Key Words: AHA Scientific Statements acute coronary syndrome ambulatory ECG monitoring antiarrhythmic drug therapy arrhythmogenic cardiomyopathy athletes cardiac electrophysiology cardiac resynchronization therapy cardiomyopathy catheter ablation congenital heart disease CT imaging ECG echocardiography electrophysiological testing genetic arrhythmias guidelines heart failure imaging implantable cardioverter- defibrillator implantable and external cardioverter devices medication- induced arrhythmias MR imaging myocardial infarction premature ventricular beats resuscitation sarcoidosis specific pathology (eg, congenital heart disease, myocarditis, renal failure) stable coronary artery disease sudden cardiac arrest sudden cardiac death torsades de pointes ventricular fibrillation ventricular tachycardia WRITING COMMITTEE MEMBERS Sana M. Al-Khatib, MD, MHS, FACC, FAHA, FHRS, Chair William G. Stevenson, MD, FACC, FAHA, FHRS, Vice Chair* Michael J. Ackerman, MD, PhD* William J. Bryant, JD, LLM David J. Callans, MD, FACC, FHRS* Anne B. Curtis, MD, FACC, FAHA, FHRS* Barbara J. Deal, MD, FACC, FAHA Timm Dickfeld, MD, PhD, FHRS* Michael E. Field, MD, FACC, FAHA, FHRS Gregg C. Fonarow, MD, FACC, FAHA, FHFSA* Anne M. Gillis, MD, FHRS* Christopher B. Granger, MD, FACC, FAHA* Stephen C. Hammill, MD, FACC, FHRS Mark A. Hlatky, MD, FACC, FAHA Jos A. Joglar, MD, FACC, FAHA, FHRS G. Neal Kay, MD Daniel D. Matlock, MD, MPH Robert J. Myerburg, MD, FACC Richard L. Page, MD, FACC, FAHA, FHRS 2017 by the American College of Cardiology Foundation, the American Heart Association, Inc., and the Heart Rhythm Society. AHA/ACC/HRS GUIDELINE 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society Circulation *Writing committee members are required to recuse themselves from voting on sections to which their specific rela- tionships with industry may apply; see Appendix 1 for detailed information. ACC/AHA Representative. HRS Rep- resentative. ACC/AHA Task Force on Performance Measures Liaison/HFSA Representative. ACC/AHA Task Force on Clinical Practice Guidelines Liaison. https://www.ahajournals.org/journal/circ ACC/AHA Task Force Members, see page e354 The American Heart Association requests that this document be cited as follows: Al-Khatib SM, Stevenson WG, Ackerman MJ, Bryant WJ, Callans DJ, Curtis AB, Deal BJ, Dickfeld T, Field ME, Fonarow GC, Gillis AM, Granger CB, Hammill SC, Hlatky MA, Joglar JA, Kay GN, Matlock DD, Myerburg RJ, Page RL. 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation. 2018;138:e272 e391. doi: 10.1161/CIR.0000000000000549. Developed in Collaboration With the Heart Failure Society of America CLINICAL STATEMENTS AND GUIDELINES TABLE OF CONTENTS Preamble e274 1. Introduction e275 1.1. Methodology and Evidence Review e275 1.2. Organization of the Writing Committee e276 1.3. Document Review and Approval e276 1.4. Scope of the Guideline e277 1.5. Abbreviations e279 2. Epidemiology e279 2.1. General Concepts e279 2.1.1. Premature Ventricular Complexes and Nonsustained VT e279 2.1.2. VT and VF During ACS e281 2.1.3. Sustained VT and VF Not Associated With ACS e281 2.2. Sudden Cardiac Death e281 2.2.1. Incidence of SCD e281 2.2.2. Population Subgroups and Risk Prediction e282 3. Mechanisms of VA e283 3.1. Cellular Mechanisms and Substrates e283 3.2. Automaticity e283 3.3. Triggered Activity e283 3.4. Reentry e284 4. General Evaluation of Patients With Documented or Suspected VA e284 4.1. History and Physical Examination e284 4.2. Noninvasive Evaluation e286 4.2.1. 12-lead ECG and Exercise Testing e286 4.2.2. Ambulatory Electrocardiography e286 4.2.3. Implanted Cardiac Monitors e287 4.2.4. Noninvasive Cardiac Imaging e287 4.2.5. Biomarkers e288 4.2.6. Genetic Considerations in Arrhythmia Syndromes e288 4.3. Invasive Testing e289 4.3.1. Invasive Cardiac Imaging: Cardiac Catheterization or CT Angiography e289 4.3.2. Electrophysiological Study for VA e289 5. Therapies for Treatment or Prevention of VA e290 5.1. Medication Therapy e290 5.1.1. Medications With Prominent Sodium Channel Blockade e290 5.1.2. Beta Blockers e293 5.1.3. Amiodarone and Sotalol e293 5.1.4. Calcium Channel Blockers e294 5.1.5. Nonantiarrhythmic Medications and Therapies e294 5.2. Preventing SCD With HF Medications e295 5.3. Defibrillators for Treatment of VA and SCD e295 5.4. Catheter Ablation e295 5.4.1. General Considerations e295 5.4.2. VA in Patients With No Apparent Structural Heart Disease e296 5.4.3. Scar-Related VT e296 5.5. Surgery and Revascularization Procedures in Patients With Ischemic Heart Disease e296 5.5.1. Surgery for Arrhythmia Management e297 5.6. Autonomic Modulation e297 6. Acute Management of Specific VA e297 7. Ongoing Management of VA and SCD Risk Related to Specific Disease States e301 7.1. Ischemic Heart Disease e301 7.1.1. Secondary Prevention of SCD in Patients With Ischemic Heart Disease e301 7.1.2. Primary Prevention of SCD in Patients With Ischemic Heart Disease e304 7.1.3. Treatment and Prevention of Recurrent VA in Patients With Ischemic Heart Disease e306 7.2. Nonischemic Cardiomyopathy e308 7.2.1. Secondary Prevention of SCD in Patients With NICM e308 7.2.2. Primary Prevention of SCD in Patients With NICM e309 7.2.3. Treatment of Recurrent VA in Patients With NICM e310 7.3. Arrhythmogenic Right Ventricular Cardiomyopathy e312 7.4. Hypertrophic Cardiomyopathy e315 7.5. Myocarditis e318 7.6. Cardiac Sarcoidosis e318 7.6.1. Other Infiltrative Cardiomyopathies e320 