Search

Acute pulmonary embolism (APE) is a life-threatening condition with a high mortality rate. The pathophysiology involves various complex processes. The systemic immune-inflammatory index (SII) is a well-known biomarker that reflects the intricate balance between pro-inflammatory and anti-inflammatory immune components. In this systematic review, we aim to determine the significance of SII as a potential biomarker for APE. We utilized PubMed, ProQuest, EBSCOHost, and Google Scholar to search for articles. We assessed bias risk using the Newcastle Ottawa Scale (NOS). The outcomes we examined included in-hospital and long-term mortality, the severity of APE, and the sensitivity and specificity of the SII in predicting APE. Four studies, involving 2,038 patients, were included for analysis. These studies discuss the use of SII in predicting APE severity, APE mortality, high-risk APE, and the occurrence of APE. SII demonstrates significant results in predicting each of these variables. Furthermore, each study establishes different SII cut-off values. Specifically, a cut-off of 1161 predicts massive APE events with a sensitivity of 91% and a specificity of 90%. A cut-off of >1235.35 differentiates high-risk APE with a sensitivity of 87.32% and a specificity of 68.85%. A cut-off of >1111x109 predicts overall mortality with a sensitivity of 72% and a specificity of 51%. Finally, a cut-off at 1839.91 predicts APE events with a sensitivity of 75.8% and a specificity of 61.9%. The SII can be employed as a potential new biomarker to predict outcomes in APE patients, particularly the occurrence, severity, and mortality of APE. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) is an incurable disease characterized by pulmonary vascular remodeling. Endothelial injury and inflammation are the key triggers of disease initiation. Recent findings suggest that STING (stimulator of IFN genes) activation plays a critical role in endothelial dysfunction and IFN signaling. Here, we investigated the involvement of STING in the pathogenesis of PH. Patients with PH and rodent PH model samples, a Sugen 5416/hypoxia PH model, and pulmonary artery endothelial cells (PAECs) were used to evaluate the hypothesis. We found that the cyclic guanosine monophosphate–AMP synthase–STING signaling pathway was activated in lung tissues from rodent PH models and patients with PH and in TNF-α–induced PAECs in vitro. Specifically, STING expression was significantly elevated in the endothelial cells in PH disease settings. In the Sugen 5416/hypoxia mouse model, genetic knockout or pharmacological inhibition of STING prevented the progression of PH. Functionally, knockdown of STING reduced the proliferation and migration of PAECs. Mechanistically, STING transcriptionally regulates its binding partner F2RL3 (F2R-like thrombin or trypsin receptor 3) through the STING-NF-κB axis, which activated IFN signaling and repressed BMPR2 (bone morphogenetic protein receptor 2) signaling both in vitro and in vivo. Further analysis revealed that F2RL3 expression was increased in PH settings and identified negative feedback regulation of F2RL3/BMPR2 signaling. Accordingly, a positive correlation of expression amounts between STING and F2RL3/IFN-stimulated genes was observed in vivo. Our findings suggest that STING activation in PAECs plays a critical role in the pathobiology of PH. Targeting STING may be a promising therapeutic strategy for preventing the development of PH. [ABSTRACT FROM AUTHOR]

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious pulmonary vascular disease characterized by residual thrombi in the pulmonary arteries and distal pulmonary microvascular remodeling. The pathogenesis of CTEPH remains unclear, but many factors such as inflammation, immunity, coagulation and angiogenesis may be involved. Monocytes are important immune cells that can differentiate into macrophages and dendritic cells and play an important role in thrombus formation. However, the distribution, gene expression profile and differentiation trajectory of monocyte subsets in CTEPH patients have not been systematically studied. This study aims to reveal the characteristics and functions of monocytes in CTEPH patients using single-cell sequencing technology, and to provide new insights for the diagnosis and treatment of CTEPH. Methods: Single-cell RNA sequencing (scRNA-seq) were performed to analyze the transcriptomic features of peripheral blood mononuclear cells (PBMCs) from healthy controls, CTEPH patients and the tissues from CTEPH patients after the pulmonary endarterectomy (PEA). We established a CTEPH rat model with chronic pulmonary embolism caused by repeated injection of autologous thrombi through a central venous catheter, and used flow cytometry to detect the proportion changes of monocyte subsets in CTEPH patients and CTEPH rat model. We also observed the infiltration degree of macrophage subsets in thrombus tissue and their differentiation relationship with peripheral blood monocyte subsets by immunofluorescence staining. Results: The results showed that the monocyte subsets in peripheral blood of CTEPH patients changed significantly, especially the proportion of CD16+ monocyte subset increased. This monocyte subset had unique functional features at the transcriptomic level, involving processes such as cell adhesion, T cell activation, coagulation response and platelet activation, which may play an important role in pulmonary artery thrombus formation and pulmonary artery intimal remodeling. In addition, we also found that the macrophage subsets in pulmonary endarterectomy tissue of CTEPH patients showed pro-inflammatory and lipid metabolism reprogramming features, which may be related to the persistence and insolubility of pulmonary artery thrombi and the development of pulmonary hypertension. Finally, we also observed that CD16+ monocyte subset in peripheral blood of CTEPH patients may be recruited to pulmonary artery intimal tissue and differentiate into macrophage subset with high expression of IL-1β, participating in disease progression. Conclusion: CD16+ monocytes subset had significant gene expression changes in CTEPH patients, related to platelet activation, coagulation response and inflammatory response. And we also found that these cells could migrate to the thrombus and differentiate into macrophages with high expression of IL-1b involved in CTEPH disease progression. We believe that CD16+ monocytes are important participants in CTEPH and potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Due to a special hemodynamic feature, pulmonary vascular disease in pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) has two stages: reversible and irreversible. So far, the mechanism involved in the transition from reversible to irreversible stage is elusive. Moreover, no recognized and reliable assessments to distinguish these two stages are available. Furthermore, we found that compared with control and reversible PAH, thrombospondin-4 (THBS4) was significantly upregulated in irreversible group by bioinformatic analysis. Hence, we further verify and investigate the expression and role of THBS4 in PAH-CHD. Methods: We established the monocrotaline plus aorto-cava shunt-induced (MCT-AV) rat model. We measured the expression of THBS4 in lung tissues from MCT-AV rats. Double immunofluorescence staining of lung tissue for THBS4 and α-SMA (biomarker of smooth muscle cells) or vWF (biomarker of endothelial cells) to identify the location of THBS4 in the pulmonary artery. Primary pulmonary artery smooth muscle cells (PASMCs) were cultivated, identified, and used in this study. THBS4 was inhibited and overexpressed by siRNA and plasmid, respectively, to explore the effect of THBS4 on phenotype transformation, proliferation, apoptosis, and migration of PASMCs. The effect of THBS4 on pulmonary vascular remodeling was evaluated in vivo by adeno-associated virus which suppressed THBS4 expression. Circulating level of THBS4 in patients with PAH-CHD was measured by ELISA. Results: THBS4 was upregulated in the lung tissues of MCT-AV rats, and was further upregulated in severe pulmonary vascular lesions. And THBS4 was expressed mainly in PASMCs. When THBS4 was inhibited, contractile markers α-SMA and MYH11 were upregulated, while the proliferative marker PCNA was decreased, the endothelial-mensenchymal transition marker N-cad was downregulated, proapototic marker BAX was increased. Additionally, proliferation and migration of PASMCs was inhibited and apoptosis was increased. Conversely, THBS4 overexpression resulted in opposite effects. And the impact of THBS4 on PASMCs was probably achieved through the regulation of the PI3K/AKT pathway. THBS4 suppression attenuated pulmonary vascular remodeling. Furthermore, compared with patients with simple congenital heart disease and mild PAH-CHD, the circulating level of THBS4 was higher in patients with severe PAH-CHD. Conclusions: THBS4 is a promising biomarker to distinguish reversible from irreversible PAH-CHD before repairing the shunt. THBS4 is a potential treatment target in PAH-CHD, especially in irreversible stage. [ABSTRACT FROM AUTHOR]

This article presents a case report of a patient who developed portopulmonary hypertension (POPH) after the closure of a congenital portosystemic shunt (CPSS). It emphasizes the importance of monitoring and intervention, as POPH can progress even after shunt closure. The article discusses the patient's medical history, diagnosis, and treatment, including the use of antipulmonary hypertension agents. It concludes by highlighting the limited understanding of the mechanism behind the rapid development of POPH after shunt closure. The article also stresses the need for early detection and screening for pulmonary vascular disease in patients with CPSS, as well as the importance of repeated screening during follow-up. It suggests that cardiac screening for pulmonary arterial hypertension (PAH) should be conducted at the time of CPSS diagnosis and throughout the treatment process. [Extracted from the article]

