Autonomic and antiarrhythmic drug modulation of ST segment elevation in patients with Brugada syndrome

Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.

OBJECTIVES. We examined the modulatory effects of autonomic nervous system and antiarrhythmic drugs on the ST segment in patients with Brugada syndrome to gain an insight into the mechanism of ST segment elevation. BACKGROUND. Right bundle branch block, ST segment elevation and ventricular tachyarrhythmias define a distinct clinical and electrocardiographic (ECG) syndrome (Brugada syndrome). However, the mechanism of ST segment elevation and the causes of this syndrome are unknown. METHODS. The study included four patients in whom structural heart or coronary artery disease was excluded by noninvasive and invasive tests. High take-off ST segment elevation of either the coved or saddle-back type in precordial leads V1, V2 and V3 was seen in all patients. Three patients experienced recurrent episodes of syncope or aborted sudden cardiac death, and the remaining patient had palpitation. Autonomic receptor stimulation and blockade and intravenous administration of antiarrhythmic drugs were performed during sinus rhythm while the 12-lead ECG was recorded. Metaiodobenzylguanidine (MIBG) scanning and Holter monitoring were also performed. RESULTS. Beta-adrenoceptor stimulation by intravenous isoproterenol consistently reduced (> or = 0.1 mV) ST segment elevation at or 80 ms after the J point in all four patients. Selective alpha-adrenoceptor stimulation by intravenous norepinephrine in the presence of propranolol or by intravenous methoxamine consistently augmented, whereas alpha-adrenoceptor blockade reduced, ST segment elevation in three patients. Intracoronary acetylcholine or intravenous edrophonium or neostigmine augmented ST segment elevation without inducing coronary spasm in three of four patients. Class IA antiarrhythmic drugs also consistently augmented (three patients), whereas class IB drugs had no effect on (two patients) ST segment elevation. No abnormality was found on MIBG imaging or heart rate variability in three patients, suggesting that autonomic dysfunction is not a primary disease process. Class IA drugs had no effect on ST segment in three control patients, suggesting that the ST segment elevation seen in patients with Brugada syndrome in response to the drugs is not a nonspecific response. CONCLUSIONS. ST segment elevation in patients with Brugada syndrome was augmented by selective stimulation of alpha-adrenoceptors or muscarinic receptors or by class IA drugs but was mitigated by beta-adrenoceptor stimulation or alpha-adrenoceptor blockade. These responses might be explained by postulating the presence of an area of early repolarization or a local "depolarized" area in the ventricle causing ST segment elevation in this syndrome. Because only a small number of patients were studied, these possibilities need further evaluation.

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				C. J. Edge, D. J. Blackman, K. Gupta, and M. Sainsbury General anaesthesia in a patient with Brugada syndrome Br. J. Anaesth., November 1, 2002; 89(5): 788 - 791. [Abstract] [Full Text] [PDF]

				J. M. Di Diego, J. M. Cordeiro, R. J. Goodrow, J. M. Fish, A. C. Zygmunt, G. J. Perez, F. S. Scornik, and C. Antzelevitch Ionic and Cellular Basis for the Predominance of the Brugada Syndrome Phenotype in Males Circulation, October 8, 2002; 106(15): 2004 - 2011. [Abstract] [Full Text] [PDF]

				T. Kurita, W. Shimizu, M. Inagaki, K. Suyama, A. Taguchi, K. Satomi, N. Aihara, S. Kamakura, J. Kobayashi, and Y. Kosakai The electrophysiologic mechanism of ST-segment elevation in Brugada syndrome J. Am. Coll. Cardiol., July 17, 2002; 40(2): 330 - 334. [Abstract] [Full Text] [PDF]

				H. Paydak, E. A. Telfer, R. F. Kehoe, P. Balasubramanian, L. Narra, M. Ezri, T. Zheutlin, P. Maheshwari, J. Nazari, and T. Wang Brugada Syndrome: An Unusual Cause of Convulsive Syncope Arch Intern Med, June 24, 2002; 162(12): 1416 - 1419. [Abstract] [Full Text] [PDF]

				C. Antzelevitch Late potentials and the Brugada syndrome J. Am. Coll. Cardiol., June 19, 2002; 39(12): 1996 - 1999. [Full Text] [PDF]

				M. Kanda, W. Shimizu, K. Matsuo, N. Nagaya, A. Taguchi, K. Suyama, T. Kurita, N. Aihara, and S. Kamakura Electrophysiologic characteristics andimplications of induced ventricular fibrillationin symptomatic patients with brugada syndrome J. Am. Coll. Cardiol., June 5, 2002; 39(11): 1799 - 1805. [Abstract] [Full Text] [PDF]

				J. R. Balser Inherited sodium channelopathies: models for acquired arrhythmias? Am J Physiol Heart Circ Physiol, April 1, 2002; 282(4): H1175 - H1180. [Full Text] [PDF]

