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Heart Rhythm. 2014 Nov;11(11):2107-15. doi: 10.1016/j.hrthm.2014.06.023. Epub 2014 Jun 19.

How do sex hormones modify arrhythmogenesis in long QT syndrome? Sex hormone effects on arrhythmogenic substrate and triggered activity.

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Department of Cardiology and Angiology I, Heart Center University of Freiburg, Freiburg, Germany. Electronic address:
Division of Cardiology, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island.


Gender differences in cardiac repolarization and the arrhythmogenic risk of patients with inherited and acquired long QT syndromes are well appreciated clinically. Enhancing our knowledge of the mechanisms underlying these differences is critical to improve our therapeutic strategies for preventing sudden cardiac death in such patients. This review summarizes the effects of sex hormones on the expression and function of ion channels that control cardiac cell excitation and repolarization as well as key proteins that regulate Ca(2+) dynamics at the cellular level. Moreover, it examines the role of sex hormones in modifying the dynamic spatiotemporal (regional and transmural) heterogeneities in action potential duration (eg, the arrhythmogenic substrate) and the susceptibility to (sympathetic) triggered activity at the tissue, organ, and whole animal levels. Finally, it explores the implications of these effects on the management of patients with LQTS.


Adrenoceptors; Animal models; Ca(2+) cycling proteins; Dispersion of cardiac repolarization; Early afterdepolarizations; Gender differences; Ion channels; Long QT syndrome; Mechanisms of arrhythmogenesis; Sex hormones

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