Abstract

Atrial fibrillation and atrial flutter, the most frequently encountered tachyarrhythmias requiring treatment, have become a major focus for clinical and basic research in recent years. Restoration and maintenance of sinus rhythmn, having been shown to improve exercise capacity, alleviate symptoms, and reduce the incidence of thromboembolic events, may be the optimal management strategy. Identification of the safest, most efficacious and cost-effective means of restoring sinus rhythm is necessary prior to the institution of optimal antiarrhythmic therapy to maintain sinus rhythm. Potential advantages of pharmacologic compared with electrical cardioversion include lack of need for general anesthesia and likely lower cost. Pharmacologic conversion include lack of need for general anesthesia and likely lower cost. Pharmacologic conversion has been accomplished with drugs that prolong atrial refractorinerss, including class Ia (quinidine, procainamide, disopyramide), class Ic (flecainide, propafenone), and class II (sotalol, amiodarone) compounds. The so-called pure class III agents were created to overcome the blocker side effects of sotalol and the complex pharmacodynamic profile of amiodarone. Two such agents are dofetilide, which selectively blocks the rapid component of the delayed rectifier current (Ikr) and ibutilide, which augments the slow inward sodium current, with a smaller component of action mediated by the block of Ikr. Reported overall conversion rates for recent onset atrial fibrillation and atrial flutter were 31% and 54% for difetilide, respectively, and 29-31% and 38-63%, respectively, for ibutilide. Proarrhythmia, manifested as polymorphic ventricular tachycardia requiring cardioversion, was a significant early side effect of both agents. Data from clinical trtials with these new agents, combined with increasing nowledge of the electrophysiologic substrate for these arrhythmias, has renewed initerest in the development of safer, more efficacious class IIIdrugs for atrial fibrillation and atrial flutter conversion.

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