Cardiovascular Research Foundation, New York, New York, USA.
Mayo Clinic, Rochester, Minnesota.
JACC Heart Fail. 2021 May;9(5):360-370. doi: 10.1016/j.jchf.2021.01.015. Epub 2021 Apr 7.
The purpose of this study was to evaluate the effects of intravenous levosimendan on hemodynamics and 6-min walk distance (6MWD) in patients with pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF).
There are no proven effective treatments for patients with PH-HFpEF.
Patients with mean pulmonary artery pressure (mPAP) ≥35 mm Hg, pulmonary capillary wedge pressure (PCWP) ≥20 mm Hg, and LVEF ≥40% underwent 6MWD and hemodynamic measurements at rest, during passive leg raise, and supine cycle exercise at baseline and after an open-label 24-h levosimendan infusion (0.1 μg/kg/min). Hemodynamic responders (those with ≥4 mm Hg reduction of exercise-PCWP) were randomized (double blind) to weekly levosimendan infusion (0.075 to 0.1 ug/kg/min for 24 h) or placebo for 5 additional weeks. The primary end point was exercise-PCWP, and key secondary end points included 6MWD and PCWP measured across all exercise stages.
Thirty-seven of 44 patients (84%) met responder criteria and were randomized to levosimendan (n = 18) or placebo (n = 19). Participants were 69 ± 9 years of age, 61% female, and with resting mPAP 41.0 ± 9.3 mm Hg and exercise-PCWP 36.8 ± 11.3 mm Hg. Compared with placebo, levosimendan did not significantly reduce the primary end point of exercise-PCWP at 6 weeks (-1.4 mm Hg; 95% confidence interval [CI]: -7.8 to 4.8; p = 0.65). However, levosimendan reduced PCWP measured across all exercise stages (-3.9 ± 2.0 mm Hg; p = 0.047). Levosimendan treatment resulted in a 29.3 m (95% CI: 2.5 to 56.1; p = 0.033) improvement in 6MWD compared with placebo.
Six weeks of once-weekly levosimendan infusion did not affect exercise-PCWP but did reduce PCWP incorporating data from rest and exercise, in tandem with increased 6MWD. Further study of levosimendan is warranted as a therapeutic option for PH-HFpEF. (Hemodynamic Evaluation of Levosimendan in Patients With PH-HFpEF [HELP]; NCT03541603).
本研究旨在评估静脉给予左西孟旦对肺动脉高压伴射血分数保留心力衰竭（PH-HFpEF）患者血流动力学和 6 分钟步行距离（6MWD）的影响。
目前尚无针对 PH-HFpEF 患者的有效治疗方法。
平均肺动脉压（mPAP）≥35mmHg、肺毛细血管楔压（PCWP）≥20mmHg、左心室射血分数（LVEF）≥40%的患者在基线时和静息、被动抬腿和仰卧位踏车运动期间进行 6MWD 和血流动力学测量，之后接受为期 24 小时的开放标签左西孟旦输注（0.1μg/kg/min）。血流动力学应答者（运动 PCWP 降低≥4mmHg）随机（双盲）接受每周左西孟旦输注（24 小时内 0.075 至 0.1μg/kg/min）或安慰剂治疗 5 周。主要终点为运动 PCWP，关键次要终点包括所有运动阶段测量的 6MWD 和 PCWP。
44 例患者中有 37 例（84%）符合应答标准，并被随机分配至左西孟旦组（n=18）或安慰剂组（n=19）。参与者年龄为 69±9 岁，61%为女性，静息 mPAP 为 41.0±9.3mmHg，运动 PCWP 为 36.8±11.3mmHg。与安慰剂相比，左西孟旦在 6 周时并未显著降低主要终点运动 PCWP（-1.4mmHg；95%置信区间：-7.8 至 4.8；p=0.65）。然而，左西孟旦降低了所有运动阶段的 PCWP（-3.9±2.0mmHg；p=0.047）。与安慰剂相比，左西孟旦治疗使 6MWD 改善了 29.3m（95%置信区间：2.5 至 56.1；p=0.033）。
每周一次左西孟旦输注 6 周并未影响运动 PCWP，但与安慰剂相比，左西孟旦确实降低了包括静息和运动时在内的 PCWP，同时增加了 6MWD。作为 PH-HFpEF 的治疗选择，进一步研究左西孟旦是有必要的。（左西孟旦对 PH-HFpEF 患者血流动力学的评估 [HELP]；NCT03541603）。
