Abstract：
OBJECTIVE: Patients with pulmonary hypertension (PH) are grouped based upon clinical and haemodynamic characteristics. Groups 2 (G2, left heart disease [LHD]) and 3 (G3, lung disease or hypoxaemia) are most common. Many patients display overlapping characteristics of heart and lung disease (G2-3), but this group is not well-characterized.
RESULTS: Patients with PH enrolled in the prospective, NHLBI-sponsored PVDOMICS network underwent intensive clinical, biomarker, imaging, gas exchange and exercise phenotyping. Patients with pure G2, pure G3, or overlapping G2-3 PH were compared across multiple phenotypic domains. Of all patients with predominant G2 (n = 136), 66 (49%) were deemed to have secondary lung disease/hypoxaemia contributors (G2/3), and of all patients categorized as predominant G3 (n = 172), 41 (24%) were judged to have a component of secondary LHD (G3/2), such that 107 had G2-3 (combined G2/3 and G3/2). As compared with G3, patients with G2 and G2-3 were more obese and had greater prevalence of hypertension, atrial fibrillation, and coronary disease. Patients with G2 and G2-3 were more anaemic, with poorer kidney function, more cardiac dysfunction, and higher N-terminal pro-B-type natriuretic peptide than G3. Lung diffusion was more impaired in G3 and G2-3, but commonly abnormal even in G2. Exercise capacity was severely and similarly impaired across all groups, with no differences in 6-min walk distance or peak oxygen consumption, and pulmonary vasoreactivity to nitric oxide did not differ. In a multivariable Cox regression model, patients with G2 had lower risk of death or transplant compared with G3 (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.30-0.86), and patients with G2-3 also displayed lower risk compared with G3 (HR 0.57, 95% CI 0.38-0.86).
CONCLUSIONS: Overlap is common in patients with a pulmonary or cardiac basis for PH. While lung structure/function is clearly more impaired in G3 and G2-3 than G2, pulmonary abnormalities are common in G2, even when clinically judged as isolated LHD. Further study is required to identify optimal systematic evaluations to guide therapeutic innovation for PH associated with combined heart and lung disease.
BACKGROUND: ClinicalTrials.gov NCT02980887.
RESULTS: Patients with PH enrolled in the prospective, NHLBI-sponsored PVDOMICS network underwent intensive clinical, biomarker, imaging, gas exchange and exercise phenotyping. Patients with pure G2, pure G3, or overlapping G2-3 PH were compared across multiple phenotypic domains. Of all patients with predominant G2 (n = 136), 66 (49%) were deemed to have secondary lung disease/hypoxaemia contributors (G2/3), and of all patients categorized as predominant G3 (n = 172), 41 (24%) were judged to have a component of secondary LHD (G3/2), such that 107 had G2-3 (combined G2/3 and G3/2). As compared with G3, patients with G2 and G2-3 were more obese and had greater prevalence of hypertension, atrial fibrillation, and coronary disease. Patients with G2 and G2-3 were more anaemic, with poorer kidney function, more cardiac dysfunction, and higher N-terminal pro-B-type natriuretic peptide than G3. Lung diffusion was more impaired in G3 and G2-3, but commonly abnormal even in G2. Exercise capacity was severely and similarly impaired across all groups, with no differences in 6-min walk distance or peak oxygen consumption, and pulmonary vasoreactivity to nitric oxide did not differ. In a multivariable Cox regression model, patients with G2 had lower risk of death or transplant compared with G3 (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.30-0.86), and patients with G2-3 also displayed lower risk compared with G3 (HR 0.57, 95% CI 0.38-0.86).
CONCLUSIONS: Overlap is common in patients with a pulmonary or cardiac basis for PH. While lung structure/function is clearly more impaired in G3 and G2-3 than G2, pulmonary abnormalities are common in G2, even when clinically judged as isolated LHD. Further study is required to identify optimal systematic evaluations to guide therapeutic innovation for PH associated with combined heart and lung disease.
BACKGROUND: ClinicalTrials.gov NCT02980887.
摘要：
目的：根据临床和血流动力学特征对肺动脉高压（PH）患者进行分组。第2组（G2，左心脏病[LHD]）和第3组（G3，肺病或低氧血症）最常见。许多患者表现出心脏和肺部疾病的重叠特征（G2-3），但是这个群体的特征不太好。
结果：前瞻性纳入的PH患者，NHLBI赞助的PVDOMICS网络接受了密集的临床，生物标志物，成像,气体交换和运动表型。将具有纯G2、纯G3或重叠G2-3PH的患者跨多个表型结构域进行比较。在所有以G2为主的患者中（n=136），66（49%）被认为有继发性肺病/低氧血症贡献者（G2/3），在所有分类为主要G3的患者中（n=172），41（24％）被判断为具有次要LHD（G3/2）的成分，这样107有G2-3（组合G2/3和G3/2）。与G3相比，G2和G2-3患者更肥胖，高血压患病率更高，心房颤动,和冠状动脉疾病。G2和G2-3患者贫血较多，肾功能较差，更多的心脏功能障碍，N末端B型利钠肽前体高于G3。G3和G2-3中的肺扩散受损更多，但即使在G2中也普遍异常。所有群体的运动能力都受到严重和类似的损害，6分钟步行距离或峰值耗氧量没有差异，对一氧化氮的肺血管反应性没有差异。在多变量Cox回归模型中，与G3相比，G2患者的死亡或移植风险较低（风险比[HR]0.51，95％置信区间[CI]0.30-0.86），与G3相比，G2-3患者的风险也较低（HR0.57，95％CI0.38-0.86）。
结论：重叠在肺源性或心脏源性PH患者中很常见。尽管G3和G2-3中的肺结构/功能明显比G2受损更多，但即使在临床上被判断为孤立的LHD时，G2中的肺异常也很常见。需要进一步的研究来确定最佳的系统评估，以指导与合并的心脏和肺部疾病相关的PH的治疗创新。
背景：ClinicalTrials.govNCT02980887。
结果：前瞻性纳入的PH患者，NHLBI赞助的PVDOMICS网络接受了密集的临床，生物标志物，成像,气体交换和运动表型。将具有纯G2、纯G3或重叠G2-3PH的患者跨多个表型结构域进行比较。在所有以G2为主的患者中（n=136），66（49%）被认为有继发性肺病/低氧血症贡献者（G2/3），在所有分类为主要G3的患者中（n=172），41（24％）被判断为具有次要LHD（G3/2）的成分，这样107有G2-3（组合G2/3和G3/2）。与G3相比，G2和G2-3患者更肥胖，高血压患病率更高，心房颤动,和冠状动脉疾病。G2和G2-3患者贫血较多，肾功能较差，更多的心脏功能障碍，N末端B型利钠肽前体高于G3。G3和G2-3中的肺扩散受损更多，但即使在G2中也普遍异常。所有群体的运动能力都受到严重和类似的损害，6分钟步行距离或峰值耗氧量没有差异，对一氧化氮的肺血管反应性没有差异。在多变量Cox回归模型中，与G3相比，G2患者的死亡或移植风险较低（风险比[HR]0.51，95％置信区间[CI]0.30-0.86），与G3相比，G2-3患者的风险也较低（HR0.57，95％CI0.38-0.86）。
结论：重叠在肺源性或心脏源性PH患者中很常见。尽管G3和G2-3中的肺结构/功能明显比G2受损更多，但即使在临床上被判断为孤立的LHD时，G2中的肺异常也很常见。需要进一步的研究来确定最佳的系统评估，以指导与合并的心脏和肺部疾病相关的PH的治疗创新。
背景：ClinicalTrials.govNCT02980887。
