and HDL carry large amounts of cholesterol;
VLDL and chylomicrons carry principally triglycerides. Affected by both genetics
and diet, increased levels of individual lipoproteins, particularly LDL and likely
some forms of VLDL, provide chronic exposure to atherogenic stimuli. The role of
HDL in atherogenesis is uncertain, but it may provide some natural regression of
developed plaque.4
545
CCIP.indb 545 3/13/18 4:19 PM

Over the past 60 years, cholesterol levels have trended down in the general
population, probably secondary to reduction in saturated and trans fat intake,
which is the major cause of mild hypercholesterolemia. Currently, average total
cholesterol levels are approximately 150 to 160 mg/dL (3.885–4.144 mmol/L).
Those at the extremes (very high or low levels) are secondary to genetic condi-
tions.5 Natural history studies that integrate lipid levels with genetic information
suggest that for approximately every 40-mg/dL (1.036-mmol/L) change in LDL
cholesterol, ASCVD risk is affected by about 50%.6

Triglyceride levels have high day-to-day variability because they reflect recent
dietary intake and other influences, including obesity and insulin resistance.
In contrast to cholesterol, triglyceride levels are increasing in children, largely
secondary to the obesity epidemic.4,5 Lipid levels are generally obtained while
the patient is fasting to minimize the contribution of chylomicrons, which reflect
absorbed dietary fat and contain high amounts of triglycerides. Unless extreme
(>500 mg/dL [>5.65 mmol/L]), a single triglyceride level should never be used
for classification. Levels less than 100 mg/dL (1.13 mmol/L) are desirable.
Levels consistently above 200 mg/dL (2.26 mmol/L) likely reflect the presence
of mild genetic conditions related to VLDL or chylomicron metabolism inter-
acting with obesity and insulin resistance. Triglyceride levels well above 100 mg/
dL (1.13 mmol/L) can be used to predict future type 2 diabetes mellitus.7
Genetic studies have confirmed the relationship between genetic causes of
increased triglyceride levels and future development of ASCVD.
The 2011 Guidelines for Integrated Cardiovascular Risk Reduction in
Children and Adolescents, endorsed by the American Academy of Pediatrics,
have recommended universal screening of blood lipid levels at the ages of 9 to
11 years and 17 to 21 years. Lipid profiles should also be obtained in the setting
of a family history positive for premature ASCVD, increased cholesterol levels,
obesity, or other cardiovascular risk factors in children 2 years of age and older.8
The initial test may be a fasting lipid profile or a nonfasting total and HDL
cholesterol level with calculation of non-HDL cholesterol level. These may be
obtained in an office laboratory. Table 34-1 provides a classification of lipid
values as acceptable, borderline, or high (low for HDL cholesterol) from the
2011 guidelines.
This chapter will provide a detailed discussion of the causes, evaluation, and
management of hypercholesterolemia and hypertriglyceridemia, with brief
discussions of rarer genetic dyslipidemias and acquired dyslipidemias.
Hypercholesterolemia
Familial Hypercholesterolemia
The most important reason to screen patients for very high cholesterol in
childhood is to find those with familial hypercholesterolemia (FH), a genetic
546
CCIP.indb 546 3/13/18 4:19 PM

Dyslipidemia
Table 34-1. Acceptable, Borderline, and High Plasma

Lipid, Lipoprotein, and Apolipoprotein Concentrations
For Children and Adolescents
Category Acceptable Borderline Higha Low
Total cholesterol <170 mg/dL 170–199 mg/dL ≥200 mg/dL —
LDL cholesterol <110 mg/dL 110–129 mg/dL ≥130 mg/dL —
Non-HDL <120 mg/dL 120–144 mg/dL ≥145 mg/dL —

cholesterol
Triglycerides
0–9 y <75 mg/dL 75–99 mg/dL ≥100 mg/dL —
10–19 y <90 mg/dL 90–129 mg/dL ≥130 mg/dL —
HDL cholesterol >45 mg/dL 40–45 mg/dL — <40 mg/dL

To convert milligrams per deciliter to millimoles per liter for cholesterol levels, multiply 0.0259. To convert milli-
grams per deciliter to millimoles per liter for triglyceride levels, multiply by 0.0113. HDL, high-density lipoprotein;
LDL, low-density lipoprotein. Adapted from Expert Panel on Integrated Guidelines for Cardiovascular Health and
Risk Reduction in Children and Adolescents, National Heart, Lung, and Blood Institute. Expert panel on integrated
guidelines for cardiovascular health and risk reduction in children and adolescents: Summary report. Pediatrics.
2011;128(Suppl 5):S213-S256.
a
Low cutoff points for HDL cholesterol represent approximately the 10th percentile. The cutoff points for high and
borderline-high values represent approximately the 95th and 75th percentiles, respectively.
condition related to LDL receptor function on the liver cell surface. The
prevalence, once thought to be 1 in 500, is now determined to be 1 in 200
to 250 individuals. Those affected typically have increased cholesterol levels,
since the mechanism for the liver to retrieve cholesterol from LDL particles
does not work, most commonly because LDL receptors do not reach the liver
cell surface or are dysfunctional. Other defects that affect binding of LDL to
receptors (defective apolipoprotein B) or enhance LDL receptor degradation
(gain of function mutations for PCSK9) have been identified. The presence of
an FH-associated gene triples the risk of ASCVD independently of cholesterol
level, presumably because of lifelong exposure to increased LDL.9,10 While an
increased LDL cholesterol level in adulthood is secondary to a combination
of environmental and genetic causes, in childhood it is much more likely to be
secondary to FH. Patients with index cases typically have LDL cholesterol levels
higher than 190 mg/dL (4.921 mmol/L), but about one-third of patients have
levels between 140 and 190 mg/dL (3.626–4.921 mmol/L). Identifying a child
with FH may also have benefits for affected parents who have not been tested
previously or are being undertreated.11
In Europe, recognition of children with FH is often accomplished by cascade
screening, where first-degree family members of patients with index cases of
FH, confirmed by genetic testing, undergo genetic testing, as well. This practice
547
CCIP.indb 547 3/13/18 4:19 PM

has not yet been widely adopted in the United States. However, screening of
first-degree relatives of individuals with the typical FH phenotype (testing is
based on the presence of LDL cholesterol >190 mg/dL [>4.921 mmol/L] and
positive family history) should occur.9
Dietary and Polygenic Causes of Hypercholesterolemia

Consumption of excess saturated fat and cholesterol has long been known to
lead to increased circulating cholesterol levels. An additional dietary source
has been trans fats, which are polyunsaturated fats modified to convert these
naturally liquid oils to solids (eg, margarine). Evidence for this has been obtained
from human feeding studies, animal feeding studies, and population-based
studies, in which average saturated fat and cholesterol intake in societies has
been linked to cholesterol levels.8 Intervention studies in which cholesterol and
saturated fat intake are limited lower LDL cholesterol levels; randomized trial
data from the Dietary Intervention Study in Children study demonstrated that
this relationship is valid in children. In the United States, cholesterol levels
have been decreasing for several decades,5 in part because of lower saturated
fat consumption and, more recently, attempts to eliminate trans-fats from the
food supply.5
Increased attention is being paid to a large number of genes that are relatively
common in the population and that have a small effect on cholesterol levels.
Studies in adults demonstrate that a markedly adverse gene score, having a
disproportionately large number of variants that raise LDL cholesterol, can
mimic the FH phenotype. The gene score also helps explain variation in LDL
cholesterol levels among those with the same FH gene defect.12 While there
are currently limited data in children, 1 pediatric study showed that in patients
with the FH phenotype, those without an FH gene were likely to have an
isoform of apolipoprotein E associated with increased LDL cholesterol levels.
More investigation of gene-environment interactions of these genetic variants
is likely forthcoming.13
Evaluation
Beyond obtaining a family history of ASCVD and increased cholesterol levels,
medical history and physical examination findings play a limited role in the
evaluation of hypercholesterolemia in children. Compiling a dietary history to
look for sources of saturated fat is important. Rarely, xanthomas—cholesterol
deposits in the skin—can be seen. When present, these are associated with the
severe form of FH, homozygous FH, or sitosterolemia.8,9

After obtaining a fasting lipid profile or calculating the non-HDL cholesterol
from a nonfasting blood sample, values are compared to those in Table 34-1.
If lipid levels are normal or acceptable, no repeat testing is needed until 17 to
21 years of age. For those with borderline or increased LDL cholesterol levels
548
CCIP.indb 548 3/13/18 4:19 PM

Dyslipidemia
(>110 mg/dL [>2.849 mmol/L]) or non-HDL cholesterol levels (>120 mg/dL

[>3.108 mmol/L]), dietary management is recommended, and repeat assessment
by using a fasting lipid profile is performed, sooner in those with extreme
values (LDL cholesterol >160 mg/dL [>4.144 mmol/L], non-HDL cholesterol
>190 mg/dL [>4.921 mmol/L]) and in 3 to 6 months in those with lower values.
Based on the follow-up assessment, dietary treatment is continued or medication
is considered (Figure 34-1). Secondary causes of hypercholesterolemia, including
hypothyroidism, nephrotic syndrome, and obstructive liver disease, should be
excluded, particularly in the presence of extreme values or suggestive signs
and symptoms.8,9

If FH is suspected, the algorithm for recognizing and managing FH in a
child that was developed by the European Atherosclerosis Society should be
used (Figure 34-1). In the United States, cholesterol testing of the child is trig-
gered by universal screening, the presence of an identified FH-associated gene
in a parent or other first-degree relative, or the presence of severely increased
cholesterol levels in the parent.8,9 By following a path similar to that described
above, the child with a positive family history and persistent LDL cholesterol
levels more than 160 mg/dL (>4.144 mmol/L) or persistent LDL cholesterol
more than 190 mg/dL (>4.921 mmol/L) is presumed to have FH. If genetic
testing results are positive, the diagnosis is confirmed.
There are special settings in which diseases present in childhood are asso
ciated with premature heart disease in young adulthood. The most important
of these are diabetes mellitus and chronic kidney disease. Others likely at risk
include cancer survivors, those with rheumatologic conditions, patients with
heart transplants, and those with HIV. Monitoring lipid levels should be con
sidered in patients with these conditions.8
Treatment
Dietary management is the cornerstone of managing increased LDL cholesterol.
Principally, this is accomplished by limiting intake of saturated fat and choles
terol to <7% of total calories and 200 mg/day, respectively. In younger children,
this is typically done by using low-fat (skim or 1%) dairy products. Cheese is
generally restricted unless there are limited other sources of protein in the diet.
Egg intake should be limited to 3 to 4 yolks per week, but egg whites and egg
substitutes are permitted. Additional major sources of saturated fats include
fried foods, processed meats (eg, hot dogs, lunch meats), and red meat. Fish
and chicken and turkey without skin and from the breast (white meat) should
be encouraged as protein sources. Shellfish are acceptable because they have
cholesterol but little saturated fat. Free-range meats (eg, game, grass-fed beef )
generally have less saturated fat. Dietary choices such as fruits, vegetables, beans,
and grains should be encouraged. Oat fiber lowers cholesterol, as do plant sterols.
549
CCIP.indb 549 3/13/18 4:19 PM

High cholesterol in a child High cholesterol in a parent
LDL-C >4 mmol/L via: Reasons for testing parent:

• screening from age 5 years • physical signs/symptoms
• premature CHD in parent • premature CHD in relative
• cascade screening • cascade screening
Parent with pathogenic FH mutation
Yes No
Lifestyle management
Test child on Re-test child and re-testing if
DNA and LDL-C on LDL-C LDL-C >3 mmol/L
No
Child has LDL-C LDL-C >4 mmol/L

No No and parent has
mutation >5 mmol/L
premature CHD
or high LDL-C
Yes Yes
Yes
Re-test LDL-C Definite

Highly
every 12 months FH
probable FH
LDL-C Clinical
No Yes
>3.5 mmol/L management
FIGURE 34-1. Algorithm for recognizing and managing familial hypercholesterolemia (FH)
in a child. CHD = coronary heart disease, LDL-C = low-density lipoprotein cholesterol. From
reference 9.
These changes should be made in the setting of a diet with appropriate energy
for normal growth and sufficient micronutrients. Weight management should
be encouraged in patients who are obese.14,15 Depending on the initial diet and
magnitude of change, lowering the LDL cholesterol level by 5% to 15% can
be achieved.
For patients with FH, dietary treatment is generally insufficient to achieve
treatment goals of lowering LDL cholesterol by 50% or trying to achieve LDL
cholesterol levels below 130 mg/dL (3.367 mmol/L). Statins are the preferred
550
CCIP.indb 550 3/13/18 4:19 PM

Dyslipidemia
medication for cholesterol lowering in childhood.9 Clinical trials have been

conducted in children with FH for all available statins, and all are approved by
the Food and Drug Administration for use in those older than 10 years of age,
with pravastatin approved beginning at 8 years of age. Future trials may increase
the availability of statin choices and lower the age at which they may be initiated.
Published trials of up to 2 years’ duration and reports of long-term experience
suggest that adverse effects appear to be minimal. High-potency statins include
atorvastatin, rosuvastatin, and pitavastatin (in clinical trials in the United States
now). Lower-potency statins include simvastatin, pravastatin, lovastatin, and
fluvastatin. The age of 8 to 10 years is reasonable to start treatment because
studies of subclinical atherosclerosis compared between affected and unaffected
siblings suggest differentiation of markers at this age.
Pharmacological treatment is based on LDL cholesterol levels. Those with
LDL cholesterol levels higher than 190 mg/dL (4.921 mmol/L) should begin
at age 8 to 10 years.9 In the presence of extreme LDL cholesterol levels higher
than 250 mg/dL (6.475 mmol/L), treatment can be considered at younger ages.
Treatment at LDL cholesterol levels above 160 mg/dL (4.144 mmol/L) can be
considered after failure to meet cholesterol level goals with implementation of
diet management, in the presence of confirmed FH, a high-risk condition (eg,
diabetes mellitus, chronic kidney disease), or additional clinically significant
cardiovascular risk factors, such as hypertension or tobacco use. Generally, a
high-potency statin is chosen at the lower end of the approved dosage range,
with dosage increased over time to achieve a 50% reduction or to get below
130 mg/dL (3.367 mmol/L). A lower-potency statin can be chosen if initial
LDL cholesterol levels are on the lower end of the treatment range. If the goal
is not achieved, ezetimibe or a bile acid sequestrant may be added to treatment.
Referral to a lipid specialist should be considered in complex situations and
when LDL cholesterol level is severely increased and homozygous FH is
suspected.
Once treatment is initiated, repeat lipid values can be assessed every 6 weeks
to 3 months until the goal level is achieved. Repeat levels can then be obtained
at 6-month to 1-year intervals. At the initiation of treatment, patients should
be cautioned to report onset of unexplained muscle pain. If this occurs, creatine
kinase levels should be checked and, if increased, statins should be stopped. They
can be reintroduced several weeks later; if pain recurs and is clearly related to
statin dosing, treatment should be stopped. Statins are contraindicated during
pregnancy; therefore, female adolescents should be counseled regarding birth
control or stopping medication if contemplating pregnancy. Liver function tests
are generally monitored after initiation of medication and then yearly, but the
necessity of doing so is unclear because hepatic complications rarely occur.
551
CCIP.indb 551 3/13/18 4:19 PM

Hypertriglyceridemia
Triglycerides are a major source of fuel for the human body, especially the heart
and muscle cells. Excess triglycerides are stored in adipose tissue for later use.
Increased levels of triglycerides can be primary (genetic mutations), secondary
(acquired conditions), or both. Mean concentrations of triglycerides in male and
female subjects 5 to 19 years of age are listed in Table 34-2.
Genetic Hypertriglyceridemia
In most individuals, hypertriglyceridemia is polygenic rather than caused by
single-gene mutation (Table 34-3). Nonetheless, several monogenic mutations
that result in severe increases in triglyceride levels have been described
(Table 34-4). Lipoprotein lipase (LPL) plays a key role in the metabolism
of triglycerides.16
Attached to the luminal surface of extrahepatic vascular endothelial cells,
LPL hydrolyses surface triglycerides carried by dietary (chylomicron) and
hepatic (VLDL)-derived triglyceride-rich particles. This allows free fatty
acids to be absorbed by muscle and fat cells for energy or storage. Several
other proteins also play key roles in the degradation of triglycerides, such as
glycosylphosphatydlinositol-anchored HDL-binding protein 1, the binding
protein for LPL. Apolipoprotein C-II facilitates, while apolipoprotein C-III
(apoC-III) inhibits, the action of LPL. Apolipoprotein 5 and lipid maturation
factor-1 act to regulate hepatic LPL expression.
Acquired Hypertriglyceridemia
Acquired conditions such as diabetes mellitus and hypothyroidism; medications
such as estrogens, vitamin A derivatives, and glucocorticoids (Tables 34-5 and
34-6); and alcohol use can independently cause hypertriglyceridemia or may
exacerbate hypertriglyceridemia in individuals with common familial forms or
in heterozygous carriers of an LPL mutation.
Acquired hypertriglyceridemia, accompanied by low HDL level and increased
small dense LDL level, is most often encountered in clinical practice in children
and adolescents who are obese. It seems to be more pronounced in those with
clinical evidence of insulin resistance, such as acanthosis nigricans and, in girls,
polycystic ovarian syndrome. The mechanism of obesity-related dyslipidemia is
complex. Essentially, excess caloric intake, particularly of simple sugars and other
carbohydrates, leads to increased circulating free fatty acids and fat deposition
with associated insulin resistance. These 2 factors stimulate increased production
of VLDL particles and changes in lipid particle metabolism that create the high
triglyceride, low HDL cholesterol phenotype typically seen.17

Acute and severe increases in triglycerides of more than 1,000 mg/dL
(11.3 mmol/L) are sometimes seen in diabetic ketoacidosis, after onset of inten-
sive chemotherapy, or in other clinical scenarios where lipase function may be
552
CCIP.indb 552 3/13/18 4:19 PM

Dyslipidemia
Table 34-2. Mean Concentration of Triglycerides in

Male and Female Subjects 5 to 19 Years of Age
Boys Girls
Triglyceride
Percentile 5–9 y 10–14 y 15–19 y 5–9 y 10–14 y 15–19 y
50th 48 mg/ 58 mg/ 68 mg/ 57 mg/ 68 mg/ 64 mg/

dL dL dL dL dL dL
75th 58 mg/ 74 mg/ 88 mg/ 74 mg/ 85 mg/ 85 mg/

dL dL dL dL dL dL
90th 70 mg/ 94 mg/ 125 mg/ 103 mg/ 104 mg/ 112 mg/
dL dL dL dL dL dL
95th 85 mg/ 111 mg/ 143 mg/ 120 mg/ 120 mg/ 126 mg/
dL dL dL dL dL dL
To convert milligrams per deciliter to millimoles per liter, multiply by 0.0113. Adapted from Tamir I, Heiss G,
Glueck CJ, Christensen B, Kwiterovich P, Rifkind BM. Lipid and lipoprotein distributions in white children ages
6–19 y. The Lipid Research Clinics Program Prevalence Study. J Chronic Dis. 1981;34(1):27–39.
Table 34-3. Copenhagen General Population Study:

Relation of Triglyceride Levels to Genetic Diagnosis
Triglyceride
Triglyceride Level of Triglyceride
Level of <88 88–177 mg/ Level of Triglyceride Level
mg/dL dL (1–2 177–797 mg/dL of 797–1,329 mg/
(<1 mmol/L) mmol/L) (2–9 mmol/L) dL (9–15 mmol/L)
Genetic — — Multigenica and Can be

origin or small-effect monogenicb
inheritance variants
Percentage 26% 46% 28% 0.1%

of the
population
Hypertri- — — Mild to high Severe

glyceridemia
Health risk — — Increase in Chylomicronemia

CVD risk Pancreatitis
CVD risk less likely
Data were obtained in >70,000 adults (aged >20 years). CVD, cardiovascular disease. Data from reference 16.
a
LPL, APOA5, GCKR, APOB, LMF1, GPIHBP1, CREBH1, APOC2, APOE, and small-effect variants.
b
LPL, APOC2, APOA5, LMF1, GPIHBP1, and GPD1.
553
CCIP.indb 553 3/13/18 4:19 PM

CCIP.indb 554
554
Table 34-4. Familial Disorders of Triglyceride Metabolism
Lipid
Condition Description Abnormality Inheritance Mutation Testing Clinical Manifestations
Familial hyperchy- Increased TG generally Autosomal Monogenic; Fasting lipid profile; Frequent episodes of
lomicronemia chylomicrons >1,000 mg/dL; recessive due to 2 mutant exclude secondary abdominal pain with or
due to LDL-C and HDL-C alleles of LPL, causes, including without recurrent attacks
very low or low APOC2, APOA5, medication effects; of acute pancreatitis, hep-
undetectable LMF1, GPIHBP1, genetic testing is atosplenomegaly, lipemia
levels of LPL; or GPD1 available retinalis, and eruptive xan-
a circulating thomas; ASCVD uncommon
inhibitor of but reported
LPL has been

reported
Heterozygous LPL Decrease in TG 200–1,000 Autosomal Heterogenous Fasting lipid profile; May have intermittent
deficiency LPL mg/dL until recessive loss-of-function exclude secondary episodes of abdominal pain
secondary trigger mutation in 1 of causes, including with or without recurrent
occurs; then TG several genes medication effects; attacks of acute pancreati-
can exceed 1,000 involved in TG genetic testing is tis, hepatosplenomegaly,
mg/dL; increased metabolism available lipemia retinalis, and
VLDL and eruptive xanthomas; ASCVD
chylomicrons can occur
Continued
3/13/18 4:19 PM
CCIP.indb 555
Table 34-4. Familial Disorders of Triglyceride Metabolism, continued
Lipid
Familial hypertri- VLDL over- TG 200–1,000 Genetically Likely polygenic Fasting lipid profile; Often not expressed until
glyceridemia production mg/dL; apoB complex apoB adulthood because of
and reduced levels are not disorder environmental factors,
VLDL catabo- increased obesity, stress
lism result in
saturation of
LPL; second-
ary causes
exacerbate
the hypertri-
glyceridemia
Dysbetalipo- Impaired Increased LDL-C Autosomal APOE2/E2 Fasting and lipid Palmar and tuberous xan-
proteinemia function and TG; approx- recessive profile; genetic thomas, increased risk of
of apoE, imately similar testing is available premature ASCVD; usually a
impaired levels of LDL-C second defect in lipoprotein
chylomicron and TG should metabolism is required
and VLDL-C raise clinical for the full expression (eg,
clearance suspicion estrogen, hypothyroidism,
obesity, insulin resistance)
ApoB, apolipoprotein B; ApoE, apolipoprotein E; ASCVD, atherosclerotic cardiovascular disease; C, cholesterol; LDL, low-density lipoprotein; TG, triglycerides; VLDL, very low-density lipoprotein. To
convert milligrams per deciliter to millimoles per liter, multiply by 0.0259.
Dyslipidemia
555
3/13/18 4:19 PM
Table 34-5. Common Secondary Causes of

Dyslipidemia
Condition Screening Tests
Hypothyroidism Free thyroxine, thyroid-stimulating

hormone
Liver diseases CMP
Kidney diseases CMP, UA
Diabetes mellitus CMP, UA, fasting or random glucose
Obesity, insulin resistance Glucose, hemoglobin A1c

CMP, fasting glucose and insulin
CMP, comprehensive metabolic profile; UA, urinalysis.
altered. Patients in the intensive care unit occasionally have chronic increases of
triglyceride levels. Obtaining levels away from the acute setting may be helpful
to confirm that these levels are atypical for the patient. Sometimes, parental
levels may be useful as markers of the presence of heterozygosity for a disorder
of triglyceride metabolism in the parents.
Clinical Manifestations of Hypertriglyceridemia

Pancreatitis is the most frequent acute complication described in individuals
with severe hypertriglyceridemia. Plasma triglycerides are usually >1,000 mg/dL
(11.3 mmol/L). Although the exact mechanism that causes pancreatitis is not
fully known, it is thought that chylomicrons and their remnants impede pancre-
atic capillary blood flow, resulting in ischemic disruption in the acinar structure,
inflammation, edema, and necrosis.
Because hypertriglyceridemia is often accompanied by low HDL and
increased small dense LDL, it is also associated with increased risk of premature
cardiovascular disease. This may be especially true in individuals with other
cardiovascular disease risk factors, such as obesity, insulin resistance or diabetes,
and a history of smoking.
Evaluation
A standard lipid panel (total cholesterol, triglycerides, HDL cholesterol, and
LDL cholesterol), obtained with or without fasting, is recommended as an initial
screening test. A nonfasting sample is often more practical and convenient.
However, since caloric intake can often increase triglyceride levels, in those with
a triglyceride level above 200 mg/dL (2.26 mmol/L), a fasting sample is often
more informative. Blood samples can be drawn via venipuncture or finger stick.
If available, point-of-care lipid testing (eg, tabletop analyzer) has proven reliable
and correlates well with standard laboratory results.
556
CCIP.indb 556 3/13/18 4:19 PM

Dyslipidemia
Table 34-6. Drugs That May Cause Dyslipidemia

LDL HDL
Cholesterol Triglycerides Cholesterol
Estrogen ↓ 7%–20% ↑ 40% ↑ 5%–20%
Some progestins ↑ variable ↓ variable ↓ 15%–40%
Selective estrogen receptor ↓ 10%–20% ↑ 0%–30% a

↔
modulators
Danazol ↑ 10%–40% ↔ ↓ 50%
Protease inhibitors ↑ 15%–30% ↑ 15%–200% ↔
Anabolic steroids ↑ 20% ↔ ↓ 20%–70%
Retinoids ↑ 15% ↑ 35%–100% ↔b
Growth hormone ↑ 10%–25% ↔ 0–↑7%
Corticosteroids ↑ variable ↑ variable ↔
Immunosuppressive drugs ↑ 0%–50% ↑ 0%–70% ↑ 0%–90%

(cyclosporine and tacrolimus)
Thiazide diuretics (high dose) ↑ 5%–10% ↑ 5%–15% ↔
Loop diuretics ↑ 5%–10% ↑ 5%–10% ↔
β-blockers c
↔ ↑ 10%–40% ↓ 5%–20%
Amiodarone ↑ variable ↔ ↔
First-generation antipsychotics ↔ ↑ 22% ↓ 20%
Second-generation antipsychotics ↔ ↑ 20%–50% ↔
Anticonvulsants ↑ variable ↔ ↑ variable

↓, decreased; ↑, increased; ↔, no change; HDL, high-density lipoprotein; LDL, low-density lipoprotein.
a
Raloxifene has not been shown to increase triglyceride levels, while increases of up to 30% have been reported with
the use of tamoxifen.
b
Data remain conflicting; some evidence shows a decrease, no effect, or increase.
c
Varies on the basis of the individual drug.
From Herink M, Ito MK. Medication induced changes in lipid and lipoproteins. In: De Groot LJ, Chrousos G, Dungan
K, et al, eds. Endotext. South Dartmouth, MA: MDText.com; 2000.
When increased levels of lipids and lipoproteins are encountered, secondary

causes of dyslipidemia should be excluded, such as hypothyroidism, liver and
kidney diseases, and use of a variety of medications. Laboratory data should be
combined with pertinent history and physical findings to help determine the
most likely etiologic origin.
The possibility of an underlying genetic disorder of lipid metabolism,
expressed or exacerbated by a secondary cause, should always be considered.
Children with highly increased triglyceride levels (generally >1,000 mg/dL
[11.3 mmol/L]) are at high risk of having a monogenic mutation. While testing
557
CCIP.indb 557 3/13/18 4:19 PM

is available, confirmation of a genetic mutation is not necessary for initiation of

therapy. Genetic testing may be critical, however, in those who are candidates
for targeted therapies (ie, gene therapy).
Treatment
Maintaining a heart-healthy lifestyle, characterized by an age-appropriate diet,
daily physical activity, maintaining a healthy weight, and avoiding smoking, is
key to avoiding premature cardiovascular disease and diabetes. Dietary guidelines
for Americans are shown in Box 34-1. A Cardiovascular Health Integrated
Lifestyle triglyceride-lowering diet should be provided for all children with
increased triglyceride levels.8 This diet includes reduction of added sugars and
simple carbohydrates, along with reduction of intake of saturated fat. When
obesity is present, a decrease of total calories is a cornerstone of comprehensive
weight management. Increased physical activity, including increasing moderately
vigorous physical activity to at least 60 minutes per day, improves vascular
function and insulin sensitivity. Dietary management should be guided by a
registered dietitian, when available.
In children who present with acute pancreatitis, intravenous hydration and
pain management remain the mainstays of medical management. Once stable,
children should be advanced to a fat-restricted diet.
Box 34-1. 2015–2020 Dietary Guidelines for Americans at

a Glance
Five Guidelines That Encourage Healthy Eating Patterns:
1. Follow a healthy eating pattern across the lifespan. All food and
beverage choices matter. Choose a healthy eating pattern at an appro-
priate calorie level to help achieve and maintain a healthy body weight,
support nutrition adequacy, and reduce the risk of chronic disease.
2. Focus on variety, nutrient density, and amount. To meet nutrient
needs within calorie limits, choose a variety of nutrient-dense foods
across and within all food groups in recommended amounts.
3. Limit calories from added sugars and saturated fats and reduce
sodium intake. Consume an eating pattern low in added sugars,
saturated fats, and sodium. Cut back on foods and beverages higher in
these components to amounts that fit within healthy eating patterns.
4. Shift to healthier food and beverage choices. Choose nutrient-dense
foods and beverages across and within all food groups in place of less
healthy choices. Consider cultural and personal preferences to make
these shifts easier to accomplish and maintain.
5. Support healthy eating patterns for all. Everyone has a role in helping
to create and support healthy eating patterns in multiple settings
nationwide, from home to school to work to communities.
From https://health.gov/dietaryguidelines/2015/guidelines/executive-summary/#figure-es-1.
558
CCIP.indb 558 3/13/18 4:19 PM

Dyslipidemia
In children with monogenic disorders (eg, LPL deficiency) and triglyceride

levels above 1,000 mg/dL (11.3 mmol/L), standard lipid-lowering therapies,
such as omega-3 fatty acids, niacin, and fibrates, are generally ineffective.
Successful management requires restricting dietary fat to 15% of the total daily
caloric intake. If triglyceride levels are not lowered to goal levels, further dietary
fat restriction may be necessary while ensuring that essential fatty acid needs
are met (2%–4% of total calories as linoleic acid). If tolerated, the fat-restricted
diet may include 10% to 15% calories from short- and long-chain fat, 60%
calories from complex carbohydrates, and 25% to 30% calories from protein,
while avoiding concentrated carbohydrates. Medium-chain triglycerides may be
helpful in providing essential fatty acids and additional calories. Adequate intake
of fat-soluble vitamins (A, D, E, and K) should be monitored.
Novel treatments, including gene and anti–apoC-III therapies, are currently
in clinical development.
For children with less severe hypertriglyceridemia (<1,000 mg/dL
[<11.3 mmol/L]), no evidence to support treatment currently exists. Statin
treatment should be considered for those with a combined dyslipidemia and
with increased non-HDL or LDL cholesterol levels that meet treatment recom-
mendations.8 Prescription fish oil treatment is currently approved for triglyceride
levels above 500 mg/dL (5.65 mmol/L) in adults. Treatment with other agents
should be provided by lipid specialists.
Rare Genetic Dyslipidemias

Rare genetic dyslipidemias sometimes confused with familial hypercholesterol-
emia are summarized in Table 34-7.
Acquired Acute Dyslipidemia

Several medical conditions can be associated with dyslipidemia. Table 34-8 lists
key characteristics of acquired dyslipidemias.
Key Points
•• Atherosclerosis begins in childhood.
•• Lifelong exposure to dyslipidemia, particularly related to genetic conditions
such as FH or in a multiple-risk setting, leads to premature ASCVD.
•• With screening for dyslipidemia in childhood, children with high-risk condi-
tions for future ASCVD can be recognized and preventive treatment initiated.
559
CCIP.indb 559 3/13/18 4:19 PM

CCIP.indb 560
560
Table 34-7. Rare Familial Disorders of Lipids and Lipoprotein Metabolism
Lipid
Lysosomal acid Lysosomal storage Increased LDL-C Autosomal LIPA Enzymatic blood test Hepatomegaly, hepatic
lipase deficiency disorder and triglyceride- recessive for lysosomal acid steatosis, accelerated ath-
levels, decreased lipase; genetic testing is erosclerosis, corneal arcus,
HDL-C level available xanthomas; liver disease
may progress to liver failure
Sitosterolemia Abnormal Increased LDL-C Autosomal ABCG5 Increased plant stanols, Xanthomas in the first
(phytosterolemia) accumulation of possible recessive or such as plasma sitosterol decade of life; increased
plant sterols, or ABCG8 and campesterol; genetic risk of premature coronary

phytosterols, in testing is available artery disease, increased
the body hepatic transaminase
levels, arthralgia, spleno-
megaly, and hematologic
findings
Cerebrotendinous 27-hydroxylase Normal to Autosomal CYP27A1 Increased plasma and Infantile-onset diarrhea,
xanthomatosis deficiency with low plasma recessive tissue levels of choleste- childhood-onset cataract,
disruption of bile cholesterol nol; genetic testing is tendon xanthomas, and
acid production concentration available progressive neurological
dysfunction
3/13/18 4:19 PM
CCIP.indb 561
Table 34-8. Conditions Associated With Dyslipidemia
Condition Lipid Abnormality Comment
Obesity Increased TG, decreased HDL-C BMI >95th percentile
Obstructive liver disease Increased total cholesterol Increased lipoprotein X level
Nephrotic syndrome Increased total and LDL-C, increased TG, and Hypoproteinemia in nephrotic syndrome is thought to stimulate
normal HDL-C protein synthesis in the liver, including overproduction of lipo-
proteins; lipid catabolism is decreased because of lower levels of
lipoprotein lipase.
Chronic renal failure Increased TG and total cholesterol, decreased Key factors that contribute to dyslipidemia in CKD include the
HDL-C primary disease process and its rate of progression, degree of renal
function and response to treatment, medication use, nutrition,
transplantation, and genetics.
Metabolic syndrome Increased TG, low HDL, increased non-HDL, There is no consensus definition of metabolic syndrome in children.
increased LDL-particle number It is a cluster of risk factors that increases the risk of premature
cardiovascular disease and T2D.
DKA Insulin deficiency can be associated with Normal TG should be confirmed after resolution of DKA.
marked increase in TG Heterogenous loss-of-function mutation in 1 of several genes
involved in TG metabolism may play a role in some.
Type 1 diabetes mellitus In poorly controlled T1D, increased TG and Replacement of insulin in these patients may correct these abnor-
total cholesterol, decreased HDL-C commonly malities; well-controlled diabetics may have increased HDL and
occur. LDL-C is not usually increased. lower-than-average TG levels.
Type 2 diabetes mellitus Diabetic dyslipidemia typically consists of Dyslipidemia in T2D is often not fully corrected with glycemic
Increased TG and total cholesterol, decreased control alone. This pattern of dyslipidemia is also often found in
Dyslipidemia
HDL-C. those with prediabetes (IFG and IGT).
561
Continued
3/13/18 4:19 PM
CCIP.indb 562
562
Table 34-8. Conditions Associated With Dyslipidemia, continued
Condition Lipid Abnormality Comment
Chronic inflammatory The most common changes are decreases Chronic inflammatory diseases include rheumatoid arthritis,
diseases in HDL levels, although the mechanism is systemic lupus erythematosus, and psoriasis, and infections, such
unknown, and increases in TG levels, due to as periodontal disease and HIV. In addition to dyslipidemia, LDL is
both an increase in hepatic VLDL production more easily oxidized, and reverse cholesterol transport pathway is
and secretion and a decrease in the clearance impaired.
of TG-rich lipoproteins. LDL levels are fre-
quently decreased, but the prevalence of small
dense LDL is increased.
Organ transplant Total cholesterol generally peaks approx- Dyslipidemia is common in recipients of renal, heart, or liver
imately 3–6 months posttransplant and transplants.
remains stable at an increased level for 12
months.
Ketogenic diet Increased total cholesterol, TG and LDL-C, Since the use of a ketogenic diet is generally restricted to 2 years or
decreased HDL-C less, temporary use in childhood is unlikely to be associated with a
long-term increase in risk of coronary heart disease in adulthood.
Medications Variable Consider monitoring lipid levels prior to and after initiation of
medications known to cause dyslipidemia.
HIV, AIDS wasting Increased TG and total cholesterol levels, Dyslipidemia may improve with use of an alternate HIV treatment.
decreased HDL-C and LDL-C levels
HIV, AIDS (HAART) Increased TG, total cholesterol, and HDL-C Dyslipidemia may improve with use of an alternate HIV treatment.
levels
Hypothyroidism Increased TG, total cholesterol, and LDL-C Dyslipidemia usually resolves after thyroid hormone replacement.
levels
3/13/18 4:19 PM
Dyslipidemia
been considered physiological, maternal hypercholesterolemia may

and genetics. Although historically dyslipidemia in pregnancy has
•• The FH Foundation. www.thefhfoundation.
of medications, BMI and weight gain during pregnancy, smoking,

including the mother’s health before and during pregnancy, use
BMI, body mass index; C, cholesterol; CKD, chronic kidney disease; DKA, diabetic ketoacidosis; HAART, highly active antiretroviral therapy; HDL, high-density lipoprotein; IFG, impaired fasting
org
•• Learn Your Lipids (Foundation of the
Maternal lipid levels may be altered by a variety of factors.
National Lipid Association).

www.learnyourlipids.com
•• CASCADE FH Registry (FH Foundation).
thefhfoundation.org/fh-research/registry/
Resources for Professionals

glucose; IGT, impaired glucose tolerance; LDL, low-density lipoprotein; TG, triglyceride; T1D, type 1 diabetes mellitus; T2D, type 2 diabetes mellitus.
affect the CVD risk of the fetus.
•• Integrated Guidelines for Cardiovascular

Health and Risk Reduction in Children
and Adolescents (National Heart, Lung,
and Blood Institute). www.nhlbi.nih.
Table 34-8. Conditions Associated With Dyslipidemia, continued
gov/health-pro/guidelines/current/
cardiovascular-health-pediatric-guidelines/
Comment
summary
•• Medical Professionals (Foundation of the
National Lipid Association).
www.lipidfoundation.org/professionals
•• National Lipid Association Annual
increased. HDL-C increases during the first
Summary of Clinical Lipidology 2016

pregnancy. Cholesterol levels may remain
increased for approximately 6 weeks after
Total cholesterol, LDL-C, and TG are all
trimester and remains high throughout
(National Lipid Association). www.

lipidjournal.com/issue/S1933-2874(16)
X0008-6
•• The Agenda for Familial
Hypercholesterolemia: A Scientific
Statement From the American Heart
Lipid Abnormality
Association (American Heart Association).

circ.ahajournals.org/content/132/22/2167
•• Consensus on Familial
Hypercholesterolemia (European
birth.
Atherosclerosis Society). www.eas-society.

org/?page=fh_consensus
•• American Heart Association Guidelines
for Primary Prevention of Atherosclerotic
Cardiovascular Disease Beginning in
Childhood (American Heart Association).
Pregnancy
Condition
circ.ahajournals.org/content/107/11/1562.full
563
CCIP.indb 563 3/13/18 4:19 PM

•• 2006 Canadian Clinical Practice Guidelines on the Management and

Prevention of Obesity in Adults and Children (Canadian Medical
Association). www.cmaj.ca/content/176/8/S1.short
Acknowledgment
The authors would like to thank Luke Hamilton, MS, and Dena Hanson, MLS,
for their assistance in the preparation of this manuscript.
References
1) Berenson GS, Srinivasan SR, Bao W, Newman WP III, Tracy RE, Wattigney WA. Association
between multiple cardiovascular risk factors and atherosclerosis in children and young adults.
The Bogalusa Heart Study. N Engl J Med. 1998;338(23):1650–1656
2) McGill HC Jr, McMahan CA, Malcom GT, Oalmann MC, Strong JP. Effects of serum
lipoproteins and smoking on atherosclerosis in young men and women. The PDAY Research
Group. Pathobiological determinants of atherosclerosis in youth. Arterioscler Thromb Vasc Biol.
1997;17(1):95–106
3) McGill HC Jr, McMahan CA, Gidding SS. Preventing heart disease in the 21st century:
implications of the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study.
Circulation. 2008;117(9):1216–1227
4) Kwiterovich PO Jr. Recognition and management of dyslipidemia in children and adolescents.
J Clin Endocrinol Metab. 2008;93(11):4200–4209
5) Kit BK, Kuklina E, Carroll MD, Ostchega Y, Freedman DS, Ogden CL. Prevalence of and
trends in dyslipidemia and blood pressure among US children and adolescents, 1999-2012.
JAMA Pediatr. 2015;169(3):272–279
6) Ference BA, Yoo W, Alesh I, et al. Effect of long-term exposure to lower low-density lipoprotein
cholesterol beginning early in life on the risk of coronary heart disease: a Mendelian randomiza-
tion analysis. J Am Coll Cardiol. 2012;60(25):2631–2639
7) Tirosh A, Shai I, Bitzur R, et al. Changes in triglyceride levels over time and risk of type 2
diabetes in young men. Diabetes Care. 2008;31(10):2032–2037
Children and Adolescents; National Heart, Lung, and Blood Institute. Expert panel on integrat-
ed guidelines for cardiovascular health and risk reduction in children and adolescents: summary
report. Pediatrics. 2011;128(Suppl 5):S213–S256
9) Wiegman A, Gidding SS, Watts GF, et al; European Atherosclerosis Society Consensus Panel.
Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing
detection and treatment. Eur Heart J. 2015;36(36):2425–2437
10) Khera AV, Won HH, Peloso GM, et al. Diagnostic yield and clinical utility of sequencing
familial hypercholesterolemia genes in patients with severe hypercholesterolemia. J Am Coll
Cardiol. 2016;67(22):2578–2589
11) Wald DS, Bestwick JP, Morris JK, Whyte K, Jenkins L, Wald NJ. Child–parent familial hyper-
cholesterolemia screening in primary care. N Engl J Med. 2016;375(17):1628–1637
12) Talmud PJ, Shah S, Whittall R, et al. Use of low-density lipoprotein cholesterol gene score
to distinguish patients with polygenic and monogenic familial hypercholesterolaemia: a case-
control study. Lancet. 2013;381(9874):1293–1301
564
CCIP.indb 564 3/13/18 4:19 PM

Dyslipidemia
13) Klančar G, Grošelj U, Kovač J, et al. Universal screening for familial hypercholesterolemia in
children. J Am Coll Cardiol. 2015;66(11):1250–1257
14) U.S. Department of Health and Human Services, U.S. Department of Agriculture. 2015-2020
Dietary Guidelines for Americans. 8th ed. Available at http://health.gov/dietaryguidelines/2015/
guidelines/. Updated December 2015. Accessed November 22, 2016
15) Gidding SS, Dennison BA, Birch LL, et al; American Heart Association; American Academy of
Pediatrics. Dietary recommendations for children and adolescents: a guide for practitioners: con-
sensus statement from the American Heart Association. Circulation. 2005;112(13):2061–2075
16) Hegele RA, Ginsberg HN, Chapman MJ, et al; European Atherosclerosis Society Consensus
Panel. The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and
management. Lancet Diabetes Endocrinol. 2014;2(8):655–666
17) Ginsberg HN, MacCallum PR. The obesity, metabolic syndrome, and type 2 diabetes mellitus
pandemic: part I. Increased cardiovascular disease risk and the importance of atherogenic
dyslipidemia in persons with the metabolic syndrome and type 2 diabetes mellitus. J Cardiometab
Syndr. 2009;4(2):113–119
565
CCIP.indb 565 3/13/18 4:19 PM

CCIP.indb 566 3/13/18 4:19 PM
CHAPTER 35
Hypertension
S. Kristen Sexson Tejtel, MD, PhD, MPH, FAAP
Introduction
Definition
New hypertension guidelines were released by the American Academy of
Pediatrics (AAP) in the fall of 2017.1 Provided in these new guidelines is a simpli-
fied table for screening blood pressure that requires further evaluation, as shown in
Table 35-1. Blood pressure higher than the documented values in the table should
be evaluated with further blood pressure measurements, preferably by auscultation
and not oscillatory measurements.
Additionally, the new guidelines have changed the definition of hypertension
in the pediatric population, as shown in Table 35-2. The normative tables have
changed and are now based on the distribution of blood pressures in healthy-
weight children (body mass index [BMI] <85th percentile), excluding overweight
and obese children who were previously included in the normal tables.
Epidemiology
The true incidence of pediatric hypertension is not well known, partially because
of lack of screening. It has been shown that blood pressure screening is only per-
formed at two-thirds of routine pediatric visits, and 20% of overweight and obese
children were not screened.2 Additionally, follow-up of a screening evaluation
that resulted in a hypertensive measurement is poor, with 75% of hypertensive
patients and 90% of prehypertensive patients not evaluated further.3 The prevalence
of hypertension in children with normal weight is 0.3% to 0.9%. The prevalence
increases to 3% to 28% in obese children.4,5 Identification of these patients is
important because early vascular aging has been seen in them.
567
CCIP.indb 567 3/13/18 4:19 PM

Table 35-1. Screening Blood Pressure Values That

Require Further Evaluation
Blood Pressure (mm Hg)
Boys Girls
Age (y) Systolic Diastolic Systolic Diastolic
1 98 52 98 54
2 100 55 101 58
3 101 58 102 60
4 102 60 103 62
5 103 63 104 64
6 105 66 105 67
7 106 68 106 68
8 107 69 107 69
9 107 70 108 71
10 108 73 109 72
11 110 74 111 74
12 113 75 114 75
≥13 120 80 120 80

From reference 1.
Table 35-2. Updated Definitions of Blood Pressure

Categories and Stages
Blood Pressure Children Aged 1–13 y Children Aged ≥13 y
Normal <90th percentile <120/<80 mm Hg
Increased ≥90th percentile to <95th per- 120/<80 to 129/<80 mm Hg

centile or 120/80 mm Hg to <95th
percentile (whichever is lower)
Stage 1 ≥95th percentile to <95th 130/80 to 139/89 mm Hg

hypertension percentile + 12 mm Hg or 130/80
to 139/89 mm Hg (whichever is
lower)
Stage 2 ≥ 95th percentile + 12 mm Hg or ≥140/90 mm Hg

hypertension ≥ 140/90 mm Hg (whichever is
lower)
Limited data are available regarding hypertension in children younger than 1 year of age. From reference 1.
568
CCIP.indb 568 3/13/18 4:19 PM

Hypertension
Etiologic Origins
Hypertension can be caused by a primary process or can be secondary to another
process. Younger children are more likely to have hypertension from a secondary
cause, as shown in Table 35-3.6 Once hypertension is proven, evaluation for
alternative causes is necessary.
Risk Factors
Many causes have been suggested as risk factors for development of pediatric
hypertension. The American Heart Association (AHA) has identified contribu-
tors to the development of hypertension, coined as “Life’s Simple 7”:
1. Not smoking
2. Normal BMI
3. Physical activity at goal levels
4. Healthy diet
5. Normal untreated cholesterol levels
6. Normal fasting blood glucose levels
7. Normal untreated blood pressure (<90% or <120/80 mm Hg)
Childhood obesity has been shown to have a high association with hypertension,
and almost one-half of the teenage population is overweight or obese.7 Obesity
is thought to have many ties to hypertension, including increased insulin levels
and insulin resistance, changes in sodium homeostasis, and activation of both the
sympathetic nervous system and the renin angiotensin and aldosterone systems.
Increased blood pressure has been shown to track into adulthood, with those
having hypertension as children continuing to have increased blood pressure in
adulthood.8 BMI, parental history of hypertension, nutrition, race, and sex are
Table 35-3. Causes of Pediatric Hypertension According

to Age Group
Toddlers and Young
Children (1–6 y) Children (7–12 y) Adolescents (13-19 y)
Renal artery or vein Renal artery stenosis Renal parenchymal

thrombosis disease
Congenital renal anomalies Renal parenchymal Renovascular

disease abnormalities
Coarctation of the aorta Tumor (Wilms, Endocrine causes

neuroblastoma) (Cushing syndrome,
hyperthyroidism)
Bronchopulmonary dysplasia Coarctation of the aorta Essential hypertension

Data from Luma GB, Spiotta RT. Hypertension in children and adolescents. Am Fam Physician. 2006;73:1158–1168;
Rodrigues-Cruz E. Pediatric hypertension. Medscape. http://emedicine.medscape.com/article/889877-overview.
Updated March 9, 2017. Accessed September 2017; Keane JF, Lock JE, Fyler DC, eds. Nadas’ Pediatric Cardiology.
2nd ed. Philadelphia, PA: Saunders; 2006:382.
569
CCIP.indb 569 3/13/18 4:19 PM

associated with increased risk of developing hypertension during childhood,

particularly in black men.
Additionally, sleep-disordered breathing is associated with increases in blood
pressure. Sleep-disordered breathing is defined as any of the following: primary
snoring, sleep fragmentation, or obstructive sleep apnea.9 Additionally, getting
an inadequate amount of sleep (<7 hours per night) is associated with increased
blood pressure.10
Children with chronic kidney disease are at a higher risk of hypertension,
as well: Approximately 50% of these children have hypertension. Uncontrolled
hypertension may also lead to chronic kidney disease.
Preterm birth, low birth weight, and small size for gestational age have
been identified as risk factors for hypertension and other cardiovascular disease
in adults.
Clinical Features
Signs and Symptoms
Hypertension typically manifests without signs or symptoms. Severe hyperten-
sion or hypertensive urgency may appear with headache, nosebleeds, stomach-
ache, nausea or vomiting, and/or flushing. These symptoms do not usually occur
until the blood pressure is at a life-threatening level; therefore, regular blood
pressure evaluation at routine well-child visits is necessary.
White-coat hypertension is defined as casual or office blood pressure levels that are
greater than the 95th percentile but normal outside of a clinical setting. Studies
have shown that up to 88% of adolescents have white-coat hypertension.11,12 It
is thought that this may be a transient, stress-induced increase in blood pressure
incited by being in the doctor’s office.
Masked hypertension is defined as a normal clinical blood pressure but
increased ambulatory levels. Masked hypertension is difficult to diagnose but
may be suspected with previous reports of increased clinical blood pressure
from other providers or if the clinical presentation (ie, left ventricular [LV]
hypertrophy) appears inconsistent with clinical blood pressure.
Diagnostic Approach
Office Blood Pressure Measurement
Blood pressure measurement should be performed in a controlled environment
after 5 minutes of rest, with the child or adolescent seated with their right
arm supported at heart level. Prior to having blood pressure measured,
children should avoid stimulant drugs (attention-deficit/hyperactivity disorder
570
CCIP.indb 570 3/13/18 4:19 PM

Hypertension
medication) or foods (caffeine, sugar, etc) and sit quietly for 5 minutes with their
back supported, feet on the floor, right arm supported, and elbow at heart level.
The use of the same arm for repeated measurements is important for consistency.
The first set of measurements obtained should include 4-extremity (or at least
both arms and 1 leg) blood pressure levels to rule out coarctation of the aorta.
The blood pressure cuff should have a bladder width that is at least 40% of
the arm circumference at the midpoint of the upper arm; the bladder length
should cover 80% to 100% of the circumference of the upper arm. A small cuff
will cause overestimation of the blood pressure; thus, one should err on the side
of the larger cuff. The auscultatory measurement of the blood pressure is based
on changes in the Korotkoff sounds (sounds heard with a stethoscope on the
brachial artery distal to the blood pressure cuff that change with decreasing cuff
pressure). The systolic blood pressure is the pressure at which the first Korotkoff
sound is heard. The diastolic blood pressure is the pressure at which the
Korotkoff sounds disappear.
Oscillometric devices can be used because of ease of use; however, if the blood
pressure is increased, this should be confirmed with an auscultatory device.
Multiple sets of guidelines and recommendations are available for pediatric
hypertension. The 2017 guidelines from the AAP for risk reduction recommend
that all children have their blood pressure measured beginning at 3 years of age.1,13
For healthy children, the blood pressure measurement can be completed
annually at the well-child visit. Children with risk factors should have their
blood pressure measured at every encounter. These risk factors include obesity
(BMI ≥95th percentile), renal disease, diabetes, aortic arch obstruction, or those
taking medications known to increase blood pressure (decongestants, caffeine,
nonsteroidal anti-inflammatory drugs, herbals, stimulants, hormones, steroids,
and illicit drugs).
Recommendations for even younger children to be screened are primarily
intended to evaluate those with risk factors for hypertension, including those
with a personal or family history of renal or urologic disease, cardiac disease,
solid organ transplant, malignancy, or evidence of increased intracranial pressure
or those who have been in neonatal intensive care or had an umbilical arterial
line. For these patients, screening should be performed beginning at birth and
at every well-child check subsequently. The blood pressure obtained should be
compared to the screening blood pressure values that require further evaluation
in Table 35-1. Should further evaluation be required, auscultatory blood pressure
measurements should be obtained.
The value obtained should be compared to the normal values established
according to age, sex, and height (Tables 35-4 and 35-5). Once the blood
pressure percentile is obtained, the next step in recommended evaluation
can be determined by using the algorithm shown in Figure 35-1. While this
571
CCIP.indb 571 3/13/18 4:19 PM

CCIP.indb 572
572
Table 35-4. Blood Pressure Levels for Boys According to Age and Height Percentile
Systolic Blood Pressure (mm Hg) Diastolic Blood Pressure (mm Hg)
Age Blood Pressure Height Percentile or Measured Height Height Percentile or Measured Height
(y) Percentile 5% 10% 25% 50% 75% 90% 95% 5% 10% 25% 50% 75% 90% 95%
1 Height (in) 30.4 30.8 31.6 32.4 33.3 34.1 34.6 30.4 30.8 31.6 32.4 33.3 34.1 34.6
Height (cm) 77.2 78.3 80.2 82.4 84.6 86.7 87.9 77.2 78.3 80.2 82.4 84.6 86.7 87.9
50th 85 85 86 86 87 88 88 40 40 40 41 41 42 42
90th 98 99 99 100 100 101 101 52 52 53 53 54 54 54
95th 102 102 103 103 104 105 105 54 54 55 55 56 57 57
95th + 12 mm Hg 114 114 115 115 116 117 117 66 66 67 67 68 69 69
2 Height (in) 33.9 34.4 35.3 36.3 37.3 38.2 38.8 33.9 34.4 35.3 36.3 37.3 38.2 38.8
Height (cm) 86.1 87.4 89.6 92.1 94.7 97.1 98.5 86.1 87.4 89.6 92.1 94.7 97.1 98.5
50th 87 87 88 89 89 90 91 43 43 44 44 45 46 46
90th 100 100 101 102 103 103 104 55 55 56 56 57 58 58
95th 104 105 105 106 107 107 108 57 58 58 59 60 61 61
95th + 12 mm Hg 116 117 117 118 119 119 120 69 70 70 71 72 73 73
3 Height (in) 36.4 37 37.9 39 40.1 41.1 41.7 36.4 37 37.9 39 40.1 41.1 41.7
Height (cm) 92.5 93.9 96.3 99 101.8 104.3 105.8 92.5 93.9 96.3 99 101.8 104.3 105.8
50th 88 89 89 90 91 92 92 45 46 46 47 48 49 49
90th 101 102 102 103 104 105 105 58 58 59 59 60 61 61
95th 106 106 107 107 108 109 109 60 61 61 62 63 64 64
95th + 12 mm Hg 118 118 119 119 120 121 121 72 73 73 74 75 76 76
3/13/18 4:19 PM
CCIP.indb 573
Table 35-4. Blood Pressure Levels for Boys According to Age and Height Percentile, continued
(y) Percentile 5% 10% 25% 50% 75% 90% 95% 5% 10% 25% 50% 75% 90% 95%
4 Height (in) 38.8 39.4 40.5 41.7 42.9 43.9 44.5 38.8 39.4 40.5 41.7 42.9 43.9 44.5
Height (cm) 98.5 100.2 102.9 105.9 108.9 111.5 113.2 98.5 100.2 102.9 105.9 108.9 111.5 113.2
50th 90 90 91 92 93 94 94 48 49 49 50 51 52 52
90th 102 103 104 105 105 106 107 60 61 62 62 63 64 64
95th 107 107 108 108 109 110 110 63 64 65 66 67 67 68
95th + 12 mm Hg 119 119 120 120 121 122 122 75 76 77 78 79 79 80
5 Height (in) 41.1 41.8 43.0 44.3 45.5 46.7 47.4 41.1 41.8 43.0 44.3 45.5 46.7 47.4
Height (cm) 104.4 106.2 109.1 112.4 115.7 118.6 120.3 104.4 106.2 109.1 112.4 115.7 118.6 120.3
50th 91 92 93 94 95 96 96 51 51 52 53 54 55 55
90th 103 104 105 106 107 108 108 63 64 65 65 66 67 67
95th 107 108 109 109 110 111 112 66 67 68 69 70 70 71
95th + 12 mm Hg 119 120 121 121 122 123 124 78 79 80 81 82 82 83
6 Height (in) 43.4 44.2 45.4 46.8 48.2 49.4 50.2 43.4 44.2 45.4 46.8 48.2 49.4 50.2
Height (cm) 110.3 112.2 115.3 118.9 122.4 125.6 127.5 110.3 112.2 115.3 118.9 122.4 125.6 127.5
50th 93 93 94 95 96 97 98 54 54 55 56 57 57 58
90th 105 105 106 107 109 110 110 66 66 67 68 68 69 69
95th 108 109 110 111 112 113 114 69 70 70 71 72 72 73
95th + 12 mm Hg 120 121 122 123 124 125 126 81 82 82 83 84 84 85
Hypertension
Continued
573
3/13/18 4:19 PM
CCIP.indb 574
574
(y) Percentile 5% 10% 25% 50% 75% 90% 95% 5% 10% 25% 50% 75% 90% 95%
7 Height (in) 45.7 46.5 47.8 49.3 50.8 52.1 52.9 45.7 46.5 47.8 49.3 50.8 52.1 52.9
Height (cm) 116.1 118 121.4 125.1 128.9 132.4 134.5 116.1 118 121.4 125.1 128.9 132.4 134.5
50th 94 94 95 97 98 98 99 56 56 57 58 58 59 59
90th 106 107 108 109 110 111 111 68 68 69 70 70 71 71
95th 110 110 111 112 114 115 116 71 71 72 73 73 74 74
95th + 12 mm Hg 122 122 123 124 126 127 128 83 83 84 85 85 86 86
8 Height (in) 47.8 48.6 50 51.6 53.2 54.6 55.5 47.8 48.6 50 51.6 53.2 54.6 55.5
Height (cm) 121.4 123.5 127 131 135.1 138.8 141 121.4 123.5 127 131 135.1 138.8 141
50th 95 96 97 98 99 99 100 57 57 58 59 59 60 60
90th 107 108 109 110 111 112 112 69 70 70 71 72 72 73
95th 111 112 112 114 115 116 117 72 73 73 74 75 75 75
95th + 12 mm Hg 123 124 124 126 127 128 129 84 85 85 86 87 87 87
9 Height (in) 49.6 50.5 52 53.7 55.4 56.9 57.9 49.6 50.5 52 53.7 55.4 56.9 57.9
Height (cm) 126 128.3 132.1 136.3 140.7 144.7 147.1 126 128.3 132.1 136.3 140.7 144.7 147.1
50th 96 97 98 99 100 101 101 57 58 59 60 61 62 62
90th 107 108 109 110 112 113 114 70 71 72 73 74 74 74
95th 112 112 113 115 116 118 119 74 74 75 76 76 77 77
95th + 12 mm Hg 124 124 125 127 128 130 131 86 86 87 88 88 89 89
3/13/18 4:19 PM
CCIP.indb 575
(y) Percentile 5% 10% 25% 50% 75% 90% 95% 5% 10% 25% 50% 75% 90% 95%
10 Height (in) 51.3 52.2 53.8 55.6 57.4 59.1 60.1 51.3 52.2 53.8 55.6 57.4 59.1 60.1
Height (cm) 130.2 132.7 136.7 141.3 145.9 150.1 152.7 130.2 132.7 136.7 141.3 145.9 150.1 152.7
50th 97 98 99 100 101 102 103 59 60 61 62 63 63 64
90th 108 109 111 112 113 115 116 72 73 74 74 75 75 76
95th 112 113 114 116 118 120 121 76 76 77 77 78 78 78
95th + 12 mm Hg 124 125 126 128 130 132 133 88 88 89 89 90 90 90
11 Height (in) 53 54 55.7 57.6 59.6 61.3 62.4 53 54 55.7 57.6 59.6 61.3 62.4
Height (cm) 134.7 137.3 141.5 146.4 151.3 155.8 158.6 134.7 137.3 141.5 146.4 151.3 155.8 158.6
50th 99 99 101 102 103 104 106 61 61 62 63 63 63 63
90th 110 111 112 114 116 117 118 74 74 75 75 75 76 76
95th 114 114 116 118 120 123 124 77 78 78 78 78 78 78
95th + 12 mm Hg 126 126 128 130 132 135 136 89 90 90 90 90 90 90
12 Height (in) 55.2 56.3 58.1 60.1 62.2 64 65.2 55.2 56.3 58.1 60.1 62.2 64 65.2
Height (cm) 140.3 143 147.5 152.7 157.9 162.6 165.5 140.3 143 147.5 152.7 157.9 162.6 165.5
50th 101 101 102 104 106 108 109 61 62 62 62 62 63 63
90th 113 114 115 117 119 121 122 75 75 75 75 75 76 76
95th 116 117 118 121 124 126 128 78 78 78 78 78 79 79
Hypertension
95th + 12 mm Hg 128 129 130 133 136 138 140 90 90 90 90 90 91 91
575
Continued
3/13/18 4:19 PM
CCIP.indb 576
576
(y) Percentile 5% 10% 25% 50% 75% 90% 95% 5% 10% 25% 50% 75% 90% 95%
13 Height (in) 57.9 59.1 61 63.1 65.2 67.1 68.3 57.9 59.1 61 63.1 65.2 67.1 68.3
Height (cm) 147 150 154.9 160.3 165.7 170.5 173.4 147 150 154.9 160.3 165.7 170.5 173.4
50th 103 104 105 108 110 111 112 61 60 61 62 63 64 65
90th 115 116 118 121 124 126 126 74 74 74 75 76 77 77
95th 119 120 122 125 128 130 131 78 78 78 78 80 81 81
95th and 12 mm Hg 131 132 134 137 140 142 143 90 90 90 90 92 93 93
14 Height (in) 60.6 61.8 63.8 65.9 68.0 69.8 70.9 60.6 61.8 63.8 65.9 68.0 69.8 70.9
Height (cm) 153.8 156.9 162 167.5 172.7 177.4 180.1 153.8 156.9 162 167.5 172.7 177.4 180.1
50th 105 106 109 111 112 113 113 60 60 62 64 65 66 67
90th 119 120 123 126 127 128 129 74 74 75 77 78 79 80
95th 123 125 127 130 132 133 134 77 78 79 81 82 83 84
95th and 12 mm Hg 135 137 139 142 144 145 146 89 90 91 93 94 95 96
15 Height (in) 62.6 63.8 65.7 67.8 69.8 71.5 72.5 62.6 63.8 65.7 67.8 69.8 71.5 72.5
Height (cm) 159 162 166.9 172.2 177.2 181.6 184.2 159 162 166.9 172.2 177.2 181.6 184.2
50th 108 110 112 113 114 114 114 61 62 64 65 66 67 68
90th 123 124 126 128 129 130 130 75 76 78 79 80 81 81
95th 127 129 131 132 134 135 135 78 79 81 83 84 85 85
95th and 12 mm Hg 139 141 143 144 146 147 147 90 91 93 95 96 97 97
3/13/18 4:19 PM
CCIP.indb 577
(y) Percentile 5% 10% 25% 50% 75% 90% 95% 5% 10% 25% 50% 75% 90% 95%
16 Height (in) 63.8 64.9 66.8 68.8 70.7 72.4 73.4 63.8 64.9 66.8 68.8 70.7 72.4 73.4
Height (cm) 162.1 165 169.6 174.6 179.5 183.8 186.4 162.1 165 169.6 174.6 179.5 183.8 186.4
50th 111 112 114 115 115 116 116 63 64 66 67 68 69 69
90th 126 127 128 129 131 131 132 77 78 79 80 81 82 82
95th 130 131 133 134 135 136 137 80 81 83 84 85 86 86
95th and 12 mm Hg 142 143 145 146 147 148 149 92 93 95 96 97 98 98
17 Height (in) 64.5 65.5 67.3 69.2 71.1 72.8 73.8 64.5 65.5 67.3 69.2 71.1 72.8 73.8
Height (cm) 163.8 166.5 170.9 175.8 180.7 184.9 187.5 163.8 166.5 170.9 175.8 180.7 184.9 187.5
50th 114 115 116 117 117 118 118 65 66 67 68 69 70 70
90th 128 129 130 131 132 133 134 78 79 80 81 82 82 83
95th 132 133 134 135 137 138 138 81 82 84 85 86 86 87
95th and 12 mm Hg 144 145 146 147 149 150 150 93 94 96 97 98 98 99
Use percentile values to stage blood pressure measurements according to the scheme in Table 35-2 (increased blood pressure, ≥90th percentile; stage 1 hypertension, ≥95th percentile; and stage
2 hypertension, ≥95th percentile + 12 mm Hg). The 50th, 90th, and 95th percentiles were derived by using quantile regression on the basis of normal-weight children (body mass index <85th
percentile). From reference 1.
Hypertension
577
3/13/18 4:19 PM
CCIP.indb 578
578
Table 35-5. Blood Pressure Levels for Girls According to Age and Height Percentile
Height Percentile or Measured Height Height Percentile or Measured Height

