Determinant of microvolt-level T-wave alternans in patients with dilated cardiomyopathy.

OBJECTIVES: The aim of this study was to clarify the clinical significance and the determinant of microvolt-level T-wave alternans (TWA) in patients with dilated cardiomyopathy (DCM). BACKGROUND: The prevention of sudden death in patients with DCM remains the therapeutic target. T-wave alternans has been proposed as a powerful tool for identification of patients at high risk for ventricular arrhythmias and sudden death in coronary artery disease. METHODS: In 58 DCM patients, TWA was measured during bicycle exercise testing using a CH 2000 system (Cambridge Heart, Bedford, Massachusetts). The New York Heart Association class, signal-averaged electrocardiogram, QT dispersion, left ventricular end-diastolic diameter (LVDd) and percent fractional shortening detected by echocardiogram and the grade of the ventricular arrhythmia were obtained in all patients. RESULTS: T-wave alternans was positive in 23 patients (TWA+ group), negative in 25 (TWA- group) and indeterminate in 10. Univariate analysis showed that the percentage of patients with ventricular tachycardia (VT) and the LVDd in the TWA+ group was significantly higher than those in the TWA- group (61% vs. 8%, p < 0.001 and 65 +/- 11 mm vs. 58 +/- 8 mm, p < 0.05, respectively). The sensitivity, specificity and predictive accuracy of TWA for VT were 88%, 72% and 77%, respectively. Multivariate analysis showed that the presence of VT was a major independent determinant of TWA in patients with DCM (p = 0.003). CONCLUSIONS: T-wave alternans was closely related to VT in patients with DCM. T-wave alternans is a useful noninvasive test for identifying high risk patients with DCM who have VT.     

Risk stratification for sudden cardiac death in dilated cardiomyopathy using microvolt-level T-wave alternans

Predicting sudden cardiac death (SCD) in patients with dilated cardiomyopathy (DCM) is difficult, so the present study evaluated the efficacy of microvolt-level T-wave alternans (TWA) and compared it with conventional parameters for prospective risk stratification of SCD in patients with DCM. Eighty-two patients with DCM (53+/-15 years old, 67M/15F) underwent assessment of TWA, left ventricular end-diastolic diameter (LVDd), left ventricular ejection fraction (LVEF), signal-averaged ECG, and analysis of 24-h Holter monitoring and QT dispersion (QTd). The endpoint of the study was defined as either SCD or documented sustained ventricular tachycardia/ventricular fibrillation (SVT/VF) during the follow-up period. During an average follow-up period of 24 months, 1 patient died suddenly and 9 patients had SVT/VF. Kaplan-Meier survival analysis showed that TWA, LVEF (< or =35%), nonsustained ventricular tachycardia, and QTd (>90ms) were significant univariate risk stratifiers (p<0.005, p<0.005, p<0.005, and p<0.05, respectively). Multivariate Cox regression analysis showed that TWA and the LVEF were statistically significant independent risk stratifiers (p<0.05 and p<0.01, respectively). A combination of TWA and LVEF identified high risk DCM patients (p<0.01); TWA for the electrical substrate and the LVEF for the hemodynamic function.     

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.     

Prediction of sudden cardiac death in patients after acute myocardial infarction using T-wave alternans: a prospective study

Background and PurposeWe assessed the value of T-wave alternans (TWA) in prediction of sudden cardiac death (SCD) in patients with acute myocardial infarction (AMI).MethodsConsecutive patients (N = 227) were enrolled and were monitored with 24-hour ambulatory electrocardiogram within 1 to 15 days after AMI. T-wave alternans was identified by a modified moving average (MMA) algorithm computer software. The primary end point was SCD or lethal ventricular arrhythmia. We analyzed the hazard ratios (HRs) using the previously determined 47 μV TWA cutpoint.ResultsDuring the 16 ± 7-month follow-up, 10 (4.4%) patients died suddenly. T-wave alternans (≥47 μV) predicted SCD (HR, 17.78 [95% confidence interval, 3.75-84.31]; P < .0001). Moreover, patients with 5 or more TWA episodes (≥47 μV) were at higher risk for SCD (HR, 20.75 [95% confidence interval, 5.77-74.57]; P < .0001).ConclusionsT-wave alternans (≥47 μV) monitored at 1 to 15 days after AMI-predicted heightened risk of SCD. Prediction is improved when the frequency of TWA episodes (≥47 μV) is analyzed.     

Prognostic value of T-wave alternans in patients with heart failure due to nonischemic cardiomyopathy: results of the ALPHA Study.

