title: Microvascular disease in chronic thromboembolic pulmonary hypertension: a role for pulmonary veins and systemic vasculature.
abstract: 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.
authors.affiliation: Paris-South University, Faculty of Medicine, Kremlin-Bicêtre, France Dept of Pathology, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France INSERM U999, Pulmonary Hypertension, Pathophysiology and Novel Therapies, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France Both authors contributed equally to this study peter.dorfmuller@u-psud.fr.
authors.forename: Peter
authors.initials: P
authors.lastname: Dorfmüller
authors.affiliation: Paris-South University, Faculty of Medicine, Kremlin-Bicêtre, France INSERM U999, Pulmonary Hypertension, Pathophysiology and Novel Therapies, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France National Reference Center of Pulmonary Hypertension, Dept of Pulmonology and Intensive Care Unit for Respiratory Diseases, Hôpital Bicêtre, AP-HP, Kremlin-Bicêtre, France Both authors contributed equally to this study.
authors.forename: Sven
authors.initials: S
authors.lastname: Günther
authors.affiliation: Paris-South University, Faculty of Medicine, Kremlin-Bicêtre, France Dept of Pathology, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France INSERM U999, Pulmonary Hypertension, Pathophysiology and Novel Therapies, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.
authors.forename: Maria-Rosa
authors.initials: MR
authors.lastname: Ghigna
authors.affiliation: Dept of Pathology, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Thomas de Montpréville
authors.affiliation: Surgical Research Lab, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.
authors.forename: David
authors.initials: D
authors.lastname: Boulate
authors.affiliation: Dept of Radiology, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Paul
authors.affiliation: Paris-South University, Faculty of Medicine, Kremlin-Bicêtre, France INSERM U999, Pulmonary Hypertension, Pathophysiology and Novel Therapies, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France National Reference Center of Pulmonary Hypertension, Dept of Pulmonology and Intensive Care Unit for Respiratory Diseases, Hôpital Bicêtre, AP-HP, Kremlin-Bicêtre, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Jaïs
authors.affiliation: Surgical Research Lab, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Decante
authors.affiliation: Paris-South University, Faculty of Medicine, Kremlin-Bicêtre, France INSERM U999, Pulmonary Hypertension, Pathophysiology and Novel Therapies, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France National Reference Center of Pulmonary Hypertension, Dept of Pulmonology and Intensive Care Unit for Respiratory Diseases, Hôpital Bicêtre, AP-HP, Kremlin-Bicêtre, France.
authors.forename: Gérald
authors.initials: G
authors.lastname: Simonneau
authors.affiliation: Paris-South University, Faculty of Medicine, Kremlin-Bicêtre, France INSERM U999, Pulmonary Hypertension, Pathophysiology and Novel Therapies, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France Dept of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Dartevelle
authors.affiliation: Paris-South University, Faculty of Medicine, Kremlin-Bicêtre, France INSERM U999, Pulmonary Hypertension, Pathophysiology and Novel Therapies, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France National Reference Center of Pulmonary Hypertension, Dept of Pulmonology and Intensive Care Unit for Respiratory Diseases, Hôpital Bicêtre, AP-HP, Kremlin-Bicêtre, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Humbert
authors.affiliation: Paris-South University, Faculty of Medicine, Kremlin-Bicêtre, France INSERM U999, Pulmonary Hypertension, Pathophysiology and Novel Therapies, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France Surgical Research Lab, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France Dept of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.
authors.forename: Elie
authors.initials: E
authors.lastname: Fadel
authors.affiliation: Paris-South University, Faculty of Medicine, Kremlin-Bicêtre, France INSERM U999, Pulmonary Hypertension, Pathophysiology and Novel Therapies, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France Surgical Research Lab, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France Dept of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.
authors.forename: Olaf
authors.initials: O
authors.lastname: Mercier
mesh_terms: D000328:Adult; D000818:Animals; D002196:Capillaries / Q000473:pathology; D002908:Chronic Disease; D004195:Disease Models, Animal; D004691:Endarterectomy; D005260:Female; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000628:therapy*; D008168:Lung / Q000473:pathology; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D011237:Predictive Value of Tests; D011651:Pulmonary Artery / Q000503:physiopathology; D011652:Pulmonary Circulation; D011655:Pulmonary Embolism / Q000503:physiopathology / Q000628:therapy*; D011667:Pulmonary Veins / Q000473:pathology / Q000503:physiopathology*; D012189:Retrospective Studies; D013552:Swine; D014680:Veins / Q000473:pathology