7.7. Heart Failure e321 7.7.1. HF With Reduced Ejection Fraction e321 7.7.2. HF With Preserved Ejection Fraction e321 7.7.3. Left Ventricular Assist Device e322 7.7.4. ICD Use After Heart Transplantation e322 7.8. Neuromuscular Disorders e322 7.9. Cardiac Channelopathies e324 7.9.1. Specific Cardiac Channelopathy Syndromes e325 8. VA in the Structurally Normal Heart e334 8.1. Outflow Tract and Atrioventricular Annular VA e335 8.2. Papillary Muscle VA e335 8.3. Interfascicular Reentrant VT (Belhassen Tachycardia) e335 8.4. Idiopathic Polymorphic VT/VF e336 9. PVC-Induced Cardiomyopathy e337 10. VA and SCD Related to Specific Populations e338 10.1. Athletes e338 10.2. Pregnancy e338 10.3. Older Patients With Comorbidities e339 10.4. Chronic Kidney Disease e340 10.5. Valvular Heart Disease e340 10.6. Sex-Related Differences in the Risk of SCD e340 10.7. Medication-Induced Arrhythmias e341 10.8. Adult Congenital Heart Disease e342 11. Defibrillators Other than Transvenous ICDs e347 11.1. Subcutaneous Implantable Cardioverter-Defibrillator e347 11.2. Wearable Cardioverter-Defibrillator e348 11.3. Automated External Defibrillator e349 12. Special Considerations for Catheter Ablation e349 13. Postmortem Evaluation of SCD e350 14. Terminal Care e351 15. Shared Decision-Making e351 CLINICAL STATEMENTS AND GUIDELINES 16. Cost and Value Considerations e352 17. Quality of Life e353 18. Evidence Gaps and Future Research Needs e354 Appendix 1: Author Relationships With Industry and Other Entities (Relevant) e387 Appendix 2: Reviewer Relationships With Industry and Other Entities (Comprehensive) e389 PREAMBLE 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 meth- ods to evaluate and classify evidence, provide a corner- stone for quality cardiovascular care. The ACC and AHA sponsor the development and publication of guidelines without commercial support, and members of each or- ganization volunteer their time to the writing and review efforts. Guidelines are official policy of the ACC and AHA. Intended Use Practice guidelines provide recommendations applica- ble to patients with or at risk of developing cardiovas- cular disease. The focus is on medical practice in the United States, but guidelines developed in collabora- tion 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. Guide- lines are intended to define practices meeting the needs of patients in most, but not all, circumstances and should not replace clinical judgment. Clinical Implementation 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 provid- ers 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 modi- fies guideline methodology on the basis of published standards from organizations including the Institute of and on the basis of internal reevaluation. Similarly, the presentation and delivery of guidelines are reevaluated and modified on the basis of evolving tech- nologies and other factors to facilitate optimal dissemi- nation 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 recommenda- tions and associated text called the modular knowledge chunk format. Each modular chunk includes a table of related recommendations, a brief synopsis, recommenda- tion-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 guide- lines 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 for- mat was instituted when this guideline was near comple- tion; therefore, the current document represents a transi- tional 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 consider- ations in certain guidelines, when appropriate and fea- sible, an analysis of the value of a medication, device, or intervention may be performed in accordance with the To ensure that guideline recommendations remain current, new data are reviewed on an ongoing basis, with full guideline revisions commissioned in approxi- mately 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 com- mittee, to determine whether a focused update should be commissioned. For additional information and poli- cies regarding guideline development, we encourage readers to consult the ACC/AHA guideline methodol- 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 commit- tee 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 re- lated 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 CLINICAL STATEMENTS AND GUIDELINES online. Appendix 1 of the current document lists writing committee members relevant RWI. For the purposes of full transparency, writing committee members compre- hensive 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 com- mittee 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, med- ication, 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 ben- efit 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 recom- mendations 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 test- ing, and pharmacological and procedural treatments. For these and all recommended medication treatment regi- mens, the reader should confirm the dosage by review- ing product insert material and evaluate the treatment regimen for contraindications and interactions. The rec- ommendations 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 esti- mated 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 guide- line are, whenever possible, evidence-based. An initial extensive evidence review, which included literature de- rived from research involving human subjects, published in English, and indexed in MEDLINE (through PubMed), EMBASE, the Cochrane Library, the Agency for Health- care Research and Quality, and other selected databas- es 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, pre- mature ventricular contractions, implantable cardioverter- defibrillator, subcutaneous implantable cardioverter-defi- brillator, 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) previ- ously published by the ACC, AHA, and the Heart Rhythm Society (HRS). References selected and published in this document are representative and not all-inclusive. 