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Background: Cardiac tamponade (CT) has an atypical presentation in patients with underlying pulmonary hypertension (PH). Evidence regarding the impact of PH on CT in-hospital outcomes is lacking. Methods: We used the National Inpatient Sample database to identify adult hospitalizations with a diagnosis of CT between 2016 and 2020, using relevant ICD-10 diagnostic codes. Baseline characteristics and in-hospital outcomes were compared in patients with and without a PH. Multivariate logistic regression analyses and case-control matching were performed, adjusting for age, race, gender, and statistically significant co-morbidities between cohorts. Results: A total of 110,285 inpatients with CT were included, of which 8,670 had PH. Patients with PH tended to be older (66 ± 15.7) and female (52.5%), had significantly higher rates of hypertension (74% vs 65%), CAD (36.9% vs. 29.6%), CKD (39% vs 23%), DM (32.1%, vs. 26.9%), chronic heart failure (19.0% vs 9.7%) and COPD (26% vs 18%)(P<0.001 for all). After multivariate logistic regression, PH was associated with higher all-cause mortality (aOR 1.29; 95% CI: 1.11–1.49), higher rates of cardiogenic shock (aOR: 1.19; 95% CI: 1.01–1.41), ventricular arrythmias (aOR: 1.63; 95% CI: 1.33–2.01), longer length of stay (11 days vs 15 days), and higher total hospitalization costs ($228,314 vs $327,429) in patients presenting with CT. Despite pericardiocentesis being associated with lower in-hospital mortality, patients with PH were less likely to undergo pericardiocentesis (aOR: 0.77; 95% CI: 0.69–0.86). Conclusion: PH was associated to increased in-hospital mortality and a higher rate of cardiovascular complications in an inpatient population with CT. Pericardiocentesis was associated with reduced mortality in patients with CT, regardless of whether they had PH. However, patients with PH underwent pericardiocentesis less frequently than those without PH. [ABSTRACT FROM AUTHOR]

A device that can evaluate human pulmonary microcirculation is currently unavailable. This study aimed to establish a novel approach for assessing pulmonary microcirculation in patients with pulmonary hypertension (PH). We used a guidewire embedded with temperature and pressure sensors to measure the following pulmonary microcirculatory function indicators: pulmonary flow reserve, pulmonary index of microcirculatory resistance (PIMR), and pulmonary resistive reserve ratio. Adenosine was administered to patients to induce hyperemia in the pulmonary artery for assessment. The correlation between these indicators and various parameters, including serum biomarkers, hemodynamic and respiratory functions, and exercise capacity, were examined. The procedure was performed in 19 patients with moderate PH, without major complications. The minimum effective adenosine dosage for maximal hyperemia, without severe side effects, was 150 μg∙kg−1∙min−1. Multivariate stepwise analysis revealed a positive correlation between the hyperemic PIMR and serum uric acid (p < 0.001) and N-terminal probrain natriuretic peptide levels (p = 0.014). Therefore, this catheter-based method offers an effective means to assess pulmonary microcirculatory function in patients with PH, and the optimal dose of adenosine for this evaluation was 150 μg∙kg−1∙min−1. [ABSTRACT FROM AUTHOR]

Background: Clear amniotic fluid aspiration syndrome (CAF-AS) is a very rare event occurring in 0.25% of our term clear amniotic fluids deliveries. The study's aims were: 1. to characterize the risk factors and outcomes associated with Clear Amniotic Fluid Aspiration Syndrome and 2. to compare the outcomes of Clear Amniotic Fluid Aspiration to Meconium Aspiration. Methods: This was an observational study over a 22-year period in a single level-3 medical center. Compared were parturient/labor characteristics and neonatal outcomes in cases with suspected Clear Amniotic Fluid Aspiration to cases suspected for Meconium Aspiration. Results: Out of 79,620 term deliveries there were 66,705 (83.8%) clear amniotic fluids and 12,915 (16.2%) meconium stained amniotic fluid (MSAF). Of neonates born with clear amniotic fluid, 166 (0.25%) were diagnosed with Clear Amniotic Fluid Aspiration Syndrome (CAF-AS), while 202 (15.7%) of those born with MSAF, were diagnosed with aspiration syndrome (MSAF-AS). Both conditions had comparable rates of mild manifestation (67.5% vs 69.2%, p = 0.63). Persistent pulmonary hypertension (PPH) occurred 5 times less in CAF-AS than MSAF-AS (4% vs 20%, OR 0.17, P< 0.0001) Both conditions presented similar rates of surfactant without PPH (11.1% vs 13.4%, p = 0.87). There was 1 postnatal death in CAF-AS vs 10 in MSAF. Conclusion: CAF-AS were quantitatively quite similar in terms of need of actual active intervention of the neonatologists in the delivery room (166 vs 202, i.e. in terms of numbers of cases and not prevalence) to MSAF-AS.We identified in these cases two major specific causes: hyperkinetic explosive deliveries in multiparas and long-lasting episodes of maternal hypotension due to epidural/spinal anaesthesia during labor. Out of 140 million births per year in the world, it should be of concern that 3 million cases are neglected nowadays. Future studies should evaluate if this CAF-AS should benefit from a more active intervention such as immediate endotracheal suction at birth, this clear fluid being very easy to suction. [ABSTRACT FROM AUTHOR]

