Advertisement

Brugada Syndrome: Current Perspectives

  • Apichai Khongphatthanayothin
  • Koonlawee Nademanee
Chapter
Part of the Cardiac and Vascular Biology book series (Abbreviated title: Card. vasc. biol.)

Abstract

Brugada syndrome was first reported as a distinct entity in 1992. It is diagnosed by signature EKG changes including at least 2-mm J-point elevation with coved-type ST elevation and T-wave inversion in at least one right precordial leads (type I Brugada marker). Initially thought of as a rare entity, Brugada syndrome is now widely recognized as a common cause of natural death among young men as a result of ventricular arrhythmia occurring at rest, particularly during sleep. The etiology of this disease is likely multifactorial, with genetic predisposition playing an important role in the pathogenesis. Mutation in the sodium channel gene SCN5A is seen in up to 20–25% of patients with at least 17 additional genes were reported to be associated with the disease. However, mutation in a single gene could be implicated in less than 30% of patients with Brugada syndrome, and a recent study showing association of this disease with common single nucleotide polymorphism of SCN5A, SCN10A, and HEY2 pointed toward polygenic or oligogenic pattern of inheritance rather than a single gene defect. Despite initial reports of normal structural heart in majority of patients, recent reports showed frequent minor structural abnormalities, especially in the right ventricular outflow tract (RVOT) in these patients. Brugada syndrome is now viewed as a spectrum of cardiomyopathy as well as channelopathy. The pathophysiologic underlying cardiac arrhythmia in Brugada syndrome is still unresolved with continued debate on depolarization versus repolarization defect. Treatment is largely dependent on the symptom with implantable cardioverter-defibrillator (ICD) implantation indicated in patients with severe symptoms. Avoiding medications and/or conditions that predispose the patient to ventricular arrhythmia is advised in all patients. Quinidine, by blocking transient outward current, has been used with some success. RF ablation of the epicardial substrate in the RVOT has been shown to prevent recurrence of ventricular arrhythmia in severe cases.

Notes

Acknowledgement

The authors would like to thank the National Research Council of Thailand (NRCT) for support on the study of Brugada syndrome.

Compliance with Ethical Standards

Conflict of Interest

Author Apichai Khongphatthanayothin declares that he has no conflict of interest. Author Koonlawee Nademanee declares that the following conflict of interests: Research grants from Medtronic Inc & Royalty from Biosense Cordis Webster Inc.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Inform consent was obtained from all individual participants included in the study.

References

  1. Abe A, Kobayashi K, Yuzawa H, Sato H, Fukunaga S, Fujino T, Okano Y, Yamazaki J, Miwa Y, Yoshino H, Ikeda T. Comparison of late potentials for 24 hours between Brugada syndrome and arrhythmogenic right ventricular cardiomyopathy using a novel signal-averaging system based on Holter ECG. Circ Arrhythm Electrophysiol. 2012;5:789–95.PubMedCrossRefPubMedCentralGoogle Scholar
  2. Ackerman MJ, Priori SG, Willems S, Berul C, Brugada R, Calkins H, Camm AJ, Ellinor PT, Gollob M, Hamilton R, Hershberger RE, Judge DP, Le Marec H, McKenna WJ, Schulze-Bahr E, Semsarian C, Towbin JA, Watkins H, Wilde A, Wolpert C, Zipes DP, HRS, EHRA. HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies: this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA). Europace. 2011;13:1077–109.PubMedCrossRefPubMedCentralGoogle Scholar
  3. Adler A. Brugada syndrome: diagnosis, risk stratification, and management. Curr Opin Cardiol. 2016;31:37–45.PubMedCrossRefGoogle Scholar
  4. Aizawa Y, Takatsuki S, Kaneko Y, Noda T, Katsumata Y, Nishiyama T, Kimura T, Nishiyama N, Fukumoto K, Niwano S, Kurita T, Mitsuhashi T, Kamakura S, Shimizu A, Horie M, Fukuda K. Comparison of circadian, weekly, and seasonal variations of electrical storms and single events of ventricular fibrillation in patients with Brugada syndrome. Int J Cardiol Heart Vasc. 2016;11:104–10.PubMedPubMedCentralGoogle Scholar
  5. Akai J, Makita N, Sakurada H, Shirai N, Ueda K, Kitabatake A, Nakazawa K, Kimura A, Hiraoka M. A novel SCN5A mutation associated with idiopathic ventricular fibrillation without typical ECG findings of Brugada syndrome. FEBS Lett. 2000;479:29–34.PubMedCrossRefGoogle Scholar
  6. Amin AS, Verkerk AO, Bhuiyan ZA, Wilde AA, Tan HL. Novel Brugada syndrome-causing mutation in ion-conducting pore of cardiac Na+ channel does not affect ion selectivity properties. Acta Physiol Scand. 2005;185:291–301.PubMedCrossRefGoogle Scholar
  7. Amin AS, de Groot EA, Ruijter JM, Wilde AA, Tan HL. Exercise-induced ECG changes in Brugada syndrome. Circ Arrhythm Electrophysiol. 2009;2:531–9.PubMedCrossRefGoogle Scholar
  8. Andres R, Cader G, Goldman P, Zierler KL. Net potassium movement between resting muscle and plasma in man in the basal state and during the night. J Clin Invest. 1957;36:723–9.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Antzelevitch C, Brugada R. Fever and Brugada syndrome. Pacing Clin Electrophysiol. 2002;25:1537–9.PubMedCrossRefPubMedCentralGoogle Scholar
  10. Antzelevitch C, Brugada P, Borggrefe M, Brugada J, Brugada R, Corrado D, Gussak I, LeMarec H, Nademanee K, Perez Riera AR, Shimizu W, Schulze-Bahr E, Tan H, Wilde A. Brugada syndrome: report of the second consensus conference: endorsed by the Heart Rhythm Society and the European Heart Rhythm Association. Circulation. 2005;111:659–70.PubMedCrossRefPubMedCentralGoogle Scholar
  11. Antzelevitch C, Yan GX, Ackerman MJ, Borggrefe M, Corrado D, Guo J, Gussak I, Hasdemir C, Horie M, Huikuri H, Ma C, Morita H, Nam GB, Sacher F, Shimizu W, Viskin S, Wilde AA. J-Wave syndromes expert consensus conference report: emerging concepts and gaps in knowledge. Heart Rhythm. 2016;13:e295–324.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Bastiaenen R, Cox AT, Castelletti S, Wijeyeratne YD, Colbeck N, Pakroo N, Ahmed H, Bunce N, Anderson L, Moon JC, Prasad S, Sharma S, Behr ER. Late gadolinium enhancement in Brugada syndrome: a marker for subtle underlying cardiomyopathy? Heart Rhythm. 2017;14:583–9.PubMedCrossRefGoogle Scholar
  13. Belhassen B, Glick A, Viskin S. Efficacy of quinidine in high-risk patients with Brugada syndrome. Circulation. 2004;110:1731–7.PubMedCrossRefGoogle Scholar
  14. Belhassen B, Rahkovich M, Michowitz Y, Glick A, Viskin S. Management of Brugada syndrome: thirty-three-year experience using electrophysiologically guided therapy with class 1A antiarrhythmic drugs. Circ Arrhythm Electrophysiol. 2015;8:1393–402.PubMedCrossRefGoogle Scholar
  15. Benito B, Sarkozy A, Mont L, Henkens S, Berruezo A, Tamborero D, Arzamendi D, Berne P, Brugada R, Brugada P, Brugada J. Gender differences in clinical manifestations of Brugada syndrome. J Am Coll Cardiol. 2008;52:1567–73.PubMedCrossRefGoogle Scholar
  16. Benson DW, Wang DW, Dyment M, Knilans TK, Fish FA, Strieper MJ, Rhodes TH, George AL. Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A). J Clin Invest. 2003;112:1019–28.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Bezzina C, Veldkamp MW, van Den Berg MP, Postma AV, Rook MB, Viersma JW, van Langen IM, Tan-Sindhunata G, Bink-Boelkens MT, van Der Hout AH, Mannens MM, Wilde AA. A single Na(+) channel mutation causing both long-QT and Brugada syndromes. Circ Res. 1999;85:1206–13.PubMedCrossRefPubMedCentralGoogle Scholar
  18. Bezzina CR, Barc J, Mizusawa Y, Remme CA, Gourraud JB, Simonet F, Verkerk AO, Schwartz PJ, Crotti L, Dagradi F, Guicheney P, Fressart V, Leenhardt A, Antzelevitch C, Bartkowiak S, Borggrefe M, Schimpf R, Schulze-Bahr E, Zumhagen S, Behr ER, Bastiaenen R, Tfelt-Hansen J, Olesen MS, Kääb S, Beckmann BM, Weeke P, Watanabe H, Endo N, Minamino T, Horie M, Ohno S, Hasegawa K, Makita N, Nogami A, Shimizu W, Aiba T, Froguel P, Balkau B, Lantieri O, Torchio M, Wiese C, Weber D, Wolswinkel R, Coronel R, Boukens BJ, Bézieau S, Charpentier E, Chatel S, Despres A, Gros F, Kyndt F, Lecointe S, Lindenbaum P, Portero V, Violleau J, Gessler M, Tan HL, Roden DM, Christoffels VM, Le Marec H, Wilde AA, Probst V, Schott JJ, Dina C, Redon R. Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death. Nat Genet. 2013;45:1044–9.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Boersma LV, Jaarsma W, Jessurun ER, Van Hemel NH, Wever EF. Brugada syndrome: a case report of monomorphic ventricular tachycardia. Pacing Clin Electrophysiol. 2001;24:112–5.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 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;20:1391–6.PubMedCrossRefGoogle Scholar
  21. Brugada J, Brugada R, Antzelevitch C, Towbin J, Nademanee K, Brugada P. 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;105:73–8.PubMedCrossRefPubMedCentralGoogle Scholar
  22. Brugada J, Brugada R, Brugada P. Electrophysiologic testing predicts events in Brugada syndrome patients. Heart Rhythm. 2011;8:1595–7.PubMedCrossRefPubMedCentralGoogle Scholar
  23. Brugada J, Pappone C, Berruezo A, et al. Brugada syndrome phenotype elimination by epicardial substrate ablation. Circ Arrhythm Electrophysiol. 2015;8:1373–81.PubMedPubMedCentralGoogle Scholar
  24. Calò L, Giustetto C, Martino A, Sciarra L, Cerrato N, Marziali M, Rauzino J, Carlino G, de Ruvo E, Guerra F, Rebecchi M, Lanzillo C, Anselmino M, Castro A, Turreni F, Penco M, Volpe M, Capucci A, Gaita F. A new electrocardiographic marker of sudden death in Brugada syndrome: the S-wave in lead I. J Am Coll Cardiol. 2016;67:1427–40.PubMedCrossRefPubMedCentralGoogle Scholar
  25. Canpolat U, Bayazit Y, Aytemir K. Brugada syndrome unmasked by heat exhaustion. Ann Noninvasive Electrocardiol. 2017;22.  https://doi.org/10.1111/anec.12356.
  26. Chen Q, Kirsch GE, Zhang D, Brugada R, Brugada J, Brugada P, Potenza D, Moya A, Borggrefe M, Breithardt G, Ortiz-Lopez R, Wang Z, Antzelevitch C, O’Brien RE, Schulze-Bahr E, Keating MT, Towbin JA, Wang Q. Genetic basis and molecular mechanism for idiopathic ventricular fibrillation. Nature. 1998;392:293–6.PubMedCrossRefGoogle Scholar
  27. Chung FP, Raharjo SB, Lin YJ, Chang SL, Lo LW, Hu YF, Tuan TC, Chao TF, Liao JN, Lin CY, Chang YT, Hung Y, Te A, Yamada S, Tasaka H, Wang CT, Chen SA. A novel method to enhance phenotype, epicardial functional substrates, and ventricular tachyarrhythmias in Brugada syndrome. Heart Rhythm. 2017;14:508–17.PubMedCrossRefPubMedCentralGoogle Scholar
  28. Conte G, Kawabata M, de Asmundis C, Taravelli E, Petracca F, Ruggiero D, Caputo ML, Regoli F, Chierchia GB, Chiodini A, Del Bufalo A, Moccetti T, Goya M, Hirao K, Vicentini A, De Ferrari GM, Brugada P, Auricchio A. High rate of subcutaneous implantable cardioverter-defibrillator sensing screening failure in patients with Brugada syndrome: a comparison with other inherited primary arrhythmia syndromes. Europace. 2017.  https://doi.org/10.1093/europace/eux009.
