Primary prevention of sudden cardiac death in heart failure and cardiomyopathy
- Joseph E Marine, MD, FACC, FHRS
Joseph E Marine, MD, FACC, FHRS
- Associate Professor of Medicine
- Associate Director of Electrophysiology
- Johns Hopkins University School of Medicine
- Andrea M Russo, MD, FACC, FHRS
Andrea M Russo, MD, FACC, FHRS
- Professor of Medicine
- Cooper Medical School of Rowan University
- Section Editors
- Samuel Lévy, MD
Samuel Lévy, MD
- Section Editor — Cardiac Arrhythmias
- Professor of Cardiology
- University of Marseille, France
- Bradley P Knight, MD, FACC
Bradley P Knight, MD, FACC
- Section Editor — Cardiac Arrhythmias
- Professor of Medicine
- Feinberg School of Medicine, Northwestern University
Life-threatening ventricular arrhythmias, including sustained ventricular tachycardia (VT) and ventricular fibrillation (VF), are common in patients with systolic heart failure (HF) and dilated cardiomyopathy and may lead to sudden cardiac death (SCD). Primary prevention of SCD refers to medical or interventional therapy undertaken to prevent SCD in patients who have not experienced symptomatic life-threatening sustained VT/VF or sudden cardiac arrest (SCA) but who are felt to be at an increased risk for such an event. The primary prevention of SCD in patients with heart failure and cardiomyopathy with reduced ejection fraction, either due to coronary heart disease or a dilated nonischemic etiology, will be reviewed here with emphasis on the role of implantable cardioverter-defibrillators (ICDs). The different types of ventricular arrhythmias, the effects of HF therapy on ventricular arrhythmias, the role of electrophysiologic testing, and the secondary prevention of SCD are discussed separately. (See "Ventricular arrhythmias in heart failure and cardiomyopathy" and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".)
The approaches to the treatment of ventricular arrhythmias related to specific heart muscle diseases or primary electrical system diseases such as hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, isolated left ventricular noncompaction, Brugada syndrome, long QT Syndrome, and other channelopathies are discussed elsewhere. (See "Hypertrophic cardiomyopathy: Assessment and management of ventricular arrhythmias and sudden cardiac death risk" and "Arrhythmogenic right ventricular cardiomyopathy: Treatment and prognosis" and "Isolated left ventricular noncompaction" and "Prognosis and management of congenital long QT syndrome" and "Brugada syndrome: Prognosis, management, and approach to screening".)
CAUSES OF DEATH IN HEART FAILURE
While the exact percentages and mode of death in patients with heart failure vary with heart failure class and type of cardiomyopathy, progressive pump failure, unexpected sudden cardiac death (SCD), and SCD during episodes of clinical worsening of HF each account for approximately one-third of deaths in HF patients. Ventricular tachycardia (VT) and ventricular fibrillation (VF) are the most common arrhythmic causes of SCD, although bradyarrhythmias and pulseless electrical activity (PEA) are responsible in 5 to 33 percent of cases. These issues are discussed in greater detail elsewhere. (See "Prognosis of heart failure", section on 'Causes of death in HF' and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy", section on 'Causes of death in heart failure'.)
Patients with New York Heart Association (NYHA) class IV heart failure have a very high mortality from progressive heart failure unless they are candidates for either cardiac transplantation, ventricular assist device implantation, or cardiac resynchronization therapy. Therefore, such patients are not usually considered appropriate candidates for implantable cardioverter-defibrillator (ICD) therapy unless this is used as a bridge to transplantation or implanted in conjunction with cardiac resynchronization therapy (CRT). The mode of death in patients with heart failure is more likely to be "sudden" in patients with class II or III heart failure, while the mode of death is more likely to be related to "pump" failure in patients with class IV heart failure (figure 1) . Therefore, primary prevention ICD trials (in the absence of CRT) have excluded patients with NYHA class IV heart failure. In fact, the 2008 ACC/AHA/HRS Device-Based Guidelines state that "ICD therapy is not indicated for NYHA Class IV patients with drug-refractory congestive heart failure who are not candidates for cardiac transplantation or CRT-D," listing this as a class III indication . (See 'Class IV heart failure' below and "Indications and contraindications for cardiac transplantation" and "Cardiac resynchronization therapy in heart failure: Indications".)
