Ambulatory ECG-based T-wave alternans predicts sudden cardiac death in high-risk post-MI patients with left ventricular dysfunction in the EPHESUS study

Abnormal TWA Predicts Sudden Death in EPHESUS. Background: Exercise microvolt T-wave alternans (TWA) identifies sudden cardiac death (SCD) risk. TWA can be measured from ambulatory ECGs (AECGs) using modified moving average (MMA) method. Whether MMA TWA from AECGs predicts SCD in post-MI patients with left ventricular dysfunction (LVD) is unknown. Methods: EPHESUS enrolled hospitalized post-MI patients with heart failure and/or diabetes with LVD. Before randomization to drug treatment, AECGs were obtained in 493 patients. Of them, 46 died of cardiovascular causes, including 18 of SCD. Patients alive at end of follow-up (N = 92) were matched with 46 nonsurvivors based on age, gender, and diabetes. MMA TWA was analyzed using MARSPC system (GE Healthcare, Milwaukee, WI, USA). The three highest TWA values from artifact-free periods were averaged for AECG channels corresponding to leads V-1 and V-3. SCD prediction was tested with a prespecified 47 mu V cutpoint and at a cutpoint maximizing the separation between SCD patients versus survivors or non-SCD. Results: TWA in either lead was higher for patients with SCD (P <= 0.05) versus survivors or non-SCD. TWA >= 47 mu V was associated with RR = 5.2 (95%CI = 1.8-13.6, P = 0.002) in V-1 and RR = 5.5 (95%CI = 2.2-13.8, P < 0.001) in V-3 for SCD. The optimal cutpoint for TWA in V-1 was >= 43 mu V (RR = 5.9 [95%CI = 2.2-15.8, P < 0.001]). The optimal cutpoint in V-3 was >= 47 mu V. TWA greater than the optimal cutpoint in either lead was associated with RR = 7.1 (95%CI = 2.7-18.3, P < 0.001) for SCD, with 11 out of 18 patients dying of SCD. Conclusions: AECG-based TWA measured with MMA is a powerful predictor of SCD in high-risk post-MI patients with LV dysfunction.