Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

T wave (repolarization) alternans: Clinical aspects

Sanjiv M Narayan, MD, PhD
Section Editor
Ary L Goldberger, MD
Deputy Editor
Brian C Downey, MD, FACC


T-wave alternans (TWA) refers to periodic beat-to-beat variability in the timing, shape, and/or amplitude of T-waves on the surface electrocardiogram (ECG) [1,2]. TWA therefore reflects sudden changes in temporal heterogeneity in ventricular repolarization, which is an important mechanism underlying reentrant arrhythmias [3,4].  

Despite the term "T-wave" alternans, alternating behavior may also involve the ST segment and U wave (figure 1) [2,5-8]. As a result, the term ventricular repolarization alternans may be more accurate, but is rarely used.

TWA of sufficient magnitude to be seen with visual inspection is uncommon. With the development of computerized filtering and spectral analysis tools, TWA on the order of microvolts can be detected, and microvolt TWA (MTWA, now often used synonymously with TWA) is both sensitive and specific for predicting ventricular arrhythmias in a number of clinical scenarios [1,2,7,9-16].

Clinical risk stratification for sudden cardiac death typically focuses on the presence of a reduced left ventricular ejection fraction and the presence of heart failure. However, these parameters identify only a minority of individuals who will die suddenly, and also identify others who will not suffer lethal ventricular arrhythmias [1,2]. As a result, there is continued interest in additional electrophysiologic indices for risk prediction, of which one of the most promising remains TWA [2].

The clinical utility of TWA will be reviewed here. The technical aspects and methods for analyzing TWA are discussed separately. (See "T wave (repolarization) alternans: Technical aspects".)


