Search

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. [ABSTRACT FROM AUTHOR]

Macitentan is beneficial for long-term treatment of pulmonary arterial hypertension. The microvasculopathy of chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension are similar. The phase 2, double-blind, randomised, placebo-controlled MERIT-1 trial assessed macitentan in 80 patients with CTEPH adjudicated as inoperable. Patients identified as WHO functional class II–IV with a pulmonary vascular resistance (PVR) of at least 400 dyn·s/cm5 and a walk distance of 150–450 m in 6 min were randomly assigned (1:1), via an interactive voice/web response system, to receive oral macitentan (10 mg once a day) or placebo. Treatment with phosphodiesterase type-5 inhibitors and oral or inhaled prostanoids was permitted for WHO functional class III/IV patients. The primary endpoint was resting PVR at week 16, expressed as percentage of PVR measured at baseline. Analyses were done in all patients who were randomly assigned to treatment; safety analyses were done in all patients who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov , number NCT02021292. Between April 3, 2014, and March 17, 2016, we screened 186 patients for eligibility at 48 hospitals across 20 countries. Of these, 80 patients in 36 hospitals were randomly assigned to treatment (40 patients to macitentan, 40 patients to placebo). At week 16, geometric mean PVR decreased to 71·5% of baseline in the macitentan group and to 87·6% in the placebo group (geometric means ratio 0·81, 95% CI 0·70–0·95, p=0·0098). The most common adverse events in the macitentan group were peripheral oedema (9 [23%] of 40 patients) and decreased haemoglobin (6 [15%]). In MERIT-1, macitentan significantly improved PVR in patients with inoperable CTEPH and was well tolerated. Actelion Pharmaceuticals Ltd. [ABSTRACT FROM AUTHOR]

Chronic thromboembolic pulmonary hypertension is a complication of pulmonary embolism and a treatable cause of pulmonary hypertension. The pathology is a unique combination of mechanical obstruction due to failure of clot resolution, and a variable degree of microvascular disease, that both contribute to pulmonary vascular resistance. Accordingly, multiple treatments have been developed to target the disease components. However, accurate diagnosis is often delayed. Evaluation includes high-quality imaging modalities, necessary for disease confirmation and for appropriate treatment planning. All patients with chronic thromboembolic pulmonary disease, and especially those with pulmonary hypertension, should be referred to expert centres for multidisciplinary team decision on treatment. The first decision remains assessment of operability, and the best improvement in symptoms and survival is achieved by the mechanical therapies, pulmonary endarterectomy and balloon pulmonary angioplasty. With the advances in multimodal therapies, excellent outcomes can be achieved with 3-year survival of >90%., Competing Interests: Conflict of interest: N.H. Kim reports consultancy fees from Bayer, Janssen, Merck, United Therapeutics and Pulnovo, payment or honoraria for lectures, presentations, manuscript writing or educational events from Bayer, Janssen and Merck, participation on a data safety monitoring board or advisory board with Bayer, Janssen, Merck and United Therapeutics, and leadership roles with International CTEPH Association and CTEPH.com. A.M. D'Armini reports payment or honoraria for lectures, presentations, manuscript writing or educational events from AOP Health and MSD, and participation on a data safety monitoring board or advisory board with AOP Health. M. Delcroix reports consultancy fees from Actelion/Janssen/J&J, Acceleron/MSD, Gossamer and Ferrer, and payment or honoraria for lectures, presentations, manuscript writing or educational events from Actelion/Janssen/J&J, Acceleron/MSD and Ferrer. X. Jaïs reports grants from Acceleron, Janssen, MSD and Bayer HealthCare, and consultancy fees and payment or honoraria for lectures, presentations, manuscript writing or educational events from MSD. M. Jevnikar reports payment or honoraria for lectures, presentations, manuscript writing or educational events and support for attending meetings from Janssen and MSD. M.M. Madani reports royalties or licences from Wexler Surgical, consultancy fees from Bayer/MSD and Actelion/Janssen/J&J, and participation on a data safety monitoring board or advisory board with International CTEPH Association. H. Matsubara reports grants from Nippon Shinyaku, payment or honoraria for lectures, presentations, manuscript writing or educational events from Bayer, Janssen, Kaneka Medix, Mochida, MSD, Nippon Shinyaku, Nipro and AOP Orphan, payment for expert testimony from MSD, participation on a data safety monitoring board or advisory board with Bayer, Janssen, Mochida and MSD, and a leadership role with International CTEPH Association. M. Palazzini reports consultancy fees, payment or honoraria for lectures, presentations, manuscript writing or educational events, and support for attending meetings from Janssen. C.B. Wiedenroth reports consultancy fees from J&J, OrphaCare and MSD, payment or honoraria for lectures, presentations, manuscript writing or educational events from J&J, AOP-Health, Bayer, Inari, MSD and Pfizer, and a leadership role with International CTEPH Association. G. Simonneau has no potential conflicts of interest to disclose. D.P. Jenkins reports consultancy fees and payment or honoraria for lectures, presentations, manuscript writing or educational events from Janssen, and and a leadership role with International CTEPH Association., (Copyright ©The authors 2024.)