Microvolt T-wave alternans: a review of techniques, interpretation, utility, clinical studies, and future perspectives.

Microvolt T-wave alternans (TWA) testing involves measuring variation in the morphology of the T-wave on an every other beat basis. The magnitude of the variation observed is typically on the order of a few microvolts. Thus in order to detect microvolt TWA, specialized recording and signal processing methods must be employed for reliable measurement. Additionally, microvolt TWA is not generally present at rest even in patients at risk of ventricular tachyarrhythmias and therefore exercise stress, pharmacologic stress, or atrial pacing must be utilized in order to elevate the heart rate. A positive MTWA test is one in which sustained TWA is present with an onset heart rate < or = 110 bpm. With current instrumentation, microvolt TWA represents an inexpensive, convenient non-invasive testing modality. Microvolt TWA has been evaluated prospectively in a variety of patient populations as a means of predicting occurrence of ventricular tachyarrhythmic events and its association with the genesis of ventricular arrhythmias has been demonstrated. Future role of microvolt TWA testing in noninvasive risk stratification is awaiting results of ongoing clinical trials. In this article, we tried to review the techniques, interpretation, indications, clinical studies, and future perspectives of microvolt TWA.

[1]  M. Nakashima,et al.  Potentiating effects of a ventricular premature beat on the alternation of the ST-T complex of epicardial electrograms and the incidence of ventricular arrhythmias during acute coronary occlusion in dogs. , 1984, Journal of electrocardiology.

[2]  H. Huikuri,et al.  Prognostic Significance of Risk Stratifiers of Mortality, Including T Wave Alternans, After Acute Myocardial Infarction: Results of a Prospective Follow‐Up Study , 2001, Journal of cardiovascular electrophysiology.

[3]  R. Cohen,et al.  Electrical alternans during rest and exercise as predictors of vulnerability to ventricular arrhythmias. , 1997, The American journal of cardiology.

[4]  E. Kaufman,et al.  Influence of heart rate and sympathetic stimulation on arrhythmogenic T wave alternans. , 2000, American journal of physiology. Heart and circulatory physiology.

[5]  J. Cinca,et al.  The dependence of T wave alternans on diastolic resting period duration. , 1978, European journal of cardiology.

[6]  Bertram Pitt,et al.  Effect of d-sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction , 1996, The Lancet.

[7]  M. Yokoyama,et al.  Relationship between the QT indices and the microvolt-level T wave alternans in cardiomyopathy. , 2001, Japanese circulation journal.

[8]  M. Yamaki,et al.  Intracoronary flecainide induces ST alternans and reentrant arrhythmia on intact canine heart: A role of 4-aminopyridine-sensitive current. , 1999, Circulation.

[9]  R J Cohen,et al.  Predicting Sudden Cardiac Death From T Wave Alternans of the Surface Electrocardiogram: , 1996, Journal of cardiovascular electrophysiology.

[10]  T. Asano,et al.  T wave alternans for predicting adverse effects of amiodarone in a patient with dilated cardiomyopathy. , 2001, Japanese circulation journal.

[11]  T. Asano,et al.  Onset heart rate and microvolt t-wave alternans during atrial pacing. , 2000, The American journal of cardiology.

[12]  Thomas Lewis,et al.  NOTES UPON ALTERNATION OF THE HEART , 1911 .

[13]  R. Verrier,et al.  Modified moving average analysis of T-wave alternans to predict ventricular fibrillation with high accuracy. , 2002, Journal of applied physiology.

[14]  M. Yokoyama,et al.  Onset heart rate of microvolt-level T-wave alternans provides clinical and prognostic value in nonischemic dilated cardiomyopathy. , 2002, Journal of the American College of Cardiology.

[15]  M. Nakashima,et al.  EFFECTS OF CALCIUM ANTAGONISTS ON THE ALTERNATION OF THE ST‐T COMPLEX AND ASSOCIATED CONDUCTION ABNORMALITIES DURING CORONARY OCCLUSION IN DOGS , 1981, British journal of pharmacology.

[16]  Y. Aizawa,et al.  Intravenous Administration of Class I Antiarrhythmic Drugs Induced T Wave Alternans in a Patient with Brugada Syndrome , 2001, Journal of cardiovascular electrophysiology.

[17]  S. Hohnloser,et al.  Effect of metoprolol and d,l-sotalol on microvolt-level T-wave alternans. Results of a prospective, double-blind, randomized study. , 2001, Journal of the American College of Cardiology.

[18]  W. Grimm,et al.  Noninvasive Arrhythmia Risk Stratification in Idiopathic Dilated Cardiomyopathy: Results of the Marburg Cardiomyopathy Study , 2003, Circulation.

