Risk stratification in patients with Brugada syndrome

Authors: M. Bébarová 1;  P. Lokaj 1,2
Authors‘ workplace: Fyziologický ústav Lékařské fakulty MU Brno, přednostka prof. MUDr. Nataša Honzíková, CSc. 1;  Interní kardiologická klinika Lékařské fakulty MU a FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Jindřich Špinar, CSc., FESC 2
Published in: Vnitř Lék 2012; 58(4): 280-285
Category: Reviews


Brugada syndrome (BrS), one of the most frequently diagnosed inherited arrhythmogenic syndromes, is responsible for more than 4% of all sudden deaths and at least 20% of sudden deaths in patients with structurally normal hearts. The sudden death is often the first symptom of BrS and appears most often already during the fourth decade of life of BrS patients. Implantation of cardioverter--defibrillator was proved to be the only effective treatment, i.e. prevention of the sudden death, in BrS. Thus, it is uniquely determined to be used in case of symptomatic BrS patients. On the contrary, the individual risk of life-threathening arrhythmias has to be thoroughly considered in case of asymptomatic BrS patients due to substantial side effects of implantation of cardioverter-defibrillator. This review first provides a summary of factors recommended for the risk stratification in BrS patients in 2005 including their support or rejection in the following studies. Subsequently, we focused on the most important risk factors newly suggested after 2005.

Key words:
Brugada syndrome – sudden death – risk stratification – risk factors – prognosis


1. Brugada P, Brugada J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. A multicenter report.J Am Coll Cardiol 1992; 20: 1391–1396.

2. Antzelevitch C, Brugada P, Borggrefe M et al. Brugada syndrome: report of the second consensus conference: endorsed by the Heart Rhythm Society and the European Heart Rhythm Association. Circulation 2005; 111: 659–670.

3. Brugada J, Brugada R, Antzelevitch C et al. 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 2002; 105: 73–78.

4. Brugada J, Brugada R, Brugada P. Pharmacological and device approach to therapy of inherited cardiac diseases associated with cardiac arrhythmias and sudden death. J Electrocardiol 2000; 33 (Suppl): 41–47.

5. Nademanee K, Veerakul G, Mower M et al. Defibrillator Versus beta-Blockers for Unexplained Death in Thailand (DEBUT): a randomized clinical trial. Circulation 2003; 107: 2221–2226.

6. Bailey SM, Wilkoff BL. Complications of pacemakers and defibrillators in the elderly. Am J Geriatr Cardiol 2006; 15: 102–107.

7. Sacher F, Probst V, Iesaka Y et al. Outcome after implantation of a cardioverter-defibrillator in patients with Brugada syndrome: a multicenter study. Circulation 2006; 114: 2317–2324.

8. Sarkozy A, Boussy T, Kourgiannides G et al. Long-term follow-up of primary prophylactic implantable cardioverter-defibrillator therapy in Brugada syndrome. Eur Heart J 2007; 28: 334–344.

9. Rosso R, Glick A, Glikson M et al. Israeli Working Group on Cardiac Pacing and Electrophysiology. Outcome after implantation of cardioverter defibrillator in patients with Brugada syndrome: a multicenter Israeli study ­(ISRABRU). Isr Med Assoc J 2008; 10: 435–439.

10. Benito B, Brugada J, Brugada R et al. Brugada syndrome. Rev Esp Cardiol 2009; 62: 1297–1315.

11. Mádle A, Kratochvíl Z, Polívková A. The Brugada syndrome. Vnitř Lék 2002; 48: 255–258.

12. Veiser T, Laurent G, Wolf JE. Brugada syndrome. Čas Lék Česk 2005; 144: 219–223.

13. Bébarová M. Brugada syndrom. Vnitř Lék 2011; 57: 551–560.

14. Amin AS, Klemens CA, Verkerk AO et al. Fever-triggered ventricular arrhythmias in Brugada syndrome and type 2 long-QT syndrome. Neth Heart J 2010; 18: 165–169.

15. Postema PG, Wolpert C, Amin AS et al. Drugs and Brugada syndrome patients: review of the literature, recommendations, and an up-to-date website (www.brugadadrugs.org). Heart Rhythm 2009; 6: 1335–1341.

16. Letsas KP, Weber R, Efremidis M et al. Long-term prognosis of asymptomatic indivi­duals with spontaneous or drug-induced type 1 electrocardiographic phenotype of Brugada syndrome. J Electrocardiol 2011; 44: 346–349.

