Clinical and genetic heterogeneity of right bundle branch block and ST-segment elevation syndrome: A prospective evaluation of 52 families

Silvia G. Priori, Carlo Napolitano, Maurizio Gasparini, Carlo Pappone, Paolo Della Bella, Michele Brignole, Umberto Giordano, Tiziana Giovannini, Carlo Menozzi, Raffaella Bloise, Lia Crotti, Liana Terreni, Peter J. Schwartz

Research output: Contribution to journalArticle

Abstract

Background - The ECG pattern of right bundle branch block and ST-segment elevation in leads V1 to V3 (Brugada syndrome) is associated with high risk of sudden death in patients with a normal heart. Current management and prognosis are based on a single study suggesting a high mortality risk within 3 years for symptomatic and asymptomatic patients alike. As a consequence, aggressive management (implantable cardioverter defibrillator) is recommended for both groups. Methods and Results - Sixty patients (45 males aged 40±15 years) with the typical ECG pattern were clinically evaluated. Events at follow-up were analyzed for patients with at least one episode of aborted sudden death or syncope of unknown origin before recognition of the syndrome (30 symptomatic patients) and for patients without previous history of events (30 asymptomatic patients). Prevalence of mutations of the cardiac sodium channel was 15%, demonstrating genetic heterogeneity. During a mean follow-up of 33±38 months, ventricular fibrillation occurred in 5 (16%) of 30 symptomatic patients and in none of the 30 asymptomatic patients. Programmed electrical stimulation was of limited value in identifying patients at risk (positive predictive value 50%, negative predictive value 46%). Pharmacological challenge with sodium channel blockers was unable to unmask most silent gene carriers (positive predictive value 35%). Conclusions - At variance with current views, asymptomatic patients are at lower risk for sudden death. Programmed electrical stimulation identifies only a fraction of individuals at risk, and sodium channel blockade fails to unmask most silent gene carriers. This novel evidence mandates a reappraisal of therapeutic management.

Original languageEnglish
Pages (from-to)2509-2515
Number of pages7
JournalCirculation
Volume102
Issue number20
Publication statusPublished - Nov 14 2000

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Genetic Heterogeneity
Bundle-Branch Block
Sudden Death
Sodium Channels
Electric Stimulation
Electrocardiography
Sodium Channel Blockers
Brugada Syndrome
Implantable Defibrillators
Syncope
Ventricular Fibrillation
Genes
Pharmacology

Keywords

  • Arrhythmia
  • Fibrillation
  • Genetics
  • Heart arrest

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

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title = "Clinical and genetic heterogeneity of right bundle branch block and ST-segment elevation syndrome: A prospective evaluation of 52 families",
abstract = "Background - The ECG pattern of right bundle branch block and ST-segment elevation in leads V1 to V3 (Brugada syndrome) is associated with high risk of sudden death in patients with a normal heart. Current management and prognosis are based on a single study suggesting a high mortality risk within 3 years for symptomatic and asymptomatic patients alike. As a consequence, aggressive management (implantable cardioverter defibrillator) is recommended for both groups. Methods and Results - Sixty patients (45 males aged 40±15 years) with the typical ECG pattern were clinically evaluated. Events at follow-up were analyzed for patients with at least one episode of aborted sudden death or syncope of unknown origin before recognition of the syndrome (30 symptomatic patients) and for patients without previous history of events (30 asymptomatic patients). Prevalence of mutations of the cardiac sodium channel was 15{\%}, demonstrating genetic heterogeneity. During a mean follow-up of 33±38 months, ventricular fibrillation occurred in 5 (16{\%}) of 30 symptomatic patients and in none of the 30 asymptomatic patients. Programmed electrical stimulation was of limited value in identifying patients at risk (positive predictive value 50{\%}, negative predictive value 46{\%}). Pharmacological challenge with sodium channel blockers was unable to unmask most silent gene carriers (positive predictive value 35{\%}). Conclusions - At variance with current views, asymptomatic patients are at lower risk for sudden death. Programmed electrical stimulation identifies only a fraction of individuals at risk, and sodium channel blockade fails to unmask most silent gene carriers. This novel evidence mandates a reappraisal of therapeutic management.",
keywords = "Arrhythmia, Fibrillation, Genetics, Heart arrest",
author = "Priori, {Silvia G.} and Carlo Napolitano and Maurizio Gasparini and Carlo Pappone and {Della Bella}, Paolo and Michele Brignole and Umberto Giordano and Tiziana Giovannini and Carlo Menozzi and Raffaella Bloise and Lia Crotti and Liana Terreni and Schwartz, {Peter J.}",
year = "2000",
month = "11",
day = "14",
language = "English",
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journal = "Circulation",
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TY - JOUR

