T-Wave Alternans and Variability: Prognostic, Diagnostic, and Therapeutic Implications

Recent advances in experimental and clinical electrophysiology have provided substantial evidence for a crucial role of repolarization abnormalities in arrhythmogenic conditions precipitating ventricular tachyarrhythmias. Early afterdepolarizations, beat-to-beat variability in diastolic time, and transmural heterogeneity of repolarization contribute to an arrhythmogenic cascade of ventricular tachyarrhythmias (1). Early afterdepolarizatons may arise from Purkinje fibers, but may also originate from M cells, which are particularly prone to exhibit selective prolongation and abnormalities of refractory periods. Transmural heterogeneity of repolarization, with action potentials in M cells longer than in endo- and epicardial cells, was demonstrated to facilitate the mechanism of reentry (1–3). The same transmural heterogeneity of action potential duration and morphology was recently shown to underlie T-wave alternans, an ECG phenomenon consisting of 2:1 changes in ST-T-complex duration and morphology (4,5). T-wave alternans has been attributed to beat-to-beat changes in the kinetics of repolarizing ionic currents leading to varying degree of transmural heterogeneity (6). As shown in schematic Figure 1 (based on the recent NASPE presentation by Shimizu and Antzelevitch [4]), biphasic T-wave alternans is caused by the alternating “direction” of transmural heterogeneity.