Objective: Congenital defects/diseases. Background: Pulmonary artery sling (PAS) is an anatomical vascular anomaly due to the origin of the left pulmonary artery from the right pulmonary artery, which runs posteriorly between the esophagus and trachea, resulting in compression of adjacent structures. Accurate evaluation for malformation of the pulmonary artery and severity of airway obstruction is essential to surgical strategy. This report presents the diagnosis and surgical management of pulmonary artery sling in a 12-year-old boy. Case Report: A 12-year-old boy had chest tightness and wheezing after exercise for 6 years. He was diagnosed with PSA based on findings from imaging tests, demonstrating the left pulmonary artery originated from the middle of the right pulmonary artery and the tracheal carina was located at the site of the T6 thoracic vertebra. The main bronchus and esophagus were compressed by the left pulmonary artery due to its ectopic origin. Then, after comprehensive preoperative assessment, the patient underwent surgical repair of PAS. Conclusions: This report highlights the importance of pulmonary artery sling diagnosis, imaging, and surgical planning, and the role of a multidisciplinary team in preoperative and postoperative patient management. An individualized strategy based on the preoperative assessment, intraoperative coordination among cardiologists, surgeons, and perfusionists, and careful postoperative management are the core elements for successful PAS repair. [ABSTRACT FROM AUTHOR]

Objective: We aimed to evaluate the mitral valve calcification and mitral structure detected by cardiac computed tomography (cardiac CT) and establish a scoring model based on cardiac CT and clinical factors to predict early good mitral valve repair (EGMR) and guide surgical strategy in rheumatic mitral disease (RMD). Materials and methods: This is a retrospective bi-center cohort study. Based on cardiac CT, mitral valve calcification and mitral structure in RMD were quantified and evaluated. The primary outcome was EGMR. A logical regression algorithm was applied to the scoring model. Results: A total of 579 patients were enrolled in our study from January 1, 2019, to August 31, 2022. Of these, 443 had baseline cardiac CT scans of adequate quality. The calcification quality score, calcification and thinnest part of the anterior leaflet clean zone, and papillary muscle symmetry were the independent CT factors of EGMR. Coronary artery disease and pulmonary artery pressure were the independent clinical factors of EGMR. Based on the above six factors, a scoring model was established. Sensitivity = 95% and specificity = 95% were presented with a cutoff value of 0.85 and 0.30 respectively. The area under the receiver operating characteristic of external validation set was 0.84 (95% confidence interval [CI] 0.73–0.93). Conclusions: Mitral valve repair is recommended when the scoring model value > 0.85 and mitral valve replacement is prior when the scoring model value < 0.30. This model could assist in guiding surgical strategies for RMD. Clinical relevance statement: The model established in this study can serve as a reference indicator for surgical repair in rheumatic mitral valve disease. Key Points: • Cardiac CT can reflect the mitral structure in detail, especially for valve calcification. • A model based on cardiac CT and clinical factors for predicting early good mitral valve repair was established. • The developed model can help cardiac surgeons formulate appropriate surgical strategies. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusions The risk of life‐threatening major cardiovascular outcomes among patients with bullous pemphigoid (BP) is inconsistent in the current literature.To evaluate the risk and prognostic outcomes of myocardial infarction (MI), cerebrovascular accident (CVA), peripheral vascular disease (PVD) and pulmonary embolism (PE) in patients with BP. We additionally aimed to explore the influence of different therapeutic approaches on the risk of these outcomes.A population‐based retrospective cohort study was conducted to compare BP patients (n = 3924) with age‐, gender‐ and ethnicity‐matched control subjects (n = 19,280) with regard to incident cases of MI, CVA, PVD and PE. Adjusted hazard ratio (HR) and 95% confidence intervals (CI) were estimated by multivariate Cox regression analysis. Data were retrieved from Clalit Health Services' computerized database.Relative to their matched controls, patients with BP were at an elevated risk of MI (fully‐adjusted HR: 1.44; 95% CI: 1.14–1.81; p = 0.002), CVA (fully‐adjusted HR: 1.24; 95% CI: 1.06–1.45; p = 0.007), PVD (fully‐adjusted HR: 1.60; 95% CI: 1.27–2.03; p = 0.003) and PE (fully‐adjusted HR: 1.72; 95% CI: 1.28–2.32; p < 0.008). Patients with BP experienced heightened risk of all‐cause mortality in the presence of comorbid MI (fully‐adjusted HR: 1.61; 95% CI: 1.44–1.81; p < 0.001), CVA (fully‐adjusted HR: 1.70; 95% CI: 1.52–1.89; p < 0.001), PVD (fully‐adjusted HR: 1.38; 95% CI: 1.20–1.58; p < 0.001) and PE (fully‐adjusted HR: 1.44; 95% CI: 1.10–1.88; p = 0.007). The therapeutic approach utilized to manage BP did not significantly influence the risk of cardiovascular outcomes.BP is associated with an elevated risk of MI, CVA, PVD, PE and cardiovascular mortality. Primary, secondary and tertiary cardiovascular prevention measures should be implemented among patients with BP. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) is a progressive disease marked by pulmonary vascular remodeling and right ventricular failure. Inflammation and oxidative stress are critical in PH pathogenesis, with early pulmonary vascular inflammation preceding vascular remodeling. Extracellular superoxide dismutase (EC-SOD), a key vascular antioxidant enzyme, mitigates oxidative stress and protects against inflammation and fibrosis in diverse lung and vascular disease models. This study utilizes a murine hypobaric hypoxia model to investigate the role of lung EC-SOD on hypoxia-induced platelet activation and platelet lung accumulation, a critical factor in PH-related inflammation. We found that lung EC-SOD overexpression blocked hypoxia-induced platelet activation and platelet accumulation in the lung. Though lung EC-SOD overexpression increased lung EC-SOD content, it did not impact plasma extracellular SOD activity. However, ex vivo, exogenous extracellular SOD treatment specifically blunted convulxin-induced platelet activation but did not blunt platelet activation with thrombin or ADP. Our data identify platelets as a novel target of EC-SOD in response to hypoxia, providing a foundation to advance the understanding of dysregulated redox signaling and platelet activation in PH and other chronic hypoxic lung diseases. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusions The clinical utility of pulmonary hypertension (PH) risk scores in non‐group 1 PH with pulmonary vascular disease (PVD) remains unresolved.We utilized the prospective multicenter PVDOMICS cohort with group 2, 3, 4 or 5 PH‐related PVD and calculated group 1 PH risk scores (REVEAL 2.0, REVEAL Lite 2, French registry score and COMPERA 2). The c‐statistic to predict death was compared separately in (i) pre‐capillary PH groups 3/4/5, and (ii) combined post‐ and pre‐capillary PH group 2. Exercise right heart catheterization reserve, ventricular interdependence and right ventricular–pulmonary artery (RV‐PA) coupling were compared across risk categories. Among 449 individuals with group 3/4/5 PH, the REVEAL 2.0 risk score had the highest c‐statistic for predicting death (0.699, 95% confidence interval [CI] 0.660–0.737, p < 0.0001) with comparable performance using the simpler REVEAL Lite 2 score (0.695, 95% CI 0.656–0.734, p < 0.0001). The French and COMPERA 2 risk scores were also predictive of mortality, but performance of both was statistically inferior to REVEAL 2.0 (c‐statistic difference −0.072, 95% CI −0.123 to −0.020, p = 0.006, and −0.043, 95% CI −0.067 to −0.018, p = 0.0007, respectively). RV function and RV‐PA coupling measures were prognostic in isolation, but did not add incremental value to REVEAL (p > 0.50 for all). Findings were similar in patients with group 2 PH (n = 239). Stratification by the REVEAL Lite 2 score non‐invasively identified non‐group 1 PH with more advanced PVD with worse exercise capacity, RV‐PA uncoupling, ventricular interdependence and impaired cardiac output reserve (p < 0.05 for all).Non‐invasive REVEAL risk predicts mortality in non‐group 1 PH without incremental prognostic value from detailed RV function or RV‐PA coupling assessment. Baseline REVEAL Lite 2 risk stratification non‐invasively identifies greater pulmonary vascular dysfunction and right heart‐related exercise limitation, which may help guide patient selection for targeted pulmonary vascular therapies in non‐group 1 PH. [ABSTRACT FROM AUTHOR]

