Sitaxsentan: a novel endothelin-A receptor antagonist for pulmonary arterial hypertension

Sitaxsentan is an orally active, selective endothelin-A receptor antagonist that may benefit patients with pulmonary arterial hypertension by blocking the vasoconstrictive effects of endothelin-A receptors, while maintaining the vasodilator and endothelin-1 clearance functions of the endothelin-B receptors. In its first randomized, placebo-controlled study, sitaxsentan improved exercise capacity assessed by the 6-min walk test, New York Heart Association functional class, cardiac index and pulmonary vascular resistance in New York Heart Association Class II, III and IV patients with idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension related to connective tissue disease or congenital heart disease. Although doses of 100 and 300 mg once daily demonstrated equivalent efficacy, the lower dose had a better safety profile. Additional studies are ongoing to assess the relative safety and efficacy of 50 and 100 mg once-daily dosing. The most common side effects include rhinitis, headache, peripheral edema, chest pain, nausea, constipation, increased prothrombin time/international normalized ratio (in patients on warfarin), flushing and insomnia. As with other endothelin receptor antagonists, increases in hepatic transaminases have been observed with sitaxsentan. Initial studies using the selective oral endothelin-A receptor antagonist sitaxsentan in pulmonary arterial hypertension patients have revealed a favorable risk–benefit therapeutic profile with the 100 mg once-daily dose.     

特发性肺纤维化合并肺动脉高压的诊治进展

特发性肺纤维化(idiopathic pulmonary fibrosis, IPF)是病因不明,组织病理学主要为普通间质性肺炎,局限于肺部的慢性纤维化型间质性肺炎。该病致死率高,对人群健康危害性高。近年来,随着人口老龄化、空气污染的加剧导致其发病率逐年上升,我们对于IPF的认识也在不断提高,研究发现IPF患者常合并其他疾病,包括肺气肿、肺癌、心血管疾病等。存在合并症的IPF患者临床症状更多,患者的生存质量差。其中合并肺动脉高压会降低IPF患者的生存率,本文就IPF合并肺动脉高压进行综述,以期为IPF合并肺动脉高压的诊疗方案与进一步研究提供新思路,以期提高 IPF患者的生活质量及改善预后。     

Venous sinus stenting as a treatment approach in patients with idiopathic intracranial hypertension and encephaloceles

BackgroundStenosis of a dural venous sinus is the most common cause of idiopathic intracranial hypertension (IIH) and can be classified as either intrinsic or extrinsic. Intrinsic stenoses are characterized by a focal filling defect within the sinus secondary to an enlarged arachnoid granulation or fibrous septa while extrinsic stenoses tend to be long and smooth-tapered and are most commonly secondary to external compression from the adjacent brain parenchyma. Brain herniations, or encephaloceles, into arachnoid granulations in dural venous sinuses have rarely been reported in the literature in patients with IIH. We propose that dural venous sinus stenting (VSS) may be a safe and effective treatment approach in patients with an encephalocele and IIH.MethodsWe retrospectively analyze three cases of patients with encephalocele who underwent VSS for treatment of medically refractory IIH at our institution.ResultsOne patient underwent stenting ipsilateral and two patients underwent stenting contralateral to the side of their encephaloceles. No technical related issues or complications occurred during either of the three stenting procedures. Two out of the three patients had complete resolution in their IIH-related symptoms and normalization of cerebrospinal (CSF) pressures shortly after stenting. We await clinical follow-up in the third patient.ConclusionsOur results suggest that VSS is a technically feasible and effective approach in treating patients with medically refractory IIH and encephaloceles.     

Intracranial pressure directly predicts headache morbidity in idiopathic intracranial hypertension

ObjectiveHeadache is the predominant disabler in idiopathic intracranial hypertension (IIH). The aim was to characterise headache and investigate the association with intracranial pressure.MethodsIIH:WT was a randomised controlled parallel group multicentre trial in the United Kingdom investigating weight management methods in IIH. Participants with active IIH (evidenced by papilloedema) and a body mass index (BMI) ≥35 kg/m² were recruited. At baseline, 12 months and 24 months headache characteristics and quality of life outcome measures were collected and lumbar puncture measurements were performed.ResultsSixty-six women with active IIH were included with a mean age of 32.0 years (SD ± 7.8), and mean body mass index of 43.9 ± 7.0 kg/m². The headache phenotype was migraine-like in 90%. Headache severity correlated with ICP at baseline (r = 0.285; p = 0.024); change in headache severity and monthly headache days correlated with change in ICP at 12 months (r = 0.454, p = 0.001 and r = 0.419, p = 0.002 respectively). Cutaneous allodynia was significantly correlated with ICP at 12 months. (r = 0.479, p < 0.001). Boot strap analysis noted a positive association between ICP at 12 and 24 months and enabled prediction of both change in headache severity and monthly headache days. ICP was associated with significant improvements in quality of life (SF-36).ConclusionsWe demonstrate a positive relationship between ICP and headache and cutaneous allodynia, which has not been previously reported in IIH. Those with the greatest reduction in ICP over 12 months had the greatest reduction in headache frequency and severity; this was associated with improvement of quality of life measures.Trial registrationThis work provides Class IIa evidence of the association of raised intracranial pressure and headache. ClinicalTrials.gov number, {"type":"clinical-trial","attrs":{"text":"NCT02124486","term_id":"NCT02124486"}}NCT02124486.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-021-01321-8.     

How to evaluate patients with congenital heart disease-related pulmonary arterial hypertension

Introduction: Patients with congenital heart disease (CHD), who develop pulmonary arterial hypertension (PAH), live longer, and have better quality of life compared to the past due to PAH-specific therapy and improved tertiary care.

Areas covered: Clinical examination, objective assessment of functional capacity, natriuretic peptide levels, cardiac imaging, and hemodynamics all play a pivotal role in the evaluation, general care, and management of PAH-specific therapy. This review discusses the epidemiology and pathophysiology of PAH-CHD and provides hints for the optimal evaluation of these patients.

Expert commentary: Further research should be performed in the field of PAH-CHD, as there are many of areas lacking evidence that should be addressed in the future. Networking, especially among the tertiary expert centers, could play a key role in this direction.     

Bosentan: a novel agent for the treatment of pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a progressive disease that, without treatment, ultimately results in right heart failure and death. For the majority of patients with advanced PAH, therapy requires cumbersome drug delivery devices with serious side effects. Endothelin, a potent endogenous vasoconstrictor, is increased in individuals with PAH. The development of bosentan, a novel, well-tolerated, orally active endothelin antagonist, has significantly changed the therapeutic approach to PAH. Recent clinical trials have demonstrated that treatment with bosentan produces favourable effects on cardiopulmonary haemodynamics, exercise capacity, WHO functional class and time to clinical worsening in PAH.     

IL-31在肺动脉高压患者中的表达及临床相关性

目的：探究肺动脉高压（pulmonary arterial hypertension, PAH）患者血浆中炎症因子白介素（interleukin, IL）-31的表达水平及其临床相关性。方法：筛选纳入PAH患者以及健康人群,分别作为PAH组和对照组。收集两组研究对象临床及随访资料。应用酶联免疫吸附实验检测血浆中IL-31、IL-1β、IL-6、IL-10、IL-12p70、单核细胞趋化蛋白（monocyte chemoattractant protein-1, MCP-1）、肿瘤坏死因子-α （tumor necrosis factor-α, TNF-α）及转化生长因子β1（transforming growth factor-β1, TGF-β1）的浓度。结果：共纳入50例PAH患者及22例健康体检人员。PAH组与对照组在年龄、性别组成、体重指数以及左室射血分数上的差异无统计学意义。与对照组相比,PAH组血浆中IL-31表达水平显著升高[168.82（149.14, 177.26）pg/ml vs 152.76（145.58, 159.41）pg/ml, P=0.001]。PAH组血浆IL-31的表达水平与肺动脉平均压（r=0.652, P < 0.001）及肺血管阻力呈线性正相关（r=0.651, P<0.001）,而与右心收缩功能呈线性负相关（r=-0.496, P<0.001）。Cox回归分析的结果显示,血浆IL-31的表达水平是PAH患者发生心衰再入院/全因死亡的独立预测因子（HR＝1.130, 95%CI 1.052～1.214, P＝0.001）。结论：PAH患者血浆IL-31的表达水平较正常对照组显著升高,且与PAH的严重程度及预后相关。     

PTA术后的维持性血液透析患者血清生物标志物水平变化对肺动脉压影响的研究

目的 探讨维持性血液透析(MHD)患者经腔内血管成形术(PTA)后对血清生物标志物和肺动脉压(PAP)的影响.方法 选取2019年9月至2021年3月在湖南省人民医院收治的50例患有动静脉内瘘(AVF)闭塞的MHD患者作为研究对象,分为PTA组37例,中心静脉导管(CVC)组13例.收集所有患者的一般资料,对比两组患者...     

HIV‐associated pulmonary arterial hypertension: from bedside to the future

Pulmonary arterial hypertension (PAH) is a life‐threatening complication of HIV infection. The prevalence of HIV‐associated PAH (HIV‐PAH) seems not to be changed over time, regardless of the introduction of highly active antiretroviral therapy (HAART). In comparison with the incidence of idiopathic PAH in the general population (1–2 per million), HIV‐infected patients have a 2500‐fold increased risk of developing PAH. HIV‐PAH treatment is similar to that for all PAH conditions and includes lifestyle changes, general treatments and specific treatments.     

酚妥拉明联合地尔硫对慢性肺心病急性加重期肺动脉高压的疗效观察

目的观察酚妥拉明联合地尔硫对慢性肺源性心脏病患者急性加重期肺动脉高压的影响。方法对照组35例,给予常规治疗;酚妥拉明组30例,给予酚妥拉明10 mg微量泵持续静脉泵入,速度0.4～0.6 mg/h;地尔硫组30例,给予口服地尔硫30 mg,3次/d;联合治疗组30例,给予酚妥拉明10 mg微量泵静脉泵入,同时给予口服地尔硫30 mg,3次/d;疗程为14天。观察治疗前后各组及组间平均肺动脉压力（mPAP）和血浆脑钠肽（BNP）的变化。结果各组治疗后较治疗前相比mPAP、BNP均显著降低,常规治疗组mPAP（55.2±6.5）mmHg vs（48.6±8.2）mmHg（P〈0.05）,BNP（602.9±96.6）pg/L vs（416.2±43.7）pg/L（P〈0.05）;酚妥拉明组mPAP（57.3±6.8）mmHg vs（42.1±9.6）mmHg（P〈0.05）,BNP（628.2±89.1）pg/L vs（356.1±37.9）pg/L（P〈0.01）;地尔硫组（56.2±6.1）mmHg vs（43.4±8.9）mmHg（P〈0.05）,BNP（612.7±87.4）pg/L vs（382.9±37.5）pg/L（P〈0.01）;联合治疗组mPAP（58.3±6.7）mmHg vs（30.5±7.7）mmHg（P〈0.01）,BNP（644.6±98.3）pg/L vs（286.5±33.4）pg/L（P〈0.01）。联合治疗组mPAP、BNP较其他治疗组下降更明显（P〈0.05或〈0.01）。结论酚妥拉明联合地尔硫能显著降低慢性肺源性心脏病患者急性加重期BNP水平及肺动脉压力。     

