Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia

Circulation. 2002 Jul 2;106(1):69-74. doi: 10.1161/01.cir.0000020013.73106.d8.


Background: Mutations in the cardiac ryanodine receptor gene (RyR2) underlie catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited arrhythmogenic disease occurring in the structurally intact heart. The proportion of patients with CPVT carrying RyR2 mutations is unknown, and the clinical features of RyR2-CPVT as compared with nongenotyped CPVT are undefined.

Methods and results: Patients with documented polymorphic ventricular arrhythmias occurring during physical or emotional stress with a normal heart entered the study. The clinical phenotype of the 30 probands and of 118 family members was evaluated, and mutation screening on the RyR2 gene was performed. Arrhythmias documented in probands were: 14 of 30 bidirectional ventricular tachycardia, 12 of 30 polymorphic ventricular tachycardia, and 4 of 30 catecholaminergic idiopathic ventricular fibrillation; RyR2 mutations were identified in 14 of 30 probands (36% bidirectional ventricular tachycardia, 58% polymorphic ventricular tachycardia, 50% catecholaminergic idiopathic ventricular fibrillation) and in 9 family members (4 silent gene carriers). Genotype-phenotype analysis showed that patients with RyR2 CPVT have events at a younger age than do patients with nongenotyped CPVT and that male sex is a risk factor for syncope in RyR2-CPVT (relative risk=4.2).

Conclusions: CPVT is a clinically and genetically heterogeneous disease manifesting beyond pediatric age with a spectrum of polymorphic arrhythmias. beta-Blockers reduce arrhythmias, but in 30% of patients an implantable defibrillator may be required. Genetic analysis identifies two groups of patients: Patients with nongenotyped CPVT are predominantly women and become symptomatic later in life; patients with RyR2 CPVT become symptomatic earlier, and men are at higher risk of cardiac events. These data provide a rationale for prompt evaluation and treatment of young men with RyR2 mutations.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Catecholamines
  • Child
  • Child, Preschool
  • Death, Sudden, Cardiac / epidemiology
  • Family Health
  • Female
  • Genetic Variation
  • Genotype
  • Humans
  • Male
  • Mutation*
  • Pedigree
  • Ryanodine Receptor Calcium Release Channel / genetics*
  • Sequence Alignment
  • Survival Rate
  • Tachycardia, Ventricular / diagnosis*
  • Tachycardia, Ventricular / genetics*
  • Tachycardia, Ventricular / mortality
  • Tachycardia, Ventricular / therapy


  • Catecholamines
  • Ryanodine Receptor Calcium Release Channel