Figure 1.

Sex differences in drug-induced arrhythmogenesis: a combined multiscale modeling and machine learning approach. We develop individual male and female low-fidelity cell and high-fidelity multiscale exposure-response simulators. These simulators take into account differences in subcellular ion channel activity between men and women for the low-fidelity exposure-response proxy. The high-fidelity model also takes into account sex differences tissue-level conductivity and organ-scale geometry. We perform an arrhythmic sensitivity study of the male and female heart to drug-specific ion channel blocking and susbsequently combine low-fidelity cell-scale and high-fidelity multiscale modeling to delineate arrhythmogenic risk classification boundaries for men and women.