The transpulmonary ratio of endothelin 1 is elevated in patients with preserved left ventricular ejection fraction and combined pre- and post-capillary pulmonary hypertension
The transpulmonary ratio of endothelin 1 is elevated in patients with preserved left ventricular ejection fraction and combined pre- and post-capillary pulmonary hypertension
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DOI：
10.1177/2045893217745019
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发表时间：
2018-01-09
影响因子：
2.6
通讯作者：
Monahan, Ken
中科院分区：
文献类型：
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作者：
Meoli, David F.;Su, Yan Ru;Monahan, Ken
左心室疾病合并肺动脉高压（PH-LHD）与发病率和死亡率增加相关，特别是在合并毛细血管前和后PH（Cpc-PH）的患者中。PH-LHD的潜在机制尚不完全清楚，特别是对于左心室射血分数（LVEF）保留的个体。我们假设，代表已知对肺循环有影响的信号传导途径的生物标志物的经皮给药浓度可以提供对LVEF保留患者PH-LHD分子病因学的深入了解。从左室射血分数正常的门诊患者的肺动脉（PA）和楔形位置收集血液样本，并进行右心导管检查。对血流动力学描记进行审查，将患者分为无PH（n=23）或PH-LHD（n=22）。生物标志物的穿髓比（TPR）计算为楔形和PA浓度的商。与无PH或孤立毛细血管后PH（Ipc-PH，n = 12）相比，Cpc-PH（n=10）中内皮素1（ET-1）的TPR升高;各组间cAMP和cGMP TPR无差异。Cpc-PH组ET-1 TPR增高是由于楔区ET-1浓度增高所致。在Cpc-PH患者中，肺血管阻力（PVR）仅与楔形ET-1密切相关。在LVEF正常和Cpc-PH的患者中，由于楔形ET-1升高，ET-1 TPR高于无PH或Ipc-PH的患者。PVR和楔形ET-1之间的强相关性仅在Cpc-PH组中观察到，可能表明这些患者中肺血管对ET-1的反应性增加。这些发现暗示肺ET-1升高是该人群中Cpc-PH发展的标志物和潜在促进因素。
Pulmonary hypertension complicating left heart disease (PH-LHD) is associated with increased morbidity and mortality, especially in patients who develop combined pre- and post-capillary PH (Cpc-PH). Mechanisms underlying PH-LHD are incompletely understood, particularly for individuals with preserved left ventricular ejection fraction (LVEF). We hypothesized that transpulmonary concentrations of biomarkers representing signaling pathways with known effects on the pulmonary circulation could provide insight into the molecular etiology of PH-LHD in patients with preserved LVEF. Blood samples were collected from the pulmonary artery (PA) and wedge positions of outpatients with normal LVEF referred for right heart catheterization. Hemodynamic tracings were reviewed to classify patients as no PH (n=23) or PH-LHD (n=22). A biomarker's transpulmonary ratio (TPR) was calculated as the quotient of wedge and PA concentrations. The TPR of endothelin 1 (ET-1) was elevated in Cpc-PH (n=10) compared to no PH or isolated post-capillary PH (Ipc-PH, n=12); cAMP and cGMP TPRs were not different among groups. Higher ET-1 TPR in Cpc-PH was due to increased wedge ET-1 concentration. Pulmonary vascular resistance (PVR) strongly correlated with wedge ET-1 exclusively in Cpc-PH patients. In patients with normal LVEF and Cpc-PH, ET-1 TPR is higher, due to elevated wedge ET-1, compared to those without PH or with Ipc-PH. Strong correlation between PVR and wedge ET-1, observed only in the Cpc-PH group, may suggest increased pulmonary vascular responsiveness to ET-1 in these patients. These findings implicate elevated pulmonary ET-1 as a marker of, and a potential contributor to, development of Cpc-PH in this population.