重度肺动脉高压合并右心功能不全患者经皮房间隔造口术的围术期护理研究

目的探讨经皮房间隔造口术(AS)在特发性肺动脉高压(IPAH)合并右心功能不全患者的围术期护理对策。方法总结6例IPAH患者经皮房间隔造口术的围术期护理,注意术前病情观察、用药护理、术前准备,术后观察生命体征及血氧监测,注意伤口护理、康复及出院指导。结果本组IPAH患者经皮房间隔造口术,通过全面的护理观察和对策的有效落实,患者均平稳出院,心功能改善,运动能力提高,血浆脑钠肽水平下降,无晕厥发生。结论房间隔造口术应用于严重IPAH患者可有效提高心功能,围术期严密的护理和有效的护理对策,对提高房间隔造口术效果提供了保障,改善了病患生活质量。     

Identification of a novel mutation in the BMPR2 gene in a pulmonary arterial hypertension patient using next‐generation sequencing

BackgroundPulmonary arterial hypertension (PAH) is a hemodynamic state that is characterized by pulmonary vasoconstriction and vascular remodeling, leading to a continuous increase in mean pulmonary arterial pressure, and eventually right heart failure. Mutations of the bone morphogenetic protein type II receptor (BMPR2) gene are the most common genetic cause of PAH.MethodsA 52‐year‐old woman was admitted to Shaoxing People''s Hospital after suffering from a cough for 2 months. In our hospital, the proband got a thorough medical examination and was diagnosed with PAH following genetic testing.ResultsGenetic test showed that the proband carried a novel heterozygous c.1481C>T (p.Ala494Val) mutation in the BMPR2 gene. The new mutation was initially discovered as a potential pathogenic variant by bioinformatics research, but it needed to be functionally verified.ConclusionsThe novel mutation may be related to the development of the PAH. In addition to general examinations, clinicians must thoroughly examine molecular genetics to provide an accurate diagnosis in the clinic, particularly for rare disorders.     

组织速度成像评估特发性肺动脉高压患者右心室心肌非同步运动

目的 探讨定量组织速度成像评估特发性肺动脉高压（IPAH）患者右心室非同步运动的意义。方法 选择26例IPAH患者和25例正常人，常规测量、计算右心室结构参数（游离壁厚度、舒张末期面积和收缩末期面积、面积变化率）和功能参数[游离壁三尖瓣环收缩期峰速（Sa）、舒张早期峰速（Ea）、舒张晚期峰速、Tei指数]。离线分析右心室3个壁基底段和中间段组织速度曲线，测量QRS波起点至6节段Sa、Ea时限（TQs、TQr）。计算同一节段3个壁间TQ-S、TQ-E最大差值（Inter-△TQ-S、Inter-△TQ-E）、同一壁内2个节段间TQ-S、TQ-E最大差值（Intra-△TQ-S、Intra-△TQ-F）及6节段间TQ-S、TQE最大差值（Max-ATQ-s、Max-△TQ-E）。结果 与正常人相比，IPAH患者Inter-△TQ-S、Inter-△TQ-E、Max-△TQ-S、Max-△TQ-E明显延长（P〈0．001），Intra-△TQ-S、Intra-△TQ-E略延长（P〉0．05）。IPAH患者Max-△TQ-S、Max-ATQ-E与右心室结构参数和功能参数均有良好相关性。结论 IPAH右心室内存在非同步运动，且与右心室结构和功能关系密切。     

Hereditary haemorrhagic telangiectasia with atrial septal defect and pulmonary hypertension during advanced pregnancy: a case report and literature review

Pregnancy complicated with hereditary haemorrhagic telangiectasia (HHT) is a rare condition. This case report presents an extremely rare case with the co-occurrence of HHT and congenital heart disease. In this report, a 43-year-old woman at 36 + 4 weeks of gestation experienced haemoptysis with a volume of approximately 300 ml for the first time. Uncommonly, her transthoracic echocardiogram revealed a previously unrecognized atrial septal defect (ASD) and pulmonary hypertension (PH) for the first time at 36 + 1 weeks of gestation. Chest computed tomography revealed an arteriovenous malformation (AVM) in the right lower lobe of the lung. Due to concerns of rebleeding of ruptured pulmonary arteriovenous malformations (PAVMs), the patient underwent a caesarean section at 36 + 6 weeks of gestation. A healthy male infant weighing 2800 g was delivered. To the best of our knowledge, there have been few reports about HHT with ASDs and PH during advanced pregnancy. This current case report highlights the necessity for clinicians to pay considerable attention to cardiac structural abnormalities, which can worsen PAVM in patients with HHT during pregnancy, for whom terminating the pregnancy in time may reduce the risk of PAVM rupture.     

