The pulmonary artery hypertension and cancer: PULAHYCA PILOT study. Initial prostanoid therapy in cancer patients with pulmonary hypertension: results from an observational study

Cancer is a leading cause of death worldwide, though new therapies have increased patient survival. These therapies, however, have also raised concerns for cardiovascular toxicities, such as cardiomyopathies, coronary artery disease, hypertension and arrhythmias. Pulmonary arterial hypertension (PAH) is a rare condition that carries a poor prognosis and is often diagnosed at an advanced stage. The annual incidence in the general population is estimated to be between 1 and 2 cases per million. The highest prevalence occurs during the third and fourth decades of life; however, there are cases whose are identified after the sixth decade. It has increasingly become evident that various cancer therapies can exacerbate pulmonary hypertension, significantly impacting patient prognosis. It is recognized that oncologic treatments can cause endothelial dysfunction, including the pulmonary vasculature, and can have thrombotic effects, worsening PAH in patients with this disease. The objective of this study is to describe our experience with patients with a concomitant diagnosis of PAH and cancer, who received prostanoid therapy to be able to complete specific cancer treatments. The PULmonary Artery HYpertension and Cancer (PULAHYCA) pilot study is an observational study of patients with a cancer diagnosis planning to initiate a specific oncologic treatment, with PAH detected during baseline assessment. Patients with PAH due to group 1and group 4 were included, defined as per the 2022 European Society of Cardiology (ESC) guidelines, that require a mean pulmonary artery pressure (mPAP) greater than 20 mm Hg at rest, increased pulmonary artery resistance of more than 2 Wood units and wedge pressure less than 15 mm Hg. The PAH risk category was established according to the ESC guidelines and the REVEAL Lite 2 score. Patients with an intermediate risk with a diagnosis of more than 6 months were included. After screening 349 PH patients, 12 patients were included in the study. All participants had a normal ejection fraction and were treated with a combination of a 5- phosphodiesterase inhibitor, an endothelin receptor antagonist, and treprostinil. Eight patients were classified under group 1 pulmonary hypertension, and four under group 4 pulmonary hypertension. During the 12-month follow-up, patients demonstrated significant clinical and hemodynamic improvement. Functional capacity, measured by the six-minute walk test (6MWT), increased significantly from 325 [304–440] meters at baseline to 401 [315–455] meters at 12 months (p = 0.0014). B-type natriuretic peptide (BNP) levels decreased notably from 321 [205–506] pg/ml to 188 [100–229] pg/ml (p = 0.0001). Pulmonary vascular resistance (PVR) also showed a significant reduction, from 3.8 [3.3–4.2] Woods Units (WU) to 3.5[2.5–3.7] WU (p = 0.00018). All patients survived during the study period and could complete their cancer treatment, which included. The PULAHYCA PILOT study demonstrates that treatment with subcutaneous Treprostinil in intermediate-risk PH patients undergoing initial oncologic therapy enables completion of cancer treatment, leading to either remission or chronic disease control. Furthermore, beyond the oncologic benefit, patients exhibited improvements in both clinical status and objective markers of pulmonary hypertension severity.