Flecainide Therapy Reduces Exercise-Induced Ventricular Arrhythmias in Patients With Catecholaminergic Polymorphic Ventricular Tachycardia

Christian van der Werf, Prince J. Kannankeril, Frederic Sacher, Andrew D. Krahn, Sami Viskin, Antoine Leenhardt, Wataru Shimizu, Naokata Sumitomo, Frank A. Fish, Zahurul A. Bhuiyan, Albert R. Willems, Maurits J. van der Veen, Hiroshi Watanabe, Julien Laborderie, Michel Haïssaguerre, Björn C. Knollmann, Arthur A. M. Wilde

Research output: Contribution to journalEditorialAcademicpeer-review

328 Citations (Scopus)

Abstract

Objectives This study evaluated the efficacy and safety of flecainide in addition to conventional drug therapy in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT). Background CPVT is an inherited arrhythmia syndrome caused by gene mutations that destabilize cardiac ryanodine receptor Ca2+ release channels. Sudden cardiac death is incompletely prevented by conventional drug therapy with beta-blockers with or without Ca2+ channel blockers. The antiarrhythmic agent flecainide directly targets the molecular defect in CPVT by inhibiting premature Ca2+ release and triggered beats in vitro. Methods We collected data from every consecutive genotype-positive CPVT patient started on flecainide at 8 international centers before December 2009. The primary outcome measure was the reduction of ventricular arrhythmias during exercise testing. Results Thirty-three patients received flecainide because of exercise-induced ventricular arrhythmias despite conventional (for different reasons, not always optimal) therapy (median age 25 years; range 7 to 68 years; 73% female). Exercise tests comparing flecainide in addition to conventional therapy with conventional therapy alone were available for 29 patients. Twenty-two patients (76%) had either partial (n = 8) or complete (n = 14) suppression of exercise-induced ventricular arrhythmias with flecainide (p <0.001). No patient experienced worsening of exercise-induced ventricular arrhythmias. The median daily flecainide dose in responders was 150 mg (range 100 to 300 mg). During a median follow-up of 20 months (range 12 to 40 months), 1 patient experienced implantable cardioverter-defibrillator shocks for polymorphic ventricular arrhythmias, which were associated with a low serum flecainide level. In 1 patient, flecainide successfully suppressed exercise-induced ventricular arrhythmias for 29 years. Conclusions Flecainide reduced exercise-induced ventricular arrhythmias in patients with CPVT not controlled by conventional drug therapy. (J Am Coll Cardiol 2011;57:2244-54) (C) 2011 by the American College of Cardiology Foundation
Original languageEnglish
Pages (from-to)2244-2254
JournalJournal of the American College of Cardiology
Volume57
Issue number22
DOIs
Publication statusPublished - 2011

Cite this