Cardiac Arrhythmias: Mechanistic Knowledge and Innovation from Computer Models

Abstract

Computational simulation is increasingly recognized as an integral aspect of modern cardiovascular research. Realistic and biophysically detailed models of the cardio-circulatory system can help interpret complex experimental observations, dissect underlying mechanisms, and explain emerging organ-scale phenomena resulting from subtle changes at the tissue, cellular, and/or sub-cellular scales. This chapter provides an overview of recent advances in the simulation of cardiac electrical behavior, focusing specifically on detailed models of the initiation, perpetuation, and termination of ventricular arrhythmias, including fibrillation. The development and validation of such models has opened several noteworthy avenues of research, including close scrutiny of arrhythmia dynamics in healthy and diseased hearts, dissection of arrhythmogenic and cardioprotective properties of specialized cardiac tissue regions such as the Purkinje system, and exploration of emerging paradigms for anti-arrhythmia treatment, such as optogenetics. Excitingly, the clinical community is currently taking the first steps towards using patient-specific ventricular models to stratify arrhythmia risk, personalize treatment planning, and optimize device placement for difficult or unusual procedures.