Abstract
Background and Objective
The T-peak to T-end (TpTe) interval has been suggested as an index of transmural dispersion and as a marker of drug-induced abnormal repolarization. In this study, we investigate the relation between TpTe and the QT interval.
Methods
Electrocardiograms (ECGs) from five different drugs (sotalol, sertindole, moxifloxacin, nalmefene, and Lu 38-135) and from a placebo group were analyzed. Semi-automatic measurements of T-peak, T-end, and QRS onset were obtained. The TpTe/QT ratio was calculated to investigate the proportional relationship of QT and TpTe.
Results
Although a significant increase of both TpTe and QT from baseline is apparent with QT-prolonging drugs, the TpTe/QT ratio remained the same at baseline and after drug administration, thus indicating that prolongation of TpTe is just a fractional part of total QT prolongation. In the presence of notched or flattened T-waves, the uncertainty associated with measurement of the TpTe interval increases. The errors in TpTe for individual subjects may be substantial, thus complicating the use of TpTe for follow-up of individuals.
Conclusions
The duration of the QT interval and TpTe are closely related. Drugs appear to prolong the TpTe interval as a predictable fraction of the total QT prolongation.
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Funding
This work was supported by the Danish Council for Strategic Research (HEARTSAFE Grant Number: 10-092799).
Conflict of interest
Jimmi Nielsen has received research grants from H. Lundbeck A/S and Pfizer and speaking fees from H. Lundbeck, Hemocue, and Bristol Myers Squibb. All other authors (Tanveer A Bhuiyan, Claus Graff, Jørgen K Kanters, Jørgen Matz, Jacob Melgaard, Egon Toft and Johannes Struijk) declare no conflict of interest.
Ethical approval
All six drug studies were in accordance with the Helsinki declaration. Ethical approvals were sought before each study.
Informed consent
Subjects from the studies sotalol, lu 35-138, moxifloxacin, nalmefene and Placebo provided written informed consent. However, informed consent was not required for the sertindole study as decided by the North Jutland Committee on Biomedical Research ethics, since the ECGs were indicated for therapeutic monitoring as recommended for patients treated with sertindole.
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Bhuiyan, T.A., Graff, C., Kanters, J.K. et al. The T-peak–T-end Interval as a Marker of Repolarization Abnormality: A Comparison with the QT Interval for Five Different Drugs. Clin Drug Investig 35, 717–724 (2015). https://doi.org/10.1007/s40261-015-0328-0
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DOI: https://doi.org/10.1007/s40261-015-0328-0