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Integrative multiomics can help elucidate the pathophysiology of pulmonary fibrosis (PF)-associated pulmonary hypertension (PH) (PF-PH). Weighted gene coexpression network analysis (WGCNA) was performed on a transcriptomic dataset of explanted lung tissue from 116 patients with PF. Patients were stratified by pulmonary vascular resistance (PVR), and differential gene expression analysis was conducted. Gene modules were correlated with hemodynamics at the time of transplantation and tested for enrichment in the lung transcriptomics signature of an independent pulmonary arterial hypertension (PAH) cohort. We found 1,250 differentially expressed genes between high and low PVR groups. WGCNA identified that black and yellowgreen modules negatively correlated with PVR, whereas the tan and darkgrey modules are positively correlated with PVR in PF-PH. In addition, the tan module showed the strongest enrichment for an independent PAH gene signature, suggesting shared gene expression patterns between PAH and PF-PH. Pharmacotranscriptomic analysis using the Connectivity Map implicated the tan and darkgrey modules as potentially pathogenic in PF-PH, given their combined module signature demonstrated a high negative connectivity score for treprostinil, a medication used in the treatment of PF-PH, and a high positive connectivity score for bone morphogenetic protein (BMP) loss of function. Pathway enrichment analysis revealed that inflammatory pathways and oxidative phosphorylation were downregulated, whereas epithelial-mesenchymal transition was upregulated in modules associated with increased PVR. Our integrative systems biology approach to the lung transcriptome of PF with and without PH identified several PH-associated coexpression modules and gene targets with shared molecular features with PAH warranting further investigation to uncover potential new therapies for PF-PH. NEW & NOTEWORTHY: An integrative systems biology approach that included transcriptomic analysis of explanted lung tissue from patients with pulmonary fibrosis (PF) with and without pulmonary hypertension (PH) undergoing lung transplantation, combined with hemodynamic correlation and pharmacotranscriptomics, identified modules of genes associated with pulmonary vascular disease severity. Comparison with an independent pulmonary arterial hypertension (PAH) dataset identified shared gene expression patterns between PAH and PF-PH. [ABSTRACT FROM AUTHOR]

The article in the Journal of Paediatrics & Child Health discusses a case of a 1-month-old infant with congenital portosystemic shunt (CPSS) who developed portopulmonary hypertension (POPH) after shunt closure. The case highlights the critical nature of POPH associated with CPSS, as it can progress even after shunt closure. The article emphasizes the importance of cardiac screening for POPH at the time of CPSS diagnosis and throughout the treatment process. The study suggests the need for further research on long-term outcomes after shunt closure to predict postoperative outcomes accurately. [Extracted from the article]

Purpose: Single lung transplantation (SLT) is a viable option for patients with end-stage pulmonary parenchymal and vascular diseases. However, various diseases can occur in native lungs after SLT. Methods: Between January 2000 and December 2021, 35 patients underwent cadaveric SLT and survived for more than 30 days in our hospital. Among these 35 patients, 10 required surgery for diseases that developed in their native lungs. The clinical characteristics of these 10 patients and the outcomes of native lung surgery (NLS) were investigated. Results: Among these ten patients, the indications for lung transplantation were chronic obstructive pulmonary disease and idiopathic interstitial pneumonia in three patients each, and lymphangioleiomyomatosis and collagen vascular disease-related interstitial pneumoniain two patients each. The causes of NLS included pneumothorax (n = 4), primary lung cancer (n = 2), native lung hyperinflation (n = 2), and pulmonary aspergilloma (n = 2). The surgical procedures were pneumonectomy (n = 7), lobectomy (n = 2), and alveolar-pleural fistula repair (n = 1). Only one postoperative complication, empyema, was treated with antibiotics. The 5-year overall survival rates after transplantation with and without NLS were 70.0% and 80.0%, respectively, and did not differ to a statistically extent (p = 0.56). Conclusion: NLS is an effective treatment option for diseases that develop in the native lungs after SLT. [ABSTRACT FROM AUTHOR]

Purposes: Delayed chest closure (DCC) is a widely accepted procedure in the context of lung transplantation (LTx); yet there are few reports detailing its long-term survival and clinical outcomes. Methods: We reviewed the medical records of recipients who underwent deceased-donor lung transplantation (LTx) at Tohoku University Hospital. Long-term survival, including overall survival, freedom from chronic lung allograft dysfunction (CLAD), and CLAD-free survival and the clinical outcomes of graft function and physical performance and constitution were reviewed in recipients with DCC. Results: Between 2009 and 2022, 116 patients underwent LTx, 33 of whom (28.4%) required DCC. The intra—and post-operative courses of the recipients who required DCC were more complicated than those of the recipients who underwent primary chest closure (PCC), with frequent volume reduction surgery and longer periods of invasive mechanical ventilation. Pulmonary vascular disease was considered a risk factor for these complications and DCC. Nonetheless, long-term survival and graft functions were comparable between the DCC and PCC groups. The physical performance and constitution of recipients who required DCC continued to improve, and by 2 years after transplantation, exhibited almost no difference from those who underwent PCC. Conclusions: In view of the profoundly complicated intra- and post-operative courses, DCC should be performed cautiously and only when clinically indicated, despite which it can result in equivalent long-term survival and acceptable outcomes to PCC. [ABSTRACT FROM AUTHOR]

Various surgical approaches address complex heart disease with arch anomalies. Bilateral pulmonary artery banding (bPAB) is a strategy for critically ill patients with complex arch anomalies. Some reports argued the potential effect of bPAB on the growth of the left ventricular outflow tract (LVOT) during inter-stage after bPAB. This study aimed to analyze the LVOT growth for biventricular repair candidates with arch anomaly and systemic ventricular outflow tract (SVOT) for univentricular repair candidates with arch anomaly. This retrospective study analyzed 17 patients undergoing initial bPAB followed by arch repair. The Z-scores of LVOT and SVOT were compared between pre-bPAB and pre-arch repair. Patient characteristics, transthoracic echocardiogram data, and PAB circumferences were reviewed. The diameter of the minimum LVOT for biventricular repair (BVR) candidates, the pulmonary valve (neo-aortic valve, neo-AoV) and the pulmonary trunk (the neo-ascending aorta, neo-AAo) for univentricular repair (UVR) candidates, and the degree of aortic or neo-aortic insufficiency in each candidate was statistically analyzed. 17 patients were divided into the UVR candidates (group U) with 9 patients and the BVR candidates (group B) with 8 patients. In group B, the median value of the Z-score of the minimum LVOT increased from -3.2 (range: − 4.1 ~ − 1.0) at pre-PAB to -2.8 (range: − 3.6 ~ − 0.3) at pre-arch repair with a significant difference (p = 0.012). In group U, the median value of the Z-score of the neo-AoV increased from 0.5 (range: − 1.0 ~ 1.7) at pre-bPAB to 1.2 (range: 0.2 ~ 1.9) at pre-arch repair with a significant difference (p < 0.01). The median value of the Z-score of the neo-AAo was also increased from 3.1 (range: 1.5 ~ 4.6) to 4.3 (range: 3.1 ~ 5.9) with a significant difference (p = 0.028). The growth of the LVOT for BVR candidates and SVOT for UVR candidates during the inter-stage between bPAB and arch repair was observed. These results suggest the potential advantage of bPAB in surgical strategies. Further research is needed to validate these findings and refine surgical approaches. [ABSTRACT FROM AUTHOR]