RISK STRATIFICATION STRATEGIES
While implantable cardioverter-defibrillators (ICDs) are highly efficacious in the treatment of ventricular tachyarrhythmias and prevention of SCD, they are costly, require ongoing follow-up, and have numerous risks (eg, infection, device and lead malfunction, etc). In addition, only a subset of patients with cardiomyopathy develops sustained ventricular tachyarrhythmias or SCD. As such, the risk stratification of patients prior to ICD therapy is important for providing therapy to patients at highest risk of SCD and minimizing the number of ICD implantations in patients who are unlikely to benefit.
- Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 1999; 353:2001.
- Epstein AE, DiMarco JP, Ellenbogen KA, et al. ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices): developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons. Circulation 2008; 117:e350.
- Bilchick KC, Stukenborg GJ, Kamath S, Cheng A. Prediction of mortality in clinical practice for medicare patients undergoing defibrillator implantation for primary prevention of sudden cardiac death. J Am Coll Cardiol 2012; 60:1647.
- Zeitler EP, Hellkamp AS, Fonarow GC, et al. Primary prevention implantable cardioverter-defibrillators and survival in older women. JACC Heart Fail 2015; 3:159.
- Zhang Y, Guallar E, Blasco-Colmenares E, et al. Clinical and serum-based markers are associated with death within 1 year of de novo implant in primary prevention ICD recipients. Heart Rhythm 2015; 12:360.
- Deo R, Norby FL, Katz R, et al. Development and Validation of a Sudden Cardiac Death Prediction Model for the General Population. Circulation 2016; 134:806.
- Woods B, Hawkins N, Mealing S, et al. Individual patient data network meta-analysis of mortality effects of implantable cardiac devices. Heart 2015; 101:1800.
- Kuruvilla S, Adenaw N, Katwal AB, et al. Late gadolinium enhancement on cardiac magnetic resonance predicts adverse cardiovascular outcomes in nonischemic cardiomyopathy: a systematic review and meta-analysis. Circ Cardiovasc Imaging 2014; 7:250.
- Kwon DH, Asamoto L, Popovic ZB, et al. Infarct characterization and quantification by delayed enhancement cardiac magnetic resonance imaging is a powerful independent and incremental predictor of mortality in patients with advanced ischemic cardiomyopathy. Circ Cardiovasc Imaging 2014; 7:796.
- Moss AJ, Hall WJ, Cannom DS, et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators. N Engl J Med 1996; 335:1933.
- Mushlin AI, Hall WJ, Zwanziger J, et al. The cost-effectiveness of automatic implantable cardiac defibrillators: results from MADIT. Multicenter Automatic Defibrillator Implantation Trial. Circulation 1998; 97:2129.
- Moss AJ, Fadl Y, Zareba W, et al. Survival benefit with an implanted defibrillator in relation to mortality risk in chronic coronary heart disease. Am J Cardiol 2001; 88:516.
- Senges JC, Becker R, Schreiner KD, et al. Variability of Holter electrocardiographic findings in patients fulfilling the noninvasive MADIT criteria. Multicenter Automatic Defibrillator Implantation Trial. Pacing Clin Electrophysiol 2002; 25:183.
- Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002; 346:877.
- Greenberg H, Case RB, Moss AJ, et al. Analysis of mortality events in the Multicenter Automatic Defibrillator Implantation Trial (MADIT-II). J Am Coll Cardiol 2004; 43:1459.
- Bigger JT Jr. Prophylactic use of implanted cardiac defibrillators in patients at high risk for ventricular arrhythmias after coronary-artery bypass graft surgery. Coronary Artery Bypass Graft (CABG) Patch Trial Investigators. N Engl J Med 1997; 337:1569.
- Buxton AE, Lee KL, Fisher JD, et al. A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators. N Engl J Med 1999; 341:1882.
- Buxton AE, Lee KL, Hafley GE, et al. Relation of ejection fraction and inducible ventricular tachycardia to mode of death in patients with coronary artery disease: an analysis of patients enrolled in the multicenter unsustained tachycardia trial. Circulation 2002; 106:2466.
- Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005; 352:225.
- Hohnloser SH, Kuck KH, Dorian P, et al. Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction. N Engl J Med 2004; 351:2481.
- Steinbeck G, Andresen D, Seidl K, et al. Defibrillator implantation early after myocardial infarction. N Engl J Med 2009; 361:1427.
- Orn S, Cleland JG, Romo M, et al. Recurrent infarction causes the most deaths following myocardial infarction with left ventricular dysfunction. Am J Med 2005; 118:752.