17. Probst V, Veltmann C, Eckardt L et al. Long--term prognosis of patients diagnosed with Brugada syndrome: Results from the FINGER Brugada Syndrome Registry. Circulation 2010; 121: 635–643.

18. Eckardt L, Probst V, Smits JP et al. Long-term prognosis of individuals with right precordial ST-segment-elevation Brugada syndrome. Circulation 2005; 111: 257–263.

19. Brugada J, Brugada R, Brugada P. Determinants of sudden cardiac death in individuals with the electrocardiographic pattern of Brugada syndrome and no previous cardiac arrest. Circulation 2003; 108: 3092–3096.

20. Benito B, Sarkozy A, Mont L et al. Gender differences in clinical manifestations of Brugada syndrome. J Am Coll Cardiol 2008; 52: 1567–1573.

21. Nakano Y, Shimizu W, Ogi H et al. A spontaneous Type 1 electrocardiogram pattern in lead V2 is an independent predictor of ventricular fibrillation in Brugada syndrome. Europace 2010; 12: 410–416.

22. Probst V, Denjoy I, Meregalli PG et al. Clinical aspects and prognosis of Brugada syndrome in children. Circulation 2007; 115: 2042–2048.

23. Delise P, Allocca G, Marras E et al. Risk stratification in individuals with the Brugada type 1 ECG pattern without previous cardiac arrest: usefulness of a combined clinical and electrophysiologic approach. Eur Heart J 2011; 32: 169–176.

24. Brugada P, Brugada R, Mont L et al. Natural history of Brugada syndrome: the prognostic value of programmed electrical stimulation of the heart. J Cardiovasc Electrophysiol 2003; 14: 455–457.

25. Priori SG, Napolitano C, Gasparini M et al. Natural history of Brugada syndrome: insights for risk stratification and management. Circulation 2002; 105: 1342–1347.

26. Kanda M, Shimizu W, Matsuo K et al. Electrophysiologic characteristics and implications of induced ventricular fibrillation in symptomatic patients with Brugada syndrome. J Am Coll Cardiol 2002; 39: 1799–1805.

27. Eckardt L, Kirchhof P, Schulze-Bahr E et al. Electrophysiologic investigation in Brugada syndrome; yield of programmed ventricular stimulation at two ventricular sites with up to three premature beats. Eur Heart J 2002; 23: 1394–1401.

28. Paul M, Gerss J, Schulze-Bahr E et al. Role of programmed ventricular stimulation in pa­tients with Brugada syndrome: a meta-analysis of worldwide published data. Eur Heart J 2007; 28: 2126–2133.

29. Gasparini M, Priori SG, Mantica M et al. Programmed electrical stimulation in Brugada syndrome: How reproducible are the results? J Cardiovasc Electrophysiol 2002; 13: 880–887.

30. Nagase S, Kusano KF, Morita H et al. Epicardial electrogram of the right ventricular outflow tract in patients with the Brugada syndrome: using the epicardial lead. J Am Coll Cardiol 2002; 39: 1992–1995.

31. Tukkie R, Sogaard P, Vleugels J et al. Delay in right ventricular activation contributes to Brugada syndrome. Circulation 2004; 109: 1272–1277.

32. Doi A, Takagi M, Maeda K et al. Conduction delay in right ventricle as a marker for identifying high-risk patients with Brugada syndrome. J Cardiovasc Electrophysiol 2010; 21: 688–696.

33. Furushima H, Chinushi M, Hirono T et al. Relationship between dominant prolongation of the filtered QRS duration in the right precordial leads and clinical characteristics in Brugada syndrome. J Cardiovasc Electrophysiol 2005; 16: 1311–1317.

34. Junttila MJ, Brugada P, Hong K et al. Differences in 12-lead electrocardiogram between symptomatic and asymptomatic Brugada syndrome patients. J Cardiovasc Electrophysiol 2008; 19: 380–383.

35. Morita H, Kusano KF, Miura D et al. Fragmented QRS as a marker of conduction abnormality and a predictor of prognosis of Brugada syndrome. Circulation 2008; 118: 1697–1704.

36. Huang Z, Patel C, Li W et al. Role of signal-averaged electrocardiograms in arrhythmic risk stratification of patients with Brugada syndrome: a prospective study. Heart Rhythm 2009; 6: 1156–1162.

