β-blockers Protect Against Dispersion of Repolarization During Exercise in Congenital Long-QT Syndrome Type 1

Overview

Journal J Cardiovasc Electrophysiol

Specialties Cardiology & Vascular Diseases
Physiology

Date 2011 Jun 4

PMID 21635612

Citations 9

Authors

Lee W Gemma

Gregory M Ward

Mary M Dettmer

Jennifer L Ball

Peter J Leo

Danielle N Doria

Elizabeth S Kaufman

Affiliations

Soon will be listed here.

Abstract

Introduction: β-Blocker therapy reduces syncope and sudden death in long-QT syndrome type 1 (LQT1), but the mechanism of protection is incompletely understood. This study tested the hypothesis that β-blockade reduces QT prolongation and dispersion of repolarization, measured as the T peak-to-end interval (T(pe) ), during exercise and recovery in LQT1 patients.

Methods And Results: QT and T(pe) were measured in 10 LQT1 patients (33 ± 13 years) and 35 normal subjects (32 ± 12 years) during exercise tests on and off β-blockade. In LQT1 patients, β-blockade reduced QT (391 ± 25 milliseconds vs 375 ± 26 milliseconds, P = 0.04 during exercise; 419 ± 41 milliseconds vs 391 ± 39 milliseconds, P = 0.02 during recovery) and markedly reduced T(pe) (91 ± 26 milliseconds vs 67 ± 19 milliseconds, P = 0.03 during exercise; 103 ± 26 milliseconds vs 78 ± 11 milliseconds, P = 0.02 during recovery). In contrast, in normal subjects, β-blockade had no effect on QT (320 ± 17 milliseconds vs 317 ± 16 milliseconds, P = 0.29 during exercise; 317 ± 13 milliseconds vs 315 ± 14 milliseconds, P = 0.15 during recovery) and mildly reduced T(pe) (69 ± 13 milliseconds vs 61 ± 11 milliseconds, P = 0.01 during exercise; 77 ± 19 milliseconds vs. 68 ± 14 milliseconds, P < 0.001 during recovery).

Conclusion: In LQT1 patients, β-blockers reduced QT and T(pe) during exercise and recovery, supporting the theory that β-blocker therapy protects LQT1 patients by reducing dispersion of repolarization during exercise and recovery.

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References

Opthof T, Coronel R, Wilms-Schopman F, Plotnikov A, Shlapakova I, Danilo Jr P . Dispersion of repolarization in canine ventricle and the electrocardiographic T wave: Tp-e interval does not reflect transmural dispersion. Heart Rhythm. 2007; 4(3):341-8. DOI: 10.1016/j.hrthm.2006.11.022. View

Gupta P, Patel C, Patel H, Narayanaswamy S, Malhotra B, Green J . T(p-e)/QT ratio as an index of arrhythmogenesis. J Electrocardiol. 2008; 41(6):567-74. DOI: 10.1016/j.jelectrocard.2008.07.016. View

Albert C, Mittleman M, Chae C, Lee I, Hennekens C, Manson J . Triggering of sudden death from cardiac causes by vigorous exertion. N Engl J Med. 2000; 343(19):1355-61. DOI: 10.1056/NEJM200011093431902. View

Ackerman M, Khositseth A, Tester D, Hejlik J, Shen W, Porter C . Epinephrine-induced QT interval prolongation: a gene-specific paradoxical response in congenital long QT syndrome. Mayo Clin Proc. 2002; 77(5):413-21. DOI: 10.4065/77.5.413. View

Vyas H, Hejlik J, Ackerman M . Epinephrine QT stress testing in the evaluation of congenital long-QT syndrome: diagnostic accuracy of the paradoxical QT response. Circulation. 2006; 113(11):1385-92. DOI: 10.1161/CIRCULATIONAHA.105.600445. View

Shimizu W, Noda T, Takaki H, Kurita T, Nagaya N, Satomi K . Epinephrine unmasks latent mutation carriers with LQT1 form of congenital long-QT syndrome. J Am Coll Cardiol. 2003; 41(4):633-42. DOI: 10.1016/s0735-1097(02)02850-4. View

Shimizu W, Tanabe Y, Aiba T, Inagaki M, Kurita T, Suyama K . Differential effects of beta-blockade on dispersion of repolarization in the absence and presence of sympathetic stimulation between the LQT1 and LQT2 forms of congenital long QT syndrome. J Am Coll Cardiol. 2002; 39(12):1984-91. DOI: 10.1016/s0735-1097(02)01894-6. View