  29. Coronel R, Casini S, Koopmann TT, Wilms-Schopman FJ, Verkerk AO, de Groot JR, Bhuiyan Z, Bezzina CR, Veldkamp MW, Linnenbank AC, van der Wal AC, Tan HL, Brugada P, Wilde AA, de Bakker JM. Right ventricular fibrosis and conduction delay in a patient with clinical signs of Brugada syndrome: a combined electrophysiological, genetic, histopathologic, and computational study. Circulation. 2005;112:2769–77.PubMedCrossRefPubMedCentralGoogle Scholar
  30. Crotti L, Marcou CA, Tester DJ, Castelletti S, Giudicessi JR, Torchio M, Medeiros-Domingo A, Simone S, Will ML, Dagradi F, Schwartz PJ, Ackerman MJ. Spectrum and prevalence of mutations involving BrS1- through BrS12-susceptibility genes in a cohort of unrelated patients referred for Brugada syndrome genetic testing: implications for genetic testing. J Am Coll Cardiol. 2012;60:1410–8.PubMedPubMedCentralCrossRefGoogle Scholar
  31. Darbar D, Kannankeril PJ, Donahue BS, Kucera G, Stubblefield T, Haines JL, George AL, Roden DM. Cardiac sodium channel (SCN5A) variants associated with atrial fibrillation. Circulation. 2008;117:1927–35.PubMedPubMedCentralCrossRefGoogle Scholar
  32. Darmon JP, Bettouche S, Deswardt P, Tiger F, Ricard P, Bernasconi F, Saoudi N. Radiofrequency ablation of ventricular fibrillation and multiple right and left atrial tachycardia in a patient with Brugada syndrome. J Interv Card Electrophysiol. 2004;11:205–9.PubMedCrossRefGoogle Scholar
  33. De Marco S, Giannini C, Chiavaroli V, De Leonibus C, Chiarelli F, Mohn A. Brugada syndrome unmasked by febrile illness in an asymptomatic child. J Pediatr. 2012;161:769–769.e761.PubMedCrossRefGoogle Scholar
  34. Dumaine R, Towbin JA, Brugada P, Vatta M, Nesterenko DV, Nesterenko VV, Brugada J, Brugada R, Antzelevitch C. Ionic mechanisms responsible for the electrocardiographic phenotype of the Brugada syndrome are temperature dependent. Circ Res. 1999;85:803–9.PubMedCrossRefGoogle Scholar
  35. Eckardt L, Kirchhof P, Loh P, Schulze-Bahr E, Johna R, Wichter T, Breithardt G, Haverkamp W, Borggrefe M. Brugada syndrome and supraventricular tachyarrhythmias: a novel association? J Cardiovasc Electrophysiol. 2001;12:680–5.PubMedCrossRefPubMedCentralGoogle Scholar
  36. Eckardt L, Probst V, Smits JP, Bahr ES, Wolpert C, Schimpf R, Wichter T, Boisseau P, Heinecke A, Breithardt G, Borggrefe M, LeMarec H, Böcker D, Wilde AA. Long-term prognosis of individuals with right precordial ST-segment-elevation Brugada syndrome. Circulation. 2005;111:257–63.PubMedCrossRefGoogle Scholar
  37. Ghouse J, Have CT, Skov MW, Andreasen L, Ahlberg G, Nielsen JB, Skaaby T, Olesen SP, Grarup N, Linneberg A, Pedersen O, Vestergaard H, Haunsø S, Svendsen JH, Hansen T, Kanters JK, Olesen MS. Numerous Brugada syndrome-associated genetic variants have no effect on J-point elevation, syncope susceptibility, malignant cardiac arrhythmia, and all-cause mortality. Genet Med. 2017;19:521–8.PubMedCrossRefPubMedCentralGoogle Scholar
  38. Giustetto C, Drago S, Demarchi PG, Dalmasso P, Bianchi F, Masi AS, Carvalho P, Occhetta E, Rossetti G, Riccardi R, Bertona R, Gaita F, Section IAoAaCA-P. Risk stratification of the patients with Brugada type electrocardiogram: a community-based prospective study. Europace. 2009;11:507–13.PubMedCrossRefGoogle Scholar
  39. Gollob MH, Blier L, Brugada R, Champagne J, Chauhan V, Connors S, Gardner M, Green MS, Gow R, Hamilton R, Harris L, Healey JS, Hodgkinson K, Honeywell C, Kantoch M, Kirsh J, Krahn A, Mullen M, Parkash R, Redfearn D, Rutberg J, Sanatani S, Woo A. Recommendations for the use of genetic testing in the clinical evaluation of inherited cardiac arrhythmias associated with sudden cardiac death: Canadian Cardiovascular Society/Canadian Heart Rhythm Society joint position paper. Can J Cardiol. 2011;27:232–45.PubMedCrossRefGoogle Scholar
  40. Haïssaguerre M, Extramiana F, Hocini M, Cauchemez B, Jaïs P, Cabrera JA, Farré J, Farre G, Leenhardt A, Sanders P, Scavée C, Hsu LF, Weerasooriya R, Shah DC, Frank R, Maury P, Delay M, Garrigue S, Clémenty J. Mapping and ablation of ventricular fibrillation associated with long-QT and Brugada syndromes. Circulation. 2003;108:925–8.PubMedCrossRefGoogle Scholar
  41. Hermida JS, Denjoy I, Clerc J, Extramiana F, Jarry G, Milliez P, Guicheney P, Di Fusco S, Rey JL, Cauchemez B, Leenhardt A. Hydroquinidine therapy in Brugada syndrome. J Am Coll Cardiol. 2004;43:1853–60.PubMedCrossRefGoogle Scholar
