Pulmonary Circulation最新文献

{"title":"The Relationship Between Vortical Flow and Pressure Gradient Reversal in Pulmonary Hypertension-A 4D Analysis of Cardiovascular Magnetic Resonance Flow Imaging.","authors":"Raheeq Karim, Alexander Fyrdahl, Joao G Ramos, Michael Melin, Patrik Sundblad, Julio Sotelo, Björn Wieslander, David Marlevi","doi":"10.1002/pul2.70350","DOIUrl":"10.1002/pul2.70350","url":null,"abstract":"<p><p>Diagnosing pulmonary hypertension (PH) requires invasive right heart catheterization (RHC). However, mean pulmonary artery pressure (mPAP) can be non-invasively estimated using 4D analysis of cardiovascular magnetic resonance (CMR) flow imaging to assess the duration of pathological vortex flow (T_vortex) in the main pulmonary artery (MPA). Early systolic pressure reversal has been hypothesized to drive vortex formation but has yet to be quantified in-vivo. The virtual work-energy relative pressure (vWERP) method enables accurate temporal characterization of intravascular pressure gradients from 4D analysis of CMR flow images. We aimed to characterize the relationship between T_vortex and early systolic pressure reversal in the MPA using 4D analysis of CMR flow images from patients with a range of RHC-determined mPAP. A total of 36 patients who underwent a clinically indicated RHC for any reason were recruited for a research-motivated CMR-exam. Intravascular MPA pressure gradients were estimated from a stack of multidirectional 2D-flow slices covering the pulmonary artery using vWERP. Correlations between continuous variables were assessed using linear regression analysis. There were significant but weak correlations between time to systolic pressure reversal (T_rev) and T_vortex (<i>R</i> ²: 0.17; <i>p</i> = 0.012), pulmonary vascular resistance (PVR) (<i>R</i> ²: 0.29; <i>p</i> = 0.001), and mPAP (<i>R</i> ²: 0.27; <i>p</i> = 0.001), respectively. Multivariable analysis showed no independent correlation between T_vortex and T_rev once either PVR or mPAP were added as predictor variables. Our results suggest that early systolic pressure reversal is associated with, but is unlikely to be the sole cause of, observed vortical flow in the MPA.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"16 3","pages":"e70350"},"PeriodicalIF":2.4,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13404771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148607046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Level and Clinical Significance of Red Blood Cell Distribution Width in Patients With Congenital Heart Disease Associated With Pulmonary Hypertension.","authors":"Xiaoqin Luo, Xianliang Xiong, Jiang Li, Jun Luo","doi":"10.1002/pul2.70339","DOIUrl":"10.1002/pul2.70339","url":null,"abstract":"<p><p>Previous studies have shown that red blood cell distribution width (RDW) is an independent risk factor for the prognosis of pulmonary arterial hypertension (PAH) and is also associated with cardiovascular events in patients with congenital heart disease (CHD). However, its role in patients with CHD-associated pulmonary hypertension (PAH-CHD) has not been reported. This study aimed to investigate the level and clinical significance of RDW in PAH-CHD patients. A total of 129 patients with CHD confirmed by right heart catheterization (RHC) were enrolled, including 109 PAH-CHD patients and 20 CHD patients without PAH. Cardiac ultrasound, blood biochemistry, and RHC hemodynamic data were collected and analyzed. The RDW level in the PAH-CHD group was significantly higher than that in the non-PAH-CHD group and the normal control group (<i>p</i> < 0.05). Using a cut-off value of 13.25% for RDW, the sensitivity and specificity for predicting severe PAH-CHD were 72.2% and 77.9%, respectively, with an area under the ROC curve of 0.798 (<i>p</i> < 0.001). RDW was significantly correlated with PAH risk stratification indicators (<i>r</i> = 0.54, <i>p</i> < 0.001). In conclusion, RDW levels are significantly elevated in patients with severe PAH-CHD, and a cut-off value of 13.25% demonstrates high predictive value for severe PAH-CHD. Therefore, RDW level could serve as an economical and practical indicator for assessing the condition and prognosis of PAH-CHD patients.