OBJECTIVES: The aim of this study was to assess the prognostic value of T-wave alternans (TWA) in New York Heart Association (NYHA) functional class II/III patients with nonischemic cardiomyopathy and left ventricular ejection fraction (LVEF) < or =40%. BACKGROUND: There is a strong need to identify reliable risk stratifiers among heart failure candidates for implantable cardioverter-defibrillator (ICD) prophylaxis. T-wave alternans may identify low-risk subjects among post-myocardial infarction patients with depressed LVEF, but its predictive role in nonischemic cardiomyopathy is unclear. METHODS: Four hundred forty-six patients were enrolled and followed up for 18 to 24 months. The primary end point was the combination of cardiac death + life-threatening arrhythmias; secondary end points were total mortality and the combination of arrhythmic death + life-threatening arrhythmias. RESULTS: Patients with abnormal TWA (65%) compared with normal TWA (35%) tests were older (60 +/- 13 years vs. 57 +/- 12 years), were more frequently in NYHA functional class III (22% vs. 19%), and had a modestly lower LVEF (29 +/- 7% vs. 31 +/- 7%). Primary end point rates in patients with abnormal and normal TWA tests were 6.5% (95% confidence interval [CI] 4.5% to 9.4%) and 1.6% (95% CI 0.6% to 4.4%), respectively. Unadjusted and adjusted hazard ratios were 4.0 (95% CI 1.4% to 11.4%; p = 0.002) and 3.2 (95% CI 1.1% to 9.2%; p = 0.013), respectively. Hazard ratios for total mortality and for arrhythmic death + life-threatening arrhythmias were 4.6 (p = 0.002) and 5.5 (p = 0.004), respectively; 18-month negative predictive values for the 3 end points ranged between 97.3% and 98.6%. CONCLUSIONS: Among NYHA functional class II/III nonischemic cardiomyopathy patients, an abnormal TWA test is associated with a 4-fold higher risk of cardiac death and life-threatening arrhythmias. Patients with normal TWA tests have a very good prognosis and are likely to benefit little from ICD therapy.     

T wave alternans and ventricular arrhythmias in arterial hypertension

Patients with a positive microvolt-level T wave alternans (TWA) are characterized by an increased risk of ventricular tachyarrhythmias. Arterial hypertension leads to an increase of sudden cardiac death risk, particularly if left ventricular hypertrophy is present. The aim of this study was to investigate the value of TWA in patients with arterial hypertension. Fifty-one consecutive patients were included in the study. TWA analysis was performed with patients sitting on a bicycle ergometer and exercising with a gradual increase of workload to maintain a heart rate of at least 105/min. After recording 254 consecutive low-noise-level heartbeats, the exercise test was stopped. The ECG signals were digitally processed by a spectral analysis method. The magnitude of TWA was measured at a frequency of 0.5 cycle per beat. A TWA was defined as positive if the ratio between TWA and noise level was >3.0 and the amplitude of the TWA was >1.8 microV. Eight of the 51 patients (16%) showed a positive TWA. If left ventricular hypertrophy was present, the prevalence of TWA was higher (33.3% versus 8.3%; P:<0.05). Sensitivity concerning a previous arrhythmic event was 73%, and specificity was 100%. The alternans ratio was significantly higher in patients with a previous event (39.3+/-62.3 versus 2.4+/-4.6; P:<0.001), as was the cumulative alternans voltage (4.7+/-4.1 versus 1.6+/-1.9 microV; P:<0.001). In 16 patients invasively investigated by an electrophysiological study, a significant correlation between inducibility of tachyarrhythmias and a positive TWA result was found (Spearman R:=0.36, P:=0.01). We conclude that the arrhythmic risk of patients with arterial hypertension is markedly increased if microvolt-level TWA is present. The prevalence of TWA is higher in patients with left ventricular hypertrophy.     

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.     

Predictive value of T-wave alternans for arrhythmic events in patients with congestive heart failure

Measurement of microvolt level T-wave alternans in the surface electrocardiogram is a novel way to assess the risk of ventricular arrhythmias. Seven tests of arrhythmic risk, including T-wave alternans, were undertaken in 107 consecutive patients with congestive heart failure and no history of sustained ventricular arrhythmias; the patients were followed up for arrhythmic events during the next 18 months. Of the patients with events, 11 had positive and two indeterminate T-wave alternans results; there were no arrhythmic events among patients with negative T-wave alternans results. Of the seven tests, only T-wave alternans was a significant (p=0.0036) and independent predictor of arrhythmic events.     