Age Blood Pressure
(y) Percentile 5% 10% 25% 50% 75% 90% 95% 5% 10% 25% 50% 75% 90% 95%
1 Height (in) 29.7 30.2 30.9 31.8 32.7 33.4 33.9 29.7 30.2 30.9 31.8 32.7 33.4 33.9
Height (cm) 75.4 76.6 78.6 80.8 83 84.9 86.1 75.4 76.6 78.6 80.8 83 84.9 86.1
50th 84 85 86 86 87 88 88 41 42 42 43 44 45 46
90th 98 99 99 100 101 102 102 54 55 56 56 57 58 58
95th 101 102 102 103 104 105 105 59 59 60 60 61 62 62
95th + 12 mm Hg 113 114 114 115 116 117 117 71 71 72 72 73 74 74
2 Height (in) 33.4 34 34.9 35.9 36.9 37.8 38.4 33.4 34 34.9 35.9 36.9 37.8 38.4
Height (cm) 84.9 86.3 88.6 91.1 93.7 96 97.4 84.9 86.3 88.6 91.1 93.7 96 97.4
50th 87 87 88 89 90 91 91 45 46 47 48 49 50 51
90th 101 101 102 103 104 105 106 58 58 59 60 61 62 62
95th 104 105 106 106 107 108 109 62 63 63 64 65 66 66
95th + 12 mm Hg 116 117 118 118 119 120 121 74 75 75 76 77 78 78
3 Height (in) 35.8 36.4 37.3 38.4 39.6 40.6 41.2 35.8 36.4 37.3 38.4 39.6 40.6 41.2
Height (cm) 91 92.4 94.9 97.6 100.5 103.1 104.6 91 92.4 94.9 97.6 100.5 103.1 104.6
50th 88 89 89 90 91 92 93 48 48 49 50 51 53 53
90th 102 103 104 104 105 106 107 60 61 61 62 63 64 65
95th 106 106 107 108 109 110 110 64 65 65 66 67 68 69
95th + 12 mm Hg 118 118 119 120 121 122 122 76 77 77 78 79 80 81
3/13/18 4:19 PM
CCIP.indb 579
Table 35-5. Blood Pressure Levels for Girls According to Age and Height Percentile, continued
(y) Percentile 5% 10% 25% 50% 75% 90% 95% 5% 10% 25% 50% 75% 90% 95%
4 Height (in) 38.3 38.9 39.9 41.1 42.4 43.5 44.2 38.3 38.9 39.9 41.1 42.4 43.5 44.2
Height (cm) 97.2 98.8 101.4 104.5 107.6 110.5 112.2 97.2 98.8 101.4 104.5 107.6 110.5 112.2
50th 89 90 91 92 93 94 94 50 51 51 53 54 55 55
90th 103 104 105 106 107 108 108 62 63 64 65 66 67 67
95th 107 108 109 109 110 111 112 66 67 68 69 70 70 71
95th + 12 mm Hg 119 120 121 121 122 123 124 78 79 80 81 82 82 83
5 Height (in) 40.8 41.5 42.6 43.9 45.2 46.5 47.3 40.8 41.5 42.6 43.9 45.2 46.5 47.3
Height (cm) 103.6 105.3 108.2 111.5 114.9 118.1 120 103.6 105.3 108.2 111.5 114.9 118.1 120
50th 90 91 92 93 94 95 96 52 52 53 55 56 57 57
90th 104 105 106 107 108 109 110 64 65 66 67 68 69 70
95th 108 109 109 110 111 112 113 68 69 70 71 72 73 73
95th + 12 mm Hg 120 121 121 122 123 124 125 80 81 82 83 84 85 85
6 Height (in) 43.3 44 45.2 46.6 48.1 49.4 50.3 43.3 44 45.2 46.6 48.1 49.4 50.3
Height (cm) 110 111.8 114.9 118.4 122.1 125.6 127.7 110 111.8 114.9 118.4 122.1 125.6 127.7
50th 92 92 93 94 96 97 97 54 54 55 56 57 58 59
90th 105 106 107 108 109 110 111 67 67 68 69 70 71 71
95th 109 109 110 111 112 113 114 70 71 72 72 73 74 74
95th + 12 mm Hg 121 121 122 123 124 125 126 82 83 84 84 85 86 86
Hypertension
Continued
579
3/13/18 4:19 PM
CCIP.indb 580
580
(y) Percentile 5% 10% 25% 50% 75% 90% 95% 5% 10% 25% 50% 75% 90% 95%
7 Height (in) 45.6 46.4 47.7 49.2 50.7 52.1 53 45.6 46.4 47.7 49.2 50.7 52.1 53
Height (cm) 115.9 117.8 121.1 124.9 128.8 132.5 134.7 115.9 117.8 121.1 124.9 128.8 132.5 134.7
50th 92 93 94 95 97 98 99 55 55 56 57 58 59 60
90th 106 106 107 109 110 111 112 68 68 69 70 71 72 72
95th 109 110 111 112 113 114 115 72 72 73 73 74 74 75
95th + 12 mm Hg 121 122 123 124 125 126 127 84 84 85 85 86 86 87
8 Height (in) 47.6 48.4 49.8 51.4 53 54.5 55.5 47.6 48.4 49.8 51.4 53 54.5 55.5
Height (cm) 121 123 126.5 130.6 134.7 138.5 140.9 121 123 126.5 130.6 134.7 138.5 140.9
50th 93 94 95 97 98 99 100 56 56 57 59 60 61 61
90th 107 107 108 110 111 112 113 69 70 71 72 72 73 73
95th 110 111 112 113 115 116 117 72 73 74 74 75 75 75
95th + 12 mm Hg 122 123 124 125 127 128 129 84 85 86 86 87 87 87
9 Height (in) 49.3 50.2 51.7 53.4 55.1 56.7 57.7 49.3 50.2 51.7 53.4 55.1 56.7 57.7
Height (cm) 125.3 127.6 131.3 135.6 140.1 144.1 146.6 125.3 127.6 131.3 135.6 140.1 144.1 146.6
50th 95 95 97 98 99 100 101 57 58 59 60 60 61 61
90th 108 108 109 111 112 113 114 71 71 72 73 73 73 73
95th 112 112 113 114 116 117 118 74 74 75 75 75 75 75
95th + 12 mm Hg 124 124 125 126 128 129 130 86 86 87 87 87 87 87
3/13/18 4:19 PM
CCIP.indb 581
(y) Percentile 5% 10% 25% 50% 75% 90% 95% 5% 10% 25% 50% 75% 90% 95%
10 Height (in) 51.1 52 53.7 55.5 57.4 59.1 60.2 51.1 52 53.7 55.5 57.4 59.1 60.2
Height (cm) 129.7 132.2 136.3 141 145.8 150.2 152.8 129.7 132.2 136.3 141 145.8 150.2 152.8
50th 96 97 98 99 101 102 103 58 59 59 60 61 61 62
90th 109 110 111 112 113 115 116 72 73 73 73 73 73 73
95th 113 114 114 116 117 119 120 75 75 76 76 76 76 76
95th + 12 mm Hg 125 126 126 128 129 131 132 87 87 88 88 88 88 88
11 Height (in) 53.4 54.5 56.2 58.2 60.2 61.9 63 53.4 54.5 56.2 58.2 60.2 61.9 63
Height (cm) 135.6 138.3 142.8 147.8 152.8 157.3 160 135.6 138.3 142.8 147.8 152.8 157.3 160
50th 98 99 101 102 104 105 106 60 60 60 61 62 63 64
90th 111 112 113 114 116 118 120 74 74 74 74 74 75 75
95th 115 116 117 118 120 123 124 76 77 77 77 77 77 77
95th + 12 mm Hg 127 128 129 130 132 135 136 88 89 89 89 89 89 89
12 Height (in) 56.2 57.3 59 60.9 62.8 64.5 65.5 56.2 57.3 59 60.9 62.8 64.5 65.5
Height (cm) 142.8 145.5 149.9 154.8 159.6 163.8 166.4 142.8 145.5 149.9 154.8 159.6 163.8 166.4
50th 102 102 104 105 107 108 108 61 61 61 62 64 65 65
90th 114 115 116 118 120 122 122 75 75 75 75 76 76 76
95th 118 119 120 122 124 125 126 78 78 78 78 79 79 79
Hypertension
95th and 12 mm Hg 130 131 132 134 136 137 138 90 90 90 90 91 91 91
581
Continued
3/13/18 4:19 PM
CCIP.indb 582
582
(y) Percentile 5% 10% 25% 50% 75% 90% 95% 5% 10% 25% 50% 75% 90% 95%
13 Height (in) 58.3 59.3 60.9 62.7 64.5 66.1 67 58.3 59.3 60.9 62.7 64.5 66.1 67
Height (cm) 148.1 150.6 154.7 159.2 163.7 167.8 170.2 148.1 150.6 154.7 159.2 163.7 167.8 170.2
50th 104 105 106 107 108 108 109 62 62 63 64 65 65 66
90th 116 117 119 121 122 123 123 75 75 75 76 76 76 76
95th 121 122 123 124 126 126 127 79 79 79 79 80 80 81
95th + 12 mm Hg 133 134 135 136 138 138 139 91 91 91 91 92 92 93
14 Height (in) 59.3 60.2 61.8 63.5 65.2 66.8 67.7 59.3 60.2 61.8 63.5 65.2 66.8 67.7
Height (cm) 150.6 153 156.9 161.3 165.7 169.7 172.1 150.6 153 156.9 161.3 165.7 169.7 172.1
50th 105 106 107 108 109 109 109 63 63 64 65 66 66 66
90th 118 118 120 122 123 123 123 76 76 76 76 77 77 77
95th 123 123 124 125 126 127 127 80 80 80 80 81 81 82
95th + 12 mm Hg 135 135 136 137 138 139 139 92 92 92 92 93 93 94
15 Height (in) 59.7 60.6 62.2 63.9 65.6 67.2 68.1 59.7 60.6 62.2 63.9 65.6 67.2 68.1
Height (cm) 151.7 154 157.9 162.3 166.7 170.6 173 151.7 154 157.9 162.3 166.7 170.6 173
50th 105 106 107 108 109 109 109 64 64 64 65 66 67 67
90th 118 119 121 122 123 123 124 76 76 76 77 77 78 78
95th 124 124 125 126 127 127 128 80 80 80 81 82 82 82
95th + 12 mm Hg 136 136 137 138 139 139 140 92 92 92 93 94 94 94
3/13/18 4:19 PM
CCIP.indb 583
(y) Percentile 5% 10% 25% 50% 75% 90% 95% 5% 10% 25% 50% 75% 90% 95%
16 Height (in) 59.9 60.8 62.4 64.1 65.8 67.3 68.3 59.9 60.8 62.4 64.1 65.8 67.3 68.3
Height (cm) 152.1 154.5 158.4 162.8 167.1 171.1 173.4 152.1 154.5 158.4 162.8 167.1 171.1 173.4
50th 106 107 108 109 109 110 110 64 64 65 66 66 67 67
90th 119 120 122 123 124 124 124 76 76 76 77 78 78 78
95th 124 125 125 127 127 128 128 80 80 80 81 82 82 82
95th + 12 mm Hg 136 137 137 139 139 140 140 92 92 92 93 94 94 94
17 Height (in) 60.0 60.9 62.5 64.2 65.9 67.4 68.4 60.0 60.9 62.5 64.2 65.9 67.4 68.4
Height (cm) 152.4 154.7 158.7 163.0 167.4 171.3 173.7 152.4 154.7 158.7 163.0 167.4 171.3 173.7
50th 107 108 109 110 110 110 111 64 64 65 66 66 66 67
90th 120 121 123 124 124 125 125 76 76 77 77 78 78 78
95th 125 125 126 127 128 128 128 80 80 80 81 82 82 82
95th + 12 mm Hg 137 137 138 139 140 140 140 92 92 92 93 94 94 94
Use percentile values to stage blood pressure measurements according to the scheme in Table 35-2 (increased blood pressure, ≥90th percentile; stage 1 hypertension, ≥95th percentile; and
stage 2 hypertension, ≥95th percentile + 12 mm Hg). The 50th, 90th, and 95th percentiles were derived by using quantile regression on the basis of normal-weight children (body mass index
<85th percentile). From reference 1.
Hypertension
583
3/13/18 4:19 PM
Select appropriate BP cuff size

Measure BP at each well-child visit over 3 years of age
Determine if BP value requires further evaluation
Measure HT and WT and calculate BMI
Determine BP category for age, HT, gender
Normal BP: Elevated BP: Stage 1 HTN: Stage 2 HTN:

1–13 y: 1–13y: 1–13y: 1–13y:
<90th percentile ≥90th percentile ≥95th percentile ≥95th percentile
≥13y: to <95th percentile to <95th percentile +12 mmHg or
<120/<80 mmHg or 120/80 to +12 mmHg ≥140/90 mmHg
<95th percentile or 130/80 to ≥13y:
139/89 mmHg ≥140/90 mmHg
≥13y: 120/<80 to
129/<80 mmHg ≥13y: 130/80 to
139/89 mmHg
Counsel on lifestyle modification

(healthy eating, activity, screen time, sleep hygiene, etc.)
Repeat in 6 months Repeat in 1–2 weeks Repeat in 1 week

by auscultation by auscultation by auscultation
Repeat BP
at next well If elevated—repeat lifestyle teaching and obtain 3 ext BP
child visit
Repeat in 6 months Repeat in 3 months If elevated at 1 week—

by auscultation by auscultation • Obtain ABPM
• Complete diagnostic
evaluation
• Initiate treatment
If BP If 3 measurements are If elevated at 3 months—

normalizes elevated then • Repeat lifestyle teaching
• Diagnostic evaluation • Obtain ABPM
• Subspecialty referral • Complete diagnostic evaluation
• Initiate treatment
FIGURE 35-1. Blood pressure (BP) measurement and categorization based on the 2017 AAP
Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and
Adolescents. ABPM = ambulatory blood pressure monitor, BMI = body mass index, HT = height,
HTN = hypertension, WT = weight.
584
CCIP.indb 584 3/13/18 4:19 PM

Hypertension
algorithm is based on the most recent AAP practice guidelines, and similar
algorithms have been the recommendation of many prominent organizations,
including the AHA, National High Blood Pressure Education Program, and
European Society of Hypertension, the U.S. Preventive Services Task Force had
concluded that there are insufficient data to support these recommendations
prior to the release of the new guidelines.14
Ambulatory Blood Pressure Monitor
The diagnostic approach to hypertension is somewhat controversial. The rule
of 3 blood pressure measurements obtained at least 24 hours apart to diagnose
hypertension in the pediatric population continues to be the method by which
most physicians diagnose hypertension in community pediatric practices.
Ambulatory blood pressure monitors (ABPMs) are being used more commonly
in the pediatric population for evaluation of hypertension and in fact have been
recommended for evaluation of blood pressure prior to initiation of treatment
in adults.15 An ABPM is a blood pressure monitor that is worn for 24 hours.
It is set to obtain a blood pressure measurement periodically (usually every
20–30 minutes) and stores the measurements. This allows evaluation of daytime,
active blood pressure, as well as nighttime sleeping blood pressure. In the pedi-
atric population, ABPMs have been shown to allow more accurate diagnosis of
hypertension than in-office evaluation;16 allow better prediction of future blood
pressure; correspond with end-organ complications of hypertension;17,18 and
provide more reproducible values than blood pressure measurements obtained
in the office.16 Some hypertension specialists will not diagnose hypertension in a
child without a supporting ABPM result.
Evaluation
Once hypertension has been diagnosed, further testing is necessary to determine
its etiologic origins to ascertain whether there is essential (primary) hypertension
or secondary hypertension due to renal issues, diabetes, congenital heart disease,
sleep apnea, and so on. The history should include factors such as a personal
history of prematurity, birth weight, need for central lines (particularly umbilical
artery catheters), history of renal disease, urinary tract infections, sleep habits,
and hygiene. A family history should be obtained, including hypertension, car-
diac disease, stroke, renal disease, urinary tract infections, solid organ transplant,
and obesity.
A nutritional history should focus on sodium and caffeine intake and, if
obese, general dietary intake, particularly related to sugar-sweetened beverage,
carbohydrate, and fat intake. A physical activity history should include types of
activities performed, as well as sedentary time and screen time evaluation.
A complete physical examination should be performed, including evaluation
for possible end-organ damage. Blood pressure measurements should be
obtained in both an arm and a leg.
585
CCIP.indb 585 3/13/18 4:19 PM

Laboratory testing must be conducted to evaluate the patient for secondary

effects of hypertension, such as LV hypertrophy and renal disease. The testing
should include the following:
•• Urinalysis
•• Chemistry panel, including electrolyte, blood urea nitrogen, and creatinine
levels
•• Cholesterol panel—fasting or nonfasting, with a minimum of high-density
lipoprotein and total cholesterol levels
•• Renal ultrasonography (US) if <6 years old or if there are abnormal renal
laboratory values
Additional testing may be necessary if other conditions are present. If hyperten-
sion is associated with obesity (BMI >95th percentile), additional testing should
include a hemoglobin A1c level, fasting lipid panel, and liver enzyme levels to
evaluate the patient for fatty liver disease. On the basis of family and personal
history, additional testing, including thyroid-stimulating hormone level, fasting
serum glucose level, complete blood count, drug screen, and sleep study may
be performed.
Further studies may be necessary if the etiologic origin of the blood pressure
is not determined and if the blood pressure is difficult to control.
Imaging
Renal US is generally expected in young children with a diagnosis of hyper-
tension but may not be necessary in adolescents with multiple risk factors.
Echocardiography should be performed to evaluate the patient for end-organ
damage and to rule out cardiac causes of hypertension, such as coarctation of
the aorta, in patients with stage 1 or 2 hypertension at the time of evaluation.
After a year of increased blood pressure measurements, echocardiography should
be performed to evaluate the patient for increased left ventricular mass index
(>51 g/m2.7 or >115 g for boys or >95 g for girls) or LV hypertrophy (>1.4 cm).
Evaluation with serial echocardiography will ensure adequate treatment to
prevent end-organ damage.
Management
Treatment Approach
The treatment of pediatric hypertension depends largely on the etiologic origin
of the disease. For secondary hypertension, treatment of the underlying cause is
typically the most effective way to treat and reduce the increased blood pressure.
For primary hypertension (essential hypertension), treatment begins with diet
and lifestyle changes.
In general, dietary recommendations minimally include reduction in
sodium intake. When obesity is a comorbid condition, the dietary treatment
586
CCIP.indb 586 3/13/18 4:19 PM

Hypertension
must be targeted not only at hypertension but also at weight reduction. The
Cardiovascular Health Integrated Lifestyle Diet (CHILD-1) is the first stage
in dietary modification for children found to be at increased cardiovascular
risk.19 This diet recommends that 30% of calories be from fat—7% to 10% of
these from saturated fat—20% from protein, and 50% from carbohydrates.
Additionally, CHILD-1 recommends less than 300 mg/day of cholesterol. Total
calories per day are dependent on the size and activity level of the child and must
be determined individually. There are no specific sodium intake recommenda-
tions, although many physicians recommend less than 2 to 3 grams per day.
Lifestyle recommendations include multiple factors, such as screen time and
physical activity. The AAP has recommended limiting screen time to less than
2 hours per day. In combination with limiting screen time, increasing activity
improves blood pressure. The AAP, AHA, and American College of Cardiology
recommend that children perform at least 60 minutes of moderate to vigorous
activity daily. Studies have shown that increasing activity to 40 minutes of
moderate or vigorous activity 3 to 5 days per week is associated with a reduction
in systolic blood pressure.20
With end-organ changes or damage, treatment of hypertension should be
initiated. A child with hypertensive urgency or emergency, defined as a blood
pressure greater than 180/100 mm Hg, should be treated as an inpatient with
a slow decrease in blood pressure, no more than 25% in the first 8 hours, with
the remaining decrease to normal occurring over several days. This should
be performed under the guidance of a physician with experience in treating
hypertensive urgency or emergency.
Specific Treatments
The goal of treatment is normotension, or a blood pressure less than the 90th
percentile or less than 130/80 mm Hg, whichever is lower.1 Many of the
medications used in adulthood are being used to treat hypertension in children.
Table 35-6 shows the medications that have been tested by the U.S. Food and
Drug Administration for use in children that are typically the first lines of treat-
ment. Angiotensin-converting enzyme inhibitors are frequently the first line of
therapy. Additional medications may be used off-label for treatment of pediatric
hypertension. Treatment also varies, depending on the other comorbidities
present, such as diabetes or renal disease.
When to Refer
Many pediatricians prefer not to provide primary treatment for hypertension.
There are different practice styles in different institutions, ranging from diagnosis
and treatment of hypertension by the pediatrician to referral to either nephrol-
ogy or cardiology after the first increased blood pressure measurement. There are
a growing number of multidisciplinary hypertension clinics involving cardiology,
587
CCIP.indb 587 3/13/18 4:19 PM

CCIP.indb 588
588
Table 35-6. Antihypertensive Medications Studied in Pediatric Patients by the U.S. Food and
Drug Administration
Suspension Pediatric
Drug Class Drug Starting Dose Maximum Dose Frequency Formulation Indication
Angiotensin-converting Enalapril 0.08 mg/kg (≤5 mg) 0.58 mg/kg or 40 mg Daily Yes All except
enzyme inhibitor neonates
Fosinopril 0.1 mg/kg (5–10 0.6 mg/kg or 40 mg Daily No Children >50 kg

mg)
Lisinopril 0.07 mg/kg (≤5 mg) 0.6 mg/kg or 40 mg Daily Yes >6 y
Benazepril 0.2 mg/kg (≤10 mg) 0.6 mg/kg or 40 mg Daily Yes >6 y
Angiotensin receptor Losartan 0.7 mg/kg (≤50 mg) 1.4 mg/kg or 100 mg Daily Yes >6 y
blocker
Valsartan 1.3 mg/kg (≤40 mg) 2.7 mg/kg or 160 mg Daily Yes >6 y
Candesartan 1–6 y, 0.2 mg/kg 1-6 y, 0.4 mg/kg Daily or Yes >1 y
divided dose
6–17 y, <50 kg: 4 6-17 y, <50 kg: 16 mg
mg
6–17 y, >50 kg: 8 6-17 y, >50 kg: 32 mg

mg
Olmesartan 20 to <35 kg: 10 mg 20 to <35 kg: 20 mg Daily Yes >6 y
≥35 kg: 20 mg ≥35 kg: 40 mg
Irbesartan No FDA pediatric indication (effectiveness not demonstrated)
β-blocker Metoprolol XL 1.0 mg/kg (<50 mg) 2 mg/kg ≤200 mg Daily No >6 y
Bisoprolol No FDA pediatric indication (effectiveness not demonstrated)
3/13/18 4:19 PM
Hypertension
nephrology, endocrinology, nutrition, physical

therapy, and psychology, or some portion of
these providers, because many children with
Indication
Table 35-6. Antihypertensive Medications Studied in Pediatric Patients by the U.S. Food and
Pediatric
essential hypertension require care from

>6 y multiple specialties.
Formulation
Suspension
Sports participation is generally encouraged

because it may help decrease blood pressure,
particularly in the population with essential
No
hypertension. Sports limitations are necessary

for patients with hypertensive urgency or
No FDA pediatric indication (effectiveness not demonstrated)
No FDA pediatric indication (effectiveness not demonstrated)

Frequency
emergency (blood pressure >180/100 mm Hg).

In patients with LV hypertrophy or increased
Daily
From Chu PY, Campbell MJ, Miller SG, Jill KD. Anti-hypertensive drugs in children and adolescents. World J Cardiol. 2014; 6(5):234–244.
LV mass index, competitive athletics should be

limited until adequate control of blood pressure
is achieved and the LV hypertrophy or LV
0.3 mg/kg or 10 mg
mass index is normalized at least to that of an

Maximum Dose
athlete. Those with stage 2 hypertension should

be limited from high-static activities, such as
weight lifting, boxing, and wrestling, until the
blood pressure is controlled.21,22
Endocarditis prophylaxis is not required for
Starting Dose
essential hypertension. Comorbidities, however,

may rarely necessitate prophylaxis on a case-by-
2.5 mg
case basis.
Drug Administration, continued
Prevention
Prevention of hypertension involves healthy
Eplerenone
Amlodipine
lifestyle choices, including maintaining a

Felodipine
healthy diet and active lifestyle. The AHA

Drug
has established criteria for preventing the

development of hypertension in the pediatric
Calcium channel blocker
population, which include the following:23

•• Abstinence from smoking
•• BMI <85th percentile
•• ≥60 minutes of moderate or vigorous
Drug Class
physical activity daily

Diuretic
589
CCIP.indb 589 3/13/18 4:19 PM

•• Adherence to a diet in which fruits, vegetables, fish, whole grains, low sodium
intake, and few sugar-laden foods and drinks are emphasized
•• Fasting total cholesterol level <170 mg/dL (<4.40 mmol/L), blood pressure
<90th percentile
•• Fasting plasma glucose level <100 mg/dL (<5.55 mmol/L)
Ongoing Care
Follow-up
For children who are evaluated for hypertension but do not have it, follow-up
should be performed as recommended by the AAP, the AHA, and the American
College of Cardiology for all children with annual blood pressure screening
at well-child visits. With the diagnosis of white-coat hypertension, the blood
pressure is likely to continue to be increased at office visits; however, a trend can
be determined, and if the blood pressure is increasing further, repeat evaluation
for hypertension is necessary. Generally, children who receive a diagnosis of
primary hypertension should be evaluated at least every 4 to 6 weeks until goal
blood pressure has been achieved. Subsequent to normalization of blood pressure
with medications, visits can be timed every 3 to 4 months to ensure adequate
treatment over time. Follow-up will be more frequent while the child is being
encouraged to adopt lifestyle modifications or after initiation of medication, to
ensure that appropriate improvement is demonstrated and to titrate medications
and evaluate the patient for side effects.
Follow-up visits should include multiple evaluations. Assessments for medica-
tion clearance should be performed at each visit. Depending on the medication,
laboratory evaluation for medication side effects may be necessary (blood urea
nitrogen and creatinine for angiotensin-converting enzyme inhibitors to ensure
no renal toxicity). Reinforcement of lifestyle changes is important because
effective treatment of hypertension requires lifestyle change. Evaluation for
target end-organ damage should be performed annually as per the current
recommendations.
ABPM may be used to evaluate adequacy of treatment. ABPM measure-
ments will help to determine medication adherence and allow medication
changes or addition of medication due to poor control.
Complications and Prognosis

Complications in pediatric hypertension are incompletely described because
many do not become evident until adulthood; however, end-organ damage can
be found during childhood. Evidence of LV hypertrophy and abnormal vascular
changes, such as vascular stiffness, have been reported.24,25 Developmental
learning and behavioral changes have also been reported.26 Patients with chronic
hypertension should be monitored for these issues.
590
CCIP.indb 590 3/13/18 4:19 PM

Hypertension
Prognosis
The prognosis for children with hypertension is dependent on the underlying
cause. For those with essential hypertension, the prognosis is generally good,
particularly with treatment. However, the best predictor for adult hypertension
is pediatric hypertension; thus, many of these children will grow up to have
hypertension and the adult issues (stroke, heart attack, renal disease, etc) that
are related to hypertension.13
Multiple adult studies have shown that there is increased risk of early
atherosclerosis in children and young adults with hypertension.27,28 Early ath-
erosclerosis is also associated with other risk factors for hypertension, including
increased BMI and cholesterol level, making it difficult to separate the effects
of each component from the outcome of isolated hypertension.
The general pediatrician must address pediatric essential hypertension on a
regular basis to prevent long-term morbidity and mortality.

•• High Blood Pressure in Children (American Academy of Pediatrics).
www.healthychildren.org/English/health-issues/conditions/heart/Pages/
High-Blood-Pressure-in-Children.aspx
•• International Pediatric Hypertension Association.
www.iphapediatrichypertension.org
•• High Blood Pressure (KidsHealth From Nemours).
kidshealth.org/en/parents/hypertension.html
•• High Blood Pressure in Children (American Heart Association).
www.heart.org/HEARTORG/Conditions/HighBloodPressure/
UnderstandSymptomsRisks/High-Blood-Pressure-in-Children_
UCM_301868_Article.jsp#.WOuhJRweXfo
References
1) Flynn JT, Kaelber DC, Baker-Smith CM, et al; Subcommittee on Screening and Management
of High Blood Pressure in Children. Clinical Practice Guideline for Screening and Management
of High Blood Pressure in Children and Adolescents. Pediatrics. 2017;140(3):e20171904
2) Shapiro DJ, Hersh AL, Cabana MD, Sutherland SM, Patel AI. Hypertension screening during
ambulatory pediatric visits in the United States, 2000-2009. Pediatrics. 2012;130(4):604–610
3) Hansen ML, Gunn PW, Kaelber DC. Underdiagnosis of hypertension in children and adoles-
cents. JAMA. 2007;298(8):874–879
4) Lo JC, Sinaiko A, Chandra M, et al. Prehypertension and hypertension in community-based
pediatric practice. Pediatrics. 2013;131(2):e415–e424
5) Koebnick C, Black MH, Wu J, et al. High blood pressure in overweight and obese youth:
implications for screening. J Clin Hypertens (Greenwich). 2013;15(11):793–805
6) Kapur G, Ahmed M, Pan C, Mitsnefes M, Chiang M, Mattoo TK. Secondary hypertension
in overweight and stage 1 hypertensive children: a Midwest Pediatric Nephrology Consortium
report. J Clin Hypertens (Greenwich). 2010;12(1):34–39
591
CCIP.indb 591 3/13/18 4:19 PM

7) Ogden CL, Carroll MD, Lawman HG, et al. Trends in obesity prevalence among
children and adolescents in the United States, 1988-1994 through 2013-2014. JAMA.
2016;315(21):2292–2299
8) Juhola J, Magnussen CG, Viikari JS, et al. Tracking of serum lipid levels, blood pressure, and
body mass index from childhood to adulthood: the Cardiovascular Risk in Young Finns study. J
Pediatr. 2011;159(4):584–590
9) Javaheri S, Storfer-Isser A, Rosen CL, Redline S. Sleep quality and elevated blood pressure in
adolescents. Circulation. 2008;118(10):1034–1040
10) Au CT, Ho CK, Wing YK, Lam HS, Li AM. Acute and chronic effects of sleep duration on
blood pressure. Pediatrics. 2014;133(1):e64–e72
11) Kouidi E, Fahadidou-Tsiligiroglou A, Tassoulas E, Deligiannis A, Coats A. White coat
hypertension detected during screening of male adolescent athletes. Am J Hypertens. 1999;12(2
Pt 1):223–226
12) Sorof JM, Poffenbarger T, Franco K, Portman R. Evaluation of white coat hypertension in
children: importance of the definitions of normal ambulatory blood pressure and the severity of
casual hypertension. Am J Hypertens. 2001;14(9 Pt 1):855–860
13) National High Blood Pressure Education Program Working Group on High Blood Pressure in
Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high
blood pressure in children and adolescents. Pediatrics. 2004;114(2 Suppl 4th Report):555–576
14) Moyer VA; U.S. Preventive Services Task Force. Screening for primary hypertension in children
and adolescents: U.S. Preventive Services Task Force recommendation statement. Ann Intern
Med. 2013;159(9):613–619
15) Díaz LN, Garin EH. Comparison of ambulatory blood pressure and Task Force criteria to
identify pediatric hypertension. Pediatr Nephrol. 2007;22(4):554–558
16) Stergiou GS, Alamara CV, Salgami EV, Vaindirlis IN, Dacou-Voutetakis C, Mountokalakis TD.
Reproducibility of home and ambulatory blood pressure in children and adolescents. Blood Press
Monit. 2005;10(3):143–147
17) Li Z, Snieder H, Harshfield GA, Treiber FA, Wang X. A 15-year longitudinal study on
ambulatory blood pressure tracking from childhood to early adulthood. Hypertens Res.
2009;32(5):404–410
18) Brady TM, Fivush B, Flynn JT, Parekh R. Ability of blood pressure to predict left ventricular
hypertrophy in children with primary hypertension. J Pediatr. 2008;152(1):73–78, 78.e1
Children and Adolescents; National Heart, Lung, and Blood Institute. Expert panel on integrat-
ed guidelines for cardiovascular health and risk reduction in children and adolescents: summary
report. Pediatrics. 2011;128(Suppl 5):S213–S256
20) Torrance B, McGuire KA, Lewanczuk R, McGavock J. Overweight, physical activity and high
blood pressure in children: a review of the literature. Vasc Health Risk Manag. 2007;3(1):139–149
21) McCambridge TM, Benjamin HJ, Brenner JS, et al; Council on Sports Medicine and Fitness.
Athletic participation by children and adolescents who have systemic hypertension. Pediatrics.
2010;125(6):1287–1294
22) Black HR, Sica D, Ferdinand K, White WB. Eligibility and disqualification recommendations
for competitive athletes with cardiovascular abnormalities: Task Force 6: hypertension: a scien-
tific statement from the American Heart Association and the American College of Cardiology. J
Am Coll Cardiol. 2015;66(21):2393–2397
23) Lloyd-Jones DM, Hong Y, Labarthe D, et al; American Heart Association Strategic Planning
Task Force and Statistics Committee. Defining and setting national goals for cardiovascular
health promotion and disease reduction: the American Heart Association’s strategic impact goal
through 2020 and beyond. Circulation. 2010;121(4):586–613
592
CCIP.indb 592 3/13/18 4:19 PM

Hypertension
24) Lande MB, Carson NL, Roy J, Meagher CC. Effects of childhood primary hypertension on
carotid intima media thickness: a matched controlled study. Hypertension. 2006;48(1):40–44
25) Drukteinis JS, Roman MJ, Fabsitz RR, et al. Cardiac and systemic hemodynamic characteristics
of hypertension and prehypertension in adolescents and young adults: the Strong Heart Study.
Circulation. 2007;115(2):221–227
26) Lande MB, Adams H, Falkner B, et al. Parental assessments of internalizing and exter-
nalizing behavior and executive function in children with primary hypertension. J Pediatr.
2009;154(2):207–212
27) Berenson GS, Srinivasan SR, Bao W, Newman WP III, Tracy RE, Wattigney WA. Association
between multiple cardiovascular risk factors and atherosclerosis in children and young adults.
The Bogalusa Heart Study. N Engl J Med. 1998;338(23):1650–1656
28) McGill HC Jr, McMahan CA, Gidding SS. Preventing heart disease in the 21st century:
implications of the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study.
Circulation. 2008;117(9):1216–1227
593
CCIP.indb 593 3/13/18 4:19 PM

CCIP.indb 594 3/13/18 4:19 PM
CHAPTER 36
Cardiac Screening
Prior to ADHD
Treatment
Kanupriya Chaturvedi, MD, FAAP, and
Christopher Snyder, MD, FAAP
Introduction
Attention-deficit/hyperactivity disorder (ADHD) is the most common neuro
behavioral disorder diagnosed in school-aged children, affecting 5% to 8% of
all children in the United States.1,2 The criteria for diagnosis are listed in the
Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, outlined by the
American Psychiatric Association in detail and available at www.psychiatry.org or
through the Centers for Disease Control and Prevention at https://www.cdc.gov/
ncbddd/adhd/diagnosis.html. The American Academy of Child and Adolescent
Psychiatry (AACAP) has characterized this disorder according to inattention,
poor impulse control, and motor hyperactivity and/or restlessness.2
ADHD causes substantial morbidity in children, including academic under-
achievement and poor interpersonal relationships, which result in low self-esteem.
Approximately 50% of children with this disorder grow up with varying mani-
festations of ADHD and experience substantial issues with employment, social
interactions, and substance use. These observations underscore the importance of
correctly identifying and treating this disorder as early as possible to allow for a
productive and fulfilling life for these patients.
The medications used for treating ADHD have been the center of controversy
regarding cardiovascular side effects and their potential to cause sudden death.
595
CCIP.indb 595 3/13/18 4:19 PM

There have been several scientific statements issued by various national asso
ciations citing guidelines for cardiac clearance and using stimulants for the
treatment of ADHD.3–5
Historical Aspects
In 1999, tricyclic antidepressant (TCA) medications were frequently used for
the treatment of ADHD, but because of concerns over their potential cardio-
vascular side effects, the American Heart Association (AHA) issued a scientific
statement entitled, “Cardiovascular Monitoring of Children and Adolescents
Receiving Psychotropic Drugs.”3 This statement addressed drug interactions and
potential cardiovascular side effects pertaining to psychotropic drugs, especially
TCAs (imipramine and desipramine). The AHA emphasized the need for
compiling a thorough history, including an explicit family history of sudden,
unexplained death, and recommended baseline electrocardiography (ECG) prior
to initiating TCA therapy. Subsequently, small cohort studies and case reports
have documented a lack of benefit for screening ECG in these patients.2,4,6
Today, TCAs are rarely used to treat ADHD.
Since that time, there have been multiple advances in the pharmacotherapy
of ADHD treatment, with more successful drugs being used—namely,
amphetamines and methylphenidates. In 2008, the AHA released a controversial
statement, the key points of which re-emphasized the importance of obtaining a
good patient and family history, as well as performing a thorough physical exam-
ination prior to initiating medications for ADHD.5 However, it stated that it
would be reasonable to perform baseline ECG to identify serious cardiovascular
abnormalities, such as long QT syndrome, hypertrophic cardiomyopathy, and
Wolff-Parkinson-White syndrome. The American Academy of Pediatrics (AAP)
endorsed the AHA policy of extensive patient and family history and a complete
physical examination but did not support the recommendation of routine ECG,
citing a lack of evidence.7,8 This AAP statement found additional support from
the AACAP, the Society for Developmental and Behavioral Pediatrics, the
National Initiative for Children’s Healthcare Quality, and Children and Adults
with Attention-deficit/Hyperactivity Disorder.
The Treatment of ADHD

Currently, the most commonly used medications to treat ADHD are the dopa-
minergic agonists, also known as stimulant medications. These drugs include
•• Methylphenidates and dexmethylphenidates
•• Amphetamine and dextroamphetamine derivatives
•• Atomoxetine, a noradrenergic reuptake inhibitor
•• Guanfacine, a nonstimulant alternative
596
CCIP.indb 596 3/13/18 4:19 PM

Cardiac Screening Prior to ADHD Treatment
These medications and their dose adjustments are typically handled by primary
care physicians.
ADHD Medications and Cardiovascular Risks

In general, the effects of ADHD medications on the cardiovascular system
consist of a minimal increase in the average heart rate of approximately 1 to
2 beats per minute and a slight increase in the blood pressure, both systolic
and diastolic, by 3 to 4 mm Hg.9 In healthy children without pre-existing
cardiovascular disease, these potential side effects are thought to be clinically
insignificant; however, they may prove to be detrimental in children with certain
rare conditions that have a predisposition for sudden cardiac death, such as
cardiac channelopathies, cardiomyopathies, and arrhythmias. Most importantly,
these drugs have yet to demonstrate any effects on either the QT interval or
the corrected QT interval.10
Sudden deaths occurring in patients with ADHD who receive methyl-
phenidates have been reported but are rare, and the underlying cause of these
deaths remains unknown. Ventricular arrhythmias have been reported with
methylphenidate and amphetamine abuse.11–14 Atomoxetine, a newer alternative
for ADHD treatment, has shown a mild but statistically significant increase in
systolic and diastolic blood pressure, as well as an increase in the mean heart
rate of 5 to 9 beats per minute; however, these changes have been seen to revert
upon discontinuation of the medication, and there are no reported clinically
significant ECG changes or sudden deaths associated with their use.15
A rare alternative treatment for ADHD, TCAs have been associated
with severe side effects, including tachycardia, atrioventricular block, atrial
and ventricular arrhythmias, and sudden death.16 However, since the advent
of methylphenidates and amphetamines as the current therapy for ADHD,
tricyclic antidepressants are rarely used.
Cardiac Screening Prior to Dispensing

ADHD Medications
The most important decisions a primary care physician faces when caring
for patients with ADHD are which children need to be screened for heart
diseases and how to detect a possible cardiac disease in a child prior to initiating
treatment. Among children found to have an abnormal ECG finding or cardiac
disease, the next important clinical decision is which children merit modification
of ADHD treatment and/or referral to a pediatric cardiologist.
The AAP and the AHA recommend that ADHD should be treated and
managed by primary care physicians, with referral to a pediatric cardiologist
when the primary screening findings are suggestive of cardiac disease.4,5
597
CCIP.indb 597 3/13/18 4:19 PM

The important issues that should be addressed prior to initiating treatment

for ADHD can be broken down as follows.
Patient History
This screening component can be helpful in eliciting cardiovascular symptoms
prior to any advanced laboratory testing. From a cardiovascular standpoint,
important history questions include
•• Exertional symptoms of fainting, dizziness, chest pain, or shortness of breath
•• Palpitations (racing heart, skipped beats, fluttering in the chest)
•• History of high blood pressure
•• History of heart murmurs
•• Failure to gain weight
•• History of other known heart problems
•• A recent change in exercise capacity
Family History
If compiled thoroughly, a family history can be used to identify asymptomatic
children who might be at risk for sudden death. Important questions for this
assessment include
•• History of sudden, unexplained death or aborted sudden death
•• Unexplained syncope during exertion
•• Heart attacks in family members younger than 50 years of age
•• Documented arrhythmias
•• Cardiomyopathy of any type—hypertrophic, dilated, or restrictive
•• Arrhythmogenic right ventricular dysplasia
•• Cardiac channelopathies—long QT syndrome, short QT syndrome, Brugada
syndrome, and catecholaminergic polymorphic ventricular tachycardia
•• Wolff-Parkinson-White syndrome
•• Marfan syndrome
A focused cardiac examination should specifically be used to evaluate the
patient for
•• Murmurs, other than innocent or Still murmurs
•• Tachycardia
•• High blood pressure
•• Irregular heart rate or rhythm on auscultation
•• Physical features of Marfan syndrome
598
CCIP.indb 598 3/13/18 4:19 PM

Electrocardiography
Whether to perform baseline ECG or not has been controversial with regard
to initiating ADHD medications. The AAP statement does not recommend
performing screening ECG in view of the lack of evidence.7 In general pediatric
practice, baseline ECG for healthy children with no clinically significant family
history is unwarranted.
If the patient history and family history or physical examination findings
raise suspicion for a cardiac condition, the primary care physician should per-
form ECG prior to initiating treatment. The ECG findings may be interpreted
by the primary physician; however, if any questions exist, the ECG findings
should be interpreted by a pediatric cardiologist.
Consulting a Pediatric Cardiologist

Routine consultation with a pediatric cardiologist is not warranted to begin
treatment for ADHD. If ECG is performed for suspicious history or physical
examination findings as outlined previously, ECG findings considered “red flags”
for consulting a pediatric cardiologist are
•• Left, right, or biventricular hypertrophy
•• Wolff-Parkinson-White pattern
•• QRS axis deviations
•• Interventricular conduction delays
•• Second- or third-degree atrioventricular blocks
•• Prolonged corrected QT interval
•• ST-T wave changes (abnormal T wave inversions in leads V5 and V6, unusual
T wave morphologic appearance, ST segment elevation or depression)
•• Arrhythmias
•• Frequent premature atrial or ventricular contractions, ie, 20% of all QRS
complexes with standard 24-hour Holter monitoring
Administration of Medication and Monitoring in Patients

Found to Have Any of These ECG Abnormalities
The treatment of patients with ADHD should be initiated and maintained by
the primary care physician and may be administered with or after consultation
with a pediatric cardiologist for patients at risk. Most children can safely be
treated with stimulants, because there is a lack of data citing increased risk
of sudden death in these patients. However, amongst the cardiac conditions
listed herein, it would not be unreasonable to have a more detailed continued
assessment at each visit, which should include a thorough cardiac examination,
evaluation of cardiovascular symptoms as outlined herein in the history section,
and elicitation of any new cardiac family history.
Assessment of blood pressure and heart rate are an essential component of
every visit; they should also be trended, taking prior results into account. Any
599
CCIP.indb 599 3/13/18 4:19 PM

abnormal cardiac examination finding, new clinically significant cardiac history

(ie, palpitations, syncope, dizziness, or a new family history of sudden death
or unexplained syncope), or changing trend of blood pressure and heart rate
should prompt an appropriate referral to a pediatric cardiologist. Despite lack of
evidence, the group that is likely to benefit from careful monitoring includes
•• Patients with pre-existing heart conditions that predispose them to sudden
cardiac death—for example, long QT syndrome, hypertrophic cardiomyopathy,
arrhythmogenic right ventricular dysplasia, Brugada syndrome, Wolff-
Parkinson-White syndrome, and Marfan syndrome
•• Those with a history of an aborted sudden death, unexplained syncope, or
documented arrhythmia
•• Heart rate or blood pressure 2 standard deviations above the mean for a given
age and sex
In the event of new arrhythmias diagnosed while a patient is being treated with
stimulants, it is reasonable to discontinue the medication until further testing
has been performed and the patient is deemed fit to restart the medication in
conjunction with a pediatric cardiologist.
Key Points
•• ADHD has the potential to decrease a child or adolescent’s quality of life.
Once diagnosed, it should be treated with the available medications, unless
there are serious side effects to these medications.
•• Consultation with a pediatric cardiologist is not routinely warranted to initiate
or maintain stimulant medications in children, because there are no data
that document any increased risk of sudden cardiac death in children taking
stimulants. The primary care physician and/or child and adolescent psychiatrist
should be the primary care provider for treating ADHD in children.
•• Prior to initiating treatment, it is important to obtain a thorough history
(including family history) and physical examination (including the cardiovas-
cular system) to identify patients at risk for sudden cardiac death.
•• ECG is not recommended in routine screening for patients to be started on
psychostimulants, because there is no evidence that it can be useful for identi-
fying patients at risk for sudden cardiac death. Even during the ongoing care
of these patients, at no point is ECG required unless cardiovascular symptoms
or arrhythmias develop during treatment.
•• For patients with a history suggestive of cardiac disorder or predisposition
to one, it is reasonable to perform ECG. If the ECG findings are abnormal,
it is appropriate to obtain consultation from a pediatric cardiologist prior to
initiating therapy.
600
CCIP.indb 600 3/13/18 4:19 PM

•• For patients who develop new cardiovascular symptoms, cardiac family history,
or abnormal cardiac examination findings while receiving treatment, ECG
should be performed, and a pediatric cardiologist should be consulted. It is
reasonable to discontinue therapy for these patients until they are deemed
ready to restart therapy, as suggested by a pediatric cardiologist.
•• There is a continued need for further studies and trials on ADHD and cardiac
clearance, because limited data are available for guidelines on cardiac testing
and involvement of a pediatric cardiologist.

•• American Academy of Child and Adolescent Psychiatry. www.aacap.org
•• National Resource Center on ADHD (Adults and Children With Attention-
deficit/Hyperactivity Disorder [CHADD]). www.chadd.org/NRC.aspx
References
1) Barbaresi WJ, Katusic SK, Colligan RC, et al. How common is attention-deficit/hyperactivity
disorder? Incidence in a population-based birth cohort in Rochester, Minn. Arch Pediatr Adolesc
Med. 2002;156(3):217–224
2) Spencer TJ, Biederman J, Mick E. Attention-deficit/hyperactivity disorder: diagnosis, lifespan,
comorbidities, and neurobiology. J Pediatr Psychol. 2007;32(6):631–642
3) Gutgesell H, Atkins D, Barst R, et al. AHA Scientific Statement: cardiovascular monitoring
of children and adolescents receiving psychotropic drugs. J Am Acad Child Adolesc Psychiatry.
1999;38(8):1047–1050
4) American Academy of Pediatrics. Clinical practice guideline: diagnosis and evaluation of the
child with attention-deficit/hyperactivity disorder. Pediatrics. 2000;105(5):1158–1170
5) Vetter VL, Elia J, Erickson C, et al; American Heart Association Council on Cardiovascular
Disease in the Young Congenital Cardiac Defects Committee; American Heart Association
Council on Cardiovascular Nursing. Cardiovascular monitoring of children and adolescents with
heart disease receiving medications for attention deficit/hyperactivity disorder [corrected]: a
scientific statement from the American Heart Association Council on Cardiovascular Disease in
the Young Congenital Cardiac Defects Committee and the Council on Cardiovascular Nursing.
Circulation. 2008;117(18):2407–2423
6) Pliszka S; AACAP Work Group on Quality Issues. Practice parameter for the assessment and
treatment of children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad
Child Adolesc Psychiatry. 2007;46(7):894–921
7) Perrin JM, Friedman RA, Knilans TK; Black Box Working Group; Section on Cardiology
and Cardiac Surgery. Cardiovascular monitoring and stimulant drugs for attention-deficit/
hyperactivity disorder. Pediatrics. 2008;122(2):451–453
8) Wilens TE, Prince JB, Spencer TJ, Biederman J. Stimulants and sudden death: what is a
physician to do? Pediatrics. 2006;118(3):1215–1219
9) Findling RL, Short EJ, Manos MJ. Short-term cardiovascular effects of methylphenidate and
adderall. J Am Acad Child Adolesc Psychiatry. 2001;40(5):525–529
10) Findling RL, Biederman J, Wilens TE, et al; SLI381.301 and. 302 Study Groups. Short- and
long-term cardiovascular effects of mixed amphetamine salts extended release in children.
J Pediatr. 2005;147(3):348–354
601
CCIP.indb 601 3/13/18 4:19 PM

11) Massello W III, Carpenter DA. A fatality due to the intranasal abuse of methylphenidate
(Ritalin). J Forensic Sci. 1999;44(1):220–221
12) Lucas PB, Gardner DL, Wolkowitz OM, Tucker EE, Cowdry RW. Methylphenidate-induced
cardiac arrhythmias. N Engl J Med. 1986;315(23):1485
13) Patel MM, Wright DW, Ratcliff JJ, Miller MA. Shedding new light on the “safe” club
drug: methylenedioxymethamphetamine (ecstasy)-related fatalities. Acad Emerg Med.
2004;11(2):208–210
14) Frishman WH, Del Vecchio A, Sanal S, Ismail A. Cardiovascular manifestations of
substance abuse: part 2: alcohol, amphetamines, heroin, cannabis, and caffeine. Heart Dis.
2003;5(4):253–271
15) Wernicke JF, Faries D, Girod D, et al. Cardiovascular effects of atomoxetine in children,
adolescents, and adults. Drug Saf. 2003;26(10):729–740
16) Moir DC, Cornwell WB, Dingwall-Fordyce I, et al. Cardiotoxicity of amitriptyline. Lancet.
1972;2(7777):561–564
602
CCIP.indb 602 3/13/18 4:19 PM

CHAPTER 37
Cardiac Screening
for Athletic
Participation
Bryan Cannon, MD, FACC, FHRS
Introduction
Sudden death in a young individual is a tragic occurrence that can have far-
reaching effects on many people. When the individual affected is a healthy athlete,
communities question the mechanisms behind the death and ask what they could
have done to prevent it. As we discuss cardiac death in child athletes, it must
be said that most studies available on this topic have included both adults and
children, so much of the information we have relates not only to pediatric patients,
but also to adult athletes, as well.
Sudden cardiac death accounts for around 250 to 350 annual deaths among all
populations in the United States, with a rate of around 1 to 8 per 100,000 patient-
years.1 Sudden death has been reported in around 1 in 200,000 athletes (including
both children and adults)2 but may occur as frequently as 1 per 44,832 athlete
years.3 However, the risk of sudden death is not higher among competitive athletes
as a whole than among nonathletes, and in 1 study was 8 times higher in non-
athletes.4 Sudden cardiac death in child athletes is rare before 13 years of age and
has a large male predominance (over 90%).5 Cardiac causes are the predominant
reason for sudden death in athletes, although asthma, heat stroke, drug abuse,
and commotio cordis (ventricular arrhythmia caused by a blunt, nonpenetrating
blow to the chest) also play a role in sudden death during athletic competition.
To try to decrease the risk of sudden death, various screening measures have been
603
CCIP.indb 603 3/13/18 4:19 PM

suggested to attempt to detect athletes potentially at risk for sudden cardiac

death. Several different modalities have been used for preparticipation screening,
including a complete history, physical examination, electrocardiography (ECG),
and echocardiography. The type of screening performed and when to perform
it are controversial, because no modality is perfect. Some of the advantages and
disadvantages of each of the methods will be discussed in this chapter.
History and Physical Examination

Most athletes who have sudden cardiac death do not have a known history of
cardiac abnormality, but 10% to 60% of patients who experience sudden cardiac
death have had prior symptoms, including fainting during exertion, chest pain
with maximal exertion, fast or irregular heartbeats, a progressive decrease in
stamina, or weight changes. The current American Heart Association (AHA)
recommendation for athletic screening in the United States is a complete history
and physical examination.6 For high school athletes, a full screening, including
compilation of a history and physical examination, should occur every 2 years.
However, the history should be updated on a yearly basis to ensure that no
concerning symptoms have developed. According to the AHA, the history
and physical examination are “the best available and most practical approach
to screening.” The AHA recommends that the examination be performed by
a health care worker (preferably a physician) who has the requisite training,
medical skills, and background to reliably obtain a detailed cardiovascular history,
perform a physical examination, and recognize heart disease.
The AHA has put forth a 14-point checklist that includes specific questions
to be included in the patient history and family history, as well as targeted focus
areas for the physical examination (see Box 37-1). However, the sensitivity and
specificity of screening solely according to history and physical examination
have been called into question. Detection rates have been reported to be as low
as 3% and as high as 60% in different studies. In addition, despite the recom-
mendations of the AHA, many states do not include all 14 of these points in
their preparticipation screening forms. Because of the limitations of the history
and physical examination, other methods to detect cardiac abnormalities have
been proposed.
Electrocardiography
Although it is not universally recommended, many advocates support the use
of ECG for routine athletic participation screening. Routine ECG screening
is controversial, and like the history and physical examination, it has positive
and negative aspects. In Italy, the addition of ECG to screening decreased
the incidence of sudden death in athletes. In a 25-year Italian experience on
systematic preparticipation screening of competitive athletes that included
604
CCIP.indb 604 3/13/18 4:19 PM

Cardiac Screening for Athletic Participation
Box 37-1. The 14-Element American Heart Association

Recommendations for Preparticipation Cardiovascular
Screening of Competitive Athletes of All Ages
Medical History
Personal History
1. Chest pain, discomfort, tightness, or pressure related to exertion
2. Unexplained syncope or near-syncope not believed to be vasovagal or
neurocardiogenic in origin
3. Excessive and unexplained dyspnea, fatigue, or palpitations associated
with exercise
4. Prior recognition of a heart murmur
5. Increased systemic blood pressure
6. Prior restriction from participation in sports
7. Prior testing for the heart, ordered by a physician
Family History
8. Premature death (sudden and unexpected or otherwise) before
50 years of age, attributable to heart disease in ≥1 relative
9. Disability from heart disease in a close relative <50 years of age
10. Hypertrophic or dilated cardiomyopathy, long QT syndrome, other
ion channelopathies, Marfan syndrome, or clinically significant
arrhythmias; specific knowledge of genetic cardiac conditions in
family embers
11. Heart murmur, not believed to be innocenta
12. Femoral pulse to exclude aortic coarctation
13. Physical stigmata of Marfan syndrome
14. Brachial artery blood pressure (sitting position) measurement,
preferably obtained in both arms
a
Auscultation should be performed with the patient in both supine and standing positions (or with the Valsalva
maneuver), specifically to identify murmurs of dynamic left ventricular outflow tract obstruction.
Adapted from Maron BJ, Friedman RA, Kligfield P, et al. Assessment of the 12-lead electrocardiogram as a screening
test for detection of cardiovascular disease in healthy general populations of young people (12-25 years of age): a
scientific statement from the American Heart Association and the American College of Cardiology. J Am Coll
Cardiol. 2014;64(14):1479–1514.
ECGs, the incidence of sudden death was decreased by 89% (from 3.6 per
100,000 person-years to 0.4 per 100,000 person-years over a 25-year period).
In this study, in which 33,375 athletes were screened, 10% had abnormal ECG
findings.7 However, only 0.018% of athletes were ultimately disqualified for
cardiac reasons. In contrast, in studies from Israel and Japan, ECG screening
has not been effective in decreasing the sudden cardiac death rate in athletes.
Critics of the Italian study have pointed out that the ultimate rate of sudden
cardiac death achieved was similar to the sudden death rate in the United States,
where screening was performed with only a history and physical examination.8
In addition, data from a national U.S. registry, including 1,866 sudden cardiac
605
CCIP.indb 605 3/13/18 4:19 PM

deaths, showed that 30% of patients who experienced sudden death would not
likely have been suspected or detected with ECG screening.4

