Hypertension artérielle pulmonaire primitive au cours de l’infection par le virus de l’immunodéficience humaine. Étude de neuf observations et revue de la littératurePrimary pulmonary hypertension and human immunodeficiency virus infection. Study of nine cases and review of the literature.

PURPOSE: In medical literature, primary pulmonary hypertension occurs in 0.5% of human immunodeficiency virus (HIV)-infected patients, irrespective of the stage of the HIV disease, and is more frequent in drug users. Plexogenic arteriopathy is the most frequent histological lesion. METHODS: We retrospectively report on nine cases of primary pulmonary hypertension during HIV infection. RESULTS: The subjects were four women and five men, mean age 38 years old. Four of them had been sexually contaminated and five had contracted the disease through intravenous drug use. At the time primary pulmonary hypertension was diagnosed, mean CD4 cell count was 234 +/- 217/mm3 and the viral load was low or undetectable. Primary pulmonary hypertension has been diagnosed an average of 7 months after the first cardiovascular clinical signs had started. Despite anti-coagulant (7/9 cases), vasodilatator (4/9 cases) and/or diuretic (7/9 cases) therapy, the progression of the disease quickly turned out to be negative (seven deaths). CONCLUSION: Diagnosis of primary pulmonary hypertension should be considered when unexplained dyspnea occurs in an HIV-positive patient. At initial evaluation, alterations of hemodynamic parameters are usually less severe than during idiopathic primary pulmonary hypertension, but their progression is quicker and more severe, independent of the patient's immune status. Current data do not allow the determination of whether antiretroviral therapy is active in primary pulmonary hypertension evolution. Therapeutic evaluation with prostacyclin is currently being carried out. While the life expectancy of HIV-infected patients extends, primary pulmonary hypertension occurrence could increase and call for early diagnosis, thus allowing for specific care.     

Primary pulmonary hypertension and thromboembolic pulmonary hypertension--similarities and differences

In a retrospective study of 36 patients with primary pulmonary hypertension (PPH) and 16 patients with chronic large vessel thromboembolic pulmonary hypertension (TPH) the diagnostic value of clinical features, chest radiographs, electrocardiographs, radionuclide lung scanning and cardiac catheterization was assessed. PPH patients were younger, had higher prevalence of Raynaud's phenomenon, right axis deviation, right ventricular hypertrophy on electrocardiograph and higher pulmonary artery pressures than TPH patients, but these features were not diagnostic. Although pulmonary angiography is considered by some to be necessary in distinguishing these two conditions, radionuclide lung scanning proved a safe and effective noninvasive method for this purpose.     

Pulmonary capillary hemangiomatosis associated with primary pulmonary hypertension: report of 2 new cases and review of 35 cases from the literature

Pulmonary capillary hemangiomatosis (PCH) is a rare cause of primary pulmonary hypertension characterized by thin-walled microvessels infiltrating the peribronchial and perivascular interstitium, the lung parenchyma, and the pleura. These proliferating microvessels are prone to bleeding, resulting in accumulation of hemosiderin-laden macrophages in alveolar spaces. Here we report 2 cases of PCH with pulmonary hypertension, 1 of them associated with mechanical intravascular hemolysis, a feature previously reported in other hemangiomatous diseases, but not in PCH. Case 2 was diagnosed by pulmonary biopsy; to our knowledge the patient is the second adult to be treated with interferon alpha-2a. Review of the literature identified 35 patients with PCH and pulmonary hypertension. The prognosis is poor and median survival was 3 years from the first clinical manifestation. Dyspnea and right heart failure are the most common findings of the disease. Hemoptysis, pleural effusion, acropachy, and signs of pulmonary capillary hypertension are less common. Chest X-ray or computed tomography scan usually shows evidence of interstitial infiltrates, pulmonary nodules, or pleural effusion. Hemodynamic features include normal wedge pressures. Radiologic and hemodynamic findings are undifferentiated from those of pulmonary veno-occlusive disease but differ from other causes of primary pulmonary hypertension. Epoprostenol therapy, considered the treatment of choice in patients with primary pulmonary hypertension, may produce pulmonary edema and is contraindicated in patients with PCH. Regression of lesions was reported in 1 patient treated with interferon therapy and 2 other patients stabilized, including our second patient. PCH was treated successfully by lung transplantation in 5 cases. Early recognition of PCH in patients with suspected primary pulmonary hypertension is possible based on clinical and radiologic characteristics. Diagnosis by pulmonary biopsy is essential for allowing appropriate treatment.     

Primary pulmonary hypertension in HIV patients: a systematic review

The relationship between grade of pulmonary hypertension and factors associated with human immunodeficiency virus among patients with HIV infection is poorly documented. This report documents the most extensive attempt made thus far to determine whether a relationship exists between degree of pulmonary hypertension and the following conditions: HIV risk factor, degree of immunosuppression, presence or absence of AIDS, and presence or absence of liver cirrhosis. A retrospective study involving a search of the published literature on primary pulmonary hypertension among HIV cases from 1987 to 1998, using the Medline and Aidsline databases was conducted. Patients for whom secondary causes of pulmonary hypertension could be excluded were selected, and the following information for each was recorded: age, gender, risk factors for HIV infection, HIV disease stage according to the Centers for Disease Control, previous opportunistic and neoplastic diseases, CD4+ cell count (cells/L), presence or absence of liver cirrhosis, pulmonary systolic artery pressure level, and lung pathology specimens. Information about the patient's survival time was also recorded. Seventy-six patients were judged to have primary pulmonary hypertension and were included in the study. While no correlation was found between pulmonary systolic artery pressure level and CD4+ cell counts, a statistically significant difference was found between HIV-positive patients with and without AIDS as determined by the Centers for Disease Control criteria with regard to the degree of pulmonary hypertension, expressed as pulmonary systolic artery pressure level (85.4 +/- 17 mm Hg vs 71.8 +/- 15 mm Hg, p < 0.013). Although a higher PAPS was present in HIV cirrhotic patients, a statistically significant difference was not found between degree of pulmonary hypertension and evidence of hepatic cirrhosis (85 +/- 21 mm Hg vs 73.1 +/- 15 mm Hg, p < 0.062). Patients with AIDS and primary pulmonary hypertension present a higher degree of pulmonary hypertension than non-AIDS patients. Pulmonary hypertension associated with HIV seems to be related to a cytokine-related stimulation and proliferation of endothelium. High levels of cytokines present in AIDS patients can favor pulmonary hypertension, but the role of a host response to HIV--determined by one or more HLA subtypes--is suspected to enhance high cytokine production levels.     

Familial pulmonary capillary hemangiomatosis resulting in primary pulmonary hypertension

We describe the first cases of familial pulmonary capillary hemangiomatosis, a disorder in which capillaries in the lungs proliferate. Three siblings died from primary pulmonary hypertension. One developed pulmonary congestion preterminally after vasodilator treatment. The inheritance pattern seems autosomal recessive. Lung specimens obtained in two siblings showed extensive pulmonary capillary hemangiomatosis, with normal capillaries proliferating into veins and alveoli. Including our patients, four of the nine patients with pulmonary capillary hemangiomatosis have presented with the clinical picture of primary pulmonary hypertension. Thus, pulmonary capillary hemangiomatosis should be considered as a histologic pattern of primary pulmonary hypertension. Most other cases of pulmonary capillary hemangiomatosis have been similar to pulmonary veno-occlusive disease. Recently, disorders involving the proliferation of cytologically normal capillaries have been termed angiogenic diseases. Pulmonary capillary hemangiomatosis may be an angiogenic disease.     

von Willebrand factor abnormalities in primary pulmonary hypertension

In primary pulmonary hypertension of recent clinical onset, pulmonary endothelial cells show injury. To characterize this phenomenon, we measured plasma von Willebrand factor (vWF) by immunologic and ristocetin cofactor assays in 6 patients with primary pulmonary hypertension, 17 patients with secondary pulmonary artery hypertension associated with congenital heart disease or cystic fibrosis, and 13 patients with congenital heart disease and normal pulmonary artery pressure. In selected cases, we also determined the vWF multimer pattern. In all 6 cases of primary pulmonary hypertension, the ristocetin cofactor activity was increased relative to the vWF antigen (vWF:Ag) concentration (a ratio of 2.55 +/- 0.36; normal range, 0.8 to 1.4); 4 of the 6 also had a similar and abnormal vWF multimer pattern--an increased proportion of the fastest moving bands. In the other 2, the multimer pattern was normal. Of the other 30 patients, a mild increase in ristocetin cofactor/vWF:Ag was seen in only 2 with secondary pulmonary hypertension and 1 with normal pulmonary artery pressure: these also had an abnormal vWF multimer pattern that was different from that observed in patients with primary pulmonary hypertension. The vWF abnormalities we describe in primary pulmonary hypertension offer a marker of the disease and could be helpful in understanding its pathogenesis.     

风湿性心脏病合并肺动脉高压的围手术期处理

目的总结风湿性心脏病合并肺动脉高压的围手术期处理和外科治疗经验,探讨提高早期生存率的方法。方法回顾性分析了自2000年6月至2005年7月体外循环下采用瓣膜置换手术治疗风湿性心脏病合并肺动脉高压患者92例。结果死亡3例,无术后心包填塞、二次开胸止血、肾功能衰竭等严重并发症。结论综合评价病情、正确掌握手术适应证、充分的术前准备、规范和恰当的围术期处理及手术技术的进步是提高外科治疗成功率的关键。     

World Health Organization Group III pulmonary hypertension

Pulmonary hypertension in the setting of parenchymal lung disease and conditions associated with chronic hypoxemia is commonly encountered in clinical practice and may adversely affect patients’ function and mortality. Diagnosis of this subgroup of pulmonary hypertension has evolved but still requires right heart catheterization for confirmation. The primary treatment goal is optimization of the underlying parenchymal lung or hypoxemia-associated condition prior to consideration of pharmacologic therapy. Limited published experience with pulmonary hypertension-specific medications for treatment of WHO Group 3 pulmonary hypertension suggests symptomatic and functional benefit in selected individuals. The potential for worsening ventilation–perfusion matching must be considered in these cases, however, since there is a paucity of data regarding the optimal approach to treatment selection. Ongoing medication trials and further investigation of mechanisms of hypoxic pulmonary vasoconstriction provide hope for these patients who in the past often had only lung transplantation as a potential treatment option.     

Palliation of systemic sclerosis–associated pulmonary hypertension by atrial septostomy

The onset of pulmonary hypertension in patients with systemic sclerosis carries a poor prognosis. Atrial septostomy has been used successfully to palliate end‐stage primary pulmonary hypertension but has not been attempted in other forms of pulmonary vascular disease. We report substantial clinical improvement following atrial septostomy in a patient with systemic sclerosis complicated by severe, isolated pulmonary hypertension. After the procedure, exercise capacity was improved and exertional syncope abolished. We suggest that this procedure should be considered for other patients with this diagnosis.     

Palliation of systemic sclerosis-associated pulmonary hypertension by atrial septostomy

The onset of pulmonary hypertension in patients with systemic sclerosis carries a poor prognosis. Atrial septostomy has been used successfully to palliate endstage primary pulmonary hypertension but has not been attempted in other forms of pulmonary vascular disease. We report substantial clinical improvement following atrial septostomy in a patient with systemic sclerosis complicated by severe, isolated pulmonary hypertension. After the procedure, exercise capacity was improved and exertional syncope abolished. We suggest that this procedure should be considered for other patients with this diagnosis.     

Primary pulmonary hypertension: natural history and the importance of thrombosis

A long-term retrospective follow-up study was made of 120 patients (33 male, 87 female patients) with primary pulmonary hypertension--diagnosed by strict clinical and hemodynamic criteria--to obtain a better understanding of the natural history and possible pathogenetic mechanisms of the disease. The mean age at diagnosis was 34 (3 to 64) years, but only 24 patients (21%) remained alive 5 years later. Lung tissue obtained at autopsy from 56 patients revealed two major pathologic types: thromboembolic pulmonary hypertension in 32 patients (57%) and plexogenic pulmonary arteriopathy in 18 (32%). Thus, in more than half the patients undergoing autopsy the major histologic feature was thrombi without any evidence of plexiform lesions. The two groups were similar with respect to their clinical and hemodynamic features and short survival. Of the variables tested for prognostic importance by stepwise multivariate analysis, only two were significant: pulmonary arterial oxygen saturation (p less than .00001) and anticoagulant therapy (p = .01). Anticoagulant therapy is recommended for patients with primary pulmonary hypertension.     

Evaluation of the effects of vasodilator therapy in primary pulmonary hypertension. Experience in 7 cases

Primary pulmonary hypertension is an uncommon but serious disease that often results in debilitating symptoms and early death. One approach to treatment has been to attempt a reduction of pulmonary artery pressure and vascular resistance by using vasodilator drugs with conflicting results in several studies. The aim of this study is to review the ten-years (1978-1988) experience of vasodilator therapy for primary pulmonary hypertension at our institute. In this period 7 patients, 5 women and 2 men, mean age 38.4 years (range 15-66) met clinical and hemodynamic criteria for primary pulmonary hypertension. At diagnosis 3/7 patients were in NYHA class III and 2/7 in class II. Diagnosis was confirmed by open lung biopsy in one case. Mean pulmonary artery pressure was 66 +/- 17 mmHg, mean value of pulmonary vascular resistances was 22.5 +/- 11 U.W. and of cardiac index 1.8 +/- 0.58 l/min/m2. Twelve different vasodilator drugs were tested during right heart catheterization in a non randomized manner. Various vasodilators were usually tested in the same patient (2 or more drugs in 6 patients). Only one patient did not tolerate acute therapy because of development of a persistent systemic hypotension. Hemodynamic responses to nitrates showed a general reduction in pulmonary artery pressure and pulmonary vascular resistances with marginal changes in cardiac index. Calcium channel-blocking agents elicited different responses in similar patients with favorable, little, no or adverse effects in pulmonary hemodynamics and sometimes a significant decrease in systemic vascular resistances. Also hydralazine showed favorable hemodynamic results in few cases but exacerbated pulmonary hypertension in others.(ABSTRACT TRUNCATED AT 250 WORDS)     

Secondary pulmonary hypertension

Opinion statement  The diagnosis of pulmonary hypertension first requires a clinical suspicion, as symptoms are often nonspecific. After the diagnosis is made, appropriate classification into the various categories of pulmonary hypertension is essential in order to manage the patient’s disease and symptoms appropriately. Therapy is targeted at the underlying cause of the pulmonary hypertension, as well as its effects on the cardiovascular system. Until recently, the treatment of both primary and secondary pulmonary arterial hypertension was limited to supportive therapy alone. With the advent of novel therapeutic agents, more focused therapies designed to treat the pulmonary vasculopathy have become available. These include pulmonary vasodilators such as continuous intravenous prostacyclin, and experimental agents currently undergoing clinical trials. For patients with pulmonary hypertension secondary to pulmonary venous hypertension, therapies differ. In cases where there is left-sided heart disease leading to pulmonary venous hypertension, treatment is aimed at repairing or ameliorating the underlying heart disease. Patients with pulmonary venous hypertension due to extrinsic compression of the central pulmonary veins, or pulmonary veno-occlusive disease have few options, and treatment is generally palliative. In patients with pulmonary hypertension that is associated with disorders of the respiratory system or hypoxemia, the pulmonary hypertension is due to a reactive pulmonary vasoconstriction. Reversal of this vasoconstriction with pulmonary vasodilators can be harmful because of the risk of increasing perfusion to nonventilated lung units. Pulmonary hypertension due to chronic thrombotic or embolic disease can be treated surgically, if the obstructive thrombi are proximal enough for the surgeon to resect them. More distal pulmonary emboli, however, cannot be resected, but there is emerging evidence that the chronic administration of pulmonary vasodilators can be effective in treating this form of the disease.     

Vasodilator therapy for primary pulmonary hypertension. Limitations and hazards

Vasodilator drugs were initially administered to patients with primary pulmonary hypertension based on the unproven hypothesis that pulmonary vasoconstriction played an important role in the pathogenesis of the disease. There were early reports of hemodynamic and clinical improvement after treatment with various vasodilating agents, but subsequent experience did not confirm these uncontrolled observations, and emphasized the limitations and hazards of this approach. Vasodilator therapy generally fails to reduce pulmonary vascular resistance selectively during long-term administration and frequently leads to systemic hypotension, exacerbation of the pulmonary hypertensive state, worsening of right ventricular failure, and systemic arterial desaturation. Beneficial hemodynamic responses are seen in only 15% to 25% of patients. Vasodilator therapy should not be considered an established treatment of patients with primary pulmonary hypertension.     

Primary pulmonary hypertension in the elderly.

Primary pulmonary hypertension is usually considered a disease of younger adults. We reviewed the natural course of primary pulmonary hypertension in patients aged 65 years or greater. During an 8-year period, 63 elderly patients were discharged from our hospital with a diagnosis of pulmonary hypertension. In eight instances, an elevated mean pulmonary arterial pressure (greater than 25 mm Hg) could not be explained by secondary causes. These elderly patients with primary pulmonary hypertension had symptoms common to younger patients with this disease, including dyspnea (eight patients), chest pain (five), pedal edema (four), and fatigue (one). In all but one patient, the initial diagnosis was incorrect, and the patients were thought to have more common diseases of the elderly that cause similar symptoms. Coexisting medical problems were common and further obscured the correct diagnosis. Survival was significantly shorter in those patients with symptoms of less than 6 months' duration. Primary pulmonary hypertension should be considered in the differential diagnosis in elderly patients with unexplained dyspnea and chest pain.     

肺假性淋巴瘤5例报告及文献复习

目的：探讨肺假性淋巴瘤的临床特点。方法：回顾性分析5例病理学诊断的肺假性淋巴瘤患者的临床表现。影像学，纤维支气管镜检查的结果及其转归。结果：所有患者无肺门、纵隔淋巴结肿大，其中1例胸片及CT片显示双肺多个椭圆形巨大肿块外，余均表现为双肺多灶性片状浸润阴影，边缘模糊不清，内见支气管充气征，均经纤支镜肺活检明确诊断，病理提示“大量成熟淋巴细胞浸润”，该5例患者中有3例最终发现成恶性淋巴瘤，另2例存活至今，病程为8－9年，5例患者中3例接受过COP等方案化疗，其中1例转恶性淋巴瘤死亡，结论：肺假性淋巴瘤罕见，临床表现无特异性，一般实验室检查无异常，确诊需依赖纤支镜肺活检，部分患者最终转归为恶性淋巴瘤，对明确诊断的患者可应用化疗并密切随访。     

Adenosine plasma concentration in pulmonary hypertension.

OBJECTIVE: In this study, we sought to appreciate the role of adenosine in the regulation of pulmonary vascular tone, especially in the case of clinical pulmonary hypertension, by investigating the relationship between endogenous plasma adenosine levels and pulmonary artery vasoconstriction. METHODS: Adenosine plasma concentrations, were measured simultaneously in the distal right pulmonary artery and in the femoral artery, both at steady state (room air) and during pure oxygen inhalation. Three clinical situations were considered: (1) normal hemodynamics [7 control subjects, mean pulmonary artery pressure (MPAP) = 18.5 +/- 1 mm Hg], (2) moderate pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD), (8 patients, MPAP = 31 +/- 3 mm Hg), (3) severe primary pulmonary hypertension (PPH), (8 patients, MPAP = 70 +/- 5 mm Hg). RESULTS: In every instance, adenosine evaluated by HPLC was higher in the pulmonary than in the systemic circulation. For room air, adenosine plasma concentrations were significantly lower in COPD (0.49 +/- 0.16 mumol l-1) and PPH patients (0.45 +/- 0.14 mumol l-1) than in controls (1.26 +/- 0.12 mumol l-1). During O2 administration, adenosine plasma concentrations all decreased but more so in COPD and PPH patients. The significant correlations between adenosine plasma concentrations and both pulmonary vascular resistance and PvO2, in controls, were not found in COPD or PPH patients. CONCLUSION: The adenosine plasma concentrations in the pulmonary circulation of PPH and COPD patients are low, and may contribute to pulmonary artery hypertension.     

成人动脉导管未闭合并重度肺动脉高压介入治疗及随访研究

目的:探讨成人动脉导管未闭合并重度肺动脉高压封堵治疗可行性及近中远期临床结果。方法:回顾分析2006年6月至2018年6月,首都医科大学附属安贞医院小儿心脏科,34例成人动脉导管未闭合并重度肺动脉高压患者临床资料,患者均行介入治疗,依据治疗前后血流动力学资料及临床资料评估封堵治疗效果,采用心电图及超声心动图进行随访。结果:34例动脉导管未闭合并重度肺动脉压患者进行动脉导管封堵,33例封堵成功,1例封堵失败,封堵成功率为97.1%。介入治疗后患者肺动脉收缩压、肺动脉平均压、肺血管阻力低于治疗前(P<0.05);介入治疗后主动脉收缩压、主动脉平均压高于治疗前(P<0.05);介入治疗前后血氧饱和度比较无统计学差异(P>0.05)。封堵后重复造影无残余分流29例,微量残余分流4例,未见其他并发症发生。患者介入治疗后LAD、LVEDD、PA均低于治疗前(P<0.05);介入治疗后LVEF与术前相比,差异无统计学意义(P>0.05)。结论:介入治疗可安全、有效改善治疗成人动脉导管未闭合并重度肺动脉高压,且近中远期疗效较好,值得广泛应用于临床。     

Chronic oral sildenafil therapy in severe pulmonary artery hypertension

BACKGROUND: Sildenafil, a selective phosphor-diesterase-5 inhibitor, may be of clincal benefit in patients with pulmonary artery hypertension. METHODS AND RESULTS: Fourteen patients, aged 5-30 years, with severe pulmonary artery hypertension (9 with primary pulmonary hypertension, 5 with operated congenital heart disease) received oral sildenafil in addition to conventional therapy. Twelve patients were in New York Heart Association functional class III or IV. The drug was started in low dose and empirically increased. Finally a median dose of 87.5 mg/day was used in children weighing less than 30 kg, and 150 mg/day in those with weight more than 30 kg. The patients were followed up by assessing their functional status, six-minute walk test, Doppler echocardiography and hemodynamic study (in selected cases). On mean follow-up of 7.3+/-2.4 months (range 3-14 months), New York Heart Association functional class improved from 3.31+/-0.75 to 2.00+/-0.71 (p<0.002). There was a remarkable improvement on the six-minute walk test from a baseline of 264.1+/-193.7 m to 408.2+/-156.97 m at 3 months (p<0.001) and 453.2+/-159.81 (p<0.0001) at 6 months. The right ventricular systolic pressure estimated echocardiographically declined from 112.40+/-45.21 mmHg to 101.86+/-47.86 mmHg (p<0.002). The mean pulmonary artery pressure decreased from 62 mmHg to 47 mmHg in 4 patients of primary pulmonary hypertension recatheterized after a mean of 7 months of sildenafil treatment. Clinical improvement was seen even when no decrease in pulmonary artery pressure was demonstrated in one patient with secondary pulmonary artery hypertension. However, 2 patients died during follow-up despite clinical improvement. CONCLUSIONS: Oral sildenafil was well tolerated and led to an improved clinical condition and exercise performance. Whether the drug improves mortality remains to be established. Larger trials a rewarranted.     

Portopulmonary hypertension: state of the art: Concise Review

Portopulmonary hypertension is an uncommon but treatable pulmonary vascular consequence of portal hypertension, which can lead to significant morbidity and mortality. Portopulmonary hypertension results from excessive pulmonary vasoconstriction and vascular remodeling that eventually leads to right-heart failure and death if left untreated. Although pulmonary vascular disease in these patients may be asymptomatic or associated with subtle and nonspecific symptoms (dyspnea, fatigue and lower extremity swelling), it should be looked for especially if patients are potential candidates for liver transplantation. Patients with clinical suspicion of portopulmonary hypertension should undergo screening testing, specifically echocardiography. Right heart catheterization remains the gold standard for the diagnosis. The existence of moderate to severe disease poses higher risks and challenges for liver transplantation. The disease has a substantial impact on survival and requires focused pharmacological therapy. New and evolving medical therapies, such as prostanoids (intravenous, inhaled or oral), endothelin receptors antagonists, phosphodiesterases inhibitors, combination therapy and other experimental drugs might change the natural course of the disease. Case reports and cases series have been published regarding the efficacy and safety of pharmacological therapy, but randomized, controlled multicenter trials are urgently needed. Liver transplantation is not the treatment of choice for portopulmonary hypertension, but after optimal hemodynamic and clinical improvement with medical therapy as a bridge, liver transplant can be considered an option in selected patients.