Activation of Isac promotes atrial fibrillation initiation and perpetuation: is this a stretch?

Abstract

c s m Atrial fibrillation (AF) is a cardiac arrhythmia that results in a rapid and irregular activation of the atrial myocardium. In humans, activation rates during AF can be as high as 400–600 pulses per minute. About 2–5 million people in he United States are afflicted by AF, and the incidence of he arrhythmia increases with age, affecting 10% of the ctogenarian population. AF is the number one cause of hospitalization for arrhythmias, and its incidence is predicted to double in two decades. Yet the therapeutic management for F is challenging; antiarrhythmic drug therapies are partially ffective, some of which are proarrhythmic. Thus, AF is a ajor challenge in cardiac electrophysiology, and a large perentage of AF patients await novel therapies for the treatment f the arrhythmia. What are the mechanisms of initiation and perpetuation f AF? It is well established that disorders such as congesive heart failure, coronary artery disease, hypertension, and itral valve disease predispose the atrial myocardium to brillation. Furthermore, it has been demonstrated that there is structural, contractile, and electrical remodeling during AF and that this remodeling, in turn, exacerbates the rrhythmia. Nevertheless, a trigger is required for initiating AF. A consensus that has emerged from human and animal studies is that ectopic focal activities originating from areas around the pulmonary veins (PVs) serve as triggers for AF. For example, in one study by Chen et al, the lectrophysiological properties of the atria and the PV reion were examined in 79 patients with frequent episodes of aroxysmal AF. The electrophysiological properties of the V region were found to be different from those of the atria. t was also shown that ectopic beats originating from the PV egion could initiate AF. In another study, Hocini et al investigated the cellular architecture and electrical properties of the canine PV region to determine what may predispose the region to the initiation of arrhythmias. The investigators demonstrated that areas of activation delay correlated with sudden changes in the orientation of muscle