Cellular mechanism and arrhythmogenic potential of T-wave alternans in the Brugada syndrome

Introduction: T-wave alternans (TWA) is characterized by beat to beat alteration in the amplitude, polarity and/or morphology of the electrocardiographic T wave. TWA has been reported in patients with the Brugada syndrome (BS) and is thought to be associated with an increased risk for development of VT/VF. The cellular mechanisms involved are not well-defined and are the subject of this investigation.
Methods: In an experimental model of BS composed of an arterially perfused canine right ventricular wedge preparation pretreated with verapamil (1–7 μM), an agent with sodium and calcium channel blocking activity, we simultaneously recorded transmembrane action potentials from two epicardial and one endocardial site, together with a pseudo-ECG. At select frequencies, verapamil induced alternans of both the T-wave amplitude and QT interval. The alternans resulted from either loss of the epicardial action potential dome on alternate beats or concealed phase 2 reentry within the epicardium on alternate beats. Loss of the epicardial action potential dome significantly increased transmural dispersion of repolarization (TDR) when compared with control (18.0 ± 7.8 ms vs. 82.1 ± 16.8 ms, P < 0.001, n = 8). During alternans, TDR was greater in beats displaying a more negative T wave (55.1 ± 45.2 ms vs. 89.8 ± 39.3 ms, P < 0.001, n = 22 data points from 8 preparations).
Conclusions: Our data indicate that TWA in an experimental model of the Brugada syndrome is due to alternating loss of the epicardial AP dome and/or concealed phase 2 reentry, both serving to increase TDR and create the substrate for the development VT/VF.     

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.     

Relation of T-wave alternans to regional left ventricular dysfunction and eccentric hypertrophy secondary to coronary heart disease

Left ventricular (LV) hypertrophy and structural disease are associated with exaggerated repolarization dispersion and risk for cardiac arrest. We hypothesized that T-wave alternans (TWA) from the electrocardiogram, reflecting proarrhythmic repolarization dispersion, would increase with extent of eccentric LV hypertrophy and vary spatially with the distribution of myocardial scar. We studied 28 patients with coronary disease, systolic dysfunction, and nonsustained ventricular tachycardia. On echocardiography, 21 patients had wall motion abnormalities and 20 had LV hypertrophy (mass index > or =100 g/m(2)). TWA magnitude (voltage of alternation), which was computed spectrally during ventricular stimulation, varied linearly with LV mass index (p = 0.003). Spatially, positive TWA (magnitude > or =1.9 microV) in orthogonal electrocardiographic axes overlaid scar or wall motion abnormalities in corresponding echocardiographic segments (p <0.05 in x and y axes). After a follow-up of 35 +/- 13 months, positive TWA predicted the combined end point of death or sustained ventricular arrhythmias in all patients (p = 0.025), with a trend for those with echocardiographic LV hypertrophy (p = 0.058). In conclusion, in patients with systolic dysfunction due to coronary artery disease, TWA may indicate arrhythmic contributions from regional myocardial scar and eccentric LV hypertrophy.     

Optimal Target Heart Rate for Exercise‐Induced T‐Wave Alternans

Objectives: This study was conducted to determine the optimal target heart rate (HR) for the use of exercise‐induced T‐wave alternans (TWA) as an index for risk of malignant ventricular tachyarrhythmias. Background: Rate‐dependent TWA is an index of vulnerability to ventricular tachyarrhythmias. However, false positive TWA was reported to occur in normal subjects at high HR. Methods: Two groups were evaluated: Group I: 50 patients with malignant ventricular tachyarrhythmias, who received an implantable cardioverter‐defibrillator (ICD); and Group II: 55 agematched normal subjects. In both Groups, TWA was evaluated during symptom‐limited bicycle exercise test. Results: Peak HR during exercise test was 103 ± 17 beats/min in Group I, versus 124 ± 18 beats/min in Group II (P < 0.001). In Group I, 4 patients were excluded from analysis, due to high noise level or frequent ectopy during exercise. Out of the remaining 46 patients, TWA was present in 28 patients (61%), and absent in 18 (39%). In group II, TWA was present in four subjects (7%), and absent in 51 (93%). HR at the onset of TWA was 91 ± 11/min in Group I, and 119 ± 12/min in Group II (P < 0.001). Receiver operated characteristics curves demonstrated that a HR of 115 beats/min was the cutoff with the best sensitivity and specificity for TWA (100 and 96%, respectively). None of the patients in Group I developed TWA at HR > 115 beats/min, while two out of four in Group II had TWA at HR > 115/minutes. However, 13 patients in Group I who had no TWA were unable to exercise to a peak HR > 115 beats/min, compared to nine subjects in Group II. Conclusions: A target HR of 115 beats/min was highly sensitive and specific for determination of exercise‐induced TWA as an index of risk of malignant ventricular tachyarrhythmias. However, a significant number of patients may not be able to achieve this target HR, resulting in an indeterminate test. The value of pharmacologic testing in this group should be assessed. A.N.E. 2001;6(2):123–128     

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.     

