Pulmonary Hypertension Drives Prognosis in Idiopathic Pulmonary Fibrosis: Insights from the European IPF Registry

Abstract

Background/Objectives: In patients with idiopathic pulmonary fibrosis (IPF), a progressive disease characterized by lung tissue scarring, the impact of comorbidities is only partially understood. In particular, the prognostic implications of pulmonary hypertension (PH) are yet to be fully disclosed. Methods: To identify distinct IPF phenotypes on the basis of comorbidities and functional data, we performed cluster mixed data retrospective analysis, as well as recursive partitioning analysis on a dataset of 324 patients from the European IPF Registry (eurIPFreg); all patients were classified as IPF on the basis of established guidelines. Diagnosis of PH was based on echocardiographic and right heart catheter criteria as indicated in the 2022 ESC/ERS guidelines. Results: Two distinct clinical clusters with significant survival differences were identified (p < 0.001). Cluster 1, with fewer comorbidities, had a median survival of 4.41 years, whereas Cluster 2, with higher rates of arterial hypertension, diabetes mellitus, cardiovascular disease, PH, and dyslipidemia, showed a shorter median survival of 2.85 years. Multivariate Cox regression analysis confirmed PH as a significant predictor of reduced survival (HR 2.03). Recursive partitioning (RP) revealed that FVC was the strongest prognostic indicator: FVC below 50% predicted poor survival, and among patients with a FVC above 50%, the presence of PH indicated a significantly worse outcome. Conclusions: In this real-world IPF cohort, comorbidity cluster and RP analysis identified PH as the most relevant comorbidity. The findings suggest that PH may be more prevalent and impactful in IPF than previously recognized, with implications for clinical management.