T-wave alternans in microwave frequency as a new indicator of disordered ventricular repolarization: pathophysiology, methodology, clinical results

Primary prevention of sudden cardiac death is hampered by the inability to accurately identify high risk patients. Various noninvasive methods such as determination of left ventricular function or heart rate variability as well as invasive electrophysiologic testing are currently used for risk stratification. Noninvasive measurement of microvolt T wave alternans (TWA) is a promising new method to assess repolarization abnormalities; in experimental studies, TWA was associated with an increased incidence of ventricular tachyarrhythmias. Since the occurrence of TWA is heart rate-dependent, it is measured either during atrial pacing or during exercise stress testing. The first clinical validation of the method was performed in patients undergoing invasive EP testing to assess prediction of inducibility of ventricular tachyarrhythmias. A first prospective validation of the noninvasive method was performed in patients surviving out-of-hospital cardiac arrest fitted with an ICD. Further studies have shown a good concordance between invasive and noninvasive TWA determination. The occurrence of TWA in this population was of predictive value with respect to arrhythmia recurrence. Recently published data confirm the value of TWA assessment with respect to identification of patients with congestive heart failure at high risk of malignant ventricular tachyarrhythmias. The use of this method in post myocardial infarction risk stratification is currently under prospective evaluation.     

Clinical significance of microvolt T-wave alternans

Several studies have recently proven that primary preventive therapy of sudden arrhythmogenic death is possible in selected patients with congestive heart failure, particularly in the setting of ischemic cardiomyopathy [1, 2]. However, a number needed to treat between 11 and 17 to save one life over three years in these studies indicates that a more accurate identification of high risk patients is desirable in order to avoid unnecessary implants of cardioverter/defibrillators (ICD). Since currently available risk stratification methods have limited predictive accuracy, development of new techniques is important in order to non-invasively assess arrhythmogenic risk in patients prone to sudden death. Microvolt level T-wave alternans (mTWA) has recently been proposed to assess abnormalities in ventricular repolarization favoring the occurrence of reentrant arrhythmias [3, 4]. In 1994, a first clinical study by Rosenbaum and coworkers [5] convincingly demonstrated that mTWA is closely related to arrhythmia induction in the electrophysiology (EP) laboratory as well as to the occurrence of spontaneous ventricular tachyarrhythmias during follow-up [5]. More recently, a number of clinical studies has examined its clinical applicability [4-7]. The present review summarizes currently available clinical data on TWA with a particular focus on risk stratifying patients with congestive heart failure and myocardial infarction.     

T-wave alternans: marker,mechanism, and methodology for predicting sudden cardiac death

Sudden cardiac death (SCD) is a leading cause of cardiovascular mortality. Therefore, identifying patients at highest risk for SCD is crucial. Conventional noninvasive markers of SCD are inadequate because of low positive predictive value. The presence of visible T-wave alternans (TWA) on electrocardiogram often predicts the occurrence of lethal ventricular arrhythmias. Signal processing methods have made it possible to detect microvolt-level and visually inapparent TWA on electrocardiogram. TWA is caused by underlying regional inhomogeneities of ventricular repolarization, which predispose patients to have ventricular arrhythmias. Microvolt TWA provoked either by atrial pacing, pharmacological stress, or exercise is a promising marker of arrhythmia vulnerability. Several large trials have shown TWA to be comparable or superior to other noninvasive markers and electrophysiologic study in the prediction of SCD. The patient populations in these trials include post myocardial infarction, both ischemic and nonischemic heart failure, and suspected arrhythmias. Prospective trials regarding benefits of implantation of cardioverter-defibrillator therapy based on TWA results are ongoing.     

