Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Sudden cardiac death: mechanisms, therapies and challenges

Nature Clinical Practice Cardiovascular Medicine volume 2, pages 352–360 (2005)Cite this article

Abstract

Sudden cardiac death (SCD) is the leading cause of cardiac death in the US. In the past few years, intensive efforts have been made to expand public awareness of SCD and to increase our understanding of its pathophysiology, medical treatment options and device therapy. Significant advances have been made in our ability to prevent SCD in both primary and secondary health care. Two critical issues remain, however: the identification of patients who would benefit from such therapies, and how to achieve even greater prevention, especially primary prevention. The goal of this article is to provide a review of the topic of SCD in the setting of abnormal myocardial substrate, to outline the techniques that are useful in identifying patients at risk, and available treatment options.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Schema showing how left-ventricular dysfunction and concomitant electrolyte disturbances can lead to ventricular arrhythmias in patients with left-ventricular dysfunction, focusing on the most common mechanisms.
Figure 2: Relative reduction in mortality with implantable cardioverter-defibrillators: primary prevention in various randomized, controlled trials.
Figure 3: Suggested schema for identifying patients at risk of sudden cardiac death and directing their therapy.

Similar content being viewed by others

References

  1. McGovern PG et al. (1996) Recent trends in acute coronary heart disease—mortality, morbidity, medical care, and risk factors. The Minnesota Heart Survey Investigators. N Engl J Med 334: 884–990

    Article  CAS  Google Scholar 

  2. Rosamond WD et al. (1998) Trends in the incidence of myocardial infarction and in mortality due to coronary heart disease, 1987 to 1994. N Engl J Med 339: 861–867

    Article  CAS  Google Scholar 

  3. Goraya TY et al. (2003) Coronary heart disease death and sudden cardiac death: a 20-year population-based study. Am J Epidemiol 157: 763–770

    Article  Google Scholar 

  4. Zheng ZJ et al. (2001) Sudden cardiac death in the United States, 1989 to 1998. Circulation 104: 2158–2163

    Article  CAS  Google Scholar 

  5. Schatzkin A et al. (1984) Sudden death in the Framingham Heart Study. Differences in incidence and risk factors by sex and coronary disease status. Am J Epidemiol 120: 888–899

    Article  CAS  Google Scholar 

  6. Zipes DP and Wellens HJ (1998) Sudden cardiac death. Circulation 98: 2334–2351

    Article  CAS  Google Scholar 

  7. Bayes de Luna A et al. (1989) Ambulatory sudden cardiac death: mechanisms of production of fatal arrhythmia on the basis of data from 157 cases. Am Heart J 117: 151–159

    Article  CAS  Google Scholar 

  8. Eisenberg MS and Mengert TJ (2001) Cardiac resuscitation. N Engl J Med 344: 1304–1313

    Article  CAS  Google Scholar 

  9. Kannel WB et al. (1988) Cardiac failure and sudden death in the Framingham Study. Am Heart J 115: 869–875

    Article  CAS  Google Scholar 

  10. Cohn JN et al. (1986) Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study. N Engl J Med 314: 1547–1552

    Article  CAS  Google Scholar 

  11. Cohn JN et al. (1991) A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med 325: 303–310

    Article  CAS  Google Scholar 

  12. The SOLVD Investigators (1992) Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med 327: 685–691

  13. Singh SN et al. (1995) Amiodarone in patients with congestive heart failure and asymptomatic ventricular arrhythmia. Survival Trial of Antiarrhythmic Therapy in Congestive Heart Failure. N Engl J Med 333: 77–82

    Article  CAS  Google Scholar 

  14. Teerlink JR et al. (2000) Ambulatory ventricular arrhythmias in patients with heart failure do not specifically predict an increased risk of sudden death. PROMISE (Prospective Randomized Milrinone Survival Evaluation) Investigators. Circulation 101: 40–46

    Article  CAS  Google Scholar 

  15. Grimm W and Maisch B (2002) Sudden cardiac death in dilated cardiomyopathy—therapeutic options. Herz 27: 750–759

    Article  Google Scholar 

  16. Vermeulen JT et al. (1994) Triggered activity and automaticity in ventricular trabeculae of failing human and rabbit hearts. Cardiovasc Res 28: 1547–1554

    Article  CAS  Google Scholar 

  17. Tomaselli GF et al. (1994) Sudden cardiac death in heart failure. The role of abnormal repolarization. Circulation 90: 2534–2539

    Article  CAS  Google Scholar 

  18. Cameron JS et al. (1983) Electrophysiologic consequences of chronic experimentally induced left ventricular pressure overload. J Am Coll Cardiol 2: 481–487

