左心疾病相关性肺动脉高压治疗的研究进展

<正>肺动脉高压是左心疾病的一种常见并发症,而左心疾病相关性肺动脉高压又是肺动脉高压中最常见的类型~〔1〕。绝大多数左心疾病相关性肺动脉高压是由左心收缩功能障碍、舒张功能障碍和(或)左心瓣膜病所致。并发肺动脉高压心力衰竭患者的预后较差,其病死率是无肺动脉高压心力衰竭患者的2倍~〔2〕。本文对左心疾病相关性肺动脉高压的治疗进展予以综述。1原发病治疗左心疾病相关性肺动脉高压的首要治疗应在给予肺动脉     

低氧性肺动脉高压相关基因的研究进展

低氧性肺动脉高压是临床常见的病理生理过程,也是慢性阻塞性肺疾病、慢性肺源性心脏病等多种心肺疾病发生发展的重要病理环节.近10余年来,国内外对低氧性肺动脉高压相关基因方面的研究取得很大进步.对肺动脉高压形成机制的各种基因的认识可应用于临床中,为临床治疗提供更有价值的信息,为进一步的靶向治疗提供帮助.     

《中国肺动脉高压诊断与治疗指南（2021版）》解读——左心疾病所致肺动脉高压

左心疾病所致肺动脉高压临床上常见,左心射血分数保留和射血分数降低的心力衰竭均可以引起肺动脉高压,与其他类型肺动脉高压相比,其肺动脉楔压>15 mmHg,属于毛细血管后肺动脉高压。临床上需要仔细鉴别动脉性肺动脉高压合并左心疾病还是左心疾病所致肺动脉高压。左心疾病所致肺动脉高压主要治疗基础疾病,不推荐应用肺动脉高压靶向药物。     

肺动脉高压血管收缩与重塑的研究

肺动脉高压（PH）可以出现在原发于肺动脉的疾病（如特发性肺动脉高压，IPAH）或者继发于心肺疾病同时伴有肺动脉高压的疾病（如继发性肺动脉高压，SPH）。由于肺动脉高压发病机制复杂且有许多机制不明，治疗效果不理想。特别是IPAH，一经确诊，平均存活时间只有2．5年，有学者认为其预后比恶性肿瘤还差。诸多致病因素参与了肺动脉高压的发生与发展并最终引起血管收缩，导致血管重塑。     

左心疾病相关性肺动脉高压和药物治疗进展

左心疾病是临床上肺动脉高压的最常见原因之一。高血压和缺血性心脏病引起的左心室舒张功能不全是这类肺动脉高压的常见病因。虽然近年来在左心疾病导致肺动脉高压机制上的研究取得了一些进展,但是尚无特异性治疗。现有临床试验提示5磷酸二酯酶抑制剂在此类肺动脉高压的治疗中可能有效,新近研究表明Rho激酶抑制剂可能为左心疾病相关性肺动脉高压的靶向治疗提供新的可能。本文就靶向药物在左心疾病相关性肺动脉高压治疗中的研究现状做一综述。     

左心疾病相关性肺动脉高压

左心疾病是引起肺动脉高压的常见病因,由其导致的肺动脉高压主要是由于左室或左房充盈压增高所致,如发展至心力衰竭则预后较差,其病死率是不伴有肺动脉高压的心力衰竭患者的2倍多。本文将对左心疾病相关性肺动脉高压的病理生理学以及诊断和治疗策略的研究现状进行阐述。     

交感神经去除术在肺动脉高压治疗中的研究进展

肺动脉高压是一种复杂的临床综合征,虽然在心肺血管疾病中发病率不高,但因其严重影响患者生活质量,致死风险高,被称为心血管疾病中的恶性疾病。靶向药物治疗使得肺动脉高压病情得到一定程度控制,但整体控制率仍不容乐观。随着肺动脉高压相关研究的推进,目前认为交感神经的过度激活在肺动脉高压的发生和维持中起到一定作用,且基于调节自主神经活性的药物和器械治疗在肺动脉高压中的研究得到了一些发现。现就交感神经在肺动脉高压发生和发展的作用、肺动脉神经分布特点和交感神经活性调节的非药物治疗研究进行综述,以探讨肺动脉高压治疗的新思路。     

低氧诱导因子在肺动脉高压发病中的作用及机制

现今,肺动脉高压患病率和病死率逐年增加,疾病进程快,但目前临床上常用的治疗肺动脉高压药物只能在一定程度上缓解肺动脉高压临床症状,不能从根本上改善肺动脉高压的肺部微循环功能障碍。因此,探索肺动脉高压发病新的分子机制,寻找新的治疗靶点,是肺动脉高压研究领域亟待解决的重要问题。低氧诱导因子家族与肺动脉高压发生发展有着紧密的联...     

