Advances in modeling ventricular arrhythmias: from mechanisms to the clinic

Modern cardiovascular research has increasingly recognized that heart models and simulation can help interpret an array of experimental data and dissect important mechanisms and interrelationships, with developments rooted in the iterative interaction between modeling and experimentation. This article reviews the progress made in simulating cardiac electrical behavior at the level of the organ and, specifically, in the development of models of ventricular arrhythmias and fibrillation, as well as their termination (defibrillation). The ability to construct multiscale models of ventricular arrhythmias, representing integrative behavior from the molecule to the entire organ, has enabled mechanistic inquiry into the dynamics of ventricular arrhythmias in the diseased myocardium, in understanding drug-induced proarrhythmia, and in the development of new modalities for defibrillation, to name a few. In this article, we also review the initial use of ventricular models of arrhythmia in personalized diagnosis, treatment planning, and prevention of sudden cardiac death. Implementing individualized cardiac simulations at the patient bedside is poised to become one of the most thrilling examples of computational science and engineering approaches in translational medicine.