[19]  A. Kuroiwa,et al.  Effects of heart rate and diltiazem hydrochloride on alternans of ST segment elevation and ventricular arrhythmia during acute myocardial ischaemia in dogs. , 1989, Cardiovascular Research.

[20]  R J Cohen,et al.  T Wave Alternans During Exercise and Atrial Pacing in Humans , 1997, Journal of cardiovascular electrophysiology.

[21]  A. Wilde,et al.  T wave alternans after sotalol: evidence for increased sensitivity to sotalol after conversion from atrial fibrillation to sinus rhythm , 1998, Heart.

[22]  Michael R Gold,et al.  Enhanced Detection of Arrhythmia Vulnerability Using T Wave Alternans, Left Ventricular Ejection Fraction, and Programmed Ventricular Stimulation: , 2004, Journal of cardiovascular electrophysiology.

[23]  M. Yokoyama,et al.  Determinant of microvolt-level T-wave alternans in patients with dilated cardiomyopathy. , 1999, Journal of the American College of Cardiology.

[24]  M. Kleinfeld,et al.  Alternans of the ST Segment in Prinzmetal's Angina , 1977, Circulation.

[25]  D. Adam,et al.  Ventricular Fibrillation and Fluctuations in the Magnitude of the Repolarization Vector , 1982 .

[26]  H. Hayakawa,et al.  Electrical and Mechanical Alternans in Canine Myocardium In Vivo Dependence on Intracellular Calcium Cycling , 1993, Circulation.

[27]  D. Durrer,et al.  The Effect of Acute Coronary Artery Occlusion on Subepicardial Transmembrane Potentials in the Intact Porcine Heart , 1977, Circulation.

[28]  A. A. Armoundas,et al.  Images in cardiovascular medicine. T-wave alternans preceding torsade de pointes ventricular tachycardia. , 2000, Circulation.

[29]  N. El-Sherif,et al.  T‐Wave Alternans and Arrhythmia Risk Stratification , 2001, Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc.

[30]  P. Hjemdahl,et al.  Renal neurohormonal and vascular responses to dynamic exercise in humans. , 1991, Journal of applied physiology.

[31]  G. Breithardt,et al.  T Wave Alternans Does not Assess Arrhythmic Risk in Patients with Brugada Syndrome , 2004, Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc.

[32]  T. Cheng Electrical alternans. An association with coronary artery spasm. , 1983, Archives of internal medicine.

[33]  R J Cohen,et al.  T Wave Alternans as a Predictor of Recurrent Ventricular Tachyarrhythmias in ICD Recipients: Prospective Comparison with Conventional Risk Markers , 1998, Journal of cardiovascular electrophysiology.

[34]  R J Cohen,et al.  Electrical alternans and cardiac electrical instability. , 1988, Circulation.

[35]  W. Grimm,et al.  Value of Time‐ and Frequency‐Domain Analysis of Signal‐Averaged Electrocardiography for Arrhythmia Risk Prediction in Idiopathic Dilated Cardiomyopathy , 1996, Pacing and clinical electrophysiology : PACE.

[36]  R. Peters,et al.  Effects of Selective Autonomic Blockade on T-Wave Alternans in Humans , 2002, Circulation.

[37]  K. Kubo,et al.  T-Wave Alternans in Patients with Right Ventricular Tachycardia , 2003, Cardiology.

[38]  S. Hohnloser,et al.  Predictive value of T-wave alternans for arrhythmic events in patients with congestive heart failure , 2000, The Lancet.

[39]  W. Shimizu,et al.  Monophasic action potential recordings during T-wave alternans in congenital long QT syndrome. , 1996, American heart journal.

[40]  T. Ikeda,et al.  Combined assessment of T-wave alternans and late potentials used to predict arrhythmic events after myocardial infarction. A prospective study. , 2000, Journal of the American College of Cardiology.

[41]  K. Ono,et al.  Relation between microvolt-level T-wave alternans and cardiac sympathetic nervous system abnormality using iodine-123 metaiodobenzylguanidine imaging in patients with idiopathic dilated cardiomyopathy. , 2003, The American journal of cardiology.

[42]  Michael R Gold,et al.  Exercise is Superior to Pacing for T Wave Alternans Measurement in Subjects with Chronic Coronary Artery Disease and Left Ventricular Dysfunction , 2002, Journal of cardiovascular electrophysiology.

[43]  M. Oliver Benefits and Risks of Drugs in Secondary Prevention of Ischaemic Heart Diseasc—a Summary , 1986 .

[44]  J. Roelandt,et al.  Images in Cardiovascular Medicine , 2000 .

[45]  S. Connolly,et al.  Randomised trial of outcome after myocardial infarction in patients with frequent or repetitive ventricular premature depolarisations: CAMIAT , 1997, The Lancet.