Combined assessment of T-wave alternans and late potentials used to predict arrhythmic events after myocardial infarction. A prospective study

OBJECTIVES: The aim of the present study was to determine whether the combination of two markers that reflect depolarization and repolarization abnormalities can predict future arrhythmic events after acute myocardial infarction (MI). BACKGROUND: Although various noninvasive markers have been used to predict arrhythmic events after MI, the positive predictive value of the markers remains low. METHODS: We prospectively assessed T-wave alternans (TWA) and late potentials (LP) by signal-averaged electrocardiogram (ECG) and ejection fraction (EF) in 102 patients with successful determination results after acute MI. The TWA was analyzed using the power-spectral method during supine bicycle exercise testing. No antiarrhythmic drugs were used during the follow-up period. The study end point was the documentation of ventricular arrhythmias. RESULTS: The TWA was present in 50 patients (49%), LP present in 21 patients (21%), and an EF <40% in 28 patients (27%). During a follow-up period of 13 +/- 6 months, symptomatic, sustained ventricular tachycardia or ventricular fibrillation occurred in 15 patients (15%). The event rates were significantly higher in patients with TWA, LP, or an abnormal EF. The sensitivity and the negative predictive value of TWA in predicting arrhythmic events were very high (93% and 98%, respectively), whereas its positive predictive value (28%) was lower than those for LP and EF. The highest positive predictive value (50%) was obtained when TWA and LP were combined. CONCLUSIONS: The combined assessment of TWA and LP was associated with a high positive predictive value for an arrhythmic event after acute MI. Therefore, it could be a useful index to identify patients at high risk of arrhythmic events.     

Pathophysiological basis and clinical application of T-wave alternans

We review the contemporary understanding of the pathophysiology of repolarization alternans and present a perspective on the use of T-wave alternans (TWA) as a risk stratification marker of malignant ventricular arrhythmias. Several studies have demonstrated a high correlation of susceptibility to ventricular arrhythmias and sudden cardiac death with the existence of TWA. We describe a number of cellular and molecular alterations in the diseased heart that may provide a link between electrical and mechanical alternans and arrhythmia susceptibility. Repolarization alternans is likely the result of distinct and diverse cellular and molecular alterations that are associated with exaggerated regional repolarization heterogeneity, which renders the heart susceptible to malignant arrhythmias.     

T Wave Alternans as a Predictor of Recurrent Ventricular Tachyarrhythmias in ICD Recipients: Prospective Comparison with Conventional Risk Markers

T Wave Alternans for Risk Stratification. Introduction: The current standard for arrhythmic risk stratification is electrophysiologic (EP) testing, which, due to its invasive nature, is limited to patients already known to be at high risk. A number of noninvasive tests, such as determination of left ventricular ejection fraction (LVEF) or heart rate variability, have been evaluated as additional risk stratifiers. Microvolt T wave alternans (TWA) is a promising new risk marker. Prospective evaluation of noninvasive risk markers in low- or moderate-risk populations requires studies involving very large numbers of patients, and in such studies, documentation of the occurrence of ventricular tachyarrhythmias is difficult. In the present study, we identified a high-risk population, recipients of an implantable cardioverter defibrillator (ICD), and prospectively compared microvolt TWA with invasive EP testing and other risk markers with respect to their ability to predict recurrence of ventricular tachyarrhythmias as documented by ICD electrograms. Methods and Results: Ninety-five patients with a history of ventricular tachyarrhythmias undergoing implantation of an ICD underwent EP testing, assessment of TWA, as well as determination of LVEF, baroreflex sensitivity, signal-averaged ECG, analysis of 24-hour Holter monitoring, and QT dispersion from the 12-lead surface ECG. The endpoint of the study was first appropriate ICD therapy for electrogram-documented ventricular fibrillation or tachycardia during follow-up. Kaplan-Meier survival analysis revealed that TWA (P < 0.006) and LVEF (P < 0.04) were the only significant univariate risk stratifiers. EP testing was not statistically significant (P < 0.2). Multivariate Cox regression analysis revealed that TWA was the only statistically significant independent risk factor. Conclusions: Measurement of microvolt TWA compared favorably with both invasive EP testing and other currently used noninvasive risk assessment methods in predicting recurrence of ventricular tachyarrhythmias in ICD recipients. This study suggests that TWA might also be a powerful tool for risk stratification in low- or moderate-risk patients, and needs to he prospectively evaluated in such populations.     

