title: Natural history of Brugada syndrome: insights for risk stratification and management.
abstract: BACKGROUND
  Treatment of patients with Brugada syndrome is complicated by the incomplete information on the natural history of the disease related to the small number of cases reported. Furthermore, the value of programmed electrical stimulation (PES) for risk stratification is highly debated. The objective of this study was to search for novel parameters to identify patients at risk of sudden death.
  
  
  RESULTS
  Clinical data were collected for 200 patients (152 men, 48 women; age, 41+/-18 years) and stored in a dedicated database. Genetic analysis was performed, and mutations on the SCN5A gene were identified in 28 of 130 probands and in 56 of 121 family members. The life-table method of Kaplan-Meier used to define the cardiac arrest-free interval in patients undergoing PES failed to demonstrate an association between PES inducibility and spontaneous occurrence of ventricular fibrillation. Multivariate Cox regression analysis showed that after adjusting for sex, family history of sudden death, and SCN5A mutations, the combined presence of a spontaneous ST-segment elevation in leads V1 through V3 and the history of syncope identifies subjects at risk of cardiac arrest (HR, 6.4; 95% CI, 1.9 to 21; P<0.002).
  
  
  CONCLUSIONS
  The information on the natural history of patients obtained in this study allowed elaboration of a risk-stratification scheme to quantify the risk for sudden cardiac death and to target the use of the implantable cardioverter-defibrillator.
authors.affiliation: Molecular Cardiology Laboratories, IRCCS Fondazione Salvatore Maugeri and University of Pavia, Pavia, Italy. spriori@fsm.it
authors.forename: Silvia G
authors.initials: SG
authors.lastname: Priori
authors.forename: Carlo
authors.initials: C
authors.lastname: Napolitano
authors.forename: Maurizio
authors.initials: M
authors.lastname: Gasparini
authors.forename: Carlo
authors.initials: C
authors.lastname: Pappone
authors.forename: Paolo
authors.initials: P
authors.lastname: Della Bella
authors.forename: Umberto
authors.initials: U
authors.lastname: Giordano
authors.forename: Raffaella
authors.initials: R
authors.lastname: Bloise
authors.forename: Carla
authors.initials: C
authors.lastname: Giustetto
authors.forename: Roberto
authors.initials: R
authors.lastname: De Nardis
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Grillo
authors.forename: Elena
authors.initials: E
authors.lastname: Ronchetti
authors.forename: Giovanna
authors.initials: G
authors.lastname: Faggiano
authors.forename: Janni
authors.initials: J
authors.lastname: Nastoli
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015897:Comorbidity; D004252:DNA Mutational Analysis; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D017147:Defibrillators, Implantable; D019468:Disease Management; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D062554:NAV1.5 Voltage-Gated Sodium Channel; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D015222:Sodium Channels / Q000235:genetics; D015996:Survival Rate; D013575:Syncope / Q000453:epidemiology / Q000235:genetics; D013577:Syndrome; D014693:Ventricular Fibrillation / Q000453:epidemiology / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels