Prognostic value of pulmonary hypertension in patients with advanced heart failure evaluated fort heart replacement therapy in the light of new definition of pulmonary hypertension

Abstract Background Pulmonary hypertension (PH) due to left heart disease is a common complication in heart failure (HF) and is associated with increased mortality. The 2022 ESC Guidelines updated the hemodynamic definition of PH lowering the threshold to mean pulmonary artery pressure (mPAP) >20 mmHg. The relevance of this classification has not been fully explored in the setting of advanced heart failure. Purpose The aim of this study was to investigate epidemiology and clinical outcomes of PH according the 2022 definition in patients with advanced HF candidate to heart replacement therapy (HRT) defined as heart transplantation (Htx) or left ventricular assist device (LVAD) implantation. Methods This study is a retrospective analysis of all adult (> 18 years old) patients that underwent HRT evaluation with an available right heart catheterization from 2003 to 2018. Patients were selected based on HLA typing as a proxy for HRT evaluation. Patients were divided into groups based on the presence of PH with mPAP < 20 mmHg, 21-24 mmHg or > 25 mmHg) to define the impact of the revised classification. Updated definition was then applied to investigate association with prognosis. Study outcome was the composite occurrence of death, urgent HTx or LVAD implantation. Patients were stratified into 3 different eras to account for the extent of the study period. Univariate and multivariate analysis was used to detect risk factors correlated to outcome. Results 625 patients were screened, of whom 619 had an available RHC and were included in the study. Median follow-up was 15 months (IQR 5-39). With the threshold of mPAP > 20 mmHg, 450 patients (73%) had PH as compared to 366 (59%) with the previous definition. Survival from endpoint was significantly lower in both patients with mPAP 21-24 [1 year: 87%; 5-years 53%; OR 1,7 (1,3-3,8); p = 0.005] and > 25 mmHg [1 year 81%, 5 years 50%; OR 2,7 (1,8-4,2); p< 0,001], as compared to those without PH (1 year 91%, 5 years 78%). No difference was found between the groups of increased mPAP. Applying the 2022 definition, 122 (19%) patients had isolated isolated pC-PH, 320 (52%) combined pC-PH and 8 a form of pre-capillary PH. Isolated pC PH and combined pC PH both correlated with worse outcome (OR respectively 2,3; p = 0.0017 and 2,7 p<0.001). In patients with combined PH, PVR > 3 WU was associated with worse survival (88% vs 76% at 1t year). Conclusion In this study of patients with advanced HF evaluated for HRT, the 2022 hemodynamic definition of PH identified an additional 13% of patients. Survival was lower in patients with mPAP > 20 mmHg and these finding support the revised threshold and its association with prognosis in this population. In patients with combined PH, PVR > 3 WU is associated with worse outcomes. In advanced HF, this threshold may retain better prognostic value.