- Strickberger SA, Hummel JD, Bartlett TG, et al. Amiodarone versus implantable cardioverter-defibrillator:randomized trial in patients with nonischemic dilated cardiomyopathy and asymptomatic nonsustained ventricular tachycardia--AMIOVIRT. J Am Coll Cardiol 2003; 41:1707.
- Tracy CM, Epstein AE, Darbar D, et al. 2012 ACCF/AHA/HRS focused update of the 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2012; 60:1297.
- Bänsch D, Antz M, Boczor S, et al. Primary prevention of sudden cardiac death in idiopathic dilated cardiomyopathy: the Cardiomyopathy Trial (CAT). Circulation 2002; 105:1453.
- Kadish A, Dyer A, Daubert JP, et al. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med 2004; 350:2151.
- Mark DB, Anstrom KJ, Sun JL, et al. Quality of life with defibrillator therapy or amiodarone in heart failure. N Engl J Med 2008; 359:999.
- Cleland JG, Daubert JC, Erdmann E, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 2005; 352:1539.
- Bristow MR, Saxon LA, Boehmer J, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 2004; 350:2140.
- Stavrakis S, Lazzara R, Thadani U. The benefit of cardiac resynchronization therapy and QRS duration: a meta-analysis. J Cardiovasc Electrophysiol 2012; 23:163.
- Sipahi I, Carrigan TP, Rowland DY, et al. Impact of QRS duration on clinical event reduction with cardiac resynchronization therapy: meta-analysis of randomized controlled trials. Arch Intern Med 2011; 171:1454.
- Kühlkamp V, InSync 7272 ICD World Wide Investigators. Initial experience with an implantable cardioverter-defibrillator incorporating cardiac resynchronization therapy. J Am Coll Cardiol 2002; 39:790.
- Desai AS, Fang JC, Maisel WH, Baughman KL. Implantable defibrillators for the prevention of mortality in patients with nonischemic cardiomyopathy: a meta-analysis of randomized controlled trials. JAMA 2004; 292:2874.
- Køber L, Thune JJ, Nielsen JC, et al. Defibrillator Implantation in Patients with Nonischemic Systolic Heart Failure. N Engl J Med 2016; 375:1221.
- Al-Khatib SM, Hellkamp AS, Fonarow GC, et al. Association between prophylactic implantable cardioverter-defibrillators and survival in patients with left ventricular ejection fraction between 30% and 35%. JAMA 2014; 311:2209.
- Al-Khatib SM, Hellkamp A, Bardy GH, et al. Survival of patients receiving a primary prevention implantable cardioverter-defibrillator in clinical practice vs clinical trials. JAMA 2013; 309:55.
- Nuttall SL, Toescu V, Kendall MJ. beta Blockade after myocardial infarction. Beta blockers have key role in reducing morbidity and mortality after infarction. BMJ 2000; 320:581.
- Friedman LM, Byington RP, Capone RJ, et al. Effect of propranolol in patients with myocardial infarction and ventricular arrhythmia. J Am Coll Cardiol 1986; 7:1.
- Brodine WN, Tung RT, Lee JK, et al. Effects of beta-blockers on implantable cardioverter defibrillator therapy and survival in the patients with ischemic cardiomyopathy (from the Multicenter Automatic Defibrillator Implantation Trial-II). Am J Cardiol 2005; 96:691.
- Domanski MJ, Exner DV, Borkowf CB, et al. Effect of angiotensin converting enzyme inhibition on sudden cardiac death in patients following acute myocardial infarction. A meta-analysis of randomized clinical trials. J Am Coll Cardiol 1999; 33:598.
- Pfeffer MA, McMurray JJ, Velazquez EJ, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003; 349:1893.
- Mitchell LB, Powell JL, Gillis AM, et al. Are lipid-lowering drugs also antiarrhythmic drugs? An analysis of the Antiarrhythmics versus Implantable Defibrillators (AVID) trial. J Am Coll Cardiol 2003; 42:81.
- Chiu JH, Abdelhadi RH, Chung MK, et al. Effect of statin therapy on risk of ventricular arrhythmia among patients with coronary artery disease and an implantable cardioverter-defibrillator. Am J Cardiol 2005; 95:490.
- Dickinson MG, Ip JH, Olshansky B, et al. Statin use was associated with reduced mortality in both ischemic and nonischemic cardiomyopathy and in patients with implantable defibrillators: mortality data and mechanistic insights from the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). Am Heart J 2007; 153:573.
- Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003; 348:1309.
