规范肺动脉高压的治疗

肺动脉高压（pulmonary hypertension,PH）是严重的、具有潜在破坏力的慢性肺循环疾病。近年来,随着对各种病因所致PH的认识提高与治疗进展,不仅进一步完善PH分类,亦改善了PH患者的预后,特别是动脉型肺动脉高压（pulmonary arterial hypertension,PAH）中的特发性肺动脉高压（IPAH）、家族性PAH及结缔组织疾病相关PAH。[第一段]     

60岁以上老年人肺动脉高压病因学研究

目的 回顾性分析老年人肺动脉高压（pulmonary hypertension,PH）的病因,以改善PH的综合管理.方法 回顾性分析2012年1月-2014年1月在上海长海医院就诊住院的年龄大于60岁的患者,超声心动图检查提示肺动脉高压者,按病因分组进行统计,对不同疾病导致的经超声心动图三尖瓣返流速度估测的肺动脉收缩压进行比较分析.结果 资料完整的60岁以上PH病例数共540例,男278例,女262例,平均年龄（74.2±8.4）岁,中位年龄70岁.其中无特发性PAH=PH,均为疾病相关性,其中心源性共287例（扩心病19例,肥厚性心肌病8例）;先心病共27例.肺脏疾病相关性PAH为31例.瓣膜疾病相关性PAH、先心病相关性PAH及结缔组织相关性PAH=PH肺动脉收缩压明显高于心肌病及高血压引起的PAH=PH.按欧洲心脏协会2009年分类标准中属于第一组动脉型肺动脉高压为30例,占5％,左心疾病相关性PH为351例,占65％;第三组为肺疾病或/和缺氧相关性PH,为31例,占6％.其中第一组患者的肺动脉收缩压明显高于其他组.按照肺动脉收缩压升高程度来分,主要为中度升高.结论老年人PAH=PH主要是疾病相关性,最主要导致PH的疾病是左心疾病相关性.     

左心疾病相关肺动脉高压的临床诊治进展

左心疾病（ LHD）不仅是导致心力衰竭的临床常见疾病,也是临床常见的导致肺动脉高压（PH）的病因之一.临床流行病学研究提示,LHD相关PH是PH最常见疾病类型之一,PH是LHD患者预后重要的预测因素之一,合并PH的LHD患者预后不良.超声心动图检查是目前临床常用的筛查LHD相关PH的无创性检查方法,同时对于LHD相关PH患者的基础疾病的诊断与病情评估也具有重要作用.LHD相关PH患者典型的血流动力学改变特点为毛细血管后PH.对于疑似LHD相关PH患者进行包括肺毛细血管楔压（PCWP）、肺动脉压力（PAP）、肺血管阻力（PVR）以及跨肺压梯度（ mPAP - mPCWP）等血流动力学参数的血流动力学评估,具有重要的临床诊断、鉴别诊断、疾病评估和治疗决策作用.LHD相关PH的治疗首先应进行LHD基础疾病的优化治疗.虽然缺乏大型临床试验和循证医学的证据支持,治疗动脉型肺动脉高压有效的PH靶向治疗药物也被初步应用于部分LHD相关PH患者的治疗.LHD相关PH研究领域可能是目前及今后PH研究领域的热点和难点之一,也可能是目前及今后心力衰竭研究领域的热点之一.     

钙拮抗剂在低氧性肺动脉高压中的治疗作用

肺动脉高压（ Pulmonary Hypertension, PH ）是严重威胁人民健康的常见病，是临床众多心、肺疾病发生、发展过程中重要的病理生理环节，成为近年来国内外临床研究的热点问题。2003年WHO威尼斯大会将PH分为五大类：一、肺动脉性肺动脉高压（ Pulmonary Arterial Hypertension, PAH），     

肺动脉高压合并铁缺乏的现状、机制、治疗研究进展

肺动脉高压（PAH）属于毛细血管前肺高血压（PH）,是一种以肺动脉压力和肺血管阻力升高为特征的肺血管疾病,常引起临床血流动力学改变,严重者可导致右心衰竭甚至死亡。部分研究表明,铁缺乏（ID）普遍存在于多种类型PH患者中,其会降低患者的运动耐量及生活质量,而适当的补铁治疗可改善患者预后。但目前国内外关于PAH合并ID的研究较少。基于此,本文综述了PAH合并ID的现状、机制、治疗研究进展,并指出未来可进一步加大PAH与ID之间的病理生理机制研究,以期为PAH提供新的治疗靶点。     

先天性心脏病相关性肺动脉高压

临床上肺高血压（PH）分为五大类，包括肺动脉高压（PAH）、左心疾病所致PH、肺部疾病和/或低氧所致PH、慢性血栓栓塞性PH和/或其他肺动脉阻塞性病变所致PH、未明原因和/或多因素所致PH，先天性心脏病相关性肺动脉高压（CHD-PAH）属于PAH。PAH会降低先天性心脏病患者的运动耐量和生活质量，增加其死亡率。但CHD-PAH的发病机制尚未完全明确，且目前关于CHD-PAH诊疗方案的相关研究较少。本文介绍了CHD-PAH的定义、分类、分期、流行病学特征、病因学、病理生理变化、诊断、病情评估、治疗方法及预后，并指出未来需要进一步研究其独特的病理生理学机制，制定专门针对此类疾病的诊疗策略，包括危险分层、手术指征评估和靶向药物选择，以期规范此类疾病的诊治，使CHD-PAH患者获益最大。     

血管重构在动脉型肺动脉高压中的研究进展

动脉型肺动脉高压（PAH）是以肺动脉压力持续升高、肺小动脉结构持续改变为特征的致命性疾病,肺动脉重构是其主要的病理学特点。许多研究发现PAH中血管重构的病理机制主要包括各种细胞的病理学改变和多种分子信号通路的参与,最新的研究指出表观遗传学也参与血管重构,从而导致疾病的发生发展。目前针对PAH发病机制的各种新型药物及新疗法正在被开发,其副作用更小、疗效更佳。本文重点阐述PAH中血管重构的病理机制包括病理学改变、新分子信号通路及表观遗传学内容,以及治疗的新进展。     

肺动脉高压靶向药物治疗进展

<正>肺动脉高压(PH)是指静息状态下右心导管测得的肺动脉平均压(mPAP)≥25 mmHg(1 mmHg=0.133 kPa)。临床分为五类:第1类动脉性肺动脉高压(PAH);第2类左心疾病引起的PH;第3类肺部疾病和(或)低氧引起的PH;第4类血栓栓塞性肺动脉高压(CTEPH)和其他肺动脉闭塞病所致PH;第5类不明原因的和(或)多重因素机制引起的PH。近20年来,PAH的药物治疗取得了突破性进展,针对不同作用靶点的药物不断涌现,     

肺动脉高压与免疫炎症反应

肺动脉高压（PAH）是一大类以肺动脉压进行性升高为特点的肺血管疾病。目前广泛采用的PAH血流动力学定义为：静息状态下肺动脉平均压〉25mmHg，或运动状态下〉30mmHg。而相应的肺毛细血管嵌压小于15mmHg。由于现代医疗技术的进步与发展，人们对肺动脉高压的认识也日趋深入。2003年威尼斯第三届世界PAH会议上，新指南将肺动脉高压分为肺动脉性高压（PAH）、左心疾病伴发肺动脉高压、     

结缔组织病相关肺动脉高压：结缔组织病相关肺动脉高压研究进展

结缔组织病相关肺动脉高压（CTD—PAH）是继发肺动脉高压（PAH）中最常见的临床类型，较原发PAH更为多见。Kurasawa认为CTD—PAH并非内科常见病，但是结缔组织病（CTD）的严重并发症；未经恰当处置的CTD—PAH患者2a病死率可达45％～60％。死亡原因主要为心功能衰竭、呼吸功能衰竭和严重感染。     

