A Multiscale Computational Model of Calcium-Mediated Ectopy in the Human Postinfarction Heart.

A variety of arrhythmias following myocardial infarction are implicated with ectopic beats (EBs) resulting from spontaneous calcium (Ca2+) release (SCR) events. However, investigation of these arrhythmias is hampered by the lack of adequate techniques to assess with certainty abnormalities at the subcellular scale and arrhythmogenic events at the organ level. The aim of this study was to construct a multiscale computational model to investigate SCR-mediated ectopy within the infarcted human heart. To achieve this goal, an experimentally based phenomenological model of SCR events was integrated in the equations for Ca2+ cycling of an human ventricular action potential model. This augmented myocyte model was used in in-silico experiments with a postinfarction biventricular (BiV) model constructed based on magnetic resonance imaging data. The infarct scar and border zone (BZ) were segmented by thresholding the voxel intensity within the ventricular wall. These were then used to build a finite element mesh. Within the multiscale human BiV model we show that SCR-mediated DADs in cells interspersed with fibrosis in the infarcted BZ are capable of overcoming local source-sink mismatches to trigger an EB. The results presented here are the first to show that EBs resulting from abnormalities at the subcellular level can be studied using highly detailed human heart models.