[46]  R J Cohen,et al.  T-wave alternans and dispersion of the QT interval as risk stratification markers in patients susceptible to sustained ventricular arrhythmias. , 1998, The American journal of cardiology.

[47]  C. Antzelevitch,et al.  Cellular and ionic basis for T-wave alternans under long-QT conditions. , 1999, Circulation.

[48]  S. Ogawa,et al.  Different responses of epicardium and endocardium to KATP channel modulators during regional ischemia. , 1996, The American journal of physiology.

[49]  D. Zipes,et al.  Amiodarone Reduces the Prevalence of T Wave Alternans in a Population with Ventricular Tachyarrhythmias , 1999, Journal of cardiovascular electrophysiology.

[50]  David S. Rosenbaum,et al.  T-Wave Alternans , 2003 .

[51]  J. Yoshikawa,et al.  Pilsicanide‐Induced Marked T Wave Alternans and Ventricular Fibrillation in a Patient with Brugada Syndrome , 2002, Journal of cardiovascular electrophysiology.

[52]  D. Rosenbaum,et al.  Mechanism linking T-wave alternans to the genesis of cardiac fibrillation. , 1999, Circulation.

[53]  A. Moss,et al.  Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators. , 1996, The New England journal of medicine.

[54]  J Hartikainen,et al.  Exercise-induced T-wave alternans as a marker of high risk in patients with hypertrophic cardiomyopathy. , 1997, Japanese circulation journal.

[55]  W. Grimm,et al.  QT dispersion and arrhythmic events in idiopathic dilated cardiomyopathy. , 1996, The American journal of cardiology.

[56]  M. Gold,et al.  Prognostic value of the signal-averaged electrocardiogram and a prolonged QRS in ischemic and nonischemic cardiomyopathy. , 1995, The American journal of cardiology.

[57]  Richard J Cohen,et al.  Interpretation and Classification of Microvolt T Wave Alternans Tests , 2002, Journal of cardiovascular electrophysiology.

[58]  K Suzuki,et al.  Effects of calcium antagonists on the electrical alternans of the ST segment and on associated mechanical alternans during acute coronary occlusion in dogs. , 1983, Circulation.

[59]  Antonis A Armoundas,et al.  Pathophysiological basis and clinical application of T-wave alternans. , 2002, Journal of the American College of Cardiology.

[60]  D. Adam,et al.  Period multupling-evidence for nonlinear behaviour of the canine heart , 1984, Nature.

[61]  D. Rosenbaum,et al.  Occult T Wave Alternans in Long QT Syndrome , 1996, Journal of cardiovascular electrophysiology.

[62]  Z. Shimoni,et al.  Electrical alternans of giant U waves with multiple electrolyte deficits. , 1984, The American journal of cardiology.

[63]  S Yasui,et al.  Significance of discordant ST alternans in ventricular fibrillation. , 1990, Circulation.

[64]  J Thomas Bigger,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 , 2004, Circulation.

[65]  D. Adam,et al.  Fluctuations in T-wave morphology and susceptibility to ventricular fibrillation. , 1984, Journal of electrocardiology.

[66]  A Malliani,et al.  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. , 1975, American heart journal.

[67]  W. Mckenna,et al.  Usefulness of signal-averaged electrocardiogram in idiopathic dilated cardiomyopathy for identifying patients with ventricular arrhythmias. , 1993, The American journal of cardiology.

[68]  J. Bigger,et al.  Ambulatory Electrocardiogram‐Based Tracking of T Wave Alternans in Postmyocardial Infarction Patients to Assess Risk of Cardiac Arrest or Arrhythmic Death , 2003, Journal of cardiovascular electrophysiology.

[69]  J. Jalife,et al.  Cardiac Electrophysiology: From Cell to Bedside , 1990 .

[70]  D Durrer,et al.  Mechanism and Time Course of S‐T and T‐Q Segment Changes during Acute Regional Myocardial Ischemia in the Pig Heart Determined by Extracellular and Intracellular Recordings , 1978, Circulation research.

[71]  Katherine A. Sheehan,et al.  Functional coupling between glycolysis and excitation—contraction coupling underlies alternans in cat heart cells , 2000, The Journal of physiology.

[72]  R. Verrier,et al.  Dynamic tracking of cardiac vulnerability by complex demodulation of the T wave. , 1991, Science.

[73]  K. Lee,et al.  A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators. , 1999, The New England journal of medicine.

[74]  J P Miller,et al.  The relationships among ventricular arrhythmias, left ventricular dysfunction, and mortality in the 2 years after myocardial infarction. , 1984, Circulation.

[75]  M R Gold,et al.  A comparison of T-wave alternans, signal averaged electrocardiography and programmed ventricular stimulation for arrhythmia risk stratification. , 2000, Journal of the American College of Cardiology.

