Natural history of Brugada syndrome: insights for risk stratification and management.
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.
Priori
Silvia G
SG
Molecular Cardiology Laboratories, IRCCS Fondazione Salvatore Maugeri and University of Pavia, Pavia, Italy. spriori@fsm.it
Napolitano
Carlo
C
Gasparini
Maurizio
M
Pappone
Carlo
C
Della Bella
Paolo
P
Giordano
Umberto
U
Bloise
Raffaella
R
Giustetto
Carla
C
De Nardis
Roberto
R
Grillo
Massimiliano
M
Ronchetti
Elena
E
Faggiano
Giovanna
G
Nastoli
Janni
J
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
D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels