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Circulation. 2016 Feb 16;133(7):622-30. doi: 10.1161/CIRCULATIONAHA.115.017885. Epub 2016 Jan 21.

Programmed Ventricular Stimulation for Risk Stratification in the Brugada Syndrome: A Pooled Analysis.

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From Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA (J.S.); Service de Cardiologue du CHU de Nantes, CHU de Nantes, Hôpital Nord, Nantes, France (V.P.); Molecular Cardiology, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (A.M., C.N., S.G.P.); Dipartimento di Medicina, Molecolare Università di Pavia, Pavia, Italy (S.G.P.); Division of Cardiology, Casa di Cura Pederzoli, Peschiera del Garda, Verona, Italy (P.D.); Arrhythmia Unit, Cardiovascular Surgery and Cardiology Institute, Havana, Cuba (J.C.H.); Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan (K.O., I.W.); Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Padova, Italy (A.Z., D.C.); Institut Universitaire de Cardiologie et Pneumologie de Québec, Quebec City, QC, Canada (J.C., I.N.); Department of Electrophysiology and Pacing, Onassis Cardiac Surgery Center, Athens, Greece (A.K., G.T.); Boston University and National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA (X.Y.); Cardiovascular Research Center and Cardiac Arrhythmia Service, Massachusetts General Hospital, Boston (D.J.M., P.T.E., S.A.L.); Heart Centre AMC, Department of Clinical and Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands (A.W.); Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia (A.W.); Bordeaux University Hospital, LIRYC Institute/INSERM 1045, Bordeaux, France (F.S.); First Department of Medicine-Cardiology, University Medical Centre Mannheim, Mannheim, Germany (M.B.); DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Mannheim, Germany (M.B.); Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA (P.T.E., S.A.L.); Department of Cardiology, General Hospital of Conegliano, Conegliano, Treviso, Italy (G.A.); and Lankenau I



The role of programmed ventricular stimulation in identifying patients with Brugada syndrome at the highest risk for sudden death is uncertain.


We performed a systematic review and pooled analysis of prospective, observational studies of patients with Brugada syndrome without a history of sudden cardiac arrest who underwent programmed ventricular stimulation. We estimated incidence rates and relative hazards of cardiac arrest or implantable cardioverter-defibrillator shock. We analyzed individual-level data from 8 studies comprising 1312 patients who experienced 65 cardiac events (median follow-up, 38.3 months). A total of 527 patients were induced into arrhythmias with up to triple extrastimuli. Induction was associated with cardiac events during follow-up (hazard ratio, 2.66; 95% confidence interval [CI], 1.44-4.92, P<0.001), with the greatest risk observed among those induced with single or double extrastimuli. Annual event rates varied substantially by syncope history, presence of spontaneous type 1 ECG pattern, and arrhythmia induction. The lowest risk occurred in individuals without syncope and with drug-induced type 1 patterns (0.23%, 95% CI, 0.05-0.68 for no induced arrhythmia with up to double extrastimuli; 0.45%, 95% CI, 0.01-2.49 for induced arrhythmia), and the highest risk occurred in individuals with syncope and spontaneous type 1 patterns (2.55%, 95% CI, 1.58-3.89 for no induced arrhythmia; 5.60%, 95% CI, 2.98-9.58 for induced arrhythmia).


In patients with Brugada syndrome, arrhythmias induced with programmed ventricular stimulation are associated with future ventricular arrhythmia risk. Induction with fewer extrastimuli is associated with higher risk. However, clinical risk factors are important determinants of arrhythmia risk, and lack of induction does not necessarily portend low ventricular arrhythmia risk, particularly in patients with high-risk clinical features.


Brugada syndrome; arrhythmias, cardiac; death, sudden, cardiac; electrophysiology; risk assessment

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