Flecainide in the treatment of high premature ventricular contractions burden: preliminary results from the UNIFLECA study

Abstract Background Persistent high premature ventricular contractions (PVCs) burden (5%) may lead to PVC-induced cardiomyopathy. Scarce evidence recommends the use of flecainide as a second line treatment for symptomatic PVCs originating from the ventricular outflow tracts (Class IIa recommendation). Purpose To evaluate the efficacy and safety of flecainide in reducing PVC burden, improving symptoms, and restoring left ventricular function in patients with frequent idiopathic PVCs. Methods This prospective observational study included 97 patients with a sustained PVC burden 5% on two separate 24-hour Holter recordings (mean duration between baseline holters 500 days). Slow-release Flecainide was administered at 100,150,200 mg/day in patients declining catheter ablation. The primary endpoint was PVC burden reduction at one, three and six months. Secondary endpoints included symptomatic improvement and recovery of left ventricular ejection fraction (LVEF) in patients with PVC-induced cardiomyopathy (LVEF 50%). Results As of November 2025, 84 patients completed at least one month of follow-up and were included in the present analysis. The mean time from initial PVC diagnosis to screening was 667 days. Prior to flecainide initiation, the mean daily PVC burden was 17.5 ± 12.2%. After one month of flecainide therapy (n = 84), the daily PVC burden markedly decreased to 3.7 ± 5.8%, representing an average reduction of 69%, with 61% of patients achieving a reduction 80% and 52% a reduction 90%. At six months of continuous therapy (n = 36), the mean daily PVC burden further declined to 1.2 ± 2.7%, corresponding to an overall mean reduction of 89%. The proportion of responders increased to 82% for 80% reduction and 74% for 90% reduction. Conclusions Flecainide proved to be safe and highly effective in reducing high PVC burden, improving symptoms, and enhancing systolic function. These findings support flecainide as a realistic and safe therapeutic alternative for patients who are not candidates for or decline catheter ablation.PVC Number over time per patientPVC Burden over time