Efficacy and safety of flecainide in catecholaminergic polymorphic ventricular tachycardia

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disorder characterized by ventricular arrhythmias causing sudden cardiac death in young individuals. Arrhythmias in stress test have been related with bad prognosis in CPVT. Betablocker (BB) therapy is the mainstay of treatment but its protection has shown to be incomplete. Purpose: To evaluate the efficacy of Flecainide to reduce the amount of arrhythmias in defibrillator (ICD) carriers with CPVT. Methods: In a large family, we have identified 179 alive RYR2 p.G357S mutation carriers. Of these, we selected 7 (3 males) because they met two conditions: to be carriers of an ICD and to present frequently ventricular arrhythmias (VA) in seriated stress tests (ET) despite BB full dose treatment. They accepted and accomplished a 6 week protocol of Flecainide treatment and progressive titration of weight adjusted dose, with frequent search of side effects. 3 ET were concurrently performed: Basal (BS) -only with BB-, half dose Flecainide (F1) -after 2 weeks-, and full dose Flecainide (F2) -after 6 weeks-. VA were measured by a quantitative Arrhythmia Score. Results: The mean half dose and total dose of Flecainide was 89.3 mg (1.36±0.22 mg/kg) and 178.6 mg (2.58±0.75 mg/kg), respectively. The median/mean (±SD) Arrhythmia Score in BS, F1 (2 weeks) and F2 (6 weeks) is: 125/166.9 (±190), 1/17.49 (±26) and 0/0.14 (±0.38) (FIGURE). Applying statistical analysis, BS Vs F1, p=0.018; BS Vs F2, p=0.018; F1 Vs F2, p=0.05. There were no differences in means of METS [Basal (12.6) Vs F1 (13.06): p=0,05; Basal Vs F2 (12.93): p=0,14. No side effects were noted. Mean arrhythmia score in stress tests Conclusionsl: Flecainide added to BB is safe and progressively effective to reduce ventricular arrhythmias in stress tests of CPVT patients after 6 weeks of follow-up.