Pulmonary Circulation最新文献

Dyspnea, a debilitating symptom of COPD, worsens health-related quality of life (HRQL), reduces daily physical activity, increases health care utilization, and is more closely associated with survival than airflow limitation. Thus, having treatments that reduce dyspnea in COPD is important. Pulmonary hypertension (PH) is a common complication of COPD that is associated with severe dyspnea, more frequent COPD exacerbations, and increased mortality. Multiple causes of PH, including a reduction in bioavailable vasodilator nitric oxide (NO), are associated with COPD (COPD-PH). Phosphodiesterase type-5 inhibitor (PDE5i) therapy restores NO signaling and improves hemodynamics and dyspnea in patients with Group 1 Pulmonary Arterial Hypertension, but has not been proven effective in COPD-PH. In a prior study (ClinicalTrials. gov identifier: NCT01862536), we investigated effects of 12 months of oral PDE5i therapy with tadalafil on 6-min walk distance (6MWD) in a multi-center, randomized, placebo-controlled trial funded by the Department of Veterans Affairs. While tadalafil did not change 6MWD at 12 months, the treatment group experienced clinically meaningful improvements in patient-reported dyspnea and HRQL at 6 months. Because of the importance of mitigating dyspnea in COPD-PH, we developed a new study protocol examining the effect of PDE-5i therapy in COPD-PH, with a reduction in dyspnea the primary outcome. In the current study (NCT05937854), we will conduct a prospective, randomized, double-blind, multi-center clinical trial to evaluate the effects of 6 months of maximally tolerated therapy with tadalafil (target dose 40 mg/day) versus placebo on dyspnea, as measured by University of California San Diego Shortness of Breath Questionnaire.

Identifying noninvasive measures to assess intravascular volume status and risk stratify patients with pulmonary hypertension (PH) and chronic kidney disease (CKD) is needed. We assessed the predictive value of estimated plasma volume status (ePVS) using the Strauss-derived Duarte formula in PH-CKD patients. This single-center retrospective cohort analysis included patients with PH and CKD Stage 3b (CKD3b), Stage 4 (CKD4), or Stage 5 (CKD5) who underwent right heart catheterization from 2018 to 2023. Patients were categorized into low ePVS (< 6.2) and high ePVS (≥ 6.2) using Youden's J statistics. We used the Cox-proportional hazards model, adjusting for age, sex, and body mass index, to investigate the association between high ePVS and major adverse cardiovascular events (MACE) and all-cause mortality within 1 year after ePVS measurement date. Of 305 patients with PH-CKD, 30% (n = 91) had low ePVS, and 70% (n = 215) had high ePVS. Compared to the low ePVS group, patients with high ePVS had higher left ventricular ejection fraction, right atrial pressure, pulmonary artery wedge pressure, and cardiac index, lower pulmonary vascular resistance, worse kidney function, and more chronic anemia. Among patients with precapillary or Cpc-PH, high ePVS was associated with a greater incidence of 1-year all-cause mortality (adjusted HR = 2.11, 95% CI 1.06-4.22 p = 0.034). Among PH-CKD patients, high ePVS was associated with hyperdynamic circulation, worse kidney function, and anemia. High ePVS was associated with greater 1-year all-cause mortality among patients with a precapillary PH component.

Pulmonary hypertension (PH) in children requires complex medical management. Health-related quality of life (HRQoL) remains understudied in this population. During an 8-month period children and parents attending PH outpatient appointments completed the generic PedsQL (measuring physical, emotional, social, and school functioning). Parents completed the Hospital Anxiety and Depression scale, a validated measure of anxiety and depression, about their own mental health. Clinical data were extracted from the medical notes. Analyses explored relationships between clinical factors, parental mental health and HRQoL and compared scores with published norms. Parents of 94 of 98 (96%) eligible children with PH and 48 of 54 (89%) eligible children aged ≥ 5 years completed the PedsQL. All HRQoL scores were significantly below healthy norms, with 49% scoring > 2 S.D. below normative means. Physical HRQoL was associated with disease severity and survival outcomes. Multiple regression analyses showed age, learning disability, functional class, and parental depression explained 38% of parent-reported HRQoL variance (F(6, 86) = 7.67; p < 0.001) while learning disability explained 33% of child-reported variance (F(3, 45) = 6.78; p < 0.001). These findings support routine HRQoL evaluation and development of disease-specific measures for paediatric PH.