- Miller AL, Wang Y, Curtis J, et al. Optimal medical therapy use among patients receiving implantable cardioverter/defibrillators: insights from the National Cardiovascular Data Registry. Arch Intern Med 2012; 172:64.
- The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 1999; 353:9.
- Torp-Pedersen C, Møller M, Bloch-Thomsen PE, et al. Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group. N Engl J Med 1999; 341:857.
- Camm AJ, Pratt CM, Schwartz PJ, et al. Mortality in patients after a recent myocardial infarction: a randomized, placebo-controlled trial of azimilide using heart rate variability for risk stratification. Circulation 2004; 109:990.
- Singer I, Al-Khalidi H, Niazi I, et al. Azimilide decreases recurrent ventricular tachyarrhythmias in patients with implantable cardioverter defibrillators. J Am Coll Cardiol 2004; 43:39.
- Pratt CM, Eaton T, Francis M, et al. The inverse relationship between baseline left ventricular ejection fraction and outcome of antiarrhythmic therapy: a dangerous imbalance in the risk-benefit ratio. Am Heart J 1989; 118:433.
- Hallstrom A, Pratt CM, Greene HL, et al. Relations between heart failure, ejection fraction, arrhythmia suppression and mortality: analysis of the Cardiac Arrhythmia Suppression Trial. J Am Coll Cardiol 1995; 25:1250.
- Slater W, Lampert S, Podrid PJ, Lown B. Clinical predictors of arrhythmia worsening by antiarrhythmic drugs. Am J Cardiol 1988; 61:349.
- Gottlieb SS, Kukin ML, Medina N, et al. Comparative hemodynamic effects of procainamide, tocainide, and encainide in severe chronic heart failure. Circulation 1990; 81:860.
- Ravid S, Podrid PJ, Lampert S, Lown B. Congestive heart failure induced by six of the newer antiarrhythmic drugs. J Am Coll Cardiol 1989; 14:1326.
- January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2014; 64:e1.
- Saba S, Atiga WL, Barrington W, et al. Selected patients listed for cardiac transplantation may benefit from defibrillator implantation regardless of an established indication. J Heart Lung Transplant 2003; 22:411.
- Chung MK, Szymkiewicz SJ, Shao M, et al. Aggregate national experience with the wearable cardioverter-defibrillator: event rates, compliance, and survival. J Am Coll Cardiol 2010; 56:194.
- Cantero-Pérez EM, Sobrino-Márquez JM, Grande-Trillo A, et al. Implantable cardioverter defibrillator for primary prevention in patients with severe ventricular dysfunction awaiting heart transplantation. Transplant Proc 2013; 45:3659.
- Barra S, Providência R, Paiva L, et al. Implantable cardioverter-defibrillators in the elderly: rationale and specific age-related considerations. Europace 2015; 17:174.
- Pun PH, Al-Khatib SM, Han JY, et al. Implantable cardioverter-defibrillators for primary prevention of sudden cardiac death in CKD: a meta-analysis of patient-level data from 3 randomized trials. Am J Kidney Dis 2014; 64:32.
- Hess PL, Al-Khatib SM, Han JY, et al. Survival benefit of the primary prevention implantable cardioverter-defibrillator among older patients: does age matter? An analysis of pooled data from 5 clinical trials. Circ Cardiovasc Qual Outcomes 2015; 8:179.
- Steinberg BA, Al-Khatib SM, Edwards R, et al. Outcomes of implantable cardioverter-defibrillator use in patients with comorbidities: results from a combined analysis of 4 randomized clinical trials. JACC Heart Fail 2014; 2:623.
- Huang DT, Sesselberg HW, McNitt S, et al. Improved survival associated with prophylactic implantable defibrillators in elderly patients with prior myocardial infarction and depressed ventricular function: a MADIT-II substudy. J Cardiovasc Electrophysiol 2007; 18:833.
- van Rees JB, Borleffs CJ, Thijssen J, et al. Prophylactic implantable cardioverter-defibrillator treatment in the elderly: therapy, adverse events, and survival gain. Europace 2012; 14:66.
- Pokorney SD, Miller AL, Chen AY, et al. Implantable Cardioverter-Defibrillator Use Among Medicare Patients With Low Ejection Fraction After Acute Myocardial Infarction. JAMA 2015; 313:2433.
- Koplan BA, Epstein LM, Albert CM, Stevenson WG. Survival in octogenarians receiving implantable defibrillators. Am Heart J 2006; 152:714.
