Pulmonary Hypertension in Advanced Heart Failure with Reduced Ejection Fraction. What are the Consequences of the New Definition?

Abstract Background The recent definition of pulmonary hypertension (PH) has expanded the category of combined pre- and post-capillary (CPC) PH. Its impact on PH prevalence and prognosis in advanced heart failure with reduced ejection fraction (HFrEF) remains unknown. Methods We retrospectively analyzed 175 HFrEF patients evaluated for heart transplantation, all of whom underwent comprehensive invasive and non-invasive work-up. To assess the prognostic impact of the updated PH definition, survival was compared according to the presence of PH and its phenotype. Results According to the 2022 definition, PH was present in 83% of patients, of whom 76% met the criteria for CPC PH. Applying the 2015 definition, PH would have been diagnosed in 77% of patients, with 46% classified as CPC PH. Subsequent analyses were performed according to the 2022 classification. Presence of PH correlated with markers of advanced HFrEF course, but only larger indexed left atrial diameter (HR 1.33; 95% CI 1.09–1.61; p = 0.004) and lower TAPSE (HR 0.811; 95% CI 0.674–0.976; p = 0.027) remained independent predictors. CPC PH patients were older, with higher prevalence of renal insufficiency, diabetes and worse central hemodynamics. Higher age (HR 1.045; 95% CI, 1.000-1.091; p = 0.048), systolic pulmonary artery pressure determined non-invasively (HR 1.064; 95% CI, 1.018–1.111; p = 0.006) and pulmonary artery wedge pressure (HR 1.131; 95% CI, 1.015–1.261; p = 0.026) were only predictors of CPC PH. Presence of both PH and CPC PH was associated with worse 2-year outcome, defined as implantation of mechanical circulatory support or all-cause mortality. Conclusions The new PH definition minimally affects PH prevalence in advanced HFrEF but substantially increases CPC PH group, which remains associated with adverse prognosis.