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Apr 2017. | This topic last updated: May 10, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Smith JM, Clancy EA, Valeri CR, et al. Electrical alternans and cardiac electrical instability. Circulation 1988; 77:110.
  2. Rosenbaum DS, Jackson LE, Smith JM, et al. Electrical alternans and vulnerability to ventricular arrhythmias. N Engl J Med 1994; 330:235.
  3. Kuo CS, Munakata K, Reddy CP, Surawicz B. Characteristics and possible mechanism of ventricular arrhythmia dependent on the dispersion of action potential durations. Circulation 1983; 67:1356.
  4. Narayan SM. T-wave alternans and the susceptibility to ventricular arrhythmias. J Am Coll Cardiol 2006; 47:269.
  5. Lee HC, Mohabir R, Smith N, et al. Effect of ischemia on calcium-dependent fluorescence transients in rabbit hearts containing indo 1. Correlation with monophasic action potentials and contraction. Circulation 1988; 78:1047.
  6. Nearing BD, Huang AH, Verrier RL. Dynamic tracking of cardiac vulnerability by complex demodulation of the T wave. Science 1991; 252:437.
  7. Narayan SM, Smith JM. Spectral analysis of periodic fluctuations in electrocardiographic repolarization. IEEE Trans Biomed Eng 1999; 46:203.
  8. Habbab MA, el-Sherif N. TU alternans, long QTU, and torsade de pointes: clinical and experimental observations. Pacing Clin Electrophysiol 1992; 15:916.
  9. Smith JM, Cohen RJ. Simple finite-element model accounts for wide range of cardiac dysrhythmias. Proc Natl Acad Sci U S A 1984; 81:233.
  10. Smith JM, Blue B, Clancy E, et al. Subtle alternating electrocardiographic morphology as an indicator of decreased cardiac electrical stability. Comput Cardiol 1985; 12:109.
  11. Estes NA 3rd, Michaud G, Zipes DP, et al. Electrical alternans during rest and exercise as predictors of vulnerability to ventricular arrhythmias. Am J Cardiol 1997; 80:1314.
  12. Hohnloser SH, Klingenheben T, Li YG, et al. T wave alternans as a predictor of recurrent ventricular tachyarrhythmias in ICD recipients: prospective comparison with conventional risk markers. J Cardiovasc Electrophysiol 1998; 9:1258.
  13. Gold MR, Bloomfield DM, Anderson KP, et al. A comparison of T-wave alternans, signal averaged electrocardiography and programmed ventricular stimulation for arrhythmia risk stratification. J Am Coll Cardiol 2000; 36:2247.
  14. Narayan SM, Smith JM. Exploiting rate-related hysteresis in repolarization alternans to improve risk stratification for ventricular tachycardia. J Am Coll Cardiol 2000; 35:1485.
  15. Hohnloser SH, Klingenheben T, Zabel M, et al. T wave alternans during exercise and atrial pacing in humans. J Cardiovasc Electrophysiol 1997; 8:987.
  16. Narayan SM, Smith JM. Differing rate dependence and temporal distribution of repolarization alternans in patients with and without ventricular tachycardia. J Cardiovasc Electrophysiol 1999; 10:61.
  17. Cantillon DJ, Stein KM, Markowitz SM, et al. Predictive value of microvolt T-wave alternans in patients with left ventricular dysfunction. J Am Coll Cardiol 2007; 50:166.
  18. Goldberger JJ, Cain ME, Hohnloser SH, et al. American Heart Association/American College of Cardiology Foundation/Heart Rhythm Society scientific statement on noninvasive risk stratification techniques for identifying patients at risk for sudden cardiac death: a scientific statement from the American Heart Association Council on Clinical Cardiology Committee on Electrocardiography and Arrhythmias and Council on Epidemiology and Prevention. Circulation 2008; 118:1497.
  19. Myles RC, Jackson CE, Tsorlalis I, et al. Is microvolt T-wave alternans the answer to risk stratification in heart failure? Circulation 2007; 116:2984.
  20. Buxton AE, Lee KL, DiCarlo L, et al. Electrophysiologic testing to identify patients with coronary artery disease who are at risk for sudden death. Multicenter Unsustained Tachycardia Trial Investigators. N Engl J Med 2000; 342:1937.
  21. Moss AJ, Daubert J, Zareba W. MADIT-II: clinical implications. Card Electrophysiol Rev 2002; 6:463.
  22. Gehi AK, Stein RH, Metz LD, Gomes JA. Microvolt T-wave alternans for the risk stratification of ventricular tachyarrhythmic events: a meta-analysis. J Am Coll Cardiol 2005; 46:75.
  23. Herring H. Experimentelle Studien an Saugentieren uber das Electrocardiogram. Z Exper Med 1909; 7:363.
  24. Lewis T. Notes upon alternation of the heart. Q J Med 1910; 4:141.
  25. Kleinfeld MJ, Rozanski JJ. Alternans of the ST segment in Prinzmetal's angina. Circulation 1977; 55:574.
  26. Schwartz PJ, Malliani A. Electrical alternation of the T-wave: clinical and experimental evidence of its relationship with the sympathetic nervous system and with the long Q-T syndrome. Am Heart J 1975; 89:45.
  27. Narayan SM. Is T-wave alternans as good or better than programmed ventricular stimulation? Heart Rhythm 2007; 4:913.
  28. Nearing BD, Verrier RL. Modified moving average analysis of T-wave alternans to predict ventricular fibrillation with high accuracy. J Appl Physiol (1985) 2002; 92:541.
  29. Leino J, Minkkinen M, Nieminen T, et al. Combined assessment of heart rate recovery and T-wave alternans during routine exercise testing improves prediction of total and cardiovascular mortality: the Finnish Cardiovascular Study. Heart Rhythm 2009; 6:1765.
  30. Ikeda T, Yoshino H, Sugi K, et al. 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 2006; 48:2268.
  31. Leino J, Verrier RL, Minkkinen M, et al. Importance of regional specificity of T-wave alternans in assessing risk for cardiovascular mortality and sudden cardiac death during routine exercise testing. Heart Rhythm 2011; 8:385.
  32. Ikeda T, Saito H, Tanno K, et al. T-wave alternans as a predictor for sudden cardiac death after myocardial infarction. Am J Cardiol 2002; 89:79.
