Noninvasive Risk Stratification of Sudden Death: T-Wave Alternans

  • Roberto F. E. Pedretti
  • Simona Sarzi Braga
  • Raffaella Vaninetti
  • Antonio Laporta
  • Sergio Masnaghetti
  • Rossella Raimondo
  • Mario Salerno
  • Francesco Santoro
Conference paper


Sudden cardiac death (SCD) accounts for approximately 400,000 deaths each year in the USA and remains a health problem of epidemic proportions. Most SCDs are caused by fatal ventricular arrhythmias, i.e., ventricular tachycardia (VT) and ventricular fibrillation (VF), in patients with and without known structural heart diseases [1, 2]. Identifying patients at risk for these arrhythmias remains a major challenge since < 2% of patients who have sudden cardiac arrest are resuscitated and survive hospital discharge. Given the large number of patients potentially at risk for developing ventricular arrhythmias, any strategy for treating them prophylactically requires efficient and effective risk stratification. A number of recently completed randomized clinical trials showed that an implantable cardioverter defibrillator (ICD) can prevent SCD in selected high-risk patients. These trials have used different methods for identifying patients at risk for SCD. The Multicenter Automatic Defibrillator Implantation Trial (MADIT) and the Multicenter Nonsustained Tachycardia Trial (MUSTT) identified patients with left ventricular (LV) dysfunction and nonsustained VT who had VT induced by programmed ventricular stimulation [3, 4]. These two studies demonstrated that implantation of an ICD can reduce the risk of death in this group of high-risk patients. In contrast, in the Coronary Artery By-pass Graft (CABG) Patch Trial, which identified a group of high-risk patients with LV dysfunction and an abnormal signal-averaged electrocardiogram who were undergoing elective CABG surgery, implantation of an ICD did not reduce all-cause mortality [5].