				H.-J. Bruns, L. Eckardt, C. Vahlhaus, E. Schulze-Bahr, W. Haverkamp, M. Borggrefe, G. Breithardt, and T. Wichter Body surface potential mapping in patients with Brugada syndrome: right precordial ST segment variations and reverse changes in left precordial leads Cardiovasc Res, April 1, 2002; 54(1): 58 - 66. [Abstract] [Full Text] [PDF]

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				K. Matsuo, M. Akahoshi, E. Nakashima, A. Suyama, S. Seto, M. Hayano, and K. Yano The prevalence, incidence and prognostic value of the Brugada-type electrocardiogram: A population-based study of four decades J. Am. Coll. Cardiol., September 1, 2001; 38(3): 765 - 770. [Abstract] [Full Text] [PDF]

				Y. Miyasaka, H. Tsuji, K. Yamada, S. Tokunaga, D. Saito, Y. Imuro, N. Matsumoto, and T. Iwasaka Prevalence and mortality of the Brugada-type electrocardiogram in one city in Japan J. Am. Coll. Cardiol., September 1, 2001; 38(3): 771 - 774. [Abstract] [Full Text] [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]

				M Takagi, N Aihara, S Kuribayashi, A Taguchi, W Shimizu, T Kurita, K Suyama, S Kamakura, S Hamada, and M Takamiya Localized right ventricular morphological abnormalities detected by electron-beam computed tomography represent arrhythmogenic substrates in patients with the Brugada syndrome Eur. Heart J., June 2, 2001; 22(12): 1032 - 1041. [Abstract] [PDF]

				H. Atarashi, S. Ogawa, K. Harumi, T. Sugimoto, H. Inoue, M. Murayama, J. Toyama, H. Hayakawa, and for the Idiopathic Ventricular Fibrillation Invest Three-year follow-up of patients with right bundle branch block and ST segment elevation in the right precordial leads: Japanese registry of Brugada syndrome J. Am. Coll. Cardiol., June 1, 2001; 37(7): 1916 - 1920. [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]

				M Bianco, S Bria, A Gianfelici, N Sanna, V Palmieri, and P Zeppilli Does early repolarization in the athlete have analogies with the Brugada syndrome? Eur. Heart J., March 2, 2001; 22(6): 504 - 510. [Abstract] [PDF]

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

				C.A Remme, E.F.D Wever, A.A.M Wilde, R Derksen, and R.N.W Hauer Diagnosis and long-term follow-up of the Brugada syndrome in patients with idiopathic ventricular fibrillation Eur. Heart J., March 1, 2001; 22(5): 400 - 409. [Abstract] [PDF]

				D. Corrado, C. Basso, G. Buja, A. Nava, L. Rossi, and G. Thiene Right Bundle Branch Block, Right Precordial ST-Segment Elevation, and Sudden Death in Young People Circulation, February 6, 2001; 103(5): 710 - 717. [Abstract] [Full Text] [PDF]

				C. R Bezzina, M. B Rook, and A. A.M Wilde Cardiac sodium channel and inherited arrhythmia syndromes Cardiovasc Res, February 1, 2001; 49(2): 257 - 271. [Full Text] [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]

				M Yasuda, Y Nakazato, H Yamashita, G Sekita, Y Kawano, Y Mineda, K Nakazato, T Tokano, M Sumiyoshi, and Y Nakata ST segment elevation in the right precordial leads following administration of class Ic antiarrhythmic drugs Heart, January 1, 2001; 85(1): 3e - 3. [Abstract] [Full Text]

				X. Wan, S. Chen, A. Sadeghpour, Q. Wang, and G. E. Kirsch Accelerated inactivation in a mutant Na+ channel associated with idiopathic ventricular fibrillation Am J Physiol Heart Circ Physiol, January 1, 2001; 280(1): H354 - H360. [Abstract] [Full Text] [PDF]

				S Viskin, R Fish, M Eldar, D Zeltser, M D Lesh, A Glick, and B Belhassen Prevalence of the Brugada sign in idiopathic ventricular fibrillation and healthy controls Heart, July 1, 2000; 84(1): 31 - 36. [Abstract] [Full Text] [PDF]

				M. W. Veldkamp, P. C. Viswanathan, C. Bezzina, A. Baartscheer, A. A. M. Wilde, and J. R. Balser Two Distinct Congenital Arrhythmias Evoked by a Multidysfunctional Na+ Channel Circ. Res., May 12, 2000; 86 (9): e91 - e97. [Abstract] [Full Text] [PDF]

				R. Brugada, J. Brugada, C. Antzelevitch, G. E. Kirsch, D. Potenza, J. A. Towbin, and P. Brugada Sodium Channel Blockers Identify Risk for Sudden Death in Patients With ST-Segment Elevation and Right Bundle Branch Block but Structurally Normal Hearts Circulation, February 8, 2000; 101(5): 510 - 515. [Abstract] [Full Text] [PDF]

				P Brugada, R Brugada, and J Brugada Sudden death in patients and relatives with the syndrome of right bundle branch block, ST segment elevation in the precordial leads V1to V3and sudden death Eur. Heart J., February 2, 2000; 21(4): 321 - 326. [Abstract] [PDF]