[76]  J. Tomcsányi,et al.  Amiodarone‐Induced Giant T Wave Alternans Hastens Proarrhythmic Response , 2002, Journal of cardiovascular electrophysiology.

[77]  R J Cohen,et al.  Prognostic significance of electrical alternans versus signal averaged electrocardiography in predicting the outcome of electrophysiological testing and arrhythmia-free survival , 1998, Heart.

[78]  Takanori Ikeda,et al.  T-wave alternans as a predictor for sudden cardiac death after myocardial infarction. , 2002, The American journal of cardiology.

[79]  M. Gold,et al.  The Effect of Procainamide on T Wave Alternans , 1999, Journal of cardiovascular electrophysiology.

[80]  J. Ruskin,et al.  Electrical alternans and vulnerability to ventricular arrhythmias. , 1994, The New England journal of medicine.

[81]  D. Rosenbaum,et al.  Role of Structural Barriers in the Mechanism of Alternans-Induced Reentry , 2000, Circulation research.

[82]  Y. Kagaya,et al.  Microvolt T Wave Alternans in Human Cardiac Hypertrophy: Electrical Instability and Abnormal Myocardial Arrangement , 2001, Journal of cardiovascular electrophysiology.

[83]  R. Verrier,et al.  Potent antifibrillatory effect of combined blockade of calcium channels and 5-HT2 receptors with nexopamil during myocardial ischemia and reperfusion in dogs: comparison to diltiazem. , 1996, Journal of cardiovascular pharmacology.

[84]  N. el-Sherif,et al.  Repolarization alternans associated with alcoholism and hypomagnesemia. , 1984, The American journal of cardiology.

[85]  R. Peters,et al.  Influence of QRS Duration on the Prognostic Value of T Wave Alternans , 2002, Journal of cardiovascular electrophysiology.

[86]  M Restivo,et al.  Electrophysiological basis of arrhythmogenicity of QT/T alternans in the long-QT syndrome: tridimensional analysis of the kinetics of cardiac repolarization. , 1998, Circulation research.

[87]  Guy Salama,et al.  Simultaneous maps of optical action potentials and calcium transients in guinea‐pig hearts: mechanisms underlying concordant alternans , 2000, The Journal of physiology.

[88]  H L Greene,et al.  Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. , 1991, The New England journal of medicine.

[89]  T. Ikeda,et al.  Assessment of noninvasive markers in identifying patients at risk in the Brugada syndrome: insight into risk stratification. , 2001, Journal of the American College of Cardiology.

[90]  S. Hohnloser,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. , 2003, Journal of the American College of Cardiology.

[91]  T. Ikeda,et al.  Comparison of T-wave alternans and QT interval dispersion to predict ventricular tachyarrhythmia in patients with dilated cardiomyopathy and without antiarrhythmic drugs: a prospective study. , 2001, Japanese heart journal.

[92]  M. Matsuzaki,et al.  Effect of long-term beta-blocker therapy on microvolt-level T-wave alternans in association with the improvement of the cardiac sympathetic nervous system and systolic function in patients with non-ischemic heart disease. , 2003, Circulation journal : official journal of the Japanese Circulation Society.

[93]  M. Puletti,et al.  Alternans of the ST segment and T wave in acute myocardial infarction. , 1980, Journal of electrocardiology.

[94]  R. Cohen,et al.  Simple finite-element model accounts for wide range of cardiac dysrhythmias. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[95]  S. Hohnloser,et al.  T wave alternans and left ventricular ejection fraction, but not QT variability index, predict appropriate ICD discharge. , 1999, Journal of cardiovascular electrophysiology.

[96]  J. Cohn,et al.  Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. , 1984, The New England journal of medicine.

[97]  H. Morita,et al.  Ventricular arrhythmia induced by sodium channel blocker in patients with Brugada syndrome. , 2003, Journal of the American College of Cardiology.

[98]  J P Amlie,et al.  Dispersion of monophasic action potential durations and activation times during atrial pacing, ventricular pacing, and ventricular premature stimulation in canine ventricles. , 1983, Cardiovascular research.

[99]  C Antzelevitch,et al.  Clinical relevance of cardiac arrhythmias generated by afterdepolarizations. Role of M cells in the generation of U waves, triggered activity and torsade de pointes. , 1994, Journal of the American College of Cardiology.

[100]  R. Verrier,et al.  Angerlike behavioral state potentiates myocardial ischemia-induced T-wave alternans in canines. , 2001, Journal of the American College of Cardiology.

[101]  M R Gold,et al.  Effect of Heart Rate on T Wave Alternans , 1997, Journal of cardiovascular electrophysiology.

[102]  M J Lab,et al.  Electrophysiological alternans and restitution during acute regional ischaemia in myocardium of anaesthetized pig. , 1988, The Journal of physiology.