The healthcare landscape is evolving rapidly due to escalating costs from the traditional fee-for-service model. Value-based care has emerged as a viable solution, and initiatives focus on areas prone to overuse, waste, or high costs, such as advanced imaging and avoidable acute care resource utilization. Improving medication use is an important component of this work, and it requires organizational commitment, interdisciplinary collaboration, and targeted strategies for specific therapeutic areas. This review article discusses the value-based care approach to optimizing medications and blood product prescribing, spotlighting opportunities to reduce the overuse of opioid, antimicrobial, and proton pump inhibitor medications, alongside the underuse of guideline-based medical therapies in managing chronic diseases like coronary artery disease, heart failure, and chronic obstructive pulmonary disease. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by vasoconstriction and remodeling of small pulmonary arteries (PAs). Central to the remodeling process is a switch of pulmonary vascular cells to a proliferative, apoptosis-resistant phenotype. Plasminogen activator inhibitors-1 and -2 (PAI-1 and PAI-2) are the primary physiological inhibitors of urokinase-type and tissue-type plasminogen activators (uPA and tPA), but their roles in PAH are unsettled. Here, we report that: 1) PAI-1, but not PAI-2, is deficient in remodeled small PAs and in early-passage PA smooth muscle and endothelial cells (PASMCs and PAECs) from subjects with PAH compared with controls; 2) PAI-1−/− mice spontaneously develop pulmonary vascular remodeling associated with upregulation of mTORC1 signaling, pulmonary hypertension (PH), and right ventricle (RV) hypertrophy; and 3) pharmacological inhibition of uPA in human PAH PASMCs suppresses proproliferative mTORC1 and SMAD3 signaling, restores PAI-1 levels, reduces proliferation, and induces apoptosis in vitro, and prevents the development of SU5416/hypoxia-induced PH and RV hypertrophy in vivo in mice. These data strongly suggest that downregulation of PAI-1 in small PAs promotes vascular remodeling and PH due to unopposed activation of uPA and consequent upregulation of mTOR and transforming growth factor-β (TGF-β) signaling in PASMCs, and call for further studies to determine the potential benefits of targeting the PAI-1/uPA imbalance to attenuate and/or reverse pulmonary vascular remodeling and PH. NEW & NOTEWORTHY: This study identifies a novel role for the deficiency of plasminogen activator inhibitor (PAI)-1 and resultant unrestricted uPA activity in PASMC remodeling and PH in vitro and in vivo, provides novel mechanistic link from PAI-1 loss through uPA-induced Akt/mTOR and TGFβ-Smad3 upregulation to pulmonary vascular remodeling in PH, and suggests that inhibition of uPA to rebalance the uPA-PAI-1 tandem might provide a novel approach to complement current therapies used to mitigate this pulmonary vascular disease. [ABSTRACT FROM AUTHOR]

The endothelium is a cell monolayer that lines vessels and separates tissues from blood flow. Endothelial cells (ECs) have a multitude of functions, including regulating blood flow and systemic perfusion through changes in vessel diameter. When an injury occurs, the endothelium is affected by altering its functions and structure, which leads to endothelial dysfunction, a characteristic of many vascular diseases. Understanding the role that the endothelium plays in pulmonary vascular and cardiopulmonary diseases, and exploring new therapeutic strategies is of utmost importance to advance clinically. Currently, there are several treatments able to improve patients' quality of life, however, none are effective nor curative. This review examines the critical role of the endothelium in the pulmonary vasculature, investigating the alterations that occur in ECs and their consequences for blood vessels and potential molecular targets to regulate its alterations. Additionally, we delve into promising non-pharmacological therapeutic strategies, such as exercise and diet. The significance of the endothelium in cardiopulmonary disorders is increasingly being recognized, making ECs a relevant target for novel therapies aimed at preserving their functional and structural integrity. [ABSTRACT FROM AUTHOR]