				N. Makita, N. Shirai, D. W. Wang, K. Sasaki, A. L. George Jr, M. Kanno, and A. Kitabatake Cardiac Na+ Channel Dysfunction in Brugada Syndrome Is Aggravated by {beta}1-Subunit Circulation, January 4, 2000; 101(1): 54 - 60. [Abstract] [Full Text] [PDF]

				C. Bezzina, M. W. Veldkamp, M. P. van den Berg, A. V. Postma, M. B. Rook, J.-W. Viersma, I. M. van Langen, G. Tan-Sindhunata, M. Th. E. Bink-Boelkens, A. H. van der Hout, et al. A Single Na+ Channel Mutation Causing Both Long-QT and Brugada Syndromes Circ. Res., December 3, 1999; 85(12): 1206 - 1213. [Abstract] [Full Text] [PDF]

				M. B. Rook, C. Bezzina Alshinawi, W.A. Groenewegen, I. C. van Gelder, A. C.G. van Ginneken, H. J. Jongsma, M. M.A.M. Mannens, and A. A.M. Wilde Human SCN5A gene mutations alter cardiac sodium channel kinetics and are associated with the Brugada syndrome Cardiovasc Res, December 1, 1999; 44(3): 507 - 517. [Abstract] [Full Text] [PDF]

				J. R. Balser Sodium "Channelopathies" and Sudden Death : Must You Be So Sensitive? Circ. Res., October 29, 1999; 85(9): 872 - 874. [Full Text] [PDF]

				G.-X. Yan and C. Antzelevitch Cellular Basis for the Brugada Syndrome and Other Mechanisms of Arrhythmogenesis Associated With ST-Segment Elevation Circulation, October 12, 1999; 100(15): 1660 - 1666. [Abstract] [Full Text] [PDF]

				K. Matsuo, T. Kurita, M. Inagaki, M. Kakishita, N. Aihara, W. Shimizu, A. Taguchi, K. Suyama, S. Kamakura, and K. Shimomura The circadian pattern of the development of ventricular fibrillation in patients with Brugada syndrome Eur. Heart J., March 2, 1999; 20(6): 465 - 470. [Abstract] [PDF]

				M. Alings and A. Wilde "Brugada" Syndrome : Clinical Data and Suggested Pathophysiological Mechanism Circulation, February 9, 1999; 99(5): 666 - 673. [Full Text] [PDF]

				I. Gussak, C. Antzelevitch, P. Bjerregaard, J. A. Towbin, and B. R. Chaitman The Brugada syndrome: clinical, electrophysiologic and genetic aspects J. Am. Coll. Cardiol., January 1, 1999; 33(1): 5 - 15. [Abstract] [Full Text] [PDF]

				J. Brugada, P. Brugada, and R. Brugada The syndrome of right bundle branch block ST segment elevation in V1 to V3 and sudden death--the Brugada syndrome Europace, January 1, 1999; 1(3): 156 - 166. [Abstract] [PDF]

				M Nomura, T Nada, J Endo, Y Kondo, M Yukinaka, K Saito, S Ito, H Mori, Y Nakaya, and H Shinomiya Brugada syndrome associated with an autonomic disorder Heart, August 1, 1998; 80(2): 194 - 196. [Abstract] [Full Text]

				K. Hirata In Response: Reply to Dr. RuDusky Angiology, July 1, 1998; 49(7): 587 - 589. [PDF]

				S. Viskin, B. Belhassen, H. Kasanuki, N. Matuda, and S. Ohnishi Increased Vagal Activity in Idiopathic VF • Response Circulation, March 10, 1998; 97 (9): 937 - 940. [Full Text]

				T Washizuka, M Chinushi, S Niwano, and Y Aizawa Bifid T waves induced by isoprenaline in a patient with Brugada syndrome Heart, March 1, 1998; 79(3): 305 - 307. [Abstract] [Full Text]

				J. Brugada, R. Brugada, and P. Brugada Right Bundle-Branch Block and ST-Segment Elevation in Leads V1 Through V3 : A Marker for Sudden Death in Patients Without Demonstrable Structural Heart Disease Circulation, February 10, 1998; 97(5): 457 - 460. [Abstract] [Full Text] [PDF]

				K. Hirata, Y. Takagi, M. Nakada, M. Kyushima, and H. Asato Beat-to-Beat Variation of the ST Segment in a Patient with Right Bundle Branch Block, Persistent ST Segment Elevation, and Ventricular Fibrillation: A Case Report Angiology, January 1, 1998; 49(1): 87 - 90. [Abstract] [PDF]

				K. Nademanee, G. Veerakul, S. Nimmannit, V. Chaowakul, K. Bhuripanyo, K. Likittanasombat, K. Tunsanga, S. Kuasirikul, P. Malasit, S. Tansupasawadikul, et al. Arrhythmogenic Marker for the Sudden Unexplained Death Syndrome in Thai Men Circulation, October 21, 1997; 96(8): 2595 - 2600. [Abstract] [Full Text]