Effect of metoprolol and d,l-sotalol on microvolt-level T-wave alternans: Results of a prospective, double-blind, randomized study

OBJECTIVESThe study evaluated the effects of metoprolol, a pure beta-blocker, and d,l-sotalol, a beta-blocker with additional class III antiarrhythmic effects, on microvolt-level T-wave alternans (TWA).BACKGROUNDAssessment of TWA is increasingly used for purposes of risk stratification in patients prone to sudden death. There are only sparse data regarding the effects of beta-blockers and antiarrhythmic drugs on TWA.METHODSPatients with a history of documented or suspected malignant ventricular tachyarrhythmias were eligible. All patients underwent invasive electrophysiologic (EP) testing including programmed ventricular stimulation and determination of TWA at increasing heart rates using atrial pacing. Reproducibility of TWA at two consecutive drug-free baseline measurements was tested in a random patient subset. Following baseline measurements, all patients were randomized either to double-blind intravenous infusion of sotalol (1.0 mg/kg) or metoprolol (0.1 mg/kg). Results of TWA assessment at baseline and after drug exposure were compared.RESULTSFifty-four consecutive patients were studied. In 12 patients, repetitive baseline measurement of TWA revealed stable alternans voltage (V_alt) values (9.1 ± 5.8 μV vs. 8.5 ± 5.7 μV, P = NS). After drug administration, V_alt decreased by 35% with metoprolol (7.9 ± 6.0 μV to 4.9 ± 4.2 μV; p < 0.001) and by 38% with sotalol (8.6 ± 6.8 μV to 4.4 ± 2.3 μV; P = 0.001). In eight patients with positive TWA at baseline, repeated measurement revealed negative test results.CONCLUSIONSIn patients prone to sudden cardiac death, there is a reduction in TWA amplitude following the administration of antiadrenergic drugs. This result indicates that TWA is responsive to the pharmacologic milieu and suggests that, to assess a patient’s risk of spontaneous ventricular arrhythmia, the patient should be tested while maintaining the pharmacologic regimen under which the risk of arrhythmia is being assessed. This applies particularly for beta-blocker therapy.     

A comparison of T-wave alternans, signal averaged electrocardiography and programmed ventricular stimulation for arrhythmia risk stratification

OBJECTIVES

The goal of this study was to compare T-wave alternans (TWA), signal-averaged electrocardiography (SAECG) and programmed ventricular stimulation (EPS) for arrhythmia risk stratification in patients undergoing electrophysiology study.

BACKGROUND

Accurate identification of patients at increased risk for sustained ventricular arrhythmias is critical to prevent sudden cardiac death. T-wave alternans is a heart rate dependent measure of repolarization that correlates with arrhythmia vulnerability in animal and human studies. Signal-averaged electrocardiography and EPS are more established tests used for risk stratification.

METHODS

This was a prospective, multicenter trial of 313 patients in sinus rhythm who were undergoing electrophysiologic study. T-wave alternans, assessed with bicycle ergometry, and SAECG were measured before EPS. The primary end point was sudden cardiac death, sustained ventricular tachycardia, ventricular fibrillation or appropriate implantable defibrillator (ICD) therapy, and the secondary end point was any of these arrhythmias or all-cause mortality.

RESULTS

Kaplan-Meier survival analysis of the primary end point showed that TWA predicted events with a relative risk of 10.9, EPS had a relative risk of 7.1 and SAECG had a relative risk of 4.5. The relative risks for the secondary end point were 13.9, 4.7 and 3.3, respectively (p < 0.05). Multivariate analysis of 11 clinical parameters identified only TWA and EPS as independent predictors of events. In the prespecified subgroup with known or suspected ventricular arrhythmias, TWA predicted primary end points with a relative risk of 6.1 and secondary end points with a relative risk of 8.0.

CONCLUSIONS

T-wave alternans is a strong independent predictor of spontaneous ventricular arrhythmias or death. It performed as well as programmed stimulation and better than SAECG in risk stratifying patients for life-threatening arrhythmias.     

