Flecainide therapy suppresses exercise-induced ventricular arrhythmias in patients with CASQ2-associated catecholaminergic polymorphic ventricular tachycardia

Heart Rhythm. 2013 Nov;10(11):1671-5. doi: 10.1016/j.hrthm.2013.08.011. Epub 2013 Aug 13.

Abstract

Background: Calsequestrin-associated catecholaminergic polymorphic ventricular tachycardia (CPVT2) can cause sudden death in young individuals in response to stress. Beta-blockers are the mainstay medical treatment for patients with CPVT2. However, they do not prevent syncope and sudden death in all patients. Flecainide was reported to reduce exercise-induced ventricular arrhythmias (EIVA) in patients with ryanodine receptor-associated CPVT. The role of flecainide in CPVT2 is not known.

Objective: To summarize our experience in combining flecainide and beta-blockers in high-risk patients with CPVT2.

Methods: All patients with CPVT2 (10 patients) who have high-risk features (syncope, EIVA, or appropriate implantable cardioverter-defibrillator [ICD] shocks) despite beta-blockers with or without calcium channel blockers were treated with a combination of flecainide and beta-blockers. Exercise test was done before and after beginning treatment with flecainide.

Results: All patients had EIVA and 4 had appropriate ICD shocks before flecainide treatment. EIVA-included frequent ventricular premature beats and or ventricular tachycardia during the exercise test while on high dose of beta-blockers with or without calcium channel blockers before treatment with flecainide. After combination therapy with flecainide and beta-blockers, EIVA were suppressed completely in all patients. During follow-up of 15.5 ± 10.4 months (range 2-29 months), 8 patients were free of symptoms and free of arrhythmias. Two patients had 1 VT storm episode with recurrent ICD shocks despite repeated normal stress test.

Conclusions: Flecainide can completely prevent ventricular arrhythmia during exercise and partially prevent recurrent ICD shocks in high-risk patients with CPVT2.

Keywords: CASQ2; CPVT; CPVT2; Calsequestrin; Catecholaminergic polymorphic ventricular tachycardia; EIVA; Flecainide; ICD; RyR2; VT; calsequestrin; calsequestrin-associated catecholaminergic polymorphic ventricular tachycardia; catecholaminergic polymorphic ventricular tachycardia; exercise-induced ventricular arrhythmias; implantable cardioverter-defibrillator; ryanodine receptor; ventricular tachycardia.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Anti-Arrhythmia Agents / therapeutic use
  • Calsequestrin / genetics
  • Calsequestrin / metabolism*
  • DNA / genetics
  • Death, Sudden, Cardiac / prevention & control*
  • Electrocardiography
  • Exercise Test / adverse effects*
  • Female
  • Flecainide / therapeutic use*
  • Follow-Up Studies
  • Humans
  • Male
  • Mutation
  • Tachycardia, Ventricular / drug therapy
  • Tachycardia, Ventricular / etiology*
  • Tachycardia, Ventricular / genetics
  • Treatment Outcome
  • Young Adult

Substances

  • Anti-Arrhythmia Agents
  • CASQ2 protein, human
  • Calsequestrin
  • DNA
  • Flecainide

Supplementary concepts

  • Polymorphic catecholergic ventricular tachycardia