Thrombosis is not the only determinant of chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is a late complication of pulmonary embolism (PE) and life-threatening condition. In a recent issue published in the Journal, Andersen et al. analyzed the biomarkers of collagen turnover and wound healing in CTEPH patients and found that these biomarkers are increased in CTEPH patients compared with healthy control; interestingly, these markers do not decrease in the patients after surgical removal of thromboembolic mass with a follow-up of 6 months [ [1] Andersen S. Reese-Petersen A.L. Braams N. Andersen M.J. Mellemkjaer S. Andersen A. Bogaard H.J. Genovese F. Nielsen-Kudsk J.E. Biomarkers of collagen turnover and wound healing in chronic thromboembolic pulmonary hypertension patients before and after pulmonary endarterectomy. Int. J. Cardiol. 2023; 384: 82-88 Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar ]. Luijten et al. analyzed the literature published in the recent 5 years, and found that about 2.7% PE survivors developed CTEPH among 6202 patients after 3 months to 8 years' follow-up [ [2] Luijten D. Talerico R. Barco S. Cannegieter S.C. Delcroix M. Ende-Verhaar Y.M. Huisman M.V. Konstantinidis S. Mairuhu A.T.A. van Mens T.E. Ninaber M. Pruszczyk P. Vonk Noordegraaf A. Klok F.A. Incidence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: an updated systematic review and meta-analysis. Eur. Respir. J. 2023; 62 Crossref Scopus (2) Google Scholar ]. And this rate is similar to a meta-analysis with 4047 patients based on the data before 2017 [ [3] Ende-Verhaar Y.M. Cannegieter S.C. Vonk Noordegraaf A. Delcroix M. Pruszczyk P. Mairuhu A.T. Huisman M.V. Klok F.A. Incidence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: a contemporary view of the published literature. Eur. Respir. J. 2017; 49 Crossref PubMed Google Scholar ]. It is a little surprising that the rate of CTEPH among PE patients did not decrease from 2017 to 2023, as more and more novel oral anticoagulants were introduced for the treatment and prevention of venous thrombosis. In parallel, a recent study indicates that rabbits receiving blood clot containing SU5416, have higher pulmonary artery pressure and enhanced right ventricular hypertrophy when compared to rabbits receiving clot with anti-fibrinolytic agents. These may implicate that endothelial dysfunction plays a more important role than defective fibrinolysis in the development of CTEPH after PE, which may partially explain why the rate of CTEPH was not significantly reduced with the progress of anticoagulation therapy in the recent years.