Renin-Angiotensin System and AtrialFibrillation:Understanding the Connection

Atrial fibrillation (AF) arises as a result of a complex interaction of triggers, perpetuators and the substrate. The recurrence of AF may be partially related to a biologic phenomenon known as remodeling, in which the electrical, mechanical, and structural properties of the atrial tissue and cardiac cells are progressively altered,creating a more favorable substrate. Atrial remodeling is in part a consequence of arrhythmia itself. Therefore,to prevent and to treat AF, much attention has been directed to upstream therapies to alter the arrhythmia substrate and to reduce atrial remodeling. The renin-angiotensin-aldosterone system (RAAS) plays a keyrole in these strategies. In this review we analyze the experimental and clinical evidence regarding the efficacy of RAAS inhibitors in AF treatment. In the primary prevention of AF, meta-analyses have shown that risk of new-onset AF in patients with congestive heart failure and left ventricular dysfunction is reduced by RAAS inhibitors, whereas in hypertensive and post-myocardial infarction patients, the results are less evident. In the secondary prevention of AF, some large, prospective, randomized, placebo-controlled studieswith angiotensin II-receptor blockers returned negative results. Unfortunately, the approach of using RAASinhibitors as antiarrhythmic drugs to prevent both new-onset and recurrent AF is in decline because negativetrial results are accumulating, with the exception of the results in patients with congestive heart failure.