  33. Ikeda T, Sakata T, Takami M, et al. Combined assessment of T-wave alternans and late potentials used to predict arrhythmic events after myocardial infarction. A prospective study. J Am Coll Cardiol 2000; 35:722.
  34. Tapanainen JM, Still AM, Airaksinen KE, Huikuri HV. 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 2001; 12:645.
  35. Chow T, Kereiakes DJ, Bartone C, et al. Prognostic utility of microvolt T-wave alternans in risk stratification of patients with ischemic cardiomyopathy. J Am Coll Cardiol 2006; 47:1820.
  36. Costantini O, Hohnloser SH, Kirk MM, et al. The ABCD (Alternans Before Cardioverter Defibrillator) Trial: strategies using T-wave alternans to improve efficiency of sudden cardiac death prevention. J Am Coll Cardiol 2009; 53:471.
  37. Bloomfield DM, Bigger JT, Steinman RC, et al. Microvolt T-wave alternans and the risk of death or sustained ventricular arrhythmias in patients with left ventricular dysfunction. J Am Coll Cardiol 2006; 47:456.
  38. Hohnloser SH, Klingenheben T, Bloomfield D, et al. 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 2003; 41:2220.
  39. Køber L, Torp-Pedersen C, Pedersen OD, et al. Importance of congestive heart failure and interaction of congestive heart failure and left ventricular systolic function on prognosis in patients with acute myocardial infarction. Am J Cardiol 1996; 78:1124.
  40. Klingenheben T, Zabel M, D'Agostino RB, et al. Predictive value of T-wave alternans for arrhythmic events in patients with congestive heart failure. Lancet 2000; 356:651.
  41. Salerno-Uriarte JA, De Ferrari GM, Klersy C, et al. Prognostic value of T-wave alternans in patients with heart failure due to nonischemic cardiomyopathy: results of the ALPHA Study. J Am Coll Cardiol 2007; 50:1896.
  42. Monasterio V, Laguna P, Cygankiewicz I, et al. Average T-wave alternans activity in ambulatory ECG records predicts sudden cardiac death in patients with chronic heart failure. Heart Rhythm 2012; 9:383.
  43. 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.
  44. 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.
  45. Hohnloser SH, Ikeda T, Cohen RJ. Evidence regarding clinical use of microvolt T-wave alternans. Heart Rhythm 2009; 6:S36.
  46. Hohnloser SH, Ikeda T, Bloomfield DM, et al. T-wave alternans negative coronary patients with low ejection and benefit from defibrillator implantation. Lancet 2003; 362:125.
  47. Bloomfield DM, Steinman RC, Namerow PB, et al. 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 2004; 110:1885.
  48. Chow T, Kereiakes DJ, Bartone C, et al. Microvolt T-wave alternans identifies patients with ischemic cardiomyopathy who benefit from implantable cardioverter-defibrillator therapy. J Am Coll Cardiol 2007; 49:50.
  49. Chow T, Kereiakes DJ, Onufer J, et al. Does microvolt T-wave alternans testing predict ventricular tachyarrhythmias in patients with ischemic cardiomyopathy and prophylactic defibrillators? The MASTER (Microvolt T Wave Alternans Testing for Risk Stratification of Post-Myocardial Infarction Patients) trial. J Am Coll Cardiol 2008; 52:1607.
  50. Gold MR, Ip JH, Costantini O, et al. Role of microvolt T-wave alternans in assessment of arrhythmia vulnerability among patients with heart failure and systolic dysfunction: primary results from the T-wave alternans sudden cardiac death in heart failure trial substudy. Circulation 2008; 118:2022.
  51. Buxton AE, Hafley GE, Lehmann MH, et al. Prediction of sustained ventricular tachycardia inducible by programmed stimulation in patients with coronary artery disease. Utility of clinical variables. Circulation 1999; 99:1843.
  52. Schwartz PJ, Moss AJ, Vincent GM, Crampton RS. Diagnostic criteria for the long QT syndrome. An update. Circulation 1993; 88:782.
  53. Zareba W, Moss AJ, le Cessie S, Hall WJ. T wave alternans in idiopathic long QT syndrome. J Am Coll Cardiol 1994; 23:1541.
  54. Burattini L, Zareba W, Rashba EJ, et al. ECG features of microvolt T-wave alternans in coronary artery disease and long QT syndrome patients. J Electrocardiol 1998; 31 Suppl:114.
  55. Chinushi M, Restivo M, Caref EB, El-Sherif N. Electrophysiological basis of arrhythmogenicity of QT/T alternans in the long-QT syndrome: tridimensional analysis of the kinetics of cardiac repolarization. Circ Res 1998; 83:614.
  56. Cruz Filho FE, Maia IG, Fagundes ML, et al. Electrical behavior of T-wave polarity alternans in patients with congenital long QT syndrome. J Am Coll Cardiol 2000; 36:167.
  57. Verrier RL, Tolat AV, Josephson ME. T-Wave alternans for arrhythmia risk stratification in patients with idiopathic dilated cardiomyopathy. J Am Coll Cardiol 2003; 41:2225.
  58. Kaufman ES, Bloomfield DM, Steinman RC, et al. "Indeterminate" microvolt T-wave alternans tests predict high risk of death or sustained ventricular arrhythmias in patients with left ventricular dysfunction. J Am Coll Cardiol 2006; 48:1399.
  59. Chan PS, Bartone C, Booth T, et al. Prognostic implication of redefining indeterminate microvolt T-wave alternans studies as abnormal or normal. Am Heart J 2007; 153:523.
  60. Lorell BH, Braunwald E. Pericardial Disease. In: Heart Disease: A Textbook of Cardiovascular Medicine, Braunwald E (Ed), WB Saunders, Philadelphia 1996. p.1476.
  61. Shusterman V, Goldberg A, London B. Upsurge in T-wave alternans and nonalternating repolarization instability precedes spontaneous initiation of ventricular tachyarrhythmias in humans. Circulation 2006; 113:2880.
  62. Houltz B, Darpö B, Edvardsson N, et al. Electrocardiographic and clinical predictors of torsades de pointes induced by almokalant infusion in patients with chronic atrial fibrillation or flutter: a prospective study. Pacing Clin Electrophysiol 1998; 21:1044.
  63. Surawicz B, Fisch C. Cardiac alternans: diverse mechanisms and clinical manifestations. J Am Coll Cardiol 1992; 20:483.
  64. Bardají A, Vidal F, Richart C. T wave alternans associated with amiodarone. J Electrocardiol 1993; 26:155.