Background: The interaction between chronic obstructive pulmonary disease (COPD) and coronary artery bypass grafting (CABG) is discussed controversial. Methods: In this population-based retrospective analysis including non-emergency CABG in Germany between 2015 and 2021, the aim was to compare in-hospital mortality, hospital length of stay (HLOS), and perioperative ventilation time (VT) in patients affected by COPD and not affected by COPD. In addition, we compared outcomes after off-pump coronary artery bypass (OPCAB) and on-pump coronary artery bypass (ONCAB) surgery and outcomes after CABG with a minimally invasive technique with and without cardiopulmonary bypass (CPB) in COPD patients. Results: Of the 274,792 analyzed cases undergoing non-emergency CABG, 7.7% suffered from COPD. COPD patients showed a higher in-hospital mortality (6.0% vs. 4.2%; p < 0.001), a longer HLOS (13 days (10–19) vs. 12 days (9–16); p < 0.001), and a longer VT (33 h (11–124) vs. 28 h (9–94); p < 0.001). In subgroup analyses, COPD patients undergoing OPCAB surgery showed a lower in-hospital mortality (3.5% vs. 6.4%; p < 0.001), a shorter HLOS (12 days (9–16) vs. 13 days (10–19); p < 0.001) and a shorter VT (20 h (10–69) vs. 36 h (11–135); p < 0.001) compared to ONCAB surgery. Regression analyses confirmed that using cardiopulmonary bypass in COPD patients is associated with a higher risk of in-hospital mortality (OR, 1.86; 95% CI: 1.51–2.29, p < 0.001), a longer HLOS (1.44 days; 95% CI: 0.91–1.97, p < 0.001), and a longer VT (33.67 h; 95% CI: 18.67–48.66, p < 0.001). In further subgroup analyses, COPD patients undergoing CABG with a minimally invasive technique without CPB showed a lower in-hospital mortality (3.5% vs. 16.5%; p < 0.001) and a shorter VT (20 h (10–69) vs. 65 h (29–210); p < 0.001) compared to CABG with a minimally invasive technique and CPB. Regression analyses confirmed that using CPB in COPD patients undergoing CABG with a minimally invasive technique is associated with a higher risk of in-hospital mortality (OR, 4.80; 95% CI: 2.42–9.51, p < 0.001). Conclusions: COPD negatively impacts outcomes after non-emergency CABG. According to our results, OPCAB surgery and CABG with a minimally invasive technique without CPB seem to be beneficial for COPD patients. Further studies should be performed to confirm this. [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]

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]

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]

Tuberculosis (TB) may cause significant long‐term cardiorespiratory complications, of which pulmonary vascular disease is most under‐recognized. TB is rarely listed as a cause of pulmonary hypertension (PH) in most PH guidelines, yet PH may develop at various stages in the time course of TB, from active infection through to the post‐TB period. Predisposing risk factors for the development of PH are likely multifactorial, involving active TB disease and post‐TB lung disease (PTLD), host‐related and environment‐related factors. Moreover, post‐TB PH should likely be classified in Group 3 PH, with the pathogenesis similarly complex and multifactorial as other Group 3 PH causes. Identifying risk factors that predispose to post‐TB PH may aid in developing risk stratification criteria for early identification and referral for confirmatory diagnostic tests. Given that universal screening for PH in TB survivors may be impractical and unfeasible, a targeted screening approach for high‐risk individuals would be sensible. In this scoping review of post‐TB PH, resulting from the proceedings of the 2nd International Post‐Tuberculosis Symposium, we aim to describe the epidemiology, risk factors, and pathophysiology of post‐TB PH. We emphasize diagnosing PH with an alternative set of diagnostic guidelines in resource‐constrained settings where right heart catheterization may not be feasible. Research to describe the burden and distribution of post‐TB PH should be prioritized as there is a current gap in knowledge regarding the prevalence and incidence of post‐TB PH among persons with TB. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is a poorly understood disease of the small pulmonary arteries. Pulmonary vascular remodeling and progressively rising pulmonary vascular resistance are hallmarks of the disease that ultimately result in right heart failure. Several genetic mutations, most notably in bone morphogenetic protein receptor type 2, have a causal association with heritable forms of PAH. Mutations in neurogenic locus notch homolog protein 3 (NOTCH3) have been reported in adults and children with PAH, but whether NOTCH3 is causally associated with PAH is debated. With this case report, we describe the clinical characteristics, comorbidities, and exposure history of an adult patient with PAH and multiple sclerosis who was found to have a NOTCH3 missense mutation and exposure to leflunomide. [ABSTRACT FROM AUTHOR]

