European Journal of Clinical Pharmacology

, Volume 74, Issue 2, pp 183–191 | Cite as

Risk factors for QTc interval prolongation

  • Charlotte P. M. Heemskerk
  • Marieke Pereboom
  • Karlijn van Stralen
  • Florine A. Berger
  • Patricia M. L. A. van den Bemt
  • Aaf F. M. Kuijper
  • Ruud T. M. van der Hoeven
  • Aukje K. Mantel-Teeuwisse
  • Matthijs L. Becker



Prolongation of the QTc interval may result in Torsade de Pointes, a ventricular arrhythmia. Numerous risk factors for QTc interval prolongation have been described, including the use of certain drugs. In clinical practice, there is much debate about the management of the risks involved. In this study, we quantified the effect of these risk factors on the length of the QTc interval.


We analyzed all ECGs that were taken during routine practice between January 2013 and October 2016 in the Spaarne Gasthuis, a general teaching hospital in the Netherlands. We collected laboratory values in the week before the ECG recording and the drugs prescribed. For the identification of risk factors, we used multilevel linear regression analysis to correct for multiple ECG recordings per patient.


We included 133,359 ECGs in our study, taken in 40,037 patients. Patients using one QT-prolonging drug had a 11.08 ms (95% CI 10.63–11.52; p < 0.001) longer QTc interval. Patients using two QT-prolonging drugs had a 3.04 ms (95% CI 2.06–4.02; p < 0.001) increase in the QTc interval compared to patients using one QT-prolonging drug. Women had a longer QTc interval compared to men (16.30 ms 95% CI 14.59–18.01; p < 0.001). The QTc interval increased with increasing age, but the difference between men and women diminished. Other independent risk factors that significantly prolonged the QTc interval with at least 10 ms were hypokalemia, hypocalcemia, and the use of loop diuretics.


We identified and quantified various risk factors for QTc interval prolongation.


Long QT syndrome/chemically induced Electrocardiography Risk assessment Drug-related side effects and adverse reactions Hospital information systems 



We would like to thank Pieter G. Postema for his useful comments in preparing this paper.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

For this type of study, formal consent is not required.

Supplementary material

228_2017_2381_MOESM1_ESM.docx (78 kb)
ESM 1 (DOCX 78 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  • Charlotte P. M. Heemskerk
    • 1
    • 2
  • Marieke Pereboom
    • 1
  • Karlijn van Stralen
    • 3
  • Florine A. Berger
    • 4
  • Patricia M. L. A. van den Bemt
    • 4
  • Aaf F. M. Kuijper
    • 3
  • Ruud T. M. van der Hoeven
    • 1
  • Aukje K. Mantel-Teeuwisse
    • 2
  • Matthijs L. Becker
    • 1
  1. 1.Pharmacy Foundation of Haarlem HospitalsHaarlemThe Netherlands
  2. 2.Division of Pharmacoepidemiology & Clinical PharmacologyUtrecht Institute for Pharmaceutical Sciences (UIPS)UtrechtThe Netherlands
  3. 3.Spaarne GasthuisHoofddorpthe Netherlands
  4. 4.Department of Hospital PharmacyErasmus University Medical CentreRotterdamthe Netherlands

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