Ambulatory ECG-Based T-Wave Alternans Monitoring for Risk Assessment and Guiding Medical Therapy: Mechanisms and Clinical Applications

Identification of individuals at risk for sudden cardiac death (SCD), the main cause of adult mortality in developed countries, remains a major challenge. The main contemporary noninvasive marker, 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, on ambulatory electrocardiogram (AECG) is an attractive approach on both scientific and clinical grounds. Specifically, TWA's capacity to assess risk for malignant arrhythmias has been shown to rest on sound electrophysiologic principles and AECG-based TWA monitoring can be performed in the flow of routine clinical evaluation. This review addresses: (1) electrophysiologic and ionic mechanisms underlying TWA's predictivity, (2) principles and practical aspects of AECG-based TWA monitoring, (3) clinical evidence supporting this approach to SCD risk stratification, and (4) current and potential applications in guiding medical therapy.