Arrhythmogenesis in the heart: Multiscale modeling of the effects of defibrillation shocks and the role of electrophysiological heterogeneity.

The mechanisms of initiation of ventricular arrhythmias as well as those behind the complex spatiotemporal wave dynamics and its filament organization during ventricular fibrillation (VF) are the topic of intense research and debate. Mechanistic inquiry into the various mechanisms that lead to arrhythmia initiation and VF maintenance is hampered by the inability of current experimental techniques to resolve, with sufficient accuracy, electrical behavior confined to the depth of the ventricles. The objective of this article is to demonstrate that realistic 3D simulations of electrical activity in the heart are capable of bringing a new level of understanding of the mechanisms that underlie arrhythmia initiation and subsequent organization. The article does this by presenting the results of two multiscale simulation studies of ventricular electrical behavior. The first study aims to uncover the mechanisms responsible for rendering the ventricles vulnerable to electric shocks during a specific interval of time, the vulnerable window. The second study focuses on elucidating the role of electrophysiological heterogeneity, and specifically, differences in action potential duration in various ventricular structures, in VF organization. Both studies share common multiscale modeling approaches and analysis, including characterization of scroll-wave filament dynamics.