T-wave alternans: reviewing the clinical performance, understanding limitations, characterizing methodologies

Accurate recognition of individuals at higher immediate risk of sudden cardiac death (SCD) is still an open question. The fortuitous nature of acute cardiovascular events just does not seem to fit the well-known model of ventricular tachycardia/fibrillation induction in a static arrhythmogenic substrate by a synchronous trigger. On the mechanism of SCD, a dynamical electrical instability would better explain the rarity of the simultaneous association of a correct trigger and an appropriate cardiac substrate. Several studies have been conducted trying to measure this cardiac electrical instability (or any valid surrogate) in an ECG beat stream. Among the current possible candidates we can number QT prolongation, QT dispersion, late potentials, T-wave alternans (TWA), and heart rate turbulence. This article reviews the particular role of TWA in the current cardiac risk stratification scenario. TWA findings are still heterogeneous, ranging from very good to nearly null prognostic performance depending on the clinical population observed and clinical protocol in use. To fill the current gaps in the TWA base of knowledge, practitioners, and researchers should better explore the technical features of the several technologies available for TWA evaluation and pay greater attention to the fact that TWA values are responsive to several factors other than medications. Information about the cellular and subcellular mechanisms of TWA is outside the scope of this article, but the reader is referred to some of the good papers available on this topic whenever this extra information could help the understanding of the concepts and facts covered herein.