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"16 3","pages":"e70339"},"PeriodicalIF":2.4,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13404773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148607017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Therapeutic Efficacy of Drugs Targeting the NO-sGC-cGMP Pathway in Treatment of Patients With Chronic Thromboembolic Pulmonary Hypertension: A Systematic Review.","authors":"Abdullah A Alqarni, Rawan H Aljedani, Abdulelah M Aldhahir, Ahmed H Alasimi, Abdulkareem A AlGarni, Jaber S Alqahtani, Saeed Mardy Alghamdi, Rayan A Siraj, Aminah Mengash, Hassan Alwafi","doi":"10.1002/pul2.70337","DOIUrl":"10.1002/pul2.70337","url":null,"abstract":"<p><p>Chronic thromboembolic pulmonary hypertension (CTEPH) is a distinct and potentially curable form of pulmonary hypertension; however, a substantial proportion of patients remain inoperable or experience persistent or recurrent disease. Pharmacological therapies targeting the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO-sGC-cGMP) pathway have emerged as promising treatment options. Therefore, this systematic review aimed to comprehensively evaluate the therapeutic efficacy of drugs targeting the NO-sGC-cGMP pathway on clinical outcomes in patients with CTEPH. We conducted a comprehensive search of electronic databases, including Embase, MEDLINE, Cochrane Library, and Scopus databases from inception to December 1, 2025. Studies involving adult patients with confirmed CTEPH receiving NO-sGC-cGMP pathway-targeted therapies were included. Exclusion criteria encompassed case reports, systematic reviews, review articles, conference abstracts with no full text (since they were not peer-reviewed), non-full-text articles, non-English manuscripts, opinion articles, and book chapters. Risk of bias was assessed using the Cochrane RoB 2 tool and the Newcastle-Ottawa Scale. A total of 23 studies involving 2815 patients were included. The most frequently investigated agents were riociguat and sildenafil. Fourteen of 15 studies demonstrated significant improvements in exercise capacity, with consistent findings reported in major trials such as CHEST-1 and its long-term extension, CHEST-2. All 16 studies assessing pulmonary hemodynamics reported significant improvements in mPAP, PVR, and CO. Additionally, 12 studies showed reductions in NT-proBNP levels and improvements in WHO-FC, indicating enhanced functional status. Quality of life was assessed in two studies, both of which demonstrated favorable outcomes. Furthermore, three studies reported improvements in right ventricular function and risk stratification. Pharmacological agents targeting the NO-sGC-cGMP pathway, particularly riociguat and sildenafil, demonstrate consistent improvements in exercise capacity, pulmonary hemodynamics, functional status, and biomarkers in patients with CTEPH. These findings support their role as effective therapeutic options, especially in inoperable or persistent CTEPH. Nevertheless, further large-scale, high-quality randomized controlled trials are warranted to strengthen the evidence base and optimize treatment strategies. Systematic review registration: CRD42024510274, https://www.crd.york.ac.uk/PROSPERO/view/CRD42024510274.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"16 3","pages":"e70337"},"PeriodicalIF":2.4,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13404768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148607202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Right Ventricular Function Improves With Pulmonary Vasodilator Treatment in Pediatric Patients With Pulmonary Hypertension and Multivessel Pulmonary Vein Stenosis in a Single Center Cohort.","authors":"Catherine M Avitabile, Kimberly Butler, Antara Mondal, David B Frank, Yan Wang, Devon Ash, Laura Mercer-Rosa, Michael L O'Byrne, Ryan Callahan","doi":"10.1002/pul2.70346","DOIUrl":"10.1002/pul2.70346","url":null,"abstract":"<p><p>Pulmonary hypertension (PH) and right ventricular (RV) dysfunction increase mortality in multivessel pediatric pulmonary vein stenosis (PVS). Pulmonary vasodilator use is limited in PVS due to the perceived risk of pulmonary edema. We aimed to describe our experience with pulmonary vasodilators in PVS and to assess changes in RV function and hemodynamics over time. Children with multi-vessel PVS (≥ 2 veins), mean pulmonary artery pressure > 20 mmHg, indexed pulmonary vascular resistance > 3 iWU, without single ventricle physiology, treated with pulmonary vasodilators from 2014 to 2024 were included in a single center, retrospective case series. RV systolic function was quantified by tricuspid annular plane systolic excursion (TAPSE), fractional area change (RVFAC), and longitudinal and free wall strain (RVLS, RVFWS). A four-point PVS severity score was calculated from angiographic data. RV function and hemodynamics were compared from baseline to the most recent by Wilcoxon rank sum tests, controlling for change in PVS severity score. Thirty-one patients (median (IQR) gestational age 27.1 (26.0, 35.9) weeks, birth weight 770 (540, 1900) grams) met the inclusion criteria. Median follow-up was 27.0 (10.5, 71.5) months. Most (65%) had Group 3, lung disease-related PH. One patient developed pulmonary edema requiring medication discontinuation. TAPSE, RVFAC, RVLS, and RVFWS improved significantly (<i>p</i> < 0.01 for all), independent of change in PVS severity score. Survivors demonstrated improved RV function compared to non-survivors. Hemodynamics were unchanged. Pulmonary vasodilators may improve RV function in patients with PVS and PH in a rigorous surveillance program. The impact of improved RV function on mortality in PVS deserves further study.