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 guide- line. Concurrent with this process, writing committee members evaluated other published data relevant to the guideline. The findings of the ERC and the writing com- mittee members were formally presented and discussed, then guideline recommendations were developed. The Systematic Review for the 2017 AHA/ACC/HRS Guide- line for Management of Patients With Ventricular Ar- rhythmias and the Prevention of Sudden Cardiac Death is published in conjunction with this guideline.S1.4-1 The ACC and AHA have acknowledged the impor- tance of value in health care and have called for even- tual development of a Level of Value for clinical practice Available cost-effectiveness data were determined to be sufficient to support 2 specific CLINICAL STATEMENTS AND GUIDELINES 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 Clini- cal 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 rec- ommendations in this guideline. 1.2. Organization of the Writing Committee The writing committee consisted of cardiac electro- physiologists (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 exper- tise 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 re- Table 1. Applying Class of Recommendation and Level of Evidence to Clinical Strategies, Interventions, Treatments, or Diagnostic Testing in Patient Care* (Updated August 2015) CLINICAL STATEMENTS AND GUIDELINES viewer nominated by the AHA; 1 organizational review- er nominated by the HFSA; and 28 individual content reviewers. Reviewers RWI information was distributed to the writing committee and is published in this docu- ment (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 pro- vide 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 It also supersedes some sections of the ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities, S1.4-5 specifi- cally 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 Hyper- Some recommendations from the earlier guidelines have been updated as war- ranted by new evidence or a better understanding of existing evidence, and irrelevant or overlapping recom- mendations 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, electrome- chanical 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 car- diac resynchronization therapy (CRT), bradycardia pac- ing, 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- 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 be- yond the scope of this document. Recommendations for interventional therapies, in- cluding ablation and the implantation of devices, apply only if these therapies can be implemented by quali- fied clinicians, such that outcomes consistent with pub- lished literature are a reasonable expectation. The writ- ing 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 re- lated 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 popu- lation ( 18 years of age) and offers no specific recom- mendations for pediatric patients, some of the litera- ture 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 recommenda- Table 2. Systematic Review Questions on SCD Prevention Question Number Question Section Number 1 For asymptomatic patients with Brugada syndrome, what is the association between an abnormal programmed ventricular stimulation study and SCD and other arrhythmia endpoints? 2 What is the impact of ICD implantation for primary prevention in older patients and patients with significant comorbidities? ICD indicates implantable cardioverter-defibrillator; and SCD, sudden cardiac death. Table 3. Proposed Integration of Level of Value Into Clinical Practice Guideline Recommendations* Level of Value High value: Better outcomes at lower cost or ICER <$50000 per QALY gained Intermediate value: $50000 to <$150000 per QALY gained Low value: $150000 per QALY gained Uncertain value: Value examined but data are insufficient to draw a conclusion because of no studies, low-quality studies, conflicting studies, or prior studies that are no longer relevant Not assessed: Value not assessed by the writing committee Proposed abbreviations for each value recommendation: Level of Value: H to indicate high value; I, intermediate value; L, low value; U, uncertain value; and NA, value not assessed *Dollar amounts used in this table are based on US GDP data from 2012 and were obtained from WHO-CHOICE Cost-Effectiveness Thresholds.S1.4-3 GDP indicates gross domestic product; ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life-years; and WHO-CHOICE, World Health Organization Choosing Interventions that are Cost-Effective. Reproduced from Anderson, et al.S1.4-2 CLINICAL STATEMENTS AND GUIDELINES tions 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 diag- nostic 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 7.9.1.4., recommendation 2 Section 10.8., recommendation 6 Readers should refer to these sections for the up- dated text. Table 4. Associated Guidelines and Statements Title Organization Publication Year (Reference) Guidelines Syncope ACC/AHA/HRS 2017S1.4 10 Heart failure ACCF/AHA 2017S1.4 11 and Valvular heart disease AHA/ACC 2017S1.4 14 Supraventricular tachycardia ACC/AHA/HRS 2015S1.4 16 Ventricular arrhythmias and the prevention of sudden cardiac death ESC 2015S1.4 17 Guidelines for cardiopulmonary resuscitation and emergency cardiovascular care AHA 2015S1.4 18 Atrial fibrillation AHA/ACC/HRS 2014S1.4 19 Non ST-elevation acute coronary syndromes AHA/ACC 2014S1.4 20 Assessment of cardiovascular risk ACC/AHA 2013S1.4 21 ST-elevation myocardial infarction ACCF/AHA 2013S1.4 22 Acute myocardial infarction in patients presenting with ST-segment elevation ESC 2012S1.4 23 Device-based therapies for cardiac rhythm abnormalities ACCF/AHA/HRS 2012S1.4 24 Coronary artery bypass graft surgery ACCF/AHA 2011S1.4 25 Hypertrophic cardiomyopathy ACCF/AHA 2011S1.4 6 Percutaneous coronary intervention ACCF/AHA/SCAI 2011S1.4 26 Secondary prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular disease Scientific Statements Wearable cardioverter-defibrillator therapy for the prevention of sudden cardiac death Optimal implantable cardioverter defibrillator programming and testing HRS/EHRA/APHRS/SOLAECE 2016S1.4 8 Treatment of cardiac arrest: current status and future directions: strategies to improve cardiac arrest survival Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities Ventricular arrhythmias EHRA/HRS/APHRS 2014S1.4 30 Arrhythmias in adult congenital heart disease PACES/HRS 2014S1.4 31 Implantable cardioverter-defibrillator therapy in patients who are not included or not well represented in clinical trials Cardiac sarcoidosis HRS 2014S1.4 33 Inherited primary arrhythmia syndromes HRS/EHRA/APHRS 2013S1.4 34 ACC indicates American College of Cardiology; ACCF, American College of Cardiology Foundation; AHA, American Heart Association; APHRS, Asia Pacific Heart Rhythm Society; EHRA, European Heart Rhythm Association; ESC, European Society of Cardiology; HRS, Heart Rhythm Society; PACES, Pediatric and Congenital Electrophysiology Society; SCAI, Society for Cardiovascular Angiography and Interventions; and, SOLAECE, Sociedad Latinoamericana de Estimulacion Cardiaca y Electrofisiologia. CLINICAL STATEMENTS AND GUIDELINES Abbreviation Meaning/Phrase 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 CPR cardiopulmonary resuscitation CRT cardiac resynchronization therapy CT computed tomography ECG electrocardiogram ERC evidence review committee ESRD end-stage renal disease GDMT guideline-directed management and therapy HCM hypertrophic cardiomyopathy HF heart failure HFpEF heart failure with preserved ejection fraction HFrEF heart failure with reduced ejection fraction ICD implantable cardioverter-defibrillator LV left ventricular LVAD left ventricular assist device LVEF left ventricular ejection fraction MI myocardial infarction NICM nonischemic cardiomyopathy NSVT nonsustained ventricular tachycardia PET positron emission tomography PCI percutaneous coronary intervention PVC premature ventricular complex QoL quality of life RCT randomized controlled trial RV right ventricular RVOT right ventricular outflow tract SCA sudden cardiac arrest SCD sudden cardiac death SVT supraventricular tachycardia TOF tetralogy of Fallot VA ventricular arrhythmia VT ventricular tachycardia 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 ageS2.2.2-5 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 in- creased risk of both ischemic heart disease events and mortality, with or without prevalent ischemic heart 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 in- In a study from Taiwan of pa- tients without sustained VT or structural heart disease who had 24-hour Holter monitoring for clinical evalu- ation, multifocal PVCs were associated with increased risk of death and nonfatal cardiovascular adverse In the same population, nonsustained ventricular tachycardia (NSVT) was independently as- sociated with increased risk of death and other cardio- vascular 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 con- sideredariskfactorforadversecardiovascularoutcomes, and such patients are generally evaluated to ensure they do not have underlying conditions (eg, ischemic heart disease, left ventricular [LV] dysfunction) that warrant further treatment to reduce risk. PVC and NSVT in pa- tients 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), treat- ment of patients with post-myocardial infarction (MI) who took antiarrhythmic medications (eg, flecainide, encainide, moricizine) increased the risk of death de- spite 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 medi- cations (eg, quinidine, flecainide) increases the risk of 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 block- CLINICAL STATEMENTS AND GUIDELINES Table 5. Table of Definitions of Commonly Used Terms in this Document Term Definition or Description Cardiac arrhythmia of 3 consecutive complexes originating in the ventricles at a rate >100 bpm (cycle length: <600 ms). Types of VT: Sustained: VT >30 s or requiring termination due to hemodynamic compromise in <30 s. Nonsustained/unsustained: 3 beats, terminating spontaneously. Monomorphic: Stable single QRS morphology from beat to beat. Polymorphic: Changing or multiform QRS morphology from beat to beat. Bidirectional: VT with a beat-to-beat alternation in the QRS frontal plane axis, often seen in the setting of digitalis toxicity or