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(Circulation. 2000;101:510.)
© 2000 American Heart Association, Inc.

Clinical Investigation and Reports

Sodium Channel Blockers Identify Risk for Sudden Death in Patients With ST-Segment Elevation and Right Bundle Branch Block but Structurally Normal Hearts

Ramon Brugada, MD; Josep Brugada, MD; Charles Antzelevitch, PhD; Glenn E. Kirsch, PhD; Domenico Potenza, MD; Jeffrey A. Towbin, MD; Pedro Brugada, MD

From the Departments of Cardiology (R.B.) and Pediatrics (J.A.T.), Baylor College of Medicine, Houston, Texas; the Arrhythmia Unit, Cardiovascular Institute, Hospital Clínic, University of Barcelona, Barcelona, Spain (J.B.); the Masonic Medical Research Laboratory, Utica, New York (C.A.); the Rammelkamp Center for Research, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio (G.E.K); the Cardiology Department, Casa Sollievo della Sofferenza, S. Giovani Rotondo, Italy (D.P.); and the Cardiovascular Center, OLV Hospital, Aalst, Belgium (P.B.).

Correspondence to Dr Josep Brugada, Arrhythmia Unit, Cardiovascular Institute, Hospital Clínic, University of Barcelona, Villarroel 170, 08036 Barcelona, Spain. E-mail jepbrugada{at}grn.es

Background—A mutation in the cardiac sodium channel gene (SCN5A) has been described in patients with the syndrome of right bundle branch block, ST-segment elevation in leads V1 to V3, and sudden death (Brugada syndrome). These electrocardiographic manifestations are transient in many patients with the syndrome. The present study examined arrhythmic risk in patients with overt and concealed forms of the disease and the effectiveness of sodium channel blockers to unmask the syndrome and, thus, identify patients at risk.

Methods and Results—The effect of intravenous ajmaline (1 mg/kg), procainamide (10 mg/kg), or flecainide (2 mg/kg) on the ECG was studied in 34 patients with the syndrome and transient normalization of the ECG (group A), 11 members of 3 families in whom a SCN5A mutation was associated with the syndrome and 8 members in whom it was not (group B), and 53 control subjects (group C). Ajmaline, procainamide, or flecainide administration resulted in ST-segment elevation and right bundle branch block in all patients in group A and in all 11 patients with the mutation in group B. A similar pattern could not be elicited in the 8 patients in group B who lacked the mutation or in any person in group C. The follow-up period (37±33 months) revealed no differences in the incidence of arrhythmia between the 34 patients in whom the phenotypic manifestation of the syndrome was transient and the 24 patients in whom it was persistent (log-rank, 0.639).

Conclusions—The data demonstrated a similar incidence of potentially lethal arrhythmias in patients displaying transient versus persistent ST-segment elevation and right bundle branch block, as well as the effectiveness of sodium channel blockers to unmask the syndrome and, thus, identify patients at risk.

Key Words: electrocardiography • death, sudden • fibrillation • antiarrhythmia agents

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				S. G. Priori, C. Napolitano, M. Gasparini, C. Pappone, P. D. Bella, U. Giordano, R. Bloise, C. Giustetto, R. De Nardis, M. Grillo, et al. Natural History of Brugada Syndrome: Insights for Risk Stratification and Management Circulation, March 19, 2002; 105(11): 1342 - 1347. [Abstract] [Full Text] [PDF]

				M. Vatta, R. Dumaine, G. Varghese, T. A. Richard, W. Shimizu, N. Aihara, K. Nademanee, R. Brugada, J. Brugada, G. Veerakul, et al. Genetic and biophysical basis of sudden unexplained nocturnal death syndrome (SUNDS), a disease allelic to Brugada syndrome Hum. Mol. Genet., February 1, 2002; 11(3): 337 - 345. [Abstract] [Full Text] [PDF]

				A. I. Bodegas, J. I. Arana, Y. Vitoria, J. R. Arriandiaga, and J. I. Barrenetxea Brugada syndrome in a patient with accessory pathway Europace, January 1, 2002; 4(1): 87 - 89. [Abstract] [PDF]

				J. Brugada, R. Brugada, C. Antzelevitch, J. Towbin, K. Nademanee, and P. Brugada Long-Term Follow-Up of Individuals With the Electrocardiographic Pattern of Right Bundle-Branch Block and ST-Segment Elevation in Precordial Leads V1 to V3 Circulation, January 1, 2002; 105(1): 73 - 78. [Abstract] [Full Text] [PDF]

				R. Brugada and R. Roberts Brugada Syndrome: Why Are There Multiple Answers to a Simple Question? Circulation, December 18, 2001; 104(25): 3017 - 3019. [Full Text] [PDF]

				F. Kyndt, V. Probst, F. Potet, S. Demolombe, J.-C. Chevallier, I. Baro, J.-P. Moisan, P. Boisseau, J.-J. Schott, D. Escande, et al. Novel SCN5A Mutation Leading Either to Isolated Cardiac Conduction Defect or Brugada Syndrome in a Large French Family Circulation, December 18, 2001; 104(25): 3081 - 3086. [Abstract] [Full Text] [PDF]

				S Sangwatanaroj, S Prechawat, B Sunsaneewitayakul, S Sitthisook, P Tosukhowong, and K Tungsanga New electrocardiographic leads and the procainamide test for the detection of the Brugada sign in sudden unexplained death syndrome survivors and their relatives Eur. Heart J., December 2, 2001; 22(24): 2290 - 2296. [Abstract] [PDF]

				C. Antzelevitch Heterogeneity of cellular repolarization in LQTS: the role of M cells Eur. Heart J. Suppl., September 1, 2001; 3(suppl_K): K2 - K16. [Abstract] [PDF]

				S.G. Priori, E. Aliot, C. Blomstrom-Lundqvist, L. Bossaert, G. Breithardt, P. Brugada, A.J. Camm, R. Cappato, S.M. Cobbe, C. Di Mario, et al. Task Force on Sudden Cardiac Death of the European Society of Cardiology Eur. Heart J., August 2, 2001; 22(16): 1374 - 1450. [PDF]

				M Furuhashi, K Uno, K Tsuchihashi, D Nagahara, M Hyakukoku, T Ohtomo, S Satoh, T Nishimiya, and K Shimamoto Prevalence of asymptomatic ST segment elevation in right precordial leads with right bundle branch block (Brugada-type ST shift) among the general Japanese population Heart, August 1, 2001; 86(2): 161 - 166. [Abstract] [Full Text] [PDF]

				T. Ikeda, H. Sakurada, K. Sakabe, T. Sakata, M. Takami, N. Tezuka, T. Nakae, M. Noro, Y. Enjoji, T. Tejima, et al. Assessment of noninvasive markers in identifying patients at risk in the brugada syndrome: insight into risk stratification J. Am. Coll. Cardiol., May 1, 2001; 37(6): 1628 - 1634. [Abstract] [Full Text] [PDF]

				I. Gussak, P. Bjerregaard, and S. C. Hammill Clinical diagnosis and risk stratification in patients with brugada syndrome J. Am. Coll. Cardiol., May 1, 2001; 37(6): 1635 - 1638. [Full Text] [PDF]

				S. G Priori, C. Napolitano, and M. Grillo Concealed arrhythmogenic syndromes: the hidden substrate of idiopathic ventricular fibrillation? Cardiovasc Res, May 1, 2001; 50(2): 218 - 223. [Abstract] [Full Text] [PDF]

				C Antzelevitch The Brugada syndrome: diagnostic criteria and cellular mechanisms Eur. Heart J., March 1, 2001; 22(5): 356 - 363. [PDF]