Treatment options for patients with coronary artery disease identified as high risk by T-wave alternans testing

Opinion statement Risk stratification for primary prevention of sudden cardiac death (SCD) remains a major challenge in cardiology. The utility of T-wave alternans (TWA) as a marker of risk of life-threatening ventricular tachycardia and fibrillation is supported by two decades of basic and clinical research. Both frequency-and time-domain methods have been developed, validated, and made available in clinical practice. A principal application of TWA testing has been to improve assessment of patients with depressed left ventricular ejection fraction (EF; ≤ 40%) who are considered for implantable cardioverter-defibrillator (ICD) implantation for primary prevention of SCD. TWA has been most useful in identifying patients who are unlikely to benefit from ICD therapy. Although patients with low EF should remain an important focus, the absolute number of SCD events is far greater among post-myocardial infarction patients with relatively preserved EF, even though the incidence of SCD in this population is low. Recent studies suggest that TWA testing is predictive in this population as well. Absolute quantification of TWA rather than binary classification into “normal” or “abnormal” appears to be valuable in more finely stratifying the magnitude of arrhythmic risk. Longitudinal testing may be warranted in certain populations, although the optimum interval remains to be determined. Combining TWA with noninvasive markers of autonomic function, such as heart rate turbulence, may further increase predictive accuracy. Future development will likely expand the role of TWA testing with routine exercise and ambulatory electrocardiographic monitoring to screen lower-risk populations and to guide medical and device-based therapy.     

T-wave alternans phase following ventricular extrasystoles predicts arrhythmia-free survival

OBJECTIVE: The purpose of this study was to assess the value of T-wave alternans (TWA) following ventricular extrasystoles in predicting arrhythmia-free survival. BACKGROUND: Stratifying risk for sudden death in patients with coronary disease and moderate left ventricular (LV) dysfunction remains a challenge. We hypothesized that, in such patients, a discontinuity in beat-to-beat T-wave alternation (TWA phase reversal) following single ventricular extrasystoles reflects transiently exaggerated repolarization dispersion, and predicts spontaneous ventricular arrhythmias. METHODS: We studied 59 patients with ischemic LV dysfunction (mean LV ejection fraction 38.7 +/- 5.3%) and nonsustained ventricular tachycardia undergoing programmed stimulation. TWA was computed spectrally from the ECG during ventricular pacing, and TWA phase reversal was reflected by a discontinuity in T-wave oscillation after single ventricular extrasystoles. RESULTS: Patients induced into ventricular arrhythmias (n = 36) had greater TWA magnitude (V(alt): 6.60 +/- 6.46 microV vs 2.61 +/- 1.97 microV; P = .001) and more frequent TWA phase reversal (62.1% vs 44.4%; P = .02) than those who were not (n = 23). During a mean follow-up of 36 +/- 12 months, positive TWA (V(alt) > or =1.9 microV) and TWA phase reversal both (P < .05) predicted events (all-cause mortality, ventricular tachycardia, ventricular fibrillation). Univariate predictors of arrhythmia-free survival were TWA phase reversal (P < .005), positive TWA (P < .05), age (P = .008), and LV mass index (P = .043). On multivariate analysis, only TWA phase reversal and age predicted events; if TWA phase was excluded, only positive TWA and age predicted events. CONCLUSION: Phase reversal in TWA following ventricular extrasystoles predicts spontaneous ventricular arrhythmias and all-cause mortality in patients with moderate ischemic LV dysfunction and was a better predictor than positive TWA or programmed ventricular stimulation.     

Predictive significance for sudden death of microvolt-level T wave alternans in New York Heart Association class II congestive heart failure patients: a prospective study

