Electro-mechanical dysfunction in long QT syndrome: Role for arrhythmogenic risk prediction and modulation by sex and sex hormones. Issue 1 (January 2016)

• Record Type: Journal Article
• Authors: Lang, C.N.; Menza, M.; Jochem, S.; Franke, G.; Perez Feliz, S.; Brunner, M.; Koren, G.; Zehender, M.; Bugger, H.; Jung, B.A.; Foell, D.; Bode, C.; Odening, K.E.
• Is Part Of: Progress in biophysics and molecular biology. Volume 120:Issue 1/3(2016)
• Page Start: 255
• Page End: 269
• Publication Date: 2016-01
• Subjects: Long QT syndrome -- Cardiac repolarization -- Mechanical dysfunction -- Contraction duration -- Diastolic relaxation -- Sex hormones; APD action potential duration (ms) -- DHT ovariectomized female LQT2 rabbit with dihydrotestosterone-treatment -- EST ovariectomized female LQT2 rabbit with estradiol-treatment -- LQTS long QT syndrome -- LQT1/2/3 long QT syndrome type 1/2/3 -- Non-VF LQT2 rabbit without ex vivo ventricular fibrillation -- OVX ovariectomized female LQT2 rabbit with placebo-treatment -- QTc heart rate corrected QT interval -- QTi heart rate corrected QT index -- SCD sudden cardiac death -- SE Strain Echocardiography -- SF female LQT2 rabbit with sham surgery and placebo-treatment -- SM male LQT2 rabbit with sham surgery and placebo-treatment -- TDI Tissue Doppler Imaging -- TPM (Magnetic Resonance) Tissue Phase Mapping -- TTP time to peak duration (ms, when heart rate corrected %) -- VF LQT2 rabbit exhibiting ex vivo ventricular fibrillation -- Vr radial velocity (cm/s) -- Vz longitudinal velocity (cm/s); Biophysics -- Periodicals; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular Biology -- Periodicals; Biophysique -- Périodiques; Biochimie -- Périodiques; 571.4
• DOI: 10.1016/j.pbiomolbio.2015.12.010
• Languages: English
• ISSNs: 0079-6107

Abstract

Abstract: Long QT syndrome (LQTS) is a congenital arrhythmogenic channelopathy characterized by impaired cardiac repolarization. Increasing evidence supports the notion that LQTS is not purely an "electrical" disease but rather an "electro-mechanical" disease with regionally heterogeneously impaired electrical and mechanical cardiac function. In the first part, this article reviews current knowledge on electro-mechanical (dys)function in LQTS, clinical consequences of the observed electro-mechanical dysfunction, and potential underlying mechanisms. Since several novel imaging techniques – Strain Echocardiography (SE) and Magnetic Resonance Tissue Phase Mapping (TPM) – are applied in clinical and experimental settings to assess the (regional) mechanical function, advantages of these non-invasive techniques and their feasibility in the clinical routine are particularly highlighted. The second part provides novel insights into sex differences and sex hormone effects on electro-mechanical cardiac function in a transgenic LQT2 rabbit model. Here we demonstrate that female LQT2 rabbits exhibit a prolonged time to diastolic peak – as marker for contraction duration and early relaxation – compared to males. Chronic estradiol-treatment enhances these differences in time to diastolic peak even more and additionally increases the risk for ventricular arrhythmia. Importantly, time to diastolic peak is particularly prolonged in rabbits exhibiting ventricular arrhythmia – regardless of hormone treatment – contrasting with a lack of differences in QT duration between symptomatic and asymptomatic LQT2 rabbits. This indicates the potential added value of the assessment of mechanical dysfunction in future risk stratification of LQTS patients.