Pulmonary Circulation最新文献

Long-term intravenous (IV) epoprostenol is a key therapy for pulmonary arterial hypertension (PAH); however, rare immune-mediated conditions occurring during therapy remain incompletely characterised. We report a 34-year-old man with idiopathic PAH who developed low-grade fever and bilateral pulmonary infiltrates after 11 years of IV epoprostenol. Despite empirical antibiotics, his condition persisted, and a lip biopsy confirmed IgG4-related disease (IgG4-RD). Systemic corticosteroids were initiated, and the patient was transitioned from IV epoprostenol to a combination of IV and inhaled treprostinil; IgG4-RD has remained in remission to date, with normalisation of serum IgG4. This case highlights a practical, minimally invasive diagnostic approach for suspected IgG4-RD in severe PAH and demonstrates the feasibility of prostacyclin modification to sustain PAH control while reducing immunosuppression.

Patients diagnosed with intermediate high-risk pulmonary embolism (IHRPE) are at significant risk for clinical deterioration during hospitalization; however, clinical tools to identify which patients will worsen are imprecise. We designed a proof-of-concept, single-center prospective study to assess IHRPE patients (using 2019 ESC criteria), measuring blood concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), troponin T (TnT), uric acid, and plasma lactate serially during the first 72 h to better understand their kinetics and associations with in-hospital adverse clinical events. Twenty subjects (mean age 62.0 ± 12.6 years) diagnosed by computed tomography angiogram were enrolled. Central pulmonary embolism was seen in 18/20, and lower extremity deep vein thrombosis in 14/20. On presentation, the mean Bova and PESI scores were 5 ± 0.7 and 105 ± 25.2, respectively. At baseline, TnT was elevated in 20/20, NT-proBNP in 18/20, uric acid in 10/20, and lactate in 8/20 subjects. Clinical outcomes included ICU admission in 7/20, clinical deterioration in 10/20, and death in 2/20. Clinical deterioration was associated with persistent elevations of TnT, NT-proBNP, uric acid and lactate (all p < 0.05). The NT-proBNP time from baseline to peak concentration was highly associated with clinical deterioration (ROC AUC = 0.82 [95% CI: 0.62-0.97, p < 0.01, RR = 2.8 at 24 h). The baseline PESI score ROC AUC for clinical deterioration was 0.75 (95% CI: 0.515-0.952, p = NS). Persistently elevated biomarkers show an association with in-hospital adverse clinical events in IHRPE and warrant further study to assist clinical management.

Reperfusion pulmonary edema (RPE) is a severe complication after pulmonary endarterectomy (PEA) and is associated with prolonged mechanical ventilation, organ dysfunction, and worse outcome. While residual pulmonary hypertension after PEA is associated with RPE, studies on preoperative risk factors for RPE after PEA are scarce. We investigated a potential association between preoperative hemodynamic values and development of RPE after PEA surgery. All adult CTEPH-patients who underwent PEA surgery at the Kerckhoff-Clinic Bad Nauheim, Germany, between 2018 and 2021 were included. The primary endpoint was development of postoperative RPE. Preoperative hemodynamic values and patient characteristics were compared between patients with and without RPE. Receiver Operating Characteristic curve analysis and logistic regression models were used for identification of risk factors for RPE. A total of 483 patients were included in this analysis (mean age 61 ± 13 years, 57% male). 75 patients developed postoperative RPE. ROC analysis revealed a significant discrimination for RPE by preoperative mean pulmonary artery pressure (mPAP) [AUC = 0.7, 95% CI: 0.622-0.779]. According to the Youden Index, the cut-off for preoperative mPAP was 54.5 mmHg. Multivariable logistic regression identified preoperative mPAP [OR: 2.684 95% CI: 1.220-5.904, p = 0.014] as independent risk factor for development of RPE after PEA surgery. Our study determines preoperative mPAP value as an independent risk factor for development of RPE after PEA surgery. These results might help to identify patients with an increased risk for RPE and adapt perioperative therapy accordingly.

