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1 Focused Issue of This Month Sudden Cardiac Death Nam-Ho Kim, MDKyeong Ho Yun, MDSeok Kyu Oh, MD Department of Interal Medicine, Wonkwang University College of Medicine E - mail : cardionh@wonkwang.ac.kr J Korean Med Assoc 2010; 53(3): Abstract Sudden cardiac death (SCD) refers to the unexpected natural death from a cardiac cause within a short time period, generally within an hour from the onset of symptoms, in a person without any prior fatal condition. Despite the tremendous advances in the field of cardiovascular medicine, the incidence of SCD continues to rise. In 60 to 80 percent of cases, SCD occurs in the patients with coronary artery disease. Most instances of SCD are thought to involve ventricular tachycardia degenerating to ventricular fibrillation and subsequent asystole. Since the implantable cardioverter defibrillator (ICD) is effective in terminating ventricular tachycardia and fibrillation, the application of ICD has increased markedly. However, the application of ICD needs to be individualized for the patient, similar to drug therapies in LV systolic dysfunction. This review discusses the current understanding on SCD, risk stratification, and management goals for reducing SCD, particularly with the ICD usage. Keywords: Sudden cardiac death; Coronary artery disease; Left ventricular ejection fraction; Implantable cardioverter defibrillator 214

2 Sudden Cardiac Death Structure Coronary Artery Disease Cardiomyopathy Valvular heart disease Congenital heart disease Ion channel disease PVCs Bradycardia VT / VF / Asystole Sudden Cardiac Death Function Ischemia Heart failure Autonomic activation Electrolyte imbalance Drugs Figure 1. The pathogenesis of sudden cardiac death. Structural cardiac abnormalities are commonly defined as the causative basis for sudden cardiac death. However, functional alterations of the abnormal anatomical substrates are usually required to alter stability of the myocardium, permitting a potentially fatal arrhythmia to be initiated. 215

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4 Sudden Cardiac Death Table 1. Summary of noninvasive risk-stratification techniques for identifying patients with coronary artery disease who are at risk for sudden cardiac death. Technique Left ventricular ejection fraction (LVEF) ECG QRS duration QT interval and QT dispersion Signal-averaged ECG (SAECG) Short-term HRV Conclusion Low LVEF is a well-demonstrated risk factor for SCD. Although low LVEF has been effectively used to select high-risk patients for application of to prevent sudden arrhythmic death, LVEF has limited sensitivity: the majority of SCDs occur in patients with more preserved LVEF. Most retrospective analyses show increased QRS duration is likely a risk factor for SCD. Clinical utility to guide selection of has not been tested. Some retrospective analyses data show that abnormalities in cardiac repolarization are risk factors for SCD. Clinical utility to guide selection of has not yet been tested. An abnormal SAECG is likely a risk factor for SCD, based predominantly on prospective analyses. Clinical utility to guide selection of has been tested, but not yet demonstrated. Limited data link impaired short-term HRV to increased risk for SCD. Clinical utility to guide selection of has not yet been tested. Holter Ventricular ectopy The presence of ventricular arrhythmias (VPBs, NSVT) on Holter monitoring is a well-demonstrated and NSVT risk factor for SCD. In some populations, the presence of NSVT has been effectively used to select high-risk patients for application of to prevent sudden arrhythmic death. This may also have limited sensitivity. Long-term HRV Low HRV is a risk factor for mortality, but likely is not specific for SCD. Clinical utility to guide selection of has been tested, but not demonstrated. Heart rate turbulence Emerging data show that abnormal heart rate turbulence is a likely risk factor for SCD. Clinical utility to guide selection of has been tested, but not yet demonstrated. Exercise test/functional status Exercise capacity Increasing severity of heart failure is a likely risk factor for SCD, although it may be more predictive and NYHA class of risk for progressive pump failure. Clinical utility to guide selection of has not yet been tested. Heart rate recovery Limited data show that low heart rate recovery and ventricular ectopy during recovery are risk and recovery factors for SCD. ventricular ectopy Clinical utility to guide selection of has not yet been tested. T-wave alternans A moderate amount of prospective data suggests that abnormal T-wave alternans is a risk factor for SCD. Clinical utility to guide selection of has been evaluated, but the results to date are inconsistent. Baroreceptor A moderate amount of data suggests that low BRS is a risk factor for SCD. sensitivity Clinical utility to guide selection of has not yet been tested. HRV: heart rate variability, NSVT: non-sustained ventricular tachycardia, SCD: sudden cardiac death 217

5 Kim NHYun KHOh SK Table 2. Summary of estimated incidence, relative risks and proposed therapies for ventricular arrhythmias post-myocardial infarction Arrhythmia type Post-myocardial infarction phase Incidence Relative risk Proposed PVCs > 10/h Acute 65~80% ~1 PVC suppression not shown to reduce Subacute/chronic 20~26% 2.4 to 3.0 at 1 to 3 ys mortality; amiodarone decreases arrhythmic deaths Nonsustained VT Acute 20~28% <13h: ~1 Correct ischemia, electrolyte; 13 to 24h: 1.0 to 7.5 d/c proarrhythmic agents Subacute/chronic 7~12% 1.7 to 3.2 at 0.5 to 3 ys Sustained Acute 1.8~2.0% 2.6 to 5.0 at 1 to 2 ys Correct ischemia, electrolyte; mornomorphic Subacute/chronic 1.5~2.0% 6.1 to 9.1 at 1 to 3 ys d/c proarrhythmic agents; cosider VT revascularization; beta-blocker, antiarrhythmic, ICD, catheter ablation Polymorphic Acute 3~5% 20 to 25 acutely; Prompt defibrillation; VT or VF ~1 for survivors restore vessel patency 218

