Abstract 4359112: Flecainide Reduces Exercise-Induced Arrhythmic Burden in PKP2-Related Arrhythmogenic Cardiomyopathy

Background: An increased burden of premature ventricular contractions (PVCs)/non-sustained ventricular tachycardia (NSVT) during the recovery phase of exercise stress testing (EST) appears to be a distinctive feature of PKP2-related arrhythmogenic cardiomyopathy (ACM) associated with an increased risk of major ventricular arrhythmia (VA) events. While flecainide may help manage VA, its impact on post-exercise VA burden and the role of EST in guiding its use remain unclear. Objective: To examine the effect of flecainide on EST-VA burden in PKP2-related ACM. Methods: A retrospective analysis of 1,049 genotype-positive ACM patients identified those with PKP2 variants who underwent ESTs on and off flecainide. Clinical data were collected and the arrhythmic burden—measured as PVCs, couplets, bigeminy, NSVT, sustained VT, ventricular fibrillation, and PVCs per minute—during each EST phase (baseline, peak, active recovery, and passive recovery) was assessed and compared between the EST performed pre- and post-initiation of flecainide. Results: Of 147 PKP2-ACM patients, 11 (35 ESTs) had at least one EST on flecainide. Eight patients (mean age 31 ± 13 years, 50% male) underwent both on and off flecainide for a total of 29 ESTs [on beta-blockers (80%), flecainide (52%), amiodarone (3%), or sotalol (3%)]. When comparing EST performed pre- and post-initiation of flecainide, the frequency of PVCs per minute was significantly lower both during exercise (3 ± 3 vs 1 ± 2, p=0.023) and during the recovery phase (12 ± 13 vs 2 ± 4, p=0.010). Similarly, the presence of PVCs during exercise (85% vs 47%, p=0.026) and recovery (85% vs 47%, p=0.027), couplets during exercise (27% vs 0%, p=0.026) and recovery (85% vs 20%, p<0.001), and bigeminy during exercise (36% vs 7%, p=0.054) and recovery (72% vs 13%, p=0.002) was significantly reduced following the initiation of flecainide. No significant differences were observed in the prevalence of NSVT or sustained VT. Five patients (63%) had prior sustained VT without breakthrough events post-flecainide. One patient without prior VT had an early event but remained event-free after dose up titration. Conclusion: Flecainide significantly reduces the EST arrhythmic burden in patients with PKP2-ACM, particularly in the recovery phase. Future studies are needed to determine if the EST can be used to guide flecainide dosing and efficacy in PKP2-ACM akin to current strategies employed for catecholaminergic polymorphic ventricular tachycardia.