Proarrhythmic Effects Of Flecainide Research Articles

Sudden Death During Flecainide Therapy for Atrial Fibrillation Complicating Wolff-Parkinson-White Syndrome.

The Wolff-Parkinson-White syndrome can be complicated by atrial fibrillation that may increase morbidity and mortality. Different pharmacologic therapy, includes class IA, IC, and III agents, has been used in such cases with variable success. We now use less pharmacologic intervention with development of an electrode catheter ablation for accessory pathways. However, antiarrhythmic agents are still being used, especially when an electrode catheter ablation is unavailable or if a patient refuses such a procedure. Therefore, it is prudent that one understands each antiarrhythmic agents' electropharmacologic properties as well as its potential proarrhythmic effect in order to accurately assess each drug's risk-benefit ratio. We present a case that illustrates electropharmacologic properties of quinidine, flecainide, sotalol, and amiodarone on various cardiac tissues, as well as possible proarrhythmic effect of flecainide on a structurally normal heart.

Flecainide Induced Atrial Tachycardia with 1:1 Ventricular Conduction During Exercise Testing

Wide complex tachycardias may represent a rare proarrhythmic effect of some antiarrhythmic agents. The authors describe a patient who developed a wide complex tachycardia developing during stress testing while on therapy with flecainide, and the difficulty in interpreting the electrocardiogram. This article reviews potential proarrhythmic effects of flecainide in the treatment of atrial dysrhythmias and the difficulty in differentiating associated wide complex tachycardias.

Arrhythmias after cardiac transplantation

The etiology and clinical significance of sustained arrhythmias, and atrial and ventricular premature complexes (APCs and VPCs, respectively) after heart transplantation are controversial. Fifty adult recipients surviving >2 weeks were studied by continuous telemetry while in the hospital and by ambulatory electrocardiographic monitoring at 2, 4, 6, 12 and 24 weeks after transplantation. The median APC frequency was greater among subjects who experienced allograft rejection in the early postoperative period (0.7/hour, range 0 to 23) than among those who did not (0.2/hour, range 0 to 10.4) (p = 0.04). The APC frequency in all subjects decreased from 0.25/hour (range 0 to 23) early to 0/hour (0 to 14) later (p = 0.04). Atrial flutter was the most frequent sustained arrhythmia; it was recorded in 5 of 21 rejectors and in 1 of 29 nonrejectors (p = 0.04), and 11 of 16 episodes (69%) were related to acute rejection temporally. VPCs were recorded in all patients early after transplantation, but the median frequency subsequently decreased from 4.6/hour (range 0.5 to 470) early to 1.25/hour (range 0 to 225) later (p < 0.001). VPC frequency was unrelated to rejection. Sustained ventricular tachycardia was recorded once and was caused by the proarrhythmic effect of flecainide. Thus, APCs and VPCs occur frequently after transplantation. Frequent APCs are associated with rejection, whereas the main determinant of VPC frequency is time after transplantation. Atrial flutter is closely associated with rejection and should be regarded as an indication for endomyocardial biopsy. Ventricular tachycardia occurs seldom, and in this study was due to proarrhythmic drug effects.

Inefficacy and Proarrhythmic Effects of Flecainide and Encainide for Sustained Ventricular Tachycardia and Ventricular Fibrillation

To assess the efficacy of encainide and flecainide in treating patients with sustained ventricular arrhythmias. Patients were treated with encainide or flecainide. Efficacy was assessed by comparing the results of programmed ventricular stimulation while patients received therapy with the results while they were drug free. The electrophysiology laboratory of the University of California at San Francisco. Forty-nine patients with spontaneous or inducible sustained ventricular tachycardia or ventricular fibrillation for whom treatment with at least one class IA antiarrhythmic agent had failed. Patients were treated with encainide, 35 to 50 mg three or four times daily, or flecainide, 100 to 200 mg twice daily. Arrhythmia worsened early in 5 of 16 patients receiving encainide and 3 of 33 patients receiving flecainide. Patients with poor left ventricular function were more likely to exhibit proarrhythmia (P = 0.02). Nine of eleven patients receiving encainide and 23 of 28 patients receiving flecainide who had repeat programmed ventricular stimulation while receiving drug therapy still had inducible, poorly tolerated ventricular tachycardia. Encainide and flecainide have a low efficacy rate and a high incidence of worsening of arrhythmia in patients with sustained ventricular arrhythmias, particularly when this condition is associated with poor left ventricular function.