Pathophysiology of pulmonary hypertension due to lung disease

Pulmonary hypertension (PH) often complicates the course of patients with advanced lung disease, and it is associated with a worse prognosis. Per the recent classification of pulmonary hypertensive disorders, PH due to lung disease is considered as a separate category within a group of disorders that was previously referred to as "secondary" PH. Among the lung diseases associated with PH, the incidence and clinical course of PH is best known for patients with COPD. Per studies in patients with COPD and other lung disorders, it is evident that the pathophysiology and treatment of these disorders is generally distinct from that of pulmonary arterial hypertensive disorders. Changes in the pulmonary vasculature that accompany elevations in pulmonary vascular pressure are generally referred to as pulmonary vascular remodeling. Chronic hypoxia is well known to cause pulmonary vascular remodeling and PH, and it is the major mechanism implicated for the development of PH in patients with lung disease. Other mediators have also been implicated in the pathogenesis of PH in animal models and patients with PH, including patients with pulmonary diseases. General features of pulmonary vascular remodeling are discussed with particular emphasis on those changes that have been described in patients with lung diseases. Recent discoveries in these areas are also reviewed, and findings in pulmonary arterial hypertensive diseases are contrasted with those found in patients with PH due to lung diseases. Some of these discoveries have already led to new treatment strategies for patients with the most severe forms of PH. PH due to lung diseases shares some common pathophysiologic features with pulmonary arterial hypertension. Therefore, it is likely that these discoveries and new treatments will also be extended to benefit patients with PH due to lung disease.     

The serotonin pathway in pulmonary hypertension

The nature of the primary defect responsible for triggering and maintaining pulmonary artery smooth muscle (PA-SMC) proliferation in pulmonary artery hypertension (PH) is poorly understood but may be either an inherent characteristic of PA-SMCs or a secondary response to an external abnormality, such as up-regulation of growth factors. In previous studies, we found that cultured PA-SMCs from patients with idiopathic PH (iPH) had an abnormally strong proliferative response to serotonin or serum (which contains high levels of serotonin). This abnormal response is due to overexpression of the serotonin transporter (5-HTT) which mediates the mitogenic action of serotonin. That 5-HTT plays a key role in pulmonary vascular remodeling is supported by experimental studies showing that transgenic animals overexpressing 5-HTT in smooth muscle (at a level close to that seen in PH) spontaneously develop pulmonary vascular remodeling and PH. Conversely, mice with targeted S-HTT gene disruption are protected against hypoxic PH, and selective 5-HTT inhibitors reverse or prevent experimental PH. In patients with chronic lung disease, a close association has been found between a 5-HTT gene polymorphism and the severity of pulmonary hypertension. Agents capable of selectively inhibiting 5-HTT-mediated PA-SMC proliferation deserve to be investigated as potential treatments for pulmonary hypertension.     

Plasma endothelin concentrations in patients with pulmonary hypertension associated with congenital heart defects. Evidence for increased production of endothelin in pulmonary circulation

BACKGROUND. To elucidate the pathophysiological significance of endothelin in pulmonary hypertension associated with congenital heart defects, we measured plasma endothelin-like immunoreactivity (ET-LI) concentrations by using radioimmunoassay in 18 patients with pulmonary hypertension (PH group; age, 6 months to 12 years) in comparison with 27 patients without pulmonary hypertension (non-PH group; age, 6 months to 12 years). METHODS AND RESULTS. Blood samples were obtained from the vena cava, right atrium, right ventricle, left or right pulmonary artery, and pulmonary vein or the pulmonary arterial wedge position (pulmonary venous blood) during cardiac catheterization. Plasma ET-LI concentrations in the PH group were significantly higher than those in the non-PH group at all sampling sites. In the PH group, plasma ET-LI concentration showed a significant increase between the right ventricle and pulmonary artery and between the pulmonary artery and pulmonary vein. The increment of plasma ET-LI concentrations from the right ventricle to the pulmonary vein was significantly larger in the PH group than in the non-PH group and was significantly correlated with pulmonary artery pressure. CONCLUSIONS. Plasma ET-LI concentrations were elevated in patients with pulmonary hypertension; the elevation was due to the increased production of ET-LI in pulmonary circulation, indicating the possible involvement of endothelin in the pathophysiology of pulmonary hypertension.     