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"16 3","pages":"e70346"},"PeriodicalIF":2.4,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13366113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148449018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulmonary Veno-Occlusive Disease: A Focused Clinicopathologic Series.","authors":"Yub Raj Sedhai, Zein Kattih, Christopher A Thomas, Junad M Chowdhury, Anju Singhal, Alan S Nyquist, Jared D Wilkinson, Haresh Mani, Vikramjit Khangoora, Christopher S King, Oksana A Shlobin, Steven D Nathan, Shambhu Aryal","doi":"10.1002/pul2.70365","DOIUrl":"10.1002/pul2.70365","url":null,"abstract":"<p><p>Pulmonary veno-occlusive disease (PVOD) is a rare and aggressive subtype of pulmonary arterial hypertension characterized by fibroproliferative obstruction of post-capillary pulmonary venules leading to increased pulmonary vascular resistance and progressive right ventricular failure. Heritable forms are linked to eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) mutations, while acquired cases have been associated with environmental exposures, including organic solvents and chemotherapeutic agents like mitomycin-C. PVOD is classified under Group 1 pulmonary hypertension in the current World Symposium on Pulmonary Hypertension classification; however, pulmonary vasodilator therapy has limited efficacy due to the frequent occurrence of acute pulmonary edema. ¹ Lung transplantation remains the only definitive and effective therapy for PVOD, and in its absence, the prognosis is uniformly poor. Given the therapeutic and prognostic implications, establishing an accurate diagnosis and early referral for lung transplantation evaluation is imperative. In this single transplant center case series of seven cases, we highlight the clinical presentation and the importance of early recognition and referral to specialized centers for optimal management.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"16 3","pages":"e70365"},"PeriodicalIF":2.4,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13404766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148607050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Iron Homeostasis at High Altitude in Patients With Pulmonary Hypertension.","authors":"Aurelia E Reiser, Markus Thiersch, Max Gassmann, Simon R Schneider, Laura Mayer, Stéphanie Saxer, Michael Furian, Richard Sparla, Esther I Schwarz, Mona Lichtblau, Martina U Muckenthaler, Silvia Ulrich","doi":"10.1002/pul2.70352","DOIUrl":"10.1002/pul2.70352","url":null,"abstract":"<p><p>Iron deficiency aggravates hypoxic pulmonary vasoconstriction, exacerbating the increase of pulmonary arterial pressure at high altitude (HA). This may be especially relevant for patients with pulmonary hypertension (PH) travelling to HA, who moreover have a high prevalence of iron deficiency. Currently, no data is available on iron parameters and their influence on HA adaptation in PH-patients. In a randomized cross-over trial, 27 patients (44% female, mean age 61.7 ± 13.6 y) with pulmonary arterial hypertension (67%) or chronic thromboembolic PH (33%) were assessed at baseline (Zurich, 470 m) and during a stay at 2500 m. Blood samples were taken at baseline and after 20 h at 2500 m. A significant increase in ferritin (131 ± 68 to 140 ± 75, <i>p</i> = 0.002), transferrin (28.0 ± 4.7 to 30.3 ± 4.4, <i>p</i> = 0.012) and soluble transferrin receptor (sTfR) levels (2.7 ± 0.7 to 2.9 ± 0.6, <i>p</i> = 0.014) was observed at HA, all of which correlated with decreasing hepcidin levels. Arterial partial pressure of carbon dioxide (PaCO₂) was inversely correlated with transferrin levels (Pearson's <i>r </i>= -0.57, <i>p</i> < 0.001), and baseline transferrin concentration was an independent predictor of PaCO₂ at baseline and HA (<i>p</i> = 0.037). Furthermore, transferrin levels < 30 µmol/L were an independent predictor of mean nocturnal oxygen saturation (SpO₂) at baseline and HA. The need for oxygen supplementation at HA could be predicted using a model including baseline transferrin, achieving a positive predictive value of 84%, suggesting that transferrin may serve as a useful clinical marker to identify PH patients at risk of oxygen desaturation at HA.