The Emerging Role of Antiarrhythmic Compounds With Atrial Selectivity in the Management of Atrial Fibrillation

Abstract

Atrial fibrillation represents a significant source of cardiovascular morbidity and mortality in the United States. Despite a relatively high clinical failure rate, pharmacologic conversion to and maintenance of normal sinus rhythm with antagonists of the HERG potassium channel responsible for carrying the delayed rectifier current I(Kr) represent a mainstay of therapy. Suppression of I(Kr) leads to restoration of normal sinus rhythm but is also associated with ventricular proarrhythmia. Given the unique electrophysiologic targets expressed in human atrium, compounds that exhibit selectivity for these targets have the potential to restore sinus rhythm with a reduced risk of ventricular proarrhythmia. Targets with expression limited to human cardiac atria and compounds that interact with these targets are reviewed.