Investigational Anti Atrial Fibrillation Pharmacology and Mechanisms by Which Antiarrhythmics Terminate the Arrhythmia: Where Are We in 2020?
Abstract: Antiarrhythmic drugs remain the mainstay therapy for patients with atrial fibrillation (AF) A major disadvantage of the currently available anti AF agents is the risk of induction of ventricular proarrhythmias. Aiming to reduce this risk, several atrial specific or selective ion channel block approaches have been introduced for AF suppression, but only the atrial selective inhibition of the sodium channel has been demonstrated to be valid in both experimental and clinical studies. Among the other pharmacological anti AF approaches, "upstream therapy" has been prominent but largely disappointing, and pulmonary delivery of anti AF drugs seems to be promising. Major contradictions exist in the literature about the electrophysiological mechanisms of AF (ie, reentry or focal? and the mechanisms by which anti AF drugs terminate AF, making the search for novel anti AF approaches largely empirical. Drug induced termination of AF may or may not be associated with prolongation of the atrial effective refractory period. Anti AF drug research has been largely based on the "suppress reentry" ideology; however, results of the AF mapping studies increasingly indicate that nonreentrant mechanism(s) plays an important role in the maintenance of AF. Also, the analysis of anti AF drug induced electrophysiological alterations during AF, conducted in the current study, leans toward the focal source as the prime mechanism of AF maintenance. More effort should be placed on the investigation of pharmacological suppression of the focal mechanisms.
Journal of cardiovascular pharmacology