In Silico Assessment of Arrhythmic Risk in Infarcted Ventricles Engrafted with Engineered Heart Tissues

Engineered heart tissues (EHTs) from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) represent novel alternatives to repair damaged cardiac tissue after myocardial infarction (MI). However, their associated slow conduction and prolonged action potential duration (APD) can favor proarrhythmicity. We coupled biventricular (BiV) and EHT in silico elec-trophysiological models. The BiV model, defined from magnetic resonance imaging, included an MI region. The EHT model was deformed to follow the epicardial surface. Different values of EHT electrical conductivity (EHTc) and degree of myocardial attachment (EHTa) were tested. Results showed that even a minimum degree of EHTa inhibited EHT automaticity. Activation time and APD were driven by myocardial tissue when engrafted. Importantly, higher EHTc and EHTa led to lower repolarization gradients (RTGs), considered as a surrogate of arrhythmic risk. Maximum RTG decreased by 52.3 ms/mm when EHTa var-iedfrom 25 % to 100 % under low EHTc and decreased by 98.8 ms/mm when EHTc raised to 90 % of the myocardium conductivity under low EHTa. Proarrhythmicity in cardiac tissue engineering highly depends on EHT conductivity and degree of engraftment on the myocardium.