射血分数保留的心力衰竭患者对药物诱导的QT间期延长反应增强。
Enhanced Response to Drug-Induced QT Interval Lengthening in Patients with Heart Failure with Preserved Ejection Fraction.
作者信息
Tisdale James E, Jaynes Heather A, Overholser Brian R, Sowinski Kevin M, Fisch Mark D, Rodgers Jo E, Aldemerdash Ahmed, Hsu Chia-Chi, Wang Nan, Muensterman Elena Tomaselli, Rao Vijay U, Kovacs Richard J
机构信息
Department of Pharmacy Practice, College of Pharmacy, Purdue University, Indianapolis, Indiana; Division of Clinical Pharmacology, Department of Medicine, School of Medicine, Indiana University, Indianapolis, Indiana.
Department of Pharmacy Practice, College of Pharmacy, Purdue University, Indianapolis, Indiana.
出版信息
J Card Fail. 2020 Sep;26(9):781-785. doi: 10.1016/j.cardfail.2020.06.008. Epub 2020 Jun 24.
BACKGROUND
Patients with heart failure (HF) with reduced ejection fraction demonstrate enhanced response to drug-induced QT interval lengthening and are at increased risk for torsades de pointes. The influence of HF with preserved ejection fraction (HFpEF) on response to drug-induced QT lengthening is unknown.
METHODS AND RESULTS
We administered intravenous ibutilide 0.003 mg/kg to 10 patients with HFpEF and 10 age- and sex-matched control subjects without HF. Serial 12-lead electrocardiograms were obtained for determination of QT intervals. Demographics, maximum serum ibutilide concentrations, area under the serum ibutilide concentration vs time curves, and baseline Fridericia-corrected QT (QT) (417 ± 14 vs 413 ± 15 ms, P = .54) were similar in the HFpEF and control groups. Area under the effect (QTvs time) curve (AUEC) from 0 to 1.17 hours during and following the ibutilide infusion was greater in the HFpEF group (519 ± 19 vs 497 ± 18 ms·h, P= .04), as was AUEC from 0 to 8.17 hours (3576 ± 125 vs 3428 ± 161 ms·h, P = .03) indicating greater QT interval exposure. Maximum QT (454 ± 15 vs 443 ± 22 ms, P = .18) and maximum percent increase in QT from baseline (8.2 ± 2.1 vs 6.7 ± 1.9%, P = .10) in the 2 groups were not significantly different.
CONCLUSIONS
HFpEF is associated with enhanced response to drug-induced QT interval lengthening.
背景
射血分数降低的心力衰竭（HF）患者对药物诱导的QT间期延长表现出增强的反应，且发生尖端扭转型室速的风险增加。射血分数保留的心力衰竭（HFpEF）对药物诱导的QT延长反应的影响尚不清楚。
方法和结果
我们对10例HFpEF患者和10例年龄及性别匹配的无HF对照受试者静脉注射0.003 mg/kg伊布利特。获取连续12导联心电图以测定QT间期。HFpEF组和对照组的人口统计学、伊布利特最大血清浓度、血清伊布利特浓度-时间曲线下面积以及基线弗里德里西亚校正QT（QTc）（417±14 vs 413±15 ms，P = 0.54）相似。伊布利特输注期间及之后0至1.17小时的效应（QTc-时间）曲线下面积（AUEC）在HFpEF组更大（519±19 vs 497±18 ms·h，P = 0.04），0至8.17小时的AUEC也是如此（（3576±125 vs 3428±161 ms·h，P = 0.03），表明QT间期暴露更多。两组的最大QTc（454±15 vs 443±22 ms，P = 0.18）和QTc相对于基线的最大百分比增加（8.2±2.1 vs 6.7±1.9%，P = 0.10）无显著差异。
结论
HFpEF与药物诱导的QT间期延长反应增强有关。
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