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T wave (repolarization) alternans: Clinical aspects

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


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 T-wave alternans (TWA) [2].

TWA refers to beat-to-beat variability in the timing or shape of T-waves on the surface electrocardiogram (ECG) [1,2]. TWA reflects temporal heterogeneity or dispersion in ventricular repolarization, which is an important mechanism underlying reentrant arrhythmias [3,4]. Several studies suggest that TWA may add value to signal-averaged ECG, heart rate variability, and other indices. TWA is approved by the United States Food and Drug Administration (FDA) for noninvasively predicting the risk for life-threatening ventricular arrhythmias [5].

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".)


TWA is primarily used as a tool for the risk stratification for sudden cardiac death (SCD) [6]. Most of the focus of such efforts has been on patients with prior myocardial infarction, reduced left ventricular (LV) ejection fraction, and/or symptomatic heart failure [7-9]. More recently, TWA has been studied in more diverse populations.

Historically, studies of TWA may be divided into three phases:


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Literature review current through: Feb 2017. | This topic last updated: Wed Oct 21 00:00:00 GMT 2015.
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  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. http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/510kClearances/ucm093462.htm (Accessed on December 15, 2010).
  6. 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.
  7. 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.
  8. Moss AJ, Daubert J, Zareba W. MADIT-II: clinical implications. Card Electrophysiol Rev 2002; 6:463.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. 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.
  21. 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.
  22. 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.
  23. 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.
  24. 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.
  25. Rashba EJ, Osman AF, MacMurdy K, et al. Influence of QRS duration on the prognostic value of T wave alternans. J Cardiovasc Electrophysiol 2002; 13:770.
  26. 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.
  27. 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.
  28. Exner DV, Kavanagh KM, Slawnych MP, et al. Noninvasive risk assessment early after a myocardial infarction the REFINE study. J Am Coll Cardiol 2007; 50:2275.
  29. Junttila MJ, Barthel P, Myerburg RJ, et al. Sudden cardiac death after myocardial infarction in patients with type 2 diabetes. Heart Rhythm 2010; 7:1396.
  30. Martin DT, Shoraki A, Nesto RW, Rutter MK. Influence of diabetes and/or myocardial infarction on prevalence of abnormal T-wave alternans. Ann Noninvasive Electrocardiol 2009; 14:355.
  31. Molon G, Costa A, Bertolini L, et al. Relationship between abnormal microvolt T-wave alternans and poor glycemic control in type 2 diabetic patients. Pacing Clin Electrophysiol 2007; 30:1267.
  32. 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.
  33. 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.
  34. 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.
  35. 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.
  36. 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.
  37. Morin DP, Zacks ES, Mauer AC, et al. Effect of bundle branch block on microvolt T-wave alternans and electrophysiologic testing in patients with ischemic cardiomyopathy. Heart Rhythm 2007; 4:904.
  38. Narayan SM, Smith JM, Schechtman KB, et al. T-wave alternans phase following ventricular extrasystoles predicts arrhythmia-free survival. Heart Rhythm 2005; 2:234.
  39. 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.
  40. 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.
  41. 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.
  42. 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.
  43. 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.
  44. 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.
  45. Chan PS, Stein K, Chow T, et al. Cost-effectiveness of a microvolt T-wave alternans screening strategy for implantable cardioverter-defibrillator placement in the MADIT-II-eligible population. J Am Coll Cardiol 2006; 48:112.
  46. 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.
  47. 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.
  48. Hohnloser SH, Ikeda T, Cohen RJ. Evidence regarding clinical use of microvolt T-wave alternans. Heart Rhythm 2009; 6:S36.