Background: Pulmonary vascular disease (PVD) and pulmonary hypertension (PH) is a significant disorder affecting prognosis of extremely preterm infants. However, there is still a lack of a consensus on the definition and optimal treatments of PH, and there is also a lack of research comparing these conditions with persistent pulmonary hypertension of newborn (PPHN), early PH, and late PH. To investigate PH in extremely preterm infants, this study compared the baseline characteristics, short-term outcomes, and treatment duration, categorized by the timing of requiring PH treatment. Methods: This study retrospectively analyzed extremely preterm infants admitted to a single tertiary center. Between 2018 and 2022, infants with clinical or echocardiographic diagnosis of PH who required treatment were divided into three groups based on the timing of treatment initiation: initial 3 days (extremely early-period), from day 4 to day 27 (early-period), and after day 28 (late-period). The study compared the outcomes, including mortality rates, bronchopulmonary dysplasia (BPD) severity, PH treatment duration, and oxygen therapy duration, among the three groups. Results: Among the 157 infants, 67 (42.7%) were treated for PH during their stay. Of these, 39 (57.3%) were treatment in extremely early, 21 (31.3%) in early, and seven (11.4%) in late periods. No significant differences were observed in maternal factors, neonatal factors, or morbidity between the three groups. However, infants who received extremely early-period treatment had a higher mortality rate, but shorter duration of noninvasive respiratory support, oxygen therapy, and PH medication use. On the other hand, the late-period treatment group received longer durations of respiratory support and treatment. Conclusions: This study revealed differences in mortality rates, respiratory outcomes, and treatment duration between the three groups, suggesting varying pathophysiologies over time in extremely preterm infants. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to evaluate the clinical significance of secondary mitral regurgitation (MR) in patients with heart failure with preserved ejection fraction (HFpEF). Methods and results: We conducted a prospective study enrolling consecutively evaluated patients with HFpEF undergoing invasive haemodynamic exercise testing with simultaneous echocardiography. Compared to HFpEF without MR (n = 145, 79.7%), those with mild or moderate MR (n = 37, 20.3%) were older, more likely to be women, had more left ventricular (LV) systolic dysfunction, and more likely to have left atrial (LA) myopathy reflected by greater burden of atrial fibrillation, more LA dilatation, and poorer LA function. Pulmonary artery (PA) wedge pressure was higher at rest in HFpEF with MR (17 ± 5 mmHg vs. 20 ± 5 mmHg, p = 0.005), but there was no difference with exercise. At rest, only 2 (1.1%) patients had moderate MR, and none developed severe MR. Pulmonary vascular resistance was higher, and right ventricular (RV)‐PA coupling was more impaired in patients with HFpEF and MR at rest and exercise. LV and LA myocardial dysfunction remained more severe in patients with MR during stress compared to those without MR, characterized by greater LA dilatation during all stages of exertion, lower LA emptying fraction and compliance, steeper and rightward‐shifted LA pressure–volume relationships, and reduced LV longitudinal contractile function. Conclusions: Patients with HFpEF and mild or moderate MR have more severe LV systolic dysfunction, LA myopathy, RV‐PA uncoupling, and more severe pulmonary vascular disease. Mitral valve incompetence in this setting is a phenotypic marker of more advanced disease but is not a causal factor in development of HFpEF. [ABSTRACT FROM AUTHOR]

Background: Oscillating x‐ray attenuation in the lungs provides an opportunity to evaluate pulmonary perfusion without contrast. Recent intensity‐based methods have been compared to pulmonary scintigraphy and CT angiography but lack rigorous phantom studies. Purpose: A new method to quantify the periodic signal amplitude was employed using spectral analysis. Performance was characterized using a water phantom capable of creating an oscillating x‐ray attenuation at physiologic amplitudes. Feasibility in detecting abnormal perfusion was performed on a volunteer with pulmonary vascular disease and compared to pulmonary angiography, the clinical gold standard. Methods: For each fluoroscopic acquisition, the normalized temporal signal from each pixel was decomposed into its frequency components using Fourier transformation, and the spectral amplitude, defined as the x‐ray pulsatility index (XPI), was determined at the desired frequency using a band‐pass filter. XPI was displayed as a pixel‐wise parametric colormap. Based on XPI maps generated using two human volunteers, a water bath phantom was constructed with a fluctuating fluid height and a 1 cm diameter pulsatility defect. Contrast‐to‐noise (CNR) of the defect was measured using fluoroscopy images acquired at variable fluid height fluctuation (0.1–1.9 mm) and oscillation frequency (30–60 bpm). Various sampling frame rates (3–30 fps) and acquisition durations (1.8–8 s) using truncated datasets were reconstructed from full datasets. Fluoroscopic images were obtained in a patient just prior to pulmonary angiography in the same projection. Results: XPI maps in human subjects showed high signal to background contrast with high central XPI measuring up to 0.5. Phantom experiments revealed CNR was linearly correlated to fluid height change (r2 = 0.998). CNR is proportional to increasing sampling frame rate and increasing acquisition duration as expected with Fourier analysis. XPI map displayed multifocal perfusion defects in good agreement with pulmonary angiography. Conclusion: Spectral analysis is an accurate and sensitive method to detect small changes in periodic x‐ray attenuation using a short fluoroscopic acquisition. This method demonstrated good agreement to pulmonary angiography and shows promise for clinical imaging of pulmonary perfusion using standard fluoroscopic methods. [ABSTRACT FROM AUTHOR]

Long term home oxygen therapy for children is defined as oxygenotherapy outside hospital environment dedicated for patients with lung diseases, diseases of pulmonary vascular system and diseases of the thoracic wall (ventilation) suffering from chronic respiratory insufficiency of type 1. This review represents the second one of two articles on long-term home oxygen therapy (LTOT) in the Czech Republic, with a focus on the indication criteria for home oxygen therapy in children with chronic respiratory conditions. The review outlines the criteria based on the practice guidelines of the American Thoracic Society (ATS) and the British Thoracic Society (BTS), as well as specific indication criteria in the Czech Republic recommended by health insurance companies. Additionally, the review addresses practical aspects of LTOT, including the types of home oxygen devices, at-home patient follow-up, and indications for weaning off LTOT. [ABSTRACT FROM AUTHOR]

Background: Adaptive immunity is an important disease mediator of pulmonary vascular remodeling during pulmonary hypertension (PH) development, especially T‐cells lymphocytes. However, data for bibliometric analysis of T cell immunity in PH is currently vacant. This aimed to provide a comprehensive and visualized view of T‐cells research in PH pathogenesis and to lay a solid foundation for further studies. Methods: The data was acquired from the Web of Science Core Collection database. Web of Science analytic tool was used to analysis the publication years, authors, journals, countries, and organizations. CiteSpace 6.2.R3, VOSviewer 1.6.16, and Scimago Graphica 1.0.35.0 were applied to conduct a visualization bibliometric analysis about authors, countries, institutions, journals, references, and keywords. Results: Nine hundred and eight publications from 1992 to 2022 were included in the analysis. The results showed that Humbert Marc was the most prolific author. American Journal of Physiology Lung Cellular and Molecular Physiology had the most related articles. The institution with the most articles was Udice French Research University. The United States was far ahead in the article output. Keywords analysis showed that "Pulmonary hypertension" was the most usually appeared keyword in the relevant literature, and included "T‐cells", "Regulatory T cells", and "Activated T cell." "miRNA" of reference co‐citation clustering analysis demonstrated the possible T‐cell immunity activation mechanisms in PH. The most cited literature was published in the European Heart Journal by Galie N in 2016. The strongest citation burst of keyword is "gene expression" and terms such as "vascular remodeling," "growth," "proliferation," and "fibrosis" are among the list, indicating that T‐cells interact with stromal vascular cells to induce pulmonary vascular remodeling. The strongest burst of cited reference is "Galie N, 2016." Conclusions: T‐cell immunity is an important pathogenesis mechanism for PH development, which may have interaction with miRNAs and stromal vascular cells, but the possible T‐cell immunity activation mechanisms in PH need to be investigated further. [ABSTRACT FROM AUTHOR]

In recent years, metabolomics, the systematic study of small-molecule metabolites in biological samples, has yielded fresh insights into the molecular determinants of pulmonary diseases and critical illness. The purpose of this article is to orient the reader to this emerging field by discussing the fundamental tenets underlying metabolomics research, the tools and techniques that serve as foundational methodologies, and the various statistical approaches to analysis of metabolomics datasets. We present several examples of metabolomics applied to pulmonary and critical care medicine to illustrate the potential of this avenue of research to deepen our understanding of pathophysiology. We conclude by reviewing recent advances in the field and future research directions that stand to further the goal of personalizing medicine to improve patient care. [ABSTRACT FROM AUTHOR]

Background: Aneurysms of the pulmonary arteries and the ascending aorta are rare, and both bear a high mortality risk if left untreated. In general, these entities are primarily caused by etiologies such as hypertension, pulmonary arterial hypertension, infection or congenital disorders. Treatment requires a rapid diagnostic work-up or even immediate surgical intervention in acute cases. Nevertheless, surgery entails serious perioperative risks, in particular in patients with multiple comorbidities. Case presentation: We discuss a 70-year-old woman presented with decompensated heart failure based on severe pulmonary artery hypertension, coincided by a massive pulmonary artery aneurysm with secondary embolism. Additional diagnostic imaging also showed a chronic post-dissection, saccular aneurysm of the ascending aorta. To our knowledge, this simultaneous diagnosis of a saccular aneurysm of the ascending aorta and a large aneurysm of the pulmonary artery with secondary embolism has not yet been described. Nonetheless, conservative treatment was chosen due to extensive pulmonal and cardiovascular comorbidities and the high-risk profile of surgery. Conclusions: Extensive aneurysmatic disease of the pulmonary arteries and ascending aorta come with a serious burden of disease, especially if coincided by severe pulmonal and cardiovascular comorbidities. Both conditions can be curatively treated by surgical intervention. However, in every case the risk of surgery and the patient's vitality, comorbidities and wishes should be taken into account to formulate an adequate treatment plan. Therefore, shared decision making is of utter importance. [ABSTRACT FROM AUTHOR]

