Author + information
- Published online September 24, 2018.
- Sana M. Al-Khatib, MD, MHS, FACC, FAHA, FHRS, Chair, Writing Committee,
- William G. Stevenson, MD, FACC, FAHA, FHRS, Vice Chair, Writing Committee∗,
- Michael J. Ackerman, MD, PhD, Writing Committee Member∗,†,
- William J. Bryant, JD, LLM, Writing Committee Member†,
- David J. Callans, MD, FACC, FHRS, Writing Committee Member∗,‡,
- Anne B. Curtis, MD, FACC, FAHA, FHRS, Writing Committee Member∗,†,
- Barbara J. Deal, MD, FACC, FAHA, Writing Committee Member†,
- Timm Dickfeld, MD, PhD, FHRS, Writing Committee Member∗,†,
- Michael E. Field, MD, FACC, FAHA, FHRS, Writing Committee Member†,
- Gregg C. Fonarow, MD, FACC, FAHA, FHFSA, Writing Committee Member∗,§,
- Anne M. Gillis, MD, FHRS, Writing Committee Member∗,†,
- Christopher B. Granger, MD, FACC, FAHA, Writing Committee Member∗,†,
- Stephen C. Hammill, MD, FACC, FHRS, Writing Committee Member‡,
- Mark A. Hlatky, MD, FACC, FAHA, Writing Committee Member†,
- José A. Joglar, MD, FACC, FAHA, FHRS, Writing Committee Member‖,
- G. Neal Kay, MD, Writing Committee Member†,
- Daniel D. Matlock, MD, MPH, Writing Committee Member†,
- Robert J. Myerburg, MD, FACC, Writing Committee Member† and
- Richard L. Page, MD, FACC, FAHA, FHRS, Writing Committee Member‡
- ACC/AHA Clinical Practice Guidelines
- acute coronary syndrome
- ambulatory ECG monitoring
- antiarrhythmic drug therapy
- arrhythmogenic cardiomyopathy
- cardiac electrophysiology
- cardiac resynchronization therapy
- catheter ablation
- congenital heart disease
- CT imaging
- electrophysiological testing
- genetic arrhythmias
- heart failure
- implantable cardioverter-defibrillator
- implantable and external cardioverter devices
- medication-induced arrhythmias
- MR imaging
- myocardial infarction
- premature ventricular beats
- specific pathology (e.g., congenital heart disease, myocarditis, renal failure)
- stable coronary artery disease
- sudden cardiac arrest
- sudden cardiac death
- torsades de pointes
- ventricular fibrillation
- ventricular tachycardia
ACC/AHA Task Force Members
Glenn N. Levine, MD, FACC, FAHA, Chair
Patrick T. O’Gara, MD, MACC, FAHA, Chair-Elect
Jonathan L. Halperin, MD, FACC, FAHA, Immediate Past Chair¶
Sana M. Al-Khatib, MD, MHS, FACC, FAHA
Joshua A. Beckman, MD, MS, FAHA
Kim K. Birtcher, MS, PharmD, AACC
Biykem Bozkurt, MD, PhD, FACC, FAHA¶
Ralph G. Brindis, MD, MPH, MACC¶
Joaquin E. Cigarroa, MD, FACC
Anita Deswal, MD, MPH, FACC, FAHA
Lesley H. Curtis, PhD, FAHA¶
Lee A. Fleisher, MD, FACC, FAHA
Federico Gentile, MD, FACC
Samuel Gidding, MD, FAHA¶
Zachary D. Goldberger, MD, MS, FACC, FAHA
Mark A. Hlatky, MD, FACC, FAHA
John Ikonomidis, MD, PhD, FAHA
José A. Joglar, MD, FACC, FAHA
Laura Mauri, MD, MSc, FAHA
Barbara Riegel, PhD, RN, FAHA
Susan J. Pressler, PhD, RN, FAHA¶
Duminda N. Wijeysundera, MD, PhD
Table of Contents
1. Introduction e95
1.1. Methodology and Evidence Review e95
1.2. Organization of the Writing Committee e95
1.3. Document Review and Approval e95
1.4. Scope of the Guideline e97
1.5. Abbreviations e99
2. Epidemiology e99
2.1. General Concepts e99
2.1.1. Premature Ventricular Complexes and Nonsustained VT e99
2.1.2. VT and VF During ACS e101
2.1.3. Sustained VT and VF Not Associated With ACS e102
2.2. Sudden Cardiac Death e102
2.2.1. Incidence of SCD e102
2.2.2. Population Subgroups and Risk Prediction e102
3. Mechanisms of VA e103
3.1. Cellular Mechanisms and Substrates e103
3.2. Automaticity e104
3.3. Triggered Activity e104
3.4. Reentry e104
4. General Evaluation of Patients With Documented or Suspected VA e105
4.1. History and Physical Examination e105
4.2. Noninvasive Evaluation e106
4.2.1. 12-lead ECG and Exercise Testing e106
4.2.2. Ambulatory Electrocardiography e107
4.2.3. Implanted Cardiac Monitors e108
4.2.4. Noninvasive Cardiac Imaging e108
4.2.5. Biomarkers e109
4.2.6. Genetic Considerations in Arrhythmia Syndromes e109
4.3. Invasive Testing e110
4.3.1. Invasive Cardiac Imaging: Cardiac Catheterization or CT Angiography e110
4.3.2. Electrophysiological Study for VA e111
5. Therapies for Treatment or Prevention of VA e111
5.1. Medication Therapy e111
5.1.1. Medications With Prominent Sodium Channel Blockade e112
5.1.2. Beta Blockers e112
5.1.3. Amiodarone and Sotalol e112
5.1.4. Calcium Channel Blockers e115
5.1.5. Nonantiarrhythmic Medications and Therapies e115
5.2. Preventing SCD With HF Medications e116
5.3. Defibrillators for Treatment of VA and SCD e116
5.4. Catheter Ablation e117
5.4.1. General Considerations e117
5.4.2. VA in Patients With No Apparent Structural Heart Disease e117
5.4.3. Scar-Related VT e117
5.5. Surgery and Revascularization Procedures in Patients With Ischemic Heart Disease e117
5.5.1. Surgery for Arrhythmia Management e118
5.6. Autonomic Modulation e118
6. Acute Management of Specific VA e119
7. Ongoing Management of VA and SCD Risk Related to Specific Disease States e123
7.1. Ischemic Heart Disease e123
7.1.1. Secondary Prevention of SCD in Patients With Ischemic Heart Disease e123
7.1.2. Primary Prevention of SCD in Patients With Ischemic Heart Disease e126
7.1.3. Treatment and Prevention of Recurrent VA in Patients With Ischemic Heart Disease e128
7.2. Nonischemic Cardiomyopathy e131
7.2.1. Secondary Prevention of SCD in Patients With NICM e132
7.2.2. Primary Prevention of SCD in Patients With NICM e133
7.2.3. Treatment of Recurrent VA in Patients With NICM e134
7.3 Arrhythmogenic Right Ventricular Cardiomyopathy e135
7.4. Hypertrophic Cardiomyopathy e139
7.5. Myocarditis e142
7.6. Cardiac Sarcoidosis e143
7.6.1. Other Infiltrative Cardiomyopathies e145
7.7. Heart Failure e146
7.7.1. HF With Reduced Ejection Fraction e146
7.7.2. HF With Preserved Ejection Fraction e146
7.7.3. Left Ventricular Assist Device e147
7.7.4. ICD Use After Heart Transplantation e147
7.8. Neuromuscular Disorders e148
7.9. Cardiac Channelopathies e149
7.9.1. Specific Cardiac Channelopathy Syndromes e150
8. VA in the Structurally Normal Heart e160
8.1. Outflow Tract and Atrioventricular Annular VA e161
8.2. Papillary Muscle VA e162
8.3. Interfascicular Reentrant VT (Belhassen Tachycardia) e162
8.4. Idiopathic Polymorphic VT/VF e163
9. PVC-Induced Cardiomyopathy e164
10. VA and SCD Related to Specific Populations e165
10.1. Athletes e165
10.2. Pregnancy e166
10.3. Older Patients With Comorbidities e166
10.4. Chronic Kidney Disease e167
10.5. Valvular Heart Disease e167
10.6. Sex-Related Differences in the Risk of SCD e168
10.7. Medication-Induced Arrhythmias e168
10.8. Adult Congenital Heart Disease e170
11. Defibrillators Other than Transvenous ICDs e175
11.1. Subcutaneous Implantable Cardioverter-Defibrillator e175
11.2. Wearable Cardioverter-Defibrillator e176
11.3. Automated External Defibrillator e177
12. Special Considerations for Catheter Ablation e177
13. Postmortem Evaluation of SCD e178
14. Terminal Care e179
15. Shared Decision-Making e180
16. Cost and Value Considerations e181
17. Quality of Life e182
18. Evidence Gaps and Future Research Needs e182
Author Relationships With Industry and Other Entities (Relevant) e214
Reviewer Relationships With Industry and Other Entities (Comprehensive) e216
Since 1980, the American College of Cardiology (ACC) and American Heart Association (AHA) have translated scientific evidence into clinical practice guidelines with recommendations to improve cardiovascular health. These guidelines, which are based on systematic methods to evaluate and classify evidence, provide a cornerstone for quality cardiovascular care. The ACC and AHA sponsor the development and publication of guidelines without commercial support, and members of each organization volunteer their time to the writing and review efforts. Guidelines are official policy of the ACC and AHA.
Practice guidelines provide recommendations applicable to patients with or at risk of developing cardiovascular disease. The focus is on medical practice in the United States, but guidelines developed in collaboration with other organizations may have a global impact. Although guidelines may be used to inform regulatory or payer decisions, their intent is to improve patients’ quality of care and align with patients’ interests. Guidelines are intended to define practices meeting the needs of patients in most, but not all, circumstances and should not replace clinical judgment.
Guideline-recommended management is effective only when followed by healthcare providers and patients. Adherence to recommendations can be enhanced by shared decision-making between healthcare providers and patients, with patient engagement in selecting interventions based on individual values, preferences, and associated conditions and comorbidities.
Methodology and Modernization
The ACC/AHA Task Force on Clinical Practice Guidelines (Task Force) continuously reviews, updates, and modifies guideline methodology on the basis of published standards from organizations including the Institute of Medicine (P-1,P-2) and on the basis of internal reevaluation. Similarly, the presentation and delivery of guidelines are reevaluated and modified on the basis of evolving technologies and other factors to facilitate optimal dissemination of information at the point of care to healthcare professionals.
Toward this goal, this guideline heralds the introduction of an evolved format of presenting guideline recommendations and associated text called the “modular knowledge chunk format”. Each modular “chunk” includes a table of related recommendations, a brief synopsis, recommendation-specific supportive text and, when appropriate, flow diagrams or additional tables. References are provided within the modular chunk itself to facilitate quick review. This format also will facilitate seamless updating of guidelines with focused updates as new evidence is published, and content tagging for rapid electronic retrieval of related recommendations on a topic of interest. This evolved format was instituted when this guideline was near completion; therefore, the current document represents a transitional formatting that best suits the text as written. Future guidelines will fully implement this format, including provisions for limiting the amount of text in a guideline.
Recognizing the importance of cost–value considerations in certain guidelines, when appropriate and feasible, an analysis of the value of a medication, device, or intervention may be performed in accordance with the ACC/AHA methodology (P-3).
To ensure that guideline recommendations remain current, new data are reviewed on an ongoing basis, with full guideline revisions commissioned in approximately 6-year cycles. Publication of new, potentially practice-changing study results that are relevant to an existing or new medication, device, or management strategy will prompt evaluation by the Task Force, in consultation with the relevant guideline writing committee, to determine whether a focused update should be commissioned. For additional information and policies regarding guideline development, we encourage readers to consult the ACC/AHA guideline methodology manual (P-4) and other methodology articles (P-5—P-8).
Selection of Writing Committee Members
The Task Force strives to avoid bias by selecting experts from a broad array of backgrounds. Writing committee members represent different geographic regions, sexes, ethnicities, races, intellectual perspectives/biases, and scopes of clinical practice. The Task Force may also invite organizations and professional societies with related interests and expertise to participate as partners, collaborators, or endorsers.
Relationships With Industry and Other Entities
The ACC and AHA have rigorous policies and methods to ensure that guidelines are developed without bias or improper influence. The complete relationships with industry and other entities (RWI) policy can be found online. Appendix 1 of the current document lists writing committee members’ relevant RWI. For the purposes of full transparency, writing committee members’ comprehensive disclosure information is available online, as is the comprehensive disclosure information for the Task Force.
Evidence Review and Evidence Review Committees
When developing recommendations, the writing committee uses evidence-based methodologies that are based on all available data (P-4—P-7). Literature searches focus on randomized controlled trials (RCTs) but also include registries, nonrandomized comparative and descriptive studies, case series, cohort studies, systematic reviews, and expert opinion. Only key references are cited.
An independent evidence review committee (ERC) is commissioned when there are ≥1 questions deemed of utmost clinical importance that merit formal systematic review. This systematic review will strive to determine which patients are most likely to benefit from a test, medication, device, or treatment strategy and to what degree. Criteria for commissioning an ERC and formal systematic review include: a) the absence of a current authoritative systematic review; b) the feasibility of defining the benefit and risk in a time frame consistent with the writing of a guideline; c) the relevance to a substantial number of patients; and d) the likelihood that the findings can be translated into actionable recommendations. ERC members may include methodologists, epidemiologists, healthcare providers, and biostatisticians. When a formal systematic review has been commissioned, the recommendations developed by the writing committee on the basis of the systematic review are marked with “SR”.
Guideline-Directed Management and Therapy
The term guideline-directed management and therapy (GDMT) encompasses clinical evaluation, diagnostic testing, and pharmacological and procedural treatments. For these and all recommended medication treatment regimens, the reader should confirm the dosage by reviewing product insert material and evaluate the treatment regimen for contraindications and interactions. The recommendations are limited to medications, devices, and treatments approved for clinical use in the United States.
Class of Recommendation and Level of Evidence
The Class of Recommendation (COR) indicates the strength of the recommendation, encompassing the estimated magnitude and certainty of benefit in proportion to risk. The Level of Evidence (LOE) rates the quality of scientific evidence that supports the intervention on the basis of the type, quantity, and consistency of data from clinical trials and other sources (Table 1) (P-4,P-6,P-8).
Glenn N. Levine, MD, FACC, FAHA
Chair, ACC/AHA Task Force on Clinical Practice Guidelines
1.1 Methodology and Evidence Review
The recommendations listed in this clinical practice guideline are, whenever possible, evidence-based. An initial extensive evidence review, which included literature derived from research involving human subjects, published in English, and indexed in MEDLINE (through PubMed), EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline, was conducted from April 2016 to September 2016. Key search words included, but were not limited, to the following: sudden cardiac death, ventricular tachycardia, ventricular fibrillation, premature ventricular contractions, implantable cardioverter-defibrillator, subcutaneous implantable cardioverter-defibrillator, wearable cardioverter-defibrillator, and catheter ablation. Additional relevant studies published through March 2017, during the guideline writing process, were also considered by the writing committee, and added to the evidence tables when appropriate. The final evidence tables are included in the Online Data Supplement and summarize the evidence used by the writing committee to formulate recommendations. Additionally, the writing committee reviewed documents related to ventricular arrhythmias (VA) and sudden cardiac death (SCD) previously published by the ACC, AHA, and the Heart Rhythm Society (HRS). References selected and published in this document are representative and not all-inclusive.
As noted in the Preamble, an independent ERC was commissioned to perform a formal systematic review of 2 important clinical questions for which clear literature and prior guideline consensus were felt to be lacking or limited (Table 2). The results of the ERC review were considered by the writing committee for incorporation into this guideline. Concurrent with this process, writing committee members evaluated other published data relevant to the guideline. The findings of the ERC and the writing committee members were formally presented and discussed, then guideline recommendations were developed. The “Systematic Review for the 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death” is published in conjunction with this guideline (S1.4-1).
The ACC and AHA have acknowledged the importance of value in health care and have called for eventual development of a Level of Value for clinical practice recommendations (S1.4-2). Available cost-effectiveness data were determined to be sufficient to support 2 specific recommendations in this guideline (see Sections 7.1.1 and 7.1.2). As a result, a Level of Value was assigned to those 2 recommendations on the basis of the “ACC/AHA Statement on Cost/Value Methodology in Clinical Practice Guidelines and Performance Measures,” as shown in Table 3 (S1.4-2). Available quality of life (QoL) data were deemed to be insufficient to support specific recommendations in this guideline.
1.2 Organization of the Writing Committee
The writing committee consisted of cardiac electrophysiologists (including those specialized in pediatrics), general adult and pediatric cardiologists (including those specialized in critical care and acute coronary syndromes [ACS], genetic cardiology, heart failure, and cost-effectiveness analyses), a geriatrician with expertise in terminal care and shared decision-making, and a lay representative, in addition to representatives from the ACC, AHA, HRS, and the Heart Failure Society of America (HFSA).
1.3 Document Review and Approval
This document was reviewed by 2 official reviewers nominated by the ACC, AHA, and HRS; 1 official lay reviewer nominated by the AHA; 1 organizational reviewer nominated by the HFSA; and 28 individual content reviewers. Reviewers’ RWI information was distributed to the writing committee and is published in this document (Appendix 2).
This document was approved for publication by the governing bodies of the ACC, the AHA, and the HRS; and endorsed by the HFSA.
1.4 Scope of the Guideline
The purpose of this AHA/ACC/HRS document is to provide a contemporary guideline for the management of adults who have VA or who are at risk for SCD, including diseases and syndromes associated with a risk of SCD from VA. This guideline supersedes the “ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death” (S1.4-4). It also supersedes some sections of the “ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities” (S1.4-5), specifically those sections on indications for the implantable cardioverter-defibrillator (ICD); and, it updates the SCD prevention recommendations in the “2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy” (S1.4-6). Some recommendations from the earlier guidelines have been updated as warranted by new evidence or a better understanding of existing evidence, and irrelevant or overlapping recommendations were deleted or modified.
In the current guideline, sudden cardiac arrest (SCA) is defined as the “sudden cessation of cardiac activity so that the victim becomes unresponsive, with no normal breathing and no signs of circulation” (S1.4-7). If corrective measures are not taken rapidly, this condition progresses to SCD. Cardiac arrest is used to signify an event that can be reversed, usually by cardiopulmonary resuscitation (CPR), administration of medications and/or defibrillation or cardioversion. SCA and SCD can result from causes other than VA, such as bradyarrhythmias, electromechanical dissociation, pulmonary embolism, intracranial hemorrhage, and aortic dissection; however, the scope of this document includes only SCA and SCD due to VA.
This guideline includes indications for ICDs for the treatment of VA and prevention of SCD, but it does not delve into details on individual device selection and programming, including considerations relevant to cardiac resynchronization therapy (CRT), bradycardia pacing, and hemodynamic monitoring. These important aspects of ICD management have been covered in an HRS expert consensus statement (S1.4-8). An AHA science advisory discusses the use of wearable cardioverter-defibrillators (S1.4-9). The findings of that document were reviewed; however, recommendations on this topic were developed independently of that document. This guideline includes indications for catheter ablation of VA, but does not provide recommendations on specific techniques or ablation technologies, which were beyond the scope of this document.
Recommendations for interventional therapies, including ablation and the implantation of devices, apply only if these therapies can be implemented by qualified clinicians, such that outcomes consistent with published literature are a reasonable expectation. The writing committee agreed that a high degree of expertise was particularly important for performance of catheter ablation of VA, and this point is further emphasized in relevant sections. In addition, all recommendations related to ICDs require that meaningful survival of >1 year is expected; meaningful survival means that a patient has a reasonable quality of life and functional status.
Although this document is aimed at the adult population (≥18 years of age) and offers no specific recommendations for pediatric patients, some of the literature on pediatric patients was examined. In some cases, the data from pediatric patients beyond infancy helped to inform this guideline.
The writing committee recognized the importance of shared decision-making and patient-centered care and, when possible, it endeavored to formulate recommendations relevant to these important concepts. The importance of a shared decision-making process in which the patient, family, and clinicians discuss risks and benefits of diagnostic and treatment options and consider the patients’ personal preferences is emphasized (see Section 15).
