Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center and School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center and School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Heart Lung. 2021 May-Jun;50(3):442-446. doi: 10.1016/j.hrtlng.2021.02.004. Epub 2021 Feb 23.
Mechanisms of exercise intolerance in patients with heart failure with preserved ejection fraction (HFpEF) are not well understood. Pulmonary hypertension, a common accompaniment in patients with HFpEF, is associated with poor outcomes. While Endothelin -1 (ET-1) plays a mechanistic role in pulmonary hypertension, its role in exercise intolerance in HFpEF is not well established.
To explore the association between plasma ET-1 levels and maximal oxygen consumption (pVO2), and their changes over 24 weeks in HFpEF.
This is a post-hoc analysis of the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction (RELAX) trial. We performed linear regressions to assess the relationship between plasma ET-1 and pVO2. We also used linear regressions to determine whether ET-1 was associated with change in peak VO2 (ΔpVO).
A total of 210 patients were included. Baseline plasma ET-1 levels were associated with older age, higher NT-proBNP levels, higher serum creatinine levels, and higher prevalence of atrial fibrillation. Patients with higher ET1 levels also had higher plasma galectin-3 and CITP levels. After multiple adjustments, baseline ET1 levels were associated with lower pVO (β -0.927, SE 0.196, p < 0.001). Over 24 weeks, the change in ET1 levels was associated with the change in pVO2 (multivariable adjusted β -0.415, SE 0.115, p = 0.018). Baseline ET1 levels did not modify the effect of sildenafil on change in peak VO.
Plasma ET1 levels are significantly associated with lower exercise oxygen consumption both at baseline and longitudinally over 24 weeks. Future studies should explore Endothelin-1 antagonism to improve exercise tolerance in HFpEF.
射血分数保留的心力衰竭（HFpEF）患者运动不耐受的机制尚不清楚。肺动脉高压是 HFpEF 患者的常见伴随疾病，与不良预后相关。虽然内皮素-1（ET-1）在肺动脉高压中起机械作用，但它在 HFpEF 中运动不耐受的作用尚未得到充分证实。
探讨 HFpEF 患者血浆 ET-1 水平与最大耗氧量（pVO2）之间的关系及其在 24 周内的变化。
这是磷酸二酯酶-5 抑制剂改善射血分数保留心力衰竭患者临床状况和运动能力（RELAX）试验的事后分析。我们进行线性回归分析，以评估血浆 ET-1 与 pVO2 之间的关系。我们还使用线性回归来确定 ET-1 是否与峰值 VO2 的变化（ΔpVO）相关。
共纳入 210 例患者。基线血浆 ET-1 水平与年龄较大、NT-proBNP 水平较高、血清肌酐水平较高以及心房颤动的患病率较高有关。ET1 水平较高的患者也具有较高的血浆半乳糖凝集素-3 和 CITP 水平。经多次调整后，基线 ET1 水平与较低的 pVO 相关（β -0.927，SE 0.196，p < 0.001）。在 24 周内，ET1 水平的变化与 pVO2 的变化相关（多变量调整后的β -0.415，SE 0.115，p = 0.018）。基线 ET1 水平不能改变西地那非对峰值 VO 变化的影响。
血浆 ET1 水平与基线时和 24 周内的运动耗氧量显著相关。未来的研究应探索内皮素-1 拮抗剂改善 HFpEF 的运动耐量。