  42. Hoogendijk MG, Potse M, Linnenbank AC, Verkerk AO, den Ruijter HM, van Amersfoorth SC, Klaver EC, Beekman L, Bezzina CR, Postema PG, Tan HL, Reimer AG, van der Wal AC, Ten Harkel AD, Dalinghaus M, Vinet A, Wilde AA, de Bakker JM, Coronel R. Mechanism of right precordial ST-segment elevation in structural heart disease: excitation failure by current-to-load mismatch. Heart Rhythm. 2010;7:238–48.PubMedCrossRefGoogle Scholar
  43. Huang Z, Patel C, Li W, Xie Q, Wu R, Zhang L, Tang R, Wan X, Ma Y, Zhen W, Gao L, Yan GX. Role of signal-averaged electrocardiograms in arrhythmic risk stratification of patients with Brugada syndrome: a prospective study. Heart Rhythm. 2009;6:1156–62.PubMedCrossRefGoogle Scholar
  44. Kakishita M, Kurita T, Matsuo K, Taguchi A, Suyama K, Shimizu W, Aihara N, Kamakura S, Yamamoto F, Kobayashi J, Kosakai Y, Ohe T. Mode of onset of ventricular fibrillation in patients with Brugada syndrome detected by implantable cardioverter defibrillator therapy. J Am Coll Cardiol. 2000;36:1646–53.PubMedCrossRefGoogle Scholar
  45. Kamakura S, Ohe T, Nakazawa K, Aizawa Y, Shimizu A, Horie M, Ogawa S, Okumura K, Tsuchihashi K, Sugi K, Makita N, Hagiwara N, Inoue H, Atarashi H, Aihara N, Shimizu W, Kurita T, Suyama K, Noda T, Satomi K, Okamura H, Tomoike H, Japan BSIi. Long-term prognosis of probands with Brugada-pattern ST-elevation in leads V1-V3. Circ Arrhythm Electrophysiol. 2009;2:495–503.PubMedCrossRefGoogle Scholar
  46. Kamakura T, Wada M, Ishibashi K, Inoue YY, Miyamoto K, Okamura H, Nagase S, Noda T, Aiba T, Yasuda S, Kusano K. Impact of electrocardiogram screening during drug challenge test for the prediction of T-wave oversensing by a subcutaneous implantable cardioverter defibrillator in patients with Brugada syndrome. Heart Vessels. 2017;32:1277–83.PubMedCrossRefGoogle Scholar
  47. Kaneko Y, Horie M, Niwano S, Kusano KF, Takatsuki S, Kurita T, Mitsuhashi T, Nakajima T, Irie T, Hasegawa K, Noda T, Kamakura S, Aizawa Y, Yasuoka R, Torigoe K, Suzuki H, Ohe T, Shimizu A, Fukuda K, Kurabayashi M. Electrical storm in patients with Brugada syndrome is associated with early repolarization. Circ Arrhythm Electrophysiol. 2014;7:1122–8.PubMedCrossRefGoogle Scholar
  48. Kapplinger JD, Tester DJ, Alders M, Benito B, Berthet M, Brugada J, Brugada P, Fressart V, Guerchicoff A, Harris-Kerr C, Kamakura S, Kyndt F, Koopmann TT, Miyamoto Y, Pfeiffer R, Pollevick GD, Probst V, Zumhagen S, Vatta M, Towbin JA, Shimizu W, Schulze-Bahr E, Antzelevitch C, Salisbury BA, Guicheney P, Wilde AA, Brugada R, Schott JJ, Ackerman MJ. An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing. Heart Rhythm. 2010;7:33–46.PubMedCrossRefPubMedCentralGoogle Scholar
  49. Kasanuki H, Ohnishi S, Ohtuka M, Matsuda N, Nirei T, Isogai R, Shoda M, Toyoshima Y, Hosoda S. Idiopathic ventricular fibrillation induced with vagal activity in patients without obvious heart disease. Circulation. 1997;95:2277–85.PubMedCrossRefGoogle Scholar
  50. Kaufman ES. Genetic testing in Brugada syndrome. J Am Coll Cardiol. 2012;60:1419–20.PubMedCrossRefGoogle Scholar
  51. Kawata H, Morita H, Yamada Y, Noda T, Satomi K, Aiba T, Isobe M, Nagase S, Nakamura K, Fukushima Kusano K, Ito H, Kamakura S, Shimizu W. Prognostic significance of early repolarization in inferolateral leads in Brugada patients with documented ventricular fibrillation: a novel risk factor for Brugada syndrome with ventricular fibrillation. Heart Rhythm. 2013;10:1161–8.PubMedCrossRefGoogle Scholar
  52. Kinoshita K, Takahashi H, Hata Y, Nishide K, Kato M, Fujita H, Yoshida S, Murai K, Mizumaki K, Nishida K, Yamaguchi Y, Kano M, Tabata T, Nishida N. SCN5A(K817E), a novel Brugada syndrome-associated mutation that alters the activation gating of NaV1.5 channel. Heart Rhythm. 2016;13:1113–20.PubMedCrossRefGoogle Scholar
  53. Krittayaphong R, Veerakul G, Nademanee K, Kangkagate C. Heart rate variability in patients with Brugada syndrome in Thailand. Eur Heart J. 2003;24:1771–8.PubMedCrossRefGoogle Scholar
  54. Kum LC, Fung JW, Sanderson JE. Brugada syndrome unmasked by febrile illness. Pacing Clin Electrophysiol. 2002;25:1660–1.PubMedCrossRefGoogle Scholar
  55. Kyndt F, Probst V, Potet F, Demolombe S, Chevallier JC, Baro I, Moisan JP, Boisseau P, Schott JJ, Escande D, Le Marec H. Novel SCN5A mutation leading either to isolated cardiac conduction defect or Brugada syndrome in a large French family. Circulation. 2001;104:3081–6.PubMedCrossRefGoogle Scholar
