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 V(1) to V(3) (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.
  
  
  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.
authors.affiliation: Molecular Cardiology Laboratories, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy. spriori@fsm.it
authors.forename: S G
authors.initials: SG
authors.lastname: Priori
authors.forename: C
authors.initials: C
authors.lastname: Napolitano
authors.forename: M
authors.initials: M
authors.lastname: Gasparini
authors.forename: C
authors.initials: C
authors.lastname: Pappone
authors.forename: P
authors.initials: P
authors.lastname: Della Bella
authors.forename: M
authors.initials: M
authors.lastname: Brignole
authors.forename: U
authors.initials: U
authors.lastname: Giordano
authors.forename: T
authors.initials: T
authors.lastname: Giovannini
authors.forename: C
authors.initials: C
authors.lastname: Menozzi
authors.forename: R
authors.initials: R
authors.lastname: Bloise
authors.forename: L
authors.initials: L
authors.lastname: Crotti
authors.forename: L
authors.initials: L
authors.lastname: Terreni
authors.forename: P J
authors.initials: PJ
authors.lastname: Schwartz
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D002037:Bundle-Branch Block / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D016757:Death, Sudden, Cardiac / Q000209:etiology; D017147:Defibrillators, Implantable; D018572:Disease-Free Survival; D004599:Electric Stimulation Therapy; D004562:Electrocardiography / Q000187:drug effects; D015716:Electrocardiography, Ambulatory; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D062554:NAV1.5 Voltage-Gated Sodium Channel; D019683:Penetrance; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D018570:Risk Assessment; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000235:genetics; D018709:Statistics, Nonparametric; D013575:Syncope / Q000209:etiology; D013577:Syndrome
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D026941:Sodium Channel Blockers; D015222:Sodium Channels