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AHA/ACC/HRS GUIDELINE
2017 AHA/ACC/HRS Guideline for Management
of Patients With Ventricular Arrhythmias and
the Prevention of Sudden Cardiac Death
A Report of the American College of Cardiology/American Heart Association
Task Force on Clinical Practice Guidelines and the Heart Rhythm Society
WRITING COMMITTEE MEMBERS Developed in Collaboration
Sana M. Al-Khatib, MD, MHS, FACC, FAHA, FHRS, Chair With the Heart Failure Society
William G. Stevenson, MD, FACC, FAHA, FHRS, Vice Chair* of America
Michael J. Ackerman, MD, PhD*† ACC/AHA Task Force Members,
William J. Bryant, JD, LLM† see page e354
David J. Callans, MD, FACC, FHRS*‡
Anne B. Curtis, MD, FACC, FAHA, FHRS*†
Barbara J. Deal, MD, FACC, FAHA†
Timm Dickfeld, MD, PhD, FHRS*†
Michael E. Field, MD, FACC, FAHA, FHRS†
Gregg C. Fonarow, MD, FACC, FAHA, FHFSA*§
Anne M. Gillis, MD, FHRS*†
Christopher B. Granger, MD, FACC, FAHA*†
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The American Heart Association requests that this document be cited as follows: Al-Khatib SM, Stevenson WG, © 2017 by the American College of
Ackerman MJ, Bryant WJ, Callans DJ, Curtis AB, Deal BJ, Dickfeld T, Field ME, Fonarow GC, Gillis AM, Granger CB, Cardiology Foundation, the American
Hammill SC, Hlatky MA, Joglar JA, Kay GN, Matlock DD, Myerburg RJ, Page RL. 2017 AHA/ACC/HRS guideline for Heart Association, Inc., and the Heart
management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the Rhythm Society.
American College of Cardiology Foundation/American Heart Association Task Force on Clinical Practice Guidelines
and the Heart Rhythm Society. Circulation. 2018;138:e272–e391. doi: 10.1161/CIR.0000000000000549. https://www.ahajournals.org/journal/circ
CLINICAL STATEMENTS
Related to Specific Disease States . . . . . . . . . . . . . . e301
Preamble . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e274
AND GUIDELINES
7.1. Ischemic Heart Disease . . . . . . . . . . . . . . . . . . e301
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e275 7.1.1. Secondary Prevention of SCD
1.1. Methodology and Evidence Review . . . . . . . . . . e275 in Patients With Ischemic Heart
1.2. Organization of the Writing Committee . . . . . . e276 Disease . . . . . . . . . . . . . . . . . . . . . . . . e301
1.3. Document Review and Approval . . . . . . . . . . . . e276 7.1.2. Primary Prevention of SCD in Patients
1.4. Scope of the Guideline . . . . . . . . . . . . . . . . . . . e277 With Ischemic Heart Disease . . . . . . . . e304
1.5. Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . e279 7.1.3. Treatment and Prevention
2. Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e279 of Recurrent VA in Patients With
2.1. General Concepts . . . . . . . . . . . . . . . . . . . . . . . e279 Ischemic Heart Disease . . . . . . . . . . . . . e306
2.1.1. Premature Ventricular Complexes 7.2. Nonischemic Cardiomyopathy . . . . . . . . . . . . e308
and Nonsustained VT . . . . . . . . . . . . . . . e279 7.2.1. Secondary Prevention of SCD
2.1.2. VT and VF During ACS . . . . . . . . . . . . . . e281 in Patients With NICM . . . . . . . . . . . . . e308
2.1.3. Sustained VT and VF Not Associated 7.2.2. Primary Prevention of SCD
With ACS . . . . . . . . . . . . . . . . . . . . . . . . e281 in Patients With NICM . . . . . . . . . . . . . e309
2.2. Sudden Cardiac Death . . . . . . . . . . . . . . . . . . . e281 7.2.3. Treatment of Recurrent VA
2.2.1. Incidence of SCD . . . . . . . . . . . . . . . . . . e281 in Patients With NICM . . . . . . . . . . . . . e310
2.2.2. Population Subgroups and 7.3. Arrhythmogenic Right
Risk Prediction . . . . . . . . . . . . . . . . . . . . e282 Ventricular Cardiomyopathy . . . . . . . . . . . . . . e312
3. Mechanisms of VA . . . . . . . . . . . . . . . . . . . . . . . . . . e283 7.4. Hypertrophic Cardiomyopathy . . . . . . . . . . . . e315
3.1. Cellular Mechanisms and Substrates . . . . . . . . . e283 7.5. Myocarditis . . . . . . . . . . . . . . . . . . . . . . . . . . e318
3.2. Automaticity . . . . . . . . . . . . . . . . . . . . . . . . . . . e283 7.6. Cardiac Sarcoidosis . . . . . . . . . . . . . . . . . . . . e318
3.3. Triggered Activity . . . . . . . . . . . . . . . . . . . . . . . e283 7.6.1. Other Infiltrative Cardiomyopathies . . . e320
3.4. Reentry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e284 7.7. Heart Failure . . . . . . . . . . . . . . . . . . . . . . . . . e321
4. General Evaluation of Patients With Documented 7.7.1. HF With Reduced Ejection Fraction . . . e321
or Suspected VA . . . . . . . . . . . . . . . . . . . . . . . . . . . . e284 7.7.2. HF With Preserved Ejection
4.1. History and Physical Examination . . . . . . . . . . . e284 Fraction . . . . . . . . . . . . . . . . . . . . . . . . e321
4.2. Noninvasive Evaluation . . . . . . . . . . . . . . . . . . . e286 7.7.3. Left Ventricular Assist Device . . . . . . . . e322
4.2.1. 12-lead ECG and Exercise Testing . . . . . . e286 7.7.4. ICD Use After Heart Transplantation . . . e322
4.2.2. Ambulatory Electrocardiography . . . . . . e286 7.8. Neuromuscular Disorders . . . . . . . . . . . . . . . . e322
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16. Cost and Value Considerations . . . . . . . . . . . . . . . . e352 nation of information at the point of care to healthcare
CLINICAL STATEMENTS
18. Evidence Gaps and Future Research Needs . . . . . . . e354 Toward this goal, this guideline heralds the introduction
Appendix 1: Author Relationships With Industry of an evolved format of presenting guideline recommenda-
and Other Entities (Relevant)��������������������� e387
tions and associated text called the “modular knowledge
Appendix 2: Reviewer Relationships With Industry
chunk format.” Each modular “chunk” includes a table of
and Other Entities (Comprehensive)����������� e389
related recommendations, a brief synopsis, recommenda-
tion-specific supportive text and, when appropriate, flow
PREAMBLE diagrams or additional tables. References are provided
within the modular chunk itself to facilitate quick review.
Since 1980, the American College of Cardiology (ACC) This format also will facilitate seamless updating of guide-
and American Heart Association (AHA) have translated lines with focused updates as new evidence is published,
scientific evidence into clinical practice guidelines with and content tagging for rapid electronic retrieval of related
recommendations to improve cardiovascular health. recommendations on a topic of interest. This evolved for-
These guidelines, which are based on systematic meth- mat was instituted when this guideline was near comple-
ods to evaluate and classify evidence, provide a corner- tion; therefore, the current document represents a transi-
stone for quality cardiovascular care. The ACC and AHA tional formatting that best suits the text as written. Future
sponsor the development and publication of guidelines guidelines will fully implement this format, including
without commercial support, and members of each or- provisions for limiting the amount of text in a guideline.
ganization volunteer their time to the writing and review Recognizing the importance of cost–value consider-
efforts. Guidelines are official policy of the ACC and AHA. ations in certain guidelines, when appropriate and fea-
sible, an analysis of the value of a medication, device, or
intervention may be performed in accordance with the
Intended Use
ACC/AHA methodology.P-3
Practice guidelines provide recommendations applica- To ensure that guideline recommendations remain
ble to patients with or at risk of developing cardiovas- current, new data are reviewed on an ongoing basis,
cular disease. The focus is on medical practice in the with full guideline revisions commissioned in approxi-
United States, but guidelines developed in collabora- mately 6-year cycles. Publication of new, potentially
tion with other organizations may have a global impact. practice-changing study results that are relevant to an
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Although guidelines may be used to inform regulatory existing or new medication, device, or management
or payer decisions, their intent is to improve patients’ strategy will prompt evaluation by the Task Force, in
quality of care and align with patients’ interests. Guide- consultation with the relevant guideline writing com-
lines are intended to define practices meeting the mittee, to determine whether a focused update should
needs of patients in most, but not all, circumstances be commissioned. For additional information and poli-
and should not replace clinical judgment. cies regarding guideline development, we encourage
readers to consult the ACC/AHA guideline methodol-
ogy manualP-4 and other methodology articles.P-5–P-8
Clinical Implementation
Guideline-recommended management is effective only
when followed by healthcare providers and patients. Selection of Writing Committee Members
Adherence to recommendations can be enhanced by The Task Force strives to avoid bias by selecting experts
shared decision-making between healthcare provid- from a broad array of backgrounds. Writing commit-
ers and patients, with patient engagement in selecting tee members represent different geographic regions,
interventions based on individual values, preferences, sexes, ethnicities, races, intellectual perspectives/biases,
and associated conditions and comorbidities. and scopes of clinical practice. The Task Force may also
invite organizations and professional societies with re-
lated interests and expertise to participate as partners,
Methodology and Modernization collaborators, or endorsers.
The ACC/AHA Task Force on Clinical Practice Guidelines
(Task Force) continuously reviews, updates, and modi-
fies guideline methodology on the basis of published
Relationships With Industry and Other
standards from organizations including the Institute of Entities
MedicineP-1,P-2 and on the basis of internal reevaluation. The ACC and AHA have rigorous policies and methods
Similarly, the presentation and delivery of guidelines are to ensure that guidelines are developed without bias
reevaluated and modified on the basis of evolving tech- or improper influence. The complete relationships with
nologies and other factors to facilitate optimal dissemi- industry and other entities (RWI) policy can be found
online. Appendix 1 of the current document lists writing basis of the type, quantity, and consistency of data from
CLINICAL STATEMENTS
committee members’ relevant RWI. For the purposes of clinical trials and other sources (Table 1).P-4,P-6,P-8
AND GUIDELINES
full transparency, writing committee members’ compre- Glenn N. Levine, MD, FACC, FAHA
hensive disclosure information is available online, as is the Chair, ACC/AHA Task Force on Clinical Practice
comprehensive disclosure information for the Task Force. Guidelines
members may include methodologists, epidemiologists, summarize the evidence used by the writing committee
healthcare providers, and biostatisticians. When a formal to formulate recommendations. Additionally, the writing
systematic review has been commissioned, the recom- committee reviewed documents related to ventricular
mendations developed by the writing committee on the arrhythmias (VA) and sudden cardiac death (SCD) previ-
basis of the systematic review are marked with“SR.” ously published by the ACC, AHA, and the Heart Rhythm
Society (HRS). References selected and published in this
document are representative and not all-inclusive.
Guideline-Directed Management and As noted in the Preamble, an independent ERC was
Therapy commissioned to perform a formal systematic review of 2
The term guideline-directed management and therapy important clinical questions for which clear literature and
(GDMT) encompasses clinical evaluation, diagnostic test- prior guideline consensus were felt to be lacking or limited
ing, and pharmacological and procedural treatments. For (Table 2). The results of the ERC review were considered by
these and all recommended medication treatment regi- the writing committee for incorporation into this guide-
mens, the reader should confirm the dosage by review- line. Concurrent with this process, writing committee
ing product insert material and evaluate the treatment members evaluated other published data relevant to the
regimen for contraindications and interactions. The rec- guideline. The findings of the ERC and the writing com-
ommendations are limited to medications, devices, and mittee members were formally presented and discussed,
treatments approved for clinical use in the United States. then guideline recommendations were developed. The
“Systematic Review for the 2017 AHA/ACC/HRS Guide-
line for Management of Patients With Ventricular Ar-
Class of Recommendation and Level rhythmias and the Prevention of Sudden Cardiac Death”
of Evidence is published in conjunction with this guideline.S1.4-1
The Class of Recommendation (COR) indicates the The ACC and AHA have acknowledged the impor-
strength of the recommendation, encompassing the esti- tance of value in health care and have called for even-
mated magnitude and certainty of benefit in proportion tual development of a Level of Value for clinical practice
to risk. The Level of Evidence (LOE) rates the quality of recommendations.S1.4-2 Available cost-effectiveness data
scientific evidence that supports the intervention on the were determined to be sufficient to support 2 specific
Table 1. Applying Class of Recommendation and Level of Evidence to Clinical Strategies, Interventions, Treatments, or Diagnostic Testing in Patient
CLINICAL STATEMENTS
recommendations in this guideline (see Sections 7.1.1 general adult and pediatric cardiologists (including
and 7.1.2). As a result, a Level of Value was assigned those specialized in critical care and acute coronary
to those 2 recommendations on the basis of the “ACC/ syndromes [ACS], genetic cardiology, heart failure, and
AHA Statement on Cost/Value Methodology in Clini- cost-effectiveness analyses), a geriatrician with exper-
cal Practice Guidelines and Performance Measures,” as tise in terminal care and shared decision-making, and
shown in Table 3.S1.4-2 Available quality of life (QoL) data a lay representative, in addition to representatives from
were deemed to be insufficient to support specific rec- the ACC, AHA, HRS, and the Heart Failure Society of
ommendations in this guideline. America (HFSA).
1.2. Organization of the Writing Committee 1.3. Document Review and Approval
The writing committee consisted of cardiac electro- This document was reviewed by 2 official reviewers
physiologists (including those specialized in pediatrics), nominated by the ACC, AHA, and HRS; 1 official lay re-
Table 2. Systematic Review Questions on SCD Prevention Guideline for the Diagnosis and Treatment of Hyper-
CLINICAL STATEMENTS
Question Section trophic Cardiomyopathy.”S1.4-6 Some recommendations
AND GUIDELINES
Number Question Number from the earlier guidelines have been updated as war-
1 For asymptomatic patients with Brugada 7.9.1.3 ranted by new evidence or a better understanding of
syndrome, what is the association between an existing evidence, and irrelevant or overlapping recom-
abnormal programmed ventricular stimulation
study and SCD and other arrhythmia
mendations were deleted or modified.
endpoints? In the current guideline, sudden cardiac arrest (SCA)
2 What is the impact of ICD implantation for 10.3 is defined as the “sudden cessation of cardiac activity so
primary prevention in older patients and that the victim becomes unresponsive, with no normal
patients with significant comorbidities?
breathing and no signs of circulation.”S1.4-7 If corrective
ICD indicates implantable cardioverter-defibrillator; and SCD, sudden measures are not taken rapidly, this condition progresses
cardiac death. to SCD. Cardiac arrest is used to signify an event that can
be reversed, usually by cardiopulmonary resuscitation
viewer nominated by the AHA; 1 organizational review- (CPR), administration of medications and/or defibrillation
er nominated by the HFSA; and 28 individual content or cardioversion. SCA and SCD can result from causes
reviewers. Reviewers’ RWI information was distributed other than VA, such as bradyarrhythmias, electrome-
to the writing committee and is published in this docu- chanical dissociation, pulmonary embolism, intracranial
ment (Appendix 2). hemorrhage, and aortic dissection; however, the scope
This document was approved for publication by the of this document includes only SCA and SCD due to VA.
governing bodies of the ACC, the AHA, and the HRS; This guideline includes indications for ICDs for the
and endorsed by the HFSA. treatment of VA and prevention of SCD, but it does
not delve into details on individual device selection and
1.4. Scope of the Guideline programming, including considerations relevant to car-
diac resynchronization therapy (CRT), bradycardia pac-
The purpose of this AHA/ACC/HRS document is to pro-
ing, and hemodynamic monitoring. These important
vide a contemporary guideline for the management of
aspects of ICD management have been covered in an
adults who have VA or who are at risk for SCD, including
HRS expert consensus statement.S1.4-8 An AHA science
diseases and syndromes associated with a risk of SCD
advisory discusses the use of wearable cardioverter-
from VA. This guideline supersedes the “ACC/AHA/
defibrillators.S1.4-9 The findings of that document were
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tions relevant to these important concepts. The importance the data and current recommended medical practice.
CLINICAL STATEMENTS
of a shared decision-making process in which the patient, These refinements were reviewed and approved by the
AND GUIDELINES
family, and clinicians discuss risks and benefits of diag- writing committee, the Task Force, and ACC, AHA, and
nostic and treatment options and consider the patients’ HRS organizational leadership. These recommendations
personal preferences is emphasized (see Section 15). were:
In developing this guideline, the writing committee • Section 7.1.1., recommendation 1
reviewed previously published guidelines and related • Section 7.1.3., recommendation 2
statements. Table 4 contains a list of guidelines and • Section 7.2.1., recommendation 1
statements deemed pertinent to this writing effort and • Section 7.9.1.4., recommendation 2
is intended for use as a resource, obviating repetition of • Section 10.8., recommendation 6
existing guideline recommendations. Readers should refer to these sections for the up-
During final production review of the guidelines, dated text.
several recommendations were refined to better reflect
ACC indicates American College of Cardiology; ACCF, American College of Cardiology Foundation; AHA, American Heart Association; APHRS, Asia Pacific Heart
Rhythm Society; EHRA, European Heart Rhythm Association; ESC, European Society of Cardiology; HRS, Heart Rhythm Society; PACES, Pediatric and Congenital
Electrophysiology Society; SCAI, Society for Cardiovascular Angiography and Interventions; and, SOLAECE, Sociedad Latinoamericana de Estimulacion Cardiaca y
Electrofisiologia.
CLINICAL STATEMENTS
conditions, and with specific family history and genetic
AND GUIDELINES
Abbreviation Meaning/Phrase
variants, and this variation has important implications
ACS acute coronary syndromes for studying and applying therapies.
AED automated external defibrillator
2.1.1. Premature Ventricular Complexes and
AMI acute myocardial infarction
Nonsustained VT
BNP B-type natriuretic peptide
PVCs are common and increase in frequency with
CABG coronary artery bypass graft age. Although PVCs were found in a healthy military
CKD chronic kidney disease population in only 0.6% of those <20 years of age
CPR cardiopulmonary resuscitation and 2.7% of those >50 years of ageS2.2.2-5 on 12-lead
CRT cardiac resynchronization therapy ECGs, longer term monitoring shows PVCs in about
CT computed tomography
50% of all people with or without heart disease.S2.2.2-6
The presence of PVCs on 2 minutes of monitoring
ECG electrocardiogram
of middle-aged patients in the ARIC (Atherosclerosis
ERC evidence review committee
Risk In Communities) study was associated with in-
ESRD end-stage renal disease creased risk of both ischemic heart disease events and
GDMT guideline-directed management and therapy mortality, with or without prevalent ischemic heart
HCM hypertrophic cardiomyopathy disease.S2.2.2-7,S2.2.2-8 In the general population, frequent
HF heart failure PVCs, which are defined as the presence of at least
HFpEF heart failure with preserved ejection fraction
1 PVC on a 12-lead ECG or >30 PVCs per hour, are
associated with increased cardiovascular risk and in-
HFrEF heart failure with reduced ejection fraction
creased mortality.S2.2.2-9 In a study from Taiwan of pa-
ICD implantable cardioverter-defibrillator
tients without sustained VT or structural heart disease
LV left ventricular who had 24-hour Holter monitoring for clinical evalu-
LVAD left ventricular assist device ation, multifocal PVCs were associated with increased
LVEF left ventricular ejection fraction risk of death and nonfatal cardiovascular adverse
MI myocardial infarction outcomes.S2.2.2-10 In the same population, nonsustained
ventricular tachycardia (NSVT) was independently as-
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Ventricular tachycardiaS2.2.2-2 Cardiac arrhythmia of ≥3 consecutive complexes originating in the ventricles at a rate >100 bpm (cycle length: <600 ms). Types of VT:
Sustained: VT >30 s or requiring termination due to hemodynamic compromise in <30 s.
Nonsustained/unsustained: ≥3 beats, terminating spontaneously.
Monomorphic: Stable single QRS morphology from beat to beat.
Polymorphic: Changing or multiform QRS morphology from beat to beat.
Bidirectional: VT with a beat-to-beat alternation in the QRS frontal plane axis, often seen in the setting of digitalis toxicity or
catecholaminergic polymorphic VT
Monomorphic VT
Polymorphic VT
Bidirectional VT
Torsades de pointesS2.2.2-2 Torsades de pointes is polymorphic VT that occurs in the setting of a long QT interval and is characterized by a waxing and
waning QRS amplitude. It often has a long-short initiating sequence with a long coupling interval to the first VT beat and
may present with salvos of NSVT. The twisting of the points, although characteristic, may not always be seen, especially if the
episode is nonsustained or if only a limited number of leads are available. Torsades de pointes can result from bradycardia
including high-grade AV block that leads to a long-short sequence initiating torsades de pointes.
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Ventricular flutterS2.2.2-2 A regular VA ≈300 bpm (cycle length: 200 ms) with a sinusoidal, monomorphic appearance; no isoelectric interval between
successive QRS complexes.
Ventricular fibrillationS2.2.2-2 Rapid, grossly irregular electrical activity with marked variability in electrocardiographic waveform, ventricular rate usually >300
bpm (cycle length: <200 ms).
Sudden cardiac arrestS2.2.2-2 SCA is the sudden cessation of cardiac activity such that the victim becomes unresponsive, with either persisting gasping
respirations or absence of any respiratory movements, and no signs of circulation as manifest by the absence of a perceptible
pulse. An arrest is presumed to be of cardiac etiology unless it is known or likely to have been caused by trauma, drowning,
respiratory failure or asphyxia, electrocution, drug overdose, or any other noncardiac cause.
Sudden cardiac deathS2.2.2-2 Sudden and unexpected death occurring within an hour of the onset of symptoms, or occurring in patients found dead within
24 h of being asymptomatic and presumably due to a cardiac arrhythmia or hemodynamic catastrophe.
VT/VF stormS2.2.2–3 VT/VF storm (electrical storm or arrhythmic storm) refers to a state of cardiac electrical instability that is defined by ≥3 episodes
of sustained VT, VF, or appropriate shocks from an ICD within 24 h.
Primary prevention ICDS2.2.2-2 ICD placement with the intention of preventing SCD in a patient who has not had sustained VT or SCA but who is at an
increased risk for these events.
Secondary prevention ICDS2.2.2-2 ICD placement in a patient with prior SCA, sustained VT, or syncope caused by VA.
Structural heart disease* This term encompasses IHD, all types of cardiomyopathy, valvular heart disease, and adult congenital heart disease.
Cardiac channelopathyS2.2.2–4 Arrhythmogenic disease due to a genetic abnormality that results in dysfunction of a cardiac ion channel (eg, long QT
syndrome, catecholaminergic polymorphic VT).
*The definition of this term may differ across publications. Refer to the entry for the definition used in this document.
AV indicates atrioventricular; ICD, implantable cardioverter-defibrillator; IHD, ischemic heart disease; NSVT, nonsustained ventricular tachycardia; SCA, sudden
cardiac arrest; SCD, sudden cardiac death; VA, ventricular arrhythmia; VF, ventricular fibrillation; and VT, ventricular tachycardia.
ers, and some antiarrhythmic medications may relieve clinical trial, 5.7% developed sustained VT or VF, with
CLINICAL STATEMENTS
symptoms of palpitations.S2.2.2-18 two thirds of these events occurring prior to the end
AND GUIDELINES
PVCs that occur during an exercise test are associ- of the catheterization, and 90% within 48 hours from
ated with a higher risk of death.S2.2.2-19 In 1 study, PVCs the procedure. VT or VF after primary PCI was associ-
that occur during recovery are a stronger predictor of ated with lower blood pressure, higher heart rate, poor
death than PVCs occurring only during exercise.S2.2.2-20 coronary flow at the end of the procedure, and incom-
However, PVCs are common in trained athletes who plete resolution of ST elevation.S2.2.2-32 Importantly, and
have palpitations, in whom there does not appear to be in contrast to some earlier studies, VT or VF at any time
increased risk of death based on studies of small num- was associated with a substantially higher risk of death
bers of athletes, at least in those without other cardio- within 90 days. Late VT or VF (after 48 hours of hos-
vascular abnormalities.S2.2.2-21,S2.2.2-22 Complex PVCs may pital presentation) was associated with a higher risk of
not represent a benign finding in endurance athletes. death than early VT or VF (within 48 hours of hospital
An electrophysiological study may be needed to as- presentation).S2.2.2-33
sess patients’ arrhythmogenic risk.S2.2.2-22 Very frequent
PVCs, >10 000 to 20 000 a day, can be associated with 2.1.3. Sustained VT and VF Not Associated
depressed LV function in some patients that is revers- With ACS
ible with control of the PVCs, and has been referred Patients with structural heart disease are at an in-
to as PVC-induced cardiomyopathy.S2.2.2-23,S2.2.2-24 (See creased risk for sustained VT and VF. Sustained VT that
also Section 8.5. PVC-Induced Cardiomyopathy.) Very is not associated with an ACS is often monomorphic
rarely, idiopathic PVCs from the outflow tract may trig- as it is usually due to scar-related reentry, but it may
ger malignant VA in patients without structural heart degenerate to VF.S2.2.2-34 The risk and predictors of VT
disease.S2.2.2-25,S2.2.2-26 in patients with structural heart disease depend on the
type, severity, and duration of structural heart disease,
2.1.2. VT and VF During ACS increasing with the severity of ventricular dysfunc-
Approximately half of patients with out-of-hospital tion and the presence of symptomatic HF. Monomor-
cardiac arrest with the first rhythm identified as VF phic VT occurring in the absence of structural heart
and who survive to hospital admission have evidence disease is commonly referred to as idiopathic VT and
of acute MI (AMI).S2.2.2-27 Of all out-of-hospital cardiac is often due to an automatic focus in a characteris-
arrests, >50% will have significant coronary artery le- tic location, giving rise to typical electrocardiographic
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sions on acute coronary angiography.S2.2.2-27 Of patients appearances. Polymorphic VT and VF occurring in the
hospitalized with AMI, 5% to 10% have VF or sus- absence of structural heart disease are rare and may
tained VT prior to hospital presentation, and another be due to a cardiac channelopathy,S2.2.2-35,S2.2.2-36 med-
5% will have VF or sustained VT after hospital arrival, ication-induced long QT syndrome,S2.2.2-36 or they may
most within 48 hours of admission. A study of patients be idiopathic.S2.2.2-37,S2.2.2-38
with non–ST-elevation ACS who underwent cardiac
catheterization within 48 hours found VT/VF in 7.6%
of patients, with 60% of those events within 48 hours 2.2. Sudden Cardiac Death
of admission.S2.2.2-28 Accelerated idioventricular rhythm 2.2.1. Incidence of SCD
is a common arrhythmia in patients with acute MI, SCA and its most common consequence, SCD,
including patients with ST-segment elevation MI un- constitute major public health problems, account-
dergoing primary percutaneous coronary intervention ing for approximately 50% of all cardiovascular
(PCI). Accelerated idioventricular rhythm is more closely deaths,S2.2.2-1,S2.2.2-39 with at least 25% being first symp-
related to the extent of infarction than to reperfusion tomatic cardiac events.S2.2.2-1,S2.2.2-40,S2.2.2-41 In addition,
itself.S2.2.2-29 analyses of the magnitude of SCD are limited, in part
Sustained VA that occurs in the setting of an ACS is because of the broad range of estimates of the risk
more often polymorphic VT or VF than monomorphic based on different epidemiological methods.S2.2.2-42
VT. Risk factors for VT/VF include prior history of hy- During the past 20 to 30 years, SCD accounted for
pertension, prior MI, ST-segment changes at presenta- approximately 230 000 to 350 000 deaths per year
tion, and chronic obstructive pulmonary disease.S2.2.2-30 in the United States, with a range of <170 000 to
A nationwide Danish study found that 11.6% of pa- >450 000, depending on epidemiological methods,
tients with ST-segment elevation MI who underwent data sources, and inclusion criteria.S2.2.2-41,S2.2.2-43 The
PCI had VF prior to the PCI, and that VF was associ- lowest of these extremes came from national extrapo-
ated with alcohol consumption, preinfarction angina, lation of data from specific local programs, while the
anterior infarct location, and complete coronary occlu- highest rates included noncardiac causes of sudden
sion at the time of coronary angiography.S2.2.2-31 In a death such as pulmonary embolism or intracranial
select group of patients undergoing primary PCI in a bleeding. The mid-range numbers were largely based
on death certificate studies that required a code inclu- bination of public location of cardiac arrest, bystander
sive of ischemic heart disease. witnesses willing to provide CPR, first responders arriv-
The 2017 update of cardiovascular statistics from ing quickly, shockable rhythm at initial contact, avail-
the AHA estimated the total annual burden of out- ability of automated external defibrillators (AEDs), and
of-hospital cardiac arrest at 356 500.S2.2.2-44 An ad- possibly a benefit from telecommunication-directed
ditional 209 000 in-hospital cardiac arrests occur CPR.S2.2.2-46,S2.2.2-47 Survival to hospital discharge after in-
annually.S2.2.2-45 Among the out-of-hospital cardiac
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2.2.2. Population Subgroups and Risk Prediction creasing proportion of ischemic heart disease (>40%
CLINICAL STATEMENTS
Risk prediction for SCA and SCD is complex. Risk analy- of cases).S2.2.2-43
AND GUIDELINES
sis is divided into 2 general categories: population risk Despite the small progress that has been made in risk
prediction and individual risk prediction.S2.2.2-41,S2.2.2-50 prediction of SCA and SCD, the greatest challenge is
Conventional epidemiological markers provide insight to identify the relatively small, high-risk subgroups con-
into probabilities for the development of ischemic heart cealed within the large general population who have
disease within a general class of subjects, but ade- no identified disease but are at risk of SCA as their first
quately tested and validated profiles for SCA risk strati- cardiac event (Figure 1).S2.2.2-50
fication of individuals in the general population do not
presently exist. The challenge of defining SCA risk in
individuals derives from a population model character- 3. MECHANISMS OF VA
ized by large numbers of events diluted into a very large 3.1. Cellular Mechanisms and Substrates
denominator (Figure 1). The overall population can be
Mechanisms of VA include enhanced normal au-
subgrouped into categories based on integration of
tomaticity, abnormal automaticity, triggered activ-
age, presence and extent of disease, and identification
ity induced by early or late afterdepolarizations, and
of small, high-risk subgroups within the large denomi-
reentry.S3.4-1–S3.4-3 Reentry requires a trigger to initiate
nator general population.
the arrhythmia and a substrate to sustain it. The trig-
Increasing age is a strong predictor of risk for SCA,
ger may be a PVC, which may be due to automaticity.
but it is not linear. Risk in the general population, over
The substrate may be structural remodeling secondary
time, beginning at 35 years of age has been estimated
to an underlying disease process, and often includes
at 1 per 1000 population per year, increasing from a
a scar secondary to a prior MI or surgical repair, or
risk <1000 at the younger end of that spectrum to a
patchy fibrosis in the setting of cardiomyopathy or
higher risk in the elderly.S2.2.2-41 However, an analysis
hypertrophy. Changes in ion channel or transporter
of lifetime risk of SCD, derived from the Framingham
function and/or expression and cell to cell coupling
data, suggested that the incidence of SCD decreases in
secondary to the underlying pathology may alter the
later years, especially in people >75 years of age.S2.2.2-51
initiation or propagation of the cardiac action poten-
The data also suggested that SCD is uniformly more
tial. The electrophysiological substrate is dynamically
common in men than in women at all age groups. influenced by a variety of factors including cardiac
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In contrast, the population of children, adolescents, metabolism, electrolytes, signaling pathways and au-
and young adults has an overall annual risk of 1 per tonomic effects. Enhanced automaticity or abnormal
100 000, and there is somewhat a higher risk of SCD automaticity causing VA may arise from subordinate
at the younger end of that age range.S2.2.2-41 An age- pacemaker cells in the His-Purkinje system or ventricu-
associated transition range, from the mid-20s to 35 to lar myocardium.
