High prevalence of exercise-induced arrhythmias in catecholaminergic polymorphic ventricular tachycardia mutation-positive family members diagnosed by cascade genetic screening

Europace. 2010 Mar;12(3):417-23. doi: 10.1093/europace/eup448. Epub 2010 Jan 26.

Abstract

Aim: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited cardiac disease predisposing to life-threatening arrhythmias. We aimed to determine the prevalence of arrhythmias and efficacy of beta-blocker treatment in mutation-positive family members diagnosed by cascade genetic screening.

Methods and results: Relatives of six unrelated CPVT patients were tested for the relevant mutation in the ryanodine receptor-2 gene. Mutation carriers underwent an exercise test at inclusion time and 3 months after the initiation of beta-blocker therapy in the highest tolerable dose. The occurrence of ventricular premature beats, couplets, and non-sustained ventricular arrhythmias (nsVT) were recorded in addition to the heart rate at which they occurred. Thirty family members were mutation carriers and were followed for 22 (13-288) months. Previous undiagnosed CPVT-related symptoms were reported by eight subjects. Exercise test induced ventricular arrhythmias in 23 of the 30 mutation carriers. On beta-blocker treatment, exercise-induced arrhythmias occurred at a lower heart rate (117 +/- 17 vs. 135 +/- 34 beats/min, P = 0.02) but at similar workload (P = 0.78). Beta-blocker treatment suppressed the occurrence of exercise-induced nsVT in three of the four patients, while less severe arrhythmias were unchanged. One patient died during follow-up.

Conclusion: Exercise test revealed a high prevalence of arrhythmias in CPVT mutation carriers diagnosed by cascade genetic screening. beta-Blocker therapy appeared to suppress the most severe exercise-induced arrhythmias, while less severe arrhythmias occurred at a lower heart rate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenergic beta-Antagonists / therapeutic use
  • Adult
  • Aged
  • Catecholamines / genetics*
  • Child
  • Defibrillators, Implantable
  • Electrocardiography
  • Exercise Test
  • Exercise*
  • Family Health
  • Female
  • Genetic Testing
  • Heart Rate
  • Humans
  • Male
  • Middle Aged
  • Point Mutation
  • Prevalence
  • Ryanodine Receptor Calcium Release Channel / genetics*
  • Tachycardia, Ventricular / drug therapy
  • Tachycardia, Ventricular / epidemiology*
  • Tachycardia, Ventricular / genetics*
  • Young Adult

Substances

  • Adrenergic beta-Antagonists
  • Catecholamines
  • Ryanodine Receptor Calcium Release Channel