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"16 3","pages":"e70352"},"PeriodicalIF":2.4,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13404762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148606941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Smoking-Related Clinical and Molecular Abnormalities in Idiopathic Pulmonary Fibrosis-Associated Pulmonary Hypertension.","authors":"Iryna Zhyvylo, Namita Sood, Janelle Vu Pugashetti, Angela L Linderholm, Ssu-Wei Hsu, Justin Oldham, Ching-Hsien Chen, Elena A Goncharova","doi":"10.1002/pul2.70349","DOIUrl":"10.1002/pul2.70349","url":null,"abstract":"<p><p>Pulmonary hypertension (PH) is a frequent complication of interstitial lung diseases (ILD) that worsens morbidity and mortality. Cigarette smoking has a detrimental effect on transplant-free survival of patients with ILD, including patients with idiopathic pulmonary fibrosis (IPF). However, smoking-related molecular alterations in patients with ILD-PH are not well understood. We performed analysis of 226 patients with ILD with and without PH (59.3% smokers, 40.3% with IPF) from the University of California, Davis cohort. Supporting previous findings, smokers with ILD had significantly shorter transplant-free survival than ILD non-smokers. Using a multivariable Cox regression model, we identified cigarette smoking as a significant independent predictor of mortality of patients with ILD. Smokers with IPF-PH have significantly lower diffusing capacity of the lungs for carbon monoxide (DLCO) compared to non-smokers. Transcriptomic analysis of whole blood of IPF-PH patients identified 616 differentially expressed genes (DEGs) in smokers compared to non-smokers with most deregulated fat cell differentiation and protein ubiquitination pathways. Three DEGs belonging to these pathways (BBS1, BARD1, and SMURF1) showed moderate negative correlation with mean pulmonary arterial pressure (mPAP) in patients with IPF-PH. These data show that, in patients with IPF-PH, smoking is associated with reduced DLCO, and suggest that BBS1, BARD1, and SMURF1 could be considered as potential biomarkers of PH severity in smokers with IPF-PH.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"16 3","pages":"e70349"},"PeriodicalIF":2.4,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13366116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148449029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activin Signaling Inhibitors in Pulmonary Hypertension: A State-of-the-Art Review.","authors":"Sudarshan Rajagopal, Joseph Abueg, Kevin M Hart, Edmund Lau, Eliana C Martinez, Nicholas W Morrell, Ioana R Preston, Sandeep Sahay, Namita Sood, Paul B Yu, Nayeli G Zayas-Hernández","doi":"10.1002/pul2.70353","DOIUrl":"10.1002/pul2.70353","url":null,"abstract":"<p><p>Pulmonary arterial hypertension (PAH) is a disease of abnormal pulmonary vascular remodeling and vascular obliteration that results in right heart failure and death. PAH pathogenesis is strongly associated with mutations of the Transforming Growth Factor Beta (TGF-β) superfamily signaling pathway, which has previously been challenging to target therapeutically. Sotatercept, a fusion protein of the extracellular portion of the activin type 2 receptor A (ACVR2A) and the human IgG1 Fc domain, is the first activin signaling inhibitor (ASI) FDA-approved for the treatment of PAH, demonstrating efficacy across the risk spectrum in PAH. This soluble protein binds to a range of circulating TGF-β superfamily ligands, including activins A and B, growth and differentiation factors (GDFs) 8 and 11, as well as some bone morphogenetic proteins (BMPs). Other ASIs have been developed primarily for hematologic indications, such as anemias and cytopenias associated with β-thalassemia, myelodysplastic syndromes, and myelodysplastic neoplasms. Fundamental questions remain regarding the basic biological mechanisms of ASIs, their short- and long-term side effect profiles, and their potential utility across the spectrum of different etiologies of pulmonary hypertension (PH). In this state-of-the-art review, we brought together basic and clinical researchers, and industry scientists under the umbrella of the Pulmonary Vascular Research Institute (PVRI) Innovative Drug Discovery Initiative (IDDI) to discuss the biology of ASIs, the importance of specific BMP ligands, efficacy and side effect profiles, and considerations in the development of next-generation ASIs.