    Article  CAS  Google Scholar 

  19. Pogwizd SM et al. (1992) Re-entrant and focal mechanisms underlying ventricular tachycardia in the human heart. Circulation 86: 1872–1887

    Article  CAS  Google Scholar 

  20. Josephson ME et al. (1987) Mechanisms of ventricular tachycardia. Circulation 75 (Pt 2): II141–II147

    Google Scholar 

  21. Josephson ME (ed.; 1993) Clinical Cardiac Electrophysiology: Techniques and Interpretations. Philadelphia, London: Lea & Febiger

    Google Scholar 

  22. Sweeney MO et al. (1996) Natural history of spontaneous sustained monomorphic ventricular tachycardia in coronary disease revealed by local bipolar electrograms retrieved from implantable cardioverter-defibrillators. [abstract]. Circulation 94 (Suppl I): 568

    Google Scholar 

  23. Mann DL et al. (1992) Adrenergic effects on the biology of the adult mammalian cardiocyte. Circulation 85: 790–804

    Article  CAS  Google Scholar 

  24. Schwartz PJ et al. (1992) Autonomic nervous system and sudden cardiac death. Experimental basis and clinical observations for post-myocardial infarction risk stratification. Circulation 85 (Suppl): I77–I91

    CAS  PubMed  Google Scholar 

  25. Delacretaz E et al. (2000) Mapping and radiofrequency catheter ablation of the three types of sustained monomorphic ventricular tachycardia in nonischemic heart disease. J Cardiovasc Electrophysiol 11: 11–17

    Article  CAS  Google Scholar 

  26. Roberts WC et al. (1987) Idiopathic dilated cardiomyopathy: analysis of 152 necropsy patients. Am J Cardiol 60: 1340–1355

    Article  CAS  Google Scholar 

  27. Pfeffer MA et al. (1992) Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. N Engl J Med 327: 669–677

    Article  CAS  Google Scholar 

  28. Packer M et al. (1991) Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group. N Engl J Med 325: 1468–1475

    Article  CAS  Google Scholar 

  29. Cohn JN et al. (1998) A dose-dependent increase in mortality with vesnarinone among patients with severe heart failure. Vesnarinone Trial Investigators. N Engl J Med 339: 1810–1816

    Article  CAS  Google Scholar 

  30. Packer M et al. (1996) The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med 334: 1349–1355

    Article  CAS  Google Scholar 

  31. No authors listed (1999) Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 353: 2001–2007

  32. No authors listed (1999) The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 353: 9–13

  33. No authors listed (1989) Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. The Cardiac Arrhythmia Suppression Trial (CAST) Investigators. N Engl J Med 321: 406–412

  34. No authors listed (1992) Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction. The Cardiac Arrhythmia Suppression Trial II Investigators. N Engl J Med 327: 227–233

  35. Teo KK et al. (1993) Effects of prophylactic antiarrhythmic drug therapy in acute myocardial infarction. An overview of results from randomized controlled trials. JAMA 270: 1589–1595

    Article  CAS  Google Scholar 

  36. Waldo AL et al. (1996) Effect of d-sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction. The SWORD Investigators. Survival With Oral d-Sotalol. Lancet 348: 7–12

    Article  CAS  Google Scholar 

  37. Torp-Pedersen C et al. (1999) 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 341: 857–865

    Article  CAS  Google Scholar 

  38. Camm AJ et al. (2004) Mortality in patients after a recent myocardial infarction: a randomised, placebo-controlled trial of azimilide using heart rate variability for risk stratification. Circulation 109: 990–996

    Article  Google Scholar 

  39. DiCarlo LA Jr et al. (1987) Effects of chronic amiodarone therapy on ventricular tachycardia induced by programmed ventricular stimulation. Am Heart J 113: 57–64

    Article  Google Scholar 

  40. Cairns JA et al. (1997) Randomised trial of outcome after myocardial infarction in patients with frequent or repetitive ventricular premature depolarisations: CAMIAT. Canadian Amiodarone Myocardial Infarction Arrhythmia Trial Investigators. Lancet 349: 675–682

    Article  CAS  Google Scholar 

  41. Julian DG et al. (1997) Randomised trial of effect of amiodarone on mortality in patients with left-ventricular dysfunction after recent myocardial infarction: EMIAT. European Myocardial Infarct Amiodarone Trial Investigators. Lancet 349: 667–674

    Article  CAS  Google Scholar 

  42. Doval HC et al. (1994) Randomised trial of low-dose amiodarone in severe congestive heart failure. Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina (GESICA). Lancet 344: 493–498

    Article  CAS  Google Scholar 

  43. Bardy G et al. (2005) Amiodarone or an Implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 352: 225–237

    Article  CAS  Google Scholar 

  44. No authors listed (1997) A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. The Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators. N Engl J Med 337: 1576–1583

  45. Connolly SJ et al. (2000) Canadian implantable defibrillator study (CIDS): a randomized trial of the implantable cardioverter defibrillator against amiodarone. Circulation 101: 1297–1302

    Article  CAS  Google Scholar 

  46. Kuck KH et al. (2000) Randomized comparison of antiarrhythmic drug therapy with implantable defibrillators in patients resuscitated from cardiac arrest: the Cardiac Arrest Study Hamburg (CASH). Circulation 102: 748–754

    Article  CAS  Google Scholar 

  47. Connolly SJ et al. (2000) Meta-analysis of the implantable cardioverter defibrillator secondary prevention trials. AVID, CASH and CIDS studies. Antiarrhythmics vs Implantable Defibrillator study. Cardiac Arrest Study Hamburg. Canadian Implantable Defibrillator Study. Eur Heart J 21: 2071–2078

    Article  CAS  Google Scholar 

  48. Moss AJ et al. (1996) 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 335: 1933–1940

    Article  CAS  Google Scholar 

  49. Bigger JT Jr (1997) 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 337: 1569–1575

    Article  Google Scholar 

  50. Buxton AE et al. (1999) A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators. N Engl J Med 341: 1882–1890

    Article  CAS  Google Scholar 

  51. Moss AJ et al. (2002) Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 346: 877–883

    Article  Google Scholar 

  52. Hohnloser SH et al. (2004) Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction. N Engl J Med 351: 2481–2488

    Article  CAS  Google Scholar 

  53. Bansch D et al. (2002) Primary prevention of sudden cardiac death in idiopathic dilated cardiomyopathy: the Cardiomyopathy Trial (CAT). Circulation 105: 1453–1458

    Article  Google Scholar 

  54. Strickberger SA et al. (2003) Amiodarone versus implantable cardioverter-defibrillator: randomized trial in patients with nonischemic dilated cardiomyopathy and asymptomatic nonsustained ventricular tachycardia—AMIOVIRT. J Am Coll Cardiol 41: 1707–1712

    Article  Google Scholar 

  55. Kadish A et al. (2004) Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med 350: 2151–2158

    Article  CAS  Google Scholar 

  56. Bigger JT Jr et al. (1984) The relationships among ventricular arrhythmias, left ventricular dysfunction, and mortality in the 2 years after myocardial infarction. Circulation 69: 250–258

    Article  Google Scholar 

  57. Cupples LA et al. (1992) Long- and short-term risk of sudden coronary death. Circulation 85 (Suppl): 11–18

    Google Scholar 

  58. Perkiomaki JS et al. (1997) Heart rate variability and dispersion of QT interval in patients with vulnerability to ventricular tachycardia and ventricular fibrillation after previous myocardial infarction. J Am Coll Cardiol 30: 1331–1338

    Article  CAS  Google Scholar 

  59. Priori SG et al. (2001) Task Force on Sudden Cardiac Death of the European Society of Cardiology. Eur Heart J 22: 1374–1450

    Article  CAS  Google Scholar 

  60. Wilber DJ et al. (1990) Electrophysiological testing and nonsustained ventricular tachycardia. Use and limitations in patients with coronary artery disease and impaired ventricular function. Circulation 82: 350–358

    Article  CAS  Google Scholar 

  61. Gregoratos G et al. (online 2002) ACC/AHA/NASPE 2002 Guideline update for implantation of cardiac pacemakers and antiarrhythmia devices: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/NASPE Committee on Pacemaker Implantation). (accessed 23 May 2005)

  62. American Heart Association (online September 2004) Cardiovascular disease statistics. (accessed 23 May 2005)

Download references

Acknowledgements

We thank Robert Guerra for his critical review of the manuscript.

Author information

Authors and Affiliations

  1. Section of Electrophysiology,

    Robert D Winslow, Davendra Mehta & Valentin Fuster

  2. Zena and Michael A Weiner Cardiovascular Institute and the Marie-Josée and Henry R Kravis Center for Cardiovascular Health, Mount Sinai Medical Center, New York, NY, USA

    Robert D Winslow, Davendra Mehta & Valentin Fuster

Authors
  1. Robert D Winslow
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Davendra Mehta
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Valentin Fuster
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Valentin Fuster.

Ethics declarations

Competing interests

D Mehta is a consultant for Guidant Corporation. V Fuster is a consultant for GlaxoSmithKline.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Winslow, R., Mehta, D. & Fuster, V. Sudden cardiac death: mechanisms, therapies and challenges. Nat Rev Cardiol 2, 352–360 (2005). https://doi.org/10.1038/ncpcardio0241

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncpcardio0241

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing