Sensitivity of Repolarization Gradients to Infarct Borderzone Properties Assessed with the Ten Tusscher and Modified Mitchell-Schaeffer Model

Post-infarction ventricular tachycardia (VT) is an important clinical problem that is often caused by a re-entrant circuit located in the infarct border zone (BZ). The main changes in the BZ are in action potential duration (APD) and conduction velocity (CV), which introduce high repolarization time gradients (RTGs) and can lead to re-entry. Computational models can help in VT-risk analysis. However, the complexity of these models and the representation of the electrophysiological properties of the BZ still require investigation. In this study we conduct a sensitivity analysis in which we apply changes in APD and CV in a BZ using the detailed biophysical Ten Tusscher (TT2) model and the phenomenological modified Mitchel-Schaeffer (mMS) ionic model. First, the effect of spatial discretization on the CV is compared for both models. The TT2 model showed much larger mesh dependency for the computed CV than the mMS model. Next, we propose a tuning method to match the mMS AP shape to the TT2 AP shape. We then compare APD restitution properties. The tuned mMS showed similar APD restitution properties for large diastolic intervals (DI), but started to deviate when decreasing the DI. Finally, for both the TT2 and tuned mMS model we found that RTG is more sensitive to variation in APD than to variation in CV. When varying the APD, differences between both models were more pronounced for short than for large APDs.