Abstract

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism, either symptomatic or not. The occlusion of proximal pulmonary arteries by fibrotic intravascular material, in combination with a secondary microvasculopathy of vessels less than 500 µm, leads to increased pulmonary vascular resistance and progressive right heart failure. The mechanism responsible for the transformation of red clots into fibrotic material remnants has not yet been elucidated. In patients with pulmonary hypertension, the diagnosis is suspected when a ventilation/perfusion lung scan shows mismatched perfusion defects and confirmed by right heart catheterisation and vascular imaging. Today, in addition to lifelong anticoagulation, treatment modalities include surgery, angioplasty and medical treatment according to the localisation and characteristics of the lesions.

This Statement outlines a review of the literature and current practice concerning diagnosis and management of CTEPH. It covers the definitions, diagnosis, epidemiology, follow up after acute pulmonary embolism, pathophysiology, treatment by pulmonary endarterectomy, balloon pulmonary angioplasty, drugs and their combination, rehabilitation and new lines of research in CTEPH.

It represents the first collaboration of the European Respiratory Society (ERS), the International CTEPH Association (ICA) and the European Reference Network (ERN)-Lung in the pulmonary hypertension domain. The Statement summarises current knowledge but does not make formal recommendations for clinical practice.

Footnotes

This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.

Conflict of interest: Dr. Delcroix reports grants and other from Actelion/J&J, other from Bayer, other from MSD, other from Reata, other from Bellarophon, other from Acceleron, outside the submitted work.

Conflict of interest: Dr. Torbicki reports grants and personal fees from Actelion/Janssen, personal fees from AOP, grants and personal fees from Bayer, grants and personal fees from MSD, personal fees from Pfizer, outside the submitted work.

Conflict of interest: Dr. Gopalan reports other from Actelion/J&J, other from Bayer, outside the submitted work.

Conflict of interest: Dr. Sitbon reports grants, personal fees and non-financial support from Actelion Pharmaceuticals, grants, personal fees and non-financial support from MSD, personal fees from Bayer, grants from GlaxoSmithKline, personal fees from Acceleron Pharmaceuticals, personal fees from Gossamer Bio, personal fees from Ferrer, outside the submitted work.

Conflict of interest: Frederikus Klok reports research grants from Bayer, Bristol-Myers Squibb, Boehringer-lngelheim, Daiichi-Sankyo, MSD and Actelion, the Dutch Heart foundation and the Dutch Thrombosis association, outside the submitted work.

Conflict of interest: Dr. Lang reports grants and personal fees from Actelion-Janssen, grants and personal fees from AOPOrphan Pharma, personal fees from Medtronic, personal fees from Ferrer, personal fees from United Therapeutics, outside the submitted work.

Conflict of interest: Dr. Jenkins reports grants from Bayer, personal fees from Actelion, outside the submitted work.

Conflict of interest: Dr. Kim reports personal fees from Actelion, personal fees from Bayer, personal fees from Merck, outside the submitted work.

Conflict of interest: Dr. Humbert reports personal fees from Acceleron, grants and personal fees from Actelion, grants and personal fees from Bayer, personal fees from GSK, personal fees from Merck, personal fees from Novartis, personal fees from Astrazeneca, personal fees from Sanofi, outside the submitted work.

Conflict of interest: Dr. JAIS reports personal fees and non-financial support from Actelion, personal fees and non-financial support from MSD, grants from Bayer, outside the submitted work.

Conflict of interest: J Pepke –Zaba has received speaker fees and honoraria for consultations from Actelion, Merck and Bayer, her institution received research and educational grants from Actelion and Merck

Conflict of interest: Dr. fadel has nothing to disclose.

Conflict of interest: Dr. Ghofrani reports personal fees and other from Actelion, personal fees and other from Bayer AG, personal fees and other from GlaxoSmithKline, personal fees and other from Novartis, personal fees and other from Pfizer, other from Bellerophon Pulse Technologies, other from MSD, grants from Deutsche Forschungsgemeinschaft (DFG), during the conduct of the study.Dr. Ghofrani reports personal fees and other from Actelion, personal fees and other from Bayer AG, personal fees and other from GlaxoSmithKline, personal fees and other from Novartis, personal fees and other from Pfizer, other from Bellerophon Pulse Technologies, other from MSD, grants from Deutsche Forschungsgemeinschaft (DFG), during the conduct of the study.

Conflict of interest: Dr. Hoeper reports personal fees from Bayer AG, personal fees from MSD, personal fees from Actelion, personal fees from Jansen, personal fees from Acceleron, personal fees from Pfizer, during the conduct of the study.

Conflict of interest: Dr. Jansa reports other from Actelion, personal fees and other from Bayer Pharma AG, Reata Pharmaceuticals, personal fees from AOP and MSD, outside the submitted work.

Conflict of interest: Dr. Madani reports personal fees from Actelion, personal fees from Wexler Surgical, outside the submitted work.

Conflict of interest: Dr. Matsubara reports personal fees from Actelion Pharmaceuticals Japan, Ltd, personal fees from AOP orphan Pharmaceuticals AG, personal fees from Bayer Yakuhin, Ltd, personal fees from Pfizer Japan, Inc, personal fees from Nippon Shinyaku, Co, Ltd, personal fees from Kaneka Medix Corporation, personal fees from Glaxo Smith Kline Pharmaceuticals, Ltd, personal fees from United Therapeutics Corporation, outside the submitted work.

Conflict of interest: Dr. Ogo has nothing to disclose.

Conflict of interest: Dr. Grünig reports fees for lectures and/or consultations from Actelion, Bayer AG, GSK, MSD, United Therapeutics, and Pfizer. outside the submitted work.

Conflict of interest: Dr. D'Armini reports personal fees from Actelion Phamaceuticals, personal fees from Bayer AG, personal fees from Merck Sharp & Dohme, outside the submitted work.

Conflict of interest: Dr. Galie reports grants and personal fees from Actelion, grants and personal fees from Janssen, personal fees from Pfizer, personal fees from Ferrer, outside the submitted work.

Conflict of interest: Dr. Meyer reports personal fees from Bayer AG, outside the submitted work.

Conflict of interest: Dr. Corkery has nothing to disclose.

Conflict of interest: Dr. Meszaros reports personal fees from Actelion Pharmaceuticals, outside the submitted work.

Conflict of interest: Dr. Mayer reports personal fees from Actelion, personal fees from Bayer, personal fees from MSD, during the conduct of the study.

Conflict of interest: Dr. simonneau reports personal fees and non-financial support from Actelion, personal fees and non-financial support from BAYER, personal fees and non-financial support from MSD, outside the submitted work.

Conflict of interest: Anton Vonk Noordegraaf is supported by the Netherlands CardioVascular Research Initiative (CVON-2012-08 PHAEDRA, CVON-2017-10 DOLPHIN-GENESIS) and the Netherlands Organization for Scientific Research (NWO-VICI: 918.16.610). In addition he received speakers money from Johnson & Johnson and Ferrer in the past 3 years. Finally he served as a member of the scientific advisory board of Morphogen-XI

Conflict of interest: Dr. BRENOT has nothing to disclose.

Conflict of interest: Dr. Dorfmüller has nothing to disclose.