Clinical and laboratory features of scleroderma patients with pulmonary hypertension

OBJECTIVE: Pulmonary hypertension (PH) is a frequent cause of death in patients with systemic sclerosis (SSc). In this study, we examined the occurrence of PH and investigated the clinical and laboratory features of SSc patients with PH. METHODS: A cross-sectional study of 125 Japanese patients with SSc was conducted using Doppler echocardiography, other multiple cardiopulmonary tests, and laboratory examination. RESULTS: PH (systolic pressure >40 mmHg) was diagnosed in 20 patients (16%) by Doppler echocardiography. In the six patients who had secondary pulmonary hypertension (SPH), PH was due to severe pulmonary fibrosis; 14 patients had isolated pulmonary hypertension (IPH). An elevated erythrocyte sedimentation rate (ESR) and increased immunoglobulin G (IgG) were found in a significantly greater proportion of the patients with PH than in those without PH. The incidence of pitting scars/ulcers was significantly greater in the patients with SPH than in those without PH. CONCLUSION: Elevated ESR and increased IgG were common features of scleroderma patients with PH, and scleroderma patients with SPH were inclined to have pitting scars/ulcers.     

Investigation of pulmonary hypertension

Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure (PAPm) superior than 25mmHg at rest or superior than 30mmHg with exercise. The classification of PH differentiates between "secondary" PH which results from a well-known disease, such as PH due to thromboembolic disease (obstructive PH), left cardiac failure (passive PH), or chronic respiratory diseases (hypoxic PH), and pulmonary arterial hypertension (PAH). PAH is a rare disease characterized by a progressive increase of pulmonary vascular resistance leading to right ventricular failure. PAH is classified as idiopathic, familial, or associated with various conditions (connective tissue diseases, congenital heart diseases with systemic-to-pulmonary shunts, portal hypertension, infection with the human immunodeficiency virus, or appetite-suppressant drugs). Transthoracic Doppler echocardiography is the investigation of choice for non invasive detection of PAH but right-heart catheterization is necessary to confirm the diagnosis of PAH and determine its mechanism. Pulmonary function tests and chest CT scan may detect an underlying chronic pulmonary disease (hypoxic PH). Lung perfusion scan and contrast-enhanced chest spiral CT scan can lead to the diagnosis of thromboembolic PH, which is to be confirmed by pulmonary angiography. Assessment of the severity of PH is based on clinical parameters (NYHA, right heart failure), functional tests (six-minute walk test), echocardiography and hemodynamics. Characterization of PH is essential in the management of PH because it determines the appropriate treatment: an etiological treatment in passive, obstructive or hypoxemic PH, or vasodilatator and antiproliferative therapies in PAH.     

Tei指数对慢性阻塞性肺病肺动脉高压患者的右心功能评价

目的:应用Tei指数评价慢性阻塞性肺病（chronic obstructive pulmonary disease,COPD）伴肺动脉高压(pulmonary hypertension,PH)患者的右心功能。方法: 临床确诊的慢性阻塞性肺病伴肺动脉高压(COPD+PH)患者68例,另30例正常人作为对照组。根据三尖瓣反流压差,超声估测肺动脉收缩压,并按其分别判定为重度PH组、中度PH组和轻度PH组。超声常规测量参数包括右心室前后径、右心房横径、肺动脉主干内径,并计算右心室Tei指数。结果: 68例COPD+PH患者中,重度PH组22例,中度PH组30例,轻度PH组16例;与对照组相比,重度PH组和中度PH组右心大小、Tei指数均有统计学差异,轻度PH组无明显右心形态改变,Tei指数无统计学差异。结论: 右心室Tei指数可作为COPD伴中重度PH患者右心功能评价的参考指标。     

A case of severe pulmonary hypertension associated with COPD treated with epoprostenol

A rare case of chronic obstructive pulmonary disease (COPD) with severe pulmonary hypertension (PH) was found in a 68-year-old man. COPD was diagnosed in his 50s, from which time he received home oxygen therapy. In January 2007, he was admitted due to progression of dyspnea. On admission to our hospital, arterial blood gas analysis showed severe hypoxemia. Moreover, echocardiographic findings demonstrated severe deviation of the interventricular septum toward the left ventricle, with right ventricular dilatation. Cardiac catheterization data demonstrated pulmonary arterial hypertension with a low cardiac output. Because severe PH is uncommon in patients with COPD and there was no apparent etiology of PH other than COPD, we thought this case was predominantly a pulmonary vascular disease such as idiopathic pulmonary arterial hypertension. Though we first treated this patient with bosentan, it was not effective. Therefore, he was treated with continuous infusion of epoprostenol. Epoprostenol administration along with bosentan resulted in decrease of BNP and right ventricular function improvement. We report a case of severe PH due to severe COPD treated with continuous administration of epoprostenol.     

