College of Pharmacy, Purdue University, Indianapolis, IN, United States.
College of Pharmacy, Purdue University, Indianapolis, IN, United States; Division of Clinical Pharmacology, School of Medicine, Indiana University, Indianapolis, IN, United States.
Int J Cardiol. 2025 Jan 1;418:132631. doi: 10.1016/j.ijcard.2024.132631. Epub 2024 Oct 10.
Heart failure (HF) with preserved ejection fraction (HFpEF) is associated with enhanced response to drug-induced QT interval lengthening. We determined the influence of HFpEF on drug-induced lengthening of dispersion of repolarization, a measure of proarrhythmic risk.
We administered intravenous ibutilide 0.003 mg/kg to 10 patients with HFpEF and 10 age- and sex-matched controls without HF. Twelve‑lead electrocardiograms were obtained prior to ibutilide and serially for 8 h post-ibutilide. Tpeak-Tend, a measure of dispersion of ventricular repolarization, and heart rate-corrected J-Tpeak (J-Tpeakc), representing early repolarization, were measured by an investigator blinded to study groups.
Baseline (pre-ibutilide) Tpeak-Tend and J-Tpeakc were not significantly different in the HFpEF and control groups. Maximum Tpeak-Tend was longer in the HFpEF group than in the control group (85 ± 10 vs 73 ± 8 ms, p = 0.01). Additionally, % change from baseline in Tpeak-Tend was greater in the HFpEF group [median (IQR) 17 (11) vs 8 (3)%, p = 0.003]. The area under the effect curve from 0 to 8 hours following ibutilide (including the 10-minute infusion) (AUEC) for Tpeak-Tend was also larger in the HFpEF group (600 ± 42 vs. 543 ± 49 ms•hr, p = 0.03). Maximum J-Tpeakc, % change from baseline in J-Tpeakc and AUEC for J-Tpeakc in the two groups were not significantly different.
HFpEF is associated with enhanced response to drug-induced increases in dispersion of repolarization.
射血分数保留的心力衰竭（HFpEF）与药物引起的 QT 间期延长的反应增强有关。我们确定了 HFpEF 对复极离散度（一种致心律失常风险的测量指标）药物诱导延长的影响。
我们给 10 例 HFpEF 患者和 10 例年龄和性别匹配的无 HF 对照患者静脉注射 0.003mg/kg 的伊布利特。在伊布利特前和伊布利特后 8 小时内获取 12 导联心电图。通过一位对研究组不知情的研究者测量 Tpeak-Tend（心室复极离散度的测量指标）和心率校正的 J-Tpeak（J-Tpeakc），代表早期复极。
HFpEF 组和对照组的基线（伊布利特前）Tpeak-Tend 和 J-Tpeakc 无显著差异。HFpEF 组的最大 Tpeak-Tend 长于对照组（85±10 比 73±8ms，p=0.01）。此外，HFpEF 组 Tpeak-Tend 从基线的变化百分比更大[中位数（IQR）17（11）比 8（3）%，p=0.003]。伊布利特后 0 至 8 小时（包括 10 分钟输注）的 Tpeak-Tend 效应曲线下面积（AUEC）在 HFpEF 组也更大（600±42 比 543±49ms·hr，p=0.03）。两组的最大 J-Tpeakc、J-Tpeakc 从基线的变化百分比和 J-Tpeakc 的 AUEC 没有显著差异。
HFpEF 与药物引起的复极离散度增加的反应增强有关。