We aimed to describe the clinical characteristics, healthcare resource utilization (HCRU) and costs, health‐related quality of life (HRQoL), and survival for patients with pulmonary arterial hypertension (PAH), stratified by 1‐year mortality risk at diagnosis. Adults diagnosed with PAH at the Sheffield Pulmonary Vascular Disease Unit between 2012 and 2019 were included. Patients were categorized as low, intermediate, or high risk for 1‐year mortality at diagnosis. Demographics, clinical characteristics, comorbidities, HCRU, costs, HRQoL, and survival were analyzed. Overall, 1717 patients were included: 72 (5%) at low risk, 941 (62%) at intermediate risk, and 496 (33%) at high risk. Low‐risk patients had lower HCRU prediagnosis and 1‐year postdiagnosis than intermediate‐ or high‐risk patients. Postdiagnosis, there were significant changes in HCRU, particularly inpatient hospitalizations and accident and emergency (A&E) visits among high‐risk patients. At 3 years postdiagnosis, HCRU for all measures was similar across risk groups. Low‐risk patients had lower EmPHasis‐10 scores (indicating better HRQoL) at diagnosis and at 1‐year follow‐up compared with intermediate‐ and high‐risk patients; only the score in the high‐risk group improved. Median overall survival decreased as risk category increased in analyzed subgroups. Low‐risk status was associated with better 1‐year survival and HRQoL compared with intermediate‐ and high‐risk patients. HCRU decreased in high‐risk patients postdiagnosis, with the most marked reduction in A&E admissions. The pattern of decreased per‐patient inpatient hospitalizations and A&E visits at 3 years postdiagnosis suggests that a diagnosis of PAH helps to decrease HCRU in areas that are key drivers of costs. [ABSTRACT FROM AUTHOR]

Over 80 Mio people worldwide live >2500 m, including at least as many patients with pulmonary vascular disease (PVD), defined as pulmonary arterial or chronic thromboembolic pulmonary hypertension (PAH/CTEPH), as elsewhere (estimated 0.1‰). Whether PVD patients living at high altitude have altered disease characteristics due to hypobaric hypoxia is unknown. In a cross‐sectional study conducted at the Hospital Carlos Andrade Marin in Quito, Ecuador, located at 2840 m, we included 36 outpatients with PAH or CTEPH visiting the clinic from January 2022 to July 2023. We collected data on diagnostic right heart catheterization, treatment, and risk factors, including NYHA functional class (FC), 6‐min walk distance (6MWD), and NT‐brain natriuretic peptide (BNP) at baseline and at last follow‐up. Thirty‐six PVD patients (83% women, 32 PAH, 4 CTEPH, mean ± SD age 44 ± 13 years, living altitude 2831 ± 58 m) were included and had the following baseline values: PaO2 8.2 ± 1.6 kPa, PaCO2 3.9 ± 0.5 kPa, SaO2 91 ± 3%, mean pulmonary artery pressure 53 ± 16 mmHg, pulmonary vascular resistance 16 ± 4 WU, 50% FC II, 50% FC III, 6MWD 472 ± 118 m, BNP 490 ± 823 ng/L. Patients were treated for 1628 ± 1186 days with sildenafil (100%), bosentan (33%), calcium channel blockers (33%), diuretics (69%), and oxygen (nocturnal 53%, daytime 11%). Values at last visit were: FC (II 75%, III 25%), 6MWD of 496 ± 108 m, BNP of 576 ± 5774 ng/L. Compared to European PVD registries, ambulatory PVD patients living >2500 m revealed similar blood gases and relatively low and stable risk factor profiles despite severe hemodynamic compromise, suggesting that favorable outcomes are achievable for altitude residents with PVD. Future studies should focus on long‐term outcomes in PVD patients dwelling >2500 m. [ABSTRACT FROM AUTHOR]

