Redefining pulmonary hypertension in cirrhosis: epidemiological expansion and divergent prognostic impact under the 2022 ESC/ERS Criteria

Background & Aims: The 2022 ESC/ERS guidelines redefined pulmonary hypertension (PulH) by lowering the diagnostic threshold to a mean pulmonary arterial pressure (mPAP) >20 mmHg and introducing an unclassified phenotype (U-PulH: mPAP >20 mmHg, PAWP ≤15 mmHg, PVR ≤2 WU). The clinical and prognostic implications of this revision in cirrhosis, where hyperdynamic circulation and systemic inflammation may confound pulmonary hemodynamics, remain unclear. We aimed to assess the epidemiological and prognostic impact of the new criteria in a large real-world cohort of patients with compensated cirrhosis. Methods: In this single-center retrospective study, 325 consecutive patients with compensated cirrhosis and portal hypertension underwent paired right heart catheterization (RHC) and hepatic venous pressure gradient (HVPG) measurement. PulH severity was categorized as borderline (mPAP 21–24 mmHg) or overt (≥25 mmHg), and phenotypes were classified according to the 2022 ESC/ERS criteria. Liver-related events (hepatocellular carcinoma, clinical ascites, variceal bleeding, and overt hepatic encephalopathy), all-cause mortality, and cardiovascular mortality were analyzed using competing-risk models. Results: Application of the revised criteria tripled the prevalence of PulH (from 20% to 61%). U-PulH was the most prevalent phenotype (30%), largely driven by borderline elevations (93%). Over a median follow-up of 4.8 years, liver-related events were independently associated with HVPG (sHR 1.04; 95% CI 1.02–1.08; p=0.003) and serum albumin (sHR 0.64; 95% CI 0.43–0.94; p=0.024), but not with pulmonary hemodynamics. Overt PulH independently predicted all-cause mortality (sHR 2.20; 95% CI 1.38–3.49; p<0.001), together with age and serum albumin, whereas borderline PulH showed no association (p>0.9). In contrast, both borderline (sHR 2.85; 95% CI 1.18–6.91; p=0.021) and overt PulH (sHR 3.39; 95% CI 1.32–8.73; p=0.011) independently predicted cardiovascular mortality, even after adjustment for pre-existing cardiac disease. Conclusions: The 2022 ESC/ERS definition markedly increases the detected prevalence of pulmonary hypertension in compensated cirrhosis, with U-PulH emerging as the predominant phenotype. While mildly elevated pulmonary pressures do not impact liver-related outcomes, they are independently associated with cardiovascular mortality, supporting a cardio-hepatic prognostic dissociation. Prospective studies are needed to determine whether these newly defined categories represent early disease stages or adaptive responses to portal hypertension.