Pulmonary hypertension in parenchymal lung disease

The pathophysiology of pulmonary hypertension (PH) in parenchymal lung diseases is partially related to hypoxic pulmonary vasoconstriction. PH treatment is controversial for these patients. This article focuses on group III PH, namely PH attributable to lung diseases and/or hypoxia. Group III includes chronic obstructive pulmonary disease and interstitial lung diseases, the most common parenchymal lung diseases associated with PH. It also includes sleep-disordered breathing and hypoventilation from any cause. Other parenchymal lung diseases associated with PH, namely sarcoidosis and systemic vasculitides (group V), are discussed. The data describing PH in specific parenchymal diseases are reviewed.     

Hyperthyroidism and pulmonary hypertension

In recent years, many authors have described several cases revealing an association between hyperthyroidism and pulmonary hypertension (PH). This observational study was designed to evaluate the incidence of PH in hyperthyroidism and was set in a department of internal medicine and pulmonary diseases with an out-patients department of endocrinology. Thirty-four patients, 25 women and nine men, with a mean age of 38 +/- 15 SD years participated. Twenty had Graves' disease and 14 had a nodular goitre. The patients were divided into two equally matched groups: those with a recently diagnosed hyperthyroidism, taking no drugs (group 1; n = 17) and those in a euthyroid state taking methimazole (group 2; n= 17). Transthoracic Doppler echocardiography was performed and systolic pulmonary artery pressurements of (PAPs) was determined by the tricuspid regurgitation method using the Bernoulli equation. Measurements of triiodothyronine, tetraiodothyronine, free thyroxine (Ft4), thyroid-stimulating hormone (TSH) and antithyroglobulin and antimicrosomal antibodies were also taken. We found a mild PH in seven patients of group 1 and in none of group 2.The mean +/- SD systolic pulmonaryartery pressurewas 28.88 +/- 6.41 in group 1 and 22.53 +/- 1.84 ingroup 2 (P<0.0001). A correlation was found between the TSH value and PAPs (r = -082;P < 0.001) and Ft4 and PAPs (r = 0 85; P < 0.001) in group 1. These findings indicate the presence of a frequent association between PH and hyperthyroidism. We suggest that hyperthyroidism be included in the differential diagnosis of PH.     

Pulmonary hypertension in idiopathic pulmonary fibrosis: a review

Idiopathic pulmonary fibrosis (IPF) is a progressive diffuse parenchymal disease with a poor prognosis. Pulmonary hypertension (PH) often complicates the course of IPF and may even be found in patients with preserved lung function. Possible pathogenetic mechanisms of PH in IPF include vascular destruction, pulmonary hypoxic vasoconstriction and vascular remodeling due to overexpression of cytokines and growth factors. PH in IPF patients is associated with decreased exercise capacity and a worse prognosis. Due to its prognostic significance, it seems important to investigate for PH in these patients. As the symptoms of PH in IPF are nonspecific, the development of PH in a patient with known IPF can be easily overlooked. Noninvasive methods provide clues for the diagnosis, but their sensitivity is limited. Doppler echocardiography is a useful tool for the detection of PH which also provides additional information regarding associated cardiac abnormalities. However, right heart catheterization remains the gold standard diagnostic test. Therapeutic options for PH in IPF are limited. Long-term oxygen administration for the correction of hypoxemia should be recommended. The availability of new pharmacological agents in the treatment of PH has raised the possibility of therapy in patients with IPF and associated PH. Whether these PH-targeted therapies may be of benefit in this patient group, in terms of improving functional outcomes and survival, remains uncertain.