Association between Tpeak-Tend interval and QT prolongation: a study of sertindole and sotalol

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Saeed Shakibfar, Johannes J. Struijk, Jørgen K. Kanters, Jimmi Nielsen, Samuel Schmidt, Claus Graff

The electrocardiographic interval between the peak and the end of the T-wave (Tpe) is believed to be an arrhythmic risk marker. However, there are also a number of reports that are inconsistent with the usefulness of Tpe for identifying abnormal repolarization. This study was designed to investigate how the Tpe prolongation is correlated to a prolonged QT interval, induced by IKr-blockers. The study included two data sets. A first group of 21 healthy subjects received 160 mg and 320 mg doses of d,l-sotalol. The second group, of 40 patients with schizophrenia, was switched to 16 mg sertindole treatment. The Fridericia corrected QT prolongations (QTcF) and the mean Tpe changes (∆Tpe) were: d,l-sotalol 160 mg: ∆QTcF=29 ms & ∆Tpe=4.7 ms, 320 mg: ∆QTcF=51 ms & ∆Tpe=6.2 ms, sertindole 16 mg: ∆QTcF=17 ms & ∆Tpe=8.5 ms. There were low correlations (r) between ∆QTcF and ∆Tpe in both d,l-sotalol groups and sertindole group. Given the lack of linear relationship between Tpe and QT in response to potential torsadogenic drugs, this study raises doubt about the usefulness of Tpe as a biomarker for repolarization changes and torsadogenic potential in drug safety studies.
Original languageEnglish
JournalPharmacology, Drug Development & Therapeutics
Volume1
Issue number2
Pages (from-to)1-6
Number of pages6
ISSN2399-7389
DOIs
Publication statusPublished - 2017

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