Pulmonary Langerhans cell histiocytosis (PLCH) frequently complicated by pulmonary hypertension (PH), which markedly worsens prognosis. We retrospectively reviewed three institutional PLCH-PH cases treated with off-label Sotatercept added to background triple therapy and performed a systematic review of published PLCH-PH reports (PubMed/Embase through May 2025). Our three patients (ages 69, 62, 49; all female) had progressive vascular disease despite optimized vasodilator therapy. Following Sotatercept, all experienced ≥ 3-fold increases in 6-min walk distance and improved functional class. Hemodynamics improved substantially: right-atrial pressure -78.6%, pulmonary vascular resistance -75.5%, pulmonary artery systolic pressure -58.5%, mean PAP - 56.0%, PA diastolic pressure -51.0%, PAWP - 47.1%; cardiac output and index rose +75.9% and +73.8%, respectively. BNP/NT-proBNP normalized. Systematic review identified 34 published cases (2010-2025): mean age 37.2 ± 13.7 years, 44.1% female, 45.7% current/former smokers. Reported management strategies included targeted vasodilators, cytotoxic PLCH therapies (e.g., cladribine), smoking cessation, and selective surgery/transplant. In this small series, Sotatercept added to background therapy produced marked clinical and hemodynamic gains in refractory PLCH-PH. These effects of Sotatercept in Group 5 PH-are encouraging but limited by sample size and retrospective design. Prospective, collaborative studies are needed to define safety, efficacy, and optimal patient selection.

Endothelial cells within chronic pulmonary artery thrombi in CTEPH overexpress transmembrane protein 100 (TMEM100), an activin A receptor-like kinase 1 (ACVRL1 or ALK1) signaling-dependent gene, and TGFβ1 upregulated TMEM100 transcription in healthy lung ECs. TMEM100 permitted the TGFβ1-induced increase of ALK1, while repressing ALK5, and preventing ALK1-TMEM100 signaling impaired angiogenesis ex vivo. Our data indicate that TGFβ1-ALK1-TMEM100 signaling is active during CTEPH thrombus revascularization.

The optimal treatment strategy for patients with acute intermediate-high-risk pulmonary embolism (PE) remains uncertain. This randomized clinical trial (PRETHA) aimed to evaluate the efficacy and safety of percutaneous reperfusion therapies-trans-catheter thrombectomy and trans-catheter thrombolysis-compared with standard anticoagulation therapy. In this single-center, prospective trial conducted between April 2020 and April 2022, 39 patients with acute intermediate-high-risk PE were randomly assigned (1:1:1) to receive trans-catheter thrombectomy, trans-catheter thrombolysis, or conservative medical therapy with anticoagulation. Echocardiographic, hemodynamic, and biomarker parameters were assessed at baseline, 48 h, and at 1-, 6-, and 12-month follow-up. At 48 h, both interventional groups demonstrated significant improvement in right ventricular (RV) function and pulmonary pressures. The RV/LV ratio decreased by 0.3 (95% CI: 0.13-0.69; p < 0.0002) in the thrombectomy group and by 0.4 (95% CI: 0.12-0.96; p < 0.0002) in the thrombolysis group. Noninvasively measured systolic pulmonary artery pressure decreased by 29% in the thrombectomy group and by 39% in the thrombolysis group (both p < 0.001). Significant reductions in direct systolic and mean pulmonary artery pressures were also observed (p = 0.0002). However, at longer (1 to 12 months) follow-up, all three treatment groups represent similar positive changes of echocardiographic parameters and cardio-specific biomarkers independent of the treatment tactic chosen in the acute period. Functional capacity and quality of life were superior in the interventional groups compared with anticoagulation alone. The incidence of adverse events was highest in the thrombolysis group (38%), whereas thrombectomy and medical therapy demonstrated more favorable safety profiles. Percutaneous reperfusion therapies were associated with earlier improvements in hemodynamic and functional surrogate parameters compared with anticoagulation alone; however, at 1-year follow-up, echocardiographic measures and biomarkers of cardiac function were similar across all treatment groups. These findings should be interpreted as mechanistic and hypothesis-generating.

A major consequence of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is pulmonary hypertension (PH), which raises morbidity and mortality rates. This study assessed biomarker profiles, clinical characteristics and diagnostic efficacy of important coagulation and inflammatory markers in AECOPD patients who have varying degrees of PH severity. A total of 248 AECOPD patients were included and divided into three groups according to the severity of their PH. Analysis of biomarker levels, such as B-type natriuretic peptide (BNP), troponin I (TNT-I), d-dimer, C-reactive protein (CRP), and coagulation markers, besides pulmonary artery systolic pressure was done. These biomarkers' diagnostic precision for PH was evaluated by receiver operating characteristic curve analysis. PH patients were much older than those without PH. The moderate to severe PH group had highest BNP levels (619.92 ± 945.81 pg/mL), which rose gradually with PH severity. TNT-I, CRP and D-dimer showed similar patterns. The most dependable biomarker for PH, according to ROC analysis, was BNP (AUC = 0.803), followed by TNT-I (AUC = 0.712) and D-dimer (AUC = 0.694). Prothrombin and Activated Partial Thromboplastin had a considerable predictive value, although fibrinogen's diagnostic utility was restricted (AUC = 0.559). BNP showed the highest predictive value with an AUC, suggested BNP is most important biomarker for PH in AECOPD patients, TNT-I and D-dimer serve as useful secondary markers. The observed elevations in coagulation and inflammatory markers indicate their potential role in PH pathogenesis.

