Investigation of potential mechanisms of sex differences in quinidine-induced torsade de pointes risk

J Electrocardiol. Jul-Aug 2015;48(4):533-8. doi: 10.1016/j.jelectrocard.2015.03.011. Epub 2015 Mar 12.

Abstract

Introduction: The electrocardiographic index Tpeak-Tend has been proposed as a marker of dispersion of repolarization and may be a stronger predictor of torsade de pointes risk than QTc prolongation.

Methods and results: We assessed whether quinidine-induced Tpeak-Tend prolongation is greater in women than men. The relationship between QTc prolongation and quinidine concentration was greater in women than men (38 ± 10 vs. 28 ± 9 ms/μg/ml, p=0.02), but there was no difference for Tpeak-Tend prolongation (39 ± 13 vs. 32 ± 13 ms/μg/ml, p=0.21). There was a delay (hysteresis) between peak concentration and both maximum QTc and Tpeak-Tend prolongation and a trend toward higher serum quinidine concentration in men than women. Analysis controlling for hysteresis showed no sex difference for QTc (55 ± 18 vs. 43 ± 19 ms/μg/ml, p=0.14), without changing the lack of sex difference with Tpeak-Tend (61 ± 22 vs. 55 ± 21 ms/μg/ml, p=0.49).

Conclusions: Women do not have a greater quinidine-induced Tpeak-Tend prolongation than men. Sex differences in hysteresis and serum quinidine concentration in this study may have contributed to sex differences in quinidine-induced QTc prolongation.

Keywords: QTc prolongation; Quinidine; Sex differences; T wave notching; Torsade de pointes.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Anti-Arrhythmia Agents / administration & dosage
  • Anti-Arrhythmia Agents / adverse effects
  • Anti-Arrhythmia Agents / pharmacokinetics
  • Dose-Response Relationship, Drug
  • Electrocardiography / drug effects*
  • Feasibility Studies
  • Female
  • Humans
  • Male
  • Quinidine / administration & dosage
  • Quinidine / adverse effects*
  • Quinidine / blood*
  • Reproducibility of Results
  • Risk Assessment / methods
  • Sensitivity and Specificity
  • Sex Factors
  • Single-Blind Method
  • Torsades de Pointes / blood*
  • Torsades de Pointes / chemically induced*
  • Torsades de Pointes / diagnosis
  • Young Adult

Substances

  • Anti-Arrhythmia Agents
  • Quinidine