Advances in perinatal intensive care have significantly enhanced the survival rates of extremely low gestation-al-age neonates but with continued high rates of bronchopulmonary dysplasia (BPD). Nevertheless, as the survival of these infants improves, there is a growing awareness of associated abnormalities in pulmonary vascular development and hemodynamics within the pulmonary circulation. Premature infants, now born as early as 22 weeks, face heightened risks of adverse development in both pulmonary arterial and venous systems. This risk is compounded by parenchymal and airway abnormalities, as well as factors such as inflammation, fibrosis, and adverse growth trajectory. The presence of pulmonary hypertension in bronchopulmonary dysplasia (BPD-PH) has been linked to an increased mortality and substantial morbidities, including a greater susceptibility to later neurodevelopmental challenges. BPD-PH is now recognized to be a spectrum of disease, with a multifactorial pathophysiology. This review discusses the challenges associated with the identification and management of BPD-PH, both of which are important in minimizing further disease progression and improving cardiopulmonary morbidity in the BPD infant. [ABSTRACT FROM AUTHOR]

Systemic sclerosis is a multisystem connective tissue disease that is associated with substantial morbidity and mortality. Visceral organ involvement is common in patients with systemic sclerosis and occurs independently of skin manifestations. Pulmonary hypertension (PH) is an important and prevalent complication of systemic sclerosis. The clinical classification of PH cohorts conditions with similar pathophysiological mechanisms into one of five groups. While patients with systemic sclerosis can manifest with a spectrum of pulmonary vascular disease, notable clinical groups include group 1 pulmonary arterial hypertension (PAH) associated with connective tissues disease, PAH with features of capillary/venous involvement, group 2 PH associated with left heart disease, and group 3 PH associated with interstitial lung disease. Considerable efforts have been made to advance screening methods for PH in systemic sclerosis including the DETECT and ASIG (Australian Scleroderma Interest Group) composite algorithms. Current guidelines recommend annual assessment of the risk of PAH as early recognition may result in attenuated hemodynamic impairment and improved survival. The treatment of PAH associated with systemic sclerosis requires a multidisciplinary team including a PH specialist and a rheumatologist to optimize immunomodulatory and PAH-specific therapies. Several potential biomarkers have been identified and there are several promising PAH therapies on the horizon such as the novel fusion protein sotatercept. This chapter provides an overview of PH in systemic sclerosis, with a specific focus on group 1 PAH. [ABSTRACT FROM AUTHOR]

BACKGROUND: Pulmonary vascular disease (PVD) is a major determinant of both morbidity and mortality in extremely low birth weight infants. It is biologically plausible that postnatal cytomegalovirus (pCMV) infection may lead to PVD in premature infants secondary to pneumonitis or via derangement of pulmonary vascular development directly through endothelial dysfunction. Uncertainty remains, however, regarding thresholds for intervention in premature infants with cardiorespiratory instability and presumed CMV infection likely secondary to the limited understanding of the natural history of the disease. METHODS/RESULTS: We describe four cases of premature infants with clinical and echocardiography features of PVD, in the setting of postnatally acquired CMV. All patients had atypical PVD trajectories, refractory to vasodilator treatment, which improved after initiation of CMV treatment. CONCLUSION: We highlight the need to consider postnatally acquired CMV infection in patients with PVD non-responsive to standard pulmonary vasodilator therapies or disease severity which is out of proportion of the usual clinical trajectory. Treatment of extremely premature infants with CMV-associated PVD may have positive impact on cardiorespiratory health, although duration of therapy remains uncertain. [ABSTRACT FROM AUTHOR]

Adult patients with congenital heart disease have now surpassed the pediatric population due to advances in surgery and improved survival. One such complex congenital heart disease seen in adult patients is the Fontan circulation. These patients have complex physiology and are at risk for several complications, including thrombosis of the Fontan pathway, pulmonary vascular disease, heart failure, atrial arrhythmias, atrioventricular valve regurgitation, and protein-losing enteropathy. This review discusses the commonly encountered phenotypes of Fontan circulatory failure and their contemporary management. [ABSTRACT FROM AUTHOR]

Health-related quality of life (HRQOL) is frequently impaired in pulmonary arterial hypertension. However, little is known about HRQOL in other forms of pulmonary hypertension (PH). Does HRQOL vary across groups of the World Symposium on Pulmonary Hypertension (WSPH) classification system? This cross-sectional study included patients with PH from the Pulmonary Vascular Disease Phenomics (PVDOMICS) cohort study. HRQOL was assessed by using emPHasis-10 (e-10), the 36-item Medical Outcomes Study Short Form survey (physical component score [PCS] and mental component score), and the Minnesota Living with Heart Failure Questionnaire. Pearson correlations between HRQOL and demographic, physiologic, and imaging characteristics within each WSPH group were tested. Multivariable linear regressions compared HRQOL across WSPH groups, adjusting for demographic characteristics, disease prevalence, functional class, and hemodynamics. Cox proportional hazards models were used to assess associations between HRQOL and survival across WSPH groups. Among 691 patients with PH, HRQOL correlated with functional class and 6-min walk distance but not hemodynamics. HRQOL was severely depressed across WSPH groups for all measures except the 36-item Medical Outcomes Study Short Form survey mental component score. Compared with Group 1 participants, Group 2 participants had significantly worse HRQOL (e-10 score, 29 vs 24 [ P =.001]; PCS, 32.9 ± 8 vs 38.4 ± 10 [ P <.0001]; and Minnesota Living with Heart Failure Questionnaire score, 50 vs 38 [ P =.003]). Group 3 participants similarly had a worse e-10 score (31 vs 24; P <.0001) and PCS (33.3 ± 9 vs 38.4 ± 10; P <.0001) compared with Group 1 participants, which persisted in multivariable models (P <.05). HRQOL was associated in adjusted models with survival across Groups 1, 2, and 3. HRQOL was depressed in PH and particularly in Groups 2 and 3 despite less severe hemodynamics. HRQOL is associated with functional capacity, but the severity of hemodynamic disease poorly estimates the impact of PH on patients' lives. Further studies are needed to better identify predictors and treatments to improve HRQOL across the spectrum of PH. [ABSTRACT FROM AUTHOR]

Pediatric lung transplantation represents a treatment option for children with advanced lung disease or pulmonary vascular disorders who are deemed an appropriate candidate. Pediatric flexible bronchoscopy is an important and evolving field that is highly relevant in the pediatric lung transplant population. It is thus important to advance our knowledge to better understand how care for children after lung transplant can be maximally optimized using pediatric bronchoscopy. Our goals are to continually improve procedural skills when performing bronchoscopy and to decrease the complication rate while acquiring adequate samples for diagnostic evaluation. Attainment of these goals is critical since allograft assessment by bronchoscopic biopsy is required for histological diagnosis of acute cellular rejection and is an important contributor to establishing chronic lung allograft dysfunction, a common complication after lung transplant. Flexible bronchoscopy with bronchoalveolar lavage and transbronchial lung biopsy plays a key role in lung transplant graft assessment. In this article, we discuss the application of bronchoscopy in pediatric lung transplant evaluation including historical approaches, our experience, and future directions not only in bronchoscopy but also in the evolving pediatric lung transplantation field. Pediatric flexible bronchoscopy has become a vital modality for diagnosing lung transplant complications in children as well as assessing therapeutic responses. Herein, we review the value of flexible bronchoscopy in the management of children after lung transplant and discuss the application of novel techniques to improve care for this complex pediatric patient population and we provide a brief update about new diagnostic techniques applied in the growing lung transplantation field. [ABSTRACT FROM AUTHOR]

The substantial computational cost of high‐fidelity models in numerical hemodynamics has, so far, relegated their use mainly to offline treatment planning. New breakthroughs in data‐driven architectures and optimization techniques for fast surrogate modeling provide an exciting opportunity to overcome these limitations, enabling the use of such technology for time‐critical decisions. We discuss an application to the repair of multiple stenosis in peripheral pulmonary artery disease through either transcatheter pulmonary artery rehabilitation or surgery, where it is of interest to achieve desired pressures and flows at specific locations in the pulmonary artery tree, while minimizing the risk for the patient. Since different degrees of success can be achieved in practice during treatment, we formulate the problem in probability, and solve it through a sample‐based approach. We propose a new offline–online pipeline for probabilistic real‐time treatment planning which combines offline assimilation of boundary conditions, model reduction, and training dataset generation with online estimation of marginal probabilities, possibly conditioned on the degree of augmentation observed in already repaired lesions. Moreover, we propose a new approach for the parametrization of arbitrarily shaped vascular repairs through iterative corrections of a zero‐dimensional approximant. We demonstrate this pipeline for a diseased model of the pulmonary artery tree available through the Vascular Model Repository. [ABSTRACT FROM AUTHOR]