40 years of age, is characterized by a steep increase in
risk from that of the adolescent group to the middle-
aged group, corresponding to the emergence of isch- 3.2. Automaticity
emic heart disease. Normal automaticity results from phase 4 spontane-
Although ischemic heart disease remains the most ous depolarization of the transmembrane action po-
common underlying substrate associated with SCD, tential arising from a normal resting potential, reach-
the incidence of ischemic heart disease-related SCD ing threshold and initiating an action potential.S3.4-1,S3.4-3
appears to be decreasing,S2.2.2-52 with various forms An initiating current (If) is responsible for spontaneous
of cardiomyopathy associated with myocardial fibro- phase 4 depolarization in the sinus node. The rate is
sis and LV hypertrophy increasing.S2.2.2-53 In addition, determined by the integration of the maximum dia-
a trend over time has suggested that out-of-hospital stolic potential at the end of repolarization, the slope
cardiac arrest patients who are admitted alive to a of phase 4 depolarization, and the threshold potential.
hospital are becoming more likely to have high-risk In contrast, abnormal automaticity arises from a par-
clinical profiles, as opposed to manifest disease.S2.2.2-54 tially depolarized membrane potential that is usually
The younger population—children, adolescents, and close to the activation potential for calcium channels
young adults—is affected by a series of disorders in the cell membrane.S3.4-1,S3.4-3 In the acute phase of an
that manifest earlier in life, including the genetic MI or during transient ischemia, increased extracellular
structural disorders and cardiac channelopathies, potassium causes partial depolarization of the resting
myocarditis, congenital heart disease, and other rare membrane potential creating injury currents between
disorders.S2.2.2-43 During the transition range, from the the infarcted/ischemic tissue and healthy myocardium.
mid-20s to the mid-30s, causes of SCA and SCD in- These injury currents may initiate spontaneous activity.
clude a lower proportion of inherited diseases and in- In ischemia, abnormal automaticity may occur in both
ventricular myocytes and Purkinje fibers, and may also a fixed anatomical obstacle, such as scar after an MI
CLINICAL STATEMENTS
enhance normal automaticity in Purkinje fibers in the or surgically repaired congenital heart disease. In this
AND GUIDELINES
current. If the membrane depolarization is sufficiently 1. P atients presenting with syncope for which
VA is documented, or thought to be a likely
large, the inward sodium current is activated resulting I B-NR
cause, should be hospitalized for evaluation,
in a triggered action potential. Delayed afterdepolar- monitoring, and management.S4.1-1–S4.1-4
izations are the underlying mechanism for VT in the
*This section covers practices that are well accepted, and a new
setting of digoxin toxicity, catecholaminergic polymor- recommendation was determined to only be warranted for syncope.
phic VT, and idiopathic outflow tract VA. Delayed af-
terdepolarizations are also considered to be an impor-
Synopsis
tant trigger of VA in the setting of HF. Purkinje cells
are more susceptible to spontaneous sarcoplasmic re- VA can produce a wide spectrum of symptoms, and the
ticulum calcium release than ventricular myocytes sug- severity of symptoms does not necessarily reflect the
gesting that delayed afterdepolarizations may be an extent of structural heart disease or the potential risk
important mechanism for some Purkinje fiber-related of SCD. Symptoms of VA include palpitations, either
VA.S3.4-3,S3.4-8,S3.4-9 skipped or extra beats or sustained palpitations, short-
ness of breath, chest pain, dizziness, near syncope, and
syncope.S4.1-5,S4.1-6 Palpitations may correlate with VA but
3.4. Reentry are frequently reported during normal rhythm.S4.1-7 The
Reentry is the underlying mechanism for most differential diagnosis of exercise intolerance, chest pain,
sustained VA in the presence of structural heart dyspnea, presyncope, and syncope includes VA but also
disease.S3.4-1–S3.4-3,S3.4-10–S3.4-12 Reentry may occur around includes other etiologies. Nonetheless, more dramatic
CLINICAL STATEMENTS
Known or Suspected VA
Assessment and Findings Relevant
AND GUIDELINES
Assessment and Findings Relevant Component for VA and/or SCD Risk
Component for VA and/or SCD Risk
Examination 1. Heart rate and regularity, blood pressure
History 1. Symptoms/events related to arrhythmia: Palpitations,
2. Jugular venous pressure
lightheadedness, syncope, dyspnea, chest pain,
cardiac arrest 3. Murmurs
2. Symptoms related to underlying heart disease: 4. Pulses and bruits
Dyspnea at rest or on exertion, orthopnea,
5. Edema
paroxysmal nocturnal dyspnea, chest pain, edema
6. Sternotomy scars
3. Precipitating factors: Exercise, emotional stress
4. Known heart disease: Coronary, valvular (eg, mitral ARVC indicates arrhythmogenic right ventricular cardiomyopathy; CPVT,
valve prolapse), congenital heart disease, other catecholaminergic polymorphic ventricular tachycardia; IHD, ischemic heart
disease; SCA, sudden cardiac arrest; SCD, sudden cardiac death; SIDS, sudden
5. Risk factors for heart disease: Hypertension, diabetes infant death syndrome; and VA, ventricular arrhythmia.
mellitus, hyperlipidemia, and smoking
6. Medications
Antiarrhythmic medications
symptoms, particularly in patients with known or dis-
covered structural or electrical heart disease should
Other medications with potential for QT
prolongation and torsades de pointes prompt focused investigation for possible association
Medications with potential to provoke or
with VA (Table 6).
aggravate VA The elucidation of precipitating factors, such as
Stimulants including cocaine and amphetamines
exertional or emotional stress, concurrent medica-
tions or illness, and alleviating factors is important.
Supplements including anabolic steroids
The presence of a family history of SCD, ischemic
Medication-medication interaction that could cause
QT prolongation and torsades de pointes
heart disease, valvular heart disease, nonischemic
cardiomyopathy (NICM), or HF raises concern for the
7. Past medical history
presence of one of these disorders associated with
Thyroid disease
VA. Obtaining a complete medication history is im-
Acute kidney injury, chronic kidney disease, or portant. Various antiarrhythmic and other medications
electrolyte abnormalities
can cause QT prolongation and torsades de pointes
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CLINICAL STATEMENTS
Text
AND GUIDELINES
Recommendation for Ambulatory Electrocardiography
Referenced studies that support the recommendation are
summarized in Online Data Supplements 3 and 4.
1. Implanted cardiac monitors provide continu-
ous rhythm monitoring and stored recordings of
COR LOE Recommendation
electrograms based on patient activation or pre-
1. Ambulatory electrocardiographic monitoring
is useful to evaluate whether symptoms,
set parameters, allowing a prolonged monitor-
I B-NR ing period of a few years. These devices require
including palpitations, presyncope, or
syncope, are caused by VA.S4.2.2-1–S4.2.2-4 a minor invasive procedure with local anesthesia
for implantation. In patients with sporadic symp-
Recommendation-Specific Supportive Text toms, including syncope, implantable recorders
are useful in diagnosing serious tachyarrhythmias
1. Ambulatory electrocardiographic monitoring is often (including VA) and bradyarrhythmias.S4.2.3-2–S4.2.3-4
used to assess the effectiveness of treatments to sup- They are generally reserved for patients in whom
press arrhythmias, but more robust data are needed
other ambulatory monitoring is nonrevealing due
on the clinical use of this practice. Continuous
to the infrequency of events. A 25% added yield
or intermittent ambulatory electrocardiographic
in diagnosis has been described after an unreveal-
recording with a Holter monitor or an event recorder
ing external ambulatory monitor.S4.2.3-5 In a study
is helpful in diagnosing suspected arrhythmias, estab-
of patients with syncope, the implantable moni-
lishing their frequency, relating them to symptoms,
tor had a greater diagnostic yield than “conven-
and assessing the response to therapy. Although the
tional” testing with external monitoring, tilt table
yield of these tests is relatively low, VT is occasion-
testing and electrophysiological study.S4.2.3-2 A
ally documented.S4.2.2-4 A 24-hour continuous Holter
systematic review in patients with syncope con-
recording is appropriate when symptoms occur at
cluded that use of these devices provide a higher
least once a day or when quantitation of PVCs/NSVT
is desired to assess possible VA-related depressed rate of diagnosis and a trend toward reduction
ventricular function. For sporadic symptoms, event in syncope relapse after diagnosis, as compared
or “looping” monitors are more appropriate because with conventional management.S4.2.3-3 A prospec-
they can be activated over extended periods of time tive study of patients after MI, with LVEF <40%,
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and increase diagnostic yield.S4.2.2-2,S4.2.2-3 Adhesive demonstrated NSVT (>16 beats long) in 13%, VT
patch electrocardiographic monitors can record for (>30 s) in 3% and VF in 3% of patients.S4.2.3-1 It
weeks and allow for continuous short-term 1-lead is important to accurately correlate the symptoms
monitoring and patient activation for symptoms. with the arrhythmias detected by implanted car-
Studies have shown satisfactory patient compli- diac monitors.
ance, and arrhythmia detection; however, with
4.2.4. Noninvasive Cardiac Imaging
some monitors, detected arrhythmias are not dis-
covered until the patch is returned for analysis.S4.2.2- Recommendations for Noninvasive Cardiac Imaging
Referenced studies that support the recommendations are
1,S4.2.2-4
Serial evaluations with exercise testing and/
summarized in Online Data Supplement 6.
or 24-hour ambulatory monitoring are also used to
COR LOE Recommendations
assess rhythm burden and response of VA to therapy.
Notably, implantable monitors are covered in Section 1. In patients with known or suspected VA
that may be associated with underlying
4.2.3. Importantly, when the suspicion of VA in a structural heart disease or a risk of SCA,
I B-NR
patient is high, outpatient ambulatory monitoring is echocardiography is recommended
inappropriate as prompt diagnosis and prevention of for evaluation of cardiac structure and
function.S4.2.4-1,S4.2.4-2
VA are warranted. It is important to accurately cor-
2. In patients presenting with VA who are
relate the symptoms with the arrhythmias detected suspected of having structural heart disease,
by ambulatory ECG monitoring. cardiac magnetic resonance imaging (MRI) or
IIa C-EO
computed tomography (CT) can be useful to
4.2.3. Implanted Cardiac Monitors detect and characterize underlying structural
heart disease.
Recommendation for Implanted Cardiac Monitors
Referenced studies that support the recommendation are
summarized in Online Data Supplement 5.
Recommendation-Specific Supportive
COR LOE Recommendation
Text
1. In patients with sporadic symptoms
(including syncope) suspected to be related 1. Assessment of global and regional myocardial
IIa B-R
to VA, implanted cardiac monitors can be function, valvular structure and function, along
useful.S4.2.3-1–S4.2.3-4
with assessment for adult congenital heart
disease is required in patients with or at high risk predicting SCD in the general population.S4.2.5-5,S4.2.5-6
CLINICAL STATEMENTS
for VA or SCD, including patients with cardiomy- In the Nurses’ Health Study, an elevated N-terminal
AND GUIDELINES
opathy, HF, prior MI, family history of cardiomy- pro-BNP was an independent risk marker for SCD in
opathy or SCD, or an inherited structural heart presumably healthy women.S4.2.5-5 In an older adult
disease associated with SCD. Echocardiography population, higher baseline levels of N-terminal
is the most readily available and commonly used pro-BNP were associated with SCD over a 16-year
imaging technique.S4.2.4-1,S4.2.4-2 LVEF is a strong, follow-up period.S4.2.5-6 These biomarkers may also
independent predictor of SCD and cardiovascular have a potential role in facilitating the identifica-
mortality and a determinant of eligibility for ICD tion of individuals at increased risk of SCD and VA
implantation for primary prevention of SCD.S4.2.4-1 in the general population, particularly in those at
In SCD-HeFT (the Sudden Cardiac Death in Heart intermediate or high risk of ischemic heart disease,
Failure Trial),S4.2.4-2 the benefit of the ICD was not but further studies are needed. Use of biomark-
dependent on the modality (ie, echocardiogra- ers has not been shown to be useful for selecting
phy, radionuclide angiography, or contrast angio- patients for ICDs. A study of 4431 patients found
grams) by which the LVEF was assessed. In clinical high-sensitivity troponin to be only weakly predic-
practice, if cardiac CTS4.2.4-3 or cardiac MRI has tive of SCD.S4.2.5-7 However, there are no data on
been performed and provides sufficient evalua- whether high-sensitivity troponin can improve the
tion, echocardiography may be unnecessary. This current SCD prediction algorithms.
recommendation for imaging differs from that of
the 2017 ACC/AHA/HRS syncope guidelineS4.2.4-4 4.2.6. Genetic Considerations in Arrhythmia
that applies to patients who may not have VA. Syndromes
2. VA or SCA can be an initial manifestation of isch- Recommendation for Genetic Counselling*
emic heart disease, cardiomyopathic processes, or COR LOE Recommendation
myocarditis. Cardiac CT and cardiac MRI allow for
1. In patients and family members in whom
evaluation of structural heart disease and assess- genetic testing for risk stratification for SCA
I C-EO
ment of LV and RV function including quantification or SCD is recommended, genetic counseling
of LVEF, LV mass and volume, valvular structure and is beneficial.
coronary anatomy including anomalous coronary *Please refer to section 7.9 for disease-specific recommendations.
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CLINICAL STATEMENTS
velop disease, indicating that additional mutations and Text
AND GUIDELINES
environmental interactions likely influence the clinical
development of disease.S4.2.6-13–S4.2.6-16 Importantly, the 1. Although randomized studies are unavailable,
absence of an identified disease-causing genetic muta- coronary angiography has an important role in
tion does not exclude the presence of disease, and as establishing or excluding the presence of sig-
such, ongoing monitoring and decision-making are done nificant obstructive ischemic heart disease in
based on the clinical phenotype. Genotyping is frequent- patients with SCA or those with life-threatening
ly most useful when a pathogenic mutation is identified VA.S4.3.1-1–S4.3.1-4 Recurrent polymorphic VT or VF
in the proband, such that screening can be applied to can be due to ongoing myocardial ischemia
relatives who are in a preclinical phase, allowing institu- that resolves with coronary revascularization.
tion of lifestyle changes, therapy, or ongoing monitoring Presence of ST-elevation on preresuscitation or
for those who are gene mutation positive.S4.2.6-7 Refer to early postresuscitation ECG suggests ischemia and
Section 7.9 for disease-specific recommendations. potential ACS warranting urgent angiography and
In young patients (<40 years of age) without structural revascularization.S4.3.1-5 ST-elevation can also result
heart disease who have unexplained cardiac arrest, unex- from coronary spasm or DC shocks. The absence of
plained near drowning, or recurrent exertional syncope, ST-elevation after cardiac arrest does not exclude
genetic testing may be important to identify an inherited obstructive or thrombotic coronary lesions. A cor-
arrhythmia syndrome as a likely cause.S4.2.6-17–S4.2.6-23 onary angiogram may not be warranted if a non-
ischemic cause of SCA is established. Coronary
and CT angiography also have an important role
Recommendation-Specific Supportive Text excluding the presence of anomalous origin of the
1. The decision to proceed with genetic testing requires coronary arteries that may cause SCD.
discussion regarding the clinical use of genetic
information to be obtained for both the proband 4.3.2. Electrophysiological Study for VA
and family members, as well as consideration of the Recommendations for Electrophysiological Study
important psychological, financial, employment, References that support the recommendations are summarized in
Online Data Supplements 8 and 9.
disability, and life insurance implications of posi-
tive genotyping.S4.2.6-17,S4.2.6-18,S4.2.6-20,S4.2.6-24 Balancing COR LOE Recommendations
Downloaded from http://ahajournals.org by on May 3, 2020
privacy of health care information for the proband 1. In patients with ischemic cardiomyopathy,
NICM, or adult congenital heart disease who
with the “right to know” for family members, and
have syncope or other VA symptoms and
the ability to provide appropriate communication of IIa B-R who do not meet indications for a primary
information to all potentially affected family mem- prevention ICD, an electrophysiological
study can be useful for assessing the risk of
bers can be challenging on many levels, including
sustained VT.S4.3.2-1–S4.3.2-7
family dynamics, geographic proximity, and access
2. In patients who meet criteria for ICD
to health care.S4.2.6-25 For these reasons, genetic III: No implantation, an electrophysiological study
counseling generally occurs before proceeding with B-R
Benefit for the sole reason of inducing VA is not
genetic testing, and, from a patient’s perspective, is indicated for risk stratification.S4.3.2-8–S4.3.2-11
optimally provided by genetic counselors, if avail- 3. A
n electrophysiological study is not
able, in collaboration with physicians.S4.2.6-26,S4.2.6-27 recommended for risk stratification for
III: No VA in the setting of long QT syndrome,
A combined approach of genetic counseling with Benefit
B-NR
catecholaminergic polymorphic ventricular
medical guidance may appropriately balance the tachycardia, short QT syndrome, or early
decision as to whether genetic testing would be repolarization syndromes.S4.3.2-12–S4.3.2-16
if VT/VF is the cause of symptoms and to guide further that antiarrhythmic medications for VA improve survival
CLINICAL STATEMENTS
therapy. Induction of VT/VF is often attempted before when given for the primary or secondary prevention of
AND GUIDELINES
catheter ablation of the arrhythmia substrate to guide SCD. However, the use of these medications is essential
the procedure and to determine the success of the in- in some patients to control arrhythmias and improve
tervention after ablation is performed. An electrophysi- symptoms. Medication use for VA is discussed, and
ological study can be used to determine the mechanism any recommendations are listed, in subsequent sec-
of a wide complex tachycardia. See Sections 7.3, 7.4, tions. Further, medication-induced proarrhythmia is ad-
7.6, 7.9.1.3, and 10.8 for recommendations regarding dressed in Section 10.7.
electrophysiological study for specific disease states. Antiarrhythmic medications are often categorized
by the Vaughan Williams 4-level schema (class I: fast
sodium channel blockers; class II: beta blockers; class
Recommendation-Specific Supportive III: repolarization potassium current blockers; class IV:
Text nondihydropyridines calcium channel blockers).S5.1.5.2-1
1. A study of electrophysiological testing in patients This system does not address the complexities in antiar-
with symptomatic NICM found inducible VT/VF rhythmic medications, since nearly every agent has mul-
in 28% of patients which was associated with a tiple effects. Table 7 shows uses, electrophysiological
higher rate of ICD events during follow-up.S4.3.2-17 effects, pharmacological effects, and common adverse
In a prospective cohort of 180 patients with isch- effects of antiarrhythmic medications.
emic or NICM and syncope, induction of VT or VF
at electrophysiological study correlated with car- 5.1.1. Medications With Prominent Sodium
diac mortality only in patients with ischemic heart Channel Blockade
disease. In patients with NICM, cardiac mortality Except in specific circumstances, sodium channel block-
correlated with LVEF but not with inducibility on ers (Vaughn-Williams class I agents) have a limited role
electrophysiological study.S4.3.2-18 in the prevention of VT/SCD; this is based on a lack of
2. In patients who meet criteria for ICD implanta- survival benefit and increased mortality observed dur-
tion (ie, HF and LVEF ≤35%), data do not sup- ing chronic therapy in patients with ischemic heart dis-
port the routine use of electrophysiological study ease (see Section 10.7). Specific circumstances where
solely for risk stratification, as such patients have sodium channel blockers have been used to treat VT/
SCA include: intravenous lidocaine for patients with re-
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CLINICAL STATEMENTS
Antiarrhythmic
AND GUIDELINES
Medication (Class) Electrophysiological Pharmacological
and Dose Uses in VA/SCA Target Effects Characteristics Common Adverse Effects
Acebutolol VT, PVCs Beta 1, Mild intrinsic Sinus rate slowed Active metabolite t1/2: Cardiac: Bradycardia,
PO 200–1200 mg daily sympathomimetic AV nodal refractoriness 8–13 h hypotension, HF, AVB
or up to 600 mg bid activity increased pProlonged with renal Other: Dizziness, fatigue,
impairment) anxiety, impotence, hyper/
Metab: H hypoesthesia
Excr: F 60%, U 40%
Amiodarone (III) VT, VF, PVC, INa, ICa, IKr, IK1, IKs, Ito, Sinus rate slowed t1/2: 26–107 d Cardiac: Hypotension,
IV: 300 mg bolus for Beta receptor, QRS prolonged Metab: H bradycardia, AVB, TdP, slows
VF/pulseless VT arrest; VT below programmed ICD
Alpha receptor QTc prolonged Excr: F
150-mg bolus for stable detection rate, increases
nuclear T3 AV nodal refractoriness defibrillation threshold
VT; 1 mg/min x 6 h,
receptor increased; increased DFT
then 0.5 mg/min x 18 h Other: Corneal microdeposits,
PO: 400 mg* q 8 to thyroid abnormalities, ataxia,
12 h for 1–2 wk, then nausea, emesis, constipation,
300–400 mg daily; photosensitivity, skin
reduce dose to 200 mg discoloration, ataxia, dizziness,
daily if possible peripheral neuropathy, tremor,
hepatitis, cirrhosis, pulmonary
fibrosis or pneumonitis
Atenolol (II) VT, PVC, ARVC, Beta 1 Sinus rate slowed t1/2: 6–7 h Cardiac: Bradycardia,
PO: 25–100 mg qd LQTS AV nodal refractoriness (prolonged with renal hypotension, HF, AVB
or bid increased impairment) Other: Dizziness, fatigue,
Metab: H depression, impotence
Excr: F 50%, U 40%
Bisoprolol (II) VT, PVC Beta 1 receptor Sinus rate slowed t1/2: 9–12 h Cardiac: Chest pain,
PO: 2.5–10 mg once AV nodal refractoriness Metab: H bradycardia, AVB
daily increased Excr: U Other: Fatigue, insomnia,
diarrhea
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Carvedilol (II) VT, PVC Beta 1 and 2 receptors, Sinus rate slowed t1/2: 7–10 h Cardiac: Bradycardia,
PO: 3.125–25 mg q Alpha AV nodal refractoriness Metab: H hypotension, AVB, edema,
12 h increased syncope
Excr: F
Other: Hyperglycemia,
dizziness, fatigue, diarrhea
Diltiazem (IV) VT specifically ICa-L Sinus rate slowed t1/2: Injection 2–5 h, Cardiac: Hypotension,
IV: 5–10 mg RVOT, PR prolonged immediate release 4.5– edema, HF, AVB, bradycardia,
12 h, extended release exacerbation of HFrEF
qd: 15–30 min idiopathic LVT AV nodal conduction
12 h, and severe hepatic Other: Headache, rash,
Extended release: PO: slowed
impairment 14–16 h constipation
120–360 mg/day
Metab: H
Excr: U
Esmolol (II) VT Beta 1 receptor Sinus rate slowed t1/2: 9 min Cardiac: Bradycardia,
IV: 0.5 mg/kg bolus, AV nodal refractoriness Metab: RBC esterases hypotension, HF, AVB
0.05 mg/kg/min increased Excr: U Other: Dizziness, nausea
Flecainide (IC) PO: VT, PVC (in INa, IKr, IKur PR prolonged t1/2: 7–22 h Cardiac: Sinus node dysfunction,
50–200 mg q 12 h the absence of QRS prolonged; Metab: H AVB, drug-induced Brugada
structural heart increased DFT syndrome, monomorphic VT in
Excr: U
disease). Has a patients with a myocardial scar,
role in treating exacerbation of HFrEF
patients with Other: Dizziness, tremor, vision
CPVT disturbance, dyspnea, nausea
Lidocaine (IB) VT, VF INa No marked effect on Initial t1/2 7–30 min; Cardiac: Bradycardia,
IV: 1 mg/kg bolus, 1–3 most intervals; QTc can terminal 90–120 min. hemodynamic collapse, AVB,
mg/min slightly shorten Prolonged in HF, liver sinus arrest
disease, shock, severe Other: Delirium, psychosis,
1–1.5 mg/kg. Repeat
renal disease Metab: H seizure, nausea, tinnitus,
0.5–0.75 mg/kg bolus
every 5–10 min (max Excr: U dyspnea, bronchospasm
cumulative dose 3
mg/kg). Maintenance
infusion is 1–4 mg/min
although one could
start at 0.5 mg/min
(Continued )
Table 7. Continued
CLINICAL STATEMENTS
Antiarrhythmic
AND GUIDELINES
Mexiletine (IB) T, VF, PVC, has a INa No marked effect on t1/2: 10–14 h Cardiac: HF, AVB
PO: 150–300 mg q 8 h role in patients most intervals; QTc can Metab: H Other: Lightheaded, tremor,
or q 12 h with LQT3 slightly shorten ataxia, paresthesias, nausea,
Excr: U
blood dyscrasias
Nadolol (II) VT, PVC, LQTS, Beta 1 and 2 receptors Sinus rate slowed t1/2: 20–24 h Cardiac: Bradycardia,
PO: 40–320 mg daily CPVT AV nodal refractoriness Metab: none hypotension, HF, AVB
increased Excr: U Other: Edema, dizziness, cold
extremities, bronchospasm
Procainamide (IA) VT INa, IKr QRS prolonged Metab: H Cardiac: TdP; AVB, hypotension
IV: loading dose 10–17 QTc prolonged; t1/2: 2–5 h; NAPA 6–8 h and exacerbation of HFrEF
mg/kg at 20–50 mg/ increased DFT t1/2 prolonged in renal Other: Lupus symptoms,
min dysfunction. Anephric: diarrhea, nausea, blood
Maintenance dose: 1–4 proc 11 h and NAPA dyscrasias
mg/min 42 h
PO (SR preparation): Excr: U
500–1250 mg q 6 h
Propafenone (IC) VT, PVC (in INa, IKr, IKur, Beta receptor, PR prolonged t1/2: 2–10 h or 10–32 h Cardiac: HF, AVB, drug-induced
PO: Immediate release the absence of Alpha receptor QRS prolonged; t1/2: extensive Brugada syndrome
150–300 mg q 8 h structural heart increased DFT metabolizers 2–10 Other: Dizziness, fatigue,
disease) h; poor metabolizers nausea, diarrhea, xerostomia,
Extended release 225–
425 mg q 12 h 10–32 h. tremor, blurred vision
Metab: H
Downloaded from http://ahajournals.org by on May 3, 2020
Excr: U
Propranolol (II) VT, PVC, LQTS Beta 1 and 2 receptors, Sinus rate slowed t1/2: Immediate release Cardiac: Bradycardia,
IV: 1–3 mg q 5 min to a INa AV nodal refractoriness 3–6 h hypotension, HF, AVB
total of 5 mg increased Extended release 8–10 h Other: Sleep disorder, dizziness,
PO: Immediate Metab: H nightmares, hyperglycemia,
release 10–40 mg q diarrhea, bronchospasm
Excr: U
6 h; Extended release
60–160 mg q 12 h
Quinidine (IA) T, VF, (including INa, Ito, IKr, M, Alpha QRS prolonged 1/2
: 6–8 h longer in HF, Cardiac: Syncope, TdP, AVB
PO: sulfate salt short QT receptor QTc prolonged; liver cirrhosis, and with Other: Dizziness, diarrhea,
200–600 mg q 6 h to syndrome, increased DFT older age nausea, esophagitis, emesis,
q 12 h Brugada) Metab: H tinnitus, blurred vision, rash,
gluconate salt Excr: U weakness, tremor; blood
324–648 mg q 8 h dyscrasias
to q 12 h
IV: loading dose: 800
mg in 50 mL infused at
50 mg/min
Ranolazine (not VT INa, IKr Sinus rate slowed t1/2: 7 h Cardiac: Bradycardia,
classified) Tc prolonged Metab: H hypotension
PO: 500–1000 mg q Excr: U 75%, F 25% Other: Headache, dizziness,
12 h syncope, nausea, dyspnea
Sotalol (III) VT, VF, PVC IKr, Beta 1 and 2 Sinus rate slowed t1/2: 12 h Cardiac: Bradycardia,
IV: 75 mg q 12 h receptor QTc prolonged Metab: none hypotension, HF, syncope, TdP
PO: 80–120 mg q 12 AV nodal refractoriness Excr: U Other: Fatigue, dizziness,
h, may increase dose increased; decreased weakness, dyspnea, bronchitis,
every 3 d; max 320 DFT depression, nausea, diarrhea
mg/d
(Continued )
Table 7. Continued
CLINICAL STATEMENTS
Antiarrhythmic
AND GUIDELINES
Medication (Class) Electrophysiological Pharmacological
and Dose Uses in VA/SCA Target Effects Characteristics Common Adverse Effects
Verapamil (IV) VT (specifically ICa-L Sinus rate slowed t1/2: 3–7 h Cardiac: Hypotension,
IV: 2.5–5 mg q 15–30 RVOT, verapamil- PR prolonged Metab: H edema, HF, AVB, bradycardia,
min sensitive exacerbation of HFrEF
AV nodal conduction Excr: U
idiopathic LVT) Other: Headache, rash, gingival
Sustained release PO: slowed
240–480 mg/d hyperplasia, constipation,
dyspepsia
*Although up to 800 mg every 8 h might be used, higher doses of amiodarone are associated with a higher risk of adverse events. Modified from Shleifer JW,
et al.S5.1.5.2-2
Alpha indicates alpha-adrenergic receptor; ARVC, arrhythmogenic right ventricular cardiomyopathy; AV, atrioventricular; AVB, atrioventricular block; Beta, beta-
adrenergic receptor; HF, heart failure; CPVT, catecholaminergic polymorphic ventricular tachycardia; DFT, defibrillation threshold; F, feces; H, hepatic; ICa, L-type
calcium channel current; IK1, inward rectifier potassium channel; IKACh, muscarinic receptor-gated potassium channel; IKATP, adenosine-activated potassium channel;
IKr, rapid delayed rectifier potassium current; IKs, slow delayed rectifier potassium current; IKur, ultra-rapid delayed rectifier potassium current; INa, fast inward sodium
current; Ito, transient outward potassium current; LQTS, long QT syndrome; LVT, left ventricular tachycardia; M, muscarinic; Metab, metabolism; NAPA, n-acetyl
procainamide; PVC, premature ventricular complex; QTc, corrected QT interval; t1/2, half-life; RVOT, right ventricular outflow tract; T3, triiodothyronine; TdP,
torsades de pointes; U, urine; VT, ventricular tachycardia; and VF, ventricular fibrillation.
ICD without a history of documented VT/VF and with line therapy for some cardiac channelopathies (eg, long
one of the following conditions: BUN ≥26 mg/dL, QRS QT syndrome, catecholaminergic polymorphic ventricu-
>120 msec, atrial fibrillation, or NSVT or >500 VPBs on lar tachycardia).
24-hour Holter recording; 2) having a primary preven-
5.1.3. Amiodarone and Sotalol
tion ICD with a history of documented VT/VF appropri-
Amiodarone possesses a wide spectrum of actions that
ately treated with ICD therapy or untreated NSVT; or 3)
include blockade of beta receptors and sodium, calci-
having a secondary prevention ICD after documented
um and potassium currents (ie, a multichannel blocker).
VT/VF or cardiac arrest. Ranolazine did not significantly
Its overall long-term effect on survival is controversial,
reduce the primary endpoint of VT/VF requiring appro-
with most studies showing no clear advantage over
priate ICD therapy or death. In a prespecified secondary
placebo. A few studies and a meta-analysis of several
analysis, ranolazine was associated with a significant
large studies have shown a reduction in SCD using ami-
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discontinuance of the medication.S5.1.5.2-26 For this rea- of death were seen in patients with serum potassium
CLINICAL STATEMENTS
son, chronic treatment of young patients with amioda- concentrations between 3.5 mmol/L and <4.5 mmol/
AND GUIDELINES
rone should be reserved as a bridge to more definitive L.S5.1.5.2-48 Interestingly, the rates of VA did not rise unless
treatment options such as catheter ablation. Baseline the potassium was <3 mmol/L or ≥5 mmol/L. Likewise,
evaluation of patients may include ECG, liver function a large randomized, double-blind trial of intravenous
tests, thyroid function tests, chest x-ray, and pulmo- magnesium in the post-MI period demonstrated no
nary function tests (including diffusing capacity of the benefit in 30-day mortality.S5.1.5.2-40 It remains quite rea-
lungs for carbon monoxide). Monitoring for toxicity sonable to monitor potassium and magnesium during
generally includes periodic history and physical exami- aggressive diuresis and in the post-MI period.
nation, as well as evaluation of the ECG, chest x-ray,
and thyroid, liver, and lung function. High-resolution 5.1.5.2. n-3 Fatty Acids and Lipids
chest CT is generally reserved for suspected pulmonary Both n-3 poly-unsaturated fatty acids and statin
toxicity.S5.1.5.2-30 therapies may have a role in the prevention of SCD,
Although sotalol has some efficacy in suppressing thought to be due to a stabilization of the bilipid myo-
VA, it has significant proarrhythmic effects and has not cyte membrane involved in maintaining electrolyte
been shown to improve survival.S5.1.5.2-31 D-sotalol was gradients.S5.1.5.2-49
shown in the SWORD (Survival With Oral d-Sotalol) Early data were promising regarding the effects of
trial to increase the risk of death in patients with heart n-3 polyunsaturated fatty acids on the reduction of
failure.S5.1.5.2-32 Unlike amiodarone and many other an- cardiovascular events and SCD. In 2006, a large meta-
tiarrhythmic agents, sotalol appears to reduce the de- analysis of 19 observational and RCTs demonstrated
fibrillation threshold.S5.1.5.2-33 Also, sotalol may lead to a significant association between the consumption
HF decompensation, and so its use in patients with an of n-3 polyunsaturated fatty acids and prevention of
LVEF <20% is generally avoided. SCD.S5.1.5.2-50 The randomized GISSI (Gruppo Italiano per
lo Studio della Sopravvivenza nell'Infarto)-Prevenzione
5.1.4. Calcium Channel Blockers trial in people with recent MI, found that fish oil 1 g/d
For the treatment of most VA, nondihydropyridines cal- reduced mortality, due to fewer SCD.S5.1.5.2-51 However,
cium channel blockers have no role. In fact, intravenous subsequent RCTs have not replicated these benefits
verapamil given for sustained VT has been associated and have shown n-3 polyunsaturated fatty acids to be
with hemodynamic collapse, especially in patients with ineffective.S5.1.5.2-52–S5.1.5.2-56 Because studies showed a
Downloaded from http://ahajournals.org by on May 3, 2020
prior MI.S5.1.5.2-34,S5.1.5.2-35 For patients with a structural- consistent lack of harm from n-3 polyunsaturated fatty
ly normal hearts, verapamil or diltiazem can suppress acids, patients can be reassured of their safety. Longer-
some outflow tract origin.S5.1.5.2-35–S5.1.5.2-39 Oral and in- term data will hopefully clarify the conflicting results.
travenous verapamil are effective in treating idiopathic In contrast, statin medications clearly reduce mor-
interfascicular reentrant LVT.S5.1.5.2-38 Calcium channel tality and appear to reduce the risk of SCD related to
bloickers should not be given to patients with VT in the ischemic heart disease.S5.1.5.2-57 The predominant mecha-
settin of HFrEF.
nism remains uncertain. Prevention of coronary plaque
5.1.5. Nonantiarrhythmic Medications and rupture or a direct cardioprotective effect reducing VA
Therapies has been suggested. Experimental ischemia/reperfu-
5.1.5.1. Electrolytes sion models demonstrate a cardioprotective effect of
Administration of potassium and magnesium has statins, and a large observational analysis observed this
been proposed as helpful adjuncts in the prevention effect in humans.S5.1.5.2-42,S5.1.5.2-56–S5.1.5.2-58 This was ex-
of VA.S5.1.5.2-40,S5.1.5.2-41 Hypokalemia and hypomagne- plored further in HF in several secondary analyses of
semia are common consequences of diuretic therapy patients on statins in ICD prevention trials, including
in HF, both have been associated with VA during an the MADIT-CRT (Multicenter Automatic Defibrillator
acute MI,S5.1.5.2-41,S5.1.5.2-42 and can increase the risk of Implantation Trial-Cardiac Resynchronization Therapy),
torsades de pointes in patients on medications or with SCD-HeFT, AVID (Antiarrhythmics versus Implantable
conditions known to prolong the QT interval.S5.1.5.2-43 In Defibrillators),S5.1.5.2-59 and DEFINITE (DEFibrillators In
fact, in patients with torsades de pointes, intravenous Non-Ischemic Cardiomyopathy Treatment Evaluation)
magnesium is first-line therapy.S5.1.5.2-44 In patients who trials that showed less SCD risk among the patients
are deficient in both magnesium and potassium, mag- on statins.S5.1.5.2-58,S5.1.5.2-60–S5.1.5.2-62 However, this general
nesium should be repleted to facilitate replacement of effect in HF was not confirmed in 2 prospective RCTs
the potassium.S5.1.5.2-45 In the case of potassium, some of rosuvastatin in HF; the CORONA (Controlled Rosu-
recommend keeping the potassium level between vastatin Multinational Trial in Heart Failure) and GISSI-
4.5 mmol/L and 5 mmol/L to prevent VA and HF (Gruppo Italiano per lo Studio della Sopravvivenza
SCD.S5.1.5.2-46,S5.1.5.2-47 A large observational study of pa- nell'Insufficienza Cardiaca-Heart Failure).S5.1.5.2-63,S5.1.5.2-64
tients with an acute MI found that the lowest rates It appears that the beneficial effects of statins are con-
fined to the population with or at risk for atheroscle- angiotensin-converting enzyme inhibitor demonstrated
CLINICAL STATEMENTS
rotic cardiovascular disease and/or ischemia, and not HF a reduction in SCD and cardiac mortality.S5.2-14
AND GUIDELINES
generally.
5.3. Defibrillators for Treatment of VA
5.2. Preventing SCD With HF and SCD
Medications See Sections 7, 10.2, 10.3, 10.8, and 10.9.
Recommendation for Pharmacological Prevention of SCD Defibrillation is highly effective in terminating life-
References that support the recommendation are summarized in threatening VA. This therapy can be delivered by a
Online Data Supplement 10. transvenous ICD, a subcutaneous implantable cardio-
COR LOE Recommendation verter-defibrillator, a wearable cardioverter-defibrillator
1. In patients with HFrEF (LVEF ≤40%), or an external defibrillator. These devices monitor the
treatment with a beta blocker, a heart rhythm continuously and deliver therapy in re-
mineralocorticoid receptor antagonist and
sponse to a tachycardia that meets preprogrammed
either an angiotensin-converting enzyme
I A
inhibitor, an angiotensin-receptor blocker, or detection rates and arrhythmia duration. The vast ma-
an angiotensin receptor-neprilysin inhibitor is jority of transvenous ICDs are implanted in the subcla-
recommended to reduce SCD and all-cause
vicular area under fluoroscopy guidance. subcutaneous
mortality.S5.2-1–S5.2-8
implantable cardioverter-defibrillators are implanted in
the left side of the chest over the sixth rib between the
Recommendation-Specific Supportive left midaxillary and left anterior axillary lines. ICDs with
Text epicardial sensing and pacing leads are still being im-
planted in some patients especially those with certain
1. For patients with HF and depressed LV func- forms of congenital heart disease.
tion, appropriate medical therapy is important The transvenous ICD has been in clinical use for
to reduce SCD. These therapies have various >3 decades, and robust data from high-quality RCTs
beneficial effects on arrhythmia mechanisms. support its use in various patient populations includ-
Beta blockers reduce myocardial oxygen demand ing survivors of cardiac arrest, patients with VT and
and electrical excitability, and counter arrhyth- structural heart disease, and patients with significant
mogenic effects of sympathetic stimulation.
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LV dysfunction.
Angiotensin-converting enzyme inhibitors and
angiotensin-receptor blockers decrease preload
and afterload, decreasing myocardial oxygen 5.4. Catheter Ablation
demand, blocking the formation of angioten- 5.4.1. General Considerations
sin II, and slowing the progression of ventricular Catheter ablation is an important treatment option for
remodeling and fibrosis. Mineralocorticoid recep- patients with VA when antiarrhythmic medications are
tor antagonists limit potassium loss, decrease ineffective, not tolerated, or not desired by the patient.
fibrosis, and increase the myocardial uptake of Monomorphic VA usually have an origin or substrate
norepinephrine.S5.2-7 that can be targeted for ablation. Ablation is an op-
RCTs in patients with HFrEF have consistently tion for selected patients with polymorphic VT/VF only
demonstrated that chronic therapy with beta if an initiating PVC focus or substrate can be identified.
blockers reduces all-cause mortality, VA, and The ablation strategy, risks and outcomes are related to
SCD.S5.2-2,S5.2-4,S5.2-5,S5.2-9 Three beta blockers (ie, biso- the mechanism and location of the VA. Most VA origi-
prolol, carvedilol, sustained-release metoprolol suc- nate close to the subendocardium and are approached
cinate) have been proven to reduce mortality in through a transvenous (for the right ventricle) or trans-
patients with current or prior symptoms of HFrEF aortic/transeptal (for the left ventricle) catheterization.
without beta-blocker contraindications. Angiotensin- Some diseases give rise to VA from the subepicardium,
converting enzyme inhibition also reduces mortality which may be approached by epicardial mapping and
and SCD.S5.2-3 Angiotensin-receptor blockers added ablation. Pericardial access is usually achieved by a per-
to angiotensin-converting enzyme inhibitor showed cutaneous subxiphoid puncture. The catheter ablation
additional benefit to angiotensin-converting enzyme procedure usually involves attempts to induce VT by
inhibitors in someS5.2-10 but not other RCTs.S5.2-8,S5.2-11 programmed electrical stimulation to confirm the di-
Therapy with the mineralocorticoid-receptor antago- agnosis and guide ablation. Problems limiting success
nists, spironolactone and eplerenone, have also dem- include inability to induce an arrhythmia for mapping
onstrated reductions in both all-cause mortality and (common with idiopathic VA), or origin of the arrhyth-
SCD.S5.2-6,S5.2-12,S5.2-13 Recent studies of the angiotensin mia from an inaccessible location in the myocardium
receptor-neprilysin inhibitor (sacubitril/valsartan) versus (common in some cardiomyopathies).
See Section 8.
Heart Disease
VA that are not associated with underlying structur-
al heart disease or a genetic arrhythmia syndrome are Recommendations for Surgery and Revascularization Procedures in
Patients With Ischemic Heart Disease
commonly referred to as idiopathic. Most idiopathic
References that support the recommendations are summarized in
VA are monomorphic and based on a focal mecha- Online Data Supplement 11.
nism of triggered activity or abnormal automaticity;
COR LOE Recommendations
a few are due to reentry. For patients who are symp-
1. P atients with sustained VA and survivors of
tomatic, and in whom antiarrhythmic medications SCA should be evaluated for ischemic heart
are ineffective, not tolerated, or not desired by the I B-NR
disease, and should be revascularized as
patient, catheter ablation is a treatment option. The appropriate.S5.5-1–S5.5-4
ablation strategy is to identify the site of origin mani- 2. In patients with anomalous origin of a
fested by the earliest site of electrical activation, or coronary artery suspected to be the cause
I C-EO
of SCA, repair or revascularization is
when this is not practical, by pace mapping. Catheter recommended.
ablation of idiopathic VA is usually accomplished with
endocardial catheterization, though an epicardial ap-
proach through the coronary venous circulation or a Recommendation-Specific Supportive
subxiphoid pericardial puncture may occasionally be Text
required. Ablation failure for idiopathic VA is often 1. Myocardial ischemia is a cause of sustained poly-
due to inability to provoke the arrhythmia to allow morphic VT/VF, and revascularization is an effec-
mapping in the electrophysiological laboratory or ori- tive treatment to prevent myocardial ischemia.
gin from an inaccessible region. For patients with life-threatening VA, observa-
5.4.3. Scar-Related VT tional studies show that patients undergoing
See Section 8. coronary artery bypass graft (CABG) had substan-
For most patients with structural heart disease, tially better survival after accounting for other
sustained monomorphic VT is due to reentry through predictors.S5.5-1,S5.5-5 The risk of SCD appears compara-
regions of surviving myocardial fibers associated with ble for patients with complex ischemic heart disease
Downloaded from http://ahajournals.org by on May 3, 2020
areas of fibrous scar. The ablation strategy for these re- randomized to treatment with PCI versus CABG.S5.5-6
entry circuits is to identify and eliminate channels of For patients with low LVEF and ischemic heart
surviving myocardium within the scar that are often as- disease amenable to CABG, the risk of SCD is
sociated with slow conduction facilitating reentry. For lower with CABG than medical therapy.S5.5-2,S5.5-7
most VTs that are related to prior MI, the substrate is Observational studies show an association between
on the subendocardial surface of the left ventricle. In a lower likelihood of death with revascularization
NICM, the reentrant circuits are more variable in loca- for survivors of SCA and CABGS5.5-3 or PCI.S5.5-4
tion, often involve the epicardial surface of either ven- Revascularization alone is usually insufficient to
tricle and frequently extending into the midmyocar- prevent recurrence of sustained monomorphic VT;
dium where ablation may be difficult to achieve from further evaluation for inducible VT is generally con-
either surface. In tetralogy of Fallot specific reentry sidered if ventricular function is depressed and/or
paths have been defined.S5.4.3-1 Electroanatomical map- scar is present.
ping that helps clarify the relation of electrophysiologi- 2. Anomalous aortic origin of the coronary arter-
cal abnormalities to cardiac anatomy is commonly em- ies is detected in approximately 1% of patients
ployed. Areas of scar can be appreciated as regions of undergoing routine coronary angiography,
relatively low electrogram voltage. For scar-related VTs, and <0.2% of children and adolescents under-
hemodynamic intolerance often limits mapping during going echocardiography.S5.5-8 Although ischemic
VT. Ablation is then often guided by substrate mapping, heart disease is detected in as many as 24% to
in which areas of scar and potential reentry circuit sub- 55% of SCD cases in young patients <35 years
strate are delineated in electroanatomic maps based of age,S5.5-9,S5.5-10 anomalous aortic origin of
on electrocardiographic and pacing characteristics as- the coronary arteries is an important cause of
sessed during hemodynamically stable sinus or paced SCD in the young, reported in 10% to 17% of
rhythm. Catheter ablation of scar-related VT requires an patients included in postmortem studies.S5.5-10,S5.5-11
advanced level of experience by the operator, electro- Anomalous origin of the coronary arteries can be
physiological laboratory staff, and anesthesiologists as identified by echocardiography, invasive coronary
well as availability of surgical back-up and specialized angiography, CT angiography or cardiac MRI. In
mapping, imaging, and ablation equipment.S5.4.3-2,S5.4.3-3 patients with SCA or life-threatening VA presumed
related to ischemia caused by anomalous origin Modulating the autonomic nervous system for the pur-
CLINICAL STATEMENTS
of a coronary artery, repair or revascularization is pose of preventing arrhythmias is an emerging thera-
AND GUIDELINES
performed to alleviate ischemia and reduce the peutic modality. For the prevention of VA, autonomic
recurrence of VA.S5.5-6,S5.5-7,S5.5-12–S5.5-14 modulation can be done either through interruption
of sympathetic outflow to the heart, pharmacological
5.5.1. Surgery for Arrhythmia Management beta blockade, or through stimulation of the parasym-
Recommendation for Surgery for Arrhythmia Management pathetic pathway (eg, vagal nerve stimulators, spinal
References that support the recommendation are summarized in cord stimulators). Although autonomic modulation has
Online Data Supplement 12.
proven efficacy for certain conditions such as long QT
COR LOE Recommendation syndrome and catecholaminergic polymorphic ventricu-
1. In patients with monomorphic VT refractory lar tachycardia (see Section 7.9), evidence is limited for
to antiarrhythmic medications and attempts
IIb C-LD its applicability to the broader group of VA, but studies
at catheter ablation, surgical ablation may be
reasonable.S5.5.1-1–S5.5.1-7 are ongoing. Currently, there are limited data on the
role of vagal nerve stimulators and spinal cord stimula-
tors for the prevention of VA/SCD in humans, and thus
Recommendation-Specific Supportive no formal recommendation could be supported.S5.6-5
Text
1. Cardiac surgery as a standalone procedure for Recommendation-Specific Supportive
VT is rarely performed, but has a role in some
Text
highly symptomatic patients, when antiarrhyth-
mic medications and catheter ablation fails or 1. Many patients with non–life-threatening VA
are not possible, particularly if the failure of abla- require only reassurance, but others have symp-
tion is due to an arrhythmia arising from an area toms that warrant therapy. A small RCT of
that is inaccessible to catheter ablation, such as patients with symptomatic VA demonstrated a
deep in the myocardium, beneath epicardial fat, significant reduction in the arrhythmic burden
or near the coronary arteries. Surgical ablation of with atenolol.S5.6-1
tachycardia can also be performed at the time of 2. VT/VF storm causes significant morbidity and
other cardiac surgical interventions, such as dur- is associated with increased mortality. For VT/
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ing surgical resection of large aneurysms due to VF storm refractory to treatment (medications,
prior MI in which the border zone is often a sub- catheter ablation), cardiac sympathetic denerva-
strate for VT, or placement of an LV assist device tion has been shown in several small, observa-
(LVAD).S5.5.1-5–S5.5.1-7 The procedure requires detailed tional studiesS5.6-3,S5.6-6 and 1 RCTS5.6-4 to reduce
characterization of the arrhythmia usually with the arrhythmia burden. This has been shown for
preoperative imaging and mapping, therefore, left or bilateral cardiac sympathetic denervation,
surgical ablation is best undertaken at tertiary and it has been suggested that bilateral cardiac
referral centers and with collaboration between sympathetic denervation may be superior.S5.6-3
experienced surgeons and electrophysiologists. Although data are limited, the significant morbid-
ity and limited options in these patients make car-
5.6. Autonomic Modulation diac sympathetic denervation a reasonable option
Recommendations for Autonomic Modulation in selected patients.
References that support the recommendations are summarized in
Online Data Supplements 13 and 14.
COR LOE Recommendations
6. Acute Management of Specific VA
1. In patients with symptomatic, non–life- Recommendations for Management of Cardiac Arrest
IIa C-LD threatening VA, treatment with a beta References that support the recommendations are summarized in
blocker is reasonable.S5.6-1 Online Data Supplements 15 and 16.
2. In patients with VT/VF storm in whom COR LOE Recommendations
a beta blocker, other antiarrhythmic
medications, and catheter ablation are 1. C
PR should be performed in patients in
IIb C-LD cardiac arrest according to published basic
ineffective, not tolerated, or not possible, I A
cardiac sympathetic denervation may be and advanced cardiovascular life support
reasonable.S5.6-2–S5.6-4 algorithms.S6-1–S6-3
2. In patients with hemodynamically unstable
VA that persist or recur after a maximal
Synopsis I A
energy shock, intravenous amiodarone
should be administered to attempt to
Sympathetic activation is proarrhythmic and parasym- achieve a stable rhythm after further
defibrillation.S6-1,S6-4–S6-6
pathetic activation is generally antiarrhythmic in VT/VF.
Recommendations for Management of Cardiac Arrest (Continued) major determinant of survival. A number of strat-
CLINICAL STATEMENTS
findings,S6-7 and emergency coronary angiogra- polymorphic VT; but there were no differences
CLINICAL STATEMENTS
phy should be considered (rather than later in the between the 2 medications in survival to hospital
AND GUIDELINES
hospital stay or not at all) for unstable patients discharge.S6-4,S6-5 However, in the subset of
with a suspected cardiac etiology regardless of patients with witnessed SCA due to initial shock-
whether the patient is comatose or awake.S6-9,S6-39 refractory VF or pulseless VT, a subgroup analysis
In 1 observational study of patients resuscitated showed that survival to hospital discharge with
from SCA who did not have ST elevation and had lidocaine was better than with placebo.S6-5,S6-42
angiography, one third were found to have a cul- 8. In a large meta-analysis of antiarrhythmic medi-
prit lesion and coronary intervention appeared to cations in the setting of AMI, beta blockers
be associated with a greater likelihood of favor- were associated with a significant reduction
able neurologic outcome.S6-10 in mortality.S6-16 Beta blockers can be effective
5. The initial management of any tachycardia should in suppressing recurrent VF in patients with
proceed according to published AHA advanced car- recent MI, with an associated improvement in
diovascular life support guidelines.S6-40 Immediate survival.S6-17
cardioversion should be performed for hemody- 9. In patients with recurrent VT/VF (VT/VF storm) in
namic instability at presentation or if it develops the setting of a recent MI that is refractory to ami-
subsequently. An ECG should be obtained for sta- odarone and/or lidocaine and repeated cardiover-
ble rhythms. Wide-complex tachycardias, defined sion, administration of a beta blocker has been
by a QRS duration ≥0.12 s,S6-37 can be due to VT, shown to improve survival at 1 week. For those
SVT with aberrancy, preexcited tachycardia, or who did not survive, mortality was mostly due to
a paced rhythm such as pacemaker-mediated recurrent VF. Survival at 1 year was also better in
tachycardia. An irregular wide-complex tachycar- those treated with a beta blocker.S6-17,S6-18 Other
dia may be AF with aberrancy, preexcited AF (ie, measures to reduce sympathetic tone including
AF using an accessory pathway for anterograde sedation and general anesthesia are also often
conduction), atrial flutter, or VT.S6-37 A diagnosis used.
should be established, and consultation with an 10. Epinephrine produces beneficial effects in patients
arrhythmia expert considered.S6-37 during cardiac arrest, primarily because of its
6. In 1 study, amiodarone was more effective alpha-adrenergic (ie, vasoconstrictor) effects.S6-1
than lidocaine in terminating incessant VT with These alpha-adrenergic effects can increase
Downloaded from http://ahajournals.org by on May 3, 2020
improved survival at 24 hours.S6-26 For patients coronary and cerebral perfusion pressure during
with recurrent, stable VT not in the setting of CPR. The value and safety of the beta-adrenergic
an AMI, intravenous procainamide has been effects of epinephrine are controversial because
shown to be superior to lidocaine for terminat- they may increase myocardial work and reduce
ing the arrhythmia.S6-11 One randomized trial of subendocardial perfusion.S6-1 One trial assessed
62 patients found procainamide superior to amio- short-term and longer-term outcomes when com-
darone for termination of stable VT.S6-13 Adverse paring standard-dose epinephrine to placebo.S6-23
events, including hypotension were more com- Standard-dose epinephrine was defined as 1 mg
mon with amiodarone, but the difference was given intravenously or intraosseously every 3 to 5
not statistically significant. Procainamide and its minutes. For both survival to discharge and sur-
metabolite n-acetylprocainamide have potassium vival to discharge with good neurologic outcome,
channel blocking properties that may prolong the there was no benefit with standard-dose epi-
QT interval. In patients who already have QT pro- nephrine; however, the study was underpowered
longation, administration of procainamide may for analysis of either of these outcomes. There
further prolong the QT interval and lead to tors- was, nevertheless, improved survival to hospital
ades de pointes.S6-11,S6-12,S6-26 admission and improved return of spontaneous
7. Intravenous lidocaine is an alternative antiar- circulation with the use of standard-dose epi-
rhythmic medication of long-standing and nephrine. A number of trials have compared out-
widespread familiarity. Compared with no comes of standard-dose epinephrine with those
antiarrhythmic medication, lidocaine did not of high-dose epinephrine. These trials did not
consistently increase a return of spontaneous demonstrate any benefit for high-dose epineph-
circulation after defibrillation and was not asso- rine over standard-dose epinephrine in relation
ciated with improvement in survival to hospital to survival to discharge with a good neurologic
discharge.S6-4,S6-14,S6-41 In prospective, blinded, recovery, survival to discharge, or survival to hos-
RCTs, lidocaine was less effective than amiodarone pital admission.S6-1,S6-19,S6-21,S6-22
in improving hospital admission rates after out-of- 11. Amiodarone was more effective than lidocaine in
hospital cardiac arrest due to shock-refractory VF or terminating incessant VT with improved survival
at 24 hours.S6-26 For patients with recurrent, sta- procainamide may further prolong the QT inter-
ble VT not in the setting of an AMI, intravenous val and lead to torsades de pointes.S6-11 A single
procainamide has been shown to be superior to RCT of 33 patients comparing sotalol with lido-
lidocaine for terminating the arrhythmia.S6-11 One caine for treating patients with hemodynami-
RCT in 62 patients found procainamide superior cally stable VT showed that VT was terminated
to amiodarone for termination of stable VT.S6-13 in 69% of patients using sotalol and 18%
Adverse events, including hypotension, were using lidocaine.S6-25 Intravenous sotalol has been
more common with amiodarone, but the differ- approved for use in the United States. Sotalol has
ence was not statistically signficant. Procainamide potassium channel blocking properties that may
and its metabolite n-acetylprocainamide have prolong the QT interval. In patients who already
potassium channel blocking properties that have QT interval prolongation, administration of
may prolong the QT interval. In patients who sotalol may further prolong the QT interval and
already have QT prolongation, administration of lead to torsades de pointes.S6-25
12. Epinephrine may increase coronary and cerebral moderate dose of amiodarone was not superior
CLINICAL STATEMENTS
perfusion pressure during CPR because of its to placebo.S6-29
AND GUIDELINES
vasoconstrictive effects. High doses of epineph- 15. With a stable, wide QRS complex tachycardia,
rine (0.1 to 0.2 mg/kg IV, as opposed to a stan- differentiation between SVT with aberrancy and
dard dose of 1 mg) have been studied in RCTs. VT is often possible by review of the patient’s
In out-of-hospital cardiac arrest unresponsive to history and the 12-lead ECG during tachycar-
defibrillation, administration of high-dose epi- dia. Patients with wide QRS complex tachycar-
nephrine improved survival to hospital admis- dia and known structural heart disease should
sion, but there was no difference compared to be presumed to have VT until proven otherwise.
standard dose epinephrine in survival to hospital Administration of a calcium channel blocker
discharge.S6-19 There was also no improvement in such as verapamil to a patient with VT may
long-term survival.S6-21 Of note, the administra- result in severe hypotension or syncope.S6-31 The
tion of vasopressin is no longer recommended in exception is verapamil-sensitive VT (interfascicu-
the most recent advanced cardiovascular life sup- lar reentry) that occurs in a structurally normal
port algorithms.S6-1 heart; but this is often difficult to recognize on
13. Magnesium may suppress automaticity, suppress initial presentation.S6-30
early and late after-depolarizations, and inhibit
calcium flux into cardiomyocytes. It is effective
in suppressing VA related to acquired long QT 7. ONGOING MANAGEMENT OF VA
syndrome. However, 2 RCTs that investigated AND SCD RISK RELATED TO SPECIFIC
the use of intravenous magnesium in patients DISEASE STATES
with cardiac arrest and refractory VF found no
benefit.S6-27,S6-28 In a study of out-of-hospital car- 7.1. Ischemic Heart Disease
diac arrest, administration of 2 to 4 g magnesium 7.1.1. Secondary Prevention of SCD in Patients
intravenously did not improve survival to hospital With Ischemic Heart Disease
admission.S6-27 In a similar study involving inpa-
Recommendations for Secondary Prevention of SCD in Patients
tient cardiac arrest, magnesium did not improve With Ischemic Heart Disease
return of spontaneous circulation, survival to References that support the recommendations are summarized in
Downloaded from http://ahajournals.org by on May 3, 2020
a significantly lower mortality rate.S6-16 Limited 3. In patients with ischemic heart disease
and unexplained syncope who have
data with amiodarone appeared to be promising,
inducible sustained monomorphic VT
but a subsequent RCT involving 1073 patients I B-NR
on electrophysiological study, an ICD is
found that administration of high-dose amio- recommended if meaningful survival of
greater than 1 year is expected.S7.1.1-7
darone led to a higher mortality rate, although a
1. In the AVID trial,S7.1.1-1 the ICD improved overall sur- trophysiological study identified positive findings in
vival compared with antiarrhythmic medication ther- 37 patients; 31 with VT. During 3 years of follow-up,
apy (primarily amiodarone) in patients who survived patients with a positive electrophysiological study had
SCD or with hemodynamically unstable VT, with a higher rates of SCD and 3-year total mortality (61%
2-year relative risk reduction in mortality of 27% and versus 15%, respectively) than those with a negative
an absolute risk reduction of 7%. CIDS (Canadian electrophysiological study.S7.1.1-7 An ICD is warranted
Implantable Defibrillator Study),S7.1.1-2 which was for patients with syncope and inducible sustained
stopped early after the results of the AVID trial were monomorphic VT even if they do not otherwise meet
released, showed a similar, but not statistically signifi- criteria for primary prevention (Figure 4).
cant, benefit of the ICD over antiarrhythmic medi- 7.1.1.1. Coronary Artery Spasm
cation therapy. A subsequent meta-analysis using Recommendations for Patients With Coronary Artery Spasm
data from 3 RCTs showed a statistically significant References that support the recommendations are summarized in
reduction in both arrhythmic and all-cause mortal- Online Data Supplement 20.
ity with secondary prevention ICDs.S7.1.1-3 COR LOE Recommendations
In survivors of life-threatening VA that may be 1. In patients with VA due to coronary artery
due to transient or reversible factors, such as AMI, spasm, treatment with maximally tolerated
proarrhythmic medication effects, or electrolyte I B-NR doses of a calcium channel blocker and
smoking cessation are indicated to reduce
disturbances, an ICD is not implanted if the cause recurrent ischemia and VA.S7.1.1.1-1,S7.1.1.1-2
may be correctable. This is a population of patients
2. In patients resuscitated from SCA due to
that still requires thorough evaluation, treatment, coronary artery spasm in whom medical
and close follow-up and, as in the AVID registry, IIa B-NR therapy is ineffective or not tolerated, an ICD
mortality was still high in the population that may is reasonable if meaningful survival of greater
than 1 year is expected.S7.1.1.1-3–S7.1.1.1-6
have had a reversible cause for their arrest.S7.1.1-8
3. In patients resuscitated from SCA due to
Small increases in troponin present a challenge in
coronary artery spasm, an ICD in addition
selecting patients for an ICD, as it often cannot IIb B-NR to medical therapy may be reasonable if
be determined whether troponin elevation is due meaningful survival of greater than 1 year is
expected.S7.1.1.1-3–S7.1.1.1-6
to ischemia from VT/VF and resuscitation, in which
Recommendation-Specific Supportive ter CABG include prior MI, ventricular scar, LV dysfunc-
CLINICAL STATEMENTS
Text tion, and placement of a bypass graft across a noncol-
AND GUIDELINES
lateralized occluded coronary vessel to a chronic infarct
1. Coronary artery spasm results from vasomotor
zone.S7.1.1.2-3 Unlike polymorphic VT and VF, sustained
dysfunction and can occur in the presence or
absence of atherosclerotic ischemic heart disease. monomorphic VT is typically not due to acute ischemia.
Vasospasm episodes can lead to VA, syncope, Many of these patients have inducible sustained VT at
and SCD. Treatment includes risk factor elimina- electrophysiological study. Management of symptomat-
tion including smoking cessation, and treatment ic VA in the early period after CABG follows the recom-
with vasodilators including dihydropyridine cal- mendations for acute and ongoing management of VT
cium channel blockers with or without nitrates. detailed elsewhere in this document. In patients without
A more detailed summary of treatments for coro- sustained VT or VF but with LV dysfunction prior to un-
nary artery spasm can be found in other guideline dergoing CABG, implantation of an ICD did not improve
documents.S7.1.1.1-7,S7.1.1.1-8 survival.S7.1.1.2-4 For patients with LV dysfunction who are
2. Patients with coronary artery spasm who survive an undergoing revascularization, there is a possibility that
SCA are a high-risk population.S7.1.1.1-5 Recurrent VA, the LV function may improve, so many advocate for re-
even life-threatening, may be prevented if coronary assessment of the LV function 3 months after revascu-
artery spasm can be effectively addressed with risk
larization before a decision about ICD implantation is
factor modification, smoking cessation, and ongo-
made.S7.1.1.2-5 For patients with a high burden of NSVT
ing treatment with nitrates and dihydropyridine cal-
and reduced LVEF, an electrophysiological study may be
cium channel blockers.S7.1.1.1-9 However, SCA or VA
can recur despite medical therapy or if compliance helpful for risk stratification; those with inducible sus-
is poor. Whether a wearable cardioverter-defibrilla- tained VT may benefit from an ICD.S7.1.1.2-6 The wearable
tor may provide protection while medical therapy cardioverter-defibrillator may play a role in patients at
is being evaluated has not been assessed but is of risk of SCD in the early phase after revascularization to
interest.S7.1.1.1-10 An ICD can terminate VT/VF initi- allow time for recovery of ventricular function.S7.1.1.2-7
ated by spasm, potentially preventing SCD.
3. Patients with coronary vasospasm who survive an 7.1.2. Primary Prevention of SCD in Patients With
SCA are a high-risk population, and some sup- Ischemic Heart Disease
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port the use of an ICD in those patients based on Recommendations for Primary Prevention of SCD in Patients With
the reported event rates from observational stud- Ischemic Heart Disease
iesS7.1.1.1-5 even before determining the patient’s References that support the recommendations are summarized in
Online Data Supplement 21.
response to or compliance with medical therapy.
COR LOE Recommendations
Recurrent SCA can occur despite medical therapy.
Regardless of the approach, risk factor modifica- 1. In patients with LVEF of 35% or less that
is due to ischemic heart disease who are
tion (eg, illicit drug use), smoking cessation, and at least 40 days’ post-MI and at least 90
ongoing treatment with dihydropyridine calcium I A days postrevascularization, and with NYHA
channel blockers with or without nitrates repre- class II or III HF despite GDMT, an ICD is
recommended if meaningful survival of
sent essential treatments.S7.1.1.1-9 greater than 1 year is expected.S7.1.2-1,S7.1.2-2
7.1.1.2. Post CABG VT/VF 2. In patients with LVEF of 30% or less that is
due to ischemic heart disease who are at
The incidence of sustained VT or VF early after CABG is least 40 days’ post-MI and at least 90 days
low, but these VAs are associated with high in-hospital postrevascularization, and with NYHA class I
I A
mortality.S7.1.1.2-1 VF occurring very early (intraoperatively HF despite GDMT, an ICD is recommended if
meaningful survival of greater than 1 year is
or within 24 hours postoperatively) may be due to the expected.S7.1.2-2,S7.1.2-3
transient effects of reperfusion, electrolyte and acid base
disturbances, and the use of inotropes. Patients who 3. A transvenous ICD provides high value in
present with VF or polymorphic VT in the postoperative the primary prevention of SCD particularly
period more often have associated ischemia, while pa- when the patient’s risk of death due
Value Statement: High to a VA is deemed high and the risk of
tients presenting with monomorphic VT usually have an Value (LOE: B-R) nonarrhythmic death (either cardiac or
old infarct and ventricular scar.S7.1.1.2-2 Polymorphic VT/VF noncardiac) is deemed low based on the
occurring after CABG warrants a therapeutic approach patient’s burden of comorbidities and
functional status.S7.1.2-4
targeting treatment of myocardial ischemia, including a
4. In patients with NSVT due to prior MI, LVEF
possible need for assessment of graft patency, as well of 40% or less and inducible sustained VT
as identification and treatment of mechanical compli- I B-R or VF at electrophysiological study, an ICD
cations and acute electrolyte or acid base disturbances. is recommended if meaningful survival of
greater than 1 year is expected.S7.1.2-5
Risk factors for occurrence of monomorphic VT early af-
Recommendations for Primary Prevention of SCD in Patients With an MI before implanting a primary prevention
CLINICAL STATEMENTS
Ischemic Heart Disease (Continued) ICD is based on the fact that such patients were
AND GUIDELINES
contrast, when survival was not increased by ICD that ICDs reduce the risk of SCD in patients with
CLINICAL STATEMENTS
implantation, as in the CABG-Patch trial,S7.1.2-18 the LVEF ≤30% who are awaiting heart transplanta-
AND GUIDELINES
ICD did not provide value, because the higher costs tion; however, this study was limited by the small
were unaccompanied by a gain in life expectancy. number of patients.S7.1.2-6 In a retrospective mul-
4. MUSTT (Multicenter Unsustained Tachycardia ticenter study of 1089 patients listed for heart
Trial) demonstrated that patients with prior MI, transplantation, 550 patients (51%) had an ICD. In
NSVT, and reduced LVEF with inducible VT at elec- 216 patients, the ICD was for primary prevention
trophysiological study have a higher overall mor-
of SCD and, in 334 patients, the ICD was for sec-
tality rate than similar patients without inducible
ondary prevention. The remaining 539 patients did
sustained VT.S7.1.2-21 Patients who received an ICD
after failing to have inducible VT suppressed by not receive an ICD. During a median time on the
an antiarrhythmic medication had lower mortal- waiting list of 8 months, the ICD was associated
ity rate than those who did not receive an ICD. with a reduction in all-cause mortality in the pri-
Although the entry criteria into MUSTT required mary and secondary prevention cohorts (estimated
an LVEF of ≤40%, the average LVEF in enrolled 1-year: 88±3% versus 77±3% versus 67±3%;
patients was 30%, and ICD placement was not P =0.0001). This relationship between the ICD and
randomized but rather was selected by the treat- improved survival persisted even after adjusting
ing physician for patients with VT that could not for potential confounders.S7.1.2-7
be suppressed with antiarrhythmic medication 6. There are insufficient data from RCTs regard-
therapy. MUSTT allowed enrollment of patients ing the value of the ICD in patients with NYHA
who were ≥4 days after an acute MI or revascu- class IV HF. Ambulatory class IV patients with HF
larization. The ICD was of no benefit in 2 other were included in the COMPANION (Comparison
RCTs that examined the efficacy of the ICD in the of Medical Therapy, Pacing, and Defibrillation
acute phase of an MI.S7.1.2-10,S7.1.2-11 In a single cen-
in Heart Failure) trial, which showed an overall
ter observational study, an electrophysiological
improved functional status and survival with a
study was performed a median of 9 days after
acute MI in 115 patients with LVEF <40% and CRT defibrillator.S7.1.2-23 Unless such a patient is a
ICDs recommended for those with inducible VT. candidate for CRT or advanced HF therapies such
Median follow-up was 12 months. Sustained as heart transplantation or an LVAD, an ICD is not
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VT was induced in 27% of patients, and 22% expected to meaningfully prolong survival.S7.1.2-23
of those who received ICDs had spontanous VT
7.1.3. Treatment and Prevention of Recurrent VA
terminated by the ICD during follow-up. None of
the patients without inducible VT had VT or SCD in Patients With Ischemic Heart Disease
during follow-up.S7.1.2-22 Recommendations for Treatment of Recurrent VA in Patients With
5. In a retrospective analysis of the UNOS (United Ischemic Heart Disease
References that support the recommendations are summarized in
Network for Organ Sharing) registry that extended
Online Data Supplements 22 and 23.
from 1999 to 2014, data on 32 599 patients
COR LOE Recommendations
showed that during a median follow-up of 154
days, 3638 patients (11%) died while on the wait- 1. In patients with ischemic heart disease and
recurrent VA, with significant symptoms
list for cardiac transplantation (9% in the ICD group or ICD shocks despite optimal device
I B-R
versus 15% in the non-ICD group; P<0.0001). The programming and ongoing treatment with a
presence of an ICD at listing was associated with beta blocker, amiodarone or sotalol is useful
to suppress recurrent VA.S7.1.3-1–S7.1.3-3
an adjusted 13% relative risk reduction in mor-
2. In patients with prior MI and recurrent
tality. In the subgroup of patients with an LVAD episodes of symptomatic sustained VT,
B-R
(n=9478), an ICD was associated with an adjusted or who present with VT storm and have
19% relative risk reduction in mortality.S7.1.2-9 In I failed or are intolerant of amiodarone
(LOE: B-R).S7.1.3-4 or other antiarrhythmic
another study of 380 patients listed for heart trans- B-NR medications (LOE: B-NR) S7.1.3-5–S7.1.3-9, catheter
plantation between 2005 and 2009 at 1 tertiary ablation is recommended S7.1.3-10–S7.1.3-12
heart transplant center, 122 patients received an 3. In patients with ischemic heart disease and
ICD before or within 3 months after being listed ICD shocks for sustained monomorphic VT or
for heart transplantation. Non-ICD patients were symptomatic sustained monomorphic VT that
IIb C-LD
is recurrent, or hemodynamically tolerated,
more likely to die while on the transplant list. In a catheter ablation as first-line therapy may be
multivariable model, the ICD was not associated considered to reduce recurrent VA.S7.1.3-10,S7.1.3-11
with improved survival; however, that analysis was 4. In patients with prior MI, class IC
limited by the small sample size.S7.1.2-8 Another small III: Harm B-R antiarrhythmic medications (eg, flecainide
and propafenone) should not be used.S7.1.3-13
study (n=79) conducted at 1 institution suggested
Recommendations for Treatment of Recurrent VA in Patients With proarrhythmia, but has an increased risk of
CLINICAL STATEMENTS
mortality among the patients with NICM who 3. Patients with prior MI who develop sustained
CLINICAL STATEMENTS
received amiodarone (P =0.07).S7.1.3-20 monomorphic VT often have recurrent episodes.
