Circulation. 2002;105:1342-1347
Published online before print February 25, 2002, doi: 10.1161/hc1102.105288
Published online before print February 25, 2002, doi: 10.1161/hc1102.105288
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(Circulation. 2002;105:1342.)
© 2002 American Heart Association, Inc.
Clinical Investigation and Reports |
Natural History of Brugada Syndrome
Insights for Risk Stratification and Management
From Molecular Cardiology Laboratories, IRCCS Fondazione Salvatore Maugeri and University of Pavia, Pavia, Italy (S.G.P., C.N., R.B., M.G., E.R., G.F., J.N.); Unità Operativa di Elettrofisiologia, Istituto Clinico Humanitas, Rozzano, Italy (M.G.); Divisione di Aritmologia, IRCCS Ospedale San Raffaele, Milan, Italy (C.P.); Centro Cardiologico, Fondazione Monzino IRCCS, Milan, Italy (P.D.B.); Divisione di Cardiologia, Ospedale Civico Di Cristina ARNAS, Palermo, Italy (U.G.); Divisione di Cardiologia, Ospedale Molinette, University of Torino, Torino, Italy (C.G.); and Ospedale Cazzavillan, Arzignano, Italy (R.D.N.).
Correspondence to Silvia G. Priori, MD, PhD, Molecular Cardiology, Fondazione Salvatore Maugeri IRCCS, University of Pavia, Via Ferrata 8, 27100 Pavia, Italy. E-mail spriori{at}fsm.it
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.
Methods and 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.
Key Words: death, sudden • tachyarrhythmias • risk factors • genetics • fibrillation
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C. R Valdivia, D. J Tester, B. A Rok, C.-b. J Porter, T. M Munger, A. Jahangir, J. C Makielski, and M. J Ackerman A trafficking defective, Brugada syndrome-causing SCN5A mutation rescued by drugs Cardiovasc Res, April 1, 2004; 62(1): 53 - 62. [Abstract] [Full Text] [PDF]
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S. G. Priori Inherited Arrhythmogenic Diseases: The Complexity Beyond Monogenic Disorders Circ. Res., February 6, 2004; 94(2): 140 - 145. [Abstract] [Full Text] [PDF]
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J. Brugada, R. Brugada, and P. Brugada Determinants of Sudden Cardiac Death in Individuals With the Electrocardiographic Pattern of Brugada Syndrome and No Previous Cardiac Arrest Circulation, December 23, 2003; 108(25): 3092 - 3096. [Abstract] [Full Text] [PDF]
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J. P. DiMarco Implantable Cardioverter-Defibrillators N. Engl. J. Med., November 6, 2003; 349(19): 1836 - 1847. [Full Text] [PDF]
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M. V. Pitzalis, M. Anaclerio, M. Iacoviello, C. Forleo, P. Guida, R. Troccoli, F. Massari, F. Mastropasqua, S. Sorrentino, A. Manghisi, et al. QT-interval prolongation inright precordial leads: an additional electrocardiographic hallmark of Brugada syndrome J. Am. Coll. Cardiol., November 5, 2003; 42(9): 1632 - 1637. [Abstract] [Full Text] [PDF]
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J.-S. Hermida, A. Leenhardt, B. Cauchemez, I. Denjoy, G. Jarry, F. Mizon, P. Milliez, J.-L. Rey, P. Beaufils, and P. Coumel Decreased nocturnal standard deviation of averaged NN intervals: An independent marker to identify patients at risk in the Brugada Syndrome Eur. Heart J., November 2, 2003; 24(22): 2061 - 2069. [Abstract] [Full Text] [PDF]
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M. Sakabe, A. Fujiki, M. Tani, K. Nishida, K. Mizumaki, and H. Inoue Proportion and prognosis of healthy people with coved or saddle-back type ST segment elevation in the right precordial leads during 10 years follow-up Eur. Heart J., August 2, 2003; 24(16): 1488 - 1493. [Abstract] [Full Text] [PDF]
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S. Rolf, H.-J. Bruns, T. Wichter, P. Kirchhof, M. Ribbing, K. Wasmer, M. Paul, G. Breithardt, W. Haverkamp, and L. Eckardt The ajmaline challenge in Brugada syndrome: Diagnostic impact, safety, and recommended protocol Eur. Heart J., June 2, 2003; 24(12): 1104 - 1112. [Abstract] [Full Text] [PDF]
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C. Antzelevitch, P. Brugada, J. Brugada, R. Brugada, J. A. Towbin, and K. Nademanee Brugada syndrome: 1992-2002: A historical perspective J. Am. Coll. Cardiol., May 21, 2003; 41(10): 1665 - 1671. [Abstract] [Full Text] [PDF]
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H. L Tan, C. R Bezzina, J. P.P Smits, A. O Verkerk, and A. A.M Wilde Genetic control of sodium channel function Cardiovasc Res, March 15, 2003; 57(4): 961 - 973. [Abstract] [Full Text] [PDF]
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W. A. Groenewegen, M. Firouzi, C. R. Bezzina, S. Vliex, I. M. van Langen, L. Sandkuijl, J. P.P. Smits, M. Hulsbeek, M. B. Rook, H. J. Jongsma, et al. A Cardiac Sodium Channel Mutation Cosegregates With a Rare Connexin40 Genotype in Familial Atrial Standstill Circ. Res., January 10, 2003; 92(1): 14 - 22. [Abstract] [Full Text] [PDF]
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E. Moric, E. Herbert, M. Trusz-Gluza, A. Filipecki, U. Mazurek, and T. Wilczok The implications of genetic mutations in the sodium channel gene (SCN5A) Europace, January 1, 2003; 5(4): 325 - 334. [Abstract] [Full Text] [PDF]
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C. Antzelevitch, P. Brugada, J. Brugada, R. Brugada, W. Shimizu, I. Gussak, and A.R. Perez Riera Brugada Syndrome: A Decade of Progress Circ. Res., December 13, 2002; 91(12): 1114 - 1118. [Abstract] [Full Text] [PDF]
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Committee Members, G. Gregoratos, J. Abrams, A. E. Epstein, R. A. Freedman, D. L. Hayes, M. A. Hlatky, R. E. Kerber, G. V. Naccarelli, M. H. Schoenfeld, et al. ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices--Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/NASPE Committee to Update the 1998 Pacemaker Guidelines) J. Am. Coll. Cardiol., November 6, 2002; 40(9): 1703 - 1719. [Full Text] [PDF]
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G. Gregoratos, J. Abrams, A. E. Epstein, R. A. Freedman, D. L. Hayes, M. A. Hlatky, R. E. Kerber, G. V. Naccarelli, M. H. Schoenfeld, M. J. Silka, et al. ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices: Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/NASPE Committee to Update the 1998 Pacemaker Guidelines) Circulation, October 15, 2002; 106(16): 2145 - 2161. [Full Text] [PDF]
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