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

• Published in: Journal of electrocardiology 2015-07, Vol.48 (4), p.533-538
• Main Authors: Vicente, Jose, MS, Simlund, Jacob, Johannesen, Lars, MS, Sundh, Frida, Florian, Jeffry, PhD, Ugander, Martin, MD, PhD, Wagner, Galen S., MD, Woosley, Raymond L., MD, PhD, Strauss, David G., MD, PhD
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Anti-Arrhythmia Agents - administration & dosage; Anti-Arrhythmia Agents - adverse effects; Anti-Arrhythmia Agents - pharmacokinetics; Cardiovascular; Dose-Response Relationship, Drug; Electrocardiography - drug effects; Feasibility Studies; Female; Humans; Male; Medicin och hälsovetenskap; QTc prolongation; Quinidine; Quinidine - administration & dosage; Quinidine - adverse effects; Quinidine - blood; Reproducibility of Results; Risk Assessment - methods; Sensitivity and Specificity; Sex differences; Sex Factors; Single-Blind Method; T wave notching; Torsade de pointes; Torsades de Pointes - blood; Torsades de Pointes - chemically induced; Torsades de Pointes - diagnosis; Young Adult
• ISSN: 0022-0736; 1532-8430; 1532-8430
• DOI: 10.1016/j.jelectrocard.2015.03.011

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.