Operability assessment in CTEPH: Lessons from the CHEST-1 study

Abstract Pulmonary endarterectomy (PEA) is the gold standard treatment for chronic thromboembolic pulmonary hypertension and is potentially curative, although some patients are unsuitable for pulmonary endarterectomy and require alternative management. Lack of standardized assessment of pulmonary endarterectomy eligibility risks suboptimal treatment in some patients. We discuss the implications for future clinical trials and practice of a unique operability assessment in patients with chronic thromboembolic pulmonary hypertension initially screened for inclusion in the CHEST-1 study. CHEST-1 evaluated riociguat for the treatment of inoperable chronic thromboembolic pulmonary hypertension or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy. Screened patients initially considered “inoperable” underwent central independent adjudication by a committee of experienced surgeons or local adjudication in collaboration with an experienced surgeon. Operability decisions were based upon accessibility of thrombi and the association between pulmonary vascular resistance and the extent of obstruction, using pulmonary angiography/computed tomography with ventilation/perfusion scintigraphy as the minimum diagnostic tests. Of 446 patients screened for CHEST-1, 188 and 124 underwent central and local adjudication, respectively, after being initially considered “inoperable”. After a second assessment by an experienced surgeon, 69 of these 312 “inoperable” patients were identified as operable. Rigorous measures in CHEST-1 guaranteed that only technically inoperable patients or patients with persistent/recurrent pulmonary hypertension were enrolled, ensuring that only patients in whom surgery was not an option were enrolled. This study design sets new standards for future clinical trials and practice in chronic thromboembolic pulmonary hypertension, helping to ensure patients with chronic thromboembolic pulmonary hypertension receive optimal treatment.