T-wave alternans: lessons learned from a biophysical ECG model

T-wave alternans (TWA) is an alteration of the ECG T-wave which repeats every other beat. An alternating pattern has been also observed at myocytes level, involving both action potential duration and morphology (mainly in phases 2 and 3). While this might happen in a specific region (i.e., myocardial ischemia), it can also involve the entire myocardium. It is still unclear how alternations at the myocytes level are reflected on surface ECG modification of T-waves, especially when in vivo human hearts are considered. We have recently proposed a simple stochastic model of ventricular repolarization (IEEE Trans. Biomed. Eng., 2011), which takes into account both repolarization heterogeneity across the myocardium as well as random beat-to-beat variations in cells' activity. In this work, we generalized that model incorporating a term which describes myocytes alternans related to T-wave variability. Starting from the model and using the electrophysiological formulation developed by van Oosterom, we derived an analytical formula relating surface ECG to variations at the myocytes' level. Several theoretical results were then obtained. First, temporal small random variations in repolarization heterogeneity affect the precision of TWA estimates in a significant way. Second, TWA theoretically differs across leads, but multilead configuration can be used to reduce the effect of noise. Finally, the dependency between TWA and T-wave amplitude was analyzed.