Porto-pulmonary hypertension (PoPH) represents a rare but significant form of pulmonary arterial hypertension (PAH) in children. Despite its clinical importance, systematic analyses of paediatric presentations and outcomes remain limited. We analysed the United Kingdom National Registry for Paediatric Pulmonary Hypertension (2001-2022) identifying children with PoPH through standardised diagnostic criteria including cardiac catheterisation and cross-sectional imaging. In our cohort of 12 patients (58% female, median age 4 years, range: 3 months-12 years), congenital porto-systemic shunts (CPSS) were the predominant pathology (58%). We found a high prevalence of genetic abnormalities (50%) and congenital heart disease (50%). Haemodynamic assessment revealed evidence of pulmonary vascular disease (mean pulmonary artery pressure 38 mmHg, range 20-52 mmHg; mean pulmonary vascular resistance index 6.1 WU·m², range 4.2-9.0 WU·m²) without vaso-reactivity. Over a median follow-up of 8.2 years, three patients achieved resolution of pulmonary hypertension after definitive treatment of underlying liver pathology. Four deaths occurred during follow-up: three from progressive PAH and one unrelated death that occurred 2 years following PAH resolution. Our analysis reveals distinctive features of paediatric PoPH, including predominant CPSS aetiology, and earlier age of onset than previously reported. Multi-modality imaging proved essential for diagnosis, as initial ultrasound missed CPSS in 5/7 cases. The variable treatment outcomes emphasise the importance of individualised therapeutic approaches and sustained clinical surveillance.

Fibrotic lung diseases are often characterized by chronic inflammation and the progressive destruction of the vasculature, parenchyma, and airways, leading to cellular metabolic changes. As a result, these changes activate several pathological pathways, contributing to the disease's progression and worsening. However, the precise impact of metabolic changes and their contributions to the progression of fibrotic lung diseases need deeper exploration. The current review highlights the interplay between immunometabolites and hypoxia in bringing out cellular and epigenetic changes that progress and further exacerbate pulmonary fibrosis. Notably, the mitochondrial-linked immunometabolites such as lactate, succinate, 2-hydroxyglutarate (2-HG), fumarate, and itaconate have the potential to determine cellular fate in health and disease. For instance, lactate accumulation is one of the vital factors associated with pulmonary fibrosis (PF). The metabolite succinate promotes hypoxia response, inflammatory markers accumulation, fibroblast activation, and PF, whereas L-2-HG impairs the TCA cycle, reduces glycolysis, and disrupts the nicotinamide adenine dinucleotide (NADH/NAD+) ratio, ultimately leading to dysfunctional mitochondrial respiration and contributing to lung fibrosis. Due to the progressive and degenerative nature of fibrotic lung diseases, individuals affected by them need ongoing clinical support and monitoring. The currently available pharmacological treatments are limited and come with multiple side effects. Therefore, the search for newer therapeutics in the form of small molecules targeting these metabolites is increasingly being formulated to treat chronic fibrotic pulmonary conditions through their exhaustive mechanistic investigations backed by robust preclinical and clinical trials.

This systematic review and meta-analysis evaluated the performance of machine learning (ML) models in predicting mortality among pulmonary embolism (PE) patients, synthesizing data from 17 studies encompassing 844,071 cases. Logistic Regression was the most commonly used algorithm, followed by advanced models like Random Forests, Support Vector Machines, XGBoost, and Neural Networks. Pooled performance metrics from 12 studies demonstrated a sensitivity of 0.88 (95% CI: 0.78-0.94, I ² = 90.43%), specificity of 0.79 (95% CI: 0.62-0.89, I ² = 99.53%), positive likelihood ratio of 4.1 (95% CI: 2.2-7.7), negative likelihood ratio of 0.16 (95% CI: 0.08-0.29), diagnostic odds ratio of 26 (95% CI: 10-71), and an AUROC of 0.91 (95% CI: 0.88-0.93), indicating excellent discriminative ability. Subgroup analyses revealed higher sensitivity in advanced ML models (89.7%) and non-USA studies (97.2%), with advanced ML showing lower specificity heterogeneity (I ² = 0%). Significant heterogeneity was observed, particularly in specificity (I ² = 99%), driven by traditional ML and USA-based studies. Minimal publication bias was noted for sensitivity (Egger's p = 0.942), but specificity showed potential bias (Egger's p = 0.038 after outlier exclusion). These findings suggest that ML models outperform traditional risk stratification tools in predicting PE mortality, offering robust potential for clinical decision-making, though heterogeneity and retrospective study designs warrant cautious interpretation. Trial Registration: PROSPERO: CRD420251026696.