In developing this guideline, the writing committee reviewed previously published guidelines and related statements. Table 4 contains a list of guidelines and statements deemed pertinent to this writing effort and is intended for use as a resource, obviating repetition of existing guideline recommendations.
During final production review of the guidelines, several recommendations were refined to better reflect the data and current recommended medical practice. These refinements were reviewed and approved by the writing committee, the Task Force, and ACC, AHA, and HRS organizational leadership. These recommendations were:
• Section 7.1.1., recommendation 1
• Section 7.1.3., recommendation 2
• Section 7.2.1., recommendation 1
• Section 126.96.36.199, recommendation 2
• Section 10.8., recommendation 6
Readers should refer to these sections for the updated text.
|ACS||acute coronary syndromes|
|AED||automated external defibrillator|
|AMI||acute myocardial infarction|
|BNP||B-type natriuretic peptide|
|CABG||coronary artery bypass graft|
|CKD||chronic kidney disease|
|CRT||cardiac resynchronization therapy|
|ERC||evidence review committee|
|ESRD||end-stage renal disease|
|GDMT||guideline-directed management and therapy|
|HFpEF||heart failure with preserved ejection fraction|
|HFrEF||heart failure with reduced ejection fraction|
|LVAD||left ventricular assist device|
|LVEF||left ventricular ejection fraction|
|NSVT||nonsustained ventricular tachycardia|
|PET||positron emission tomography|
|PCI||percutaneous coronary intervention|
|PVC||premature ventricular complex|
|QoL||quality of life|
|RCT||randomized controlled trial|
|RVOT||right ventricular outflow tract|
|SCA||sudden cardiac arrest|
|SCD||sudden cardiac death|
|TOF||tetralogy of Fallot|
2.1 General Concepts
VA include a spectrum that ranges from premature ventricular complex (PVC) to ventricular fibrillation (VF), with a clinical presentation that ranges from a total lack of symptoms to cardiac arrest. Most life-threatening VA are associated with ischemic heart disease, particularly in older patients (S2.2.2-1). The risks of VA and SCD vary in specific populations with different underlying cardiac conditions, and with specific family history and genetic variants, and this variation has important implications for studying and applying therapies.
2.1.1 Premature Ventricular Complexes and Nonsustained VT
PVCs are common and increase in frequency with age. Although PVCs were found in a healthy military population in only 0.6% of those <20 years of age and 2.7% of those >50 years of age (S2.2.2-5) on 12-lead ECGs, longer term monitoring shows PVCs in about 50% of all people with or without heart disease (S2.2.2-6). The presence of PVCs on 2 minutes of monitoring of middle-aged patients in the ARIC (Atherosclerosis Risk In Communities) study was associated with increased risk of both ischemic heart disease events and mortality, with or without prevalent ischemic heart disease (S2.2.2-7,S2.2.2-8). In the general population, frequent PVCs, which are defined as the presence of at least 1 PVC on a 12-lead ECG or >30 PVCs per hour, are associated with increased cardiovascular risk and increased mortality (S2.2.2-9). In a study from Taiwan of patients without sustained VT or structural heart disease who had 24-hour Holter monitoring for clinical evaluation, multifocal PVCs were associated with increased risk of death and nonfatal cardiovascular adverse outcomes (S2.2.2-10). In the same population, nonsustained ventricular tachycardia (NSVT) was independently associated with increased risk of death and other cardiovascular adverse outcomes, including stroke (S2.2.2-11). An association of PVCs with increased risk of stroke was also seen in the ARIC population (S2.2.2-8).
Because some studies have shown an association of PVCs with adverse outcomes, the detection of PVCs, particularly if multifocal and frequent, is generally considered a risk factor for adverse cardiovascular outcomes, and such patients are generally evaluated to ensure they do not have underlying conditions (e.g., ischemic heart disease, left ventricular [LV] dysfunction) that warrant further treatment to reduce risk. PVC and NSVT in patients with cardiovascular disease are common and have been associated with adverse outcomes (S2.2.2-12,S2.2.2-13). In CAST (Cardiac Arrhythmia Suppression Trials), treatment of patients with post-myocardial infarction (MI) who took antiarrhythmic medications (e.g., flecainide, encainide, moricizine) increased the risk of death despite suppression of VA (S2.2.2-14,S2.2.2-15). Treatment of PVCs with antiarrhythmic medications has not been shown to reduce mortality and, in the post- MI population, treatment with class I sodium channel–blocking medications (e.g., quinidine, flecainide) increases the risk of death (S2.2.2-15,S2.2.2-16). Likewise, in patients with a reduced LVEF class I, sodium channel–blocking medications and d-sotalol increase the risk of death (S2.2.2-16,S2.2.2-17). Beta blockers, nondihydropyridines calcium channel blockers, and some antiarrhythmic medications may relieve symptoms of palpitations (S2.2.2-18).
PVCs that occur during an exercise test are associated with a higher risk of death (S2.2.2-19). In 1 study, PVCs that occur during recovery are a stronger predictor of death than PVCs occurring only during exercise (S2.2.2-20). However, PVCs are common in trained athletes who have palpitations, in whom there does not appear to be increased risk of death based on studies of small numbers of athletes, at least in those without other cardiovascular abnormalities (S2.2.2-21,S2.2.2-22). Complex PVCs may not represent a benign finding in endurance athletes. An electrophysiological study may be needed to assess patients’ arrhythmogenic risk (S2.2.2-22). Very frequent PVCs, >10,000 to 20,000 a day, can be associated with depressed LV function in some patients that is reversible with control of the PVCs, and has been referred to as PVC-induced cardiomyopathy (S2.2.2-23,S2.2.2-24). (See also Section 8.5. PVC-Induced Cardiomyopathy.) Very rarely, idiopathic PVCs from the outflow tract may trigger malignant VA in patients without structural heart disease (S2.2.2-25,S2.2.2-26).
2.1.2 VT and VF During ACS
Approximately half of patients with out-of-hospital cardiac arrest with the first rhythm identified as VF and who survive to hospital admission have evidence of acute MI (AMI) (S2.2.2-27). Of all out-of-hospital cardiac arrests, >50% will have significant coronary artery lesions on acute coronary angiography (S2.2.2-27). Of patients hospitalized with AMI, 5% to 10% have VF or sustained VT prior to hospital presentation, and another 5% will have VF or sustained VT after hospital arrival, most within 48 hours of admission. A study of patients 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 of admission (S2.2.2-28). Accelerated idioventricular rhythm is a common arrhythmia in patients with acute MI, including patients with ST-segment elevation MI undergoing primary percutaneous coronary intervention (PCI). Accelerated idioventricular rhythm is more closely related to the extent of infarction than to reperfusion itself (S2.2.2-29).
Sustained VA that occurs in the setting of an ACS is more often polymorphic VT or VF than monomorphic VT. Risk factors for VT/VF include prior history of hypertension, prior MI, ST-segment changes at presentation, and chronic obstructive pulmonary disease (S2.2.2-30). A nationwide Danish study found that 11.6% of patients with ST-segment elevation MI who underwent PCI had VF prior to the PCI, and that VF was associated with alcohol consumption, preinfarction angina, anterior infarct location, and complete coronary occlusion at the time of coronary angiography (S2.2.2-31). In a select group of patients undergoing primary PCI in a clinical trial, 5.7% developed sustained VT or VF, with two thirds of these events occurring prior to the end of the catheterization, and 90% within 48 hours from the procedure. VT or VF after primary PCI was associated with lower blood pressure, higher heart rate, poor coronary flow at the end of the procedure, and incomplete resolution of ST elevation (S2.2.2-32). Importantly, and in contrast to some earlier studies, VT or VF at any time was associated with a substantially higher risk of death within 90 days. Late VT or VF (after 48 hours of hospital presentation) was associated with a higher risk of death than early VT or VF (within 48 hours of hospital presentation) (S2.2.2-33).
2.1.3 Sustained VT and VF Not Associated With ACS
Patients with structural heart disease are at an increased risk for sustained VT and VF. Sustained VT that is not associated with an ACS is often monomorphic as it is usually due to scar-related reentry, but it may degenerate to VF (S2.2.2-34). The risk and predictors of VT in patients with structural heart disease depend on the type, severity, and duration of structural heart disease, increasing with the severity of ventricular dysfunction and the presence of symptomatic HF. Monomorphic VT occurring in the absence of structural heart disease is commonly referred to as idiopathic VT and is often due to an automatic focus in a characteristic location, giving rise to typical electrocardiographic appearances. Polymorphic VT and VF occurring in the absence of structural heart disease are rare and may be due to a cardiac channelopathy (S2.2.2-35,S2.2.2-36), medication-induced long QT syndrome (S2.2.2-36), or they may be idiopathic (S2.2.2-37,S2.2.2-38).
2.2 Sudden Cardiac Death
2.2.1 Incidence of SCD
SCA and its most common consequence, SCD, constitute major public health problems, accounting for approximately 50% of all cardiovascular deaths (S2.2.2-1,S2.2.2-39), with at least 25% being first symptomatic cardiac events (S2.2.2-1,S2.2.2-40,S2.2.2-41). In addition, analyses of the magnitude of SCD are limited, in part because of the broad range of estimates of the risk based on different epidemiological methods (S2.2.2-42). During the past 20 to 30 years, SCD accounted for approximately 230,000 to 350,000 deaths per year in the United States, with a range of <170,000 to >450,000, depending on epidemiological methods, data sources, and inclusion criteria (S2.2.2-41,S2.2.2-43). The lowest of these extremes came from national extrapolation of data from specific local programs, while the highest rates included noncardiac causes of sudden death such as pulmonary embolism or intracranial bleeding. The mid-range numbers were largely based on death certificate studies that required a code inclusive of ischemic heart disease.
The 2017 update of cardiovascular statistics from the AHA estimated the total annual burden of out-of-hospital cardiac arrest at 356,500 (S2.2.2-44). An additional 209,000 in-hospital cardiac arrests occur annually (S2.2.2-45). Among the out-of-hospital cardiac arrest group, approximately 357,000 events trigger emergency rescue response, with 97% occurring in adults >18 years of age.
The survival statistics for out-of-hospital cardiac arrest remain disappointing, with an estimated 10% overall survival rate (S2.2.2-44). Among the subgroup of 70% of out-of-hospital cardiac arrests that occur in the home, survival is 6%. The best reported outcomes are from locations with highly developed and publicly visible emergency rescue response, along with the combination of public location of cardiac arrest, bystander witnesses willing to provide CPR, first responders arriving quickly, shockable rhythm at initial contact, availability of automated external defibrillators (AEDs), and possibly a benefit from telecommunication-directed CPR (S2.2.2-46,S2.2.2-47). Survival to hospital discharge after in-hospital cardiac arrests is estimated to be 24% (S2.2.2-48). In all settings, survival statistics appear to be better when rhythms recorded by responders are shockable (VF, pulseless VT), compared with pulseless electrical activity or asystole (S2.2.2-49). Although the apparent increase in the incidence of pulseless electrical activity or asystole could be due to the later arrival of medical care, the decrease in the incidence of shockable rhythm has also been attributed, in part, to improvements in diagnosis and treatment of structural heart disease (S2.2.2-40).
2.2.2 Population Subgroups and Risk Prediction
Risk prediction for SCA and SCD is complex. Risk analysis is divided into 2 general categories: population risk prediction and individual risk prediction (S2.2.2-41,S2.2.2-50). Conventional epidemiological markers provide insight into probabilities for the development of ischemic heart disease within a general class of subjects, but adequately tested and validated profiles for SCA risk stratification of individuals in the general population do not presently exist. The challenge of defining SCA risk in individuals derives from a population model characterized by large numbers of events diluted into a very large denominator (Figure 1⇓⇓). The overall population can be subgrouped into categories based on integration of age, presence and extent of disease, and identification of small, high-risk subgroups within the large denominator general population.
Increasing age is a strong predictor of risk for SCA, but it is not linear. Risk in the general population, over time, beginning at 35 years of age has been estimated at 1 per 1000 population per year, increasing from a risk <1000 at the younger end of that spectrum to a higher risk in the elderly (S2.2.2-41). However, an analysis of lifetime risk of SCD, derived from the Framingham data, suggested that the incidence of SCD decreases in later years, especially in people >75 years of age (S2.2.2-51). The data also suggested that SCD is uniformly more common in men than in women at all age groups. In contrast, the population of children, adolescents, and young adults has an overall annual risk of 1 per 100,000, and there is somewhat a higher risk of SCD at the younger end of that age range (S2.2.2-41). An age-associated transition range, from the mid-20s to 35 to 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 ischemic heart disease.
Although ischemic heart disease remains the most common underlying substrate associated with SCD, the incidence of ischemic heart disease-related SCD appears to be decreasing (S2.2.2-52), with various forms of cardiomyopathy associated with myocardial fibrosis and LV hypertrophy increasing (S2.2.2-53). In addition, a trend over time has suggested that out-of-hospital cardiac arrest patients who are admitted alive to a hospital are becoming more likely to have high-risk clinical profiles, as opposed to manifest disease (S2.2.2-54). The younger population—children, adolescents, and young adults—is affected by a series of disorders that manifest earlier in life, including the genetic structural disorders and cardiac channelopathies, myocarditis, congenital heart disease, and other rare disorders (S2.2.2-43). During the transition range, from the mid-20s to the mid-30s, causes of SCA and SCD include a lower proportion of inherited diseases and increasing proportion of ischemic heart disease (>40% of cases) (S2.2.2-43).
Despite the small progress that has been made in risk prediction of SCA and SCD, the greatest challenge is to identify the relatively small, high-risk subgroups concealed within the large general population who have no identified disease but are at risk of SCA as their first cardiac event (Figure 1) (S2.2.2-50).
3 Mechanisms of VA
3.1 Cellular Mechanisms and Substrates
Mechanisms of VA include enhanced normal automaticity, abnormal automaticity, triggered activity induced by early or late afterdepolarizations, and reentry (S3.4-1—S3.4-3). Reentry requires a trigger to initiate the arrhythmia and a substrate to sustain it. The trigger may be a PVC, which may be due to automaticity. The substrate may be structural remodeling secondary to an underlying disease process, and often includes a scar secondary to a prior MI or surgical repair, or patchy fibrosis in the setting of cardiomyopathy or hypertrophy. Changes in ion channel or transporter function and/or expression and cell to cell coupling secondary to the underlying pathology may alter the initiation or propagation of the cardiac action potential. The electrophysiological substrate is dynamically influenced by a variety of factors including cardiac metabolism, electrolytes, signaling pathways and autonomic effects. Enhanced automaticity or abnormal automaticity causing VA may arise from subordinate pacemaker cells in the His-Purkinje system or ventricular myocardium.
Normal automaticity results from phase 4 spontaneous depolarization of the transmembrane action potential arising from a normal resting potential, reaching threshold and initiating an action potential (S3.4-1,S3.4-3). An initiating current (If) is responsible for spontaneous phase 4 depolarization in the sinus node. The rate is determined by the integration of the maximum diastolic potential at the end of repolarization, the slope of phase 4 depolarization, and the threshold potential. In contrast, abnormal automaticity arises from a partially depolarized membrane potential that is usually close to the activation potential for calcium channels in the cell membrane (S3.4-1,S3.4-3). In the acute phase of an MI or during transient ischemia, increased extracellular potassium causes partial depolarization of the resting membrane potential creating injury currents between the infarcted/ischemic tissue and healthy myocardium. These injury currents may initiate spontaneous activity. In ischemia, abnormal automaticity may occur in both ventricular myocytes and Purkinje fibers, and may also enhance normal automaticity in Purkinje fibers in the ischemic zone.
3.3 Triggered Activity
Early afterdepolarizations occur during late phase 2 or early phase 3 of the action potential (S3.4-3—S3.4-5), usually in the setting of action potential prolongation due to an increase in inward currents (the late sodium current, the inward calcium current or the sodium calcium exchange current) or a decrease in repolarizing potassium currents. Under these conditions, early afterdepolarizations may be initiated when reactivation of the inward L-type calcium channel occurs before the membrane has returned to a more negative potential than that required for calcium channel reactivation. Spontaneous calcium release from the sarcoplasmic reticulum may also result in activation of a depolarizing sodium/calcium exchange current. Early afterdepolarizations are the trigger for torsades de pointes VT associated with QT prolongation either induced by medications or other acquired factors or due to mutations of ion channels causing the long QT syndrome. In these cases, it is possible that the early afterdepolarization/triggered activity sequence is the trigger that culminates in polymorphic VT/VF.
Delayed afterdepolarizations occur after complete membrane repolarization and develop under conditions of intracellular calcium overload. Factors contributing to elevated intracellular calcium load include tachycardia, catecholamines, hypokalemia, digoxin toxicity, cardiac hypertrophy, and HF (S3.4-6,S3.4-7). Elevated sarcoplasmic calcium content or increased sensitivity of the ryanodine receptor can initiate spontaneous calcium release, which activates a transient inward current driven predominantly by the sodium–calcium exchange current. If the membrane depolarization is sufficiently large, the inward sodium current is activated resulting in a triggered action potential. Delayed afterdepolarizations are the underlying mechanism for VT in the setting of digoxin toxicity, catecholaminergic polymorphic VT, and idiopathic outflow tract VA. Delayed afterdepolarizations are also considered to be an important trigger of VA in the setting of HF. Purkinje cells are more susceptible to spontaneous sarcoplasmic reticulum calcium release than ventricular myocytes suggesting that delayed afterdepolarizations may be an important mechanism for some Purkinje fiber-related VA (S3.4-3,S3.4-8,S3.4-9).
Reentry is the underlying mechanism for most sustained VA in the presence of structural heart disease (S3.4-1—S3.4-3,S3.4-10—S3.4-12). Reentry may occur around a fixed anatomical obstacle, such as scar after an MI or surgically repaired congenital heart disease. In this setting, an excitable gap separates the excitation wavefront from its tail of refractoriness. The existence of structural reentrant substrates provide the rationale for VT ablation in scar-related VTs (S3.4-11,S3.4-12).
Functional reentry around areas of functional block without anatomical obstacles can also occur. Two main models of functional reentry have been proposed (S3.4-2,S3.4-3). The leading circle model has a functionally refractory core and no excitable gap. Spiral wave reentry is driven by a rotor with a curved wavefront and wavetail pivoting around an excitable but unexcited core. There remains much debate about the precise mechanism(s) of VF (rotor versus multiple wavelet reentry). Both mechanisms may be operational in different phases of VF (S3.4-10).
Phase 2 reentry may occur due to heterogeneity of ventricular repolarization. Electrotonic currents may flow from endocardial sites with longer action potential durations to the epicardium with shorter action potential durations which can result in reexcitation when these sites have recovered from refractoriness. This is believed to be one potential mechanism of VT/VF in Brugada syndrome (S3.4-3) and may also be operative during ischemia.
4 General Evaluation of Patients With Documented or Suspected VA
4.1 History and Physical Examination
↵∗ This section covers practices that are well accepted, and a new recommendation was determined to only be warranted for syncope.
VA can produce a wide spectrum of symptoms, and the severity of symptoms does not necessarily reflect the extent of structural heart disease or the potential risk of SCD. Symptoms of VA include palpitations, either skipped or extra beats or sustained palpitations, shortness of breath, chest pain, dizziness, near syncope, and syncope (S4.1-5,S4.1-6). Palpitations may correlate with VA but are frequently reported during normal rhythm (S4.1-7). The differential diagnosis of exercise intolerance, chest pain, dyspnea, presyncope, and syncope includes VA but also includes other etiologies. Nonetheless, more dramatic symptoms, particularly in patients with known or discovered structural or electrical heart disease should prompt focused investigation for possible association with VA (Table 6).
The elucidation of precipitating factors, such as exertional or emotional stress, concurrent medications or illness, and alleviating factors is important. The presence of a family history of SCD, ischemic heart disease, valvular heart disease, nonischemic cardiomyopathy (NICM), or HF raises concern for the presence of one of these disorders associated with VA. Obtaining a complete medication history is important. Various antiarrhythmic and other medications can cause QT prolongation and torsades de pointes (www.crediblemeds.org) (S4.1-8); some medications can also induce Brugada type I electrocardiographic pattern and VF (www.brugadadrugs.org) (S4.1-9,S4.1-10).
Patients with bigeminy and trigeminy can present with effective bradycardia, an apical-radial pulse deficit and relative hypertension with a wide pulse pressure. Effective bradycardia from PVCs can result in inaccurate estimation of the heart rate. Although premature beats on auscultation of the heart can be detected, the physical examination is focused largely on finding evidence of structural heart disease. Carotid bruits or diminished peripheral pulses may be indicators of atherosclerotic disease associated with ischemic heart disease. Jugular venous distention, rales, gallops, and peripheral edema provide evidence of HF. Auscultation may reveal cardiac murmurs consistent with valvular heart disease, such as aortic stenosis or mitral regurgitation, and may be associated with HF and VA. A midsystolic click may indicate mitral valve prolapse that can be associated with VA (S4.1-11—S4.1-13). Many VA are asymptomatic and detected only on an ECG or telemetry. Such cases highlight the need to search for evidence of underlying heart disease.
Recommendation-Specific Supportive Text
1. Rapid, sustained VT may result in syncope secondary to marked reduction in cardiac output, followed by spontaneous recovery if VT terminates, or SCA if VT persists and is not treated promptly. Syncope or SCA may be the first manifestation of structural or electrical heart disease (S4.1-14), and some SCA victims have preceding “sentinel” syncope episodes (S4.1-15). Syncope, or its forewarnings of dizziness, lightheadedness, or near-syncope, may constitute a risk factor for SCA and SCD (S4.1-2). The initial evaluation at any age focuses on detection or exclusion of heart disease. Syncope during exercise should prompt thorough evaluation to rule out cardiac causes. Cardiac evaluation with echocardiography, ambulatory monitoring, and exercise testing may be warranted depending on the clinical information elicited (S4.1-3,S4.1-4). Cardiac causes of syncope include sustained VT, high-grade atrioventricular block or severe sinus bradycardia or prolonged sinus pauses, supraventricular tachycardia (SVT), malfunction of pacemakers, VA from cardiac channelopathies or structural heart disease syndromes, such as hypertrophic cardiomyopathy (HCM) or congenital heart disease (S4.1-3,S4.1-4,S4.1-16). Cardiac channelopathies and HCM are particularly important to consider in adolescents and young adults. Arrhythmic causes of syncope are often associated with very short periods of premonitory symptoms, or palpitations, and known preexisting heart disease, especially a history of a low LVEF or HF (S4.1-1). Among nonarrhythmic cardiac causes, considerations should include myocardial ischemia, severe aortic stenosis, HCM, HF, and prosthetic valve malfunction, pulmonary embolism, medications, and illicit drug use (S4.1-3).
4.2 Noninvasive Evaluation
4.2.1 12-lead ECG and Exercise Testing
Recommendation-Specific Supportive Text
1. A 12-lead ECG during tachycardia is the first diagnostic test that should be done in any patient found to be in a stable wide QRS complex tachycardia on a monitor. VT is the diagnosis in most adults with wide complex tachycardia and underlying structural heart disease (S4.2.1-3). Criteria that support a diagnosis of VT include AV dissociation, a QRS complex >0.14 s, monophasic R wave in aVR, specific QRS morphologies (e.g., positively or negatively concordant QRS complexes in the precordial leads), the absence of an RS complex in all precordial leads and an RS interval >100 ms in at least 1 precordial lead (S4.2.1-2). Exceptions occur, particularly in patients with advanced heart disease and with the use of certain antiarrhythmic medications (S4.2.1-1). For patients with preexisting bundle branch block, comparison of the QRS morphology during sinus rhythm with that during wide complex tachycardia is often relevant.
2. For exertion-related arrhythmic symptoms, exercise in a monitored setting may reproduce the symptoms and/or the related arrhythmia, allowing for diagnosis. Exercise testing is particularly important when catecholaminergic polymorphic ventricular tachycardia is a possibility. However, exertion-related symptoms and findings may not be reliably reproducible with exercise testing, and long-term electrocardiographic monitoring with external or implantable recorders may be necessary.
3. A 12-lead ECG may indicate the presence of structural heart disease such as prior MI or chamber enlargement that would increase the likelihood that a patient’s symptoms might be due to VA, or it may provide evidence of the underlying substrate for documented VA. An ECG may also reveal evidence of inherited arrhythmia disorders, such as long QT syndrome, Brugada syndrome, and arrhythmogenic right ventricular cardiomyopathy. In patients with structural heart disease, QRS duration and the presence of conduction abnormalities provide prognostic information (S4.2.1-7—S4.2.1-14). Data on the use of microvolt T wave alternans and the signal averaged ECG are inconclusive, as such these tests are not routinely used in clinical practice (S4.2.1-15—S4.2.1-19); the one exception is the potential use of signal averaged ECG in patients with arrhythmogenic right ventricular cardiomyopathy (see Section 7.3).
4.2.2 Ambulatory Electrocardiography
Recommendation-Specific Supportive Text
1. Ambulatory electrocardiographic monitoring is often used to assess the effectiveness of treatments to suppress arrhythmias, but more robust data are needed on the clinical use of this practice. Continuous or intermittent ambulatory electrocardiographic recording with a Holter monitor or an event recorder is helpful in diagnosing suspected arrhythmias, establishing their frequency, relating them to symptoms, and assessing the response to therapy. Although the yield of these tests is relatively low, VT is occasionally documented (S4.2.2-4). A 24-hour continuous Holter recording is appropriate when symptoms occur at least once a day or when quantitation of PVCs/NSVT is desired to assess possible VA-related depressed ventricular function. For sporadic symptoms, event or “looping” monitors are more appropriate because they can be activated over extended periods of time and increase diagnostic yield (S4.2.2-2,S4.2.2-3). Adhesive patch electrocardiographic monitors can record for weeks and allow for continuous short-term 1-lead monitoring and patient activation for symptoms. Studies have shown satisfactory patient compliance, and arrhythmia detection; however, with some monitors, detected arrhythmias are not discovered until the patch is returned for analysis (S4.2.2-1,S4.2.2-4). Serial evaluations with exercise testing and/or 24-hour ambulatory monitoring are also used to assess rhythm burden and response of VA to therapy. Notably, implantable monitors are covered in Section 4.2.3. Importantly, when the suspicion of VA in a patient is high, outpatient ambulatory monitoring is inappropriate as prompt diagnosis and prevention of VA are warranted. It is important to accurately correlate the symptoms with the arrhythmias detected by ambulatory ECG monitoring.
4.2.3 Implanted Cardiac Monitors
Recommendation-Specific Supportive Text
1. Implanted cardiac monitors provide continuous rhythm monitoring and stored recordings of electrograms based on patient activation or preset parameters, allowing a prolonged monitoring period of a few years. These devices require a minor invasive procedure with local anesthesia for implantation. In patients with sporadic symptoms, including syncope, implantable recorders are useful in diagnosing serious tachyarrhythmias (including VA) and bradyarrhythmias (S4.2.3-2—S4.2.3-4). They are generally reserved for patients in whom other ambulatory monitoring is nonrevealing due to the infrequency of events. A 25% added yield in diagnosis has been described after an unrevealing external ambulatory monitor (S4.2.3-5). In a study of patients with syncope, the implantable monitor had a greater diagnostic yield than “conventional” testing with external monitoring, tilt table testing and electrophysiological study (S4.2.3-2). A systematic review in patients with syncope concluded that use of these devices provide a higher rate of diagnosis and a trend toward reduction in syncope relapse after diagnosis, as compared with conventional management (S4.2.3-3). A prospective study of patients after MI, with LVEF <40%, demonstrated NSVT (>16 beats long) in 13%, VT (>30 s) in 3% and VF in 3% of patients (S4.2.3-1). It is important to accurately correlate the symptoms with the arrhythmias detected by implanted cardiac monitors.
4.2.4 Noninvasive Cardiac Imaging
Recommendation-Specific Supportive Text
1. Assessment of global and regional myocardial function, valvular structure and function, along with assessment for adult congenital heart disease is required in patients with or at high risk for VA or SCD, including patients with cardiomyopathy, HF, prior MI, family history of cardiomyopathy or SCD, or an inherited structural heart disease associated with SCD. Echocardiography is the most readily available and commonly used imaging technique (S4.2.4-1,S4.2.4-2). LVEF is a strong, independent predictor of SCD and cardiovascular mortality and a determinant of eligibility for ICD implantation for primary prevention of SCD (S4.2.4-1). In SCD-HeFT (the Sudden Cardiac Death in Heart Failure Trial) (S4.2.4-2), the benefit of the ICD was not dependent on the modality (i.e., echocardiography, radionuclide angiography, or contrast angiograms) by which the LVEF was assessed. In clinical practice, if cardiac CT (S4.2.4-3) or cardiac MRI has been performed and provides sufficient evaluation, echocardiography may be unnecessary. This recommendation for imaging differs from that of the 2017 ACC/AHA/HRS syncope guideline (S4.2.4-4) that applies to patients who may not have VA.
2. VA or SCA can be an initial manifestation of ischemic heart disease, cardiomyopathic processes, or myocarditis. Cardiac CT and cardiac MRI allow for evaluation of structural heart disease and assessment of LV and RV function including quantification of LVEF, LV mass and volume, valvular structure and coronary anatomy including anomalous coronary origins. Cardiac MRI can be useful in the evaluation for myocardial scar and infiltrative processes evident as late gadolinium enhancement (S4.2.4-5—S4.2.4-9). Cardiac MRI also provides high-quality assessment of LV and RV function, size, and degree of fibrosis and is particularly useful in arrhythmogenic right ventricular cardiomyopathy and HCM.
Recommendation-Specific Supportive Text
1. Elevated levels of natriuretic peptides—B-type natriuretic peptide (BNP) or N-terminal pro-BNP—are associated with increased risk of SCA and appropriate ICD therapies, even after adjustment of LVEF and other risk factors (S4.2.5-1—S4.2.5-4). These biomarkers are also predictive of nonsudden cardiovascular mortality and thus are not specific to SCD risk alone. Natriuretic peptides have also been evaluated for predicting SCD in the general population (S4.2.5-5,S4.2.5-6). In the Nurses’ Health Study, an elevated N-terminal pro-BNP was an independent risk marker for SCD in presumably healthy women (S4.2.5-5). In an older adult population, higher baseline levels of N-terminal pro-BNP were associated with SCD over a 16-year follow-up period (S4.2.5-6). These biomarkers may also have a potential role in facilitating the identification of individuals at increased risk of SCD and VA in the general population, particularly in those at intermediate or high risk of ischemic heart disease, but further studies are needed. Use of biomarkers has not been shown to be useful for selecting patients for ICDs. A study of 4431 patients found high-sensitivity troponin to be only weakly predictive of SCD (S4.2.5-7). However, there are no data on whether high-sensitivity troponin can improve the current SCD prediction algorithms.
4.2.6 Genetic Considerations in Arrhythmia Syndromes
↵∗ Please refer to section 7.9 for disease-specific recommendations.
The diagnosis of most inherited arrhythmia syndromes is based on clinical features and family history. The availability of genetic testing for inherited arrhythmia syndromes can: 1) provide opportunity to confirm a suspected clinical diagnosis and sometimes provide prognostic information for the proband and 2) offer cascade screening of potentially affected family members when a disease-causing mutation is identified in the proband. The yield of genetic testing varies by disease. The verification of pathogenicity of suspected mutations is an evolving field, and exome sequencing has identified an increasing number of variants of uncertain significance in the general population (S4.2.6-1—S4.2.6-5). Genotyping can have therapeutic implications for some arrhythmogenic phenotypes such as long QT syndrome and Fabry’s disease (S4.2.6-6—S4.2.6-9), where a monogenic pathogenic mutation has been clearly identified, the risk to mutation positive individuals has been extensively studied, and effective therapy relevant to the mutation can be instituted. In other diseases, such as Brugada syndrome, the role of a clear monogenic disease-causing mutation is less certain, and the genotype does not provide therapeutic or prognostic information for the proband (S4.2.6-5,S4.2.6-10—S4.2.6-12). In arrhythmogenic right ventricular cardiomyopathy, some desmosomal mutation positive individuals do not develop disease, indicating that additional mutations and environmental interactions likely influence the clinical development of disease (S4.2.6-13—S4.2.6-16). Importantly, the absence of an identified disease-causing genetic mutation does not exclude the presence of disease, and as such, ongoing monitoring and decision-making are done based on the clinical phenotype. Genotyping is frequently most useful when a pathogenic mutation is identified in the proband, such that screening can be applied to relatives who are in a preclinical phase, allowing institution of lifestyle changes, therapy, or ongoing monitoring for those who are gene mutation positive (S4.2.6-7). Refer to Section 7.9 for disease-specific recommendations.
In young patients (<40 years of age) without structural heart disease who have unexplained cardiac arrest, unexplained near drowning, or recurrent exertional syncope, genetic testing may be important to identify an inherited arrhythmia syndrome as a likely cause (S4.2.6-17—S4.2.6-23).
Recommendation-Specific Supportive Text
1. The decision to proceed with genetic testing requires discussion regarding the clinical use of genetic information to be obtained for both the proband and family members, as well as consideration of the important psychological, financial, employment, disability, and life insurance implications of positive genotyping (S4.2.6-17,S4.2.6-18,S4.2.6-20,S4.2.6-24). Balancing privacy of health care information for the proband with the “right to know” for family members, and the ability to provide appropriate communication of information to all potentially affected family members can be challenging on many levels, including family dynamics, geographic proximity, and access to health care (S4.2.6-25). For these reasons, genetic counseling generally occurs before proceeding with genetic testing, and, from a patient’s perspective, is optimally provided by genetic counselors, if available, in collaboration with physicians (S4.2.6-26,S4.2.6-27). A combined approach of genetic counseling with medical guidance may appropriately balance the decision as to whether genetic testing would be beneficial on an individual basis.
4.3 Invasive Testing
4.3.1 Invasive Cardiac Imaging: Cardiac Catheterization or CT Angiography
Recommendation-Specific Supportive Text
1. Although randomized studies are unavailable, coronary angiography has an important role in establishing or excluding the presence of significant obstructive ischemic heart disease in patients with SCA or those with life-threatening VA (S4.3.1-1—S4.3.1-4). Recurrent polymorphic VT or VF can be due to ongoing myocardial ischemia that resolves with coronary revascularization. Presence of ST-elevation on preresuscitation or early postresuscitation ECG suggests ischemia and potential ACS warranting urgent angiography and revascularization (S4.3.1-5). ST-elevation can also result from coronary spasm or DC shocks. The absence of ST-elevation after cardiac arrest does not exclude obstructive or thrombotic coronary lesions. A coronary angiogram may not be warranted if a nonischemic cause of SCA is established. Coronary and CT angiography also have an important role excluding the presence of anomalous origin of the coronary arteries that may cause SCD.
4.3.2 Electrophysiological Study for VA
|III: No Benefit||B-R|
|III: No Benefit||B-NR|
Electrophysiological study can be used to induce sustained VA in patients with known or suspected VA. With the advent of the ICD and its proven benefit in the primary and secondary prevention of SCD, there are fewer indications for programmed stimulation to provoke VA. Patients with HF and LVEF ≤35% generally will have an indication for an ICD and specific induction of VT/VF before implantation is not necessary. Patients with LVEF >35% and unexplained syncope or near-syncope may benefit from an electrophysiological study to determine if VT/VF is the cause of symptoms and to guide further therapy. Induction of VT/VF is often attempted before catheter ablation of the arrhythmia substrate to guide the procedure and to determine the success of the intervention after ablation is performed. An electrophysiological study can be used to determine the mechanism of a wide complex tachycardia. See Sections 7.3, 7.4, 7.6, 188.8.131.52, and 10.8 for recommendations regarding electrophysiological study for specific disease states.
Recommendation-Specific Supportive Text
1. A study of electrophysiological testing in patients with symptomatic NICM found inducible VT/VF in 28% of patients which was associated with a higher rate of ICD events during follow-up (S4.3.2-17). In a prospective cohort of 180 patients with ischemic or NICM and syncope, induction of VT or VF at electrophysiological study correlated with cardiac mortality only in patients with ischemic heart disease. In patients with NICM, cardiac mortality correlated with LVEF but not with inducibility on electrophysiological study (S4.3.2-18).
2. In patients who meet criteria for ICD implantation (i.e., HF and LVEF ≤35%), data do not support the routine use of electrophysiological study solely for risk stratification, as such patients have been shown to derive survival benefit from the ICD (S4.3.2-8—S4.3.2-11). An electrophysiological study may be helpful, however, in selected patients suspected to have preexcitation or supraventricular arrhythmias as the cause of symptoms or wide complex tachycardias that warrant definitive diagnosis and management. SVT leading to VT/VF or aberrantly conducted SVT may also be suspected in younger patients or those with a preserved LVEF. Induction of SVT and ablation may then be curative, with no need for an ICD. In such cases, failure to induce VT/VF after elimination of the substrate for SVT would be expected.
3. Risk stratification for channelopathies is generally made on the basis of symptoms, the ECG (S4.3.2-13,S4.3.2-19—S4.3.2-24), exercise treadmill testing (S4.3.2-25—S4.3.2-27), and the results of genetic testing (S4.3.2-28—S4.3.2-32). The electrophysiological study (i.e., programmed ventricular stimulation) does not have prognostic value for risk stratification in patients with these cardiac channelopathies (S4.3.2-12—S4.3.2-15).
5 Therapies for Treatment or Prevention of VA
5.1 Medication Therapy
With the exception of beta blockers (e.g., metoprolol succinate, carvedilol), there is no evidence from RCTs that antiarrhythmic medications for VA improve survival when given for the primary or secondary prevention of SCD. However, the use of these medications is essential in some patients to control arrhythmias and improve symptoms. Medication use for VA is discussed, and any recommendations are listed, in subsequent sections. Further, medication-induced proarrhythmia is addressed in Section 10.7.
Antiarrhythmic medications are often categorized by the Vaughan Williams 4-level schema (class I: fast sodium channel blockers; class II: beta blockers; class III: repolarization potassium current blockers; class IV: nondihydropyridines calcium channel blockers) (S184.108.40.206-1). This system does not address the complexities in antiarrhythmic medications, since nearly every agent has multiple effects. Table 7 shows uses, electrophysiological effects, pharmacological effects, and common adverse effects of antiarrhythmic medications.
5.1.1 Medications With Prominent Sodium Channel Blockade
Except in specific circumstances, sodium channel blockers (Vaughn-Williams class I agents) have a limited role in the prevention of VT/SCD; this is based on a lack of survival benefit and increased mortality observed during chronic therapy in patients with ischemic heart disease (see Section 10.7). Specific circumstances where sodium channel blockers have been used to treat VT/SCA include: intravenous lidocaine for patients with refractory VT/cardiac arrest (especially witnessed) (S220.127.116.11-3); oral mexiletine for congenital long QT syndrome (S18.104.22.168-4); quinidine for patients with Brugada syndrome; and flecainide for patients with catecholaminergic polymorphic ventricular tachycardia (S22.214.171.124-5). These medications could also be used in ICD patients with drug- and ablation-refractory VT.
One newer medication of potential benefit, based on very limited data, is ranolazine. This medication, developed and FDA-approved as an antianginal agent, provides relatively specific late sodium channel current blockade in addition to less potent blockade of the phase 3 repolarizing potassium current; that is, the rapid delayed rectifier potassium current; IKr. The potential for clinical antiarrhythmic efficacy is supported by basic studies and experimental models (S126.96.36.199-6). Clinical data are scant. In a study of 12 patients, ranolazine reduced ICD shocks in otherwise medication-resistant VT/VF in 11 patients (S188.8.131.52-7). In MERLIN TIMI-36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes-Thrombolysis In Myocardial Infarction 36), ranolazine did not reduce SCD but did reduce VT in the first few days after a non-ST-segment elevation ACS (S184.108.40.206-8). In 1 RCT, high-risk ICD patients with ischemic or NICM were randomly assigned to ranolazine 1000 mg twice a day versus placebo (S220.127.116.11-9). High risk was defined as: 1) having a primary prevention ICD without a history of documented VT/VF and with one of the following conditions: BUN ≥26 mg/dL, QRS >120 msec, atrial fibrillation, or NSVT or >500 VPBs on 24-hour Holter recording; 2) having a primary prevention ICD with a history of documented VT/VF appropriately treated with ICD therapy or untreated NSVT; or 3) having a secondary prevention ICD after documented VT/VF or cardiac arrest. Ranolazine did not significantly reduce the primary endpoint of VT/VF requiring appropriate ICD therapy or death. In a prespecified secondary analysis, ranolazine was associated with a significant reduction in VT events treated with anti-tachycardia pacing (S18.104.22.168-9).