Effects of Flecainide on Occlusion and Reperfusion Arrhythmias in Dogs

Summary: To assess flecainide's ability to suppress ventricular fibrillation during reperfusion, we compared flecainide acetate (2 mg/kg i.v.) with saline placebo in 50 pentobarbital-anesthetized dogs undergoing proximal anterior descending coronary artery occlusion for 20 min followed by sudden release. Treatment selection was blinded and randomized. Flecainide (1 mg/kg) was given for 5 min before ligation and 1 mg/kg over the 20 min occlusion period. Heart rate, blood pressure, myocardium at risk, and QRS duration before drug infusion were similar between treatment groups. Flecainide prolonged the QRS duration 12% with no effect on heart rate or blood pressure. Dogs successfully cardioverted from ventricular fibrillation during occlusion were subjected to reperfusion. One of the 25 dogs treated with placebo fibrillated during occlusion, whereas 13 of the 25 dogs treated with flecainide fibrillated during occlusion and 10 of these 13 could not be resuscitated. Thirteen of the 25 dogs in the placebo group fibrillated during reperfusion, whereas 3 of the remaining 15 dogs in the flecainide treatment group fibrillated during reperfusion. The proarrhythmic effects of flecainide during occlusion confound interpretation of its antiarrhythmic activity during reperfusion. Thus, although flecainide may have prevented ventricular fibrillation during reperfusion, it clearly caused ventricular fibrillation during occlusion in this preparation of acute myocardial ischemia.

Effects of Flecainide on Occlusion and Reperfusion Arrhythmias in Dogs

To assess flecainide's ability to suppress ventricular fibrillation during reperfusion, we compared flecainide acetate (2 mg/kg i.v.) with saline placebo in 50 pentobarbital-anesthetized dogs undergoing proximal anterior descending coronary artery occlusion for 20 min followed by sudden release. Treatment selection was blinded and randomized. Flecainide (1 mg/kg) was given for 5 min before ligation and 1 mg/kg over the 20 min occlusion period. Heart rate, blood pressure, myocardium at risk, and QRS duration before drug infusion were similar between treatment groups. Flecainide prolonged the QRS duration 12% with no effect on heart rate or blood pressure. Dogs successfully cardioverted from ventricular fibrillation during occlusion were subjected to reperfusion. One of the 25 dogs treated with placebo fibrillated during occlusion, whereas 13 of the 25 dogs treated with flecainide fibrillated during occlusion and 10 of these 13 could not be resuscitated. Thirteen of the 25 dogs in the placebo group fibrillated during reperfusion, whereas 3 of the remaining 15 dogs in the flecainide treatment group fibrillated during reperfusion. The proarrhythmic effects of flecainide during occlusion confound interpretation of its antiarrhythmic activity during reperfusion. Thus, although flecainide may have prevented ventricular fibrillation during reperfusion, it clearly caused ventricular fibrillation during occlusion in this preparation of acute myocardial ischemia.

Evaluation of the efficacy of flecainide acetate in the treatment of ventricular premature contractions

The efficacy of flecainide acetate in suppressing ventricular premature contractions in 14 patients was evaluated in a double-blind, cross-over, placebo controlled, randomized and balanced study. Each treatment period was 2 weeks followed by a 3-4 d placebo washout period and the study lasted 5 weeks. Flecainide was given in a dose of 200 mg twice daily. A significant reduction in the total number of QRS complexes in a 24 h period was observed during the active compared with placebo treatment (P less than 0.05). In comparison with placebo, flecainide reduced the number of aberrant and premature aberrant QRS complexes (P less than 0.01). The mean suppression rate of aberrant QRS complexes during flecainide treatment was 85.4% and that of premature aberrant complexes was 93.2%. Maximum heart rate measured by 24 h ECG decreased significantly during flecainide therapy (P less than 0.01), although no change occurred with resting heart rate measured clinically or by ECG. Severe dizziness associated with flecainide therapy necessitated withdrawal of 2 patients from the study. A proarrhythmic effect of flecainide, ventricular tachycardia, was observed in one patient.