Computational modeling: What does it tell us about atrial fibrillation therapy?

Atrial fibrillation (AF) is a complex cardiac arrhythmia with diverse etiology that negatively affects morbidity and mortality of millions of patients. Technological and experimental advances have provided a wealth of information on the pathogenesis of AF, highlighting a multitude of mechanisms involved in arrhythmia initiation and maintenance, and disease progression. However, it remains challenging to identify the predominant mechanisms for specific subgroups of AF patients, which, together with an incomplete understanding of the pleiotropic effects of antiarrhythmic therapies, likely contributes to the suboptimal efficacy of current antiarrhythmic approaches. Computer modeling of cardiac electrophysiology has advanced in parallel to experimental research and provides an integrative framework to attempt to overcome some of these challenges. Multi-scale cardiac modeling and simulation integrate structural and functional data from experimental and clinical work with knowledge of atrial electrophysiological mechanisms and dynamics, thereby improving our understanding of AF mechanisms and therapy. In this review, we describe recent advances in our quantitative understanding of AF through mathematical models. We discuss computational modeling of AF mechanisms and therapy using detailed, mechanistic cell/tissue-level models, including approaches to incorporate variability in patient populations. We also highlight efforts using whole-atria models to improve catheter ablation therapies. Finally, we describe recent efforts and suggest future extensions to model clinical concepts of AF using patient-level models.