catecholaminergic polymorphic VT Monomorphic VT Polymorphic VT Bidirectional VT Torsades de pointesS2.2.2-2 Torsades de pointes is polymorphic VT that occurs in the setting of a long QT interval and is characterized by a waxing and waning QRS amplitude. It often has a long-short initiating sequence with a long coupling interval to the first VT beat and may present with salvos of NSVT. The twisting of the points, although characteristic, may not always be seen, especially if the episode is nonsustained or if only a limited number of leads are available. Torsades de pointes can result from bradycardia including high-grade AV block that leads to a long-short sequence initiating torsades de pointes. A regular VA 300 bpm (cycle length: 200 ms) with a sinusoidal, monomorphic appearance; no isoelectric interval between successive QRS complexes. Rapid, grossly irregular electrical activity with marked variability in electrocardiographic waveform, ventricular rate usually >300 bpm (cycle length: <200 ms). Sudden cardiac arrestS2.2.2-2 SCA is the sudden cessation of cardiac activity such that the victim becomes unresponsive, with either persisting gasping respirations or absence of any respiratory movements, and no signs of circulation as manifest by the absence of a perceptible pulse. An arrest is presumed to be of cardiac etiology unless it is known or likely to have been caused by trauma, drowning, respiratory failure or asphyxia, electrocution, drug overdose, or any other noncardiac cause. Sudden cardiac deathS2.2.2-2 Sudden and unexpected death occurring within an hour of the onset of symptoms, or occurring in patients found dead within 24 h of being asymptomatic and presumably due to a cardiac arrhythmia or hemodynamic catastrophe. VT/VF storm (electrical storm or arrhythmic storm) refers to a state of cardiac electrical instability that is defined by 3 episodes of sustained VT, VF, or appropriate shocks from an ICD within 24 h. Primary prevention ICDS2.2.2-2 ICD placement with the intention of preventing SCD in a patient who has not had sustained VT or SCA but who is at an increased risk for these events. Secondary prevention ICDS2.2.2-2 ICD placement in a patient with prior SCA, sustained VT, or syncope caused by VA. Structural heart disease* This term encompasses IHD, all types of cardiomyopathy, valvular heart disease, and adult congenital heart disease. Arrhythmogenic disease due to a genetic abnormality that results in dysfunction of a cardiac ion channel (eg, long QT syndrome, catecholaminergic polymorphic VT). *The definition of this term may differ across publications. Refer to the entry for the definition used in this document. AV indicates atrioventricular; ICD, implantable cardioverter-defibrillator; IHD, ischemic heart disease; NSVT, nonsustained ventricular tachycardia; SCA, sudden cardiac arrest; SCD, sudden cardiac death; VA, ventricular arrhythmia; VF, ventricular fibrillation; and VT, ventricular tachycardia. CLINICAL STATEMENTS AND GUIDELINES ers, and some antiarrhythmic medications may relieve symptoms of palpitations.S2.2.2-18 PVCs that occur during an exercise test are associ- ated 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 num- bers of athletes, at least in those without other cardio- Complex PVCs may not represent a benign finding in endurance athletes. An electrophysiological study may be needed to as- sess patients arrhythmogenic risk.S2.2.2-22 Very frequent PVCs, >10000 to 20000 a day, can be associated with depressed LV function in some patients that is revers- ible 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 trig- ger malignant VA in patients without structural heart 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 le- sions on acute coronary angiography.S2.2.2-27 Of patients hospitalized with AMI, 5% to 10% have VF or sus- tained 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 Accelerated idioventricular rhythm is a common arrhythmia in patients with acute MI, including patients with ST-segment elevation MI un- dergoing primary percutaneous coronary intervention (PCI). Accelerated idioventricular rhythm is more closely related to the extent of infarction than to reperfusion 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 hy- pertension, prior MI, ST-segment changes at presenta- tion, and chronic obstructive pulmonary disease.S2.2.2-30 A nationwide Danish study found that 11.6% of pa- tients with ST-segment elevation MI who underwent PCI had VF prior to the PCI, and that VF was associ- ated with alcohol consumption, preinfarction angina, anterior infarct location, and complete coronary occlu- sion 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 associ- ated with lower blood pressure, higher heart rate, poor coronary flow at the end of the procedure, and incom- plete 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 hos- pital presentation) was associated with a higher risk of death than early VT or VF (within 48 hours of hospital 2.1.3. Sustained VT and VF Not Associated With ACS Patients with structural heart disease are at an in- creased 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 dysfunc- tion and the presence of symptomatic HF. Monomor- phic 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 characteris- tic 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 med- ication-induced long QT syndrome,S2.2.2-36 or they may 2.2. Sudden Cardiac Death 2.2.1. Incidence of SCD SCA and its