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The T-peak–T-end Interval as a Marker of Repolarization Abnormality: A Comparison with the QT Interval for Five Different Drugs

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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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Authors and Affiliations

  1. Department of Health Science and Technology, Aalborg University, Frederik Bajers vej-7 C1, 9220, Aalborg, Denmark

    Tanveer A. Bhuiyan, Claus Graff, Jacob Melgaard, Egon Toft & Johannes J. Struijk

  2. Laboratory of Experimental Cardiology, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

    Jørgen K. Kanters

  3. Department of Cardiology, Herlev and Gentofte University Hospitals, Copenhagen, Denmark

    Jørgen K. Kanters

  4. Department of Clinical Medicine, Aalborg University, Aalborg, Denmark

    Jimmi Nielsen

  5. Psychiatry, Aalborg University Hospital, Aalborg, Denmark

    Jimmi Nielsen

  6. Global Pharmacovigilance, H. Lundbeck A/S, Copenhagen, Denmark

    Jørgen Matz

  7. College of Medicine, Qatar University, Doha, Qatar

    Egon Toft

Authors
  1. Tanveer A. Bhuiyan
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  2. Claus Graff
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  3. Jørgen K. Kanters
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  4. Jimmi Nielsen
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  5. Jacob Melgaard
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  7. Egon Toft
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  8. Johannes J. Struijk
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Corresponding author

Correspondence to Tanveer A. Bhuiyan.

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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

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