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7 Kim NHYun KHOh SK Risk Factors Angina Hypertension Dyslipidemia C Atherosclerosis Myocardial Diabetes A Infarction Smoking D Alcohol drinking Exercise deficiency SCD age 20 age 30 age 40 age 50 Figure 2. Prevention of sudden cardiac death. The identification and control of atherosclerotic risk factors are important to prevent the sudden cardiac death. CAD: coronary artery disease, SCD: sudden cardiac 220

8 Sudden Cardiac Death Table 3. Primary prevention of sudden cardiac death in ischemic or non-ischemic cardiomyopathy with implantable cardioverter defibrillator. Trial Mean Mortality (%) Control NO. of Population follow-up Control ICD p-vlue patients (Mo) patient MADIT I Antiarrhythmic 196 Prior MI; LVEF35% CABG-Patch Antiarrhythmic 900 Patients scheduled for CABG; LVEF35% positive SAECG MUSTT Conventional 704 Prior MI; LVEF40%; NSVT; inducible VT on EP study MADIT II Conventional 1,232 Prior MI; LVEF30% DINAMIT Conventional 674 Recent MI (within 6~40 d), LVEF35% impaired cardiac autonomic modulation(hrv) CAT Conventional 104 NYHA II/III, NIDCM, LVEF30% asymptomatic NSVT AMIOVIRT Amiodarone 103 NYHA I-III, NIDCM, LVEF35%, asymptomatic NSVT DEFINITE Conventional 458 NIDCM, LVEF36%, NSVT or PVCs SCD-HeFT Conventional 2,521 NYHA II/III CHF(ischemic & nonischemic), LVEF35% 221

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13 Kim NHYun KHOh SK H, Levine JH, Saksena S, Waldo AL, Wilber D, Brown MW, Heo M. 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: Buxton AE, Lee KL, Fisher JD, Josephson ME, Prystowsky EN, Hafley G. 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: Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS, Daubert JP, Higgins SL, Brown MW, Andrews ML. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002; 346: Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau R, Domanski M, Troutman C, Anderson J, Johnson G, McNulty SE, Clapp-Channing N, Davidson-Ray LD, Fraulo ES, Fishbein DP, Luceri RM, Ip JH. Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) Investigators. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005; 352: Hohnloser SH, Kuck KH, Dorian P, Roberts RS, Hampton JR, Hatala R, Fain E, Gent M, Connolly SJ. Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction. N Engl J Med 2004; 351: Nanthakumar K, Epstein AE, Kay GN, Plumb VJ, Lee DS. Prophylactic implantable cardioverter-defibrillator in patients with left ventricular systolic dysfunction: a pooled analysis of 10 primary prevention trials. J Am Coll Cardiol 2004; 44: Epstein AE, DiMarco JP, Ellenbogen KA, Estes NA 3rd, Freedman RA, Gettes LS, Gillinov AM, Gregoratos G, Hammill SC, Hayes DL, Hlatky MA, Newby LK, Page RL, Schoenfeld MH, Silka MJ, Stevenson LW, Sweeney MO, Smith SC Jr, Jacobs AK, Adams CD, Anderson JL, Buller CE, Creager MA, Ettinger SM, Faxon DP, Halperin JL, Hiratzka LF, Hunt SA, Krumholz HM, Kushner FG, Lytle BW, Nishimura RA, Ornato JP, Page RL, Riegel B, Tarkington LG, Yancy CW; 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); American Association for Thoracic Surgery; Society of Thoracic Surgeons. 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-e Kadish A, Dyer A, Daubert JP, Quigg R, Estes NA, Anderson KP, Calkins H, Hoch D, Goldberger J, Shalaby A, Sanders WE, Schaechter A, Levine JH. Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) Investigators. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med 2004; 350: Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De Marco T, Carson P, DiCarlo L, DeMets D, White BG, DeVries DW, Feldman AM; Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) Investigators. Cardiac-resynchronization with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 2004; 350: The Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators. A comparison of antiarrhythmic-drug with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med 1997; 337: Connolly SJ, Gent M, Roberts RS, et al. Canadian Implantable Defibrillator Study (CIDS): a randomized trial of the implantable cardioverter defibrillator against amiodarone. Circulation 2000; 101: Kuck KH, Cappato R, Siebels J, Ruppel R. Randomized comparison of antiarrhythmic drug with implantable defibrillators in patients resuscitated from cardiac arrest: the Cardiac Arrest Study Hamburg (CASH). Circulation 2000; 102: Oseroff O, Retyk E, Bochoeyer A. Subanalyses of secondary prevention implantable cardioverter-defibrillator trials: antiarrhythmics versus implantable defibrillators (AVID), Canadian Implantable Defibrillator Study (CIDS), and Cardiac Arrest Study Hamburg (CASH). Curr Opin Cardiol 2004; 19: Waalewijn RA, de Vos R, Koster RW. Out-of-hospital cardiac arrests in Amsterdam and its surrounding areas: results from the Amsterdam resuscitation study (ARREST) in Utstein style. Resuscitation 1998; 38:

14 Sudden Cardiac Death Peer Reviewers Commentary 227

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ºÎÁ¤¸ÆV10N³»Áö A case of nonischemic dilated cardiomyopathy with ventricular tachycardia treated by ICD ABSTRACT Dilated cardiomyopathy (DCM) is a syndrome characterized by left or biventricular dilatation and impaired