most common consequence, SCD, constitute major public health problems, account- ing for approximately 50% of all cardiovascular with at least 25% being first symp- tomatic 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 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 extrapo- lation 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 CLINICAL STATEMENTS AND GUIDELINES on death certificate studies that required a code inclu- sive 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 356500.S2.2.2-44 An ad- ditional 209000 in-hospital cardiac arrests occur Among the out-of-hospital cardiac arrest group, approximately 357000 events trigger emergency rescue response, with 97% occurring in adults >18 years of age. The survival statistics for out-of-hospital cardiac ar- rest 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 vis- ible emergency rescue response, along with the com- bination of public location of cardiac arrest, bystander witnesses willing to provide CPR, first responders arriv- ing quickly, shockable rhythm at initial contact, avail- ability of automated external defibrillators (AEDs), and possibly a benefit from telecommunication-directed 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 activ- ity 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 Figure 1A. SCD incidence and total events.S2.2.2-1 EF indicates ejection fraction; and SCD, sudden cardiac death. Figure 1B. SCD and clinical subsets.S2.2.2-1 SCD indicates sudden cardiac death. CLINICAL STATEMENTS AND GUIDELINES 2.2.2. Population Subgroups and Risk Prediction Risk prediction for SCA and SCD is complex. Risk analy- sis 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 ade- quately tested and validated profiles for SCA risk strati- fication of individuals in the general population do not presently exist. The challenge of defining SCA risk in individuals derives from a population model character- ized 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 denomi- nator 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 100000, 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 isch- emic 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 fibro- sis 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 During the transition range, from the mid-20s to the mid-30s, causes of SCA and SCD in- clude a lower proportion of inherited diseases and in- creasing proportion of ischemic heart disease (>40% 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 con- cealed 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 au- tomaticity, abnormal automaticity, triggered activ- ity induced by early or late afterdepolarizations, and Reentry requires a trigger to initiate the arrhythmia and a substrate to sustain it. The trig- ger 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 poten- tial. The electrophysiological substrate is dynamically influenced by a variety of factors including cardiac metabolism, electrolytes, signaling pathways and au- tonomic effects. Enhanced automaticity or abnormal automaticity causing VA may arise from subordinate pacemaker cells in the His-Purkinje system or ventricu- lar myocardium. Normal automaticity results from phase 4 spontane- ous depolarization of the transmembrane action po- tential arising from a normal resting potential, reach- ing 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 dia- stolic potential at the end of repolarization, the slope of phase 4 depolarization, and the threshold potential. In contrast, abnormal automaticity arises from a par- tially 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 CLINICAL STATEMENTS AND GUIDELINES 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 cur- rent, the inward calcium current or the sodium cal- cium exchange current) or a decrease in repolarizing potassium currents. Under these conditions, early afterdepolarizations may be initiated when reacti- vation of the inward L-type calcium channel occurs before the membrane has returned to a more nega- tive 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 condi- tions of intracellular calcium overload. Factors con- tributing 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 calci- um 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 afterdepolar- izations are the underlying mechanism for VT in the setting of digoxin toxicity, catecholaminergic polymor- phic VT, and idiopathic outflow tract VA. Delayed af- terdepolarizations are also considered to be an impor- tant trigger of VA in the setting of HF. Purkinje cells are more susceptible to spontaneous sarcoplasmic re- ticulum calcium release than ventricular myocytes sug- gesting that delayed afterdepolarizations may be an important mechanism for some Purkinje fiber-related Reentry is the underlying mechanism for most sustained VA in the presence of structural heart 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 wave- front 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 (ro- tor 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 poten- tial durations to the epicardium with shorter action po- tential 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 and may also be operative dur- ing ischemia. 