Pulmonary Circulation最新文献

Pulmonary arterial hypertension (PAH) is a life-threatening condition with no cure, making research into its underlying mechanisms critical. The platelet-derived growth factor (PDGF) signaling pathway plays a crucial role in vascular remodeling, a key factor in PAH progression. Anti-PDGF receptor therapies, such as imatinib, show promise but are associated with significant side effects. Recent research identified PDGF-D as a new risk gene in idiopathic PAH, highlighting the need for further investigation into the PDGF pathway in the disease. In this study, we investigated PDGF-D, a specific PDGFRβ ligand, as a potential therapeutic target. RNA-Seq data from healthy lungs indicated that PDGF-D is predominantly expressed in inflammatory cells, whereas in vascular lesions of idiopathic PAH patients, PDGF-D was produced by various cell types. In vitro, PDGF-D induced mitogenic effects on pulmonary arterial smooth muscle cells. However, genetic deletion of PDGF-D in the chronic hypoxia mouse model of pulmonary hypertension showed no significant impact on vascular muscularization, hemodynamic parameters, or right ventricular hypertrophy. But, the absence of hypoxia-induced Pdgfrb upregulation and the lack of increased expression of PAH-regulated genes, Fgf2 and Notch3, in PDGF-D-deficient mice, suggests activation of alternative mechanisms. MicroRNA analyses revealed PDGF-d-related alterations in the expression of miR-21 and miR-451, both important regulators in PAH, further supporting the notion that PDGF-D plays a unique role in PAH development. Taken together, our data suggest that PDGF-D may target a distinct population of PDGFRβ-expressing cells, separate from those stimulated by PDGF-B, positioning PDGF-D as a potentially unique and compelling therapeutic target for PAH.

Pulmonary artery wedge pressure is a crucial measurement for differentiating between hemodynamic categories of pulmonary hypertension (PH), particularly Groups 1 and 2. In this prospective study, we analyzed the diagnostic utility of checking wedge oxygen saturation to confirm wedge position during right heart catheterization in patients referred for PH.

Pulmonary Arterial Hypertension (PAH) is a rare, chronic and progressive disease affecting the heart and lungs. Endothelin receptor antagonist (ERA) + phosphodiesterase type 5 inhibitor (PDE5i) treatment is recommended for all PAH patients. The two approved PDE5is are tadalafil and sildenafil. To determine the efficacy and safety outcomes for tadalafil and sildenafil as monotherapies or in combination with ERAs for treating PAH, from randomized controlled trials (RCTs) and real-world evidence studies (RWEs) identified by a systematic literature review (SLR). MEDLINE, Embase and Cochrane Libraries were searched in May 2024. Relevant outcomes included 6-min walk distance (6MWD), pulmonary vascular resistance (PVR) and safety. This report includes studies where patients were treated with either sildenafil or tadalafil. Fifteen RCTs and three RWEs investigated tadalafil (tadalafil 40 mg or 20 mg once daily) or sildenafil (20 mg three times a day). Mean 6MWD change from baseline (CFB) in patients receiving tadalafil or sildenafil monotherapy were comparable, however, in combination with an ERA, tadalafil may be more effective. Generally, there was more data for tadalafil + ERAs, showing marked improvement in mean PVR CFB, compared with patients receiving sildenafil. Conclusions on safety were limited. Risk of bias in RCTs was generally low but moderate in RWEs. Two studies reported patients who switched from sildenafil to tadalafil treatment, treatment transition was feasible. Although comparable when used as monotherapy, this qualitative analysis suggests that tadalafil + ERA combination therapy may have more favorable 6MWD improvements than sildenafil + ERA combination therapy.

Pericardial effusion (PEF) in PAH may be a marker of worsening disease or associated with autoimmune conditions. Sotatercept was not initially reported as associated with the development or progression of PEF. We describe PAH patients taking sotatercept who were found to have new or worsening PEF and examine associated comorbidities.

High-risk acute pulmonary embolism (PE) is associated with significant in-hospital mortality. Large-Bore Mechanical Thrombectomy (LBMT) is a treatment option for acute PE, but data on its efficacy in high-risk PE was limited. This prospective case series reported the outcomes of 14 patients with high-risk PE treated using a novel multipurpose mechanical aspiration system (MMAS). Most patients were in hemodynamic decompensation, requiring inotropic or mechanical circulatory support. The mean procedural time was 73.5 ± 39.2 min. Complete procedural success was achieved in 78.6% of the cases, while two patients required bailout therapies. The mean pulmonary arterial pressure decreased by 27.2%, and the right-ventricle/left-ventricle ratio normalized in 85.7% of patients. The primary endpoint-in-hospital mortality-was 0%, while the major bleeding rate was 27.2%. These findings suggest that MMAS is a safe and effective intervention for acute high-risk PE.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of pulmonary embolism that is characterized by chronic obstruction of pulmonary arteries because of organized thrombi. Pulmonary endarterectomy (PEA) is the primary treatment of choice for CTEPH, which aims to clear the pulmonary arteries as completely as possible to decrease right ventricular afterload, thereby improving pulmonary hypertension (PH). PEA is a complex surgical procedure involving cardiopulmonary bypass and deep hypothermic circulatory arrest. Although it provides excellent outcomes, it is associated with frequent complications, including lung reperfusion injury, endobronchial hemorrhage, and persistent PH. Therefore, patients with CTEPH need to be referred to specialized centers. Germany performs approximately 150 PEA procedures annually. However, in Japan, the availability of PEA facilities is limited. The present study aims to delineate the differences in CTEPH management between Japan and Germany, evaluate the underlying reasons for the limited implementation of PEA in Japan, and underscore the need for specialized assessment and referral of patients who are eligible for PEA. The limited utilization of PEA in Japan appears to be attributable not to underestimation of the procedure itself, but rather to anatomical and institutional constraints.