Introduction: Pulmonary Embolism (PE) represents a lifethreatening medical emergency that, given the serious complications, requires urgent application of anticoagulant therapy. In addition to various traditional factors for the development of PE, obesity has recently been considered as an independent risk factor for the development of PE. Aim: to determine whether there is a difference in body mass index (BMI) values in subjects with confirmed and excluded PE. Materials and methods: the study included 100 patients with suspected PE, which was confirmed or excluded by using MSCT and/or V/P SPECT and for all patients BMI was calculated based on body height and weight values. Results: Out of 100 subjects, PE was not diagnosed in 37 subjects, while 63 subjects PE was diagnosed. All subjects were divided into 2 groups: a group of subjects with confirmed PE and a group of subjects with excluded PE. Average BMI values were calculated for both groups. Statistical analysis showed that there was no significant difference in BMI values between subjects with confirmed and excluded PE. Conclusion: the results of our study did not confirm the association between elevated BMI and PE. [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]

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]

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]

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]

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]

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]

This article explores the relationship between the heart and lungs in cardiopulmonary diseases, with a specific focus on pulmonary hypertension (PH). PH can occur as a result of various heart and lung diseases and is categorized into different groups based on the underlying causes. The study by Borlaug et al. examines the differences in patients with isolated PH due to left-sided heart disease, PH due to lung diseases, and mixed forms of PH. The study highlights the similarities and differences in clinical characteristics, hemodynamics, and outcomes among these groups, emphasizing the need for a comprehensive approach to understanding and managing PH. The article also includes references to two scientific articles that provide valuable insights into heart failure and pulmonary hypertension in chronic obstructive pulmonary disease (COPD). [Extracted from the article]

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]

Statin therapy is a cornerstone in the treatment of systemic vascular diseases. However, statins have failed to translate as therapeutics for pulmonary vascular disease. Early pulmonary vascular disease in the setting of congenital heart disease (CHD) is characterized by endothelial dysfunction, which precedes the more advanced stages of vascular remodeling. These features make CHD an ideal cohort in which to re-evaluate the potential pulmonary vascular benefits of statins, with a focus on endothelial biology. However, it is critical that the full gamut of the pleiotropic effects of statins in the endothelium are uncovered. The purpose of this investigation was to evaluate the therapeutic potential of simvastatin for children with CHD and pulmonary over-circulation, and examine mechanisms of simvastatin action on the endothelium. Our data demonstrate that daily simvastatin treatment preserves endothelial function in our shunt lamb model of pulmonary over-circulation. Further, using pulmonary arterial endothelial cells (PAECs) isolated from Shunt and control lambs, we identified a new mechanism of statin action mediated by increased expression of the endogenous Akt1 inhibitor, C-terminal modifying protein (CTMP). Increases in CTMP were able to decrease the Akt1-mediated mitochondrial redistribution of endothelial nitric oxide synthase (eNOS) which correlated with increased enzymatic coupling, identified by increases in NO generation and decreases in NOS-derived superoxide. Together our data identify a new mechanism by which simvastatin enhances NO signaling in the pulmonary endothelium and identify CTMP as a potential therapeutic target to prevent the endothelial dysfunction that occurs in children born with CHD resulting in pulmonary over-circulation. • Congenital heart disease results in early dysfunction of the pulmonary vascular endothelium. • In a model of congenital heart disease, statins improve endothelial dysfunction. • Statins increase levels of C-terminal modifying protein (CTMP), inhibiting Akt1 activity. • Akt1 inhibition decreases the mitochondrial redistribution of endothelial nitric oxide synthase. • Statins and CTMP restore bioavailable NO and improve eNOS coupling. [ABSTRACT FROM AUTHOR]

Alagille syndrome (ALGS) is a multisystem autosomal dominant disorder caused by variants in one of the JAG1 or the NOTCH2 genes. It presents with a wide spectrum of clinical manifestations that most commonly include hepatic, cardiac, skeletal, ophthalmologic and renal abnormalities, along with characteristic facial features. The prognosis and mortality risk vary according to the different organ involvement and its severity, and the management requires a multidisciplinary approach, depending on the findings of each affected individual. We report the case of a 2-year-old boy who presented with neonatal cholestasis, distinctive facial features and pulmonary artery stenosis, who progressively developed severe hypercholesterolemia, hypertriglyceridemia and intractable pruritus, with a significant decrease in the quality of life. [ABSTRACT FROM AUTHOR]