Pulmonary Circulation最新文献

This study quantified prior authorization (PA)-insurance-required approval-burden for pediatric pulmonary hypertension (PH) at an accredited center. Among 53 patients, 72% of 283 prescriptions between 2021 and 2023 required PA, with non-FDA-approved medications showing highest volume. Despite 97% approval and all patients ultimately obtaining medication, delays (mean 4.2 days), repeat requests (39%), and reliance on patient assistance programs created significant administrative burden. Results highlight the need for policy reform to ensure timely, equitable access to essential therapies.

Assessing operability in late-presenting ventricular septal defects (VSD) with pulmonary arterial hypertension (PAH) is complex. Although a comprehensive assessment is often recommended, pulmonary vascular resistance index (PVRI) is the cornerstone of most decisions. PVRI-based operability assessment, nonetheless, is not infallible. Cases with PVRI much higher than operability cut-offs have done well, while some with lower PVRI have experienced late recurrence of PAH. We propose the Diastolic Pulmonary Shunt Index (DiPSI), defined as the diastolic pulmonary gradient (DPG = PADP - PAWP) divided by Qp/Qs, as an adjunct to aid clinical judgment. DiPSI, by offering a physiologically grounded, flow-adjusted index, may help clarify borderline cases, providing a more nuanced assessment of operability in late presenters with large VSD than PVRI alone.

Transition from parenteral prostanoids to oral selexipag may be considered in select patients with pulmonary arterial hypertension (PAH) to reduce the therapeutic burden imposed on patients and caregivers, but its safety and efficacy remain uncertain. A retrospective cohort study was conducted involving adult patients with PAH who transitioned from parenteral prostanoids to selexipag at Canadian tertiary referral centers between January 2016 and November 2020. The primary outcome was transition failure at 12 months, defined as a composite of death or PAH-related worsening. Baseline predictors of transition failure were identified using univariate Cox regression, with follow-up data collected up to 36 months post-transition or until site-specific data submission, occurring between May 2021 and February 2023. At 12 months post-transition, 11 of 36 patients (31%) experienced transition failure, including 4 deaths, all classified as high-risk pre-transition. Of the 25 patients (69%) who successfully transitioned, only one (4%) experienced transition failure over the subsequent observation period (median follow-up 28 months). Pre-transition variables protective against transition failure included a right atrial pressure (RAP) < 8 mmHg (HR 0.290, 95% CI 0.084-0.999, p = 0.049), absence of hospitalizations in the year preceding transition (HR 0.239, 95% CI 0.064-0.885, p = 0.032), lower brain natriuretic peptide (< 50 pg/mL)/N-terminal pro-B-type natriuretic peptide (< 300 pg/mL) levels (HR 0.174, 95% CI 0.045-0.676, p = 0.011), and REVEAL 2.0 score < 7 (HR 0.162, 95% CI 0.049-0.541, p = 0.003). These findings suggest that transition from parenteral prostanoids to selexipag carries the risk of clinical deterioration and should only be considered in carefully selected, low-risk patients.

Pulmonary hypertension (PH) significantly impacts outcomes in heart failure with preserved ejection fraction (HFpEF), especially with right ventricular dysfunction (RVD), yet effective treatments are limited. This study retrospectively evaluated sacubitril-valsartan's effects on pulmonary pressures, RV function, and clinical outcomes in 20 severe HFpEF-PH patients. Significant improvements were observed over a median 397-day follow-up. Sacubitril-valsartan notably reduced RV systolic pressure (RVSP) by 27.50 mmHg (p < 0.0001) and peak tricuspid regurgitation (TR) velocity by 0.825 m/s (p < 0.0001). TR severity improved significantly (p = 0.0426). RV dimensions decreased significantly (basal: p = 0.0083; mid-cavity: p = 0.0025). RV-pulmonary arterial coupling (TAPSE/RVSP) improved from 0.27 to 0.47 (p < 0.0001), and NYHA functional class improved from mean III to II (p = 0.0164). Systolic blood pressure also decreased by 24.0 mmHg (p < 0.0001). Diastolic function parameters (E velocity, E/e', LAVI) did not show significant changes. These findings suggest that sacubitril-valsartan could improve pulmonary pressures, RV dimensions, RV-PA coupling, TR severity, and functional status in HFpEF-PH patients, supporting its potential therapeutic role.

Pulmonary arterial hypertension (PAH) is a pulmonary disease associated with alterations in gut microbiota. We aimed to identify potential diagnostic genes causally associated with gut microbiota and PAH. Mendelian randomization (MR) was performed to screen gut microbiota causally associated with PAH and to identify gut microbiota-related genes. A regulatory network was constructed to reveal the relationships among genes, gut microbiota and PAH. Diagnostic genes were screened and used to construct a diagnostic model for PAH. Characteristics of immune infiltration and diagnostic gene expression in each cell type were evaluated at the transcriptome and single-cell levels. Family. Porphyromonadaceae and genus. Eubacteriumfissicatena were risk factors for PAH, whereas phylum. Actinobacteria, class. Bacilli, genus. Erysipelatoclostridium, and genus. Ruminococcaceae were protective factors for PAH. The gene-gut microbiota-PAH network showed causal associations among six gut microbiota taxa, 13 PAH-associated genes and PAH. Copper metabolism MURR1 domain (COMMD) containing 10 (COMMD10), FES proto-oncogene, tyrosine kinase (FES), nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1), solute carrier family 22 member 4 (SLC22A4), and synaptogyrin 1 (SYNGR1) were identified as diagnostic genes, with Area Under Curve (AUC) values ranging from 0.79 to 0.99. The abundances of activated B cells, activated CD8 T cells, eosinophils, mast cells, and T helper cells were increased, whereas the abundances of activated dendritic cells (DCs), gamma delta T cells, MDSCs, macrophages, neutrophils, plasmacytoid DCs, and regulatory T cells were decreased in PAH. NUCKS1 was expressed in each cell type and was lower in T/NK and NK cells. The study deepens the understanding of PAH pathogenesis, and may provide diagnostic targets for PAH.

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.