Aim: To assess cause‐specific death in patients with heart failure with preserved, mildly reduced, and reduced ejection fraction (HFpEF, HFmrEF, and HFrEF). Methods and results: Data were analysed from the Swedish Heart Failure Registry (SwedeHF) and the National Patient Register of patients enrolled in SwedeHF 2000–2021. Cox proportional hazards regression models were performed and adjusted for age, sex and time period. Among 100 584 patients (23% HFpEF, 23% HFmrEF, 53% HFrEF), median age (interquartile range) was 75 (66–82) and 36% were female. Of those who died within 5 years, most deaths were ascribed to cardiovascular (CV) causes across all ejection fraction (EF) categories. Within 5 years, HFpEF had higher adjusted risk of non‐CV death (hazard ratio [HR] 1.33, 95% confidence interval [CI] 1.28–1.38, p < 0.001) and lower adjusted risk of CV death (HR 0.85, 95% CI 0.82–0.88, p < 0.001) compared to HFrEF. Ischaemic heart disease (IHD) and cancer were the most common causes of CV and non‐CV death regardless of EF category. The incidence rate of CV death due to IHD was highest in HFrEF while incidence rates of CV death due to pulmonary vascular disease, stroke, valvular heart disease and atrial fibrillation increased with increasing EF. The incidence rates of non‐CV deaths due to cancer, respiratory disease, and infections increased with increasing EF. Conclusion: Cardiovascular death was more common than non‐CV death across all EF categories although the risk of non‐CV death within 5 years was higher with increasing EF. IHD and cancer were the most common causes of CV and non‐CV deaths, respectively, regardless of EF category. [ABSTRACT FROM AUTHOR]

Several parameters of widely used risk assessment tools for pulmonary arterial hypertension (PAH) have been linked to hemodynamic outcomes of balloon pulmonary angioplasty (BPA). Therefore, we aimed to determine whether these risk assessment tools could be used to predict hemodynamic outcomes following BPA. In this retrospective study, we included 139 patients with chronic thromboembolic pulmonary hypertension who had undergone BPA at Center for Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College (Beijing, China). We compared the accuracies of seven well-validated risk assessment tools for predicting hemodynamic outcomes following BPA. A favorable hemodynamic outcome was defined as a mean pulmonary arterial pressure < 30 mmHg at follow-up. The baseline risk profiles varied significantly among the risk assessment tools. The US Registry to Evaluate Early and Long-Term PAH Disease Management risk scales and the French risk assessment tools rated most patients as high-risk, while the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) series and laboratory examination-based risk scales categorized most patients as having intermediate-risk profile. COMPERA 2.0 (4-strata) exhibited the highest predictive power among all risk stratifications. Noninvasive risk stratification (COMPERA 2.0 [3-strata]) showed a comparable predictive ability to that of invasive risk stratification (COMPERA 1.0) (area under the curve 0.649 vs. 0.648). Moreover, incorporating diffusing capacity of the lungs for carbon monoxide and tricuspid regurgitation velocity into COMPERA 2.0 (4-strata) further enhanced its predictive power (net reclassification index 0.153, 95% confidence interval 0.009–0.298, p = 0.038). Additionally, this refined COMPERA version had a high calibration accuracy (slope 0.96). Although the risk strata distribution varied among different risk assessment tools, the proportion of patients achieving favorable hemodynamics decreased with the escalation of risk stratification in most models. The well-validated risk assessment tools for PAH could also predict hemodynamic outcomes following BPA, and the refined COMPERA 2.0 model exhibited the highest predictive ability among these. Applying risk assessment tools before BPA can facilitate early identification of patients in need of closer monitoring and more intensive interventions, contributing to a better prognosis after BPA. [ABSTRACT FROM AUTHOR]

Introduction: Hypoxia is a common pathological driver contributing to various forms of pulmonary vascular diseases leading to pulmonary hypertension (PH). Pulmonary interstitialmacrophages (IMs) play pivotal roles in immune and vascular dysfunction, leading to inflammation, abnormal remodeling, and fibrosis in PH. However, IMs' response to hypoxia and their role in PH progression remain largely unknown. We utilized a murine model of hypoxia-induced PH to investigate the repertoire and functional profiles of IMs in response to acute and prolonged hypoxia, aiming to elucidate their contributions to PH development. Methods: We conducted single-cell transcriptomic analyses to characterize the repertoire and functional profiles of murine pulmonary IMs following exposure to hypobaric hypoxia for varying durations (0, 1, 3, 7, and 21 days). Hallmark pathways from the mouse Molecular Signatures Database were utilized to characterize the molecular function of the IM subpopulation in response to hypoxia. Results: Our analysis revealed an early acute inflammatory phase during acute hypoxia exposure (Days 1-3), which was resolved by Day 7, followed by a proremodeling phase during prolonged hypoxia (Days 7-21). These phases were marked by distinct subpopulations of IMs: MHCIIhiCCR2+EAR2+ cells characterized the acute inflammatory phase, while TLF+VCAM1hi cells dominated the pro-remodeling phase. The acute inflammatory phase exhibited enrichment in interferon-gamma, IL-2, and IL-6 pathways, while the proremodeling phase showed dysregulated chemokine production, hemoglobin clearance, and tissue repair profiles, along with activation of distinct complement pathways. Discussion: Our findings demonstrate the existence of distinct populations of pulmonary interstitial macrophages corresponding to acute and prolonged hypoxia exposure, pivotal in regulating the inflammatory and remodeling phases of PH pathogenesis. This understanding offers potential avenues for targeted interventions, tailored to specific populations and distinct phases of the disease. Moreover, further identification of triggers for pro-remodeling IMs holds promise in unveiling novel therapeutic strategies for pulmonary hypertension. [ABSTRACT FROM AUTHOR]

Background: Pulmonary hypertension (PH) is a leading cause of death in patients with systemic sclerosis (SSc). An important component of SSc patient management is early detection and treatment of PH. Recently the threshold for the diagnosis of PH has been lowered to a mean pulmonary artery pressure (mPAP) threshold of > 20 mmHg on right heart catheterization (RHC). However, it is unknown if PH-specific therapy is beneficial in SSc patients with mildly elevated pressure (SSc-MEP, mPAP 21–24 mmHg). Methods: The SEPVADIS trial is a randomized, double-blind, placebo-controlled phase 2 trial of sildenafil in SSc-MEP patients with a target enrollment of 30 patients from two academic sites in the United States. The primary outcome is change in six-minute walk distance after 16 weeks of treatment. Secondary endpoints include change in pulmonary arterial compliance by RHC and right ventricular function by cardiac magnetic resonance imaging at 16 weeks. Echocardiography, serum N-terminal probrain natriuretic peptide, and health-related quality of life is being measured at 16 and 52 weeks. Discussion: The SEPVADIS trial will be the first randomized study of sildenafil in SSc-MEP patients. The results of this trial will be used to inform a phase 3 study to investigate the efficacy of treating patients with mild elevations in mPAP. Trial registration: ClinicalTrials.gov Identifier NCT04797286. [ABSTRACT FROM AUTHOR]

Background: Pulmonary hypertension (PH) is a progressive disorder characterized by elevated pulmonary arterial pressure. It is caused by a multitude of intrinsic and extrinsic pulmonary vascular disease processes that cause hemodynamic alterations which overcome the normal pulmonary vaso regulatory mechanisms. PH is diagnosed when the mean pulmonary artery pressure (mPAP) is =25 mmHg at rest in right heart catheterization (RHC). Pulmonary hypertension (PH) in patients with interstitial lung diseases (ILDs) is not well recognized and can occur in the absence of advanced pulmonary dysfunction or hypoxemia. Methodology: The above study was conducted at the tertiary care hospital, department of radiology on total of 130 patients. Patients fulfilling the inclusion criteria were selected for the study. HRCT was performed. All patients were scanned from lung apices to lung bases at full suspended inspiration using standard exposure parameters (90 mA and 120kVp) in a single breath hold. The results were analyzed, studied and also compared with similar studies of the past with elucidation of the diseases where HRCT gave a specific diagnosis. Results: The mean size of main or central pulmonary arterial diameter(dPA) is 27.16±3.96, ratio between main pulmonary and aorta diameter(rPA) is 9.53±1.43, right pulmonary arterial diameter (RPAD) 19.62±3.02 and left pulmonary arterial diameter (LPAD) is 18.77±3.63. Conclusion: Main pulmonary artery is dilated more in smoking related lung disease than the rest of the Interstitial Lung disease. [ABSTRACT FROM AUTHOR]

