Pulmonary Microvascular Disease in Chronic Thromboembolic Pulmonary Hypertension

and Division of Pulmonary and Critical Care Medicine, University of California, San Diego, La Jolla, California, USA.
Proceedings of the American Thoracic Society 10/2006; 3(7):571-6. DOI: 10.1513/pats.200605-113LR
Source: PubMed


Distal, small-vessel vasculopathy is generally considered a major contributor to the progression of pulmonary hypertension (PH) as chronic thromboembolic pulmonary hypertension (CTEPH) develops over time and is a major determinant of postoperative outcome after pulmonary endarterectomy (PEA). The pathogenesis and natural history of microvascular disease in CTEPH remain uncharacterized. Mechanisms for significant distal disease may involve the following processes: (1) predominant obstructions of "small" subsegmental elastic pulmonary arteries, (2) classical pulmonary arteriopathy of small muscular arteries and arterioles distal to nonobstructed vessels, (3) pulmonary arteriopathy of small muscular arteries and arterioles distal to totally or partially obstructed vessels. Patients in whom obstructed vessels are mainly subsegmental are considered poor surgical candidates. Distal pulmonary vasculopathy in both the occluded and nonoccluded pulmonary vascular bed is characterized by lesions considered typical for idiopathic pulmonary arterial hypertension, including plexiform lesions. The pathogenesis and time course of these vascular lesions remain unclear, but may involve endothelial and/or platelet production and release of mediators and/or altered pulmonary blood flow. The reciprocal contribution of large-vessel (operable) and small-vessel lesions in CTEPH is crucial for the indication and results of PEA. A combination of investigations is used to identify the extent of small-vessel disease, including right-heart catheterization, perfusion lung scan, multidetector spiral computed tomography, pulmonary angiography, and pulmonary arterial occlusion wave-form analysis. Preliminary evidence suggests that medical therapy may provide hemodynamic and clinical benefits for patients in whom PEA cannot be applied, in those who have persistent postoperative PH, or in selected patients with advanced preoperative hemodynamic changes.

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    • "These may completely occlude the lumen or form areas of stenosis, webs, or bands. Interestingly, histological changes in the non-occluded pulmonary arteries are similar to those seen in pulmonary artery hypertension (PAH), such as medial hypertrophy and the intimal proliferative and fibrotic changes that include plexiform lesions (Galiè and Kim, 2006). As the pathological changes in the pulmonary vasculature appear similar, new pulmonary vasodilating drugs used to treat PAH have also been used in CTEPH: prostanoids (Ono et al., 2003; Cabrol et al., 2007; Skoro-Sajer et al., 2007), endothelin-receptor antagonists (ERAs) (Becattini et al., 2010), and phosphodiesterase type-5 (PDE5) inhibitors (Suntharalingam et al., 2008) are reported to have hemodynamic and clinical benefits, although these have not been established in randomized , placebo-controlled trials. "
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    ABSTRACT: Aims Chronic thromboembolic pulmonary hypertension (CTEPH) is a devastating disease, and treating patients with CTEPH who are not eligible for pulmonary endarterectomy is particularly challenging. Short-term bosentan or phosphodiesterase type-5-inhibitor treatment can greatly improve symptoms and hemodynamics in these patients; however, the long-term benefits of advanced pulmonary vasodilators are not known. We retrospectively investigated the long-term effects of advanced pharmacological therapy in Japanese patients with inoperable CTEPH. Main methods Seven consecutive patients with inoperable CTEPH (five women; mean age, 62.6 ± 6.9 years) treated with bosentan were included. World Health Organization functional class (WHO-FC), hemodynamics, exercise capacity, and plasma B-type natriuretic peptide (BNP) concentration were evaluated at baseline and for more than 2 years. Time to clinical worsening was also examined during long-term follow-up. Key findings WHO-FC improved significantly, from 3.1 ± 0.4 to 2.1 ± 0.4 (p = 0.005). Significant improvement was also seen in pulmonary vascular resistance, which decreased from 786.9 ± 300.0 to 352.2 ± 210.7 5 (p < 0.05). Plasma BNP concentration decreased significantly from 1,160.0 ± 971.4 to 305.1 ± 285.9 pg/mL (p < 0.05). No patient required hospitalization during the follow-up period (mean, 896 ± 564 days). Significance Long-term advanced therapy with bosentan significantly improves symptoms, pulmonary vascular resistance, plasma BNP concentration, and time to clinical worsening in Japanese patients with inoperable CTEPH. We consider bosentan to be an essential treatment for these patients.
    Full-text · Article · Mar 2014 · Life sciences
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    • "These may completely occlude the lumen or form different grades of stenoses, webs, and bands [4]. Interestingly, in the non-occluded areas, a pulmonary arteriopathy indistinguishable from that of PAH (including plexiform lesions) can develop [10]. Obstructive lesions observed in the distal pulmonary arteries of non-obstructed areas may be related to a variety of factors, such as shear stress, pressure, inflammation , and the release of cytokines and vasculopathic mediators. "
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    ABSTRACT: In the 2009 European Guidelines on the diagnosis and treatment of pulmonary hypertension (PH), one section covers aspects of pathophysiology, diagnosis and treatment of chronic thromboembolic pulmonary hypertension (CTEPH). The practical implementation of the guidelines for this disease is of crucial importance, because CTEPH is a subset of PH which can potentially be cured by pulmonary endarterectomy (PEA). Nowadays, CTEPH is commonly underdiagnosed and not properly managed. Any patient with unexplained PH should be evaluated for the presence of CTEPH, and a ventilation/perfusion (V/Q) lung scan is recommended as screening method of choice. If the V/Q scan or CT angiography reveals signs of CTEPH, the patient should be referred to a specialized center with expertise in the medical and surgical management of this disease. Every case has to be reviewed by an experienced PEA surgeon for the assessment of operability. In this updated recommendation, important contents of the European guidelines were commented, and more recent information regarding diagnosis and treatment was added.
    Full-text · Article · Dec 2011 · International journal of cardiology
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    • "These may completely occlude the lumen or form different grades of stenosis, webs, and bands.19 Interestingly, in the nonoccluded areas, a pulmonary arteriopathy indistinguishable from that of pulmonary arterial hypertension (including plexiform lesions) can develop.20 Collateral vessels from the systemic circulation (from bronchial, costal, diaphragmatic, and coronary arteries) can grow to reperfuse, at least partially, the areas distal to complete obstructions. "
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    ABSTRACT: In recent years, there has been a major advance in the treatment of pulmonary hypertension. New medications are continually added to the therapeutic arsenal. The prostanoids are among the first agents used to treat pulmonary hypertension and are currently considered the most effective. This case study describes a 63-year-old man who was diagnosed with chronic thromboembolic pulmonary hypertension and successfully treated with subcutaneously administered treprostenil for 6 months before a successful pulmonary thromboendarterectomy. Treatment of chronic thromboembolic pulmonary hypertension often requires a multidisciplinary approach before surgery. Further evaluation of prostanoids is needed to define their role and time of initiation of medical therapy in these patients.
    Full-text · Article · Nov 2011 · International Journal of General Medicine
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