  56. Le Scouarnec S, Karakachoff M, Gourraud JB, Lindenbaum P, Bonnaud S, Portero V, Duboscq-Bidot L, Daumy X, Simonet F, Teusan R, Baron E, Violleau J, Persyn E, Bellanger L, Barc J, Chatel S, Martins R, Mabo P, Sacher F, Haïssaguerre M, Kyndt F, Schmitt S, Bézieau S, Le Marec H, Dina C, Schott JJ, Probst V, Redon R. Testing the burden of rare variation in arrhythmia-susceptibility genes provides new insights into molecular diagnosis for Brugada syndrome. Hum Mol Genet. 2015;24:2757–63.PubMedCrossRefPubMedCentralGoogle Scholar
  57. Letsas KP, Sacher F, Probst V, Weber R, Knecht S, Kalusche D, Haïssaguerre M, Arentz T. Prevalence of early repolarization pattern in inferolateral leads in patients with Brugada syndrome. Heart Rhythm. 2008;5:1685–9.PubMedCrossRefGoogle Scholar
  58. Makimoto H, Nakagawa E, Takaki H, Yamada Y, Okamura H, Noda T, Satomi K, Suyama K, Aihara N, Kurita T, Kamakura S, Shimizu W. Augmented ST-segment elevation during recovery from exercise predicts cardiac events in patients with Brugada syndrome. J Am Coll Cardiol. 2010;56:1576–84.PubMedCrossRefGoogle Scholar
  59. Matsuo K, Kurita T, Inagaki M, Kakishita M, Aihara N, Shimizu W, Taguchi A, Suyama K, Kamakura S, Shimomura K. The circadian pattern of the development of ventricular fibrillation in patients with Brugada syndrome. Eur Heart J. 1999;20:465–70.PubMedCrossRefGoogle Scholar
  60. Maury P, Rollin A, Sacher F, Gourraud JB, Raczka F, Pasquié JL, Duparc A, Mondoly P, Cardin C, Delay M, Derval N, Chatel S, Bongard V, Sadron M, Denis A, Davy JM, Hocini M, Jaïs P, Jesel L, Haïssaguerre M, Probst V. Prevalence and prognostic role of various conduction disturbances in patients with the Brugada syndrome. Am J Cardiol. 2013;112:1384–9.PubMedCrossRefGoogle Scholar
  61. Maury P, Sacher F, Gourraud JB, Pasquié JL, Raczka F, Bongard V, Duparc A, Mondoly P, Sadron M, Chatel S, Derval N, Denis A, Cardin C, Davy JM, Hocini M, Jaïs P, Jesel L, Carrié D, Galinier M, Haïssaguerre M, Probst V, Rollin A. Increased Tpeak-Tend interval is highly and independently related to arrhythmic events in Brugada syndrome. Heart Rhythm. 2015;12:2469–76.PubMedCrossRefGoogle Scholar
  62. Meregalli PG, Tan HL, Probst V, Koopmann TT, Tanck MW, Bhuiyan ZA, Sacher F, Kyndt F, Schott JJ, Albuisson J, Mabo P, Bezzina CR, Le Marec H, Wilde AA. Type of SCN5A mutation determines clinical severity and degree of conduction slowing in loss-of-function sodium channelopathies. Heart Rhythm. 2009;6:341–8.PubMedCrossRefGoogle Scholar
  63. Miyazaki T, Mitamura H, Miyoshi S, Soejima K, Aizawa Y, Ogawa S. Autonomic and antiarrhythmic drug modulation of ST segment elevation in patients with Brugada syndrome. J Am Coll Cardiol. 1996;27:1061–70.PubMedCrossRefGoogle Scholar
  64. Mizumaki K, Fujiki A, Nishida K, Iwamoto J, Sakamoto T, Sakabe M, Tsuneda T, Sugao M, Inoue H. Postprandial augmentation of bradycardia-dependent ST elevation in patients with Brugada syndrome. J Cardiovasc Electrophysiol. 2007;18:839–44.PubMedCrossRefGoogle Scholar
  65. Mizusawa Y, Sakurada H, Nishizaki M, Hiraoka M. Effects of low-dose quinidine on ventricular tachyarrhythmias in patients with Brugada syndrome: low-dose quinidine therapy as an adjunctive treatment. J Cardiovasc Pharmacol. 2006;47:359–64.PubMedGoogle Scholar
  66. Morita H, Kusano-Fukushima K, Nagase S, Fujimoto Y, Hisamatsu K, Fujio H, Haraoka K, Kobayashi M, Morita ST, Nakamura K, Emori T, Matsubara H, Hina K, Kita T, Fukatani M, Ohe T. Atrial fibrillation and atrial vulnerability in patients with Brugada syndrome. J Am Coll Cardiol. 2002a;40:1437–44.PubMedCrossRefGoogle Scholar
  67. Morita H, Nagase S, Kusano K, Ohe T. Spontaneous T wave alternans and premature ventricular contractions during febrile illness in a patient with Brugada syndrome. J Cardiovasc Electrophysiol. 2002b;13:816–8.PubMedCrossRefGoogle Scholar
  68. Morita H, Kusano KF, Miura D, Nagase S, Nakamura K, Morita ST, Ohe T, Zipes DP, Wu J. Fragmented QRS as a marker of conduction abnormality and a predictor of prognosis of Brugada syndrome. Circulation. 2008;118:1697–704.PubMedCrossRefPubMedCentralGoogle Scholar
  69. Murakami M, Nakamura K, Kusano KF, Morita H, Nakagawa K, Tanaka M, Tada T, Toh N, Nishii N, Nagase S, Hata Y, Kohno K, Miura D, Ohe T, Ito H. Efficacy of low-dose bepridil for prevention of ventricular fibrillation in patients with Brugada syndrome with and without SCN5A mutation. J Cardiovasc Pharmacol. 2010;56:389–95.PubMedCrossRefPubMedCentralGoogle Scholar
