Abstract 12698: Effects of Flecainide on Exercise-Induced Arrhythmias and Recurrences in Genotype-Negative Patients with Catecholaminergic Polymorphic Ventricular Tachycardia
Background [[Unable to Display Character: ―]] Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome and has been associated with mutations in three causative genes resulting in spontaneous Ca2+ release from destabilized ryanodine channels. The efficacy of conventional therapy with β-blockers is incomplete to prevent arrhythmia events. We have previously discovered that flecainide directly inhibits ryanodine channels and prevents ventricular arrhythmias in genotype-positive CPVT patients. Here, we studied the effects of flecainide in clinically overt, but genotype-negative CPVT patients.
Methods and Results [[Unable to Display Character: ―]] This study included 13 genotype-negative CPVT patients (mean age, 17±13 years; 7 females) who were treated with flecainide (mean dose, 167±45 mg). Five patients had a history of syncope or cardiac arrest. Conventional therapy failed to control CPVT in 12 patients. Flecainide was initiated because of significant ventricular arrhythmias (n=9), syncope (n=3) or cardiac arrest (n=1). At the baseline exercise test before flecainide, 7 patients (54%) had ventricular tachycardia and 5 patients (38%) had bigeminal or frequent ventricular premature beats. Flecainide suppressed ventricular arrhythmias at the exercise test in 9 patients (69%) compared to conventional therapy, similarly to genotype-positive patients in our previous report (76%, p=0.30). Notably, flecainide completely prevented ventricular arrhythmias in 7 patients (54%). Flecainide was continued in all patients except for one who had ventricular tachycardia at the exercise test on flecainide. During a median follow-up of 20 months (range, 3 to 326 months), none of the patients had arrhythmia events, and the incidence of events (0%) was similar to genotype-positive patients in our previous report (3%, p=0.63). Flecainide was not discontinued due to side effects in any of the patients.
Conclusion [[Unable to Display Character: ―]] Flecainide was effective in genotype-negative CPVT patients, suggesting that spontaneous Ca2+ release from ryanodine channels plays a role for arrhythmia susceptibility similarly to genotype-positive patients. Flecainide can be used regardless of genotyping results in CPVT patients in whom conventional pharmacological therapy fails to control their arrhythmias.
- © 2012 by American Heart Association, Inc.