title: Effect of Age and Sex on the QTc Interval in Children and Adolescents With Type 1 and 2 Long-QT Syndrome.
abstract: BACKGROUND
  In congenital long-QT syndrome, age, sex, and genotype have been associated with cardiac events, but their effect on the trend in QTc interval has never been established. We, therefore, aimed to assess the effect of age and sex on the QTc interval in children and adolescents with type 1 (LQT1) and type 2 (LQT2) long-QT syndrome.
  
  
  RESULTS
  QTc intervals of 12-lead resting electrocardiograms were determined, and trends over time were analyzed using a linear mixed-effects model. The study included 278 patients with a median follow-up of 4 years (interquartile range, 1-9) and a median number of 6 (interquartile range, 2-10) electrocardiograms per patient. Both LQT1 and LQT2 male patients showed QTc interval shortening after the onset of puberty. In LQT2 male patients, this was preceded by a progressive QTc interval prolongation. In LQT1, after the age of 12 years, male patients had a significantly shorter QTc interval than female patients. In LQT2, during the first years of life and from 14 to 26 years, male patients had a significantly shorter QTc interval than female patients. On the contrary, between 5 and 14 years, LQT2 male patients had significantly longer QTc interval than LQT2 female patients.
  
  
  CONCLUSIONS
  There is a significant effect of age and sex on the QTc interval in long-QT syndrome, with a unique pattern per genotype. The age of 12 to 14 years is an important transitional period. In the risk stratification and management of long-QT syndrome patients, clinicians should be aware of these age-, sex-, and genotype-related trends in QTc interval and especially the important role of the onset of puberty.
authors.affiliation: From the Department of Cardiology, Heart Centre (A.S.V., N.H., A.A.M.W.), Department of Pediatric Cardiology, Emma Children's Hospital (A.S.V., S.-A.B.C., N.A.B.), and Department of Clinical Epidemiology, Biostatistics and Bioinformatics (R.B.G.), Academic Medical Centre, Amsterdam, The Netherlands; Department of Pediatric Cardiology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, The Netherlands (A.C.B.); Department of Pediatrics, Elisabeth-TweeSteden Hospital, Tilburg, The Netherlands (C.C.A.D.K.); Department of Pediatrics, National Hospital Organization Kagoshima Medical Center, Japan (M.Y.); and Department of Pediatric Cardiology, Willem-Alexander Children's Hospital, University Medical Centre Leiden, The Netherlands (N.A.B.). a.s.vink@amc.uva.nl.
authors.forename: Arja S
authors.initials: AS
authors.lastname: Vink
authors.affiliation: From the Department of Cardiology, Heart Centre (A.S.V., N.H., A.A.M.W.), Department of Pediatric Cardiology, Emma Children's Hospital (A.S.V., S.-A.B.C., N.A.B.), and Department of Clinical Epidemiology, Biostatistics and Bioinformatics (R.B.G.), Academic Medical Centre, Amsterdam, The Netherlands; Department of Pediatric Cardiology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, The Netherlands (A.C.B.); Department of Pediatrics, Elisabeth-TweeSteden Hospital, Tilburg, The Netherlands (C.C.A.D.K.); Department of Pediatrics, National Hospital Organization Kagoshima Medical Center, Japan (M.Y.); and Department of Pediatric Cardiology, Willem-Alexander Children's Hospital, University Medical Centre Leiden, The Netherlands (N.A.B.).
authors.forename: Sally-Ann B
authors.initials: SB
authors.lastname: Clur
authors.affiliation: From the Department of Cardiology, Heart Centre (A.S.V., N.H., A.A.M.W.), Department of Pediatric Cardiology, Emma Children's Hospital (A.S.V., S.-A.B.C., N.A.B.), and Department of Clinical Epidemiology, Biostatistics and Bioinformatics (R.B.G.), Academic Medical Centre, Amsterdam, The Netherlands; Department of Pediatric Cardiology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, The Netherlands (A.C.B.); Department of Pediatrics, Elisabeth-TweeSteden Hospital, Tilburg, The Netherlands (C.C.A.D.K.); Department of Pediatrics, National Hospital Organization Kagoshima Medical Center, Japan (M.Y.); and Department of Pediatric Cardiology, Willem-Alexander Children's Hospital, University Medical Centre Leiden, The Netherlands (N.A.B.).
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Geskus
authors.affiliation: From the Department of Cardiology, Heart Centre (A.S.V., N.H., A.A.M.W.), Department of Pediatric Cardiology, Emma Children's Hospital (A.S.V., S.-A.B.C., N.A.B.), and Department of Clinical Epidemiology, Biostatistics and Bioinformatics (R.B.G.), Academic Medical Centre, Amsterdam, The Netherlands; Department of Pediatric Cardiology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, The Netherlands (A.C.B.); Department of Pediatrics, Elisabeth-TweeSteden Hospital, Tilburg, The Netherlands (C.C.A.D.K.); Department of Pediatrics, National Hospital Organization Kagoshima Medical Center, Japan (M.Y.); and Department of Pediatric Cardiology, Willem-Alexander Children's Hospital, University Medical Centre Leiden, The Netherlands (N.A.B.).