Comparison of inhaled nitric oxide with aerosolized prostacyclin or analogues for the postoperative management of pulmonary hypertension: a systematic review and meta-analysis

Abstract

Background: This study aims to compare the effectiveness of inhaled prostacyclin or its analoguesversus nitric oxide (NO) in treating pulmonary hypertension (PH) after cardiac or pulmonary surgery remains unclear.

Methods: PubMed, Cochrane, and Embase databases were searched for literature published prior to December 2019 using the following keywords: inhaled, nitric oxide, prostacyclin, iloprost, treprostinil, epoprostenol, Tyvaso, flolan, and pulmonary hypertension. Randomized controlled trials and multiple-armed prospective studies that evaluated inhaled NO versus prostacyclin (or analogues) in patients for perioperative and/or postoperative PH after either cardiac or pulmonary surgery were included. Retrospective studies, reviews, letters, comments, editorials, and case reports were excluded.

Results: Seven studies with a total of 195 patients were included. No difference in the improvement of mean pulmonary arterial pressure (pooled difference in mean change= ?0.10, 95% CI: ?3.98 to 3.78, p?=?.959) or pulmonary vascular resistance (pooled standardized difference in mean change= ?0.27, 95% CI: ?0.60 to 0.05, p?=?.099) were found between the two treatments. Similarly, no difference was found in other outcomes between the two treatments or subgroup analysis.

Conclusions: Inhaled prostacyclin (or analogues) was comparable to inhaled NO in treating PH after cardiac or pulmonary surgery.

• Key messages

• This study compared the efficacy of inhaled prostacyclin or its analogues versus inhaled NO to treat PH after surgery. The two types of agent exhibited similar efficacy in managing MPAP, PVR, heart rate, and cardiac output was observed.

• Inhaled prostacyclin may serve as an alternative treatment option for PH after cardiac or pulmonary surgery.

     

Continuous intravenous iloprost to revert treatment failure of first-line inhaled iloprost therapy in patients with idiopathic pulmonary arterial hypertension

AIMS: To describe the clinical and haemodynamic effects during the first 6 months of continuous intravenous iloprost treatment in patients with idiopathic pulmonary arterial hypertension (IPAH) and relevant disease progression despite continued mono therapy with aerosolized iloprost. METHODS AND RESULTS: Twenty-four IPAH patients with clinical decompensation to NYHA class IV despite therapy with aerosolized iloprost and optimized conservative treatment were assessed clinically, haemodynamically and by cardiopulmonary exercise testing for at least 6 months. Upon switching from inhaled to intravenous iloprost all patients improved clinically (NYHA III) while pulmonary vascular resistance (PVR) and right atrial pressure decreased from 2386 +/- 243 to 1381 +/- 124 dyne .s .cm(-5) and 12 +/- 1 to 8.5 +/- 1 mmHg, respectively (both p < 0.05). Despite this acute improvement haemodynamic (PVR increased from 1462+/-223 to 1978 +/- 327 dyne .s .cm(-5)) and clinical (4 deaths, 4 transplantations) deterioration occurred with continued intravenous treatment during the following 6 months. CONCLUSIONS: In the group of patients described in this report the clinical and haemodynamic deterioration occurring while on mono therapy with inhaled iloprost could be stopped by switching to continuous application of intravenous iloprost. However, with continued intravenous therapy only a subgroup of patients could clinically be stabilized and transplanted successfully.