T波电交替预测心力衰竭病人心源性猝死价值的新分歧

有半数的心力衰竭病AN致命性室性心律失常事件死于心源性猝死。T波电交替是公认的预测心源性猝死的重要指标。早在许多年前就发现T波电交替与心源性猝死有关,近年来新建了频域和时域测量方法。跨室壁复极离散度异常增大是T波电交替的机制。最近研究发布的用微伏级T波电交替进行心肌梗死后危险性分层的初步结果否定心肌梗死后左室射血分数〈30％的病人发生致死性快速室性心律失常的价值。但体内除颤器置入前T波电交替的对心源性猝死一级预防试验和非缺血性心肌病心力衰竭T波电交替的预测价值试验则强有力地支持T波电交替能预测心律失常。     

Prediction of adverse cardiac events in patients with acute anterior wall myocardial infarction treated with PCI

Despite common use of reperfusion therapy, particularly primary PCI during acute myocardial infarction, steadily increasing number of patients with low left ventricular ejection fraction, with heart failure (HF), requiring frequent rehospitalisation justifies the study establishing the best indices of prediction of major adverse cardiac events (MACE) occurrence. The aim of the study was to define the frequency of MACE (death, re MI, sVT, rehospitalisation for HF) in patients with acute anterior wall myocardial infarction in 6 month follow up and the factors determinatig its occurence. The 115 consecutive patients (86 males of age 57.7 +/- 11 yrs) with first anterior MI were studied. After successful PCI (TIMI 3) the angiographic assessment was performed (MBG 0-1 - no perfusion, MBG 2-3 - perfusion preserved). During first 48 hours 12-lead ECG was monitored in order to analyse the time to reduction of ST elevation in the lead with the highest elevation (deltatST 50%). On 2nd day LV function (LVEF and WMSI) and dyssfunctional segment perfusion (RPSI) were assessed. On 5th day Holter monitoring with arrhythmia and time domain parameters (SDNN, rMSSD) of heart rate variability were performed, on 30 day TWA test was done. RESULTS: During 180 follow-up 18 MACE occurred (3 death, 2 MI, 11 rehospitalisations for HF). In univariate analysis cigarette smoking, higher maximum troponin I value, LVEDV, LVESV, ST elevation sum, longer time to reduction of ST elevation, lower LVEF and RPSI, lack of microvessel integrity and positive TWA test had significant relationship with occurrence of MACE. The multivariate analysis of Cox proportional risk regression demonstrated that only lower value of RPSI and LVEF, longer time of ST elevation reduction in the lead with the highest ST elevation and positive TWA test were independent indices of MACE prediction. CONCLUSIONS: Cumulative evaluation of LVEF, indices of preserved perfusion and results of TWA test turned out to be the best predictors of MACE occurrence in 6 month follow up in patients after anterior MI treated with PCI.     

Effect of metoprolol and d,l-sotalol on microvolt-level T-wave alternans. Results of a prospective, double-blind, randomized study.

OBJECTIVES

The study evaluated the effects of metoprolol, a pure beta-blocker, and d,l-sotalol, a beta-blocker with additional class III antiarrhythmic effects, on microvolt-level T-wave alternans (TWA).

BACKGROUND

Assessment of TWA is increasingly used for purposes of risk stratification in patients prone to sudden death. There are only sparse data regarding the effects of beta-blockers and antiarrhythmic drugs on TWA.

METHODS

Patients with a history of documented or suspected malignant ventricular tachyarrhythmias were eligible. All patients underwent invasive electrophysiologic (EP) testing including programmed ventricular stimulation and determination of TWA at increasing heart rates using atrial pacing. Reproducibility of TWA at two consecutive drug-free baseline measurements was tested in a random patient subset. Following baseline measurements, all patients were randomized either to double-blind intravenous infusion of sotalol (1.0 mg/kg) or metoprolol (0.1 mg/kg). Results of TWA assessment at baseline and after drug exposure were compared.

RESULTS

Fifty-four consecutive patients were studied. In 12 patients, repetitive baseline measurement of TWA revealed stable alternans voltage (V_alt) values (9.1 ± 5.8 μV vs. 8.5 ± 5.7 μV, P = NS). After drug administration, V_alt decreased by 35% with metoprolol (7.9 ± 6.0 μV to 4.9 ± 4.2 μV; p < 0.001) and by 38% with sotalol (8.6 ± 6.8 μV to 4.4 ± 2.3 μV; P = 0.001). In eight patients with positive TWA at baseline, repeated measurement revealed negative test results.

