慢性血栓塞栓性肺高血圧症

BACKGROUND: Chronic thromboembolic pulmonary hypertension is exceptionally rare in children and is typically associated with major acquired prothrombotic conditions. CASE SUMMARY: We report a 14-year-old girl with acute lymphoblastic leukemia who developed chronic thromboembolic pulmonary artery obstruction following necrotizing pneumonia and septic thromboembolic disease. Computed tomography, ventilation-perfusion scintigraphy, and pulmonary angiography demonstrated complete right pulmonary arterial occlusion with absent perfusion to the right middle and lower lobe territories. Despite mildly elevated pulmonary artery pressures (mean pulmonary artery pressure 23 mm Hg), the patient presented with severe functional limitation, oxygen dependence, and surgically accessible disease. Bilateral pulmonary thromboendarterectomy was successfully performed, achieving restoration of pulmonary perfusion and favorable postoperative recovery. Molecular analysis of the resected thrombotic material identified Mycobacterium tuberculosis. DISCUSSION: This case highlights the feasibility of pulmonary thromboendarterectomy in pediatric chronic thromboembolic pulmonary hypertension and emphasizes that surgical candidacy should integrate symptom burden, anatomical operability, and multidisciplinary assessment beyond hemodynamic severity alone. TAKE-HOME MESSAGES: Pulmonary thromboendarterectomy is feasible and associated with favorable outcomes in pediatric patients and remains the only potentially curative treatment. Early multidisciplinary evaluation is essential to identify operable disease, integrating anatomical burden, clinical and hemodynamic status, and the risk of disease progression.

Mutations in BMPR2 are the most common genetic cause of heritable pulmonary arterial hypertension (PAH). We report a 47-years-old male with a BMPR2 variant (c.246A > G) who presented with dyspnea and recurrent hemoptysis. Right heart catheterization confirmed PAH with a mean PAP of 46 mmHg, PAWP of 3 mmHg, and PVR of 10.75 WU. A pulmonary artery biopsy was performed to exclude alternative diagnoses such as vasculitis and chronic thromboembolism. Histology showed foam cell accumulation in the intima, infiltration of CD3+ T cells, CD20+ B cells, and CD68+ histiocytes in the intima and media, and mucoid deposition. These findings suggest an active inflammatory component and dysregulation of lipid metabolism in early-stage PAH. Targeted PAH therapy improved symptoms, and resolved hemoptysis after bronchial artery embolization. Although the variant is of uncertain significance, this rare biopsy provides early pathological insights into BMPR2-associated PAH. Further studies are needed to clarify mechanisms linking BMPR2, inflammation, and lipid metabolism in vascular remodeling.

BACKGROUND: Sex-based differences in long-term respiratory and pulmonary vascular outcomes after acute pulmonary embolism remain incompletely defined. OBJECTIVES: To compare long-term mortality, pulmonary vascular outcomes, and chronic respiratory sequelae between women and men after acute pulmonary embolism. METHODS: We conducted a retrospective cohort study and included adults diagnosed with acute pulmonary embolism from 2000 to 2025. A 90-day landmark analysis was used to examine long-term outcomes. Women and men were matched 1:1 by propensity scores based on demographic characteristics and baseline comorbidities. The primary outcome was all-cause mortality from 90 days to 3 years. Secondary outcomes included pulmonary hypertension, chronic thromboembolic pulmonary hypertension, chronic respiratory failure, long-term oxygen use, and right heart failure or chronic cor pulmonale. RESULTS: After matching, 397,669 women and 397,669 men were included. Women had lower 3-year all-cause mortality than men (9.50% vs. 9.97%; hazard ratio, 0.91; 95% CI, 0.90-0.93). Conversely, women had higher risks of pulmonary hypertension (3.16% vs. 2.73%; hazard ratio, 1.10; 95% CI, 1.07-1.13), chronic respiratory failure (1.96% vs. 1.61%; hazard ratio, 1.16; 95% CI, 1.12-1.20), and long-term oxygen use (2.65% vs. 2.20%; risk ratio, 1.21; 95% CI, 1.17-1.24). Chronic thromboembolic pulmonary hypertension was numerically more frequent among women but did not differ significantly in the 3-year time-to-event analysis. Right heart failure or chronic cor pulmonale did not differ significantly. Similar patterns persisted in 5-year analyses. CONCLUSIONS: Women demonstrated a distinct post-pulmonary embolism respiratory and pulmonary vascular outcome profile, with higher chronic pulmonary vascular and respiratory morbidity despite modestly lower long-term mortality.

To elucidate the complex pathophysiology of chronic thromboembolic pulmonary hypertension (CTEPH), a disease associated with bilateral fibrotic obstructions of the pulmonary arteries (PA) and microvascular changes, research relies on animal models, which often depend on invasive techniques, including open surgery. As animal welfare is a major priority for the future of experimental research, and in accordance with the principles of the 3Rs (Replacement, Reduction, and Refinement), this project aimed to develop a fully minimally invasive porcine CTEPH model. In five female large white pigs (50 kg, 3-4 months), an intravascular plug was inserted into the left PA. The right lower lobe artery was embolized weekly for 5 weeks with non-resolving n-butyl-2-cyanoacrylate-glue. Magnetic resonance imaging (MRI) was performed at each intervention. At week 6, plasma molecular and macro- and microscopic analyses were performed. Implantation of the intravascular plug was successful in all animals, without any residual perfusion seen in MRI angiography. Significant increases in mean pulmonary artery pressure (mPAP) (p = 0.005) and mean total pulmonary resistance (TPR) (p = 0.043) were observed. Right ventricle dimensions were significantly increased in all animals. Macroscopically, the left lung developed hypertrophy of bronchial arteries and the right upper lobe overperfusion. Histologically, microvascular wall thickness was increased in both the over-perfused and ischemic territories. Plasma molecular analysis revealed elevated circulating endothelin-1 (p < 0.0001) and reduced nitric oxide metabolites (p = 0.0007). In conclusion, this study establishes a fully minimally invasive refinement of a previously described porcine CTEPH model, including relevant hemodynamic, morphologic, molecular and imaging features of CTEPH while increasing welfare for experimental animals.