title: QT dynamics during treatment with sertindole.
abstract: OBJECTIVE
  Sertindole is a nonsedating atypical antipsychotic drug with low propensity to cause extrapyramidal side effects but it has been associated with a 20 ms QTc prolongation and increased risk of cardiac events. It is uncertain whether this drug-induced increase in cardiac risk might also be revealed by dynamic measures of the QT interval such as the ratio of QT variability to heart rate variability (variability ratio [VR]). The aim of this study was to investigate the effect of sertindole on QT dynamics.
  
  
  METHODS
  QTc and the VR were assessed in an observational study using 24-hour Holter monitoring at baseline and after 3 weeks of treatment with sertindole 16 mg. The VR was calculated by dividing the standard deviation of QT intervals with the standard deviation of heart rates. Outcome measures were compared using paired t-test.
  
  
  RESULTS
  A total of 18 patients participated in the study, two were excluded from further analysis due to low amplitude of the T-wave. When patients were shifted to sertindole, the VR increased from 0.192 (SD 0.045) to 0.223 (SD 0.061), p = 0.02. The QTcF interval increased from 388 (SD 16) to 403 ms (SD 14), p = 0.002. There was no difference in heart rate 78 bpm (SD 8) versus 80 bpm (SD 10), p = 0.3 or heart rate variability (SDNN) 127 (SD 40) versus 115 ms (SD 45), p = 0.4.
  
  
  CONCLUSIONS
  Sertindole was associated with 19 ms QTc prolongation and an increased ratio of QT variability to heart rate variability. Both measures may contribute to the increased cardiovascular mortality found with sertindole.
authors: Clinical Department of medicine, Centre for Schizophrenia, Aalborg Psychiatric Hospital, Brandevej 5, 9220 Aalborg Ø, Denmark, UK.
authors: Jimmi
authors: J
authors: Nielsen
authors: Laboratory of Experimental Cardiology, Danish National Foundation Centre of Arrhythmias, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark, UK.
authors: Fan
authors: F
authors: Wang
authors: Medical Informatics Group (MI), Department of Health Science and Technology, Aalborg University, Aalborg, Denmark, UK.
authors: Claus
authors: C
authors: Graff
authors: Laboratory of Experimental Cardiology, Danish National Foundation Centre of Arrhythmias, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark, UK.
authors: Jørgen K
authors: JK
authors: Kanters
keywords: QT dynamics; QT interval variability; QTc; SDNN; cardiac safety; heart rate variability; sertindole; variability ratio
references: Expert Opin Pharmacother. 2014 Sep;15(13):1943-53
references: 25084209
references: Clin Pharmacol Ther. 2012 Jul;92(1):72-9
references: 22588605
references: Acta Psychiatr Scand. 2010 Nov;122(5):341-4
references: 21029051
references: Clin Pharmacol Ther. 2012 Feb;91(2):281-8
references: 22205197
references: Eur Psychiatry. 2012 Apr;27(3):213-8
references: 21316200
references: Ann Noninvasive Electrocardiol. 2004 Jan;9(1):3-11
references: 14731210
references: Acta Psychiatr Scand. 2010 May;121(5):385-8
references: 20085555
references: Eur Neuropsychopharmacol. 2009 Oct;19(10):702-7
references: 19457646
references: Am J Psychiatry. 2011 Feb;168(2):193-201
references: 21041245
references: Heart Rhythm. 2005 Apr;2(4):357-64
references: 15851335
references: Expert Opin Pharmacother. 2010 Dec;11(18):3053-64
references: 21080854
references: J Clin Pharmacol. 2009 Nov;49(11):1331-42
references: 19843657
references: Schizophr Res. 2007 Sep;95(1-3):115-23
references: 17630259
references: Acta Psychiatr Scand. 2010 Nov;122(5):345-55
references: 20384598
references: J Clin Psychopharmacol. 2012 Apr;32(2):173-8
references: 22367659
references: N Engl J Med. 2009 Jan 15;360(3):225-35
references: 19144938
references: J Electrocardiol. 2009 Nov-Dec;42(6):555-60
references: 19643432
references: Depress Anxiety. 2002;16(3):93-9
references: 12415532
references: Expert Opin Drug Saf. 2013 May;12(3):321-6
references: 23432404
references: J Clin Psychopharmacol. 2001 Feb;21(1):8-13
references: 11199953
references: Drug Saf. 2009;32(7):599-611
references: 19530746
references: Am J Psychiatry. 2013 Dec;170(12):1468-76
references: 24306340
references: Expert Opin Drug Saf. 2011 May;10(3):341-4
references: 21504386
references: CNS Drugs. 2011 Jun 1;25(6):473-90
references: 21649448
references: J Electrocardiol. 2008 Nov-Dec;41(6):603-8
references: 18822425
references: Depress Anxiety. 2000;11(3):126-30
references: 10875054
references: Neuropsychiatr Dis Treat. 2010 Sep 07;6:429-41
references: 20856607
references: Eur J Clin Invest. 2001 Jul;31(7):555-7
references: 11454006
references: Aust N Z J Psychiatry. 2012 Aug;46(8):793-4
references: 22492267
references: J Clin Psychopharmacol. 2008 Dec;28(6):694-8
references: 19011440
references: Drug Des Devel Ther. 2010 Sep 07;4:187-201
references: 20856845
references: Expert Opin Drug Saf. 2012 Nov;11(6):1047-62
references: 22992213
references: Schizophr Res. 2009 Sep;113(2-3):176-80
references: 19570654
references: Circ Cardiovasc Genet. 2011 Oct;4(5):516-22
references: 21836130