Pulmonary
endarterectomy 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 who have chronic thromboembolic
pulmonary hypertension and were initially screened for inclusion in the CHEST-1 (Chronic Thromboembolic
Pulmonary Hypertension Soluble Guanylate Cyclase Stimulator Trial-1) study. The CHEST-1 study evaluated
riociguat for the treatment of inoperable chronic thromboembolic
pulmonary hypertension (CTEPH) or persistent/recurrent
pulmonary hypertension after pulmonary
endarterectomy. Screened patients who were 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 on accessibility of thrombi and the association between pulmonary vascular resistance (PVR) 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, a total of 188 and 124 underwent central and local adjudication, respectively, after being initially considered to be "inoperable." After a second assessment by an experienced surgeon, 69 of these 312 "inoperable" patients were deemed operable. Rigorous measures in CHEST-1 guaranteed that only technically inoperable patients, or patients who had persistent/recurrent
pulmonary hypertension, were enrolled, thus ensuring that only patients for whom surgery was not an option were enrolled. This study design sets new standards for future clinical trials and practice in CTEPH, helping to ensure that patients who have CTEPH receive optimal treatment.