Hemodynamic variants of pulmonary hypertension and their prognostic significance in cirrhosis: evidence from a large patient cohort

Background & Aim: The prevalence and clinical implications of pulmonary hypertension (PulH) in patients with cirrhosis remain poorly defined. In 2022, the ESC/ERS guidelines revised the diagnostic threshold for PulH, lowering the mean pulmonary artery pressure (mPAP) cut-off to >20 mmHg. A new phenotype “unclassified PulH” was defined by mPAP > 20 mmHg, pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg, and pulmonary vascular resistance (PVR) ≤ 2 Wood Units (WU). This form appears common in cirrhosis, yet its prognostic relevance is unclear. We conducted a retrospective study of consecutive patients with compensated cirrhosis who underwent both hepatic and right heart catheterization between January 2012 and December 2023. The aim was to identify asymptomatic patients with cirrhosis and PulH and evaluate long-term outcomes, including all-cause mortality, hepatic decompensation, and major adverse cardiovascular events (MACE). Methods: PulH was defined as mPAP > 20 mmHg and classified as pre-capillary, post-capillary, or unclassified according to PCWP and PVR. Patients with decompensated cirrhosis, known cardiopulmonary disease, or prior PulH-specific therapy were excluded. Baseline clinical, laboratory, and hemodynamic data were collected. Time-dependent outcomes were analyzed with a competing risk framework. Results: Among 1333 patients with cirrhosis who underwent hemodynamic assessment, 578 (43%) met the current PulH definition with mPAP > 20 mmHg. However, when applying the previous diagnostic threshold of mPAP > 25 mmHg, PulH prevalence dropped to 21%, highlighting the impact of the new cut-off in identifying a broader at-risk population. After applying exclusion criteria, 209 compensated patients were included. Based on ESC/ERS classification, 22%, 29%, and 49% had pre-capillary, post-capillary, and unclassified PulH, respectively. The 5-year cumulative incidence of all-cause mortality was 27% (95% CI 21–33). Unclassified PulH was associated with significantly lower mortality compared to pre- and post-capillary forms (18% vs. 29% vs. 40%, p = 0.009). Independent predictors of mortality included unclassified PulH (sHR 0.58), right ventricular systolic work index (RVSWI) (sHR 1.09), age (sHR 1.09), etiologic factor clearance (sHR 0.46), and Child–Pugh score (sHR 1.55). Notably, mortality was nearly doubled in patients with mPAP > 25 mmHg compared to those with mPAP 20–25 mmHg (38% vs. 22%, p = 0.003). The 5-year cumulative incidence of hepatic decompensation was 29% (95% CI 23–36), with HVPG > 12 mmHg (sHR 3.43), MELD score (sHR 1.09), hemoglobin (sHR 0.86), and diabetes (sHR 1.85) as independent risk factors; PulH phenotype and RHC parameters were not independently associated. Five-year MACE occurrence reached 13% (95% CI 9–19%), driven solely by traditional cardiovascular risk factors (male sex, smoking, prior cardiovascular disease, serum sodium). Conclusion: Unclassified PulH is the most common form in compensated cirrhosis and is associated with better survival than pre- and post-capillary types. While the newer mPAP threshold improves sensitivity, PulH severity based on mPAP > 25 mmHg remains prognostically relevant, and HVPG confirmed its predominant role in predicting hepatic decompensation. These findings underline the value of PulH screening and classification in patients with cirrhosis. Further prospective, controlled studies are warranted to clarify the prognostic role of unclassified mild PulH.