5.1.2 Beta Blockers
Because of their excellent safety profile and effectiveness in treating VA and reducing the risk of SCD, beta blockers are often first-line antiarrhythmic therapy (S22.214.171.124-10,S126.96.36.199-11). Their antiarrhythmic efficacy is related to the effects of adrenergic-receptor blockade on sympathetically mediated triggering mechanisms, slowing of the sinus rate, and possibly inhibition of excess calcium release by the ryanodine receptor (S188.8.131.52-12).
Beta blockers reduce all-cause mortality and SCD in patients with HF with reduced EF (HFrEF) (S184.108.40.206-13—S220.127.116.11-15). Although beta blockers have long been proven to reduce mortality after MI (S18.104.22.168-16), registry data confirm that early beta blocker use in patients with MI and risk factors for shock (>70 years of age, symptoms <12 hours [ST-elevation MI patients], systolic blood pressure <120 mm Hg, and heart rate >110 beat/min on presentation) is associated with an increased risk of shock or death (S22.214.171.124-17). In the setting of polymorphic VT after MI, beta blockers reduce mortality (S126.96.36.199-18). Beta blockers suppress VA in some patients with structurally normal hearts (S188.8.131.52-19). When used in combination with membrane-stabilizing antiarrhythmic medications, beta blockers can enhance antiarrhythmic efficacy (S184.108.40.206-20). Beta blockers (e.g., nadolol, propranolol) are also first-line therapy for some cardiac channelopathies (e.g., long QT syndrome, catecholaminergic polymorphic ventricular tachycardia).
5.1.3 Amiodarone and Sotalol
Amiodarone possesses a wide spectrum of actions that include blockade of beta receptors and sodium, calcium and potassium currents (i.e., a multichannel blocker). Its overall long-term effect on survival is controversial, with most studies showing no clear advantage over placebo. A few studies and a meta-analysis of several large studies have shown a reduction in SCD using amiodarone in patients with LV dysfunction due to prior MI and NICM (S220.127.116.11-21—S18.104.22.168-23), but SCD-HeFT showed no survival benefit from amiodarone compared with placebo (S22.214.171.124-24). A secondary analysis of the SCD-HeFT showed increased risk of mortality with amiodarone in patients with New York Heart Association (NYHA) class III symptoms (S126.96.36.199-25). A systematic review of the literature in high-risk patients (LVEF <40%, with or without coronary disease), concluded that, for primary prevention, amiodarone, compared with no treatment or placebo, decreased the risk of SCD (Risk ratio: 0.76; 95% CI: 0.66–0.88) and all-cause mortality (Risk ratio: 0.88; 95% CI: 0.78–1.00), but the quality of the supporting evidence was very low (S188.8.131.52-26). For secondary prevention of SCD, the same systematic review identified neither risk nor benefit with amiodarone (S184.108.40.206-26). Compared with beta-blocker therapy and other antiarrhythmic medications (including sotalol), amiodarone appears to reduce the risk of SCD and all-cause mortality (S220.127.116.11-26). Intravenous amiodarone has a role in reducing recurrent VF/VF during resuscitation (S18.104.22.168-3,S22.214.171.124-27—S126.96.36.199-29).
Chronic administration of amiodarone is associated with complex medication interactions and a host of adverse effects involving the lung, liver, thyroid, skin, and nervous system. As a general rule, the longer the therapy and the higher dose of amiodarone, the greater the likelihood of adverse effects that will require discontinuance of the medication (S188.8.131.52-26). For this reason, chronic treatment of young patients with amiodarone should be reserved as a bridge to more definitive treatment options such as catheter ablation. Baseline evaluation of patients may include ECG, liver function tests, thyroid function tests, chest x-ray, and pulmonary function tests (including diffusing capacity of the lungs for carbon monoxide). Monitoring for toxicity generally includes periodic history and physical examination, as well as evaluation of the ECG, chest x-ray, and thyroid, liver, and lung function. High-resolution chest CT is generally reserved for suspected pulmonary toxicity (S184.108.40.206-30).
Although sotalol has some efficacy in suppressing VA, it has significant proarrhythmic effects and has not been shown to improve survival (S220.127.116.11-31). D-sotalol was shown in the SWORD (Survival With Oral d-Sotalol) trial to increase the risk of death in patients with heart failure (S18.104.22.168-32). Unlike amiodarone and many other antiarrhythmic agents, sotalol appears to reduce the defibrillation threshold (S22.214.171.124-33). Also, sotalol may lead to HF decompensation, and so its use in patients with an LVEF <20% is generally avoided.
5.1.4 Calcium Channel Blockers
For the treatment of most VA, nondihydropyridines calcium channel blockers have no role. In fact, intravenous verapamil given for sustained VT has been associated with hemodynamic collapse, especially in patients with prior MI (S126.96.36.199-34,S188.8.131.52-35). For patients with a structurally normal hearts, verapamil or diltiazem can suppress some outflow tract origin (S184.108.40.206-35—S220.127.116.11-39). Oral and intravenous verapamil are effective in treating idiopathic interfascicular reentrant LVT (S18.104.22.168-38). Calcium channel blockers should not be given to patients with VT in the settin of HFrEF.
5.1.5 Nonantiarrhythmic Medications and Therapies
Administration of potassium and magnesium has been proposed as helpful adjuncts in the prevention of VA (S22.214.171.124-40,S126.96.36.199-41). Hypokalemia and hypomagnesemia are common consequences of diuretic therapy in HF, both have been associated with VA during an acute MI (S188.8.131.52-41,S184.108.40.206-42), and can increase the risk of torsades de pointes in patients on medications or with conditions known to prolong the QT interval (S220.127.116.11-43). In fact, in patients with torsades de pointes, intravenous magnesium is first-line therapy (S18.104.22.168-44). In patients who are deficient in both magnesium and potassium, magnesium should be repleted to facilitate replacement of the potassium (S22.214.171.124-45). In the case of potassium, some recommend keeping the potassium level between 4.5 mmol/L and 5 mmol/L to prevent VA and SCD (S126.96.36.199-46,S188.8.131.52-47). A large observational study of patients with an acute MI found that the lowest rates of death were seen in patients with serum potassium concentrations between 3.5 mmol/L and <4.5 mmol/L (S184.108.40.206-48). Interestingly, the rates of VA did not rise unless the potassium was <3 mmol/L or ≥5 mmol/L. Likewise, a large randomized, double-blind trial of intravenous magnesium in the post-MI period demonstrated no benefit in 30-day mortality (S220.127.116.11-40). It remains quite reasonable to monitor potassium and magnesium during aggressive diuresis and in the post-MI period.
18.104.22.168 n-3 Fatty Acids and Lipids
Both n-3 poly-unsaturated fatty acids and statin therapies may have a role in the prevention of SCD, thought to be due to a stabilization of the bilipid myocyte membrane involved in maintaining electrolyte gradients (S22.214.171.124-49).
Early data were promising regarding the effects of n-3 polyunsaturated fatty acids on the reduction of cardiovascular events and SCD. In 2006, a large meta-analysis of 19 observational and RCTs demonstrated a significant association between the consumption of n-3 polyunsaturated fatty acids and prevention of SCD (S126.96.36.199-50). The randomized GISSI (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto)-Prevenzione trial in people with recent MI, found that fish oil 1 g/d reduced mortality, due to fewer SCD (S188.8.131.52-51). However, subsequent RCTs have not replicated these benefits and have shown n-3 polyunsaturated fatty acids to be ineffective (S184.108.40.206-52—S220.127.116.11-56). Because studies showed a consistent lack of harm from n-3 polyunsaturated fatty acids, patients can be reassured of their safety. Longer-term data will hopefully clarify the conflicting results.
In contrast, statin medications clearly reduce mortality and appear to reduce the risk of SCD related to ischemic heart disease (S18.104.22.168-57). The predominant mechanism remains uncertain. Prevention of coronary plaque rupture or a direct cardioprotective effect reducing VA has been suggested. Experimental ischemia/reperfusion models demonstrate a cardioprotective effect of statins, and a large observational analysis observed this effect in humans (S22.214.171.124-42,S126.96.36.199-56—S188.8.131.52-58). This was explored further in HF in several secondary analyses of patients on statins in ICD prevention trials, including the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy), SCD-HeFT, AVID (Antiarrhythmics versus Implantable Defibrillators) (S184.108.40.206-59), and DEFINITE (DEFibrillators In Non-Ischemic Cardiomyopathy Treatment Evaluation) trials that showed less SCD risk among the patients on statins (S220.127.116.11-58,S18.104.22.168-60—S22.214.171.124-62). However, this general effect in HF was not confirmed in 2 prospective RCTs of rosuvastatin in HF; the CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure) and GISSI-HF (Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca-Heart Failure) (S126.96.36.199-63,S188.8.131.52-64). It appears that the beneficial effects of statins are confined to the population with or at risk for atherosclerotic cardiovascular disease and/or ischemia, and not HF generally.
5.2 Preventing SCD With HF Medications
Recommendation-Specific Supportive Text
1. For patients with HF and depressed LV function, appropriate medical therapy is important to reduce SCD. These therapies have various beneficial effects on arrhythmia mechanisms. Beta blockers reduce myocardial oxygen demand and electrical excitability, and counter arrhythmogenic effects of sympathetic stimulation. Angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers decrease preload and afterload, decreasing myocardial oxygen demand, blocking the formation of angiotensin II, and slowing the progression of ventricular remodeling and fibrosis. Mineralocorticoid receptor antagonists limit potassium loss, decrease fibrosis, and increase the myocardial uptake of norepinephrine (S5.2-7).
RCTs in patients with HFrEF have consistently demonstrated that chronic therapy with beta blockers reduces all-cause mortality, VA, and SCD (S5.2-2,S5.2-4,S5.2-5,S5.2-9). Three beta blockers (i.e., bisoprolol, carvedilol, sustained-release metoprolol succinate) have been proven to reduce mortality in patients with current or prior symptoms of HFrEF without beta-blocker contraindications. Angiotensin-converting enzyme inhibition also reduces mortality and SCD (S5.2-3). Angiotensin-receptor blockers added to angiotensin-converting enzyme inhibitor showed additional benefit to angiotensin-converting enzyme inhibitors in some (S5.2-10) but not other RCTs (S5.2-8,S5.2-11). Therapy with the mineralocorticoid-receptor antagonists, spironolactone and eplerenone, have also demonstrated reductions in both all-cause mortality and SCD (S5.2-6,S5.2-12,S5.2-13). Recent studies of the angiotensin receptor-neprilysin inhibitor (sacubitril/valsartan) versus angiotensin-converting enzyme inhibitor demonstrated a reduction in SCD and cardiac mortality (S5.2-14).
5.3 Defibrillators for Treatment of VA and SCD
Defibrillation is highly effective in terminating life-threatening VA. This therapy can be delivered by a transvenous ICD, a subcutaneous implantable cardioverter-defibrillator, a wearable cardioverter-defibrillator or an external defibrillator. These devices monitor the heart rhythm continuously and deliver therapy in response to a tachycardia that meets preprogrammed detection rates and arrhythmia duration. The vast majority of transvenous ICDs are implanted in the subclavicular area under fluoroscopy guidance. subcutaneous implantable cardioverter-defibrillators are implanted in the left side of the chest over the sixth rib between the left midaxillary and left anterior axillary lines. ICDs with epicardial sensing and pacing leads are still being implanted in some patients especially those with certain forms of congenital heart disease.
The transvenous ICD has been in clinical use for >3 decades, and robust data from high-quality RCTs support its use in various patient populations including survivors of cardiac arrest, patients with VT and structural heart disease, and patients with significant LV dysfunction.
5.4 Catheter Ablation
5.4.1 General Considerations
Catheter ablation is an important treatment option for patients with VA when antiarrhythmic medications are ineffective, not tolerated, or not desired by the patient. Monomorphic VA usually have an origin or substrate that can be targeted for ablation. Ablation is an option for selected patients with polymorphic VT/VF only if an initiating PVC focus or substrate can be identified. The ablation strategy, risks and outcomes are related to the mechanism and location of the VA. Most VA originate close to the subendocardium and are approached through a transvenous (for the right ventricle) or transaortic/transeptal (for the left ventricle) catheterization. Some diseases give rise to VA from the subepicardium, which may be approached by epicardial mapping and ablation. Pericardial access is usually achieved by a percutaneous subxiphoid puncture. The catheter ablation procedure usually involves attempts to induce VT by programmed electrical stimulation to confirm the diagnosis and guide ablation. Problems limiting success include inability to induce an arrhythmia for mapping (common with idiopathic VA), or origin of the arrhythmia from an inaccessible location in the myocardium (common in some cardiomyopathies).
5.4.2 VA in Patients With No Apparent Structural Heart Disease
See Section 8.
VA that are not associated with underlying structural heart disease or a genetic arrhythmia syndrome are commonly referred to as idiopathic. Most idiopathic VA are monomorphic and based on a focal mechanism of triggered activity or abnormal automaticity; a few are due to reentry. For patients who are symptomatic, and in whom antiarrhythmic medications are ineffective, not tolerated, or not desired by the patient, catheter ablation is a treatment option. The ablation strategy is to identify the site of origin manifested by the earliest site of electrical activation, or when this is not practical, by pace mapping. Catheter ablation of idiopathic VA is usually accomplished with endocardial catheterization, though an epicardial approach through the coronary venous circulation or a subxiphoid pericardial puncture may occasionally be required. Ablation failure for idiopathic VA is often due to inability to provoke the arrhythmia to allow mapping in the electrophysiological laboratory or origin from an inaccessible region.
5.4.3 Scar-Related VT
See Section 8.
For most patients with structural heart disease, sustained monomorphic VT is due to reentry through regions of surviving myocardial fibers associated with areas of fibrous scar. The ablation strategy for these reentry circuits is to identify and eliminate channels of surviving myocardium within the scar that are often associated with slow conduction facilitating reentry. For most VTs that are related to prior MI, the substrate is on the subendocardial surface of the left ventricle. In NICM, the reentrant circuits are more variable in location, often involve the epicardial surface of either ventricle and frequently extending into the midmyocardium where ablation may be difficult to achieve from either surface. In tetralogy of Fallot specific reentry paths have been defined (S5.4.3-1). Electroanatomical mapping that helps clarify the relation of electrophysiological abnormalities to cardiac anatomy is commonly employed. Areas of scar can be appreciated as regions of relatively low electrogram voltage. For scar-related VTs, hemodynamic intolerance often limits mapping during VT. Ablation is then often guided by substrate mapping, in which areas of scar and potential reentry circuit substrate are delineated in electroanatomic maps based on electrocardiographic and pacing characteristics assessed during hemodynamically stable sinus or paced rhythm. Catheter ablation of scar-related VT requires an advanced level of experience by the operator, electrophysiological laboratory staff, and anesthesiologists as well as availability of surgical back-up and specialized mapping, imaging, and ablation equipment (S5.4.3-2,S5.4.3-3).
5.5 Surgery and Revascularization Procedures in Patients With Ischemic Heart Disease
Recommendation-Specific Supportive Text
1. Myocardial ischemia is a cause of sustained polymorphic VT/VF, and revascularization is an effective treatment to prevent myocardial ischemia. For patients with life-threatening VA, observational studies show that patients undergoing coronary artery bypass graft (CABG) had substantially better survival after accounting for other predictors (S5.5-1,S5.5-5). The risk of SCD appears comparable for patients with complex ischemic heart disease randomized to treatment with PCI versus CABG (S5.5-6). For patients with low LVEF and ischemic heart disease amenable to CABG, the risk of SCD is lower with CABG than medical therapy (S5.5-2,S5.5-7). Observational studies show an association between a lower likelihood of death with revascularization for survivors of SCA and CABG (S5.5-3) or PCI (S5.5-4). Revascularization alone is usually insufficient to prevent recurrence of sustained monomorphic VT; further evaluation for inducible VT is generally considered if ventricular function is depressed and/or scar is present.
2. Anomalous aortic origin of the coronary arteries is detected in approximately 1% of patients undergoing routine coronary angiography, and <0.2% of children and adolescents undergoing echocardiography (S5.5-8). Although ischemic heart disease is detected in as many as 24% to 55% of SCD cases in young patients <35 years of age (S5.5-9,S5.5-10), anomalous aortic origin of the coronary arteries is an important cause of SCD in the young, reported in 10% to 17% of patients included in postmortem studies (S5.5-10,S5.5-11). Anomalous origin of the coronary arteries can be identified by echocardiography, invasive coronary angiography, CT angiography or cardiac MRI. In patients with SCA or life-threatening VA presumed related to ischemia caused by anomalous origin of a coronary artery, repair or revascularization is performed to alleviate ischemia and reduce the recurrence of VA (S5.5-6,S5.5-7,S5.5-12—S5.5-14).
5.5.1 Surgery for Arrhythmia Management
Recommendation-Specific Supportive Text
1. Cardiac surgery as a standalone procedure for VT is rarely performed, but has a role in some highly symptomatic patients, when antiarrhythmic medications and catheter ablation fails or are not possible, particularly if the failure of ablation is due to an arrhythmia arising from an area that is inaccessible to catheter ablation, such as deep in the myocardium, beneath epicardial fat, or near the coronary arteries. Surgical ablation of tachycardia can also be performed at the time of other cardiac surgical interventions, such as during surgical resection of large aneurysms due to prior MI in which the border zone is often a substrate for VT, or placement of an LV assist device (LVAD) (S5.5.1-5—S5.5.1-7). The procedure requires detailed characterization of the arrhythmia usually with preoperative imaging and mapping, therefore, surgical ablation is best undertaken at tertiary referral centers and with collaboration between experienced surgeons and electrophysiologists.
5.6 Autonomic Modulation
Sympathetic activation is proarrhythmic and parasympathetic activation is generally antiarrhythmic in VT/VF. Modulating the autonomic nervous system for the purpose of preventing arrhythmias is an emerging therapeutic modality. For the prevention of VA, autonomic modulation can be done either through interruption of sympathetic outflow to the heart, pharmacological beta blockade, or through stimulation of the parasympathetic pathway (e.g., vagal nerve stimulators, spinal cord stimulators). Although autonomic modulation has proven efficacy for certain conditions such as long QT syndrome and catecholaminergic polymorphic ventricular tachycardia (see Section 7.9), evidence is limited for its applicability to the broader group of VA, but studies are ongoing. Currently, there are limited data on the role of vagal nerve stimulators and spinal cord stimulators for the prevention of VA/SCD in humans, and thus no formal recommendation could be supported (S5.6-5).
Recommendation-Specific Supportive Text
1. Many patients with non–life-threatening VA require only reassurance, but others have symptoms that warrant therapy. A small RCT of patients with symptomatic VA demonstrated a significant reduction in the arrhythmic burden with atenolol (S5.6-1).
2. VT/VF storm causes significant morbidity and is associated with increased mortality. For VT/VF storm refractory to treatment (medications, catheter ablation), cardiac sympathetic denervation has been shown in several small, observational studies (S5.6-3,S5.6-6) and 1 RCT (S5.6-4) to reduce the arrhythmia burden. This has been shown for left or bilateral cardiac sympathetic denervation, and it has been suggested that bilateral cardiac sympathetic denervation may be superior (S5.6-3). Although data are limited, the significant morbidity and limited options in these patients make cardiac sympathetic denervation a reasonable option in selected patients.
6 Acute Management of Specific VA
|III: No Benefit||A|
|III: No Benefit||A|
Recommendation-Specific Supportive Text
1. The most common electrical mechanisms for cardiac arrest are VF and pulseless VT, but substantial numbers of cardiac arrests begin as severe bradyarrhythmias or asystole. Survival is better for patients presenting with VT or VF than for those with bradyarrhythmic or asystolic mechanisms (S6-32). Rapid arrival of paramedical personnel is the major determinant of survival. A number of strategies for responding to unexpected cardiac arrest, including rapid defibrillation and initiation of CPR for a witnessed cardiac arrest, have improved survival probabilities for cardiac arrest victims (S6-2,S6-3). Nonetheless, the absolute number and proportion of survivors remain low, except in unique circumstances where there is an extraordinarily rapid response time to victims in VF or VT such as in monitored intensive care units, where survival is >90% (S6-33—S6-36). Survival decreases rapidly after the initial 2 minutes from the onset of cardiac arrest, so that by 4 to 5 minutes, survival may be ≤25%, and by 10 minutes it is 0% (S6-33,S6-35,S6-36). Advanced life support activities, other than those directly related to cardioversion and defibrillation for control of tachyarrhythmias, have led to the generation of comprehensive protocols to guide responders. These AHA documents cover the broad expanse of clinical circumstances and considerations of mechanisms (S6-1,S6-37).
