Abstract Rationale The inability to obtain pulmonary arterial tissue safely from living patients has left the histopathology of pulmonary arterial hypertension (PAH) poorly characterized, hindering precise subtyping and molecular assessment. To bridge this gap, we developed a novel percutaneous transluminal peripheral pulmonary artery biopsy (PT-PPAB) technique for the safe sampling of peripheral pulmonary arteries. Methods In this prospective pilot study (ChiCTR2300074436), 15 patients with PAH or unexplained pulmonary artery anomalies underwent PT-PPAB. The procedure was designed to obtain specimens from targeted peripheral pulmonary arteries under fluoroscopic guidance. Retrieved specimens were systematically evaluated using H45mmHg: n = 1). WHO classification among these 11 PAH patients included Group 1 (n = 5), Group 3 (n = 2), and undefined cases (n = 4). PT-PPAB was successfully performed in all patients with no major procedural complications. A median of 2.4 samples (median total specimens’ volume: 5.00 mm³, IQR: 2.50-9.50) per patient were obtained from pulmonary arteries. Histopathological analysis enabled classification into distinct subtypes: Remodeling (R-type, 27%), Inflammatory (I-type, 20%), Thrombotic (T-type, 7%), Mixed (M-type, 13%), and Non-significant (NS, 33%). Molecular profiling revealed nuclear localization of p-SMAD2/3 in a subset of R-type cases, suggesting TGF-β pathway activation—a potential biomarker for anti-proliferative therapies such as Sotatercept. Concurrent alterations in endothelin receptor (EDNRA) and nitric oxide synthase (p-eNOS) pathways were also detected, indicating potential guidance for tailored targeted therapies. Conclusions This proof-of-concept study establishes PT-PPAB as a feasible and safe method for obtaining peripheral pulmonary arterial tissue in vivo. The technique enables pathological subtyping and reveals actionable molecular signals, laying the groundwork for a transformative, histology-guided precision medicine approach to PAH. This abstract is funded by: None
Wu et al. (Fri,) studied this question.