CONCLUSIONS

In patients prone to sudden cardiac death, there is a reduction in TWA amplitude following the administration of antiadrenergic drugs. This result indicates that TWA is responsive to the pharmacologic milieu and suggests that, to assess a patient’s risk of spontaneous ventricular arrhythmia, the patient should be tested while maintaining the pharmacologic regimen under which the risk of arrhythmia is being assessed. This applies particularly for beta-blocker therapy.     

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.

OBJECTIVES: We conducted a collaborative cohort study to evaluate the predictive power of microvolt T-wave alternans (TWA) in patients with preserved left ventricular ejection fraction (LVEF) after myocardial infarction (MI). BACKGROUND: There is little information available about the prognostic value of risk stratification markers in this population. Although these patients have a relatively good prognosis, identifying high-risk patients is important in clinical practice. METHODS: This study enrolled 1,041 post-MI patients with an LVEF > or =40% (average 55 +/- 10%). Microvolt TWA testing was performed 48 +/- 66 days after acute MI, and 10 other risk variables were also evaluated. The end points were prospectively defined as sudden cardiac death or life-threatening arrhythmic events. RESULTS: During a follow-up of 32 +/- 14 months, 38 patients (3.7%) died of nonarrhythmic causes and were not considered for analysis. Of the 1,003 evaluable patients, 18 (1.8%) reached an end point. Microvolt TWA was positive in 169 patients (17%), negative in 747 (74%), and indeterminate in 87 (9%). A positive microvolt TWA test, nonsustained ventricular tachycardia, and ventricular late potentials were predictors of events, and percutaneous coronary intervention decreased the risk rate. On multivariate analysis, a positive microvolt TWA test was the most significant predictor, with a hazard ratio of 19.7 (p < 0.0001). This marker had the highest sensitivity and negative predictive value for events. CONCLUSIONS: In patients with preserved cardiac function, the incidence of indeterminate results of microvolt TWA is low, and a positive test result is associated with arrhythmic events. Microvolt TWA could be used for risk stratification in this low-risk population.     

T wave alternans for ventricular arrhythmia risk stratification

Sudden cardiac death remains one of the leading causes of death in western societies. Accordingly, the ability to identify patients at high risk of sudden cardiac death is important so that appropriate treatments can be used efficiently. Recently, T wave alternans (TWA) has emerged as a promising new test for such risk stratification. TWA is a heart rate-dependent measure of arrhythmia vulnerability, with maximal predictive accuracy at sustained, regular heart rates of 100 to 120 bpm. In the clinical setting, these conditions may be achieved by either exercise or atrial pacing. TWA has been shown to predict inducibility of ventricular tachycardia with programmed stimulation and also spontaneous arrhythmic events. TWA has been successfully applied to diverse populations, including patients with coronary artery disease, nonischemic cardiomyopathy, congestive heart failure, and implantable defibrillators. Despite these encouraging results, the role of TWA to guide clinical therapy still needs to be elucidated better.     

