Microvolt T-wave alternans and electrophysiologic testing predict distinct arrhythmia substrates: Implications for identifying patients at risk for sudden cardiac death

Background: Better risk stratification of patients receiving an implantable cardioverter-defibrillator (ICD) for primary prevention of sudden cardiac death (SCD) is needed. Although microvolt T-wave alternans (MTWA) and electrophysiologic study (EPS) are independent markers for SCD, the Alternans Before Cardioverter Defibrillator (ABCD) trial found the combination to be more predictive than either test alone. Objective: The purpose of this study was to test the hypothesis that EPS and MTWA measure different elements of the arrhythmogenic substrate and, therefore, predict distinct arrhythmia outcomes. Methods: The ABCD trial enrolled 566 patients with ischemic cardiomyopathy, left ventricular ejection fraction (LVEF) ≤0.40, and nonsustained ventricular tachycardia. All patients underwent both MTWA test and EPS. The performance of MTWA and EPS in predicting stable ventricular tachyarrhythmic events (S-VTEs) versus unstable ventricular tachyarrhythmic events (U-VTEs), defined as either polymorphic ventricular tachycardia or ventricular fibrillation, was analyzed using Kaplan-Meier event rates and the log rank test. Results: MTWA and EPS were abnormal in 71% and 39% of patients, respectively. There were 28 S-VTEs and 10 U-VTEs. MTWA was predictive of U-VTEs (event rate 2.7% in abnormals vs 0% in normals, P = .04), whereas EPS was not (1.5% vs 3.2%, P = .55). In contrast, EPS predicted S-VTEs (9.7% vs 2.2%, P <.01), but MTWA did not (5.5% vs 4.4%, P = .57). Whereas the extent of left ventricular contractile dysfunction alone (LVEF ≤0.30 vs LVEF 0.31-0.40) did not predict events, MTWA predicted events better than did EPS in subjects with LVEF ≤0.30. In contrast, EPS predicted events better than did MTWA test in subjects with LVEF >0.30. Conclusion: The study data suggest that EPS and MTWA identify distinct arrhythmogenic substrates and, when used in combination, may better predict the complex electroanatomic substrates that underlie the risk for SCD.