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

Abstract

Objective This study evaluated the efficacy and safety of flecainide in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) on top of conventional drug therapy. Background CPVT is an inherited arrhythmia syndrome caused by gene mutations that destabilize cardiac ryanodine receptor Ca2+ release channels. Sudden death is incompletely prevented by conventional drug therapy with β-blockers +/− Ca2+ channel blockers. The anti-arrhythmic 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 eight international centers before November 13, 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 of 25 years, range 7 to 68; 70% female). Exercise tests comparing flecainide with conventional therapy alone were available in 29 patients. Twenty-two (76%) patients had either a partial (n=8) or complete (n=14) suppression of exercise-induced ventricular arrhythmias by flecainide (p<0.001). No patient experienced worsening of exercise-induced ventricular arrhythmias. 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) one patient experienced ICD shocks for polymorphic ventricular arrhythmias, which was associated with low flecainide levels. In one patient, flecainide successfully suppressed exerciseinduced ventricular arrhythmias for 29 years. Conclusions Flecainide reduced exercise-induced ventricular arrhythmias patients with CPVT uncontrolled by conventional drug therapy.

Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) Associated With Ryanodine Receptor (RyR2) Gene Mutations – Long-Term Prognosis After Initiation of Medical Treatment –

“…Since the first report by Watanabe et al, 18 the efficacy of flecainide in CPVT patients with RyR2 mutations has been reported. 19 In our study, 60% of the CPVT patients were on flecainide during the follow-up. Flecainide is reported to cause partial or complete suppression of high-risk VAs.…”

Effect of flecainide derivatives on sarcoplasmic reticulum calcium release suggests a lack of direct action on the cardiac ryanodine receptor

“…More recently, flecainide has emerged as an effective therapeutic agent for the treatment of CPVT both in combination with conventional β‐adrenoceptor blockade (van der Werf et al ., 2011; van der Werf et al ., 2012; Watanabe et al ., 2013) and as a monotherapy (Napolitano, 2016; Padfield et al ., 2016). …”

Exercise induced a rare cardiac arrest: A case with catecholaminergic polymorphic ventricular tachycardia

“…Beta-blokör tedavisi olguların büyük kısmında aritmi ataklarını önlemiştir (8) . Beta-blokör tedavisi altında semptomatik olan hastalarda flekainid başlanmalıdır (9) . Optimal medikal tedavi altında semptomların devam etmesi veya polimorfik VT atağı geçirmeleri durumunda ICD implantasyonu ve/veya sol kardiyak sempatik denervasyon önerilmektedir (10,11) .…”