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.