Mechanisms for the initiation of human atrial fibrillation

Understanding of the mechanisms underlying atrial fibrillation (AF) remain limited. However, both persistent and paroxysmal AF likely initiate via the interaction of triggers such as premature atrial beats with ‘substrate’, that includes static components such as fibrosis and scar, as well as dynamic alterations that may include the rate-response of repolarization and conduction, autonomic modulation and stretch. This article attempts to synthesize concepts for AF initiation from in silico, in vitro and in vivo animal data and human studies and apply them to the spectrum of disease processes that comprise clinical AF. Further investigation is urgently needed to translate these discoveries into effective therapy.