title: Electromechanical window negativity in genotyped long-QT syndrome patients: relation to arrhythmia risk.
abstract: OBJECTIVE
  Prolonged and dispersed left-ventricular (LV) contraction is present in patients with long-QT syndrome (LQTS). Electrical and mechanical abnormalities appear most pronounced in symptomatic individuals. We focus on the 'electromechanical window' (EMW; duration of LV-mechanical systole minus QT interval) in patients with genotyped LQTS. Profound EMW negativity heralds torsades de pointes in animal models of drug-induced LQTS.
  
  
  RESULTS
  We included 244 LQTS patients from three centres, of whom 97 had experienced arrhythmic events. Seventy-six matched healthy individuals served as controls. QT interval was subtracted from the duration of Q-onset to aortic-valve closure (QAoC) midline assessed non-invasively by continuous-wave echocardiography, measured in the same beat. Electromechanical window was positive in controls but negative in LQTS patients (22 ± 19 vs. -43 ± 46 ms; P < 0.0001), being even more negative in symptomatic than event-free patients (-67 ± 42 vs. -27 ± 41 ms; P < 0.0001). QT, QTc, and QAoC were longer in LQTS subjects (451 ± 57, 465 ± 50, and 408 ± 37 ms, P < 0.0001). Electromechanical window was a better discriminator of patients with previous arrhythmic events than resting QTc (AUC 0.77 (95% CI, 0.71-0.83) and 0.71 (95% CI, 0.65-0.78); P = 0.03). In multivariate analysis, EMW predicted arrhythmic events independently of QTc (odds ratio 1.25; 95% CI, 1.11-1.40; P = 0.001). Adding EMW to QTc for risk assessment led to a net reclassification improvement of 13.3% (P = 0.03). No EMW differences were found between the three major LQTS genotypes.
  
  
  CONCLUSIONS
  Patients with genotype-positive LQTS express EMW negativity, which is most pronounced in patients with documented arrhythmic events.
authors.affiliation: Department of Cardiology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, PO Box 5800, 6202 AZ Maastricht, The Netherlands.
authors.forename: Rachel M A
authors.initials: RM
authors.lastname: ter Bekke
authors.affiliation: Department of Cardiology, Oslo University Hospital, Rikshospitalet and University of Oslo, Oslo, Norway.
authors.forename: Kristina H
authors.initials: KH
authors.lastname: Haugaa
authors.affiliation: Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Arthur
authors.initials: A
authors.lastname: van den Wijngaard
authors.affiliation: Department of Medicine, The Long QT Syndrome/Genetic Heart Rhythm Clinic, Rochester, MN, USA Department of Pediatrics, The Long QT Syndrome/Genetic Heart Rhythm Clinic, Rochester, MN, USA Department of Molecular Pharmacology and Experimental Therapeutics, The Long QT Syndrome/Genetic Heart Rhythm Clinic, Rochester, MN, USA The Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, MN, USA.
authors.forename: J Martijn
authors.initials: JM
authors.lastname: Bos
authors.affiliation: Department of Medicine, The Long QT Syndrome/Genetic Heart Rhythm Clinic, Rochester, MN, USA Department of Pediatrics, The Long QT Syndrome/Genetic Heart Rhythm Clinic, Rochester, MN, USA Department of Molecular Pharmacology and Experimental Therapeutics, The Long QT Syndrome/Genetic Heart Rhythm Clinic, Rochester, MN, USA The Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, MN, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ackerman
authors.affiliation: Department of Cardiology, Oslo University Hospital, Rikshospitalet and University of Oslo, Oslo, Norway.
authors.forename: Thor
authors.initials: T
authors.lastname: Edvardsen
authors.affiliation: Department of Cardiology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, PO Box 5800, 6202 AZ Maastricht, The Netherlands p.volders@maastrichtuniversity.nl.
authors.forename: Paul G A
authors.initials: PG
authors.lastname: Volders
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000328:Adult; D000704:Analysis of Variance; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000235:genetics; D016022:Case-Control Studies; D016757:Death, Sudden, Cardiac / Q000517:prevention & control; D000072237:ERG1 Potassium Channel; D004562:Electrocardiography; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000502:physiology; D051657:KCNQ1 Potassium Channel / Q000235:genetics; D008133:Long QT Syndrome / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D009154:Mutation / Q000235:genetics; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D012307:Risk Factors; D018608:Ultrasonography, Doppler
chemical_list: D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D007473:Ion Channels; C489622:KCNE1 protein, human; C489619:KCNE2 protein, human; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D062554:NAV1.5 Voltage-Gated Sodium Channel; D024642:Potassium Channels, Voltage-Gated; C568320:SCN5A protein, human
keywords: Arrhythmia; Echocardiography; Ion channels; Long-QT syndrome; Sudden death