Although ECG has its flaws, it can be useful in athletic screening. The
advantages of ECG are that it is relatively inexpensive and noninvasive. It may
demonstrate abnormalities not detected by any other means. Findings are fre-
quently abnormal in many clinically significant cardiovascular diseases, including
long QT syndrome, hypertrophic cardiomyopathy, and Wolff-Parkinson-White
syndrome, although many causes of athletic sudden death may have completely
normal ECG findings (see Box 37-2 and Box 37-3).
One criticism of ECG screening is the relatively high false-positive rate,
which leads to further, often unnecessary cardiac evaluation and follow-up.
The incidence of what would generally be considered an abnormal ECG
finding is relatively high in athletes, with an incidence of up to 40% in truly
elite athletes.9 For this reason, modified criteria have been developed to try to
Box 37-2. Conditions That Are Likely Detected with ECG

Screening
Hypertrophic cardiomyopathy
Short or long QT syndrome
Brugada syndrome
Pre-excitation Wolff-Parkinson-White syndrome
Clinically significant congenital heart disease
Aortic valve disease
Mitral valve disease
Dilated cardiomyopathy
Myocarditis
Arrhythmogenic right ventricular cardiomyopathy
Box 37-3. Conditions That Are Likely Missed with ECG

Screening
Coronary anomalies
Paroxysmal arrhythmias
Catecholaminergic polymorphic ventricular tachycardia
Marfan syndrome
606
CCIP.indb 606 3/13/18 4:19 PM

Cardiac S
creening for Athletic P
articipation
decrease the false-positive rate of ECG screening while still detecting athletes
at risk for sudden cardiac death. These criteria eliminate certain findings that are
commonly seen in athletes from flagging an ECG finding as “abnormal” (see
Box 37-4).10 There are several sets of ECG criteria that can be used to determine
abnormal findings in athletes, including the European Society of Cardiology11
and the “Seattle Criteria,”12 among others. In 1 study in athletes, the overall
false-positive rate for ECG (6%) was less than that for history (8%) or physical
examination findings (10%).13 The false-negative rate for ECG screening is not
known. In the Italian study of Corrado et al, there were 55 sudden cardiac deaths
in athletes who had been screened with ECG (1 in 606 athletes screened).7
A study in which elite high-school athletes were compared to patients with
hypertrophic cardiomyopathy, one of the most common causes of sudden death
in athletes, showed that although there were criteria to distinguish hypertrophic
cardiomyopathy from normal athletic changes, 16% of patients with hypertro-
phic cardiomyopathy had normal ECG findings.14 In addition, there may be
substantial overlap between normal and abnormal ECG findings. This is partic-
ularly true with the QT interval, which may be above what is considered normal
in athletes and individuals with no cardiac pathologic processes. This overlap
may cause difficulty in distinguishing individuals with long QT syndrome from
normal subjects.
However, despite these limitations, ECG may demonstrate serious cardiovas-
cular abnormalities and conditions that may be missed with other methods of
screening. ECG machines are relatively portable and may be taken to large-scale
screening events to perform testing on a large number of athletes at one time.
ECG is also fairly quick to perform, and ECG images can be transferred
electronically for interpretation or incorporation into a patient’s medical record.
It is important to have a physician who is familiar with interpretation of
ECG findings in athletes be the one to interpret the screening ECG results
to avoid a large number of false-positive and/or false-negative interpretations.
In a study in which 53 cardiologists interpreted 18 ECG results (consisting of
patients with conditions that caused pediatric sudden cardiac death intermixed
Box 37-4. ECG Variants That May Be Normal in an Athlete

Sinus bradycardia
Isolated QRS voltage criteria for left ventricular hypertrophy
Prolonged PR interval (first-degree atrioventricular block)
Premature atrial contractions
ST and T wave changes consistent with early repolarization
Incomplete right bundle branch block (QRS duration <120 ms)
607
CCIP.indb 607 3/13/18 4:19 PM

with normal ECG findings), a mean of 12 of 18 ECG results were correctly

interpreted (67%; range, 34%–98%).15 In contrast, 2 pediatric electrophysiolo-
gists with expertise in ECG interpretation had 100% concordance in correctly
interpreting ECG results. Physicians should follow a standard protocol by using
established criteria and have a follow-up process to ensure that athletes who
have a positive ECG screening result get further evaluation, because a substantial
percentage of patients with “positive” ECG screening results will ultimately be
determined to be normal and have a low risk for sudden death and therefore
allowed to participate in competitive sports.
Echocardiography
Because some abnormalities that cause sudden death can be missed at history
compilation, physical examination, and ECG screening, echocardiography has
been considered for inclusion in athletic screening. Echocardiography, which
allows direct visualization of structures in the heart by using ultrasonography,
may be useful in detecting hypertrophic cardiomyopathy and coronary artery
abnormalities, 2 of the most common causes of sudden cardiac death in athletes.
However, the rapid screening echocardiography performed during athletic
screening typically does not include a full evaluation of the coronary arteries,
which in some studies is the second leading cause of sudden death among
athletes.4 The coronary artery abnormalities seen in athletes typically do not
relate to atherosclerotic changes seen in adults but are rather related to anatomic
abnormalities of the coronary arteries (eg, the left coronary artery coming off
the right, rather than the left, sinus of Valsalva in the aorta). Interrogation of the
coronary arteries is time consuming, and it can be challenging to obtain images
that ensure that the origin of each coronary artery is from the correct sinus of
Valsalva. In addition, interpretation of the echocardiographic results in athletes
may present a diagnostic dilemma. In athletes, the ventricular septal thickness
is 14% thicker than in nonathletes. In a study of professional basketball players,
14% of the professional athletes screened had a ventricular septum thicker than
14 mm, and 10% had a septal or post wall thickness ratio of >1.3, both of which
are diagnostic criteria for hypertrophic cardiomyopathy.16 In the clinical setting,
it can be difficult to determine if thickening of the heart is due to athletic
training or to abnormal myocardium, as in hypertrophic cardiomyopathy. In
addition, abnormal myocardial thickening may be localized to a single segment
in one-third of patients with hypertrophic cardiomyopathy and thus may be
missed if a complete interrogation of the ventricular septum is not performed.17
It is important that the person performing the echocardiography be well versed
in pediatric echocardiography by using proper equipment and technique and
that abnormal findings be corroborated with formal echocardiographic findings
interpreted by a pediatric cardiologist.
608
CCIP.indb 608 3/13/18 4:19 PM

Other Factors to Consider in Screening

Other factors may play a role in screening, including cost and access to
medical care to evaluate positive screening results. In addition, it is important
to recognize the potential psychological impact of a false-positive screening
result and the potential for unnecessarily restricting an athlete who may be
at a very low risk for sudden death. The importance of each school having
an emergency response plan for all students that includes rapid initiation of
cardiopulmonary resuscitation, activation of an emergency response plan that
has been orchestrated with the local emergency response team, and access to
automated external defibrillators, cannot be overemphasized. These measures are
just as important as (if not more) preparticipation screening. In addition, it is
important to ensure that athletes get proper follow-up and care if they do have
a positive initial screening result. In a study in which a state-sponsored athletic
screening program was examined in Texas, 69 of 201 pediatric patients (34%)
with abnormal screening results did not seek follow-up, despite many of these
patients having a direct discussion with a pediatric cardiologist regarding the
importance of follow-up. Most were ultimately cleared for participation by a
different physician, with the family withholding the positive screening informa-
tion from that physician because they did not want to interfere with their child’s
sports participation.18
Key Points
•• Controversy exists over which method of athletic screening—history and
physical examination, ECG, or echocardiography—is optimal.
•• The AHA recommends athletic screening with a history and physical exam-
ination based on a 14-point guideline checklist.
•• ECG screening may demonstrate cardiac conditions not detected with other
means but has a relatively high incidence of false-positive results that require
further testing.
•• Echocardiography has also been used but must be performed and results
interpreted by skilled personnel, and it may be time consuming to obtain
adequate imaging data.
•• Ultimately, there is no perfect solution for screening, and each individual
practitioner and community must decide what method of screening is
the best use of time and resources. Having an emergency action plan,
as well as automated external defibrillators available, is as important as
preparticipation screening.
609
CCIP.indb 609 3/13/18 4:19 PM


•• Screening Young Athletes for Heart Disease (American Heart Association).
news.heart.org/screening-young-athletes-for-heart-disease
References
1) Driscoll DJ, Edwards WD. Sudden unexpected death in children and adolescents. J Am Coll
Cardiol. 1985;5(6 Suppl):118B–121B
2) Maron BJ, Shirani J, Poliac LC, Mathenge R, Roberts WC, Mueller FO. Sudden death
in young competitive athletes. Clinical, demographic, and pathological profiles. JAMA.
1996;276(3):199–204
3) Harmon KG, Asif IM, Maleszewski JJ, et al. Incidence and etiology of sudden cardiac arrest and
death in high school athletes in the United States. Mayo Clin Proc. 2016;91(11):1493–1502
4) Maron BJ, Haas TS, Duncanson ER, Garberich RF, Baker AM, Mackey-Bojack S. Comparison
of the frequency of sudden cardiovascular deaths in young competitive athletes versus nonath-
letes: should we really screen only athletes? Am J Cardiol. 2016;117(8):1339–1341
5) Rowland T. Sudden unexpected death in young athletes: reconsidering “hypertrophic cardiomy-
opathy”. Pediatrics. 2009;123(4):1217–1222
6) Maron BJ, Thompson PD, Ackerman MJ, et al; American Heart Association Council on
Nutrition, Physical Activity, and Metabolism. Recommendations and considerations related to
preparticipation screening for cardiovascular abnormalities in competitive athletes: 2007 update:
a scientific statement from the American Heart Association Council on Nutrition, Physical
Activity, and Metabolism: endorsed by the American College of Cardiology Foundation.
Circulation. 2007;115(12):1643–455
7) Corrado D, Basso C, Pavei A, Michieli P, Schiavon M, Thiene G. Trends in sudden cardiovas-
cular death in young competitive athletes after implementation of a preparticipation screening
program. JAMA. 2006;296(13):1593–1601
8) Maron BJ, Haas TS, Doerer JJ, Thompson PD, Hodges JS. Comparison of U.S. and Italian
experiences with sudden cardiac deaths in young competitive athletes and implications for
preparticipation screening strategies. Am J Cardiol. 2009;104(2):276–280
9) Pelliccia A, Maron BJ, Culasso F, et al. Clinical significance of abnormal electrocardiographic
patterns in trained athletes. Circulation. 2000;102(3):278–284
10) Riding NR, Sheikh N, Adamuz C, et al. Comparison of three current sets of electrocardiograph-
ic interpretation criteria for use in screening athletes. Heart. 2015;101(5):384–390
11) Corrado D, Pelliccia A, Heidbuchel H, et al; Section of Sports Cardiology, European
Association of Cardiovascular Prevention and Rehabilitation. Recommendations for interpreta-
tion of 12-lead electrocardiogram in the athlete. Eur Heart J. 2010;31(2):243–259
12) Drezner JA, Ackerman MJ, Anderson J, et al. Electrocardiographic interpretation in athletes: the
‘Seattle criteria’. Br J Sports Med. 2013;47(3):122–124
13) Harmon KG, Zigman M, Drezner JA. The effectiveness of screening history, physical exam, and
ECG to detect potentially lethal cardiac disorders in athletes: a systematic review/meta-analysis.
J Electrocardiol. 2015;48(3):329–338
14) Thompson AJ, Cannon BC, Wackel PL, et al. Electrocardiographic abnormalities in elite
high school athletes: comparison to adolescent hypertrophic cardiomyopathy. Br J Sports Med.
2016;50(2):105–110
15) Hill AC, Miyake CY, Grady S, Dubin AM. Accuracy of interpretation of preparticipation
screening electrocardiograms. J Pediatr. 2011;159(5):783–788
610
CCIP.indb 610 3/13/18 4:19 PM

16) Roeske WR, O’Rourke RA, Klein A, Leopold G, Karliner JS. Noninvasive evaluation of
ventricular hypertrophy in professional athletes. Circulation. 1976;53(2):286–291
17) Panza JA, Maron BJ. Relation of electrocardiographic abnormalities to evolving left
ventricular hypertrophy in hypertrophic cardiomyopathy during childhood. Am J Cardiol.
1989;63(17):1258–1265
18) Zeltser I, Cannon B, Silvana L, et al. Lessons learned from preparticipation cardiovascular
screening in a state funded program. Am J Cardiol. 2012;110(6):902–908
611
CCIP.indb 611 3/13/18 4:19 PM

CCIP.indb 612 3/13/18 4:19 PM
CHAPTER 38
Autonomic
Dysfunction
Alison Black, MD, and Joshua D. Sparks, MD
Introduction
The autonomic or “automatic” nervous system controls and influences the
function of the internal organs, including the blood vessels, heart, abdominal
viscera, genitals, lungs, pupils, body temperature, and sweat and salivary glands.
It is comprised of the sympathetic and parasympathetic branches. As seen in
Table 38-1, symptoms of autonomic dysfunction are often nonspecific because
the autonomic nervous system is involved with nearly every organ system. Many
of these symptoms overlap with other diseases.
From a cardiovascular perspective, symptoms of autonomic dysfunction include
orthostatic intolerance, dizziness, fatigue, palpitations, and syncope. These are very
common complaints of older children and adolescents at office visits; though gen-
erally benign, the clinical overlap of these symptoms with rare, but life-threatening
heart problems, such as arrhythmias, creates concern for patients and their families.
Additionally, the lack of published literature and the complex nature of these
disorders make the development of diagnostic criteria difficult.
The goal of this chapter is to provide a basic overview of the autonomic nervous
system and disorders of autonomic dysfunction that affect the cardiovascular sys-
tem in children, with a focus on assessment, diagnosis, confounding and comorbid
conditions, and therapy.
613
CCIP.indb 613 3/13/18 4:19 PM

Table 38-1. Noncardiovascular Symptoms of

Dysautonomia
Organ System Symptoms
Neurological system Fatigue

Dizziness
Cognitive impairment
Vertigo
Migraines
Syncope
Ear, nose, and throat Dry mouth

Dry eyes
Sluggish pupils
Vision changes
Gastrointestinal system Gallbladder sludging

Abdominal pain
Colonic dysmotility
Constipation
Diarrhea
Genitourinary system Urinary retention

Nocturia
Frequent urination
The Autonomic Nervous System and the

Cardiovascular System
The autonomic nervous system, which is similar to the sensory nervous system,
arises from migratory neural crest cells.1 Transcription factors, including Mash1
and Phox2a, promote maturation and neurotransmitter synthesis. The sympa-
thetic and parasympathetic branches of the autonomic nervous system have
distinct physiological profiles. The primary purpose of the sympathetic nervous
system is to sustain delivery of energy substrate for a “fight or flight” response.
It acts via vertebral ganglia, which stimulate postganglionic norepinephrine
receptors within tissues to augment blood pressure via vascular constriction and
increase cardiac contractility and heart rate.2 This response is further augmented
by sympathetic nervous system stimulation of the adrenal gland to release
catecholamines secreted by the adrenal medulla. In contrast, the parasympathetic
response, primarily via the vagal system, acts to release acetylcholine to nicotinic
and muscarinic receptors directly on peripheral tissues. This results in a “rest
and digest” response, with decreased heart rate and blood pressure. The overall
effector profile of each branch of the autonomic nervous system acts in concert
to maintain cardiovascular homeostasis by modulating systemic resistance
614
CCIP.indb 614 3/13/18 4:19 PM

Autonomic Dysfunction
and cardiac output to help maintain end-organ perfusion over a wide range of
vascular volume, systemic blood pressure, and metabolic states.2–4

Cardiac preload can vary with orthostatic position because upon standing,
venous blood pools in the peripheral blood vessels and splanchnic system,
resulting in decreased venous return to the heart.4–6 Blood pressure across these
changes in preload is controlled by mechanisms that include arterial barorecep-
tors (in the aorta and the carotid artery) and cardiac mechanoreceptors. These
receptors regulate autonomic control by manipulating vascular tone and cardiac
output (heart rate and contractility).7
Particularly in the setting of clinically significant dehydration, some individ-
uals can develop a cardioinhibitory phenomenon known as the Bezold-Jarisch
reflex. Upon standing, an underfilled ventricle responds with an increase in
heart rate and contractility. This hyperdynamic functioning activates the vol-
ume-sensitive C-fibers (cardiac mechanoreceptors), which inhibit sympathetic
tone, causing a paradoxical decrease in heart rate, vasodilation, and subsequent
hypotension.4,5 This is one mechanism that leads to symptomatic intolerance
of orthostasis.
Epidemiology and Clinical Entities

Disruption of developmental pathways of autonomic development leads to
a familial or genetic abnormality in both sensory and autonomic systems.1,8,9
Distinct dysautonomia syndromes are rare but can have a clinically significant
effect on cardiovascular functioning; a brief description of these can be found in
Table 38-2. Further review of these very uncommon entities is beyond the scope
of this text.
Children with autonomic dysfunction present with a variety of symptoms,
but the most common phenotype, orthostatic intolerance and neurocardiogenic
syncope, will be the primary focus of this chapter.
Orthostatic Intolerance and Postural Orthostatic

Tachycardia Syndrome
Orthostatic (ortho- meaning “upright,” and -static meaning “movement”)
refers to the change in a person’s position from supine to standing. Orthostatic
intolerance (OI) refers to the development of symptoms that include dizziness,
lightheadedness, palpitations, sweating, vision changes, headache, and fainting
related to decreased systemic blood pressure upon standing.2,10,11 Under normal
conditions, standing will lead to some degree of reflexive increase in heart rate;
however, reduced preload or inappropriate vasomotor compensation lead to
hypotension.5,6 This can be measured clinically by testing the heart rate and
blood pressure in a supine, seated, and standing position. Orthostatic hypoten-
sion is a common sign associated with OI and is defined as a decrease in systolic
615
CCIP.indb 615 3/13/18 4:19 PM

Table 38-2. Familial Dysautonomia in Children

Diagnosis Gene Clinical Features and Diagnosis Prognosis
Hereditary IKBKAP • Ashkenazi Jew • 40% of surviv-

sensory • Decreased pain and temperature ing patients
radicular perception (sparing the neck, soles are >20 y of
neuropathy of the feet, and genitals) age
Riley-Day • Hypotonia and absent deep tendon • Most
syndrome reflexes succumb to
(HSAN III) • Decreased lacrimation pulmonary
• Optic nerve atrophy illness
• Esophageal dysmotility • Unexplained
• Breath-holding spells deaths may
• Absence of axon flare after intra- be caused by
dermal histamine unopposed
• Sural nerve biopsy vagal stimulus
HSAN IV: NTRK1 • May be confused with HSAN III in Variable

congenital neonates
insensitivity • Profound sensory abnormalities
to pain with • Severe insensitivity to pain, leading
anhidrosis to self-mutilation, autoamputation,
and corneal scarring
• Anhidrosis with thermoregulation
issues
• Clinical diagnosis based on both
sensory and autonomic features
• Absence of axon flare after intra-
dermal histamine
HSAN II: No • Profound decrease in pain and Variable

congenital gene temperature perception
sensory testing • Profound self-mutilation
neuropathy available • Excessive sweating
• Skin blotching
• Acrocyanosis
• Feeding problems
• Developmental delay, contractures,
and apnea may be present
• Sural nerve biopsy
Congenital PHOX2B • Presents as cyanosis during sleep in Variable

central newborns due to hypoventilation
hypoven- with hypercarbia and/or hypoxemia
tilation • Hirschsprung disease (20% of
syndrome cases)
• Neural crest tumors
• Abnormal facies
• Neurocognitive dysfunction
616
CCIP.indb 616 3/13/18 4:19 PM

Table 38-2. Familial Dysautonomia in Children,

continued
Diagnosis Gene Clinical Features and Diagnosis Prognosis
Mitochon- Variable presentation, including: Variable

drial diseases • Cardiac arrhythmia
• Hypotonia
• Ophthalmoplegia
• Seizures
• Extrapyramidal signs
• Ataxia
• Lactic acidosis
• Endocrinopathies
• Impaired respiratory function
Biochemical assays for mitochondrial
enzyme activity
HSAN, hereditary sensory and autonomic neuropathy.
(>20 mm Hg) or diastolic (>10 mm Hg) blood pressure within 3 minutes of

standing.12 Neurological symptoms occur when the resulting hypotension is
sustained or significant enough to cause a decrease in cerebral blood flow. Often,
symptoms can be treated with education, adequate hydration, and salt intake,
but occasionally, patients may need medication. Also, OI can occur because of
autonomic deconditioning in the setting of bed rest or intercurrent or recent
illness. These cases are treated similarly but may respond to time or to low-
impact cardiovascular exercise and rehabilitation.
Postural orthostatic tachycardia syndrome (POTS) is defined as sustained
symptoms of OI but, in contrast, is defined by a heart rate increase more than
30 beats per minute while maintaining normal blood pressure.2 For young,
healthy individuals aged 8 to 19 years, it has been recommended that a higher
heart rate increment of 40 beats per minute be used. It is one of the most
common causes of orthostatic intolerance, currently affecting more than 500,000
people in the United States alone.2 Progression to syncope is rare. Symptoms are
thought to be caused by abnormalities in autoregulatory function in maintaining
adequate cerebral blood flow. This has been shown via Doppler studies in
individuals with POTS.6
There are 2 predominant subtypes of POTS, which are differentiated on the
basis of sympathetic response. Neuropathic POTS seems to be caused by an
autonomic neuropathy of the peripheral vasculature, leading to blood pooling
in response to gravity.2,11,13 This subtype has a female predominance and may be
correlated with a postviral syndrome.13 In hyperadrenergic POTS, individuals
have an increase in sympathetic activity, with increased norepinephrine levels.
These individuals tend to have symptoms not only with orthostasis but also
617
CCIP.indb 617 3/13/18 4:19 PM

during times of exaggerated stress, such as emotional stimuli or physical activ-

ity.11 This type will often have a strong family history.13
Syncope is the spontaneous, recoverable, transient loss of consciousness asso-
ciated with loss of postural tone. It results from a sudden decrease or cessation
in cerebral blood flow, which causes a loss or near-loss of consciousness.5
Syncopal episodes caused by autonomic dysfunction typically result in sponta-
neous recovery and tend to last less than a minute, with a spontaneous return
to baseline activity.6
A full review of syncope is beyond the scope of this chapter; however, auto-
nomic dysfunction can have a substantial effect on a patient’s risk and likelihood
of a syncopal event. Autonomic mechanisms outlined previously in OI can
contribute to autonomic dysregulation and syncope or near-syncope symptoms.
As mentioned previously, one clinically significant mechanism that leads to
syncope is the Bezold-Jarisch reflex. Affected individuals are initially tachycardic
in the setting of high sympathetic tone, then develop sinus arrhythmia, followed
by reflexive bradycardia. As many as 6% of patients may experience asystole
(sometimes lasting up to 40 seconds) prior to return of normal cardiac rhythm
after the event.5
Events tend to peak at the end of adolescence and are more commonly seen
in teenage girls.5 Syncope in children is typically benign, with neurocardiogenic
syncope accounting for well over one-half of pediatric patients (75%–80%);
however, syncopal episodes can present similarly to an episode of spontaneously
aborted arrhythmia and must be further evaluated to rule out the risk of
sudden cardiac death.5,14 This includes a detailed personal history of the event,
including prodromal symptoms, activity surrounding the event, and witnesses;
a detailed family history; a focused physical examination; electrocardiography;
and echocardiography, as indicated. Although these episodes are often medically
benign, the psychosocial morbidity to an adolescent and his or her family can
be profound.
Clinical Findings and Diagnostic Approach

The symptoms of autonomic dysfunction can have substantial overlap with
specific conditions that can be life-threatening and require immediate or urgent
attention. Therefore, a thorough history and physical examination are imperative
to ensure that these conditions have been ruled out.
History
The most important diagnostic tool in patients with autonomic dysfunction is a
careful and thorough history. This should focus on circumstances and activities
leading up to and occurring during symptoms—specifically, the chronology of
618
CCIP.indb 618 3/13/18 4:19 PM

events in detail. It is important to consider the activity of the patient and any
prodromal symptoms. An event that occurs midexercise is concerning and man-
dates further evaluation. The patient should also be asked about any associated
symptoms, including (a) palpitations, chest pain, shortness of breath, headache,
nausea, diaphoresis, visual or auditory changes, and syncope, (b) the length of
time that he or she had loss of consciousness, and (c) whether any resuscitation
was needed.
A thorough family history can be very informative when evaluating the
patient for the risk of a life-threatening familial condition, such as congenital
heart disease (CHD), arrhythmia syndromes such as Wolff-Parkinson-White
syndrome, cardiomyopathy, and channelopathies. A detailed review of any
known diagnoses or unexplained death, including unusual accidents or
drownings, can assist in further evaluation. As described previously, some forms
of autonomic dysfunction such as POTS can be familial, as can several comorbid
conditions described later in this chapter. Social history, particularly in adoles-
cents, is imperative, including fluid and caffeine consumption, sporting activities,
sexual history, and drug and alcohol use. Past medical history and family history
should include questions about any cardiac history, including CHD, previous
cardiac surgery, arrhythmias, metabolic syndromes, and seizure.
Examination
A thorough physical examination should be completed in any patient who
presents with autonomic symptoms. Initial evaluation should start with vital
signs, including assessment of orthostatic hypotension with a blood pressure
and heart rate in the lying, sitting, and standing positions at 1 and 5 minutes,
particularly in patients who state that their symptoms are exacerbated by
standing. This maneuver is easy and cost-effective and can be done during
dynamic heart rate evaluation to rule out POTS.3 Cardiac examination should
include assessment for murmur, abnormal or irregular rhythm, or abnormal point
of maximal impulse.14 Neurological examination should include evaluation for
any focal deficits, including cranial nerve evaluation, deep tendon reflexes, gait
evaluation, cerebellar function, proprioception, Romberg sign, and assessment
for joint hypermobility.15
Testing
The approach to a patient with autonomic dysfunction and, specifically, patients
with cardiac symptoms described previously in the “Examination” section should
be to rule out any primary cardiac condition as a cause for their symptoms.
Electrocardiography (ECG) can be helpful when assessing patients for the
suggestion of cardiac rhythm syndromes or channelopathies, cardiomyopathy,
or CHD, particularly if syncope is part of a patient’s clinical presentation.
The QRS complex should be evaluated for any pre-excitation suggestive of
619
CCIP.indb 619 3/13/18 4:19 PM

Wolff-Parkinson-White syndrome, prolongation of the corrected QT interval,

repolarization abnormalities, or any signs of ventricular hypertrophy that should
be further evaluated.15 A Holter monitor and/or portable event monitor may
be helpful when correlating symptoms with ECG findings. Screening echocar-
diography has low yield in this patient population with unremarkable personal
and family history and normal ECG findings. In most cases, this test should be
reserved for patients who have any “red flag” symptoms or examination findings
(exertional symptoms of chest pain, dyspnea, or syncope), concerning cardiac
family history, or abnormal ECG findings.5,16 Appropriate use criteria have been
published regarding the use of echocardiography and can be helpful for patients
with chest pain, palpitations, or syncope.17
Historically, tilt testing has been used to assist in the diagnosis of cardioinhib-
itory syncope and orthostatic intolerance; however, the clinical utility of this test
is poor and relates to the lack of standardized protocols for pediatric patients.
Thus, the reported false-negative rate is as high as 30%.5,15 During evaluation of
patients for POTS, plasma catecholamines during supine and standing positions
can be considered for those who are challenging the diagnosis.2

Further evaluation is warranted on a case-by-case basis and should be con-
sidered to investigate comorbidities or assess for potential alternative diagnoses,
including catecholamine-secreting tumors, endocrine disorders, drug abuse,
neurological conditions, and gastrointestinal disorders.2,5,11
Treatment
Nonpharmacological Management
For patients with IO, treatment should first be focused on lifestyle change.
Sodium and water intake should be increased to aid in intravascular volume
expansion to reduce the effect of dehydration. Patients may be advised to add salt
to their food or snack on salty foods like pretzels. Salt tablets can be considered
if the patient is unable to achieve adequate salt intake via nutrition; however, be
advised that these can cause nausea. Caffeine should be avoided. Recommended
daily water intake should be at least 1.5 to 2 L of water a day. Water intake
should be increased if individuals are out in the heat or are physically active.
Particularly, the patient should hydrate until the urine appears light yellow to
clear.2,11 Patients may also perform maneuvers such as crossing their legs and
bringing their knees to their chest prior to standing or bending forward, all to
prevent lower-extremity venous pooling with orthostatic changes.2,6,18,19 Support
garments are another option to prevent pooling in the lower limbs; abdominal
binders may be used to increase abdominal pressure.2,20 Exercise training is
essential for all patients with POTS.
620
CCIP.indb 620 3/13/18 4:19 PM

Medications
For patients for whom lifestyle modification is inadequate or unsuccessful,
medications can be considered. When initiating pharmacological management,
it is imperative to set up realistic expectations because many patients with severe
autonomic dysfunction do not see complete resolution of symptoms. Table 38-3
lists the commonly used medications for treatment of orthostatic intolerance.
Fludrocortisone is a mineralocorticoid that works by increasing blood
volume. It causes sodium and water retention at the expense of potassium
excretion.2,5 In theory, the increased blood volume should reduce venous
pooling, but this has not been shown to work in syncopal patients.5 When
using this in patients with POTS, there is a risk for worsening migraine and
headache symptoms.2
Midodrine, an a-receptor agonist, can be taken 3 times a day (4 hours apart)
and increases peripheral vascular resistance. It tends to be a more effective medi-
cation for patients with reflex syncope.5 It may be considered in any patient with
Table 38-3. Commonly Used Drugs as Treatment for

Orthostatic Intolerance
Drug Dosage Adverse Effects Contraindications
Fludrocortisone 0.1 mg daily Hypokalemia Systemic fungal

Titrate by additional Headache infections
0.1 mg/day Supine Hypersensitivity to
weekly hypertension drug class
Maximum dose, 1 Heart failure
mg/day Edema
β-blockers Propranolol 10 mg Hypotension Reactive airway

orally twice daily disease
Titrate to maximum Diabetes
of 20 mg 4 times
daily
Midodrine 2.5 mg 3 times daily Supine Acute renal failure

Titrate by additional hypertension Severe heart disease
2.5 mg/dose Piloerection Urinary retention
weekly Pruritus Thyrotoxicosis
Maximum dose, 10 Paresthesia Pheochromocytoma
mg/day
Pyridostigmine 30 mg 2–3 times Cholinergic effects Hypersensitivity to

daily drug or bromides
Titrate to 60 mg 3 Mechanical intes-
times daily tinal or urinary
obstruction
From Lanier JB, Mote MB, Clay EC. Evaluation and management of orthostatic hypotension. Am Fam Physician.
2011;84(5):527–536.
621
CCIP.indb 621 3/13/18 4:19 PM

OI, but it may worsen visceral symptoms, including gastrointestinal dysmotility

and urinary retention, and could potentiate headaches.11 Blood pressure must be
monitored during initiation of the medication.5
β-blockers are a good option for normotensive patients with POTS who
have comorbid migraines or anxiety.2 They tend to be poor options in patients
with reflex syncope because they can exacerbate symptoms as a result of lowering
blood pressure. They must also be avoided in patients with reactive airway disease
or diabetes.5
Pyridostigmine works as a cholinesterase inhibitor and increases blood
pressure during orthostasis. This can increase GI motility, resulting in cramping
and diarrhea in some patients.21
Additional therapies used in the treatment of these patients have included
antidepressants such as selective serotonin reuptake inhibitors, octreotide,
methylphenidate, and desmopressin.21
Prognosis and Comorbidities

Overall, patients with benign OI, including those with neurocardiogenic
syncope, have an excellent prognosis. The psychological burden of this disease
can be high, particularly in susceptible individuals.
Autonomic dysfunction can be associated with many comorbid conditions.
It has been reported that as many as 30% of female teenagers who experience
autonomic dysfunction have additional symptoms of headache, abdominal
pain, and morning fatigue on a weekly basis.22 Migraines are common.11,23,24
Gastrointestinal dysfunction, dysmotility, and functional abdominal pain
syndrome are commonly reported, with as many as 39% of patients with
POTS experiencing some degree of nausea.24
It has been noted that as many as 48% of patients with POTS experience
chronic fatigue syndrome, specifically those with disinhibited sympathetic activa-
tion. Additionally, many others report chronic sleep issues and myofascial pain.11
It is not uncommon to see increased joint hypermobility in patients with
autonomic dysfunction. After a detailed family history and physical examination,
a genetics workup may need to be considered.11 A link between Ehlers-Danlos
syndrome and POTS has been reported.25 It has been postulated, though not yet
proven, that abnormal connective tissue results in abnormal venous return and
reflexive tachycardia. Regardless, a thorough examination for connective tissue
disorders should be performed for any patient with autonomic dysfunction.
622
CCIP.indb 622 3/13/18 4:19 PM

Key Points
•• The role of the autonomic nervous system in the regulation of heart rate,
vascular tone, and blood pressure is critical for upright positioning to be
attained while maintaining normal cerebral perfusion pressure.
•• Dysfunction of the autonomic nervous system, regardless of cause, leads to a
variety of symptoms that will bring patients to seek care; the most common
diagnosis is OI.
•• A thorough history and physical examination are imperative to rule out rare
but serious heart disorders that can have similar clinical profiles to OI.
•• Overall, autonomic dysfunction is a benign condition, but for patients
with persistent and pervasive symptoms, the effect on quality of life can be
profound; they require much time, understanding, and education.

•• Dysautonomia International. www.dysautonomiainternational.org
References
1) Axelrod FB, Chelimsky GG, Weese-Mayer DE. Pediatric autonomic disorders. Pediatrics.
2006;118(1):309–321
2) Stewart JM. Common syndromes of orthostatic intolerance. Pediatrics. 2013;131(5):968–980
3) Brignole M, Alboni P, Benditt D, et al; Task Force on Syncope, European Society of
Cardiology. Guidelines on management (diagnosis and treatment) of syncope. Eur Heart J.
2001;22(15):1256–1306
4) Allen HD, Shaddy RE, Penny DJ, Feltes TF, Cetta F. Moss & Adams’ Heart Disease in Infants,
Children, and Adolescents, Including the Fetus and Young Adult. 9th ed. Philadelphia, PA: Wolters
Kluwer; 2016
5) Cannon B, Wackel P. Syncope. Pediatr Rev. 2016;37(4):159–167
6) Wieling W, Ganzeboom KS, Saul JP. Reflex syncope in children and adolescents. Heart. 2004;
90(9):1094–1100
7) Heesch CM. Reflexes that control cardiovascular function. 1999;22(1):234–244
8) Edlund T, Jessell TM. Progression from extrinsic to intrinsic signaling in cell fate specification:
a view from the nervous system. Cell. 1999;96(2):211–224
9) Thoenen H, Barde YA. Physiology of nerve growth factor. Physiol Rev. 1980;60(4):1284–1335
10) Okamoto LE, Raj SR, Peltier A, et al. Neurohumoral and haemodynamic profile in postural
tachycardia and chronic fatigue syndromes. Clin Sci (Lond). 2012;122(4):183–192
11) Benarroch EE. Postural tachycardia syndrome: a heterogeneous and multifactorial disorder.
Mayo Clin Proc. 2012;87(12):1214–1225
12) Axelrod FB. Hereditary sensory and autonomic neuropathies. Familial dysautonomia and other
HSANs. Clin Auton Res. 2002;12:12–14
13) Grubb BP. Neurocardiogenic syncope and related disorders of orthostatic intolerance.
Circulation. 2005;111(22):2997–3006
14) Taylor DH, Sittnikow KL. The diagnosis of canine cardiac disease. J Small Anim Pract.
1968;9(12):589–595
623
CCIP.indb 623 3/13/18 4:19 PM

15) Lewis DA, Dhala A. Syncope in the pediatric patient. The cardiologist’s perspective. Pediatr Clin
North Am. 1999;46(2):205–219
16) Paris Y, Toro-Salazar OH, Gauthier NS, et al; New England Congenital Cardiology Association
(NECCA). Regional implementation of a pediatric cardiology syncope algorithm using
standardized clinical assessment and management plans (SCAMPS) methodology. J Am Heart
Assoc. 2016;5(2):1–13
17) Sachdeva R, Allen J, Benavidez OJ, et al. Pediatric appropriate use criteria implementation
project: a multicenter outpatient echocardiography quality initiative. J Am Coll Cardiol.
2015;66(10):1132–1140
18) Aviado DM, Guevara Aviado D. The Bezold-Jarisch reflex. A historical perspective of cardiopul-
monary reflexes. Ann N Y Acad Sci. 2001;940:48–58
19) Sharpey-Schafer EP. Syncope. Br Med J. 1956;1(4965):506–509
20) Hainsworth R. Syncope: what is the trigger? Heart. 2003;89(2):123–124
21) Jarjour IT. Postural tachycardia syndrome in children and adolescents. Semin Pediatr Neurol.
2013;20(1):18–26
22) Ghandour RM, Overpeck MD, Huang ZJ, Kogan MD, Scheidt PC. Headache, stomachache,
backache, and morning fatigue among adolescent girls in the United States: associations
with behavioral, sociodemographic, and environmental factors. Arch Pediatr Adolesc Med.
2004;158(8):797–803
23) Mack KJ, Johnson JN, Rowe PC. Orthostatic intolerance and the headache patient. Semin
Pediatr Neurol. 2010;17(2):109–116
24) Thieben MJ, Sandroni P, Sletten DM, et al. Postural orthostatic tachycardia syndrome: the Mayo
clinic experience. Mayo Clin Proc. 2007;82(3):308–313
25) Grigoriou E, Boris JR, Dormans JP. Postural orthostatic tachycardia syndrome (POTS):
association with Ehlers-Danlos syndrome and orthopaedic considerations. Clin Orthop Relat Res.
2015;473(2):722–728
624
CCIP.indb 624 3/13/18 4:19 PM

PART 8
General Issues
in Primary
Cardiac Care
39. Neurodevelopmental and Psychosocial O utcomes
in Children With Congenital Heart Disease........................ 627
40. Lifestyle Counseling............................................................. 643
41. Cardiac Pharmacology.......................................................... 655
42. Transition and Transfer From P

ediatric to
Adult-Centered Cardiac Care.............................................. 685
625
CCIP.indb 625 3/13/18 4:19 PM

O
CCIP.indb 626 3/13/18 4:19 PM

CHAPTER 39
Neurodevelopmental
and Psychosocial
Outcomes in Children
With Congenital
Heart Disease
Kiona Y. Allen, MD, Melissa Smith-Parrish, MD,
Kathleen A. Mussatto, PhD, RN, and
Bradley S. Marino, MD, MPP, MSCE, FAAP
Introduction
As medical and surgical treatments for children with congenital heart disease
(CHD) have advanced over the past several decades, survival has improved
significantly. Most children with CHD now survive into young adulthood.1 As of
2011, there were more adults living with CHD than children.2 As the population
of survivors has increased, a profile of specific developmental deficits has emerged,3
characterized by
•• Mild cognitive impairment and reduced academic achievement
•• Impairments in core communication skills and social interaction
•• Neuropsychological issues in executive functioning, visual construction and
perception, and working memory
•• Behavioral difficulties—inattention and increased impulsivity
•• Delayed acquisition of fine and gross motor skills
627
CCIP.indb 627 3/13/18 4:19 PM

Deficits in any of these areas can markedly affect the functional outcome and
health-related quality of life (QOL) of this population. They may also complicate
the transition to independent adulthood.
Children with CHD are a diverse group, with varied experiences that range
from a short hospital stay after a single infant surgery to prolonged hospital-
izations and multiple palliative surgeries throughout childhood. Additionally,
children with CHD may have underlying genetic conditions associated with
developmental deficits. While the incidence and severity of developmental
deficits increases with CHD complexity, children with even a single procedure
in the neonatal period may require rehabilitative services in childhood.3 Much
of the framework for the developmental challenges faced by such children has
been gleaned from nearly 20 years of follow-up of the Boston Circulatory Arrest
Study (BCAS) cohort.4 What is clear is that even children with a single, short
exposure to cardiopulmonary bypass are at risk for developmental deficits. The
most recent follow-up of these children in both elementary and high school was
notable for increased use of academic and/or behavioral services when compared
to the general population (approximately 65% by adolescence), with 15% to 30%
of the cohort performing at a below-average level in academic achievement and
on tests of memory, executive functioning, visual-spatial skills, attention, and/or
social cognition despite relatively normal IQ test results.5,6
Historically, children with CHD have not always been recognized as being
at high risk for developmental deficits by the general pediatric community; this
oversight can result in delayed implementation of services that might improve
functional outcome. The American Heart Association currently recognizes 3 cat-
egories of pediatric patients with CHD who are at high risk for developmental
deficits (Box 39-1) and who should receive early evaluation and treatment.3
Increased identification of neurodevelopmental and psychosocial problems and
focused intervention coordinated by the medical home is the key to increasing
the number of individuals not just living with CHD but experiencing success in
all phases of life, even into adulthood.
Neurodevelopmental Profile
The ability to quantify the outcomes in these patients is extrapolated from
multiple small studies of children with CHD (Table 39-1). Survivors of heart
transplantation, mechanical circulatory support, and cardiopulmonary resusci-
tation have also been shown to be at risk for neurodevelopmental disabilities,
particularly those with underlying CHD.3,7,8 While it is now known that devel-
opmental deficits among children with CHD emerge in infancy, they may not
be identified until children reach school age and must perform more complex
tasks. Mild delays in multiple areas may go unrecognized without formal testing.
Early developmental intervention has been shown to improve outcomes in other
628
CCIP.indb 628 3/13/18 4:19 PM

NEURODEVELOPMENTAL OUTCOMES IN CHILDREN WITH CONGENITAL HEART DISEASE
Box 39-1. Categories of High-Risk Patients Who Require

Developmental Screening and/or Referral
1. Survivors of neonatal or infant open heart surgerya (palliative or
corrective)
2. Children with cyanotic heart disease not requiring infant open heart
surgeryb
3. Other high-risk comorbidities
•• Prematurity (<37 wk)
•• Microcephaly
•• Developmental delay recognized in infancy
•• Underlying genetic abnormality or syndrome
•• History of mechanical circulatory support (VAD or ECMO)
•• History of heart transplantation
•• History of cardiopulmonary resuscitation
•• Prolonged postoperative hospitalization (length of stay >14 days)
•• History of perioperative seizures
•• Abnormalities previously identified at neuroimaging
ECMO, extracorporeal membrane oxygenation; VAD, ventricular assist device.
a
Examples of congenital heart disease that may require infant open heart surgery include double-inlet left ventricle,
double-outlet right ventricle, hypoplastic left-sided heart syndrome, interrupted aortic arch, pulmonary atresia with
intact ventricular septum, tetralogy of Fallot, transposition of the great arteries, tricuspid atresia, total anomalous
pulmonary venous connection.
b
Examples of cyanotic heart disease include (a) tetralogy of Fallot with pulmonary atresia and major aortopulmonary
collaterals and (b) Ebstein anomaly.
high-risk populations.9,10 Clinicians must both identify populations at high risk

for developmental deficits and recognize findings within each developmental
domain that should trigger a more in-depth evaluation in children who would
otherwise be considered lower risk.
Infants, Toddlers, and Young Children (Birth to Age

4 Years)
Cognitive Functioning
Studies of cognitive functioning in infant survivors of congenital heart surgery
typically show only mild cognitive impairment as measured with the Bayley
Scales of Infant Development (BSID-II) Mental Developmental Index (MDI).
Multiple, smaller studies of specific cardiac populations, including separate
groups with transposition of the great arteries, total anomalous pulmonary
venous connection (TAPVC), and single-ventricle physiology11,15,19,20,26–29 have
all demonstrated some reduction in the mean MDI score when compared
to published norms. In the largest study to date, the International Cardiac
Collaborative on Neurodevelopment, investigators recently looked at pooled
data from more than 1,700 survivors of all types of infant cardiac surgery from
629
CCIP.indb 629 3/13/18 4:19 PM

Table 39-1. Summary of Available Literature on

Neurodevelopmental Outcomes in Children with
Congenital Heart Disease
Reference
Cohort No. Type of CHD Ages Evaluated
BCAS 4, 6, TGA Infants, toddlers, school-age

11–13 children, adolescents
SVR 14, 15 Hypoplastic left heart Infants, toddlers

syndrome
Montreal 16–18 All comers Infants, toddlers, school-age

children
Western 19, 20 TGA, TAPVC Toddlers

Canada
Belgium 21 Tetralogy of Fallot School-aged children
Boston 22 Fontan procedure School-aged children
Belfast 23 All comers School-aged children
PCQLI 24 All comers School-aged children,

adolescents
CHOP 25 Single-ventricle physiology School-aged children

BCAS, Boston Circulatory Arrest Study; CHOP, Children’s Hospital of Philadelphia; PCQLI, Pediatric Cardiac Quality
of Life Inventory; SVR, Single Ventricle Reconstruction Trial; TAPVC, total anomalous pulmonary venous connection;
TGA, transposition of the great arteries.
22 institutions at a mean age of 14.5 months.30 While the mean MDI scores
were only slightly decreased for the cohort as a whole, more than 15% scored at
least 2 standard deviations (SDs) below the normative mean, which is consistent
with moderate to severe disability. Interestingly, a more severe underlying heart
defect was not associated with a lower MDI score in this series. Looking ahead
to 3 years of age, children with single-ventricle physiology continued to show
deficits in cognitive functioning as measured by using the problem-solving
domain on the Ages and Stages Questionnaire (ASQ). An abnormal MDI at
14 months was associated with an abnormal ASQ score at 3 years; however,
even children with a normal assessment on the MDI were shown to be at risk
when reassessed at 3 years of age.14
Fine and Gross Motor Skills
Delays in the fine and gross motor domains have been demonstrated in multiple
studies of young children after open-heart surgery and appear to be more
pervasive than cognitive deficits. At 12 months of age, nearly 20% of the BCAS
cohort scored more than 2 SDs below the mean on the BSID-II Psychomotor
Development Index (PDI), which is used to assess motor function in infants.11
630
CCIP.indb 630 3/13/18 4:19 PM

In addition, approximately 30% had detectable abnormalities in tone, coordina-

tion, or focal findings at neurological examination.11 A significant proportion of
these infants also failed to achieve age-appropriate developmental milestones,
including pincer grasp (31%), pat-a-cake (45%), and walking unassisted (39%).31
Looking ahead to children 18 to 24 months of age, the Western Canadian
Complex Pediatric Therapies Project follow-up group demonstrated a prevalence
of motor delay nearly 3 times higher than expected on the basis of population
norms for the PDI.19 Similarly, a study from Montreal demonstrated moderate
or severe disability in the mobility domain in approximately two-thirds of
children after open-heart surgery as measured by using the Pediatric Functional
Independence Measure at a mean age of 20 months.16 Children who underwent
palliative procedures that resulted in persistent cyanosis appeared to be at the
highest risk. Other studies of children with single-ventricle physiology support
an increased prevalence of motor deficits in this subpopulation. In the Single
Ventricle Reconstruction Trial cohort of children with hypoplastic left heart
syndrome, PDI scores at 14 months of age were markedly lower than the nor-
mative values, with 44% of children scoring more than 2 SDs below the expected
mean.15 Children with a more complicated postoperative course appeared to be
more severely affected. For every third additional day of hospitalization after
surgical repair, there was an additional 13-point decrease in the PDI score. At
follow-up at 3 years of age, nearly one-third of children demonstrated clinically
significant delay in the gross and/or fine motor domains measured by using the
ASQ. The risk was highest in children who scored less than 70 on the PDI at
14 months.
Communication, Social Interaction, Behavior, and QOL
The first 3 years of life are critical for language acquisition. Follow-up of the
BCAS cohort by using parent-completed questionnaires at 2.5 years of age
demonstrated an average language delay of 2 to 4 months.31 In fact, 6% of the
cohort was unable to combine 2 words together at this age, which is consistent
with a diagnosis of expressive language delay. Children who experienced clinical
or subclinical perioperative seizures were at highest risk for both expressive
language delay and abnormalities in interpersonal interactions.32 Evaluation of
children with single-ventricle physiology at 3 years of age demonstrated similar
delays in communication and social domains measured by using the ASQ.14 They
also had lower parent-proxy health-related QOL scores in emotional and social
functioning as measured by using the Pediatric Quality of Life Inventory. Early
language delay has been shown to allow prediction of further deficits in literacy
and language skills and can lead to problems with behavior and socialization due
to difficulties with age-appropriate communication.32,33
631
CCIP.indb 631 3/13/18 4:19 PM

School-Aged Children and Adolescents (Age 5 Years

and Older)
As children prepare to enter school, even subtle delays in cognitive functioning,
motor skills, communication, or executive functioning can have a lasting effect
on academic achievement, peer interactions, and social integration, which may in
turn affect self-esteem and QOL. Developmental surveillance is essential in this
age group as children begin to integrate individual skills into the higher-order
processes necessary for successful completion of the increasingly complex tasks
required in adolescence and adulthood. Data from the BCAS cohort suggest that
while children with abnormal developmental scores in infancy are at the highest
risk for subsequent developmental abnormalities, even children with normal
BSID-II scores in infancy may demonstrate clinically significant developmental
deficits later in life,34 which further emphasizes the need for longitudinal
evaluation and surveillance.
Cognitive Functioning and Academic Achievement
While multiple investigators have looked prospectively at infant and early
childhood cognitive outcomes in patients with CHD, long-term follow-up
is limited. The preschool and school-age outcomes of the BCAS cohort have
been studied in greatest depth by using the Wechsler Preschool and Primary
Scale of Intelligence–Revised, or WPPSI, and the Wechsler Intelligence Scale
for Children, or WISC, to assess IQ in preschool and school-aged children,
respectively. At both 4 and 8 years of age, the mean full-scale WPPSI and
WISC IQ scores in the BCAS cohort were slightly but significantly lower than
the population mean, although most scores fell within the average range.5,12
Risk factors for a lower IQ score included a longer circulatory arrest time and
lower socioeconomic status. In the multivariable regression model, social class
was a stronger predictor of outcomes at 4 years of age than any of the surgical
factors, which suggests that children with lower socioeconomic status may
require special attention. Additionally, a more complicated perioperative course
allowed prediction of a lower full-scale IQ score. The occurrence of perioperative
seizures was associated with a mean decrease in IQ of 12.6 points at 4 years of
age. These findings persisted at 8 years of age. Academic achievement was also
affected. Despite generally normal IQ, many of these children struggled with
school performance when compared to their peers. Nearly 40% received remedial
school services, and 10% had already repeated a grade by 8 years of age.
Academic underperformance is even more prevalent in adolescents with
CHD. Reassessment of the BCAS cohort at age 16 demonstrated use of reme-
dial school services in 65% of the cohort.6 These findings have been duplicated
in children with tetralogy of Fallot and single-ventricle physiology.21,22 This is
further supported by a study from the Children’s Hospital of Philadelphia in
which a heterogeneous group of all survivors of infant open-heart surgery were
632
CCIP.indb 632 3/13/18 4:19 PM

studied, with results notable for 15% of children who received full-time special
education and an additional 34% who received remedial help in math and/or
reading during the school day.35 Despite their exposure to both chronic cyanosis
and repeated open-heart surgeries, patients with single-ventricle physiology,
including hypoplastic left heart syndrome, had similar outcomes to open-heart
surgery survivors after biventricular repair.
Fine and Gross Motor Skills
Motor delays are less evident in older children but remain a concern. While
severe disability is rare, subtle deficits measured on the PDI during infancy
persist as mild difficulties with movement and coordination in later childhood.
For example, the BCAS cohort scored below the 10th percentile on average
for both fine and gross motor domains on the Peabody Developmental Motor
Scale at 4 years of age.12 Similarly, nearly 50% of subjects in the Montreal group
had a Peabody score consistent with gross motor delay, and 40% of subjects
met criteria for fine motor delay at the age of school entry.17 Despite this, most
of the patients were independently mobile (eg, transferring and ambulating),
with less than 5% exhibiting moderate or severe mobility restrictions. Children
who underwent surgical palliation rather than complete repair appeared to be
at greatest risk—for example, those with single-ventricle physiology. Prolonged
exposure to hypoxemia during critical periods of development may be 1 potential
factor that contributes to the increased risk of developmental deficits in this
particularly vulnerable population.36

In addition to fine and gross motor deficits, school-aged survivors of
CHD demonstrate difficulty with integrating motor and sensory information.
Examination of the Children’s Hospital of Philadelphia cohort showed that
patients who have undergone single-ventricle palliation had more severe impair-
ment of visual-motor integration than patients with biventricular physiology,
although both groups were affected.25 The ability to translate sensory inputs into
fine movements is essential to perform many future academic functions and has
been shown to predict future academic achievement.37 Multiple studies have
demonstrated clinically significant deficits in visual-spatial and visual-motor
skills in older school-aged children with CHD, with specific problems in manual
dexterity, handwriting, and expressive language.14,38
Communication and Social Skills
As children age, communication becomes more complex. Simple production of
words and short phrases gives way to creation of complex sentences and abstract
thought. The ability to communicate effectively is essential to developing inter-
personal interactions, and children with language impairment often experience
social difficulties.39 Many children with CHD exhibit problems with oromotor
coordination, as manifested by problems with coordinating oral movements
and articulating words, as well as apraxia.12 In addition, they may have problems
633
CCIP.indb 633 3/13/18 4:19 PM

communicating complex concepts because of poor comprehension of multistep

instructions, limited vocabulary, delayed processing speed, and deficient narrative
memory.21 These skills are an important part of the higher-order communication
required for social functioning at this age. Deficits in social cognition, social
functioning, and peer relationships have been documented with neuropsycholog-
ical testing and/or parental surveys in multiple CHD subgroups.40–43 These chil-
dren may also demonstrate difficulty with grasping the theory of mind concepts
necessary to relate to and empathize normally with peers.42,44 Environmental
factors may further influence social functioning. Athletic restrictions related to
their underlying heart disease may prevent children with CHD from partici-
pating in sports teams and other school activities. Children with complex CHD
may have also spent a substantial amount of time socially isolated from their
peers during repeated hospitalizations.
Behavior and Executive Functioning
Executive functioning refers to the set of cognitive functions required to
plan and carry out complex tasks. Successful executive functioning requires
self-regulation and behavioral control, in addition to “metacognition” (working
memory, planning, organization, reasoning, and problem solving), all of which
may be impaired in children with CHD.45 Children with CHD often demon-
strate a decrease in executive functioning, as measured with neurocognitive
testing,5,38,44 but this likely leads to underestimation of the degree of functional
deficits that manifest in the classroom, where executive functioning is a critical
part of day-to-day performance. In fact, deficits in executive functioning,
particularly metacognition, have been shown to independently allow prediction
of problems with school performance in children with CHD45—even in those
with a normal IQ. Additionally, the adolescents in the BCAS cohort often failed
to self-report issues with executive functioning despite marked concern by their
parents and teachers.6 Difficulty with planning and organization, in addition to a
lack of insight into these problems, becomes particularly problematic during the
transition to independent adulthood. Studies of adults with CHD have demon-
strated that reduced executive functioning is associated with higher receipt of
disability services, lower occupational status, and inability to live independently
from parents.46,47

Attention-deficit/hyperactivity disorder (ADHD) and related symptoms are
also observed with a relatively high prevalence in children with CHD. A study of
patients with complex CHD demonstrated symptoms of ADHD in nearly 30%
of patients.35 Similar outcomes have been published for other specific subgroups
of patients with CHD, including TAPVC, tetralogy of Fallot, and ventricular
septal defects.48,49 Patients with single-ventricle physiology may be at even
higher risk, with attention and hyperactivity symptoms in as many as 50% of
patients with hypoplastic left heart syndrome.50
634
CCIP.indb 634 3/13/18 4:19 PM

Health-Related QOL
The neurodevelopmental and psychosocial morbidities experienced by children
with cardiac disease can have a substantial effect on their QOL. Health-related
QOL (HRQOL) describes the effect of a specific illness on 3 QOL domains:
physical, psychological, and social functioning. Multiple studies have demon-
strated a decrease in self-reported HRQOL in all domains for children with
clinically significant CHD when compared to healthy control subjects.24,51
In the largest study to date, the Pediatric Cardiac Quality of Life Inventory
(PCQLI), a disease-specific tool designed for use in children with congenital
or acquired heart disease, was used to evaluate the HRQOL in thousands of
patient-parent pairs in the United States and the United Kingdom.52–54 Results
demonstrated a lower HRQOL in patients with more severe cardiac disease
and in those with higher health care usage rates as measured by using both
parent-proxy and patient reporting. Presence of neurodevelopmental problems
(impaired executive functioning, gross motor delays, decreased self-perception,
and other issues) were used to predict a lower PCQLI score when compared
to healthy control subjects. A substantial amount of variation in PCQLI score
remained unexplained by physical factors. The investigators demonstrated that
both external factors (eg, parental stress, family functioning, socioeconomic
status) and internal factors (resilience, self-perception, psychological disorders)
accounted for a substantial proportion of the variation in HRQOL score.55 By
strengthening psychosocial support and optimizing patient and family mental
health, QOL may ultimately be improved in this cohort of high-risk patients
with CHD.
Management
Treatment Approach
The primary medical home is uniquely positioned to conduct careful develop-
mental monitoring to provide timely developmental surveillance, screening, and
referral for more in-depth evaluation. Children with CHD should be stratified
into low- and high-risk categories for developmental deficits (Box 39-1).
The current American Heart Association algorithm recommends that
high-risk children should receive direct referral for a formal multidisciplinary
developmental evaluation and early intervention (Figure 39-1). A formal devel-
opmental assessment should be repeated at 12 to 24 months, 3 to 5 years, and
11 to 12 years of age. Children identified as low risk should undergo heightened
surveillance and screening according to the general American Academy of
Pediatrics guidelines, including standard developmental screening at 9, 18, 30,
and 48 months, in addition to autism-specific screening at 18 to 24 months of
age.56 In addition, all children should be referred for formal evaluation based on
any clinical concern on the part of the treating physician.
635
CCIP.indb 635 3/13/18 4:19 PM

1
Medical home visit
of patient with CHD
Schedule
2 next medical
Perform home visit
risk stratification
No
3a
Does patient Does Is this visit
No Perform surveillance No at 9, 18, 24, 30,
meet criteria
in Box 39-1? surveillance demonstrate or 48 months
risk? of age?†
Yes
Yes* Yes
3b Is this the
Increasing developmental concern
patient’s initial Administer

No
high-risk stratification screening
or periodic tool
reevaluation?
Yes
Are the
4 Make referrals for early intervention
Yes screening tool
Make referrals for formal developmental results positive
and medical evaluation or concerning?
5 No
Formal developmental and medical evaluation
Schedule
6 No next medical
Is a developmental disorder identified? home visit
Yes
7b 7a
Schedule intervention and supportive therapies Schedule next
medical home visit
Schedule periodic
8
Neurodevelopmental
Monitor progress reevaluation§ if
with continued patient meets criteria
High-risk
periodic reevaluation§ in Box 39-1
Population
Start Action/Process Decision
*The decision of screening versus evaluation is at the discretion of the medical home provider.
†Per AAP guidelines, developmental screening should take place at 9, 18, 30, and 48 months of age.
Screening for autism spectrum disorders should also occur during the 18- and 24-month visits.
‡Referrals for early intervention may be made if the child is <5 years of age or not yet in kindergarten.
§Periodic reevaluation should take place at 12 to 24 months, 3 to 5 years, and 11 to 12 years of age.
If a patient is identified as high risk after 12 years of age, an evaluation plan should be determined
at the discretion of the medical home provider.
FIGURE 39-1. Congenital heart disease algorithm for surveillance, screening, evaluation, and
management of developmental disorders and disabilities. AAP = American Academy of Pediatrics,
CHD = congenital heart disease. From reference 3.
636
CCIP.indb 636 3/13/18 4:19 PM

Because older children with CHD may manifest subtle difficulties in multiple
domains, specialized testing for deficits in executive function, processing speed,
memory, and visual motor integration may be necessary in school-aged children.
This often requires coordination between the school and a multidisciplinary team
with specific expertise in children with CHD. In addition, specific screening for
ADHD may be necessary. Presence of cardiac disease is often not a contraindi-
cation to medical treatment of ADHD, but consultation should occur with the
child’s primary cardiologist.
Finally, early identification of mental health and psychosocial dysfunction in
adolescents and young adults may foster improved academic achievement and
interpersonal interactions. Early identification of patient anxiety, depression, or
low self-esteem and additional family support with regard to the socioeconomic
challenges of managing chronic disease and coping with stress may influence the
QOL for the entire family. Adolescents may need additional supports, such as
referral for educational and vocational counseling, to help them develop social,
medical, and financial independence as they transition to adulthood.
Key Points
•• Children with CHD are at risk for neurodevelopmental and psychosocial
impairment.
•• The highest risk for developmental disability is seen in
—— Survivors of neonatal or infant open-heart surgery
—— Children with cyanotic CHD not requiring infant open-heart surgery
—— Children with CHD and other high-risk comorbidities, including a
history of prematurity, microcephaly, developmental delay recognized in
infancy, underlying genetic abnormality or syndrome, cardiopulmonary
resuscitation, mechanical support, heart transplantation, prolonged
postoperative hospitalization, postoperative seizures, or previously iden
tified neuroimaging abnormality
•• Early recognition and intervention are critical to ensure the best possible
functional outcome in these patients.

