Emerging pro-arrhythmic mechanisms underlying atrial fibrillation

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with significant morbidity and mortality. It is increasingly recognized that there is a significant heritable component to AF, yet the underlying mechanisms by which genetic variants lead to AF are poorly understood. In this review, we discuss AF molecular mechanisms with a focus on emerging cell and developmental mechanisms. We describe how genetic variants identified in genome-wide association and genome sequencing studies point to changes in developmental transcription factors, cardiomyocyte structural proteins, and metabolic regulators underlying AF disease. We discuss the evolving roles for these factors and the mechanisms through which these genes and pathways contribute to AF progression.