Comparison of 5 methods of QT interval measurements on electrocardiograms from a thorough QT/QTc study: effect on assay sensitivity and categorical outliers

J Electrocardiol. 2011 Mar-Apr;44(2):96-104. doi: 10.1016/j.jelectrocard.2010.11.010. Epub 2011 Jan 15.


Introduction: We studied moxifloxacin-induced QT prolongation and proportion of categorical QTc outliers when 5 methods of QT measurement were used to analyze electrocardiograms (ECGs) from a thorough QT study.

Methods: QT interval was measured by the threshold, tangent, superimposed median beat, automated global median beat, and longest QT methods in a central ECG laboratory in 2730 digital ECGs from 39 subjects during placebo and moxifloxacin treatment.

Results: All 5 methods were able to demonstrate statistically significant moxifloxacin-induced QTcF prolongation. However, lower bound of 95% 1-sided confidence interval of QTcF prolongation did not exceed 5 milliseconds with the longest QT method. More QTcF outliers were observed with the longest QT and tangent methods, whereas the other 3 methods were comparable. QTcF values greater than 500 milliseconds were observed only with moxifloxacin by the tangent method, and with moxifloxacin and placebo by the longest QT method.

Conclusion: The method of QT measurement must be considered when interpreting individual thorough QT/QTc studies.

Publication types

  • Comparative Study
  • Evaluation Study

MeSH terms

  • Algorithms*
  • Animals
  • Artifacts*
  • Diagnosis, Computer-Assisted / methods*
  • Electrocardiography / methods*
  • Heart Rate
  • Long QT Syndrome / diagnosis*
  • Observer Variation
  • Reproducibility of Results
  • Sensitivity and Specificity