•• Learn the Signs. Act Early (U.S. Centers for Disease Control and Prevention).
www.cdc.gov/actearly
•• Center for Parent Information & Resources. www.parentcenterhub.org
637
CCIP.indb 637 3/13/18 4:19 PM

References
1) Williams WG. Surgical outcomes in congenital heart disease: expectations and realities.
Eur J Cardiothorac Surg. 2005;27(6):937–944
2) Moodie D. Adult congenital heart disease: past, present, and future. Tex Heart Inst J.
2011;38(6):705–706
3) Marino BS, Lipkin PH, Newburger JW, et al; American Heart Association Congenital
Heart Defects Committee, Council on Cardiovascular Disease in the Young, Council on
Cardiovascular Nursing, and Stroke Council. Neurodevelopmental outcomes in children with
congenital heart disease: evaluation and management: a scientific statement from the American
Heart Association. Circulation. 2012;126(9):1143–1172
4) Newburger JW, Jonas RA, Wernovsky G, et al. A comparison of the perioperative neurologic
effects of hypothermic circulatory arrest versus low-flow cardiopulmonary bypass in infant heart
surgery. N Engl J Med. 1993;329(15):1057–1064
5) Bellinger DC, Wypij D, duPlessis AJ, et al. Neurodevelopmental status at eight years in children
with dextro-transposition of the great arteries: the Boston Circulatory Arrest Trial. J Thorac
Cardiovasc Surg. 2003;126(5):1385–1396
6) Bellinger DC, Wypij D, Rivkin MJ, et al. Adolescents with d-transposition of the great arteries
corrected with the arterial switch procedure: neuropsychological assessment and structural brain
imaging. Circulation. 2011;124(12):1361–1369
7) Uzark K, Spicer R, Beebe DW. Neurodevelopmental outcomes in pediatric heart transplant
recipients. J Heart Lung Transplant. 2009;28(12):1306–1311
8) Cassidy J, Haynes S, Kirk R, et al. Changing patterns of bridging to heart transplantation in
children. J Heart Lung Transplant. 2009;28(3):249–254
9) Shonkoff JP, Hauser-Cram P. Early intervention for disabled infants and their families: a
quantitative analysis. Pediatrics. 1987;80(5):650–658
10) Spittle A, Orton J, Anderson PJ, Boyd R, Doyle LW. Early developmental intervention
programmes provided post hospital discharge to prevent motor and cognitive impairment in
preterm infants. Cochrane Database Syst Rev. 2015;(11):CD005495
11) Bellinger DC, Jonas RA, Rappaport LA, et al. Developmental and neurologic status of children
after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass. N
Engl J Med. 1995;332(9):549–555
12) Bellinger DC, Wypij D, Kuban KC, et al. Developmental and neurological status of children at 4
years of age after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary
bypass. Circulation. 1999;100(5):526–532
13) Bellinger DC, Newburger JW, Wypij D, Kuban KC, duPlesssis AJ, Rappaport LA. Behaviour
at eight years in children with surgically corrected transposition: the Boston Circulatory Arrest
Trial. Cardiol Young. 2009;19(1):86–97
14) Goldberg CS, Lu M, Sleeper LA, et al; Pediatric Heart Network Investigators. Factors
associated with neurodevelopment for children with single ventricle lesions. J Pediatr.
2014;165(3):490–496.e8
15) Newburger JW, Sleeper LA, Bellinger DC, et al; Pediatric Heart Network Investigators. Early
developmental outcome in children with hypoplastic left heart syndrome and related anomalies:
the single ventricle reconstruction trial. Circulation. 2012;125(17):2081–2091
16) Limperopoulos C, Majnemer A, Shevell MI, et al. Functional limitations in young children with
congenital heart defects after cardiac surgery. Pediatrics. 2001;108(6):1325–1331
17) Majnemer A, Limperopoulos C, Shevell M, Rosenblatt B, Rohlicek C, Tchervenkov C. Long-
term neuromotor outcome at school entry of infants with congenital heart defects requiring
open-heart surgery. J Pediatr. 2006;148(1):72–77
638
CCIP.indb 638 3/13/18 4:19 PM

18) Limperopoulos C, Majnemer A, Shevell MI, Rosenblatt B, Rohlicek C, Tchervenkov C.

Neurodevelopmental status of newborns and infants with congenital heart defects before and
after open heart surgery. J Pediatr. 2000;137(5):638–645
19) Freed DH, Robertson CM, Sauve RS, et al; Western Canadian Complex Pediatric Therapies
Project Follow-up Group. Intermediate-term outcomes of the arterial switch operation
for transposition of great arteries in neonates: alive but well? J Thorac Cardiovasc Surg.
2006;132(4):845–852
20) Alton GY, Robertson CM, Sauve R, et al; Western Canadian Complex Pediatric Therapies
Project Follow-Up Group. Early childhood health, growth, and neurodevelopmental outcomes
after complete repair of total anomalous pulmonary venous connection at 6 weeks or younger. J
Thorac Cardiovasc Surg. 2007;133(4):905–911
21) Miatton M, De Wolf D, François K, Thiery E, Vingerhoets G. Intellectual, neuropsychological,
and behavioral functioning in children with tetralogy of Fallot. J Thorac Cardiovasc Surg.
2007;133(2):449–455
22) Wernovsky G, Stiles KM, Gauvreau K, et al. Cognitive development after the Fontan operation.
Circulation. 2000;102(8):883–889
23) McCusker CG, Doherty NN, Molloy B, et al. A randomized controlled trial of interventions to
promote adjustment in children with congenital heart disease entering school and their families.
J Pediatr Psychol. 2012;37(10):1089–1103
24) Mellion K, Uzark K, Cassedy A, et al; Pediatric Cardiac Quality of Life Inventory Testing Study
Consortium. Health-related quality of life outcomes in children and adolescents with congenital
heart disease. J Pediatr. 2014;164(4):781–788.e1
25) Gaynor JW, Ittenbach RF, Gerdes M, et al. Neurodevelopmental outcomes in preschool
survivors of the Fontan procedure. J Thorac Cardiovasc Surg. 2014;147(4):1276–1282, discussion
1282–1283.e5
26) Andropoulos DB, Easley RB, Brady K, et al. Changing expectations for neurological outcomes
after the neonatal arterial switch operation. Ann Thorac Surg. 2012;94(4):1250–1255, discussion
1255–1256
27) Ohye RG, Sleeper LA, Mahony L, et al; Pediatric Heart Network Investigators. Comparison
of shunt types in the Norwood procedure for single-ventricle lesions. N Engl J Med.
2010;362(21):1980–1992
28) Mussatto KA, Hoffmann R, Hoffman G, et al. Risk factors for abnormal developmental
trajectories in young children with congenital heart disease. Circulation. 2015;132(8):755–761
29) Mussatto KA, Hoffmann RG, Hoffman GM, et al. Risk and prevalence of developmental delay
in young children with congenital heart disease. Pediatrics. 2014;133(3):e570–e577
30) Gaynor JW, Stopp C, Wypij D, et al; International Cardiac Collaborative on Neurodevelopment
(ICCON) Investigators. Neurodevelopmental outcomes after cardiac surgery in infancy.
Pediatrics. 2015;135(5):816–825
31) Bellinger DC, Rappaport LA, Wypij D, Wernovsky G, Newburger JW. Patterns of developmen-
tal dysfunction after surgery during infancy to correct transposition of the great arteries. J Dev
Behav Pediatr. 1997;18(2):75–83
32) Rappaport LA, Wypij D, Bellinger DC, et al; Boston Circulatory Arrest Study Group. Relation
of seizures after cardiac surgery in early infancy to neurodevelopmental outcome. Circulation.
1998;97(8):773–779
33) Schuele CM. The impact of developmental speech and language impairments on the acquisition
of literacy skills. Ment Retard Dev Disabil Res Rev. 2004;10(3):176–183
34) McGrath E, Wypij D, Rappaport LA, Newburger JW, Bellinger DC. Prediction of IQ and
achievement at age 8 years from neurodevelopmental status at age 1 year in children with
D-transposition of the great arteries. Pediatrics. 2004;114(5):e572–e576
639
CCIP.indb 639 3/13/18 4:19 PM

35) Shillingford AJ, Glanzman MM, Ittenbach RF, Clancy RR, Gaynor JW, Wernovsky G.
Inattention, hyperactivity, and school performance in a population of school-age children with
complex congenital heart disease. Pediatrics. 2008;121(4):e759–e767
36) Stieh J, Kramer HH, Harding P, Fischer G. Gross and fine motor development is impaired in
children with cyanotic congenital heart disease. Neuropediatrics. 1999;30(2):77–82
37) Taylor Kulp M. Relationship between visual motor integration skill and academic performance
in kindergarten through third grade. Optom Vis Sci. 1999;76(3):159–163
38) Miatton M, De Wolf D, François K, Thiery E, Vingerhoets G. Neuropsychological perfor-
mance in school-aged children with surgically corrected congenital heart disease. J Pediatr.
2007;151(1):73–78, 78.e1
39) Vissers C, Koolen S. Theory of mind deficits and social emotional functioning in preschoolers
with specific language impairment. Front Psychol. 2016;7:1734
40) Schaefer C, von Rhein M, Knirsch W, et al. Neurodevelopmental outcome, psychological
adjustment, and quality of life in adolescents with congenital heart disease. Dev Med Child
Neurol. 2013;55(12):1143–1149
41) Utens EM, Verhulst FC, Meijboom FJ, et al. Behavioural and emotional problems in children
and adolescents with congenital heart disease. Psychol Med. 1993;23(2):415–424
42) Bellinger DC. Are children with congenital cardiac malformations at increased risk of deficits in
social cognition? Cardiol Young. 2008;18(1):3–9
43) Hövels-Gürich HH, Konrad K, Wiesner M, et al. Long term behavioural outcome after
neonatal arterial switch operation for transposition of the great arteries. Arch Dis Child.
2002;87(6):506–510
44) Calderon J, Bonnet D, Courtin C, Concordet S, Plumet MH, Angeard N. Executive function
and theory of mind in school-aged children after neonatal corrective cardiac surgery for transpo-
sition of the great arteries. Dev Med Child Neurol. 2010;52(12):1139–1144
45) Gerstle M, Beebe DW, Drotar D, Cassedy A, Marino BS. Executive functioning and school
performance among pediatric survivors of complex congenital heart disease. J Pediatr.
2016;173:154–159
46) Opić P, Roos-Hesselink JW, Cuypers JA, et al. Psychosocial functioning of adults with
congenital heart disease: outcomes of a 30-43 year longitudinal follow-up. Clin Res Cardiol.
2015;104(5):388–400
47) Ilardi D, Ono KE, McCartney R, Book W, Stringer AY. Neurocognitive functioning in adults
with congenital heart disease. Congenit Heart Dis. 2017;12(2):166–173
48) Hövels-Gürich HH, Konrad K, Skorzenski D, Herpertz-Dahlmann B, Messmer BJ, Seghaye
MC. Attentional dysfunction in children after corrective cardiac surgery in infancy. Ann Thorac
Surg. 2007;83(4):1425–1430
49) Kirshbom PM, Flynn TB, Clancy RR, et al. Late neurodevelopmental outcome after repair of
total anomalous pulmonary venous connection. J Thorac Cardiovasc Surg. 2005;129(5):1091–1097
50) Mahle WT, Wernovsky G. Neurodevelopmental outcomes in hypoplastic left heart syndrome.
Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 2004;7:39–47
51) Uzark K, Jones K, Slusher J, Limbers CA, Burwinkle TM, Varni JW. Quality of life in children
with heart disease as perceived by children and parents. Pediatrics. 2008;121(5):e1060–e1067
52) Marino BS, Shera D, Wernovsky G, et al. The development of the pediatric cardiac quality of life
inventory: a quality of life measure for children and adolescents with heart disease. Qual Life Res.
2008;17(4):613–626
53) Marino BS, Tomlinson RS, Wernovsky G, et al; Pediatric Cardiac Quality of Life Inventory
Testing Study Consortium. Validation of the pediatric cardiac quality of life inventory. Pediatrics.
2010;126(3):498–508
640
CCIP.indb 640 3/13/18 4:19 PM

54) Marino BS, Drotar D, Cassedy A, et al. External validity of the pediatric cardiac quality of life
inventory. Qual Life Res. 2011;20(2):205–214
55) Marino BS, Cassedy A, Drotar D, Wray J. The impact of neurodevelopmental and psychosocial
outcomes on health-related quality of life in survivors of congenital heart disease. J Pediatr.
2016;174:11–22.e2
56) Council on Children with Disabilities; Section on Developmental Behavioral Pediatrics; Bright
Futures Steering Committee; Medical Home Initiatives for Children with Special Needs Project
Advisory Committee. Identifying infants and young children with developmental disorders
in the medical home: an algorithm for developmental surveillance and screening. Pediatrics.
2006;118(1):405–420
641
CCIP.indb 641 3/13/18 4:19 PM

CCIP.indb 642 3/13/18 4:19 PM
CHAPTER 40
Lifestyle
Counseling
Jessica Bowman, MD, and Jason Cole, MD
Introduction
Cardiovascular disease (CVD) is commonly viewed as a disease of adulthood;
however, it is now understood that this is a process that begins in childhood and
lays the foundation that can ultimately lead to atherosclerotic blood vessel changes
later in life. These blood vessel changes can lead to many long-term cardiovascular
complications seen in adulthood, such as hypertension, hyperlipidemia, coronary
artery disease, cardiac dysfunction, heart failure, and premature death.1,2 While the
effects of a heart-healthy lifestyle in childhood and adolescence may not be fully
apparent until later in life, the importance of such a lifestyle cannot be understated.
The implementation of primary preventive methods from infancy through
adolescence may help to alter the staggering trends of obesity, metabolic disease,
and CVD in pediatric patients as they reach adulthood. In doing so, long-term
morbidity and mortality may be reduced, along with overall health care costs.3
This chapter contains pediatric primary preventive care strategies for diet, exercise,
smoking, and sleep to promote long-term cardiovascular health.
Nutrition and Diet

Heart-healthy dietary habits begin at birth and continue throughout an
individual’s life. Setting healthy eating habits early in one’s life has the potential
to prevent numerous complications, such as obesity, dyslipidemia, hypertension,
and insulin-resistant diabetes mellitus, all of which have the potential to lead to
CVD in adulthood.4–6 The promotion of healthy dietary habits in a child’s life
643
CCIP.indb 643 3/13/18 4:19 PM

is initially fully dependent on parental reinforcement, which makes parental

counseling at office visits vital at even the earliest stages of a patient’s life. The
National Heart, Lung, and Blood Institute (NHLBI) published a study in
2011 that lays out dietary recommendations along each age group regarding
long-term cardiovascular health. Depicted in Table 40-1, the recommendations
begin with the institution of breast milk as primary nutrition for babies through
6 to 12 months of age. This corresponds to recommendations from the World
Health Organization, the American Academy of Pediatrics (AAP), and the
American Academy of Family Practice.2,3,7 Additionally, the NHLBI study
included age-specific fat quantity and quality guidelines, sugar intake limitations,
and sodium and fiber recommendations for patients in the pediatric population,
also noted in Table 40-1. As shown in the Table, nutritional recommendations
change throughout the developmental spectrum, which emphasize the impor-
tance of annual evaluations in primary care and age-appropriate recommenda-
tions for patients regarding their nutrition.
Caloric intake is another crucial element to a heart-healthy diet.8 Diets that
contain large portions of processed foods increase caloric intake and are one of
many factors that have led to the increasing number of overweight and obese
children in the United States.1 Unfortunately, there is no simple universal guide-
line that every child and adolescent can follow regarding caloric intake, because
the calories needed for growth and development are variable for each individual.
One must take into account the child’s sex, age, family history, and activity level
to be able to determine the specific caloric demands for each patient. Table 40-2
depicts the NHLBI caloric intake recommendations for children determined in
accordance to their sex, age, and activity level.1,5 Additional recommendations
for regulating calories in a patient’s diet include limiting fast food intake to
1 or fewer meals per week; eating fresh meat, grains, fruits, and vegetables
rather than processed meals; and controlling portion size with a plan similar to
ChooseMyPlate, which is available through the U.S. Department of Agriculture
at Choosemyplate.gov.6 This plan focuses on balanced meals with portioned
fruits, vegetables, proteins, grains, and dairy products and has sex- and age-spe-
cific quantities for each to help plan healthy meals. These are simple and practical
recommendations that can be made to parents and patients as methods to
prevent excessive caloric intake. Ultimately, a healthy diet for pediatric patients
is a byproduct of parental eating habits; therefore, counseling parents regarding
meals created for themselves and their children is paramount to establishing
healthy food habits that will continue throughout a lifetime.8,9
644
CCIP.indb 644 3/13/18 4:19 PM

Lifestyle Counseling
Table 40-1. Dietary Recommendations from Infancy

Through Adolescence
Age and Recommendations
Birth to 6 mo
Infants should be exclusively breastfed (no supplemental

formula or other foods) until the age of 6 mo
7–12 mo
Continue breastfeeding until at least 12 mo of age, while

gradually adding solids; transition to iron-fortified formula until
12 mo if reducing breastfeeding
Fat intake in infants <12 mo of age should not be restricted

without medical indication
Limit other drinks to 100% fruit juice (≤4 oz/d); no sweetened

beverages; encourage water
13–24 mo
Transition to reduced-fat (2% to fat-free) unflavored cow’s milk
Avoid or limit sugar-sweetened beverage intake; encourage

water
Transition to table Total fat 30% of daily kilocalories or EER

food with
Saturated fat 8%–10% of daily kilocalories or EER
Avoid trans fat as much as possible
Monounsaturated and polyunsaturated fat up to 20% of daily

kilocalories or EER
Cholesterol <300 mg/d
Supportive The fat content of cow’s milk to introduce at 12–24 mo of

actions age should be decided together by parents and health care
providers on the basis of the child’s growth, appetite, intake of
other nutrient-dense foods, intake of other sources of fat, and
potential risk for obesity and cardiovascular disease
Offer 100% fruit juice (from a cup), no more than 4 oz/d
Limit sodium intake
Consider a DASH-type diet rich in fruits, vegetables, whole

grains, and low-fat/fat-free milk and milk products and lower
in sugar
Continued
645
CCIP.indb 645 3/13/18 4:19 PM


Through Adolescence, continued
2–10 y
Primary beverage: fat-free unflavored milk
Avoid or limit sugar-sweetened beverages; encourage water
Fat content Total fat 25%–30% of daily kilocalories or EER
Avoid trans fats as much as possible

kilocalories or EER
Encourage high dietary fiber intake from foods
Supportive Teach portions based on EER for age, sex, and activity level
actions
Encourage moderately increased energy intake during periods

of rapid growth and/or regular moderate to vigorous physical
activity
Encourage dietary fiber from foods: age + 5 g/d
Limit naturally sweetened juice (no added sugar) to 4 oz/d
Limit sodium intake
Support DASH-style eating plan
11–21 y
Primary beverage: fat-free unflavored milk
Avoid or limit sugar-sweetened beverages; encourage water
Fat content Total fat 25%–30% of daily kilocalories or EER
Avoid trans fat as much as possible

kilocalories or EER
Encourage high dietary fiber intake from foods
Supportive Teach portions based on EER for age, sex, and activity level
actions
646
CCIP.indb 646 3/13/18 4:19 PM


Through Adolescence, continued
11–21 y, continued
Encourage moderately increased energy intake during periods

of rapid growth and/or regular moderate to vigorous physical
activity
Advocate dietary fiber: goal of 14 g per 1,000 kcal
Limit naturally sweetened juice (no added sugar) to 4–6 oz/d
Limit sodium intake
Encourage healthy eating habits: eating breakfast every day,

eating meals as a family, limiting fast-food meals
Support DASH-style eating plan

DASH, dietary approaches to stop hypertension (emphasis on portion control, lower amount of processed food
consumption, and limiting dietary salt intake); EER, estimated energy requirement. From reference 1.
Table 40-2. Caloric Intake Based on Sex, Age, and

Activity Level
Caloric Requirements (kcals) by Activity Level
Patient Group Age (y) Sedentary Moderately Active Active
Toddlers 2–3 1,000–1,200 1,000–1,400 1,000–1,400
Females 4–8 1,200–1,400 1,400–1,600 1,400–1,800
9–13 1,400–1,600 1,600–2,000 1,800–2,200
14–18 1,800 2,000 2,400
19–30 1,800–2,000 2,000–2,200 2,400
Males 4–8 1,200–1,400 1,400–1,600 1,600–2,000
9–13 1,600–2,000 1,800–2,200 2,000–2,600

14–18 2,000–2,400 2,400–2,800 2,800–3,200
19–30 2,400–2,600 2,600–2,800 3,000

From reference 1.
Exercise
Emerging data within the past 20 years have depicted the link between
sedentary lifestyles in the pediatric population and the long-term and short-term
cardiovascular effects of such lifestyles. Recent studies have shown that sedentary
adolescents are at an increased risk for hyperlipidemia, hypertension, and aortic
intimal thickening secondary to subclinical atherosclerosis when compared
647
CCIP.indb 647 3/13/18 4:19 PM

to their active peers.10–13 These data represent changes to previous schools of

thought that sedentary lifestyles did not contribute to long-term cardiovascular
risks until adulthood. Additionally, numerous studies have also shown that
exercise habits in children often translate to continued active lifestyles in
adulthood, further reducing the risk of long-term CVD.1 Thus, the promotion of
active lifestyles in children and adolescents is crucial to the prevention of CVD
in adulthood, from both short-term and long-term perspectives. The NHLBI
recommends that individuals older than 5 years of age participate in at least 1
hour of moderate physical activity per day (eg, jogging, active play), with vigor-
ous physical activity (eg, running) comprising this requirement 3 days per week.1
The hour of physical activity does not have to be a continuous event; rather, it
can be a collection of small segments of activity spread throughout the course of
the day that cumulatively equals 1 hour. Patients under the age of 5 are recom-
mended to have unrestricted play to promote active lifestyles. One of the major
factors that inhibit both children and adolescents from participating in physical
activity is the ease of accessibility to screen time (computers, tablets, phones,
etc). As a result, children under the age of 12 months should not be exposed to
these devices, and minimizing use to educational programing after this age is
essential to cultivating an active and heart-healthy lifestyle.1 Furthermore, from
the age of 12 months through 21 years of age, the amount of screen time should
be limited to 1 to 2 hours of essential use to avoid sedentary habits. All of the
aforementioned recommendations can be found in Table 40-3.
Smoking
Lifelong smoking habits often begin during the teenage and adolescent years.14
Approximately 90% of adult smokers began smoking prior to the age of 18 years.
Furthermore, 80% of individuals who began smoking during adolescence will
continue smoking into adulthood, and one-third of these patients will die from
a smoking-related disease.15 These staggering facts depict the importance of
preventing children from smoking to promote lifelong cardiovascular health.
The cardiovascular effects of nicotine and smoking have been well studied and
include increased myocardial demand secondary to hypertension and tachycardia,
transient coronary artery vasoconstriction, vascular endothelial dysfunction and
inflammation, lipid deposition along vascular walls, and a generalized hyperco-
agulable state.16–18 These consequences of smoking can lead to CVD later in life.
Thus, the aims of all providers in pediatrics, especially primary care physicians,
should focus on primary prevention of smoking behaviors among patients. The
AAP recommends that all patients 5 years and older be screened and given
anticipatory guidance regarding smoke exposure and risks of smoking. The
recommended screening tool can be remembered by the “6 A’s” mnemonic15,19:
Anticipate smoking risk secondary to parental smoking, ask the patient about
648
CCIP.indb 648 3/13/18 4:19 PM

Table 40-3. Evidence-Based Activity Recommendations

for Cardiovascular Health
Age Recommendations
Newborn to 12 mo
Parents should create an environment that promotes and models

physical activity and limits sedentary time
Supportive Discourage TV viewing altogether

actions
1 to 4 y
Allow unlimited active playtime in safe, supportive environments
Limit sedentary time, especially TV and video
Supportive Limit total media time to no more than 1–2 hours of quality
actions programming per day
For children ≤2 y old, discourage TV viewing altogether
No TV in the child’s bedroom
Encourage family activity at least once per week
Counsel routine activity for parents as role models for children
5 to 10 y Moderate to vigorous physical activity every day
Limit daily leisure screen time (TV, video, computer, video games,
tablets, phones)
Supportive Prescribe moderate to vigorous activity 1 h/d with vigorous-inten-

actions sity physical activity 3 d/wk
Limit total media time to no more than 1–2 h/d of quality

programming
No TV in the child’s bedroom
Obtain an activity and screen-time history from the child once per
year
Match physical activity recommendations with energy intake
Recommend appropriate safety equipment relative to each sport
Support recommendations for daily physical education in schools

11 to 17 y
Moderate to vigorous physical activity every day
Limit leisure time and TV, video, and computer use
Supportive Encourage adolescents to aim for 1 h/d of moderate to vigorous

actions daily activity, with vigorous intense physical activity 3 d/wk
Encourage no TV in the bedroom
Continued
649
CCIP.indb 649 3/13/18 4:19 PM

Table 40-3. Evidence-Based Activity Recommendations

for Cardiovascular Health, continued
Age Recommendations
11 to 17 y, continued
Limit total media time to no more than 1–2 h/d of quality

programming
Match activity recommendations with energy intake
Obtain an activity and screen-time history from adolescents at

health supervision visits
Encourage involvement in year-round physical activities
Support continued family activity once per week and/or family

support of adolescent’s physical activity program
Endorse appropriate safety equipment relative to each sport
18 to 21 y
Moderate to vigorous physical activity every day
Limit leisure time and TV, video, and computer use
Supportive Support a goal of 1 h/d of moderate to vigorous activity, with

actions vigorous intense physical activity 3 d/wk
Recommend that combined leisure screen time not exceed 2 h/d
Obtain an activity and screen-time history at health supervision

visits
Encourage involvement in year-round, lifelong physical activities

From reference 1.
smoking habits, advise the patient about the risks and benefits of smoking, assess
the risk factors for smoking initiation, assist with parental smoking resistance
and/or cessation, and arrange follow-up to monitor smoking behaviors.19,20
Sleep
Poor quality or short duration of sleep has many detrimental side effects for
patients, including adverse cardiovascular outcomes. Decreased quality of sleep
has been associated with increased rates of hypertension in adults who were fol-
lowed up from the age of 18 years into adulthood.21 Studies have also shown that
decreased sleep over the long term leads to increased cholesterol levels, coronary
artery calcification, and higher rates of stroke and myocardial infarction.22,23
Finally, increased rates of obesity and diabetes mellitus have been associated
with poor sleep, both of which have clinically significant long-term effects on
650
CCIP.indb 650 3/13/18 4:19 PM

cardiovascular health. As a result of the aforementioned morbidity associated

with poor sleep, the AAP and the American Academy of Sleep Medicine
have recommended age-specific sleep quantities for each age range depicted in
Box 40-1.24 Additionally, the AAP recommends establishing good sleep hygiene
rituals, even from infancy, to promote restful sleep. These recommendations
include setting a presleep ritual and bedtime, limiting screen time for at least
1 hour prior to sleep, having no distractions present in the bedroom (tablets,
television, video games, etc), and establishing a quiet and dark environment for
the patient to sleep.
Box 40-1. Sleep Duration Recommendation According

to Age
Infants 4 to 12 months: 12 to 16 hours (including naps)
Toddlers 1 to 2 years: 11 to 14 hours (including naps)
Children 3 to 5 years: 10 to 13 hours (including naps)
Children 6 to 12 years: 9 to 12 hours
Teens 13 to 18 years: 8 to 10 hours

From reference 24.
Key Points
•• Primary preventive methods in key areas of lifestyle in pediatric patients can
reduce the long-term morbidity and mortality from CVD in adulthood.
•• Dietary recommendations should focus on age- and sex-specific caloric, fat,
fiber, and salt intake goals.
—— Regulating the amount of trans fats, the quantity of total fat ingested,
and the amounts of foods and beverages high in glucose can help prevent
obesity in the pediatric population.
—— Promoting complete family dietary goals is the best way to establish healthy
eating habits in the pediatric population that translate into adulthood.
—— Resources such as ChooseMyPlate can be used to assist with portion control.
•• Exercise recommendations should focus on age-specific goals.
—— Patients under the age of 5 should have unrestricted play and limited screen
time to promote a physically active lifestyle.
—— Over the age of 5, patients should engage in a total of 60 minutes of
physical activity throughout the day and limit screen time to 1 to 2 hours of
“essential use” to promote long-term cardiovascular health.
651
CCIP.indb 651 3/13/18 4:19 PM

•• Most adults who are smokers begin smoking in adolescence.

—— Smoking can lead to cardiovascular disease in adulthood, and prevention of
and screening for smoking in pediatric patients should focus on the “6 A’s”
at each visit: anticipate, ask, advise, assess, assist, and arrange for follow-up.
•• Adequate quantity and quality of sleep can promote long-term cardiovascular
health by helping prevent hypertension, hyperlipidemia, obesity, and diabetes
mellitus.
—— Promoting sleep hygiene and bedtime routine counseling should be an
essential component of every patient visit.

•• How to Reduce Fat and Cholesterol in Your Child’s Diet (American Academy
of Pediatrics). www.healthychildren.org/English/ages-stages/gradeschool/
nutrition/Pages/How-to-Reduce-Fat-and-Cholesterol-in-Your-Childs-Diet.
aspx
•• Fiber: An Important Part of Your Teen’s Diet (American Academy of
Pediatrics). www.healthychildren.org/English/ages-stages/teen/nutrition/
Pages/Fiber-An-Important-Part-of-Your-Teens-Diet.aspx
•• Tips for Healthy Families: More and Less (American Academy of Pediatrics).
patiented.solutions.aap.org/handout.aspx?gbosid=208920#Purchase
SubscriptionBox
•• Energy Out: Daily Physical Activity Recommendations (American Academy
of Pediatrics). www.healthychildren.org/English/healthy-living/fitness/Pages/
Energy-Out-Daily-Physical-Activity-Recommendations.aspx
•• The Risks of Tobacco Use (American Academy of Pediatrics). patiented.
solutions.aap.org/handout.aspx?resultClick=1&gbosid=156626
•• Sleep Problems in Children (American Academy of Pediatrics). patiented.
solutions.aap.org/handout.aspx?resultClick=24&gbosid=156710
References
Children and Adolescents; National Heart, Lung, and Blood Institute. Expert panel on
integrated guidelines for cardiovascular health and risk reduction in children and adolescents:
summary report. Pediatrics. 2011;128(Suppl 5):S213–S256
2) American Academy of Pediatrics. Cardiovascular risk reduction in high-risk pediatric popula-
tions. Pediatrics. 2007;119(3):618–621
3) Steinberger J, Daniels SR, Hagberg N, et al; American Heart Association Atherosclerosis,
Hypertension, and Obesity in the Young Committee of the Council on Cardiovascular Disease
in the Young; Council on Cardiovascular and Stroke Nursing; Council on Epidemiology
and Prevention; Council on Functional Genomics and Translational Biology; and Stroke
Council. Cardiovascular Health Promotion in Children: Challenges and Opportunities for
2020 and Beyond: a Scientific Statement from the American Heart Association. Circulation.
2016;134(12):e236–e255
652
CCIP.indb 652 3/13/18 4:19 PM

4) Liu K, Daviglus ML, Loria CM, et al. Healthy lifestyle through young adulthood and the
presence of low cardiovascular disease risk profile in middle age: the Coronary Artery Risk
Development in (Young) Adults (CARDIA) study. Circulation. 2012;125(8):996–1004
5) Hagan JF, Shaw JS, Duncan PM, eds. Promoting healthy nutrition. In: Bright Futures: Guidelines
for Health Supervision of Infants, Children, and Adolescents. 3rd ed. Elk Grove Village, IL:
American Academy of Pediatrics; 2008:121
6) United States Department of Agriculture. Choosemyplate.gov. Accessed November 7, 2017
7) Nupponen M, Pahkala K, Juonala M, et al. Metabolic syndrome from adolescence to early
adulthood: effect of infancy-onset dietary counseling of low saturated fat: the Special Turku
Coronary Risk Factor Intervention Project (STRIP). Circulation. 2015;131(7):605–613
8) Gidding SS, Lichtenstein AH, Faith MS, et al. Implementing American Heart Association
pediatric and adult nutrition guidelines: a scientific statement from the American Heart
Association Nutrition Committee of the Council on Nutrition, Physical Activity and
Metabolism, Council on Cardiovascular Disease in the Young, Council on Arteriosclerosis,
Thrombosis and Vascular Biology, Council on Cardiovascular Nursing, Council on
Epidemiology and Prevention, and Council for High Blood Pressure Research. Circulation.
2009;119(8):1161–1175
9) Gidding SS, Dennison BA, Birch LL, et al; American Heart Association. Dietary recommenda-
tions for children and adolescents: a guide for practitioners. Pediatrics. 2006;117(2):544–559
10) Pahkala K, Heinonen OJ, Lagström H, et al. Clustered metabolic risk and leisure-time physical
activity in adolescents: effect of dose? Br J Sports Med. 2012;46(2):131–137
11) Pahkala K, Laitinen TT, Heinonen OJ, et al. Association of fitness with vascular intima-media
thickness and elasticity in adolescence. Pediatrics. 2013;132(1):e77–e84
12) Ekelund U, Luan J, Sherar LB, Esliger DW, Griew P, Cooper A; International Children’s
Accelerometry Database (ICAD) Collaborators. Moderate to vigorous physical activity
and sedentary time and cardiometabolic risk factors in children and adolescents. JAMA.
2012;307(7):704–712
13) Gidding SS, Barton BA, Dorgan JA, et al. Higher self-reported physical activity is associated
with lower systolic blood pressure: the Dietary Intervention Study in Childhood (DISC).
Pediatrics. 2006;118(6):2388–2393
14) Committee on Environmental HealthHealth; Committee on Substance Abuse; Committee
on Adolescence; Committee on Native American Child. From the American Academy of
Pediatrics: Policy statement—tobacco use: a pediatric disease. Pediatrics. 2009;124(5):1474–1487
15) Centers for Disease Control and Prevention (CDC). Cigarette use among high school
students—United States, 1991-2005. MMWR Morb Mortal Wkly Rep. 2006;55(26):724–726
16) Iida M, Iida H, Dohi S, Takenaka M, Fujiwara H. Mechanisms underlying cerebrovascular
effects of cigarette smoking in rats in vivo. Stroke. 1998;29(8):1656–1665
17) Kannel WB, D’Agostino RB, Belanger AJ. Fibrinogen, cigarette smoking, and risk of cardiovas-
cular disease: insights from the Framingham Study. Am Heart J. 1987;113(4):1006–1010
18) Benowitz NL. The role of nicotine in smoking-related cardiovascular disease. Prev Med. 1997;
26(4):412–417
19) Knutson KL, Van Cauter E, Rathouz PJ, et al. Association between sleep and blood pressure in
midlife: the CARDIA sleep study. Arch Intern Med. 2009;169(11):1055–1061
20) Pbert L, Farber H, Horn K, et al; American Academy of Pediatrics, Julius B. Richmond Center
of Excellence Tobacco Consortium. State-of-the-art office-based interventions to eliminate
youth tobacco use: the past decade. Pediatrics. 2015;135(4):734–747
21) King CR, Knutson KL, Rathouz PJ, Sidney S, Liu K, Lauderdale DS. Short sleep duration and
incident coronary artery calcification. JAMA. 2008;300(24):2859–2866
653
CCIP.indb 653 3/13/18 4:19 PM

22) Hoevenaar-Blom MP, Spijkerman AM, Kromhout D, Verschuren WM. Sufficient sleep
duration contributes to lower cardiovascular disease risk in addition to four traditional lifestyle
factors: the MORGEN study. Eur J Prev Cardiol. 2014;21(11):1367–1375
23) Sabanayagam C, Shankar A. Sleep duration and cardiovascular disease: results from the National
Health Interview Survey. Sleep. 2010;33(8):1037–1042
24) Paruthi S, Brooks LJ, D’Ambrosio C, et al. Recommended Amount of Sleep for Pediatric
Populations: a Consensus Statement of the American Academy of Sleep Medicine. J Clin Sleep
Med. 2016;12(6):785–786
654
CCIP.indb 654 3/13/18 4:19 PM

CHAPTER 41
Cardiac
P
harmacology
Miwa Geiger, MD, and Hari Rajagopal, MD
Introduction
The pharmacological management of pediatric cardiac patients is a complex and
constantly evolving field. When selecting the best drug for a patient, one must
not only try to identify a safe and effective medication but also recognize that this
population often requires individualized therapy, rather than a “one size fits all”
approach. However, physicians’ ability to make evidence-based treatment decisions
is limited by the relative lack of large-scale pharmacological studies in pediatrics.
Many of these medications can act at multiple sites, some with multiple
mechanisms of action, and should therefore be used with caution, especially in
combination with other drugs. This chapter presents a brief summary of the drugs
most commonly used in pediatric cardiology, which can serve as a foundation for
further inquiry and clinical therapeutic decision-making. A pediatric cardiologist
should be consulted before initiation of most of these medications, particularly if
the patient is known to have cardiac pathologic findings.
The most commonly used medications in pediatric cardiology are listed in
Box 41-1.
Heart Failure Treatment

Diuretics
Diuretics are a mainstay of anticongestive therapy because they acutely improve
symptoms of pulmonary and systemic vascular congestion from myocardial dys-
function or large left-to-right shunts by decreasing preload. Like most drugs used
655
CCIP.indb 655 3/13/18 4:19 PM

Box 41-1. Commonly Used Drugs in Pediatric Cardiology

1. Heart failure treatment
a. Diuretics
•• Loop: furosemide, ethacrynic acid, bumetanide
•• Thiazide: chlorothiazide, hydrochlorothiazide, metolazonea
•• Potassium sparing: spironolactone
b. Inotropes, chronotropes, vasopressors
•• Digoxin
•• Milrinone
•• Adrenergic agonists: dobutamine, dopamine, epinephrine, norepi-
nephrine, isoproterenol, phenylephrine, vasopressin
c. Systemic vasodilators
•• Angiotensin-converting enzyme inhibitors, angiotensin receptor
blockers, nitroprusside
d. β-blockers
•• Propranolol, metoprolol, atenolol, carvedilol
2. Pulmonary hypertension management
•• Nitric oxide, sildenafil, bosentan, prostacyclin, tadalafil, treprostinil
3. Arrhythmia treatment
•• Class I
—
—Subclass IA: procainamide, disopyramide
—
—Subclass IB: lidocaine, mexiletine
—
—Subclass IC: phenytoin, flecainide, propafenone
•• Class II, β-blockers: propranolol, esmolol, atenolol, nadolol,
metoprolol
•• Class III: amiodarone, sotalol, bretylium
•• Class IV, calcium channel blockers: verapamil, diltiazem
•• Other: adenosine and digoxin
4. Ductus arteriosus management
•• Prostaglandin E1
•• Indomethacin
5. Anticoagulation, platelet inhibition: aspirin, clopidogrel, warfarin,
enoxaparin, heparin
6. Other: atropine, calcium magnesium, potassium
a
Metolazone is a thiazide-like diuretic, though not truly a thiazide.
in pediatric heart failure, few pediatric data validate their use independently;
justification has come from extrapolation from adult studies. Cardiologists
rely on 3 general classes of diuretics: loop, thiazide, and potassium-sparing
diuretics (see Table 41-1). The combination of a loop or thiazide diuretic with a
potassium-sparing drug is common. Spironolactone, an aldosterone antagonist
with weak diuretic effect, is also thought to have additional effects on the
renin-angiotensin system, allowing for cardiac remodeling. Diuretics should
be used with caution when in combination with other antihypertensive agents
because this can result in hypotension, volume depletion, or renal insufficiency.
They cause electrolyte imbalances; therefore, serum electrolyte levels should be
checked before initiation of these medications and when adjusting doses.
656
CCIP.indb 656 3/13/18 4:19 PM

CCIP.indb 657
Table 41-1. Diuretics
Drug Pharmacology Dose Common Side Effects Comments
Furosemide Onset: PO: 0.5–4 mg/kg/dose every Dehydration Prolonged use in neonates may
IV: 5 min 4–24 h Hypotension cause nephrocalcinosis
PO: 30–60 min (maximum initial dose: 20 mg) Hypokalemia Consider hearing screening after
Reduces reabsorption IV bolus: 1–2 mg/kg/dose Hypochloremia frequent use in neonates
of Na+Cl-K+ at ascending every 6–12 hours (maximum Metabolic alkalosis
loop of Henle initial dose, 20 mg) Hyperglycemia
Hypercalciuria
Continuous infusion:
Ototoxicity
0.1–1.0 mg/kg/h
Chlorothiazide Onset: PO: 10–20 mg/kg/dose every Dehydration Synergistic with loop diuretics
IV: 5–10 min 12 h Hypokalemia Use with caution in patients with
PO: 1–2 h Hyponatremia severe renal disease or hepatic
Reduces reabsorption of Metabolic alkalosis dysfunction
Na+ in the distal tubule Hypercalcemia
Ototoxicity
Hydrochlorothiazide Onset: PO: 1–2 mg/kg/dose every Similar to Similar to chlorothiazide

PO: 60–120 min 12 h chlorothiazide
Mechanism similar to
chlorothiazide
Metolazone Onset: PO: 0.1–0.2 mg/kg/dose Hepatic dysfunction Often used after furosemide
PO: 60 min Maximum single dose, 5 mg Calcium retention therapy has been maximized
Mechanism similar to every 12–24 h Hypokalemia Use with caution in patients with
chlorothiazide Metabolic alkalosis hepatic dysfunction
Cardiac Pharmacology
Hyperglycemia
657
Continued
3/13/18 4:19 PM
Digoxin
IV, intravenous; PO, per os. Data from Engorn B, Flerlage J. The Harriet Lane Handbook: A Manual for Pediatric House Officers. 20th ed. Philadelphia, PA: Mosby Elsevier; 2015; and Severin PN, Awad
renal disease, with K+ supplemen-
Use with caution in patients with
Digoxin is a cardiac glycoside that has
tation or other K+-sparing drugs

Weak diuretic; often used with
historically been used to treat both congestive
heart failure (CHF) and arrhythmias. Digoxin
is a moderate inotrope that can improve
myocardial contractility and has been used in
the outpatient setting for mild to moderate
other diuretics
heart failure. It also has sympatholytic effects

Comments
that are thought to somewhat counteract the

maladaptive neurohormonal response to heart
failure. There are no randomized controlled
trials in which digoxin was used in the
Common Side Effects
management of pediatric heart failure, and no

studies in adults have demonstrated improved
Agranulocytosis
Gynecomastia
Hyperkalemia
survival in patients treated with digoxin. The

use of digoxin in treating pediatric heart
Nausea
failure from pulmonary overcirculation (where

Rash
systolic function is usually preserved) has

been controversial; many physicians no longer
prescribe it for this purpose. However, its use
Maximum single dose, 50 mg
in patients with a single right ventricle after

in children every 12–24 h
PO: 0.5–1.5 mg/kg/dose
S, Shields B, et al. The pediatric cardiology pharmacopeia: 2013 update. Pediatr Cardiol. 2013;34:1–29.
Norwood surgery has been associated with

improved interstage survival.1 The etiologic
origin for this improved survival is unclear,
though some suspect it could be due to
prevention of occult arrhythmias.
Dose
Digoxin has been used to treat arrhythmias

that occur because of a re-entrant mechanism:
It slows conduction in the atrioventricular
Table 41-1. Diuretics, continued
Competitive aldosterone
absorption and sodium

resulting in potassium
(AV) node, which can cause an interruption

Onset: Hours to days
the re-entrant circuit. It is often used for the

receptor blocker
Pharmacology
treatment of supraventricular tachycardia

(SVT) in neonates and infants.
excretion
In patients with atrial flutter or fibrillation,

digoxin has been used to achieve rate control
by blocking the response of the AV node. It
can be proarrhythmic because of its different
effects on the automaticity of atrial and
Spironolactone
ventricular tissue and a reduction in resting

membrane potentials.
Drug
658
CCIP.indb 658 3/13/18 4:19 PM

Mechanism of Action
The cellular effects are caused by binding of digoxin to sodium-potassium
adenosine triphosphatase, which inhibits the sodium pump and ultimately
increases intracellular calcium. The increased availability of calcium results in
improved myocardial contraction and an increased cardiac output. The electrical
effects are related to direct cellular effects on the action potential of myocardial
cells, as well as autonomic effects. The net result is an increased refractory period
at both the sinoatrial and AV nodes. Digoxin affects the autonomic nervous
system by increasing parasympathetic baroreceptor activity.
Adverse Effects
The more common side effects include sinus bradycardia, AV block, tach
yarrhythmia, nausea, anorexia, somnolence, and visual changes (“halo sign”)
(Table 41-2). Characteristic electrocardiographic findings include sinus brady-
cardia, PR interval prolongation, shortening of the QT interval, mild depression
of the ST segment, and flattening of the T wave, the latter 2 being a sign of
digoxin effect and not toxicity. There is increased risk of digoxin toxicity in patients
with renal impairment, hypokalemia, hypercalcemia, or hypomagnesemia.
Contraindications
Digoxin should not be used in patients with Wolff-Parkinson-White syndrome
because of its ability to shorten the accessory pathway effective refractory period
and potentially enhance antegrade accessory pathway conduction, allowing atrial
fibrillation to lead to ventricular fibrillation.
Drug Interaction
Amiodarone increases the serum concentration of digoxin by decreasing its elim-
ination; therefore, the dose is commonly reduced by 30% to 50%. Loop diuretics
should be used with caution because hypokalemia and hypomagnesemia can
bring on digoxin toxicity.
Milrinone
Milrinone has inotropic, lusitropic, and vasodilatory effects. It has a mild
chronotropic effect, as well. It is administered via continuous intravenous (IV)
infusion and is used to prevent or treat low cardiac output syndrome in patients
after cardiac surgery or in those with myocarditis or cardiomyopathy. Although
no data thus far have demonstrated improved outcomes in chronic heart failure,
it has been shown to reduce the incidence of low cardiac output when used
prophylactically in postoperative patients.2
Mechanism of Action
Milrinone specifically blocks cyclic nucleotide phosphodiesterase III, which
increases intracellular myocardial and vascular cyclic adenosine monophosphate.
This results in increased intracellular calcium concentration, which leads to
659
CCIP.indb 659 3/13/18 4:19 PM

CCIP.indb 660
660
Table 41-2. Digoxin
Drug Metabolism Dosing Side Effects Comments
Digoxin Onset: PO load: >24 h Nausea Contraindication: WPW,

PO: 30 min to 2 h Preterm infants, load 20 µg/kg Anorexia AV block, hypertrophic
IV: 5–30 min total Vision changes (“halo sign”) cardiomyopathy
Half-life: Term infants, load 30 µg/kg Sinus bradycardia Increased risk of digoxin
Preterm infants, 60–170 h total AV block toxicity with renal impairment,
Full-term infants, 35–45 h Children, load 40 µg/kg total Tachyarrhythmia hypokalemia hypercalcemia,
Toddlers, 18–25 h (Give one-half loading dose, ECG changes: sinus brady- and hypomagnesemia
Children, 35 h then give one-quarter of the cardia, prolonged PR interval, Amiodarone increases the
total dose for each of 2 sub- shortened QT interval, mild
Mechanism: Blocks Na+/K+ serum digoxin levels; reduce
sequent doses at 6- to 8-hour depression of the ST segment,
pump, leading to increases in digoxin dose by 30% to 50%

intervals; prior to additional and flattening of the T wave
intracellular Ca++ Patients taking loop diuretics:
doses, clinical response
Not removed with dialysis or should be fully evaluated) increased risk for digoxin
cardiopulmonary bypass toxicity if hypokalemic or
Maintenance:
hypomagnesemic
Preterm infants, 5–8 µg/kg/day
Term infants and children, 6–10 Toxicity usually associated with
µg/kg/day digoxin level >2 ng/mL
Intravenous dose approximately

75%–80% that of oral dose
AV, atrioventricular; ECG, electrocardiography; IV, intravenous; PO, per os; WPW, Wolff-Parkinson-White. Data from Engorn B, Flerlage J. The Harriet Lane Handbook: A Manual for Pediatric House
Officers. 20th ed. Philadelphia, PA: Mosby Elsevier; 2015; and Severin PN, Awad S, Shields B, et al. The pediatric cardiology pharmacopeia: 2013 update. Pediatr Cardiol. 2013;34:1–29.
3/13/18 4:19 PM
improved myocardial contractility, as well as relaxation (improves systolic and

diastolic function). It also causes systemic and—to some extent—pulmonary
vasodilation, which reduces the pressure the ventricles have to generate to eject
blood (afterload reduction).
Metabolism
Primarily excreted by the kidney, milrinone should be avoided in patients with
renal failure. The half-life is relatively long—2.5 hours in patients with CHF.
Contraindications
Use with caution in patients with any renal dysfunction (renal dosing), atrial
arrhythmias, hypotension, or known milrinone-induced thrombocytopenia.
Adverse Effects
More serious side effects include hypotension, ventricular arrhythmia, and
thrombocytopenia (Table 41-3).
Angiotensin-Converting Enzyme Inhibitors

Angiotensin-converting enzyme (ACE) inhibitors are used to treat heart failure,
often in conjunction with an inotrope, and to treat some types of hypertension.
In pediatrics, the most commonly used drugs of this class are captopril and enal-
april (Table 41-4). Enalapril has been shown to improve symptoms and survival
in adults with CHF3 and prolong development of symptoms in asymptomatic
adults with left ventricular dysfunction.4 In children, prospective studies have
been limited and have yielded conflicting results, although most children treated
Table 41-3. Milrinone

Drug Pharmacology Dosing Side Effects Comments
Milrinone Onset: IV 5–15 Infusion load: Ventricular Avoid or

min 50 mg/kg, arrhythmias adjust dose
Half-life: 2.5 h; over 10–15 Hypotension in patients
clearance min Thrombocytopenia with renal
increases (load can Hypokalemia dysfunction
linearly with be skipped Bronchospasm Half-life is
age if there is Transaminitis longer in
Primarily renal increased risk neonates
excretion for severe than in older
Phosphodiesterase hypotension) children
III inhibitor Maintenance:
0.25–1.0 mg/
kg/min
IV, intravenous. Data from Engorn B, Flerlage J. The Harriet Lane Handbook: A Manual for Pediatric House Officers.
20th ed. Philadelphia, PA: Mosby Elsevier; 2015; and Severin PN, Awad S, Shields B, et al. The pediatric cardiology
pharmacopeia: 2013 update. Pediatr Cardiol. 2013;34:1–29.
661
CCIP.indb 661 3/13/18 4:19 PM

CCIP.indb 662
662
Table 41-4. Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers
Captopril Onset: 15–60 min Neonates, initial dose of 0.05–0.1 mg/ Rash Caution: avoid with renal
Peak effect: 60–90 min kg (titrate dose to maximum, 0.5 mg/ Cough dysfunction
Duration: dose related kg/dose) every 8–24 Pruritus Contraindicated in pregnancy
Half-life: 1–12 h Infants and children, initial dose of Proteinuria
Drug interactions: potassium
0.15–0.5 mg/kg/dose (titrate dose to Neutropenia
Inhibits conversion of angiotensin I to supplements or potassi-
maximum, 6 mg/kg/day) Hyperkalemia
angiotensin II um-sparing drugs increase the
every 8–24 Tachycardia
risk of hyperkalemia
Hypotension
Enalapril Onset: PO: 0.05–0.1 mg/kg/dose initial PO Rash Caution: avoid or adjust the
PO: 30–60 min daily (titrate as required every 3–5 Cough dose in patients with renal
IV: 10–15 min days to maximum of 0.5 mg/kg/day) Pruritus failure
Peak effect: Adults, initial dose of 2.5 mg PO every Proteinuria Contraindications: idiopathic
PO 1 h 12–24 h Neutropenia or hereditary angioedema and

IV 15 min Hyperkalemia pregnancy
Tachycardia
Half-life: PO depends on age or Drug interactions: similar to
Hypotension
presence of CHF (2–10 h) captopril
Angioedema
Inhibits conversion of angiotensin I to Liver failure
angiotensin II Renal failure
Losartan Onset: 6 h PO: Flulike syndrome Contraindications: bilateral

Peak effect: 1 h Infants, not used Arthralgias renal artery stenosis; preg-
Half-life: 1–2 h Children (6–16 years old), 0.7 mg/kg Hyperkalemia nancy, breastfeeding
PO daily (maximum dose, 50 mg/day) Tachycardia Drug interactions: similar to
Angiotensin II receptor blocker
Adults, initial dose of 25–50 mg PO Hypotension captopril
daily (maximum dose, 100 mg PO Less likely to
twice daily) cause cough
CHF, congestive heart failure; IV, intravenous; PO, per os. Data from Engorn B, Flerlage J. The Harriet Lane Handbook: A Manual for Pediatric House Officers. 20th ed. Philadelphia, PA: Mosby Elsevier;
2015; and Severin PN, Awad S, Shields B, et al. The pediatric cardiology pharmacopeia: 2013 update. Pediatr Cardiol. 2013;34:1–29.
3/13/18 4:19 PM
for chronic cardiomyopathy are maintained on ACE inhibitors unless there

are contraindications.
In the largest study of infants with single-ventricle physiology, enalapril use
was not associated with improved outcomes (improved growth or degree of
heart failure),5 though it is still commonly used in this population.
Mechanism of Action
ACE inhibitors hinder the conversion of angiotensin I to angiotensin II (a
potent vasoconstrictor), resulting in reduced systemic blood pressure or afterload.
Adverse Effects
Adverse effects include chronic cough, hyperkalemia, renal failure, liver failure,
and neutropenia, among others (Table 41-4).
Angiotensin Receptor Blockers

As an alternative to the use of ACE inhibitors, angiotensin receptors can be
directly blocked to lower blood pressure. Losartan is the most commonly used
angiotensin receptor blocker in pediatrics. It can be used to treat hypertension
and heart failure and has also been used in patients with Marfan syndrome to try
to prevent progression of aortic dilatation. However, a multicenter randomized
control trial did not show the expected advantages of losartan over atenolol
for this indication; the rate of change in the aortic-root z score over the 3-year
period did not differ significantly.6
Angiotensin receptor blockers tend not to cause the dry cough associated
with ACE inhibitors, although they can cause hyperkalemia and hypotension.
Nitroprusside
Sodium nitroprusside is a potent vasodilator used for hypertensive emergencies
and for afterload reduction in postoperative cardiac patients because of the
controlled manner in which the medication can be titrated to effect.
Mechanism of Action
Nitroprusside causes a release of nitric oxide (NO) in the bloodstream, which
activates guanylyl cyclase, causing increased intracellular cyclic guanosine
monophosphate (GMP), leading to arterial and venous vasodilation.
Adverse Effects
Cyanide and thiocyanate toxicity can result from the use of nitroprusside;
thus, thiocyanate levels should be monitored. Other side effects are listed in
Table 41-5.
Adrenergic Agonists
The cardiac and vascular responses to adrenergic agonists are mediated by
several specific receptors; as a result, these drugs have multiple effects, including
663
CCIP.indb 663 3/13/18 4:19 PM

CCIP.indb 664
664
Table 41-5. Nitroprusside
Nitroprusside Onset: 1–10 min Infusion Nausea Caution: monitor thiocy-

Half-life: 2 min 0.2–10 mg/kg/min Sweating anate level if used >48 h;
Mechanism: causes Neonates, maximum dose Thiocyanate toxicity keep level <35 mg/L
NO release in vascular of 6 mg/kg/min Methemoglobinemia Drug is light sensitive
smooth muscle, leading Hypothyroidism
Contraindication: reduced
to increased cyclic gua- Hypotension
cerebral perfusion, renal
nosine monophosphate Metabolic acidosis
failure, left ventricular
Increased intracranial
production and resulting outflow tract obstruction

in vasodilation pressure
Metabolism: reacts with

hemoglobin, producing
the metabolites thiosulfate
and thiocyanate, which
are renally excreted
NO, nitric oxide. Data from Engorn B, Flerlage J. The Harriet Lane Handbook: A Manual for Pediatric House Officers. 20th ed. Philadelphia, PA: Mosby Elsevier; 2015; and Severin PN, Awad S, Shields B,
et al. The pediatric cardiology pharmacopeia: 2013 update. Pediatr Cardiol. 2013;34:1–29.
3/13/18 4:19 PM
inotropic effects, chronotropic effects, vasoconstriction, and vasodilatation. In

simple terms, stimulation of β1 receptors increases heart rate and contractility,
stimulation of β2 results in systemic vasodilatation in skeletal muscle, and activa-
tion of α1 receptors will cause systemic vasoconstriction. Dopaminergic receptors
in the splanchnic and renal vascular beds respond to dopamine by causing vaso-
dilatation in these tissues. These differences allow for tailoring to patient-specific
needs, yet in general, they are used to treat symptoms of circulatory instability
of various etiologic origins. Their short half-life allows their effects to be titrated
(see Table 41-6).
β-Blockers
In pediatrics, β-blockers are used for a variety of indications. They are often used
to treat arrhythmias of abnormal automaticity, especially those that are catechol-
amine driven and re-entry tachyarrhythmias. They slow spontaneous discharge
from the sinus node and reduce automaticity in other cardiac tissues. β-blockers
are used for arrhythmia prophylaxis in several channelopathies, including long
QT syndrome, chronic heart failure, hypertension, aortopathies, and dynamic
outflow tract obstruction.7 Patients with CHF have increased sympathetic
nervous system activity, and β-blocker therapy is thought to interfere with this
debilitating neurohormonal pathway by blocking the adrenergic response. There
are nonselective β1 and β2 blockers (eg, propranolol, nadolol), those selective
for β1 (eg, metoprolol, atenolol), and third-generation drugs with additional α
blockade and antioxidant effect (eg, carvedilol).
Propranolol has been used for prevention and treatment of hypercyanotic
episodes in patients with unrepaired tetralogy of Fallot (by reducing the heart
rate, allowing for more ventricular filling, thereby improving outflow to the
pulmonary artery). Similarly, it has been used in hypertrophic cardiomyopathy
to reduce outflow tract obstruction.
Carvedilol is a nonselective β-blocker and α-blocker that reduces blood pres-
sure without the side effect of reflex tachycardia. It is also an antioxidant and is
thought to play a beneficial role in cardiac remodeling. It is typically used to treat
heart failure from myocardial dysfunction. Some smaller studies have shown a
clinical improvement in children, although results from the largest randomized
trial did not definitively demonstrate an improvement in outcomes.8,9 The more
commonly used β-blockers are listed in Table 41-7.
Pulmonary Hypertension Management

Medical therapies are effective only in alleviating symptoms of pulmonary
hypertension and, thus far, are not curative. In the past 2 decades, the long-term
survival of children with pulmonary arterial hypertension (PAH) has improved
with the introduction of targeted pulmonary vasodilatory drug therapies.
665
CCIP.indb 665 3/13/18 4:19 PM

CCIP.indb 666
666
Table 41-6. Adrenergic Agonists
Dopamine Onset: 5 min Infusion Headache Contraindication: pheo-

Half-life: 2 min Low dose: 1–5 µg/kg/min Nausea chromocytoma, ventricular
Low dose stimulates Intermediate dose: 5–15 µg/kg/min Tachyarrhythmias (atrial arrhythmia
dopamine receptor (renal or ventricular)
High dose: 15–20 µg/kg/min
vasodilatation) Ectopic beats
Intermediate dose stimulates
β receptor (increases heart
rate and contractility)
High dose stimulates α
receptor (vasoconstriction)
Dobutamine Onset: 1–10 min Infusion Headache Contraindication: hyper-
Peak: 10–20 min 2–20 µg/kg/min Tachycardia trophic cardiomyopathy

Half-life: 2 min Max dose: 30–40 µg/kg/min Palpitation arrhythmias, hypertension
Stimulates β1 receptors Hypertension Less frequently used in
(increases heart rate and Angina children; causes tachy-
contractility) Atrial, ventricular cardia and increases the
arrhythmias myocardial oxygen demand
Epinephrine Onset: IV, IO: 1:10,000 Nausea Contraindication: acute

hydrochloride IV, 1–5 min 0.01 mg/kg (maximum, 1 mg) every Vomiting coronary artery disease,
SQ, 5–10 min 3–5 min Headache angle closure glaucoma
Stimulates α1, β1, β2 Endotracheal: 1:1,000 0.1 mg/kg Hypertension
receptors (increases heart (maximum, 2.5 mg) every 3–5 min Leukocytosis
rate, contractility and Decreased renal blood
SQ, IM:1,000 (0.01 mg/kg) (maxi-
vasoconstriction) flow
mum, 0.3 mg) every 5–10 min
Half-life: 2–3 min Tachyarrhythmias
Infusion: 0.05–1.0 µg/kg/min
3/13/18 4:19 PM
CCIP.indb 667
Table 41-6. Adrenergic Agonists, continued
Norepinephrine Onset: very rapid Infusion Headache Contraindication: pheo-