4. GENERAL EVALUATION OF PATIENTS WITH DOCUMENTED OR SUSPECTED VA 4.1. History and Physical Examination Recommendation for Syncope* Referenced studies that support the recommendation are summarized in Online Data Supplement 1. COR LOE Recommendation I B-NR Patients presenting with syncope for which VA is documented, or thought to be a likely cause, should be hospitalized for evaluation, monitoring, and management.S4.1-1 S4.1-4 *This section covers practices that are well accepted, and a new recommendation was determined to only be warranted for syncope. Synopsis 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, short- ness of breath, chest pain, dizziness, near syncope, and 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 CLINICAL STATEMENTS AND GUIDELINES symptoms, particularly in patients with known or dis- covered 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 medica- tions 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 im- portant. Various antiarrhythmic and other medications can cause QT prolongation and torsades de pointes ; some medications can also induce Brugada type I electrocardiographic pat- tern 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 physi- cal 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 as- sociated with HF and VA. A midsystolic click may indi- cate mitral valve prolapse that can be associated with 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 sec- ondary to marked reduction in cardiac output, Table 6. Important Considerations in the Evaluation of Patients With Known or Suspected VA Component Assessment and Findings Relevant for VA and/or SCD Risk History 1. Symptoms/events related to arrhythmia: Palpitations, lightheadedness, syncope, dyspnea, chest pain, cardiac arrest Symptoms related to underlying heart disease: Dyspnea at rest or on exertion, orthopnea, paroxysmal nocturnal dyspnea, chest pain, edema 3. Precipitating factors: Exercise, emotional stress Known heart disease: Coronary, valvular (eg, mitral valve prolapse), congenital heart disease, other Risk factors for heart disease: Hypertension, diabetes mellitus, hyperlipidemia, and smoking Antiarrhythmic medications Other medications with potential for QT prolongation and torsades de pointes Medications with potential to provoke or aggravate VA Stimulants including cocaine and amphetamines Supplements including anabolic steroids Medication-medication interaction that could cause QT prolongation and torsades de pointes 7. Past medical history Thyroid disease Acute kidney injury, chronic kidney disease, or electrolyte abnormalities Stroke or embolic events Lung disease Epilepsy (arrhythmic syncope can be misdiagnosed as epilepsy) Alcohol or illicit drug use Use of over-the-counter medications that could cause QT prolongation and torsades de pointes Unexplained motor vehicle crashes Family History 1. SCD, SCA, or unexplained drowning in a first-degree relative SIDS or repetitive spontaneous pregnancy losses given their potential association with cardiac channelopathies 3. Heart disease IHD Cardiomyopathy: Hypertrophic, dilated, ARVC Congenital heart disease Cardiac channelopathies: Long QT, Brugada, Short QT, CPVT Arrhythmias Conduction disorders, pacemakers/ICDs Neuromuscular disease associated with cardiomyopathies Muscular dystrophy (Continued) Examination 1. Heart rate and regularity, blood pressure 2. Jugular venous pressure 4. Pulses and bruits 6. Sternotomy scars ARVC indicates arrhythmogenic right ventricular cardiomyopathy; CPVT, catecholaminergic polymorphic ventricular tachycardia; IHD, ischemic heart disease; SCA, sudden cardiac arrest; SCD, sudden cardiac death; SIDS, sudden infant death syndrome; and VA, ventricular arrhythmia. Table 6. Continued Component Assessment and Findings Relevant for VA and/or SCD Risk CLINICAL STATEMENTS AND GUIDELINES followed by spontaneous recovery if VT termi- nates, or SCA if VT persists and is not treated promptly. Syncope or SCA may be the first manifestation of structural or electrical heart and some SCA victims have preced- ing 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 informa- 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 syn- dromes, such as hypertrophic cardiomyopathy (HCM) or congenital heart disease.S4.1-3,S4.1-4,S4.1-16 Cardiac channelopathies and HCM are particu- larly important to consider in adolescents and young adults. Arrhythmic causes of syncope are often associated with very short periods of pre- monitory symptoms, or palpitations, and known preexisting heart disease, especially a history of a low LVEF or HF.S4.1-1 Among nonarrhythmic car- diac causes, considerations should include myo- cardial 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 Recommendations for 12-lead ECG and Exercise Testing Referenced studies that support the recommendations are summarized in Online Data Supplement 2. COR LOE Recommendations I B-NR In patients with sustained, hemodynamically stable, wide complex tachycardia, a 12- lead ECG during tachycardia should be I B-NR In patients with VA symptoms associated with exertion, suspected ischemic heart disease, or catecholaminergic polymorphic ventricular tachycardia, exercise treadmill testing is useful to assess for exercise-induced I B-NR In patients with suspected or documented VA, a 12-lead ECG should be obtained in sinus rhythm to look for evidence of heart 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 tachy- cardia on a monitor. VT is the diagnosis in most adults with wide complex tachycardia and under- lying structural heart disease.S4.2.1-3 Criteria that support a diagnosis of VT include AV dissocia- tion, a QRS complex >0.14 s, monophasic R wave in aVR, specific QRS morphologies (eg, 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 anti- 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, exer- cise in a monitored setting may reproduce the symptoms and/or the related arrhythmia, allow- ing 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 syn- drome, Brugada syndrome, and arrhythmogenic right ventricular cardiomyopathy. In patients with structural heart disease, QRS duration and the presence of conduction abnormalities pro- vide 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 ; the one exception is the potential use of signal averaged ECG in patients with arrhythmogenic right ventricular cardiomy- opathy (see Section 7.3). CLINICAL STATEMENTS AND GUIDELINES 4.2.2. Ambulatory Electrocardiography Recommendation for Ambulatory Electrocardiography Referenced studies that support the recommendation are summarized in Online Data Supplements 3 and 4. COR LOE Recommendation I B-NR Ambulatory electrocardiographic monitoring is useful to evaluate whether symptoms, including palpitations, presyncope, or syncope, are caused by VA.S4.2.2-1 S4.2.2-4 Recommendation-Specific Supportive Text 1. Ambulatory electrocardiographic monitoring is often used to assess the effectiveness of treatments to sup- press 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, estab- lishing their frequency, relating them to symptoms, and assessing the response to therapy. Although the yield of these tests is relatively low, VT is occasion- 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 compli- ance, and arrhythmia detection; however, with some monitors, detected arrhythmias are not dis- covered until the patch is returned for analysis.S4.2.2- 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 cor- relate the symptoms with the arrhythmias detected by ambulatory ECG monitoring. 4.2.3. Implanted Cardiac Monitors Recommendation for Implanted Cardiac Monitors Referenced studies that support the recommendation are summarized in Online Data Supplement 5. COR LOE Recommendation IIa B-R In patients with sporadic symptoms (including syncope) suspected to be related to VA, implanted cardiac monitors can be Recommendation-Specific Supportive Text 1. Implanted cardiac monitors provide continu- ous rhythm monitoring and stored recordings of electrograms based on patient activation or pre- set parameters, allowing a prolonged monitor- ing period of a few years. These devices require a minor invasive procedure with local anesthesia for implantation. In patients with sporadic symp- toms, 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 unreveal- ing external ambulatory monitor.S4.2.3-5 In a study of patients with syncope, the implantable moni- tor had a greater diagnostic yield than conven- tional testing with external monitoring, tilt table testing and electrophysiological study.S4.2.3-2 A systematic review in patients with syncope con- cluded 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 prospec- tive 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 car- diac monitors. 4.2.4. Noninvasive Cardiac Imaging Recommendations for Noninvasive Cardiac Imaging Referenced studies that support the recommendations are summarized in Online Data Supplement 6. COR LOE Recommendations I B-NR In patients with known or suspected VA that may be associated with underlying structural heart disease or a risk of SCA, echocardiography is recommended for evaluation of cardiac structure and IIa C-EO In patients presenting with VA who are suspected of having structural heart disease, cardiac magnetic resonance imaging (MRI) or computed tomography (CT) can be useful to detect and characterize underlying structural heart disease. Recommendation-Specific Supportive Text 1. Assessment of global and regional myocardial function, valvular structure and function, along with assessment for adult congenital heart CLINICAL STATEMENTS AND GUIDELINES disease is required in patients with or at high risk for VA or SCD, including patients with cardiomy- opathy, HF, prior MI, family history of cardiomy- opathy or SCD, or an inherited structural heart disease associated with SCD. Echocardiography is the most readily available and commonly used 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 the benefit of the ICD was not dependent on the modality (ie, echocardiogra- phy, radionuclide angiography, or contrast angio- grams) by which the LVEF was assessed. In clinical practice, if cardiac CTS4.2.4-3 or cardiac MRI has been performed and provides sufficient evalua- tion, echocardiography may be unnecessary. This recommendation for imaging differs from that of the 2017 ACC/AHA/HRS syncope guidelineS4.2.4-4 that applies to patients who may not have VA. 2. VA or SCA can be an initial manifestation of isch- emic heart disease, cardiomyopathic processes, or myocarditis. Cardiac CT and cardiac MRI allow for evaluation of structural heart disease and assess- ment 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 evi- dent 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 for Biomarkers Referenced studies that support the recommendation are summarized in Online Data Supplement 7. COR LOE Recommendation IIa B-NR In patients with structural heart disease, measurement of natriuretic peptides (BNP or N-terminal pro-BNP) can be useful by adding prognostic information to standard risk factors for predicting SCD or SCA.S4.2.5-1 S4.2.5-4 Recommendation-Specific Supportive Text 1. 