Shedding new light on the pathophysiology of conversion of paroxysmal atrial fibrillation into persistent atrial fibrillation

Investigators have found increased fibrosis, altered cellular junction proteins, and apoptosis.28-32 An area of increasing interest in understanding the pathogenesis of AF and the changes supporting persistent AF is the role that renin angiotensin aldosterone receptors play.33-35 Atrial interstitial fibrosis has been linked to enhanced expression of protein kinases activated by angiotensin II.36 Lower levels of activated protein kinases were seen when patients had been treated with angiotensin converting enzyme inhibitor (ACEI).36 Using cultured atrial neonatal rat myocytes, stretch was shown to increase the density of IK1 and IKur, changes that shorten action potential duration and predispose to AF.37 Losartan, an angiotensin receptor blocker, attenuated these changes.37 Clinically, ACEI have been shown to decrease the incidence of hospitalization with atrial tachyarrhythmias in patients with systolic dysfunction.38 Using echocardiographic measures, investigators demonstrated attenuation of post cardioversion stunning in patients pretreated with irbesartan.39 The addition of an ACEI or an angiotensin II receptor blocker to low-dose amiodarone was associated with a significantly lower incidence of relapse into AF and smaller left atrium size when compared with patients with PAF treated with amiodarone alone.40 The use of an implanted pacemaker to study the natural history of AF has been reported before.10-12 However, compared with other studies, this study offers a rare insight into the natural history of paroxysmal AF without the confounding impact of an intervention such as atrioventricular node ablation and specifically focuses on a commonly observed and poorly understood phenomenon: the transition of paroxysmal AF to persistent AF. Atrial fibrillation and sinus node dysfunction commonly coexist, and AF may lead to sinus node dysfunction; hence, the findings from this study may be unique to this patient population, and the findings cannot be generalized.41 Findings from larger studies using implantable rhythm control devices such as the TRENDS study will complement the study by Saksena et al in offering us an insight into the natural history of AF.42