Half-life: 1–2 min 0.05–2.0 µg/kg/min Anxiety chromocytoma, severe
Stimulates α receptors Vomiting hypertension, ventricular
(vasoconstriction) Diaphoresis tachyarrhythmias, severe
Palpitation coronary artery disease
Hypertension
Chest pain
Respiratory distress
Phenylephrine Onset: IV: Headache Contraindication: pheo-
IV, immediate 5–20 µg/kg (maximum dose, 0.5 Tremor chromocytoma, severe
IM and SQ, 10–15 min mg) every 10–20 min Insomnia hypertension, ventricular
Half-life: SQ, IM: Sinus bradycardia arrhythmias
IV, 2.5 h 1.1 mg/kg (maximum dose, 5 mg) Palpitation Used for hypercyanotic
IM/SQ, 2.5 h every 1–2 h Hypertension “Tet” spells
Chest pain
Stimulates α receptors
Arrhythmias
(vasoconstriction)
Isoproterenol Onset: Continuous IV infusion Flushing Contraindication: ventricu-
IV, immediate 0.05–2.0 µg/kg/min, titrate to Chest pain lar arrhythmia
Half-life: 2.5–5 minutes response Tachyarrhythmia Used for bradycardia
Stimulates β receptors with Headache caused by AV block or
no α effects (increases heart Tremor sinus node dysfunction; is
rate and contractility) a temporary measure until
pacing can be instituted
AV, atrioventricular; IM, intramuscular; IO, intraosseous; IV, intravenous; SQ, subcutaneous. Data from Engorn B, Flerlage J. The Harriet Lane Handbook: A Manual for Pediatric House Officers.
20th ed. Philadelphia, PA: Mosby Elsevier; 2015; and Severin PN, Awad S, Shields B, et al. The pediatric cardiology pharmacopeia: 2013 update. Pediatr Cardiol. 2013;34:1–29.
667
3/13/18 4:19 PM
CCIP.indb 668
668
Table 41-7. Commonly Used β-Adrenergic Receptor Blockers
Drug Indications Pharmacology Dosing Side Effects Comments
Propranolol Supraventricular arrhythmias Onset: PO: 1–4 mg/kg/day, Hypoglycemia Use caution in lung
Dynamic outflow tract PO: 40–120 min divided into doses admin- Depression disease and heart,
obstruction: tetralogy IV: rapid istered every 6–8 h Bronchospasm hepatic, or renal
of Fallot or hypertrophic Nonselective Hypotension failure
cardiomyopathy β-blocker Bradycardia Contraindications:
Aortopathies Negative inotropic asthma, cardio-
Hypertension effect genic shock, and
Channelopathies, including heart block
long QT syndrome
Esmolol Infusion for emergent situa- Onset: rapid IV: Similar to propranolol Contraindication:
tions in patients with arrhyth- Selective β1-blocker Loading 500 µg/kg IV, cardiogenic shock
mia or severe hypertension followed by maintenance
of 50 µg/kg/min, titrate
to effect with gradual
increase
Metoprolol Heart failure, hypertension, Onset: 15–30 min PO initial: 1–2 mg/kg/day Similar to propranolol Contraindication:
also other indications as Selective β1-blocker Maximum dose: 6 mg/ similar to
listed for propranolol kg/day propranolol
Twice daily
3/13/18 4:19 PM
CCIP.indb 669
Table 41-7. Commonly Used β-Adrenergic Receptor Blockers, continued
Carvedilol Heart failure and Onset: Infants and children: Myalgia Contraindication:
hypertension α blockade, 30 min Initial dose: 0.03–0.08 Fatigue severe liver
β blockade, 60 min mg/kg/dose twice daily Peripheral edema dysfunction
α and β blocker (maximum initial dose, Hypotension
3.125 mg) Bradycardia
Half-life: 2–10 h
Maintenance dose: to be Bronchospasm
increased every 2 weeks Hyperglycemia
for average dose 0.3–0.9 Liver dysfunction
mg/kg/dose twice daily Microalbuminuria
(maximum dose, 25 mg
PO twice daily)
Atenolol Supraventricular arrhythmia Onset: oral <1 h, PO 0.5–1.0 mg/kg/day Bradycardia Use caution in
Channelopathies peak effect in 2–4 h once daily or every Hypotension bronchospasm and
Aortopathies Selective β1-blocker 12 hours Confusion asthma
Hypertension
Nadolol Supraventricular arrhythmia Similar to atenolol PO 0.5–1.0 mg/kg/day Similar to atenolol Similar to atenolol
Channelopathies including once daily
long QT syndrome
IV, intravenous; PO, per os. Data from Engorn B, Flerlage J. The Harriet Lane Handbook: A Manual for Pediatric House Officers. 20th ed. Philadelphia, PA: Mosby Elsevier; 2015; and Severin PN,
Awad S, Shields B, et al. The pediatric cardiology pharmacopeia: 2013 update. Pediatr Cardiol. 2013;34:1–29.
669
3/13/18 4:19 PM
Although recent treatment strategies in children have improved their prognosis

dramatically, the management of pediatric PAH remains challenging, with most
therapies based on expert opinion. Other than inhaled NO, which is licensed
for the treatment of newborns with persistent pulmonary hypertension of
the newborn and severe respiratory failure, there are no U.S. Food and Drug
Administration (FDA)–approved therapies for children with PAH.
Inhaled NO
Inhaled NO acts directly on the pulmonary arteries by increasing cyclic GMP,
which reduces intracellular calcium and causes vasodilatation. It is rapidly
metabolized and thus requires continuous administration and careful weaning.
It can displace hemoglobin and cause methemoglobinemia.
Sildenafil
Sildenafil is a phosphodiesterase 5 inhibitor that increases cyclic GMP, thus
causing pulmonary vasodilation. It is usually taken orally, but it is available for IV
use. It can also cause systemic vasodilation; therefore, hypotension and flushing
are side effects. Sildenafil and other pulmonary commonly used vasodilators are
described in more detail in Table 41-8.
Sildenafil has been used extensively in an off-label manner for the treatment
of PAH, although its use has been somewhat controversial. In 2012, on the basis
of a relatively large randomized trial, the FDA released a strong warning against
the use of sildenafil for pediatric patients with PAH and stated that children
who take high-dose sildenafil have a higher risk of death than children taking
a low dose, although the study did show an improvement in symptoms.10 In
2014, after publication of the second part of this randomized study,11 the FDA
clarified that the earlier warning was mainly against high-dose and chronic
use of sildenafil and that sildenafil may be considered in situations where the
benefits of treatment with the drug are likely to outweigh its potential risks. It
has also been used in patients with single ventricles who have undergone Fontan
palliation to improve physiology and exercise tolerance, as well as treat those
with failing Fontan palliation.12
Arrhythmia Treatment
Arrhythmia treatment (pharmacological or interventional) depends on numerous
factors: type of arrhythmia, age, duration, frequency, clinical presentation,
tolerance, and cardiac function. Ultimately, treatment should be determined by
a pediatric cardiologist and, in some cases, by an electrophysiologist. For hemo-
dynamically stable supraventricular arrhythmias, adenosine can be administered
initially by using the American Heart Association (AHA) Pediatric Advanced
Life Support algorithm, ideally with cardiology consultation thereafter for fur-
ther arrhythmic management. Children receiving antiarrhythmic drugs require
670
CCIP.indb 670 3/13/18 4:19 PM

CCIP.indb 671
Table 41-8. Commonly Used Drugs in Pediatric Pulmonary Hypertension
Nitric oxide Onset: rapid Continuous inhalation (face mask, a Methemoglobinemia Caution: risk of rebound
Direct vasodilator of pulmonary nasal cannula, or ventilator) pulmonary hypertension if
arteries leading to increased Neonates, children: 10–40 ppm not weaned
cyclic GMP and reduced (although doses >20 ppm are not Used to test pulmonary
intracellular calcium, causing shown to be more effective and may vasoreactivity during
smooth-muscle relaxation lead to adverse outcomes) cardiac catheterization
Duration: short
Sildenafil Onset: 15–30 min PO: Neonates and children, 1 mg/kg/ Headaches FDA warns against high
Phosphodiesterase 5 inhibitor dose every 6–8 h Flushing doses and long-term
that increases cyclic GMP → Hypotension therapy
reduced intracellular calcium → Anemia
smooth-muscle relaxation Leukopenia
Duration: 4 h
Bosentan Onset: variable with peak effect PO: Hepatic dysfunction Caution: potentially
in 3–5 h <10 kg: teratogenic—screen for
Endothelin receptor α- and Initial dose, 15.625 mg daily pregnancy
β-antagonist → inhibits Maintenance, 15.625 mg twice daily Safety and effectiveness
endothelin-mediated 10–20 kg: has not been well estab-
vasoconstriction Initial dose, 31.25 mg daily lished in pediatrics
Half-life: 5 h Maintenance, 31.25 mg twice daily Monitor liver function
21–40 kg:
Initial dose, 31.25 mg twice daily
Maintenance, 62.5 mg twice daily
671
Continued
3/13/18 4:19 PM
serial electrocardiographic (ECG)
Pediatric House Officers. 20th ed. Philadelphia, PA: Mosby Elsevier; 2015; and Severin PN, Awad S, Shields B, et al. The pediatric cardiology pharmacopeia: 2013 update. Pediatr Cardiol. 2013;34:1–29.
pulmonary hypertension if
FDA, Food and Drug Administration; GMP, guanosine monophosphate; IV, intravenous; PO, per os; ppm, parts per million. Data from Engorn B, Flerlage J. The Harriet Lane Handbook: A Manual for
examinations and close monitoring
Caution: risk of rebound

by a cardiologist because of adverse
effects, including proarrhythmic
effects.
not weaned
Comments
The most commonly used antiar-

Table 41-8. Commonly Used Drugs in Pediatric Pulmonary Hypertension, continued
rhythmic drugs in pediatrics are pro-

pranolol, digoxin, and amiodarone.13,14
The first 2 have already been reviewed
and are used mainly for SVT;
Thrombocytopenia
amiodarone is discussed herein.

The Vaughan Williams classifi-
Bronchospasm
Less systemic
Hypotension
hypotension
cation system of antiarrhythmics

Tachycardia
Side Effects
Chest pain
Bleeding
organizes the drugs by their basic

mechanism of action. Since this classi-
fication was developed, antiarrhythmic
therapies have expanded, and more is
understood about their actions. Some
Inhalation: 2.5 mg 5–9 times daily
of the more commonly used drugs are

IV: 0.001–0.002 µg/kg/min via
described in Table 41-9.
Amiodarone
continuous infusion
Indications
Amiodarone is a broad-spectrum anti-
arrhythmic that has increasingly been
Dosing
used to prevent and treat a variety

of arrhythmias, including re-entrant
SVT, ectopic atrial tachycardia,
Direct vasodilator of pulmonary
junctional ectopic tachycardia, and

Inhaled form of epoprostenol
ventricular arrhythmias.
Amiodarone is recommended in
the AHA Pediatric Advanced Life
Support protocol for shock-resistant
Pharmacology
Half-life: 3 min
ventricular tachycardia and ventric-

Onset: 6 min
vascular bed
ular fibrillation (a choice between

amiodarone and lidocaine is suggested
because one has not been proven over
the other to improve outcomes).15
Epoprostenol
Pediatric cardiologists often choose

this drug in combination with another
Iloprost
Drug
antiarrhythmic or as monotherapy for
672
CCIP.indb 672 3/13/18 4:19 PM

CCIP.indb 673
Table 41-9. Commonly Used Antiarrhythmic Drugs in Pediatricsa
Procainamide Sustained symptomatic Onset: IV load: 3–6 mg/kg/ Rash Caution: monitor for
or life-threatening IV: rapid dose, may repeat up to Myalgia hypotension during
ventricular tachycardia PO: 2–4 h 15 mg/kg; maximum Thrombocytopenia loading dose
Can be used in certain IM: 10–30 min dose, 100 mg/dose GI symptoms Contraindication:
cases of supraventricu- Class IA (Na++ channel Hypotension myasthenia gravis
lar tachycardia blocker) SLE-like symptoms and heart block
Positive Coombs test
Reference range in
result
serum: 4–10 µg/mL
ECG changes: prolongs
QRS and QT durations
Lidocaine Treatment of ventric- Onset: rapid IV: 1-mg/kg loading Hypotension Caution: hepatic
ular fibrillation and Class IA (Na++ channel dose, repeat after 5 min Nausea disease and heart
ventricular tachycardia blocker) as needed Seizures failure
Anxiety Contraindication: AV
Reference range in
Drowsiness block
serum: 1.5–5.0 µg/mL
Agitation
Flecainide Sustained VT, Onset: rapid PO: Proarrhythmia (VT or Caution: risk of
prevention of disabling Class IC (Na++ channel <6 mo, 50 mg/m2 BSA incessant supraventricular arrhythmia, including
SVT, atrial flutter or blocker) daily, twice or thrice arrhythmia) negative torsades de pointes
fibrillation (refractory daily inotropic effect Reduce dose by
Reference range in
and life-threatening >6 mo, 100 mg/m2 BSA Rash 25%–50% in renal
serum: 0.2–1.0 µg/mL
arrhythmias) daily, twice or thrice ECG changes: causes failure
daily with maximum prolongation of QRS Contraindication:
dose of 200 mg/m2 per duration second- or third-
day degree AV block
673
Continued
3/13/18 4:19 PM
CCIP.indb 674
674
Table 41-9. Commonly Used Antiarrhythmic Drugs in Pediatricsa, continued
Amiodarone Prevention and treat- Onset: 3 days to 3 PO loading: 5–10 mg/ Bradycardia Contraindications:
ment of multiple types wks, with oral load- kg/day (maximum dose, Hypotension AV block, sinus node
of arrhythmias, including; may see effect 1,600 mg) Corneal deposits dysfunction, and
ing supraventricular within 30 min with IV Maintenance: 2.5–5.0 Photosensitivity sinus bradycardia
arrhythmia, ectopic Class III (K+ channel mg/kg/day (maximum Pulmonary fibrosis
atrial tachycardia, blocker) dose, 800 mg) daily for Hypothyroidism
junctional ectopic 7–14 days Liver dysfunction
tachycardia, and Ataxia
Infusion load: 5 mg/kg
ventricular arrhythmias ECG changes: sinus
over 30–60 min; may
bradycardia, PR interval
repeat 4 times
prolongation, widening
Maintenance: 5–15 µg/
of QRS complex,
kg/min
and QT interval
prolongation
Sotalol VT and to maintain Onset: 2.5–4 h Consult electrophysiol- Proarrhythmic (VT or Caution: torsades de
sinus rhythm in Combined β-blocker ogist for dosage guide- supraventricular pointes
patients with atrial and class III lines and hospitalization arrhythmia Contraindication:
flutter or atrial Negative inotropic effect baseline pro-
fibrillation Hypotension longed corrected
ECG changes: causes QT QT interval and
interval prolongation heart block
3/13/18 4:19 PM
CCIP.indb 675
Verapamil Slows the ventricular Onset: PO: 2–8 mg/kg/day, up Dizziness Caution: Avoid use
rate in patients with PO: 60–120 min to 480 mg/day, divided Fatigue in neonates and
chronic atrial flutter or IV: rapid into doses administered Constipation young infants and in
atrial fibrillation Class IV (Ca++ channel every 8 h Negative inotropic effect patients with WPW
blocker) Hypotension due to hypotensive
reactions and
cardiac arrest
Contraindication:
CHF, shock, and AV
block
Atropineb Severe bradycardia Onset: rapid IV: 0.01–0.02 mg/kg Dry mouth Contraindication:
(vagal) Acetylcholine with minimum total dose Blurred vision glaucoma, tachycar-
antagonist of 0.1 mg and maximum Dry, hot skin dia, GI obstruction
total dose of 0.5 mg Difficult micturition
Endotracheal 0.04–0.06 Impaired GI motility
mg/kg, minimum single CNS symptoms
dose of 0.1 mg; a second
dose can be given if
indicated
Magnesium Torsades de pointes Onset: rapid IV: 25 to 50 mg/kg Depressed reflexes Caution: hypoten-
sulfate (maximum dose, 2 g) Flaccid paralysis sion and bradycardia
Respiratory failure with bolus dose
Hypotension Contraindication:
Bradycardia renal failure
Cardiac arrest
675
Continued
3/13/18 4:19 PM
CCIP.indb 676
676
Adenosine Termination of re-entry Onset: very rapid IV: rapid push followed Palpitations Caution: broncho-
SVT; can aid in the Half-life: seconds by saline flush of 0.1 mg/ Flushing spasm in asthmatics
diagnosis of other atrial kg/dose Headache
Slows AV node
arrhythmias Increase to 0.15 then Dyspnea
conduction
to 0.2 mg/kg/dose with Chest pain
successive doses Lightheadedness
Maximum dose is 0.3 Bradycardia
mg/kg, up to 12 mg
AV, atrioventricular; BSA, body surface area; CHF, congestive heart failure; CNS, central nervous system; ECG, electrocardiography; GI, gastrointestinal; IM, intramuscular; IV, intravenous; SLE,
systemic lupus erythematosus; SVT, supraventricular tachycardia; VT, ventricular tachycardia; WTW, Wolff-Parkinson-White. Data from Engorn B, Flerlage J. The Harriet Lane Handbook: A Manual for
a
β-blockers are presented in Table 41-7.
b
The American Heart Association no longer advises that atropine be used in asystole or pulseless electrical activity.
dia that have
Metabolism
Adverse Reactions
Mechanism of Action
PR interval prolongation,
period in myocardial cells.
of its ability to prolong the
ventricular contractility can
amiodarone include corneal

Hypotension and depressed
amiodarone is classified as a
However, it is also a sodium
tinuation of the medication.

calcium channel blocker and
than 1 month. Because of its

I, II, and IV antiarrhythmics.
The noncardiac side effects of

A potassium channel blocker,
occur with IV administration.
pulmonary interstitial fibrosis,

the liver; the half-life is longer
action potential and refractory
and QT interval prolongation.

The corresponding ECG find-
ings include sinus bradycardia,
Amiodarone is metabolized by
thyroidism, chemical hepatitis,

microdeposits, hyper- or hypo-
channel blocker, β-blocker, and
SVT, ectopic atrial tachycardia,
widening of the QRS complex,
high lipid solubility, drug levels

therefore has properties of class
peripheral neuropathy, skin dis-

coloration, and photosensitivity.
class III antiarrhythmic because
and junctional ectopic tachycar-
can persist months after discon-

been refractory to other therapies.
3/13/18 4:19 PM
Contraindications
AV block, sinus node dysfunction, and bradycardia are contraindications for the
use of amiodarone.
Drug Interactions
Amiodarone increases digoxin, flecainide, procainamide, quinidine, phenytoin,
and warfarin levels. Coadministration of other drugs that prolong the QT
interval increases the risk for torsades de pointes.
Adenosine
Adenosine can terminate re-entry SVT and can aid in the diagnosis of other
atrial arrhythmias that it does not terminate, such as atrial flutter.
Mechanism of Action
Adenosine is an endogenous purine nucleoside that blocks AV node conduction.
Administration
Adenosine is rapidly administered intravenously and immediately followed
with a saline flush. The most common reason for failure of adenosine to convert
to sinus rhythm is probably poor administration (not given as a rapid bolus),
resulting in complete metabolism by erythrocyte deamination prior to reaching
the heart. The dose can be doubled until an effect is seen or the maximum dose
is reached. One should print the ECG tracing before, during, and after admin-
istration. Resuscitation equipment, including a defibrillator, should be present
because new arrhythmias can occur at the time of conversion back to sinus
rhythm, including complex ventricular ectopy and fibrillation. Because adenosine
blocks the AV node, a brief period of asystole or AV block may be seen at ECG.
Metabolism
The rapid metabolism by deamination in erythrocytes results in a half-life less
than 10 seconds.
Adverse Effects
Bradycardia, palpitations, dyspnea, chest discomfort, headache, and flushing are
some adverse reactions. Asthmatics may have bronchospasm.
Drug Interactions
Dipyridamole potentiates and theophylline antagonizes the effects of adenosine.
Ductus Arteriosus Management

Prostaglandin E1
IV prostaglandin E1 directly causes vascular smooth-muscle relaxation and
prevents the neonatal ductus arteriosus from closing. It can sometimes cause
677
CCIP.indb 677 3/13/18 4:19 PM

the ductus to reopen if it has recently closed. It is used in the treatment of

ductal-dependent cardiac lesions.
Adverse Effects
Fever, apnea, flushing, and bradycardia are potential side effects. A secure airway
may be preferable in some newborns who are receiving prostaglandin E1 and
who require transport due to the possible risk of apnea. With chronic adminis-
tration, gastric obstruction and cortical hyperostosis can develop.
Indomethacin
Indomethacin is used to promote closure of the ductus arteriosus in premature
infants with excessive pulmonary blood flow.
Mechanism of Action
A nonsteroidal anti-inflammatory drug (NSAID), indomethacin inhibits
cyclo-oxygenase, reducing endogenous prostaglandin production. In the absence
of prostaglandins, the ductus arteriosus of a premature infant will often contract.
Adverse Reactions
As with other NSAIDs, indomethacin can cause gastric ulcers, reduced platelet
aggregation, and renal failure (see Table 41-10).
Contraindications
Indomethacin should not be used in patients with renal insufficiency, necrotizing
enterocolitis, thrombocytopenia, active bleeding, or clinically suspected ductal-
dependent heart defects.
Anticoagulation and Platelet Inhibition

Thrombosis prophylaxis and treatment guidelines in pediatric cardiac patients
are, like many others, largely based on smaller or nonrandomized studies
and on extrapolation from adult data due to a lack of randomized pediatric
studies. However, children, particularly those with congenital heart disease,
have differences in hemostatic regulation that can make their response to these
drugs unpredictable. Aside from perhaps aspirin use in Kawasaki disease, the
use of antiplatelet drugs and anticoagulants varies and is often dictated by the
cardiologist’s and/or the surgeon’s preference (see Table 41-11). In the 2013
AHA Scientific Statement on this topic, published data and expert opinions
were used to consolidate what is known and set out general guidelines.16 Infants
and children with systemic to pulmonary artery shunts are usually prescribed
low-dose aspirin for prophylaxis. Patients with single-ventricle physiology who
have undergone Fontan palliation and are at increased risk for thrombosis most
commonly take aspirin or warfarin, although this population still has a high
678
CCIP.indb 678 3/13/18 4:19 PM

Table 41-10. Drugs Used for Management of Patent

Ductus Arteriosus
Prostaglandin Direct effect Infusion Apnea Caution: risk of

E1 on vascular Initial: Fever apnea
smooth 0.05–0.1 µg/ Hypotension
muscles, kg/min Flushing
causing ductus Maintenance: Tachycardia
arteriosus 0.01–0.4 µg/ Pyloric
vasodilatation kg/min stenosis
Cortical
hyperostosis
Indomethacin Prostaglandin IV: 0.1–0.2 GI bleeding Contraindication:

synthesis mg/kg every Oliguria neonates with
inhibitor 12–24 h for 3 Renal failure renal failure,
doses Hepatitis thrombocytope-
nia, necrotizing
enterocolitis,
recent intraven-
tricular hemor-
rhage, or active
bleeding
GI, gastrointestinal. Data from Engorn B, Flerlage J. The Harriet Lane Handbook: A Manual for Pediatric House
Officers. 20th ed. Philadelphia, PA: Mosby Elsevier; 2015; and Severin PN, Awad S, Shields B, et al. The pediatric
cardiology pharmacopeia: 2013 update. Pediatr Cardiol. 2013;34:1–29.
rate of thrombus formation despite taking these medications. Patients with

mechanical valves are usually maintained on warfarin, with or without aspirin
or another platelet inhibitor. Patients with myocarditis or cardiomyopathy who
have left ventricular ejection fraction less than 45% can undergo anticoagulation
therapy with warfarin or low–molecular-weight heparin with or without aspirin,
depending on the situation. Chronic or recurrent atrial fibrillation with a history
of heart failure or stroke should be treated with warfarin as anticoagulation ther-
apy.16 In Kawasaki disease, in addition to treatment with IV immunoglobulin, a
high anti-inflammatory dose of aspirin is administered until fever has subsided
for 48 hours, followed by the lower antiplatelet dose for 6 to 8 weeks in the
absence of coronary abnormalities. Patients with coronary dilatation are contin-
ued on low-dose aspirin; those with giant aneurysms undergo anticoagulation
therapy with warfarin plus aspirin.17
Other Emergency Medications

Indications, dosing, and side effects of other emergency medications are listed in
Table 41-12.
679
CCIP.indb 679 3/13/18 4:19 PM

CCIP.indb 680
680
Table 41-11. Thrombosis Prevention and Anticoagulation
Aspirin Half-life: 15–20 PO GI bleeding Caution: possible risk of Reye
min Low dose: 5–10 mg/kg daily (thrombosis prophy- Bronchospasm syndrome in infants
Platelet inhibition laxis with shunts or Fontan procedure and after Tinnitus
achieved in 60 acute phase of Kawasaki disease for 6–8 weeks)
min High dose: 80–100 mg/kg every 6 to 8 h (acute
Prostaglandin inflammatory phase of Kawasaki disease)
synthesis inhibitor
Warfarin Half-life: 20–60 h PO: 0.2 mg/kg/dose; maximum dose, 5 mg Excessive bleeding Contraindications: pregnancy,
Inhibits synthesis Adjust to target INR: usually 2–3 except mechanical Necrosis of skin bleeding disorders, recent
of vitamin K– mitral valves (2.5–3.5) Hepatitis surgery
dependent factors Nausea Heparin and warfarin are
Vomiting overlapped for 4–5 days until

Hypersensitivity the warfarin has produced the
desired therapeutic response as
measured with INR
Heparin Half-life: 0.5–2.5 h IV bolus: 50–75 units/kg/dose Bleeding Caution: monitor the patient for
Binds to anti- Continuous infusion Allergy bleeding
thrombin III and Age: Heparin-induced Reversal agent: protamine
inactivates factors <12 mo: 28 units/kg/h thrombocyto-
II, X, XI, and XII 12 mo to 12 y: 20 units/kg/h penia
>12 y: 18 units/kg/h Osteopenia
Titrate dose by PTT, anti-Xa level

PTT: 1.5–3 times control
Anti-Xa level 0.35–0.7 units/mL
3/13/18 4:19 PM
Atropine
Caution: monitor the patient for
Reversal agent: protamine (only

Atropine is used as an emergency IV
GI, gastrointestinal; INR, international normalized ratio; IV, intravenous; PO, per os; PTT, partial thrombopolastin time. Data from Engorn B, Flerlage J. The Harriet Lane Handbook: A Manual for
treatment for bradycardia suspected to be
vagal in origin.
a partial reversal, 70%)
Mechanism of Action
Atropine is an acetylcholine antagonist
Comments
and therefore dampens parasympathetic

bleeding
tone, increasing the rate of sinoatrial

node firing, as well as conduction
through the AV node.
Dose
Table 41-11. Thrombosis Prevention and Anticoagulation, continued
Atropine is administered intravenously,

Side Effects
0.02 mg/kg (with a minimum dose of 0.1

Bleeding
mg and a maximum single dose of 1 mg).

Allergy
Adverse Reactions
Atropine can cause dry mouth, blurry
Titrate dose by anti-Xa peak level: 0.5–1.0 units/mL
vision, hyperthermia, urinary retention,

Daily or every 12 hours subcutaneous injection
impaired gastrointestinal motility, fatigue,

and confusion.
Contraindications
>2 mo: 0.5 mg/kg/dose every 12 h
Atropine is contraindicated in angle

closure glaucoma, gastrointestinal
obstruction, and uropathy.
<2 mo: 1.5 mg/kg/dose
>2 mo: 1 mg/kg/dose
Calcium
Prophylactic dose
Calcium chloride can be administered

intravenously to improve myocardial
contractility and increase systemic blood
Dosing
pressure. In the past, it had also been

Age:
used as a first-line treatment for cardiac

arrest, but the AHA no longer makes
inactivates factors
thrombin III and
this recommendation. Calcium is also

Half-life: 3–6 h
Pharmacology
Binds to anti-
used to treat patients with hyperkalemia

or hypocalcemia and patients receiving
X and II
large volumes of citrated blood products.

The hemodynamic effects of calcium are
more significant in the newborn, possibly
molecular
because of increased sensitivity of the

heparin
weight
Low–
Drug
immature myocardium to calcium and

lower intracellular calcium concentration.
681
CCIP.indb 681 3/13/18 4:19 PM

Table 41-12. Other Emergency Medications

Drug and Indication Dosing Side Effects
Calcium: Calcium chloride IV: 5–10 Bradycardia

Hypocalcemia mg/kg/dose for hypocal- Hypotension
Hyperkalemia cemia, 10–20 mg/kg/dose Skin necrosis
β-blocker toxicity for arrhythmias related to Contraindicated in ventricular
hypocalcemia, hyperka- fibrillation
lemia, hypermagnesemia,
and hypotension
Calcium gluconate
60–100 mg/kg
Magnesium: IV, IO: 25–50 mg/kg/dose; Flushing

Torsades de pointes if pulseless, administer as a Hypotension
Hypomagnesemia bolus; if pulse, administer
over 10–20 min
Potassium: Treatment of hypokalemia Extravasation can cause

Hypokalemia Oral 2–5 mEq/kg/day necrosis
IV 0.5–1.0 mEq/kg/dose Use with caution or avoid
(maximum dose, 40 mEq) use in patients with
predisposing conditions for
hyperkalemia (eg, severe
renal impairment)
IO, intraosseous; IV, intravenous. Data from Engorn B, Flerlage J. The Harriet Lane Handbook: A Manual for Pediatric
House Officers. 20th ed. Philadelphia, PA: Mosby Elsevier; 2015; and Severin PN, Awad S, Shields B, et al. The
pediatric cardiology pharmacopeia: 2013 update. Pediatr Cardiol. 2013;34:1–29.
Mechanism of Action
Intracellular calcium increases cardiac myocyte contractility and causes vascular
smooth-muscle vasoconstriction.
Dose
IV calcium chloride, 20 mg/kg, and calcium gluconate, 60 to 100 mg/kg, can
be used for hypocalcemia-induced hypotension and calcium channel blocker
toxicity.
Adverse Reactions
Calcium can cause severe skin necrosis, bradycardia, and asystole.
Contraindications
Calcium should be used with caution in the presence of digoxin, because it can
potentiate digoxin and result in toxicity.
682
CCIP.indb 682 3/13/18 4:19 PM

Key Points
•• While an abundance of medications are available to treat a variety of pediatric
cardiac disorders by improving symptoms, it has been hard to demonstrate
improvements in long-term outcomes for most of these drugs.
•• Large randomized trials are uncommon in pediatrics, and most guidelines are
based on limited published data, anecdotal experience, and extrapolation from
adult studies.
•• Children typically need higher doses of medications per unit weight and more
frequent dosing.
•• Drugs used safely in adults may have a different side effect profile in children
because of physiological immaturity, nonlinear association with body size, and
changing dynamics with rapid growth.
•• Pediatric cardiologists should be consulted prior to starting most cardiac
medications, with the exception of adenosine for SVT, which should be
administered in an emergency department or an intensive care unit setting.

•• CardioSmart (American College of Cardiology). www.cardiosmart.org
•• CredibleMeds (AZCert). www.crediblemeds.org
References
1) Oster ME, Kelleman M, McCracken C, Ohye RG, Mahle WT. Association of digoxin with
interstage mortality: results from the Pediatric Heart Network Single Ventricle Reconstruction
Trial public use dataset. J Am Heart Assoc. 2016;5(1):e002566
2) Hoffman TM, Wernovsky G, Atz AM, et al. Prophylactic intravenous use of milrinone after
cardiac operation in pediatrics (PRIMACORP) study. Prophylactic intravenous use of milrinone
after cardiac operation in pediatrics. Am Heart J. 2002;143(1):15–21
3) Yusuf S, Pitt B, Davis CE, Hood WB, Cohn JN; SOLVD Investigators. Effect of enalapril on
survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N
Engl J Med. 1991;325(5):293–302
4) Yusuf S, Pitt B, Davis CE, Hood WB Jr, Cohn JN; SOLVD Investigators. Effect of enalapril
on mortality and the development of heart failure in asymptomatic patients with reduced left
ventricular ejection fractions. N Engl J Med. 1992;327(10):685–691
5) Hsu DT, Zak V, Mahony L, et al; Pediatric Heart Network Investigators. Enalapril in infants
with single ventricle: results of a multicenter randomized trial. Circulation. 2010;122(4):333–340
6) Lacro RV, Dietz HC, Sleeper LA, et al; Pediatric Heart Network Investigators. Atenolol
versus losartan in children and young adults with Marfan’s syndrome. N Engl J Med.
2014;371(22):2061–2071
7) López-Sendón J, Swedberg K, McMurray J, et al; Task Force On Beta-Blockers of the European
Society of Cardiology. Expert consensus document on b-adrenergic receptor blockers. Eur Heart
J. 2004;25(15):1341–1362
8) Bruns LA, Chrisant MK, Lamour JM, et al. Carvedilol as therapy in pediatric heart failure: an
initial multicenter experience. J Pediatr. 2001;138(4):505–511
683
CCIP.indb 683 3/13/18 4:19 PM

9) Shaddy RE, Boucek MM, Hsu DT, et al; Pediatric Carvedilol Study Group. Carvedilol
for children and adolescents with heart failure: a randomized controlled trial. JAMA.
2007;298(10):1171–1179
10) Barst RJ, Ivy DD, Gaitan G, et al. A randomized, double-blind, placebo-controlled,
dose-ranging study of oral sildenafil citrate in treatment-naive children with pulmonary arterial
hypertension. Circulation. 2012;125(2):324–334
11) Barst RJ, Beghetti M, Pulido T, et al; STARTS-2 Investigators. STARTS-2: long-term survival
with oral sildenafil monotherapy in treatment-naive pediatric pulmonary arterial hypertension.
Circulation. 2014;129(19):1914–1923
12) Goldberg DJ, French B, McBride MG, et al. Impact of oral sildenafil on exercise performance in
children and young adults after the Fontan operation: a randomized, double-blind, placebo-con-
trolled, crossover trial. Circulation. 2011;123(11):1185–1193
13) Guerrier K, Shamszad P, Czosek RJ, Spar DS, Knilans TK, Anderson JB. Variation in
antiarrhythmic management of infants hospitalized with supraventricular tachycardia: a
multi-institutional analysis. Pediatr Cardiol. 2016;37(5):946–952
14) Seslar SP, Garrison MM, Larison C, Salerno JC. A multi-institutional analysis of inpatient
treatment for supraventricular tachycardia in newborns and infants. Pediatr Cardiol.
2013;34(2):408–414
15) de Caen AR, Maconochie IK, Aickin R, et al; Pediatric Basic Life Support and Pediatric
Advanced Life Support Chapter Collaborators. Part 6: Pediatric Basic Life Support and
Pediatric Advanced Life Support: 2015 International Consensus on Cardiopulmonary
Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations.
Circulation. 2015;132(16 Suppl 1):S177–S203
16) Giglia TM, Massicotte MP, Tweddell JS, et al; American Heart Association Congenital
on Cardiovascular and Stroke Nursing, Council on Epidemiology and Prevention, and Stroke
Council. Prevention and treatment of thrombosis in pediatric and congenital heart disease: a
management of Kawasaki disease: a statement for health professionals from the Committee on
Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease in the
Young, American Heart Association. Circulation. 2004;110(17):2747–2771
684
CCIP.indb 684 3/13/18 4:19 PM

CHAPTER 42
Transition and
Transfer From
Pediatric to
Adult-Centered
Cardiac Care
Mark D. Norris, MD, MS, and Adam Putschoegl, DO, FAAP
Introduction
Since the first surgical palliation of congenital heart disease (CHD) was performed
by Drs Blalock, Thomas, and Taussig in 1944, great advances in surgical and
medical care have allowed for drastically improved survival of those with CHD.
It is now estimated that more than 1.4 million adults and 1 million children in the
United States are living with CHD.1 Given this finding, it is crucial that transition
from pediatric to adult medical care is conducted in a systematic and effective
manner. However, this transition is often met with many challenges. This chapter
will cover the reasons for transition, optimal timing and preparation for transition,
and barriers to the process.
685
CCIP.indb 685 3/13/18 4:19 PM

Definitions
Although often incorrectly used interchangeably with “transfer,” “transition” is a
distinct concept, referring to the process of a “purposeful, planned process that
addresses the medical, psychological, and educational needs of adolescents and
young adults with chronic physical and medical conditions as they move from
child-centered to adult-oriented health care systems.”2 The goal of this process
is to move toward the more definitive act of transfer. This can be defined as a
physical change in providers and/or health care systems that can include new
locations, buildings, and ancillary support team members, including nurses, social
workers, and others. On the basis of these definitions, transition is a process
that typically plays out over many years, leading to transfer of care to an adult-
oriented setting. Ultimately, the act of transfer is an event that follows the initial
process of transition. However, the process of transition is not yet complete for
many patients, as they continue to mature and increase their understanding of
the adult system.
Importance of Transition and Transfer Systems

The magnitude of the transition and transfer of care needs for patients with
CHD has historically been underappreciated; only recently has a formal field
of adult congenital cardiology developed. Previously, most young adult patients
with CHD continued care with a pediatric cardiologist, sought out a general
adult cardiologist with limited knowledge of congenital conditions, or were
lost to cardiac follow-up.3 It is now estimated that the growth of this unique
population measures nearly 5% per year.4 The critical need for transition and
transfer has been increasingly recognized, as evidenced by recommendations
from the 2008 adult CHD guidelines published by the American College of
Cardiology and the American Heart Association. They outline a set of class I
recommendations, including a goal to “transition and ultimately transfer the
patient into adult care settings.”5
Transition of care has also been evaluated in other chronic diseases with clear
benefits.6,7 When transition and transfer preparation are not completed, studies
show a decline in attendance to medical follow-up visits at adult-centered
clinics, with increased morbidity.7,8
Transition Timing
Transition is not a single point in time. It is a process that involves many
steps that lead to the transfer of care to the adult system (Figure 42-1).9 The
goal is to “provide uninterrupted health care that is patient-centered, age and
developmentally appropriate, flexible, and comprehensive.”8 There is a paucity
of clinical trials in which the effectiveness of starting transition was tested at
different ages.10 However, it is generally believed that earlier is better, with
686
CCIP.indb 686 3/13/18 4:19 PM

Transition and Transfer From Pediatric to Adult-Centered Cardiac Care
Transition Process
Administration Preparation Transfer Follow-up

Institutional support Health education Identify adult Support
Resources Readiness provider continuity
assessment tool Meet adult practice of care
Transition
coordinator Transition plan Appropriate
Review transition Create health documentation
guidelines passport Choose transfer
Develop transition Promote self date
protocol management
Barriers
• Numerous team members • Peers and High Risk
• Patient development/maturity Behavior
• Parents/guardians • Patient and provider fears
• Pediatric care providers • Location
• Adult providers • Insurance
FIGURE 42-1. Transition process and barriers to transition. From Putschoegl A, Dipchand AI, Ross
H, Chaparro C, Johnson JN. Transitioning from pediatric to adult care after thoracic transplantation.
J Heart Lung Transplant. 2017;36(8):823–829.
some advocating discussions of lifelong continuity of cardiac care with families

shortly after birth and/or diagnosis.10 Beyond this, early adolescence is thought
to be the ideal time to initiate a formal transition plan, with most study authors
and published guidelines advocating for age 12;5,11–13 however, flexibility on the
basis of psychosocial maturity should be emphasized.8,14 Other investigators
have suggested that a transition and transfer plan is put into writing by age 14,
which, at a minimum, should include what services need to be provided, who
will provide them, and how they will be financed.8,15 If a patient has received
a diagnosis as a teenager, the discussions should begin as soon as the patient
is stable as an outpatient.16 Sudden transfer of care should be avoided during
a medical crisis.17 The physical transfer to an adult physician or other provider
is targeted to occur in earlier adulthood, often sometime between ages 18 and
21. Flexibility of this system is paramount and allows for different cognitive
and emotional maturation, neurocognitive development, family dynamics, and
adequacy of accessible adult care systems. Timing should balance the anticipated
progression in personal health care responsibility and autonomy with the risk of
gaps in care at the time of transfer.13
687
CCIP.indb 687 3/13/18 4:19 PM

Transition Preparation
The first steps in preparation are helping the patient and family understand
that lifelong congenital cardiac care is essential and that a transfer of care
will eventually occur. This can be framed as a positive graduation and not as
a loss of the pediatric team. The frequency of discussions of transition can
be dependent on psychosocial development, patient circumstances, and age
of initial treatment. As they age, children move from simplistic constructs to
more complex analytical models of explanations and action in their chronic
medical management.18 Importantly, major developmental milestones achieved
during adolescence are often underdeveloped in children with chronic medical
conditions.19 Neurodevelopmental effects of CHD and cardiac interventions
are the topic of much ongoing research and clinical program development.20–23
The cumulative effects of physical changes, peer and family relationships, and
academic challenges make adolescence a particularly vulnerable time for those
who are coping with chronic medical conditions.24
Adolescents are more likely to take ownership of their chronic medical
condition when they perceive a shared management between themselves, their
parents, and their health care providers.24 To foster this, institutions may use a
patient-specific readiness assessment tool to reveal areas of strength and weak-
ness, so education can focus on gaps in self-management and lay the groundwork
for transition.13 Such readiness assessment tools are under multicenter study but
have yet to be validated.
One to 2 years before the anticipated transfer of medical care, the pediatric
provider should inform patients and caregivers of the options for adult practices
for ongoing care. Whether there is 1 option or multiple options, the pediatric
provider should prepare appropriate summary documentation and facilitate
orientation and introduction to the adult practice and key team members.13
This practice has been shown to increase a patient’s sense of security.25 Physical
introduction to new facilities and providers may improve retention in care. Some
adult congenital cardiology groups have provided online video introductions and
facility tours.26
Promoting Self-Management
Self-management is the “active, daily, and flexible process in which youth and
their parents share responsibility and decision-making for achieving disease
control, health, and well-being through a wide range of illness-related activi-
ties.”24 Adolescents may have difficulties with medication scheduling, appearance
changes, and interruptions in routine due to the medical regimen, creating a
barrier to self-management.24
In 1 study, both patients and their parents expressed a goal of transition
to self-management.24 A review of successful transitions demonstrated
shared responsibility between parents and adolescents, with a gradual shift
688
CCIP.indb 688 3/13/18 4:19 PM

from parent-directed management to adolescent self-management. Younger

adolescents needed help in managing medications, and older adolescents needed
assistance with insurance issues and making appointments. Adolescents who
accepted ownership of their medical regimen and successfully incorporated it
into their day-to-day lives were more successful with self-management.24
The primary care physician or other provider also plays a vital role in
fostering self-management. A patient may only see their cardiologist once a
year but may require more frequent visits with their primary care physician for
non–cardiac-related sick visits or regular checkups. The primary care physician
can encourage patients to make their own appointments and attend the visits
without their parents or caregivers when developmentally appropriate. If the
patient experiences this approach both at the cardiologist’s office and with the
primary care physician, it is likely that the process of transition and transfer will
be increasingly effective.
Health Education
Health education during transition is critical. Patients with more knowledge
about their diagnosis have demonstrated better understanding of transition to
adult care.12 Topics to discuss with patients include basic disease knowledge,
medications and their side effects, symptoms that require urgent care, childbear-
ing and pregnancy concerns, dental and exercise recommendations, the effects
of high-risk behaviors, and long-term prognosis (Box 42-1). In addition, it is
critical to discuss disease effects on education, vocation, and insurability, and the
timing and frequency of follow-up (Box 42-2).5,12,27 Multiple team members can
engage the patient and family on these topics, as discussed in the next section.
It is critical to discuss pregnancy, sexuality, heredity (ie, the risk of disease for
offspring), and contraception openly, because patients may want to discuss these
topics but fear asking.2,28 These topics may be outside of the common practice
area for some pediatric providers, and a genetics or gynecology consultation may
be needed. Beginning in adolescence, a confidential portion of the routine visits
should be conducted without family members in the consultation room. These
confidential portions of the visits are usually well received by the family.
Barriers to a Successful Transition and Transfer

Numerous Team Members
The most important member of the health care team is the patient, who is
supported by various family members, caregivers, and friends. Numerous
medical personnel are involved, including pediatric and adult physicians, nurse
practitioners, physician assistants, surgeons, social workers, nurses, psychologists,
schedulers, and primary care providers, among others. With so many people
involved, the patient may become overwhelmed or overburdened with
689
CCIP.indb 689 3/13/18 4:19 PM

Box 42-1. Example of a Transition Intervention Protocol

Introduction to transition and its importance
Discussion of confidentiality and what it means when promoting trust with
the transition coordinator and nurse
Creation of a MyHealth passport,a including
•• Name of cardiac condition
•• Previous cardiac interventions
•• Name and purpose of medications
•• Need for endocarditis prophylaxis (yes/no)b
Discussion of 3 potential future cardiac complications (participant specific)
Review of contact names and location of local cardiologists who special-
ize in adult congenital heart disease
Introduction to websites such as ACHA, CCHA, Hospital for Sick Children
Good2Go program, and IHeartChange.org
Discussion of 3 brief third-person scenarios to address alcohol, smoking
and street drugs, and sexuality and contraception
Introduction of youth-oriented take-home written materials (sexually
transmitted infections, substance abuse)
Providing contact information to the transition coordinator and nurse
contact and encourage follow-up communication
ACHA, Adult Congenital Heart Association; CCHA, Canadian Congenital Heart Alliance.
a
A wallet-sized paper copy is provided to the participant in a plastic protective sheath, and an electronic copy is
e-mailed to the participant.
b
On the basis of chart-documented recommendation by the participant’s cardiologist.
navigating the system, leading to an unintended barrier to transition progress

and autonomy.
Given the numerous members of the health care team, the primary care
provider becomes exceedingly important because they are often the centerpiece
and the primary contact for the patient. They help in coordinating visits with
multiple subspecialists and often synthesize the information from each of these
providers in 1 central location.
Parental Care
Parents are the best advocates and allies in transitioning. However, a well-
intentioned parent may be hesitant to yield medical responsibility to their child. The
culture change between pediatric and adult care settings should not be underes-
timated. Adult providers, including primary care physicians and subspecialists,
often address the individual patient directly throughout the visit, leaving family
feeling excluded or their input marginalized. Adult providers voice surprise when
parents interject without allowing the patient to answer for themselves. Parents
may respond with distrust or discomfort with the new provider and health care
setting, feeling that their child might be less vigilant to health care needs and
690
CCIP.indb 690 3/13/18 4:19 PM

Transition and Transfer From P
ediatric to Adult-Centered Cardiac Care
Box 42-2. Transition Curriculum Topics

Residual hemodynamic considerations
•• Hemodynamic issues
•• Symptoms and how to respond
•• Diagnostic tools in follow-up
•• Management options
Arrhythmia considerations
•• Risks
•• Signs and symptoms
•• Screening tools
•• Diagnostic tools
•• Management options
Endocarditis considerations
•• Risks, implications, recognition, and response
•• Prevention
Contraception and pregnancy planning
•• Contraceptive options and risks
•• Risks of pregnancy to mother and fetus
•• Management of pregnancy plan
Noncardiac surgery considerations
•• Risks
•• Location of surgery
•• Knowledge and skills of the surgical and intensive care unit teams
Noncardiac medical problems
•• Access to appropriate care
Career, vocational, and insurance planning
•• Lifestyle issues
•• Marriage and family planning
•• Education
•• Employment
•• Life and health insurance
•• Learning disabilities
•• Anxiety and depression
•• High-risk behaviors
•• Healthy eating and physical fitness
•• Salt and fluid restriction (if warranted)
•• Relative safety of exercise and hobbies
End-of-life decisions
Skills training
•• Communication
•• Decision-making
•• Creative problem-solving
•• Assertiveness
•• Self-care
•• Self-advocacy
691
CCIP.indb 691 3/13/18 4:19 PM

receive suboptimal care.8 In 1 study, parents expressed more anxiety in contrast

to their children, who expressed more apathy.7 More than one-half of pediatric
patients perceive their parents as overprotective.29 If patients interpret this as a
lack of parental trust or confidence, the patient may in turn disengage from the
transition process.7 Thus, parents need counseling and support to encourage their
child to speak directly to the physician and engage in medical decision-making.
Despite parental concern, most teens actually prefer this direct and more
engaging approach.30,31 A higher level of psychosocial maturity and parental
fostering of autonomy are both associated with better perceived mental health
status and quality of life in adolesents.29 Patients need support from parents and
providers to develop independence, with transfer to an adult provider the natural
next step.28 Children can also get this support through support groups and
various online resources.8,12,32,33
Pediatric Care Providers

Health care providers play a crucial role in promoting gradual self-manage-
ment.32,33 A 2011 survey showed that many pediatricians are not aware of con-
sensus statements on transition and that most pediatric practices neither initiate
transition planning early in adolescence nor offer transition support services.13
Similarly, many care providers do not ask questions directly of the patient or
see them without their parents when it becomes developmentally appropriate.8
One significant predictor of follow-up at adult centers is attendance at pediatric
appointments without the parents (an indication that health care responsibility
has shifted).8 Despite these challenges, many cardiac patients maintain contact
with their primary care providers, yet there may be concomitant lapses in their
specialty care. These lapses are known to have detrimental effects on patient out-
comes.34 One of the primary reasons patients ultimately return to specialty care
is because of a recommendation from another provider.35 Primary care specialists
should continue to encourage follow-up with adult CHD specialists.
Success in transfer is directly related to pediatric specialists recommending
the transfer and the patient’s belief that care should be transitioned. This is espe-
cially important for the primary care provider because they may be the primary
point of contact for the patient or the only provider they see if there are lapses in
subspecialty care. They can emphasize the importance of reconnecting with their
cardiologist to facilitate a successful transfer of care and also discuss the need for
ongoing care of general adult comorbidities. Moons and colleagues showed that,
ultimately, adolescents consider it normal to leave pediatric specialties when they
reach adulthood.36 To further facilitate this process, each pediatric cardiology
program should identify a regional adult CHD center where their patients can
be referred.37
692
CCIP.indb 692 3/13/18 4:19 PM

Adult Care Providers

A successful transition program requires the active participation and interest of
the receiving adult service. However, adult providers may find it challenging to
care for a child with special health care needs when the patient lacks preparation
to be his or her own health advocate and when the referring physician sends
only minimal information about the patient.13 Adult providers may feel they
lack training in the care of adolescents and have difficulty meeting patients’
psychosocial needs and families’ high expectations.38 Many of these concerns can
be addressed with an appropriate and orderly transition process.39 Additionally,
this process should include transfer to specialized adult CHD providers, which
improves compliance with guidelines and overall outcomes.40,41
Peers and High-Risk Behaviors

As patients age, their primary social group will change from family to friends.
This may highlight differences patients feel when compared to medically healthy
friends. They may break from activities to take medications or self-regulate
exertion. They may struggle with different physical appearances. This can lead to
feelings of inadequacy, and to compensate, they may succumb to peer pressure
involving high-risk behaviors. To combat this, receiving consistent health
education throughout adolescence is critical. In addition, attendance at camps
for children with CHD can result in improved knowledge, adherence to therapy,
emotional well-being, self-esteem, and adaptation to illness.8
Some patients may feel as if they have been “cured.”8,42 This can portend
feelings of invincibility and of no longer needing to take medications or attend
health supervision visits while asymptomatic. On the other hand, some may
experience sadness in knowing they have decreased life expectancy and may
subsequently throw caution to the wind. Ultimately, patients show improved
resilience if a good network of friends and other support is established.16 Patients
have suggested having a mentor, such as a patient who has already navigated
transition and transfer.30
Patient and Provider Fears

Patients may have fear or anxiety of seeing an adult provider. Patients report
a feeling of the adult systems being less nurturing, busier, and more compli-
cated.7,25,28,43,44 Patients and parents may feel that child-centered care is more
familiar and comfortable and that they have built attachment for and feelings of
trust toward their pediatric providers.30 Some of this anxiety may be mirrored by
pediatric providers, who may be overprotective and attached to the patient and
family. They may also fear that the adult provider will undo decisions they have
made and that the patient may experience declining health because of this.8,43,45
693
CCIP.indb 693 3/13/18 4:19 PM

Despite these fears, patients are more likely to follow up with an adult provider
if they were referred by the pediatric provider.44 Patients report feeling reassured
when their pediatric providers showed trust in the adult care providers.30 To
strengthen this relationship, both adult and pediatric providers should be involved
in creating the transition program, which includes monitoring of patient follow-up.
The use of a standard “transition note” in the medical record has been suggested.43
This may include a concise medical summary and strategies for working with
and using the medical expertise of the young adult and his or her family.43
Moving Locations
Depending on the situation, transitions of care may occur within an institution
or may involve transfer to another health care system. If transfer is planned for
a distant clinic, adolescents and their families should make 1 visit to the adult
clinic prior to transfer. However, this transfer to a distant clinic is less ideal
because it has been shown to be a risk factor for gaps in care.35,46 Patients who
were most satisfied with their transition were those who had been transferred
to adult clinics within the same hospital and had met the providers before the
transfer.30 Additionally, patients who were an older age at their last pediatric visit
were more independent during these visits, kept their first and second appoint-
ments with their adult provider, and were less likely to have gaps in care.46
Insurance Issues
Insurance issues vary, depending on the country and the health care system in
question. In some countries, insurance coverage will be maintained throughout
the patient’s lifetime, while in others, patients may be required to obtain their
own insurance in early adulthood. In either case, the patient must understand
the insurance system as part of education during the transition process. Delays
in care due to insurance gaps have been described, leading to morbidity and
mortality in young adults with specialized health care needs.44
Key Points
•• The process of transition and transfer of care can be a complicated process
for patients with CHD and their families, but it is essential for maximizing
health, quality of life, and longevity.
•• Successful transition requires education, knowledge acquisition, self-
management skills, and uninterrupted cardiac care.
•• Transition protocols and programs have measurable benefits for young
patients and their parents—for example, improved follow-up, better disease
control, and improved documentation. Therefore, it is vital that transition is
conducted in a systematic and efficient manner to optimize patient outcomes
with collaboration between primary providers and cardiologists.
694
CCIP.indb 694 3/13/18 4:19 PM

References
1) Gilboa SM, Devine OJ, Kucik JE, et al. Congenital heart defects in the United States: estimating
the magnitude of the affected population in 2010. Circulation. 2016;134(2):101–109
2) Niwa K. Adults with congenital heart disease transition. Curr Opin Pediatr. 2015;27(5):576–580
3) Mackie AS, Ionescu-Ittu R, Therrien J, Pilote L, Abrahamowicz M, Marelli AJ. Children
and adults with congenital heart disease lost to follow-up: who and when? Circulation.
2009;120(4):302–309
4) Marelli AJ, Mackie AS, Ionescu-Ittu R, Rahme E, Pilote L. Congenital heart disease in the
general population: changing prevalence and age distribution. Circulation. 2007;115(2):163–172
5) Warnes CA, Williams RG, Bashore TM, et al; American College of Cardiology; American
Heart Association Task Force on Practice Guidelines (Writing Committee to Develop
Guidelines on the Management of Adults with Congenital Heart Disease); American Society
of Echocardiography; Heart Rhythm Society; International Society for Adult Congenital
Heart Disease; Society for Cardiovascular Angiography and Interventions; Society of Thoracic
Surgeons. ACC/AHA 2008 guidelines for the management of adults with congenital heart dis-
ease: a report of the American College of Cardiology/American Heart Association Task Force
on Practice Guidelines (Writing Committee to Develop Guidelines on the Management of
Adults with Congenital Heart Disease). Developed in Collaboration with the American Society
of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart
Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic
Surgeons. J Am Coll Cardiol. 2008;52(23):e143–e263
6) Crowley R, Wolfe I, Lock K, McKee M. Improving the transition between paediatric and adult
healthcare: a systematic review. Arch Dis Child. 2011;96(6):548–553
7) Anthony SJ, Martin K, Drabble A, Seifert-Hansen M, Dipchand AI, Kaufman M. Perceptions
of transitional care needs and experiences in pediatric heart transplant recipients. Am J
Transplant. 2009;9(3):614–619
8) Saidi A, Kovacs AH. Developing a transition program from pediatric- to adult-focused
cardiology care: practical considerations. Congenit Heart Dis. 2009;4(4):204–215
9) Schumacher KL, Meleis AI. Transitions: a central concept in nursing. Image J Nurs Sch. 1994;
26(2):119–127
10) McDonagh JE, Southwood TR, Shaw KL; British Society of Paediatric and Adolescent
Rheumatology. The impact of a coordinated transitional care programme on adolescents with
juvenile idiopathic arthritis. Rheumatology (Oxford). 2007;46(1):161–168
11) McDonagh JE, Kelly DA. Trans-plan-sition! Transplantation and transition. Pediatr Transplant.
2007;11(6):578–581
12) Harbison AL, Grady S Jr, Chi K, Fernandes SM. Provision of transition education and referral
patterns from pediatric cardiology to adult cardiac care. Pediatr Cardiol. 2016;37(2):232–238
13) Cooley WC, Sagerman PJ; American Academy of Pediatrics; American Academy of Family
Physicians; American College of Physicians; Transitions Clinical Report Authoring Group.
Supporting the health care transition from adolescence to adulthood in the medical home.
Pediatrics. 2011;128(1):182–200
14) Jordan A, McDonagh JE. Transition: getting it right for young people. Clin Med (Lond). 2006;
6(5):497–500
15) American Academy of Pediatrics; American Academy of Family Physicians; American College
of Physicians-American Society of Internal Medicine. A consensus statement on health care
transitions for young adults with special health care needs. Pediatrics. 2002;110(6 Pt 2):
1304–1306
16) Webb N, Harden P, Lewis C, et al. Building consensus on transition of transplant patients from
paediatric to adult healthcare. Arch Dis Child. 2010;95(8):606–611
695
CCIP.indb 695 3/13/18 4:19 PM

17) Knauth Meadows A, Bosco V, Tong E, Fernandes S, Saidi A. Transition and transfer from
pediatric to adult care of young adults with complex congenital heart disease. Curr Cardiol Rep.
2009;11(4):291–297
18) Kieckhefer GM, Trahms CM. Supporting development of children with chronic conditions:
from compliance toward shared management. Pediatr Nurs. 2000;26(4):354–363
19) Lopez KN, Karlsten M, Bonaduce De Nigris F, et al. Understanding age-based transition needs:
perspectives from adolescents and adults with congenital heart disease. Congenit Heart Dis. 2015;
10(6):561–571
20) Goldberg CS, Lu M, Sleeper LA, et al; Pediatric Heart Network Investigators. Factors
associated with neurodevelopment for children with single ventricle lesions. J Pediatr.
2014;165(3):490–496.e8
21) Marino BS, Cassedy A, Drotar D, Wray J. The impact of neurodevelopmental and psychosocial
outcomes on health-related quality of life in survivors of congenital heart disease. J Pediatr.
2016;174:11–22.e2
22) Marino BS, Lipkin PH, Newburger JW, et al; American Heart Association Congenital
Heart Defects Committee, Council on Cardiovascular Disease in the Young, Council on
Cardiovascular Nursing, and Stroke Council. Neurodevelopmental outcomes in children with
congenital heart disease: evaluation and management: a scientific statement from the American
Heart Association. Circulation. 2012;126(9):1143–1172
23) Marino BS. New concepts in predicting, evaluating, and managing neurodevelopmental
outcomes in children with congenital heart disease. Curr Opin Pediatr. 2013;25(5):574–584
24) Meaux JB, Green A, Nelson MK, et al. Transition to self-management after pediatric heart
transplant. Prog Transplant. 2014;24(3):226–233
25) Asp A, Bratt EL, Bramhagen AC. Transfer to adult care—experiences of young adults with
congenital heart disease. J Pediatr Nurs. 2015;30(5):e3–e10
26) Heart Change I. I Heart Change. 2016; https://iheartchange.org/welcome.aspx?ReturnUrl=%2f.
Accessed 20 December, 2016
27) Skorton DJ, Garson A Jr, Allen HD, et al. Task force 5: adults with congenital heart disease:
access to care. J Am Coll Cardiol. 2001;37(5):1193–1198
28) Burström Å, Öjmyr-Joelsson M, Bratt EL, Lundell B, Nisell M. Adolescents with congenital
heart disease and their parents: needs before transfer to adult care. J Cardiovasc Nurs. 2016;
31(5):399–404
29) Mackie AS, Rempel GR, Islam S, et al. Psychosocial maturity, autonomy, and transition
readiness among young adults with congenital heart disease or a heart transplant. Congenit
Heart Dis. 2016;11(2):136–143
30) Lugasi T, Achille M, Stevenson M. Patients’ perspective on factors that facilitate transition from
child-centered to adult-centered health care: a theory integrated metasummary of quantitative
and qualitative studies. J Adolesc Health. 2011;48(5):429–440
31) Williams RG. Fumbling the handoff: managing the transition to adult care for adolescents with
chronic conditions. J Adolesc Health. 2009;44(4):307–308
32) Gorter JW, Stewart D, Cohen E, et al; TRACE Study group. Are two youth-focused inter
ventions sufficient to empower youth with chronic health conditions in their transition to adult
healthcare: a mixed-methods longitudinal prospective cohort study. BMJ Open. 2015;5(5):
e007553
33) Nguyen T, Henderson D, Stewart D, Hlyva O, Punthakee Z, Gorter JW. You never transition
alone! Exploring the experiences of youth with chronic health conditions, parents and healthcare
providers on self-management. Child Care Health Dev. 2016;42(4):464–472
34) Yeung E, Kay J, Roosevelt GE, Brandon M, Yetman AT. Lapse of care as a predictor for morbid-
ity in adults with congenital heart disease. Int J Cardiol. 2008;125(1):62–65
696
CCIP.indb 696 3/13/18 4:19 PM