There is an association between hyperthyroidism and pulmonary hypertension. However, the prevalence of pulmonary hypertension in hyperthyroidism and the underlying mechanisms are incompletely defined. Consecutive patients with severe hyperthyroidism, mostly due to Graves disease, were included in this single-center study. Echocardiographic assessment of pulmonary hemodynamics was performed at the time of hyperthyroidism diagnosis (baseline) and after normalization of thyroid hormones (follow-up; median 11 months). In a subset of patients, right heart catheterization and noninvasive assessment of central hemodynamics was performed. Among all 99 patients, 31% had pulmonary hypertension at baseline. The estimated systolic pulmonary artery pressure correlated significantly with the estimated left ventricular filling pressure (E/e′). The invasively measured systolic pulmonary artery pressure correlated well with the estimated systolic pulmonary artery pressure. Cardiac output, E/e′, left and right ventricular dimensions were significantly reduced from baseline to follow-up, whereas the estimated pulmonary vascular resistance did not differ. Diastolic blood pressure was significantly higher at follow-up, with no change in systolic blood pressure. The central systolic blood pressure, however, exhibited a trend for a reduction at follow-up, while the pulse wave velocity was significantly lower at follow-up. Approximately one-third of patients with hyperthyroidism have evidence of pulmonary hypertension. Our data suggest that an increased cardiac output and left ventricular filling pressure are the main mechanisms underlying the elevated systolic pulmonary artery pressure in hyperthyroidism, whereas there is no evidence of significant pulmonary vascular disease. [ABSTRACT FROM AUTHOR]

Pollution and climate change constitute a combined, grave and pervasive threat to humans and to the life‐support systems on which they depend. Evidence shows a strong association between pollution and climate change on cardiovascular and respiratory diseases, and pulmonary vascular disease (PVD) is no exception. An increasing number of studies has documented the impact of environmental pollution and extreme temperatures on pulmonary circulation and the right heart, on the severity and outcomes of patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (PH), on the incidence of pulmonary embolism, and the prevalence and severity of diseases associated with PH. Furthermore, the downstream consequences of climate change impair health care systems' accessibility, which could pose unique obstacles in the case of PVD patients, who require a complex and sophisticated network of health interventions. Patients, caretakers and health care professionals should thus be included in the design of policies aimed at adaptation to and mitigation of current challenges, and prevention of further climate change. The purpose of this review is to summarize the available evidence concerning the impact of environmental pollution and climate change on the pulmonary circulation, and to propose measures at the individual, healthcare and community levels directed at protecting patients with PVD. [ABSTRACT FROM AUTHOR]

Lung transplantation remains an important therapeutic option for idiopathic pulmonary arterial hypertension (IPAH), yet short‐term survival is the poorest among the major diagnostic categories. We sought to develop a prediction model for 90‐day mortality using the United Network for Organ Sharing database for adults with IPAH transplanted between 2005 and 2021. Variables with a p value ≤ 0.1 on univariate testing were included in multivariable analysis to derive the best subset model. The cohort comprised 693 subjects, of whom 71 died (10.2%) within 90 days of transplant. Significant independent predictors of early mortality were: extracorporeal circulatory support and/or mechanical ventilation at transplant (OR: 3; CI: 1.4–5), pulmonary artery diastolic pressure (OR: 1.3 per 10 mmHg; CI: 1.07–1.56), forced expiratory volume in the first second percent predicted (OR: 0.8 per 10%; CI: 0.7–0.94), recipient total bilirubin >2 mg/dL (OR: 3; CI: 1.4–7.2) and ischemic time >6 h (OR: 1.7, CI: 1.01–2.86). The predictive model was able to distinguish 25% of the cohort with a mortality of ≥20% from 49% with a mortality of ≤5%. We conclude that recipient variables associated with increasing severity of pulmonary vascular disease, including pretransplant advanced life support, and prolonged ischemic time are important risk factors for 90‐day mortality after lung transplant for IPAH. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH, or PH Group 1), a disease of aberrant pulmonary vascular remodeling, causing progressive right heart failure (RHF) due to elevation of pulmonary vascular resistance (PVR). Patient mortality risk stratification guides choice and intensity of pharmacological intervention and is assessed by haemodynamics (especially PVR) as well as noninvasive tools including WHO functional class (FC), 6‐min walk distance (6MWD), and NT‐proBNP levels. Quality of life (QOL) assessment is acknowledged as a central aspect of patient‐centered care, but our study sought to extend QOL's role as an additional noninvasive risk marker that could further refine risk stratification and hence therapeutic choices within a "treatment to target" paradigm (aiming to achieve low‐risk status). This study found that QOL assessment using the PAH‐SYMPACT© physical activity tool provided enhanced, independent mortality risk information, with one unit rise in this score associated with a 41% increase in likelihood risk (odds ratio 1.41, 95% confidence interval: 1.01–1.98 (p < 0.05)) of falling within intermediate versus low‐group category. We therefore found further support for additional prognostic value being conferred by measurement of QOL as part of routine PAH evaluation, reinforcing its critical role. [ABSTRACT FROM AUTHOR]

Purpose: The interaction between 129Xe atoms and pulmonary capillary red blood cells provides cardiogenic signal oscillations that display sensitivity to precapillary and postcapillary pulmonary hypertension. Recently, such oscillations have been spatially mapped, but little is known about optimal reconstruction or sensitivity to artifacts. In this study, we use digital phantom simulations to specifically optimize keyhole reconstruction for oscillation imaging. We then use this optimized method to re‐establish healthy reference values and quantitatively evaluate microvascular flow changes in patients with chronic thromboembolic pulmonary hypertension (CTEPH) before and after pulmonary thromboendarterectomy (PTE). Methods: A six‐zone digital lung phantom was designed to investigate the effects of radial views, key radius, and SNR. One‐point Dixon 129Xe gas exchange MRI images were acquired in a healthy cohort (n = 17) to generate a reference distribution and thresholds for mapping red blood cell oscillations. These thresholds were applied to 10 CTEPH participants, with 6 rescanned following PTE. Results: For undersampled acquisitions, a key radius of 0.14kmax$$ 0.14{k}_{\mathrm{max}} $$ was found to optimally resolve oscillation defects while minimizing excessive heterogeneity. CTEPH participants at baseline showed higher oscillation defect + low (32 ± 14%) compared with healthy volunteers (18 ± 12%, p < 0.001). For those scanned both before and after PTE, oscillation defect + low decreased from 37 ± 13% to 23 ± 14% (p = 0.03). Conclusions: Digital phantom simulations have informed an optimized keyhole reconstruction technique for gas exchange images acquired with standard 1‐point Dixon parameters. Our proposed methodology enables more robust quantitative mapping of cardiogenic oscillations, potentially facilitating effective regional quantification of microvascular flow impairment in patients with pulmonary vascular diseases such as CTEPH. [ABSTRACT FROM AUTHOR]

The Fontan procedure is the palliative procedure of choice for patients with single ventricle physiology. Pulmonary vascular disease (PVD) is an important contributor to Fontan circulatory failure. We review the pathophysiology of PVD in patients with Fontan palliation and share our initial experience with optical coherence tomography (OCT) in supplementing standard hemodynamics in characterizing Fontan-associated PVD. In the absence of a sub-pulmonary ventricle, low pulmonary vascular resistance (PVR; ≤2 WU/m2) is required to sustain optimal pulmonary blood flow. PVD is associated with adverse pulmonary artery (PA) remodeling resulting from the non-pulsatile low-shear low-flow circulation. Predisposing factors to PVD include impaired PA growth, endothelial dysfunction, hypercoagulable state, and increased ventricular end-diastolic pressure. OCT parameters that show promise in characterizing Fontan-associated PVD include the PA intima-to-media ratio and wall area ratio (i.e. difference between the whole-vessel area and the luminal area divided by the whole-vessel area). OCT carries potential in characterizing PVD in patients with Fontan palliation. PA remodeling is marked by intimal hyperplasia, with medial regression. Further studies are required to determine the role of OCT in informing management decisions and assessing therapeutic responses. [ABSTRACT FROM AUTHOR]

The European Society of Cardiology (ESC) Working Group on Pulmonary Circulation and Right Ventricular Function focuses on the assessment and management of severe forms of pulmonary hypertension (PH) and acute pulmonary embolism (PE). The working group aims to improve patient outcomes through a multidisciplinary approach and active involvement of patients. They provide education through various platforms and support early-career researchers. The working group collaborates with other societies to publish guidelines and position papers. The COVID-19 pandemic has led to changes in their operations, with remote educational meetings becoming more prominent. They have also established a network called EXPERT-PE to improve outcomes for severe acute PE patients. [Extracted from the article]

This article discusses the heterogeneity of heart failure with preserved ejection fraction (HFpEF) and the need for more practical phenotyping in this condition. The authors explore the cardiovascular-kidney-metabolic (CKM) comorbidities in HFpEF and their impact on clinical outcomes. They found that the majority of HFpEF patients have at least one CKM comorbidity, and a higher CKM burden is associated with worse clinical characteristics and outcomes. The authors propose a CKM model to guide therapy and improve shared decision-making in HFpEF patients. [Extracted from the article]

Transient perivascular inflammation of the carotid artery (TIPIC) is a rare vascular disease characterized by inflammation of the carotid artery, leading to thickening of the carotid wall and unilateral carotidynia. This case report presents a 48-year-old woman who was diagnosed with TIPIC syndrome in a rheumatology outpatient clinic. The patient experienced right neck pain and numbness in the right hand, accompanied by local tenderness and increased arterial pulse. Laboratory tests showed no abnormalities, and imaging studies revealed inflammatory processes in the carotid artery. TIPIC syndrome is a self-limiting condition with a good prognosis and can be treated with nonsteroidal anti-inflammatory drugs. It is important for healthcare providers to be aware of this syndrome to prevent unnecessary treatment and to differentiate it from systemic vasculitis. [Extracted from the article]

Background: : Veterinary knowledge regarding feline heartworm has been increasing significantly over the past two decades. Necropsy surveys of shelter cats have shown feline adult heartworm infection prevalence to be 5–20% of the rate in unprotected dogs; however, other studies have shown feline heartworm antibody prevalence up to 33%, reflecting higher exposure rates and potential immature adult infections. Thus, the true prevalence of feline heartworm infection is likely underestimated due to the limitations of current diagnostic techniques, inadequate testing protocols, and the high likelihood of cats exhibiting transient clinical signs or dying without confirmation of infection. Diagnosing Feline Heartworm Disease (FHWD), also referred to as Heartworm Associated Respiratory Disease (HARD), is one of the conundrums of veterinary medicine. The purpose of this study was to evaluate and characterize the occurrence of Heartworm Associated Respiratory Disease [HARD] in shelter cats, naturally-infected with D.immitis. Methods: Fifty shelter cats slated for euthanasia between December 2009 and June 2010 were investigated by gross necropsy, radiography, serology, and lung histopathology using techniques that have been established in experimental models of cat heartworm infection. The relationship between pulmonary vascular disease and serological markers for heartworm was also examined using correlations and statistical modeling. Serology included standard heartworm antigen test and a commonly used heartworm antibody test. Also included were heat-treated heartworm antigen test and two additional heartworm antibody tests previously evaluated on experimentally-infected cats. Results: None of the cats were heartworm antibody (HW Ab) positive on a commonly used HW Ab test used by many reference laboratories even though 20% of the study cats were heartworm antigen (HW Ag) positive on heat-treated samples. Two additional HW Ab test were positive on 26% and 22% of the study cats. The combination of heat-treated HW Ag, HW Ab tests, and histopathology indicated 34% of the study cats had HARD. Conclusions: Utilizing both, the above tests, and thoracic radiographs, enhanced the ability to predict vascular disease, possibly caused by infection with immature and adult heartworms and supported the premise that cats develop heartworm disease at the same rate as dogs. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) is a malignant disease with progressive increase of pulmonary vascular pressure, which eventually leads to right heart failure. More and more evidences show that immune cells and inflammation play an important role in the occurrence and development of PH. In the context of pulmonary vascular diseases, immune cells migrate into the walls of the pulmonary vascular system. This leads to an increase in the levels of cytokines and chemokines in both the bloodstream and the surrounding tissues of the pulmonary vessels. As a result, new approaches such as immunotherapy and anti-inflammatory treatments are being considered as potential strategies to halt or potentially reverse the progression of PH. We reviewed the potential mechanisms of immune cells, cytokines and chemokines in PH development. The potential relationship of vascular cells or bone morphogenetic protein receptor 2 (BMPR2) in immune regulation was also expounded. The clinical application and future prospect of immunotherapy were further discussed. [ABSTRACT FROM AUTHOR]

Background: Cardiac dysfunction from pulmonary vascular disease causes characteristic findings on cardiopulmonary exercise testing (CPET). We tested the accuracy of CPET for detecting inadequate stroke volume (SV) augmentation during exercise, a pivotal manifestation of cardiac limitation in patients with pulmonary vascular disease. Methods: We reviewed patients with suspected pulmonary vascular disease in whom CPET and right heart catheterization (RHC) measurements were taken at rest and at anaerobic threshold (AT). We correlated CPET-determined O2·pulseAT/O2·pulserest with RHC-determined SVAT/SVrest. We evaluated the sensitivity and specificity of O2·pulseAT/O2·pulserest to detect SVAT/SVrest below the lower limit of normal (LLN). For comparison, we performed similar analyses comparing echocardiographically-measured peak tricuspid regurgitant velocity (TRVpeak) with SVAT/SVrest. Results: From July 2018 through February 2023, 83 simultaneous RHC and CPET were performed. Thirty-six studies measured O2·pulse and SV at rest and at AT. O2·pulseAT/O2·pulserest correlated highly with SVAT/SVrest (r = 0.72, 95% CI 0.52, 0.85; p < 0.0001), whereas TRVpeak did not (r = -0.09, 95% CI -0.47, 0.33; p = 0.69). The AUROC to detect SVAT/SVrest below the LLN was significantly higher for O2·pulseAT/O2·pulserest (0.92, SE 0.04; p = 0.0002) than for TRVpeak (0.69, SE 0.10; p = 0.12). O2·pulseAT/O2·pulserest of less than 2.6 was 92.6% sensitive (95% CI 76.6%, 98.7%) and 66.7% specific (95% CI 35.2%, 87.9%) for deficient SVAT/SVrest. Conclusions: CPET detected deficient SV augmentation more accurately than echocardiography. CPET-determined O2·pulseAT/O2·pulserest may have a prominent role for noninvasive screening of patients at risk for pulmonary vascular disease, such as patients with persistent dyspnea after pulmonary embolism. [ABSTRACT FROM AUTHOR]

Aims: We aimed to clarify the extent to which cardiac and peripheral impairments to oxygen delivery and utilization contribute to exercise intolerance and risk for adverse events, and how this relates to diversity and multiplicity in pathophysiologic traits. Methods and results: Individuals with heart failure with preserved ejection fraction (HFpEF) and non‐cardiac dyspnoea (controls) underwent invasive cardiopulmonary exercise testing and clinical follow‐up. Haemodynamics and oxygen transport responses were compared. HFpEF patients were then categorized a priori into previously‐proposed, non‐exclusive descriptive clinical trait phenogroups, including cardiometabolic, pulmonary vascular disease, left atrial myopathy, and vascular stiffening phenogroups based on clinical and haemodynamic profiles to contrast pathophysiology and clinical risk. Overall, patients with HFpEF (n = 643) had impaired cardiac output reserve with exercise (2.3 vs. 2.8 L/min, p = 0.025) and greater reliance on peripheral oxygen extraction augmentation (4.5 vs. 3.8 ml/dl, p < 0.001) compared to dyspnoeic controls (n = 219). Most (94%) patients with HFpEF met criteria for at least one clinical phenogroup, and 67% fulfilled criteria for multiple overlapping phenogroups. There was greater impairment in peripheral limitations in the cardiometabolic group and greater cardiac output limitations and higher pulmonary vascular resistance during exertion in the other phenogroups. Increasing trait multiplicity within a given patient was associated with worse exercise haemodynamics, poorer exercise capacity, lower cardiac output reserve, and greater risk for heart failure hospitalization or death (hazard ratio 1.74, 95% confidence interval 1.08–2.79 for 0–1 vs. ≥2 phenogroup traits present). Conclusions: Though cardiac output response to exercise is limited in patients with HFpEF compared to those with non‐cardiac dyspnoea, the relative contributions of cardiac and peripheral limitations vary with differing numbers and types of clinical phenotypic traits present. Patients fulfilling criteria for greater multiplicity and diversity of HFpEF phenogroup traits have poorer exercise capacity, worsening haemodynamic perturbations, and greater risk for adverse outcome. [ABSTRACT FROM AUTHOR]

Aims Pulmonary hypertension (PH) is a pulmonary vascular disease characterized by a high mortality rate. Pulmonary arterial endothelium cells (PAECs) serve as a primary sensor of various environmental cues, such as shear stress and hypoxia, but PAEC dysfunction may trigger vascular remodelling during the onset of PH. This study aimed to illustrate the role of Sirtuin 7 (SIRT7) in endothelial dysfunction during PH and explore the potential therapeutic strategy for PH. Methods and results SIRT7 levels were measured in human and murine experimental PH samples. Bioinformatic analysis, immunoprecipitation, and deacetylation assay were used to identify the association between SIRT7 and Krüpple-like factor 4 (KLF4), a key transcription factor essential for endothelial cell (EC) homeostasis. Sugen5416 + hypoxia (SuHx)-induced PH mouse models and cell cultures were used for the study of the therapeutic effect of SIRT7 for PH. SIRT7 level was significantly reduced in lung tissues and PAECs from PH patients and the SuHx-induced PH mouse model as compared with healthy controls. Pulmonary endothelium-specific depletion of Sirt7 increased right ventricular systolic pressure and exacerbated right ventricular hypertrophy in the SuHx-induced PH model. At the molecular level, we identified KLF4 as a downstream target of SIRT7, which deacetylated KLF4 at K228 and inhibited the ubiquitination-proteasome degradation. Thus, the SIRT7/KLF4 axis maintained PAEC homeostasis by regulating proliferation, migration, and tube formation. PAEC dysfunction was reversed by adeno-associated virus type 1 vector-mediated endothelial overexpression of Sirt7 or supplementation with nicotinamide adenine dinucleotide (NAD)+ intermediate nicotinamide riboside which activated Sirt7; both approaches successfully reversed PH phenotypes. Conclusion The SIRT7/KLF4 axis ensures PAEC homeostasis, and pulmonary endothelium-specific SIRT7 targeting might constitute a PH therapeutic strategy. [ABSTRACT FROM AUTHOR]

