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Cardiovascular Research 2002 53(3):770-776; doi:10.1016/S0008-6363(01)00477-1
© 2002 by European Society of Cardiology
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Copyright © 2002, European Society of Cardiology

Gender differences in the long QT syndrome: effects of β-adrenoceptor blockade

Chantal E Conratha,b,*, Arthur A.M Wildec, Rosalie J.E Jongbloedd, Mariëlle Alderse, Irene M van Langene, J Peter van Tintelenf, Pieter A Doevendansg and Tobias Opthofb

aDepartment of Cardiology, University Medical Center, Utrecht, The Netherlands
bDepartment of Medical Physiology, University Medical Center, Utrecht, The Netherlands
cExperimental and Molecular Cardiology Group, Academic Medical Center, Amsterdam, The Netherlands
dDepartment of Molecular Cell Biology and Genetics, University of Maastricht, Maastricht, The Netherlands
eDepartment of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands
fDepartment of Clinical Genetics, University Hospital Groningen, Groningen, The Netherlands
gDepartment of Cardiology, University Hospital Maastricht, Maastricht, The Netherlands and the Interuniversitary Cardiology Institute of the Netherlands (ICIN), The Netherlands

* Corresponding author. Department of Cardiology, E03.406 University Medical Center Heidelberglaan 100-PO Box 85500 3508 GA, Utrecht, The Netherlands. Tel.: +31-30-253-8900; fax: +31-30-253-9036 c.e.conrath{at}med.uu.nl

Background: Gender differences have been reported in patients with the congenital long QT syndrome (LQTS). We analyzed whether electrocardiographic differences existed in females, males, girls and boys in response to β-adrenoceptor blockade. Methods: 12-lead ECGs before and during β-adrenoceptor blockade were collected in 87 genotyped LQTS patients (48 women, 14 men, 12 girls and 13 boys). Up to three QTc intervals were determined in each lead of the ECG. V4 was used for QT/QTc analysis. Difference between longest and shortest QT interval was taken as a measure for dispersion of QT intervals. Results: (1) Adult males had the greatest shortening of the QTc interval upon treatment with β-adrenoceptor blockade. During treatment, adult males with LQTS1 (mutation in the KCNQ1 gene, affecting IKs current) were found to have shorter QTc intervals than adult females; this difference did not exist in LQTS2 patients (mutation in the HERG gene, affecting IKr current). (2) Female LQTS2 patients had a 50% larger dispersion than female LQTS1 patients both before and during treatment. (3) Adult male LQTS1 patients constitute the only patient group with a marked decrease in QTc intervals and dispersion associated with a 100% efficacy of treatment in response to β-adrenoceptor blockade. Conclusions: These findings indicate that, in addition to underlying differences in repolarization between men and women, cardiac electrophysiological responses to β-adrenoceptor blockade can be modulated by gender-related factors.

KEYWORDS Adrenergic (ant)agonists; ECG; Gender; Long QT syndrome; QT dispersion


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