Antazoline for termination of atrial fibrillation during the procedure of pulmonary veins isolation

Abstract

Purpose

Pulmonary vein isolation is a well established method of definite treatment of atrial fibrillation (AF). Periprocedural onset of AF usually terminates spontaneously within minutes, but not in all cases. Antazoline is an antihistaminic agent with antiarrhythmic properties. The aim of our retrospective study was to evaluate the efficacy of antazoline in termination of AF in patients undergoing pulmonary vein isolation.

Materials and methods

Consecutive 141 patients who received antazoline to terminate AF during pulmonary vein isolation were analyzed. The antazoline was administered at the rate of 30–50 mg/min (max. 500 mg) after the circumferential ablation in the ostia of pulmonary veins and before confirmation of isolation. Success was defined as restoration of sinus rhythm within 20 min after antazoline infusion.

Results

The efficacy of antazoline was 83.6% in paroxysmal and 31.1% in persistent AF patients. Clinical variables that were independently predictive of antazoline ineffectiveness were female (odds ratio [OR]: 4.35; 95% confidence interval [CI]: 1.26–14.3; p = 0.018) and AF at the beginning of procedure (OR 28.4; 95% CI 3.89–208.0; p = 0.001). Due to antazoline related side effects infusion was discontinued in 7 patients (5%).

Conclusions

Antazoline seems to be safe agent in termination of AF in patients undergoing pulmonary vein isolation. We also observed satisfying efficacy, which needs to be proved in a randomized clinical trial.

Introduction

Pulmonary vein isolation is established method of treatment of atrial fibrillation (AF). AF may occur during the procedure hindering the verification of successful isolation of pulmonary veins. Periprocedural onset of AF usually terminates spontaneously within minutes, but not in all cases. Particularly, it is uncommon in patients with persistent AF. In such cases rapid conversion to sinus rhythm may be achieved by electrical cardioversion (ECV). However, it requires general anaesthesia and does not prevent from immediate AF recurrence. The pharmacological cardioversion (PCV) of AF to sinus rhythm (SR) may be achieved by administration of class IA, IC and III antiarrhythmic drugs: flecainide, ibutilide, dofetilide, propafenone or amiodarone [1]. Beta-adrenergic blocking agents alone are not considered suitable for PCV due to their low or lack of efficacy [1]. Another drug for rapid PCV of AF is vernakalant [2], [3].

Antazoline is an antihistaminic agent with antiarrhythmic quinidine-like properties [4], [5]. In some countries it is registered for intravenous termination of cardiac arrhythmias. It has been used for many years for rapid termination of AF [6], [7]. In Poland it has registration for using it for termination of supraventricular arrhythmias – it was used according to this registration. However, due to the lack of large randomized trials the drug is not listed in any of the formal guidelines. Antazoline prolongs the action potential duration and lowers its amplitude, prolongs duration of phase 0, reduces phase 4 of resting potential and reduces excitability of cardiac tissue. Clinically, antazoline lowers the velocity of intra-atrial conduction, prolongs the atrial refraction period and may improve atrioventricular conduction allowing fast ventricular response to supraventricular arrhythmias [4], [8].

There are no widely known, randomized clinical trials evaluating the antiarrhythmic effect of antazoline. Published studies are mainly single-arm clinical trials with no control group or a different series of cases where antazoline was administered either orally or intravenously in different doses and in different arrhythmias. These studies suggested high efficacy of antazoline in rapid conversion of AF to SR if administered intravenously up to the cumulated dose of 350 mg. Most adverse effects were observed after cumulated doses exceeding 250 mg and they were mainly comprised of mild hypotension, hot flushes and mild tachycardia. Antazoline can unmask the underlying sick sinus syndrome or atrio-ventricular block [4], [8], [9], [10], [11], [12]. According to information from the trials journal there is one randomized trial, which is being currently conducted [13].