  49. Kitamura H, Ohnishi Y, Okajima K, et al. Onset heart rate of microvolt-level T-wave alternans provides clinical and prognostic value in nonischemic dilated cardiomyopathy. J Am Coll Cardiol 2002; 39:295.
  50. Grimm W, Christ M, Bach J, et al. Noninvasive arrhythmia risk stratification in idiopathic dilated cardiomyopathy: results of the Marburg Cardiomyopathy Study. Circulation 2003; 108:2883.
  51. Schwartz PJ, Moss AJ, Vincent GM, Crampton RS. Diagnostic criteria for the long QT syndrome. An update. Circulation 1993; 88:782.
  52. Zareba W, Moss AJ, le Cessie S, Hall WJ. T wave alternans in idiopathic long QT syndrome. J Am Coll Cardiol 1994; 23:1541.
  53. 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.
  54. Habbab MA, el-Sherif N. TU alternans, long QTU, and torsade de pointes: clinical and experimental observations. Pacing Clin Electrophysiol 1992; 15:916.
  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. Momiyama Y, Hartikainen J, Nagayoshi H, et al. Exercise-induced T-wave alternans as a marker of high risk in patients with hypertrophic cardiomyopathy. Jpn Circ J 1997; 61:650.
  58. Kleiger RE, Miller JP, Bigger JT Jr, Moss AJ. Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol 1987; 59:256.
  59. Farrell TG, Bashir Y, Cripps T, et al. Risk stratification for arrhythmic events in postinfarction patients based on heart rate variability, ambulatory electrocardiographic variables and the signal-averaged electrocardiogram. J Am Coll Cardiol 1991; 18:687.
  60. Schmidt G, Malik M, Barthel P, et al. Heart-rate turbulence after ventricular premature beats as a predictor of mortality after acute myocardial infarction. Lancet 1999; 353:1390.
  61. Zabel M, Klingenheben T, Franz MR, Hohnloser SH. Assessment of QT dispersion for prediction of mortality or arrhythmic events after myocardial infarction: results of a prospective, long-term follow-up study. Circulation 1998; 97:2543.
  62. Burnes JE, Ghanem RN, Waldo AL, Rudy Y. Imaging dispersion of myocardial repolarization, I: comparison of body-surface and epicardial measures. Circulation 2001; 104:1299.
  63. Klingenheben T, Grönefeld G, Li YG, Hohnloser SH. Effect of metoprolol and d,l-sotalol on microvolt-level T-wave alternans. Results of a prospective, double-blind, randomized study. J Am Coll Cardiol 2001; 38:2013.
  64. Kaufman ES, Mackall JA, Julka B, et al. Influence of heart rate and sympathetic stimulation on arrhythmogenic T wave alternans. Am J Physiol Heart Circ Physiol 2000; 279:H1248.
  65. Zacks ES, Morin DP, Ageno S, et al. Effect of oral beta-blocker therapy on microvolt T-wave alternans and electrophysiology testing in patients with ischemic cardiomyopathy. Am Heart J 2007; 153:392.
  66. Rashba EJ, Cooklin M, MacMurdy K, et al. Effects of selective autonomic blockade on T-wave alternans in humans. Circulation 2002; 105:837.
  67. Komiya N, Seto S, Nakao K, Yano K. The influence of beta-adrenergic agonists and antagonists on T-wave alternans in patients with and without ventricular tachyarrhythmia. Pacing Clin Electrophysiol 2005; 28:680.
  68. Kavesh NG, Shorofsky SR, Sarang SE, Gold MR. Effect of heart rate on T wave alternans. J Cardiovasc Electrophysiol 1998; 9:703.
  69. 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.
  70. Surawicz B, Fisch C. Cardiac alternans: diverse mechanisms and clinical manifestations. J Am Coll Cardiol 1992; 20:483.
  71. Bardají A, Vidal F, Richart C. T wave alternans associated with amiodarone. J Electrocardiol 1993; 26:155.
  72. Narayan SM. Is T-wave alternans as good or better than programmed ventricular stimulation? Heart Rhythm 2007; 4:913.
  73. 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.
  74. Nearing BD, Wellenius GA, Mittleman MA, et al. Crescendo in depolarization and repolarization heterogeneity heralds development of ventricular tachycardia in hospitalized patients with decompensated heart failure. Circ Arrhythm Electrophysiol 2012; 5:84.
  75. Swerdlow C, Chow T, Das M, et al. Intracardiac electrogram T-wave alternans/variability increases before spontaneous ventricular tachyarrhythmias in implantable cardioverter-defibrillator patients: a prospective, multi-center study. Circulation 2011; 123:1052.
  76. Armoundas AA, Weiss EH, Sayadi O, et al. A novel pacing method to suppress repolarization alternans in vivo: implications for arrhythmia prevention. Heart Rhythm 2013; 10:564.
  77. Kovach JA, Nearing BD, Verrier RL. Angerlike behavioral state potentiates myocardial ischemia-induced T-wave alternans in canines. J Am Coll Cardiol 2001; 37:1719.
  78. Lampert R. ECG signatures of psychological stress. J Electrocardiol 2015; 48:1000.
  79. 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.