  70. Nademanee K, Veerakul G, Nimmannit S, Chaowakul V, Bhuripanyo K, Likittanasombat K, Tunsanga K, Kuasirikul S, Malasit P, Tansupasawadikul S, Tatsanavivat P. Arrhythmogenic marker for the sudden unexplained death syndrome in Thai men. Circulation. 1997;96:2595–600.PubMedCrossRefPubMedCentralGoogle Scholar
  71. Nademanee K, Veerakul G, Mower M, Likittanasombat K, Krittayapong R, Bhuripanyo K, Sitthisook S, Chaothawee L, Lai MY, Azen SP. Defibrillator versus beta-blockers for unexplained death in Thailand (DEBUT): a randomized clinical trial. Circulation. 2003;107:2221–6.PubMedCrossRefGoogle Scholar
  72. Nademanee K, Veerakul G, Chandanamattha P, Chaothawee L, Ariyachaipanich A, Jirasirirojanakorn K, Likittanasombat K, Bhuripanyo K, Ngarmukos T. Prevention of ventricular fibrillation episodes in Brugada syndrome by catheter ablation over the anterior right ventricular outflow tract epicardium. Circulation. 2011;123:1270–9.PubMedCrossRefGoogle Scholar
  73. Nademanee K, Raju H, de Noronha SV, Papadakis M, Robinson L, Rothery S, Makita N, Kowase S, Boonmee N, Vitayakritsirikul V, Ratanarapee S, Sharma S, van der Wal AC, Christiansen M, Tan HL, Wilde AA, Nogami A, Sheppard MN, Veerakul G, Behr ER. Fibrosis, Connexin-43, and conduction abnormalities in the Brugada syndrome. J Am Coll Cardiol. 2015;66:1976–86.PubMedPubMedCentralCrossRefGoogle Scholar
  74. Nagase S, Kusano KF, Morita H, Fujimoto Y, Kakishita M, Nakamura K, Emori T, Matsubara H, Ohe T. Epicardial electrogram of the right ventricular outflow tract in patients with the Brugada syndrome: using the epicardial lead. J Am Coll Cardiol. 2002;39:1992–5.PubMedCrossRefGoogle Scholar
  75. Nakagawa E, Takagi M, Tatsumi H, Yoshiyama M. Successful radiofrequency catheter ablation for electrical storm of ventricular fibrillation in a patient with Brugada syndrome. Circ J. 2008;72:1025–9.PubMedCrossRefGoogle Scholar
  76. Nakajima T, Kaneko Y, Saito A, Ota M, Iijima T, Kurabayashi M. Enhanced fast-inactivated state stability of cardiac sodium channels by a novel voltage sensor SCN5A mutation, R1632C, as a cause of atypical Brugada syndrome. Heart Rhythm. 2015;12:2296–304.PubMedCrossRefGoogle Scholar
  77. Nimmannit S, Malasit P, Chaovakul V, Susaengrat W, Vasuvattakul S, Nilwarangkur S. Pathogenesis of sudden unexplained nocturnal death (lai tai) and endemic distal renal tubular acidosis. Lancet. 1991;338:930–2.PubMedCrossRefGoogle Scholar
  78. Nogami A, Nakao M, Kubota S, Sugiyasu A, Doi H, Yokoyama K, Yumoto K, Tamaki T, Kato K, Hosokawa N, Sagai H, Nakamura H, Nitta J, Yamauchi Y, Aonuma K. Enhancement of J-ST-segment elevation by the glucose and insulin test in Brugada syndrome. Pacing Clin Electrophysiol. 2003;26:332–7.PubMedCrossRefPubMedCentralGoogle Scholar
  79. Ohgo T, Okamura H, Noda T, Satomi K, Suyama K, Kurita T, Aihara N, Kamakura S, Ohe T, Shimizu W. Acute and chronic management in patients with Brugada syndrome associated with electrical storm of ventricular fibrillation. Heart Rhythm. 2007;4:695–700.PubMedCrossRefGoogle Scholar
  80. Ohkubo K, Nakai T, Watanabe I. Alcohol-induced ventricular fibrillation in a case of Brugada syndrome. Europace. 2013;15:1058.PubMedCrossRefPubMedCentralGoogle Scholar
  81. Olde Nordkamp LR, Conte G, Rosenmöller BR, Warnaars JL, Tan HL, Caputo ML, Regoli F, Moccetti T, Auricchio A, Knops RE, Wilde AA. Brugada syndrome and the subcutaneous implantable cardioverter-defibrillator. J Am Coll Cardiol. 2016;68:665–6.PubMedCrossRefPubMedCentralGoogle Scholar
  82. Olson TM, Michels VV, Ballew JD, Reyna SP, Karst ML, Herron KJ, Horton SC, Rodeheffer RJ, Anderson JL. Sodium channel mutations and susceptibility to heart failure and atrial fibrillation. JAMA. 2005;293:447–54.PubMedPubMedCentralCrossRefGoogle Scholar
  83. Paul M, Gerss J, Schulze-Bahr E, Wichter T, Vahlhaus C, Wilde AA, Breithardt G, Eckardt L. Role of programmed ventricular stimulation in patients with Brugada syndrome: a meta-analysis of worldwide published data. Eur Heart J. 2007;28:2126–33.PubMedCrossRefPubMedCentralGoogle Scholar
  84. Porres JM, Brugada J, Urbistondo V, García F, Reviejo K, Marco P. Fever unmasking the Brugada syndrome. Pacing Clin Electrophysiol. 2002;25:1646–8.PubMedCrossRefPubMedCentralGoogle Scholar
  85. Postema PG. About Brugada syndrome and its prevalence. Europace. 2012;14:925–8.PubMedCrossRefPubMedCentralGoogle Scholar
  86. Postema PG, Wolpert C, Amin AS, Probst V, Borggrefe M, Roden DM, Priori SG, Tan HL, Hiraoka M, Brugada J, Wilde AA. Drugs and Brugada syndrome patients: review of the literature, recommendations, and an up-to-date website (www.brugadadrugs.org). Heart Rhythm. 2009;6:1335–41.
