Pulmonary Circulation最新文献

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.

Exercise testing has long been essential for evaluating diagnosis, prognosis, and functional status in pulmonary hypertension (PH). Recent advances have clarified its role in defining reference values and prognostic markers. Nonetheless, substantial knowledge gaps persist regarding the implementation of invasive cardiopulmonary exercise testing (iCPET) and its potential to inform pathophysiology and therapeutic decision-making. This statement addresses the knowledge gaps that hinder the application of iCPET and exercise right heart catheterization (RHC) in the assessment of PH. We present research priorities and scenarios in which these tests may clarify drug mechanisms and support PH subphenotyping. An international, multidisciplinary task force of cardiology and pulmonology experts reviewed the literature and formulated consensus recommendations through iterative discussions.

Methamphetamine-associated pulmonary arterial hypertension (Meth-PAH) is an increasingly prevalent but understudied subtype of Group 1 pulmonary arterial hypertension (PAH). While most prevalent in the Western United States, its reach continues to expand with the evolving global methamphetamine epidemic. Despite its designation as a definite cause of PAH, there are no standardized diagnostic criteria or treatment guidelines specific to Meth-PAH. This review summarizes its epidemiology, proposed pathophysiology, clinical management, and treatment challenges. We outline a pragmatic approach to Meth-PAH, emphasizing structured screening for substance use, initiation of oral PAH-specific therapies regardless of abstinence, and therapy escalation based on adherence and serial risk assessment. Key knowledge gaps include Meth-PAH pathophysiology, performance of risk stratification tools, and the safety and efficacy of PAH therapies in patients with ongoing use. A multidisciplinary approach is needed to address both Meth-PAH and methamphetamine use disorder to improve outcomes in this high-risk, stigmatized population.

Noninvasive imaging markers may be helpful in identifying higher-risk patients with various lung diseases. Pulmonary artery to aorta ratio (PA/A ratio) on computed tomography (CT) is an indicator of pulmonary hypertension, but its relationship with other hemodynamic, imaging, and physiologic measurements, functional status, and outcomes requires further investigation. We set out to determine if the PA/A ratio is related to components of right ventricular (RV) afterload (pulmonary vascular resistance (PVR), PA compliance), lung diffusion capacity, radiographic emphysema, or honeycombing on chest CT, six-minute-walk distance, and transplant-free survival in COPD and/or interstitial lung disease (ILD). Data including PA/A ratio, hemodynamics, imaging, physiologic measurements, and survival in Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics (PVDOMICS) cohort participants with COPD, ILD, or both were analyzed in regression and survival models to determine the association between PA/A ratio and various outcomes. We found that PA/A ratio analyzed as a continuous variable or dichotomized (> 0.9 vs. ≤ 0.9) was associated with higher PVR and lower PA compliance in fully adjusted models. Having either a PA/A ratio > 0.9 or a more elevated PVR was associated with worse transplant-free survival, while PA compliance was not associated with survival. PVR did not appear to mediate the relationship of PA/A ratio with survival. PA/A ratio did not correlate with six-minute walk distance or presence of emphysema or honeycombing, but was related to lower lung diffusion capacity. In conclusion, PA/A ratio on CT is related to aspects of RV afterload and to survival in COPD and ILD.

Catheter-directed intervention (CDI) in patients presenting with pulmonary embolism (PE) is suggested to improve in-hospital outcomes. We aimed to compare the effect of early versus late initiation of CDI on in-hospital outcomes. A systematic review and meta-analysis were conducted according to PRISMA guidelines. A comprehensive search of PubMed, Scopus, Web of Science, and Embase databases was performed from inception to May 2025. Data extraction was conducted independently by multiple reviewers. Statistical analysis was performed using R software version 4.3.2, and odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) were combined using a random-effects model. Six studies, including 53,472 patients, were included. Early intervention before 24 h significantly reduced mortality (OR 0.61, 95% CI [0.44-0.84]; I² = 0%). Moreover, Early intervention before 24 h significantly reduced the all-cause readmission in patients with acute PE (OR = 0.81 (95% CI: [0.73, 0.89]; I² = 0%). There was no significant difference in risk of major bleeding in early vs late intervention (OR = 0.82; 95% CI: [0.48, 1.39]; I² = 69.3%). Also, early intervention before 24 h significantly reduced the length of hospital stay (LOS) (MD = -3.11 days (95% CI: [-4.33, -1.89]; I² = 0%). This meta-analysis showed that early CDI, particularly within 24 h of presentation, is associated with a significant reduction in both mortality and all-cause readmission in patients with acute PE, without increasing the risk of bleeding. These findings support the concept of "time-is-myocardium" and reinforce the need for structured protocols that enable early therapeutic intervention. Further randomized controlled trials are needed to confirm these findings and to establish the optimal timing for this potentially life-saving therapy.

In this single-blind, crossover pilot study, supplemental oxygen at 2 L/min during 6-min walk test reduced Cardiac Effort in patients with pulmonary arterial hypertension, while 6-min walk distance remained unchanged. This decrease suggests improved physiology for an unchanged workload. Continuous electrocardiogram heart rate monitoring adds considerable value to the 6-min walk.

Intermediate-high-risk (IHR) pulmonary embolism (PE) represents a heterogeneous group in whom guideline-based criteria may insufficiently capture biologic and hemodynamic variability relevant to early deterioration. Data-driven phenotyping may improve risk stratification and support individualized decisions regarding reperfusion therapy. In this retrospective cohort study (2012-2025), 553 guideline-defined IHR PE patients were analyzed using unsupervised machine learning. Thirty-six demographic, clinical, laboratory, echocardiographic, and CT variables were standardized and encoded as appropriate for clustering. Multiple algorithms were compared, and the optimal model was selected using silhouette width and stability metrics. Clinical characteristics, imaging findings, treatment patterns, and outcomes were compared across phenotypes. The primary outcome was in-hospital mortality; secondary outcome was all-cause long-term mortality. Multivariable logistic regression and Cox models assessed associations with outcomes, and pre-post-treatment changes were evaluated. Two phenotypes were identified using the k-prototypes algorithm (silhouette width = 0.697). Cluster 1 (RV-failure phenotype; n = 360) exhibited younger age, lower systolic blood pressure, more severe RV dysfunction, higher thrombotic burden, and lower baseline TAPSE/PASP ratios. Cluster 2 (comorbidity-dominant phenotype; n = 193) comprised older patients with more cardiovascular/metabolic comorbidities but relatively preserved hemodynamics. In-hospital mortality was 6.0% overall and lower in Cluster 2 (3.6% vs. 7.2%); Cluster 2 remained independently associated with reduced early mortality (OR: 0.43; 95% CI: 0.19-0.98). The CDT-cluster interaction term was not statistically significant. Both phenotypes demonstrated significant improvements in RV function after reperfusion, with greater gains-including TAPSE/PASP-in Cluster 1. Over a median follow-up of 73.2 months, long-term mortality did not differ significantly between phenotypes (log-rank p = 0.11). Unsupervised ML revealed two clinically meaningful IHR PE phenotypes with divergent early risk but comparable long-term outcomes. These findings suggest that phenotype-based assessment may refine risk stratification and help guide individualized decisions regarding CDT and other reperfusion strategies in acute PE.