Pulmonary Circulation最新文献

{"title":"An Unsupervised Approach to Derive Right Ventricular Pressure-Volume Loop Phenotypes in Pulmonary Hypertension.","authors":"Nikita Sivakumar, Cindy Zhang, Connie Chang-Chien, Pan Gu, Yikun Li, Yi Yang, Darin Rosen, Tijana Tuhy, Ilton M Cubero Salazar, Matthew Kauffman, Rachel L Damico, Casey Overby Taylor, Joseph L Greenstein, Steven Hsu, Paul M Hassoun, Catherine E Simpson","doi":"10.1002/pul2.70057","DOIUrl":"10.1002/pul2.70057","url":null,"abstract":"<p><p>Although right ventricle (RV) dysfunction drives clinical worsening in pulmonary hypertension (PH), information about RV function has not been well integrated in PH risk assessment. The gold standard for assessing RV function and ventriculo-arterial coupling is the construction of multi-beat pressure-volume (PV) loops. PV loops are technically challenging to acquire and not feasible for routine clinical use. Therefore, we aimed to map standard clinically available measurements to emergent PV loop phenotypes. One hundred and one patients with suspected PH underwent right heart catheterization (RHC) with exercise, multi-beat PV loop measurement, and same-day cardiac magnetic resonance imaging (CMR). We applied unsupervised <i>k</i>-means clustering on 10 PV loop metrics to obtain three patient groups with unique RV functional phenotypes and times to clinical worsening. We integrated RHC and CMR measurements to train a random forest classifier that predicts the PV loop patient group with high discrimination (AUC = 0.93). The most informative variable for PV loop phenotype prediction was exercise mean pulmonary arterial pressure (mPAP). Distinct and clinically meaningful PV loop phenotypes exist that can be predicted using clinically accessible hemodynamic and RV-centric measurements. Exercise mPAP may inform RV pressure-volume relationships.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"15 1","pages":"e70057"},"PeriodicalIF":2.2,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483970","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":"RNA-Seq and ChIP-Seq Identification of Unique and Overlapping Target Genes and Pathways Regulated by TBX4 in Human Pulmonary Fibroblasts and Pericytes.","authors":"Ying Cai, Ling Yan, Joy D Cogan, Lora K Hedges, Bethany Nunley, Nick Negretti, Jennifer M S Sucre, James West, Eric D Austin, Rizwan Hamid","doi":"10.1002/pul2.70058","DOIUrl":"10.1002/pul2.70058","url":null,"abstract":"<p><p>Transcription factor <i>TBX4</i> rare variants associate with pulmonary arterial hypertension (PAH), particularly in children, and are the second most common cause of heritable PAH. However, TBX4's down-stream targets and the molecular and cellular pathways these targets regulate remain largely unknown in PAH. We combined RNA-seq and ChIP-seq results to identify TBX4 direct targets in lung fibroblasts and pericytes, respectively. There were 555 genes with altered expression with TBX4 knockdown in both fibroblasts and pericytes by RNA-seq, and which also were found to be bound by TBX4 by ChIP-seq. Gene ontology analysis found that these were dominated by genes related to extracellular matrix, actin organization, and migration guidance, although there were also significant groups related to serine/threonine kinase signaling, GTPase mediated signaling, and glycoprotein metabolism. Migration and proliferation studies using TBX4 knockdown fibroblasts confirmed functional effects. These studies provide the first insights into how genes and pathways regulated by TBX4 are impacted and inform future studies about the key biological processes that lead to PAH in patients who carry pathologic TBX4 rare variants.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"15 1","pages":"e70058"},"PeriodicalIF":2.2,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468910","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":"Introducing Historical Vignettes in <i>Pulmonary Circulation</i>.","authors":"Harold I Palevsky, Ghazwan Butrous, C Gregory Elliott","doi":"10.1002/pul2.70061","DOIUrl":"10.1002/pul2.70061","url":null,"abstract":"","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"15 1","pages":"e70061"},"PeriodicalIF":2.2,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468861","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":"Developing a Neonatal Pulmonary Hypertension Core Outcome Set (NeoPH COS)-A Study Protocol.","authors":"Cara Ellen Morgan, Kerry Woolfall, Natasharazia Aikman, Crhistopher Gale, Nimish Subhedar","doi":"10.1002/pul2.70052","DOIUrl":"10.1002/pul2.70052","url":null,"abstract":"<p><p>Pulmonary hypertension (PH) in newborn babies is a relatively rare, heterogeneous condition that has high associated mortality in the neonatal period and beyond. There are limited evidence-based strategies to treat or prevent this condition. Over the last two decades, there has been an increase in the number of studies assessing new therapies and treatment strategies in babies with PH. However, comparison of different treatments between studies is limited by inconsistency in outcome reporting. To address this issue, we aim to develop a core outcome set (COS) for neonates and infants less than 3 months of age, corrected for prematurity, diagnosed with PH, through international consensus with key stakeholders including parents and/or guardians, healthcare professionals and researchers. The development of the COS will be divided into two stages: (1) identification of potential outcomes through a mixed methods systematic literature review and qualitative interviews with parents and/or guardians of babies with pulmonary hypertension; (2) determining core outcomes through an online Delphi survey and consensus meeting. An advisory group with global membership including parents and/or guardians, healthcare professionals, and researchers recruited internationally was formed to guide the COS. The methodology utilized to develop a neonatal PH COS aims to ensure applicability and adoption in international settings and relevance across disciplines. The COS will help to improve trial design and homogeneity of outcomes reported in neonatal trials of PH. This will translate into higher-quality evidence for therapeutic strategies for PH in neonates.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"15 1","pages":"e70052"},"PeriodicalIF":2.2,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468857","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 Role of Ion Channels in Pulmonary Hypertension: A Review.","authors":"Han-Fei Li, Xin-Yao Li, Yu-Qing Sun, Ze-Ying Zhi, Liao-Fan Song, Meng Li, Yi-Ming Feng, Zhi-Hao Zhang, Yan-Feng Liu, Yu-Jing Chen, Fan-Rong Zhao, Tian-Tian Zhu","doi":"10.1002/pul2.70050","DOIUrl":"10.1002/pul2.70050","url":null,"abstract":"<p><p>Pulmonary hypertension (PH) constitutes a critical challenge in cardiopulmonary medicine with a pathogenesis that is multifaceted and intricate. Ion channels, crucial determinants of cellular electrochemical gradient modulation, have emerged as significant participants in the pathophysiological progression of PH. These channels, abundant on the membranes of pulmonary artery smooth muscle cells (PASMCs) and pulmonary artery endothelial cells (PAECs), pivotally navigate the nuanced interplay of cell proliferation, migration, and endothelial function, each vital to the pulmonary vascular remodeling (PVR) hallmark of PH. Our review delves into the mechanistic insights of potassium, calcium, magnesium, zinc, and chloride ion channels in relation to their involvement in PH. It not only emphasizes the notable advances and discoveries that cast these ion channels as underlying factors in the etiology and exacerbation of PH but also highlights their potential as innovative therapeutic targets.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"15 1","pages":"e70050"},"PeriodicalIF":2.2,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11830494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432842","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":"Estrogen and Cyp1b1 Regulate Pparγ in Pulmonary Hypertension Through a Ubiquitin-Dependent Mechanism.","authors":"Jingyuan Chen, Xinping Chen, Vineet Agrawal, Christy S Moore, Tom Blackwell, Nivedita Rathaur, Santhi Gladson, Anandharajan Rathinasabapathy, Anna Hemnes, Eric Austin, James West","doi":"10.1002/pul2.70054","DOIUrl":"10.1002/pul2.70054","url":null,"abstract":"<p><p>Female sex increases risk of Group I pulmonary arterial hypertension by roughly threefold, but the mechanism is unclear. Low expression of Cyp1b1, an enzyme that metabolizes estrogens, is associated with disease penetrance, particularly in women. We previously found that lower Pparγ levels in murine PAH models, which may drive disease, are rescued by estrogen blockade. The goal of the current studies was to examine interaction of estrogen, Cyp1b1, and energy metabolism in cell culture and in knockout mice. We found that both estrogen and siRNA to Cyp1b1 resulted in reduction of Pparγ at a protein, but not transcript level, in addition to regulating Pparγ cofactors. siCyp1b1 reduced both basal and maximal respiration rates in a fatty acid oxidation Seahorse protocol. This Pparγ inhibition could be eliminated by blocking ubiquitination. RNA-seq suggested that Cyp1b1 may be having important pulmonary hypertension effects both in concert with and independently of its effect on estrogen. Cyp1b1 knockout mice have lower Pparγ levels than WT mice both in normoxia and hypoxia, and develop mild pulmonary hypertension on a high fat diet. RNA-seq on their lungs reflected similar pathways to those altered in endothelial cells alone - lipid metabolism, cytokines, and vasoreactivity-associated genes, among others, but added genes associated with circadian rhythm. These data suggest multiple potential points for intervention in estrogen and Cyp1b1 mediated etiology of PAH, in particular Pparγ ubiquitination, but also suggests that both the difference between E2 and 16aOHE and the impact of Cyp1b1 is more complex than simply \"degree of estrogenicity\".</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"15 1","pages":"e70054"},"PeriodicalIF":2.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432543","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":"Heart Rate Variability in Pulmonary Arterial Hypertension.","authors":"Bishal Gyawali, Dominick Roto, Michael Lachant, R James White, Daniel Lachant","doi":"10.1002/pul2.70048","DOIUrl":"10.1002/pul2.70048","url":null,"abstract":"<p><p>Resting heart rate has been incorporated in REVEAL risk assessment. Rest and sleep heart rate variability (HRV) measured in the home setting could provide early insight into worsening physiology in patients with pulmonary arterial hypertension (PAH). We hypothesized continuous HRV monitoring in the home setting for 7 days would be a treatment responsive measure and be associated with outcomes in PAH. This was a prospective observational study completed at the University of Rochester. We recruited two groups, one with stable background therapy and another with therapy intensification during the study. MC10 Biostamp (continuous electrocardiogram heart rate monitoring) was worn for 7 days at baseline and follow up; stable patients completed monitoring twice within 4 weeks while treatment intensification patients were assessed 3 months later. HRV was calculated using MC10 proprietary algorithm. Baseline, follow up, and changes in heart rate and HRV (rest and sleep) were compared between the groups and correlated to clinical outcomes at 2 years. Periods of activity were excluded from analysis. Non-parametric testing was performed. Twenty-four (10 stable and 14 treatment intensification) PAH patients had paired monitoring sessions during sleep and rest. There were no statistical differences in heart rate or HRV values at baseline or follow-up within either stable PAH patients or those requiring treatment escalation. Additionally, the change in heart rate from baseline to follow-up did not differ significantly between the two groups. There was no difference in HRV between patients who had clinical worsening (parenteral therapy, hospitalization, or death) within 2 years, while elevated rest and sleep heart rate did predict clinical worsening at 2 years. Unlike left ventricular systolic failure, continuous HRV for 7 days in the home setting does not appear to improve assessment in PAH, and functional testing appears to be a better way to assess treatment response and risk for clinical worsening.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"15 1","pages":"e70048"},"PeriodicalIF":2.2,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383203","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":"Cardiopulmonary Exercise Testing With Simultaneous Echocardiography After Pulmonary Embolism.","authors":"Karys Khilzi, Lucilla Piccari, Gerard Franco, Anna Rodó-Pin, Anna Herranz, Isabel Blanco, Giuseppe Paciocco, Lorenzo Volpiano, Jose Gonzalez Garcia, Ana Diez-Llaneza, Lluis Molina, Diego A Rodríguez Chiaradía","doi":"10.1002/pul2.70045","DOIUrl":"10.1002/pul2.70045","url":null,"abstract":"<p><p>Although current guidelines recommend standard cardiopulmonary exercise testing (CPET) to evaluate symptomatic patients after pulmonary embolism (PE), CPET with simultaneous echocardiography could provide relevant information to evaluate right ventricular-pulmonary arterial coupling. The aim of this study was to investigate exercise-induced changes in echocardiographic variables of RV function or RV- arterial coupling in patients with residual thrombotic defects at 3 months after PE. This retrospective study investigated patients with residual thromboembolic disease on V/Q scintigraphy with persistent symptoms despite adequate anticoagulation after 3 months of acute PE, and resting echocardiography with a low probability of PH. At rest and during exercise, CPET and doppler echocardiography were performed following a standard protocol. Forty-five patients were included, completing a follow-up period of at least 24 months. The mean (standard deviation) age was 63 (15) years, and 24 (53%) patients were male. Four patients developed CTEPH after 2 years follow up. Correlation analyses showed that the peak TAPSE was significantly associated with peak workload (<i>r</i> = 0.454, <i>p</i> = 0.003), peak VO₂ (<i>r</i> = 0.558, <i>p</i> < 0.001), VE/VECO₂ (AT) (<i>r</i> = -0.531, <i>p</i> < 0.001), and oxygen pulse (<i>r</i> = 0.375, <i>p</i> = 0.02). TAPSE/PASP was only slightly associated with peak workload (<i>r</i> = 0.300, <i>p</i> = 0.045). By contrast, the change on TAPSE (from rest to peak) was significantly correlate with peak oxygen uptake (<i>r</i> = 0.491, <i>p</i> = 0.01). Also, reduced VO₂ at AT and TAPSE/PASP was seen in patients with CTEPH. CPET with synchronic echocardiography could be a useful tool in early assessment of symptomatic patients with perfusion defects on imaging after 3 months of correctly treated PE.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"15 1","pages":"e70045"},"PeriodicalIF":2.2,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11798863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365801","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":"Treatment pathways in Finnish patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH).","authors":"Markku Pentikäinen, Piia Simonen, Pauliina Leskelä, Terttu Harju, Pertti Jääskeläinen, Christian Asseburg, Minna Oksanen, Erkki Soini, Christina Wennerström, Airi Puhakka, Katriina Kahlos","doi":"10.1002/pul2.12440","DOIUrl":"10.1002/pul2.12440","url":null,"abstract":"<p><p>Treatment patterns of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) in Finland are unknown. Guidelines now recommend early escalation of treatment for PAH. We evaluated how well Finnish practice follows guidelines, and how treatment initiations and outcomes are related. The pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension patients in Finland cohort includes all PAH and CTEPH patients diagnosed between 2008 and 2020 in all Finnish university hospitals. Drug therapy was analysed in patients with medical/procedural history available, and changes in the 4-tier comparative, prospective registry of newly initiated therapies for pulmonary hypertension (COMPERA) 2.0 risk score were evaluated. PAH patients (<i>n</i> = 268) were initially treated with monotherapy (52%) or double therapy (24%). After year 2015, double therapy use increased to 39%. PAH treatment at 1 year after diagnosis included phosphodiesterase 5 inhibitors (71%), endothelin-receptor antagonist (48%), prostacyclin analogue (7%), calcium channel blocker (12%) and selexipag (1%). 35% achieved low risk at 1 year, increasing to 44% for patients diagnosed after 2015. Those remaining at intermediate-high (IH) or high risk (H) (28%) were not treated less aggressively than others but were older, had more comorbidities, and often history of smoking. CTEPH patients (<i>n</i> = 189) were treated with pulmonary endarterectomy (PEA) (27%), balloon pulmonary angioplasty (BPA) (11%) and medical therapy only (41%) within 1 year from diagnosis. 45% achieved low risk at 1 year. We present additional results on treatment of IH and H patients, patient characteristics preceding death, and treatment persistence. We found less treatment of PAH patients with double or triple therapies and of CTEPH patients with PEA and BPA than expected but with good results. Patients not reaching low or intermediate COMPERA 2.0 were old and had comorbidities.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"15 1","pages":"e12440"},"PeriodicalIF":2.2,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190340","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 Hypertension: A Personal Journey.","authors":"Lewis J Rubin","doi":"10.1002/pul2.70047","DOIUrl":"10.1002/pul2.70047","url":null,"abstract":"","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"15 1","pages":"e70047"},"PeriodicalIF":2.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190339","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}