2. Paramedic administration of amiodarone after at least 3 failed shocks and administration of epinephrine improved hospital admission rates when compared with placebo (S6-6) or 1.5 mg/kg lidocaine (S6-1,S6-4) in RCTs in adults with out-of-hospital cardiac arrest due to refractory VF or polymorphic VT, although survival to hospital discharge and survival with favorable neurologic outcome were not improved with amiodarone or lidocaine (S6-5). However, in the subset of patients with witnessed cardiac arrest due to initial shock-refractory VF or pulseless VT, survival to hospital discharge after amiodarone administration was higher than with placebo (S6-5). The administration of procainamide in out-of-hospital cardiac arrest due to VF or pulseless VT has been associated with more shocks, more pharmacologic interventions, longer resuscitation times, and lower survival (S6-38).
3. VA with hemodynamic instability, including VF and pulseless monomorphic or polymorphic VT, causes loss of consciousness and leads to death if untreated. A short time to direct current cardioversion is the major determinant of survival, and defibrillation should be performed as quickly as possible. CPR is used until a perfusing rhythm is restored. If defibrillation is unsuccessful in returning spontaneous circulation, responders follow advanced cardiovascular life support activities (S6-1—S6-3).
4. Quickly identifying and treating patients with out-of-hospital cardiac arrest related to acute coronary occlusion is associated with improved survival and better functional recovery (S6-37). Coronary occlusion as a cause of cardiac arrest is not reliably predicted by clinical and electrocardiographic findings (S6-7), and emergency coronary angiography should be considered (rather than later in the hospital stay or not at all) for unstable patients with a suspected cardiac etiology regardless of whether the patient is comatose or awake (S6-9,S6-39). In 1 observational study of patients resuscitated from SCA who did not have ST elevation and had angiography, one third were found to have a culprit lesion and coronary intervention appeared to be associated with a greater likelihood of favorable neurologic outcome (S6-10).
5. The initial management of any tachycardia should proceed according to published AHA advanced cardiovascular life support guidelines (S6-40). Immediate cardioversion should be performed for hemodynamic instability at presentation or if it develops subsequently. An ECG should be obtained for stable rhythms. Wide-complex tachycardias, defined by a QRS duration ≥0.12 s (S6-37), can be due to VT, SVT with aberrancy, preexcited tachycardia, or a paced rhythm such as pacemaker-mediated tachycardia. An irregular wide-complex tachycardia may be AF with aberrancy, preexcited AF (i.e., AF using an accessory pathway for anterograde conduction), atrial flutter, or VT (S6-37). A diagnosis should be established, and consultation with an arrhythmia expert considered (S6-37).
6. In 1 study, amiodarone was more effective than lidocaine in terminating incessant VT with improved survival at 24 hours (S6-26). For patients with recurrent, stable VT not in the setting of an AMI, intravenous procainamide has been shown to be superior to lidocaine for terminating the arrhythmia (S6-11). One randomized trial of 62 patients found procainamide superior to amiodarone for termination of stable VT (S6-13). Adverse events, including hypotension were more common with amiodarone, but the difference was not statistically significant. Procainamide and its metabolite n-acetylprocainamide have potassium channel blocking properties that may prolong the QT interval. In patients who already have QT prolongation, administration of procainamide may further prolong the QT interval and lead to torsades de pointes (S6-11,S6-12,S6-26).
7. Intravenous lidocaine is an alternative antiarrhythmic medication of long-standing and widespread familiarity. Compared with no antiarrhythmic medication, lidocaine did not consistently increase a return of spontaneous circulation after defibrillation and was not associated with improvement in survival to hospital discharge (S6-4,S6-14,S6-41). In prospective, blinded, RCTs, lidocaine was less effective than amiodarone in improving hospital admission rates after out-of-hospital cardiac arrest due to shock-refractory VF or polymorphic VT; but there were no differences between the 2 medications in survival to hospital discharge (S6-4,S6-5). However, in the subset of patients with witnessed SCA due to initial shock-refractory VF or pulseless VT, a subgroup analysis showed that survival to hospital discharge with lidocaine was better than with placebo (S6-5,S6-42).
8. In a large meta-analysis of antiarrhythmic medications in the setting of AMI, beta blockers were associated with a significant reduction in mortality (S6-16). Beta blockers can be effective in suppressing recurrent VF in patients with recent MI, with an associated improvement in survival (S6-17).
9. In patients with recurrent VT/VF (VT/VF storm) in the setting of a recent MI that is refractory to amiodarone and/or lidocaine and repeated cardioversion, administration of a beta blocker has been shown to improve survival at 1 week. For those who did not survive, mortality was mostly due to recurrent VF. Survival at 1 year was also better in those treated with a beta blocker (S6-17,S6-18). Other measures to reduce sympathetic tone including sedation and general anesthesia are also often used.
10. Epinephrine produces beneficial effects in patients during cardiac arrest, primarily because of its alpha-adrenergic (i.e., vasoconstrictor) effects (S6-1). These alpha-adrenergic effects can increase coronary and cerebral perfusion pressure during CPR. The value and safety of the beta-adrenergic effects of epinephrine are controversial because they may increase myocardial work and reduce subendocardial perfusion (S6-1). One trial assessed short-term and longer-term outcomes when comparing standard-dose epinephrine to placebo (S6-23). Standard-dose epinephrine was defined as 1 mg given intravenously or intraosseously every 3 to 5 minutes. For both survival to discharge and survival to discharge with good neurologic outcome, there was no benefit with standard-dose epinephrine; however, the study was underpowered for analysis of either of these outcomes. There was, nevertheless, improved survival to hospital admission and improved return of spontaneous circulation with the use of standard-dose epinephrine. A number of trials have compared outcomes of standard-dose epinephrine with those of high-dose epinephrine. These trials did not demonstrate any benefit for high-dose epinephrine over standard-dose epinephrine in relation to survival to discharge with a good neurologic recovery, survival to discharge, or survival to hospital admission (S6-1,S6-19,S6-21,S6-22).
11. Amiodarone was more effective than lidocaine in terminating incessant VT with improved survival at 24 hours (S6-26). For patients with recurrent, stable VT not in the setting of an AMI, intravenous procainamide has been shown to be superior to lidocaine for terminating the arrhythmia (S6-11). One RCT in 62 patients found procainamide superior to amiodarone for termination of stable VT (S6-13). Adverse events, including hypotension, were more common with amiodarone, but the difference was not statistically significant. Procainamide and its metabolite n-acetylprocainamide have potassium channel blocking properties that may prolong the QT interval. In patients who already have QT prolongation, administration of procainamide may further prolong the QT interval and lead to torsades de pointes (S6-11). A single RCT of 33 patients comparing sotalol with lidocaine for treating patients with hemodynamically stable VT showed that VT was terminated in 69% of patients using sotalol and 18% using lidocaine (S6-25). Intravenous sotalol has been approved for use in the United States. Sotalol has potassium channel blocking properties that may prolong the QT interval. In patients who already have QT interval prolongation, administration of sotalol may further prolong the QT interval and lead to torsades de pointes (S6-25).
12. Epinephrine may increase coronary and cerebral perfusion pressure during CPR because of its vasoconstrictive effects. High doses of epinephrine (0.1 to 0.2 mg/kg IV, as opposed to a standard dose of 1 mg) have been studied in RCTs. In out-of-hospital cardiac arrest unresponsive to defibrillation, administration of high-dose epinephrine improved survival to hospital admission, but there was no difference compared to standard dose epinephrine in survival to hospital discharge (S6-19). There was also no improvement in long-term survival (S6-21). Of note, the administration of vasopressin is no longer recommended in the most recent advanced cardiovascular life support algorithms (S6-1).
13. Magnesium may suppress automaticity, suppress early and late after-depolarizations, and inhibit calcium flux into cardiomyocytes. It is effective in suppressing VA related to acquired long QT syndrome. However, 2 RCTs that investigated the use of intravenous magnesium in patients with cardiac arrest and refractory VF found no benefit (S6-27,S6-28). In a study of out-of-hospital cardiac arrest, administration of 2 to 4 g magnesium intravenously did not improve survival to hospital admission (S6-27). In a similar study involving inpatient cardiac arrest, magnesium did not improve return of spontaneous circulation, survival to 24 hours, or survival to hospital discharge (S6-28). There are exceptions such as marked hypokalemia or medication-induced torsades de pointes in which administration of intravenous magnesium is warranted.
14. Several studies have tested the hypothesis that prophylactic administration of antiarrhythmic medications could reduce the incidence of post-MI VA and lead to better outcomes. One meta-analysis assessed studies in which beta blockers, class I antiarrhythmic agents such as lidocaine and procainamide, and amiodarone were given in the setting of AMI. The routine use of lidocaine and procainamide was associated with increased mortality, whereas beta blockers were associated with a significantly lower mortality rate (S6-16). Limited data with amiodarone appeared to be promising, but a subsequent RCT involving 1073 patients found that administration of high-dose amiodarone led to a higher mortality rate, although a moderate dose of amiodarone was not superior to placebo (S6-29).
15. With a stable, wide QRS complex tachycardia, differentiation between SVT with aberrancy and VT is often possible by review of the patient’s history and the 12-lead ECG during tachycardia. Patients with wide QRS complex tachycardia and known structural heart disease should be presumed to have VT until proven otherwise. Administration of a calcium channel blocker such as verapamil to a patient with VT may result in severe hypotension or syncope (S6-31). The exception is verapamil-sensitive VT (interfascicular reentry) that occurs in a structurally normal heart; but this is often difficult to recognize on initial presentation (S6-30).
7 Ongoing Management of VA and SCD Risk Related to Specific Disease States
7.1 Ischemic Heart Disease
7.1.1 Secondary Prevention of SCD in Patients With Ischemic Heart Disease
|Value Statement: Intermediate Value|
Recommendation-Specific Supportive Text
1. In the AVID trial (S7.1.1-1), the ICD improved overall survival compared with antiarrhythmic medication therapy (primarily amiodarone) in patients who survived SCD or with hemodynamically unstable VT, with a 2-year relative risk reduction in mortality of 27% and an absolute risk reduction of 7%. CIDS (Canadian Implantable Defibrillator Study) (S7.1.1-2), which was stopped early after the results of the AVID trial were released, showed a similar, but not statistically significant, benefit of the ICD over antiarrhythmic medication therapy. A subsequent meta-analysis using data from 3 RCTs showed a statistically significant reduction in both arrhythmic and all-cause mortality with secondary prevention ICDs (S7.1.1-3).
In survivors of life-threatening VA that may be due to transient or reversible factors, such as AMI, proarrhythmic medication effects, or electrolyte disturbances, an ICD is not implanted if the cause may be correctable. This is a population of patients that still requires thorough evaluation, treatment, and close follow-up and, as in the AVID registry, mortality was still high in the population that may have had a reversible cause for their arrest (S7.1.1-8). Small increases in troponin present a challenge in selecting patients for an ICD, as it often cannot be determined whether troponin elevation is due to ischemia from VT/VF and resuscitation, in which case an ICD is likely warranted, or an indication that ischemia caused the arrhythmia, in which case prevention of ischemia would be the therapeutic focus.
ICDs may improve the outcomes of patients with hemodynamically tolerated sustained VT and structural heart disease (S7.1.1-5); however, this has not proved in any RCT. VT ablation has been used as an alternative in selected patients with well-tolerated VT and appears to reduce recurrences, but the impact on long-term mortality is unknown; there is not yet sufficient evidence to recommend this approach as an alternative to ICD implantation (S7.1.1-9,S7.1.1-10).
2. Economic outcomes of ICD implantation for secondary prevention of SCD were assessed in the AVID and CIDS trials (S7.1.1-11,S7.1.1-12), as well as in a simulation model (S7.1.1-13) and an observational study of Medicare beneficiaries (S7.1.1-14). All studies compared ICD recipients with non-ICD recipients, and all found that ICD recipients had longer overall survival and higher lifetime costs of medical care. All studies reported incremental cost-effectiveness ratios between $64,000 and $100,000 per year of life added by an ICD (S7.1.1-11—S7.1.1-14), which is in the range of intermediate value by the benchmarks applied in the ACC/AHA cost/value statement (S7.1.1-15).
3. VAs are an important cause of syncope or near syncope in patients with ischemic heart disease, particularly those with prior infarction. A study of 70 patients with unexplained syncope who underwent an electrophysiological study identified positive findings in 37 patients; 31 with VT. During 3 years of follow-up, patients with a positive electrophysiological study had higher rates of SCD and 3-year total mortality (61% versus 15%, respectively) than those with a negative electrophysiological study (S7.1.1-7). An ICD is warranted for patients with syncope and inducible sustained monomorphic VT even if they do not otherwise meet criteria for primary prevention (Figure 4).
184.108.40.206 Coronary Artery Spasm
Recommendation-Specific Supportive Text
1. Coronary artery spasm results from vasomotor dysfunction and can occur in the presence or absence of atherosclerotic ischemic heart disease. Vasospasm episodes can lead to VA, syncope, and SCD. Treatment includes risk factor elimination including smoking cessation, and treatment with vasodilators including dihydropyridine calcium channel blockers with or without nitrates. A more detailed summary of treatments for coronary artery spasm can be found in other guideline documents (S220.127.116.11-7,S18.104.22.168-8).
2. Patients with coronary artery spasm who survive an SCA are a high-risk population (S22.214.171.124-5). Recurrent VA, even life-threatening, may be prevented if coronary artery spasm can be effectively addressed with risk factor modification, smoking cessation, and ongoing treatment with nitrates and dihydropyridine calcium channel blockers (S126.96.36.199-9). However, SCA or VA can recur despite medical therapy or if compliance is poor. Whether a wearable cardioverter-defibrillator may provide protection while medical therapy is being evaluated has not been assessed but is of interest (S188.8.131.52-10). An ICD can terminate VT/VF initiated by spasm, potentially preventing SCD.
3. Patients with coronary vasospasm who survive an SCA are a high-risk population, and some support the use of an ICD in those patients based on the reported event rates from observational studies (S184.108.40.206-5) even before determining the patient’s response to or compliance with medical therapy. Recurrent SCA can occur despite medical therapy. Regardless of the approach, risk factor modification (e.g., illicit drug use), smoking cessation, and ongoing treatment with dihydropyridine calcium channel blockers with or without nitrates represent essential treatments (S220.127.116.11-9).
18.104.22.168 Post CABG VT/VF
The incidence of sustained VT or VF early after CABG is low, but these VAs are associated with high in-hospital mortality (S22.214.171.124-1). VF occurring very early (intraoperatively or within 24 hours postoperatively) may be due to the transient effects of reperfusion, electrolyte and acid base disturbances, and the use of inotropes. Patients who present with VF or polymorphic VT in the postoperative period more often have associated ischemia, while patients presenting with monomorphic VT usually have an old infarct and ventricular scar (S126.96.36.199-2). Polymorphic VT/VF occurring after CABG warrants a therapeutic approach targeting treatment of myocardial ischemia, including a possible need for assessment of graft patency, as well as identification and treatment of mechanical complications and acute electrolyte or acid base disturbances. Risk factors for occurrence of monomorphic VT early after CABG include prior MI, ventricular scar, LV dysfunction, and placement of a bypass graft across a noncollateralized occluded coronary vessel to a chronic infarct zone (S188.8.131.52-3). Unlike polymorphic VT and VF, sustained monomorphic VT is typically not due to acute ischemia. Many of these patients have inducible sustained VT at electrophysiological study. Management of symptomatic VA in the early period after CABG follows the recommendations for acute and ongoing management of VT detailed elsewhere in this document. In patients without sustained VT or VF but with LV dysfunction prior to undergoing CABG, implantation of an ICD did not improve survival (S184.108.40.206-4). For patients with LV dysfunction who are undergoing revascularization, there is a possibility that the LV function may improve, so many advocate for reassessment of the LV function 3 months after revascularization before a decision about ICD implantation is made (S220.127.116.11-5). For patients with a high burden of NSVT and reduced LVEF, an electrophysiological study may be helpful for risk stratification; those with inducible sustained VT may benefit from an ICD (S18.104.22.168-6). The wearable cardioverter-defibrillator may play a role in patients at risk of SCD in the early phase after revascularization to allow time for recovery of ventricular function (S22.214.171.124-7).
7.1.2 Primary Prevention of SCD in Patients With Ischemic Heart Disease
|Value Statement: High Value|
|III: No Benefit||C-EO|
Recommendation-Specific Supportive Text
1. The rationale for recommending that an ICD be offered to patients with NYHA class II or III HF, in addition to LVEF ≤35%, is based on the survival benefit observed in SCD-HeFT and MADIT-II (which used LVEF cutoff of below 35% and 30%, respectively). Selection for implantation of an ICD must be individualized. Patients with serious comorbidities associated with a survival of <1 year are generally not considered ICD candidates. The recommendation to wait at least 40 days after an MI before implanting a primary prevention ICD is based on the fact that such patients were excluded from MADIT-II and SCD-HeFT and 2 other RCTs showed no survival benefit from ICDs implanted early after an acute MI (S7.1.2-10,S7.1.2-11).
2. In the MADIT-II trial (S7.1.2-2), which randomized patients with LVEF ≤30% and prior MI to an ICD or not, approximately one third of the patients had NYHA class I symptoms. A subgroup analysis supported benefit of the ICD on survival in this subgroup (S7.1.2-2).
3. Economic outcomes of ICD implantation for primary prevention of SCD were assessed in 3 RCTs [MADIT-I (S7.1.2-12), MADIT-II (S7.1.2-13), and SCD-HeFT (S7.1.2-14)], 1 observational study (S7.1.2-15), and 4 simulation models (S7.1.2-16—S7.1.2-19), which all had generally consistent results. All studies reported increased survival and life expectancy, and higher lifetime costs of medical care with an ICD than without an ICD. The incremental cost-effectiveness ratios were generally <$50,000 per year of life added by an ICD, which provides high value according to the benchmarks adopted for the current guideline (S7.1.2-20). The value provided by an ICD was consistently high when life expectancy was projected to increase by >1.4 years (S7.1.2-18). In contrast, when survival was not increased by ICD implantation, as in the CABG-Patch trial (S7.1.2-18), the ICD did not provide value, because the higher costs were unaccompanied by a gain in life expectancy.
4. MUSTT (Multicenter Unsustained Tachycardia Trial) demonstrated that patients with prior MI, NSVT, and reduced LVEF with inducible VT at electrophysiological study have a higher overall mortality rate than similar patients without inducible sustained VT (S7.1.2-21). Patients who received an ICD after failing to have inducible VT suppressed by an antiarrhythmic medication had lower mortality rate than those who did not receive an ICD. Although the entry criteria into MUSTT required an LVEF of ≤40%, the average LVEF in enrolled patients was 30%, and ICD placement was not randomized but rather was selected by the treating physician for patients with VT that could not be suppressed with antiarrhythmic medication therapy. MUSTT allowed enrollment of patients who were ≥4 days after an acute MI or revascularization. The ICD was of no benefit in 2 other RCTs that examined the efficacy of the ICD in the acute phase of an MI (S7.1.2-10,S7.1.2-11). In a single center observational study, an electrophysiological study was performed a median of 9 days after acute MI in 115 patients with LVEF <40% and ICDs recommended for those with inducible VT. Median follow-up was 12 months. Sustained VT was induced in 27% of patients, and 22% of those who received ICDs had spontaneous VT terminated by the ICD during follow-up. None of the patients without inducible VT had VT or SCD during follow-up (S7.1.2-22).
