Global Pulmonary Vascular Remodeling in Pulmonary Hypertension Associated With Heart Failure and Preserved or Reduced Ejection Fraction.
Global Pulmonary Vascular Remodeling in Pulmonary Hypertension Associated With Heart Failure and Preserved or Reduced Ejection Fraction.
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DOI：
10.1161/circulationaha.117.031608
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发表时间：
2018-04-24
期刊：
影响因子：
37.8
通讯作者：
Redfield MM
中科院分区：
文献类型：
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作者：
Fayyaz AU;Edwards WD;Maleszewski JJ;Konik EA;DuBrock HM;Borlaug BA;Frantz RP;Jenkins SM;Redfield MM
我们假设心力衰竭（HF）患者的肺静脉高压导致肺静脉重构，而肺静脉重构的严重程度与心力衰竭患者的肺动脉高压（PH）的严重程度相关。将PH值（HF-PH，肺动脉收缩压(PASP)≥40 mmHg）的HF患者（n=108，保留53例，射血分数降低55例）与正常对照（n=12）和原发性肺静脉闭塞疾病（PVOD, n=17）患者进行比较。在尸检（对照，HF-PH和7 PVOD）或手术（10 PVOD）的肺标本中，对所有可分析的动脉（n=4,949），静脉（n=7,630）和小不确定血管（IV, n=2,168）进行定量组织形态学测量，以确定相对于外径的%内侧厚度（%MT）[动脉]和%内膜厚度（%IT）[动脉，静脉和IV]。平均动脉MT %（对照组6.9,HF-PH 11.0, PVOD 15.0）；动脉IT %（对照组4.9,HF-PH 14.9, PVOD 31.1）；静脉%IT（对照组14.0;HF-PH 24.9; PVOD 43.9）和静脉%IT（对照组10.6;HF-PH 25.8; PVOD 50.0）的HF-PH高于对照组（p<0.0001），低于PVOD （p≤0.005）。HF-PH组PASP (mmHg)（中位数59 [IQR 50-70]）低于PVOD组（中位数91[82-103]）。PASP与动脉%MT （r=0.41）和动脉%IT （r=0.35）相关，但与静脉%IT （r=0.49）和静脉%IT （r=0.55）相关性更强（均p<0.0001）。在调整了动脉%MT和%IT后，PASP与静脉或静脉%IT之间的相关性仍然显著，并且不因HF类型而变化。在右心导管患者（30 HF-PH; 14 PVOD）中，经肺梯度与肺血管重构之间存在类似的关联，在数值上与静脉和静脉IT的关联更强。HF-PH合并右室功能不全患者的PASP略高，但肺血管重构并不严重。肺血管重构的严重程度与肺弥散能力的降低有关。在HF中，PH与整体肺血管重构相关，但PH的严重程度与静脉和小静脉内膜增厚相关性最强，与PVOD中观察到的模式相似。这些发现扩大了我们对HF中PH病理生物学的理解。
We hypothesized that pulmonary venous hypertension in heart failure (HF) leads to predominate remodeling of pulmonary veins and that the severity of venous remodeling is associated with the severity of pulmonary hypertension (PH) in HF. Patients with HF (n=108; 53 preserved and 55 reduced ejection fraction) with PH (HF-PH; pulmonary artery systolic pressure (PASP) ≥ 40 mmHg) were compared to normal Controls (n=12) and patients with primary pulmonary veno-occlusive disease (PVOD; n=17). In lung specimens from autopsy (Control, HF-PH and 7 PVOD) or surgery (10 PVOD), quantitative histomorphometry was performed in all analyzable arteries (n=4,949), veins (n=7,630) and small indeterminate vessels (IV, n=2,168) to define % medial thickness (%MT) [arteries] and % intimal thickness (%IT) [arteries, veins and IV] relative to external diameter. The average arterial %MT (Control 6.9; HF-PH 11.0; PVOD 15.0); arterial %IT (Control 4.9; HF-PH 14.9; PVOD 31.1); venous %IT (Control 14.0; HF-PH 24.9; PVOD 43.9) and IV %IT (Control 10.6; HF-PH 25.8; PVOD 50.0) in HF-PH were higher than Controls (p<0.0001 for all) but lower than PVOD (p≤0.005 for all). PASP (mmHg) was lower in HF-PH (median 59 [IQR 50-70]) than PVOD (91 [82-103]). PASP correlated with arterial %MT (r=0.41) and arterial %IT (r=0.35) but more strongly with venous %IT (r=0.49) and IV %IT (r=0.55) (p<0.0001 for all). Associations between PASP and venous or IV %IT remained significant after adjusting for arterial %MT and %IT and did not vary by HF type. In patients with right heart catheterization (30 HF-PH; 14 PVOD) similar associations between the transpulmonary gradient and pulmonary vascular remodeling existed, with numerically stronger associations for venous and IV %IT. While the PASP was slightly higher in HF-PH patients with right ventricular dysfunction, pulmonary vascular remodeling was not more severe. Pulmonary vascular remodeling severity was associated with reductions in the diffusing capacity of the lungs. In HF, PH is associated with global pulmonary vascular remodeling but the severity of PH correlates most strongly with venous and small IV intimal thickening, similar to the pattern observed in PVOD. These findings expand our understanding of the pathobiology of PH in HF.