© 1999 by European Society of Cardiology
REGULAR ARTICLE: THE GENETIC AND MOLECULAR BASES OF CLINICAL ARRHYTHMIC DISEASES
The syndrome of right bundle branch block ST segment elevation in V1 to V3 and sudden death—the Brugada syndrome
*Arrhythmia Unit, Cardiovascular Institute, Hospital Clínic, University of Barcelona Barcelona, Spain;
Cardiovascular Research and Teaching Institute Aalst, Cardiovascular Center Aalst, Belgium;
Department of Cardiology, Baylor College of Medicine Houston, Texas, U.S.A.
In 1992 a new syndrome was described consisting of syncopal episodes and/or sudden death in patients with a structurally normal heart and an electrocardiogram (ECG) characteristic of right bundle branch block with ST segment elevation in leads V1to V3. The disease is genetically determined, with an autosomal dominant pattern of transmission. Three different mutations that affect the structure and function of the cardiac sodium channel gene SCN5A have been identified. Two mutations result in total loss of function of the sodium channel. The other mutation results in acceleration of the recovery of the sodium channel from inactivation. The incidence of the disease is difficult to estimate, but it causes 4 to 10 sudden deaths per 10 000 inhabitants per year in areas like Thailand and Laos. In these countries, the disease represents the most frequent cause of death in young adults. Up to 50% of the yearly sudden deaths in patients with a structurally normal heart are caused by this syndrome. The diagnosis is easily made by means of the ECG. The presence of concealed and intermittent forms, however, make the diagnosis difficult in some patients. The ECG can be modulated by changes in autonomic balance and the administration of antiarrhythmic drugs. Beta-adrenergic stimulation normalizes the ECG, while intravenous ajmaline, flecainide or procainamide accentuate ST segment elevation and are capable of unmasking concealed and intermittent forms of the disease. Recent data suggest that loss of the action potential dome in the right ventricular epicardium but not the endocardium underlies ST segment elevation seen in the Brugada syndrome. Also, electrical heterogeneity within the right ventricular epicardium leads to the development of closely coupled extrasystoles via a phase 2 reentrant mechanism, which then precipitates ventricular tachycardia–ventricular fibrillation. Right ventricular epicardium is preferentially affected because of the predominance of transient outward current in this tissue. Antiarrhythmic drugs like amiodarone and beta-blockers do not prevent sudden death in symptomatic or asymptomatic individuals. Gene therapy may offer a cure in future years. Implantation of an automatic cardioverter–defibrillator is the only currently proven effective therapy.
Key Words: Sudden death, bundle branch block, Brugada syndrome, genetic diseases, cardiac arrhythmias
Correspondence: Dr Pedro Brugada, Cardiovascular Center, O.L.V. Hospital, Moorselbaan 190, 9300 Aalst, Belgium.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  V. Z. Miloushev, J. A. Levine, M. A. Arbing, J. F. Hunt, G. S. Pitt, and A. G. Palmer III Solution Structure of the NaV1.2 C-terminal EF-hand Domain J. Biol. Chem., March 6, 2009; 284(10): 6446 - 6454. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Noseworthy and C. Newton-Cheh Genetic Determinants of Sudden Cardiac Death Circulation, October 28, 2008; 118(18): 1854 - 1863. [Full Text] [PDF]
|
|
|
|
 |
|
 Developed in Collaboration With the European Heart, D. P. Zipes, A. J. Camm, M. Borggrefe, A. E. Buxton, B. Chaitman, M. Fromer, G. Gregoratos, G. Klein, A. J. Moss, et al. ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death) J. Am. Coll. Cardiol., September 5, 2006; 48(5): e247 - e346. [Full Text] [PDF]
|
|
|
|
 |
|
 Writing Committee Members, D. P. Zipes, A. J. Camm, M. Borggrefe, A. E. Buxton, B. Chaitman, M. Fromer, G. Gregoratos, G. Klein, A. J. Moss, et al. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: A report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death) Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society Europace, September 1, 2006; 8(9): 746 - 837. [Full Text] [PDF]
|
|
|
|
 |
|
 E Aksay, T Okan, and S Yanturali Brugada syndrome, manifested by propafenone induced ST segment elevation Emerg. Med. J., October 1, 2005; 22(10): 748 - 750. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Krittayaphong, G. Veerakul, K. Nademanee, and C. Kangkagate Heart rate variability in patients with Brugada syndrome in Thailand Eur. Heart J., October 1, 2003; 24(19): 1771 - 1778. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
Task Force on Syncope, European Society of Cardiol, M Brignole, P Alboni, D Benditt, L Bergfeldt, J.J Blanc, P.E Bloch Thomsen, J.G van Dijk, A Fitzpatrick, S Hohnloser, et al. Guidelines on management (diagnosis and treatment) of syncope Eur. Heart J., August 1, 2001; 22(15): 1256 - 1306. [Abstract] [PDF]
|
|
|
|
|
|
P. Brugada, J. Brugada, and R. Brugada The yet unresolved dilemma of syncope in Brugada syndrome Europace, January 1, 2001; 3(2): 157 - 158. [PDF]
|
|
|
|
|
|
N. Samniah, D. Iskos, S. Sakaguchi, K. G. Lurie, and D. G. Benditt Syncope in pharmacologically unmasked Brugada syndrome: indication for an implantable defibrillator or an unresolved dilemma? Europace, January 1, 2001; 3(2): 159 - 163. [Abstract] [PDF]
|
|
|
|
|
|
S. G. Priori, C. Napolitano, M. Gasparini, C. Pappone, P. Della Bella, M. Brignole, U. Giordano, T. Giovannini, C. Menozzi, R. Bloise, et al. Clinical and Genetic Heterogeneity of Right Bundle Branch Block and ST-Segment Elevation Syndrome : A Prospective Evaluation of 52 Families Circulation, November 14, 2000; 102(20): 2509 - 2515. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. JORDAENS Development of Europace Europace, January 1, 1999; 1(3): 149 - 150. [PDF]
|
|
|
|
|
|
P. Brugada Unravelling the mechanisms of symptoms in patients at risk of genetically determined cardiac arrhythmias Europace, January 1, 1999; 1(4): 218 - 219. [PDF]
|
|