Computer modelling of beat-to-beat repolarization heterogeneity in human cardiac ventricles

• Beat-to-beat changing action potential durations were assumed.
• Transmural action potential profiles were represented by mesoscopic tissue layers.
• Beat-to-beat repolarization dispersion was characterized by QRST integrals.
• Impact of cell-to-cell coupling resistance on heterogeneity dispersion was studied.
• Parabolic relationship of SAI QRST and AP transmural gradient was observed.

Based on our numerical heart and chest model with stochastically modifiable action potential duration (APD) parameters, the consequences of diminished subepicardial cell-to-cell coupling were studied on beat-to-beat repolarization heterogeneity. Pathological action potential durations and transmural gradient (TG) mean values (M) were assumed in the apical segment of the five-layer heart model, while in the rest of the model the action potential parameters were kept in the normal range. APD mean values and the associated APD standard deviations (SDs) were fitted to experimental data. SD was causally related to APD mean. Repolarization heterogeneity was characterized by QRST integral maps and by the non-dipolarity index (NDI). The TG of −15 model time units (mtu) yielded an NDI of 12%. By sweeping beat-to-beat TG from −15 mtu up to +14 mtu, NDI increased from 12% up to 71%. In healthy heart M is large compared to the SD value; consequently NDI is in the stable <20% range. In arrhythmia patients TG diminishes, M and SD increase, consequently, NDI shows temporally random, increased beat-to-beat fluctuations, suitable for the characterization of repolarization heterogeneity.