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

Background-The ECG pattern of right bundle branch block and ST-segment elev ation in leads V-1 to V-3 (Brugada syndrome) is associated with high risk o f sudden death in patients with a normal heart. Current management and prog nosis are based on a single study suggesting a high mortality risk within 3 years for symptomatic and asymptomatic patients alike, As a consequence, a ggressive management (implantable cardioverter defibrillator) is recommende d for both groups, Methods and Results-Sixty patients (45 males aged 40+/-15 years) with the t ypical ECG pattern were clinically evaluated, Events at follow-up were anal yzed for patients with at least one episode of aborted sudden death or sync ope of unknown origin before recognition of the syndrome (30 symptomatic pa tients) and for patients without previous history of events (30 asymptomati c patients). Prevalence of mutations of the cardiac sodium channel was 15%, demonstrating genetic heterogeneity. During a mean follow-up of 33+/-38 mo nths, ventricular fibrillation occurred in 5 (16%) of 30 symptomatic patien ts and in none of the 30 asymptomatic patients, Programmed electrical stimu lation was of limited value in identifying patients at risk (positive predi ctive 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 lo wer risk for sudden death, Programmed electrical stimulation identifies onl y a fraction of individuals at risk, and sodium channel blockade fails to u nmask most silent gene carriers, This novel evidence mandates a reappraisal of therapeutic management.