Left Ventricular Ejection Fraction Implantable Cardioverter Defibril Implantable Cardioverter Defibril Therapy Implantable Cardioverter Defibril Implantation Nonischemic Cardiomyopathy 
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  1. 1.
    Myerburg RJ, Interian AJ, Mitrani RM et al (1997) Frequency of sudden cardiac death and profiles of risk. Am J Cardiol 80:10F–19FPubMedCrossRefGoogle Scholar
  2. 2.
    Zipes DP, Wellens HJ (1998) Sudden cardiac death. Circulation 98:2334–2351PubMedGoogle Scholar
  3. 3.
    Moss AK, Hall WJ, Cannom DS 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 335:1993–1940CrossRefGoogle Scholar
  4. 4.
    Buxton AE, Hafley G (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 341:1882–1890PubMedCrossRefGoogle Scholar
  5. 5.
    Bigger JT (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 337:1569–1575PubMedCrossRefGoogle Scholar
  6. 6.
    Hohnloser SH, Kuck KH, Dorian P et al; DINAMIT Investigators (2004) Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction. N Engl J Med 351:2481–2488PubMedCrossRefGoogle Scholar
  7. 7.
    Moss AJ, Zareba W, Hall WJ et al for the Multicenter Automatic Defibrillator Implantation Trial II Investigators (2002) Prophylactic implantation of a defibrillator in patients with myocardial infarction and a reduced ejection fraction. N Engl J Med 346:877–883PubMedCrossRefGoogle Scholar
  8. 8.
    Kadish A, Dyer A, Daubert JP et al; Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) Investigators (2004) Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med 350:2151–2158PubMedCrossRefGoogle Scholar
  9. 9.
    Bristow MR, Saxon LA, Boehmer J et al; Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) Investigators (2004) Cardiacresynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 350:2140–2150PubMedCrossRefGoogle Scholar
  10. 10.
    Bardy GH, Lee KL, Mark DB et al; SCD-HeFT Investigators (2005) Amiodarone or implantable cardioverter defibrillator for congestive heart failure. N Engl J Med 352:225–237PubMedCrossRefGoogle Scholar
  11. 11.
    Julian DG, Camm AJ, Frangin G 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 349:667–674PubMedCrossRefGoogle Scholar
  12. 12.
    Cairns JA, Connolly SJ, Roberts R, Gent M (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. 349:675–682PubMedCrossRefGoogle Scholar
  13. 13.
    Anonymous (2006) ACC/AHA/ESC guidelines 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 and the European Society of Cardiology Committee for practice guidelines. Circulation 114:1088–1132CrossRefGoogle Scholar
  14. 14.
    Schwartz PJ, Malliani A (1975) Electrical alternans of the T-wave: clinical and experimental evidence of its relationship with the sympathetic nervous system and with the long Q-T sindrome. Am Heart J 89:45–50PubMedCrossRefGoogle Scholar
  15. 15.
    Puletti M, Curione M, Righetti G, Jacobellis G (1980) Alternans of the ST segment and T wave in acute myocardial infarction. J Electrocardiol 13:297–300PubMedCrossRefGoogle Scholar
  16. 16.
    Hohnloser SH, Huikuri HV, Schwartz PJ et al (1999) T wave alternans in post myocardial infarction patients (ACES Pilot Study). J Am Coll Cardiol 33:144ACrossRefGoogle Scholar
  17. 17.
    Kleinfeld MJ, Rozanski JJ (1977) Alternans of the ST segment in Prinzmetal’s angina. Circulation 55:574–577PubMedGoogle Scholar
  18. 18.
    Cheng TC (1983) Electrical alternans. An association with coronary artery spasm. Arch Intern Med 143:1052–1053PubMedCrossRefGoogle Scholar
  19. 19.
    Reddy CV, Kiok JP, Khan RG, El-Sherif N (1984) Repolarization alternans associated with alcoholism and hypomagnesemia. Am J Cardiol 53:390–391PubMedCrossRefGoogle Scholar
  20. 20.
    Shimoni Z, Flatau E, Shiller D et al (1984) Electrical alternans of giant U waves with multiple electrolyte deficits. Am J Cardiol 54:920–921PubMedCrossRefGoogle Scholar
  21. 21.
    Pastore JM, Girouard SD, Laurita KR et al (1999) Mechanisms linking T-wave alternans to the genesis of cardiac fibrillation. Circulation 99:1385–1394PubMedGoogle Scholar
  22. 22.
    Watanabe MA, Fenton FH, Evans SJ et al (2001) Mechanisms for discordant alternans. J Cardiovasc Electrophysiol 12:196–206PubMedCrossRefGoogle Scholar
  23. 23.
    Rosenbaum DS, Jackson LE, Smith JM et al (1994) Electrical alternans and vulnerability to ventricular arrhythmias. N Engl J Med 330:235–241PubMedCrossRefGoogle Scholar
  24. 24.
    Estes NAM III, Michaud G, Zipes DP et al (1997) Electrical alternans during rest and exercise as predictors of vulnerability to ventricular arrhythmias. Am J Cardiol 80:1314–1318PubMedCrossRefGoogle Scholar
  25. 25.
    Gold MR, Bloomfield DM, Anderson KP et al (2000) A comparison of T-wave alternans signal-averaged electrocardiography and programmed ventricular stimulation for arrhythmia risk stratification. J Am Coll Cardiol 36:2247–2253PubMedCrossRefGoogle Scholar
  26. 26.
    Hohnloser SH, Klingenheben T, Li YG et al (1998) T-wave alternans as a predictor of recurrent ventricular tachyarrhythmias in ICD recipients: prospective comparison with conventional risk markers. J Cardiovasc Electrophysiol 9:1258–1268PubMedCrossRefGoogle Scholar
  27. 27.
    Hohnloser SH, Klingenheben T, Zabel M et al (1997) T wave alternans during exercise and atrial pacing in humans. J Cardiovasc Electrophysiol 8:987–993PubMedCrossRefGoogle Scholar
  28. 28.
    Klingenheben T, Hohnloser SH, Cohen RJ et al (2000) Predictive value of T-wave alternans in patients with congestive heart failure. Lancet 356:651–652PubMedCrossRefGoogle Scholar
  29. 29.
    Sarzi Braga S, Vaninetti R, Laporta A et al (2004) T-wave alternans is a predictor of death in patients with congestive heart failure. Int J Cardiol 93:31–38PubMedCrossRefGoogle Scholar
  30. 30.
    Hohnloser SH, Klingenheben T, Bloomfield D et al (2003) Usefulness of microvolt T-wave alternans for prediction of ventricular tachyarrhythmic events in patients with dilated cardiomyopathy: results from a prospective observational study. J Am Coll Cardiol 41:2220–2224PubMedCrossRefGoogle Scholar
  31. 31.
    Costantini O, Kaufman ES, Bloomfield DM et al (2004) Patients with a nonischemic cardiomyopathy and a negative T-wave alternans stress test are at a low risk of death. American Heart Association Scientific Session, New Orleans, LA, Nov 7–10Google Scholar
  32. 32.
    Grimm W, Christ M, Bach J et al (2003) Noninvasive arrhythmia risk stratification in idiopathic dilated cardiomyopathy: results of the Marburg Cardiomyopathy Study. Circulation 108:2883–2891PubMedCrossRefGoogle Scholar
  33. 33.
    Kaufman ES, Bloomfield DM, Steinman RC et al (2006)9 “Indeterminate” microvolt T-wave tests predict high risk of death or sustained ventricular arrhythmias in patients with left ventricular dysfunction. J Am Coll Cardiol 48:1399–140PubMedCrossRefGoogle Scholar
  34. 34.
    Salerno-Uriarte JA, Pedretti RF, Tritto M et al (2004) The ALPHA study (T-wave alternans in patients with heart failure): rationale, design and endpoints. Ital Heart J 5:587–592PubMedGoogle Scholar
  35. 35.
    Ikeda T, Saito H, Tanno K et al (2002) T-wave alternans as a predictor for sudden cardiac death after myocardial infarction. Am J Cardiol 89:79–82PubMedCrossRefGoogle Scholar
  36. 36.
    Tapanainen JM, Still AM, Airaksinen KE, Huikuri HV (2001) Prognostic significance of risk stratifiers of mortality, including T-wave alternans, after acute myocardial infarction. Results of a prospective follow-up study. J Cardiovasc Electrophysiol 12:645–652PubMedCrossRefGoogle Scholar
  37. 37.
    Hohnloser SH, Ikeda T, Bloomfield DM et al (2003) T-wave alternans negative coronary patients with low ejection and benefit from defibrillator implantation. Lancet 362:125–126PubMedCrossRefGoogle Scholar
  38. 38.
    Bloomfield DM, Steinman RC, Namerow PB et al (2004) Microvolt T-wave alternans distinguishes between patients likely and patients not likely to benefit from implanted cardiac defibrillator therapy: a solution to the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II conundrum. Circulation 110:1885–1889PubMedCrossRefGoogle Scholar
  39. 39.
    Chow T, Kereiakes DJ, Bartone C et al (2007) Microvolt T-wave alternans identifies patients with ischemic cardiomyopathy who benefit from implantable cardioverter-defibrillator therapy. J Am Coll Cardiol 49:50–58PubMedCrossRefGoogle Scholar
  40. 40.
    Ikeda T, Yoshino H, Sugi K et al (2006) Predictive value of microvolt T-wave alternans for sudden cardiac death in patients with preserved cardiac function after acute myocardial infarction: results of a collaborative cohort study. J Am Coll Cardiol 48:2268–2274PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2007

Authors and Affiliations

  • Roberto F. E. Pedretti
    • 1
  • Simona Sarzi Braga
    • 1
  • Raffaella Vaninetti
    • 1
  • Antonio Laporta
    • 1
  • Sergio Masnaghetti
    • 1
  • Rossella Raimondo
    • 1
  • Mario Salerno
    • 1
  • Francesco Santoro
    • 1
  1. 1.Division of Cardiology, IRCCS Fondazione Salvatore MaugeriScientific Institute of TradateTradate (VA)Italy

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