Pulmonary Circulation最新文献

{"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}

{"title":"The Role of Piezo Ion Channels in Pulmonary Hypertension.","authors":"Kewei Chen, Lingchen Li, Yajie Huang, Lixia Ye, Yu Wang, Ziming Zhang, Chengcheng Hang, Qiqi Li, Qianyun Cao, Lizhong Du","doi":"10.1002/pul2.70360","DOIUrl":"10.1002/pul2.70360","url":null,"abstract":"<p><p>Pulmonary hypertension (PH) is a chronic and devastating disease that currently lacks effective therapies, often ultimately requiring lung transplantation. Pulmonary vascular cells are subjected to various mechanical forces, which contribute to cardiovascular remodeling in PH. In recent years, Piezo ion channels have been instrumental in shaping the field of mechanobiology. However, a growing body of evidence underscores the critical role of Piezo channels in PH. As mechanosensitive channels, Piezo1 and Piezo2 directly transduce external mechanical stimuli into vascular cells and, as such, initiate intracellular biochemical cascades. Piezo ion channels contribute to the pathogenesis of pulmonary hypertension. In this review, we summarize the latest advances in Piezo channels research and focus on their role as key mechanotransducers in the progression of PH. Additionally, we explore the multifunctionality of Piezo channels in mechanobiology and propose new insights for preclinical animal studies and clinical trials. With a deeper understanding of Piezo-mediated activation and modulation mechanisms, Piezo channels are emerging as promising therapeutic targets for the future treatment of PH.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"16 3","pages":"e70360"},"PeriodicalIF":2.4,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13404761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148607054","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":"Shared Decision-Making During Pulmonary Arterial Hypertension Therapy Selection: A Patient and Clinician Survey.","authors":"Paresh C Giri, Jeanette Merrill-Henry, Tiffany Rajah, Donald R Sullivan, Udochukwu Oyoyo, Katrina Barry, Jean M Elwing, Vijay P Balasubramanian","doi":"10.1002/pul2.70364","DOIUrl":"10.1002/pul2.70364","url":null,"abstract":"<p><p>Selection of therapy for pulmonary arterial hypertension (PAH) requires tradeoffs among disease severity, therapeutic benefit, adverse effects, treatment burden, quality of life, and patient values. Although professional societies endorse shared decision-making (SDM) in this context, empirical data describing SDM in PAH are limited. We conducted a survey to characterize SDM during PAH treatment selection from both patient and clinician perspectives. Using the Ottawa Decision-Making Framework, we administered parallel surveys to patients and clinicians at the Pulmonary Hypertension Association's 2022 International PH Conference (Atlanta, GA). Survey items assessed decisional characteristics including role preference, confidence, self-efficacy, decisional support and the factors considered most important during PAH therapy selection. Surveys were administered electronically and analyses were performed using Python. A total of 89 participants (51 patients, 38 clinicians) completed the survey. Preference for SDM was nearly universal among patients (96%) and clinicians (95%). However, priorities differed significantly. Patients more frequently emphasized quality of life (81% vs. 54%) and efficacy of therapy (42% vs. 29%), whereas clinicians prioritized risk of disease progression (67% vs. 30%; all <i>p</i> < 0.01). Although 92% of clinicians reported eliciting patient values, only 75% of patients perceived that this occurred (<i>p</i> = 0.20). Decisional conflict, defined by a SURE score of less than 4, was reported in 39% of patients. Despite widespread support for SDM, there is a discordance in treatment priorities between patients and clinicians and a high level of decisional conflict among patients suggesting a gap between intent and execution of SDM.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"16 3","pages":"e70364"},"PeriodicalIF":2.4,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13404765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148607061","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":"Changes in Arterial-Alveolar Oxygen Gradient and Mixed Venous Oxygen Saturations in Mechanical Thrombectomy for Pulmonary Embolism: A Prospective Cohort Study.","authors":"Adam D Walsh, James Warner, Anna Dunn, Kabir Ahmad","doi":"10.1002/pul2.70345","DOIUrl":"10.1002/pul2.70345","url":null,"abstract":"<p><p>Large bore mechanical thrombectomy (LBMT) is an effective therapy for intermediate-high risk PE, however, objective physiological endpoints to guide intraprocedural decision-making remain poorly defined. The alveolar-arterial (A-a) oxygen gradient, mixed venous oxygen saturation (SvO₂), and cardiac index (CI) may provide clinically useful insights during LBMT. We sought to determine if changes in alveolar-arterial gradients and estimated cardiac index were sufficiently consistent to be used to inform clinical decision making. This was a single-center, prospective, pre-post cohort study of patients undergoing LBMT for intermediate-high risk PE. Arterial and mixed venous blood gases were aspirated immediately before and after thrombectomy. CI was estimated via the indirect Fick method. Primary outcomes were changes in A-a gradient and mixed venous oxygen saturations; secondary outcomes included estimated CI and Modified Borg Dyspnea Scale. Sensitivity analyses excluded physiologically implausible outliers and accounted for intraprocedural hemoglobin changes. Twenty-seven patients were included. LBMT was associated with a nonsignificant reduction in A-a gradient (-38.5 ± 129.9 mmHg, <i>p</i> = 0.052), which became significant after exclusion of outliers (-41.5 ± 62.9 mmHg, <i>p</i> = 0.0096). Mixed SvO₂ decreased in most patients by 3.8% ± 7.3% (<i>p</i> = 0.015), corresponding to a modest reduction in estimated CI (-0.16 ± 0.67 L/min/m², <i>p</i> = 0.032) which persisted after controlling for hemoglobin loss. Dyspnea scores improved in most patients with paired measurements. Acute improvements in oxygenation efficiency were reflected by reductions in A-a gradient, while paradoxical reductions in SvO₂ and estimated CI suggest altered oxygen extraction ratio post-procedure. These parameters may serve as novel intraprocedural physiological markers to complement thrombectomy endpoints.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"16 2","pages":"e70345"},"PeriodicalIF":2.4,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13305666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346288","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":"Patient Perspectives on Palliative Care in Pulmonary Arterial Hypertension in the United States.","authors":"Karim El-Kersh, Rebecca Crawford, Hilary DuBrock, Peter Classi, Phuong Phan, Lori McLeod, Benjamin Wu, Denise Sese","doi":"10.1002/pul2.70330","DOIUrl":"10.1002/pul2.70330","url":null,"abstract":"<p><p>Palliative care can be offered concurrently as a treatment option to patients with pulmonary arterial hypertension (PAH) to relieve symptoms and improve quality of life. However, it is infrequently used and is associated with misconceptions. Limited studies have reported patients' perspectives of palliative care as a treatment option for PAH. We conducted a web-based survey, informed by a brief targeted literature review and input from patients and clinicians, which was completed by adults (≥ 18 years) in the United States (US) with self-reported PAH. Patients reported demographic and disease variables and their perspectives and experiences with palliative care. Patients self-reported their Pulmonary Hypertension Functional Class Self-Report class, EmPHasis-10, and 6-min walk test. A total of 200 respondents (86.5% female; mean age 58.5 years) from 42 US states completed the survey between 19 September and 3 October 2023. Most respondents described palliative care as \"end-of-life care\" (<i>n</i> = 43, 25.7%) and associated it with the need for extra support (<i>n</i> = 111, 55.5%). Many respondents (<i>n</i> = 171, 85.5%) had not discussed palliative care services, nor had a palliative care consultation with their healthcare provider (HCP); most had not been offered a consultation (<i>n</i> = 109/171, 63.7%). Despite this low frequency of discussions, respondents reported feeling comfortable discussing palliative care with their HCPs (<i>n</i> = 177, 88.5%). The survey results demonstrated that these patients with PAH had limited experiences with palliative care, where palliative care was frequently subject to misinterpretation. These findings emphasize the need for proactive engagement between patients and HCPs to ensure palliative care is optimally used and understood.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"16 2","pages":"e70330"},"PeriodicalIF":2.4,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13292157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148332562","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":"Sotatercept as a Therapeutic Option for Systemic Sclerosis-Associated Pulmonary Arterial Hypertension With Features of PVOD/PCH.","authors":"Yujin Nishioka, Keita Imanishi, Erika Matsuda, Wataru Nakamura, Ryosuke Shirayanagi, Hiroto Ojiro, Akira Katagiri","doi":"10.1002/pul2.70347","DOIUrl":"10.1002/pul2.70347","url":null,"abstract":"<p><p>A 53-year-old woman with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) presented with severe exertional desaturation, markedly reduced diffusing capacity (%DLCO 30%), and computed tomography findings demonstrating features of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis (PVOD/PCH). Despite triple oral therapy, pulmonary hypertension progressively worsened, with mean pulmonary arterial pressure increasing from 34 to 51 mmHg. Sotatercept was initiated because of concerns about the risk of pulmonary edema with parenteral prostacyclin therapy. Despite intermittent treatment interruption due to hemoglobin elevation, improvements were observed in World Health Organization functional class (III-II), 6-min walk distance (217-301 m), brain natriuretic peptide (206.4-52.8 pg/mL), and mean pulmonary arterial pressure (51-45 mmHg), without pulmonary edema. This case suggests a potential benefit of sotatercept in selected patients with SSc-PAH with features of PVOD/PCH.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"16 2","pages":"e70347"},"PeriodicalIF":2.4,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13291711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148332565","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 Mechanical Dyssynchrony Reflects Hemodynamic Load in Pre-Capillary Pulmonary Hypertension.","authors":"Sachiyo Igata, Nobuhiro Tahara, Atsuko Tahara, Akihiro Honda, Tadahiro Kugai, Yoshiko Eto, Shoko Maeda-Ogata, Yoshihiro Fukumoto","doi":"10.1002/pul2.70343","DOIUrl":"10.1002/pul2.70343","url":null,"abstract":"<p><p>Right ventricular (RV) mechanical dyssynchrony represents a maladaptive response to increased afterload in pulmonary hypertension (PH). However, its hemodynamic and biochemical determinants remain unclear. This study aimed to identify the clinical, hemodynamic, and biochemical correlates of RV dyssynchrony in patients with pre-capillary PH. Thirty patients with pre-capillary PH (83% female; age 56 ± 19 years), all without intraventricular conduction delay (QRS < 120 ms), underwent right heart catheterization, cardiac magnetic resonance imaging, and two-dimensional speckle-tracking echocardiography. RV dyssynchrony was quantified using the coefficient of variation of time-to-peak systolic strain in four mid-basal RV segments (RV-CV4) adjusted for heart rate. Mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), and RV-CV4 averaged 34.1 ± 11.2 mmHg, 522.3 (interquartile range, 289.4-692.6) dyn·s·cm^-5, and 0.134 ± 0.083, respectively, in a cohort with predominantly mild-to-moderate RV systolic dysfunction. RV dyssynchrony correlated significantly with mPAP (<i>β</i> = 0.509) PVR (<i>β</i> = 0.507), and RV-pulmonary artery coupling (<i>β</i> = -0.406) (all <i>p</i> < 0.05). In multivariate analysis, mPAP remained the sole independent predictor of RV dyssynchrony (<i>β</i> = 0.509, 95% CI 0.001-0.006, <i>p</i> = 0.004), accounting for 26% of its variance. Neither RV end-diastolic volume nor RV ejection fraction were independently associated with dyssynchrony. RV mechanical dyssynchrony reflects hemodynamic afterload, particularly elevated mPAP, rather than structural remodeling. Notably, dyssynchrony was evident even in mild-to-moderate RV dysfunction, indicating an early manifestation of pressure-induced impairment. RV-CV4 may serve as a noninvasive marker of pulmonary vascular load and highlight the importance of afterload reduction in optimizing RV mechanical coordination. Accordingly, RV dyssynchrony assessment may provide a practical echocardiographic surrogate for invasive hemodynamic evaluation in clinical practice.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"16 2","pages":"e70343"},"PeriodicalIF":2.4,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13288177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148318524","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":"HIV-Associated Pulmonary Arterial Hypertension in Resource-Limited Settings: A \"Forgotten\" Diagnosis, a Great Imitator, and a Multi-Hit Pulmonary Vasculopathy.","authors":"Emmanuel Eroume A Egom, Mfopa Adamou, Ibrahima Djouldé, Njimona Ibrahim, Mountchissi Célestin, Lum Abenwi Ambe, Medou Mba Fabrice, Moustapha, René Kamgang","doi":"10.1002/pul2.70341","DOIUrl":"10.1002/pul2.70341","url":null,"abstract":"<p><p>HIV-associated pulmonary arterial hypertension (HIV-PAH) remains one of the most consequential cardiopulmonary complications in people living with HIV (PLWH), persisting despite expanded antiretroviral therapy (ART) coverage. Although contemporary hemodynamic criteria define pulmonary hypertension (PH) as mean pulmonary arterial pressure (mPAP) > 20 mmHg and pulmonary arterial hypertension (PAH) as pre-capillary physiology confirmed by right heart catheterization (mPAP > 20 mmHg, pulmonary arterial wedge pressure ≤ 15 mmHg, pulmonary vascular resistance > 2 Wood units), global epidemiologic certainty remains uneven. In high-income settings, prospective screening paradigms incorporating catheter confirmation estimate HIV-PAH prevalence at approximately 0.5%, exemplified by the multicenter French study reporting 0.46%. In contrast, in sub-Saharan Africa-home to more than 26 million PLWH-the population prevalence of catheter-confirmed HIV-PAH remains undefined, with echocardiography-based studies in symptomatic cohorts reporting substantially higher rates of elevated pulmonary pressures. Mechanistically, HIV-PAH is best conceptualized as a multi-hit pulmonary vasculopathy driven by viral proteins (Tat, Nef, gp120), chronic immune activation, endothelial dysfunction, oxidative stress, dysregulated endothelin signaling, and growth-factor pathways, with amplification by endemic co-factors and host susceptibility. Clinically, HIV-PAH is a \"clinically nonspecific phenotype\", frequently obscured by tuberculosis-related lung disease, anemia, left heart disease, and other causes of dyspnea in resource-limited settings. Early recognition is critical because prognosis depends on preservation of right ventricular function. A practical, resource-appropriate strategy is required: heightened clinical suspicion, echocardiography-anchored detection, systematic exclusion of alternative PH etiologies, rational biomarker use, and referral pathways to right heart catheterization where feasible. ART optimization is necessary but insufficient; PAH-targeted therapies can improve functional and hemodynamic outcomes, though HIV-specific randomized evidence remains limited. Implementation science and mechanism-informed research in endemic regions are urgently needed to close the diagnostic and therapeutic gap.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"16 2","pages":"e70341"},"PeriodicalIF":2.4,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13280555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148296101","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}