Efficacy and safety of flecainide in patients with reduced ejection fraction and high premature ventricular complex burden: a single-center experience

Abstract Background The administration of flecainide in patients with structural heart disease and reduced left ventricular ejection fraction (LVEF) is historically contraindicated due to the pro-arrhythmic risk of the Cardiac Arrhythmia Suppression Trial (CAST). However, contemporary evidence suggests a potential role for flecainide in carefully selected patients, particularly when guided by advanced cardiac imaging and in conjunction with cardiac resynchronization therapy (CRT), though safety data remain limited. Objective To evaluate the safety and efficacy of flecainide acetate in a cohort of patients with heart failure with reduced ejection fraction (HFrEF) and a high burden of premature ventricular complexes (PVCs). Methods We conducted a retrospective analysis of 24 consecutive patients with LVEF 50% and a high PVC burden who were initiated on flecainide. All patients were on stable, guideline-directed medical therapy for heart failure and had an implantable cardioverter-defibrillator (ICD) or CRT-D device. Flecainide was initiated at a low dose (50-100 mg BID) and up-titrated as tolerated. Device-based interrogation was used to assess PVC burden and CRT metrics before and after a minimum of 3 months of flecainide therapy. The primary safety endpoint was the occurrence of any adverse event, including pro-arrhythmia, heart failure hospitalization, or death. The primary efficacy endpoints were the change in PVC burden and the percentage of effective biventricular pacing (CRT%). Results Over a mean follow-up period of 6.97 months, no adverse events were observed. There were no episodes of sustained ventricular tachycardia, appropriate ICD therapies, or drug-related hospitalizations. Flecainide administration was associated with a highly significant reduction in PVC burden. Concomitantly, a significant improvement in CRT% was recorded. Conclusion In this carefully monitored cohort of HFrEF patients, flecainide therapy was safe and well-tolerated, with no adverse events reported. Its use resulted in a profound suppression of PVCs and a corresponding significant enhancement in the delivery of cardiac resynchronization therapy. These findings suggest that flecainide may represent a viable and effective treatment option for select HFrEF patients with debilitating PVCs refractory to other therapies, potentially improving CRT efficacy and clinical outcomes. Larger, prospective studies are warranted to confirm these findings