Influence of QRS duration on the prognostic value of T wave alternans

INTRODUCTION: T wave alternans (TWA) is a promising new noninvasive marker of arrhythmia vulnerability that quantifies beat-to-beat changes in ventricular repolarization. Secondary repolarization abnormalities are common in subjects with wide QRS complexes. However, the relationship between TWA and QRS prolongation has not been evaluated. The goal of this study was to determine if QRS prolongation influences the prevalence or prognostic value of TWA. METHODS AND RESULTS: The study consisted of 108 consecutive patients with coronary artery disease and left ventricular ejection fraction < or = 40% who were referred for electrophysiologic studies. Patients underwent TWA testing using bicycle ergometry in the absence of beta-blockers or antiarrhythmic drugs. The primary endpoint was the combined incidence of death, sustained ventricular arrhythmias, and appropriate implantable cardioverter defibrillator therapy. The prognostic value of TWA was assessed in the entire cohort and in two subgroups: QRS < 120 msec (normal, n = 62) and QRS > or = 120 msec (prolonged, n = 46). TWA (hazard ratio 2.2, P = 0.03) and QRS prolongation (hazard ratio 2.2, P = 0.01) were both significant and independent predictors of arrhythmic events. QRS prolongation had no effect on the prevalence of positive TWA tests (QRS < 120 msec: 48%, QRS > or = 120 msec: 50%, P = NS). TWA was a highly significant predictor of events in patients with a normal QRS (hazard ratio 5.8, P = 0.02). In contrast, TWA was not useful for risk stratification in subjects with QRS prolongation (hazard ratio 1.1, P = 0.8). CONCLUSION: TWA is useful only for risk stratification in the absence of QRS prolongation. The presence of QRS prolongation and left ventricular ejection fraction < or = 40% may be sufficient evidence of an adverse prognosis that additional risk stratification is not useful or necessary.     

T波电交替预测扩张性心肌病患者恶性室性心律失常的作用

扩张型心肌病（DCM）是一种以心腔扩大与心肌收缩功能障碍为主要特征的原因不明的心肌疾病,不但易导致心力衰竭及心律紊乱,且易并发复杂或严重的恶性室性心律失常引起猝死（SCD）。研究表明,T波电交替（TWA）与恶性室性心律失常（单形／多形室速、尖端扭转型室速、室颤）、SCD之间有着极为密切的联系,经大量临床试验证实TWA是当前对心律失常事件最具预测价值的无创电生理检测指标。     

T wave alternans for ventricular arrhythmia risk stratification

Sudden cardiac death remains one of the leading causes of death in Europe and the United States. Accordingly, the ability to identify patients at high risk of sudden cardiac death is important so that appropriate treatments can be used efficiently. Recently, T wave alternans (TWA) has emerged as a promising new test for such risk stratification. TWA is a heart rate dependent measure of arrhythmia vulnerability, with maximal predictive accuracy at sustained, regular heart rates of 100-120 bpm. In the clinical setting these conditions may be achieved by either exercise or atrial pacing. TWA has been shown to predict inducibility of ventricular tachycardia with programmed stimulation and also spontaneous arrhythmic events. TWA has been successfully applied to diverse populations, including patients with coronary artery disease, nonischemic cardiomyopathy, congestive heart failure and those with implantable defibrillators. Despite these encouraging results, the role of TWA to guide clinical therapy still needs to be better elucidated.     

Microvolt level T wave alternans: a new marker for noninvasive risk stratification

Prospective identification of patients with structural heart disease who could profit from prophylactic ICD therapy is hampered by the low predictive power of the currently available risk stratification parameters. Microvolt T wave alternans measured noninvasively is a new promising parameter to assess impaired ventricular repolarization which has been associated with an increased incidence of ventricular tachyarrhythmias. T wave alternans is rate-dependent; to induce alternans, heart rate may be increased by atrial stimulation during invasive EP testing or noninvasively by exercise stress testing. The first clinical validation with respect to prediction of inducibility of ventricular tachyarrhythmias and of arrhythmic events during follow-up in patients undergoing invasive EP testing was reported in 1994. Subsequently, a good concordance between the results of invasive and noninvasive assessment of T wave alternans was demonstrated by our group. The first prospective evaluation of the noninvasive alternans measurement using submaximal exercise testing was performed in patients surviving prehospital ventricular fibrillation or sustained ventricular tachycardia referred to our institution. The occurrence of T wave alternans in this patient population was predictive of future tachyarrhythmic events with subsequent appropriate ICD therapy. The results of the currently performed prospective trials in various patient populations will help to establish the utility of T wave alternans assessment as a risk stratifier in clinical practice.     

Changing capacity of electrocardiographic ventricular repolarization in post-myocardial infarction patients with and without nonfatal cardiac arrest

Prolonged and labile ventricular repolarization and decreased heart rate variability may be associated with susceptibility to ventricular fibrillation (VF) after myocardial infarction (MI). The response of ventricular repolarization related to abrupt heart rate changes may also be associated with arrhythmia vulnerability. We investigated whether diurnal maximal values or changing capacities of QT and T-wave peak to T-wave end (TPE) intervals are different in patients after MI with and without a history of VF. With an automated computerized program, Holter recordings from 29 patients after MI resuscitated from VF not associated with new MI (VF group) and 27 patients after MI without clinical ventricular arrhythmias (control group) were analyzed. Maximal QT and maximal TPE intervals were shorter in the VF group than in the control group. Patients with VF exhibited smaller capacity to change QT and TPE intervals, with differences between study groups being greatest at heart rates from 60 to 75 beats/min (p = 0.002 and 0.01, respectively). Capacity to change QT and TPE intervals correlated with vagally mediated measurements of heart rate variability (r from 0.35 to 0.46, p from 0.01 to <0.001, respectively). In conclusion, long maximal QT interval may not be the key factor exposing patients after MI to VF. Impaired capacity to change QT and TPE intervals seems to be associated with risk of VF after MI.     

The many faces of repolarization instability: which one is prognostic?

Instabilities of the STT segment's magnitude, and particularly the 0.5 beat/cycle oscillations (T-wave alternans, or TWA), have been linked to the heightened risk of ventricular tachyarrhythmias (VTA) and sudden cardiac death (SCD). During the last decade theoretical, experimental and clinical research efforts have focused primarily on TWA, examining its mechanisms and predictive value using time-invariant cutoff values. However, recent evidence suggests that such a single-snapshot test of a single-frequency (TWA) oscillation using a constant cutoff value might be suboptimal for risk stratification because of several reasons.First, it is well known that the risk of VTA/SCD evolves over time with changes in electrophysiologic substrate, environmental and physiologic triggers, and the impact of other physiologic (eg, circadian) rhythmicity. Hence, the outcome of TWA testing might depend on the time of day, as Holter-based TWA studies have demonstrated. Furthermore, currently used single-snapshot testing with a binary cutoff value may not coincide with the periods of heightened risk for VTA/SCD and may not yield prognostic information, as a recent TWA substudy of the sudden cardiac death in heart failure trial has showed. Second, the analysis focused on TWA alone ignores the existence of multiple (alternating and nonalternating) forms of repolarization instability that have been shown to arise or increase before the onset of VTA/SCD.Summarizing, recent studies have identified multiple forms of repolarization instabilities modulated by distinct mechanisms, which might have different prognostic values. Therefore, the assessment of TWA needs to be dynamic and personalized to take into account the time evolution of risk and individual history.     

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.

Microvolt T-wave alternans (TWA) and QT interval dispersion (QTD), which reflect temporal and spatial repolarization abnormalities, respectively, have been proposed as useful indices to identify patients at risk for ventricular tachyarrhythmias (VTs). The purpose of this study was to clarify which repolarization abnormality marker is more useful in predicting arrhythmic events in patients with dilated cardiomyopathy (DCM). Forty-two consecutive nonischemic DCM patients underwent the assessment of TWA and QTD. Patients undergoing antiarrhythmic pharmacotherapy, except beta-blockers and those with irregular basic rhythms, were excluded from entry. Eight patients were also excluded because of indeterminate test results. Therefore, 34 DCM patients were prospectively assessed. The end point of the study was the documentation of VT defined as > or = 5 consecutive ectopic beats during the follow-up period. TWA and QTD (> or = 65 msec) were positive in 24 (80%) and 11 (37%) of 30 patients with available follow-up data, respectively. There was no relationship between TWA and QTD. During a follow-up of 13+/-11 months, VTs occurred in 13 patients (43%). In Cox regression analysis, TWA was a significant risk stratifier (p=0.02), whereas QTD was not. The sensitivity, specificity, and positive and negative predictive values of TWA in predicting VTs were 100%, 35%, 54%, and 100%, respectively. TWA could be a useful noninvasive index to identify patients at risk for VTs in the setting of DCM. This study may suggest that temporal repolarization abnormality is associated more with arrhythmogenesis than with spatial repolarization abnormality in DCM patients.