肺静脉闭塞病的临床特征分析

目的:分析肺静脉闭塞病(PVOD)患者的临床特征,以提高PVOD诊断水平。方法:纳入2016年1月至2018年7月就诊于阜外医院肺血管病中心且诊断为动脉性肺动脉高压(PAH)的患者217例。结合患者的基因检测结果及临床资料,217例患者中,确诊特发性肺动脉高压(IPAH)175例,可遗传性动脉性肺动脉高压(HPAH)19例,可遗传性出血性毛细血管扩张症11例,余12例存在真核生物翻译起始因子2α激酶4(EIF2AK4)致病突变被确诊为PVOD。分析对比PVOD患者与IPAH和(或)HPAH患者临床表现、影像学特点及临床预后情况。结果:PVOD患者临床症状与IPAH相似,易误诊,但前者生存率更低(P0.0001)。PVOD患者肺部高分辨CT最显著的特征性影像学表现为小叶中心型弥漫性磨玻璃样改变。PVOD患者入院时体重指数和动脉血氧饱和度较IPAH患者更低(P均0.05),肺功能检测多提示重度弥散功能下降。一氧化碳弥散量占预测值百分比≤38.5%,可预测PVOD的敏感度为96.45%,特异度为100%。结论:PVOD患者早期无特异性临床表现,肺功能检查、肺部高分辨CT结合PAH基因检测有助于提高PVOD的早期确诊率。     

肺静脉堵塞病:1例报道及文献复习

目的 提高对肺静脉堵塞病(PVOD)的认识.方法 对1例PVOD患者的临床资料进行分析,并结合文献复习.结果 PVOD是一种临床少见病,临床表现为进行加重的劳力性呼吸困难和肺动脉高压.影像学特征为肺水肿、Kerley B线、肺动脉高压和右心房室扩大等征象,左心房正常.血流动力学表现为肺动脉压升高,肺动脉楔压(PAWP)和左房压正常.组织病理学可见弥漫性的肺小静脉管腔狭窄和闭塞.结论 重度肺动脉高压、肺水肿和PAWP正常(或左心房内径正常)被称为PVOD三联征,可作为PVOD的临床诊断标准.血管扩张剂可诱发急性肺水肿和猝死,应谨慎使用.PVOD预后不良,肺移植是惟一确定有效的治疗方法.     

肺静脉闭塞病1例

肺静脉闭塞病（pulmonaryvenoocclusivedisease,PVOD）是一种罕见的疾病,由于PVOD和特发性肺动脉高压具有相似的临床表现、遗传背景和血流动力学,有5％～10％的患者被初步考虑为特发性肺动脉高压,PVOD必须通过活检来确定诊断,但因肺活检存在着高风险,因此,一般是通过胸部高分辨率CT（highresolutioncomputedtomography,HRCT）、动脉血气、肺功能和支气管肺泡灌洗等临床诊断PVOD。现将1例通过肺活检病理确诊病例的临床表现、影像学表现、病理结果及相关检查报道如下。     

肺动脉高压患者肺功能特点分析

目的 探讨国人肺动脉高压患者肺功能特点及其在肺动脉高压诊断中的价值.方法 连续入选经右心导管确诊的41例肺动脉高压患者为研究对象,所有患者均进行6分钟步行距离试验和肺功能检查,并与健康对照组比较其肺功能变化特点.结果 肺动脉高压组肺总量、肺活量和第1秒用力呼出量百分比对照组明显下降(分别为80.27±11.46和94.24±6.82;79.09±14.89和97.35±9.51;75.40±16.58和95.12±12.01,P＜0.001),残气量与肺总量比值较对照显著升高(分别为117.67±25.73和93.39±10.87,P＜0.001),第1秒用力呼出量与用力肺活量比值百分比与呼气中期流速百分比与对照组分别下降6.O%和19.4%(P=0.21和0.09),一氧化碳弥散量百分比与弥散量/肺泡通气量百分比较对照组分别下降36.6%和29.8%(P＜0.001),呼吸总阻力、总气道阻力和中心气道阻力和与对照组均无明显差异.有12.2%的患者肺功能检查结果完全正常.结论 特发性肺动脉高压、先天性心脏病相关性肺动脉高压和结缔组织病相关性肺动脉高压的肺功能改变相似,"动脉型"肺高压患者不仅可以存在不同程度外周气道阻塞性通气功能障碍,同时可合并弥散功能障碍,而肺阻力无明显变化.肺功能检查正常不能作为排除肺动脉高压的筛查手段.     

《中国肺动脉高压诊断与治疗指南(2021版)》解读——具有明显肺静脉或肺毛细血管受累的肺动脉高压

肺静脉闭塞病(PVOD)和肺毛细血管瘤病(PCH)是一类引起肺动脉高压的罕见疾病,目前统称为具有明显肺静脉或肺毛细血管受累的肺动脉高压,是动脉性肺动脉高压(PAH)中的一个亚类.这一类型肺动脉高压以肺小静脉或肺毛细血管受累为主要特点,临床表现、病理特征上具有高度相似性,目前认为这两种疾病是同一种疾病的两种表现.PVOD...     

左心功能相关参数及左右心室内径比值与中重度肺动脉高压患者预后的关系

目的:探讨超声心动图无创测量左心功能相关参数及左右心室内径比值与中重度肺动脉高压患者预后的关系.方法:回顾性分析2019年1月至2020年11月我院心内科住院的中重度肺动脉高压患者90例,并依据随访中临床恶化[包括全因死亡、肺移植、因肺动脉高压恶化再住院、肺动脉高压治疗升级(增加口服靶向药物种类或增加剂量或增加皮下或静...     

老年慢性血栓栓塞性肺动脉高压患者的临床特征及预后危险因素分析

目的 分析老年慢性血栓栓塞性肺动脉高压(CTEPH)患者的临床特征,并探讨其死亡的危险因素.方法 连续入选2013年6月～2019年6月于本中心就诊的老年CTEPH患者132例,其中单纯靶向药物治疗54例,血运重建+靶向药物治疗78例,血运重建包括肺动脉内膜剥脱术19例,行肺动脉球囊扩张术59例,根据随访结果分为存活组...     

结缔组织病继发肺动脉高压的临床分析

目的 总结结缔组织病(CTD)继发肺动脉高压(PAH)患者的临床特点.方法 回顾性分析1997～ 2011年复旦大学附属华山医院收治的53例结缔组织病继发肺动脉高压患者的临床资料,对患者的疾病种类、临床表现、实验室检查以及诊治和预后情况进行统计学分析.结果 1530例结缔组织病患者共发生肺动脉高压53例,其中女46例,男7例,平均年龄(43.9±13.8)岁,病程(5.1 ±4.2)年.肺动脉高压在系统性红斑狼疮中最为常见.主要临床表现为呼吸困难(84.9％)和肢端雷诺征(56.6％).肺动脉高压患者体内的ANA、nRNP和SSA抗体的比例明显升高.53例患者中7例(13.2％)死亡,死亡主要原因为右心功能衰竭.死亡者与存活者相比,肺动脉压力显著升高,动脉氧分压(PaO2)明显降低.47例患者(88.7％)使用传统的降压药治疗肺动脉高压,新型血管扩张药使用较少.结论 不同结缔组织病间肺动脉高压的发生率有较大差异.结缔组织病继发肺动脉高压的主要表现是呼吸困难和肢端雷诺征.严重肺动脉高压将影响结缔组织病患者的生存率,肺动脉压力和PaO2的检测有利于判断预后.     

艾森曼格综合征的诊疗及随访分析

目的:观察了解艾森曼格综合征(ES)患者的诊治情况。方法:回顾性分析2007年7月至2012年11月期间,入住北京安贞医院小儿心脏科,且均经心导管检查的ES患者69例,男性18例,女性51例,平均年龄为(16.2±8.5)岁,平均随访时间为(2.0±1.1)年。随访期间所有患者存活,无死亡病例。临床诊断包括房间隔缺损4例,室间隔缺损16例,完全型房室间隔缺损3例,动脉导管未闭8例,并存2或3种以上所述心脏畸形27例,复杂心脏畸形11例。结果:69例患者中有54例患者应用肺动脉高压的靶向药物治疗,其中波生坦治疗23例,西地那非治疗26例,以上两种药物的联合治疗5例,无特殊药物治疗15例。应用波生坦治疗后,患者的肺动脉平均压(mPAP)由(74.8±7.6)mmHg(1 mmHg=0.133 kPa)下降至(70.2±7.3)mmHg(P=0.012),肺主动脉压力比Pp/Ps由[(1.029±0.073)降至(0.943±0.088),P=0.021],肺/体循环流量比(Qp/Qs)由[(0.969±0.235)升至(1.107±0.251),P=0.014],Rp/Rs由(1.005±0.297)降至(0.829±0.220),P=0.014,肺小动脉阻力指数(PVRI)由[(21.9±7.9)Wood.m2降至(18.0±7.4)Wood.m2,P=0.06];应用西地那非治疗后,患者的mPAP由[(82.7±7.5)mmHg下降至(75.7±7.8)mmHg,P=0.014],Pp/Ps由[(1.068±0.495)降至(0.997±0.973),P=0.235],Qp/Qs由(0.928±0.290)升至(1.105±0.304),P=0.100,肺/体循环阻力比(Rp/Rs)由(1.129±0.374)降至(0.798±0.155),P=0.036,PVRI由[(25.8±6.1)Wood.m2降至(20.6±4.6)Wood.m2,P=0.039]。SpO2、6 min步行试验距离、超声心动图、BNP等均有不同程度的改善,纽约心脏病学会心功能分级保持稳定,且未发生不良反应。结论:超过78%的ES患者开始应用肺动脉高压靶向药物进行治疗。ES患者应用肺动脉高压的长期靶向药物治疗是安全有效的,且耐受性好。波生坦和西地那非能够显著降低ES患者的mPAP、Rp/Rs等心导管检查血流动力学参数,并改善运动能力和临床症状。     

妊娠合并特发性肺动脉高压8例临床分析

目的分析和总结妊娠合并特发性肺动脉高压(IPAH)患者的临床资料及治疗效果。方法回顾性分析2012年1月到2013年12月武汉亚洲心脏病医院收治的8例妊娠合并IPAH患者(妊娠组),将同期IPAH患者中非妊娠的18例患者作为对照(非妊娠组)。比较两组患者临床资料、实验室检查和心导管检查结果,评价IPAH的治疗效果和预后。结果两组患者年龄、性别、体重、气促、黑矇、咯血、发绀、心包积液、Brog评分等比较,差异均无统计学意义(均P0.05)。妊娠组晕厥(2/8比0,P=0.027)及水肿(8/8比4/18,P0.001)比例显著高于非妊娠组;妊娠组患者初诊时世界卫生组织肺动脉高压功能(WHO-FC)分级Ⅲ级(5/8)、Ⅳ级(2/8)居多,非妊娠组以Ⅱ级(13/18)居多,组间比较差异有统计学意义(P=0.004)。妊娠组患者三尖瓣反流速度[(4.19±0.57)m/s比(4.78±0.68)m/s,P=0.042]、心脏指数[(1.74±0.51)L/(min·m~2)比(2.62±0.79)L/(min·m~2),P=0.030]小于非妊娠组,而左心室收缩末期内径[(3.21±0.58)cm比(2.16±0.67)cm,P=0.001]大于非妊娠组,差异均有统计学意义。8例妊娠组患者急性肺血管扩张试验均为阴性,除1例失访外,其余7例随访14～30(17.38±9.52)个月。2例患者因经济原因仅在住院期间使用靶向肺血管扩张药,其中1例因肺动脉高压危象死亡,另1例WHO-FC由Ⅲ级及降为Ⅳ级;5例接受规律靶向肺血管扩张药,其中1例死亡,1例效果不佳,3例心功能改善。3例心功能改善患者治疗后12个月复查脑钠肽下降了(287±256)pg/ml,6 min步行距离试验平均距离增加了(43.0±10.4)m,Borg呼吸困难评分降低了(1.8±1.6)分。结论妊娠可缩短既往无症状IPAH患者的疾病进程并对生命造成严重危害。坚持继续妊娠的患者早期足量使用靶向肺血管扩张药可改善妊娠合并IPAH的预后。     

COPD a social disease: inappropriateness and pharmaco-economics. The role of the specialist: present and future

Despite the development of specific therapies for pulmonary arterial hypertension (PAH) some patients fail to respond to such treatment. One of the potential reasons for the unresponsiveness to targeted therapies may be the presence of fibrous occlusion of small pulmonary veins that accompanies pre-capillary arteriopathy. This type of pathologic change is called pulmonary veno-occlusive disease (PVOD). Underdiagnosed PVOD occurs probably in 5-10% of idiopathic pulmonary hypertension (IPAH) and in a substantial proportion of PAH related to connective tissue diseases (mainly in scleroderma). A definite diagnosis of PVOD requires histological examination of lung sample, but surgical lung biopsy in pulmonary hypertension is combined with high risk of bleeding. Thus major interest is focused on a non-invasive diagnostic approach enabling early recognition of PVOD and referral for lung transplantation. The present review is focused on the radiological features suggestive of PVOD-like vasculopathy in PAH.     

Occult alveolar haemorrhage in pulmonary veno-occlusive disease.

Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary arterial hypertension that affects predominantly post-capillary pulmonary vessels. A major concern with PVOD is the poor response to available therapies and the risk of pulmonary oedema with continuous intravenous epoprostenol. The present authors hypothesised that alveolar haemorrhage may be a characteristic feature of pulmonary veno-occlusive disease, as compared with other forms of pulmonary arterial hypertension that predominantly involve pre-capillary pulmonary arteries. This paper reports a series of 19 patients with either PVOD (n = 8) or idiopathic pulmonary arterial hypertension (IPAH; n = 11) who underwent bronchoalveolar lavage. Cytological analyses were performed and differential counts were made on Perls-stained preparations. The Golde score was used to assess alveolar haemorrhage. As compared with IPAH, PVOD was characterised by a higher percentage of haemosiderin-laden macrophages (40+/-37 versus 3+/-6%), resulting in elevated Golde scores (81+/-88 versus 4+/-10). It was concluded that occult alveolar haemorrhage is a common feature of pulmonary veno-occlusive disease. Detecting occult alveolar haemorrhage may be of interest in the diagnostic approach of pulmonary veno-occlusive disease.     

Pulmonale veno-okklusive Erkrankung

Pulmonary veno-occlusive disease (PVOD) is an important differential diagnosis of idiopathic (IPAH) and hereditary pulmonary arterial hypertension (HPAH), where the primary obstruction of the pulmonary blood is located in the small pulmonary venules. The obstruction is due to fibrotic material which is located in the intima of the veins and the interlobular septae where the veins are located. In addition thickened interalveolar pulmonary capillaries form a patchy capillary hemangiomatosis. Mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 protein (EIF2AK4) gene have recently been identified as the cause of most cases of hereditary PVOD and some 25?% of sporadic PVOD cases. Another set of PVOD patients develop the disease after therapy with mitomycin C or alkylating substances. Therapy is very difficult. Targeted IPAH therapy is prone to adverse effects caused by lung edema. Lung transplantation should be considered early after diagnosis.     

Good response to pulmonary arterial hypertension-targeted therapy in 2 pulmonary veno-occlusive disease patients: A case report

Rationale:Pulmonary veno-occlusive disease (PVOD) is a kind of rare and fatal pulmonary arterial hypertension (PAH). Different from other subtypes of PAH, PVOD patients have a very poor prognosis because of the progressive nature of pulmonary vascular involvement and fatal pulmonary edema induced by PAH-targeted drugs. Lung transplantation is the only choice for these patients.Patient concerns:We reported 2 cases of PVOD which was misdiagnosed as idiopathic pulmonary arterial hypertension initially due to the lack of typical findings of PVOD. Right heart catheterization was done. The results showed severe PAH with mean pulmonary artery pressure at 76 mmHg and 68 mmHg.Diagnosis:The diagnosis of idiopathic pulmonary arterial hypertension was corrected by eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) mutation screening. Biallelic mutations (c.1387delT (p. Arg463fs); c.989-990 delAA (p. Lys330fs)) were detected by next-generation sequencing for whole exome from blood sample. The presence of biallelic EIF2AK4 mutation was sufficient to confirm the diagnosis of PVOD.Interventions:The 2 patients had good response to PAH-targeted therapy (Ambrisentan 10 mg once a day and tadalafil 20 mg once a day) in the following 1 year.Outcomes:Because the patients had a good response to targeted drugs, the treatment of the 2 cases was unchanged. Over 1-year period, they still have a good response to PAH-targeted drugs. There was no sign of pulmonary edema.Lessons:All these results may indicate that PVOD is not so rare and typical findings of PVOD are lacking in some patients. EIF2AK4 mutation screening by next-generation sequencing maybe useful to differentiate PVOD from other PAH subtypes. PVOD is a heterogeneity population and different patients have different characteristics including response to PAH-targeted therapy. How to pick off this portion of patients timely is the core issue. Further study is necessary to answer this question.     

Ventilation/perfusion lung scan in pulmonary veno-occlusive disease

Pulmonary veno-occlusive disease (PVOD), a rare form of pulmonary arterial hypertension (PAH), requires histological proof for definitive diagnosis; however, lung biopsy is not recommended in PAH. Recent conjoint European Respiratory Society/European Society of Cardiology guidelines suggest that nonmatched perfusion defects on ventilation/perfusion (V'/Q') lung scanning in PAH patients may suggest PVOD. The aim of our study was to evaluate V'/Q' lung scans in a large cohort of PVOD and idiopathic or heritable PAH patients. V'/Q' lung scans from 70 patients with idiopathic or heritable PAH and 56 patients with confirmed or highly probable PVOD were reviewed in a double-blind manner. The vast majority of V'/Q' lung scans were normal or without significant abnormalities in both groups. No differences in ventilation or perfusion lung scans were observed between PAH and PVOD patients (all p>0.05). Furthermore, no differences were observed between confirmed (n=31) or highly probable PVOD (n=25). Nonmatched perfusion defects were found in seven (10%) idiopathic PAH patients and four (7.1%) PVOD patients (p>0.05). Nonmatched perfusion defects were rarely seen in a large cohort of idiopathic or heritable PAH and PVOD patients. Future recommendations should be amended according to these results suggesting that V'/Q' lung scanning is not useful in discriminating PVOD from idiopathic PAH.     

Pulmonary veno-occlusive disease: clinical, functional, radiologic, and hemodynamic characteristics and outcome of 24 cases confirmed by histology

Pulmonary veno-occlusive disease (PVOD) is defined by specific pathologic changes of the pulmonary veins. A definite diagnosis of PVOD thus requires a lung biopsy or pathologic examination of pulmonary explants or postmortem lung samples. However, lung biopsy is hazardous in patients with severe pulmonary hypertension, and there is a need for noninvasive diagnostic tools in this patient population. Patients with PVOD may be refractory to pulmonary arterial hypertension (PAH)-specific therapy and may even deteriorate with it. It is important to identify such patients as soon as possible, because they should be treated cautiously and considered for lung transplantation if eligible. High-resolution computed tomography of the chest can suggest PVOD in the setting of pulmonary hypertension when it shows nodular ground-glass opacities, septal lines, lymph node enlargement, and pleural effusion. Similarly, occult alveolar hemorrhage found on bronchoalveolar lavage in patients with pulmonary hypertension is associated with PVOD. We conducted the current study to identify additional clinical, functional, and hemodynamic characteristics of PVOD.We retrospectively reviewed 48 cases of severe pulmonary hypertension: 24 patients with histologic evidence of PVOD and 24 randomly selected patients with idiopathic, familial, or anorexigen-associated PAH and no evidence of PVOD after meticulous lung pathologic evaluation. We compared clinical and radiologic findings, pulmonary function, and hemodynamics at presentation, as well as outcomes after the initiation of PAH therapy in both groups.Compared to PAH, PVOD was characterized by a higher male:female ratio and higher tobacco exposure (p < 0.01). Clinical presentation was similar except for a lower body mass index (p < 0.02) in patients with PVOD. At baseline, PVOD patients had significantly lower partial pressure of arterial oxygen (PaO2), diffusing lung capacity of carbon monoxide/alveolar volume (DLCO/VA), and oxygen saturation nadir during the 6-minute walk test (all p < 0.01). Hemodynamic parameters showed a lower mean systemic arterial pressure (p < 0.01) and right atrial pressure (p < 0.05), but no difference in pulmonary capillary wedge pressure. Four bone morphogenetic protein receptor II (BMPR2) mutations have been previously described in PVOD patients; in the current study we describe 2 additional cases of BMPR2 mutation in PVOD. Computed tomography of the chest revealed nodular and ground-glass opacities, septal lines, and lymph node enlargement more frequently in patients with PVOD compared with patients with PAH (all p < 0.05). Among the 16 PVOD patients who received PAH-specific therapy, 7 (43.8%) developed pulmonary edema (mostly with continuous intravenous epoprostenol, but also with oral bosentan and oral calcium channel blockers) at a median of 9 days after treatment initiation. Acute vasodilator testing with nitric oxide and clinical, functional, or hemodynamic characteristics were not predictive of the subsequent occurrence of pulmonary edema on treatment. Clinical outcomes of PVOD patients were worse than those of PAH patients.     

Enfermedad pulmonar venooclusiva en una mujer jardinera

Pulmonary veno-occlusive disease (PVOD) is a subgroup of pulmonary arterial hypertension with a poor prognosis. The diagnosis is usually delayed and treatment options other than lung transplantation are unfortunately limited. We report the case of 51-year-old female gardener diagnosed with PVOD by open lung biopsy before her death. Although there are many reported cases of hepatic veno-occlusive disease due to toxic agents present in nature, such as pyrrolizidine alkaloid exposure, to date this has not been linked to PVOD.     

"High probability" perfusion lung scans in pulmonary venoocclusive disease

"High-probability" ventilation/perfusion (V/Q) lung scans generally indicate proximal pulmonary arterial occlusion by thromboemboli or, rarely, other processes such as tumors, fibrosing mediastinitis, or vasculitis. In this report we describe three patients with high probability V/Q scans in whom pulmonary angiography failed to demonstrate arterial occlusion. All three patients were determined to have pulmonary venoocclusive disease (PVOD). In two patients, a tissue diagnosis of PVOD was made, in one case with explanted tissue taken after a successful heart-lung transplant and in the other case with tissue taken at autopsy. PVOD in the third patient was diagnosed with pulmonary venography. A potential explanation for the discrepancy between perfusion lung scan and pulmonary angiographic findings in PVOD is discussed.     

Effects of continuous IV prostacyclin in a patient with pulmonary veno-occlusive disease

Pulmonary veno-occlusive disease (PVOD) is a rare but life-threatening disease. Although prostacyclin (PGI(2)) attenuates pulmonary hypertension and improves the prognosis in patients with primary pulmonary hypertension, little information is available regarding the effect of PGI(2) on patients with PVOD. This report describes a patient with severe PVOD who showed marked improvement in exercise capacity and pulmonary hemodynamics with continuous IV PGI(2) treatment. Furthermore, he experienced no clinical events for 12 months and survived for 25 months after the initiation of PGI(2) therapy. These results suggest that continuous IV PGI(2) therapy may serve as a bridge to transplantation in some cases of PVOD.     

Venous and arterial changes in pulmonary veno-occlusive disease, mitral stenosis and fibrosing mediastinitis.

The pathogenesis of pulmonary veno-occlusive disease (PVOD) is not known. The diagnosis of PVOD frequently relies on its histological changes since it is often difficult to distinguish clinically from primary pulmonary hypertension. This study carried out a systematic analysis of the pulmonary venous and arterial remodelling that occurs in PVOD (n=5) and compared these changes to two other diseases affecting the pulmonary veins, mitral stenosis (MS; n=6) and fibrosing mediastinitis (FM; n=2), using established morphometric techniques. In PVOD, pronounced intimal and adventitial thickening were noted in veins of all sizes and arterialization of veins >50 microm external diameter was found. Similar changes were evident in the arterial wall, but intimal thickening was less severe than in the veins and medial thickening was more pronounced in arteries <300 microm external diameter. Eccentric intimal fibrosis of the veins was also noted for the first time in PVOD, although this feature occurred less frequently (approximately one third) than in MS. Less pronounced structural remodelling was also encountered in the veins in cases of MS and FM. The severity of the venous changes in PVOD may aid its diagnosis and lend insight into its pathogenesis. However, the similarity of the vascular changes in each form of venous hypertension also suggests that pathology alone may not always differentiate between these disease states. The similarity of the vascular changes in the three forms of venous hypertension suggests that, as in pulmonary artery hypertension, pressure, per se, is one of the triggers to vascular remodelling.