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. 2015 Nov;35(11):717-24. doi: 10.1007/s40261-015-0328-0.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers
  • Clinical Trials as Topic
  • Dihydropyridines / adverse effects*
  • Electrocardiography / drug effects*
  • Female
  • Fluoroquinolones / adverse effects*
  • Humans
  • Imidazoles / adverse effects*
  • Indoles / adverse effects*
  • Male
  • Moxifloxacin
  • Naltrexone / adverse effects
  • Naltrexone / analogs & derivatives*
  • Pharmaceutical Preparations
  • Sotalol / adverse effects*

Substances

  • 3-(1-(2-(1-acetyl-2,3-dihydro-1H-indol-3-yl)ethyl)-3,6-dihydro-2H-pyridin-4-yl)-6-chloro-1H-indole
  • Biomarkers
  • Dihydropyridines
  • Fluoroquinolones
  • Imidazoles
  • Indoles
  • Pharmaceutical Preparations
  • Naltrexone
  • Sotalol
  • sertindole
  • nalmefene
  • Moxifloxacin