- Goldenberg I, Moss AJ, McNitt S, et al. Relations among renal function, risk of sudden cardiac death, and benefit of the implanted cardiac defibrillator in patients with ischemic left ventricular dysfunction. Am J Cardiol 2006; 98:485.
- Kusumoto FM, Calkins H, Boehmer J, et al. HRS/ACC/AHA expert consensus statement on the use of implantable cardioverter-defibrillator therapy in patients who are not included or not well represented in clinical trials. Circulation 2014; 130:94.
- Russo AM, Stainback RF, Bailey SR, et al. ACCF/HRS/AHA/ASE/HFSA/SCAI/SCCT/SCMR 2013 appropriate use criteria for implantable cardioverter-defibrillators and cardiac resynchronization therapy: a report of the American College of Cardiology Foundation appropriate use criteria task force, Heart Rhythm Society, American Heart Association, American Society of Echocardiography, Heart Failure Society of America, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance. J Am Coll Cardiol 2013; 61:1318.
- Ruwald MH, Solomon SD, Foster E, et al. Left ventricular ejection fraction normalization in cardiac resynchronization therapy and risk of ventricular arrhythmias and clinical outcomes: results from the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT) trial. Circulation 2014; 130:2278.
- Kini V, Soufi MK, Deo R, et al. Appropriateness of primary prevention implantable cardioverter-defibrillators at the time of generator replacement: are indications still met? J Am Coll Cardiol 2014; 63:2388.
- Zhang Y, Guallar E, Blasco-Colmenares E, et al. Changes in Follow-Up Left Ventricular Ejection Fraction Associated With Outcomes in Primary Prevention Implantable Cardioverter-Defibrillator and Cardiac Resynchronization Therapy Device Recipients. J Am Coll Cardiol 2015; 66:524.
- Poole JE, Johnson GW, Hellkamp AS, et al. Prognostic importance of defibrillator shocks in patients with heart failure. N Engl J Med 2008; 359:1009.
- Daubert JP, Zareba W, Cannom DS, et al. Inappropriate implantable cardioverter-defibrillator shocks in MADIT II: frequency, mechanisms, predictors, and survival impact. J Am Coll Cardiol 2008; 51:1357.
- Dichtl W, Wolber T, Paoli U, et al. Appropriate therapy but not inappropriate shocks predict survival in implantable cardioverter defibrillator patients. Clin Cardiol 2011; 34:433.
- Moss AJ, Schuger C, Beck CA, et al. Reduction in inappropriate therapy and mortality through ICD programming. N Engl J Med 2012; 367:2275.
- Gasparini M, Proclemer A, Klersy C, et al. Effect of long-detection interval vs standard-detection interval for implantable cardioverter-defibrillators on antitachycardia pacing and shock delivery: the ADVANCE III randomized clinical trial. JAMA 2013; 309:1903.
- Wilkoff BL, Fauchier L, Stiles MK, et al. 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement on optimal implantable cardioverter-defibrillator programming and testing. Heart Rhythm 2016; 13:e50.
- CAUSES OF DEATH IN HEART FAILURE
- RISK STRATIFICATION STRATEGIES
- Identifying high-risk patients
- Sudden cardiac death risk prediction in the general population
- USE OF AN ICD
- Ischemic cardiomyopathy
- - Our approach
- - Late post-MI trials
- MADIT-I trial
- MADIT-II trial
- CABG Patch trial
- MUSTT trial
- SCD-HeFT trial and ischemic cardiomyopathy
- - Early post-MI trials
- DINAMIT trial
- IRIS trial
- Possible explanations for lack of benefit in early post-MI trials
- Nonischemic dilated cardiomyopathy
- - Our approach
- - CAT and AMIOVIRT trials
- - DEFINITE trial
- - SCD-HeFT trial and nonischemic cardiomyopathy
- - COMPANION trial of ICD combined with CRT
- - 2004 meta-analysis of ICD trials in nonischemic cardiomyopathy
- - DANISH trial
- LVEF and risk
- Randomized trial outcomes compared with clinical practice
- GUIDELINE-DIRECTED MEDICAL THERAPY
- Antiarrhythmic drugs
- SPECIAL POPULATIONS
- Class IV heart failure
- Older adults and patients with comorbidities
- GAPS IN THE GUIDELINES
- Possible indications not addressed by guidelines
- Patients with improvement or normalization of LVEF
- PROGNOSTIC SIGNIFICANCE OF ICD SHOCKS AND DEVICE PROGRAMMING
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS