Microvascular disease in chronic thromboembolic pulmonary hypertension: a role for pulmonary veins and systemic vasculature

• Published in: The European respiratory journal Vol. 44; no. 5; pp. 1275 - 1288
• Main Authors: Dorfmüller, Peter, Günther, Sven, Ghigna, Maria-Rosa, Thomas de Montpréville, Vincent, Boulate, David, Paul, Jean-François, Jaïs, Xavier, Decante, Benoit, Simonneau, Gérald, Dartevelle, Philippe, Humbert, Marc, Fadel, Elie, Mercier, Olaf
• Format: Journal Article
• Language: English
• Published: Leeds Maney 01.11.2014
• Subjects: Adult; Animals; Biological and medical sciences; Blood and lymphatic vessels; Capillaries - pathology; Cardiology. Vascular system; Chronic Disease; Disease Models, Animal; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Endarterectomy; Female; Hemodynamics; Humans; Hypertension, Pulmonary - therapy; Lung - pathology; Male; Medical sciences; Microcirculation; Middle Aged; Pneumology; Predictive Value of Tests; Pulmonary Artery - physiopathology; Pulmonary Circulation; Pulmonary Embolism - physiopathology; Pulmonary Embolism - therapy; Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases; Pulmonary Veins - pathology; Pulmonary Veins - physiopathology; Retrospective Studies; Swine; Veins - pathology; Respiratory disease; Cardiovascular disease; Systemic; Thrombosis; Embolism; Pulmonary hypertension; Vascularization; Vascular disease; Microcirculation; Chronic; Microangiopathy; Blood vessel; Disseminated; Thromboembolism; Pulmonary vein
• ISSN: 0903-1936; 1399-3003; 1399-3003
• DOI: 10.1183/09031936.00169113

Limited numbers of operated patients with chronic thromboembolic pulmonary hypertension (CTEPH) are refractory to pulmonary endarterectomy (PEA) and experience persistent pulmonary hypertension (PH). We retrospectively assessed lung histology available from nine patients with persistent PH (ineffective PEA (inPEA) group) and from eight patients transplanted for distal CTEPH inaccessible by PEA (noPEA group). Microscopically observed peculiarities were compared with the histology of a recently developed CTEPH model in piglets. Pre-interventional clinical/haemodynamic data and medical history of patients from the inPEA and noPEA groups were collected and analysed. Conspicuous remodelling of small pulmonary arteries/arterioles, septal veins and pre-septal venules, including focal capillary haemangiomatosis, as well as pronounced hypertrophy and enlargement of bronchial systemic vessels, were the predominant pattern in histology from both groups. Most findings were reproduced in our porcine CTEPH model. Ink injection experiments unmasked abundant venular involvement in so-called small vessel or microvascular disease, as well as post-capillary bronchopulmonary shunting in human and experimental CTEPH. Microvascular disease is partly due to post-capillary remodelling in human and experimental CTEPH and appears to be related to bronchial-to-pulmonary venous shunting. Further studies are needed to clinically assess the functional importance of this finding.