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(Circulation. 1998;98:2334-2351.)
© 1998 American Heart Association, Inc.

Clinical Cardiology: New Frontiers

Sudden Cardiac Death

Douglas P. Zipes, MD; ; Hein J. J. Wellens, MD

From the Krannert Institute of Cardiology, Indiana University School of Medicine and the Roudebush Veterans Administration Medical Center, Indianapolis (D.P.Z.), and the Department of Cardiology, Academic Hospital Maastricht and the Interuniversity Cardiology Institute of the Netherlands, Utrecht (H.J.J.W.).

Correspondence to Douglas P. Zipes, MD, Krannert Institute of Cardiology, 1111 W 10th St, Indianapolis, IN 46202-4800.

Key Words: death, sudden • mortality • coronary disease

Sudden cardiac death describes the unexpected natural death from a cardiac cause within a short time period, generally 1 hour from the onset of symptoms, in a person without any prior condition that would appear fatal.^{1 2} Such a rapid death is often attributed to a cardiac arrhythmia, but with the advent of monitoring capabilities from implantable cardioverter-defibrillators (ICDs), it is now well recognized that classifications based on clinical circumstances can be misleading and often impossible, because 40% of sudden deaths can be unwitnessed.³ Only an ECG or a ventricular electrogram recorded from an implanted device at the time of death can provide definitive information about an arrhythmia. Prodromal symptoms are often nonspecific, and even those taken to indicate ischemia (chest pain), a tachyarrhythmia (palpitations), or congestive heart failure symptoms (dyspnea) can only be considered suggestive. For these reasons, total mortality, rather than classifications of cardiac and arrhythmic mortality, should be used as primary objectives for many outcome studies.

Magnitude of the Problem

Sudden cardiac death accounts for 300 000 to 400 000 deaths annually in the United States, depending on the definition used.^{1 2} When restricted to death <2 hours from the onset of symptoms, 12% of all natural deaths were classified as sudden in one study, and 88% of those were due to cardiac disease.¹ Sudden cardiac death is the most common and often the first manifestation of coronary heart disease and is responsible for 50% of the mortality from cardiovascular disease in the United States and other developed countries. In less-developed countries, sudden . . . [Full Text of this Article]

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				S. M.J.M. Straus, J. A. Kors, M. L. De Bruin, C. S. van der Hooft, A. Hofman, J. Heeringa, J. W. Deckers, J. H. Kingma, M. C.J.M. Sturkenboom, B. H. Ch. Stricker, et al. Prolonged QTc Interval and Risk of Sudden Cardiac Death in a Population of Older Adults J. Am. Coll. Cardiol., January 17, 2006; 47(2): 362 - 367. [Abstract] [Full Text] [PDF]

				V. Bito, D. Dauwe, F. Verdonck, K. Mubagwa, and K. R. Sipido The Amiodarone Derivative KB130015 [2-Methyl-3-(3,5-diiodo-4-carboxymethoxybenzyl)benzofuran] Induces an Na+-Dependent Increase of [Ca2+] in Ventricular Myocytes J. Pharmacol. Exp. Ther., January 1, 2006; 316(1): 162 - 168. [Abstract] [Full Text] [PDF]

				J. A. Fallavollita, B. J. Riegel, G. Suzuki, U. Valeti, and J. M. Canty Jr. Mechanism of sudden cardiac death in pigs with viable chronically dysfunctional myocardium and ischemic cardiomyopathy Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2688 - H2696. [Abstract] [Full Text] [PDF]

				T. H. Marwick Dyspnea and risk in suspected coronary disease. N. Engl. J. Med., November 3, 2005; 353(18): 1963 - 1965. [Full Text] [PDF]

				X. Jouven, R. N. Lemaitre, T. D. Rea, N. Sotoodehnia, J.-P. Empana, and D. S. Siscovick Diabetes, glucose level, and risk of sudden cardiac death Eur. Heart J., October 2, 2005; 26(20): 2142 - 2147. [Abstract] [Full Text] [PDF]

				E Aksay, T Okan, and S Yanturali Brugada syndrome, manifested by propafenone induced ST segment elevation Emerg. Med. J., October 1, 2005; 22(10): 748 - 750. [Abstract] [Full Text] [PDF]

				V. Ovchinnikov, G. Suzuki, J. M. Canty Jr., and J. A. Fallavollita Blunted functional responses to pre- and postjunctional sympathetic stimulation in hibernating myocardium Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1719 - H1728. [Abstract] [Full Text] [PDF]