T1 - Clinical and genetic heterogeneity of right bundle branch block and ST-segment elevation syndrome

T2 - A prospective evaluation of 52 families

AU - Priori, Silvia G.

AU - Napolitano, Carlo

AU - Gasparini, Maurizio

AU - Pappone, Carlo

AU - Della Bella, Paolo

AU - Brignole, Michele

AU - Giordano, Umberto

AU - Giovannini, Tiziana

AU - Menozzi, Carlo

AU - Bloise, Raffaella

AU - Crotti, Lia

AU - Terreni, Liana

AU - Schwartz, Peter J.

PY - 2000/11/14

Y1 - 2000/11/14

N2 - Background - The ECG pattern of right bundle branch block and ST-segment elevation in leads V1 to V3 (Brugada syndrome) is associated with high risk of sudden death in patients with a normal heart. Current management and prognosis are based on a single study suggesting a high mortality risk within 3 years for symptomatic and asymptomatic patients alike. As a consequence, aggressive management (implantable cardioverter defibrillator) is recommended for both groups. Methods and Results - Sixty patients (45 males aged 40±15 years) with the typical ECG pattern were clinically evaluated. Events at follow-up were analyzed for patients with at least one episode of aborted sudden death or syncope of unknown origin before recognition of the syndrome (30 symptomatic patients) and for patients without previous history of events (30 asymptomatic patients). Prevalence of mutations of the cardiac sodium channel was 15%, demonstrating genetic heterogeneity. During a mean follow-up of 33±38 months, ventricular fibrillation occurred in 5 (16%) of 30 symptomatic patients and in none of the 30 asymptomatic patients. Programmed electrical stimulation was of limited value in identifying patients at risk (positive predictive value 50%, negative predictive value 46%). Pharmacological challenge with sodium channel blockers was unable to unmask most silent gene carriers (positive predictive value 35%). Conclusions - At variance with current views, asymptomatic patients are at lower risk for sudden death. Programmed electrical stimulation identifies only a fraction of individuals at risk, and sodium channel blockade fails to unmask most silent gene carriers. This novel evidence mandates a reappraisal of therapeutic management.

AB - Background - The ECG pattern of right bundle branch block and ST-segment elevation in leads V1 to V3 (Brugada syndrome) is associated with high risk of sudden death in patients with a normal heart. Current management and prognosis are based on a single study suggesting a high mortality risk within 3 years for symptomatic and asymptomatic patients alike. As a consequence, aggressive management (implantable cardioverter defibrillator) is recommended for both groups. Methods and Results - Sixty patients (45 males aged 40±15 years) with the typical ECG pattern were clinically evaluated. Events at follow-up were analyzed for patients with at least one episode of aborted sudden death or syncope of unknown origin before recognition of the syndrome (30 symptomatic patients) and for patients without previous history of events (30 asymptomatic patients). Prevalence of mutations of the cardiac sodium channel was 15%, demonstrating genetic heterogeneity. During a mean follow-up of 33±38 months, ventricular fibrillation occurred in 5 (16%) of 30 symptomatic patients and in none of the 30 asymptomatic patients. Programmed electrical stimulation was of limited value in identifying patients at risk (positive predictive value 50%, negative predictive value 46%). Pharmacological challenge with sodium channel blockers was unable to unmask most silent gene carriers (positive predictive value 35%). Conclusions - At variance with current views, asymptomatic patients are at lower risk for sudden death. Programmed electrical stimulation identifies only a fraction of individuals at risk, and sodium channel blockade fails to unmask most silent gene carriers. This novel evidence mandates a reappraisal of therapeutic management.

KW - Arrhythmia

KW - Fibrillation

KW - Genetics

KW - Heart arrest

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