authors.forename: Andreas C
authors.initials: AC
authors.lastname: Blank
authors.affiliation: From the Department of Cardiology, Heart Centre (A.S.V., N.H., A.A.M.W.), Department of Pediatric Cardiology, Emma Children's Hospital (A.S.V., S.-A.B.C., N.A.B.), and Department of Clinical Epidemiology, Biostatistics and Bioinformatics (R.B.G.), Academic Medical Centre, Amsterdam, The Netherlands; Department of Pediatric Cardiology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, The Netherlands (A.C.B.); Department of Pediatrics, Elisabeth-TweeSteden Hospital, Tilburg, The Netherlands (C.C.A.D.K.); Department of Pediatrics, National Hospital Organization Kagoshima Medical Center, Japan (M.Y.); and Department of Pediatric Cardiology, Willem-Alexander Children's Hospital, University Medical Centre Leiden, The Netherlands (N.A.B.).
authors.forename: Charlotte C A
authors.initials: CC
authors.lastname: De Kezel
authors.affiliation: From the Department of Cardiology, Heart Centre (A.S.V., N.H., A.A.M.W.), Department of Pediatric Cardiology, Emma Children's Hospital (A.S.V., S.-A.B.C., N.A.B.), and Department of Clinical Epidemiology, Biostatistics and Bioinformatics (R.B.G.), Academic Medical Centre, Amsterdam, The Netherlands; Department of Pediatric Cardiology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, The Netherlands (A.C.B.); Department of Pediatrics, Elisabeth-TweeSteden Hospital, Tilburg, The Netherlands (C.C.A.D.K.); Department of Pediatrics, National Hospital Organization Kagoshima Medical Center, Japan (M.Y.); and Department of Pediatric Cardiology, Willem-Alexander Children's Hospital, University Medical Centre Leiden, The Netherlands (N.A.B.).
authors.forename: Masao
authors.initials: M
authors.lastname: Yoshinaga
authors.affiliation: From the Department of Cardiology, Heart Centre (A.S.V., N.H., A.A.M.W.), Department of Pediatric Cardiology, Emma Children's Hospital (A.S.V., S.-A.B.C., N.A.B.), and Department of Clinical Epidemiology, Biostatistics and Bioinformatics (R.B.G.), Academic Medical Centre, Amsterdam, The Netherlands; Department of Pediatric Cardiology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, The Netherlands (A.C.B.); Department of Pediatrics, Elisabeth-TweeSteden Hospital, Tilburg, The Netherlands (C.C.A.D.K.); Department of Pediatrics, National Hospital Organization Kagoshima Medical Center, Japan (M.Y.); and Department of Pediatric Cardiology, Willem-Alexander Children's Hospital, University Medical Centre Leiden, The Netherlands (N.A.B.).
authors.forename: Nynke
authors.initials: N
authors.lastname: Hofman
authors.affiliation: From the Department of Cardiology, Heart Centre (A.S.V., N.H., A.A.M.W.), Department of Pediatric Cardiology, Emma Children's Hospital (A.S.V., S.-A.B.C., N.A.B.), and Department of Clinical Epidemiology, Biostatistics and Bioinformatics (R.B.G.), Academic Medical Centre, Amsterdam, The Netherlands; Department of Pediatric Cardiology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, The Netherlands (A.C.B.); Department of Pediatrics, Elisabeth-TweeSteden Hospital, Tilburg, The Netherlands (C.C.A.D.K.); Department of Pediatrics, National Hospital Organization Kagoshima Medical Center, Japan (M.Y.); and Department of Pediatric Cardiology, Willem-Alexander Children's Hospital, University Medical Centre Leiden, The Netherlands (N.A.B.).
authors.forename: Arthur A M
authors.initials: AA
authors.lastname: Wilde
authors.affiliation: From the Department of Cardiology, Heart Centre (A.S.V., N.H., A.A.M.W.), Department of Pediatric Cardiology, Emma Children's Hospital (A.S.V., S.-A.B.C., N.A.B.), and Department of Clinical Epidemiology, Biostatistics and Bioinformatics (R.B.G.), Academic Medical Centre, Amsterdam, The Netherlands; Department of Pediatric Cardiology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, The Netherlands (A.C.B.); Department of Pediatrics, Elisabeth-TweeSteden Hospital, Tilburg, The Netherlands (C.C.A.D.K.); Department of Pediatrics, National Hospital Organization Kagoshima Medical Center, Japan (M.Y.); and Department of Pediatric Cardiology, Willem-Alexander Children's Hospital, University Medical Centre Leiden, The Netherlands (N.A.B.).
authors.forename: Nico A
authors.initials: NA
authors.lastname: Blom
mesh_terms: D000293:Adolescent; D000367:Age Factors; D002648:Child; D015331:Cohort Studies; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008133:Long QT Syndrome / Q000175:diagnosis* / Q000453:epidemiology* / Q000235:genetics; D008297:Male; D011379:Prognosis; D012189:Retrospective Studies; D012720:Severity of Illness Index; D012737:Sex Factors
keywords: aging; electrocardiography; long-QT syndrome; pediatrics; sex