BACKGROUND: Sudden cardiac death (SDC) is responsible for approximately 60-70% of deaths in New York Heart Association (NYHA) class II congestive heart failure (CHF) patients. Recently, microvolt-level T wave alternans has been proposed as a new noninvasive tool to identify CHF patients at risk for SCD and ventricular tachycardia/fibrillation (VT/VF). OBJECTIVES: To determine the prognostic value of MTWA in NYHA class II patients. METHODS: Among 181 consecutive CHF patients with ischemic and nonischemic cardiomyopathy, 73 patients in NYHA class II with left ventricular ejection fraction <45% were selected and prospectively investigated. MTWA was determined during bicycle exercise testing. The study end point was defined as SCD, documented sustained VT/VF and appropriate implantable cardioverter defibrillator (ICD) shock. RESULTS: MTWA was positive in 30 (41%) patients, negative in 26(36%) patients and indeterminate in 17 (23%) patients. During an average follow-up of 17.1+/-7.4 months, seven patients had an arrhythmic event in the MTWA positive group, whereas one and no events occurred in the indeterminate and negative group, respectively. From Kaplan-Meier univariate analysis and multivariate Cox analysis, MTWA was a significant arrhythmic risk stratifier (p=0.01 and p=0.03, respectively). Sensitivity, specificity, negative and positive predictive values of MTWA were 100%, 53%, 100% and 24%, respectively. CONCLUSION: Our data suggest that MTWA is a promising predictor of arrhythmic events in NYHA class II CHF patients.     

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.     

Prognostic value of average T-wave alternans and QT variability for cardiac events in MADIT-II patients

Background

Identifying which patients might benefit the most from ICD therapy remains challenging. We hypothesize that increased T-wave alternans (TWA) and QT variability (QTV) provide complementary information for predicting appropriate ICD therapy in patients with previous myocardial infarction and reduced ejection fraction.

Methods

We analyzed 10-min resting ECGs from MADIT-II patients with baseline heart rate > 80 beats/min. TWA indices IAA and IAA₉₀ were computed with the multilead Laplacian Likelihood ratio method. QTV indices QTVN and QTVI were measured using a standard approach. Cox proportional hazard models were adjusted considering appropriate ICD therapy and sudden cardiac death (SCD) as endpoints.

Results

TWA and QTV were measured in 175 patients. Neither QTV nor TWA predicted SCD. Appropriate ICD therapy was predicted by combining IAA₉₀ and QTVN after adjusting for relevant correlates.

Conclusion

Increased TWA and QTV are independent predictors of appropriate ICD therapy in MADIT-II patients with elevated heart rate at baseline.     

T wave alternans in patients with cardiac sarcoidosis

There has been no report on T wave alternans (TWA) in patients with cardiac sarcoidosis. In this study, we investigated TWA in patients with cardiac sarcoidosis. Electrocardiographic recording for TWA was performed in 6 patients, using the CH2000 (Cambridge Heart). TWA was defined as positive in cases where alternans voltage of >1.9 μV and alternans ratio of >3.0 persisted more than 1 minute during exercise with ergometer with heart rate above 105 beats/min. TWA was positive in 3 patients, negative in 2 patients, and not determined in 1 patient. Arrhythmia was noted on Holter electrocardiogram in all 3 patients with positive TWA: sustained ventricular tachycardia in 1 patient and nonsustained ventricular tachycardia in 2 patients. Mean left ventricular ejection fraction in the 3 patients with positive TWA was 39.0%, whereas in the 2 patients with negative TWA it was 58.5%. A close relationship was suggested between TWA and severity of cardiac sarcoidosis.     

Effect of Heart Rate on T Wave Alternans

Heart Rate and T Wave Alternans. Introduction : T wave alternans (TWA) is a promising technique for detecting arrhythmia vulnerability. Previous studies in animals demonstrated that the magnitude of TWA is dependent on heart rate. However, the effects of heart rate on TWA in humans and the clinical relevance of this effect remain controversial.
Methods and Results : This was a prospective evaluation of pacing rate and monitoring lead configuration on TWA in subjects undergoing electrophysiologic study. Measurements of TWA were performed on 45 patients in the absence of antiarrhythmic drugs. Recordings were made in normal sinus rhythm and during atrial pacing at 100 and 120 beats/min. Sustained monomorphic ventricular tachycardia (VT) was induced in 29 patients with programmed stimulation. TWA in the vector magnitude lead increased with heart rate, independent of VT inducibility (0.4 ± 0.7 μ V, 1.6 ± 1.9 μ V, and 2.4 ± 2.1 μ V in sinus rhythm and at 100 and at 120 beats/min, respectively; P < 0.001). In addition, the diagnostic performance of TWA for inducible VT was dependent on heart rate (sensitivity 4%, 42%, and 65%, and specificity 100%, 93%, and 63% at 77, 100, and 120 beats/min, respectively). By analyzing orthogonal leads rather than the vector magnitude lead, the sensitivity is increased from 42% to 59% at 100 beats/min, but the specificity is reduced from 93% to 72%.
Conclusion : These results indicate that TWA in humans is strongly dependent on heart rate with regard to both magnitude and diagnostic performance. The optimal heart rate for the measurement of TWA is between 100 and 120 beats/min and multiple leads should be monitored.