title: Electro-mechanical dysfunction in long QT syndrome: Role for arrhythmogenic risk prediction and modulation by sex and sex hormones.
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.
authors.affiliation: Heart Center University of Freiburg, Department of Cardiology and Angiology I, Freiburg, Germany.
authors.forename: C N
authors.initials: CN
authors.lastname: Lang
authors.affiliation: University Medical Center Freiburg, Department of Radiology, Medical Physics, Freiburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Menza
authors.affiliation: Heart Center University of Freiburg, Department of Cardiology and Angiology I, Freiburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Jochem
authors.affiliation: Heart Center University of Freiburg, Department of Cardiology and Angiology I, Freiburg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Franke
authors.affiliation: Heart Center University of Freiburg, Department of Cardiology and Angiology I, Freiburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Perez Feliz
authors.affiliation: Heart Center University of Freiburg, Department of Cardiology and Angiology I, Freiburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Brunner
authors.affiliation: Cardiovascular Research Center, Division of Cardiology, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA.
authors.forename: G
authors.initials: G
authors.lastname: Koren
authors.affiliation: Heart Center University of Freiburg, Department of Cardiology and Angiology I, Freiburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Zehender
authors.affiliation: Heart Center University of Freiburg, Department of Cardiology and Angiology I, Freiburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Bugger
authors.affiliation: University Medical Center Freiburg, Department of Radiology, Medical Physics, Freiburg, Germany; Department of Diagnostic, Interventional and Pediatric Radiology, University Hospital of Bern, Bern, Switzerland.
authors.forename: B A
authors.initials: BA
authors.lastname: Jung
authors.affiliation: Heart Center University of Freiburg, Department of Cardiology and Angiology I, Freiburg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Foell
authors.affiliation: Heart Center University of Freiburg, Department of Cardiology and Angiology I, Freiburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Bode
authors.affiliation: Heart Center University of Freiburg, Department of Cardiology and Angiology I, Freiburg, Germany. Electronic address: katja.odening@uniklinik-freiburg.de.
authors.forename: K E
authors.initials: KE
authors.lastname: Odening
mesh_terms: D000200:Action Potentials; D000818:Animals; D001696:Biomechanical Phenomena; D055724:Electrophysiological Phenomena; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood*; D008133:Long QT Syndrome / Q000097:blood* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D055595:Mechanical Phenomena; D011817:Rabbits; D012306:Risk; D012727:Sex Characteristics
chemical_list: D012739:Gonadal Steroid Hormones
keywords: Cardiac repolarization; Contraction duration; Diastolic relaxation; Long QT syndrome; Mechanical dysfunction; Sex hormones