A reliability analysis of cardiac repolarization time markers

Only a limited number of studies have addressed the reliability of extracellular markers of cardiac repolarization time, such as the classical marker RTeg defined as the time of maximum upslope of the electrogram T wave. This work presents an extensive three-dimensional simulation study of cardiac repolarization time, extending the previous one-dimensional simulation study of a myocardial strand by Steinhaus [B.M. Steinhaus, Estimating cardiac transmembrane activation and recovery times from unipolar and bipolar extracellular electrograms: a simulation study, Circ. Res. 64 (3) (1989) 449]. The simulations are based on the bidomain - Luo-Rudy phase I system with rotational fiber anisotropy and homogeneous or heterogeneous transmural intrinsic membrane properties. The classical extracellular marker RTeg is compared with the gold standard of fastest repolarization time RTtap, defined as the time of minimum derivative during the downstroke of the transmembrane action potential (TAP). Additionally, a new extracellular marker RT 90eg is compared with the gold standard of late repolarization time RT 90tap, defined as the time when the TAP reaches 90% of its resting value. The results show a good global match between the extracellular and transmembrane repolarization markers, with small relative mean discrepancy (≤ 1.6 %) and high correlation coefficients (≥ 0.92), ensuring a reasonably good global match between the associated repolarization sequences. However, large local discrepancies of the extracellular versus transmembrane markers may ensue in regions where the curvature of the repolarization front changes abruptly (e.g. near front collisions) or is negligible (e.g. where repolarization proceeds almost uniformly across fiber). As a consequence, the spatial distribution of activation-recovery intervals (ARI) may provide an inaccurate estimate of (and weakly correlated with) the spatial distribution of action potential durations (APD).