Pulmonary vascular steal in chronic thromboembolic pulmonary hypertension

After pulmonary thromboendarterectomy, performed for relief of chronic thromboembolic pulmonary hypertension, perfusion lung scans have frequently disclosed new perfusion defects in segments served by undissected pulmonary arteries. Our hypotheses were that these new postoperative defects occurred with great frequency and did not represent postoperative vessel occlusion. We retrospectively reviewed the preoperative and postoperative perfusion scans of 33 consecutive patients undergoing pulmonary thromboendarterectomy. New postoperative perfusion defects were noted in 23 of 33 patients. The incidence of new defects was increased tenfold in segments that had (1) normal preoperative angiographic findings, (2) normal preoperative radionuclide perfusion, and (3) not been entered at the time of surgery. Postoperative angiograms, available in 15 of 33 patients, documented the nonembolic, nonocclusive nature of the new perfusion scan defects. The most plausible alternate explanation for this previously undescribed finding is a redistribution of pulmonary arterial resistance induced by the thromboendarterectomy, namely, a pulmonary vascular "steal."     

Update on chronic thromboembolic pulmonary hypertension

Chronic, unresolved thromboemboli are an important cause of pulmonary hypertension (PH) with specific treatment strategies differing from other types of PH. Chronic thromboembolic pulmonary hypertension (CTEPH) is classified as group 4 PH by the World Health Organization. It is a rare, but underdiagnosed, complication of acute pulmonary embolism that does not resolve and results in occlusion of large pulmonary arteries with a fibro-thrombotic material. The etiology of CTEPH remains uncertain, and it is unknown why certain patients with acute pulmonary embolism develop this disorder. The evaluation for CTEPH is an important part of the evaluation for PH in general, and it is crucial not to overlook this diagnosis, as it is the only form of PH that is potentially curable. Patients diagnosed with CTEPH should be referred to an expert center for consideration of pulmonary endarterectomy, and surgical removal of the chronic thromboembolic material. Not all patients with CTEPH are surgical candidates, however, and there are emerging treatments—medical therapy and balloon pulmonary angioplasty—that have shown benefit in this patient population. Without treatment, CTEPH can lead to progressive pulmonary vascular obstruction, right heart failure, and death. Thus, it is important for clinicians to recognize this subtype of PH. In this review, we provide an overview of current understanding of the pathogenesis of CTEPH and highlight recommendations and recent advances in the evaluation and treatment of CTEPH.     

慢性血栓栓塞性肺动脉高压的研究进展

1 概念及流行病学 慢性血栓栓塞性肺动脉高压(claronic throm boembolic pulmonary hypertension,CTEPH)是指肺动脉及其主要分支由于血栓栓塞所导致的血流受阻,长期不能缓解或进行性加重,导致肺动脉高压.CTEPH是肺血栓栓塞症中的一种特殊类型,是血栓不能完全溶解,或者是在深静脉血栓形成反复脱落的基础上继发反复多次栓塞肺动脉、血栓机化,肺动脉内膜慢性炎症并增厚,发展为慢性肺栓塞.CTEPH进一步发展可出现呼吸功能不全和右心衰竭.     

Iloprost for chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension (CTPH) is an uncommon complication of pulmonary embolism. The treatment of choice is thromboendarterectomy, a safe and effective surgical procedure in expert hands. However, a fair number of patients are not considered candidates for thromboendarterectomy or do not accept the risk involved. Such patients may respond well to prostacyclin or its derivatives. In recent years new vasodilator drugs administered by a variety of routes have appeared on the market. These drugs have been studied mainly for their effects on primary pulmonary hypertension or hypertension associated with connective-tissue diseases. Few trials have assessed their efficacy in patients with CTPH, however. We report 2 cases of CTPH in which thromboendarterectomy was rejected. Neither of the patients responded to the conventional treatment of anticoagulants, diuretics, calcium antagonists, and angiotensin-converting enzyme inhibitors, but they did respond very well clinically, hemodynamically, and functionally to an inhaled prostacyclin analog, iloprost. We discuss the effects of iloprost in patients with CTPH, its mechanism of action, and its use as a potential pharmacological alternative to thromboendarterectomy. We also discuss new pulmonary vasodilators in general.     