Sy R, Chattha I, Klein G, Gula L, Skanes A, Yee R . Repolarization dynamics during exercise discriminate between LQT1 and LQT2 genotypes. J Cardiovasc Electrophysiol. 2010; 21(11):1242-6. DOI: 10.1111/j.1540-8167.2010.01788.x. View

Xia Y, Liang Y, Kongstad O, Holm M, Olsson B, Yuan S . Tpeak-Tend interval as an index of global dispersion of ventricular repolarization: evaluations using monophasic action potential mapping of the epi- and endocardium in swine. J Interv Card Electrophysiol. 2005; 14(2):79-87. DOI: 10.1007/s10840-005-4592-4. View

10.

Xia Y, Liang Y, Kongstad O, Liao Q, Holm M, Olsson B . In vivo validation of the coincidence of the peak and end of the T wave with full repolarization of the epicardium and endocardium in swine. Heart Rhythm. 2005; 2(2):162-9. DOI: 10.1016/j.hrthm.2004.11.011. View

11.

Tanabe Y, Inagaki M, Kurita T, Nagaya N, Taguchi A, Suyama K . Sympathetic stimulation produces a greater increase in both transmural and spatial dispersion of repolarization in LQT1 than LQT2 forms of congenital long QT syndrome. J Am Coll Cardiol. 2001; 37(3):911-9. DOI: 10.1016/s0735-1097(00)01200-6. View

12.

Viitasalo M, Oikarinen L, Swan H, Vaananen H, Glatter K, Laitinen P . Ambulatory electrocardiographic evidence of transmural dispersion of repolarization in patients with long-QT syndrome type 1 and 2. Circulation. 2002; 106(19):2473-8. DOI: 10.1161/01.cir.0000036369.16112.7d. View

13.

Shimizu W, Antzelevitch C . Differential effects of beta-adrenergic agonists and antagonists in LQT1, LQT2 and LQT3 models of the long QT syndrome. J Am Coll Cardiol. 2000; 35(3):778-86. DOI: 10.1016/s0735-1097(99)00582-3. View

14.

MOSS A, Zareba W, Hall W, Schwartz P, Crampton R, Benhorin J . Effectiveness and limitations of beta-blocker therapy in congenital long-QT syndrome. Circulation. 2000; 101(6):616-23. DOI: 10.1161/01.cir.101.6.616. View

15.

Kaltman J, Ro P, Stephens P, McBride M, Cohen M, Tanel R . Effects of beta-adrenergic antagonists on the QT measurements from exercise stress tests in pediatric patients with long QT syndrome. Pediatr Cardiol. 2003; 24(6):553-8. DOI: 10.1007/s00246-003-0436-0. View

16.

Goldenberg I, Bradley J, Moss A, McNitt S, Polonsky S, Robinson J . Beta-blocker efficacy in high-risk patients with the congenital long-QT syndrome types 1 and 2: implications for patient management. J Cardiovasc Electrophysiol. 2010; 21(8):893-901. PMC: 4005824. DOI: 10.1111/j.1540-8167.2010.01737.x. View

17.

Swan H, Viitasalo M, Piippo K, Laitinen P, Kontula K, Toivonen L . Sinus node function and ventricular repolarization during exercise stress test in long QT syndrome patients with KvLQT1 and HERG potassium channel defects. J Am Coll Cardiol. 1999; 34(3):823-9. DOI: 10.1016/s0735-1097(99)00255-7. View

18.

Schwartz P, Locati E . The idiopathic long QT syndrome: pathogenetic mechanisms and therapy. Eur Heart J. 1985; 6 Suppl D:103-14. DOI: 10.1093/eurheartj/6.suppl_d.103. View

19.

Yan G, Martin J . Electrocardiographic T wave: a symbol of transmural dispersion of repolarization in the ventricles. J Cardiovasc Electrophysiol. 2003; 14(6):639-40. DOI: 10.1046/j.1540-8167.2003.03155.x. View

20.

Antzelevitch C . T peak-Tend interval as an index of transmural dispersion of repolarization. Eur J Clin Invest. 2001; 31(7):555-7. DOI: 10.1046/j.1365-2362.2001.00849.x. View