37. Ikeda T, Sakurada H, Sakabe K et al. Assessment of noninvasive markers in identifying patients at risk in the Brugada syndrome: Insight into risk stratification. J Am Coll Cardiol 2001; 37: 1628–1634.

38. Tatsumi H, Takagi M, Nakagawa E et al. Risk stratification in patients with Brugada syndrome: analysis of daily fluctuations in 12-lead electrocardiogram (ECG) and signal-averaged electrocardiogram (SAECG). J Cardiovasc Electrophysiol 2006; 17: 705–711.

39. Take Y, Morita H, Wu J et al. Spontaneous ECG alterations predict ventricular fibrillation in Brugada syndrome. Heart Rhythm 2011; 8: 1014–1021.

40. Castro Hevia J, Antzelevitch C, Tornés Bárzaga F et al. Tpeak-Tend and Tpeak-Tend dispersion as risk factors for ventricular tachycardia//ventricular fibrillation in patients with the Brugada syndrome. J Am Coll Cardiol 2006; 47: 1828–1834.

41. Letsas KP, Weber R, Astheimer K et al. Tpeak-Tend interval and Tpeak-Tend/QT ratio as markers of ventricular tachycardia inducibility in subjects with Brugada ECG phenotype. Europace 2010; 12: 271–274.

42. Sangawa M, Morita H, Nakatsu T et al. Abnormal transmural repolarization process in patients with Brugada syndrome. Heart Rhythm 2009; 6: 1163–1169.

43. Pierre B, Babuty D, Poret P et al. Abnormal nocturnal heart rate variability and QT dynamics in patients with Brugada syndrome. Pacing Clin Electrophysiol 2007; 30 (Suppl 1): S188–S191.

44. Rosenbaum DC, Jackson LE, Smith JH et al. Electrical alternans and vulnerability to ventricular arrhythmias. N Engl J Med 1994; 330: 235–241.

45. Kirchof P, Eckardt L, Rolf S et al. T Wave Alternans Does Not Assess Arrhythmic Risk in Patients with Brugada Syndrome. Ann Noninvas Electrophysiol 2004; 9: 162–165.

46. Evain S, Briec F, Kyndt F et al. Sodium channel blocker tests allow a clear distinction of electrophysiological characteristics and prognosis in patients with a type 2 or 3 Brugada electrocardiogram pattern. Heart Rhythm 2008; 5: 1561–1564.

47. Richter S, Sarkozy A, Paparella G et al. Number of electrocardiogram leads displaying the diagnostic coved-type pattern in Brugada syndrome: a diagnostic consensus criterion to be revised. Eur Heart J 2010; 31: 1357–1364.

48. Letsas KP, Sacher F, Probst V et al. Prevalence of early repolarization pattern in inferolateral leads in patients with Brugada syndrome. Heart Rhythm 2008; 5: 1685–1689.

49. Sarkozy A, Chierchia GB, Paparella G et al. Inferior and lateral electrocardiographic repolarization abnormalities in Brugada syndrome. Circ Arrhythm Electrophysiol 2009; 2: 154–161.

50. Francis J, Antzelevitch C. Atrial fibrillation and Brugada syndrome. J Am Coll Cardiol 2008; 51: 1149–1153.

51. Kusano KF, Taniyama M, Nakamura K et al. Atrial fibrillation in patients with Brugada syndrome relationships of gene mutation, electrophysiology, and clinical backgrounds. J Am Coll Cardiol 2008; 51: 1169–1175.

52. Toh N, Morita H, Nagase S et al. Atrial electrophysiological and structural remodeling in high-risk patients with Brugada syndrome: asses­sment with electrophysiology and echocardio­graphy. Heart Rhythm 2010; 7: 218–224.

53. Makimoto H, Nakagawa E, Takaki H et al. Augmented ST-segment elevation during recovery from exercise predicts cardiac events in patients with Brugada syndrome. J Am Coll Cardiol 2010; 56: 1576–1584.

54. Bigi MA, Aslani A, Aslani A. Significance of cardiac autonomic neuropathy in risk stratification of Brugada syndrome. Europace 2008; 10: 821–824.

55. Babaee Bigi MA, Moaref AR, Aslani A. Interventricular mechanical dyssynchrony: a novel marker of cardiac events in Brugada syndrome. Heart Rhythm 2008; 5: 79–82.

56. Meregalli PG, Tan HL, Probst V et al. Type of SCN5A mutation determines clinical severity and degree of conduction slowing in loss-of-function sodium channelopathies. Heart Rhythm 2009; 6: 341–348.

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