Transition and Transfer From P
ediatric to Adult-Centered C
ardiac Care
35) Gurvitz M, Valente AM, Broberg C, et al; Alliance for Adult Research in Congenital
Cardiology (AARCC) and Adult Congenital Heart Association. Prevalence and predictors
of gaps in care among adult congenital heart disease patients: HEART-ACHD (the Health,
Education, and Access Research Trial). J Am Coll Cardiol. 2013;61(21):2180–2184
36) Moons P, Pinxten S, Dedroog D, et al. Expectations and experiences of adolescents with
congenital heart disease on being transferred from pediatric cardiology to an adult congenital
heart disease program. J Adolesc Health. 2009;44(4):316–322
37) Said SM, Driscoll DJ, Dearani JA. Transition of care in congenital heart disease from pediatrics
to adulthood. Semin Pediatr Surg. 2015;24(2):69–72
38) Okumura MJ, Ong T, Dawson D, et al. Improving transition from paediatric to adult cystic fi-
brosis care: programme implementation and evaluation. BMJ Qual Saf. 2014;23(Suppl 1):i64–i72
39) Landzberg MJ, Murphy DJ Jr, Davidson WR Jr, et al. Task force 4: organization of delivery
systems for adults with congenital heart disease. J Am Coll Cardiol. 2001;37(5):1187–1193
40) Mylotte D, Pilote L, Ionescu-Ittu R, et al. Specialized adult congenital heart disease care: the
impact of policy on mortality. Circulation. 2014;129(18):1804–1812
41) Gerardin JFMJS, Menk JS, Pyles LA, Martin CM, Lohr JL. Compliance with adult congenital
heart disease guidelines: are we following the recommendations? Congenit Heart Dis. 2016;
11(3):245–253
42) Mackie AS, Islam S, Magill-Evans J, et al. Healthcare transition for youth with heart disease: a
clinical trial. Heart. 2014;100(14):1113–1118
43) Reiss JG, Gibson RW, Walker LR. Health care transition: youth, family, and provider perspec-
tives. Pediatrics. 2005;115(1):112–120
44) Bohun CM, Woods P, Winter C, et al. Challenges of intra-institutional transfer of care from
paediatric to adult congenital cardiology: the need for retention as well as transition. Cardiol
Young. 2016;26(2):327–333
45) Moodie D. Transition—a pediatric cardiology problem. Congenit Heart Dis. 2015;10(2):95
46) Goossens E, Bovijn L, Gewillig M, Budts W, Moons P. Predictors of care gaps in adolescents
with complex chronic condition transitioning to adulthood. Pediatrics. 2016;137(4):e20152413
697
CCIP.indb 697 3/13/18 4:19 PM

CCIP.indb 698 3/13/18 4:19 PM
PART 9
Special Conditions
43. Cardiac Transplantation........................................................701
44. Pulmonary Hypertension......................................................713
699
CCIP.indb 699 3/13/18 4:19 PM

CCIP.indb 700 3/13/18 4:19 PM
CHAPTER 43
Cardiac
ransplantation
T
Sharon Chen, MD, MPH, and Beth D. Kaufman, MD
Introduction
More than 500 pediatric heart transplantations are performed each year, with
most in North America and Europe.1 Survival after heart transplantation has
steadily improved since the 1980s (Figure 43-1). Based on the International
Society of Heart and Lung Transplantation (ISHLT) 2016 annual report, the
FIGURE 43-1. Kaplan-Meier survival for pediatric heart transplant recipients according to era.
NA = not available. From reference 1.
701
CCIP.indb 701 3/13/18 4:19 PM

median posttransplant survival was 20.7 years for infants, 18.2 years for children
aged 1 to 5 years, 14.0 years for those aged 6 to 10 years, and 12.7 years for
those aged 11 to 17 years (Figure 43-2).1 Pediatric heart transplant recipients
require lifelong immunosuppression and close monitoring of graft function and
adverse events. Despite posttransplant complications, overall quality of life and
functional status are good, with more than 80% of survivors reporting normal
activity or minor limitations in strenuous activity and quality of life metric
scores comparable to those of normative populations.1–3
Immunosuppression
Pediatric heart transplant recipients require lifelong immunosuppression, and
most take a combination of immunosuppressive agents. Complications and side
effects from these medications are not trivial and require constant monitoring.
Table 43-1 lists common immunosuppressive agents used in pediatric heart
transplantation and associated side effects. Some side effects require treatment
with additional medications, such as calcium channel blockers for hypertension,
insulin for diabetes, and magnesium replacement for hypomagnesemia. Renal
toxicity is a common side effect of several immunosuppressive agents, and when
combined with pretransplantation acute renal injury from prior cardiac surgeries
or heart failure, many pediatric heart transplant recipients develop chronic renal
disease. All immunosuppressive agents increase the risk for infections and may
require infection prophylaxis.
FIGURE 43-2. Kaplan-Meier survival for pediatric heart transplant recipients according to age at
time of transplantation (1982–2014). From reference 1.
702
CCIP.indb 702 3/13/18 4:19 PM

Table 43-1. Common Immunosuppressive Agents Used

in Pediatric Heart Transplant Recipients
Medication Side Effects
Tacrolimus Diabetes, hypertension, renal toxicity, hypercholesterol-

emia, PRES
Cyclosporine Hirsuitism, gingival hyperplasia, renal toxicity, hypertension,

hypercholesterolemia, PRES
Mycophenolate Gastrointestinal distress, bone marrow suppression, birth

mofetil defects
Prednisone Hypertension, weight gain, diabetes, Cushingnoid features,

bone fractures, behavioral changes
Sirolimus, everolimus Impaired wound healing, hypercholesterolemia, oral ulcers,

rhabdomyolysis, restrictive lung disease (bronchiolitis
obliterans organizing pneumonia)
Azathioprine Pancytopenia
PRES, posterior reversible encephalopathy syndrome.
Posterior reversible encephalopathy syndrome (PRES) is an uncommon but

potentially fatal condition associated with immunosuppressive medications,
notably cyclosporine and tacrolimus. PRES manifests as seizures, headaches,
altered consciousness, visual disturbances, and hypertension. It is diagnosed by
means of magnetic resonance imaging, with findings of white matter edema in
the posterior cerebral hemispheres, particularly the parieto-occipital regions.
PRES requires prompt recognition, because it is usually reversible with removal
of the offending agent and treatment of hypertension.
Certain immunosuppressive agents, such as tacrolimus, cyclosporine, and
sirolimus, require monitoring of serum drug levels. Drug levels can be altered
by other medications; thus, medication interactions should be considered when
prescribing new medications, especially antibiotics. Drug levels can also be
altered by certain foods (for example, grapefruit increases tacrolimus and cyclo-
sporine levels), and transplant recipients may be counseled to take medications
on an empty stomach. Common pediatric gastrointestinal illnesses may impair
absorption of immunosuppression medications, and closer monitoring of drug
levels during illness may be needed until gastrointestinal symptoms resolve.
Inability to absorb immunosuppression medications during a gastrointestinal
illness may require hospital admission for intravenous administration of
immunosuppression agents.
703
CCIP.indb 703 3/13/18 4:19 PM

Acute Rejection
Rejection is one of the most important morbidities associated with pediatric
heart transplantation and one of the leading causes of death in pediatric heart
transplant recipients.4 Acute rejection is mediated through both T cell and
humoral immune mechanisms and can be characterized as cellular rejection
or antibody-mediated rejection. As shown in Tables 43-2 and 43-3, rejection
is classified on the basis of pathologic examination of endomyocardial tissue
obtained from biopsy.5,6
Table 43-2. ISHLT Classification of Acute Cellular

Rejection
Gradea Histologic Findings
0 No acute rejection
1R (1A) Focal interstitial and/or perivascular infiltrate without myocyte damage
1R (1B) Diffuse interstitial and/or perivascular infiltrate without myocyte damage
1R (2) Focal interstitial and/or perivascular infiltrate with up to 1 focus of

myocyte damage
2R (3A) Two or more foci of infiltrate with associated myocyte damage
3R (3B/4) Diffuse infiltrate with multifocal myocyte damage

From reference 5.
Based on 2004 International Society of Heart and Lung Transplantation (ISHLT) classification (1990 ISHLT classifi
a
cation is shown in parentheses).
Table 43-3. ISHLT Pathologic Classification of

Antibody-Mediate Rejection
Grade Definition
AMR 0: No AMR Histologic and immunopathologic studies both have

negative findings
AMR 1 (H+): histo- Histologic findings are present and immunopathologic
pathologic AMR alone findings are negative
AMR 1 (I+): immuno- Histologic findings are negative and immunopathologic

pathologic AMR alone findings are positive (CD68 positive and/or C4d positive)
AMR 2: pathologic AMR Histologic and immunologic findings are both present
AMR 3: severe patho- Interstitial hemorrhage, capillary fragmentation, mixed

logic AMR inflammatory infiltrates, endothelial cell pyknosis, and/or
karyorrhexis, and marked edema and immunopathologic
findings are present
AMR, antibody-mediated rejection; ISHLT, International Society of Heart and Lung Transplantation. From reference 6.
704
CCIP.indb 704 3/13/18 4:19 PM

Presentation
Presentation for acute rejection can range from no or minimal signs and
symptoms to frank hemodynamic collapse. Most rejection episodes in pediatric
heart transplant recipients are asymptomatic.7 Thus, anyone caring for pediatric
heart transplant recipients should have a high index of suspicion for rejection
and a low threshold for pursuing further testing for rejection. Infants may
present with decreased activity, irritability, or poor feeding. Older patients may
complain of flu-like symptoms without fever. Congestive heart failure symptoms
in pediatric transplant recipients can be nonspecific, and include orthopnea,
shortness of breath, fatigue, nausea, emesis, and decreased appetite. Examination
findings include tachycardia, tachypnea, presence of gallop, hepatomegaly, ascites,
and edema.
Diagnosis
The standard of reference for diagnosis of acute rejection is an endomyocardial
biopsy.8 However, in the setting of high suspicion and clinical concern,
treatment for rejection is often initiated even without biopsy confirmation.
Echocardiography can be useful in diagnosing rejection: While many heart
transplant recipients have abnormal echocardiography findings at baseline,
a finding of newly reduced systolic or diastolic function, new or increased
valve regurgitation, and/or pericardial effusion is suggestive of rejection.
Electrocardiographic (ECG) findings of rejection include low voltages or
new-onset supraventricular or ventricular arrhythmias. Some investigators
suggest that serum biomarkers, such as B-type natriuretic peptide and troponin,
can aid in excluding severe rejection.9 Serum gene expression profiling to identify
rejection is available but not well validated in children.10
Treatment
Treatment for rejection depends on severity classification and whether there
is hemodynamic compromise. Specific treatment strategies also vary by center.
In general, asymptomatic mild cellular rejection (grade 1R) generally does not
require treatment, given the high rate of spontaneous improvement and lack of
association with graft survival and outcome. Symptomatic rejection episodes
require treatment with increased immunosuppression and, often, hospital
admission. Commonly, a short course of high-dose steroids is given. Target
serum immunosuppression levels may be increased and/or a switch made to a
different immunosuppressive agent. Ongoing or refractory cellular rejection
may require therapies such as antilymphocyte therapies (for example, anti
thymoglobulin antibodies), total body lymphoid irradiation, and photopheresis.
Antibody-mediated rejection may be treated with corticosteroids, intravenous
immunoglobulins, plasmapheresis, and monoclonal antibody therapies such
as rituximab.
705
CCIP.indb 705 3/13/18 4:19 PM

Prognosis
On the basis of data from the Pediatric Heart Transplant Study, almost one-half
of all pediatric heart transplant recipients will experience at least 1 episode of
rejection within 5 years of transplant, with the highest risk during the first year.4
Rejection is one of the most common causes of death in heart transplant recip-
ients.4 Those who have experienced rejection are also at increased risk of overall
mortality, graft coronary artery disease, and subsequent rejection episodes.8 Late
rejection has been shown to be associated with noncompliance.8 Thus, while
survival outcomes after pediatric heart transplantation are favorable, any medical
provider for pediatric heart transplant recipients should maintain a high index
of suspicion for diagnosing rejection.
Infection
Infection is an important source of morbidity and mortality for pediatric heart
transplant recipients. Within the Pediatric Heart Transplant Study database,
infection is the second most common cause of death, after rejection.4 More
than 40% of pediatric heart transplant patients experience a serious infection,
defined as requiring intravenous antibiotics or hospitalization, within 5 years of
transplantation.4 Bacterial infections are most common (60% of all infections),
followed by viral (31%), fungal (7%), and protozoal (2%).11 Certain infections
in pediatric heart transplant recipients that warrant special consideration are
discussed herein.
Cytomegalovirus
Cytomegalovirus (CMV) infection merits special consideration not only because
it is the most common single infectious agent identified after pediatric heart
transplantation but also because it is associated with increased risk of rejection,
coronary allograft vasculopathy (CAV), and graft failure.8 Primary CMV infec-
tion and CMV reactivation disease both cause a wide constellation of symptoms,
including fever, leukopenia, thrombocytopenia, pneumonia, myocarditis,
hepatitis, gastrointestinal symptoms, and retinitis. Transplant recipients most at
risk for CMV disease are seronegative recipients of a seropositive donor. CMV
prophylaxis is commonly used, typically with oral valganciclovir.
Epstein-Barr Virus
Like CMV, Epstein-Barr virus (EBV) disease can be caused by primary infec-
tion or reactivation of disease. Transplant recipients most at risk are seronegative
recipients with a seropositive donor. EBV can cause a spectrum of symptoms,
including mononucleosis-like syndrome and polyclonal lymphoproliferation.
Most importantly, EBV is associated with the development of posttransplant
lymphoproliferative disease (PTLD), discussed separately in this chapter.
706
CCIP.indb 706 3/13/18 4:19 PM

Fungal Infections
While fungal infections account for only 7% of all infections in pediatric patients
with heart transplants, mortality after fungal infection is high, with 42% survival
at 6 months after a fungal infection.12 Candida species account for 66% of fungal
infections, followed by Aspergillus (16%) and Pneumocystis jirovecii (13%).12
Prophylaxis for Candida and P jirovecii is commonly administered in the first
few months after transplant.
Immunizations
Pediatric heart transplant recipients are at increased risk for vaccine-preventable
diseases. Every effort should be made to ensure that patients who are waiting for
a heart transplant are up to date on vaccinations prior to transplantation. After
transplantation, inactivated vaccines are safe to administer, and routine pediatric
vaccinations, with the exception of live vaccines, should be administered as
scheduled. Administration of live attenuated virus vaccines is contraindicated
after transplant, given the risk of vaccine-related infection due to immunocom-
promised state. Table 43-4 lists recommendations from the American Society of
Transplantation for vaccinations for pediatric solid-organ transplant recipients.13
Given the concern for inadequate vaccine response while highly immunosup-
pressed in the early posttransplant period, most centers wait 3 to 6 months
between transplantation and reinitiation of vaccinations. The exception is the
inactivated influenza vaccination, which can be safely administered 4 weeks
after transplantation.14 Family members and close contacts should also receive
standard immunizations, including yearly influenza vaccination. In general, non-
live vaccines are preferred for household members, although the risk of actual
transmission of disease after live vaccination in family members is low.13
Coronary Allograft Vasculopathy

CAV, or graft vasculopathy, refers to diffuse luminal narrowing of the coronary
arteries and microvasculature due to intimal wall thickening, as opposed to
vessel narrowing due to atherosclerotic plaques and related thrombi that occlude
coronary blood flow in atherosclerotic disease. CAV develops over time and
leads to myocyte ischemia. Ongoing ischemic injury leads to graft dysfunction
and a risk of sudden death. Per the 2016 ISHLT Registry report, freedom from
CAV is 86% 5 years after heart transplantation and 66% 10 years after heart
transplantation.1
Presentation
Presentation of CAV can range from asymptomatic to congestive heart failure
to sudden death. Symptoms related to systolic or diastolic cardiac dysfunction,
such as dyspnea on exertion, fatigue, gastrointestinal symptoms, and/or loss of
707
CCIP.indb 707 3/13/18 4:19 PM

Table 43-4. List of Recommended Vaccinations for

Solid-Organ Transplant Recipients
Inactivated or Recommended Recommended
Vaccine Live Attenuated Before Transplant After Transplant
Influenza Inactivated Yes Yes
Influenza Live attenuated No No
Hepatitis B Inactivated Yes Yes
Hepatitis A Inactivated Yes Yes
Pertussis Inactivated Yes Yes
Diphtheria Inactivated Yes Yes
Tetanus Inactivated Yes Yes
Inactivated polio Inactivated Yes Yes
Haemophilus influenzae Inactivated Yes Yes
Streptococcus Inactivated Yes Yes

pneumoniae
Neisseria meningitidis Inactivated Yes Yes
Human papillomavirus Inactivated Yes Yes
Rabies Inactivated Yes Yes
Varicella Live attenuated Yes No
Rotavirus Live attenuated Yes No
MMR Live attenuated Yes No

MMR, measles, mumps, and rubella. Adapted from reference 13.
appetite, may occur—as may palpitations and/or syncope related to arrhythmias.

Typical anginal ischemic chest pain is often not reported because of the denerva-
tion of the transplanted heart.
Diagnosis
CAV is suspected in transplant recipients with abnormal cardiac function,
regional wall motion abnormality at echocardiography, ischemic changes at
ECG, arrhythmias, and/or hemodynamic abnormalities at catheterization with-
out evidence of rejection (which may present similarly). Coronary angiography
is diagnostic and may demonstrate focal or diffuse narrowing of proximal or
distal vessels. Intravascular ultrasonography can also be used to visualize vessel
narrowing in larger children. Nuclear perfusion imaging is also performed at
some centers.
708
CCIP.indb 708 3/13/18 4:19 PM

Treatment
Statins and changes in immunosuppression regimen are common medical
interventions with a diagnosis of CAV for immunomodulatory effects. While
percutaneous coronary interventions with stent implants may be attempted for
focal lesions, these interventions typically provide relatively short-term palliation,
because CAV is a progressive diffuse disorder that eventually requires another
heart transplant. Prevention strategies for CAV vary amongst heart transplant
programs. Initiation of statin therapy for potential beneficial anti-inflammatory
and immunologic effects is common as routine posttransplant management.
Other therapies, such as coronary vasodilators, are also used.
Prognosis
CAV continues to be one of the primary causes for late graft failure and death
in children, with 2-year graft survival after diagnosis of CAV between 50% and
75% on the basis of age group.1 From analysis of cause of death of pediatric heart
transplant recipients from the ISHLT registry from 1998 to 2010 (n = 9,248),
mortality from CAV increases over time, with a prevalence of 3%, 5%, and 8%
at 5 years, 10 years, and 20 years after transplantation, respectively. Overall, CAV
accounted for 11% of all deaths in pediatric heart transplant recipients.15
Posttransplant Malignancy
Malignancy is a known risk of being in an immunocompromised state that
affects all solid-organ transplant recipients. The incidence of malignancy
increases over time, with a cumulative rate of 10% in pediatric heart transplant
recipients alive 10 years after transplantation per the 2016 ISHLT registry
report.1 PTLD accounts for more than 90% of all malignancies in pediatric heart
transplant recipients.16 PTLD is a lymphoma that may have intra- or extranodal
manifestation. It is typically a B cell proliferation related to T cell suppression.
Primary EBV infection in the milieu of T cell immunosuppression has been
most consistently associated with the risk for PTLD.17
Presentation
PTLD can manifest anywhere there is lymphoid tissue. The most common sites,
in order of frequency, are the tonsils and adenoids, manifesting as hypertrophy
with related nasal and/or upper airway symptoms; the gastrointestinal tract,
with presentation varying from intestinal obstruction to volvulus, perforation, or
persistent diarrhea; and the lungs, manifesting as cough or airway obstruction.
PTLD may also manifest as diffuse adenopathy or with an isolated rapidly
enlarging mass, such as an inguinal or cervical lymph node. Constitutional
symptoms, such as fever, fatigue, diaphoresis, and weight loss, may occur.
709
CCIP.indb 709 3/13/18 4:19 PM

Diagnosis
Diagnosis varies, depending on site of involvement. Full-body computed
tomography and positron emission tomography are commonly used modalities.
Biopsy of the affected site is necessary to confirm diagnosis and specify PTLD
type. A World Health Organization categorization for PTLD has been
established and includes early lesions and polyclonal, monoclonal, and Hodgkin-
type lymphomas.
Treatment
Treatment is specific to the type of malignancy and ranges from reduction in
immune suppression therapy as initial intervention for early lesions to advanced
oncologic protocols. Pediatric oncologists with expertise in lymphoma typically
manage therapy. New chemotherapy regimens based on monoclonal antibody
therapies against B cell surface markers, such as rituximab, are contributing to
improved outcomes.17 Advancements in cytotoxic therapies are also underway.
Prognosis
In a 2015 ISHLT analysis of pediatric heart transplant recipients, the preva-
lence of mortality from malignancy was 4% 20 years after transplantation.15
The prognosis, though, is specific to the type of malignancy. An important
treatment-related morbidity of PTLD and other malignancies is rejection in
the setting of reduced immunosuppression, infections, and end-organ toxicities
related to oncologic treatment.
Ongoing Care
Pediatric heart transplant recipients often have complex medical histories and
comorbidities that involve long-term follow-up with multiple subspecialists.
The underlying diagnoses prior to heart transplantation often require continued
management after transplantation. For example, recipients with a history
of congenital heart disease, particularly heterotaxy syndrome, may also have
asplenia, gut malrotation, and/or ciliary dyskinesia. Recipients with a history of
cardiomyopathy may have underlying myopathies or genetic disorders. Most
heart transplant recipients have a history of prior cardiac surgeries and prolonged
hospitalizations, which can contribute to neurodevelopmental, behavioral, and
psychosocial concerns.
Pediatric heart transplant recipients should receive all routine pediatric
care. Somatic growth needs to be monitored closely, because many recipients
may have feeding difficulties due to prolonged hospitalizations and aspiration
risks, and growth may be stunted from side effects of long-term steroid
use. Neurodevelopmental screening assessments should be performed and
findings addressed. Advocacy within the school system is important to provide
710
CCIP.indb 710 3/13/18 4:19 PM

individualized education plans as needed, support intermittent absences due to

medical appointments and hospitalizations, and provide appropriate infection
control, such as notification of varicella outbreaks or other scenarios in which
immunocompromised students are at increased risk. It is also important to
prevent excessive limitations on the heart transplant recipient, most of whom
have normal functional status and no exercise-related restrictions on their
physical activity. Ongoing collaboration between heart transplant specialists,
other subspecialists, and primary care physicians is of utmost importance in the
successful long-term care of pediatric heart transplant recipients.
Key Points
•• Pediatric heart transplant recipients are surviving longer, with good quality of
life and functional status.
•• Pediatric heart transplant recipients require lifelong immunosuppression and
ongoing surveillance for rejection, infection, CAV, and malignancies.
•• Common childhood illnesses can manifest atypically, while conversely,
symptoms of typical childhood illnesses could indicate the presence of an
underlying heart transplant complication, such as rejection or malignancy;
thus, pediatric heart transplant recipients with symptoms or other issues
should be evaluated thoroughly.
•• Pediatric heart transplant recipients frequently have other comorbidities
due to underlying diagnoses or complex medical history; close collaboration
between primary care physicians, subspecialists, and heart transplant specialists
is critical for successful management.

•• Scientific Registry of Transplant Recipients. www.srtr.org
•• United Network for Organ Sharing. www.unos.org
•• Pediatric Heart Transplant Study (University of Alabama at Birmingham).
www.uab.edu/medicine/phts
References
1) Rossano JW, Dipchand AI, Edwards LB, et al; International Society for Heart and Lung
Transplantation. The Registry of the International Society for Heart and Lung Transplantation:
Nineteenth Pediatric Heart Transplantation Report-2016; Focus Theme: Primary Diagnostic
Indications for Transplant. J Heart Lung Transplant. 2016;35(10):1185–1195
2) Hollander SA, Chen S, Luikart H, et al. Quality of life and metrics of achievement in long-term
adult survivors of pediatric heart transplant. Pediatr Transplant. 2015;19(1):76–81
3) Pollock-BarZiv SM, Anthony SJ, Niedra R, Dipchand AI, West LJ. Quality of life and function
following cardiac transplantation in adolescents. Transplant Proc. 2003;35(7):2468–2470
4) Dipchand AI, Kirk R, Mahle WT, et al. Ten yr of pediatric heart transplantation: a report from
the Pediatric Heart Transplant Study. Pediatr Transplant. 2013;17(2):99–111
711
CCIP.indb 711 3/13/18 4:19 PM

5) Stewart S, Winters GL, Fishbein MC, et al. Revision of the 1990 working formulation for the
standardization of nomenclature in the diagnosis of heart rejection. J Heart Lung Transplant.
2005;24(11):1710–1720
6) Berry GJ, Burke MM, Andersen C, et al. The 2013 International Society for Heart and Lung
Transplantation Working Formulation for the standardization of nomenclature in the pathologic
diagnosis of antibody-mediated rejection in heart transplantation. J Heart Lung Transplant.
2013;32(12):1147–1162
7) Mills RM, Naftel DC, Kirklin JK, et al. Heart transplant rejection with hemodynamic
compromise: a multiinstitutional study of the role of endomyocardial cellular infiltrate. Cardiac
Transplant Research Database. J Heart Lung Transplant. 1997;16(8):813–821
8) International Society for Heart and Lung Transplantation. ISHLT Monograph Series, Vol 2:
Pediatric Heart Transplantation. Elsevier; 2007
9) Hill DA, Drazner MH, de Lemos JA. Do established biomarkers such as B-type natriuretic
peptide and troponin predict rejection? Curr Opin Organ Transplant. 2013;18(5):581–588
10) Deng MC, Eisen HJ, Mehra MR, et al; CARGO Investigators. Noninvasive discrimination
of rejection in cardiac allograft recipients using gene expression profiling. Am J Transplant.
2006;6(1):150–160
11) Schowengerdt KO, Naftel DC, Seib PM, et al; The Pediatric Heart Transplant Study Group.
Infection after pediatric heart transplantation: results of a multiinstitutional study. J Heart Lung
Transplant. 1997;16(12):1207–1216
12) Zaoutis TE, Webber S, Naftel DC, et al; Pediatric Heart Transplant Study Investigators.
Invasive fungal infections in pediatric heart transplant recipients: incidence, risk factors, and
outcomes. Pediatr Transplant. 2011;15(5):465–469
13) Danzinger-Isakov L, Kumar D, Infectious Diseases AST; AST Infectious Diseases Community
of Practice. Guidelines for vaccination of solid organ transplant candidates and recipients. Am J
Transplant. 2009;9(Suppl 4):S258–S262
14) Cordero E, Manuel O. Influenza vaccination in solid-organ transplant recipients. Curr Opin
Organ Transplant. 2012;17(6):601–608
15) Vanderlaan RD, Manlhiot C, Edwards LB, Conway J, McCrindle BW, Dipchand AI. Risk
factors for specific causes of death following pediatric heart transplant: an analysis of the
registry of the International Society of Heart and Lung Transplantation. Pediatr Transplant.
2015;19(8):896–905
16) Chinnock R, Webber SA, Dipchand AI, Brown RN, George JF; Pediatric Heart Transplant
Study. A 16-year multi-institutional study of the role of age and EBV status on PTLD incidence
among pediatric heart transplant recipients. Am J Transplant. 2012;12(11):3061–3068
17) Haynes SE, Saini S, Schowengerdt KO. Post-transplant lymphoproliferative disease and other
malignancies after pediatric cardiac transplantation: an evolving landscape. Curr Opin Organ
Transplant. 2015;20(5):562–569
712
CCIP.indb 712 3/13/18 4:19 PM

CHAPTER 44
Pulmonary
H
ypertension
Kristin Anton, RN, MSN, CPNP-AC, and
Bibhuti B. Das, MD, FAAP, FACC
Definition, Classification, and Epidemiology

Pulmonary hypertension is present when resting mean pulmonary artery pressure
(mPAP) exceeds 25 mm Hg in children at sea level who are more than 3 months
of age. However, the lack of increased mPAP does not exclude the presence of
pulmonary hypertensive vascular disease (PHVD) in some settings, including
congenital heart disease (CHD). In the setting of CHD, particularly with
single-ventricle physiology, other parameters obtained during right-sided heart
catheterization, such as pulmonary vascular resistance and transpulmonary pressure
gradient, are important to establish a diagnosis of pulmonary hypertension.1

Pediatric pulmonary hypertension is currently classified in a similar fashion
to adult pulmonary hypertension, on the basis of the 2013 revision of the World
Health Organization (WHO) classification.2 Because pediatric pulmonary
hypertension is distinct from adult pulmonary hypertension in several ways, the
pediatric task force of the Pulmonary Vascular Research Institute proposed a novel
system, the modified Panama classification, which may be more useful for children
(see Box 44-1).3

Pulmonary hypertension in children is a rare disease; the exact incidence and
prevalence are unknown. From various registries, the prevalence of pulmonary
hypertension is estimated to be <1 per 100,000 children, with an incidence of 1 to
2 new cases per million children per year.4–6
713
CCIP.indb 713 3/13/18 4:19 PM

Box 44-1. Modified Panama Classification of Pulmonary

Hypertension in Children
Prenatal or developmental PHVD, such as congenital diaphragmatic hernia
Perinatal pulmonary vascular maladaptation to various perinatal insults,

including chorioamnionitis
Congenital heart disease with left-to-right shunt lesions (endocardial

cushion defect, ventricular septal defect, patent ductus arteriosus, atrial
septal defects, etc)
Bronchopulmonary dysplasia
Idiopathic pulmonary arterial hypertension
Pulmonary hypertension in syndromic patients (eg, Down syndrome)
Parenchymal lung disease
Chronic thromboembolic diseases
All causes of alveolar hypoxia
Miscellaneous: collagen vascular disease, HIV infection, toxins, etc

PHVD, pulmonary hypertensive vascular disease. Adapted from reference 3.
Etiologic Origins
In children, idiopathic pulmonary arterial hypertension and pulmonary
hypertension associated with CHD constitute most cases. Cases of pulmonary
hypertension associated with connective tissue diseases are relatively rare in
childhood. Pulmonary hypertension in children is distinct from adult pulmonary
hypertension in several ways. Most importantly, pulmonary hypertension in
children is intrinsically linked to issues of lung growth and development, includ-
ing many prenatal and early postnatal influences.7 The causes of pulmonary
hypertension in children can be categorized into 5 broad groups: pulmonary
hypertension associated with CHD—increased pulmonary blood flow (as seen
with large left-right shunt lesions); pulmonary hypertension associated with
respiratory diseases and/or hypoxia; pulmonary hypertension associated with left
side of the heart–associated diseases; idiopathic pulmonary arterial hypertension;
and miscellaneous.
Pathophysiology
Pulmonary hypertension is an angioproliferative pulmonary vasculopathy, char-
acterized by loss of normal endothelial function, abnormal response of vascular
714
CCIP.indb 714 3/13/18 4:19 PM

Pulmonary Hypertension
smooth muscle cell to stimuli, and activation of multiple molecular pathways.8 In

normal pulmonary artery vasculature, smooth muscle tone is balanced by natural
homeostatic mechanisms governed by genes, vasodilators (prostacyclin and nitric
oxide [NO]), and vasoconstrictors (thromboxane A2 and endothelin-1), which
balance each other.9 Transforming growth factor gene is a gene that has long
been implicated in tissue repair, connective tissue growth, control and production
of cytokines, synthesis of endothelin, ion channel regulation, and angiogenesis.
In genetically susceptible individuals, when there is insult to pulmonary vascula-
ture in the form of shear stress or stretch, all the components of the pulmonary
artery (endothelium, smooth muscle cells, and fibroblasts) react excessively.
This reaction results in an imbalance between vasodilator and vasoconstrictor
mediators, causes a defect in potassium ion channels, and increases synthesis
of inflammatory mediators, which results in vasoconstriction, thrombosis, and
remodeling (distal extension of smooth muscle into small peripheral, normally
nonmuscular pulmonary arteries).10 Thus, pulmonary hypertension is associated
with conditions that cause chronic vasoconstriction, thrombosis, and abnormali-
ties of vessel function.
In children with lung and respiratory diseases, reduced alveolar oxygen
tension (alveolar hypoxia) induces vasoconstriction by reducing NO production
and increases endothelin production.11 Acidosis markedly causes vasocon-
striction, acting synergistically with hypoxia. High altitude (with low alveolar
oxygen tension) is associated with pulmonary vasoconstriction (and pulmonary
hypertension), for which a large species and individual variation exists.12
Children with pulmonary hypertension may present with shortness of breath,
exercise intolerance, and failure to thrive. They may experience chest pain,
chronic cough, hemoptysis, and recurrent syncope. The most frequent initial
presenting symptom in idiopathic pulmonary hypertension and pulmonary
hypertension associated with CHD is dyspnea on exertion. Near syncope or
syncope is a marker of severe disease and is more frequently seen in patients
with idiopathic pulmonary hypertension and familial pulmonary hypertension.
Cyanosis is only seen in patients with clinically significant lung disease or
intracardiac right-to-left shunting (Eisenmenger physiology). Infants may
present with irritability, failure to thrive, poor feeding, or tachypnea. Establishing
the diagnosis of pulmonary hypertension in children remains difficult because
their presentation is often nonspecific. Because of variable presentation and
often-nonspecific symptoms, a high index of suspicion is required to improve
the time to diagnosis in children.
715
CCIP.indb 715 3/13/18 4:19 PM

General Approach to Care of Children With

The care of a child with pulmonary hypertension begins with the child and the
child’s family or caregivers. Ideally, a major partner for the child and family
will be a specialty team of pulmonary hypertension–focused clinicians with
experience in the comprehensive management of children with pulmonary
hypertension.13 Therefore, the best approach will be collaboration among
multiple medical disciplines. Those required to collaborate can be linked in part
to the various causes of pulmonary hypertension in children. For example, in
the neonatal intensive care unit (NICU), patients with underlying pulmonary
pathologic processes may require a collaborative approach among NICU
providers, pulmonologists, and pediatric cardiologists. In contrast, the young
child with CHD in the cardiac care unit may require a cardiothoracic surgeon,
cardiologists, intensivists, and cardiac anesthesiologists. An older child with
connective tissue disease (miscellaneous cause of pulmonary hypertension) and
pulmonary hypertension will require rheumatology expertise. In this sense, the
care of a child with pulmonary hypertension involves a wide variety of medical
expertise, and thoughtful communication is imperative to be successful.
However, the care of a child with pulmonary hypertension extends well
beyond individuals with medical expertise. Auxiliary hospital or communi-
ty-based resources may aid in providing age-appropriate supportive care to
the child and family. For example, dietitians with expertise in children with
cardiopulmonary disease offer valuable contributions because growth and
nutrition are critical components of pulmonary hypertension care in children.
Meanwhile, child-life experts will assist in supporting the child and siblings
in the understanding of the disease process on a developmentally appropriate
level. Individuals with expertise in palliative care approaches guide health care
providers and families in complicated discussions pertinent to goals of care and
end-of life issues. Social workers, especially within the community, contribute to
provide the best school environment, arrange transport for the families, and help
advocate for the child to receive necessary resources.
Care of the child with pulmonary hypertension is complicated and requires
active communication between the child’s primary care physician (PCP), teach-
ers, physical exercise leaders and coaches, and school health nurses. The PCP is
the vital team leader for management of the child with pulmonary hypertension
related to acute illness, routine child care visits, and routine and specialty
vaccinations, such as influenza, respiratory syncytial virus, and pneumococcal
vaccinations. PCPs may also provide resources such as serial laboratory moni-
toring or refer the patient for psychosocial support, as appropriate. Education
and involvement of PCPs, school nurses, and local emergency response teams
can help to proactively address these problems. For example, aside from
disease-specific complications such as syncope, therapeutic side effects may
716
CCIP.indb 716 3/13/18 4:19 PM

include challenges such as headache, nausea, vomiting, and diarrhea at home

and at school. As a result, the care of the child with pulmonary hypertension is a
complicated orchestra, typically coordinated by pulmonary hypertension–focused
clinicians but requiring an integrated team approach.
Some pulmonary hypertension–specific medications have a substantial effect
on quality of life, and delivery of medication can be logistically complex. The
issues that need to be considered for continual infusion (prostacyclin and its
derivatives) include how best to carry it with them at all times without discon-
tinuation of therapies and the fact that continued monitoring of indwelling
central lines and subcutaneous infusions may be associated with marked pain
at insertion sites. Meanwhile, limitations on daily activities require vigilance,
such as with swimming, participation in sports, and general bathing. All of
these aspects of care not only require special training for the families and local
care providers but also highlight the importance of education for all individuals
who have routine contact with children. The patient survival guide published
by the Pulmonary Hypertension Association is valuable for patients, families,
nurses, physicians, and anyone else involved with children who have this disease
(the latest updates are available at www.phassociation.org. PHA offers monthly
telephone support groups for patients, caregivers, and parents. Parents can also
find a support group in their community by going to www.PHAssociation.org/
FindaSupportGroup.
Diagnosis and Assessment

A diagnostic workup algorithm for children with pulmonary hypertension is
shown in Figure 44-1. The first step toward diagnosis is to perform a physical
examination and obtain a history, including onset and duration of symptoms;
heart defect(s); previous surgeries; birth history, including prematurity and
chronic lung disease; sleep disorders; history of gastroesophageal reflux;
medications; and any toxin ingestion (such as cocaine, methamphetamine, and
anorexigens). A thorough family history should also be obtained to explore
whether hereditary factors may contribute to the child’s risk for the disease.
Cardiac examination may demonstrate a right ventricular heave, palpable or loud
second heart sound, systolic murmur due to tricuspid regurgitation, and diastolic
murmur of pulmonary insufficiency. The child with right-sided heart failure may
have increased jugular venous pressure, hepatomegaly, ascites, or pedal edema.
The second step includes performing noninvasive cardiac tests, such as chest
radiography, electrocardiography (ECG), and echocardiography. According to
the Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension
(TOPP) registry, chest radiography, ECG, and echocardiography were the
most frequent studies performed, and results of at least 1 were abnormal in
456 patients reviewed.14 Echocardiography is the primary noninvasive test
717
CCIP.indb 717 3/13/18 4:19 PM

History and physical examination:

suspect pulmonary hypertension and
assign a functional class
ECG, chest radiography, echocardiography
Lab tests:
PFTs, 6-minute walk, CPET, CVD workup,
coagulopathy workup, V/Q scan, sleep
study, HRCT, TFTs, HIV, BNP
Cardiac catheterization and

pulmonary vasoreactivity testing
Lung biopsy, MRI
Transplantation evaluation
FIGURE 44-1. Pulmonary hypertension workup. BNP = brain natriuretic peptide, CPET = cardio-
pulmonary exercise testing, CVD = collagen vascular disease, ECG = electrocardiography, HRCT =
high-resolution (thin-section) computed tomography, MRI = magnetic resonance imaging, PFT =
pulmonary function testing, TFT = thyroid function testing, V/Q = ventilation-perfusion.
used to evaluate and follow pulmonary hypertension. It serves multiple roles,

including identification of CHD and estimation of right ventricular systolic
pressure (RVSP), which is equivalent to pulmonary artery pressure in the
absence of significant pulmonary valve stenosis. RVSP is calculated by using
the Bernoulli equation (RVSP = 4 × tricuspid regurgitation jet velocity2).15
In the TOPP registry, echocardiographic findings were reported to be
abnormal 99% of the time it was used in catheterization-confirmed pulmonary
hypertension cases.14
The third step involves additional laboratory tests, performed to rule out
secondary forms of pulmonary hypertension. This includes evaluation for lung
disease as part of the workup for pulmonary hypertension, with the use of chest
radiography, pulmonary function testing, and, often, chest computed tomography.
718
CCIP.indb 718 3/13/18 4:19 PM

The fourth and final step involves the use of cardiac catheterization, which
remains the standard of reference for the diagnosis and treatment of pulmonary
hypertension, to confirm the presence of pulmonary hypertension, make the dis-
tinction between disease related to the right and left sides of the heart, measure
pulmonary vascular resistance, calculate shunts, delineate vascular anatomy and
pressure gradients, and test vasoreactivity to stratify patient treatment.13
During the initial assessment, a patient’s functional status is determined as
scored by WHO guidelines, which are a modification of the New York Heart
Association heart failure classification.16 This classification scale allows prognosis
of long-term outcomes and provides treatment recommendations. However, this
assessment does not work well to describe the functional status of infants and
young children. Therefore, a pediatric-specific classification divided according
to age group has been proposed (modified from the original description in
Box 44-2).17 This format has an advantage in its applicability to children, but
it has not been fully validated.18
Treatment
The therapeutic approach to the child with pulmonary hypertension begins with
a thorough identification of the underlying cause(s), with treatment directed
accordingly. The treatment may include use of supplemental oxygen for patients
with parenchymal lung disease, early surgical repair of cardiac defects, anti-
inflammatory therapy for collagen vascular disease, continuous positive airway
pressure therapy and adenotonsillectomy for patients with obstructive sleep
apnea, and anticoagulation therapy for chronic thromboembolic disease. Nearly
all children with pulmonary hypertension may need at least some conventional
therapy: oxygen, anticoagulants, digoxin, and diuretics. An overview of the
current approach and guidelines for treatment is shown in Figure 44-2.
Box 44-2. Pediatric Functional Classification Scale for

Newborns to Adolescents 16 Years of Age
Class I: Asymptomatic, normal growth and development, normal physical
activities
Class II: Normal growth, dyspnea with playing or exertion, slight limitation
in physical activity, 75% attendance rate if in school
Class III: Marked limitation in physical activity, asymptomatic at rest, <50%

school attendance
Class IV: Symptomatic at rest, unable to do any physical activity,

wheelchair bound in a previously walking child, right-sided heart failure,
syncope, unable to interact with family.
Adapted from reference 18.
719
CCIP.indb 719 3/13/18 4:19 PM

Confirmation of diagnosis of PH by cardiac catheterization
Evaluation of Pulmonary
Vasoreactivity
-Acute Vasodilator Testing
• Inhaled nitric oxide
• Intravenous epoprostenol
• Intravenous diltiazem
• Inhaled iloprost
• Oral sildenafil
Responder* Nonresponder
Oral calcium Oral Right heart Functional Functional

channel sildenafil failure class III or IV class I or II
blocker
testing
Digoxin, Anticoagulation General

Diuretics ERA measures
Sustained response Anticoagulation PGI2 analogue ? ERA
ERA Sildenafil
PGI2 analogue Combination
Sildenafil therapy
Yes No
Continue Treatment failure
calcium
channel Lung or heart-lung
blocker transplantation
*Responder is defined as a patient who has a significant response

to acute pulmonary vasodilator testing with a reduction in mean
PAP of at least 20%, with no change or an increase in cardiac
output.
FIGURE 44-2. Current treatment strategies for children with pulmonary hypertension (PH). ERA
= endothelin receptor antagonist, PAP = pulmonary arterial pressure, PGI2 = prostacyclin.
The PCP plays an important role in the care of children with pulmonary
hypertension. Annual influenza and pneumococcal vaccination is recommended
unless there are contraindications. Patients should receive adequate antipyretic
and hydration during febrile illness. However, decongestants with pseudoephed-
rine should be avoided because they may exacerbate pulmonary hypertension.
Diet and/or medical therapy should be used to prevent constipation, since the
720
CCIP.indb 720 3/13/18 4:19 PM

Valsalva maneuver transiently decreases venous return to the right side of the
heart and may precipitate a syncopal episode.
Currently, there is no cure for idiopathic pulmonary hypertension; however,
therapy has dramatically improved over the past several decades, resulting in
sustained clinical and hemodynamic improvement, as well as increased survival
in children with various types of pulmonary hypertension.19 The 2015 American
Heart Association and American Thoracic Society guidelines outline the current
approach and summarize recommendations for treatment.13 At the current time,
no targeted therapy for pulmonary hypertension in children is U.S. Food and
Drug Administration approved; therefore, all of the medications are used off-
label on the basis of smaller studies in children. Hemodynamic and noninvasive
studies performed prior to initiating therapy (as well as periodically thereafter)
are useful in guiding changes in therapeutic regimens, particularly in light of
recent advances with various novel therapeutics.20–21

Therapy of pulmonary hypertension is targeted against 3 well-characterized
vascular changes: vasoconstriction, thrombus formation, and proliferation of
smooth muscle or endothelial cells in the pulmonary vessels. Although the prin-
ciples of treatment of pulmonary hypertension in children are often derived from
observations in adults, data from adults are not easily extrapolated to children.
Treatment of children with pulmonary hypertension remains individualized on
the basis of the underlying etiologic origin, functional class, and vasoreactivity of
pulmonary vasculature, as determined with cardiac catheterization. Commonly
used targeted pulmonary hypertension therapies for children, their mechanisms
of action, dose and therapeutic ranges, adverse effects, and contraindications are
described in Table 44-1.
In patients with progressive PHVD, combination therapy (coadministration
of multiple pulmonary hypertension therapies) is an attractive option.22 By
simultaneously addressing the multiple pathophysiological pathways present in
pulmonary hypertension, combination therapy may be more effective because
of additive or synergistic effects. However, combination therapies should be
administered cautiously because of risk of drug interactions. For example,
adding sildenafil to prostacyclin may cause hypotension or precipitate headache.
Currently, there are limited data on the safety and effectiveness of combination
therapy in children; more studies are needed to help establish guidelines for
combination therapy in children.
Refractory Pulmonary Hypertension

Recent advances in the understanding of molecular genetics, cell biology,
pathophysiology, and treatment strategies have revolutionized the care of chil-
dren with pulmonary hypertension, resulting in improved survival and quality
of life for these patients. Because of the rarity and heterogeneous etiologic
721
CCIP.indb 721 3/13/18 4:19 PM

CCIP.indb 722
722
Table 44-1. Targeted Therapy for Pulmonary Hypertension in Children
Mechanism of
Agent Action Dose or Therapeutic Range Adverse Effects and Contraindications
Sildenafil Phosphodiesterase-5 Age <1 y: 0.5–1.0 mg/kg 3 times daily orally Adverse effects: Headache, flushing, agitation, nasal
inhibition, acts via Weight <20 kg: 10 mg 3 times daily orally congestion, hypotension, diarrhea, priapism
eNOS-NO-cGMP Weight >20 kg: 20 mg/kg 3 times daily orally Contraindications: hypersensitivity, pulmonary veno-oc-
pathway clusive disease, patient taking nitrates in any form
Inhaled Vasodilation, Dose 5 ppm up to 20 ppm of NO, dose titrated Adverse effects: Rebound pulmonary hypertension,
NO antiproliferation to effect methemoglobinemia
Contraindications: Pulmonary vein stenosis
Bosentan Dual endothelin Starting dose is half the maintenance dose Adverse effects: Transaminase level increases, hepatic
receptor antagonist Maintenance dose: toxicity; teratogenicity, anemia, fluid retention, male
(both ETA and ETB Weight <10 kg: 2 mg/kg twice daily orally infertility, may decrease sildenafil level
antagonist) Weight 10–20 kg: 31.25 mg twice daily Contraindications: pregnancy, hypersensitivity
Weight >20–40 kg: 62.5 mg twice daily
Weight >40 kg: 125 mg twice daily
PGI2 Vasodilation Epoprostenol: continuous intravenous infusion Adverse effects: Headache, flushing, diarrhea, jaw pain,
analogue Inhibition of plate- Starting dose 1–2 ng/kg/min leg pain, rash, nausea, syncope, hypotension, central line
lets aggregation Dose: up-titrate to effect, as tolerated complications.
Trepostinil: intravenous or subcutaneous Half-life of epoprostenol is 2–5 min, so pulmonary hyper-
Starting dose: 2 ng/kg/min tension crisis may occur rapidly if infusion is stopped.
Dose: up-titrate to effect, as tolerated Subcutaneous injection site may limit the subcutaneous
Iloprost: intermittent inhalation; optimal dose is route for trepostinil.
not determined, but 6–9 inhalations per day are Intravenous form of trepostinil and iloprost inhalation can
required worsen reactive airway disease.
Start with 2.5-mg dose and up-titrate to 5 mg as
tolerated
cGMP = cyclic guanosine monophosphate, eNOS = endothelial nitric oxide synthase, ETA = endothelin A receptor agonist, ETB = endothelin B receptor agonist, NO = nitric oxide, PGI2 = prostacyclin,
ppm = parts per million.
3/13/18 4:19 PM
origins of pulmonary hypertension in children, the recent pediatric pulmonary

hypertension guidelines16 emphasize that children with pulmonary hypertension
merit evaluation and treatment by multidisciplinary care teams at medical
centers with experience in the medical, interventional, and surgical management
of this disorder.
Despite advances in medical management of pulmonary hypertension,
patients can be nonresponsive to such therapies or develop treatment-refractory
disease. Patients who often have marked symptoms of right-sided heart failure
or recurrent syncope have limited treatment options. Atrial septostomy, which
facilitates right-to-left shunting, can improve cardiac output for some patients
and may contribute to improved survival for patients with refractory pulmonary
hypertension.23 Atrial septostomy does not alter the underlying disease process
but may improve quality of life and serve as a bridge to transplantation.
The use of palliative Potts shunt for children with suprasystemic pulmonary
hypertension was reported from France, where 24 children underwent a
surgical or interventional procedure for a Potts shunt and were studied over
a 10-year period, with significant improvement in WHO functional class,
growth, and symptomatology in 21 of the 24 children.24 Thus, this procedure
could be another modality that allows prolonged survival and possibly a
bridge to lung transplantation in selected children with severe refractory
Single or bilateral lung transplantation, as well as heart-lung transplantation,
has been performed in a limited number of patients with refractory pulmonary
hypertension. Currently, the overall 1-year, 5-year, and 10-year survival for lung
transplantation in patients with pulmonary hypertension are 64%, 44%, and
20%, respectively.25 For untreated patients with Eisenmenger physiology, the
5-year and 25-year survival rates are greater than 80% and 40%, respectively, as
opposed to survival rates after lung transplantation, which are 52% and 39%,
respectively.26 Thus, transplantation should be reserved for WHO functional class
IV patients with pulmonary hypertension who have progressed despite optimal
medical therapy. Ideally, children should be listed when their probability of
2-year survival without transplantation is 50% or less. The use of extracorporeal
membrane oxygenation and a right-ventricle assist device as a bridge to recovery
(in acutely decompensated patients) or to transplant may also be a viable option
in selected patients.27
Key Points
•• The PCP plays a crucial role in the general health maintenance of a child with
•• Timely referral of a child with a suspected diagnosis of pulmonary hyperten-
sion remains difficult because the presentation is often nonspecific.
723
CCIP.indb 723 3/13/18 4:19 PM

•• Successful evaluation and treatment of children with pulmonary hypertension

often involve a specialized pediatric pulmonary hypertension program, which
decreases the time to diagnosis and provides patient-tailored specific pulmo-
nary hypertension therapy.
•• Serial reassessment of the response to pulmonary hypertension therapy remains
a critical part of long-term care in children with pulmonary hypertension.
•• A close collaboration between the PCP, community and auxiliary hospi-
tal-based resources, subspecialists, and pulmonary hypertension specialists is
critical for successful management of a child with pulmonary hypertension.
•• The goal of pulmonary hypertension treatment is to improve survival and
quality of life in children, especially allowing normal activities of childhood
without the need to self-limit.

•• Pulmonary Hypertension Association. www.phassociation.org
•• PHA Online University (Pulmonary Hypertension Association). www.
PHAOnlineUniv.org/journal
•• International Society for Heart and Lung Transplantation. www.ishlt.org
References
1) Del Cerro MJ, Moledina S, Haworth SG, et al. Cardiac catheterization in children with pulmo-
nary hypertensive vascular disease: consensus statement from the Pulmonary Vascular Research
Institute, Pediatric and Congenital Heart Disease Task Forces. Pulm Circ. 2016;6(1):118–125
2) Simonneau G, Gatzoulis MA, Adatia I, et al. Updated clinical classification of pulmonary
hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D34–D41
3) Cerro MJ, Abman S, Diaz G, et al. A consensus approach to the classification of pediatric
pulmonary hypertensive vascular disease: report from the PVRI Pediatric Taskforce, Panama
2011. Pulm Circ. 2011;1(2):286–298
4) van Loon RL, Roofthooft MT, Hillege HL, et al. Pediatric pulmonary hypertension in the
Netherlands: epidemiology and characterization during the period 1991 to 2005. Circulation.
2011;124(16):1755–1764
5) Moledina S, Hislop AA, Foster H, Schulze-Neick I, Haworth SG. Childhood idiopathic
pulmonary arterial hypertension: a national cohort study. Heart. 2010;96(17):1401–1406
6) Fraisse A, Jais X, Schleich JM, et al. Characteristics and prospective 2-year follow-up of children
with pulmonary arterial hypertension in France. Arch Cardiovasc Dis. 2010;103(2):66–74
7) Abman SH, Raj U. Towards improving the care of children with pulmonary hypertension: The
rationale for developing a Pediatric Pulmonary Hypertension Network. Prog Pediatr Cardiol.
2009;27(1-2):3–6
8) Barst RJ, McGoon M, Torbicki A, et al. Diagnosis and differential assessment of pulmonary
arterial hypertension. J Am Coll Cardiol. 2004;43(12 Suppl S):40S–47S
9) Farber HW, Loscalzo J. Pulmonary arterial hypertension. N Engl J Med.
2004;351(16):1655–1665
724
CCIP.indb 724 3/13/18 4:19 PM

10) Newman JH, Trembath RC, Morse JA, et al. Genetic basis of pulmonary arterial hypertension:
current understanding and future directions. J Am Coll Cardiol. 2004;43(12 Suppl S):33S–39S
11) Abman SH. Pulmonary hypertension in chronic lung disease of infancy. Pathogenesis, patho-
physiology and treatment. In: Bland RD, Coalson JJ, eds. Chronic Lung Disease of Infancy. New
York, NY: Marcel Dekker; 2000:619–668
12) Maggiorini M, Léon-Velarde F. High-altitude pulmonary hypertension: a pathophysiological
entity to different diseases. Eur Respir J. 2003;22(6):1019–1025
13) Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and
treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment
of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European
Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital
Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur
Heart J. 2016;37(1):67–119
14) Ivy DD, Abman SH, Barst RJ, et al. Pediatric pulmonary hypertension. J Am Coll Cardiol.
2013;62(25 Suppl):D117–D126
15) Ling LF, Obuchowski NA, Rodriguez L, Popovic Z, Kwon D, Marwick TH. Accuracy and
interobserver concordance of echocardiographic assessment of right ventricular size and systolic
function: a quality control exercise. J Am Soc Echocardiogr. 2012;25(7):709–713
16) Abman SH, Hansmann G, Archer SL, et al; American Heart Association Council on
Cardiopulmonary, Critical Care, Perioperative and Resuscitation; Council on Clinical
Cardiology; Council on Cardiovascular Disease in the Young; Council on Cardiovascular
Radiology and Intervention; Council on Cardiovascular Surgery and Anesthesia; and the
American Thoracic Society. Pediatric Pulmonary Hypertension: Guidelines from the American
Heart Association and American Thoracic Society. Circulation. 2015;132(21):2037–2099
17) Beghetti M, Berger RM, Schulze-Neick I, et al; TOPP Registry Investigators. Diagnostic
evaluation of paediatric pulmonary hypertension in current clinical practice. Eur Respir J.
2013;42(3):689–700
18) Lammers AE, Adatia I, Cerro MJ, et al. Functional classification of pulmonary hyper-
tension in children: Report from the PVRI pediatric taskforce, Panama 2011. Pulm Circ.
2011;1(2):280–285
19) Barst RJ, Ertel SI, Beghetti M, Ivy DD. Pulmonary arterial hypertension: a comparison between
children and adults. Eur Respir J. 2011;37(3):665–677
20) van Loon RL, Roofthooft MT, van Osch-Gevers M, et al. Clinical characterization of pediatric
pulmonary hypertension: complex presentation and diagnosis. J Pediatr. 2009;155(2):176–82.e1
21) Douwes JM, van Loon RL, Hoendermis ES, et al. Acute pulmonary vasodilator response in
paediatric and adult pulmonary arterial hypertension: occurrence and prognostic value when
comparing three response criteria. Eur Heart J. 2011;32(24):3137–3146
22) Barst RJ, McGoon MD, Elliott CG, Foreman AJ, Miller DP, Ivy DD. Survival in childhood
pulmonary arterial hypertension: insights from the registry to evaluate early and long-term
pulmonary arterial hypertension disease management. Circulation. 2012;125(1):113–122
23) Barst RJ. Role of atrial septostomy in the treatment of pulmonary vascular disease. Thorax.
2000;55(2):95–96
24) Baruteau AE, Belli E, Boudjemline Y, et al. Palliative Potts shunt for the treatment of children
with drug-refractory pulmonary arterial hypertension: updated data from the first 24 patients.
Eur J Cardiothorac Surg. 2015;47(3):e105–e110
25) Trulock EP, Edwards LB, Taylor DO, et al. The Registry of the International Society for
Heart and Lung Transplantation: Twentieth Official Adult Lung and Heart-Lung Transplant
Report—2003. J Heart Lung Transplant. 2003;22(6):625–635
725
CCIP.indb 725 3/13/18 4:19 PM

26) Clarkson PM, Frye RL, DuShane JW, Burchell HB, Wood EH, Weidman WH. Prognosis
for patients with ventricular septal defect and severe pulmonary vascular obstructive disease.
Circulation. 1968;38(1):129–135
27) Lang G, Taghavi S, Aigner C, et al. Primary lung transplantation after bridge with extracorpo-
real membrane oxygenation: a plea for a shift in our paradigms for indications. Transplantation.
2012;93(7):729–736
726
CCIP.indb 726 3/13/18 4:19 PM

Index
Page numbers followed by an f, a t, or a b denote Activity restrictions, 238–239. See also Athletic
a figure, a table, or a box, respectively. participation
acute pericarditis, 531–532
A tetralogy of Fallot (TOF), 333
Acute chest syndrome, 121
AAP. See American Academy of Pediatrics (AAP)
Acute pericarditis, 529–534
Aberrant left subclavian artery (aLSCA), 348, 349f
activity restrictions, 531–532
Ablation procedures, supraventricular tachycardia
clinical features and diagnostic criteria, 530–531
(SVT), 156
colchicine, 533
Abnormal coronary anatomy, 122
corticosteroids, 533
ABPM. See Ambulatory blood pressure monitor
electrocardiogram, 531f
(ABPM)
etiologic origins, 530b
Academic performance, 632–633
follow-up, 533
Accelerated ventricular rhythm (AVR), 39, 156
management, 531
ACE inhibitors. See Angiotensin-converting
NSAIDs, 532
enzyme (ACE) inhibitors
pericardial effusion, 531
Acetaminophen, 208
pericardial friction rub, 530
Acetylsalicylic acid (ASA), 433, 434
prognosis, 533–534
Acid Maltase Deficiency Association, 265
triage system, 531, 532f
Acid-phosphatase-positive vacuoles, 264
Acute rheumatic fever (ARF) and rheumatic
Acid-Schiff-positive vacuolar myopathic
abnormalities, 264 heart disease (RHD), 443–461
anatomic changes in ARF valvulitis, 445b
ACMG Work Group on Management of Pompe
aortic regurgitation, 446, 449f, 456
Disease, 265
aortic stenosis, 446, 456
Acquired acute dyslipidemia, 559, 561–563t
aspirin, 455t
Acquired cardiac diseases, 421–473
athletic participation, 457, 459
acute rheumatic fever (ARF), 443–461
bioprosthetic replacement valves, 456
cardiotoxicity among childhood cancer
clinical features of ARF, 447–448
survivors, 463–473
clinical features of RHD, 448–450
Kawasaki disease (KD), 423–442
complications, 457
rheumatic heart disease (RHD), 443–461
definitions, 443
Acquired hypertriglyceridemia, 552, 556
diagnosis of ARF, 450, 451b
Acquired immunodeficiency syndrome. See AIDS
diagnostic approach, 449–450
Acrocyanosis, 6, 178
differential diagnosis, 450–453
727
CCIP.indb 727 3/13/18 4:19 PM

INDEX
Acute rheumatic fever (ARF) and rheumatic neurodevelopmental profile, 632–635

heart disease (RHD) (continued) physical activity, 649–650t
Doppler findings in rheumatic valvulitis, sleep, 651t
452b smoking, 648–650
endocarditis prophylaxis, 457 transition to adult care. See Transition from
epidemiology, 443–444 pediatric to adult care
etiologic origins, 444 Adrenergic agonists, 663, 665, 666–667t
florid heart failure, 454 Adult Congenital Heart Association, 284
follow-up, 457 Adults with congenital heart disease, 269–286
group A β-hemolytic Streptococcus activity and fitness, 280
(GABHS), 444, 450 anticoagulation, 279
management, 453–457 arrhythmia, 275–278
medications for group A streptococcal cardiovascular risk factors, 281
infection, 454t clinical concerns, 275–279
mitral regurgitation, 446, 455 contraception and pregnancy, 281–283
mitral stenosis, 446, 455–456 end-of-life issues, 283
natural history, 447 epidemiology, 269–270
ongoing care, 457 follow-up, 279
pathophysiology of ARF, 445–446 genetic counseling, 281
pathophysiology of RHD, 446–447 health care costs, 272
physical examination, 448 health maintenance, 280
primary prevention, 453 heart failure, 273b, 278–279
primordial prevention, 453 heterogeneity of CHD, 270–271
revised Jones criteria, 451b history, 272
secondary prophylaxis, 456–457, 458t long-term complications, 277t
steroids, 455t loss to follow-up, 271–272
treatment of ARF, 453–454 mental health, 280
treatment of RHD, 455–456 natural history and history of interventions,
tricuspid and pulmonary regurgitation, 447 271
worldwide prevalence of RHD, 444f neurocognitive issues, 280
Acute thrombosis of the fenestration, 231 noncardiac procedures, 279
Acyanotic patient, 92f physical examination, 272–275
Adenosine, 155, 676t, 677 referral for adult CHD care, 279. See also
ADHD. See Attention-deficit/hyperactivity Transition from pediatric to adult care
disorder (ADHD) resources for families, 284
Adolescents. See also Adults with congenital signs and symptoms of heart failure, 273b
heart disease AHA. See American Heart Association (AHA)
blood pressure categories, 568t AIDS, 481t, 562t
blood pressure charts, 576–577t, 582–583t Alagille syndrome, 253
blood pressure values of concern, 568t Alcohol, 552
caloric intake, 647t Alcohol septal ablation, 371
congenital heart procedures, 207t Aldosterone antagonists, 523
dietary recommendations, 646–647t Aliasing, 59
ECG parameters, 19t Alkylating agents, 466
fatty streaks, 545 α-Adrenergic agents, 142
history, 4 aLSCA. See Aberrant left subclavian artery
lifestyle counseling, 643–654 (aLSCA)
lipid levels, 547t Ambulatory blood pressure monitor (ABPM),
mean concentrations of triglycerides, 553t 585, 590
myocarditis, 519, 520b
728
CCIP.indb 728 3/13/18 4:19 PM

INDEX
American Academy of Child and Adolescent Pediatric Cardiomyopathies, 408

Psychiatry, 601 psychotropic drugs, 596
American Academy of Pediatrics (AAP) pulmonary hypertension (PH), 721
ADHD, 596 Pulmonary Valve Stenosis, 319
developmental deficits, 635 Restrictive Cardiomyopathy, 393
diet, 652 rheumatic fever, 459
Down syndrome, 247 Screening Young Athletes for Heart Disease,
dyslipidemia risk assessment, 123 610
Guidelines for Integrated Cardiovascular Syncope (Fainting), 144
Risk Reduction in Children and Tetralogy of Fallot, 333
Adolescents, 546 Transesophageal Echocardiography, 68
Heart Murmur, 169 Truncus Arteriosus, 347
High Blood Pressure in Children, 591 Ventricular Septal Defect, 357
hypertension guidelines, 567 warfarin, 284
influenza vaccine, 478 Amiodarone
Irregular Heartbeat (Arrhythmia), 158 adverse reactions, 674t, 676
Lyme Disease, 495 contraindications, 677
Newborn Screening for CCHD, 203 dosing, 674t
physical activity, 652 drug interactions, 677
pulse oximetry screening algorithm, 200, dyslipidemia, 557t
201f indications, 672, 674t, 676
screen time, 587 mechanism of action, 676
sleep, 651, 652 metabolism, 676
smoking, 648, 652 Amlodipine, 589t
Williams syndrome, 258 Amoxicillin
American Academy of Sleep Medicine, 651 group A streptococcal infection, 454t
American Heart Association (AHA) infective endocarditis (IE), 513t
anticoagulation and platelet inhibition, 678 Lyme disease, 493t
aortic valve problems, 290 Amphetamine, 596
atherosclerotic cardiovascular disease, 563 Ampicillin, 513t
athletic screening, 604, 605b, 610 Amplitude, 15
Atrial Septal Defect (ASD), 296 Anakinra, 434
Coarctation of the Aorta, 304 Anderson disease, 264
Common Tests for Congenital Heart Angiotensin-converting enzyme (ACE)
Defects, 107 inhibitors, 661–663
Complete Atrioventricular Canal Defect, 300 acute rheumatic fever (ARF), 454
Congenital Heart Defects, 183, 233 adverse effects, 662t, 663
developmental deficits, 629b, 635, 636f captopril, 662t
familial hypercholesterolemia, 563 childhood cancer survivors, 467, 469
Fetal Echocardiogram Test, 68 chronic heart failure/reduced ejection
Heart Murmurs, 169 fraction, 384t
High Blood Pressure in Children, 591 dosing, 662t
infective endocarditis (IE), 505, 506, 509, enalapril, 661, 662t
511, 512–514 hypertension, 588t
Kawasaki disease diagnostic algorithm, 432f left ventricular (LV) noncompaction
“Life’s Simple 7,” 569 (LVNC), 403
L-Transposition of the Great Arteries, 308 losartan, 662t
patent foramen ovale (PFO), 315 mechanism of action, 663
pediatric advanced life support algorithm, myocarditis, 523
670, 672 Angiotensin receptor blockers, 523, 588t, 663
729
CCIP.indb 729 3/13/18 4:19 PM

INDEX
Anhidrosis, 616t heart murmurs, 166t

Annulus, 339 progressive disease, 290
Anomalies of the great vessels, 208–212 Aortic valve, 287, 354f
coarctation repair, 210–211 Aortic valve problems, 287–291
PDA closure, 208–210 anatomy, 287
TAPVR repair, 211–212, 213f aortic dissection, 289
Anomalous left coronary artery from pulmonary aortic insufficiency, 287, 289
artery, 86t aortic stenosis, 287, 289, 290
Anomalous left pulmonary artery from coronary audio recordings, 291
artery, 88f bicuspid aortic valve (BAV), 287–291
Anophthalmia, 250 clinical features, 289
Anthracyclines, 465–466 “critical” aortic stenosis, 289
Antiarrhythmic drugs, 670–677 diagnostic testing, 289
adenosine, 676t, 677 echocardiographic images, 288f
amiodarone. See Amiodarone endocarditis prophylaxis, 290
atropine, 675t management, 290
flecainide, 673t ongoing care, 290–291
lidocaine, 673t Ross procedure, 290
magnesium sulfate, 675t screening of first-degree relatives, 291
procainamide, 673t subaortic membrane, 289, 290
sotalol, 674t supravalvar aortic stenosis, 289
Vaughan Williams classification system, 672 Apex (mitral area), 9f
verapamil, 675t Apical imaging window, 52f, 61f
Anticoagulants, 384t Apical impulse, 6
Anticoagulation and platelet inhibition, Apolipoprotein C-II, 552
678–679, 680–681t Apolipoprotein C-III, 552
Anticonvulsants, 557t Apolipoprotein 5, 552
Antidromic atrioventricular reentrant tachycar- ARF. See Acute rheumatic fever (ARF) and
dia, 28f rheumatic heart disease (RHD)
Antiplatelet agents, 239 Arrhythmia, 147–159
Antipsychotics, 557t accelerated ventricular rhythm (AVR), 156
Aortic arch, 100f adults with CHD, 275–278
Aortic arch sidedness, 181 chest pain, 122b, 123
Aortic area, 8, 9f clinical presentation, 147–148
Aortic atresia, 287 ECG, 150
Aortic coarctation, 210–211 event recorder, 150
Aortic dissection, 124, 289 extrasystoles, 152–154
Aortic insufficiency, 287, 289 history, 149
Aortic ligation, 209 Holter monitor, 150
Aortic regurgitation implantable loop recorder, 151
acute rheumatic fever and rheumatic heart left ventricular (LV) noncompaction
disease, 446, 449f, 452b, 456 (LVNC), 404–405
audio recording, 12, 291 loop recorder, 150–151
ventricular septal defect (VSD), 353 medication, 670–677. See also
Aortic root dissection, 124 Antiarrhythmic drugs
Aortic stenosis, 287 physical examination, 149
acute rheumatic fever and rheumatic heart postoperative, 239
disease, 446, 456 premature atrial contractions (PACs),
chest radiographic findings, 85t 152–153
“critical,” 289
730
CCIP.indb 730 3/13/18 4:19 PM

INDEX
premature ventricular contractions (PVCs), electrocardiography (ECG), 604–608

153–154 emergency response plan, 609
resources for families, 158 false-positive screening, 609
sinus tachycardia, 152 follow-up, 609
smartphone technology, 151 history, 604
supraventricular tachycardia (SVT), 154–156 hypertension, 589
syncope, 148 hypertrophic cardiomyopathy (HCM),
tests, 150–151 369–370t, 372
tetralogy of Fallot (TOF), 332 left ventricular (LV) noncompaction
typical/“classic” manner of presentation, 149, (LVNC), 406–407
149b myocarditis, 524
vagal maneuvers, 155 physical examination, 604
ventricular tachycardia (VT), 156–158 resources, 450
Arterial blood gas analysis, 109–111 resources for families, 610
Arterial oxygen tension (Pao2), 110, 111, 180 restrictive cardiomyopathy (RCM), 392
Arterial partial pressure of CO2 (Paco2), 110 “Seattle criteria,” 607
Arterial pulmonary vascular markings (PVMs), Atomoxetine, 597
83–84 Atorvastatin, 551
Arterial switch procedure, 220–222, 338 Atrial enlargement, 20b
Artificial patch materials, 207 Atrial flutter, 30–31, 31f
ASA. See Acetylsalicylic acid (ASA) Atrial-level shunt, 327
Ascending aorta, 103f Atrial septal defect (ASD), 292–296
ASCVD. See Atherosclerotic cardiovascular audio recording, 169, 294
disease (ASCVD) chest radiographic findings, 85t
ASD. See Atrial septal defect (ASD) coronary sinus ASD, 292f, 293
Aspirin diagnostic and preconsult testing, 294
acute pericarditis, 532 heart murmurs, 166t
acute rheumatic fever and rheumatic heart location, 292f
disease, 455t long-term complications, 277t
dosing, 680t management, 294–295
Kawasaki disease (KD), 679 ongoing care, 295
myopericarditis, 534 pathophysiology, 293
pharmacology, 680t physical examination, 294
restrictive cardiomyopathy (RCM), 391 prevalence, 292
side effects, 680t primum ASD, 212–214, 292, 292f
single-ventricle CHD, 226 repair, 212–216
Asplenia, 82 resources for families, 296
Asymmetrical septal hypertrophy, 361. See also secundum ASD, 214, 292, 292f
Hypertrophic cardiomyopathy (HCM) signs and symptoms, 293
Atenolol, 669t sinus venosus ASD, 214–216, 292–293, 292f
Atherosclerotic cardiovascular disease types, 292–293, 292f
(ASCVD), 545–547 Atrial septectomy, 228–229, 228f
Athletic heart, 370 Atrial septostomy, 723
Athletic participation. See also Activity Atrial septum, 190, 314
restrictions Atrial tachycardia
acute rheumatic fever and rheumatic heart ECG, 29, 29t, 30f
disease, 457, 459 sinus tachycardia, compared, 29t
AHA recommendations, 604, 605b SVT, compared, 29t
cardiac screening, 603–611
echocardiography, 608
731
CCIP.indb 731 3/13/18 4:19 PM

INDEX
Atrioventricular (AV) block heart murmurs, 169

complete heart block, 35–37, 37f patent ductus arteriosus (PDA), 169, 311–312
first-degree AV block, 34, 34f pulmonary artery banding, 226
Lyme carditis, 489–490 pulmonary stenosis, 169, 317
second-degree AV block, 34–35, 35f, 36f Still murmur, 169
Atrioventricular (AV) canal defects (AVCDs), transposition of the great arteries (TGA), 336
296–300 ventricular septal defect (VSD), 11, 12,
age at which to repair AVCDs, 299 356–357
chest radiographic findings, 85t Autologous pericardium, 207
complete AVCD, 216–219, 296, 297f, 299 Autonomic dysfunction, 613–624
diagnostic and preconsult testing, 299 anhidrosis, 616t
endocarditis prophylaxis, 299 autonomic nervous system, 613, 614
management, 216–219, 299 Bezold-Jarisch reflex, 615, 618
ongoing care, 299–300 cardiac preload, 615
partial AVCD, 296 comorbidities, 622
pathophysiology, 297–298 congenital central hypoventilation syndrome,
physical examination, 298–299 616t
repair, 216–219, 299 congenital sensory neuropathy, 616t
resources for families, 300 diagnostic testing, 619–620
schematic representation, 297f dysautonomia syndromes, 615, 616–617t
signs and symptoms, 298 electrocardiography (ECG), 619–620
transitional AVCD, 296 epidemiology, 615
unbalanced AV valve, 224, 296 “fight or flight” response, 614
Atrioventricular reentrant tachycardia (AVRT), history, 618–619
27, 28f medications, 621–622, 621t
Atropine, 675t, 681 mitochondrial diseases, 617t
Attention-deficit/hyperactivity disorder neurocardiogenic syncope, 618
(ADHD), 413, 595–602 nonpharmacological management, 620
cardiac screening prior to dispensing orthostatic intolerance (OI), 615–617, 621t
medication, 597–600 parasympathetic nervous system, 614
cardiovascular risks, 597 physical examination, 619
development deficits, 634, 637 postural orthostatic tachycardia syndrome
Diagnostic and Statistical Manual of Mental (POTS), 616–617, 620–622
Disorders, Fifth Edition, 595 prognosis, 622
electrocardiography (ECG), 599 resources for families, 623
family history, 598 “rest and digest” response, 614
historical aspects, 596 Riley-Day syndrome, 616t
medications, 596–597 sympathetic nervous system, 614
monitoring, 599–600 symptoms of dysautonomia, 614t
patient history, 598 tilt testing, 620
pediatric cardiologist, 599 treatment, 620–622
physical examination, 598 Autonomic imbalance, 135
resources for families, 601 Autonomic nervous system, 613, 614
Audio recordings AV block. See Atrioventricular (AV) block
aortic valve problems, 291 AV canal defects. See Atrioventricular (AV)
atrial septal defect (ASD), 169, 294 canal defects (AVCDs)
bicuspid aortic valve (BAV), 291 AV dissociation, 36
clinical history and physical examination, AVR. See Accelerated ventricular rhythm (AVR)
11–12 AVRT. See Atrioventricular reentrant tachycar-
dia (AVRT)
732
CCIP.indb 732 3/13/18 4:19 PM

INDEX
Azalide, 458t β-Myosin heavy chain, 362

Azathioprine, 703t Bezold-Jarisch reflex, 135, 615, 618
Azithromycin Bicuspid aortic valve (BAV), 287–291, 302. See
group A streptococcal infection, 454t also Aortic valve problems
infective endocarditis (IE), 513t Bidirectional Glenn procedure, 229–230, 230f,
321, 323, 323f
B Bile acid sequestrant, 551
Bacterial endocarditis, 511–516. See also Biomarkers, 111–112
Infective endocarditis (IE) BNP. See Brain natriuretic peptide (BNP)
Balloon atrial septostomy, 338 dilated cardiomyopathy (DCM), 380
Balloon valvuloplasty Bioprosthetic pulmonary valve replacement
aortic valve problems, 290 (PVR), 219, 220f
pulmonary stenosis, 318–319 Bioprosthetic replacement valves, 456
Barlow syndrome, 124 Bisoprolol, 588t
BART, 59 Black-blood approach, 96, 97f
Barth syndrome, 398, 407 Blalock-Taussig shunt
BAV. See Bicuspid aortic valve (BAV) modified, 194, 225, 226f, 228, 321, 322f
Bazett formula, 44 original, 225
BCAS cohort. See Boston Circulatory Arrest Blocked premature atrial contraction (PAC), 152
Study (BCAS) cohort Blocking, 31
Beckwith-Wiedemann syndrome, 381t, 382t Blood gas analysis, 109–111
Behavior and executive functioning, 634 Blood pressure, 568t. See also Hypertension
Benazepril, 588t “Blue” tetralogy of Fallot, 330, 332
Benzathine penicillin G. See Penicillin G BNP. See Brain natriuretic peptide (BNP)
benzathine Boot-shaped heart, 85t, 87f, 181, 331
Bernoulli equation, 718 Borrelia burgdorferi, 487
β-Blockers, 665, 668–669t Bosentan, 671t, 722t
atenolol, 669t Boston Circulatory Arrest Study (BCAS)
autonomic dysfunction, 621t, 622 cohort, 628, 630t, 632, 634
carvedilol, 665, 669t Bounding pulse, 6
childhood cancer survivors, 469 Brain natriuretic peptide (BNP), 111–112
chronic heart failure/reduced ejection dilated cardiomyopathy (DCM), 380
fraction, 384t left ventricular (LV) noncompaction
CPVT, 415 (LVNC), 403
dyslipidemia, 557t myocarditis, 520, 521t
esmolol, 668t restrictive cardiomyopathy (RCM), 390
hypertension, 588t Branching enzyme deficiency, 264
left ventricular (LV) noncompaction Breast milk, 644
(LVNC), 403 Breast tenderness, 121
long QT syndrome (LQTS), 413 Breath-holding spells, 135, 136–137
metoprolol, 668t Bright-blood approach, 96, 98f
myocarditis, 523 Bronchopulmonary dysplasia, 569t
nadolol, 669t BrS. See Brugada syndrome (BrS)
propranolol, 665, 668t Bruce treadmill protocol, 74
restrictive cardiomyopathy (RCM), 391 Brugada syndrome (BrS), 414
SVT, 155 Bundle branch block, 40–42
syncope, 142
toxicity (calcium), 682t
β-Blocker toxicity, 682t
733
CCIP.indb 733 3/13/18 4:19 PM

INDEX
C cine phase contrast imaging, 96

coarctation of the aorta, 99f
Café au lait spots, 381t
complications, 101
Calcium, 681–682, 682t
contraindications, 98–99
Calcium channel blockers, 155, 589t
dilated cardiomyopathy (DCM), 383
Caloric intake, 644, 647t
flow velocity mapping, 96, 100f
Cancer. See Childhood cancer survivors
hypertrophic cardiomyopathy (HCM),
Candesartan, 588t
365–366, 367f
Candida, 517
indications, 96–98
Captopril, 662t
left ventricular (LV) noncompaction (LVNC),
Cardiac and pericardial inflammation, 122b, 124
400, 402f
Cardiac catheterization, 391
myocardial fibrosis, 97, 101f
Cardiac chamber enlargement, 82t
myocardial perfusion, 98
Cardiac channelopathies, 411–419
nephrogenic systemic fibrosis (NSF), 101
Brugada syndrome (BrS), 414
pulmonary artery, 100f
cardiac conduction disease, 416
pulmonary vein, 100f
catecholaminergic polymorphic ventricular
Qp:Qs ratio, 96
tachycardia (CPVT), 415
resources for families, 107
defined, 411
spin-echo approach, 96, 97f
early repolarization syndrome (ERP), 416
steady-state free-precession imaging, 96, 98f
general evaluation and management,
tissue characterization, 97–98
411–412
Cardiac murmurs, 8–10. See also Heart murmurs
long QT syndrome (LQTS), 412–414
Cardiac pharmacology, 655–684
short QT syndrome (SQTS), 416
anticoagulation and platelet inhibition,
Cardiac computed tomography (CT), 102–107
678–679, 680–681t
ALARA, 106
arrhythmia treatment, 670–677
ascending aorta, 103f
attention-deficit/hyperactivity disorder
cardiac and extracardiac vasculature,
(ADHD), 596–597
102–103
autonomic dysfunction, 621–622, 621t
cardiac function, 106
commonly used drugs, 656b
cardiac MR imaging, compared, 107t
dilated cardiomyopathy (DCM), 384t
circumflex aorta, 105f
ductus arteriosus management, 677–678, 679t
contraindications and complications, 106
group A streptococcal infection, 454t
coronary arteries, 103f, 105f
heart failure treatment, 655–665. See also
indications, 102–106
Heart failure medications
Kommerell diverticulum, 104f
hypertension, 588–589t
postoperative anatomy, 106
infective endocarditis (IE), 505
Lyme carditis, 492, 493t
respiratory infection, 104f
mitral valve anomalies, 310
sedation/anesthesia, 106
other emergency medications, 679, 681–682
stridor, 104f
patent ductus arteriosus (PDA), 312,
Cardiac conduction disease, 416
677–678, 679t
Cardiac cycle, 6, 7f
postoperative office care, 239–240
Cardiac magnetic resonance (MR) imaging,
pulmonary hypertension management, 665,
95–102
670, 671–672t, 722t
anesthesia, 101–102
aortic arch, 100f
syncope, 142
black-blood approach, 96, 97f
tricuspid valve anomalies, 342
bright-blood approach, 96, 98f
Cardiac preload, 615
cardiac CT, compared, 107t
734
CCIP.indb 734 3/13/18 4:19 PM

INDEX
Cardiac surgery. See Surgical procedures for CDC. See Centers for Disease Control and
congenital heart disease Prevention (CDC)
Cardiac syncope, 136, 137 Cefazolin, 513t
Cardiac tamponade, 536. See also Pericardial Cefotaxime, 493t
effusion and cardiac tamponade Ceftriaxone
Cardiac total anomalous pulmonary venous infective endocarditis (IE), 505, 513t
return (TAPVR), 326 Lyme disease, 493t
Cardiac transplantation. See Heart Cefuroxime, 493t
transplantation Center for Parent Information & Resources, 637
Cardiac ultrasonography (US), 49. See also Centers for Disease Control and Prevention
Echocardiography (CDC)
Cardiofaciocutaneous syndrome, 262, 381t, 382t ADHD, 595
Cardiogenic shock, 178–179 Congenital Heart Defects (CHDs), 183, 233
Cardiomyopathies and channelopathies, Learn the Signs. Act Early, 637
359–419 Lyme carditis, 491
chest radiographic findings, 86t Pulse Oximetry Screening for Critical
dilated cardiomyopathy (DCM), 377–386 Congenital Heart Defects, 203
hypertrophic cardiomyopathy (HCM), Centre for Genetics Education, 250
361–375 Cephalexin, 513t
long QT syndrome and other channelopa- Cerebrotendinous xanthomatosis, 560t
thies, 411–419 Cervical adenopathy, 427
LV noncompaction (LVNC), 395–410 Cervical lymphadenopathy, 427
noncompaction cardiomyopathy, 395–410 Channelopathies, 411–419. See also Cardiac
restrictive cardiomyopathy (RCM), 387–394 channelopathies
Cardiopulmonary bypass, 207–208 CHARGE syndrome, 248, 253
CardioSmart, 683 CHD. See Congenital heart disease (CHD)
Cardiothoracic ratio, 81–82 Cheese, 549
Cardiothoracic Surgery Network, 233 Chemotherapy agents, 466
Cardiovascular Health Integrated Lifestyle Diet Chest asymmetry, 275
(CHILD-1), 587 Chest pain, 117–132
Cardiovascular Health Integrated Lifestyle acute chest syndrome, 121
triglyceride-lowering diet, 558 aortic dissection, 124
“Cardiovascular Monitoring of Children and aortic root dissection, 124
Adolescents Receiving Psychotropic arrhythmia, 122b, 123
Drugs,” 596 associated complaints, 126
Carotid bruit, 163 breast tenderness, 121
Carvedilol, 665, 669t cardiac and pericardial inflammation, 122b,
CASCADE FH Registry, 563 124
Cataplexy, 140 cardiac causes, 122–124
Cataracts, 382t character and location of pain, 125
Catecholaminergic polymorphic ventricular chest radiography, 127, 128t
tachycardia (CPVT), 415 conversion disorder, 121
CAV. See Coronary allograft vasculopathy coronary artery abnormalities, 122–123, 122b
(CAV) costochondritis, 118–119
CAVC. See Complete atrioventricular canal ECG, 127, 128t
(CAVC) “elephant-sitting-on-chest” sensation, 125
Cavopulmonary shunt, 229 evaluation, 124–127
CCHD. See Critical CHD (CCHD) exercise-induced asthma (EIA), 121
CCHD screening. See Pulse oximetry frequency of causes, 118t
735
CCIP.indb 735 3/13/18 4:19 PM

INDEX
Chest pain (continued) pulmonary vascular markings (PVMs),

gastrointestinal causes, 119b, 121 83–84
GERD, 121 resources for families, 93
history, 125–126 thymus, 81
idiopathic chest wall pain, 120, 121 venous PVMs, 84
investigations, 127, 128t Child Cancer Survivor Study, 464
Kehr sign, 125 Childhood cancer survivors, 463–473
left ventricular outflow obstruction, 123–124 anthracyclines, 465–466
lower rib pain syndrome, 120 chemotherapy agents, 466
management, 127–130 Child Cancer Survivor Study, 464
Marfan syndrome, 124, 126 Children’s Oncology Group (COG), 468
mitral valve prolapse (MVP), 124 echocardiography, 469
musculoskeletal causes, 118–120 follow-up, 468–469
myocarditis, 124 future prospects, 470
noncardiac causes, 118–121 health effects of cardiotoxicity, 464
onset and duration of pain, 125 history, 468
pericarditis, 124 IOM report (2003), 468
physical examination, 126–127 markers of cardiac disease, 469
precipitating and relieving factors, 125 preventing cardiotoxicity, 467–468
precordial catch syndrome, 120 radiation therapy, 466
pulmonary and upper airway causes, 119b, resources for families, 470
120–121 risk factors for cardiotoxicity, 464–467
referral to cardiologist, 130 screening, 468–469
SCAMP algorithm, 129f St Jude Lifetime Cohort Study, 464
slipping rib syndrome, 120 treatment, 469
structural cardiac defects, 122b, 123–124 www.survivorshipguidelines.org, 468, 470
“Texidor twinge,” 120 “Childhood Cancer Survivorship: Improving
Tietze syndrome, 119 Care and Quality of Life,” 468
xiphoid pain, 120 CHILD-1 diet. See Cardiovascular Health
Chest radiography, 79–94 Integrated Lifestyle Diet (CHILD-1)
acyanotic patient, 92f Children’s Cardiomyopathy Foundation, 384,
anteroposterior (AP) view, 81, 82 393
arterial PVMs, 83–84 Children’s Hospital of Philadelphia (CHOP)
boot-shaped heart, 85t, 87f cohort, 630t, 632, 633
cardiac chamber enlargement, 82t Children’s Oncology Group (COG), 468
cardiac position and visceroatrial situs, 82 Chlorothiazide, 657t
cardiothoracic ratio, 81–82 Cholesterol, 547t. See also Hypercholesterolemia
CHD, 181 ChooseMyPlate, 644
chest pain, 127, 128t CHOP cohort. See Children’s Hospital of
cyanotic patient, 93f Philadelphia (CHOP) cohort
diagnostic algorithms, 92f, 93f Chorionic villi, 191
diseases/disorders and typical radiographic Chromosome 22 Central, 255
findings, 85–86t Chromosome 22q11.2 deletion syndrome,
figure “3” sign, 85t 252–255
great vessels, 83 Chronic inflammatory diseases, 562t
heart size, 81–82 Chronic kidney disease, 570
images, 87f, 88f, 89f, 90f, 91f Chronic renal failure, 561t
left-to-right shunt, 83–84 Chylomicrons, 545
normal findings, 80–81, 80f Chylothorax, 211
posteroanterior (PA) view, 81 Cigarette smoking, 648–650
736
CCIP.indb 736 3/13/18 4:19 PM

INDEX
Cine phase contrast imaging, 96 Conformal radiation, 467

Circumflex aorta, 105f Congenital central hypoventilation syndrome,
Clarithromycin, 513t 616t
Cleft mitral valve, 309 Congenital heart disease (CHD)
Clindamycin adults. See Adults with congenital heart
group A streptococcal infection, 454t disease
infective endocarditis (IE), 513t age of death, 270f
Clopidogrel, 433 closing of ductus arteriosus, 194–195
Closing of ductus arteriosus, 194–195 consequences of late detection, 199
Closure of patent ductus arteriosus (PDA), critical CHD (CCHD), 197, 198
208–210 developmental disorders and disabilities. See
Coarctation of the aorta, 300–304 Neurodevelopmental and psychosocial
bicuspid aortic valve, 302 outcomes
cardiac MR imaging, 99f dysmorphic features/anatomic abnormalities,
chest radiographic findings, 85t 183
closing of ductus arteriosus, 194 health care costs, 272
diagnostic and preconsult testing, 303 heart murmurs, 164t, 175–176
ductal dependent conditions, 302 lesions. See Congenital heart lesions
endocarditis prophylaxis, 303 management, 182
“juxtaductal,” 301 neonatal screening. See Pulse oximetry
long-term complications, 277t neonate. See Evaluation of neonate with
management, 303 congenital heart disease
ongoing care, 303 ongoing care, 182–183
pathophysiology, 301–302 prematurity, 172
physical examination, 302 prevalence, 171, 685
resources for families, 304 resources for families, 183
schematic representation, 301f single-ventricle CHD, 112
signs and symptoms, 302 surgery. See Surgical procedures for congeni-
Coarctation repair, 210–211 tal heart disease
Cocaine, 124 syndromes. See Syndromes associated with
COG. See Children’s Oncology Group (COG) cardiac lesions
Cognitive functioning, 629–630, 632–633 unmasking of congenital lesions, 194–195
Colchicine variations in clinical presentation, 270
acute pericarditis, 533 Congenital heart lesions, 287–357. See also
myopericarditis, 534 Congenital heart disease (CHD)
postcardiac injury syndrome (PCIS), 538 aortic valve problems, 287–291
recurrent pericarditis, 534 atrial septal defect (ASD), 292–296
Collagenoma syndrome, 382t atrioventricular (AV) canal defects, 296–300
Color Doppler imaging, 59 bicuspid aortic valve (BAV), 287–291
Communication and social skills (older coarctation of the aorta, 300–304
children), 631, 633–634 levo-transposition of the great arteries
Complete atrial septectomy, 228–229, 228f (L-TGA), 305–308
Complete atrioventricular canal (CAVC), 216– mitral valve anomalies, 308–311
219, 296, 297f. See also Atrioventricular patent ductus arteriosus (PDA), 311–313
(AV) canal defects (AVCDs) patent foramen ovale (PFO), 314–316
Complete heart block, 35. See also Third-degree pulmonary stenosis, 316–320
atrioventricular (AV) block pulmonary vein anomalies, 325–329
Computed tomography (CT). See Cardiac single-ventricle lesions, 320–325. See also
computed tomography (CT) Single-ventricle heart disease
Cone reconstruction, 342 subaortic membrane, 289, 290
737
CCIP.indb 737 3/13/18 4:19 PM

INDEX
Congenital heart lesions (continued) C282Y hemochromatosis gene mutation, 466

systemic venous anomalies, 325–329 Culture-negative infective endocarditis (IE), 501
tetralogy of Fallot (TOF), 329–334 Cushing syndrome, 569t
transposition of the great arteries (TGA), Cutis aplasia, 250
334–339 Cutis laxa, 381t
tricuspid valve anomalies, 339–343 CW Doppler. See Continuous wave (CW)
truncus arteriosus, 343–347 Doppler
vascular rings and slings, 347–352 Cyanosis, 176–178, 198
ventricular septal defect (VSD), 353–357 acrocyanosis, 178
Congenitally corrected transposition of chest radiography, 93f
the great arteries, 36, 305. See also detection, 6
Levo-transposition of the great arteries differential, 177, 195, 274f
(L-TGA) pulmonary hypertension (PH), 715
Congenital mitral valve disease, 308. See also reversed differential, 177
Mitral valve anomalies systemic venous anomalies, 326
Congenital sensory neuropathy, 616t tetralogy of Fallot (TOF), 176, 330
Congestive (biventricular) failure, 273b Cyanotic breath-holding spells, 136
Conotruncal heart defects, 220–223 Cyanotic congenital heart lesions, 176
Constant work exercise protocol, 74 Cyclo-oxygenase inhibitors, 312
Constitutional delay, 259 Cyclophosphamide, 434, 466
Constrictive pericarditis, 537 Cyclosporine, 434, 557t, 703, 703t
Continuous murmurs, 9 Cytomegalovirus (CMV), 706
Continuous wave (CW) Doppler, 58
Contraceptive pills, 281, 282t D
Conversion disorder, 121 DAA. See Double aortic arch (DAA)
Convulsive syncope, 139 Damus-Kay-Stansel (DKS) procedure, 227
Copenhagen General Population Study, 553t Danazol, 557t
Cori disease, 264 Danon disease, 264, 370
Coronary allograft vasculopathy (CAV), Daunorubicin, 465
707–708 DCM. See Dilated cardiomyopathy (DCM)
Coronary arteries, 103f, 105f Debrancher deficiency, 264
Coronary artery abnormalities, 122–123, 122b Deep hypothermic circulatory arrest, 208
Coronary artery aneurysms, 429, 436 Deep plantar furrows, 381t
Coronary sinus ASD, 292f, 293 DEET. See Diethylethanolamine (DEET)
Corticosteroids. See Steroids Defective apolipoprotein B, 547
Costello syndrome, 262, 381t Deformation imaging, 62
Costochondritis, 118–119 Delta wave, 32, 156f
Costosternal syndrome, 118 Desipramine, 596
Couplet (PVCs), 39 Desmopressin, 622
CPVT. See Catecholaminergic polymorphic Developmental disorders and disabilities. See
ventricular tachycardia (CPVT) Neurodevelopmental and psychosocial
Craniofacial characteristics, 382t outcomes
CredibleMeds (www.crediblemeds.org), 45, 683 Dexmethylphenidates, 596
Critical aortic stenosis, 179 Dexrazoxane, 467
Critical CHD (CCHD), 197, 198 Dextroamphetamine derivatives, 596
Cryptorchidism, 250, 382t Dextro-transposition of the great arteries
CT. See Cardiac computed tomography (CT) (D-TGA). See also Transposition of the
CTA. See CT angiography (CTA) great arteries (TGA)
CT angiography (CTA), 102 anatomy, 334
ctsnet.org, 233 arterial switch procedure, 220–222, 338
738
CCIP.indb 738 3/13/18 4:19 PM

INDEX
long-term complications, 277t inborn errors of metabolism, 377

parallel pulmonary and systemic circulations, medications, 384t
176 pathophysiology, 378
radiographic findings, 86t, 89f Pediatric Cardiomyopathy Registry, 377
Diabetes mellitus resources for families, 384
dyslipidemia, 561t Ross classification, 379, 379t
heart murmurs, 165t signs and symptoms, 378–380
sleep, 650 treatment, 383, 384t
Diabetic ketoacidosis (DKA), 561t Diuretics
Diagnostic procedures. See Evaluation of patient acute rheumatic fever (ARF), 454
Diastole, 6 atrial septal defect (ASD), 295
Diastolic murmurs, 8–9 AV canal defect, 299
Diet, 643–647 cautionary note, 240, 656, 659
AAP recommendations, 652 chlorothiazide, 657t
caloric intake, 644, 647t digoxin toxicity, 660t
CHILD-1, 587 dilated cardiomyopathy (DCM), 383
ChooseMyPlate, 644 dyslipidemia, 557t
dietary recommendations over life span, fluid overload, 240
645–647t furosemide, 657t
dyslipidemia, 549–550 heart failure, 655–658, 656b
hypertriglyceridemia, 558 hydrochlorothiazide, 657t
ketogenic, 562t hypertension, 589t
pulmonary hypertension (PH), 720 metolazone, 657t
Dietary Guidelines for Americans, 558b mitral regurgitation, 455
Diethylethanolamine (DEET), 492 mitral stenosis, 456
Differential cyanosis, 177, 195, 274f myocarditis, 523
DiGeorge syndrome, 81, 252. See also 22q11.2 noncompaction cardiomyopathy, 404
deletion syndrome pericardial disease, 536
Digital clubbing, 6 pulmonary hypertension, 719, 720f
Digoxin, 658–659, 660t restrictive cardiomyopathy (RCM), 392
acute rheumatic fever (ARF), 454 rheumatic heart disease (RHD), 455, 456
adverse effects, 659, 660t spironolactone, 656, 658t
chronic heart failure/reduced ejection stage C heart failure, 384t
fraction, 384t tricuspid valve anomaly, 342
contraindications, 659 ventricular septal defect (VSD), 355
dosing, 660t Diverticulum of Kommerell, 104f, 348, 351
drug interaction, 659 DKA. See Diabetic ketoacidosis (DKA)
mechanism of action, 659, 660t DKS maneuver, 228
single-ventricle CHD, 229 DKS procedure. See Damus-Kay-Stansel (DKS)
Dilated ascending aorta, 289 procedure
Dilated cardiomyopathy (DCM), 377–386 D-loop transposition of the great arteries. See
biomarkers, 380 Dextro-transposition of the great arteries
cardiac MR imaging, 383 (D-TGA)
definition, 377 Dobutamine, 666t
diagnostic testing, 381 Docetaxel, 466
endomyocardial biopsy, 382 Dopamine, 666t
etiologic origins and epidemiology, 377–378 Dopaminergic agonists, 596
genetic cardiomyopathy, 381, 381–382t Doppler imaging, 58–59
heart failure staging, 380t Doppler principle, 50
heart transplantation, 383 Double aortic arch (DAA), 348, 350, 350f
739
CCIP.indb 739 3/13/18 4:19 PM

INDEX
Double-chambered RV, 353 lysosomal acid lipase deficiency, 560t

Double-inlet left ventricle, 278f phytosterolemia, 560t
Double-inlet single ventricle, 224 resources for families, 563
Double-orifice mitral valve, 309 resources for professionals, 563–564
Double-outlet right ventricle (RV), 86t sitosterolemia, 560t
Double standard ECG, 15 very low-density lipoprotein (VLDL), 545
Double switch procedure, 307 Dyslipidemia risk assessment, 123
Down syndrome
associated cardiovascular findings, 246 E
diagnostic approach, 246–247 Ear creases, 382t
differential diagnosis, 246 Early repolarization, 23
key clinical findings, 246 Early repolarization syndrome (ERP), 416
management, 247 Early systolic click, 175
ongoing care, 247 EAT. See Ectopic atrial tachycardia (EAT)
pathophysiology, 245 Ebstein anomaly, 86t, 89f, 340, 341f, 342–343
resources, 247 EBV. See Epstein-Barr virus (EBV)
Doxorubicin, 465 ECG. See Electrocardiography (ECG)
Doxycycline, 493t Echocardiography, 49–70
Drop attacks, 139 aliasing, 59
Drugs. See Cardiac pharmacology apical imaging window, 52f, 61f
D-TGA. See Dextro-transposition of the great appropriate use criteria, 53, 54–57t
arteries (D-TGA) athletic participation, 608
Ductal-dependent CCHD, 198 BART, 59
Ductal-dependent left-sided heart lesions, 179 basic principles, 49–50
Ductal stent, 321, 322f cardiac ultrasonography (US), 49
Ductus arteriosus, 190, 194–195, 311. See also CHD, 181–182
Patent ductus arteriosus (PDA) childhood cancer survivors, 469
Ductus venosus, 188–190 Doppler imaging, 58–59
Duke criteria, 501, 502–503b Doppler principle, 50
Dysautonomia International, 623 duration of session, 52
Dysautonomia syndromes, 615, 616–617t. See ejection fraction (EF), 60–62
also Autonomic dysfunction fetal, 66–68
Dysbetalipoproteinemia, 555t hypertension, 586
Dyslipidemia, 545–565 hypertrophic cardiomyopathy (HCM),
AAP screening recommendations, 546 364–365, 366f, 367f
acceptable, borderline, high lipid levels, 546, imaging windows, 51, 52f
547t indications, 53–58
acquired acute, 559, 561–563t infective endocarditis (IE), 504
cerebrotendinous xanthomatosis, 560t intracardiac echocardiography (ICE), 65
chylomicrons, 545 Kawasaki disease (KD), 429
conditions associated with dyslipidemia, left ventricular (LV) noncompaction
561–563t (LVNC), 399, 401f
drug-related causes, 557t method of disks, 61–62
high-density lipoprotein (HDL), 545 M-mode measurements, 60–61
hypercholesterolemia, 546–551. See also modified Bernoulli equation, 50
Hypercholesterolemia myocardial “strain” imaging, 62–63
hypertriglyceridemia, 552–559. See also myocarditis, 521–522
Hypertriglyceridemia neonatal indications, 53
lipid profile, 546 parasternal imaging window, 52f, 60f
low-density lipoprotein (LDL), 545 pulmonary hypertension (PH), 717–718
740
CCIP.indb 740 3/13/18 4:19 PM

INDEX
resources for families, 68 bundle branch block, 40–42

Simpson method, 61–62 CHD, 181
strain analysis, 62–63 chest pain, 127, 128t
stress, 65 conditions likely/unlikely to be detected,
subcostal imaging window, 52f, 59f 606b
suprasternal imaging window, 52f, 62f delta wave, 32
3D imaging, 63, 63f double standard ECG, 15
transesophageal echocardiography (TEE), ectopic atrial tachycardia (EAT), 29, 29t, 30f
64–65 escape rhythms, 33
2D imaging, 58 15-step ECG evaluation method, 25, 26b
ventricular systolic function, 60–62 “half standard” ECG, 15
what patients should expect, 51–52 hypertrophic cardiomyopathy (HCM), 364,
Ectopic atrial tachycardia (EAT), 29, 29t, 30f. 365f
See also Atrial tachycardia infective endocarditis (IE), 504
Edwards syndrome, 247–250 interpretation method, 16
associated cardiovascular findings, 248 J point, 23
diagnostic approach, 249 junctional tachycardia, 37–38, 38f
differential diagnosis, 248 left bundle branch block (LBBB), 41, 42f
key clinical findings, 248 left ventricular (LV) noncompaction
management, 249 (LVNC), 402
ongoing care, 249 limb leads, 13, 14f, 15
pathophysiology, 248 myocarditis, 46–47, 46f
resources, 250 normal heartbeat, 16–17, 17f
EF. See Ejection fraction (EF) pericarditis, 47, 47f
Egg intake, 549 precordial leads, 13, 14f, 16
“Egg on a string,” 86t, 89f, 181, 337f pre-excitation, 32
Ehlers-Danlos syndrome, 622 premature ventricular contractions (PVCs),
EIA. See Exercise-induced asthma (EIA) 38–40
Eisenmenger physiology, 715, 723. See also prolonged QT interval, 44–45, 46b
Eisenmenger syndrome P wave, 17, 20
Eisenmenger syndrome QRS complex, 21–23
atrial septal defect (ASD), 293 QTc values, 24–25, 25f
long-term complications, 277t QT interval, 24–25, 25f
pulmonary hypertension (PH), 715, 723 Q wave, 21, 21b
Ejection fraction (EF), 60–62, 384t rate determination, 25
Ejection systolic murmur, 9 right bundle branch block (RBBB), 40–41,
Electric storm, 412 41f
Electrocardiography (ECG), 13–48 right/left axis deviation, 22
age-related ECG parameters, 18–19t sinus bradycardia, 33
arrhythmia, 150 sinus tachycardia, 27, 29t
athletes, 607b standard ECG, 15f
athletic participation, 604–608 ST segment, 23
atrial enlargement, 20b ST segment abnormalities, 42–44
atrial flutter, 30–31, 31f supraventricular tachycardia (SVT), 27–29,
atrial tachycardia, 29, 29t, 30f 29t
attention-deficit/hyperactivity disorder syncope, 142
(ADHD), 599 TP segment, 23
autonomic dysfunction, 619–620 T wave, 23–24
AV block, 34–37 T wave abnormalities, 42–44
741
CCIP.indb 741 3/13/18 4:19 PM

INDEX
Electrocardiography (ECG) (continued) Evaluation of neonate with congenital heart

ventricular hypertrophy, 38 disease, 171–184
ventricular tachycardia, 38–40, 40f cardiogenic shock, 178–179
Wolff-Parkinson-White (WPW), 31–32, 32f chest radiography, 181
“Elephant-sitting-on-chest” sensation, 125 clinical presentation, 173
ELN gene, 255, 256 cyanosis, 176–178
Emergency medications, 679, 681–682. See also differential diagnosis, 175–179
Cardiac pharmacology ECG, 181
Enalapril, 588t, 661, 662t echocardiography, 181–182
Endocardial cushion defects, 296. See also heart failure, 178
Atrioventricular (AV) canal defects history, 172–173
(AVCDs) hyperoxia test, 180
Endocarditis, 275, 497–516. See also Infective laboratory evaluation, 180
endocarditis (IE) murmur, 175–176
Endocarditis prophylaxis physical examination, 173–175
acute rheumatic fever and rheumatic heart pulse oximetry. See Pulse oximetry
disease, 457 resources for families, 183
aortic valve problems, 290 vital signs, 174
atrioventricular (AV) canal defects, 299 Evaluation of patient, 1–114
coarctation of the aorta, 303 audio recordings. See Audio recordings
hypertension, 589 cardiac murmurs, 8–10. See also Heart
levo-transposition of the great arteries murmurs
(L-TGA), 307 CT, 102–107, 107t
patent foramen ovale (PFO), 315 ECG. See Electrocardiography (ECG)
restrictive cardiomyopathy (RCM), 392 echocardiography. See Echocardiography
vascular rings and slings, 351 exercise testing, 71–78
ventricular septal defect (VSD), 356 heart sounds, 7–8
Endomyocardial biopsy, 382, 522 history, 3–5
Endomyocardial fibroelastosis, 390 laboratory studies, 109–114
Endothelin-1, 715 MR imaging, 95–102, 107t
Energy Out: Physical Activity physical examination, 5–8
Recommendations, 652 vital signs, 5
Eparterial bronchus, 82 x-ray. See Chest radiography
Epicardium, 529 Event recorder, 150
Epinephrine hydrochloride, 666t Everolimus, 703t
Epithelialization, 239 Executive functioning, 634
Eplerenone, 589t Exercise, 647–648, 649–650t
Epoprostenol, 672t Exercise-induced asthma (EIA), 121
Epstein-Barr virus (EBV), 706 Exercise testing, 71–78
Ergometer, 73 blood pressure, 72
ERP. See Early repolarization syndrome (ERP) Bruce treadmill protocol, 73–74
Erythema migrans rash, 488, 488f constant work exercise protocol, 74
Escape rhythms, 33 exercise time, 72
Esmolol, 668t heart rate, 72
Esophagus, 64 high-risk patients, 76b
Estrogen-containing contraceptive pills, 281, hypertrophic cardiomyopathy (HCM),
282t 366–368
Estrogens, 552, 557t indications/contraindications, 75–76
maximum oxygen uptake, 72
742
CCIP.indb 742 3/13/18 4:19 PM

INDEX
metabolic equivalents, 72 patent ductus arteriosus (PDA), 190–191

multistage incremental exercise protocol, 73 placenta, 191
oxygen pulse, 73 transitional circulation, 192–194
pharmacological tests, 73 Fever
physiology, 71–73 Kawasaki disease (KD), 426–427
preparing for the test, 76–77 post-cardiac surgery, 241
progressive exercise protocol, 74 FH. See Familial hypercholesterolemia (FH)
protocols, 74–75 FH Foundation, 563
resources for families, 78 Fiber: An Important Part of Your Teen’s Diet,
6-minute walk test, 74 652
treadmills/cycles, 73 Fibrates, 559
types of tests, 73 “Fight or flight” response, 614
typical setup, 74f Figure “3” sign, 85t
ventilatory anaerobic threshold, 73 Final Fontan circulation, 224
External genitalia abnormalities, 382t Fio2. See Fraction of inspired oxygen (Fio2)
External loop recorder, 150–151 First-degree atrioventricular (AV) block, 34, 34f
Extracardiac conduit Fontan procedure, 231 First heart sound (S1), 7, 8
Extracorporeal membrane oxygenation, 212 Fish oil, 559
Extrasystoles, 152–154 Flecainide, 673t
Ezetimibe, 551 Florid heart failure, 454
Flow murmur, 162, 166t
F Flow velocity mapping, 96, 100f
Fludrocortisone, 142, 621, 621t
Fabry disease, 370
Fontan palliation, 123
Fainting. See Syncope
Fontan procedure, 230–233, 323, 324f
“Fainting Lark,” 137
Fontan takedown, 231
Familial hypercholesterolemia (FH), 546–551.
Foramen ovale, 190, 314
See also Hypercholesterolemia
Forbes disease, 264
Familial hyperchylomicronemia, 554t
45,X monosomy, 259
Familial hypertriglyceridemia, 555t
Fosinopril, 588t
Family history, 5
Fossa ovalis, 190
Fasting lipid profile, 548, 549
Fourth heart sound (S4), 8
Fatty streaks, 545
Fraction of inspired oxygen (Fio2), 111
Felodipine, 589t
Fruits, 549
Fenestration, 231, 232
Furosemide, 536, 657t
Fetal akinesia sequence, 248
Fetal alcohol syndrome, 164t, 256
Fetal circulation, 188–192 G
Fetal echocardiography, 66–68 GAA gene, 263, 264
Fetal lungs, 191 GABHS. See Group A β-hemolytic Streptococcus
Fetal placenta, 191 (GABHS)
Fetus Gastroesophageal reflux disease (GERD), 121
atherosclerosis, 545 Genetic cardiomyopathy, 381, 381–382t
circulation, 188–192 Genetic counseling
diagram of fetal circulation, 189f CHD, 281
ductus venosus, 188–190 hypertrophic cardiomyopathy (HCM), 371
echocardiography, 66–68 Genetic hypertriglyceridemia, 552, 553t, 554–555t
fetal alcohol syndrome, 164t Genetics
foramen ovale, 190 hypertrophic cardiomyopathy (HCM), 362
intrauterine infection, 165t left ventricular (LV) noncompaction
lungs, 191 (LVNC), 396–397
743
CCIP.indb 743 3/13/18 4:19 PM

INDEX
GERD. See Gastroesophageal reflux disease angiotensin receptor blockers, 663

(GERD) β-blockers, 665, 668–669t
Glenn procedure, 229–230, 230f, 321, 323, 323f digoxin, 658–659, 660t
Glomerulonephritis, 501 diuretics, 655–658
Glucocorticoids, 552 milrinone, 659, 661, 661t
Glutaraldehyde, 207 nitroprusside, 663, 664t
Glycogen storage disease type II, 263–265 Heart failure staging, 380t
Glycosylphosphatidylinositol-anchored HDL- Heart-healthy diet, 643–647. See also Diet
binding protein 1, 552 Heart-healthy lifestyle, 558
Gonadal dysgenesis, 259 Heart murmurs, 8–10, 161–170
Graft vasculopathy, 707–708 audio recordings, 11–12, 169
Great arteries. See Transposition of the great carotid bruit, 163
arteries (TGA) CHD, 175–176
Great vessels, 83. See also Anomalies of the great flowchart (suggested approach), 168f
vessels innocent murmurs, 10, 161–163
Group A β-hemolytic Streptococcus (GABHS), listening areas for murmurs, 9f
444, 450 pathological murmurs. See Pathological
Group A streptococcal infection, 454t murmurs
Growth abnormalities, 381t peripheral pulmonary stenosis murmur, 162
Growth hormone, 557t physiology, 8–10
Guanfacine, 596 pulmonary flow murmur, 162, 166t
Guidelines for Integrated Cardiovascular Risk resources for families, 169
Reduction in Children and Adolescents Still murmur, 161–162, 166t
(2011), 546 venous hum, 163
Heart size, 81–82
H Heart sounds, 7–8
“Half standard” ECG, 15 Heart surgery. See Surgical procedures for
Hallucinations, 140 congenital heart disease
Halo sign, 659 Heart transplantation, 701–712
HCM. See Hypertrophic cardiomyopathy acute cellular rejection, 704t
(HCM) acute rejection, 704–706
HDL. See High-density lipoprotein (HDL) antibody-mediated rejection, 704t
HDL cholesterol, 547t coronary allograft vasculopathy (CAV),
Head-up tilt-table testing, 142 707–708
Health care costs, 272 cytomegalovirus (CMV), 706
Health-related quality of life (HRQOL), 635 dilated cardiomyopathy (DCM), 383
Healthy eating patterns, 558b dyslipidemia, 562t
Heart block, 34. See also Atrioventricular (AV) Epstein-Barr virus (EBV), 706
block fungal infections, 707
Heart failure, 178 immunization, 479, 484, 707, 708t
adults with CHD, 278–279 immunosuppression, 702–703
differential diagnosis, 452t infection, 706–707
florid heart failure in ARF, 454 Kaplan-Meier survival, 701f, 702f
left ventricular (LV) noncompaction left ventricular (LV) noncompaction
(LVNC), 404 (LVNC), 405–406
medication. See Heart failure medications ongoing care, 710–711
signs and symptoms, 273b Pediatric Heart Transplant Study, 406, 706,
Heart failure medications, 655–665 711
ACE inhibitors, 661–663 posterior reversible encephalopathy
adrenergic agonists, 663, 665, 666–667t syndrome (PRES), 703
744
CCIP.indb 744 3/13/18 4:19 PM

INDEX
posttransplant lymphoproliferative disease HSAN. See Hereditary sensory and autonomic

(PTLD), 709–710 neuropathy (HSAN)
posttransplant malignancy, 709 Human immunodeficiency virus. See HIV
resources for families, 711 Hydralazine with isosorbide dinitrate, 384t
survival, 701–702, 701f, 702f Hydrochlorothiazide, 657t
United Network of Organ Sharing registry, Hydronephrosis, 250
405, 711 Hyparterial bronchus, 82
vaccination, 479, 484 Hyperactive precordium, 6
Hematocrit, 110 Hyperadrenergic POTS, 617–618
Hemodynamic cardiac catheterization, 271 Hypercholesterolemia, 546–551
Heparin, 680t, 681t cascade screening, 547
Hepatic vein drainage anomalies, 326 dietary and polygenic causes, 548
Hereditary hemochromatosis, 467 dietary management, 549–550
Hereditary sensory and autonomic neuropathy evaluation, 548–549
(HSAN), 616t fasting lipid profile, 548, 549
Hereditary sensory radicular neuropathy, 616t liver function tests, 551
Herpes zoster, 121 overview, 550f
Heterotaxy, 82, 90f, 224, 326 screening of relatives, 548
Heterozygous LPL deficiency, 554t secondary causes, 549
High blood pressure. See Hypertension statins, 550–551
High-density lipoprotein (HDL), 545 treatment, 549–551
High-frequency murmurs, 10 weight management, 550
High-grade atrioventricular (AV) block, 35, 36f xanthomas, 548
Histamine-2 (H2) blockers, 121 Hypereosinophilia syndrome, 390
Histoplasma, 517 Hyperkalemia, 682t
History, 3–5 Hyperoxia test, 110, 180
compilation techniques, 5 Hypertension, 567–593. See also Pulmonary
family, 5 hypertension (PH)
HIV, 481t, 562t ambulatory blood pressure monitor
HLHS. See Hypoplastic left heart syndrome (ABPM), 585, 590
(HLHS) athletic participation, 589
HOCM. See Hypertrophic obstructive cardio- blood pressure categories and stages, 568t
myopathy (HOCM) blood pressure charts, 572–583t
Holoprosencephaly, 250 blood pressure measurement, 570–571, 585
Holosystolic murmurs, 9 blood pressure values of concern, 568t
Holter monitoring, 150 causes, 569t
hypertrophic cardiomyopathy (HCM), 368 CHILD-1 diet, 587
left ventricular (LV) noncompaction complications, 590
(LVNC), 405 definition, 567
Home births, 202 differential diagnosis, 570
Homozygous familial hypercholesterolemia echocardiography, 586
(FH), 548 endocarditis prophylaxis, 589
Hooking maneuver, 120 epidemiology, 567
Hope for Trisomy 13 and 18, 250 etiologic origins, 569
Hormonal contraception, 281, 282t evaluation, 585–586
Horseshoe kidney, 250 family history, 585
How to Reduce Fat and Cholesterol in Your follow-up, 590
Child’s Diet, 652 goal of treatment, 587
HRQOL. See Health-related quality of life imaging, 586
(HRQOL) laboratory testing, 586
745
CCIP.indb 745 3/13/18 4:19 PM

INDEX
Hypertension (continued) genotype-positive findings, 371

“Life’s Simple 7,” 569 heart murmurs, 166t
lifestyle recommendations (screen time/ Holter monitoring, 368
physical activity), 587 implantable cardiac defibrillator (ICD), 366,
management, 586–590 368, 371
masked, 570 LVOT obstruction, 361, 362–363
medications, 588–589t management approach, 371
nutritional history, 585 myocardial disarray, 362
ongoing care, 590 ongoing care, 372
physical activity history, 585 other names for HCM, 361
prevention, 589–590 pathophysiology, 362–364
prognosis, 591 phenotype-negative findings, 371
referral to cardiologist, 587–589 physical examination, 364
resources for families, 591 pre-sports evaluation, 372–373
risk factors, 569–570 prognosis, 372
screening and management flowchart, 584f referral to cardiologist, 371
signs and symptoms, 570 resources for families, 373
treatment approach, 586–587 sarcomeric genes, 373
white-coat, 570 schematic representations, 363f
Hyperthyroidism, 569t signs and symptoms, 364
Hypertriglyceridemia, 552–559 sudden cardiac death, 368, 368b
acquired, 552, 556 Hypertrophic Cardiomyopathy Association, 373
clinical manifestations, 556 Hypertrophic obstructive cardiomyopathy
Copenhagen General Population Study, 553t (HOCM), 361. See also Hypertrophic
diet, 558 cardiomyopathy (HCM)
dysbetalipoproteinemia, 555t Hypocalcemia, 682t
evaluation, 556–558 Hypoglycemia, 141
familial, 555t Hypogonadism, 382t
familial hyperchylomicronemia, 554t Hypokalemia, 682t
genetic, 552, 553t, 554–555t Hypomagnesemia, 682t
healthy eating patterns, 558b Hypoplastic left heart syndrome (HLHS), 86t,
heart-healthy lifestyle, 558 224, 227
heterozygous LPL deficiency, 554t Hypoplastic left-sided heart, 179
lipid panel, 556 Hypoproteinemia, 561t
mean concentrations of triglycerides, 553t Hypotelorism, 250
point-of-care lipid testing, 556 Hypothyroidism, 252, 562t
treatment, 558–559 Hypotonia, 382t
Hypertrophic cardiomyopathy (HCM), 361–375
athletic participation, 369–370t, 372 I
cardiac MR imaging, 365–366, 367f Ibuprofen
definition, 361 acute pericarditis, 533
differential diagnosis, 370 PDA closure, 208
echocardiography, 364–365, 366f, 367f ICD. See Implantable cardiac defibrillator (ICD)
electrocardiography (ECG), 364, 365f ICE. See Intracardiac echocardiography (ICE)
epidemiology, 362 Idiopathic chest wall pain, 120, 121
evaluation of family members, 371 Idiopathic hypertrophic subaortic stenosis, 361.
exercise stress testing, 366–368 See also Hypertrophic cardiomyopathy
follow-up, 372 (HCM)
genetic counseling, 371 Idiopathic pulmonary hypertension, 721
genetics, 362 Idioventricular rhythm, 39
746
CCIP.indb 746 3/13/18 4:19 PM

INDEX
IDSA. See Infectious Diseases Society of myocarditis, 519, 520b

America (IDSA) neurodevelopmental profile, 629–631
IE. See Infective endocarditis (IE) physical activity, 649t
Ifosfamide, 466 screen time, 648
IKBKAP gene, 616t sleep, 651t
Iloprost, 672t Infantile-onset Pompe disease, 264
Image Gently, 93 Infectious diseases, 475–541
Imaging techniques. See Evaluation of patient endocarditis, 497–516
Imipramine, 596 Lyme carditis, 487–496
Immunization, 477–486 myocarditis, 517–527
cardiac transplantation, 479, 484, 707, 708t pericardial diseases, 529–541
DiGeorge syndrome, 479 vaccination, 477–486
household members living with patient, Infectious Diseases Society of America (IDSA),
478–479 478
IDSA guidelines, 478 Infective endocarditis (IE), 497–516
immunoglobulin administration, 484, AHA recommendations, 505, 506, 509, 511,
485–486t 512–514
Kawasaki disease (KD), 485 antibiotics, 505, 508
live vs inactivated vaccines, 477–478 antimicrobial prophylaxis, 513–514t
measles vaccine, 484, 485–486t clinical features, 500–501
overview, 480–483t complications, 507–508
primary immune deficiency, 480–481t culture-negative IE, 501
secondary immune deficiency, 481–483t dental procedures, 511–512, 513, 515
timing of vaccination, 478 diagnostic approach and laboratory tests,
Immunoglobulin administration, 484, 485–486t 501–504
Implantable cardiac defibrillator (ICD) Duke criteria, 501, 502–503b
Brugada syndrome, 414 echocardiography, 504
cardiac channelopathies, 412 electrocardiography (ECG), 504
CPVT, 415 epidemiology, 498–500
hypertrophic cardiomyopathy (HCM), 366, follow-up, 507
368, 371 fundamental principles, 511
long QT syndrome (LQTS), 413 imaging, 504
restrictive cardiomyopathy (RCM), 392 management, 505
Implantable loop recorder, 151 medications, 505
Inborn errors of metabolism, 377 neonates, 501
Incomplete atrioventricular (AV) canal defect, nonbacterial thrombotic endocarditis
296 (NBTE), 497
Incomplete DiGeorge syndrome, 479 ongoing care, 507–508
Incomplete Kawasaki disease (KD), 427 pathogenesis, 497–498
Indomethacin, 312, 678, 679t prevention, 506, 511–516
Infant primary care providers, 506–507
blood pressure categories, 568t prognosis, 508
blood pressure charts, 572t, 578t respiratory tract procedures, 513
blood pressure values of concern, 568t specific procedure sites, 514t
breast milk, 644 surgery, 505
caloric intake, 647t underlying conditions, 498f, 499f
congenital heart procedures, 206t Inferior vena cava (IVC), 325
dietary recommendations, 645t Infliximab, 434, 436
ECG parameters, 18–19t Infracardiac total anomalous pulmonary venous
history, 4 return (TAPVR), 212, 326
747
CCIP.indb 747 3/13/18 4:19 PM

INDEX
Inhaled nitric oxide (NO), 670, 671t, 722t K

Innocent murmurs, 10, 161–163
Kabuki syndrome, 256
Inotropic agents, 384t
Kaplan-Meier survival, 701f, 702f
Integrated Guidelines for Cardiovascular Health
Kawasaki disease (KD), 423–442
and Risk Reduction in Children and
acetylsalicylic acid (ASA), 433, 434
Adolescents, 563
adjunctive primary therapy, 435–436
International Cardiac Collaborative on
AHA diagnostic algorithm, 427, 432f
Neurodevelopment, 629
aspirin, 679
International Pediatric Hypertension
complications, 436
Association, 591
coronary artery aneurysms, 429, 436
International Pompe Association (IPA), 265
corticosteroids, 435–436
International Society for Heart and Lung
diagnostic approach, 428–429, 428b
Transplantation, 724
differential diagnosis, 429–431
International 22q11.2 Foundation, 255
Interrupted aortic arch, 179
epidemiology and etiologic origins, 424–425
Interrupted inferior vena cava (IVC), 326, 327
fever, 426–427
Intracardiac baffling procedure, 213
heart murmurs, 164t
Intracardiac conduit Fontan procedure, 231
incomplete KD, 427
Intracardiac echocardiography (ICE), 65
infliximab, 436
Intracranial pathologic processes, 141
intravenous immunoglobulin (IVIg), 431
Intrauterine infection, 165t
juvenile idiopathic arthritis ( JIA), 431
Intravenous immunoglobulin (IVIg)
Kawasaki shock syndrome (KSS), 428
Kawasaki disease (KD), 431
linked processes, 425
myocarditis, 523
long-term management, 437–439
Irbesartan, 588t
management, 431–436
Irregular heartbeat. See Arrhythmia
ongoing care, 436–439
Isolated TBX1 mutations, 253
pathologic changes, 425–426
Isoproterenol
prognosis, 437
dosing, 667t
recurrent and refractory KD, 434
Lyme disease, 493t, 494f
pharmacology, 667t
risk stratification, 438t
side effects, 667t
signs and symptoms, 426–428
Isovolumetric contraction, 7
skin rash, 427
Isovolumetric relaxation, 7
slit lamp examination, 427
IVC. See Inferior vena cava (IVC)
systemic vasculitis, 427
IVIg. See Intravenous immunoglobulin (IVIg)
toxic shock syndrome (TSS), 431
Ixodes scapularis, 487
treatment approach, 431–434
vaccination, 485
J z scores, 429
Jervell and Lange-Nielsen syndrome, 413 Kawasaki Disease Foundation, 439
JET. See Junctional ectopic tachycardia ( JET) Kawasaki shock syndrome (KSS), 428
JIA. See Juvenile idiopathic arthritis ( JIA) KD. See Kawasaki disease (KD)
Joint laxity, 381t Kehr sign, 125
J point, 23 Ketogenic diet, 562t
J point elevation, 23 Kidney abnormalities, 250
Junctional ectopic tachycardia ( JET), 37–38, 37f Kommerell diverticulum, 104f, 348, 351
Junctional escape, 33 KSS. See Kawasaki shock syndrome (KSS)
Junctional tachycardia, 37–38, 38f Kyphoscoliosis, 381t
Juvenile idiopathic arthritis ( JIA), 431
748
CCIP.indb 748 3/13/18 4:19 PM

INDEX
L etiologic origin, 396

genetics, 396–397
Laboratory studies, 109–114
heart failure, 404
biomarkers, 111–112
heart transplantation, 405–406
blood gas analysis, 109–111
Holter monitoring, 405
brain natriuretic peptide (BNP), 111–112
Fontan procedure, 112
mechanical circulatory support, 404
N-terminal (NT) proBNP, 111–112
nonembryogenic hypothesis, 396
100% Fio2, 111
ongoing care, 407
Paco2 level, 110
overdiagnosis, 403
Pao2 level, 110, 111
overview, 397f
single-ventricle CHD, 112
pathophysiology, 398
LAMP2 cardiomyopathy, 370
referral to cardiologist, 407
Language acquisition, 631
Laryngeal nerve palsy, 211
risk factors, 397–398
Late-onset Pompe disease, 264
schematic representation, 400f
Lateral chest/axilla, 9f
screening of relatives, 407
Lateral tunnel Fontan procedure, 231
signs and symptoms, 398
LBBB. See Left bundle branch block (LBBB)
thromboembolic events, 405
LDL. See Low-density lipoprotein (LDL)
troponin I testing, 403
LDL cholesterol, 547t
Left ventricular (LV) outflow tract (LVOT)
Learn the Signs. Act Early, 637
obstruction, 123–124, 361, 362–363
Learn Your Lipids, 563
Left ventricular (LV) systolic function, 60–62
Leber congenital amaurosis, 382t
Legius syndrome, 262
LeCompte maneuver, 221
Lentigines, 381t
Left axis deviation, 22
LEOPARD syndrome, 262
Left bundle branch block (LBBB), 41, 42f
Lesions. See Congenital heart lesions
Left infraclavicular area, 9f
Levine system, 9
Left IVC to coronary sinus, 325–327
Levo-transposition of the great arteries
Left lower sternal border, 9f
(L-TGA), 305–308
Left MH sternal border, 9f
AV block, 36
Left posterolateral thoracotomy, 207
“deconditioned” LV, 306
Left pulmonary artery ligation, 209
diagnostic and preconsult testing, 307
Left-sided heart obstructive disease, 179
double switch procedure, 307
Left thoracotomy, 210
endocarditis prophylaxis, 307
Left-to-right shunt, 83–84
long-term complications, 277t
Left upper sternal border, 9f
Lyme carditis, contrasted, 491
Left ventricular (LV) noncompaction (LVNC),
management, 307
395–410
additional workup, 403
arrhythmia, 404–405
physical examination, 306
athletic participation, 406–407
cardiac MR imaging, 400, 402f
definition, 395
diagnostic approach, 399
Lidocaine, 672, 673t
differential diagnosis, 399
“Life’s Simple 7,” 569
echocardiography, 399, 401f
Lifestyle counseling, 643–654
electrocardiography (ECG), 402
exercise, 647–648, 649–650t
embryogenic hypothesis, 396
nutrition and diet. See Diet
epidemiology, 395–396
physical activity, 647–648, 649–650t
749
CCIP.indb 749 3/13/18 4:19 PM

INDEX
Lifestyle counseling (continued) LV systolic function. See Left ventricular (LV)

resources for families, 652 systolic function
sleep, 650–651, 651t Lyme carditis, 487–496
smoking, 648–650 AV block, 489–490
Ligamentum venosum, 194 diagnosis, 491
Limb leads, 13, 14f, 15 differential diagnosis, 491
Limb length discrepancy, 275 erythema migrans rash, 488, 488f
Limbus of the fossa ovalis, 190 etiologic origins and epidemiology, 487
Lipid levels. See Dyslipidemia Lyme disease, 487, 488–489
Lipid maturation factor-1, 552 male-to-female predominance, 488
Lipid panel, 556 management, 492–494
Lipodystrophy, 381t medications, 492, 493t
Lipoprotein lipase (LPL), 552 myocarditis, 491
Lipoprotein metabolism, 560t. See also ongoing care, 494
Dyslipidemia overview, 494f
Lisinopril, 588t pathogenesis, 488
Liver function tests, 551 pericarditis, 491
L-loop transposition of the great arteries. See prevalence, 487–488
Levo-transposition of the great arteries prevention, 492
(L-TGA) resources for families, 495
LMP. See Luminal myofibroblastic proliferation signs and symptoms, 488–491
(LMP) 3-stage clinical manifestation of Lyme
Long QT syndrome (LQTS), 412–414 disease, 488–489
Loop recorder, 150–151 treatment, 492, 493t
Loose skin, 381t 2-step antibody testing, 491
Losartan, 588t, 662t Lyme disease, 487, 488–489. See also Lyme
Lovastatin, 551 carditis
Low-density lipoprotein (LDL), 545 Lysosomal acid lipase deficiency, 560t
Lower rib pain syndrome, 120 Lysosomal storage disorder, 560t
Low-frequency murmurs, 10
Low-molecular weight heparin, 681t M
LPL. See Lipoprotein lipase (LPL) Macroglossia, 382t
LPL deficiency, 559 Macrolide, 458t
LQT1, 412, 413 Macrosomia, 381t
LQT2, 412, 413 MAGIC Foundation, 261
LQT3, 412, 413 Magnesium, 682t
LQT7, 413 Magnesium sulfate, 675t
LQT8, 413 Marden-Walker syndrome, 382t
LQTS. See Long QT syndrome (LQTS) Marfan syndrome, 124, 126, 164t, 663
L-TGA. See Levo-transposition of the great Marijuana, 124
arteries (L-TGA) Mash1, 614
Luminal myofibroblastic proliferation (LMP), Masked hypertension, 570
425 Maternal placenta, 191
LVNC. See Left ventricular (LV) noncompac- Maximum oxygen uptake, 72
tion (LVNC) MCA syndrome, 382t
LVOT obstruction. See Left ventricular (LV) MCV4 vaccine, 481t, 482t
outflow tract (LVOT) obstruction Mean pulmonary artery pressure (mPAP), 713
LV outflow obstruction. See Left ventricular Measles vaccine, 484, 485–486t
(LV) outflow tract (LVOT) obstruction Mechanical circulatory support, 404
750
CCIP.indb 750 3/13/18 4:19 PM

INDEX
Meckel-Gruber syndrome, 251 Modified Fontan techniques, 231

Median sternotomy, 205–207 Modified Jones criteria, 451b
Medications. See Cardiac pharmacology Modified Panama classification, 713, 714b
Mental “blackouts,” 140 Modified single-patch repair of atrioventricular
Mental health, 280 (AV) canal defect, 218–219
Metabolic syndrome, 561t Monomorphic ventricular tachycardia, 40, 40f,
Methamphetamine, 124 157
Method of disks, 61–62 Montreal cohort, 630t, 631
Methylphenidate, 597, 622 Motor skills, 630–631, 633
Methylprednisolone, 434, 455t Moya-moya disease, 140
Metolazone, 657t mPAP. See Mean pulmonary artery pressure
Metoprolol, 668t (mPAP)
Metoprolol XL, 588t MRI. See Cardiac magnetic resonance (MR)
“Mickey Mouse heart,” 387, 390, 391f imaging
Microcephaly, 382t Mucopolysaccharidosis, 381t, 382t
Microphthalmia, 250 Multicystic kidney disease, 250
Midodrine, 142, 621–622, 621t Multifocal premature ventricular contractions
Mid-systolic click, 175–176 (PVCs), 39
Migraine, 141 Multiple lentigines, 381t
Mild stenosis, audio recordings, 11, 12 Multistage incremental exercise protocol, 73
Milrinone, 659, 661, 661t Murmur. See Heart murmurs
Mineralocorticoid receptor antagonists, 384t Muscular ventricular septal defect, 356
Mitochondrial diseases, 617t MVP. See Mitral valve prolapse (MVP)
Mitral area, 8, 9f Mycophenolate mofetil, 703t
Mitral regurgitation, 446, 452b, 455 Mycoplasma, 517
Mitral stenosis, 446, 455–456 Myocardial disarray, 362
Mitral valve, 309, 354f Myocardial fibrosis, 97, 101f
Mitral valve anomalies, 308–311 Myocardial perfusion, 98
anatomy, 309 Myocardial “strain” imaging, 62–63
cleft mitral valve, 309 Myocarditis, 517–527
diagnostic and preconsult testing, 309 adolescents, 519, 520b
double-orifice mitral valve, 309 athletic participation, 524
male-to-female ratio, 308 bimodal age distribution, 518, 518f
management, 310 chest pain, 124
medication, 310 chest radiographic findings, 86t
mitral valve arcade, 309 definition, 517
ongoing care, 310 diagnostic tests and imaging, 520–522
parachute mitral valve, 309 differential diagnosis, 519–520, 520b
signs and symptoms, 309 ECG, 46–47, 46f
Mitral valve arcade, 309 echocardiography, 521–522
Mitral valve prolapse (MVP), 124 endomyocardial biopsy, 522
M-mode measurements, 60–61 epidemiology, 518
Mobitz type I atrioventricular (AV) block, etiologic origins, 517
34–35, 35f infants, 519, 520b
Mobitz type II atrioventricular (AV) block, inpatient management, 522–524
35, 36f intravenous immunoglobulin (IVIg), 523
Modified Bernoulli equation, 50 laboratory findings, 520, 521t
Modified Blalock-Taussig shunt, 194, 225, 226f, Myocarditis Treatment Trial, 518
228, 321, 322f nonviral pathogens, 517
Modified Duke criteria, 501, 502–503b outcomes, 523–524
751
CCIP.indb 751 3/13/18 4:19 PM

INDEX
Myocarditis (continued) Neuroblastoma, 569t

outpatient follow-up, 524 Neurocardiogenic syncope (NCS), 135, 136, 618
signs and symptoms, 519 Neurocognitive issues, 280
steroids, 523 Neurodevelopmental and psychosocial
supportive treatment, 522–523 outcomes, 627–641
viral prodrome, 519 academic performance (older children),
young children, 519, 520b 632–633
Myocarditis Treatment Trial, 518 ADHD, 634, 637
Myopericarditis, 534 behavior and executive functioning (older
Myosin-binding protein C, 362 children), 634
children aged 5 years and older, 632–635
N children from birth to 4 years of age,
629–631
Nadolol, 415, 669t
cognitive functioning (older children),
Naproxen, 455t
632–633
Narcolepsy, 141
cognitive functioning (younger children),
National Down Syndrome Society, 247
629–630
National Heart, Lung, and Blood Institute
cohorts under investigation, 630t
(NHLBI), 644, 648
communication and social skills (older
National Lipid Association Annual Summary of
children), 633–634
Clinical Lipidology 2016, 563
communication and social skills (younger
National Resource Center on ADHD, 601
children), 631
NBTE. See Nonbacterial thrombotic endocardi-
health-related quality of life (HRQOL), 635
tis (NBTE)
high-risk patients, 629b
NCS. See Neurocardiogenic syncope (NCS)
management (treatment), 635–637
Near-syncope, 133
motor skills (older children), 633
Neck webbing, 382t
motor skills (younger children), 630–631
Necrotizing arteritis, 425
overview (management algorithm), 636f
Necrotizing enterocolitis, 346
Neonatal palliation procedure, 224–229
types of developmental deficits, 627
Neonatal pulse oximetry. See Pulse oximetry
Neurofibroma, 381t
Neonate. See also Fetus
Neurofibromatosis type 1, 262, 381t
aortic coarctation, 210–211
Neuropathic POTS, 617
CHD. See Evaluation of neonate with
Newborn. See Neonate
congenital heart disease
New-onset aortic valve insufficiency, 216
congenital heart procedures, 206t
New York Heart Association Classification, 379t
dextro-transposition of the great arteries,
NHLBI. See National Heart, Lung, and Blood
86t, 89f
Institute (NHLBI)
ECG parameters, 18t
Niacin, 559
Nitric oxide (NO), 670, 671t, 715, 722t
home births, 202
Nitroprusside, 663, 664t
infective endocarditis (IE), 501
NO. See Nitric oxide (NO)
preterm delivery, 165t
Nonbacterial thrombotic endocarditis (NBTE),
pulmonary atresia, 194
497
pulse oximetry screening. See Pulse oximetry
Noncompaction cardiomyopathy, 395–410. See
transitional circulation, 192–194
also Left ventricular (LV) noncompac-
unmasking of congenital lesions, 194–195
tion (LVNC)
Nephrogenic systemic fibrosis (NSF), 101
Non-HDL cholesterol, 547t
Nephrotic syndrome, 561t
Nesiritide, 384t
752
CCIP.indb 752 3/13/18 4:19 PM

INDEX
Nonsteroidal anti-inflammatory drugs (NSAIDs) Orthostatic intolerance (OI), 615–617, 621t

acute pericarditis, 532 Osler, William, 237
aspirin. See Aspirin Osler nodes, 501
myopericarditis, 534 Ostium secundum, 190
postcardiac injury syndrome (PCIS), 538 Overriding fingers, 248
recurrent pericarditis, 534 Oxygen pulse, 73
Noonan syndrome Oxygen saturation, 5
clinical features, 261–262
diagnostic approach, 262 P
differential diagnosis, 262 Paclitaxel, 466
genetic cardiomyopathies, 381t, 382t Paco2. See Arterial partial pressure of CO2
management, 262–263 (Paco2)
ongoing care, 263 Paco2 level, 110
pathophysiology, 261 PACs. See Premature atrial contractions (PACs)
resources, 263 PAH. See Pulmonary arterial hypertension
Noonan Syndrome Association, 263 (PAH)
Noonan Syndrome Foundation, 263 Pain. See Chest pain
Norepinephrine, 667t Palivizumab, 484
Norwood procedure, 227–229, 321, 322f Palmar keratosis, 381t
Norwood-type aortic reconstruction, 229 Palmoplantar keratosis, 381t
NSAIDs. See Nonsteroidal anti-inflammatory Palpitations, 147. See also Arrhythmia
drugs (NSAIDs) Pancreatitis, 556
NSF. See Nephrogenic systemic fibrosis (NSF) Pao2. See Arterial oxygen tension (Pao2)
N-terminal (NT) proBNP, 111–112, 380, 403. Pao2 level, 110, 111
See also Brain natriuretic peptide (BNP) PAPVR. See Partial anomalous pulmonary
NT-proBNP. See N-terminal (NT) proBNP venous return (PAPVR)
NTRK1 gene, 616t Parachute mitral valve, 309
Nutrition and diet, 643–647. See also Diet Paradoxical embolus, 315
Nystagmus, 382t Parasternal imaging window, 52f, 60f
Parasympathetic nervous system, 614
O Parietal pericardium, 529
Oat fiber, 549 Partial anomalous pulmonary venous return
Obesity (PAPVR), 85t, 326–328
Canadian guidelines, 564 Partial atrioventricular (AV) canal defect, 296
dyslipidemia, 561t Parvovirus B19, 517
hypertension, 569 Past medical history, 4–5
sleep, 650 Patau syndrome
Obstructive liver disease, 561t associated cardiovascular findings, 250
Octreotide, 622 diagnostic approach, 251
OI. See Orthostatic intolerance (OI) differential diagnosis, 251
Olmesartan, 588t key clinical findings, 250
Omega-3 fatty acids, 559 management, 251
100% Fio2, 111 ongoing care, 251
Organ transplant, 562t. See also Heart pathophysiology, 250
transplantation resources, 251
Original Blalock-Taussig shunt, 225 Patent ductus arteriosus (PDA), 311–313
Orthodromic atrioventricular reentrant anatomy, 311
tachycardia, 28f audio recording, 169, 311–312
Orthostasis, 135 chest radiographic findings, 85t
Orthostatic hypotension, 133, 615 clinical features, 311–312
753
CCIP.indb 753 3/13/18 4:19 PM

INDEX
Patent ductus arteriosus (PDA) (continued) Penicillin G benzathine

closure of PDA, 208–210 group A streptococcal infection, 454t
fetal circulation, 190–191 Lyme disease, 493t
goal of treatment, 312 rheumatic fever, 458t
management, 312 Penicillin V
medication, 312, 677–678, 679t group A streptococcal infection, 454t
ongoing care, 313 rheumatic fever, 458t
surgical ligation, 312 Pericardial diseases, 529–541
Patent foramen ovale (PFO), 190, 314–316 acute pericarditis, 529–534
AHA recommendations, 315 chest pain, 124
anatomy, 314 constrictive pericarditis, 537
clinical features, 314–315 ECG, 47, 47f
echocardiography, 314f myopericarditis, 534
endocarditis prophylaxis, 315 pericardial effusion and cardiac tamponade,
management, 315 534–537
ongoing care, 315 postcardiac injury syndrome (PCIS), 538
prevalence, 314 recurrent pericarditis, 534
Pathological murmurs, 163–169. See also Heart resources for families, 539
murmurs Pericardial effusion and cardiac tamponade, 88f,
characteristics/differential diagnosis, 166, 167b 534–537
flowchart (suggested approach), 168f classification, 534–535
history, 163–165 clinical features, 535
management, 167–169 diagnosis, 536
murmur intensity, 166, 166t etiologic origins, 535
physical examination, 165–167 follow-up and prognosis, 537
Pathologic early repolarization, 411. See also physical examination, 535
Early repolarization syndrome (ERP) pulsus paradoxus, 535
PCIS. See Postcardiac injury syndrome (PCIS) signs and symptoms, 535
PCQLI cohort. See Pediatric Cardiac Quality of therapy, 536
Life Inventory (PCQLI) cohort ventricular diastolic collapse, 536
PDA. See Patent ductus arteriosus (PDA) Pericardial friction rub, 530
PE. See Pulmonary embolism (PE) Pericardial window, 536
Pediatric Cardiac Quality of Life Inventory Pericardiectomy, 536, 537
(PCQLI) cohort, 630t, 635 Pericardiocentesis, 536
Pediatric cardiac surgery. See Surgical procedures Pericarditis. See Pericardial diseases
for congenital heart disease Pericardium, 529
Pediatric Cardiomyopathy Registry, 377 Peripheral pulmonary stenosis, 316, 317
Pediatric functional classification scale, 719, Peripheral pulmonary stenosis murmur, 162
719b PFO. See Patent foramen ovale (PFO)
Pediatric heart failure. See Heart failure PGE1. See Prostaglandin E1 (PGE1)
Pediatric Heart Network Study (2007), 435 PGI2 analogue, 722t
Pediatric heart transplantation. See Heart PH. See Pulmonary hypertension (PH)
transplantation PHA. See Pulmonary Hypertension Association
Pediatric Heart Transplant Study, 406, 706, 711 (PHA)
Pediatric hypertension. See Hypertension PHA Online University, 724
Pediatric Quality of Life Inventory, 631 Pharmacological stress tests, 73
Pena Shokeir syndrome type 1, 248 Pharmacology. See Cardiac pharmacology
Phase velocity mapping, 96
Phenylephrine, 667t
754
CCIP.indb 754 3/13/18 4:19 PM

INDEX
Phox2a, 614 Posttransplant lymphoproliferative disease

PHOX2B gene, 616t (PTLD), 709–710
Physical activity, 647–648, 649–650t Posttraumatic pericarditis, 538
Physical examination, 5–8 Postural orthostatic tachycardia syndrome
Phytosterolemia, 560t (POTS), 137, 616–617, 620–622
“Pink” tetralogy of Fallot, 176, 330, 332 Potassium, 682t
Pitavastatin, 551 POTS. See Postural orthostatic tachycardia
Placenta, 191 syndrome (POTS)
Plant sterols, 549 Potts shunt, 225, 723
Plasma catecholamines, 620 PPSV23 vaccine, 481t, 482t
Point-of-care lipid testing, 556 Pravastatin, 551
Polyethylene terephthalate, 207 Precordial catch syndrome, 120
Polyhydramnios with joint contractures, 248 Precordial leads, 13, 14f, 16
Polymorphic premature ventricular contractions Prednisolone, 455t
(PVCs), 39 Prednisone, 703t
Polymorphic ventricular tachycardia, 157, 157f Preductal arterial oxygen tension (Pao2), 110, 111
Polysplenia, 82 Pre-excitation, 32
Polysplenic heterotaxy, 326. See also Heterotaxy Pregnancy
Polytetrafluoroethylene, 207 adults with CHD, 283
Polyvalvular disease, 248 dyslipidemia, 563t
Pompe disease, 382t rheumatic heart disease (RHD), 457
clinical features, 264 single-ventricle lesions, 324
diagnostic approach, 264 transposition of the great arteries (TGA), 338
differential diagnosis, 264 Premature atrial contractions (PACs), 152–153
management, 265 Premature infants, 165t, 172, 312, 570
ongoing care, 265 Premature ventricular contractions (PVCs),
pathophysiology, 263 38–40, 153–154
resources, 265 PRES. See Posterior reversible encephalopathy
Positive inotropic agents, 384t syndrome (PRES)
Postaxial polydactyly, 250 Preterm delivery. See Premature infants
Postcardiac injury syndrome (PCIS), 538 Preventive cardiology, 543–624
Posterior reversible encephalopathy syndrome athletic participation, 603–611
(PRES), 703 attention-deficit/hyperactivity disorder
Postmyocardial infarction pericarditis, 538 (ADHD), 595–602
Postoperative arrhythmias, 239 autonomic dysfunction, 613–624
Postoperative office care, 237–244 dyslipidemia, 545–565
activity restrictions, 238–239 hypertension, 567–593
chest pain, 241 Primum atrial septal defect (ASD), 212–214,
fever, 241 292, 292f
goals of postoperative office visit, 238 Principles and Practice of Medicine, The (Osler),
history, 238 237
medications, 239–240 PRKAG2 genetic mutation, 370
physical examination, 242–243 Procainamide, 673t
postoperative arrhythmias, 239 Progestin-only contraceptive pills, 281, 282t
postoperative symptoms, 240–241 Progressive exercise protocol, 74
shortness of breath, 241 Prohormone N-terminal BNP, 111–112, 380.
vital signs, 241–242 See also Brain natriuretic peptide (BNP)
wound care, 243 Prolonged QT interval, 44–45, 46b
Postpericardiotomy syndrome, 214, 538 Propafenone, 416
755
CCIP.indb 755 3/13/18 4:19 PM

INDEX
Propranolol, 665, 668t Eisenmenger physiology, 715, 723

Prostacyclin, 715 etiologic origins, 714
Prostaglandin, 182 general approach to care, 716–717
Prostaglandin E1 (PGE1), 677–678 idiopathic, 721
adverse effects, 678, 679t mean pulmonary artery pressure (mPAP), 713
dosing, 679t medications, 665, 670, 671–672t, 722t
newborn, 194, 195 modified Panama classification, 713, 714b
pharmacology, 679t overview, 718f, 720f
transposition of the great arteries (TGA), 336 pathophysiology, 714–715
Protease inhibitors, 557t pediatric functional classification scale, 719,
Protein-losing enteropathy, 232 719b
Protein sources, 549 Pulmonary Hypertension Association
Proton pump inhibitors, 121 (PHA), 717, 724
Pseudotrisomy 13 syndrome, 251 refractory, 721–723
Psychogenic syncope, 133 resources for families, 724
Psychotropic drugs, 596 right ventricular systolic pressure (RVSP), 718
PTLD. See Posttransplant lymphoproliferative support groups, 717
disease (PTLD) targeted therapy, 721, 722t
PTPN11 gene, 261 TOPP registry, 717, 718
Pulmonary arterial hypertension (PAH), 665, 670. treatment, 719–721
See also Pulmonary hypertension (PH) vascular changes, 721
Pulmonary artery, 100f ventricular septal defect (VSD), 356
Pulmonary artery banding, 226–227 WHO classification scale, 719
audio recording, 226 Pulmonary Hypertension Association (PHA),
AV canal defect, 299 717, 724
schematic representation, 227f Pulmonary stenosis, 316–320
single-ventricle lesions, 321 audio recordings, 12, 169, 317
ventricular septal defect (VSD), 355–356 chest radiographic findings, 85t
Pulmonary artery sling, 348f diagnostic testing, 318
Pulmonary atresia echocardiography, 318, 318f
chest radiographic findings, 86t, 87f management, 318–319
neonate, 194 ongoing care, 319
single-ventricle heart disease, 224 pathophysiology, 316–317
Pulmonary edema, 275 peripheral, 316, 317
Pulmonary ejection click, 317 physical examination, 317
Pulmonary embolism (PE), 121 prevalence, 316
Pulmonary flow murmur, 162, 166t pulmonary ejection click, 317
Pulmonary hypertension (PH), 713–726. See also resources for families, 319
Hypertension signs and symptoms, 317
AHA and American Thoracic Society supravalvar, 316
guidelines, 721 tetralogy of Fallot (TOF), 330f
atrial septal defect (ASD), 294 Pulmonary systolic ejection murmur, 162
chest pain, 124 Pulmonary valve, 354f
clinical presentation, 715 Pulmonary valve replacement (PVR)
cyanosis, 715 surgical procedure, 219–220, 220f
definition, 713 tetralogy of Fallot (TOF), 332
diagnosis and assessment, 717–719 Pulmonary valve stenosis, 316. See also
diet, 720 Pulmonary stenosis
echocardiography, 717–718 Pulmonary vascular markings (PVMs), 83–84
756
CCIP.indb 756 3/13/18 4:19 PM

INDEX
Pulmonary vascular resistance (PVR) R

AV canal defect, 298
RAA with aLSCA. See Right aortic arch (RAA)
heart failure, 178
with aberrant left subclavian artery
trisomy 21, 298
(aLSCA)
ventricular septal defect (VSD), 353
Rabbit ears pattern, 40
Pulmonary vein, 100f
Radial-to-femoral pulse delay, 302
Pulmonary vein anomalies, 325–329. See also
Radiation therapy, 466
Systemic and pulmonary vein anomalies
Radiograph. See Chest radiography
Pulmonic area, 8, 9f
RAISE study, 435
Pulse oximeter, 198
rarechromo.org, 251
Pulse oximetry, 53, 180, 197–204
RASopathies, 261, 262
AAP screening algorithm, 200, 201f
RASopathiesNet, 263
cost effectiveness, 199
RBBB. See Right bundle branch block (RBBB)
false-positive findings, 202
RCM. See Restrictive cardiomyopathy (RCM)
home births, 202
Recurrent pericarditis, 534
positive screening results (failing the
Reduced ejection fraction, 384t
screening), 200–202
Referral to cardiologist
primary targets of CCHD screening, 199
chest pain, 130
principles, 198
hypertension, 587–589
rationale for, 199
hypertrophic cardiomyopathy (HCM), 371
left ventricular (LV) noncompaction
secondary targets of CCHD screening,
(LVNC), 407
199–200
restrictive cardiomyopathy (RCM), 392
timing and technique, 200
syncope, 143
Pulse oximetry screening algorithm, 200, 201f
Refractory cardiogenic shock, 523
Pulse wave (PW) Doppler, 58
Refractory pulmonary hypertension, 721–723
Pulsus paradoxus, 535
Renal artery stenosis, 569t
PVCs. See Premature ventricular contractions
Renal parenchymal disease, 569t
(PVCs)
Renin inhibitors, 384t
PVMs. See Pulmonary vascular markings
Renovascular abnormalities, 569t
(PVMs)
Repair of aortic coarctation, 210–211
PVR. See Pulmonary valve replacement (PVR);
Repair of atrial septal defect (ASD), 212–216
Pulmonary vascular resistance (PVR)
Repair of complete AV canal defect, 216–219
P wave, 17, 20
Repair of secundum ASD, 214
PW Doppler. See Pulse wave (PW) Doppler
Repair of sinus venous ASD with PAPVR,
Pyridostigmine, 621t, 622
214–216
Repair of tetralogy of Fallot (TOF), 222–223,
Q 223f, 224f
Qp:Qs ratio, 96 Repair of total anomalous pulmonary venous
QRS complex, 21–23 return (TAPVR), 211–212, 213f
QRS notching, 416 Repair of ventricular septal defect (VSD), 216,
QTc values, 24–25, 25f 217f
QT interval, 24–25, 25f Resection and end-to-end anastomosis, 210, 211f
QT interval-prolonging medications, 46b Residual arch obstruction, 229
QT syndrome. See Long QT syndrome (LQTS); Resources. See also Resources for families
Short QT syndrome (SQTS) AAP. See American Academy of Pediatrics
Quinidine (AAP)
Brugada syndrome, 414 AHA. See American Heart Association
short QT syndrome (SQTS), 416 (AHA)
Q wave, 21, 21b
757
CCIP.indb 757 3/13/18 4:19 PM

INDEX
Resources (continued) restrictive cardiomyopathy (RCM), 393

athletic participation, 450 surgical procedures for congenital heart
audio recordings. See Audio recordings disease, 233
Down syndrome, 247 syncope, 144
Edwards syndrome, 250 tetralogy of Fallot (TOF), 333
Noonan syndrome, 263 truncus arteriosus, 347
Patau syndrome, 251 vascular rings and slings, 352
Pompe disease, 265 ventricular septal defect (VSD), 357
Turner syndrome, 261 Respiratory infection, 104f
22q11.2 deletion syndrome, 255 “Rest and digest” response, 614
Williams syndrome, 258 Restrictive apical muscular ventricular septal
Resources for families. See also Resources defect, 12
adults with congenital heart disease, 284 Restrictive cardiomyopathy (RCM), 387–394
arrhythmia, 158 athletic participation, 392
athletic participation, 610 cardiac catheterization, 391
atrial septal defect (ASD), 296 definition, 387
atrioventricular (AV) canal defects, 300 diagnostic approach, 390
attention-deficit/hyperactivity disorder diagnostic procedures, 391
(ADHD), 601 diagnostic tests, 390
autonomic dysfunction, 623 differential diagnosis, 389
cardiac computed tomography (CT), 107 endocarditis prophylaxis, 392
cardiac magnetic resonance (MR) imaging, epidemiology, 388
107 etiologic origin, 388, 389b
cardiac pharmacology, 683 imaging, 390
chest radiography, 93 implantable cardiac defibrillator (ICD), 392
childhood cancer survivors, 470 “Mickey Mouse heart,” 387, 390, 391f
coarctation of the aorta, 304 pathophysiology, 387
congenital heart disease (CHD), 183 referral to cardiologist, 392
dilated cardiomyopathy (DCM), 384 resources for families, 393
dyslipidemia, 563 signs and symptoms, 388
echocardiography, 68 treatment approach, 391–392
evaluation of neonate with CHD, 183 Restrictive high muscular ventricular septal
exercise testing, 78 defect, 12
heart murmurs, 169 Restrictive membranous ventricular septal
heart transplantation, 711 defect, 11, 357
hypertension, 591 Restrictive mid muscular ventricular septal
hypertrophic cardiomyopathy (HCM), 373 defect, 12
Kawasaki disease (KD), 439 Restrictive muscular ventricular septal defect,
left ventricular (LV) noncompaction 12, 357
(LVNC), 408 Retinoids, 557t
levo-transposition of the great arteries Retroesophageal diverticulum (Kommerell
(L-TGA), 308 diverticulum), 104f
lifestyle counseling, 652 Reversed differential, 336, 337f
Lyme carditis, 495 Reversed differential cyanosis, 177
neurodevelopmental and psychosocial Revised Jones criteria, 451b
outcomes, 637 RHD. See Rheumatic heart disease (RHD)
pericardial diseases, 539 RHD Action Alliance, 459
pulmonary hypertension (PH), 724 RHD Australia, 459
pulmonary stenosis, 319 Rheumatic fever, 164t
pulse oximetry, 203 Rheumatic Fever Helpline, 459
758
CCIP.indb 758 3/13/18 4:19 PM

INDEX
Rheumatic heart disease (RHD), 443–461. See Screen time, 648

also Acute rheumatic fever (ARF) and “Seattle criteria,” 607
rheumatic heart disease (RHD) Second-degree atrioventricular (AV) block,
Rheumatic valvulitis, 445b, 452b 34–35, 35f
Rickettsia, 517 Second heart sound (S2), 7, 8
Right aortic arch (RAA) with aberrant left Secundum atrial septal defect (ASD), 214, 292,
subclavian artery (aLSCA), 348, 349f 292f
Right axis deviation, 22 Seizure, 140
Right bundle branch block (RBBB), 40–41, 41f Selective estrogen receptor modulators, 557t
Right infraclavicular area, 9f Selective serotonin reuptake inhibitors, 622
Right-sided heart enlargement, 328 Sengers syndrome, 382t
Right upper sternal border, 9f Septal hypertrophy, 363f, 367f
Right ventricular hypertrophy, 330f Septum primum, 190
Right ventricular systolic pressure (RVSP), 718 Septum secundum, 190
Riley-Day syndrome, 616t Serial echocardiography, 504
Risks of Tobacco Use, The, 652 Shallow inspiration, 81
Robertsonian translocation, 245, 250 Shellfish, 549
Ross Heart Failure Classification, 379, 379t Shingles, 121
Ross procedure, 290 Shortness of breath, 241, 340
Rosuvastatin, 551 Short QT syndrome (SQTS), 416
Rotavirus vaccine, 481t Short stature, 259, 381t
Roth spots, 501 Sickle cell anemia, 121
rSR’ pattern, 40, 41 Sildenafil, 670, 671t, 722t
RVSP. See Right ventricular systolic pressure Simpson method, 61–62
(RVSP) Simvastatin, 551
RV to pulmonary artery (Sano) shunt, 225, 228, Single-patch repair of atrioventricular (AV)
229, 321, 322f canal defect, 218
Single-ventricle heart disease, 112, 224–233,
S 320–325, 322f
anatomy, 320
S1, 7, 8
bidirectional Glenn procedure, 229–230,
S2, 7, 8
230f, 321, 323, 323f
S3, 8, 11
S4, 8
diagnostic testing, 321
Salt tablets, 620
ductal stent, 321, 322f
Sano shunt. See RV to pulmonary artery (Sano)
fenestration, 231, 232
shunt
final Fontan circulation, 224
Sarcomeric genes, 373
Fontan procedure, 230–233, 323, 324f
Saturated fats, 549, 558b
Fontan takedown, 231
Sawtooth (ECG tracing), 30
forms of single-ventricle CHD, 224
SCAMP algorithm, chest pain, 129f
Glenn procedure, 229–230, 230f, 321, 323,
School-aged children. See Young children
323f
(children aged 1–12 years)
life-shortening complications, 324
Scientific Registry of Transplant Recipients, 711
Scimitar syndrome, 85t, 88f, 215–216
management, 224–233, 321–323
Scoliosis, 275, 276f
modified Fontan techniques, 231
Screening of relatives
neonatal palliation procedure, 224–229
aortic valve problems, 291
Norwood and Damus-Daye-Stansel (DKS)
hypercholesterolemia, 548
procedures, 227–229, 321, 322f
left ventricular (LV) noncompaction
(LVNC), 407
759
CCIP.indb 759 3/13/18 4:19 PM

INDEX
Single-ventricle heart disease (continued) STARS, 144

pregnancy, 324 Statins, 384t, 550–551, 559
prenatal diagnosis, 320 Steady-state free-precession imaging, 96, 98f
pulmonary artery banding, 226–227 Steroids
systemic to pulmonary artery shunt, acute pericarditis, 533
225–226 acute rheumatic fever and rheumatic heart
3-stage Fontan pathway, 224–233, 321–323 disease, 455t
Single-ventricle lesions, 320–325. See also dyslipidemia, 557t
Single-ventricle heart disease Kawasaki disease (KD), 435–436
Single Ventricle Reconstruction Trial cohort, Lyme carditis, 492
630t, 631 myocarditis, 523
Sinotubular junction, 287 Stethoscope, 10
Sinus bradycardia, 33 Still murmur, 10, 161–162, 166t, 169
Sinus tachycardia Stimulant medications, 596
arrhythmia, 152 St Jude Lifetime Cohort Study, 464
atrial tachycardia, compared, 29t Strain analysis, 62–63
electrocardiography (ECG), 27, 29t Streptococcus, 517
SVT, compared, 29t Streptococcus pneumoniae, 497
Sinus venosus ASD, 214–216, 292–293, 292f Streptococcus pyogenes, 497
Sirolimus, 703, 703t Streptococcus viridans, 501
Sitosterolemia, 548, 560t Stress echocardiography, 65
Situs ambiguous, 82 Stress testing, 71. See also Exercise testing
“6 A’s” mnemonic, 648 Stridor, 104f
6-minute walk test, 74 Structural cardiac defects, 122b, 123–124
Skeleton abnormalities, 381t ST segment, 23
Skin and hair abnormalities, 381t ST segment abnormalities, 42–44
Sleep, 650–651, 651t Subacute chronic vasculitis, 425
Sleep-disordered breathing, 570 Subaortic membrane, 289, 290
Sleep Problems in Children (handout), 652 Subcostal imaging window, 52f, 59f
Slipping rib syndrome, 120 Subpulmonary ventricular failure, 273b
Small muscular ventricular septal defect, 11 Sudden cardiac death
Smartphone technology, arrhythmia, 151 annual deaths, 603
Smith-Lemli-Opitz syndrome, 251, 253 athletes, 603
Smoking, 648–650 hypertrophic cardiomyopathy (HCM), 368
Snowman sign, 86t long QT syndrome (LQTS), 412
Sodium, 558b, 620 risk factors, 368b
Sodium nitroprusside, 663, 664t Sugars, 558b
SOFT. See Support Organization for Trisomy Sulfadiazine, 458t
18, 13, and Related Disorders (SOFT) Superior vena cava (SVC), 325
Sotalol, 416, 674t Support Organization for Trisomy 18, 13, and
Speckle tracking, 62 Related Disorders (SOFT), 251
Spectral Doppler imaging, 58 Supracardiac total anomalous pulmonary venous
Spinal muscular atrophy type 1, 264 return (TAPVR), 212, 213f, 326
Spin-echo MR imaging approach, 96, 97f Suprasternal imaging window, 52f, 62f
Spironolactone, 275, 656, 658t Suprasternal notch, 9f
Sports participation. See Athletic participation Supravalvar aortic stenosis, 289
SQTS. See Short QT syndrome (SQTS) Supravalvar pulmonary stenosis, 316
Standardized clinical assessment and manage- Supraventricular tachycardia (SVT)
ment plan. See SCAMP algorithm ablation procedures, 156
Staphylococcus aureus, 497, 499, 500 atrial tachycardia, compared, 29t
760
CCIP.indb 760 3/13/18 4:19 PM

INDEX
clinical features, 155b breath-holding spells, 135, 136–137

ECG, 27–29, 29t, 154f cardiac, 136, 137
long-term management, 155–156 causes, 134b
most common abnormal mechanism of clinical features, 136–137
tachycardia, 154 complications, 144
sinus tachycardia, compared, 29t definitions, 133
vagal maneuvers, 155 diagnostic procedures, 142
Surgical PDA closure, 208–210 differential diagnosis, 139–140
Surgical procedures for congenital heart disease, drop attacks, 139
205–235 ECG, 142
anomalies of the great vessels, 208–212 etiologic origins, 133
cardiopulmonary bypass, 207–208 evaluation, 137–139
closure of patent ductus arteriosus, 208–210 “Fainting Lark,” 137
common surgical procedures, 206t, 207t follow-up care, 143
conotruncal heart defects, 220–222 head-up tilt-table testing, 142
left posterolateral thoracotomy, 207 history, 137–139
median sternotomy, 205–207 hypoglycemia, 141
pulmonary valve replacement (PVR), imaging, 142–143
219–220, 220f intracranial pathologic processes, 141
repair of aortic coarctation, 210–211 laboratory evaluation, 142
repair of ASD, 212–216 management, 142–143
repair of complete AV canal defect, 216–219 medications, 142
repair of secundum ASD, 214 migraine, 141
repair of sinus venous ASD with PAPVR, narcolepsy, 141
214–216 neurocardiogenic syncope (NCS), 135, 136
repair of TAPVR, 211–212, 213f nonpharmacological treatment measures,
repair of TOF, 222–223, 223f, 224f 142
repair of VSD, 216, 217f orthostatic hypotension, 133
resources for families, 233 pathophysiology, 135–136
Scimitar syndrome, 215–216 physical examination, 139
septal defects, 212–219 postural orthostatic tachycardia syndrome
single-ventricle heart disease, 224–233. See (POTS), 137
also Single-ventricle heart disease prevention, 143
Warden procedure, 215, 215f prognosis, 144
Surgical pulmonary valve replacement (PVR), psychogenic, 133
219–220, 220f red flags, 138
survivorshipguidelines.org, 468, 470 referral to cardiologist, 143
SVC. See Superior vena cava (SVC) resources for families, 144
SVR. See Single Ventricle Reconstruction Trial seizure, 140
cohort; Systemic vascular resistance Syndromes associated with cardiac lesions,
(SVR) 245–268
SVT. See Supraventricular tachycardia (SVT) Down syndrome, 245–247
Sympathetic nervous system, 614 Edwards syndrome, 247–250
Symptomatic constrictive pericarditis, 537 glycogen storage disease type II, 263–265
Syncope, 133–146 Noonan syndrome, 261–263
arrhythmia, 148 Patau syndrome, 250–251
athletic participation, 143 Pompe disease, 263–265
autonomic dysfunction, 618 trisomy 13, 250–251
autonomic imbalance, 135 trisomy 18, 247–250
Bezold-Jarisch reflex, 135 trisomy 21, 245–247
761
CCIP.indb 761 3/13/18 4:19 PM

INDEX
Syndromes associated with cardiac lesions physical examination, 331

(continued) “pink” TOF, 176, 330, 332
Turner syndrome, 258–261 pregnancy, 333
22q11.2 deletion syndrome, 252–255 pulmonary stenosis, 330f
Williams syndrome, 255–258 repair, 222–223, 223f, 224f, 332
Systemic and pulmonary vein anomalies, resources for families, 333
325–329 signs and symptoms, 331
anatomy, 325–326 survival rate, 329
clinical features, 326–327 Tet spells, 330
diagnostic testing, 327 transannular patch, 220f, 332
interrupted IVC, 326, 327 types, 329–330
left IVC to coronary sinus, 325–327 “valve-sparing” approach, 332
management, 327 Tet spells, 330
ongoing care, 327–328 “Texidor twinge,” 120
PAPVR, 326–328 TGA. See Transposition of the great arteries
TAPVR, 326–328 (TGA)
Systemic to pulmonary artery shunt, 225–226 Third-degree atrioventricular (AV) block,
Systemic vascular resistance (SVR), 353 35–37, 37f
Systemic ventricular failure, 273b Third heart sound (S3), 8, 11
Systole, 6 Three-dimensional (3D) echocardiographic
Systolic anterior motion of mitral valve, 362 imaging, 63, 63f
Systolic click, 11, 175–176 3-stage Fontan pathway, 224–233, 321–323
Systolic murmurs, 8, 9 Thromboembolic events, 405
Thrombosis prevention and anticoagulation,
T 678–679, 680–681t
Thromboxane A, 715
Tacrolimus, 557t, 703, 703t
Thymic aplasia, 252
TAPVC. See Total anomalous pulmonary venous
Thymus, 81
connection (TAPVC)
Tietze syndrome, 119
TAPVR. See Total anomalous pulmonary venous
Tilt testing, 620
return (TAPVR)
Tilt training, 142
Taxanes, 466
Timothy syndrome, 413
TCA medication. See Tricyclic antidepressant
Tips for Healthy Families: More and Less, 652
(TCA) medications
Tissue characterization, 97–98
TEE. See Transesophageal echocardiography
TNF-α. See Tumor necrosis factor (TNF-α)
(TEE)
Toddlers. See Young children (children aged
Telecanthus, 382t
1–12 years)
Tetralogy of Fallot (TOF), 329–334
TOF. See Tetralogy of Fallot (TOF)
activity restrictions, 333
TOPP registry. See Tracking Outcomes
arrhythmia, 332
and Practice in Pediatric Pulmonary
“blue” TOF, 330, 332
Hypertension (TOPP) registry
“boot-shaped heart,” 331
Torsades de pointes, 682t
chest radiographic findings, 85t, 87f
Total anomalous pulmonary venous connection
cyanosis, 176, 330
(TAPVC), 177
Total anomalous pulmonary venous return
(TAPVR), 325–329
cardiac TAPVR, 326
management, 222–223, 223f, 224f, 332
infracardiac TAPVR, 212, 326
pathophysiology, 329–330
management, 327
762
CCIP.indb 762 3/13/18 4:19 PM

INDEX
ongoing care, 328 L-TGA. See Levo-transposition of the great

radiographic findings, 86t arteries (L-TGA)
repair, 211–212, 213f management, 336–338
supracardiac TAPVR, 212, 213f, 326 ongoing care, 338
Total cholesterol, 547t pregnancy, 338
Toxic shock syndrome (TSS), 431 red flags, 339
TP segment, 23 reversed differential, 336, 337f
Tracking Outcomes and Practice in Pediatric schematic representation, 335f
Pulmonary Hypertension (TOPP) Transthoracic echocardiography (TTE), 49. See
registry, 717, 718 also Echocardiography
Transannular patch, 220f, 332 Tricuspid area, 8, 9f
Transcription factors, 614 Tricuspid atresia
Transesophageal echocardiography (TEE), chest radiographic findings, 85t
64–65, 504. See also Echocardiography single-ventricle heart disease, 224
Transforming growth factor gene, 715 tricuspid valve anomaly, 339–340
Transgastric imaging, 64 Tricuspid regurgitation
Transient constrictive pericarditis, 537 acute rheumatic fever and rheumatic heart
Transitional atrioventricular (AV) canal defect, disease, 447
296 tricuspid valve anomalies, 339, 340
Transitional circulation, 192–194 Tricuspid stenosis, 339, 340
Transition from pediatric to adult care, 279, Tricuspid valve, 339, 354f
685–697 Tricuspid valve anomalies, 176, 339–343
adult care providers, 693 anatomy, 339
barriers to successful transition, 687b, clinical features, 340
689–694 cone reconstruction, 342
definitions, 686 diagnostic testing, 340
health care providers, 692 Ebstein anomaly, 340, 341f, 342
health education, 689, 691b management, 340–342
high-risk behaviors, 693 medication, 342
importance of transition systems, 686 ongoing care, 342
insurance issues, 694 Tricyclic antidepressant (TCA) medications,
moving locations, 694 596, 597
overview, 687f Triglycerides, 547t, 552. See also
parents, 690–692 Hypertriglyceridemia
patient/provider fears, 693–694 Triplet (PVCs), 39
peers, 693 Trisomy 13, 250–251
self-management, 688–689 Trisomy 18, 247–250
transition preparation, 688 Trisomy 18 Foundation, 250
transition timing, 686–687 Trisomy 21, 164t, 245–247, 298
Transplantation. See Heart transplantation Troponin I testing, 403
Transposition of the great arteries (TGA), Troponin T, 469
334–339 Truncal valve, 344
anatomy, 334–335 Truncus arteriosus, 343–347
arterial switch procedure, 338 chest radiographic findings, 86t
audio recording, 336 cyanosis, 177
clinical features, 336 diagnostic testing, 345
D-TGA. See Dextro-transposition of the management, 346
great arteries (D-TGA) ongoing care, 346
“egg on a string,” 337f pathophysiology, 344–345
763
CCIP.indb 763 3/13/18 4:19 PM

INDEX
Truncus arteriosus (continued) V

prevalence, 343
Vaccination, 477–486. See also Immunization
VAD. See Ventricular-assist device (VAD)
Vagal maneuvers, 155
VAGER, 253
tricuspid, quadricuspid, bicuspid truncal
Valsalva maneuver
valve, 344–345
adults with CHD, 280
Trypanosoma cruzi, 517
athletic participation, 605b
TSS. See Toxic shock syndrome (TSS)
chest pain, 123, 127, 130, 130b
TTE. See Transthoracic echocardiography
“Fainting Lark,” 137
(TTE)
hypertrophic cardiomyopathy (HCM), 364
Tumor necrosis factor (TNF-α), 436
pulmonary hypertension, 721
Turner, Henry, 258
structural cardiac defects, 123
Turner syndrome, 164t
supraventricular tachycardia (SVT), 155, 155b
clinical features, 259
Valsartan, 588t
“Valve-sparing” approach, 332
Vancomycin, 505
management, 260
Variable conduction, 31, 31f
Vascular rings and slings, 347–352
definitions, 347–348
resources, 261
Turner Syndrome Foundation, 261
double aortic arch (DAA), 348, 350, 350f
Turner Syndrome Society of the United States,
261
management, 351
T wave, 23–24
T wave abnormalities, 42–44
22q11.2 deletion syndrome
right aortic arch (RAA) with aberrant left
subclavian artery (aLSCA), 348, 349f
management, 254
schematic representations, 348f, 349f, 350f
Vasoconstrictors, 715
resources, 255
Vasodilators, 715
vaccination, 479
Vasovagal syncope, 135. See also
27-hydroxylase deficiency, 560t
Neurocardiogenic syncope (NCS)
2-dimensional (2D) echocardiographic imaging,
Vaughan Williams classification system, 672
58
Vegetables, 549
2-patch repair of atrioventricular (AV) canal
Velocardiofacial syndrome, 252
defect, 218, 218f
Venous hum, 163
Venous pulmonary vascular markings (PVMs),
U 84
Unbalanced complete AV canal defect, 224, 296 Ventilatory anaerobic threshold, 73
Unifocal premature ventricular contractions Ventricular-assist device (VAD), 523
(PVCs), 39 Ventricular diastolic collapse, 536
Unifocal ventricular tachycardia, 40, 40f Ventricular dysfunction, 520b
United Network of Organ Sharing registry, 405, Ventricular escape, 33, 33f
711 Ventricular hypertrophy, 38
764
CCIP.indb 764 3/13/18 4:19 PM

INDEX
Ventricular inversion, 305, 491. See also W

Levo-transposition of the great arteries
Warden procedure, 215, 215f
(L-TGA)
Warfarin
Ventricular septal defect (VSD), 353–357
adults with CHD, 279
aortic regurgitation, 353
American Heart Association patient’s guide,
audio recordings, 11, 12, 356–357
284
chest radiographic findings, 85t
dosing, 680t
classification by location, 353
pharmacology, 680t
restrictive cardiomyopathy (RCM), 391
double-chambered RV, 353
side effects, 680t
Waterston shunt, 225
Weight management, 550
ongoing care, 356
Wenckebach heart block, 34–35
Western blot, 491
Western Canadian Complex Pediatric Therapies
prevalence, 353
Project follow-up group, 630t, 631
repair, 216, 217f
When to refer. See Referral to cardiologist
White-coat hypertension, 570
Williams-Beuren syndrome, 255
signs and symptoms, 354–355
Williams syndrome
special issues, 353
clinical features, 256
Ventricular systolic function, 60–62
diagnostic approach, 257
Ventricular tachycardia (VT), 38–40, 40f, 156–158
Ventriculoarterial discordance, 220, 334. See also
Dextro-transposition of the great arteries
ongoing care, 258
(D-TGA)
Ventriculotomy, 222
resources, 258
Verapamil, 675t
Williams Syndrome Association, 258
Vertical vein, 212
Williams Syndrome Foundation, 258
Very low-density lipoprotein (VLDL), 545
Wilms tumor, 569t
Viral prodrome, 519
Wiry hair, 381t
Viridans group streptococci, 499
Wolff-Parkinson-White (WPW), 31–32, 32f,
Vital signs
156f, 340, 341f
assessment of, 5
WPW. See Wolff-Parkinson-White (WPW)
CHD, 174
WPW pattern, 32, 32f
postoperative office care, 241–242
Vitamin A derivatives, 552
VLDL. See Very low-density lipoprotein X
(VLDL) Xanthomas, 548
Volume overload, 523 Xiphodynia, 120
VSD. See Ventricular septal defect (VSD) Xiphoid pain, 120
VT. See Ventricular tachycardia (VT) X-ray. See Chest radiography
765
CCIP.indb 765 3/13/18 4:19 PM

INDEX
Y
Young children (children aged 1–12 years)
blood pressure categories, 568t
blood pressure charts, 572–575t, 578–581t
blood pressure values of concern, 568t
caloric intake, 647t
congenital heart procedures, 207t
dietary recommendations, 645–646t
history, 4
lipid levels, 547t
mean concentrations of triglycerides, 553t
myocarditis, 519, 520b
neurodevelopmental profile, 629–635
physical activity, 649–650t
sleep, 651t
Z
z scores, 429
766
CCIP.indb 766 3/13/18 4:19 PM

Common Cardiac I ssues in Pediatrics
Common Cardiac
Issues in Pediatrics
Common
Editors
Jonathan N. Johnson, MD, FACC, FAAP, and
Cardiac Issues
in Pediatrics
Learn from leading experts the latest information on cardiac

issues that present most often in a pediatric office. The
scope of focus includes signs and symptoms, management
of patients with acquired or congenital heart disease, cardiac
implications of common infectious diseases, preventive
cardiology, and other issues that are frequently managed or
evaluated by the primary care pediatrician.
Topics include
• Electrocardiography
• Heart Murmur
• Syncope
• Cardiomyopathies and Channelopathies
• Rheumatic Heart Disease
• Endocarditis
JOHNSON ∞ KAMAT
• Cardiac Pharmacology
• Transition From Pediatric to Adult-Centered
C
ardiac Care
Editors
For other pediatric resources, visit the
American Academy of Pediatrics
at shop.aap.org. Deepak M. Kamat, MD, PhD, FAAP
ISBN 978-1-61002-144-9
90000>
9 781610 021449
AAP
Common_Cardiac_issues_cover-spread_final.indd 1 3/13/18 3:31 PM

AAP Common Cardiac Issues in Pediatrics 2018 PDF

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

AAP Common Cardiac Issues in Pediatrics 2018 PDF

Uploaded by

Copyright:

Available Formats

Common Cardiac I­ ssues in Pediatrics

Learn from leading experts the latest information on ­cardiac

Common_Cardiac_issues_cover-spread_final.indd 1 3/13/18 3:31 PM

CCIP.indb 1 3/13/18 4:18 PM

CCIP.indb 2 3/13/18 4:18 PM

CCIP.indb 3 3/13/18 4:18 PM

Allison K. Black, MD Kanupriya Chaturvedi, MD, FAAP

CCIP.indb 4 3/13/18 4:18 PM

CCIP.indb 5 3/13/18 4:18 PM

Kelley K. Hutchins, DO, MPH Sonya Kirmani, MD

CCIP.indb 6 3/13/18 4:18 PM

Bradley S. Marino, MD, MPP, MSCE, FAAP Mark D. Norris, MD, MS

CCIP.indb 7 3/13/18 4:18 PM

Kristen Sexson Tejtel, MD, PhD, MPH, Joshua D. Sparks, MD

CCIP.indb 8 3/13/18 4:18 PM

Philip L. Wackel, MD Melissa Yamauchi, MD, MPH

Don P. Wilson, MD, FNLA

CCIP.indb 9 3/13/18 4:18 PM

Part 1: Evaluation of the Patient

Part 2: Common Signs and Symptoms

CCIP.indb 11 3/13/18 4:18 PM

Part 3: Congenital Heart Disease

CCIP.indb 12 3/13/18 4:18 PM

Single-Ventricle Lesions................................................................... 320

Part 5: Acquired Cardiac Diseases

CCIP.indb 13 3/13/18 4:18 PM

Part 6: Infectious Diseases

Part 8: General Issues in Primary Cardiac Care

CCIP.indb 14 3/13/18 4:18 PM

42. Transition and Transfer From ­Pediatric to Adult-Centered

Part 9: Special Conditions

CCIP.indb 15 3/13/18 4:18 PM

CCIP.indb 17 3/13/18 4:18 PM

and cardiac surgeons of the Publications and Communications Workgroup

Jonathan N. Johnson, MD, FACC, FAAP

CCIP.indb 18 3/13/18 4:18 PM

3. The Role of ­Echocardiography..................................................49

4. Basics of Exercise Testing..........................................................71

6. Cardiac MR ­Imaging and CT...................................................95

7. Laboratory Studies................................................................. 109

CCIP.indb 1 3/13/18 4:18 PM

CCIP.indb 3 3/13/18 4:18 PM

Past Medical History

CCIP.indb 4 3/13/18 4:18 PM

History Compilation Techniques

CCIP.indb 5 3/13/18 4:18 PM

CCIP.indb 6 3/13/18 4:18 PM

FIGURE 1-1. The cardiac cycle. AV = atrioventricular. From https://courses.lumenlearning.com/ap2/

CCIP.indb 7 3/13/18 4:18 PM

valve because of normal nonsynchronous contraction of the ventricles, with the

Physiology of Cardiac Murmurs

CCIP.indb 8 3/13/18 4:18 PM

Right Infraclavicular Area Suprasternal Notch

CCIP.indb 9 3/13/18 4:18 PM

wall. Grading diastolic murmurs is subjective and listener dependent. Grade I

CCIP.indb 10 3/13/18 4:18 PM

Audio Recordings ()

CCIP.indb 11 3/13/18 4:18 PM

•• Restrictive Muscular Ventricular Septal Defect (Willam Buck Kyle,

CCIP.indb 12 3/13/18 4:18 PM

CCIP.indb 13 3/13/18 4:18 PM

A Frontal plane leads

Frontal plane formed

Common Cardiac I ssues in Pediatrics

Learn from leading experts the latest information on cardiac

42. Transition and Transfer From Pediatric to Adult-Centered

3. The Role of Echocardiography..................................................49

6. Cardiac MR Imaging and CT...................................................95