Echocardiographic assessment for responder analysis in pulmonary arterial hypertension patients treated with parenteral prostanoids

Abstract Background Although pulmonary arterial hypertension (PAH) prognosis has improved in the last two decades, patient outcomes are still unfavorable and there are unresolved issues regarding current therapeutic strategies. OBJECTIVES The present study aims to identify echocardiographic changes at 1-year assessment from parenteral prostanoid initiation, predictive of long-term survival. Methods One hundred and sixty-three consecutive PAH patients referred to our center and started on parenteral prostanoids from January 1998 to December 2021 were included in the study. The diagnosis of PAH was confirmed according to the European guidelines. Baseline evaluation included medical history, physical examination, a non-encouraged 6-minute walk test (6MWT), right heart catheterization (RHC), and echocardiographic assessment. The complete assessment was repeated at 1 year from prostanoid initiation and before any further combination therapy. All patients were prospectively followed, with clinical examination (every 1-3 months), echocardiographic evaluation (every 3-6 months). Results Improvement in RVEDA and RVFAC at 1-year assessment was independently predictive of survival (c-statistic: 0.83, C.I. 0.75-0.92). ROC-derived cut-points of ΔRVEDA -2.5 cm2 and ΔRVFAC 5.6% were used for patients’ clinically meaningful responsiveness definition. After a mean follow-up of 33 (IQR 10-69) months, 68 patients (42%) died. Fifty-five (34%) patients met the clinically meaningful responsiveness definition and were considered as full-responders with significantly better survival rates compared with partially-responders (108 patients, 66%), respectively, 100%, 100%, 100%, and 100% versus 69%, 44%, 33%, and 13% after 1, 3, 5 and 10 years of follow-up (p0.0001). PVR reduction at 1-year assessment was the only independent determinant of both ΔRVEDA and Δ RVFAC improvement (O.R. 0.76, 95% C.I. 0.66-0.89, p0.001). Although there was no significant difference in maximal dosage reached over time between full-responders and partially-responders (55.8±33.2 vs 48.1±25.9 ng/kg/min, respectively; p=ns), full-responders were characterized by a progressive improvement of RVEDA and RVFAC with increasing prostanoid dosage compared with partially-responders. Conclusions Echocardiography assessment at 1 year from prostanoid initiation allows for a clinically meaningful responsiveness definition, able to identify patients characterized by long-term survival.