Modelling and Simulation Reveals Density-Dependent Re-Entry Risk in The Infarcted Ventricles After Stem Cell-Derived Cardiomyocyte Delivery

Delivery of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is a potential therapy to improve cardiac function after injury. However, hPSCCMs express immature electrophysiological and structural properties and may be pro-arrhythmic. Our goal is to identify key factors determining arrhythmic risk of hPSC-CM therapy in the infarcted human ventricles through modelling and simulation. We model three densities of hPSC-CMs covering 4%, 22%, and 39% of the infarct and border zone and induce re-entry through ectopic stimulation. We furthermore simulate the effect of different therapeutic agents on re-entry susceptibility. Due to the increased refractory period of the hPSC-CMs, the vulnerable window increases from 20ms in control, to 60ms in the low- and 80ms in the medium- and high-density scenarios. Our results highlight the density-dependent effect of hPSC-CM delivery on arrhythmic risk after myocardial infarction and show the effect of therapeutic strategies on this increased re-entry susceptibility.