Pulmonary hypertension (PH) causes progressive pulmonary vascular resistance and right heart failure. We investigated whether beta-alanine (β-Ala) improves right ventricular (RV) remodeling and dysfunction in a monocrotaline (MCT)-induced PH rat model. Male Wistar rats were assigned to control, MCT-PH, and β-Ala-treated PH groups. RV function was assessed by RVSP and RVHI; molecular changes were examined by western blotting and qPCR; histology evaluated RV hypertrophy and fibrosis. β-Ala significantly improved RVSP and RVHI versus MCT. Mechanistically, β-Ala reduced ERK and p38 MAPK signaling while enhancing AKT activation. It decreased proapoptotic Bax and cleaved Caspase-3 and increased antiapoptotic Bcl-2. qPCR showed downregulation of ANP, BNP, β-MHC, and TGF-β, with upregulation of β-MHC. Histological analyses confirmed attenuation of RV hypertrophy and fibrosis. Overall, β-Ala mitigates RV remodeling and dysfunction in MCT-induced PH, likely via modulation of MAPK/AKT pathways and apoptosis, supporting its potential as a therapy for PH-related right heart dysfunction.

The proliferation of pulmonary artery smooth muscle cells (PASMCs) is a key mechanism in hypoxic pulmonary hypertension (HPH). Resistin-like Molecule Beta (RELM-β) promotes the hypoxia-induced proliferation of PASMCs, and calcium ions (Ca²⁺) play an important role in cell proliferation. However, the mechanism by which RELM-β regulates Ca²⁺ and the pathogenesis of HPH remain unclear. We established a RELM-β-knockout (RELM-β^-/-) model and assessed the mechanism by which RELM-β affects Ca²⁺ regulation, cell proliferation, and pulmonary haemodynamics. In the rat HPH model and hypoxia-treated PASMCs, the expression of RELM-β was increased, which led to changes in pulmonary haemodynamics (elevated right ventricular systolic pressure [RVSP], right ventricular hypertrophy, and pulmonary artery thickening) and PASMC proliferation. Conversely, after RELM-β knockout, the opposite effects were observed. RELM-β regulated the intracellular Ca²⁺ concentration ([Ca²⁺]_i) through the Phospholipase C-Inositol 1,4,5-Trisphosphate Receptor (PLC-IP₃R) pathway, which promoted the release of intracellular Ca²⁺ and its binding to calcium-sensing receptor (CaSR), ultimately increasing store-operated calcium entry (SOCE) and extracellular Ca²⁺ influx and promoting PASMC proliferation. RELM-β, which is a cytokine-like growth factor, plays a role in the proliferation of PASMCs and the promotion of HPH.

We report a novel genetic variant in a patient with treatment-resistant peripheral pulmonary artery stenosis (PPS) and progressive pulmonary arterial hypertension (PAH). A premature infant was diagnosed with bilateral PPS requiring multiple surgical reconstructions and interventional procedures with refractory proximal stenoses. Despite adequate anatomic repair preserving nearly all right lung segments, the child developed progressive PAH with elevated pressures in preserved segments out of proportion to residual obstruction. Genetic evaluation revealed a de novo heterozygous variant in FGD5, a critical regulator of VEGF signaling essential for pulmonary vascular development and homeostasis. We propose that FGD5 haploinsufficiency could disrupt endothelial function during development, leading to aberrant vascular patterning. This dysfunction may lead to PPS and ongoing endothelial dysfunction contributing to PAH. This represents a potential novel genetic cause of PPS with PAH, expanding the understanding of critical regulators in pulmonary vascular development and pathology. Comprehensive genetic evaluation in treatment-resistant pulmonary vascular disease may identify novel mechanisms and eventually guide personalized therapeutic approaches through enhanced genotype-phenotype correlation.