Single Test‐Based Diagnosis and Subtyping of Pulmonary Hypertension Caused by Fibrosing Mediastinitis Using Plasma Metabolic Analysis

Abstract Pulmonary hypertension (PH) often leads to poor survival outcomes and encompasses diverse subtypes with distinct underlying causes. Specifically, PH resulting from fibrosing mediastinitis (FM‐PH) presents significant diagnostic challenges due to nonspecific symptoms and overlap of clinical characterization with other PH subtypes, leading to frequent misdiagnosis and delayed treatment. Moreover, the complex diagnostic procedures impose a significant burden on FM‐PH patients, many of whom already experience mobility difficulties. This study represents a single test‐based diagnosis of FM‐PH, using the plasma metabolites obtained through ferric particle‐enhanced laser desorption/ionization mass spectrometry analysis. Distinct metabolic alterations in FM‐PH are identified compared to healthy controls and other PH subtypes, achieving an area under the curve (AUC) of 0.987 for FM‐PH diagnosis and 0.728 for differentiating FM‐PH from other subtypes. By addressing existing gaps in diagnostic strategies, this research highlights the potential of metabolic analysis in elucidating the metabolic landscape of PH.