左心疾病相关性肺动脉高压诊断和治疗进展

左心疾病是临床上导致肺动脉高压的最常见的原因之一。近年来高血压和缺血性心脏病引起的左心室舒张功能不全成为这类肺动脉高压的常见病因。左心疾病合并肺动脉高压后患者病死率明显升高,但是目前对于这类肺动脉高压尚没有特异性治疗。下面就左心疾病相关性肺动脉高压的诊断和治疗的研究现状做一综述。     

内皮祖细胞和肺动脉高压

肺动脉高压是以肺动脉压和肺血管阻力进行性增加及右心功能衰竭为特征,内皮功能障碍为主的恶性肺血管疾病.本文总结了近年来内皮祖细胞(EPC)动员、归巢分子生物学的研究进展.研究了血管内皮生长因子等生长因子和他汀类等药物对EPC动员,归巢治疗肺动脉高压的影响以及EPC、基因修饰后EPC移植对肺动脉高压治疗的影响.同时讨论了EPC治疗的潜在不良反应.EPC为肺动脉高压患者提供新的治疗方法.     

Pulmonary arterial hypertension and porto-caval fistula in a 17 year old patient

The authors report the case of a 17 year old patient with severe pulmonary arterial hypertension accompanied with a congenital porto-caval shunt. This patient had been admitted with dyspnoea on exertion with signs of pulmonary arterial hypertension on clinical examination. Echocardiography revealed a systolic pulmonary arterial pressure of 80 mmHg with no left heart anomaly or intracardiac shunt. Pulmonary investigations, as well as immunology, clotting, liver function and retroviral serology were all negative. A routine abdominal ultrasound showed a 10 mm proximal porto-caval fistula with no sign of portal hypertension. This case shows that anomalies of the portal system can cause pulmonary arterial hypertension even in the absence of any symptoms suggestive of hepatic disorder.     

Successful management of portopulmonary hypertension with beraprost

Portopulmonary hypertension is a complication of chronic liver disease, which has significant effects on survival and prognosis. Although the pathogenesis of pulmonary arterial hypertension has been well known, portopulmonary hypertension is often underestimated in patients with chronic liver disease. Every clinician who manages patients with chronic liver disease complaining of dyspnea should consider portopulmonary hypertension because this disorder requires special treatment. Herein, a 40-year-old woman with liver cirrhosis who complained of dyspnea on exercise is presented. She was diagnosed with portopulmonary hypertension by echocardiography and right-heart catheterization. Beraprost was used to reduce the pulmonary arterial pressure and improve the symptoms. Her symptoms were improved after 2 weeks, and improved symptoms and reduced pulmonary arterial pressure were sustained for 18 months.     

Hypertension artérielle pulmonaire et hémopathies malignes

Many recent publications have evidenced a statistical link between pulmonary arterial hypertension and myeloproliferative disorders, once excluded secondary causes of pulmonary arterial hypertension (more particularly, portal hypertension or thromboembolic events). Nonetheless, the frequency of such an association is quite variable, from 10 to 50 % and depends both on the population studied and on the type of myeloproliferative disorder. The most robust association is observed with essential thrombocythemia. Pulmonary arterial hypertension has also been described in association with lymphoma, acute leukemia, myeloma or large granular lymphocyte proliferation. The absence of large series call for a prospective study of pulmonary arterial hypertension in malignant hematologic disorders to firmly establish the exact frequency of such an association, to define more precisely its physiopathology in order to elaborate more specific diagnostic criteria together with guidelines for both treatment and follow-up.     

Pulmonary vascular disease in adults with congenital heart disease

Pulmonary arterial hypertension of variable degree is commonly associated with adult congenital heart disease. Depending on size and location of the underlying cardiac defect as well as on repair status, pulmonary arterial hypertension may present with or without reversed shunting and associated cyanosis (ie, Eisenmenger syndrome). We review available data on etiology, clinical presentation, prognosis, and management strategies of pulmonary arterial hypertension in adult patients with congenital heart disease. In addition, we discuss the numerous complications associated with Eisenmenger syndrome, representing a multisystem disorder. Finally, we present general management strategies and emerging disease-targeting therapies.     

Evaluation and management of the patient with pulmonary arterial hypertension

Increased pressure in the pulmonary circulation, or pulmonary hypertension, is a common disorder that may complicate various cardiopulmonary conditions, including severe obstructive airways disease and left ventricular dysfunction. An increase in pulmonary arterial pressure that is not due to coexistent cardiopulmonary disease, known as pulmonary arterial hypertension, may occur in the absence of a demonstrable cause (idiopathic or familial); as a complication of systemic conditions, such as connective tissue disease, HIV infection, or chronic liver disease; or as a result of the use of fenfluramine anorexigens, amphetamines, or cocaine. The development of disease-specific therapies for pulmonary arterial hypertension over the past decade underscores the importance of diagnosing pulmonary hypertension early in the course of the condition and implementing a treatment strategy that is based on the condition's cause and severity. In this review, the authors present approaches to the diagnosis and management of pulmonary arterial hypertension, using a hypothetical case to highlight the key management points.     

