Targeted pharmacological reversal of electrical remodeling after cardioversion—Rationale and design of the Flecainide Short-Long (Flec-SL) trial

Abstract

Persistent atrial fibrillation (AF) causes relevant mortality and cardiovascular and noncardiovascular morbidity. Therefore, maintenance of sinus rhythm is an important clinical goal, especially when the patient is symptomatic, despite the fact that current treatment strategies are not sufficient to completely prevent recurrent AF. In addition to underlying atrial disease that predisposes to AF, AF in itself induces structural and electrical adaptations ("electrical remodeling" and "structural remodeling"). Underlying disease processes and parts of structural remodeling are not always reversible. Electrical remodeling, in contrast, is reversed by a few weeks of maintenance of sinus rhythm under experimental conditions. This corresponds to the period when most of the recurrent episodes of AF occur after cardioversion. Antiarrhythmic drugs that prolong the atrial action potential can assist in the prevention of recurrent AF by promoting the reversal of electrical remodeling. Such drugs, which are currently used over long periods after cardioversion, may only be needed until the physiological action potential duration is restored, for example, during the first few weeks after cardioversion of persistent AF. This treatment concept that we call "targeted pharmacological reversal of electrical remodeling" would limit both cost and drug-induced side effects of antiarrhythmic drug therapy after cardioversion. The Flec-SL trial, ISECTN62728743, therefore tests the main hypothesis that targeted pharmacological reversal of electrical remodeling by short-term antiarrhythmic drug therapy for 4 weeks after cardioversion is not inferior to standard long-term antiarrhythmic drug therapy for the prevention of recurrent AF after cardioversion in a parallel group, randomized, multicenter, open, blinded end point analysis design. Based on its effectiveness and pharmacokinetic profile, flecainide is used to test the study hypothesis. The trial uses daily transtelephonic electrocardiographic monitoring for all patients and will be conducted within the German Atrial Fibrillation Competence NETwork (AFNET) to facilitate inclusion of patients from electrophysiologically oriented cardiology centers, ordinary hospitals, and office-based physicians.