Published online before print March 1, 2004, doi: 10.1161/01.CIR.0000118467.53182.D1
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2004;109:1272-1277.)
© 2004 American Heart Association, Inc.
Clinical Investigation and Reports |
Delay in Right Ventricular Activation Contributes to Brugada Syndrome
From the Department of Cardiology, Academic Medical Center, Amsterdam, the Netherlands (R.T., J.V., I.K.L.M.d.G., A.A.M.W., H.L.T.), and the Heart Center Aalborg, Aarhus University Hospitals, Aarhus, Denmark (P.S.).
Correspondence to Hanno L. Tan, MD, PhD, Department of Cardiology, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands. E-mail h.l.tan{at}amc.uva.nl
Received September 23, 2003; revision received November 21, 2003; accepted December 5, 2003.
Background— Although Brugada syndrome revolves around reduced net depolarizing force, the electrophysiological mechanisms of its defining features (right precordial ST-segment elevation and ventricular tachyarrhythmias) remain unresolved. Two proposed mechanisms are (1) right ventricular (RV) conduction delay and (2) selective and significant RV subepicardial action potential shortening. Both mechanisms must cause disparate contractile changes: delay in RV contraction and reduction of contractile force, respectively. We aimed to establish the electrophysiological mechanism of Brugada syndrome by studying the timing and force of RV contraction.
Methods and Results— Using tissue Doppler echocardiography, we studied how these contractile variables change on induction of the characteristic ST-segment changes of Brugada syndrome by flecainide challenge. Accordingly, we studied patients in whom flecainide induced these changes (inducible) and those in whom these changes were not induced (control). We found that (1) the occurrence of a positive response (coved-type ST elevation) after flecainide coincides with delay in the onset of contraction between the RV and left ventricle (LV); (2) the extent of contraction delay between RV and LV correlates with the magnitude of ST elevation; and (3) RV ejection time (duration of RV ejection phase) shortens as the Brugada ECG pattern emerges.
Conclusions— These results indicate that both proposed mechanisms of Brugada syndrome may be operative.
Key Words: arrhythmia • Brugada syndrome • conduction • death, sudden • electrophysiology
This article has been cited by other articles:
 |
|
 |
|
  P.D. Lambiase, A.K. Ahmed, E.J. Ciaccio, R. Brugada, E. Lizotte, S. Chaubey, R. Ben-Simon, A.W. Chow, M.D. Lowe, and W.J. McKenna High-Density Substrate Mapping in Brugada Syndrome: Combined Role of Conduction and Repolarization Heterogeneities in Arrhythmogenesis Circulation, July 14, 2009; 120(2): 106 - 117. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Zumhagen, T. Spieker, J. Rolinck, H. A. Baba, G. Breithardt, W. Bocker, L. Eckardt, M. Paul, T. Wichter, and E. Schulze-Bahr Absence of Pathognomonic or Inflammatory Patterns in Cardiac Biopsies From Patients With Brugada Syndrome Circ Arrhythm Electrophysiol, February 1, 2009; 2(1): 16 - 23. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J.D. Boukens, V. M. Christoffels, R. Coronel, and A. F.M. Moorman Developmental Basis for Electrophysiological Heterogeneity in the Ventricular and Outflow Tract Myocardium As a Substrate for Life-Threatening Ventricular Arrhythmias Circ. Res., January 2, 2009; 104(1): 19 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. G. Postema, P. F.H.M. van Dessel, J. M.T. de Bakker, L. R.C. Dekker, A. C. Linnenbank, M. G. Hoogendijk, R. Coronel, J. G.P. Tijssen, A. A.M. Wilde, and H. L. Tan Slow and Discontinuous Conduction Conspire in Brugada Syndrome: A Right Ventricular Mapping and Stimulation Study Circ Arrhythm Electrophysiol, December 1, 2008; 1(5): 379 - 386. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Peters Arrhythmogenic right ventricular dysplasia-cardiomyopathy and provocable coved-type ST-segment elevation in right precordial leads: clues from long-term follow-up Europace, July 1, 2008; 10(7): 816 - 820. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Veeraraghavan and S. Poelzing Mechanisms underlying increased right ventricular conduction sensitivity to flecainide challenge Cardiovasc Res, March 1, 2008; 77(4): 749 - 756. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Casini, H. L. Tan, Z. A. Bhuiyan, C. R. Bezzina, P. Barnett, E. Cerbai, A. Mugelli, A. A.M. Wilde, and M. W. Veldkamp Characterization of a novel SCN5A mutation associated with Brugada syndrome reveals involvement of DIIIS4-S5 linker in slow inactivation Cardiovasc Res, December 1, 2007; 76(3): 418 - 429. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Remme, A. O. Verkerk, D. Nuyens, A. C. G. van Ginneken, S. van Brunschot, C. N. W. Belterman, R. Wilders, M. A. van Roon, H. L. Tan, A. A. M. Wilde, et al. Overlap Syndrome of Cardiac Sodium Channel Disease in Mice Carrying the Equivalent Mutation of Human SCN5A-1795insD Circulation, December 12, 2006; 114(24): 2584 - 2594. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Aiba, W. Shimizu, I. Hidaka, K. Uemura, T. Noda, C. Zheng, A. Kamiya, M. Inagaki, M. Sugimachi, and K. Sunagawa Cellular Basis for Trigger and Maintenance of Ventricular Fibrillation in the Brugada Syndrome Model: High-Resolution Optical Mapping Study J. Am. Coll. Cardiol., May 16, 2006; 47(10): 2074 - 2085. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. O. Verkerk, R. Wilders, E. Schulze-Bahr, L. Beekman, Z. A. Bhuiyan, J. Bertrand, L. Eckardt, D. Lin, M. Borggrefe, G. Breithardt, et al. Role of sequence variations in the human ether-a-go-go-related gene (HERG, KCNH2) in the Brugada syndrome Cardiovasc Res, December 1, 2005; 68(3): 441 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Coronel, S. Casini, T. T. Koopmann, F. J.G. Wilms-Schopman, A. O. Verkerk, J. R. de Groot, Z. Bhuiyan, C. R. Bezzina, M. W. Veldkamp, A. C. Linnenbank, et al. Right Ventricular Fibrosis and Conduction Delay in a Patient With Clinical Signs of Brugada Syndrome: A Combined Electrophysiological, Genetic, Histopathologic, and Computational Study Circulation, November 1, 2005; 112(18): 2769 - 2777. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A.B. van Veen, M. Stein, A. Royer, K. Le Quang, F. Charpentier, W. H. Colledge, C. L.-H. Huang, R. Wilders, A. A. Grace, D. Escande, et al. Impaired Impulse Propagation in Scn5a-Knockout Mice: Combined Contribution of Excitability, Connexin Expression, and Tissue Architecture in Relation to Aging Circulation, September 27, 2005; 112(13): 1927 - 1935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. G. Meregalli, A. A.M. Wilde, and H. L. Tan Pathophysiological mechanisms of Brugada syndrome: Depolarization disorder, repolarization disorder, or more? Cardiovasc Res, August 15, 2005; 67(3): 367 - 378. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Royer, T. A.B. van Veen, S. Le Bouter, C. Marionneau, V. Griol-Charhbili, A.-L. Leoni, M. Steenman, H. V.M. van Rijen, S. Demolombe, C. A. Goddard, et al. Mouse Model of SCN5A-Linked Hereditary Lenegre's Disease: Age-Related Conduction Slowing and Myocardial Fibrosis Circulation, April 12, 2005; 111(14): 1738 - 1746. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Antzelevitch, P. Brugada, M. Borggrefe, J. Brugada, R. Brugada, D. Corrado, I. Gussak, H. LeMarec, K. Nademanee, A. R. Perez Riera, et al. Brugada Syndrome: Report of the Second Consensus Conference: Endorsed by the Heart Rhythm Society and the European Heart Rhythm Association Circulation, February 8, 2005; 111(5): 659 - 670. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Martini, H. L. Tan, R. Tukkie, J. Vleugels, I. K.L.M. de Groot, A. A.M. Wilde, and P. Sogaard Further Confirmation That a Conduction Disturbance Underlies the Electrocardiographic Pattern of the So-Called Brugada Syndrome * Response Circulation, August 3, 2004; 110(5): e53 - e53. [Full Text] [PDF]
|
|