Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia

Silvia G. Priori, Carlo Napolitano, Mirella Memmi, Barbara Colombi, Fabrizio Drago, Maurizio Gasparini, Luciano DeSimone, Fernando Coltorti, Raffaella Bloise, Roberto Keegan, Fernando E S Cruz Filho, Gabriele Vignati, Abraham Benatar, Angelica DeLogu

Research output: Contribution to journalArticle

Abstract

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. β-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.

Original languageEnglish
Pages (from-to)69-74
Number of pages6
JournalCirculation
Volume106
Issue number1
DOIs
Publication statusPublished - Jul 1 2002

Fingerprint

Ryanodine Receptor Calcium Release Channel
Cardiac Arrhythmias
Mutation
Polymorphic catecholergic ventricular tachycardia
Genes
Phenotype
Implantable Defibrillators
Syncope
Ventricular Tachycardia
Psychological Stress
Genotype
Pediatrics

Keywords

  • Arrhythmia
  • Catecholamines
  • Death, sudden
  • Genetics

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia. / Priori, Silvia G.; Napolitano, Carlo; Memmi, Mirella; Colombi, Barbara; Drago, Fabrizio; Gasparini, Maurizio; DeSimone, Luciano; Coltorti, Fernando; Bloise, Raffaella; Keegan, Roberto; Cruz Filho, Fernando E S; Vignati, Gabriele; Benatar, Abraham; DeLogu, Angelica.

In: Circulation, Vol. 106, No. 1, 01.07.2002, p. 69-74.

Research output: Contribution to journalArticle

Priori, Silvia G. ; Napolitano, Carlo ; Memmi, Mirella ; Colombi, Barbara ; Drago, Fabrizio ; Gasparini, Maurizio ; DeSimone, Luciano ; Coltorti, Fernando ; Bloise, Raffaella ; Keegan, Roberto ; Cruz Filho, Fernando E S ; Vignati, Gabriele ; Benatar, Abraham ; DeLogu, Angelica. / Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia. In: Circulation. 2002 ; Vol. 106, No. 1. pp. 69-74.
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abstract = "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. β-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.",
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T1 - Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia

AU - Priori, Silvia G.

AU - Napolitano, Carlo

AU - Memmi, Mirella

AU - Colombi, Barbara

AU - Drago, Fabrizio

AU - Gasparini, Maurizio

AU - DeSimone, Luciano

AU - Coltorti, Fernando

AU - Bloise, Raffaella

AU - Keegan, Roberto

AU - Cruz Filho, Fernando E S

AU - Vignati, Gabriele

AU - Benatar, Abraham

AU - DeLogu, Angelica

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N2 - 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. β-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.

AB - 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. β-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.

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KW - Catecholamines

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