Published online before print April 12, 2004, doi: 10.1161/01.CIR.0000127423.75608.A4
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2004;109:2136-2142.)
© 2004 American Heart Association, Inc.
Basic Science Reports |
Epicardial Activation of Left Ventricular Wall Prolongs QT Interval and Transmural Dispersion of Repolarization
Implications for Biventricular Pacing
From the Masonic Medical Research Laboratory, Utica, NY.
Correspondence to Dr Charles Antzelevitch, Masonic Medical Research Laboratory, 2150 Bleecker St, Utica, NY 13501-1787. E-mail ca{at}mmrl.edu
Received August 20, 2003; revision received December 30, 2003; accepted January 23, 2004.
Background— Epicardial pacing of the left ventricle (LV) has been shown to prolong the QT interval and predispose to the development of torsade de pointes arrhythmias. The present study examines the cellular basis for QT prolongation and arrhythmogenesis after reversal of the direction of activation of the LV wall.
Methods and Results— A transmural ECG and transmembrane action potentials were simultaneously recorded from epicardial, M, and endocardial cells of arterially perfused canine LV wedge preparations. QT interval increased from 297.6±3.9 to 314.0±5.7 ms (n=12; P<0.001) and transmural dispersion of repolarization (TDR) increased from 35.5±5.2 to 70.3±6.2 ms (n=12; P<0.001) as pacing was shifted from endocardium to epicardium. Conduction time between M and epicardial cells increased from 12.1±1.2 to 24.2±1.5 ms (n=12; P<0.001). Amplification of TDR was further accentuated in the presence of rapidly activating delayed rectifier potassium current blockers (E-4031 and cisapride), increasing from 50.5±7.6 to 86.1±6.2 ms (n=8; P<0.01). Torsade de pointes arrhythmias could be induced during epicardial, but not endocardial, pacing of LV in the presence of rapidly activating delayed rectifier potassium current blockade.
Conclusions— Reversal of the direction of activation of the LV wall, as occurs during biventricular pacing, leads to a prominent increase in QT and TDR as a result of earlier repolarization of epicardium and delayed activation and repolarization of the midmyocardial M cells. The increase in TDR creates the substrate for the development of torsade de pointes under long-QT conditions.
Key Words: electrocardiography • torsade de pointes • heart failure • pacemakers • electrophysiology
This article has been cited by other articles:
 |
|
 |
|
  P. Dilaveris, G. Giannopoulos, A. Synetos, C. Aggeli, L. Raftopoulos, P. Arsenos, K. Gatzoulis, and C. Stefanadis Effect of biventricular pacing on ventricular repolarization and functional indices in patients with heart failure: lack of association with arrhythmic events Europace, June 1, 2009; 11(6): 741 - 750. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Aiba, G. G. Hesketh, A. S. Barth, T. Liu, S. Daya, K. Chakir, V. L. Dimaano, T. P. Abraham, B. O'Rourke, F. G. Akar, et al. Electrophysiological Consequences of Dyssynchronous Heart Failure and Its Restoration by Resynchronization Therapy Circulation, March 10, 2009; 119(9): 1220 - 1230. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Patel, J. F. Burke, H. Patel, P. Gupta, P. R. Kowey, C. Antzelevitch, and G.-X. Yan Is there a significant transmural gradient in repolarization time in the intact heart?: Cellular Basis of the T Wave: A Century of Controversy Circ Arrhythmia Electrophysiol, February 1, 2009; 2(1): 80 - 88. [Full Text] [PDF]
|
|
|
|
|
|
T. Opthof, R. Coronel, and M. J. Janse Is there a significant transmural gradient in repolarization time in the intact heart?: Repolarization Gradients in the Intact Heart Circ Arrhythmia Electrophysiol, February 1, 2009; 2(1): 89 - 96. [Full Text] [PDF]
|
|
|
|
 |
|
 T. G. Zhu, C. Patel, S. Martin, X. Quan, Y. Wu, J. F. Burke, M. Chernick, P. R. Kowey, and G.-X. Yan Ventricular transmural repolarization sequence: its relationship with ventricular relaxation and role in ventricular diastolic function Eur. Heart J., February 1, 2009; 30(3): 372 - 380. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G Lin, R F Rea, S C Hammill, D L Hayes, and P A Brady Effect of cardiac resynchronisation therapy on occurrence of ventricular arrhythmia in patients with implantable cardioverter defibrillators undergoing upgrade to cardiac resynchronisation therapy devices Heart, February 1, 2008; 94(2): 186 - 190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. W. Kimmel, N. D. Skadsberg, C. L. Byrd, D. J. Wright, T. G. Laske, and P. A. Iaizzo Single-site ventricular and biventricular pacing: investigation of latest depolarization strategy Europace, December 1, 2007; 9(12): 1163 - 1170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Mantravadi, B. Gabris, T. Liu, B.-R. Choi, W. C. de Groat, G. A. Ng, and G. Salama Autonomic Nerve Stimulation Reverses Ventricular Repolarization Sequence in Rabbit Hearts Circ. Res., April 13, 2007; 100(7): e72 - e80. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Bai, X. Y. Yang, Y. Song, L. Lin, J. G. Lu, C. K. Ching, J. Pu, R. Kam, L. F. Hsu, C. T. Zhang, et al. Impact of left ventricular epicardial and biventricular pacing on ventricular repolarization in normal-heart individuals and patients with congestive heart failure. Europace, November 1, 2006; 8(11): 1002 - 1010. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Chalil, Z. R. Yousef, S. A. Muyhaldeen, R. E. A. Smith, P. Jordan, C. R. Gibbs, and F. Leyva Pacing-Induced Increase in QT Dispersion Predicts Sudden Cardiac Death Following Cardiac Resynchronization Therapy J. Am. Coll. Cardiol., June 20, 2006; 47(12): 2486 - 2492. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Castro Hevia, C. Antzelevitch, F. Tornes Barzaga, M. Dorantes Sanchez, F. Dorticos Balea, R. Zayas Molina, M. A. Quinones Perez, and Y. Fayad Rodriguez Tpeak-Tend and Tpeak-Tend Dispersion as Risk Factors for Ventricular Tachycardia/Ventricular Fibrillation in Patients With the Brugada Syndrome J. Am. Coll. Cardiol., May 2, 2006; 47(9): 1828 - 1834. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Fish, J. Brugada, and C. Antzelevitch Potential Proarrhythmic Effects of Biventricular Pacing J. Am. Coll. Cardiol., December 20, 2005; 46(12): 2340 - 2347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Viskin and C. Antzelevitch The Cardiologists' Worst Nightmare: Sudden Death From "Benign" Ventricular Arrhythmias J. Am. Coll. Cardiol., October 4, 2005; 46(7): 1295 - 1297. [Full Text] [PDF]
|
|
|
|
|
|
G.-B. Nam, A. Burashnikov, and C. Antzelevitch Cellular Mechanisms Underlying the Development of Catecholaminergic Ventricular Tachycardia Circulation, May 31, 2005; 111(21): 2727 - 2733. [Abstract] [Full Text] [PDF]
|
|