title: Cardiac Mechanical Alterations and Genotype Specific Differences in Subjects With Long QT Syndrome.
abstract: OBJECTIVE
  This study aimed to explore systolic and diastolic function and to investigate genotype-specific differences in subjects with long QT syndrome (LQTS).
  
  
  BACKGROUND
  LQTS is an arrhythmogenic cardiac ion channelopathy that traditionally has been considered a purely electrical disease. The most commonly affected ion channels are the slow potassium channel, IKs (KCNQ1 gene/LQT1), and the rapid potassium channel, IKr (KCNH2 gene/LQT2). Recent reports have indicated mechanical abnormalities in patients with LQTS.
  
  
  METHODS
  We included 192 subjects with genotyped LQTS (139 LQT1, 53 LQT2). Healthy persons of similar age and sex as patients served as controls (n = 60). Using echocardiography, we assessed systolic function by left ventricular (LV) ejection fraction (EF), global longitudinal strain (GLS), and contraction duration (16 LV segments). Mechanical dispersion was calculated as standard deviation of contraction duration. Time difference between contraction duration and QT interval from electrocardiography (ECG) was defined as electromechanical time difference. We assessed diastolic function by transmitral filling velocities, early diastolic myocardial velocity (e'), and left atrial volume index (LAVI). Heart rate corrected QT interval (QTc) was assessed from 12-lead ECG.
  
  
  RESULTS
  Systolic function by GLS was reduced in subjects with LQTS compared with healthy controls (-22.1 ± 2.1% vs. -23.0 ± 2.0%, p = 0.01), and GLS was worse in subjects with LQT2 compared with subjects with LQT1 (p = 0.01). Subjects with LQTS had longer contraction duration (426 ± 41 ms vs. 391 ± 36 ms, p < 0.001) and more dispersed contractions (33 ± 14 ms vs. 21 ± 7 ms, p < 0.001) compared with healthy controls. Diastolic function was also reduced in subjects with LQTS compared with healthy controls; e' was lower (10.7 ± 2.7 cm/s vs. 12.5 ± 2.0 cm/s, p < 0.001), and LAVI was increased (30 ± 8 ml/m(2) vs. 26 ± 5 ml/m(2), p = 0.01), also when adjusted for age and other possible confounders.
  
  
  CONCLUSIONS
  Subjects with LQTS had a consistent reduction in both systolic and diastolic function compared with healthy controls. Differences in myocardial function between subjects with LQT1 and subjects with LQT2 may indicate that mechanical alterations in LQTS are genotype specific.
authors.affiliation: Department of Cardiology and Center for Cardiological Innovation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute for Surgical Research, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Ida S
authors.initials: IS
authors.lastname: Leren
authors.affiliation: Department of Cardiology and Center for Cardiological Innovation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute for Surgical Research, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Nina E
authors.initials: NE
authors.lastname: Hasselberg
authors.affiliation: Department of Cardiology and Center for Cardiological Innovation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute for Surgical Research, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Jørg
authors.initials: J
authors.lastname: Saberniak
authors.affiliation: Department of Cardiology and Center for Cardiological Innovation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Trine F
authors.initials: TF
authors.lastname: Håland
authors.affiliation: Department of Cardiology and Center for Cardiological Innovation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Erik
authors.initials: E
authors.lastname: Kongsgård
authors.affiliation: Department of Cardiology and Center for Cardiological Innovation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute for Surgical Research, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Otto A
authors.initials: OA
authors.lastname: Smiseth
authors.affiliation: Department of Cardiology and Center for Cardiological Innovation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute for Surgical Research, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Thor
authors.initials: T
authors.lastname: Edvardsen
authors.affiliation: Department of Cardiology and Center for Cardiological Innovation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute for Surgical Research, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway. Electronic address: kristina.haugaa@rr-research.no.
authors.forename: Kristina H
authors.initials: KH
authors.lastname: Haugaa
mesh_terms: D000328:Adult; D001696:Biomechanical Phenomena; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D000072237:ERG1 Potassium Channel; D015150:Echocardiography, Doppler; D004562:Electrocardiography; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D008133:Long QT Syndrome / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D008875:Middle Aged; D009154:Mutation; D009200:Myocardial Contraction / Q000235:genetics*; D010641:Phenotype; D029597:Romano-Ward Syndrome / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D013318:Stroke Volume / Q000235:genetics*; D013997:Time Factors; D016277:Ventricular Function, Left / Q000235:genetics*; D055815:Young Adult
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human
keywords: genotyped; long QT syndrome; myocardial function; strain echocardiography; ventricular arrhythmia