  87. Priori SG, Gasparini M, Napolitano C, Della Bella P, Ottonelli AG, Sassone B, Giordano U, Pappone C, Mascioli G, Rossetti G, De Nardis R, Colombo M. Risk stratification in Brugada syndrome: results of the PRELUDE (PRogrammed ELectrical stimUlation preDictive valuE) registry. J Am Coll Cardiol. 2012;59:37–45.PubMedCrossRefPubMedCentralGoogle Scholar
  88. Priori SG, Wilde AA, Horie M, Cho Y, Behr ER, Berul C, Blom N, Brugada J, Chiang CE, Huikuri H, Kannankeril P, Krahn A, Leenhardt A, Moss A, Schwartz PJ, Shimizu W, Tomaselli G, Tracy C. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm. 2013;10:1932–63.PubMedCrossRefPubMedCentralGoogle Scholar
  89. Probst V, Denjoy I, Meregalli PG, Amirault JC, Sacher F, Mansourati J, Babuty D, Villain E, Victor J, Schott JJ, Lupoglazoff JM, Mabo P, Veltmann C, Jesel L, Chevalier P, Clur SA, Haissaguerre M, Wolpert C, Le Marec H, Wilde AA. Clinical aspects and prognosis of Brugada syndrome in children. Circulation. 2007;115:2042–8.PubMedCrossRefPubMedCentralGoogle Scholar
  90. Probst V, Wilde AA, Barc J, Sacher F, Babuty D, Mabo P, Mansourati J, Le Scouarnec S, Kyndt F, Le Caignec C, Guicheney P, Gouas L, Albuisson J, Meregalli PG, Le Marec H, Tan HL, Schott JJ. SCN5A mutations and the role of genetic background in the pathophysiology of Brugada syndrome. Circ Cardiovasc Genet. 2009;2:552–7.PubMedCrossRefGoogle Scholar
  91. Probst V, Veltmann C, Eckardt L, Meregalli PG, Gaita F, Tan HL, Babuty D, Sacher F, Giustetto C, Schulze-Bahr E, Borggrefe M, Haissaguerre M, Mabo P, Le Marec H, Wolpert C, Wilde AA. Long-term prognosis of patients diagnosed with Brugada syndrome: results from the FINGER Brugada Syndrome Registry. Circulation. 2010;121:635–43.PubMedCrossRefGoogle Scholar
  92. Rattanawong P, Vutthikraivit W, Charoensri A, Jongraksak T, Prombandankul A, Kanjanahattakij N, et al. Fever-induced Brugada syndrome is more common than previously suspected: a cross-sectional study from an endemic area. Ann Noninvasive Electrocardiol. 2016;21(2):136–41.PubMedCrossRefPubMedCentralGoogle Scholar
  93. Rodríguez-Mañero M, Namdar M, Sarkozy A, Casado-Arroyo R, Ricciardi D, de Asmundis C, Chierchia GB, Wauters K, Rao JY, Bayrak F, Van Malderen S, Brugada P. Prevalence, clinical characteristics and management of atrial fibrillation in patients with Brugada syndrome. Am J Cardiol. 2013;111:362–7.PubMedCrossRefPubMedCentralGoogle Scholar
  94. Rodríguez-Mañero M, Sacher F, de Asmundis C, Maury P, Lambiase PD, Sarkozy A, Probst V, Gandjbakhch E, Castro-Hevia J, Saenen J, Fukushima Kusano K, Rollin A, Arbelo E, Valderrábano M, Arias MA, Mosquera-Pérez I, Schilling R, Chierchia GB, García-Bolao I, García-Seara J, Hernandez-Ojeda J, Kamakura T, Martínez-Sande L, González-Juanatey JR, Haïssaguerre M, Brugada J, Brugada P. Monomorphic ventricular tachycardia in patients with Brugada syndrome: a multicenter retrospective study. Heart Rhythm. 2016;13:669–82.PubMedCrossRefPubMedCentralGoogle Scholar
  95. Sacher F, Probst V, Iesaka Y, Jacon P, Laborderie J, Mizon-Gérard F, Mabo P, Reuter S, Lamaison D, Takahashi Y, O’Neill MD, Garrigue S, Pierre B, Jaïs P, Pasquié JL, Hocini M, Salvador-Mazenq M, Nogami A, Amiel A, Defaye P, Bordachar P, Boveda S, Maury P, Klug D, Babuty D, Haïssaguerre M, Mansourati J, Clémenty J, Le Marec H. Outcome after implantation of a cardioverter-defibrillator in patients with Brugada syndrome: a multicenter study. Circulation. 2006;114:2317–24.PubMedCrossRefPubMedCentralGoogle Scholar
  96. Sakabe M, Fujiki A, Tsuneda T, Nishida K, Sugao M, Mizumaki K, Inoue H. Brugada syndrome occurring in an identical twin: a case report. J Cardiol. 2002a;40:111–5.PubMedPubMedCentralGoogle Scholar
  97. Sakabe M, Fujiki A, Tsuneda T, Nishida K, Sugao M, Mizumaki K, Inoue H. Brugada syndrome occurring in an identical twin: a case report. J Cardiol. 2002b;40:111–5.PubMedPubMedCentralGoogle Scholar
  98. Sarkozy A, Boussy T, Kourgiannides G, Chierchia GB, Richter S, De Potter T, Geelen P, Wellens F, Spreeuwenberg MD, Brugada P. Long-term follow-up of primary prophylactic implantable cardioverter-defibrillator therapy in Brugada syndrome. Eur Heart J. 2007;28:334–44.PubMedCrossRefPubMedCentralGoogle Scholar
  99. Saura D, García-Alberola A, Carrillo P, Pascual D, Martínez-Sánchez J, Valdés M. Brugada-like electrocardiographic pattern induced by fever. Pacing Clin Electrophysiol. 2002;25:856–9.PubMedCrossRefPubMedCentralGoogle Scholar
  100. Shimada M, Miyazaki T, Miyoshi S, Soejima K, Hori S, Mitamura H, Ogawa S. Sustained monomorphic ventricular tachycardia in a patient with Brugada syndrome. Jpn Circ J. 1996;60:364–70.PubMedCrossRefPubMedCentralGoogle Scholar
  101. Shimizu W, Matsuo K, Takagi M, Tanabe Y, Aiba T, Taguchi A, Suyama K, Kurita T, Aihara N, Kamakura S. Body surface distribution and response to drugs of ST segment elevation in Brugada syndrome: clinical implication of eighty-seven-lead body surface potential mapping and its application to twelve-lead electrocardiograms. J Cardiovasc Electrophysiol. 2000;11:396–404.PubMedCrossRefPubMedCentralGoogle Scholar
  102. Shirai N, Makita N, Sasaki K, Yokoi H, Sakuma I, Sakurada H, Akai J, Kimura A, Hiraoka M, Kitabatake A. A mutant cardiac sodium channel with multiple biophysical defects associated with overlapping clinical features of Brugada syndrome and cardiac conduction disease. Cardiovasc Res. 2002;53:348–54.PubMedCrossRefPubMedCentralGoogle Scholar
