Pharmacotherapy of Atrial Fibrillation: A Pathophysiological Perspective and Review

Abstract

Atrial fibrillation (AF) is one of the most common arrhythmia encountered in clinical practice. Although AF is due to the structural and electrophysiological alterations in the atria, its sustainability is multifactorial, and the actual mechanisms are still not clear. Despite the recent advances in catheter ablation technology and techniques, pharmacotherapy still remains the first-line therapy for the management of AF. Current pharmacotherapy targets ion channel alterations that in fact represent only one aspect of the management of this complex arrhythmia. Successful pharmacological treatment of AF and restoration of sinus rhythm is limited and is in part due to its potential deleterious side effects. Newer agents having diverse mechanisms acting on the recently uncovered pathophysiological processes are on the horizon. These include atrial repolarization delaying agents, newer class III agents, Na(+)-Ca(2+) channel blockers, stretch receptor blockers, I(KACH) blockers, gap junction modifiers, upstream therapies, and agents targeting ischemia-induced AF. Gene- and cell-specific therapies including 'tailored nanopharmacy,' newer rate control medications with minimal side effects and the emergence of novel drugs targeting multiple areas of AF arrhythmogenesis in tandem with electrical therapy may be the future direction in the management of AF.

Influence of Continuous Training on Atrial Myocytes IK1 and IKAch and on Induction of Atrial Fibrillation in a Rabbit Model

“…Improved understanding of the mechanisms of continuous training-related AF may help in the development of novel therapeutic approaches [6] and in training method selection. In current study, we designed a rabbit model to test if continuous training can increase AF vulnerability and the potential mechanisms including changes in ion channel currents and gene expression.…”

Advances in the management of atrial fibrillation

“…Atrial repolarisation-delaying agents that selectively target atrial ion channels, theoretically reducing the risk of proarrhythmia, are in development. 64 The most promising agents target the Kv1.5 channel that is responsible for the ultra-rapid delayed rectifier potassium current (I Kur ). Many of these agents, such as Vernakalant, which has been licensed in Europe for intravenous acute cardioversion of AF, act on multiple ion channels (I Kur , I to and I Na ).…”