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"16 3","pages":"e70353"},"PeriodicalIF":2.4,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13404764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148606813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Minimally Invasive Porcine Model for Chronic Thromboembolic Pulmonary Hypertension.","authors":"Bianca Battilana, Christian T Stoeck, Fabien Robert, Ömer Senbaklavaci, Miriam Weisskopf, Isabelle Opitz","doi":"10.1002/pul2.70344","DOIUrl":"10.1002/pul2.70344","url":null,"abstract":"<p><p>To elucidate the complex pathophysiology of chronic thromboembolic pulmonary hypertension (CTEPH), a disease associated with bilateral fibrotic obstructions of the pulmonary arteries (PA) and microvascular changes, research relies on animal models, which often depend on invasive techniques, including open surgery. As animal welfare is a major priority for the future of experimental research, and in accordance with the principles of the 3Rs (Replacement, Reduction, and Refinement), this project aimed to develop a fully minimally invasive porcine CTEPH model. In five female large white pigs (50 kg, 3-4 months), an intravascular plug was inserted into the left PA. The right lower lobe artery was embolized weekly for 5 weeks with non-resolving n-butyl-2-cyanoacrylate-glue. Magnetic resonance imaging (MRI) was performed at each intervention. At week 6, plasma molecular and macro- and microscopic analyses were performed. Implantation of the intravascular plug was successful in all animals, without any residual perfusion seen in MRI angiography. Significant increases in mean pulmonary artery pressure (mPAP) (<i>p</i> = 0.005) and mean total pulmonary resistance (TPR) (<i>p</i> = 0.043) were observed. Right ventricle dimensions were significantly increased in all animals. Macroscopically, the left lung developed hypertrophy of bronchial arteries and the right upper lobe overperfusion. Histologically, microvascular wall thickness was increased in both the over-perfused and ischemic territories. Plasma molecular analysis revealed elevated circulating endothelin-1 (<i>p</i> < 0.0001) and reduced nitric oxide metabolites (<i>p</i> = 0.0007). In conclusion, this study establishes a fully minimally invasive refinement of a previously described porcine CTEPH model, including relevant hemodynamic, morphologic, molecular and imaging features of CTEPH while increasing welfare for experimental animals.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"16 3","pages":"e70344"},"PeriodicalIF":2.4,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13366112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148448963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Clinical and Economic Burden of Pulmonary Arterial Hypertension in Israel, 2014-2022: A Retrospective Analysis of Healthcare Costs and Utilization.","authors":"Yaki Saciuk, Carole Mamane, Tal Patalon, Laurie Lévy-Bachelot, Moshe Hoshen, Sarah Sharman Moser, Inbal Shafran, Mohamed Safwat, Yochai Adir, Ran Numa, Eliad Ben-Dayan, Sivan Gazit, Michael J Segel","doi":"10.1002/pul2.70366","DOIUrl":"10.1002/pul2.70366","url":null,"abstract":"<p><p>Pulmonary arterial hypertension (PAH) is a rare, progressive disease with high morbidity and mortality. Real-world data from Israel are scarce. This study aimed to estimate the incidence, describe treatment patterns, and quantify healthcare utilization and costs associated with PAH in Israel. We conducted a retrospective cohort study using electronic medical records from Maccabi Healthcare Services. Patients diagnosed with PAH between 2014 and 2022 were identified using a multi-criteria case definition combining administrative, clinical, and free-text data. Patients with PAH were compared to two control groups: a matched non-PAH cohort and a cohort with heart failure with reduced ejection fraction (HFrEF). Healthcare resource utilization (HCRU) and costs were annualized and compared using adjusted regression models accounting for age, sex, comorbidities, and socioeconomic status. A total of 106 patients met the diagnostic criteria for PAH, corresponding to an incidence of 0.83 cases per 100,000 person-years (95% CI: 0.66 to 1.00). The cohort was predominantly female (74%) with a mean age of 65 years. One-year mortality among patients with PAH was approximately 20 times higher than in non-PAH controls and 5 times higher than in patients with HFrEF. Mean annual healthcare costs were 12.2 times higher than in non-PAH controls and 6.5 times higher than in patients with HFrEF, with medications accounting for 79% of total expenditures. PAH imposes a substantial clinical and economic burden in Israel, driven by medication costs with widespread use of monotherapy despite full coverage of combination therapy, supporting the case for concentrated care in expert centers.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"16 3","pages":"e70366"},"PeriodicalIF":2.4,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13404763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148607041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}