AND GUIDELINES
2. Patients with prior MI may present with fre- The VTACH (Ventricular Tachycardia Ablation in
quent episodes of sustained monomorphic VT or Addition to Implantable Defibrillators in Coronary
recurrent VF episodes that are initiated by PVCs Heart Disease) trialS7.1.3-11 randomized patients
arising from Purkinje Fibers in the peri-infarct undergoing ICD implantation for stable sustained
zone. VA storms are associated with increased monomorphic VT, who had not failed antiarrhyth-
mortality.S7.1.3-12 The arrhythmia substrate is mic medication therapy, to catheter ablation ver-
usually in the subendocardium. The random- sus ICD implantation alone. At 2 years, any VT
ized VANISH (Ventricular Tachycardia Ablation had recurred in 53% of the ablation group and
versus Escalated Antiarrhythmic Drug Therapy 71% of the control group. Ablation prolonged
in Ischemic Heart Disease) trialS7.1.3-4 compared the time to recurrent VT from a median of 5.9
escalating antiarrhythmic medication therapy months to 18.6 months.S7.1.3-11 Several non-
versus catheter ablation for patients with prior randomized studies have shown that catheter
MI and recurrent sustained monomorphic VT ablation reduces the risk of recurrent VT or ICD
despite antiarrhythmic medications. The primary shocks in patients with sustained VT related to
outcome, a composite of death, VT storm, or prior MI.S7.1.3-5,S7.1.3-7,S7.1.3-8 In a multicenter study
ICD shocks occurred in 59.1% in the ablation of catheter ablationS7.1.3-7 for patients with ≥3
group and in 68.5% in the escalated-therapy episodes of sustained VT in the prior 6 months,
group. There was no difference in mortality 53% were free from recurrent VT at 6 months fol-
between the groups. Recurrent ICD shocks and low-up; the median number of VT episodes was
VT storm and treatment-related adverse events reduced from 11.5 to 0. A meta-analysis of 5 VT
were lower in the ablation group. In a subgroup ablation studiesS7.1.3-5 reported that VT recurred
analysis, patients having VT on amiodarone had in 35% of patients after catheter ablation com-
better outcomes with ablation compared with pared with 55% on antiarrhythmic medications.
increasing amiodarone or adding mexiletine Another study of 63 patients with recurrent VT
to amiodarone. For patients receiving medica- after MI demonstrated acute success with cath-
tions other than amiodarone, catheter abla- eter ablation in 83% of mappable VTs and 40%
tion did not reduce the risk of ICD shocks or of nonmappable VTs.S7.1.3-8 Superiority of ablation
Downloaded from http://ahajournals.org by on May 3, 2020
VT storm compared with switching to amioda- over escalating medication therapy for patients
rone. Although recurrent VT after catheter abla- with recurrent VT despite antiarrhythmic medica-
tion is associated with increased mortality,S7.1.3-9 tions was shown by the VANISH trial.S7.1.3-4 See
whether mortality is reduced by catheter abla- Section 5.6.
tion has not been established. Procedural com- 4. CASTS7.1.3-21 demonstrated higher rates of mortal-
plications occur in approximately 6% of patients, ity or nonfatal cardiac arrest in post-MI patients
most of which are related to vascular access but treated with encainide or flecainide when used
stroke, tamponade, and atrioventricular block to suppress PVCs and NSVT.S7.1.3-13 Propafenone is
can occur. Procedure mortality is <1% in experi- associated with increased mortality in SCA survi-
enced centers.S7.1.3-4,S7.1.3-9 vors compared with beta blockers, amiodarone,
Sustained monomorphic VT often occurs as and the ICD.S7.1.3-22
occasional isolated episodes in patients with 5. Implantation of an ICD prior to achieving sup-
prior MI. Several nonrandomized studies have pression of frequent or incessant VA places the
shown that catheter ablation reduces recurrent patient at high risk of repetitive shocks, which can
VT or ICD shocks.S7.1.3-5,S7.1.3-7,S7.1.3-8 A meta-anal- be psychologically detrimental and has been asso-
ysis of 5 VT ablation studiesS7.1.3-5 reported that ciated with increased mortality.S7.1.3-23,S7.1.3-24
VT recurred in 35% of patients after catheter 6. Sustained monomorphic VT in the setting of
ablation compared with 55% on antiarrhythmic prior MI is typically due to scar-related reentry
medications. In a multicenter study of catheter and is not due to acute ischemia. Although it
ablationS7.1.3-7 for patients with ≥3 episodes of may be appropriate to recommend revascular-
sustained VT in the prior 6 months, 53% were ization when another indication for revascular-
free from recurrent VT at 6 months follow-up; ization exists, revascularization alone is unlikely
the median number of VT episodes was reduced to reduce the recurrence of monomorphic VT
from 11.5 to 0. Superiority of ablation over es- and specific therapies such as antiarrhythmic
calating medication therapy was shown in the medications or ablation may be needed to pre-
composite endpoint of death, VT storm, or ICD vent recurrence.S7.1.3-16 On the contrary, revascu-
shocks by the VANISH trial.S7.1.3-4 larization might be beneficial in patients with
ischemic heart disease and VF, polymorphic VT, 7.2.1. Secondary Prevention of SCD in Patients
CLINICAL STATEMENTS
References that support the recommendations are 1. In patients with NICM who either survive SCA
summarized in Online Data Supplement 24. B-R due to VT/VF or experience hemodynamically
unstable VT (LOE: B-R) S7.2.1-1–S7.2.1-4 or stable
COR LOE Recommendations
I sustained VT (LOE: B-NR) S7.2.1-5 not due to
1. In patients with suspected NICM reversible causes, an ICD is recommended
from myocardial infiltrative B-NR if meaningful survival greater than 1 year is
I B-NR processes, cardiac MRI with late expected.
gadolinium enhancement is useful for 2. In patients with NICM who experience
diagnosis.S7.2-1–S7.2-3 syncope presumed to be due to VA
2. In patients with suspected NICM, and who do not meet indications for
cardiac MRI with late gadolinium a primary prevention ICD, an ICD or
IIa B-NR IIa B-NR
enhancement can be useful for an electrophysiological study for risk
assessing risk of SCA/SCD.S7.2-1–S7.2-3 stratification for SCD can be beneficial if
meaningful survival greater than 1 year is
3. In patients with NICM who develop expected.S7.2.1-6–S7.2.1-11
conduction disease or LV dysfunction
at less than 40 years of age, or who 3. In patients with NICM who survive a
have a family history of NICM or cardiac arrest, have sustained VT, or have
SCD in a first-degree relative (<50 symptomatic VA who are ineligible for an
IIa C-EO IIb B-R ICD (due to a limited life-expectancy and/
years of age), genetic counseling
and genetic testing are reasonable to or functional status or lack of access to an
detect a heritable disease that may ICD), amiodarone may be considered for
clarify prognosis and facilitate cascade prevention of SCD.S7.2.1-12,S7.2.1-13
screening of relatives.S7.2-4,S7.2-5
Recommendation-Specific Supportive
Recommendation-Specific Supportive Text
Text
Downloaded from http://ahajournals.org by on May 3, 2020
2. Small observational studies demonstrated high for the secondary prevention of SCD in patients
CLINICAL STATEMENTS
mortality and frequent appropriate ICD shocks in with NICM.
AND GUIDELINES
patients with syncope and NICM.S7.2.1-7–S7.2.1-9 The
assumption that malignant VAs are the likely cause 7.2.2. Primary Prevention of SCD in Patients With
of syncope and that the ICD would be protec- NICM
tive has recently been challenged. In a subgroup Recommendations for Primary Prevention of SCD in Patients With
analysis of SCD-HeFT that included 472 patients, NICM
References that support the recommendations are summarized in
the ICD did not reduce either recurrent syncope
Online Data Supplements 27 and 28.
or the increased risk of mortality associated
COR LOE Recommendations
with syncope.S7.2.1-10 A subgroup analysis of the
MADIT-RIT (Multicenter Automatic Defibrillator 1. In patients with NICM, HF with NYHA class
II–III symptoms and an LVEF of 35% or less,
Implantation Trial-Reduce Inappropriate Therapy) I A despite GDMT, an ICD is recommended if
trial found syncope to be arrhythmic only in 39% meaningful survival of greater than 1 year is
of patients.S7.2.1-11 These studies suggest that expected.S7.2.2-1–S7.2.2-6
syncope in some HF patients may be an indica- 2. In patients with NICM due to a Lamin A/C
mutation who have 2 or more risk factors
tor of an end-stage cardiomyopathy associated (NSVT, LVEF <45%, nonmissense mutation,
with a poor prognosis.S7.2.1-11 In a substudy of IIa B-NR
and male sex), an ICD can be beneficial if
DEFINITE, inducible sustained VT/VF was found in meaningful survival of greater than 1 year is
expected.S7.2.2-7–S7.2.2-10
a minority of patients, but it was associated with
appropriate ICD therapy.S7.2.1-14 Another study 3. In patients with NICM, HF with NYHA class
I symptoms and an LVEF of 35% or less,
of electrophysiological testing in NICM found IIb B-R despite GDMT, an ICD may be considered if
inducible VT/VF in 27.8% of patients, which meaningful survival of greater than 1 year is
was associated with future ICD events.S7.2.1-15 In expected.S7.2.2-5
a study of patients with NICM, cardiac mortality 4. In patients with medication-refractory NYHA
class IV HF who are not also candidates for
correlated with LVEF but not with inducibility on
III: No cardiac transplantation, an LVAD, or a CRT
electrophysiological study.S7.2.1-16 Based on these Benefit
C-EO
defibrillator that incorporates both pacing
data, many experts are uncomfortable withhold- and defibrillation capabilities, an ICD should
not be implanted.
ing an ICD from patients with NICM who expe-
rience syncope potentially due to a VA even if
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therapy arms. Therefore, the results of DANISH 7.2.3. Treatment of Recurrent VA in Patients
CLINICAL STATEMENTS
who are ineligible for CRT. During a median Recommendations for Treatment of Recurrent VA in Patients With
follow-up of 5.6 years, ICD reduced SCD from NICM
8.4% to 4.3%, but there was no difference in References that support the recommendations are summarized in
Online Data Supplement 29.
all-cause mortality.S7.2.2-11 Several meta-analyses
have been published.S7.2.2-12,S7.2.2-13 One provided COR LOE Recommendations
data on ICDs with and without CRT and showed 1. In patients with NICM and an ICD who
experience spontaneous VA or recurrent
survival benefit from the ICD.S7.2.2-13 The second
appropriate shocks despite optimal device
used patient level data from 2 trials and adopted IIa B-R
programming and treatment with a beta
a more robust approach to reducing heterogene- blocker, amiodarone or sotalol can be
beneficial.S7.2.3-1
ity by excluding patients with CRT and those ran-
domized to antiarrhythmic medications; a 25% 2. In patients with NICM and recurrent
sustained monomorphic VT who fail
relative risk reduction in mortality with an ICD or are intolerant of antiarrhythmic
IIa B-NR
was shown.S7.2.2-12 medications, catheter ablation can be
useful for reducing recurrent VT and ICD
2. Laminopathies are diseases caused by mutations
shocks.S7.2.3-2,S7.2.3-3
mainly in the Lamin A/C gene that produce various
inherited diseases including subtypes of muscular
dystrophy and progeria. Isolated cardiac involve- Recommendation-Specific Supportive
ment is also observed and is an important cause Text
of familial cardiomyopathy.S7.2.2-9 The disease is
1. ICDs reduce mortality from VA, yet ICD shocks
highly penetrant such that all affected individu-
are painful and associated with significant
als have evidence of disease by 60 years of age.
morbidity and poor QoL. Although ICDs are
Cardiac manifestations may include atrial fibril-
highly programmable and provide antitachy-
lation, conduction disturbances, VA, and NICM. cardia pacing therapy that can terminate most
A number of observational studies reported a VT episodes without the need for a shock, pre-
high risk of SCD when cardiac involvement is vention of shocks, both appropriate and inap-
present.S7.2.2-7–S7.2.2-10 One study reported SCD as propriate, remains an important concern. In
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the most frequent mode of death (46%) in both the OPTIC (Optimal Pharmacological Therapy
the isolated cardiac and the neuromuscular phe- in Cardioverter Defibrillator Patients) study,
notypes of Lamin diseases.S7.2.2-9 In a cohort of 269 412 patients with documented VT and VF who
LMNA mutation positive individuals,S7.2.2-10 NSVT received an ICD within 21 days of the docu-
during ambulatory electrocardiographic monitor- mented arrhythmiaS7.2.3-1 were randomized to
ing, LVEF <45% at first evaluation, male sex, and amiodarone plus beta blocker, sotalol alone, or
nonmissense mutations were independent risk beta blocker alone. Over 1 year, shocks occurred
factors for VA. Malignant VA were observed only in 38.5% assigned to beta blocker alone,
in persons with ≥2 of these risk factors.S7.2.2-10 No 24.3% assigned to sotalol, and 10.3% assigned
studies have tested the effect of the ICD on long- to amiodarone plus beta blocker. The rates of
term survival. study medication discontinuation at 1 year were
3. Patients with NICM and class I HF symptoms were 18.2% for amiodarone, 23.5% for sotalol, and
not included in SCD-HeFT or DANISH.S7.2.2-1,S7.2.2-11 5.3% for beta blocker alone. Adverse pulmonary
Although such patients were included in the and thyroid events and symptomatic bradycar-
DEFINITE trial, only 99 (21.6%) of 458 patients in dia were more common among patients ran-
the DEFINITE trial had class I HF.S7.2.2-5 Therefore, it domized to amiodarone. Thus, amiodarone plus
is uncertain whether a primary prevention ICD in beta blocker were more effective than sotalol
such patients improves survival. in preventing ICD shocks but at the expense
4. There are insufficient data from RCTs regarding of increased risk of medication-related adverse
the value of the ICD in patients with NYHA class effects.S7.2.3-1 Sotalol should not be used in
IV. Ambulatory class IV HF patients were included patients with an LVEF <20% due to its negative
in the COMPANION trial that, overall, showed inotropic effects.
improved functional status and survival with a 2. Sustained monomorphic VT due to NICM is
CRT defibrillator.S7.2.2-3 Unless such a patient is a most often due to scar-related reentry. Cardiac
candidate for CRT or advanced HF therapies such MRI often indicates scar location, which tends
as heart transplantation or an LVAD, an ICD is not to be basal along the mitral annulus or in the
expected to meaningfully prolong survival.S7.2.2-3 septum.S7.2.3-4,S7.2.3-5 The VT substrate can be
CLINICAL STATEMENTS
AND GUIDELINES
Figure 6. Secondary and primary prevention of SCD in patients with NICM.
Colors correspond to Class of Recommendation in Table 1. See Section 7.2 for discussion. *ICD candidacy as determined by functional status, life expectancy
or patient preference. 2° indicates secondary; EP, electrophysiological; GDMT, guideline-directed management and therapy; HF, heart failure; ICD, implantable
cardioverter-defibrillator; LVEF, left ventricular ejection fraction; NICM, nonischemic cardiomyopathy; SCA, sudden cardiac arrest; SCD, sudden cardiac death; VA,
ventricular arrhythmia; and WCD, wearable cardioverter-defibrillator.
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11. In asymptomatic patients with clinical genetic counseling to discuss the cost of test-
evidence of arrhythmogenic right ventricular ing, the potential lack of a single gene as the
IIb B-NR cardiomyopathy, an electrophysiological
study may be considered for risk determinant for disease expression, psychological
stratification.S7.3-9,S7.3-36 implications of uncertain disease progression, and
implications for lifestyle modification, screening,
and potential treatment.
Synopsis 2. Cardiac MRI provides high-quality assess-
Arrhythmogenic right ventricular cardiomyopathy is ment of ventricular function, size, regional wall
an inherited cardiomyopathy that predominantly af- motion abnormalities, and extent of scar and
fects the right ventricle but can affect the left ven- fibrosis (late gadolinium enhancement) that are
tricle causing areas of myocardial replacement with seen in 30% to 95% of patients with the clini-
fibrosis and adipose tissue that frequently causes VA cal diagnosis of arrhythmogenic right ventricu-
and SCD. lar cardiomyopathy.S7.3-5,S7.3-6,S7.3-37,S7.3-38 Cardiac
MRI detects biventricular involvement in 34%
to 56% of patients, with isolated LV involve-
Recommendation-Specific Supportive ment noted in 4% to 9% of patients.S7.3-37–S7.3-40
Text Cardiac MRI should include assessment of late
gadolinium enhancement with quantification
1. Selected first-degree relatives refers to rela- of fibrosis. Application of the 2010 Task Force
tives who are willing to undergo further testing Criteria to cardiac MRI criteria for diagnosis of
and who could benefit from further screening arrhythmogenic right ventricular cardiomyopa-
and testing (and not the terminally ill patients thy has improved the specificity of this test.S7.3-
or those who do not want to be screened and 5,S7.3-8
Electrocardiographic and Holter findings
tested). Arrhythmogenic right ventricular cardio- precede detectable cardiac MRI abnormalities in
myopathy is often due to a mutation involving arrhythmogenic right ventricular cardiomyopa-
a desmosomal protein, and it usually has auto- thy mutation-positive individuals, with only 4%
somal dominant inheritance with variable pen- of patients with normal electrocardiographic and
etrance. SCD can be the initial manifestation of Holter results having cardiac MRI abnormalities,
suggesting that evaluation of cardiac structure and right ventricular cardiomyopathy has been shown
CLINICAL STATEMENTS
function using cardiac MRI may be unnecessary to impair myocardial function by echocardiogra-
AND GUIDELINES
in mutation-positive individuals who do not have phy and cardiac MRI.S7.3-19 Participation in high
electrical abnormalities.S7.3-7 The presence of both intensity/duration or endurance physical activity
electrocardiographic abnormalities and abnor- accelerates the penetrance/disease progression
mal cardiac MRI findings may identify patients and arrhythmic risk for arrhythmogenic right
at an increased risk for developing sustained ventricular cardiomyopathy patients and muta-
VA.S7.3-7,S7.3-38 Areas of scar identified on cardiac tion positive individuals, as well as mutation
MRI have correlated with the location of VT sub- positive family members.S7.3-17,S7.3-19–S7.3-21 Patients
strate identified by endocardial and epicardial with arrhythmogenic right ventricular cardiomy-
mapping.S7.3-38 During early stages of disease, a opathy who participate in competitive sports are
baseline cardiac MRI may provide useful informa- at increased risk for VT or SCD, compared with
tion along with electrocardiographic and rhythm those who participate in recreational sports or
abnormalities to monitor disease progression over are inactive.S7.3-17–S7.3-19,S7.3-21 Exercise influences
time. Experience and expertise in interpretation of disease progression in a linear manner; family
cardiac MRI are important.S7.3-5,S7.3-8 members who limited activity to less than the
3. Arrhythmogenic right ventricular cardiomy- AHA recommended minimum for activity guide-
opathy is characterized by progressive ven- lines (<650 metabolic equivalent hours per year
tricular myocyte loss with replacement by [MET-Hr/year]) were less likely to develop VA or
fatty or fibrous tissue, and is associated with disease progression.S7.3-21 In a study of arrhyth-
progressive ventricular dysfunction that may mogenic right ventricular cardiomyopathy pro-
involve both ventricles. VA, syncope, and bands and exercise, athletes (defined as subjects
SCD may occur at a relatively young age, with ≥4 h vigorous exercise/week) were found to
particularly in the second and third decades have reduced biventricular function compared
of life and often occurring during physical with nonathletes in arrhythmogenic right ven-
activity.S7.3-1,S7.3-16,S7.3-22,S7.3-41 Sustained VT is an tricular cardiomyopathy patients and in muta-
important predictor of SCA and SCD or appropri- tion-positive family members.S7.3-19 Many advise
ate ICD shocks in patients with arrhythmogenic limiting exercise intensity and duration to <650
right ventricular cardiomyopathy.S7.3-10,S7.3-13 In MET-Hr/year, or 12.5 MET-Hr/week.S7.3-21
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patients receiving an ICD for primary prevention, 6. The proband with arrhythmogenic right ven-
appropriate ICD shocks are reported in 24% to tricular cardiomyopathy is usually diagnosed by
48% of patients.S7.3-9,S7.3-10,S7.3-12,S7.3-13 As sustained the presence of clinical symptoms along with
VT in arrhythmogenic right ventricular cardiomy- the presence of arrhythmogenic right ventricu-
opathy patients is monomorphic in 55% to 90% lar cardiomyopathy Task Force criteria including:
of episodes based on ICD interrogation or elec- abnormalities on ECG, structural and functional
trophysiological studies,S7.3-12,S7.3-36 antitachycardia changes of either ventricle, arrhythmias, and
pacing algorithms are used to terminate VT. arrhythmogenic right ventricular cardiomyopathy
4. Frequent PVCs, >760 to 1000 per 24 hours dur- in first-degree relatives.S7.3-6 A pathogenic genetic
ing ambulatory rhythm monitoring, correlate with mutation was added to the major Task Force
arrhythmic risk.S7.3-9,S7.3-23 The presence of NSVT or criteria in 2010.S7.3-44 The yield of genetic test-
sustained VT is an important predictor of adverse ing in probands with suspected arrhythmogenic
cardiac events.S7.3-9,S7.3-12,S7.3-13,S7.3-42,S7.3-43 The right ventricular cardiomyopathy is generally
increased arrhythmia risk conferred by intense 30% to 54%, and is up to 58% among patients
exercise is consistent with beta-adrenergic modu- with a strong family history of SCD in multiple
lation of disease expression.S7.3-17,S7.3-20,S7.3-21 An members.S7.3-3,S7.3-25,S7.3-45 A negative genetic test
observational registry reported that treatment for arrhythmogenic right ventricular cardiomyop-
with atenolol or amiodarone was associated with athy does not exclude the disease, and a positive
less clinically relevant VA, while sotalol was associ- genetic test currently does not guide therapy.S7.3-22
ated with no effect or increased arrhythmia.S7.3-15 For the proband with a clinical diagnosis of
Ambulatory monitoring to assess VA burden arrhythmogenic right ventricular cardiomyopathy,
and adequacy of beta-blocker therapy is usually identification of pathogenic mutations provides
used.S7.3-9,S7.3-14,S7.3-23,S7.3-42 limited prognostic information relative to the risk
5. Patients with arrhythmogenic right ventricular of VT/VFS7.3-22,S7.3-26 or development of HF.S7.3-22 In
cardiomyopathy have a significantly increased a large multicenter study, the presence of posi-
risk of SCD during exertion.S7.3-16,S7.3-17,S7.3-20,S7.3-21 tive mutations among probands was not asso-
Vigorous exercise in patients with arrhythmogenic ciated with a difference in mortality or cardiac
transplantation.S7.3-1 However, the identification cardiomyopathy patients does not eliminate the
CLINICAL STATEMENTS
of a pathogenic mutation facilitates targeted need for an ICD in appropriate candidates. The
AND GUIDELINES
genetic screening for that mutation in first- potential risk of VT recurrence due to disease pro-
degree relatives, that may identify approximately gression should be reviewed with patients when
60% to 70% as gene positive,S7.3-1 highest among considering ablation. There are no randomized
siblings, and those with symptoms.S7.3-4 Screening comparisons of antiarrhythmic therapy to sup-
for the specific mutation can identify some gene press recurrent VT. Beta blockers, sotalol and ami-
positive family members prior to disease expres- odarone have been used.S7.3-15 In an observational
sion, while relieving others from the need for life- series, sotalol suppressed inducible VT in 58%
style changes and long-term monitoring.S7.3-2,S7.3-3 of patients with <10% of patients experienc-
7. Syncope is reported in 16% to 39% of arrhythmo- ing arrhythmia recurrence during follow-up.S7.3-48
genic right ventricular cardiomyopathy patients at Effectiveness of the different medications appears
the time of diagnosis,S7.3-13,S7.3-14,S7.3-16,S7.3-41,S7.3-43 is to be variable, and so more studies are needed.
frequently exercise-related, and has been 10. In arrhythmogenic right ventricular cardiomyop-
associated with high arrhythmic risk in some athy, areas of fibrofatty scar in the RV free wall
studies.S7.3-10,S7.3-41 Among patients with arrhyth- create areas of delayed ventricular activation
mogenic right ventricular cardiomyopathy and causing fractionated deflections following the
implanted ICDs, syncope was an important pre- QRS, known as epsilon waves on the surface ECG
dictor of appropriate shocks in 1 study,S7.3-10 but (a major criterion) and late potentials in the signal
not in other studies.S7.3-9,S7.3-12,S7.3-13,S7.3-43 Studies averaged ECG (minor criterion) in the 2010 Task
have not provided information about ventricular Force Criteria for diagnosis of arrhythmogenic
function or abnormalities on ECG in patients with right ventricular cardiomyopathy.S7.3-6 When the
syncope, limiting its assessment as an indepen- standard ECG QRS duration is ≤110 ms, criteria
dent risk factor. Syncope may be a harbinger of
for abnormal signal-averaged ECG include any 1
progression of underlying disease and should be
of the following: filtered QRS duration ≥114 ms,
integrated into the decision-making process for
duration of the terminal QRS <40 uV exceeding 37
ICD implantation with the patient.
ms, or a root mean square voltage in the terminal
8. Asymptomatic patients with arrhythmogenic right
40 ms of ≤20 uV.S7.3-6 Abnormal findings on sig-
ventricular cardiomyopathy and no VA or ventric-
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7.4. Hypertrophic Cardiomyopathy Table 8. Major Clinical Features Associated With Increased Risk of
CLINICAL STATEMENTS
SCD in Patients With HCM
AND GUIDELINES
Recommendations for HCM
Established risk factors*
References that support the recommendations are summarized in
Online Data Supplement 31. Survival from a cardiac arrest due to VT or VF S7.4-1,S7.4–5,S7.4–6
b. SCD in 1 or more first-degree relatives aneurysm warrant consideration for ICD implantation.S7.4-52
presumably caused by HCM HCM indicates hypertrophic cardiomyopathy; ICD, implantable cardioverter-
(LOE: C-LD).S7.4-25,S7.4-26 defibrillator; LV, left ventricular; LVEF, left ventricular ejection fraction; LVOT,
c. 1 or more episodes of unexplained left ventricular outflow tract; NSVT, nonsustained ventricular tachycardia; SCD,
C-LD syncope within the preceding 6 months sudden cardiac death; VT, ventricular tachycardia; and VF, ventricular fibrillation.
(LOE: C-LD).S7.4-8,S7.4-26
7. In patients with HCM who have spontaneous Refer to the ACCF/AHA HCM guideline for the defi-
B-NR NSVT (LOE: C-LD) S7.4-2,S7.4-26,S7.4-27 or an nition of HCM.S7.4-36
abnormal blood pressure response with
IIa exercise (LOE: B-NR) S7.4-5,S7.4-28,S7.4-29, who also
C-LD
have additional SCD risk modifiers or high-risk
features, an ICD is reasonable if meaningful
Recommendation-Specific Supportive
survival greater than 1 year is expected. Text
8. In patients with HCM who have NSVT 1. Patients with HCM have approximately a 1% risk
B-NR (LOE: B-NR)S7.4-2,S7.4-26,S7.4-27 or an abnormal
blood pressure response with exercise (LOE: of SCD per year.S7.4-1,S7.4-6 Selection of patients
IIb
B-NR)S7.4-5,S7.4-28,S7.4-29 but do not have any who are appropriate candidates for implanta-
B-NR other SCD risk modifiers, an ICD may be tion of an ICD can be a difficult clinical decision
considered, but its benefit is uncertain.
because of the individuality of each patient and
9. In patients with HCM and a history of
family, variable definitions of risk factors and risk
sustained VT or VF, amiodarone may be
IIb C-LD
considered when an ICD is not feasible or not modifiers, sparse clinical data, the relative infre-
preferred by the patient.S7.4-30,S7.4-31 quency of both HCM and SCD in most clinical
10. In patients with HCM, an invasive practices, and the potential complications of liv-
III: No
B-NR
electrophysiological study with programmed ing with an ICD. Table 8 lists risk factors and risk
Benefit ventricular stimulation should not be
performed for risk stratification.S7.4-32,S7.4-33
modifiers associated with SCD in patients with
HCM. ICD risk stratification should be performed
11. In patients with an identified HCM genotype
III: No
B-NR in the absence of SCD risk factors, an ICD every 1 to 3 years in patients with HCM. There
Benefit
should not be implanted.S7.4-7,S7.4-34,S7.4-35 is increasing evidence supporting the association
of late gadolinium enhancement on cardiac MRI
with the risk of sudden death and it is included
as a risk modifier.S7.4-37–S7.4-39 LV aneurysm may be
VT.S7.4-40 Age is also an important consideration, Because familial HCM is a dominant disorder, the
AND GUIDELINES
as sudden death risk is greater in those <30 years risk that an affected patient will transmit disease to
of age, and low in patients whose initial presenta- each offspring is 50%. When a pathogenic mutation
tion is after the age of 60 years,S7.4-5,S7.4-26.S7.4-41 is identified in an index patient, the genetic status
2. HCM is the most common cause of SCD in of each family member can be readily ascertained.
individuals <40 years of age.S7.4-26 Individuals Relatives with overt HCM will have the same patho-
who have survived an episode of SCD, genic HCM mutation as the index patient. Pathogenic
VF, or sustained VT resulting in syncope mutations may also be identified in other relatives
or hemodynamic compromise warrant ICD with unknown clinical status. These mutation-
implantation.S7.4-1,S7.4-6,S7.4-9,S7.4-10 Although there positive individuals should be evaluated by physi-
are no RCTs assessing the use of the ICD in cal examination, electrocardiography,S7.4-11,S7.4-17
patients with HCM who have survived SCD, 1 and echocardiographyS7.4-12,S7.4-16,S7.4-17 and, if HCM
study reported that 54% of patients with an ICD is identified, these individuals should undergo
placed for secondary prevention received appro- risk stratification. Gene-positive subjects with-
priate ICD therapy during an average follow-up of out evidence of HCM may be at risk for future
4.6 years.S7.4-10 Select patients with HCM may be development of HCM and benefit from ongoing
candidates for implantation of the subcutaneous clinical evaluation.S7.4-15,S7.4-46,S7.4-47 If the proband’s
implantable cardioverter-defibrillatorS7.4-42; how- implicated mutation is the bona fide disease–
ever, more data on this group are needed especially causing mutation, then mutation-negative fam-
given their higher risk of T wave oversensing that ily members and their descendants are not at an
may increase the risk of inappropriate ICD shocks. increased risk for developing HCM and do not
3. Clinical and/or genetic screening of first- and need further evaluation. However, such muta-
second-degree family members of patients with tion-negative family members must have an
HCM is important to identify those with unrec- echocardiogram to ensure genotype and pheno-
ognized disease. Genetic counseling should type concordance.
precede genetic testing of family members to 4. In a study of 1053 unrelated patients with clini-
enhance their understanding of the useful- cally manifest HCM, 359 patients (34%) were
ness and cost of testing.S7.4-18,S7.4-20,S7.4-43 On genotype positive for an HCM-associated muta-
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the basis of family history, clinical screening, tion in ≥1 HCM-associated genes.S7.4-22 Whether
and pedigree analyses, the pattern of inheri- the results of genetic testing in the proband
tance is ascertained to identify and manage improve outcomes is uncertain, but identification
of a mutation can help inform screening of HCM have an abnormal blood pressure response
CLINICAL STATEMENTS
relatives. during exercise testing (defined variably as either a
AND GUIDELINES
5. Genetic counseling is important in patients with 20 mm Hg decrease in blood pressure or a failure
HCM, and genetic screening of relatives is also to increase systolic blood pressure by at least 20
important unless there are no living first- or mm Hg during effort).S7.4-28,S7.4-29 This finding has
second-degree relatives. Most HCM is caused been postulated to be a risk factor for SCD; how-
by an autosomal dominant mutation in genes ever, it is unclear how this relates to the increase in
that encode sarcomere proteins or sarcomere- dynamic LV outflow tract obstruction that occurs
associated proteins. Presence of a pathogenic with exertion, a hemodynamic condition that is
sarcomere protein gene mutation in patients readily modifiable with medication or mechanical
with HCM identifies risk of LV dysfunction and procedures. The significance of an abnormal blood
adverse outcome irrespective of the myofilament pressure response with exercise predicting SCD risk
involved.S7.4-13–S7.4-15,S7.4-18,S7.4-19,S7.4-22 A single muta- increases in the presence of risk modifiers (Table 8).
