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Circulation. 2000;102:2509-2515

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(Circulation. 2000;102:2509.)
© 2000 American Heart Association, Inc.

Clinical Investigation and Reports

Clinical and Genetic Heterogeneity of Right Bundle Branch Block and ST-Segment Elevation Syndrome

A Prospective Evaluation of 52 Families

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

From the Molecular Cardiology Laboratories (S.G.P., C.N., L.T., R.B.), IRCCS Fondazione Salvatore Maugeri, Pavia, Italy; Unità operativa di Cardiologia (M.G.), Istituto Clinico Humanitas, Rozzano, Italy; Divisione di Aritmologia (C.P.), IRCCS Ospedale San Raffaele, Milan, Italy; Centro Cardiologico (P.D.B.), Fondazione Monzino IRCCS, Milan, Italy; Servizio di Cardiologia-UTIC (M.B.), Ospedale di Lavagna, Lavagna, Italy; Divisione di Cardiologia (U.G.), Ospedale Civico Di Cristina ARNAS, Palermo, Italy; Unità operativa di Cardiologia Ospedale di Prato (T.G.), Prato, Italy; Unità di Cardiologia Interventistica (C.M.), Arcispedale S. Maria Nuova, Reggio Emilia, Italy; and the Department of Cardiology (L.C., P.J.S.), IRCCS Policlinico S. Matteo and University of Pavia, Pavia, Italy.

Correspondence to Silvia G. Priori, Molecular Cardiology, Fondazione Salvatore Maugeri IRCCS, Via Ferrata 8, 27100 Pavia, Italy. E-mail spriori{at}fsm.it

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.


Key Words: heart arrest • genetics • fibrillation • arrhythmia




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