The pathophysiology of chronic thromboembolic pulmonary hypertension (CTEPH) is largely unknown. Although pulmonary endarterectomy (PEA) is potentially curative, inoperable patients and persistent pulmonary hypertension (PH) following surgery remain a significant problem. In this study, we aim to describe the histopathological characteristics of CTEPH and explore the potential relationship between pulmonary arterial lesions, radiological parameters, and clinical manifestations. Endarterectomized tissues from 81 consecutive patients of CTEPH were carefully collected, sectioned, and examined by experienced pathologists. Pertinent clinical and radiological data were obtained from medical records and operative reports. Neointima, fresh/organized thrombi, recanalized regions, and atherosclerotic lesions were microscopically examined as previously described. Thrombi and atherosclerosis were dominant in UCSD classification level I PEA materials, while recanalized neo-vessels were more frequently observed in UCSD classification level III cases. Degenerative changes of the extracellular matrix were also noticed in the vascular bed. Atherosclerotic lesions were more frequently observed in cases with higher ratio of the pulmonary artery diameter to ascending aorta diameter (PA/AA) reflected by computed tomographic pulmonary arterial scanning. Furthermore, the removal of pulmonary artery complex lesions (with the combination of three to four types of lesions) by PEA was associated with lower postoperative mean pulmonary arterial pressure (mPAP) and decreased incidences of persistent PH. Our study demonstrates that the histopathological features of CTEPH are strongly linked with clinical manifestations and the postoperative outcome after PEA. These data may provide possible evidence for further studies in searching for appropriate causal factors underlying this disease.

Background: Ferroptosis plays a significant role in pulmonary arterial hypertension (PAH), although its underlying mechanisms and key pathogenic genes remain unclear. Methods: Transcriptomic data from human PAH and control lung tissue were obtained from the Gene Expression Omnibus (GEO) database, whereas ferroptosis-related genes (FRGs) were sourced from the MsigDb and FerrDb databases. Differentially expressed FRGs (DE-FRGs) were identified through the intersection of FRGs with differentially expressed genes (DEGs). Functional enrichment analysis was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Key hub genes were identified through Least Absolute Shrinkage and Selection Operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), and weighted correlation network analysis (WGCNA). Gene set enrichment analysis (GSEA) was conducted to explore the functional roles and associated pathways of hub genes. The relationship between hub genes and immune infiltration was investigated. Expression levels of potential biomarkers were validated via Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) in two PAH animal models (monocrotaline-induced and Sugen5416 plus hypoxia-induced PAH). Finally, molecular docking was employed to screen potential therapeutic compounds. Results: A total of 133 DE-FRGs were identified, with KEGG and GO analyses highlighting their involvement in intracellular iron homeostasis and ferroptosis. Hub genes, notably FZD7 and NFE2, were identified using LASSO, SVM-RFE, and WGCNA. Immune infiltration analysis suggested that monocytes and neutrophils play key roles in PAH pathogenesis. Validation in PAH animal models showed significant upregulation of Fzd7 and downregulation of Nfe2 in lung tissues of both MCT- and SuHx-induced PAH models. Molecular docking identified tetrachlorodibenzodioxin (TCDD) has good binding affinity. Conclusion: In summary, we investigated two ferroptosis-related biomarkers, FZD7 and NFE2, in PAH using transcriptomics, offering new insights into molecular mechanisms and potential targeted therapies for the disease. Export

Background: Coronavirus disease 2019 (COVID-19) infection and post-acute COVID-19 are linked to thromboembolic complications. The impact on pulmonary embolism (PE) patients, known for a pro-inflammatory state, remains unstudied under the pandemic. Methods: Observational, multicenter study was performed in seven teaching hospital in mainland China, based on the ongoing nationwide cohort study of PE. During the omicron pandemic in China between Dec 1st, 2022 to June 1st, 2023. Patients were followed-up to obtain the disease condition and outcomes related to COVID-19. Overlap weighting based on the propensity score matching was conducted among comparisons. Results: Out of 1032 PE patients, 694 (67.2%) contracted COVID-19; 47.8% were on anticoagulation. COVID-19 patients on anticoagulants had a higher bleeding risk (10.5%) compared to non-COVID-19 patients (2.2%, p<0.001), with the adjusted OR of 4.79 (95%CI 1.04-22.21, p=0.045). 202 individuals (29.1%) with COVID-19 reported long COVID-19. Survival curve presented a significant higher risk of long-term bleeding and venous thromboembolism (VTE) recurrence in those with long COVID (log-rank p=0.011 and p<0.0001, respectively). Conclusion: COVID-19 escalated the risk of bleeding in patients with history of PE who were under anticoagulation therapy. Patients with long COVID-19 exhibit a considerably increased risk of long-term bleeding and VTE recurrence. Close monitoring of coagulopathy complications and meticulous adjustment of anticoagulation strategies are crucial in the treatment of PE patients with COVID-19, particularly in those with long COVID-19.

Treatment of intermediate–high-risk pulmonary embolism is still debated. Interventional therapy is being increasingly widely applied in clinical prac