Use of the Prostacyclin Receptor Agonist Selexipag in Patients With Pulmonary Arterial Hypertension Associated With Eisenmenger Syndrome

Eisenmenger syndrome is a multisystem disorder and the most severe form of pulmonary arterial hypertension in adult congenital heart disease. Pulmonary arterial hypertension represents a fatal disease, characterized by increased pulmonary vascular resistance, right heart failure, and death. Although therapeutic management has rapidly advanced in recent years, these patients were not included in randomized controlled trials for specific pulmonary arterial hypertension drugs, except for bosentan. However, in clinical practice we apply treatment strategies combining drugs targeting multiple pathobiological pathways. We present 3 patients with Eisenmenger syndrome and their improvement after starting treatment with selexipag, an oral selective IP prostacyclin receptor agonist.     

Pulmonary arterial hypertension and type-I glycogen-storage disease: the serotonin hypothesis.

A case of pulmonary arterial hypertension in a patient with type-Ia glycogen-storage disease, a rare autosomal recessive disorder caused by a deficiency of glucose-6-phosphatase is reported in this study. It has been suggested that the occurrence of pulmonary arterial hypertension in type-Ia glycogen-storage disease could be due to an abnormal production of vasoconstrictive amines such as serotonin. To test this hypothesis, plasma serotonin concentrations were prospectively measured in 13 patients with type-Ia glycogen-storage disease, one patient with severe pulmonary hypertension and type-Ia glycogen-storage disease, 16 patients displaying severe pulmonary arterial hypertension, and 26 normal healthy controls. Elevated plasma serotonin concentrations were found in patients with either severe pulmonary arterial hypertension (38.8+/-7.3 nmol x L(-1)) or type-Ia glycogen-storage disease (36.8+/-11.5 nmol x L(-1)), as compared with controls (8.8+/-0.6 nmol x L(-1), p<0.001). Plasma serotonin was dramatically elevated in the patient with type-Ia glycogen-storage disease and pulmonary arterial hypertension (113.4 nmol x L(-1)). It is concluded that type-Ia glycogen-storage disease may be another condition in which abnormal handling of serotonin is one event in a multistep process leading to severe pulmonary arterial hypertension.     

Hypertension and liver disease

Arterial hypertension is a common disorder with a frequency of 10% to 15% in subjects in the 40- to 60-year age group. Yet most reports find the prevalence of arterial hypertension in patients with chronic liver disease (cirrhosis) much lower. In this review, we consider the alterations in systemic hemodynamics in cirrhosis. The most characteristic findings in cirrhotic patients are vasodilatation with low systemic vascular resistance, increased cardiac output, high arterial compliance, secondary activation of counterregulatory systems (sympathetic nervous system, renin-angiotensin-aldosterone system, neuropituitary release of vasopressin), and resistance to vasopressors. The vasodilatory state is mediated through nitric oxide, calcitonin gene-related peptide, adrenomedullin, and other vasodilators, and is most pronounced in the splanchnic area. This constitutes an effective (although relative) counterbalance to increased arterial blood pressure. Subjects with established arterial hypertension (essential, secondary) may become normotensive during the development of cirrhosis, and arterial hypertension is rarely manifested in patients with cirrhosis, even in cases with renovascular disease and high circulating renin activity. There is much dispute as to the understanding of homeostatic regulation in cirrhotic patients with manifest arterial hypertension. This is a topic for future research.     

Genetics of pulmonary hypertension: from bench to bedside.

Primary pulmonary hypertension has been described as either sporadic or clustered in families. Familial primary pulmonary hypertension segregates as an autosomal dominant trait with markedly reduced disease gene penetrance. Defects within bone morphogenetic protein receptor type II gene, coding for a receptor member of the transforming growth factor-beta family, underlie familial primary pulmonary hypertension. Several lines of evidence point to the potential requirement of additional factors, either environmental or genetic, in the pathogenesis of the disease. In addition, a proportion of so-called sporadic primary pulmonary hypertension turns out to have an inherited basis, as demonstrated by germline bone morphogenetic protein receptor type II gene mutations. Analysis of cases in association with hereditary haemorrhagic telangiectasia led to the demonstration that pulmonary arterial hypertension can involve activin-receptor-like kinase 1 mutations, a type I transforming growth factor-beta receptor. These findings emphasise the critical role of the transforming growth factor-beta signalling pathway in pulmonary arterial hypertension. While this achievement has generated extreme interest, the pathobiology of severe pulmonary arterial hypertension remains unclear and genomic approaches to pulmonary hypertension research may identify additional molecular determinants for this disorder. Finally, there is an urgent need to develop relevant guidelines for genetic counselling to assist patients, their relatives and pulmonary vascular specialists to utilise these recent observations.     

The role of the kidneys in the pathogenesis of late-onset hypertension

The investigation of the functional activity of the kidneys in old hypertensives revealed that the changes in partial functions of the kidneys observed in hypertension tend to diminish the effectiveness of the mechanisms controlling arterial blood pressure. This means that this disorder of function constitutes an important link in the pathogenesis of hypertension. Mild and severe disturbances of renal function in old hypertensives can be regarded as evidence of the growing role of the kidneys in the pathogenesis of late-onset hypertension. They are attributable to pre-existing physiological changes taking place in the kidneys at advanced age and to the declining reliability of the kidneys in the homeostatic control of arterial blood pressure.