T-Wave Alternans in Patients With Heart Failure - ALPHA


The goal of the trial was to evaluate the predictive role of T-wave alternans (TWA) abnormalities compared with normal TWA among patients with nonischemic cardiomyopathy.

Study Design

Patients Screened: 3,513
Patients Enrolled: 446
Mean Follow Up: 24 months
Mean Patient Age: Mean age, 59 years
Female: 22

Patient Populations:

NYHA II and III with nonischemic cardiomyopathy, LVEF <40%, and no previous malignant arrhythmias

Primary Endpoints:

Composite of cardiac death or life-threatening arrhythmias

Secondary Endpoints:

Total mortality; composite of sudden death or life-threatening arrhythmias

Drug/Procedures Used:

TWA tests were performed at baseline on nonischemic cardiomyopathy patients with New York Heart Association (NYHA) class II or III and left ventricular ejection fraction (LVEF) <40%. Patients were classified as TWA positive or TWA negative, and were followed for 18-24 months for the occurrence of life-threatening arrhythmias and death.

Principal Findings:

An abnormal TWA test was present in 65% of patients in the study (200 patients had negative TWA and 92 had indeterminate TWA, all grouped as abnormal TWA). Heart failure duration averaged 4 years at study entry. Compared with patients with a normal TWA test, those with abnormal TWA were older (60 years vs. 57 years), had a slightly lower LVEF (29% vs. 31%), a higher frequency of left bundle branch block (LBBB), and a higher frequency of NYHA class III.

The primary composite endpoint of cardiac death or life-threatening arrhythmias occurred more frequently in those with an abnormal TWA compared with patients with a normal TWA (hazard ratio [HR] 4.01, 95% CI 1.41-11.41, p = 0.002). The negative predictive value of a normal TWA test was 97.3% at 18 months for the primary endpoint. Likewise, total mortality was also higher among patients with an abnormal TWA (n = 25 vs. n = 3, HR 4.60, 95% CI 1.39-15.25, p = 0.002), as was the composite of arrhythmic death or life-threatening arrhythmias (HR 5.53, 95% CI 1.29-23.65, p = 0.004).


Among patients with nonischemic cardiomyopathy, abnormal TWA was associated with a 4-fold increase in cardiac death or life-threatening arrhythmias through 2 years compared with patients with normal TWA.

Identification of heart failure patients at high-risk for life-threatening arrhythmias and death is necessary to target patients who would derive the greatest benefit from implantable cardioverter defibrillator (ICD) implantation. TWA has previously been shown to identify low-risk post-MI patients with low LVEF who are unlikely to benefit from an ICD.

The present study extends these findings to the nonischemic cardiomyopathy population. There were imbalances in clinical characteristics for patients with a positive abnormal TWA test, including older age, lower EF, more LBBB, and a higher rate of NYHA class III, which raises the question of whether the abnormal test is predictive of higher risk or whether the sicker population is predictive of higher risk. However, in a multivariable model adjusting for these higher risk clinical factors, presence of an abnormal TWA remained associated with a threefold increase in cardiac death or life-threatening arrhythmias, suggesting that the test provides additional risk stratification.


Presented at ACC 2007

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 Nov 6;50(19):1896-904.

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Implantable Devices, EP Basic Science, SCD/Ventricular Arrhythmias, Acute Heart Failure

Keywords: Cardiomyopathies, Heart Failure, Bundle-Branch Block, Stroke Volume, Glucans, Defibrillators, Implantable

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