Pulmonary arterial hypertension (PAH) is a chronic, progressive, and ultimately life-threatening disease characterized by vascular remodeling and increasing pulmonary vascular resistance. Despite significant advances in diagnostic tools and therapeutic strategies, clinical intervention often begins only when patients become symptomatic-typically at New York Heart Association (NYHA) functional class II or higher. Paradoxically, while early detection of PAH is strongly encouraged to preempt irreversible vascular, cardiac, and multisystem damage, treatment remains largely restricted to those already exhibiting symptoms. Patients in NYHA class I, though experiencing pathophysiological progression, are systematically excluded from approved pharmacological therapies. This disjunction represents not only a clinical and ethical conundrum but also a conceptual paradox: why invest in early diagnosis if early treatment is withheld? Emerging evidence on various chronic diseases, including cancer, infectious diseases like HIV and hepatitis, and even other cardiovascular diseases, underscores the benefits of initiating treatment before the onset of symptoms. In contrast, the current approach to PAH inadvertently promotes a nihilistic "wait and see" policy, exposing asymptomatic patients to preventable deterioration. Herein, we call for a reassessment of clinical guidelines, regulatory frameworks, and access policies with the goal of better aligning them with the biological realities of PAH. While we advocate for a paradigm shift toward the inclusion of NYHA class I patients in treatment strategies, we explicitly acknowledge the current limitations of the evidence base and emphasize the need for ongoing, high-quality research including counterarguments and the practical challenges of early treatments.

Children with single ventricle heart disease (SVHD) demonstrate decreased arginine/NO metabolism following Stage 2 (Glenn) palliation, associated with poor postoperative outcomes. It is unknown if arginine dysregulation persists at Stage 3 (Fontan). The purpose of this study is to quantify circulating arginine metabolites in children undergoing Fontan palliation for SVHD to evaluate the relationship between metabolite concentrations and outcomes. Prospective cohort study of children undergoing Fontan operation (n = 82) and similar age healthy controls (n = 49). We measured circulating arginine metabolites pre- and post-op by tandem mass spectrometry. Postoperative outcomes included length of stay (LOS) and pleural drainage. Pre-op cases showed lower arginine, argininosuccinate, cysteine, NMMA, higher glutathione, and lower arginine/ADMA, arginine/citrulline, and arginine/ornithine ratios compared to controls. Post-op cases experienced progressively decreasing citrulline concentration and higher arginine/ADMA, arginine/citrulline, and arginine/ornithine ratios compared to pre-op. In uncorrected analysis, postoperative decreased citrulline level (31.4% and 33.9% longer LOS for 50% decrease in [citrulline] at 2 and 24 h, respectively) was associated with longer LOS. Decreased arginine/ADMA and arginine/ornithine ratios were significantly associated with longer LOS and greater pleural drainage. Arginine metabolism is altered in children with SVHD in both the pre- and post-Stage 3 period. Patients with greater postoperative derangements, including lower arginine/ADMA and arginine/ornithine ratios, experienced more morbidity. We speculate that alterations in arginine metabolism may be a modifiable risk factor for adverse post-Stage 3 outcomes in SVHD.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but severe complication of pulmonary embolism (PE), yet its underlying mechanisms remain poorly understood. Peptidyl-prolyl cis/trans isomerase (Pin1), a regulatory enzyme involved in thrombosis, inflammation, and vascular remodeling, may contribute to pulmonary vascular disease. We investigated whether circulating Pin1 levels are associated with the risk of CTEPH and its severity. In this case-control study, we measured circulating Pin1 levels by ELISA and compared them across 329 patients with CTEPH, 350 patients after acute PE, and 350 healthy individuals. Associations between Pin1 levels and clinical parameters were assessed with multivariable regression, stratified by sex. Overall, circulating Pin1 levels did not differ between patients with CTEPH, patients after acute PE, and healthy individuals. However, male patients with CTEPH had higher Pin1 levels than the two control groups, while female patients with CTEPH had slightly lower levels than female healthy individuals. Elevated Pin1 levels were associated with improved hemodynamics and exercise capacity, lower N-terminal prohormone of brain natriuretic peptide, and increased probability of CTEPH in men. Among healthy individuals, circulating Pin1 levels varied based on age, sex, and history of cancer. In conclusion, circulating Pin1 did not distinguish between patients with CTEPH, acute PE or healthy individuals. Nonetheless, our results suggest a possible sex-specific association between circulating Pin1 levels and CTEPH. Although Pin1 is unlikely to serve as a standalone biomarker, it may reflect underlying sex-specific pathological mechanisms, and further investigation on its utility within multimodal strategies for early risk stratification of CTEPH is warranted.