TY - JOUR
T1 - Association between Tpeak-Tend interval and QT prolongation
T2 - a study of sertindole and sotalol
AU - Shakibfar, Saeed
AU - Struijk, Johannes J.
AU - Kanters, Jørgen K.
AU - Nielsen, Jimmi
AU - Schmidt, Samuel
AU - Graff, Claus
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
U2 - 10.15761/PDDT.1000106
DO - 10.15761/PDDT.1000106
M3 - Review
SN - 2399-7389
VL - 1
SP - 1
EP - 6
JO - Pharmacology, Drug Development & Therapeutics
JF - Pharmacology, Drug Development & Therapeutics
IS - 2
ER -