5. In a retrospective analysis of the UNOS (United Network for Organ Sharing) registry that extended from 1999 to 2014, data on 32,599 patients showed that during a median follow-up of 154 days, 3,638 patients (11%) died while on the waitlist for cardiac transplantation (9% in the ICD group versus 15% in the non-ICD group; p<0.0001). The presence of an ICD at listing was associated with an adjusted 13% relative risk reduction in mortality. In the subgroup of patients with an LVAD (n=9,478), an ICD was associated with an adjusted 19% relative risk reduction in mortality (S7.1.2-9). In another study of 380 patients listed for heart transplantation between 2005 and 2009 at 1 tertiary heart transplant center, 122 patients received an ICD before or within 3 months after being listed for heart transplantation. Non-ICD patients were more likely to die while on the transplant list. In a multivariable model, the ICD was not associated with improved survival; however, that analysis was limited by the small sample size (S7.1.2-8). Another small study (n=79) conducted at 1 institution suggested that ICDs reduce the risk of SCD in patients with LVEF ≤30% who are awaiting heart transplantation; however, this study was limited by the small number of patients (S7.1.2-6). In a retrospective multicenter study of 1,089 patients listed for heart transplantation, 550 patients (51%) had an ICD. In 216 patients, the ICD was for primary prevention of SCD and, in 334 patients, the ICD was for secondary prevention. The remaining 539 patients did not receive an ICD. During a median time on the waiting list of 8 months, the ICD was associated with a reduction in all-cause mortality in the primary and secondary prevention cohorts (estimated 1-year: 88 ± 3% versus 77 ± 3% versus 67 ± 3%; p = 0.0001). This relationship between the ICD and improved survival persisted even after adjusting for potential confounders (S7.1.2-7).
6. There are insufficient data from RCTs regarding the value of the ICD in patients with NYHA class IV HF. Ambulatory class IV patients with HF were included in the COMPANION (Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure) trial, which showed an overall improved functional status and survival with a CRT defibrillator (S7.1.2-23). Unless such a patient is a candidate for CRT or advanced HF therapies such as heart transplantation or an LVAD, an ICD is not expected to meaningfully prolong survival (S7.1.2-23).
7.1.3 Treatment and Prevention of Recurrent VA in Patients With Ischemic Heart Disease
|III: No Benefit||C-LD|
Recommendation-Specific Supportive Text
1. The most common antiarrhythmic medications used for suppression of VA include amiodarone and sotalol, while mexiletine, quinidine, and ranolazine are occasionally used (S7.1.3-17,S7.1.3-18). Amiodarone appears to be more effective than sotalol and has a low rate of ventricular proarrhythmia, but has an increased risk of medication-related adverse effects that lead to its discontinuation in many patients within 18 to 24 months from initiation of therapy (S7.1.3-1,S7.1.3-19). Data supporting effectiveness of sotalol for suppression of VA are conflicting, but given its more favorable adverse effect profile than amiodarone, it may be a better first-line antiarrhythmic medication in appropriate patients (S7.1.3-1–S7.1.3-3). However, sotalol is generally avoided in patients with a severely reduced LVEF <20% due to its negative inotropic effects and the risk of torsades de pointes. In a double-blind placebo-controlled study of 674 patients with HF and ≥10 PVCs/h and an LVEF ≤40% randomly assigned to receive amiodarone (336 patients) or placebo (338 patients), there was no significant difference in overall mortality or SCD between the 2 arms. There was a trend toward a reduction in overall mortality among the patients with NICM who received amiodarone (p=0.07) (S7.1.3-20).
2. Patients with prior MI may present with frequent episodes of sustained monomorphic VT or recurrent VF episodes that are initiated by PVCs arising from Purkinje Fibers in the peri-infarct zone. VA storms are associated with increased mortality (S7.1.3-12). The arrhythmia substrate is usually in the subendocardium. The randomized VANISH (Ventricular Tachycardia Ablation versus Escalated Antiarrhythmic Drug Therapy in Ischemic Heart Disease) trial (S7.1.3-4) compared escalating antiarrhythmic medication therapy versus catheter ablation for patients with prior MI and recurrent sustained monomorphic VT despite antiarrhythmic medications. The primary outcome, a composite of death, VT storm, or ICD shocks occurred in 59.1% in the ablation group and in 68.5% in the escalated-therapy group. There was no difference in mortality between the groups. Recurrent ICD shocks and VT storm and treatment-related adverse events were lower in the ablation group. In a subgroup analysis, patients having VT on amiodarone had better outcomes with ablation compared with increasing amiodarone or adding mexiletine to amiodarone. For patients receiving medications other than amiodarone, catheter ablation did not reduce the risk of ICD shocks or VT storm compared with switching to amiodarone. Although recurrent VT after catheter ablation is associated with increased mortality (S7.1.3-9), whether mortality is reduced by catheter ablation has not been established. Procedural complications occur in approximately 6% of patients, most of which are related to vascular access but stroke, tamponade, and atrioventricular block can occur. Procedure mortality is <1% in experienced centers (S7.1.3-4,S7.1.3-9).
Sustained monomorphic VT often occurs as occasional isolated episodes in patients with prior MI. Several nonrandomized studies have shown that catheter ablation reduces recurrent VT or ICD shocks (S7.1.3-5,S7.1.3-7,S7.1.3-8). A meta-analysis of 5 VT ablation studies (S7.1.3-5) reported that VT recurred in 35% of patients after catheter ablation compared with 55% on antiarrhythmic medications. In a multicenter study of catheter ablation (S7.1.3-7) for patients with ≥3 episodes of sustained VT in the prior 6 months, 53% were free from recurrent VT at 6 months follow-up; the median number of VT episodes was reduced from 11.5 to 0. Superiority of ablation over escalating medication therapy was shown in the composite endpoint of death, VT storm, or ICD shocks by the VANISH trial (S7.1.3-4).
3. Patients with prior MI who develop sustained monomorphic VT often have recurrent episodes. The VTACH (Ventricular Tachycardia Ablation in Addition to Implantable Defibrillators in Coronary Heart Disease) trial (S7.1.3-11) randomized patients undergoing ICD implantation for stable sustained monomorphic VT, who had not failed antiarrhythmic medication therapy, to catheter ablation versus ICD implantation alone. At 2 years, any VT had recurred in 53% of the ablation group and 71% of the control group. Ablation prolonged the time to recurrent VT from a median of 5.9 months to 18.6 months (S7.1.3-11). Several nonrandomized studies have shown that catheter ablation reduces the risk of recurrent VT or ICD shocks in patients with sustained VT related to prior MI (S7.1.3-5,S7.1.3-7,S7.1.3-8). In a multicenter study of catheter ablation (S7.1.3-7) for patients with ≥3 episodes of sustained VT in the prior 6 months, 53% were free from recurrent VT at 6 months follow-up; the median number of VT episodes was reduced from 11.5 to 0. A meta-analysis of 5 VT ablation studies (S7.1.3-5) reported that VT recurred in 35% of patients after catheter ablation compared with 55% on antiarrhythmic medications. Another study of 63 patients with recurrent VT after MI demonstrated acute success with catheter ablation in 83% of mappable VTs and 40% of nonmappable VTs (S7.1.3-8). Superiority of ablation over escalating medication therapy for patients with recurrent VT despite antiarrhythmic medications was shown by the VANISH trial (S7.1.3-4). See Section 5.6.
4. CAST (S7.1.3-21) demonstrated higher rates of mortality or nonfatal cardiac arrest in post-MI patients treated with encainide or flecainide when used to suppress PVCs and NSVT (S7.1.3-13). Propafenone is associated with increased mortality in SCA survivors compared with beta blockers, amiodarone, and the ICD (S7.1.3-22).
5. Implantation of an ICD prior to achieving suppression of frequent or incessant VA places the patient at high risk of repetitive shocks, which can be psychologically detrimental and has been associated with increased mortality (S7.1.3-23,S7.1.3-24).
6. Sustained monomorphic VT in the setting of prior MI is typically due to scar-related reentry and is not due to acute ischemia. Although it may be appropriate to recommend revascularization when another indication for revascularization exists, revascularization alone is unlikely to reduce the recurrence of monomorphic VT and specific therapies such as antiarrhythmic medications or ablation may be needed to prevent recurrence (S7.1.3-16). On the contrary, revascularization might be beneficial in patients with ischemic heart disease and VF, polymorphic VT, or exercise-induced arrhythmias associated with ischemia (S7.1.3-25).
7.2 Nonischemic Cardiomyopathy
Recommendation-Specific Supportive Text
1. Cardiac MRI allows for evaluation of structural heart disease and assessment of LV and RV function including quantification of LVEF, LV mass and volume, and valvular structure. Cardiac MRI can help in the evaluation for myocardial infiltrative processes and evidence of scar, indicated by delayed hyperenhancement, associated with VA (S7.2-1–S7.2-4,S7.2-6).
2. The presence of delayed hyperenhancement has been associated with worse outcomes, including SCD (S7.2-1–S7.2-3).
3. It is important to consider genetic etiologies for NICM. Goals of genetic testing for NICM are to identify at-risk relatives who host a disease-causing mutation and to help clarify prognosis. Lamin A/C and NKX 2.5 mutations (S7.2-7–S7.2-12) are associated with a particularly high risk of early conduction disease, arrhythmias, and SCD, and their identification often prompts consideration of early use of an ICD. It is unknown, however, whether early pharmacological treatment of mutation-positive, asymptomatic subjects can prevent or delay manifestation of the disease or whether genetic testing ultimately improves survival.
7.2.1 Secondary Prevention of SCD in Patients With NICM
Recommendation-Specific Supportive Text
1. Three prospective RCTs compared the ICD with pharmacological therapy in patients resuscitated from SCA due to VT/VF or hemodynamically significant VT (S7.2.1-1,S7.2.1-2,S7.2.1-4). The antiarrhythmic medications most commonly used were amiodarone, a beta blocker, or both, although in the CASH (Cardiac Arrest Study Hamburg) trial (S7.2.1-4), there was also a propafenone arm that was terminated early due to increased mortality. The 3 trials enrolled 1,963 patients, but only 292 (14.8%) had NICM. A meta-analysis in which data from AVID and CIDS were pooled found a nonsignificant 31% reduction in all-cause mortality relative to medical therapy in patients with NICM (S7.2.1-3). Although this analysis was underpowered, the observed mortality reduction was consistent with the observed benefit in the entire study population. In the AVID trial (S7.2.1-1), patients who were ineligible for the RCT were included in a registry, and sustained VT without serious symptoms or hemodynamic compromise was associated with a mortality rate similar to that of patients with unstable VT who were assigned to medical therapy. Therefore, stable VT is likely a marker for a substrate capable of producing subsequent lethal arrhythmias (S7.2.1-5).
2. Small observational studies demonstrated high mortality and frequent appropriate ICD shocks in patients with syncope and NICM (S7.2.1-7—S7.2.1-9). The assumption that malignant VAs are the likely cause of syncope and that the ICD would be protective has recently been challenged. In a subgroup analysis of SCD-HeFT that included 472 patients, the ICD did not reduce either recurrent syncope or the increased risk of mortality associated with syncope (S7.2.1-10). A subgroup analysis of the MADIT- RIT (Multicenter Automatic Defibrillator Implantation Trial - Reduce Inappropriate Therapy) trial found syncope to be arrhythmic only in 39% of patients (S7.2.1-11). These studies suggest that syncope in some HF patients may be an indicator of an end-stage cardiomyopathy associated with a poor prognosis (S7.2.1-11). In a substudy of DEFINITE, inducible sustained VT/VF was found in a minority of patients, but it was associated with appropriate ICD therapy (S7.2.1-14). Another study of electrophysiological testing in NICM found inducible VT/VF in 27.8% of patients, which was associated with future ICD events (S7.2.1-15). In a study of patients with NICM, cardiac mortality correlated with LVEF but not with inducibility on electrophysiological study (S7.2.1-16). Based on these data, many experts are uncomfortable withholding an ICD from patients with NICM who experience syncope potentially due to a VA even if the electrophysiological study shows no inducible sustained VT.
3. Access to ICDs may be limited by financial, medical, or personal considerations. In addition, not all patients at high risk of SCD meet ICD indications, such as those with class IV HF without CRT possibility or with a life expectancy <1 year. A meta-analysis of RCTs, which examined the use of amiodarone for the prevention of SCD, included 15 studies with 8522 patients assigned to amiodarone or placebo/control (S7.2.1-12). Amiodarone reduced the risk of SCD by 29%; however, it did not reduce all-cause mortality and was associated with an increased risk of pulmonary and thyroid toxicity. In a subgroup analysis, the benefit of amiodarone appeared similar in patients with ischemic cardiomyopathy and those with NICM (S7.2.1-12). In a separate meta-analysis (S7.2.1-13), the evidence was insufficient to support amiodarone’s efficacy for reduction of SCD and all-cause mortality in survivors of cardiac arrest or those with syncope due to VA. A subgroup analysis of the VALIANT (Valsartan in Acute Myocardial Infarction) trial found that amiodarone was associated with increased mortality in patients with NYHA class III HF (S7.2.1-17). These data call for a careful and nuanced approach to using amiodarone for the secondary prevention of SCD in patients with NICM.
7.2.2 Primary Prevention of SCD in Patients With NICM
|III: No Benefit||C-EO|
Recommendation-Specific Supportive Text
1. For all patients with NICM, it is imperative that patients be on GDMT for HF for at least 3 months before a primary prevention ICD is offered. Four prospective RCTs (S7.2.2-1,S7.2.2-2,S7.2.2-5,S7.2.2-6) initially evaluated ICDs for primary prevention of SCD in patients with NICM. Two (S7.2.2-2,S7.2.2-6) were small studies that were terminated early due to a low event rate. In DEFINITE (S7.2.2-5), an ICD reduced the risk of SCD, with a trend toward reduced all-cause mortality. SCD-HeFT included 792 NICM patients (S7.2.2-1). Total mortality at 5 years was 27% in the placebo group and 21% in the ICD group (p=0.06). A pooled analysis of these studies demonstrated a significant 31% reduction in all-cause mortality for ICD relative to medical therapy (S7.2.2-4). The DANISH (Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on Mortality) trial (S7.2.2-11) raised questions about the role of primary prevention ICDs in patients with NICM. This trial randomized 1116 patients with NICM LVEF <35% and class II, III, or IV (if CRT was planned) HF to an ICD or no ICD. CRT (either ICD or pacemaker) was present in 58% of patients in the ICD and medical therapy arms. Therefore, the results of DANISH should not be generalized to patients with NICM who are ineligible for CRT. During a median follow-up of 5.6 years, ICD reduced SCD from 8.4% to 4.3%, but there was no difference in all-cause mortality (S7.2.2-11). Several meta-analyses have been published (S7.2.2-12,S7.2.2-13). One provided data on ICDs with and without CRT and showed survival benefit from the ICD (S7.2.2-13). The second used patient level data from 2 trials and adopted a more robust approach to reducing heterogeneity by excluding patients with CRT and those randomized to antiarrhythmic medications; a 25% relative risk reduction in mortality with an ICD was shown (S7.2.2-12).
2. Laminopathies are diseases caused by mutations mainly in the Lamin A/C gene that produce various inherited diseases including subtypes of muscular dystrophy and progeria. Isolated cardiac involvement is also observed and is an important cause of familial cardiomyopathy (S7.2.2-9). The disease is highly penetrant such that all affected individuals have evidence of disease by 60 years of age. Cardiac manifestations may include atrial fibrillation, conduction disturbances, VA, and NICM. A number of observational studies reported a high risk of SCD when cardiac involvement is present (S7.2.2-7—S7.2.2-10). One study reported SCD as the most frequent mode of death (46%) in both the isolated cardiac and the neuromuscular phenotypes of Lamin diseases (S7.2.2-9). In a cohort of 269 LMNA mutation positive individuals (S7.2.2-10), NSVT during ambulatory electrocardiographic monitoring, LVEF <45% at first evaluation, male sex, and nonmissense mutations were independent risk factors for VA. Malignant VA were observed only in persons with ≥2 of these risk factors (S7.2.2-10). No studies have tested the effect of the ICD on long-term survival.
3. Patients with NICM and class I HF symptoms were not included in SCD-HeFT or DANISH (S7.2.2-1,S7.2.2-11). Although such patients were included in the DEFINITE trial, only 99 (21.6%) of 458 patients in the DEFINITE trial had class I HF (S7.2.2-5). Therefore, it is uncertain whether a primary prevention ICD in such patients improves survival.
4. There are insufficient data from RCTs regarding the value of the ICD in patients with NYHA class IV. Ambulatory class IV HF patients were included in the COMPANION trial that, overall, showed improved functional status and survival with a CRT defibrillator (S7.2.2-3). Unless such a patient is a candidate for CRT or advanced HF therapies such as heart transplantation or an LVAD, an ICD is not expected to meaningfully prolong survival (S7.2.2-3).
7.2.3 Treatment of Recurrent VA in Patients With NICM
Recommendation-Specific Supportive Text
1. ICDs reduce mortality from VA, yet ICD shocks are painful and associated with significant morbidity and poor QoL. Although ICDs are highly programmable and provide antitachycardia pacing therapy that can terminate most VT episodes without the need for a shock, prevention of shocks, both appropriate and inappropriate, remains an important concern. In the OPTIC (Optimal Pharmacological Therapy in Cardioverter Defibrillator Patients) study, 412 patients with documented VT and VF who received an ICD within 21 days of the documented arrhythmia (S7.2.3-1) were randomized to amiodarone plus beta blocker, sotalol alone, or beta blocker alone. Over 1 year, shocks occurred in 38.5% assigned to beta blocker alone, 24.3% assigned to sotalol, and 10.3% assigned to amiodarone plus beta blocker. The rates of study medication discontinuation at 1 year were 18.2% for amiodarone, 23.5% for sotalol, and 5.3% for beta blocker alone. Adverse pulmonary and thyroid events and symptomatic bradycardia were more common among patients randomized to amiodarone. Thus, amiodarone plus beta blocker were more effective than sotalol in preventing ICD shocks but at the expense of increased risk of medication-related adverse effects (S7.2.3-1). Sotalol should not be used in patients with an LVEF <20% due to its negative inotropic effects.
2. Sustained monomorphic VT due to NICM is most often due to scar-related reentry. Cardiac MRI often indicates scar location, which tends to be basal along the mitral annulus or in the septum (S7.2.3-4,S7.2.3-5). The VT substrate can be subendocardial, subepicardial, or intramyocardial, and all locations may be affected and require endocardial and epicardial ablation. In the HELP-VT (Heart Center of Leipzig VT) study (S7.2.3-2), successful ablation of all VT morphologies was achieved in 66.7% of patients with NICM, compared with the 77.4% success rate in ischemic cardiomyopathy. An epicardial approach to ablation was required in 30.2% of NICM patients, compared with only 1.2% with ischemic cardiomyopathy. Epicardial ablation was an independent predictor of successful ablation. Acute and long-term success of ablation is lower for NICM, compared with post-MI patients. The long-term survival-free of VT recurrence after catheter ablation appears to be better for patients with ischemic than NICM (57% versus 40.5% at 1 year) (S7.2.3-2). Risks are similar to those observed for post-MI VT ablation, with additional risks of epicardial access and ablation when required. Although any NICM can produce scar-related VT, cardiac sarcoidosis (see Section 7.6) and Lamin mutations are particularly associated with sustained monomorphic VT (S7.2.3-6).
7.3 Arrhythmogenic Right Ventricular Cardiomyopathy
Arrhythmogenic right ventricular cardiomyopathy is an inherited cardiomyopathy that predominantly affects the right ventricle but can affect the left ventricle causing areas of myocardial replacement with fibrosis and adipose tissue that frequently causes VA and SCD.
Recommendation-Specific Supportive Text
1. Selected first-degree relatives refers to relatives who are willing to undergo further testing and who could benefit from further screening and testing (and not the terminally ill patients or those who do not want to be screened and tested). Arrhythmogenic right ventricular cardiomyopathy is often due to a mutation involving a desmosomal protein, and it usually has autosomal dominant inheritance with variable penetrance. SCD can be the initial manifestation of arrhythmogenic right ventricular cardiomyopathy. Clinical screening with ECG, cardiac imaging, and ambulatory rhythm monitoring and/or exercise testing may identify family members at risk for arrhythmogenic right ventricular cardiomyopathy. Arrhythmogenic right ventricular cardiomyopathy is detected clinically in approximately 35% to 40% of first-degree relatives (S7.3-3,S7.3-4), most commonly in siblings or symptomatic first-degree relatives (S7.3-4). When a proband is identified with a disease-causing mutation, targeted genotype screening can identify mutation positive relatives (S7.3-1), with approximately 35% of mutation positive individuals ultimately developing progressive disease expression (S7.3-1,S7.3-4). In studies of arrhythmogenic right ventricular cardiomyopathy mutation-positive individuals who do not initially manifest the disease, 8% to 16% have a major arrhythmic event over the next 7 to 39 years (S7.3-1,S7.3-4,S7.3-26). Early identification of affected or potentially affected family members can allow lifestyle modifications in sports participation and serial monitoring for development of electrocardiographic abnormalities, symptoms, ventricular dysfunction, or arrhythmia. As genetic testing for arrhythmogenic right ventricular cardiomyopathy has subtle complexities, the decision to proceed with family screening is facilitated by informed genetic counseling to discuss the cost of testing, the potential lack of a single gene as the determinant for disease expression, psychological implications of uncertain disease progression, and implications for lifestyle modification, screening, and potential treatment.
