Quantitative T-wave alternans analysis for guiding medical therapy: An underexploited opportunity

Reducing the toll of sudden cardiac death (SCD) remains a major challenge in cardiology, as it is the leading cause of adult mortality in the industrially developed world, claiming 310,000 lives annually in the United States alone. The main contemporary noninvasive index of cardiovascular risk, left ventricular ejection fraction (LVEF), has not proved adequately reliable, as the majority of individuals who die suddenly have relatively preserved cardiac mechanical function. Monitoring of T-wave alternans (TWA), a beat-to-beat fluctuation in ST-segment or T-wave morphology, is an attractive approach to risk stratification on both scientific and clinical grounds, as this ECG phenomenon has been shown using the FDA-cleared Spectral and Modified Moving Average methods to assess risk for cardiovascular mortality including SCD in studies enrolling >12,000 individuals with depressed or preserved LVEF. The evidence supporting TWA as a therapeutic target is reviewed.