Long-term bosentan in chronic thromboembolic pulmonary hypertension

BACKGROUND: There is no approved pharmacological treatment for patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are not suitable for pulmonary endarterectomy (PEA). OBJECTIVE: The study investigates the effect of the dual endothelin receptor antagonist bosentan on exercise tolerance (6-min walking distance, 6MWD) and right ventricular function (Tei index) in patients with CTEPH over 24 months. METHODS: Twelve consecutive patients (5 males and 7 females) with CTEPH not eligible for PEA or following partial or complete failure of PEA were included in a non-randomized, open-label prospective study. All patients were WHO class III. They were included, if progressive pulmonary hypertension was diagnosed despite best supportive treatment. Bosentan was started at 62.5 mg b.i.d. and increased to the final dose of 125 mg b.i.d. RESULTS: 6MWD and the Tei index were assessed every 6 months. We observed a significant increase in 6MWD from 319 +/- 85.0 m at baseline to 391 +/- 76.9 m at 6 months and a significant decrease in the Tei index from 0.39 +/- 0.10 at baseline to 0.34 +/- 0.08 at 6 months. This improvement was maintained over 24 months (6 MWD: 381 +/- 101 m; Tei index: 0.31 +/- 0.03). Six patients exhibited an improvement in WHO class at 6, 12 and 18 months, 5 demonstrated improvement at the 24-month follow-up. The remainder were stable throughout the study period. CONCLUSION: This is the first study demonstrating a long-term beneficial effect of bosentan on exercise tolerance (6MWD) and right heart function (Tei index) in CTEPH.     

Plasma monocyte chemoattractant protein-1 and pulmonary vascular resistance in chronic thromboembolic pulmonary hypertension.

The pathogenesis of severe pulmonary hypertension seems to be related to inflammatory response in diseased sites. Monocyte chemoattractant protein-1 (MCP-1) has been reported to play a role in the development of congestive heart failure. In this immunological response, activation and migration of leukocytes including macrophages to the inflammatory region are important factors. We hypothesized that the severity of pulmonary hypertension may be related to MCP-1, which is thought to be upregulated by blood pressure or shear stress in pulmonary vasculature as well as by immunological and inflammatory reactions in chronic thromboembolic pulmonary hypertension (CTEPH). Circulating levels of MCP-1, interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNF-alpha) were measured by sandwich ELISA in 14 patients with CTEPH. The plasma level of MCP-1 was significantly correlated with pulmonary vascular resistance. In IL-1beta and TNF-alpha, on the other hand, there was no correlation between cytokines and pulmonary hemodynamics. Pathological specimens obtained from the patients with CTEPH undergoing thromboendarterectomy demonstrated immunoreactivity of MCP-1 in endothelium, smooth muscle cells, and macrophages within neointima in the hypertensive large elastic pulmonary artery. We conclude that MCP-1 is upregulated in the remodeling of pulmonary arteries in close association with increased pulmonary vascular resistance in CTEPH.     

Mechanisms of hypoxemia in chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension is characterized by widespread central obstruction of the pulmonary arteries with organized thrombus and thereby differs substantially from other forms of pulmonary hypertension. We studied 25 patients using the multiple inert gas elimination technique to identify and quantitate the physiologic mechanisms of hypoxemia in this disorder. All patients had chronic obstruction of the central pulmonary arteries, which was demonstrated angiographically and later surgically confirmed. All patients but one were hypoxemic (PaO2 = 65 +/- 11 mm Hg, PaCO2 = 32 +/- 4 mm Hg, AaPO2 = 45 +/- 14 mm Hg), and all patients had pulmonary hypertension (mean Ppa = 45 +/- 11 mm Hg) with an elevated pulmonary vascular resistance (mean PVR = 1,000 +/- 791 dyne/s/cm5, normal less than 300). The cardiac index was reduced (1.7 +/- 0.6 L/min/m2), as was the P-vO2 (31 +/- 5 mm Hg). Inert gas studies revealed widened unimodal Va/Q distributions in 20 of 25 subjects, with a log standard deviation of 1.01 +/- 0.32 (upper limit of normal, 0.6; ages 20 to 40), shunt = 0.03 +/- 0.05 of cardiac output, and dead space of 3.4 +/- 1.1 ml/kg (upper limit of normal, 2.9). The VD/VT ratio was 0.51 +/- 0.10. No low (VA/Q less than 0.1) or high (VA/Q greater than 10.0) regions were present, and no evidence for diffusion limitation of O2 transfer at rest was found. The low cardiac output and resulting low P-VO2 were responsible for approximately 33% of the increased AaPO2. The magnitude of the VA/Q abnormality correlated poorly with the PVR, the mean Ppa, or the magnitude of vascular obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)     

慢性血栓栓塞性肺动脉高压的介入治疗

慢性血栓栓塞性肺动脉高压(CTEPH)是肺栓塞的潜在致命结果。目前肺动脉内膜剥脱术(PEA是首选的治疗方法,但多种因素限制了其临床应用和开展。对于不能行PEA治疗的CTEPH患者,经皮球囊肺动脉成形术是近年来发展迅速的一种能够改善患者临床症状、降低肺动脉压力和肺血管阻力并改善患者预后的新的介入治疗方法。     

Surgical treatment of chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension is a commonly overlooked cause of physical incapacity and dyspnoea, with a higher incidence than is generally appreciated and a poor prognosis. The diagnosis can be suspected based on echocardiographic examinations and ventilation perfusion scanning of the lung. Pulmonary angiography still remains the gold standard for the diagnosis of thromboembolic pulmonary hypertension and the assessment of operability. Pulmonary endarterectomy is a complex surgical procedure, which provides permanent relief of thromboembolic pulmonary hypertension and cure for most of the patients. The operation resembles a true endarterectomy of the pulmonary artery branches using extracorporeal circulation and periods of hypothermic circulatory arrest. In experienced centres, the operative risk has been decreased to an acceptable level. Following successful surgery, long-term survival and quality of life are excellent. Earlier referral to surgery might avoid the occurrence of a secondary vasculopathy in the unaffected areas of the pulmonary vascular tree, and therefore further improve early and late results. A multidisciplinary approach and surgical experience are the prerequisites for success of this demanding procedure.     

慢性血栓栓塞性肺动脉高压的误诊分析

慢性血栓栓塞性肺动脉高压(CTEPH)是指肺动脉及其主要分支由于血栓栓塞导致的血流受阻,长期不能缓解或进行性加重,导致肺动脉高压。CTEPH的误诊率很高,笔者对近3年所收治的7例CHEPH患者进行误诊分析,以提高对CTEPH的认识。1对象与方法近3年我院心内科确诊的CTEPH患者共7例,男2例,女5例。年龄40~66(52±9.52)岁。均经螺旋CT肺血管造影(CTPA)和肺通气灌注扫描证实的至少有1个肺段以上的肺栓塞。患者均经过超声多普勒检测肺动脉收缩压>30mmHg(1mmHg=0·133kPa)以上,均排除其他非血栓栓塞性肺动脉高压。2结果症状体征:主要症状有…     

Assessment of operability in chronic thromboembolic pulmonary hypertension

Pulmonary endarterectomy surgery (PEA) offers the possibility of a cure for patients suffering from chronic thromboembolic pulmonary hypertension (CTEPH). Despite growing experience worldwide, the approach and criteria for patient selection remain variable and center- or expert-dependent. A significant proportion of patients with CTEPH may be turned down for PEA for a number of reasons, most frequently over concerns of distal or inaccessible disease. Although traditional preoperative testing and currently available tools are adequate in identifying the presence of proximal disease in CTEPH, they provide only limited information on the status of the microvasculature. Because persistent pulmonary hypertension is the most important determinant of post-PEA outcome, the preoperative identification of patients with CTEPH with concomitant small-vessel disease and/or microvascular disease is crucial. Pulmonary vascular resistance (PVR) is a useful parameter for assessing potential concomitant small-vessel disease. By assessing the relative contribution of small vessels to the PVR, the pulmonary artery occlusion technique represents a promising tool for determining the risk of surgery in patients with high PVR. More information is required regarding the potential value or risk of preoperative medical therapies. Although traditional surgical classification of CTEPH takes place intraoperatively, there is a need for a preoperative classification system and consensus on operability. A preliminary preoperative classification system has been proposed.     

慢性血栓栓塞性肺动脉高压机制研究进展

慢性血栓栓塞性肺动脉高压(chronic thromboembolic pulmonary hypertension,CTEPH)是急性肺栓塞(pulmonary embolism,PE)或肺动脉原位血栓形成的长期后果,由于种种原因血栓未溶解而持续存在,通过机化、纤维化造成肺动脉狭窄性重塑,从而引起肺动脉高压.CTEPH的发病机制尚未完全阐明,目前认为,肺动脉内皮功能障碍、肺动脉血管重塑在CTEPH的进展中发挥了重要的作用.     

Thrombophilic factors in chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTE-PH) is an infrequent cause of pulmonary hypertension that develops in 0.1-0.2% of patients who survive after an acute venous thromboembolic event. According to the largest series so far reported, 15-30% of patients with diagnosis of CTE-PH have an underlying congenital or acquired hypercoagulable state. To determine the prevalence of thrombophilic factors in our population, we analyzed 24 patients admitted to our institution between November 1992 and March 2000 fulfilling criteria for CTE-PH. Eighteen patients disclosed abnormal results in the screening for thrombophilia. The presence of antiphospholipid antibodies (lupus anticoagulant and/or anticardiolipin antibodies) was the abnormality most frequently found (12 out of 24 patients). We found hyperhomocysteinaemia in 7/14, true protein S deficiency in 1/10, protein C deficiency in 1/13, activated protein C resistance in 1/22, antithrombin III deficiency in 1/24, and prothrombin gene G20210A mutation in 1/18 patients. Factor V Leiden was normal in all 18 patients studied. Five patients (20.8%) disclosed more than one thrombophilic abnormality. In conclusion, contrary to the largest series of patients with CTE-PH so far reported, we found that 75% of patients with CTE-PH presented at least one thrombophilic risk factor, being antiphospholipid antibodies in 50% of the cases. We recommend a thorough screening for thrombophilia in all patients with diagnosis of CTE-PH.     

Thromboendarterectomy for severe chronic thromboembolic pulmonary hypertension

Pulmonary thromboendarterectomy is a curative surgical procedure for chronic thromboembolic pulmonary hypertension. The aim of this study was to clarify whether severe hemodynamic compromise affects surgical outcome. We studied 19 patients who underwent pulmonary thromboendarterectomy and compared 11 with pulmonary vascular resistance < 1,000 dyne x s x cm(-5) (group 1) and 8 with pulmonary vascular resistance > 1,000 dyne x s x cm(-5) (group 2). Mean pulmonary artery pressure and pulmonary vascular resistance decreased significantly after surgery in both groups. The incidence of postoperative complications did not differ between groups; however, one patient in group 2 died of multiorgan failure. The overall mortality rate was 5.3%, and the rate in group 2 was 13%. Our results indicate that preoperative hemodynamic compromise does not affect surgical outcome. Patients with high pulmonary vascular resistance can be treated effectively by thromboendarterectomy, with acceptable morbidity and mortality.