"Lung perfusion" in the context of imaging conventionally refers to the delivery of blood to the pulmonary capillary bed through the pulmonary arteries originating from the right ventricle required for oxygenation. The most important physiological mechanism in the context of imaging is the so‐called hypoxic pulmonary vasoconstriction (HPV, also known as "Euler‐Liljestrand‐Reflex"), which couples lung perfusion to lung ventilation. In obstructive airway diseases such as asthma, chronic‐obstructive pulmonary disease (COPD), cystic fibrosis (CF), and asthma, HPV downregulates pulmonary perfusion in order to redistribute blood flow to functional lung areas in order to conserve optimal oxygenation. Imaging of lung perfusion can be seen as a reflection of lung ventilation in obstructive airway diseases. Other conditions that primarily affect lung perfusion are pulmonary vascular diseases, pulmonary hypertension, or (chronic) pulmonary embolism, which also lead to inhomogeneity in pulmonary capillary blood distribution. Several magnetic resonance imaging (MRI) techniques either dependent on exogenous contrast materials, exploiting periodical lung signal variations with cardiac action, or relying on intrinsic lung voxel attributes have been demonstrated to visualize lung perfusion. Additional post‐processing may add temporal information and provide quantitative information related to blood flow. The most widely used and robust technique, dynamic‐contrast enhanced MRI, is available in clinical routine assessment of COPD, CF, and pulmonary vascular disease. Non‐contrast techniques are important research tools currently requiring clinical validation and cross‐correlation in the absence of a viable standard of reference. First data on many of these techniques in the context of observational studies assessing therapy effects have just become available. Level of Evidence: 5 Technical Efficacy: Stage 5 [ABSTRACT FROM AUTHOR]

Aim: Left atrial (LA) myopathy is increasingly recognized as an important phenotypic trait in heart failure (HF) with preserved ejection fraction (HFpEF). Right atrial (RA) remodelling and dysfunction also develop in HFpEF, but little data are available regarding the clinical characteristics and pathophysiology among patients with isolated LA, RA, or biatrial myopathy. Methods and results: Patients with HFpEF underwent invasive haemodynamic exercise testing, comprehensive imaging including speckle tracking strain echocardiography, and clinical follow‐up at Mayo Clinic between 2006 and 2018. LA myopathy was defined as LA volume index >34 ml/m2 and/or LA reservoir strain ≤24% and RA myopathy by RA volume index >39 ml/m2 in men and >33 ml/m2 in women and/or RA reservoir strain ≤19.8%. Of 476 consecutively evaluated patients with HFpEF defined by invasive exercise testing with evaluable atrial structure/function, 125 (26%) had no atrial myopathy, 147 (31%) had isolated LA myopathy, 184 (39%) had biatrial myopathy, and 20 (4%) had isolated RA myopathy. Patients with HFpEF and biatrial myopathy had more atrial fibrillation, poorer left ventricular systolic and diastolic function, more severe pulmonary vascular disease, tricuspid regurgitation, ventricular interdependence and right ventricular dysfunction, and poorer cardiac output reserve with exercise. There were 94 patients with events over a median follow‐up of 2.9 (interquartile range 1.4–4.6) years. Individuals with biatrial myopathy had an 84% higher risk of HF hospitalization or death as compared to those with isolated LA myopathy (hazard ratio 1.84; 95% confidence interval 1.16–2.92, p = 0.01). Conclusions: Biatrial myopathy identifies patients with more advanced HFpEF characterized by more severe pulmonary vascular disease, right HF, poorer cardiac reserve, and a greater risk for adverse outcomes. Further study is required to define optimal strategies to treat and prevent biatrial myopathy in HFpEF. [ABSTRACT FROM AUTHOR]

Thoracic imaging with CT scan has become an essential component in the evaluation of respiratory and thoracic diseases. Providers have historically used conventional single-energy CT; however, prevalence of dual-energy CT (DECT) is increasing, and as such, it is important for thoracic physicians to recognize the utility and limitations of this technology. The technical aspects of DECT are presented, and practical approaches to using DECT are provided. Imaging at multiple energy spectra allows for postprocessing of the data and the possibility of creating multiple distinct image reconstructions based on the clinical question being asked. The data regarding utility of DECT in pulmonary vascular disorders, ventilatory defects, and thoracic oncology are presented. A pictorial essay is provided to give examples of the strengths associated with DECT. DECT has been most heavily studied in chronic thromboembolic pulmonary hypertension; however, it is increasingly being used across a wide spectrum of thoracic diseases. DECT combines morphologic and functional assessments in a single imaging acquisition, providing clinicians with a powerful diagnostic tool. Its role in the evaluation and treatment of thoracic diseases will likely continue to expand in the coming years as clinicians become more experienced with the technology. [ABSTRACT FROM AUTHOR]

Pulmonary vascular disease (PVD) represents an important clinical indication for lung transplant (LTx) in infants, children, and adolescents. There is limited information on LTx outcomes in these patients. We explored LTx volumes and post-LTx survival in children with PVD compared to other diagnoses. The UNOS Registry was queried from 1989 to 2020 to identify first-time pediatric LTx recipients (< 18 yo). PVD was categorized as idiopathic pulmonary arterial hypertension (IPAH) and non-idiopathic arterial hypertension (non-IPAH) and compared to all other patients as other diagnoses. Univariate and multivariate regression models were performed. 984 pediatric LTx patients (593 before 2010 and 391 during/after 2010) were identified, of which 145 (14.7%) had PVD. There has been no significant change in annual rate of all LTxs over comparative eras. However, there has been a decrease in rate of LTxs for PVD patients. Children with PVD had similar survival to other LTx groups in the early era (p = 0.2) and the latter era (p = 0.9). Univariate Cox models, showed that LTx in patients with PVD was associated with a significantly less risk of mortality for children aged 6–11 years compared to younger and older cohorts (HR = 0.4 [0.17–0.98]; p = 0.045), whereas multivariate analysis showed a trend toward higher mortality in 11–17-year-olds (HR = 1.54 [0.97–2.45]; p = 0.06). For PVD patients, oxygen supplementation and ventilator support at LTx were associated with worse post-transplant survival (p = 0.029 and p = 0.01). There has been a decrease in LTx volume for pediatric patients with PVD in the modern era. Post-LTx outcomes for children with PVD are similar to those of other diagnoses in both eras, with children aged 6–11 years having the best survival. Given these findings, LTx should be considered for this patient population. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 39-year-old woman with chronic juvenile idiopathic arthritis experiencing dyspnea, progressing over months, exacerbated by positional changes and relieved by arm positioning, raising concerns of recurrent thromboembolic disease despite normal D-dimer levels, with additional considerations for psychogenic dyspnea due to anxiety history.

Pulmonary hypertension (PH) is a chronic pulmonary vascular disease and causes massive deaths. Here, we intended to investigate the function and mechanism of SOCS5 in PH. We engineered a hypoxia-induced PH model in mice. HE staining were implemented to evaluate pathological alterations in the lung tissues. The potential mechanism of SOCS5 in regulating hypoxia-induced pulmonary artery smooth muscle cell (PASMC) function was explored in vitro. RT-qPCR and western blot revealed that the level of SOCS5 was decreased both in PH mice and hypoxia-induced HPASMCs. Functional assays were performed for confirming the role of SOCS5 in modulating the cell phenotype and JAK2/STAT3 pathway in HPASMCs. Results revealed that overexpression of SOCS5 suppressed proliferation, migration and contraction of HPASMCs and negatively regulated the JAK2/STAT3 signaling pathway in HPASMCs under hypoxia in vitro, while knockdown of SOCS5 accelerated it. As evidenced by mechanism studies, SOCS5 was targeted and regulated by miR-155-5p, hence affecting on HPASMC proliferation, migration and contraction. These outcomes indicated that the decreased level of SOCS5 in hypoxia-induced HPASMCs promoted the cell proliferation, cell migration, and cell contraction through activating JAK2/STAT3 signaling pathway. Moreover, SOCS5 was targeted by miR-155-5p. All in all, our work hinted that miR-155-5p/SOCS5/JAK2/STAT3 axis played a crucial part in PH. [ABSTRACT FROM AUTHOR]

This article focuses on vascular biology and medicine, specifically discussing new therapeutic targets in atherosclerosis, aortic dissection, and peripheral artery disease. The first study examines the role of microvascular dysfunction in critical limb-threatening ischaemia (CLTI) and its implications for treatment. The second study explores the role of the P2Y6 receptor in macrophage foam cell formation and atherosclerosis, suggesting it as a potential therapeutic target. The third study investigates the activator protein-1 complex and its role in triggering aortic dissection and rupture. Lastly, the article discusses the effects of high altitude exposure on pulmonary hypertension patients and the need for supplemental oxygen therapy. Overall, these studies provide valuable insights into the pathogenesis and potential treatments for these vascular diseases. [Extracted from the article]