Pulmonary hypertension (PH) is a severe complication observed in pediatric patients after hematopoietic cell transplantation or chemotherapy. A review of records at Hokkaido University Hospital (2014-2024) identified four cases of PH, each with different etiologies, including pulmonary arterial hypertension, pulmonary veno-occlusive disease, and microthromboembolism. Contributing factors included splenic atrophy, corticosteroid-responsive inflammation, and potential drug-induced vascular remodeling. Although transient PH usually resolves, late-onset PH emphasizes the need for long-term echocardiographic monitoring. These findings underscore the importance of individualized management, avoiding pulmonary vasodilators without proper evaluation, and addressing underlying conditions such as thrombotic microangiopathy or interstitial lung disease.

Adhesive reactions are common complications of continuous treprostinil infusions, limiting their recommended use as a treatment for severe pulmonary hypertension. We present the case of a 10-year-old male with recurrent adhesive-related skin reactions, which compromised both subcutaneous and intravenous continuous treatment. Due to comorbid atopic dermatitis (AD), dupilumab was initiated to decrease skin reactions to adhesives. Within 48 h of initiation, skin reactions completely resolved. With sustained dupilumab treatment, he remains symptom-free and is successfully tolerating intravenous treprostinil infusion.

Pulmonary hypertension (PHTN) in infants with developmental lung disease, such as bronchopulmonary dysplasia (BPD), chronic lung disease of infancy (CLD), or congenital diaphragmatic hernia (CDH), can be exacerbated by atrial septal shunts secondary to atrial septal defects (ASD). While transcatheter ASD closure may reduce pulmonary overcirculation, data on post-closure hemodynamic and pharmacologic outcomes remain limited. This single-center retrospective study aimed to characterize changes in PHTN severity, respiratory support, and medication use 1 year after early transcatheter ASD closure (defined as closure at ≤ 1 year of age). Eligible patients were infants with BPD, CLD, or CDH who underwent early transcatheter ASD closure between 2021 and 2024 and had preprocedural PHTN medication use and respiratory support. Sixteen infants met the inclusion criteria. At 1 year, excluding the 3 who died, 10 of 13 infants (76.9%) showed improved PHTN severity, including 6 (60%) with complete resolution. Of the 13 infants, 6 (46.2%) weaned off all respiratory support. Average diuretic dosage (mg/kg/day) decreased by 92.9%, and vasodilator dosage declined by 47.0%. Infants with ASDs ≥ 5 mm and gestational age (GA) < 32 weeks required significantly longer diuretic therapy than those with smaller ASDs (< 5 mm) and GA ≥ 32 weeks. No similar associations were found with vasodilator weaning. These findings suggest early transcatheter ASD closure may offer therapeutic benefit in select high-risk infants, resulting in improved hemodynamics and reduced medication dependence. Although limited by small sample size and retrospective design, this study supports the potential for individualized weaning strategies and the need for prospective multicenter investigations.

The activin signaling inhibitor sotatercept was approved for Group 1 pulmonary arterial hypertension (PAH) based on Phase 2 and 3 clinical trials showing significant improvements in primary outcomes; reduced pulmonary vascular resistance (PVR) and increased 6-min walk distance (6MWD), respectively. However, the efficacy and safety of transitioning off background therapies, including infusion prostacyclins, in patients receiving sotatercept are currently unknown. We report here a patient who was enrolled in sotatercept clinical trials (STELLAR/SOTERIA); during this period, he gradually transitioned from intravenous treprostinil. Subjective, physiologic, echocardiographic, and hemodynamic data after 2.5 years without intravenous therapy are presented. These results suggest that weaning off intravenous PGI2 may be feasible in some patients, but questions remain about the durability of the response and possible long-term adverse side effects.