2. Cardiac MRI provides high-quality assessment of ventricular function, size, regional wall motion abnormalities, and extent of scar and fibrosis (late gadolinium enhancement) that are seen in 30% to 95% of patients with the clinical diagnosis of arrhythmogenic right ventricular 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 involvement noted in 4% to 9% of patients (S7.3-37—S7.3-40). Cardiac MRI should include assessment of late gadolinium enhancement with quantification of fibrosis. Application of the 2010 Task Force Criteria to cardiac MRI criteria for diagnosis of arrhythmogenic right ventricular cardiomyopathy has improved the specificity of this test (S7.3-5,S7.3-8). Electrocardiographic and Holter findings precede detectable cardiac MRI abnormalities in arrhythmogenic right ventricular cardiomyopathy mutation-positive individuals, with only 4% of patients with normal electrocardiographic and Holter results having cardiac MRI abnormalities, suggesting that evaluation of cardiac structure and function using cardiac MRI may be unnecessary in mutation-positive individuals who do not have electrical abnormalities (S7.3-7). The presence of both electrocardiographic abnormalities and abnormal cardiac MRI findings may identify patients at an increased risk for developing sustained VA (S7.3-7,S7.3-38). Areas of scar identified on cardiac MRI have correlated with the location of VT substrate identified by endocardial and epicardial mapping (S7.3-38). During early stages of disease, a baseline cardiac MRI may provide useful information along with electrocardiographic and rhythm abnormalities to monitor disease progression over time. Experience and expertise in interpretation of cardiac MRI are important (S7.3-5,S7.3-8).
3. Arrhythmogenic right ventricular cardiomyopathy is characterized by progressive ventricular myocyte loss with replacement by fatty or fibrous tissue, and is associated with progressive ventricular dysfunction that may involve both ventricles. VA, syncope, and SCD may occur at a relatively young age, particularly in the second and third decades of life and often occurring during physical activity (S7.3-1,S7.3-16,S7.3-22,S7.3-41). Sustained VT is an important predictor of SCA and SCD or appropriate ICD shocks in patients with arrhythmogenic right ventricular cardiomyopathy (S7.3-10,S7.3-13). In patients receiving an ICD for primary prevention, appropriate ICD shocks are reported in 24% to 48% of patients (S7.3-9,S7.3-10,S7.3-12,S7.3-13). As sustained VT in arrhythmogenic right ventricular cardiomyopathy patients is monomorphic in 55% to 90% of episodes based on ICD interrogation or electrophysiological studies (S7.3-12,S7.3-36), antitachycardia pacing algorithms are used to terminate VT.
4. Frequent PVCs, >760 to 1000 per 24 hours during ambulatory rhythm monitoring, correlate with arrhythmic risk (S7.3-9,S7.3-23). The presence of NSVT or sustained VT is an important predictor of adverse cardiac events (S7.3-9,S7.3-12,S7.3-13,S7.3-42,S7.3-43). The increased arrhythmia risk conferred by intense exercise is consistent with beta-adrenergic modulation of disease expression (S7.3-17,S7.3-20,S7.3-21). An observational registry reported that treatment with atenolol or amiodarone was associated with less clinically relevant VA, while sotalol was associated with no effect or increased arrhythmia (S7.3-15). Ambulatory monitoring to assess VA burden and adequacy of beta-blocker therapy is usually used (S7.3-9,S7.3-14,S7.3-23,S7.3-42).
5. Patients with arrhythmogenic right ventricular cardiomyopathy have a significantly increased risk of SCD during exertion (S7.3-16,S7.3-17,S7.3-20,S7.3-21). Vigorous exercise in patients with arrhythmogenic right ventricular cardiomyopathy has been shown to impair myocardial function by echocardiography and cardiac MRI (S7.3-19). Participation in high intensity/duration or endurance physical activity accelerates the penetrance/disease progression and arrhythmic risk for arrhythmogenic right ventricular cardiomyopathy patients and mutation positive individuals, as well as mutation positive family members (S7.3-17,S7.3-19—S7.3-21). Patients with arrhythmogenic right ventricular cardiomyopathy who participate in competitive sports are at increased risk for VT or SCD, compared with those who participate in recreational sports or are inactive (S7.3-17—S7.3-19,S7.3-21). Exercise influences disease progression in a linear manner; family members who limited activity to less than the AHA recommended minimum for activity guidelines (<650 metabolic equivalent hours per year [MET-Hr/year]) were less likely to develop VA or disease progression (S7.3-21). In a study of arrhythmogenic right ventricular cardiomyopathy probands and exercise, athletes (defined as subjects with ≥4 h vigorous exercise/week) were found to have reduced biventricular function compared with nonathletes in arrhythmogenic right ventricular cardiomyopathy patients and in mutation-positive family members (S7.3-19). Many advise limiting exercise intensity and duration to <650 MET-Hr/year, or 12.5 MET-Hr/week (S7.3-21).
6. The proband with arrhythmogenic right ventricular cardiomyopathy is usually diagnosed by the presence of clinical symptoms along with the presence of arrhythmogenic right ventricular cardiomyopathy Task Force criteria including: abnormalities on ECG, structural and functional changes of either ventricle, arrhythmias, and arrhythmogenic right ventricular cardiomyopathy in first-degree relatives (S7.3-6). A pathogenic genetic mutation was added to the major Task Force criteria in 2010 (S7.3-44). The yield of genetic testing in probands with suspected arrhythmogenic right ventricular cardiomyopathy is generally 30% to 54%, and is up to 58% among patients with a strong family history of SCD in multiple members (S7.3-3,S7.3-25,S7.3-45). A negative genetic test for arrhythmogenic right ventricular cardiomyopathy does not exclude the disease, and a positive genetic test currently does not guide therapy (S7.3-22). For the proband with a clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy, identification of pathogenic mutations provides limited prognostic information relative to the risk of VT/VF (S7.3-22,S7.3-26) or development of HF (S7.3-22). In a large multicenter study, the presence of positive mutations among probands was not associated with a difference in mortality or cardiac transplantation (S7.3-1). However, the identification of a pathogenic mutation facilitates targeted genetic screening for that mutation in first-degree relatives, that may identify approximately 60% to 70% as gene positive (S7.3-1), highest among siblings, and those with symptoms (S7.3-4). Screening for the specific mutation can identify some gene positive family members prior to disease expression, while relieving others from the need for lifestyle changes and long-term monitoring (S7.3-2,S7.3-3).
7. Syncope is reported in 16% to 39% of arrhythmogenic right ventricular cardiomyopathy patients at the time of diagnosis (S7.3-13,S7.3-14,S7.3-16,S7.3-41,S7.3-43), is frequently exercise-related, and has been associated with high arrhythmic risk in some studies (S7.3-10,S7.3-41). Among patients with arrhythmogenic right ventricular cardiomyopathy and implanted ICDs, syncope was an important predictor of appropriate shocks in 1 study (S7.3-10), but not in other studies (S7.3-9,S7.3-12,S7.3-13,S7.3-43). Studies have not provided information about ventricular function or abnormalities on ECG in patients with syncope, limiting its assessment as an independent risk factor. Syncope may be a harbinger of progression of underlying disease and should be integrated into the decision-making process for ICD implantation with the patient.
8. Asymptomatic patients with arrhythmogenic right ventricular cardiomyopathy and no VA or ventricular dysfunction are generally observed without antiarrhythmic therapy other than beta-blocker therapy, with ongoing periodic reassessment for the development of arrhythmias or ventricular dysfunction (S7.3-46,S7.3-47). Atenolol was shown to reduce VA in 1 study (S7.3-15). Ambulatory monitoring and/or exercise testing can be performed to assess adequacy of beta-blocking dosing.
9. Interrogation of ICDs shows that >90% of spontaneous sustained VTs in arrhythmogenic right ventricular cardiomyopathy are monomorphic (S7.3-12), while sustained monomorphic VT is inducible at electrophysiological study in 55% of patients (S7.3-36). VT is usually related to scar-related reentry, and the subepicardium usually has more extensive scar than the endocardium (S7.3-27). In experienced centers, use of epicardial mapping and ablation is associated with better outcomes (S7.3-27,S7.3-28,S7.3-30,S7.3-31,S7.3-33). Important complications including pericardial tamponade, MI, and death occur in 2.3% to 3.3% of ablation cases (S7.3-27–S7.3-29), emphasizing the need for performance in centers with specialized expertise in epicardial procedures. Ablation reduces the frequency of recurrent VT, although 27% to 55% of patients (S7.3-27,S7.3-28) have at least 1 recurrence; ablation of VT in arrhythmogenic right ventricular cardiomyopathy patients does not eliminate the need for an ICD in appropriate candidates. The potential risk of VT recurrence due to disease progression should be reviewed with patients when considering ablation. There are no randomized comparisons of antiarrhythmic therapy to suppress recurrent VT. Beta blockers, sotalol and amiodarone have been used (S7.3-15). In an observational series, sotalol suppressed inducible VT in 58% of patients with <10% of patients experiencing arrhythmia recurrence during follow-up (S7.3-48). Effectiveness of the different medications appears to be variable, and so more studies are needed.
10. In arrhythmogenic right ventricular cardiomyopathy, areas of fibrofatty scar in the RV free wall create areas of delayed ventricular activation causing fractionated deflections following the QRS, known as epsilon waves on the surface ECG (a major criterion) and late potentials in the signal averaged ECG (minor criterion) in the 2010 Task Force Criteria for diagnosis of arrhythmogenic right ventricular cardiomyopathy (S7.3-6). When the standard ECG QRS duration is ≤110 ms, criteria for abnormal signal-averaged ECG include any 1 of the following: filtered QRS duration ≥114 ms, duration of the terminal QRS <40 µV exceeding 37 ms, or a root mean square voltage in the terminal 40 ms of ≤20 µV (S7.3-6). Abnormal findings on signal averaged ECG correlated with disease severity on cardiac MRI (S7.3-35), and increased adverse events in males (S7.3-34). In an assessment of the diagnostic use of testing for arrhythmogenic right ventricular cardiomyopathy, signal averaged ECG was of greater value than cardiac MRI or biopsy (S7.3-14).
11. The value of an electrophysiological study is uncertain in asymptomatic arrhythmogenic right ventricular cardiomyopathy patients with preserved ventricular function in predicting subsequent risk for SCD. Studies of programmed ventricular stimulation in patients with definite or probable arrhythmogenic right ventricular cardiomyopathy include most symptomatic patients, making recommendations on asymptomatic patients difficult. Electrophysiological studies induce sustained VT in approximately 60% of patients (S7.3-10,S7.3-36); many of whom have had prior spontaneous episodes of sustained VT. In patients with primary prevention ICDs, inducible sustained VT did not predict subsequent appropriate ICD shocks (S7.3-13). In 1 study including symptomatic patients, patients without inducible VT were less likely to receive appropriate ICD shocks (S7.3-9). In asymptomatic patients without evidence of VA on ambulatory monitoring, a negative electrophysiological study may have limited value in decision-making for an ICD.
7.4 Hypertrophic Cardiomyopathy
|III: No Benefit||B-NR|
|III: No Benefit||B-NR|
Refer to the ACCF/AHA HCM guideline for the definition of HCM (S7.4-36).
Recommendation-Specific Supportive Text
1. Patients with HCM have approximately a 1% risk of SCD per year (S7.4-1,S7.4-6). Selection of patients who are appropriate candidates for implantation of an ICD can be a difficult clinical decision because of the individuality of each patient and family, variable definitions of risk factors and risk modifiers, sparse clinical data, the relative infrequency of both HCM and SCD in most clinical practices, and the potential complications of living with an ICD. Table 8 lists risk factors and risk modifiers associated with SCD in patients with HCM. ICD risk stratification should be performed every 1 to 3 years in patients with HCM. There 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 associated with a risk of sustained monomorphic VT (S7.4-40). Age is also an important consideration, as sudden death risk is greater in those <30 years of age, and low in patients whose initial presentation is after the age of 60 years (S7.4-5,S7.4-26), (S7.4-41).
2. HCM is the most common cause of SCD in individuals <40 years of age (S7.4-26). Individuals who have survived an episode of SCD, VF, or sustained VT resulting in syncope or hemodynamic compromise warrant ICD implantation (S7.4-1,S7.4-6,S7.4-9,S7.4-10). Although there are no RCTs assessing the use of the ICD in patients with HCM who have survived SCD, 1 study reported that 54% of patients with an ICD placed for secondary prevention received appropriate ICD therapy during an average follow-up of 4.6 years (S7.4-10). Select patients with HCM may be candidates for implantation of the subcutaneous implantable cardioverter-defibrillator (S7.4-42); however, more data on this group are needed especially given their higher risk of T wave oversensing that may increase the risk of inappropriate ICD shocks.
3. Clinical and/or genetic screening of first- and second-degree family members of patients with HCM is important to identify those with unrecognized disease. Genetic counseling should precede genetic testing of family members to enhance their understanding of the usefulness and cost of testing (S7.4-18,S7.4-20,S7.4-43). On the basis of family history, clinical screening, and pedigree analyses, the pattern of inheritance is ascertained to identify and manage relatives at risk (S7.4-13,S7.4-14,S7.4-18,S7.4-19,S7.4-43—S7.4-45). Because familial HCM is a dominant disorder, the risk that an affected patient will transmit disease to each offspring is 50%. When a pathogenic mutation is identified in an index patient, the genetic status of each family member can be readily ascertained. Relatives with overt HCM will have the same pathogenic HCM mutation as the index patient. Pathogenic mutations may also be identified in other relatives with unknown clinical status. These mutation-positive individuals should be evaluated by physical examination, electrocardiography (S7.4-11,S7.4-17), and echocardiography (S7.4-12,S7.4-16,S7.4-17) and, if HCM is identified, these individuals should undergo risk stratification. Gene-positive subjects without evidence of HCM may be at risk for future development of HCM and benefit from ongoing clinical evaluation (S7.4-15,S7.4-46,S7.4-47). If the proband’s implicated mutation is the bona fide disease–causing mutation, then mutation-negative family members and their descendants are not at an increased risk for developing HCM and do not need further evaluation. However, such mutation-negative family members must have an echocardiogram to ensure genotype and phenotype concordance.
4. In a study of 1,053 unrelated patients with clinically manifest HCM, 359 patients (34%) were genotype positive for an HCM-associated mutation in ≥1 HCM-associated genes (S7.4-22). Whether the results of genetic testing in the proband improve outcomes is uncertain, but identification of a mutation can help inform screening of relatives.
5. Genetic counseling is important in patients with HCM, and genetic screening of relatives is also important unless there are no living first- or second-degree relatives. Most HCM is caused by an autosomal dominant mutation in genes that encode sarcomere proteins or sarcomere-associated proteins. Presence of a pathogenic sarcomere protein gene mutation in patients with HCM identifies risk of LV dysfunction and adverse outcome irrespective of the myofilament involved (S7.4-13—S7.4-15,S7.4-18,S7.4-19,S7.4-22). A single mutation in 1 of the 2 alleles (or copies) of a gene is sufficient to cause HCM; however, 5% of patients with HCM have ≥2 mutations in the same gene or different genes, which can be a marker for worse outcomes (S7.4-13,S7.4-34,S7.4-48). When genetic testing reveals a mutation in the index patient, ascertainment of genetic status in first- and second-degree relatives can be predictive of risk for developing HCM (S7.4-14,S7.4-49). Relatives with overt HCM will have the same pathogenic HCM mutation as the index patient.
6. Several studies have described an independent relationship between hypertrophy and SCD when the magnitude of hypertrophy is ≥30 mm (S7.4-2,S7.4-3,S7.4-23,S7.4-24). Risk does not abruptly increase for patients with a ≥30 mm wall thickness, but it rather increases in a linear manner (S7.4-24) and appears to carry more prognostic significance in younger patients. A young adult with hypertrophy that approaches 30 mm may have similar or greater SCD risk than an older patient with maximum wall thickness ≥30 mm (S7.4-23,S7.4-50).
Patients with HCM are at an increased risk for SCD if they have a first-degree relative who experienced SCD presumably caused by HCM. Family history appears to be an independent predictor of SCD although the supportive studies are small and observational (S7.4-25,S7.4-26). Syncope can be neurally mediated or medication-related as well as due to VA and requires a careful evaluation before considering it a risk factor for SCD (S7.4-8,S7.4-26). In an analysis, syncope that was unexplained or thought not to be neurally mediated was associated with SCD risk only when it occurred within the past 6 months but not if the most episode occurred >5 years previously (S7.4-8).
7. Although sustained VT is clearly associated with SCD, the data for NSVT are less robust. Most studies do not support NSVT as an independent risk factor for SCD in patients with HCM (S7.4-2,S7.4-26,S7.4-27), but the risk increases if risk modifiers are present, especially in patients <30 years of age (S7.4-27). Up to one third of patients with HCM have an abnormal blood pressure response during exercise testing (defined variably as either a 20 mm Hg decrease in blood pressure or a failure to increase systolic blood pressure by at least 20 mm Hg during effort) (S7.4-28,S7.4-29). This finding has been postulated to be a risk factor for SCD; however, it is unclear how this relates to the increase in dynamic LV outflow tract obstruction that occurs with exertion, a hemodynamic condition that is readily modifiable with medication or mechanical procedures. The significance of an abnormal blood pressure response with exercise predicting SCD risk increases in the presence of risk modifiers (Table 8).
8. Most studies have found that NSVT alone has a low positive predictive value for SCD (S7.4-2,S7.4-26,S7.4-27); therefore, use of an ICD is more appropriate if risk modifiers are also present. An abnormal blood pressure response to exercise has also been associated with the risk of sudden death (S7.4-5,S7.4-28,S7.4-29), but it is unclear how this relates to the increase in dynamic LV outflow tract obstruction that occurs with effort, which is often treatable. The significance of an abnormal blood pressure response with exercise for predicting SCD risk increases when risk modifiers are present (Table 8).
9. The ICD is recommended for the prevention of SCD in patients with HCM who have survived sustained VT or VF as antiarrhythmic medications have limited effectiveness (S7.4-31). Amiodarone has been associated with improved survival in observational studies and is an option for patients for whom an ICD is not feasible due to limited expectation for survival or patient preference (S7.4-30,S7.4-31).
10. Approximately one third of consecutive patients with HCM undergoing an electrophysiological study have polymorphic VT or VF induced by programmed ventricular stimulation, but the results of programmed stimulation do not predict SCD risk. Programmed ventricular stimulation in patients with HCM has low predictive value and a nontrivial risk of complications (S7.4-32,S7.4-33,S7.4-51). Electrophysiological studies can help to clarify the diagnosis of wide complex tachycardia or guide therapy for supraventricular tachycardia or bundle branch reentry.
11. SCD may cluster in certain families with HCM, and the possibility that specific sarcomere mutations may confer SCD risk has been hypothesized. However, subsequent studies of selected patients with HCM (S7.4-34,S7.4-35) were unable to establish a clinically useful relation between genotype and SCD risk. In some cases, the rate of adverse events (and prevalence of associated SCD risk factors) was lower in patients with mutations initially felt to be malignant than it was in those with mutations believed to be benign (S7.4-34,S7.4-35). Data from series of unselected consecutive outpatients suggest that most mutations are novel and limited to particular families (S7.4-34,S7.4-35). Therefore, routine mutation screening would appear to be of little prognostic value in HCM (S7.4-52). The short-term risk of sudden death in patients who are genotype positive but have no other manifestations of the disease appears to be low (S7.4-53). Therefore, an ICD is not indicated in these individuals.
