Long‐Term Serial Exercise Stress Testing in Catecholaminergic Polymorphic Ventricular Tachycardia on Beta‐Blocker and Flecainide Therapy

INTRODUCTION: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially life-threatening arrhythmic disorder typically treated with beta-blockers and, occasionally, with flecainide. METHODS: All patients underwent genetic testing, electrocardiogram, echocardiogram, and exercise testing. Ventricular arrhythmias were assessed using qualitative and quantitative scoring systems. Flecainide dosing was progressively titrated, and follow-up extended from 2007 to 2024. RESULTS: Among 235 genetically confirmed carriers of the RyR2 (ryanodine receptor 2) p.Gly357Ser mutation, 32 required combination therapy with beta-blockers and flecainide (age at diagnosis 18 [1-55] years; age at flecainide initiation 32 [15-66] years; 50% male). Forty-seven percent had an implantable cardioverter defibrillator (ICD). Flecainide was indicated for exercise-induced ventricular arrhythmias despite beta-blocker therapy, and the median treatment duration was 7.3 years. All patients received propranolol (median dose 65 mg/day). Flecainide (median dose 100 mg/day) was well tolerated, with no syncope or stress-induced symptoms. Before flecainide, five patients (16%) experienced ventricular arrhythmic events recorded by the ICD, including two requiring appropriate shocks; no events occurred after treatment initiation. Both qualitative (2.07 ± 0.77 vs. 1.22 ± 1.08, p < 0.001) and quantitative (69.78 ± 83.17 vs. 15.29 ± 5.53, p < 0.001) arrhythmic scores improved significantly. Additionally, maximum heart rate and the percentage of age-predicted maximum heart rate were significantly reduced, while metabolic equivalents increased significantly (12.3 ± 3.8 vs. 14.7 ± 7.5; p = 0.010). CONCLUSION: In CPVT patients, the addition of flecainide to beta-blocker therapy was associated with a significant reduction in arrhythmic burden and improvement in exercise-related parameters during long-term follow-up.