Atrial Fibrillation Increases Proarrhythmic Mechanisms in the Ventricle.

Ventricular arrhythmias and sudden cardiac death are a leading cause of death in patients with atrial fibrillation (AF). This study investigated how AF promotes ventricular arrhythmias. Cellular electrophysiology of AF patients was characterized using human left ventricular (LV) samples from patients with sinus rhythm (n = 25) or rate-controlled AF (n = 16). In LV cardiomyocytes from AF patients, delayed afterdepolarizations and Ca2+ waves, both established triggers for ventricular arrhythmias, were significantly more frequent compared to sinus rhythm patients. In vitro AF simulation in murine LV cardiomyocytes confirmed increased ventricular proarrhythmic activity upon AF. Oxidative Ca2+/calmodulin-dependent protein kinase II activation was increased in murine LV cardiomyocytes after AF simulation. MMVV knock-in mice with genetic ablation of Ca2+/calmodulin-dependent protein kinase II oxidation did not develop ventricular proarrhythmic activity after AF simulation. This study demonstrates that AF promotes ventricular arrhythmogenesis. The findings offer new mechanistic insights into the interaction of AF and ventricular arrhythmias.