Circulating Endothelin 1 but Not Transforming Growth Factor-β Levels Are Reduced after Pulmonary Endarterectomy in Subjects Affected by Chronic Thromboembolic Pulmonary Hypertension: A Prospective Cohort Study

Abstract

Background and objectives: Endothelin-1 (ET-1) and transforming growth factor-β (TGF-β) play a pivotal role in the pathophysiology and vascular remodeling of chronic thromboembolic pulmonary hypertension (CTEPH) which is an under-diagnosed complication of acute pulmonary embolism (PE). Currently, pulmonary endarterectomy (PEA) is still the treatment of choice for selected patients suffering from CTEPH. The aim of this study was to evaluate the preoperative and postoperative circulating levels of ET-1 and TGF-β in subjects affected by CTEPH undergoing successful surgical treatment by PEA. Methods: The data from patients diagnosed with CTEPH who underwent PEA at the Foundation IRCCS Policlinico San Matteo Hospital (Pavia, Italy) were prospectively recorded in the Institutional database. Circulating ET-1 and TGF-β levels were assessed by an ELISA commercial kit before PEA, at 3 months and 1 year after PEA. The demographic data, preoperatory mean pulmonary arterial pressure (mPAP), cardiac output (CO), and pulmonary vascular resistance (PVR) were also recorded. Univariate and multivariate analyses were performed. Results: The analysis included 340 patients with complete ET-1 measurements and 206 patients with complete TGF-β measurements. ET-1 significantly decreased both at 3 months (p < 0.001) and at 1 year (p = 0.009) after PEA. On the other hand, preoperatory TGF-β levels did not significantly change after PEA. Furthermore, ET-1, but not TGF-β, was a good predictor for increased mPAP in multivariate analyses (p < 0.05). Conclusions: ET-1 but not TGF β was significantly modulated by PEA in subjects affected by CTEPH up to 1 year after surgery. The mechanisms leading to prolonged elevated circulating TGF-β levels and their clinical significance have to be further elucidated.