Mechanisms of termination of atrial fibrillation by Class I antiarrhythmic drugs: evidence from clinical, experimental, and mathematical modeling studies.

Sodium channel blocking drugs (Class I antiarrhythmic agents) have been used for the termination of atrial fibrillation (AF) and for sinus rhythm maintenance for almost 100 years. Despite this long history, the mechanisms that underlie their efficacy in AF remain poorly understood. Classic notions about the determinants of cardiac reentry, as embodied in leading circle theory, and of AF, as reflected in the multiple wavelet hypothesis, suggest that cardiac conduction slowing should promote, rather than prevent, AF. This article reviews the evidence (both clinical and experimental) for the efficacy and mechanisms of action of Class I antiarrhythmic agents in AF. Application of mathematical models of AF to the evaluation of Class I mechanisms is discussed, and recent insights into the latter are presented. A better understanding of the ways in which Na+ channel blockers affect AF will be useful, not only for new antiarrhythmic drug development but also for gaining insight into the mechanisms of the arrhythmia.