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Heart Rhythm. 2010 Aug;7(8):1067-74. doi: 10.1016/j.hrthm.2010.05.012. Epub 2010 May 12.

Gene-specific paradoxical QT responses during rapid eye movement sleep in women with congenital long QT syndrome.

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  • 1Department of Internal Medicine, Division of Hypertension, Mayo Clinic, Rochester, Minnesota, USA.



Patients with congenital long QT syndrome (LQTS) type 2 (LQT2) may develop arrhythmias during emotional stress, acoustic stimuli, or sleep. Women with LQT2 are more susceptible to fatal arrhythmias than are men.


The purpose of this study was to examine the effects of sleep on RR and QT intervals in patients with LQT1, in those with LQT2, and in controls and to test the hypothesis that there is a gene-specific effect of sleep on the QT interval in LQT2 that may be especially evident in women with LQT2.


Thirty-four subjects with genotyped LQTS and 18 healthy controls were studied. Among the 34 subjects with LQTS, 16 (10 women, age 32 +/- 3 years) had LQT1 and 18 (11 women, age 38 +/- 3 years) had LQT2. Subjects underwent standard polysomnography including ECG recordings. RR, QT, and QTc (Bazett and Fridericia formulas) were measured over recordings obtained during stable conditions during wakefulness, during stage 2 and stages 3-4 of non-rapid eye movement (NREM), and during rapid eye movement (REM) sleep.


LQT2 women showed a marked RR decrease and marked QT and QTc increase from NREM to REM sleep, changes that were not observed in either women or men with LQT1 or in men with LQT2.


Pronounced cardiac activation during REM and substantial QTc prolongation is noted in a sex- and gene-specific fashion among women with LQT2. REM-related changes in cardiac activation and ventricular repolarization may be implicated in sleep-related malignant arrhythmias in women with the LQT2 genotype.

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