Antiarrhythmic Agents in Atrial Fibrillation: A New Role in the Context of a Hybrid Approach?

Abstract

A series of antiarrhythmic agents have been demonstrated to be highly effective in terminating recent-onset atrial fibrillation, with class 1C agents being the most effective [1,2]. In the conversion of recent-onset atrial fibrillation, flecainide has an efficacy of 65%-96% (intravenous administration) or 78%-95% (oral loading) [1,2]. In contrast with the high efficacy in recent-onset atrial fibrillation, however, the results obtained in the prevention of atrial fibrillation recurrences are not satisfactory, and this has led to the development both of new nonpharmacological treatments and of combined or hybrid approaches [3,6]. Prevention of atrial fibrillation differs from termination of atrial fibrillation in respect of a series of factors involving the electrophysiological substrate, the pharmacological properties of antiarrhythmic agents, and the influence of the autonomic nervous system (Table 1). Experimental studies have clearly demonstrated that repeated inductions of atrial fibrillation up to the development of stable atrial fibrillation produce important electrophysiological and structural changes in the atria. The most striking electrophysiological alterations are shortening of the atrial effective refractory period and loss of the physiological rate adaptation of refractoriness and were associated with shortening of the atrial fibrillation cycle and development of sustained atrial fibrillation (atrial fibrillation begets atrial fibrillation) [3,5]. The evidence of electrical remodeling has important implications as far as the use of drugs is concerned. First, the development of remodeling (after some hours of atrial fibrillation or brief episodes of paroxysmal atrial fibrillation) may change the electrophysiological substrate for drug action. Second, agents able to counteract development of remodeling and to reduce its severity can be considered in the future as a useful tool to couple with antiarrhythmic drugs or antiarrhythmic interventions used to treat atrial fibrillation.