奎尼丁诱发尖端扭转型室性心动过速风险中性别差异潜在机制的研究。
Investigation of potential mechanisms of sex differences in quinidine-induced torsade de pointes risk.
作者信息
Vicente Jose, Simlund Jacob, Johannesen Lars, Sundh Frida, Florian Jeffry, Ugander Martin, Wagner Galen S, Woosley Raymond L, Strauss David G
机构信息
Division of Biomedical Physics, Office of Science and Engineering Laboratories, Center for Device and Radiological Health, US Food and Drug Administration, Silver Spring, MD, USA; Division of Cardiovascular and Renal Products, Office of New Drugs, Center of Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA; BSICoS Group, Aragón Institute for Engineering Research (I3A), IIS Aragón, University of Zaragoza, Zaragoza, Spain.
Duke Clinical Research Institute, Durham, NC, USA; Department of Clinical Physiology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
出版信息
J Electrocardiol. 2015 Jul-Aug;48(4):533-8. doi: 10.1016/j.jelectrocard.2015.03.011. Epub 2015 Mar 12.
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.
引言
心电图指标Tpeak-Tend已被提议作为复极离散度的标志物，并且可能是比QTc延长更强的尖端扭转型室速风险预测指标。
方法与结果
我们评估了奎尼丁诱导的Tpeak-Tend延长在女性中是否比男性更显著。女性中QTc延长与奎尼丁浓度之间的关系比男性更显著（38±10对28±9毫秒/微克/毫升，p=0.02），但Tpeak-Tend延长无差异（39±13对32±13毫秒/微克/毫升，p=0.21）。在峰值浓度与最大QTc及Tpeak-Tend延长之间存在延迟（滞后），且男性血清奎尼丁浓度有高于女性的趋势。控制滞后因素的分析显示，QTc无性别差异（55±18对43±19毫秒/微克/毫升，p=0.14），同时Tpeak-Tend仍无性别差异（61±22对55±21毫秒/微克/毫升，p=0.49）。
结论
女性奎尼丁诱导的Tpeak-Tend延长并不比男性更显著。本研究中滞后及血清奎尼丁浓度的性别差异可能导致了奎尼丁诱导的QTc延长的性别差异。
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