Recommendation-Specific Supportive Text
1. Myocarditis is an inflammatory process often related to infection (S7.5-1,S7.5-5—S7.5-9). When patients are treated in centers with the availability of mechanical hemodynamic support procedures, cardiac catheterization, endomyocardial biopsy, advanced cardiac imaging procedures, and arrhythmia management including ICD implantation, outcomes appear improved (S7.5-1). The acute course of myocarditis varies ranging from an asymptomatic finding of transient ST-T changes noted on ECG to cardiogenic shock and recurrent VA (S7.5-10—S7.5-12). Acute management is largely supportive and can rapidly advance to requiring mechanical support (S7.5-13,S7.5-14). Cardiac arrhythmias range from conduction abnormalities to life-threatening VT and VF (S7.5-15—S7.5-17). Arrhythmias may require antiarrhythmic medications and/or device therapy (S7.5-18). Giant cell myocarditis is fairly uncommon, but it is of particular importance because it typically affects young individuals and is usually fatal if untreated (S7.5-2—S7.5-4,S7.5-19). VT may require antiarrhythmic medications such as amiodarone and/or an ICD that in some instances can be used as a bridge to more advanced HF therapies such as LVAD or transplant. Myocarditis and SCD have been reported with HIV infection (S7.5-20,S7.5-21). Systemic lupus erythematous can cause myocarditis but only rarely VT or VF (S7.5-8,S7.5-22). In patients with Chagas disease, acute myocarditis is rare but more than one third of affected patients develop late myocardial damage with progressive HF. Conduction defects with progression to complete heart block and VT or VF are common. Amiodarone appears to be effective in treating VA (S7.5-23). An ICD is frequently used in the late phase of myocarditis (S7.5-24), and radiofrequency catheter ablation has been successfully used to control recurrent VA in some patients (S7.5-25).
2. Giant cell myocarditis is fairly uncommon, but it is of particular importance as it typically affects young individuals and is usually fatal if untreated. The diagnosis is confirmed by endomyocardial biopsy. Patients may develop heart block, requiring a temporary or a permanent pacemakers. An ICD and antiarrhythmic medications, such as amiodarone are often used in the acute phase to treat VT or VF and reduce the risk of SCD (S7.5-2—S7.5-4,S7.5-19,S7.5-26—S7.5-28).
7.6 Cardiac Sarcoidosis
Recommendation-Specific Supportive Text
1. Sarcoidosis is a systemic granulomatous disease of unknown cause. Pulmonary involvement is most frequent but any organ can be affected. Cardiac involvement, diagnosed by cardiac MRI or positron emission tomography (PET), has been reported in up to 55% of patients with extracardiac disease, while isolated cardiac sarcoidosis was seen in most patients diagnosed with cardiac sarcoidosis in 1 report (S7.6-17). Cardiac manifestations include conduction abnormalities, VA, and depressed ventricular function with or without HF, and these contribute greatly to a higher mortality in cardiac sarcoidosis compared with sarcoidosis without cardiac involvement (S7.6-2). In a 25-year study of 110 patients with cardiac sarcoidosis in Finland with HF at presentation, marked LV dysfunction at diagnosis (LVEF <35%), and isolated cardiac sarcoidosis predicted an adverse outcome (S7.6-1). VA can also occur in patients with relatively normal LV function, some of whom have RV involvement that can mimic arrhythmogenic right ventricular cardiomyopathy. Several reports of patients with cardiac sarcoidosis and ICDs implanted for either primary or secondary prevention of SCD show a high frequency of appropriate ICD therapies (S7.6-3—S7.6-5), supporting use of ICDs for primary and secondary prevention of SCD according to the indications applied for other cardiomyopathies. The frequency of conduction abnormalities often warrants a device that provides bradycardia pacing as well.
2. Patients with cardiac sarcoidosis can experience VA and SCD, even if the LVEF is normal, and approaches to identification of patients at risk of SCD despite preserved LV function are not well defined. A number of studies have evaluated the role of cardiac MRI for predicting VA and SCD. A meta-analysis (S7.6-6), which included 760 patients in 10 studies, found that late gadolinium enhancement was associated with increased all-cause mortality and more VA compared with those without late gadolinium enhancement. Applicability is limited by the lack of precise quantification of late gadolinium enhancement burden that may allow for more nuanced risk stratification. Some studies suggested that a threshold effect exists, with extensive LV and RV involvement being a particularly high-risk feature (S7.6-7,S7.6-8). However, late gadolinium enhancement can be present even if the LVEF is >50% and was associated with a risk of death or VT of 4.9% per year compared to 0.24% per year when late gadolinium enhancement was absent in 1 observational study (S7.6-7). PET for assessing inflammation and scar is also being increasingly used, but data are limited. In 1 report, the presence of inflammation and RV involvement on PET scanning was associated with increased risk of death or e g of relatives (S7.6-10). Electrophysiological studies in a series of 76 patients with evidence of cardiac sarcoid found that 11% had inducible VT. During a median follow-up of 5 years, 75% of patients with inducible VT had spontaneous VT or death compared with 1.5% of those who did not have inducible VT (S7.6-18).
3. Electrophysiological study has been proposed as a potential tool for risk stratification of VA and SCD in patients who had demonstrable evidence of cardiac sarcoidosis based on imaging studies or biopsy, but do not have documented arrhythmias or arrhythmic symptoms nor meet standard primary prevention criteria for ICD implantation.
One study evaluated 76 patients with documented cardiac sarcoidosis by PET or cardiac MRI who underwent electrophysiological study (S7.6-12). Eight (11%) were inducible for sustained VAs and received an ICD, while the rest did not receive an ICD because they were not inducible. LVEF was lower in patients with inducible VA (36.4 + 4.2% versus 55.8 + 1.5%). Over a median follow-up of 5 years, 6 of 8 patients in the group with inducible VA had VA or died, compared with 1 death in the negative group (S7.6-12). An important caveat is that it remains unclear if electrophysiological study is more predictive than LVEF alone, because inducibility appears to reversely correlate with LVEF. Furthermore, in this study the average LVEF of the inducible patients declined further during the followup period (S7.6-12).
4. In addition to VA and LV dysfunction, conduction abnormalities, including heart block, can also be a common manifestation of cardiac sarcoidosis. Patients with documented VA and LV dysfunction are at increased risk of cardiac events including cardiac death. One study compared outcomes in 22 patients with high-degree atrioventricular block as the initial manifestation of cardiac sarcoidosis, to 31 patients who initially presented with VT and/or HF. After a median follow up of 34 months, the patients who presented with heart block had fewer HF hospitalization, yet fatal cardiac events, including sustained VAs, were similar to those with VT and/or HF, suggesting that the risk of fatal cardiac events is high regardless of the initial clinical presentation (S7.6-13). In the same study, administration of steroids led to some clinical improvement, with some patients recovering conduction, yet steroid effectiveness was not universal and did not seem to be protective against adverse cardiac events (S7.6-13).
5. Several studies have attempted to evaluate the role of immunosuppression for reducing VA in patients with cardiac sarcoidosis, but results have been inconsistent (S7.6-14—S7.6-16). Furthermore, a worsening of VA has been reported with immunosuppressive therapy (usually glucocorticoids) in a number of patients, including electrical storm developing in some within 12 months of initiating therapy (S7.6-15). One study reported a decrease of arrhythmia burden with steroid therapy but only when given in the early stages of the disease; those with advanced LV dysfunction did not experience benefit (S7.6-16). A systematic combined treatment approach was successful in 63% of patient in a series in which medical therapy included both steroids and antiarrhythmic medications, followed by radiofrequency catheter ablation if needed (S7.6-14). Immunosuppressive therapy may serve a dual purpose beyond arrhythmia effects as it may help stabilize disease progression and prevent further deterioration of LV function, although this has yet to be demonstrated in RCTs. Steroids do not appear to reverse advanced ventricular dysfunction once present, which supports the importance of early diagnosis and intervention (S7.6-1). PET scanning for assessing inflammation and scar is being increasingly used in sarcoidosis as well, but data supporting its use for guiding therapy of arrhythmias are limited.
7.6.1 Other Infiltrative Cardiomyopathies
Infiltrative cardiomyopathies are a heterogeneous group of uncommon systemic diseases with associated cardiac involvement. In some infiltrative cardiomyopathies, such as Fabry’s disease, VAs are uncommon. Some, such as hemochromatosis, are highly treatable especially when diagnosed early. In all cases, treatment of the underlying condition must accompany management of cardiac arrhythmias. Most studies of infiltrative cardiomyopathies and arrhythmias are small and observational (S7.6.1-1) but, in general, unless contraindications are present, VAs should be treated as in any other cardiomyopathy. See Section 7.6 for sarcoidosis. Until recently, cardiac amyloidosis was associated with a very poor prognosis with patients ultimately succumbing to progressive HF (S7.6.1-2). This perception is changing with advances in medical therapy for light-chain amyloidosis, which have led to improved outcomes (S7.6.1-3). Yet, decisions must be individualized because data remain too limited to allow formal recommendations as published reports on ICD effectiveness in amyloidosis are small, observational and with limited follow up (S7.6.1-4). Whether there is greater benefit to ICD placement in light chain amyloidosis versus transthyreitin-related amyloidosis remains uncertain, because most studies included mainly patients with amyloid light-chain amyloidosis for which the rate of VA may be greater and prognosis is generally worse. Whether ICDs are effective for primary prevention of SCD is uncertain, but many deaths in patients with cardiac amyloidosis do not appear to be preventable by an ICD (S7.6.1-2).
7.7 Heart Failure
7.7.1 HF With Reduced Ejection Fraction
Patients with HFrEF are at an increased risk for VA and SCD. The risk is increased irrespective of HFrEF etiology (S7.7.1-6). SCD makes up a greater proportion of deaths in patients with milder HF symptoms and lesser proportion in those with moderate/severe HF symptoms (S7.7.1-7). The reported incidence of SCD varies depending on the definition used and the population studied. Although many deaths, classified as sudden, are indeed due to lethal VA, others may be due to bradyarrhythmias, pulseless electrical activity, and sudden hemodynamic deterioration (S7.7.1-7—S7.7.1-9).
Medical therapy with neurohormonal agents decreases the risk of SCD by reducing both the incidence of VA and disease progression (S7.7.1-7,S7.7.1-10—S7.7.1-12). Despite GDMT for HFrEF, some patients remain at risk for SCD, and an ICD may be helpful. See Sections 7.1 and 7.2 for the indications on ICDs in patients with reduced LVEF. CRT, in appropriate patients, has also been shown to reduce the incidence of SCD (S7.7.1-13).
The pathophysiology of SCD in HF is complex, resulting from interactions between both functional and structural changes that occur in patients with HFrEF that result in increased susceptibility to SCD (S7.7.1-14). Although many of the risk factors are shared among HFrEF patients, the reason that SCD strikes a particular individual is usually unknown; however, some individuals may have a genetic susceptibility (S7.7.1-15). Varying degrees of myocardial fibrosis, neurohormonal activation, and increased wall stress alter the electrophysiological properties with changes in cell coupling, ionic currents (electrical remodeling), and calcium handling that likely contribute to the development of lethal VA (S7.7.1-16). Contributing factors extrinsic to the heart include electrolyte abnormalities related to volume shifts and diuretic use, sympathetic activation, hemodynamic stress, and hypoxia.
Recommendation-Specific Supportive Text
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 status and/or use of inotropic infusion. Although no randomized data on ICD use in this population exist, data from observational and large registry studies of patients awaiting heart transplant suggest improved survival in patients with an ICD (S7.7.1-1,S7.7.1-4,S7.7.1-5). One alternative to ICD in this population is the wearable cardioverter-defibrillator (S7.7.1-2,S7.7.1-3). The recommendation in this section is relevant to those patients without an ICD where there is a plan to discharge the patient to home to await cardiac transplant and not, for example, to those patients who remain hospitalized with no intention to discharge home until transplant occurs. For those patients with an LVAD, the decision to place an ICD is generally independent of whether they are awaiting heart transplant but rather the indication in those patients is generally based on the need to treat VA (S7.7.1-17).
7.7.2 HF With Preserved Ejection Fraction
Nearly half of the patients with HF have a preserved LVEF (S7.7.2-1). These patients tend to be older and have more comorbidities than patients with HFrEF. However, although the rate of SCD is lower in patients with HF with preserved ejection fraction (HFpEF) than in patients with HFrEF (S7.7.2-2), nearly a quarter of all deaths among patients with HFpEF are sudden (S7.7.2-3—S7.7.2-5). The challenge in preventing SCD in patients with HFpEF is identifying which patients are at a high enough risk to benefit from preventive therapies. Studies exploring noninvasive risk factors for SCD in patients with HFpEF do not identify consistent factors with the exception of ischemic heart disease (S7.7.2-2,S7.7.2-6). Consequently, there is no accepted noninvasive test to identify high-risk patients with HFpEF. Invasive risk stratification with an electrophysiological study shows promise in this population (S7.7.2-7,S7.7.2-8). This topic is currently being studied in the PRESERVE-EF (Risk Stratification in Patients With Preserved Ejection Fraction) trial (NCT02124018).
Whether to include a recommendation related to an electrophysiological study in patients with HFpEF and ischemic heart disease was carefully considered by the writing committee. However, evidence was deemed insufficient to support a formal recommendation. Still, the pros and cons of an electrophysiological study can reasonably be considered in select patients with HFpEF and ischemic heart disease who are experiencing symptoms suggestive of a VA.
7.7.3 Left Ventricular Assist Device
Recommendation-Specific Supportive Text
1. Patients with an LVAD have a high risk of VA, particularly those with a history of arrhythmias (S7.7.3-2—S7.7.3-4). The increased risk of VA may be due to myocardial irritation from insertion of the LVAD inflow cannula, LV compression due to a suctioning effect from the LVAD, inotropic support frequently needed by some patients, and repolarization changes that can occur after LVAD placement. Although VT/VF is tolerated by some patients with an LVAD, others experience a decrease in flow as the RV is unsupported; syncope and hypoperfusion can result. Having an ICD can allow for prompt termination of VA before significant hemodynamic consequences occur. Data on ICDs in patients with an LVAD are from observational series. A systematic review of 6 observational studies observed that within 7 months, 26% of patients with an LVAD had died (S7.7.3-1). The death rate was lower among patients who previously had an ICD (16% versus 32%), suggesting a 39% relative-risk reduction in all-cause mortality in an adjusted analysis (S7.7.3-1). Patients with a history of pre-LVAD VA have nearly a ≥10-fold risk of post-LVAD VA (S7.7.3-2—S7.7.3-4). In many of the initial studies demonstrating ICD benefit, older pulsatile LVAD devices were in use (S7.7.3-2,S7.7.3-5). Studies of ICD use with the newer, continuous flow LVADs have inconsistently shown benefit (S7.7.3-1,S7.7.3-4,S7.7.3-6,S7.7.3-7). Of note, approximately 2 of 10 patients with an LVAD develop an LVAD related infection in the first year (S7.7.3-8,S7.7.3-9).
7.7.4 ICD Use After Heart Transplantation
Recommendation-Specific Supportive Text
1. Development of disease in the transplanted heart places some patients at an increased risk of SCD that has ranged from 10% to 35% in observational studies (S7.7.4-4,S7.7.4-5). Both rejection and a decreased LVEF are predictors of SCD. The mechanisms underlying SCD in patients with a heart transplant include damage to the conduction system itself and VA due to coronary vasculopathy or during episodes of acute rejection. Several small case series observing appropriate ICD termination of VA suggest that an ICD can be beneficial in selected patients, particularly those with severe allograft vasculopathy, unexplained syncope, a history of SCA, and severe LV dysfunction (S7.7.4-1—S7.7.4-3). Additionally, a patient with severe allograft vasculopathy who is being considered for retransplant may be appropriate for an ICD as a bridging device. Secondary prevention indications for an ICD in patients with a heart transplant are identical to those in other patients.
7.8 Neuromuscular Disorders
The muscular dystrophies are a group of inherited diseases affecting skeletal and cardiac muscle. Some present primarily as a NICM (e.g., Duchenne, Becker, and limb-girdle types 2C, 2F, and 2I), while others present primarily as conduction system degeneration with a variable association with cardiomyopathy (e.g., myotonic dystrophy types 1 and 2, Emery-Dreifuss, limb-girdle type 1B; summarized in Table 9) (S7.8-15). Because SCD can occur either due to VA or due to bradyarrhythmias from rapid and unpredictable progression of conduction system disease, the clinician is faced with the challenge of identifying those patients who would benefit from prophylactic pacemaker or ICD implantation. There should be a high level of concern for those patients with muscular dystrophy who present with arrhythmia symptoms (S7.8-15). The current guideline focuses on VA and indications for implantation of an ICD. The indications for permanent pacemaker are discussed in another ACC/AHA/HRS guideline (S7.8-16).
Recommendation-Specific Supportive Text
1. In general, the indications for an ICD in patients with muscular dystrophy should follow standard ICD recommendations for patients with NICM (see Section 7.2.1 on Secondary Prevention and Section 7.2.2 on Primary Prevention of SCD with NICM). A high index of suspicion for bundle-branch reentrant tachycardia is warranted in patients with myotonic dystrophy who exhibit wide QRS complex tachycardia or tachycardia-related symptoms (S7.8-2).
2. In patients with Emery-Dreifuss and limb-girdle type 1B muscular dystrophies associated with Lamin A/C mutations, SCD accounts for about one third of all deaths (S7.8-4). Observational studies show a significant rate of appropriate ICD therapy in patients with cardiac conduction disorders who are gene positive for Lamin A/C mutation even if LV function is preserved (S7.8-3,S7.8-5,S7.8-17). In an observational study in which 38% had isolated skeletal muscular involvement but included patients with conduction defects and other risk factors (including PR interval >240 ms, left bundle-branch block, NSVT, or bradycardia requiring a permanent pacemaker) life-threatening VAs were relatively common; with 52% of patients receiving appropriate ICD therapy including approximately 40% of those patients with an LVEF ≥45% (S7.8-3). A study of patients who had Lamin A/C mutation, in which approximately 21% had a skeletal muscular dystrophy phenotype, SCD and appropriate ICD therapy were associated with NSVT, LVEF <45%, male sex, and Lamin A/C nonmissense mutations (S7.8-4). These observational studies support the use of an ICD when a pacing indication is present and likely also when evidence of progressive cardiac involvement such as cardiac conduction defects, NSVT or reduced LVEF is present (S7.8-8).
There is a paucity of data regarding the rare form of x-linked recessive Emery-Dreifuss muscular dystrophy (related to the Emerin gene mutation), but arrhythmias may be less frequent than for the Lamin A/C mutations (S7.8-15).
3. Cardiac involvement can occur in a number of neuromuscular dystrophies (Table 9). To determine cardiac involvement, a 12-lead ECG and echocardiogram are important for the initial clinical assessment, independent of symptom status. In general, the more extensive the cardiac involvement, including evidence of distal conduction disease, ventricular dysfunction, and atrial arrhythmias, the more likely a VA will occur. The initial evaluation for myotonic dystrophy patients includes ambulatory monitoring. In asymptomatic patients, some experts advocate for annual follow-up during the concealed phase of the disease with an annual 12-lead ECG to screen for development of conduction abnormalities. However, the optimal frequency of electrocardiographic screening is unknown (S7.8-18). Once cardiac involvement is present, either on the basis of conduction delay, atrial arrhythmias, or ventricular dysfunction, a low threshold for investigating symptoms or electrocardiographic findings by the clinician to determine the need for pacemaker implantation, invasive electrophysiological studies, or ICD implantation is optimal.
4. Up to one third of deaths in myotonic dystrophy patients are sudden (S7.8-9). Although commonly attributed to conduction block and asystole, SCD due to VT/VF has been recognized in patients with functioning permanent pacemakers, and spontaneous VA have been documented in some (S7.8-13,S7.8-19). The risk of SCD in patients with pacemakers suggests that an ICD may be preferred to a pacemaker. However, these patients are also at high risk of respiratory failure as a competing cause of death. Therefore, in patients with severe skeletal muscle involvement, a pacemaker or ICD may not improve outcomes (S7.8-15). A shared decision-making approach to selecting ICD or pacing therapy is warranted. Compared with myotonic type 1 patients, myotonic dystrophy type 2 patients are not well studied but may also benefit from the same approach.
7.9 Cardiac Channelopathies