  103. Skinner JR, Chung SK, Nel CA, Shelling AN, Crawford JR, McKenzie N, Pinnock R, French JK, Rees MI. Brugada syndrome masquerading as febrile seizures. Pediatrics. 2007;119:e1206–11.PubMedCrossRefPubMedCentralGoogle Scholar
  104. Steven D, Roberts-Thomson KC, Inada K, Seiler J, Koplan BA, Tedrow UB, Sweeney MO, Epstein LE, Stevenson WG. Long-term follow-up in patients with presumptive Brugada syndrome treated with implanted defibrillators. J Cardiovasc Electrophysiol. 2011;22:1115–9.PubMedCrossRefPubMedCentralGoogle Scholar
  105. Szél T, Antzelevitch C. Abnormal repolarization as the basis for late potentials and fractionated electrograms recorded from epicardium in experimental models of Brugada syndrome. J Am Coll Cardiol. 2014;63:2037–45.PubMedPubMedCentralCrossRefGoogle Scholar
  106. Takagi M, Yokoyama Y, Aonuma K, Aihara N, Hiraoka M, Investigators JIVFSJ-I. Clinical characteristics and risk stratification in symptomatic and asymptomatic patients with Brugada syndrome: multicenter study in Japan. J Cardiovasc Electrophysiol. 2007;18:1244–51.PubMedCrossRefPubMedCentralGoogle Scholar
  107. Tan HL, Bink-Boelkens MT, Bezzina CR, Viswanathan PC, Beaufort-Krol GC, van Tintelen PJ, van den Berg MP, Wilde AA, Balser JR. A sodium-channel mutation causes isolated cardiac conduction disease. Nature. 2001;409:1043–7.PubMedCrossRefPubMedCentralGoogle Scholar
  108. Tanaka H, Kinoshita O, Uchikawa S, Kasai H, Nakamura M, Izawa A, Yokoseki O, Kitabayashi H, Takahashi W, Yazaki Y, Watanabe N, Imamura H, Kubo K. Successful prevention of recurrent ventricular fibrillation by intravenous isoproterenol in a patient with Brugada syndrome. Pacing Clin Electrophysiol. 2001;24:1293–4.PubMedCrossRefGoogle Scholar
  109. Tokioka K, Kusano KF, Morita H, Miura D, Nishii N, Nagase S, Nakamura K, Kohno K, Ito H, Ohe T. Electrocardiographic parameters and fatal arrhythmic events in patients with Brugada syndrome: combination of depolarization and repolarization abnormalities. J Am Coll Cardiol. 2014;63:2131–8.PubMedCrossRefGoogle Scholar
  110. Tsuchiya T, Ashikaga K, Honda T, Arita M. Prevention of ventricular fibrillation by cilostazol, an oral phosphodiesterase inhibitor, in a patient with Brugada syndrome. J Cardiovasc Electrophysiol. 2002;13:698–701.PubMedCrossRefPubMedCentralGoogle Scholar
  111. Valdivia CR, Tester DJ, Rok BA, Porter CB, Munger TM, Jahangir A, Makielski JC, Ackerman MJ. A trafficking defective, Brugada syndrome-causing SCN5A mutation rescued by drugs. Cardiovasc Res. 2004;62:53–62.PubMedCrossRefPubMedCentralGoogle Scholar
  112. Vatta M, Dumaine R, Varghese G, Richard TA, Shimizu W, Aihara N, Nademanee K, Brugada R, Brugada J, Veerakul G, Li H, Bowles NE, Brugada P, Antzelevitch C, Towbin JA. Genetic and biophysical basis of sudden unexplained nocturnal death syndrome (SUNDS), a disease allelic to Brugada syndrome. Hum Mol Genet. 2002;11:337–45.PubMedCrossRefGoogle Scholar
  113. Veerakul G, Nademanee K. Brugada syndrome: two decades of progress. Circ J. 2012;76:2713–22.PubMedCrossRefPubMedCentralGoogle Scholar
  114. Veerakul G, Chaothawee L, Nademanee K. Usefulness of positioning ECG leads at V1-3 at higher intercostal spaces to detect Brugada syndrome. Circulation. 2000;102(Suppl):18.Google Scholar
  115. Veerakul G, Camblock J, Schwab M, Nademanee K. Low mortality rate among asymptomatic Brugada syndrome patients: a multi-center control-randomized study comparing ICD versus no-ICD treatment. Circulation. 2008;118:S982.Google Scholar
  116. Viskin S, Rogowski O. Asymptomatic Brugada syndrome: a cardiac ticking time-bomb? Europace. 2007;9:707–10.PubMedCrossRefPubMedCentralGoogle Scholar
  117. Viskin S, Antzelevitch C, Márquez MF, Belhassen B. Quinidine: a valuable medication joins the list of ‘endangered species’. Europace. 2007;9:1105–6.PubMedCrossRefPubMedCentralGoogle Scholar
  118. Wang Q, Shen J, Splawski I, Atkinson D, Li Z, Robinson JL, Moss AJ, Towbin JA, Keating MT. SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell. 1995;80:805–11.PubMedCrossRefPubMedCentralGoogle Scholar
  119. Wilde AA, Antzelevitch C, Borggrefe M, Brugada J, Brugada R, Brugada P, Corrado D, Hauer RN, Kass RS, Nademanee K, Priori SG, Towbin JA, Cardiology SGotMBoAotESo. Proposed diagnostic criteria for the Brugada syndrome: consensus report. Circulation. 2002;106:2514–9.PubMedCrossRefPubMedCentralGoogle Scholar
  120. Wilde AA, Postema PG, Di Diego JM, Viskin S, Morita H, Fish JM, Antzelevitch C. The pathophysiological mechanism underlying Brugada syndrome: depolarization versus repolarization. J Mol Cell Cardiol. 2010;49:543–53.PubMedPubMedCentralCrossRefGoogle Scholar
  121. Yan GX, Antzelevitch C. Cellular basis for the Brugada syndrome and other mechanisms of arrhythmogenesis associated with ST-segment elevation. Circulation. 1999;100:1660–6.PubMedCrossRefGoogle Scholar
  122. Zhang P, Tung R, Zhang Z, et al. Characterization of the epicardial substrate for catheter ablation of Brugada syndrome. Heart Rhythm. 2016;11:2151–8.CrossRefGoogle Scholar
  123. Zumhagen S, Zeidler EM, Stallmeyer B, Ernsting M, Eckardt L, Schulze-Bahr E. Tpeak-Tend interval and Tpeak-Tend/QT ratio in patients with Brugada syndrome. Europace. 2016;18:1866–72.PubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Apichai Khongphatthanayothin
    • 1
  • Koonlawee Nademanee
    • 1
    • 2
  1. 1.Chulalongkorn UniversityBangkokThailand
  2. 2.Pacific Rim Electrophysiology Research InstituteLos AngelesUSA

Personalised recommendations