				M. M. Bassan, I. G. Harnik, X. Jouven, J. P. Empana, and P. Ducimetiere Heart-Rate Profile during Exercise as a Predictor of Sudden Death N. Engl. J. Med., August 18, 2005; 353(7): 734 - 735. [Full Text] [PDF]

				K. W. Hewett, L. W. Norman, D. Sedmera, R. J. Barker, C. Justus, J. Zhang, S. W. Kubalak, and R. G. Gourdie Knockout of the neural and heart expressed gene HF-1b results in apical deficits of ventricular structure and activation Cardiovasc Res, August 15, 2005; 67(3): 548 - 560. [Abstract] [Full Text] [PDF]

				A. J. Luisi Jr., G. Suzuki, R. deKemp, M. S. Haka, S. A. Toorongian, J. M. Canty Jr., and J. A. Fallavollita Regional 11C-Hydroxyephedrine Retention in Hibernating Myocardium: Chronic Inhomogeneity of Sympathetic Innervation in the Absence of Infarction J. Nucl. Med., August 1, 2005; 46(8): 1368 - 1374. [Abstract] [Full Text] [PDF]

				G. Thorgeirsson, G. Thorgeirsson, H. Sigvaldason, and J. Witteman Risk factors for out-of-hospital cardiac arrest: the Reykjavik Study Eur. Heart J., August 1, 2005; 26(15): 1499 - 1505. [Abstract] [Full Text] [PDF]

				S. Guzzetti, E. Borroni, P. E. Garbelli, E. Ceriani, P. D. Bella, N. Montano, C. Cogliati, V. K. Somers, A. Mallani, and A. Porta Symbolic Dynamics of Heart Rate Variability: A Probe to Investigate Cardiac Autonomic Modulation Circulation, July 26, 2005; 112(4): 465 - 470. [Abstract] [Full Text] [PDF]

				M. Ando, R. G. Katare, Y. Kakinuma, D. Zhang, F. Yamasaki, K. Muramoto, and T. Sato Efferent Vagal Nerve Stimulation Protects Heart Against Ischemia-Induced Arrhythmias by Preserving Connexin43 Protein Circulation, July 12, 2005; 112(2): 164 - 170. [Abstract] [Full Text] [PDF]

				H. L. Tan, N. Hofman, I. M. van Langen, A. C. van der Wal, and A. A.M. Wilde Sudden Unexplained Death: Heritability and Diagnostic Yield of Cardiological and Genetic Examination in Surviving Relatives Circulation, July 12, 2005; 112(2): 207 - 213. [Abstract] [Full Text] [PDF]

				X. H. T. Wehrens, S. E. Lehnart, S. Reiken, R. van der Nagel, R. Morales, J. Sun, Z. Cheng, S.-X. Deng, L. J. de Windt, D. W. Landry, et al. Enhancing calstabin binding to ryanodine receptors improves cardiac and skeletal muscle function in heart failure PNAS, July 5, 2005; 102(27): 9607 - 9612. [Abstract] [Full Text] [PDF]

				S. D. Solomon, S. Zelenkofske, J. J.V. McMurray, P. V. Finn, E. Velazquez, G. Ertl, A. Harsanyi, J. L. Rouleau, A. Maggioni, L. Kober, et al. Sudden Death in Patients with Myocardial Infarction and Left Ventricular Dysfunction, Heart Failure, or Both N. Engl. J. Med., June 23, 2005; 352(25): 2581 - 2588. [Abstract] [Full Text] [PDF]

				A. Kadish and M. Mehra Heart Failure Devices: Implantable Cardioverter-Defibrillators and Biventricular Pacing Therapy Circulation, June 21, 2005; 111(24): 3327 - 3335. [Full Text] [PDF]

				P. S. Chan and R. A. Hayward Mortality Reduction by Implantable Cardioverter-Defibrillators in High-Risk Patients With Heart Failure, Ischemic Heart Disease, and New-Onset Ventricular Arrhythmia: An Effectiveness Study J. Am. Coll. Cardiol., May 3, 2005; 45(9): 1474 - 1481. [Abstract] [Full Text] [PDF]

				R. E Lane, M. R Cowie, and A. W C Chow Prediction and prevention of sudden cardiac death in heart failure Heart, May 1, 2005; 91(5): 674 - 680. [Full Text] [PDF]

				S. M. Al-Khatib, K. J. Anstrom, E. L. Eisenstein, E. D. Peterson, J. G. Jollis, D. B. Mark, Y. Li, C. M. O'Connor, L. K. Shaw, and R. M. Califf Clinical and Economic Implications of the Multicenter Automatic Defibrillator Implantation Trial-II Ann Intern Med, April 19, 2005; 142(8): 593 - 600. [Abstract] [Full Text] [PDF]