tion in 1 of the 2 alleles (or copies) of a gene is 8. Most studies have found that NSVT alone has a
sufficient to cause HCM; however, 5% of patients low positive predictive value for SCDS7.4-2,S7.4-26,
with HCM have ≥2 mutations in the same gene or S7.4-27
; therefore, use of an ICD is more appropriate if
different genes, which can be a marker for worse risk modifiers are also present. An abnormal blood
outcomes.S7.4-13,S7.4-34,S7.4-48 When genetic testing pressure response to exercise has also been associ-
reveals a mutation in the index patient, ascertain- ated with the risk of sudden death,S7.4-5,S7.4-28,S7.4-29
ment of genetic status in first- and second-degree but it is unclear how this relates to the increase in
relatives can be predictive of risk for developing dynamic LV outflow tract obstruction that occurs
HCM.S7.4-14,S7.4-49 Relatives with overt HCM will with effort, which is often treatable. The signifi-
have the same pathogenic HCM mutation as the cance of an abnormal blood pressure response
index patient. with exercise for predicting SCD risk increases
6. Several studies have described an indepen- when risk modifiers are present (Table 8).
dent relationship between hypertrophy and 9. The ICD is recommended for the prevention of
SCD when the magnitude of hypertrophy is SCD in patients with HCM who have survived
≥30 mm.S7.4-2,S7.4-3,S7.4-23,S7.4-24 Risk does not abruptly sustained VT or VF as antiarrhythmic medications
increase for patients with a ≥30 mm wall thick- have limited effectiveness.S7.4-31 Amiodarone has
Downloaded from http://ahajournals.org by on May 3, 2020
ness, but it rather increases in a linear mannerS7.4-24 been associated with improved survival in obser-
and appears to carry more prognostic significance vational studies and is an option for patients for
in younger patients. A young adult with hypertro- whom an ICD is not feasible due to limited expec-
phy that approaches 30 mm may have similar or tation for survival or patient preference.S7.4-30,S7.4-31
greater SCD risk than an older patient with maxi- 10. Approximately one third of consecutive patients
mum wall thickness ≥30 mm.S7.4-23,S7.4-50 with HCM undergoing an electrophysiologi-
Patients with HCM are at an increased risk for cal study have polymorphic VT or VF induced
SCD if they have a first-degree relative who expe- by programmed ventricular stimulation, but the
rienced SCD presumably caused by HCM. Family results of programmed stimulation do not predict
history appears to be an independent predictor SCD risk. Programmed ventricular stimulation in
of SCD although the supportive studies are small patients with HCM has low predictive value and
and observational.S7.4-25,S7.4-26 Syncope can be neu- a nontrivial risk of complications.S7.4-32,S7.4-33,S7.4-51
rally mediated or medication-related as well as Electrophysiological studies can help to clarify the
due to VA and requires a careful evaluation be- diagnosis of wide complex tachycardia or guide
fore considering it a risk factor for SCD.S7.4-8,S7.4-26 therapy for supraventricular tachycardia or bun-
In an analysis, syncope that was unexplained or dle branch reentry.
thought not to be neurally mediated was associ- 11. SCD may cluster in certain families with HCM,
ated with SCD risk only when it occurred within and the possibility that specific sarcomere muta-
the past 6 months but not if the most episode tions may confer SCD risk has been hypothe-
occurred >5 years previously.S7.4-8 sized. However, subsequent studies of selected
7. Although sustained VT is clearly associated patients with HCMS7.4-34,S7.4-35 were unable to
with SCD, the data for NSVT are less robust. establish a clinically useful relation between
Most studies do not support NSVT as an inde- genotype and SCD risk. In some cases, the rate
pendent risk factor for SCD in patients with of adverse events (and prevalence of associated
HCM,S7.4-2,S7.4-26,S7.4-27 but the risk increases if risk SCD risk factors) was lower in patients with
modifiers are present, especially in patients <30 mutations initially felt to be malignant than
years of age.S7.4-27 Up to one third of patients with it was in those with mutations believed to be
benign.S7.4-34,S7.4-35 Data from series of unselected such as LVAD or transplant. Myocarditis and
CLINICAL STATEMENTS
consecutive outpatients suggest that most SCD have been reported with HIV infection.S7.5-
AND GUIDELINES
related to infection.S7.5-1,S7.5-5–S7.5-9 When patients 1. In patients with cardiac sarcoidosis who
have sustained VT or are survivors of SCA
are treated in centers with the availability I B-NR or have an LVEF of 35% or less, an ICD is
of mechanical hemodynamic support proce- recommended, if meaningful survival of
dures, cardiac catheterization, endomyocardial greater than 1 year is expected.S7.6-1–S7.6-5
biopsy, advanced cardiac imaging procedures, 2. In patients with cardiac sarcoidosis and LVEF
greater than 35% who have syncope and/
and arrhythmia management including ICD or evidence of myocardial scar by cardiac
implantation, outcomes appear improved.S7.5-1 MRI or positron emission tomographic
The acute course of myocarditis varies ranging IIa B-NR (PET) scan, and/or have an indication
for permanent pacing, implantation
from an asymptomatic finding of transient ST-T of an ICD is reasonable, provided that
changes noted on ECG to cardiogenic shock meaningful survival of greater than 1 year is
and recurrent VA.S7.5-10–S7.5-12 Acute management expected.S7.6-6–S7.6-10
is largely supportive and can rapidly advance to 3. In patients with cardiac sarcoidosis and LVEF
greater than 35%, it is reasonable to perform
requiring mechanical support.S7.5-13,S7.5-14 Cardiac an electrophysiological study and to implant
arrhythmias range from conduction abnormali- IIa C-LD
an ICD, if sustained VA is inducible, provided
ties to life-threatening VT and VF.S7.5-15–S7.5-17 that meaningful survival of greater than 1
year is expected.S7.6-11,S7.6-12
Arrhythmias may require antiarrhythmic medi-
4. In patients with cardiac sarcoidosis
cations and/or device therapy.S7.5-18 Giant cell who have an indication for permanent
myocarditis is fairly uncommon, but it is of IIa C-LD
pacing, implantation of an ICD can be
particular importance because it typically beneficial.S7.6-13
affects young individuals and is usually fatal if 5. In patients with cardiac sarcoidosis
with frequent symptomatic VA and
untreated.S7.5-2–S7.5-4,S7.5-19 VT may require antiar-
evidence of myocardial inflammation,
rhythmic medications such as amiodarone and/ IIa C-LD
immunosuppression in combination with
or an ICD that in some instances can be used antiarrhythmic medication therapy can be
useful to reduce VA burden.S7.6-14–S7.6-16
as a bridge to more advanced HF therapies
CLINICAL STATEMENTS
Text of SCD according to the indications applied for
AND GUIDELINES
other cardiomyopathies. The frequency of con-
1. Sarcoidosis is a systemic granulomatous disease duction abnormalities often warrants a device
of unknown cause. Pulmonary involvement is that provides bradycardia pacing as well.
most frequent but any organ can be affected. 2. Patients with cardiac sarcoidosis can experience
Cardiac involvement, diagnosed by cardiac MRI VA and SCD, even if the LVEF is normal, and
or positron emission tomography (PET), has been approaches to identification of patients at risk of
reported in up to 55% of patients with extra- SCD despite preserved LV function are not well
cardiac disease, while isolated cardiac sarcoidosis defined. A number of studies have evaluated the
was seen in most patients diagnosed with cardiac role of cardiac MRI for predicting VA and SCD. A
sarcoidosis in 1 report.S7.6-17 Cardiac manifesta- meta-analysis,S7.6-6 which included 760 patients in
tions include conduction abnormalities, VA, and 10 studies, found that late gadolinium enhance-
depressed ventricular function with or without HF, ment was associated with increased all-cause
and these contribute greatly to a higher mortality mortality and more VA compared with those with-
in cardiac sarcoidosis compared with sarcoidosis out late gadolinium enhancement. Applicability is
without cardiac involvement.S7.6-2 In a 25-year limited by the lack of precise quantification of late
study of 110 patients with cardiac sarcoidosis gadolinium enhancement burden that may allow
in Finland with HF at presentation, marked LV for more nuanced risk stratification. Some stud-
dysfunction at diagnosis (LVEF <35%), and iso- ies suggested that a threshold effect exists, with
lated cardiac sarcoidosis predicted an adverse extensive LV and RV involvement being a particu-
outcome.S7.6-1 VA can also occur in patients with larly high-risk feature.S7.6-7,S7.6-8 However, late gad-
relatively normal LV function, some of whom olinium enhancement can be present even if the
have RV involvement that can mimic arrhythmo- LVEF is >50% and was associated with a risk of
genic right ventricular cardiomyopathy. Several death or VT of 4.9% per year compared to 0.24%
reports of patients with cardiac sarcoidosis and per year when late gadolinium enhancement was
ICDs implanted for either primary or secondary absent in 1 observational study.S7.6-7 PET for assess-
prevention of SCD show a high frequency of ing inflammation and scar is also being increas-
appropriate ICD therapies,S7.6-3–S7.6-5 supporting ingly used, but data are limited. In 1 report, the
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PET scanning was associated with increased risk of a worsening of VA has been reported with
AND GUIDELINES
to reversely correlate with LVEF. Furthermore, in this Infiltrative cardiomyopathies are a heterogeneous
study the average LVEF of the inducible patients de- group of uncommon systemic diseases with associat-
clined further during the followup period.S7.6-12 ed cardiac involvement. In some infiltrative cardiomy-
4. In addition to VA and LV dysfunction, conduction opathies, such as Fabry’s disease, VAs are uncommon.
abnormalities, including heart block, can also be Some, such as hemochromatosis, are highly treatable
a common manifestation of cardiac sarcoidosis. especially when diagnosed early. In all cases, treat-
Patients with documented VA and LV dysfunction ment of the underlying condition must accompany
are at increased risk of cardiac events including management of cardiac arrhythmias. Most studies
cardiac death. One study compared outcomes of infiltrative cardiomyopathies and arrhythmias are
in 22 patients with high-degree atrioventricular small and observationalS7.6.1-1 but, in general, unless
block as the initial manifestation of cardiac sar- contraindications are present, VAs should be treated
coidosis, to 31 patients who initially presented as in any other cardiomyopathy. See Section 7.6 for
with VT and/or HF. After a median follow up of 34 sarcoidosis. Until recently, cardiac amyloidosis was
months, the patients who presented with heart associated with a very poor prognosis with patients
block had fewer HF hospitalization, yet fatal car- ultimately succumbing to progressive HF.S7.6.1-2 This
diac events, including sustained VAs, were similar perception is changing with advances in medical
to those with VT and/or HF, suggesting that the therapy for light-chain amyloidosis, which have led
risk of fatal cardiac events is high regardless of to improved outcomes.S7.6.1-3 Yet, decisions must be
the initial clinical presentation.S7.6-13 In the same individualized because data remain too limited to al-
study, administration of steroids led to some clini- low formal recommendations as published reports on
cal improvement, with some patients recovering ICD effectiveness in amyloidosis are small, observa-
conduction, yet steroid effectiveness was not uni- tional and with limited follow up.S7.6.1-4 Whether there
versal and did not seem to be protective against is greater benefit to ICD placement in light chain
adverse cardiac events.S7.6-13 amyloidosis versus transthyreitin-related amyloidosis
5. Several studies have attempted to evaluate the remains uncertain, because most studies included
role of immunosuppression for reducing VA in mainly patients with amyloid light-chain amyloidosis
patients with cardiac sarcoidosis, but results for which the rate of VA may be greater and prog-
CLINICAL STATEMENTS
for primary prevention of SCD is uncertain, but many Text
AND GUIDELINES
deaths in patients with cardiac amyloidosis do not ap-
pear to be preventable by an ICD.S7.6.1-2 1. Many patients with advanced HF listed for heart
transplant would not otherwise qualify for ICD
given the severity of illness including NYHA class IV
7.7. Heart Failure status and/or use of inotropic infusion. Although
no randomized data on ICD use in this popula-
7.7.1. HF With Reduced Ejection Fraction
tion exist, data from observational and large
Recommendation for HFrEF registry studies of patients awaiting heart trans-
References that support the recommendation are summarized in plant suggest improved survival in patients with
Online Data Supplement 35.
an ICD.S7.7.1-1,S7.7.1-4,S7.7.1-5 One alternative to ICD
COR LOE Recommendation
in this population is the wearable cardioverter-
1. In patients with HFrEF who are awaiting heart defibrillator.S7.7.1-2,S7.7.1-3 The recommendation in
transplant and who otherwise would not
IIa B-NR qualify for an ICD (eg, NYHA class IV and/ this section is relevant to those patients without
or use of inotropes) with a plan to discharge an ICD where there is a plan to discharge the
home, an ICD is reasonable.S7.7.1-1–S7.7.1-5
patient to home to await cardiac transplant and
not, for example, to those patients who remain
hospitalized with no intention to discharge home
Synopsis until transplant occurs. For those patients with
Patients with HFrEF are at an increased risk for VA an LVAD, the decision to place an ICD is gener-
and SCD. The risk is increased irrespective of HFrEF ally independent of whether they are awaiting
etiology.S7.7.1-6 SCD makes up a greater proportion heart transplant but rather the indication in those
of deaths in patients with milder HF symptoms and patients is generally based on the need to treat
lesser proportion in those with moderate/severe HF VA.S7.7.1-17
symptoms.S7.7.1-7 The reported incidence of SCD varies
depending on the definition used and the population 7.7.2. HF With Preserved Ejection Fraction
studied. Although many deaths, classified as sudden, Nearly half of the patients with HF have a preserved
are indeed due to lethal VA, others may be due to LVEF.S7.7.2-1 These patients tend to be older and have
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bradyarrhythmias, pulseless electrical activity, and sud- more comorbidities than patients with HFrEF. Howev-
den hemodynamic deterioration.S7.7.1-7–S7.7.1-9 er, although the rate of SCD is lower in patients with
Medical therapy with neurohormonal agents de- HF with preserved ejection fraction (HFpEF) than in
creases the risk of SCD by reducing both the incidence patients with HFrEF,S7.7.2-2 nearly a quarter of all deaths
of VA and disease progression.S7.7.1-7,S7.7.1-10–S7.7.1-12 De- among patients with HFpEF are sudden.S7.7.2-3–S7.7.2-5
spite GDMT for HFrEF, some patients remain at risk for The challenge in preventing SCD in patients with HF-
SCD, and an ICD may be helpful. See Sections 7.1 and pEF is identifying which patients are at a high enough
7.2 for the indications on ICDs in patients with reduced risk to benefit from preventive therapies. Studies ex-
LVEF. CRT, in appropriate patients, has also been shown ploring noninvasive risk factors for SCD in patients
to reduce the incidence of SCD.S7.7.1-13 with HFpEF do not identify consistent factors with
The pathophysiology of SCD in HF is complex, re- the exception of ischemic heart disease.S7.7.2-2,S7.7.2-6
sulting from interactions between both functional and Consequently, there is no accepted noninvasive test
structural changes that occur in patients with HFrEF to identify high-risk patients with HFpEF. Invasive risk
that result in increased susceptibility to SCD.S7.7.1-14 stratification with an electrophysiological study shows
Although many of the risk factors are shared among promise in this population.S7.7.2-7,S7.7.2-8 This topic is cur-
HFrEF patients, the reason that SCD strikes a particular rently being studied in the PRESERVE-EF (Risk Strati-
individual is usually unknown; however, some individu- fication in Patients With Preserved Ejection Fraction)
als may have a genetic susceptibility.S7.7.1-15 Varying de- trial (NCT02124018).
grees of myocardial fibrosis, neurohormonal activation, Whether to include a recommendation related to an
and increased wall stress alter the electrophysiological electrophysiological study in patients with HFpEF and
properties with changes in cell coupling, ionic currents ischemic heart disease was carefully considered by the
(electrical remodeling), and calcium handling that likely writing committee. However, evidence was deemed
contribute to the development of lethal VA.S7.7.1-16 Con- insufficient to support a formal recommendation. Still,
tributing factors extrinsic to the heart include electro- the pros and cons of an electrophysiological study can
lyte abnormalities related to volume shifts and diuretic reasonably be considered in select patients with HFpEF
use, sympathetic activation, hemodynamic stress, and and ischemic heart disease who are experiencing symp-
hypoxia. toms suggestive of a VA.
7.7.3. Left Ventricular Assist Device of SCD that has ranged from 10% to 35% in
CLINICAL STATEMENTS
atic review of 6 observational studies observed that 1. In patients with neuromuscular disorders,
primary and secondary prevention ICDs are
within 7 months, 26% of patients with an LVAD I B-NR recommended for the same indications as for
had died.S7.7.3-1 The death rate was lower among patients with NICM if meaningful survival of
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patients who previously had an ICD (16% versus greater than 1 year is expected.S7.8-1,S7.8-2
32%), suggesting a 39% relative-risk reduction 2. In patients with Emery-Dreifuss and limb-
in all-cause mortality in an adjusted analysis.S7.7.3-1 girdle type IB muscular dystrophies with
IIa B-NR progressive cardiac involvement, an ICD is
Patients with a history of pre-LVAD VA have nearly reasonable if meaningful survival of greater
a ≥10-fold risk of post-LVAD VA.S7.7.3-2–S7.7.3-4 In many than 1 year is expected.S7.8-3–S7.8-8
of the initial studies demonstrating ICD benefit, 3. In patients with muscular dystrophy, follow-
older pulsatile LVAD devices were in use.S7.7.3-2,S7.7.3-5 IIa B-NR
up for development of cardiac involvement
is reasonable, even if the patient is
Studies of ICD use with the newer, continuous flow asymptomatic at presentation.S7.8-9–S7.8-12
LVADs have inconsistently shown benefit.S7.7.3-1,S7.7.3-
4. In patients with myotonic dystrophy type 1 with
4,S7.7.3-6,S7.7.3-7
Of note, approximately 2 of 10 patients an indication for a permanent pacemaker, an
with an LVAD develop an LVAD related infection in IIb B-NR ICD may be considered to minimize the risk of
SCA from VT if meaningful survival of greater
the first year.S7.7.3-8,S7.7.3-9 than 1 year is expected.S7.8-9,S7.8-13,S7.8-14
er or ICD implantation. There should be a high level of NSVT, or bradycardia requiring a permanent pace-
CLINICAL STATEMENTS
concern for those patients with muscular dystrophy who maker) life-threatening VAs were relatively com-
AND GUIDELINES
present with arrhythmia symptoms.S7.8-15 The current mon; with 52% of patients receiving appropriate
guideline focuses on VA and indications for implantation ICD therapy including approximately 40% of
of an ICD. The indications for permanent pacemaker are those patients with an LVEF ≥45%.S7.8-3 A study of
discussed in another ACC/AHA/HRS guideline.S7.8-16 patients who had Lamin A/C mutation, in which
approximately 21% had a skeletal muscular dys-
trophy phenotype, SCD and appropriate ICD ther-
Recommendation-Specific Supportive apy were associated with NSVT, LVEF <45%, male
Text sex, and Lamin A/C nonmissense mutations.S7.8-4
1. In general, the indications for an ICD in patients These observational studies support the use of
with muscular dystrophy should follow standard an ICD when a pacing indication is present and
ICD recommendations for patients with NICM likely also when evidence of progressive cardiac
involvement such as cardiac conduction defects,
(see Section 7.2.1 on Secondary Prevention and
NSVT or reduced LVEF is present.S7.8-8
Section 7.2.2 on Primary Prevention of SCD with
There is a paucity of data regarding the rare
NICM). A high index of suspicion for bundle-
form of x-linked recessive Emery-Dreifuss muscular
branch reentrant tachycardia is warranted in
dystrophy (related to the Emerin gene mutation),
patients with myotonic dystrophy who exhibit
but arrhythmias may be less frequent than for the
wide QRS complex tachycardia or tachycardia- Lamin A/C mutations.S7.8-15
related symptoms.S7.8-2 3. Cardiac involvement can occur in a number of
2. In patients with Emery-Dreifuss and limb-girdle neuromuscular dystrophies (Table 9). To determine
type 1B muscular dystrophies associated with cardiac involvement, a 12-lead ECG and echocar-
Lamin A/C mutations, SCD accounts for about diogram are important for the initial clinical assess-
one third of all deaths.S7.8-4 Observational studies ment, independent of symptom status. In general,
show a significant rate of appropriate ICD therapy the more extensive the cardiac involvement, includ-
in patients with cardiac conduction disorders who ing evidence of distal conduction disease, ven-
are gene positive for Lamin A/C mutation even if tricular dysfunction, and atrial arrhythmias, the
LV function is preserved.S7.8-3,S7.8-5,S7.8-17 In an obser- more likely a VA will occur. The initial evaluation
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vational study in which 38% had isolated skeletal for myotonic dystrophy patients includes ambula-
muscular involvement but included patients with tory monitoring. In asymptomatic patients, some
conduction defects and other risk factors (includ- experts advocate for annual follow-up during the
ing PR interval >240 ms, left bundle-branch block, concealed phase of the disease with an annual
Frequency
Gene/Protein Primary Cardiac of Cardiac Associated With
Muscular Dystrophy Inheritance Affected Pathology Involvement Causes of Death Sudden Death?
Duchenne X-linked recessive Dystrophin NICM >90% Respiratory, HF Yes, uncertain etiology
Becker X-linked recessive Dystrophin NICM 60%–75% HF, respiratory Yes, uncertain etiology
Limb-girdle type 1B Autosomal dominant Lamin A/C Conduction system >90% Sudden, HF Yes
disease and NICM
Limb-girdle type 2C-2F Autosomal recessive Sarcoglycan NICM <25% Respiratory, HF Uncertain
Limb-girdle type 2I Autosomal recessive Fukutin-related NICM 20%–80% Respiratory, HF Uncertain
protein
Myotonic type 1 Autosomal dominant CTG repeat Conduction system 60%–80% Respiratory, 30% of deaths,
expansion disease and NICM sudden, HF uncertain bradycardia
versus tachycardia
Myotonic type 2 Autosomal dominant CCTG repeat Conduction system 10%–25% Normal causes Reported
expansion disease
Emery-Dreifuss X-linked and Emerin, Lamin A/C Conduction system >90% Sudden, HF Yes
autosomal dominant disease and NICM
or recessive
Facioscapulohumeral Autosomal dominant D4Z4 repeat Possibly conduction 5%–15% Normal causes, Not reported
contraction disease respiratory rarely
12-lead ECG to screen for development of conduc- is crucial to identifying affected family mem-
CLINICAL STATEMENTS
tion abnormalities. However, the optimal frequency bers. Due to the increased risk of adverse car-
AND GUIDELINES
CLINICAL STATEMENTS
ICD.S7.9-40 but, in selected patients, beta blockers can be
AND GUIDELINES
protective against SCA.S7.9.1.1-36,S7.9.1.1-37 Several
7.9.1. Specific Cardiac Channelopathy Syndromes
observational studies have reported effectiveness
7.9.1.1. Congenital Long QT Syndrome
for risk reduction in long QT syndrome with pro-
Recommendations for Long QT Syndrome pranolol, atenolol, and nadolol with appropriate
References that support the recommendations are summarized in dosing,S7.9.1.1-26,S7.9.1.1-28,S7.9.1.1-38–S7.9.1.1-40 while meto-
Online Data Supplement 40.
prolol appears less effective.S7.9.1.1-41 RCTs to assess
COR LOE Recommendations
comparative efficacy of specific beta blockers are
1. In patients with long QT syndrome with a unavailable, although many centers favor the use
I B-NR resting QTc greater than 470 ms, a beta
blocker is recommended.S7.9.1.1-1–S7.9.1.1-5
of nadolol. For long QT syndrome type 1, 1 study
reported atenolol reduced risk of VA while nado-
2. In high-risk patients with symptomatic long
QT syndrome in whom a beta blocker is lol was not associated with risk reduction.S7.9.1.1-2
ineffective or not tolerated, intensification For long QT syndrome type 2, nadolol was
of therapy with additional medications reported to show superior efficacy.S7.9.1.1-1,S7.9.1.1-2
I B-NR
(guided by consideration of the particular
long QT syndrome type), left cardiac Patients receiving a beta blocker should undergo
sympathetic denervation, and/or an ICD is ongoing monitoring to assess changes in QTc
recommended.S7.9.1.1-2,S7.9.1.1-6–S7.9.1.1-12 over time, and adequacy of beta blockade with
3. In patients with long QT syndrome and exertion.S7.9.1.1-26,S7.9.1.1-28
recurrent appropriate ICD shocks despite
2. High-risk patients with long QT syndrome
maximum tolerated doses of a beta
blocker, intensification of medical therapy include those with QTc >500 ms, genotypes
I B-NR with additional medications (guided by long QT syndrome type 2 and long QT syn-
consideration of the particular long QT
drome type 3, females with genotype long QT
syndrome type) or left cardiac sympathetic
denervation, is recommended.S7.9.1.1-6, syndrome type 2, <40 years of age, onset of
S7.9.1.1-7,S7.9.1.1-10,S7.9.1.1-13–S7.9.1.1-16
symptoms at <10 years of age, and patients
4. In patients with clinically diagnosed long QT with prior cardiac arrest or recurrent
I B-NR syndrome, genetic counseling and genetic syncope. S7.9.1.1-3,S7.9.1.1-8,S7.9.1.1-11,S7.9.1.1-30,S7.9.1.1-38
testing are recommended.S7.9.1.1-17–S7.9.1.1-21
Women with long QT syndrome type 2 are at
5. In patients with suspected long QT a higher risk of postpartum cardiac arrest/
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8. In patients with long QT syndrome, QT- Procainamide Phenothiazines Pentamidine Probucol
III: Harm B-NR prolonging medications are potentially (N-acetylprocainamide)
harmful.S7.9.1.1-5,S7.9.1.1-12,S7.9.1.1-32–S7.9.1.1-34
Quinidine Citalopram Azithromycin Droperidol
Dofetilide Tricyclic Chloroquine Ondansetron
Recommendation-Specific Supportive Dronedarone antidepressants Ciprofloxacin
Text Ibutilide Fluconazole
with recurrent syncope or cardiac arrest reported long QT syndrome type 3.S7.9.1.1-16 Complications
in 7% to 24% of patients.S7.9.1.1-44–S7.9.1.1-47 In related to left cardiac sympathetic denervation
high-risk patients, observational studies sup- occur in 8% to 20% of patients.S7.9.1.1-48,S7.9.1.1-51
port effectiveness of the ICD in preventing SCD, Syncope in patients with long QT syndrome may
with consideration of left cardiac sympathetic occur due to vasovagal syncope, noncompliance
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denervation to reduce the frequency of ICD with medications, or proarrhythmia from concur-
shocks.S7.9.1.1-16,S7.9.1.1-48,S7.9.1.1-49 Left cardiac sympa- rent medications.S7.9.1.1-5 Clinical evaluation that
thetic denervation can reduce VA burden, but up incorporates consideration of genotype, QTc inter-
to 27% of high-risk patients experience at least val, medication compliance, and shared decision-
1 recurrence.S7.9.1.1-16,S7.9.1.1-48,S7.9.1.1-50 Left cardiac making regarding the need to change or escalate
sympathetic denervation may be more effective therapy is important. Use of additional medica-
in patients with long QT syndrome type 1 and tions is guided by long QT syndrome type. In long
CLINICAL STATEMENTS
AND GUIDELINES
Figure 11. Long QT syndrome type 2.
QT syndrome type 3 ranolazine, mexiletine, and reduced risk of recurrent ICD shocks and fre-
flecainide shorten the QTc and have been used to quency of symptomsS7.9.1.1-16,S7.9.1.1-52; however,
reduce recurrent arrhythmias.S7.9.1.1-6,S7.9.1.1-7,S7.9.1.1-10 SCD or SCA is reported in 3% to 10% of
3. Mexiletine is an additional medication that can patients.S7.9.1.1-15,S7.9.1.1-16,S7.9.1.1-48,S7.9.1.1-50 Although
be used in patients with long QT syndrome arrhythmia burden is often reduced, up to
and recurrent ICD shocks. Left cardiac sympa- 27% of high-risk patients experience at least
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syndrome type. In long QT syndrome type 3, intervals ≤440 ms, most commonly patients with
CLINICAL STATEMENTS
ranolazine, mexiletine, and flecainide shorten long QT syndrome type 1.S7.9.1.1-31,S7.9.1.1-35 Patients
AND GUIDELINES
the QTc and have been used to reduce recurrent with long QT syndrome and normal QTc have
arrhythmias.S7.9.1.1-6,S7.9.1.1-7,S7.9.1.1-10 a lower risk of VA and SCD compared to those
4. Genetic testing for disease-causing mutations with prolonged QTc,S7.9.1.1-35 but still have an
in long QT syndrome offers important diagnos- increased risk of SCA or SCD compared with gen-
tic, prognostic, and therapeutic information in otype-negative, age- and sex-matched general
addition to the clinical evaluation, and a posi- patients.S7.9.1.1-31 Beta blockers reduce the risk of
tive test can facilitate establishing risk for family adverse cardiac events substantially.S7.9.1.1-1–S7.9.1.1-5,
members. The yield of genetic testing in long QT S7.9.1.1-30,S7.9.1.1-36,S7.9.1.1-38,S7.9.1.1-41,S7.9.1.1-57
During the
syndrome phenotype-positive patients is 50% to periods of highest risk in the first 3 decades of
86%, with the higher range present in patients life,S7.9.1.1-11,S7.9.1.1-18 treatment with a beta blocker
with marked QT prolongation or positive family may reduce risk of SCA.S7.9.1.1-26,S7.9.1.1-28,S7.9.1.1-36,
history of SCD.S7.9.1.1-17,S7.9.1.1-21,S7.9.1.1-53 A negative S7.9.1.1-38
Changes in QTc occur over time, particu-
genetic test does not exclude the diagnosis of larly during puberty and during and after preg-
long QT syndrome, which relies on the clinical nancy, indicating the need for assessment of QTc
evaluation. In asymptomatic patients with oth- on ECG annually or with medication changes,
erwise unexplained prolonged QTc ≥480 ms and assessing medication efficacy with exercise
on serial ECGs, genetic testing may help con- testing as feasible. Asymptomatic adult (male)
firm the diagnosis and supplement prognostic long QT syndrome patients with normal QTc
information in addition to clinical symptoms intervals may choose to decline beta-blocker
and QTc duration.S7.9.1.1-5,S7.9.1.1-18–S7.9.1.1-20,S7.9.1.1-30, therapy.S7.9.1.1-11,S7.9.1.1-34
S7.9.1.1-35,S7.9.1.1-54–S7.9.1.1-56
7. The risk of adverse cardiac events from VA is
5. In a prospective, observational study of patients influenced by the patient’s resting QTc inter-
with suspected long QT syndrome, patients with val, age, sex, and long QT syndrome genotype/
a history of syncope or cardiac arrest and either mutation. For asymptomatic males with long QT
an affected first-degree relative or a borderline syndrome, the risk of cardiac events is highest in
or prolonged QTc interval underwent exercise childhood,S7.9.1.1-2,S7.9.1.1-8,S7.9.1.1-11,S7.9.1.1-30 during a
treadmill testing and bicycle exercise, with ECGs time when medication compliance is challeng-
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recorded before, during, and after exercise, as ing. Young women with LQT2 and QTc >500
well as in different positions.S7.9.1.1-27 long QT syn- ms are at increased risk of SCAS7.9.1.1-2,S7.9.1.1-11,
drome was confirmed by genetic testing in all S7.9.1.1-18–S7.9.1.1-20,S7.9.1.1-30,S7.9.1.1-35
especially in the 9
affected individuals. Among patients with border- months postpartum, and may be candidates for
line-to-normal resting QTc intervals, prolongation primary prevention ICD placement or use of a
of the 4-minute recovery QTc ≥445 ms had high wearable cardioverter-defibrillator.S7.9.1.1-30
sensitivity for correctly identifying patients with 8. The risk of adverse events increases in patients with
long QT syndrome.S7.9.1.1-27 A study in younger long QT syndrome with prolongation of the QTc
patients demonstrated QTc prolongation >460 >500 ms.S7.9.1.1-2,S7.9.1.1-12,S7.9.1.1-26,S7.9.1.1-35,S7.9.1.1-41,S7.9.1.1-58
ms at 7 minutes of recovery predicted long QT QT-prolonging medications (www.crediblemeds.
syndrome type 1 or long QT syndrome type 2 org)S7.9.1.1-59 should not be used in patients with
patients versus controls.S7.9.1.1-23 In a study using long QT syndrome unless there is no suitable
burst bicycle exercise, patients with latent long alternative; careful monitoring of the QTc during
QT syndrome had a significantly greater increase therapy is recommended, with consideration for
in QTc with exercise than either controls or those discontinuing therapy with marked QTc prolonga-
with QTc prolongation at baseline.S7.9.1.1-24 These tion. Concurrent use of stimulant or nonstimu-
findings can be useful in establishing whether lant attention deficit/hyperactivity medications
long QT syndrome is present. Monitoring ade- was associated with an increased risk of syncope/
quacy of beta-blocker therapy using exercise cardiac arrest in long QT syndrome, particularly
testing can be beneficial, particularly in school- males, in 1 study,S7.9.1.1-34 but it did not appear to
aged patients.S7.9.1.1-26,S7.9.1.1-28 Beta-blocker ther- be associated with increased risk in another ret-
apy may be associated with a decrease in supine rospective study.S7.9.1.1-60 Episodes of torsades de
and peak exercise QTc, with the exception of pointes can be precipitated by exposure to a QT
long QT syndrome type 1 patients with C-loop prolonging medication, or hypokalemia induced
mutations.S7.9.1.1-25 by diuretics or gastrointestinal illenss. Attention
6. Approximately 10% to 36% of genotype-pos- to maintaining normal potassium and magne-
itive patients with long QT syndrome have QTc sium balance when medications or situations
CLINICAL STATEMENTS
important component of management. Rare polymorphic ventricular tachycardia should be
AND GUIDELINES
case reports exist of fever prolonging the QT reserved for patients with prior SCA, or patients
interval in patients with long QT syndrome type 2; with refractory VAs on combination medical
fever should be reduced with antipyreticsS7.9.1.1-61 therapy. Inappropriate shocks are reported
(Table 10). in 20% to 30% of catecholaminergic poly-
morphic ventricular tachycardia patients with
7.9.1.2. Catecholaminergic Polymorphic Ventricular ICDs.S7.9.1.2-2,S7.9.1.2-13–S7.9.1.2-16 ICD programming in
Tachycardia patients with catecholaminergic polymorphic
Recommendations for Catecholaminergic Polymorphic Ventricular ventricular tachycardia should be optimized to
Tachycardia deliver therapy for VF and to minimize inappro-
References that support the recommendations are summarized in priate shocks and the risk of potentially fatal
Online Data Supplement 41.
electrical storms.S7.9.1.2-13,S7.9.1.2-15 Left cardiac
COR LOE Recommendations
sympathetic denervation for catecholaminer-
1. In patients with catecholaminergic gic polymorphic ventricular tachycardia may
I B-NR polymorphic ventricular tachycardia, a beta
blocker is recommended.S7.9.1.2-1,S7.9.1.2-2 reduce the frequency of recurrent ICD shocks
2. In patients with catecholaminergic
by 32% to 75%S7.9.1.2-3–S7.9.1.2-5,S7.9.1.2-17,S7.9.1.2-18
polymorphic ventricular tachycardia although recurrent syncope, SCA, or SCD
and recurrent sustained VT or syncope, is reported in 9% to 32% of patients, with
while receiving adequate or maximally
tolerated beta blocker, treatment
other minor complications in 20% to 70%
I B-NR
intensification with either combination of patients. It is best if the left cardiac sym-
medication therapy (eg, beta blocker, pathetic denervation is performed in centers
flecainide), left cardiac sympathetic
denervation, and/or an ICD is with expertise in this procedure. Intensification
recommended.S7.9.1.2-2–S7.9.1.2-6 of medical therapy or left cardiac sympathetic
3. In patients with catecholaminergic denervation is important in treating patients
polymorphic ventricular tachycardia and who present with recurrent appropriate ICD
IIa B-NR with clinical VT or exertional syncope,
genetic counseling and genetic testing are
shocks.S7.9.1.2-19
reasonable.S7.9.1.2-7 3. Genetic testing may be useful to confirm the
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References that support the recommendations are summarized in 6. In patients with asymptomatic
Online Data Supplement 42 and Systematic Review Report. Brugada syndrome and a spontaneous
type 1 Brugada electrocardiographic
COR LOE Recommendations
Downloaded from http://ahajournals.org by on May 3, 2020
2. In patients with Brugada syndrome 7. In patients with suspected or established
with spontaneous type 1 Brugada Brugada syndrome, genetic counseling
electrocardiographic pattern and IIb C-EO and genetic testing may be useful
cardiac arrest, sustained VA or a recent to facilitate cascade screening of
I B-NR relatives.S7.9.1.3-18–S7.9.1.3-20
history of syncope presumed due to VA,
an ICD is recommended if meaningful
SR indicated systematic review.
survival of greater than 1 year is
expected.S7.9.1.3-4,S7.9.1.3-6
3. In patients with Brugada syndrome
experiencing recurrent ICD shocks for
Synopsis
I B-NR polymorphic VT, intensification of therapy Refer to the “Systematic Review for the 2017 ACC/
with quinidine or catheter ablation is
recommended.S7.9.1.3-7–S7.9.1.3-11
AHA/HRS Guideline for Management of Patients With
4. In patients with spontaneous
Ventricular Arrhythmias and the Prevention of Sudden
type 1 Brugada electrocardiographic Cardiac Death” for the complete systematic evidence
I B-NR
pattern and symptomatic VA who either review for additional data and analyses.S7.9.1.3-15 The
are not candidates for or decline an
ICD, quinidine or catheter ablation is results from the question “For asymptomatic patients
recommended.S7.9.1.3-7,S7.9.1.3-9–S7.9.1.3-11 with Brugada syndrome, what is the association be-
5. In patients with suspected Brugada tween an abnormal EP study and SCD and other ar-
syndrome in the absence of a spontaneous rhythmia endpoints? (Part 1)” and the writing commit-
type 1 Brugada electrocardiographic
IIa B-NR
pattern, a pharmacological challenge using tee’s review of the totality of the literature were used
a sodium channel blocker can be useful for to frame decision-making. Recommendations that are
diagnosis.S7.9.1.3-12–S7.9.1.3-14
based on a body of evidence that includes the system-
CLINICAL STATEMENTS
AND GUIDELINES
Figure 14. Prevention of SCD in patients with Brugada syndrome.
Colors correspond to Class of Recommendation in Table 1. See Section 7.9.1.3 for discussion. *ICD candidacy as determined by functional status, life expec-
tancy or patient preference. 1° indicates primary; ECG, electrocardiogram; EP, electrophysiological; ICD implantable cardioverter-defibrillator; SCD, sudden cardiac
death; VT, ventricular tachycardia; and VF, ventricular fibrillation.
Downloaded from http://ahajournals.org by on May 3, 2020
atic review conducted by the ERC are denoted by the type 1 electrocardiographic changes of Brugada
superscript SR (eg, LOE: B-RSR). syndrome (Figure 15), or with only medica-
Factors identified as potential triggers of VF and SCA tion-induced electrocardiographic changes,
in Brugada syndrome include some psychotropic medica- is low. S7.9.1.3-1–S7.9.1.3-5
A positive family history
tions, and anesthetic agents, cocaine, excessive alcohol of Brugada syndrome or SCA is not a signifi-
intake, and fever (www.brugadadrugs.org).S7.9.1.3-21,S7.9.1.3-22 cant predictor of adverse events in Brugada
These agents should be avoided, and fever war- syndrome.S7.9.1.3-1,S7.9.1.3-2,S7.9.1.3-4,S7.9.1.3-5 Implantation
rants early and aggressive measures to reduce of an ICD in an asymptomatic patient without a
temperature.S7.9.1.3-23 spontaneous type 1 Brugada electrocardiographic
has not been shown to confer any benefit.
2. Brugada syndrome is characterized by coved ST
Recommendation-Specific Supportive elevation in leads V1 or V2 positioned in the
Text second, third, or fourth intercostal space either
1. The risk of major adverse cardiac events in spontaneously or induced by administration of
asymptomatic patients without spontaneous a sodium channel–blocking drug in the absence
of other causes of ST elevationS7.9.1.3-24 and nega- with a family history of Brugada syndrome may
CLINICAL STATEMENTS
tive T waves in the right precordial leads, and is be offered sodium channel blocker challenge for
AND GUIDELINES
associated with syncope or SCA due to VF, pre- diagnostic evaluation, although a positive test
dominantly in young males, although it has been does not require chronic therapy due to a low risk
reported in all age groups. The type 1 Brugada in this setting.S7.9.1.3-12 In asymptomatic patients
ECG with coved ST elevation in right precordial with type 1 Brugada electrocardiographic find-
leads may be present spontaneously, during ings, medication challenge does not offer addi-
fever or vagotonic states, or after medication tional diagnostic value.
challenge with sodium channel blockers. QRS 6. Polymorphic VT/VF induced by programmed stim-
complex fractionation is seen in a minority of ulation has been associated with an increased risk
patients. Patients with spontaneous coved type of VA in some patients with spontaneous type
ST elevation and a history of syncope or prior 1 Brugada ECG.S7.9.1.3-13 The specificity of pro-
SCA are at the highest risk for potentially lethal grammed stimulation for assessing risk decreases
VA. ICD implantation has been shown to reduce with the inclusion of triple extrastimuli.S7.9.1.3-6,
mortality in symptomatic patients with Brugada S7.9.1.3-13
The value of programmed stimulation in
syndrome.S7.9.1.3-25,S7.9.1.3-26 asymptomatic patients with spontaneous type
3. Ablation of abnormal areas of epicardial 1 Brugada ECGs has been the subject of mul-
late activation in the RV can suppress recur- tiple studies.S7.9.1.3-1,S7.9.1.3-2,S7.9.1.3-4,S7.9.1.3-5 A report
rent VA as shown in a small number of found that the prognostic value has decreased
patients.S7.9.1.3-8,S7.9.1.3-9,S7.9.1.3-11,S7.9.1.3-27 In these over time, possibly as patients with less
reports, the spontaneous type 1 Brugada pat- severe phenotypes have been recognized and
tern on ECG may be eliminated in >75% of studied.S7.9.1.3-1 Some experts use the results of
patients, and recurrences of VT/VF are markedly programmed ventricular stimulation for inform-
reduced.S7.9.1.3-9–S7.9.1.3-11 Experience and follow-up
ing shared decision-making in consideration of
after ablation are limited, and an ICD for patients
the ICD. In symptomatic patients with Brugada
who have had syncope or SCA is recommended.
syndrome, programmed ventricular stimula-
A series of patients with Brugada syndrome
tion for risk stratification does not add anything
treated with quinidine had no deaths during a
to the evaluation of the patients as an ICD is
mean follow-up of over 9 years, although adverse
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warranted.S7.9.1.3-2,S7.9.1.3-4,S7.9.1.3-6
effects of quinidine were reported in 38% of
7. The yield of genetic testing in phenotype positive
patients, these authors felt that quinidine could
patients is approximately 20% to 30% in Brugada
be used as an alternative to the ICD in selected
syndrome. S7.9.1.3-4,S7.9.1.3-16,S7.9.1.3-18,S7.9.1.3-19,S7.9.1.3-30,
patients.S7.9.1.3-7
4. Observational studies show that quinidine can
S7.9.1.3-31
SCN5A variants account for most of
suppress VF storm in patients with Brugada syn- this subset of genotype positive Brugada
drome, and a low risk of arrhythmia was observed syndrome. However, 2% to 10% of other-
in a long-term observational study.7.9.1.3-7 wise healthy individuals host a rare variant of
No patient treated with quinidine experienced SCN5A.S7.9.1.3-20,S7.9.1.3-31 A negative genetic test does
SCD. Adverse effects of quinidine occur in up to not exclude the diagnosis of Brugada syndrome,
37% of patients. Catheter ablation targeting the which is usually based on electrocardiographic
epicardial right ventricular areas of abnormality and clinical characteristics. Risk stratification is
has also been shown to reduce recurrent VF epi- based on symptoms and clinical findingsS7.9.1.3-32;
sodes and normalize the ECG.7.9.1.3-9–7.9.1.3-11 genotype status is not correlated with the risk
5. Administration of procainamide, flecainide, or of adverse events.S7.9.1.3-5,S7.9.1.3-18,S7.9.1.3-19,S7.9.1.3-33
ajmaline may be useful to provoke type 1 ST Identification of a pathogenetic mutation may
elevation in patients suspected to have Brugada help facilitate recognition of carrier status in fam-
syndrome as a cause of symptoms but who do ily members, allowing for lifestyle modification
not have a type 1 electrocardiographic pattern and potential treatment.
at baseline. Medication challenge should be ter- 8. Factors identified as potential triggers of VF and
minated with the development of VA, marked SCA in Brugada syndrome include some psy-
QRS widening, or type 1 Brugada electrocardio- chotropic medications, and anesthetic agents,
graphic pattern.S7.9.1.3-14,S7.9.1.3-28 The use of high cocaine, excessive alcohol intake, and fever
electrocardiographic electrode positioning in the (www.brugadadrugs.org).S7.9.1.3-21,S7.9.1.3-22 These
second and third interspaces for electrocardio- agents should be avoided and fever warrants
graphic recording improves detection of a type early and aggressive measures to reduce tempera
1 Brugada ECG.S7.9.1.3-29 Asymptomatic patients ture.S7.9.1.3-23
7.9.1.4. Early Repolarization “J-wave” Syndrome Recommendations for Short QT Syndrome (Continued)
CLINICAL STATEMENTS
AND GUIDELINES
Recommendations for Early Repolarization Syndrome COR LOE Recommendations
References that support the recommendations are summarized in 2. In patients with short QT syndrome
Online Data Supplement 43. who have a cardiac arrest or sustained
COR LOE Recommendations I B-NR VA, an ICD is recommended if
meaningful survival greater than 1 year
1. In asymptomatic patients with an is expected.S7.9.1.5-3–S7.9.1.5-5
early repolarization pattern on ECG,
I B-NR 3. In patients with short QT syndrome and
observation without treatment is
recommended.S7.9.1.4-1,S7.9.1.4-2 IIa C-LD recurrent sustained VA, treatment with
quinidine can be useful.S7.9.1.5-3,S7.9.1.5-5,S7.9.1.5-6
2. In patients with early repolarization
pattern on ECG and cardiac arrest or 4. In patients with short QT syndrome and VT/
I B-NR sustained VA, an ICD is recommended if IIa C-LD VF storm, isoproterenol infusion can be
meaningful survival greater than 1 year is effective.S7.9.1.5-7
expected.S7.9.1.4-3,S7.9.1.4-4 5. In patients with short QT syndrome, genetic
3. In patients with early repolarization IIb C-EO testing may be considered to facilitate
III: No screening of first-degree relatives.S7.9.1.5-4
B-NR pattern on ECG, genetic testing is not
Benefit
recommended.S7.9.1.4-5
Recommendation-Specific Supportive
Recommendation-Specific Supportive Text Text
1. The prevalence of an early repolarization pattern 1. The prevalence of short QTc ≤340 ms is esti-
on ECG with J point elevation in the inferior or mated to be 5 in 10 000 in persons <21
lateral leads of at least 0.1 mV has been reported years of age and is more common in
to be as high as 5.8% in adultsS7.9.1.4-1 and is more males.S7.9.1.5-1,S7.9.1.5-4,S7.9.1.5-8,S7.9.1.5-9 An incidental
common in males. The early repolarization pat- finding of a short QTc ≤320 ms in an asymp-
tern was lost during 10-year follow-up in >60% tomatic patient warrants monitoring and
of young males.S7.9.1.4-2 Patients are determined follow-up without prophylactic medication
to have an early repolarization syndrome when, treatment.S7.9.1.5-1,S7.9.1.5-2
in addition to having early repolarization pattern 2. Patients with cardiac arrest in the setting of
on an ECG, they either have symptoms such as short QT syndrome are known to be at increased
Downloaded from http://ahajournals.org by on May 3, 2020
syncope or present with an arrhythmia. When risk for recurrent cardiac arrest.S7.9.1.5-3–S7.9.1.5-5
patients present with an early repolarization pat- Approximately 18% of the small number of
tern on an ECG, it is important to rule out revers- reported patients with short QT and implanted
ible causes such as ischemia. Patients with early ICDs have experienced appropriate ICD therapies
repolarization are more susceptible to the devel- during short-term follow-up.S7.9.1.5-3,S7.9.1.5-5,S7.9.1.5-6
opment of VF during acute cardiac ischemia and/ Therapy with quinidine may reduce the number
or in the presence of QRS abnormalities due to LV of ICD shocks.S7.9.1.5-3,S7.9.1.5-5,S7.9.1.5-6
hypertrophy or bundle-branch block.S7.9.1.4-6–S7.9.1.4-8 3. Markedly shortened QTc values ≤300 ms
2. Patients with cardiac arrest or VF in the setting of are associated with increased risk of SCD,
an electrocardiographic pattern of early repolar- especially during sleep or rest, in young
ization are at increased risk for subsequent recur- persons, in whom the median QTc was
rent episodes of VF, occurring in at least 40% 285 ms.S7.9.1.5-5,S7.9.1.5-9 A clinical score including QTc
of patients.S7.9.1.4-3,S7.9.1.4-4,S7.9.1.4-9 Antiarrhythmic duration, clinical history of documented polymor-
medications, with the exception of quindine/ phic VT or VF, unexplained syncope, family history
hydroquinidine, have limited efficacy in prevent- of autopsy-negative SCD or sudden infant death
ing recurrent VA.S7.9.1.4-3,S7.9.1.4-4 syndrome, and positive genotype results has
3. To date, genetic testing has not reliably identified been proposed to identify patients at increased
mutations predisposing to early repolarization.S7.9.1.4-5 risk for SCD.S7.9.1.5-4,S7.9.1.5-10 Treatment with quini-
dine results in lengthening of the QTc and, in
7.9.1.5. Short QT Syndrome selected patients, may be an alternative to ICD
Recommendations for Short QT Syndrome implantation.S7.9.1.5-3,S7.9.1.5-5,S7.9.1.5-6
References that support the recommendations are summarized in 4. In the setting of electrical storm with refractory VF
Online Data Supplement 44. and short QT syndrome, infusion of isoproterenol
COR LOE Recommendations can be effective in restoring/maintaining sinus
1. In asymptomatic patients with a short QTc rhythm.S7.9.1.5-7
I B-NR interval, observation without treatment is 5. Pathogenic mutations in potassium channels
recommended.S7.9.1.5-1,S7.9.1.5-2
have been identified in approximately 10% to
20% of patients with short QT syndrome includ- origin manifested by the earliest site of electrical activa-
CLINICAL STATEMENTS
ing in KCNH2 (SQT1), KCNQ1 (SQT2), and KCNJ2 tion or, when this is not feasible, by pace-mapping. The
AND GUIDELINES
(SQT3).S7.9.1.5-4 Due to the rarity of the disease, most common site of origin for idiopathic VA is from the
genotype/phenotype correlations are unavailable, right ventricular outflow tract (RVOT) or the ostium of
limiting the use of knowledge of genotype status. the LV, which is comprised of the oval opening of the
LV to which the aorta is attached anteriorly and the left
atrium is attached posteriorly. The likely origin can be
8. VA IN THE STRUCTURALLY NORMAL reasonably predicted from the QRS morphology of the
HEART VA, which provides a good indication of the type of ap-
proach required and the likelihood of success and risks.
Recommendations for VA in the Structurally Normal Heart
Ablation failure is often related to the absence of the VA
References that support the recommendations are summarized in
Online Data Supplement 45.
for mapping at the time of the procedure, or origin of
the VA in an inaccessible region of the heart. These foci
COR LOE Recommendations
occasionally produce sustained monomorphic VT.S8-5–S8-7
1. In patients with symptomatic PVCs in an
otherwise normal heart, treatment with
a beta blocker or nondihydropyradine
I B-R
calcium channel blocker is useful to
Recommendation-Specific Supportive Text
reduce recurrent arrhythmias and improve 1. In a randomized, double-blinded, placebo-con-
symptoms.S8-1,S8-2
trolled study of 52 patients with symptomatic VA
2. In patients with symptomatic VA in an
otherwise normal heart, treatment with
and a mean PVC count of 21 407±1740 beats
an antiarrhythmic medication is reasonable per 24 hours, atenolol significantly decreased
IIa B-R
to reduce recurrent symptomatic symptom frequency (P =0.03) and PVC count
arrhythmias and improve symptoms if
beta blockers and nondihydropyradine
(P =0.001), whereas placebo had no effect on PVC
calcium channel blockers are ineffective or count (P =0.78) or average heart rate (P =0.44).S8-8
not tolerated.S8-3,S8-4 A prospective randomized comparison of antiar-
rhythmic medications versus catheter ablation,
metoprolol or propafenone had modest efficacy
Synopsis to suppress RVOT VA although with a far higher
Most idiopathic VA are due to a focal mechanism of rate of recurrence than catheter ablation.S8-9
Downloaded from http://ahajournals.org by on May 3, 2020
triggered activity or abnormal automaticity, some, no- 2. In an RCT of 233 patients with ≥30 PVCs per
tably interfascicular reentrant LV tachycardias, are due hour, d-sotalol was shown to reduce frequent
to reentry. The clinical manifestations of idiopathic VA PVCs, but only racemic dl-sotalol is presently
are highly variable and range from benign, asymptom- available.S8-10 In a prospective randomized com-
atic PVCs to sustained VT or even VF. On initial discovery, parison of antiarrhythmic medications versus
an evaluation for structural heart disease is warranted catheter ablation, therapy with metoprolol or
with physical examination, an ECG, and imaging, usu- propafenone was shown to have modest effi-
ally with echocardiography. In the absence of any ab- cacy when used to suppress RVOT PVCs although
normality or a family history of SCD, further assessment with a far higher rate of recurrence than catheter
and treatment are guided by symptoms. If the patient is ablation.S8-9 Nondihydropyridine calcium channel
asymptomatic and does not have evidence of a cardiac blockers reduce arrhythmias.S8-1,S8-2,S8-11,S8-12
channelopathy, reassurance as to the benign nature is
sufficient. If the arrhythmia is suspected of being suf-
ficiently frequent to cause ventricular dysfunction over 8.1. Outflow Tract and Atrioventricular
time, periodic follow-up with reassessment of ventricular Annular VA
function is warranted (see Section 10.8). For mild symp- Recommendations for Outflow Tract VA
toms, avoidance of aggravating factors such as excessive References that support the recommendations are summarized in
consumption of caffeine or sympathomimetic agents, Online Data Supplement 46.
may be sufficient. Therapy with a beta blocker or non- COR LOE Recommendations
dihydropyradine calcium channel blocker reduces symp- 1. In patients with symptomatic outflow tract
toms for some patients. Class I antiarrhythmic medica- VA in an otherwise normal heart for whom
tions can be effective, but those are generally avoided I B-NR antiarrhythmic medications are ineffective,
not tolerated, or not the patient’s preference,
due to concerns for adverse effects. For patients who catheter ablation is useful.S8.1-1–S8.1-3
require arrhythmia suppression for whom antiarrhythmic
2. In patients with symptomatic outflow tract
medications are ineffective, not tolerated, or undesired, VT in an otherwise normal heart, a beta
I B-NR
catheter ablation can be a highly effective treatment (see blocker or a calcium channel blocker is
Section 9). The ablation strategy is to identify the site of useful.S8.1-1–S8.1-3
CLINICAL STATEMENTS
Text 1. The papillary muscles of the LV or RV can be the site
AND GUIDELINES
1. In 1 RCT, catheter ablation was superior to anti- of origin of VA in the presence or absence of struc-
arrhythmic medications at suppressing frequent tural heart disease.S8.2-1–S8.2-5 Idiopathic left and right
ventricular papillary muscle VA are most commonly
PVCs arising from the RVOT.S8.1-4 Observational
PVCs and NSVT, and are usually exercise-related
studies have shown that radiofrequency cath-
and may be induced by intravenous epinephrine or
eter ablation is effective in the treatment of idio- isoproterenol administration.S8.2-3 These arrhythmias
pathic VA arising from the RVOT and LV outflow have a focal, nonreentrant mechanism. Any of the
tract.S8.1-2,S8.1-5–S8.1-16 The site of ablation may be below 3 RV papillary muscles may be the site of origin and
or above the pulmonic valve in the RVOT.S8.1-9,S8.1-13 catheter ablation is usually effective.S8.2-2 In 1 study,
Although most RVOT VA can be ablated within the successful ablation was achieved in all 8 patients
RV, 10% may require ablation within the pulmonic with a reduction in PVC burden from 17±20% to
sinus cusps.S8.1-9 Serious complications are infre- 0.6±0.8%.S8.2-2 In the left ventricle, the site of origin
quent. For LV outflow tract VA, the site of ablation may be either the posteromedial or the anterolat-
may be within the aortic cusp sinuses,S8.1-11,S8.1-14,S8.1-16 eral papillary muscles.S8.2-1,S8.2-4,S8.2-5 Multiple VA QRS
below the aortic valve,S8.1-2,S8.1-6 at the aorto-mitral morphologies were observed in 47% of patients,
continuityS8.1-1–S8.1-3 or on the epicardial surface of and ablation on both sides of the papillary muscle is
the LV summit.S8.1-3,S8.1-17,S8.1-18 The mitral and tricus- required in some patients.S8.2-4 Achieving adequate
catheter stability can be challenging. Acute abla-
pid annulae are less common sites of idiopathic VA,
tion success is high, but recurrences are more fre-
but these VA can also be effectively treated with
quent than for idiopathic outflow tract VA. Serious
catheter ablation.S8.1-1,S8.1-19,S8.1-20 Approximately complications, including valve injury, appear to be
10% of idiopathic VA may arise from the summit of infrequent. The risks of catheter ablation include
the LV. Some can be ablated from the great cardiac bleeding related to arterial and venous access and
vein or the epicardial surface, but others arise from a low risk of pericardial tamponade.
an inaccessible region in close proximity to the left
coronary artery precluding effective ablation.S8.1-14
8.3. Interfascicular Reentrant VT
Downloaded from http://ahajournals.org by on May 3, 2020
sensitive.S8.3-1–S8.3-3 These VTs are typically sustained Recommendations for Idiopathic Polymorphic VT/VF (Continued)
CLINICAL STATEMENTS
ers or verapamil typically terminate these arrhyth- 3. F or patients with recurrent episodes of
idiopathic VF initiated by PVCs with a
mias, but they fail to prevent recurrences in some I B-NR
consistent QRS morphology, catheter
patients.S8.3-1–S8.3-3 The target of catheter ablation for ablation is useful.S8.4-11,S8.4-14
the most common form is usually the distal insertion
of the anterograde limb of the Purkinje system along
the inferior portion of the LV septum near its junc- Recommendation-Specific Supportive
tion with the left posterior fascicle. Catheter abla- Text
tion is acutely successful in >90% of patients with 1. When combined with clinical evaluation, genetic
a risk of recurrence of approximately 10%. This VT testing can provide a diagnosis in up to 13%
may resemble fascicular VA that are due to a focal to 60% of younger (<40 years of age) survivors
mechanism in the left anterior or left posterior fas- of SCA,S8.4-3 with the most common genotypes
cicles of the LV His-Purkinje system. These fascicular identified associated with long QT syndrome,
arrhythmias usually have a focal mechanism with the catecholaminergic polymorphic ventricular tachy-
target of catheter ablation being the site of earliest cardia, and Brugada syndrome.S8.4-8 Drowning/
electrical activation recorded with a presystolic fas- near drowning events are particularly associated
cicular potential. Catheter ablation is highly effective with LQT1 and catecholaminergic polymorphic
for intrafascicular and fascicular VA. Serious compli- ventricular tachycardia; genetic mutations in long
cations are infrequent and include bleeding at the QT syndrome and catecholaminergic polymorphic
site of arterial or venous access and a small risk of ventricular tachycardia have been identified in
bundle branch block or atrioventricular block. 23% of patients with unexplained near-drown-
2. Idiopathic LVT is based on reentrant mechanism ing episodes.S8.4-15 In 1 study,S8.4-6 exertion-related
involving tissue with slow conduction properties cardiac arrest, particularly in children, may be
along the LV septum as the anterograde limb
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CLINICAL STATEMENTS
cated to prevent SCD. Catheter ablation of the
AND GUIDELINES
Recommendations for PVC-Induced Cardiomyopathy
triggering focus has proved to be highly effective References that support the recommendations are summarized in
in eliminating the repetitive PVCs which induce Online Data Supplement 50.
VF in these patients.S8.4-11 During a median post- COR LOE Recommendations
procedural follow-up of 63 months, 7 (18%) of 1. F or patients who require arrhythmia
suppression for symptoms or declining
38 patients undergoing catheter ablation of idio-
ventricular function suspected to be due to
pathic VF induced by short coupled PVCs experi- frequent PVCs (generally >15% of beats
I B-NR
and predominately of 1 morphology) and
enced VF recurrence at a median follow-up of 4
for whom antiarrhythmic medications are
months. Five of these 7 patients underwent repeat ineffective, not tolerated, or not the patient’s
preference, catheter ablation is useful.S9-1,S9-2
ablation without VF recurrence. Thus, although
catheter ablation is very effective in idiopathic VF, 2. In patients with PVC-induced
cardiomyopathy, pharmacological treatment
the recurrence risk remains substantial after an IIa B-NR (eg, beta blocker, amiodarone) is reasonable
apparently successful procedure and the patient to reduce recurrent arrhythmias and improve
symptoms and LV function.S9-3,S9-4
should be protected with an ICD. The subcuta-
neous ICD may not be a good therapy for these
patients due to the higher risk of T-wave over- Recommendation-Specific Supportive
sensing seenin this population; however, data are Text
limited.S8.4-10 1. Frequent PVCs (usually >15% of the total num-
3. Idiopathic VF may be initiated by PVCs that ber of beats) may produce a reversible form of
arise from the outflow tracts or the His-Purkinje LV dysfunction.S9-5–S9-18 However, it is sometimes
system within either the right ventricle or left difficult to ascertain whether the PVCs caused LV
ventricle.S8.4-11,S8.4-14,S8.4-19–S8.4-21 Some patients have dysfunction or whether progressive LV dysfunc-
tion caused frequent PVCs. LV dysfunction has
clusters of VF episodes (electrical storm) that typi-
been associated with greater PVC burden (>10%
cally present as PVCs initiating polymorphic VT/VF.
and usually >20%), NSVT, a retrograde P-wave
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The PVCs usually have a consistent QRS morphol- after the PVCs, and interpolated PVCs.S9-6,S9-15
ogy and a short coupling interval and can be tar- In a prospective study of catheter ablation for
geted for ablation to control the arrhythmia.S8.4-11 PVC-induced cardiomyopathy, ablation was com-
For PVCs from the Purkinje system, the ablation pletely successful in 80% of patients.S9-19 LV func-
target is a high-frequency Purkinje potential pre- tion normalized within 6 months in 82% of the
ceding the PVCs. When episodes are induced by 22 patients who had depressed ventricular dys-
short-coupled PVCs arising from the outflow tracts, function at baseline. Thus, frequent PVCs may
the ablation target is the site of earliest ventricular be a reversible cause of LV dysfunction that can
be effectively treated with catheter ablation. It is
activation. Patients with idiopathic VF often have
often difficult to determine if apparent LV dys-
periods of frequent VT/VF interspersed with peri-
function reflects impaired LV function or inability
ods of relative quiescence.S8.4-11,S8.4-14 To maximize to accurately assess LV function due to the fre-
the probability of successful ablation, the proce- quent ectopic activity. In patients who have a high
dure is best performed during periods of frequent density of PVCs with normal ventricular function,
PVCs. Less-frequent episodes of VF may be ame- optimal treatment and surveillance for prevention
nable to ablation if frequent PVCs with a consis- and detection of decline in ventricular function
tent QRS morphology are present. When the PVCs have not been established.
can be identified, ablation is highly successful, but 2. In a double-blind parallel study of 30 patients
late recurrences are observed in approximately with or without ischemic heart disease with >30
PVCs per hour comparing sotalol to propranolol,
10% of patients such that implantation of an ICD
proarrhythmic effects were present in 1 patient
is prudent even if ablation is acutely successful.
on sotalol. There was no significant difference
The risks of catheter ablation include bleeding at in suppression of PVCs (sotalol 65%, proprano-
the site of arterial or venous access and a small risk lol 44%), with reduction in ventricular couplets
of pericardial tamponade. Therapy with quinidine being 99% for sotalol and 49% for propranolol.
acutely and chronically can suppress recurrent VF There was a significant increase in QTc in patients
episodes in some patients.S8.4-22 on sotalol.S9-20 In a double-blind, randomized,
and LVEF <0.40 attributed to ischemic or NICM letes remain the most common medical cause of death
AND GUIDELINES
and ≥10 PVCs per hour, amiodarone significantly and many occur as the first cardiac event.
reduced VA, slowed heart rate, and was associ- The most common structural cause of SCAs and
ated with an increase in LVEF by 42% at 2 years SCDs in athletes in the United States is HCM, fol-
with a nonsignificant trend toward reduction in lowed by anomalous origins of coronary arteries,
mortality.S9-4 Whether the VA was contributing with myocarditis contributing a smaller but significant
to ventricular dysfunction in these patients is proportion.S10.1-15 Beyond these, the other inherited
unknown. disorders contribute to the distribution of causes of a
SCD in athletes, many of which can be suspected or
identified by a careful family history and preparticipa-
10. VA AND SCD RELATED TO SPECIFIC tion ECGs.
POPULATIONS In general, management of arrhythmias in athletes
10.1. Athletes follows that in nonathletes. In regard to interventions, it
is now generally recommended that AEDs be available
In athletes, VAs range from isolated PVCs, cou- at training and facilities for competitive athletes,S10.1-16
plets, and NSVT, to sustained VT and SCA leading to with less specific statements for AED availability at ven-
SCD.S10.1-1 Infrequent PVCs and short runs of repetitive ues (eg, tennis courts) or circumstances (eg, jogging or
NSVT, especially in the absence of structural heart dis- small group runs) in which recreational athletics are oc-
ease, are more common in nonathletes, but they are curring.
generally benign, requiring only a limited workup and Many athletes who have had corrective procedures
rarely lead to disqualification for sports.S10.1-2,S10.1-3 In (repair of congenital or developmental defects such as
contrast, longer runs of NSVT, especially when exer-
anomalous origins of coronary arteries)S10.1-17,S10.1-18 are
cise-induced, and sustained VT and SCA/SCD are in-
on therapy for inherited disordersS10.1-19 or have ICD im-
frequent, but they have a higher incidence in athletes
plantsS10.1-1 and are able to participate in athletics de-
than that reported for the general population in the
pending on the nature and severity of the disease and
corresponding age groups. Reported estimates of SCD
with appropriate precautions and counseling regarding
range from 1 per 53 703 athlete-years in the National
potential residual risks.S10.1-19,S10.1-20 For example, ath-
Collegiate Athletic Association databaseS10.1-4 to <1
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pregnancy to ensure ongoing beta-blocker ther- 10.3. Older Patients With Comorbidities
CLINICAL STATEMENTS
apy. The risk of SCA or SCD is significantly higher
AND GUIDELINES
Recommendation for Older Patients With Comorbidities
during the 9 months after delivery, most notably
See Systematic Review Report.S10.3-1
among women with LQT2.S10.2-1,S10.2-6,S10.2-7 A large
COR LOE Recommendation
retrospective analysis from the long QT syndrome
registry demonstrated an odds ratio of 40.8 1. F or older patients and those with significant
comorbidities, who meet indications for a
for syncope, SCA, or SCD among women with IIa B-NRSR primary prevention ICD, an ICD is reasonable
long QT syndrome in the 9 months’ postpartum; if meaningful survival of greater than 1 year
treatment with beta blockers during pregnancy is expected.S10.3-1
tion, yet the risk versus benefit of primary prevention Mitral valve prolapse has been implicated as a cause
CLINICAL STATEMENTS
ICDs has been unclear; data from observational stud- of SCD, although a study of 18 786 patients found no
AND GUIDELINES
ies have been conflicting, and patients with moderate increased risk of SCA for patients with bileaflet mitral
or severe CKD, especially patients with end-stage renal valve prolapse versus single leaflet mitral valve prolapse
disease (ESRD) on dialysis were not included in the piv- or no mitral valve prolapse.S10.6-5 LV fibrosis in the papil-
otal RCTs of ICDs.S10.4-1–S10.4-5 Furthermore, prior data had lary muscles has been described in some mitral valve
significant limitations given that patients who received prolapse patients with VA or SCD.S10.6-6 Further, a possi-
ICDs have been compared inconsistently with a control ble syndrome for SCD has been described that includes
group with CKD that did not receive primary prevention bileaflet mitral valve prolapse, female sex, T wave ab-
ICDs and the degree of renal insufficiency likely influ- normality, and complex ventricular ectopy.S10.6-7 Guid-
ences survival benefit.S10.4-6 Patients with CKD, especially ance for treatment of patients with NICM, whether val-
ESRD on dialysis, appear to be at increased risk of ICD- vular or otherwise in origin, is provided in the current
related complications. A significant number of sudden guideline (see Sections 7.2.1 and 7.2.2 for primary and
deaths are unassociated with VA in this population.S10.4-7 secondary prevention).
Therefore, the ERC was asked to address the impact of
ICDs on mortality in patients with CKD.
10.6. Sex-Related Differences in the Risk
The ERC conducted a specific analysis of 5 studies
that explored renal dysfunction. A meta-analysis of of SCD
these studies suggested that an association exists be- The information on associations between sex and VA
tween ICD implantation and improved survival.S10.4-8 and SCD is largely limited to epidemiological, cohort,
An important limitation is that only 2 studies specifi- and observational studies. Various population studies,
cally studied patients with ESRD and most data ana- primarily focused on SCD due to ischemic heart disease,
lyzed were from observational studies.S10.4-8,S10.4-9 In view have demonstrated age gradients in SCD risk among
of these limitations, the writing committee concluded men and women.S10.6-8–S10.6-10 These include a 10-year lag
there was not enough data to inform a recommenda- in SCD incidence in women compared with men. How-
tion on ICD implantation in patients with ESRD on di- ever, risk factor burden among women has the same
alysis. Decisions regarding ICDs in patients with CKD, proportional effect as in men, with a 17-fold increase
especially those with ESRD, should be individualized in risk from the lowest to highest deciles.S10.6-9 Impor-
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and take into consideration the patient’s functional sta- tantly, 69% of the SCDs in women were first cardiac
tus, number of comorbidities, and preferences, among events.S10.6-8 A study of lifetime risk of SCD stratified at
other factors. 45, 55, 65, and 75 years of age identified persistently
lower and similar proportions of lifetime risk of SCD
among women versus men in each of the strata.S10.6-10
10.5. Valvular Heart Disease The difference between women and men is somewhat
Patients with valvular heart disease should be evaluated smaller at ages below and above 75 years, largely be-
and treated according to GDMT for valvular heart dis- cause of a reduced risk in men. The overall lifetime risk
ease and, when LVEF is depressed, GDMT that applies of SCD was 1 in 9 among men and 1 in 30 among
to NICM to reduce the risk of SCD.S10.6-23 VA in patients women.S10.6-10
with valvular heart disease can be caused by any of the In studies of outcomes after out-of-hospital car-
mechanisms responsible for VA in other cardiac disease diac arrest, women were older, had more SCAs in
including ischemic heart disease, MI, severe LV hyper- homes, and fewer shockable rhythms (VT/VF) than
trophy, adrenergic-dependent rhythm disturbances, men.S10.6-11,S10.6-12 This was associated with a somewhat
or an inherited molecular abnormality. Patients with lower probability of survival overall; however, women
valvular heart disease and VA are generally evaluated with VT/VF and those with pulseless electrical activity had
and treated using current recommendations for each better outcomes than men.S10.6-12 A retrospective analy-
disorder.S10.6-1 The presence of a VA alone does not con- sis of out-of-hospital cardiac arrest reported that survival
stitute an indication for valve repair or replacement. In improved over a 10-year period, with more favorable
general, there is more knowledge on the risk for SCD in outcomes in men as well as younger women.S10.6-13
patients with aortic stenosis than other valvular lesions Two studies demonstrated better outcomes in wom-
with a risk of 1% to 1.5% per year.S10.6-2 Most patients en with VT/VF, despite adverse risk factor profiles in
who die suddenly have been symptomatic from their women.S10.6-14,S10.6-15 Another large study demonstrated
valve disease.S10.6-3,S10.6-4 Although recurrent NSVT may that despite similar prehospital return of spontaneous cir-
place a patient with severe aortic stenosis at risk for culation and survival to discharge, younger women had
syncope, the management of such a patient is guided lower 1-month neurologically intact survival than the 50
by the severity of the valvular lesion. to 60 age group.S10.6-16 A 17-year retrospective analysis
did not demonstrate any difference between men and Recommendations for Medication-Induced Arrhythmias (Continued)
CLINICAL STATEMENTS
women, although total outcomes improved.S10.6-17
AND GUIDELINES
COR LOE Recommendations
The proportion of ischemic heart disease-associated
4. F or patients with torsades de pointes
SCAs among women surviving out-of-hospital cardiac associated with acquired QT prolongation,
arrest was significantly lower than in men, but ischemic I C-LD potassium repletion to 4.0 mmol/L or more
heart disease remained the most powerful predictor and magnesium repletion to normal values
(eg, ≥2.0 mmol/L) are beneficial.S10.7-6,S10.7-7
etiologically,S10.6-18 and women were also significantly
Sodium channel blocker–related toxicity
less likely to have severe LV dysfunction (LVEF ≤35%)
or previously recognized ischemic heart disease.S10.6-19 COR LOE Recommendations
Women appear to be less likely to benefit from thera- 5. In patients taking sodium channel blockers
who present with elevated defibrillation
peutic hypothermia postcardiac arrest; however, in the
or pacing thresholds, discontinuing the
younger age group, neurologic recovery in women was IIa C-LD
presumed responsible medication or
better than in older women.S10.6-20 Women are less likely reprogramming the device can be useful to
restore effective device therapy.S10.7-8,S10.7-9
to have SCA during competitive athletic events. A large
study including both recreational and competitive ath- 6. In patients with congenital or acquired long
III: Harm B-NR QT syndrome, QT-prolonging medications are
letes across a large age range noted that SCA in women potentially harmful.S10.7-10
during athletic events was 1 in 20 of that in men.S10.6-21
A large literature review from 1980 to 1992 dem-
onstrated that women accounted for 70% of re- Recommendation-Specific Supportive
corded cases of cardiovascular medication–related Text
arrhythmias.S10.6-22 This is consistent with QT interval dif-
1. Typical arrhythmias related to digoxin toxicity
ferences among men and women. A retrospective anal-
include enhanced atrial, junctional, or ventricu-
ysis of quinidine discontinuation reported a significant
difference in discontinuation between men and women lar automaticity (with ectopic beats or tachy-
(66% versus 84%) largely due to prolonged QT.S10.6-23 A cardia) often combined with atrioventricular
study of catheter ablation for VT reported that overall block.S10.7-11 VT that is fascicular or bidirectional
outcome was similar between men and women.S10.6-24 in origin is suggestive of digoxin toxicity.S10.7-12
The only sex difference was the greater probability of Severe digoxin overdose causes hyperkalemia and
women having RVOT VT and a greater probability of cardiac standstill. The diagnosis is established by
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men having LV outflow tract VT. the combination of characteristic rhythm distur-
bances, ancillary symptoms (visual disturbances,
nausea, changes in mentation), and elevated
10.7. Medication-Induced Arrhythmias serum concentrations. Potentiating factors may
Recommendations for Medication-Induced Arrhythmias include hypothyroidism, hypokalemia, or renal
References that support the recommendations are summarized in dysfunction.S10.7-12 Treatment of digoxin toxic-
Online Data Supplements 52 and 53. ity is based on the severity. In mild cases, dis-
Digoxin continuing the medication, monitoring rhythm,
COR LOE Recommendation and maintaining normal serum potassium may
1. Administration of digoxin antibodies is be sufficient.S10.7-11 Intravenous magnesium is
I B-NR
recommended for patients who present often administered if VAs are present.S10.7-12
with sustained VA potentially due to digoxin
toxicity.S10.7-1,S10.7-2
Occasionally, temporary pacing may be needed
for atrioventricular block or asystole.S10.7-13 For
Medication-induced QT prolongation and torsades de pointes
more severe intoxication (serum digoxin con-
COR LOE Recommendations
centrations exceeding 4 ng/mL and with serious
2. In patients with recurrent torsades de arrhythmias such as VT), the treatment of choice
pointes associated with acquired QT
prolongation and bradycardia that cannot is digoxin-specific Fab antibody.S10.7-1 In 1 series
I B-NR
be suppressed with intravenous magnesium of 150 severely intoxicated patients, response
administration, increasing the heart rate with
was rapid (30 minutes to 4 hour), and 54% of
atrial or ventricular pacing or isoproterenol
are recommended to suppress the patients presenting with a cardiac arrest sur-
arrhythmia.S10.7-3 vived hospitalization.S10.7-1 Adverse effects include
3. For patients with QT prolongation due to a worsening of the underlying disease (increased
medication, hypokalemia, hypomagnesemia, ventricular rate during AF, exacerbation of HF)
or other acquired factor and recurrent torsades
I C-LD
de pointes, administration of intravenous and hypokalemia. Doses lower (and less expen-
magnesium sulfate is recommended to sive) than the full neutralizing dose are sufficient
suppress the arrhythmia.S10.7-4,S10.7-5
as long as cardiac arrest is not imminent.S10.7-2
Digoxin concentration monitoring is unreliable Sodium channel blockers, like procainamide and
CLINICAL STATEMENTS
after antidigoxin antibody administration. flecainide, can occasionally precipitate the typical
AND GUIDELINES
2. Monitoring high-risk patients during initiation of Brugada syndrome ECG.S10.7-24,S10.7-25 This has been
QT-prolonging antiarrhythmic medications and reported not only with antiarrhythmic medications
recognition of the syndrome when it occurs are the but also with tricyclic antidepressantsS10.7-26 and
first steps. Temporary pacing is highly effective in cocaineS10.7-27 (www.brugadadrugs.org).S10.7-28
managing torsades de pointes that is recurrent after Whether this represents unmasking individuals
potassium and magnesium supplementation.S10.7-3 with clinically unapparent Brugada syndrome (see
Isoproterenol can also be used to increase heart Section 7.9.1.3) or one end of a broad spectrum of
rate and abolish postectopic pauses.S10.7-3 responses to sodium channel blockers is unknown.
3. Intravenous magnesium can suppress episodes of In the setting of sodium-channel blocker tox-
torsades de pointes without necessarily shortening icity, limited animal data suggest that adminis-
QT, even when serum magnesium is normal.S10.7-4,S10.7-5 tration of sodium, as sodium chloride or sodium
Repeated doses may be needed, titrated to suppress bicarbonate, may improve conduction slowing
ectopy and nonsustained VT episodes while precipi- or suppress frequent or cardioversion-resistant
tating factors are corrected.S10.7-4 Magnesium toxicity VT.S10.7-29 Successful treatment with beta block-
(areflexia progressing to respiratory depression) can ersS10.7-30 and intravenous fat emulsion and/or
occur at high serum concentrations, but this risk is extracorporeal membrane oxygenation has also
very small with the doses usually used to treat tors- been reported.S10.7-31
ades de pointes, 1 to 2 g intravenously.S10.7-14 6. QT-prolonging medications (www.crediblemeds.
Allelic variants in clinical long QT disease genes org)S10.7-32 are not used in patients with congenital
have been identified in patients with medication- or acquired long QT syndrome unless there is no
induced torsades de pointes.S10.7-7,S10.7-15–S10.7-18 suitable alternative or the benefit greatly exceeds
Further, whole exome sequencing implicates an the risk. Episodes of torsades de pointes can be
increased burden of rare potassium channel vari- precipitated by exposure to a QT-prolonging medi-
ants in the risk of medication-induced torsades de cation, and underlying prolongation of the QT
pointes.S10.7-17,S10.7-19 These findings do not yet sup- (from genetic and clinical risk factors) increases
port general genetic screening for prediction of this risk.S10.7-10 Medications implicated in torsades
medication-induced torsades de pointes. In long de pointes are found in several medication classes,
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Sodium channel blockers increase defibrillation 2. In patients with adult congenital heart
energy requirement and pacing thresholdsS10.7-8,S10.7-9; disease and complex or sustained VA
in the presence of important residual
as a consequence, patients may require repro- hemodynamic lesions, treatment of
I B-NR
gramming or revision of pacing or ICD systems or hemodynamic abnormalities with catheter
changes in their medication regimens (although or surgical intervention as feasible is
indicated prior to consideration of ablation
modern pacing systems that provide automatic or an ICD.S10.8-3,S10.8-7–S10.8-12
pacing threshold testing and adjustment of pac- 3. In patients with adult congenital heart
ing output have mitigated the risk of loss of cap- disease and hemodynamically unstable VT,
ture). Sodium channel blockers can “convert” AF I B-NR
an ICD is recommended after evaluation and
appropriate treatment for residual lesions/
to slow atrial flutter, which can show 1:1 atrioven- ventricular dysfunction if meaningful survival
tricular conduction with wide QRS complexes that of greater than 1 year is expected.S10.8-13–S10.8-17
can be confused with VT.S10.7-23
Recommendations for Adult Congenital Heart Disease (Continued) includes transposition of the great arteries, truncus ar-
CLINICAL STATEMENTS
teriosus, and single ventricle anatomy (Figure 16).
AND GUIDELINES
COR LOE Recommendations
4. In patients with adult congenital heart
I B-NR
disease with SCA due to VT or VF in the
absence of reversible causes, an ICD is
Recommendation-Specific Supportive
recommended if meaningful survival of Text
greater than 1 year is expected.S10.8-13–S10.8-17
1. The association of VT with RV hemodynamic
5. In adults with repaired tetralogy of Fallot
physiology with high-risk characteristics abnormalities was first established in patients
IIa B-NR and frequent VA, an electrophysiological with repaired TOF.S10.8-33 Multiple studies since
study can be useful to evaluate the risk of that time have demonstrated the correlation of
sustained VT/VF.S10.8-18,S10.8-19
hemodynamic residue and ventricular dysfunction
6. In adults with repaired tetralogy of Fallot
physiology and inducible VT/VF or spontaneous
with risk of VT or SCD in patients with congeni-
IIa B-NR sustained VT, implantation of an ICD is tal heart disease.S10.8-1,S10.8-3–S10.8-6,S10.8-18,S10.8-34–S10.8-36
reasonable if meaningful survival greater than Presentation with frequent or complex VA may
1 year is expected.S10.8-1,S10.8-19,S10.8-20
indicate worsening hemodynamic function, coro-
7. In patients with adult congenital heart disease nary artery compromise, or decreased perfusion in
with recurrent sustained monomorphic VT or
IIa B-NR
recurrent ICD shocks for VT, catheter ablation the setting of ventricular hypertrophy. Evaluation
can be effective.S10.8-21–S10.8-25 may also include exercise testing to assess func-
8. In adults with repaired severe complexity tional capacity.S10.8-35 Careful evaluation of hemo-
IIa B-NR
adult congenital heart disease and frequent dynamic status for optimization of management
or complex VA, a beta blocker can be
is important.S10.8-9 Potentially treatable residual
beneficial to reduce the risk of SCA.S10.8-26
hemodynamic problems may be identified dur-
9. In patients with repaired moderate or
severe complexity adult congenital heart
ing hemodynamic evaluation, such as outflow
disease with unexplained syncope and at tract stenosis or significant regurgitation, which
least moderate ventricular dysfunction may benefit from either catheter or surgical
or marked hypertrophy, either ICD
IIa B-NR
implantation or an electrophysiological
intervention.S10.8-3,S10.8-7,S10.8-10,S10.8-12,S10.8-37 Patients
study with ICD implantation for inducible with markedly reduced ventricular function,
sustained VA is reasonable if meaningful elevated end-diastolic pressures, or pulmonary
survival of greater than 1 year is
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expected.S10.8-5,S10.8-16,S10.8-27–S10.8-29
hypertension should be treated for underlying
hemodynamic problems as part of their arrhyth-
10. In patients with adult congenital heart
disease and severe ventricular dysfunction mia management.
(LVEF <35%) and symptoms of heart failure 2. The correlation of residual hemodynamic abnor-
IIb B-NR despite GDMT or additional risk factors,
malities with VA has been most extensively studied
ICD implantation may be considered if
meaningful survival of greater than 1 year is in patients with repaired TOF, where RV hyperten-
expected.S10.8-14–S10.8-16,S10.8-20 sion, residual pulmonary outflow tract obstruction
11. In patients with adult congenital heart or regurgitation, and RV dilation are risk factors
disease who have asymptomatic VA, for VT/SCD.S10.8-1,S10.8-2,S10.8-4,S10.8-8,S10.8-33,S10.8-34,S10.8-36
prophylactic antiarrhythmic therapy
III: Harm B-NR
with class Ic medications (ie, flecainide,
In these studies, frequent PVCs correlated with
propafenone) or amiodarone is potentially risk of clinical or inducible sustained VT. A com-
harmful.S10.8-30–S10.8-32 bined approach of surgery for structural abnor-
malities with map-guided arrhythmia surgery has
been used with success,S10.8-3,S10.8-8,S10.8-10,S10.8-12 but
Synopsis
elimination of VT circuits may be limited by deep
Tetralogy of Fallot (TOF) is defined as, congenital heart endocardial or LV origin of VT and limitations of
disease with RVOT obstruction and ventricular septal operative mapping; an empiric approach to VT
defect, often requiring right ventricle to pulmonary surgery is generally not recommended as it has
artery conduit placement or pulmonary valve replace- limited effectiveness and carries risk of ventricu-
ment; includes TOF and double-outlet right ventricle. lar proarrhythmia.S10.8-38 Pulmonary valve replace-
Moderate complexity congenital heart disease is de- ment in patients with TOF may result in improved
fined as congenital heart disease requiring intracardiac hemodynamics and functional status, but it may
surgical repair, other than isolated atrial and ventricular not eliminate the risk of VTS10.8-3,S10.8-12; postopera-
septal defects; includes TOF, aortic stenosis, coarctation tive reassessment for the need for an ICD is per-
of aorta, and Ebstein anomaly of the tricuspid valve. formed after the early recovery period.
Severe complexity congenital heart disease is defined 3. Correction of residual hemodynamic/structural
as cyanotic congenital heart disease requiring intracar- abnormalities contributing to VT may improve
diac repair in infancy, often with staging procedures; ventricular function and reduce symptoms, but
Simple complexity
ASDS10.8–44,S10.8–47,S10.8–57—S10.8–62 2%–6% <1.5% Ventricular pacing
RV dilatation
Pulmonary hypertension
NKX2.5 gene
VSDS10.8–27,S10.8–44,S10.8–47,S10.8–57—S10.8–63 3%–18% <3%
Moderate complexity
Tetralogy of FallotS10.8-1,S10.8-2,S10.8-5,S10.8-6,S10.8–28,S10.8–34,S10.8–36,S10.8– 14%–31% 1.4%–8.3% Unexplained syncope
44,S10.8–46,S10.8–47,S10.8–54—S10.8–56,S10.8–62—S10.8–65
Frequent or complex VA
Sustained VT
QRS duration ≥180 ms
Inducible sustained VT
Atrial tachycardia
Decreased LVEF
Dilated right ventricle
Severe PR
Severe PS
Aortic stenosis S10.8–27,S10.8–44,S10.8–56 10%–34% 3%–20% Unexplained syncope
Severe LV hypertrophy
Aortic stenosis mean pressure
gradient >40 mm Hg
Ventricular dysfunction
Coarctation of aortaS10.8–28,S10.8–29, 2% 2% Aneurysm at repair site
S10.8–44,S10.8–46,S10.8–56,S10.8–62
Aortic stenosis
Systemic hypertension
Premature coronary artery disease
Ebstein’s anomalyS10.8–45,S10.8–47,S10.8–55 2% 3%–6% Cardiomegaly
Atrial fibrillation
Wide complex tachycardia
Mitral regurgitation
Dilated RVOT
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Severe complexity
Transposition of the great arteriesS10.8–27,S10.8–44—S10.8–48,S10.8– Atrial switch
51,S10.8–55,S10.8–56,S10.8–62
*Univentricular physiology includes: Tricuspid atresia, Double inlet left ventricle, Mitral atresia, Hypoplastic left heart, Unbalanced AV septal defect.
ASD indicates atrial septal defect; cc-TGA, congenitally corrected transposition of the great arteries; LV, left ventricular; LVEF, left ventricular ejection fraction;
PR, pulmonary regurgitation; PS, pulmonary stenosis; RV, right ventricular; RVOT, right ventricular outflow tract; SCD, sudden cardiac death; VA, ventricular
arrhythmia; VSD, ventricular septal defect; and VT, ventricular tachycardia.
it may inadequately prevent the risk of subse- 41 years.S10.8-13–S10.8-17 Patients with adult congenital
quent VT or SCA. The use of ICDs in adult con- heart disease experience appropriate shock rates
genital heart disease patients for secondary of 3% to 6% per year, with equivalent or slightly
prevention accounts for approximately 50% of increased frequency of appropriate shocks for sec-
implantations presently, at a mean age of 36 to ondary prevention indications.S10.8-14,S10.8-15,S10.8-17
CLINICAL STATEMENTS
AND GUIDELINES
Figure 16. Prevention of SCD in patients with adult congenital heart disease.
Colors correspond to Class of Recommendation in Table 1. See Section 10.8 for discussion. *High-risk features: prior palliative systemic to pulmonary shunts,
unexplained syncope, frequent PVC, atrial tachycardia, QRS duration ≥180 ms, decreased LVEF or diastolic dysfunction, dilated right ventricle, severe pulmonary
regurgitation or stenosis, or elevated levels of BNP. †Frequent VA refers to frequent PVCs and/or nonsustained VT. ACHD indicates adult congenital heart disease;
BNP, B-type natriuretic peptide; EP, electrophysiological; ICD, implantable cardioverter-defibrillator; LVEF, left ventricular ejection fraction; PVC, premature ventricu-
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lar complexes; SCD, sudden cardiac death; TOF, tetralogy of Fallot; VA, ventricular arrhythmia; and VT, ventricular tachycardia.
Patients with adult congenital heart disease expe- surgeries, may benefit from earlier consideration
rience a higher rate of complications and inap- of heart transplantation before renal or liver dys-
propriate shocks compared with other adult function progresses.
populations.S10.8-13–S10.8-17,S10.8-39 5. Patients with repaired TOF who are at an increased
4. Challenges of ICD implantation in patients with risk of sustained VT include those with prior pal-
adult congenital heart disease may include ana- liative systemic to pulmonary shunts, unexplained
tomic complexity, intracardiac shunts, and limited syncope, frequent PVCs, atrial tachycardia, QRS
vascular access to the ventricle. Patients with adult duration ≥180 ms, decreased LVEF or diastolic
congenital heart disease receiving an ICD have an dysfunction, dilated right ventricle, severe pulmo-
increased rate of complications of 26% to 45%, nary regurgitation or stenosis, or elevated levels
as well as inappropriate shocks in 15% to 25% of of BNP. Patients with TOF physiology and subop-
patients.S10.8-13–S10.8-16,S10.8-40 Limited studies on the timal hemodynamic status are more likely to have
use of subcutaneous implantable cardioverter- inducible sustained VT,S10.8-18,S10.8-19,S10.8-33,S10.8-35
defibrillator implantation, particularly in patients and inducible sustained VT correlated with an
with single ventricle anatomy,S10.8-41 report increased risk of SCA in a multicenter cohort
improved success by using right in addition to left study.S10.8-19 Evaluation of hemodynamics for
parasternal lead positioning for screening.S10.8-42 residual abnormalities is important, with catheter
Patients with a single ventricle or a systemic right or surgical treatment of important lesions prior to
ventricle may not tolerate defibrillation thresh- consideration of ICD implantation.
old testing, resulting in multiorgan system fail- 6. In a multicenter cohort, inducible sustained VT
ure. Patients with complex anatomy, such as in patients with TOF was an independent risk
older patients with univentricular physiology, or factor for subsequent clinical VT or SCDS10.8-19;
patients with significantly reduced ventricular patients in that early study had cardiomegaly and
function, marked hypertrophy, or multiple prior prior palliative shunts. Patients with repaired
TOF account for approximately 50% of and beta blockers are important to reduce ICD
CLINICAL STATEMENTS
disease.S10.8-13–S10.8-16,S10.8-40 Appropriate ICD shocks 9. The risk of SCD is increased among patients
occur in up to 7.7% per year of patients with TOF with adult congenital heart disease compared
receiving the ICD for primary prevention, compared with the general population, with the median
with 9.8% per year in patients with a secondary pre- age at death ranging from 30 to 49 years of
vention ICD.S10.8-20 In another study including patients age.S10.8-27,S10.8-44,S10.8-47,S10.8-54,S10.8-55 The risk of SCD
with TOF as well as other lesions, inducible sustained is highest among patients with moderate or
VT did not correlate with subsequent appropriate severe complexity congenital heart disease, and
ICD shocks.S10.8-14 Because of the high incidence of accounts for approximately 25% of cardiac causes
inappropriate shocks in 20% to 30% and compli- of death.S10.8-5,S10.8-27,S10.8-28,S10.8-44–S10.8-46,S10.8-55,S10.8-56
cations in at least 30% of patients with adult con- Patients with septal defects and a positive fam-
genital heart disease,S10.8-14–S10.8-17,S10.8-39,S10.8-40,S10.8-43 ily history of septal defects, cardiomyopathy, or
in addition to financial and psychological burdens, bundle-branch block/conduction defects may
shared decision-making regarding primary preven- have the gene mutation NKX2.5, which portends
tion ICDs is essential. an increased risk of early SCD; genetic testing and
7. In patients with recurrent sustained monomorphic VT, early consideration of ICD implantation if positive
catheter ablation of VT can be effective.S10.8-21–S10.8-25 is warranted.S10.8-57–S10.8-59 Patients with repaired
Hemodynamic repair, at the time that an arrhythmia complex forms of congenital heart disease have
is being ablated surgically, should be considered. For undergone multiple intracardiac surgeries in the
patients with complex adult congenital heart disease, first few decades of life with resultant hypertro-
care should be provided at experienced centers. After phy and risk for subendocardial ischemia as well
successful catheter ablation of VT, implantation of an as scar formation contributing to VT/VF. Risk fac-
ICD for those who do not have an ICD is an individu-
tors for SCD include increasing complexity of
alized decision based on overall functional and physi-
heart disease, VA, SVT, progressive increase in QRS
ological status and shared decision making. Careful
duration, systemic ventricular dysfunction, and
monitoring during follow-up for recurrent arrhyth-
subpulmonary ventricular dysfunction.S10.8-1,S10.8-5,
mias is essential. S10.8-6,S10.8-14,S10.8-28,S10.8-29,S10.8-36,S10.8-45–S10.8-47,S10.8-55
8. The highest risk of SCD associated with repaired
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CLINICAL STATEMENTS
appropriate option for some patients.S10.8-42,S10.8-53 cardioverter-defibrillator consists of a pulse generator
AND GUIDELINES
11. Adult patients with complex adult congenital that is placed at the midaxillary line between the fifth
heart disease typically have hypertrophy and and sixth intercostal spaces and a lead with 2 sensing
ventricular dysfunction of varying degrees, electrodes and a shocking coil, positioned subcutane-
increasing their risk for worsening ventricular ously adjacent to the sternum. As with the transvenous
function with antiarrhythmic medications. In ICD, the pulse generator housing serves as an electrode
the only large study of antiarrhythmic medi- for defibrillation but, in addition, it can also serve as
cations for congenital heart disease, the use an optional electrode for sensing. The subcutaneous
of flecainide was associated with proarrhyth- implantable cardioverter-defibrillator cannot achieve
mia in 5.8% of patients and SCA in 3.9% of adequate arrhythmia sensing for all patients, and elec-
patients.S10.8-30 The use of amiodarone is gener- trocardiographic screening to assess sensing is required
ally reserved for refractory symptomatic VA or prior to implantation.S11.1-10,S11.1-11 Some advocate exer-
asymptomatic VA that can aggravate ventricu- cise testing after device implantation to ensure proper
lar dysfunction, due to the high risk of adverse sensing with exercise.
effects including thyroid dysfunction, particularly Both transvenous and subcutaneous implantable
among females and patients with univentricular cardioverter-defibrillators have SVT-VT discriminators
physiology.S10.8-31,S10.8-32 that can be programmed to facilitate discrimination
of SVT from VT; however, these discriminators do not
always work. If sustained VT is confirmed, therapy to
11. DEFIBRILLATORS OTHER THAN terminate the arrhythmia is delivered. All ICDs provide
TRANSVENOUS ICDS shocks to terminate VT or VF, but shocks in an awake
patient are painful and associated with decreased QoL.
11.1. Subcutaneous Implantable Transvenous ICDs are capable of bradycardia pacing as
Cardioverter-Defibrillator well as antitachycardia pacing that can terminate many
Recommendations for Subcutaneous Implantable Cardioverter-
VTs painlessly. Subcutaneous implantable cardioverter-
Defibrillator defibrillators provide limited postshock bradycardia
References that support the recommendations are summarized in pacing but do not provide either bradycardia or antit-
Online Data Supplement 55. achycardia pacing.
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VF events were treated in 59 patients; 90.1% Administration for patients who are “at risk for SCA
were terminated with 1 shock, and 98.2% were and are not candidates for or refuse an implantable
terminated within the 5 available shocks. The defibrillator.”S11.2-6 A science advisory from the AHA
estimated 3-year inappropriate shock rate was summarizes the data and recommendations for the use
13.1% most due to oversensing of cardiac sig- of the wearable cardioverter-defibrillator.S11.2-4 Effective-
nals, and mortality was 4.7%. Device-related ness of the wearable cardioverter-defibrillator in recog-
complications occurred in 11.1% of patients. An nition and defibrillation of VF has been demonstrated in
ongoing trial will compare the effect of the sub- a number of studies, although no RCTs support the use
cutaneous implantable cardioverter-defibrillator of the wearable cardioverter-defibrillator. Among 3569
with that of the transvenous ICD on the out- patients who received the device for various reasons,
comes of inappropriate shocks, complications, for at least 1 day in the US manufacturer registry, there
shock efficacy, and mortality.S11.1-13 were 80 VT/VF events in 59 patients, with a frequency
3. The subcutaneous implantable cardioverter- of 1.7% per patient-year. First shock efficacy was 99%,
defibrillator is incapable of bradycardia pac- with postshock survival of 90%. Overall, 2% of the pa-
ing, biventricular pacing, or antitachycardia tients received an inappropriate shock.S11.2-1
pacing. Therefore, patients who need any of
these types of pacing from an ICD should not be Recommendation-Specific Supportive
offered a subcutaneous implantable cardioverter-
defibrillator.S11.1-6 Some clinical scenarios may
Text
come up in which a transvenous pacemaker for 1. Removal of an ICD for a period of time, most
bradycardia pacing in a patient with a subcutane- commonly due to infection, exposes the patient
ous implantable cardioverter-defibrillator which to risk of untreated VT/SCD unless monitoring
is needed; this can be performed as long as the and access to emergency external defibrillation
pacing is not unipolar. Leadless pacing devices is maintained. In 1 series of 354 patients who
for patients who require bradycardia pacing will received the wearable cardioverter-defibrillator,
be evaluated with the subcutaneous implantable the indication was infection in 10%.S11.2-3 For
cardioverter-defibrillator in the near future. patients with a history of SCA or sustained VA,
the wearable cardioverter-defibrillator may allow cal. In addition to prevention, critical components of
CLINICAL STATEMENTS
the patient to be discharged from the hospital survival from SCA include immediate recognition and
AND GUIDELINES
with protection from VT/SCA until the clinical activation of the emergency response system, early
situation allows reimplantation of an ICD. high-quality CPR, and rapid defibrillation for shockable
2. The patients listed in this recommendation are rhythms.S11.3-13
represented in clinical series and registries that
demonstrate the safety and effectiveness of
the wearable cardioverter-defibrillator. Patients 12. SPECIAL CONSIDERATIONS FOR
with recent MI, newly diagnosed NICM, recent CATHETER ABLATION
revascularization, myocarditis, and secondary
cardiomyopathy are at increased risk of VT/SCA. Recommendations for Catheter Ablation
References that support the recommendations are summarized in
However, the wearable cardioverter-defibrillator
Online Data Supplement 57.
is of unproven benefit in these settings, in part
COR LOE Recommendations
because the clinical situation may improve with
therapy and time. In patients awaiting transplant, 1. In patients with bundle-branch reentrant VT,
I C-LD catheter ablation is useful for reducing the
even with anticipated survival <1 year without risk of recurrent VT and ICD shocks.S12-1–S12-3
transplant, and depending on clinical factors such 2. In patients with structural heart disease who
as use of intravenous inotropes and ambient VA, have failed endocardial catheter ablation,
a wearable cardioverter-defibrillator may be an IIa B-NR epicardial catheter ablation can be useful for
reducing the risk of recurrent monomorphic
alternative to an ICD. VT.S12-4–S12-6
HELP-VT trial,S12-4 epicardial ablation was required circumstances of death that could be reasonably
CLINICAL STATEMENTS
in 30% of patients with VT related to NICM com- implicated in the cause of unexpected SCD.S13-1
AND GUIDELINES
pared with 1.2% of patients with ischemic car- One study documented the added value of post-
diomyopathy. A wide QRS with marked slurring mortem examination at a specialized cardiac
of the initial portion of the QRS and a QS com- pathology center,S13-2 with particular value for
plex in the lateral or inferior leads during VT sug- clarifying an apparent overdiagnosis of cardiomy-
gests an epicardial circuit in NICM, but the ECG opathy by nonspecialized centers. Pathological
does not reliably predict epicardial VT locations in findings limited to the specialized conduction sys-
patients with prior MI. Preprocedural cardiac MRI tem were demonstrated in 22% of cases.S13-9 A
and intraprocedural electroanatomic mapping misdiagnosis of cardiomyopathy was reported in
are useful tools to guide the localization of epi- 37% of referred cases that were ultimately deter-
cardial scar that may be the source of reentrant mined to be structurally normal. The etiologic data
VT.S12-8,S12-10 Pericardial adhesions prevent percu- for specialized cardiac evaluation are not general-
taneous access in some patients, notably many izable to the overall population because of skew-
with prior cardiac surgery. Percutaneous pericar- ing of age at the time of SCD. In another study
dial access for mapping and ablation is associated of SCD patients at ages ranging from <1 year to
with a serious complication rate of approximately >80 years (mean, 38.2 years; median, 38 years),
5% and tamponade from RV puncture or lac- the peak incidence of SCD occurred between the
eration that can require emergent surgery or be ages of 31 and 60 years, with a 5- to 7-fold excess
fatal, coronary artery injury and phrenic nerve of males/females in that age range.S13-10 For the
injury can occur.S12-11,S12-12 Reported experience is overall group, 42% of SCD were due to ischemic
from tertiary referral centers. heart disease, 12% viral myocarditis, and 5%
cardiomyopathy, with 15% being unexplained
by autopsy. For the subgroup <35 years of age,
13.5% were attributed to ischemic heart disease
13. POSTMORTEM EVALUATION
and 24.9% were unexplained. In the subgroup
OF SCD >55 years of age, only 0.8% were unexplained.
Recommendations for Postmortem Evaluation of SCD In patients who die suddenly despite an ICD,
interrogation of the ICD is important to confirm
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in the proband. To be able to harvest quality about deactivation in advance care planning
CLINICAL STATEMENTS
DNA for such testing, medical examiners, hos- documents.S14-6 Consequently, surrogates usually
AND GUIDELINES
pital pathologists, and private pathologists need make decisions about ICD deactivation without
standards for harvesting and storing samples for any prior discussions with the patient.S14-6 In hypo-
later genetic testing. Family members of SCD thetical scenarios, patients with ICDs were able to
probands who died suddenly (first cardiac event, identify scenarios in which they might choose to
death from natural causes, last seen alive and well deactivate their ICD.S14-1,S14-7 This discussion can
within 12 hours), with autopsy findings showing occur at any time, but it is particularly important
structural abnormalities of uncertain significance to have it at the time of initial ICD implantation,
(eg, ventricular hypertrophy, myocardial fibrosis, at the time of reimplantation, and during prepa-
or minor ischemic heart disease [n=41]) had a ration of advance care plans.
51% prevalence of genetic variants associated 2. When ICDs are not deactivated at the end of life,
with sudden arrhythmic deaths, compared with patients and families suffer unnecessarily. Families
47% among a comparison group in which pro- have had unpleasant experiences of watching
band autopsies were completely negative.S13-15 their loved one die while getting shocked repeat-
4. Identification of the genotype can facilitate family edly by an ICD.S14-8 In 1 survey of hospice staff, half
screening.S13-16 of those surveyed noted that a deceased patient
had been shocked by an ICD during the year prior
to the survey.S14-9 This is unnecessary and easily
14. TERMINAL CARE preventable by having caring, patient-centered
discussions with patients and their loved ones. In
Recommendations for Terminal Care
general, patients want their clinicians to initiate
References that support the recommendations are summarized in
Online Data Supplement 59.
these discussions,S14-2,S14-10 so this recommenda-
tion is carefully worded to put the responsibility of
COR LOE Recommendations
initiating the discussion on the clinician. Ethically,
1. At the time of ICD implantation or
replacement, and during advance care
patients and surrogates are free to choose to
planning, patients should be informed that deactivate antitachycardia function.S14-11–S14-13
I C-EO
their ICD shock therapy can be deactivated Most patients only elect deactivation of the anti-
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giving a patient a list of risks and benefits and Economic assessments of alternative management
telling them to make a decision—a practice some strategies for VA and prevention of SCD have primarily
authors have called “abandonment.”S15-8 Notably, evaluated ICDs, including several RCTsS16-3–S16-7 and obser-
a recommendation based on evidence or guide- vational studies,S16-8,S16-9 and simulation models.S16-10–S16-14
lines alone is not shared decision-making. Rather, In all studies, patients who received ICDs had higher
a recommendation based both on the evidence long-term costs. The high initial cost of the ICD device
as well as an understanding of the patients’ and the implantation procedure leads to higher long-
health goals, preferences, and values is essential term costs, because there are few, if any, subsequent
to achieving true shared decision-making. Also, cost-savings from implanting an ICD. ICDs without
the possibility of deactivation of an existing ICD resynchronization capability do not reduce hospital re-
should be discussed with patients who have ter- admissions and may increase late costs due to device
minal illnesses. monitoring, complications, and replacement. However,
2. ICDs prolong lives as highlighted in many places the cost of the device and the procedure may change
within this guideline. However, a patient with HF significantly over time.
or advanced noncardiac illness may elect to forgo The trial based assessments of the cost-effectiveness
replacement of an ICD when faced with the pros- of the ICD are based on 3 to 6 years of follow-up, which
pect of continual decline in health and functional is considerably shorter than the lifetime perspective that
status from either progressive HF or some other is standard in cost-effectiveness models. Because most
competing morbidity. of the incremental cost of the ICD is incurred imme-
Unfortunately, research suggests that patients diately, while most of the potential effectiveness (life-
are ill-informed when faced with understanding years of survival added by the ICD) is accrued over many
the risks, benefits, and downstream burdens of years, estimates of ICD cost-effectiveness based on lim-
their ICDs. Patients with an ICD tend to overes- ited trial follow-up have a systematic bias toward show-
timate the benefit of this therapy and underes- ing lower value. Trial based economic studies that pro-
timate its risks.S15-1–S15-3 Likewise, patients who jected long-term ICD outcomes have consistently found
decline an ICD also frequently underestimate more favorable cost-effectiveness ratios than estimates
their personal risk of VA and SCD.S15-4,S15-5 Stud- restricted to the duration of trial follow-up.S16-4–S16-7 A
CLINICAL STATEMENTS
AND GUIDELINES
Figure 17. Incremental cost-effectiveness of ICD by years of life added* (example).
*Figure based on formula: Incremental cost-effectiveness ratio = $50 000/QALYs. CE indicated cost effectiveness, ICD, implantable cardioverter-defibrillator; LYA,
life year added; and QALYs, quality-adjusted life-years.
lifetime simulation model applied to each major trial el data from 3 secondary prevention trialsS16-18 showed
of primary prevention ICDs also reported consistently a significant variation (P =0.011) in the clinical effec-
more favorable estimates of cost-effectiveness than the tiveness of ICDs between patients with an LVEF ≤35%
estimates based on limited trial follow-up.S16-11 Because (hazard ratio: 0.66) and an LVEF >35% (hazard ratio:
the framework proposed for assessing value in ACC/ 1.2). Some studies and simulation models suggest
AHA clinical practice guidelines uses benchmarks based that ICDs might prolong life expectancy to a greater
on lifetime estimates,S16-1 we have generally relied on extent when used in higher-risk patients than in lower-
the model-based estimates of ICD cost-effectiveness risk patients.S16-19 In contrast, there is little evidence of
variation in the effectiveness or cost-effectiveness of
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Abdul R. Abdullah, MD, Science and Medicine Advisor American Heart Association Task Force on Performance Measures
CLINICAL STATEMENTS
and Task Force on Practice Guidelines. Circulation. 2014;129:
Sam Shahid, MBBS, MPH, Associate Science and
AND GUIDELINES
2329–45.
Medicine Advisor P-4. ACCF/AHA Task Force on Practice Guidelines. Methodology Manual
and Policies From the ACCF/AHA Task Force on Practice Guidelines.
American College of Cardiology and American Heart Association, 2010.
American Heart Association Available at: http://assets.cardiosource.com/Methodology_Manual_
for_ACC_AHA_Writing_Committees.pdf and http://professional.heart.
John J. Warner, MD, President org/idc/groups/ahamahpublic/@wcm/@sop/documents/downloadable/
Nancy Brown, Chief Executive Officer ucm_319826.pdf.
P-5. Arnett DK, Goodman RA, Halperin JL, et al. AHA/ACC/HHS strategies to
Rose Marie Robertson, MD, FAHA, Chief Science and enhance application of clinical practice guidelines in patients with car-
Medicine Officer diovascular disease and comorbid conditions: from the American Heart
Gayle R. Whitman, PhD, RN, FAHA, FAAN, Senior Vice Association, American College of Cardiology, and US Department of
Health and Human Services. Circulation. 2014;130:1662–7.
President, Office of Science Operations P-6. Halperin JL, Levine GN, Al-Khatib SM, et al. Further evolution of the
Prashant Nedungadi, PhD, Associate Science and ACC/AHA clinical practice guideline recommendation classification
Medicine Advisor, Office of Science Operations system: a report of the American College of Cardiology Foundation/
American Heart Association Task Force on Clinical Practice Guidelines.
Jody Hundley, Production and Operations Manager, Circulation. 2016;133:1426–8.
Scientific Publications, Office of Science Operations P-7. Jacobs AK, Anderson JL, Halperin JL. The evolution and future of ACC/
AHA clinical practice guidelines: a 30-year journey: a report of the
American College of Cardiology/American Heart Association Task Force
on Practice Guidelines. Circulation. 2014;130:1208–17.
ARTICLE INFORMATION P-8. Jacobs AK, Kushner FG, Ettinger SM, et al. ACCF/AHA clinical prac-
This document was approved by the American College of Cardiology Clinical tice guideline methodology summit report: a report of the American
Policy Approval Committee, the American Heart Association Science Advi- College of Cardiology Foundation/American Heart Association Task
sory and Coordinating Committee, and the Heart Rhythm Society in Sep- Force on Practice Guidelines. Circulation. 2013;127:268–310.
tember 2017, and the American Heart Association Executive Committee in
October 2017.
The Comprehensive RWI Data Supplement table is available with this article
at https://www.ahajournals.org/doi/suppl/10.1161/CIR.0000000000000549. 1. INTRODUCTION
A Data Supplement is available with this article at https://www.ahajournals. S1.4-1. Kusumoto FM, Bailey KR, Chaouki AS, et al. Systematic review for
org/doi/suppl/10.1161/CIR.0000000000000549. the 2017 AHA/ACC/HRS guideline for management of patients with
This article has been copublished in the Journal of the American College of ventricular arrhythmias and the prevention of sudden cardiac death:
Cardiology and HeartRhythm. a report of the American College of Cardiology/American Heart
Copies: This document is available on the World Wide Web sites of the Association Task Force on Clinical Practice Guidelines and the Heart
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American College of Cardiology (www.acc.org), the American Heart Associa- Rhythm Society. Circulation. 2018;138:e392–e414.
tion (professional.heart.org), and the Heart Rhythm Society (www.hrsonline. S1.4-2. Anderson JL, Heidenreich PA, Barnett PG, et al. ACC/AHA statement on
org). A copy of the document is available at http://professional.heart.org/ cost/value methodology in clinical practice guidelines and performance
statements by using either “Search for Guidelines & Statements” or the
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on Practice Guidelines. Circulation. 2014;129:2329–45.
The expert peer review of AHA-commissioned documents (eg, scientific
S1.4-3. World Health Organization. CHOosing Interventions that are Cost
statements, clinical practice guidelines, systematic reviews) is conducted by the
Effective (WHO-CHOICE): cost-effectiveness thresholds. Available at:
AHA Office of Science Operations. For more on AHA statements and guide-
http://www.who.int/choice/en/. Accessed March 26, 2013.
lines development, visit https://professional.heart.org/statements. Select the
S1.4-4. Zipes DP, Camm AJ, Borggrefe M, et al. ACC/AHA/ESC 2006 guide-
“Guidelines & Statements” drop-down menu near the top of the webpage,
lines for management of patients with ventricular arrhythmias and
then click “Publication Development.”
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S1.4-5. Epstein AE, DiMarco JP, Ellenbogen KA, et al. ACC/AHA/HRS 2008
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CLINICAL STATEMENTS
septal defect is associated with reduced survival in adult men. Eur ing physician factors associated with mortality and complications
AND GUIDELINES
Cardioverter-Defibrillator
S11.1-1. Bardy GH, Smith WM, Hood MA, et al. An entirely subcuta- 11.3. Automated External Defibrillator
neous implantable cardioverter-defibrillator. N Engl J Med.
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Downloaded from http://ahajournals.org by on May 3, 2020
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CLINICAL STATEMENTS
Cardiovascular Care Science With Treatment Recommendations. autopsy in cases of sudden unexplained death in the young. Heart
AND GUIDELINES
Circulation. 2015;132:S51–83. Rhythm. 2014;11:655–62.
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CLINICAL STATEMENTS
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S14-13. Mueller PS, Jenkins SM, Bramstedt KA, et al. Deactivating implanted brillator therapy or amiodarone in chronic stable heart failure.
cardiac devices in terminally ill patients: practices and attitudes. Results from the Sudden Cardiac Death in Heart Failure Trial (SCD-
Pacing Clin Electrophysiol. 2008;31:560–8. HeFT). Circulation. 2006;114:135–42.
S16-8. Weiss JP, Saynina O, McDonald KM, et al. Effectiveness and cost-
effectiveness of implantable cardioverter defibrillators in the treat-
ment of ventricular arrhythmias among Medicare beneficiaries. Am
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S15-1. Lewis KB, Stacey D, Matlock DD. Making decisions about S16-9. Al-Khatib SM, Anstrom KJ, Eisenstein EL, et al. Clinical and eco-
implantable cardioverter-defibrillators from implantation to end nomic implications of the Multicenter Automatic Defibrillator
of life: an integrative review of patients’ perspectives. Patient. Implantation Trial-II. Ann Intern Med. 2005;142:593–600.
2014;7:243–60. S16-10. Buxton M, Caine N, Chase D, et al. A review of the evidence on the
S15-2. Stewart GC, Weintraub JR, Pratibhu PP, et al. Patient expectations effects and costs of implantable cardioverter defibrillator therapy in
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electronic device. Pacing Clin Electrophysiol. 2014;37:1306–14. with ischaemic or non-ischaemic heart disease: A European analysis.
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S15-8. Quill TE, Brody H. Physician recommendations and patient auton- S16-15. Bigger JT, Prophylactic use of implanted cardiac defibrillators in
omy: finding a balance between physician power and patient patients at high risk for ventricular arrhythmias after coronary-artery
choice. Ann Intern Med. 1996;125:763–9. bypass graft surgery. N Engl J Med. 1997;337:1569–75.
S16-16. Hohnloser SH, Kuck KH, Dorian P, et al. Prophylactic use of an
implantable cardioverter-defibrillator after acute myocardial infarc-
tion. N Engl J Med. 2004;351:2481–8.
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16. COST AND VALUE S16-17. Steinbeck G, Andresen D, Seidl K, et al. Defibrillator implantation
early after myocardial infarction. N Engl J Med. 2009;361:1427–36.
CONSIDERATIONS S16-18. Connolly SJ, Hallstrom AP, Cappato R, et al. Meta-analysis of the
S16-1. Anderson JL, Heidenreich PA, Barnett PG, et al. ACC/AHA state- implantable cardioverter defibrillator secondary prevention trials.
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2014;129:2329–45. S16-20. Ezekowitz JA, Rowe BH, Dryden DM, et al. Systematic review:
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conduct, methodological practices, and reporting of cost-effective- systolic dysfunction. Ann Intern Med. 2007;147:251–62.
ness analyses: Second Panel on Cost-Effectiveness in Health and
Medicine. JAMA. 2016;316:1093–103.
S16-3. Mushlin AI, Hall J, Zwanziger J, et al. The cost-effectiveness of
automatic implantable cardiac defibrillators. Results from MADIT.
17. QUALITY OF LIFE
Circulation. 1998;97:2129–35. S17-1. Mark DB, Anstrom KJ, Sun JL, et al. Quality of life with defibril-
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of the implantable cardioverter-defibrillator. Results from the 2008;359:999–1008.
Canadian Implantable Defibrillator Study (CIDS). Circulation. S17-2. Noyes K, Corona E, Veazie P, et al. Examination of the effect of
2001;103:1416–21. implantable cardioverter-defibrillators on health-related quality of
S16-5. Larson G, Hallstrom A, McAnulty J, et al. Cost-effectiveness of the life: based on results from the Multicenter Automatic Defibrillator
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in survivors of serious ventricular tachyarrhythmias. Results of the and other interventions. 2009;9:393–400.
Antiarrhythmics Versus Implantable Defibrillators (AVID) Economic S17-3. Passman R, Subacius H, Ruo B, et al. Implantable cardioverter defi-
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S16-6. Zwanziger J, Hall WJ, Dick AW, et al. The cost-effectiveness of ischemic cardiomyopathy treatment evaluation study. Archives of
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Appendix 1. Author Relationships With Industry and Other Entities (Relevant)—2017 AHA/ACC/HRS Guideline for Management of Patients With
CLINICAL STATEMENTS
Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death (October 2017)
AND GUIDELINES
Institutional,
Ownership/ Organizational,
Committee Speakers Partnership/ or Other Financial Expert Voting Recusals by
Member Employment Consultant Bureau Principal Personal Research Benefit Witness Section*
Sana M. Duke Clinical Research None None None None None None None
Al-Khatib, Chair Institute; Duke University—
Professor of Medicine
Michael J. Mayo Clinic—Professor of • Audentes None None None • Transgenomic None 4.1, 4.2.2, 4.2.3, 5 (except
Ackerman Medicine, Pediatrics, and Therapeutics (Familion)† 5.1.5.2, 5.5), 6, 7, 8, 9, 10
Pharmacology; Long QT • Boston Scientific • Blue Ox Health (except 10.2) 11, 13, 15
Syndrome/Genetic Heart • Gilead Sciences Corporation‡
Rhythm Clinic and the Mayo • Invitae • AliveCor‡
Clinic Windland Smith Rice • Medtronic • StemoniX‡
Sudden Death Genomics • MyoKardia
Laboratory—Director • St. Jude Medical
William J. Bryant Dominick Feld Hyde— None None None None None None None
Attorney at Law
Anne B. Curtis University at Buffalo—SUNY • Medtronic None None None None None 4.1, 4.2.2, 4.2.3, 5.1.1,
Distinguished Professor; • St. Jude Medical 5.1.2, 5.1.3, 5.1.4, 5.2,
Charles and Mary Bauer 5.4, 5.6, 6, 7, 8, 9, 10,
Professor and Chair 12, 13, 15
Barbara J. Deal Getz Professor of Cardiology None None None None None None None
Feinberg School of Medicine
Northwestern University
Timm Dickfeld University of Maryland— • Biosense None None • Biosense† • Impulse None 4.1, 4.2 (except 4.2.6),
Associate Professor of • St. Jude Medical • General Electric† Dynamics‡ 4.3, 5.3, 5.4, 5.6, 6, 7, 8,
Medicine • Siemens • Siemens† 9 (except 9.7), 10.1, 11,
Downloaded from http://ahajournals.org by on May 3, 2020
13, 15
Anne M. Gillis University of Calgary— None None None • Medtronic None None 4.2, 5.2.2, 5.3.2, 6.4.1,
Professor of Medicine 6.4.2, 6.4.4, 6.5, 6.7, 7,
8, 9, 10, 11 (except 11.7),
13, 15
Christopher B. Duke Clinical Research • AstraZeneca† None None • AstraZeneca† • GE Healthcare† None 4, 5.1 (except 5.1.5), 5.2,
Granger Institute; Duke University— • Gilead Sciences† • GlaxoSmithKline • Medtronic† 5.3, 5.4, 5.6, 6, 7, 8, 9,
Professor of Medicine; • GlaxoSmithKline† • Janssen • ZOLL Medical† 12, 13, 15
Director, Cardiac Care Unit • Janssen Pharmaceuticals† • Spacelabs†
Pharmaceuticals† • Medtronic† • Phillips†
• Medtronic† • Pfizer
• Pfizer† • Sanofi-aventis†
• Sanofi-aventis†
Stephen C. Mayo Clinic—Professor None None None None None None None
Hammill Emeritus of Medicine
Mark A. Hlatky Stanford University School None None None None None None None
of Medicine—Professor of
Health and Research Policy,
and of Cardiovascular
Medicine
José A. Joglar UT Southwestern Medical None None None None None None None
Center—Professor of Internal
Medicine; Clinical Cardiac
EP—Fellowship Program
Director
G. Neal Kay University of Alabama at None None None None None None None
Birmingham—Professor
Emeritus
Michael E. Field University of Wisconsin None None None None None None None
School of Medicine and
Public Health—Director,
Clinical EP and Cardiac
Arrhythmia Service, Associate
Professor of Medicine
(Continued )
Appendix 1. Continued
CLINICAL STATEMENTS
Institutional,
AND GUIDELINES
Ownership/ Organizational,
Committee Speakers Partnership/ or Other Financial Expert Voting Recusals by
Member Employment Consultant Bureau Principal Personal Research Benefit Witness Section*
Gregg C. Ahmanson-UCLA • Amgen None None • Medtronic– None None 4.1, 4.2.2, 4.2.3, 5.1
Fonarow Cardiomyopathy Center— • Janssen IMPROVE-HF (except 5.1.5.1), 5.2, 5.3,
Director; UCLA Division of Pharmaceuticals (Steering 5.4, 5.6, 6, 7, 8, 9, 10,
Cardiology—Co-Chief • Medtronic Committee)‡ 12, 13, 15
• ZS Pharma • Medtronic†
Daniel D. University of Colorado School None None None None None None None
Matlock of Medicine—Associate
Professor of Medicine
Robert J. University of Miami Miller None None None None None None None
Myerburg School of Medicine—
Professor of Medicine and
Physiology
Richard L. Page University of Wisconsin None None None None None None None
Hospital and Clinics—Chair,
Department of Medicine
This table represents the relationships of committee members with industry and other entities that were determined to be relevant to this document. These relationships were reviewed and updated in
conjunction with all meetings and/or conference calls of the writing committee during the document development process. The table does not necessarily reflect relationships with industry at the time of
publication. A person is deemed to have a significant interest in a business if the interest represents ownership of ≥5% of the voting stock or share of the business entity, or ownership of ≥$5,000 of the fair
market value of the business entity; or if funds received by the person from the business entity exceed 5% of the person’s gross income for the previous year. Relationships that exist with no financial benefit
are also included for the purpose of transparency. Relationships in this table are modest unless otherwise noted.
According to the ACC/AHA, a person has a relevant relationship IF: a) the relationship or interest relates to the same or similar subject matter, intellectual property or asset, topic, or issue addressed in the
document; or b) the company/entity (with whom the relationship exists) makes a drug, drug class, or device addressed in the document, or makes a competing drug or device addressed in the document; or
c) the person or a member of the person’s household, has a reasonable potential for financial, professional or other personal gain or loss as a result of the issues/content addressed in the document.
*Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry and other entities may apply.
†Significant relationship.
‡No financial benefit.
ACC indicates American College of Cardiology; AHA, American Heart Association; EP, Electrophysiology; HRS, Heart Rhythm Society; IMPROVE-HF, Improve the Use of Evidence-Based Heart Failure
Therapies in the Outpatient Setting; PI, principal investigator; SUNY, State University of New York; and UT, University of Texas.
Downloaded from http://ahajournals.org by on May 3, 2020
Appendix 2. Reviewer Relationships With Industry and Other Entities (Comprehensive)—2017 AHA/ACC/HRS Guideline for Management of
CLINICAL STATEMENTS
Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death (July 2017)
AND GUIDELINES
Institutional,
Ownership/ Organizational,
Partnership/ or Other Financial
Reviewer Representation Employment Consultant Speakers Bureau Principal Personal Research Benefit Salary Expert Witness
Alfred E. Content Reviewer Professor of Medicine— None None None • NHLBI (DSMB)† Medtronic†
• None None
Buxton Harvard Medical School— Biosense Webster†
•
Beth Israel Deaconess
Medical Center
Andrew E. Content Reviewer Professor of • Zoll* None None • Biotronik* None None • Defendant,
Epstein Medicine—Cardiovascular • Boston Scientific* Amiodarone
Division University of pulmonary
Pennsylvania—Chief of • Boston Scientific toxicity, 2016
Cardiology Section— (DSMB)*
• Defendant,
Philadelphia VA Medical • Medtronic* Appropriateness
Center • Medtronic (DSMB) of pacemaker
• St Jude Medical/ implantation,
Abbott* 2016*
Brian Content Reviewer Adjunct Professor of • Boehringer Ingleheim • Lundbeck Inc* None • Amarin (DSMB)* None None Plaintiff, Long
•
Olshansky Medicine—Des Moines • Lundbeck Inc* • On-X/Cryolife QT sudden
University—Professor death, 2017
Emeritus—University • On-X/Cryolife
of Iowa
Charles I. Content Reviewer Division Chief of Pediatric None None None None Circulation*
• None None
Berul Cardiology—Children’s
National Medical Center
Darren Content Reviewer Executive Director— None None None None None None None
Sudman Simon’s Fund
George J. Content Reviewer Chief of Cardiology— • Biotronik None None None None None None
Klein London Health Sciences • Boston Scientific
Center
• Medtronic*
Glenn N. Content Professor of None None None None None None • Defendant,
Levine Reviewer—ACC/ Medicine—Baylor Catheterization
Downloaded from http://ahajournals.org by on May 3, 2020
Gurusher S. Content Director Heart Failure • Amgen Inc.* None None None • BEAT-HF‡ None None
Panjrath Reviewer—ACC and Mechanical Support • ENDEAVOUR‡
Heart Failure Program—George
and Transplant Washington University
Council
James P. Official Duke University Medical • Biosense Webster None None • ARCA biopharma • Biosense* ACC
• None
Daubert Reviewer—AHA Center • Boston Scientific • Biosense Webster* • Biotronik*
• CardioFocus • Boston Scientific* • Boston Scientific*
• Gilead • Gilead* • Gilead Scienes,
• Heart Metabolics • Gilead (DSMB) Inc.*
John L. Sapp Official Interim Head—Division • Biosense Webster* None None • Biosense Webster* • ARTESiA‡ None None
Reviewer—HRS of Cardiology QEII • Medtronic • Canadian Institute • Medtronic‡
Health Sciences Centre— of Health Research*
Professor of Medicine— • St. Jude • Optisure Registry‡
Dalhousie University • DSMB† • St. Jude‡
• Phillips healthcare*
• St. Jude Medical*
(Continued )
Appendix 2. Continued
CLINICAL STATEMENTS
Institutional,
AND GUIDELINES
Ownership/ Organizational,
Partnership/ or Other Financial
Reviewer Representation Employment Consultant Speakers Bureau Principal Personal Research Benefit Salary Expert Witness
Joseph Official Associate Professor of None None None None • UpToDate None None
Edward Reviewer—ACC Medicine—Johns Hopkins
Marine University School of
Medicine
Kathleen T. Official Professor of Nursing— None None None None None None None
Hickey Reviewer—AHA Columbia University
Medical Center
Kenneth A. Content Reviewer Chief of Cardiology— • AHA None None • AtriCure* Biosense Webster*
• None None
Ellenbogen Virginia Commonwealth • AtriCure* • Biosense Webster* Boston Science*
•
University Medical Center
• Biosense Webster* • Boston Science* Circulation†
•
• Biotronik* • Daiichi Sankyo Heart Rhythm†
•
• Boston Science* • Medtronic* JACC†
•
• Capricor • Medtronic (DSMB)* Medtronic*
•
• HRS • NIH* PACE†
•
• Janssen • Pfizer* Sanofi Aventis
•
• Medtronic*
• Pfizer*
• Sentra heart
• St. Jude Medical*
Kim K. Content University of Houston— • Jones and Bartlett None None None • Accreditation University
• None
Birtcher Reviewer—ACC/ College of Pharmacology Learning Council for Clinical of Houston
AHA Task Lipidology College of
Force on Pharmacology*
Clinical Practice Walgreens*
•
Guidelines
Kristen B. Content Reviewer Duke University Hospital None None None None None None None
Campbell
Kristen K. Content Reviewer Professor of Medicine— None None None None • ABIM None None
Patton University of Washington • ACGME†
• AHA†
• FDA
• HRS†
Downloaded from http://ahajournals.org by on May 3, 2020
L. Brent Content Reviewer Professor—Department of • Boehringer None None • Boston Scientific* ARTESIA‡
• None None
Mitchell Cardiac Sciences—Libin Ingelheim* Health Protection
•
Cardiovascular Institute • Forest Branch,
of Alberta—University of Pharmaceuticals Government of
Calgary—Alberta Health Canada
Services • Guidnat Canada*
• Medtronic Canada*
• Medtronic Inc*
• Merck
• Pfizer*
• Servier Canada*
Martin Content Reviewer I Medizinische • Bayer Health Care None None • German Centre None None None
Borggrefe KlinikKlinikum Mannheim • Boehringer Ingelheim for Cardiovascular
GmbHUniversitätsklinikum Research*
• Impulse Dynamics
• Sanofi Aventis
• St. Jude Medical
Mathew D. Official Professor of Medicine— • St. Jude Medical None None None None None None
Hutchinson Reviewer—HRS University of Arizona
College of Medicine—
Tucson
Matthew W. Content Lehigh Valley Health None None None None None None None
Martinez Reviewer—Sports Network
and Exercise EP
Council
Melissa R. Content Reviewer Director—Complex • Medtronic* None None None None None None
Robinson Ablation Program— • Abbott*
University of Washington
• Boston Scientific*
Michael J. Content Reviewer Children’s Hospital Los None None None None None None • Defendant,
Silka Angeles ICD
implantation,
2017
Miguel A. Content Reviewer Methodist DeBakey Heart None None None None • Houston None None
Quinones and Vascular Center Methodist
Hospital*
Mitchell T. Organizational Jefferson Medical None None • Nephroceuticals* None None None None
Saltzberg Reviewer—HFSA College—Christiana Care • Stem Cell
Health System Theranostics*
(Continued )
Appendix 2. Continued
CLINICAL STATEMENTS
Institutional,
AND GUIDELINES
Ownership/ Organizational,
Partnership/ or Other Financial
Reviewer Representation Employment Consultant Speakers Bureau Principal Personal Research Benefit Salary Expert Witness
N.A. Mark Content Reviewer Professor of Medicine— • Boston Scientific* None None • Boston Scientific* None None None
Estes III Tufts University School of • Medtronic* • International Board
Medicine of Heart Rhythm
• St. Jude Medical*
Examiners†
• Medtronic*
• St. Jude Medical*
Norma M. Official New York University None None None None None None None
Keller Reviewer—ACC Medical Center
Peter Content Associate Professor of • Medtronic Canada • Bayer Healthcare None None None • Bayer Healthcare None
Leong-Sit Reviewer—HRS Medicine—Western Pharmaceuticals Pharmaceuticals*
University—London • Biosense
Health Sciences Centre Webster
• Johnson and
Johnson
Rachel J. Content Reviewer Yale University School • Medtronic* None None • Boston Scientific* None None None
Lampert of Medicine—Section of • GE Medical*
Cardiology
• Medtronic, Inc.*
• St. Jude Medical*
Sami Viskin Content Reviewer Tel Aviv Medical • Boston Scientific None None None None None None
Center—Department of European Strategy
Cardiology Advisory Board
Samuel S. Content Dupont Hospital for • Familial None None • Familial • Cardiology Division None None
Gidding Reviewer—ACC/ Children—Nemours Hypercholesterolemia Hypercholestrolemia Head†
AHA Task Cardiac Center Foundation† Foundation†
Force on • Regenxbio • NIH Grants*
Clinical Practice
Guidelines
Silvia G. Content Reviewer Professore Ordinario di • Ambry Genetics None • Audentes • Gilead Sciences* HRS
• None None
Priori Cardiologia—Università • Boston Scientific Therapeutics GS-US-372–1234‡
•
di Pavia—Direttore Inc*
Scientifico—Istituti Clinici • Medtronic
Scientifici Maugeri— • Medtronic, Inc.
Pavia, Italia
Susan Official Sabin Middle School None None None None None None None
Downloaded from http://ahajournals.org by on May 3, 2020
Strong Reviewer—AHA
Win-Kuang Content Reviewer Professor of Medicine— None None None None None None None
Shen Consultant—Mayo Clinic
Arizona, Phoenix Campus
Zachary D. Official Assistant Professor of • RubiconMD None None None None None None
Goldberger Reviewer—ACC/ Medicine—Division of
AHA Task Cardiology—Harborview
Force on Medical Center—
Clinical Practice University of Washington
Guidelines Lead School of Medicine
Reviewer
This table represents the relationships of reviewers with industry and other entities that were disclosed at the time of peer review, including those not deemed to be relevant to this document, at the time this document was
under review. The table does not necessarily reflect relationships with industry at the time of publication. A person is deemed to have a significant interest in a business if the interest represents ownership of ≥5% of the voting
stock or share of the business entity, or ownership of ≥$5000 of the fair market value of the business entity; or if funds received by the person from the business entity exceed 5% of the person’s gross income for the previous
year. Relationships that exist with no financial benefit are also included for the purpose of transparency. Relationships in this table are modest unless otherwise noted. Names are listed in alphabetical order within each category
of review. Please refer to http://www.acc.org/guidelines/about-guidelines-and-clinical-documents/relationships-with-industry-policy for definitions of disclosure categories or additional information about the ACC/AHA Disclosure
Policy for Writing Committees.
*Significant relationship.
†No financial benefit.
‡This disclosure was entered under the Clinical Trial Enroller category in the ACC’s disclosure system. To appear in this category, the author acknowledges that there is no direct or institutional relationship with the trial
sponsor as defined in the ACC/AHA Disclosure Policy for Writing Committees.
ABIM indicates American Board of Internal Medicine; ACC, American College of Cardiology; ACGME, Accreditation Council for Graduate Medical Education; AHA, American Heart Association; ARTESiA, Apixaban for the
Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation; BEAT-HF, Better Effectiveness After Transition–Heart Failure DSMB, data safety monitoring board; ENDEAVOUR, carfilzomib and
dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma; EP, electrophysiology; FDA, US Food and Drug Administration; HFSA, Heart Failure Society of America; HRS, Heart
Rhythm Society; ICD, implantable cardioverter-defibrillator; JACC, Journal of the American College of Cardiology; NIH, National Institutes of Health; NHLBI, National Heart, Lung, and Blood Institute; and PACE, Programs of All-
Inclusive Care for the Elderly.