Introduction: Patients with pulmonary hypertension (PH) have an impaired functional capacity and poor health-related quality of life (HRQoL). The one-minute sit-to-stand test (1-min STST) can be used for the assessment of functional capacity. Aims: Our aim was to evaluate the 1-min STST performance and its association with patient-reported HRQoL in patients with PH. Methods: We prospectively assessed functional capacity in 98 PH patients (mean age 66 ± 15 years, 55% female) using the 1-min STST. Patients had to stand up and sit down from a chair as many times as possible within one minute. Patients' HRQoL was evaluated with the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) questionnaire, which consists of the three subcategories symptoms, activities and quality of life (QoL). Results: We observed a significant correlation of the 1-min STST performance with all HRQoL subcategories assessed with the CAMPHOR questionnaire: A lower number of 1-min STST repetitions correlated with more symptoms (rs = -.398, p <.001), worse functioning (rs = -.551, p <.001) and a decreased QoL (rs = -.407, p <.001). Furthermore, in the multivariable linear regression analysis, adjusted for age, sex, body mass index (BMI) and mean pulmonary artery pressure (mPAP), lower 1-min STST performance was an independent predictor for worse symptoms (est. β = -0.112, p =.003), activities (est. β = -0.198, p <.001) and QoL (est. β = -0.130, p <.001) assessed with the CAMPHOR questionnaire. Conclusion: Our results indicate that regardless of age, sex, BMI and mPAP the 1-min STST performance is associated with all CAMPHOR HRQoL subcategories in patients with PH. Therefore, the 1-min STST performance might be a new option to assess functional capacity correlated to HRQoL in patients with PH. [ABSTRACT FROM AUTHOR]

Cardiac output (CO) is one of the primary prognostic factors evaluated during the follow-up of patients treated for pulmonary hypertension (PH). It is recommended that it be measured using the thermodilution technique during right heart catheterization. The difficulty to perform iterative invasive measurements on the same individual led us to consider a non-invasive option. The aims of the present study were to assess the agreement between CO values obtained using bioreactance (Starling™ SV) and thermodilution, and to evaluate the ability of the bioreactance monitor to detect patients whose CO decreased by more than 15% during follow-up and, accordingly, its usefulness for patient monitoring. A prospective cohort study evaluating the performance of the Starling™ SV monitor was conducted in patients with clinically stable PH. Sixty patients referred for hemodynamic assessment were included. CO was measured using both the thermodilution technique and bioreactance during two follow-up visits. A total of 60 PH patients were included. All datasets were available at the baseline visit (V0) and 50 of them were usable during the follow-up visit (V1). Median [IQR] CO was 4.20 l/min [3.60–4.70] when assessed by bioreactance, and 5.30 l/min [4.57–6.20] by thermodilution (p<0.001). The Spearman correlation coefficient was 0.51 [0.36–0.64], and the average deviation on Bland-Altman plot was -1.25 l/min (95% CI [-1.48–1.01], p<0.001). The ability of the monitor to detect a variation in CO of more than 15% between two follow-up measurements, when such variation existed using thermodilution, was insufficient for clinical practice (AUC = 0.54, 95% CI [0.33–0.75]). [ABSTRACT FROM AUTHOR]

Background and purpose: Mean pulmonary artery pressure (mPAP) is a key index for chronic thromboembolic pulmonary hypertension (CTEPH). Using machine learning, we attempted to construct an accurate prediction model for mPAP in patients with CTEPH. Methods: A total of 136 patients diagnosed with CTEPH were included, for whom mPAP was measured. The following patient data were used as explanatory variables in the model: basic patient information (age and sex), blood tests (brain natriuretic peptide (BNP)), echocardiography (tricuspid valve pressure gradient (TRPG)), and chest radiography (cardiothoracic ratio (CTR), right second arc ratio, and presence of avascular area). Seven machine learning methods including linear regression were used for the multivariable prediction models. Additionally, prediction models were constructed using the AutoML software. Among the 136 patients, 2/3 and 1/3 were used as training and validation sets, respectively. The average of R squared was obtained from 10 different data splittings of the training and validation sets. Results: The optimal machine learning model was linear regression (averaged R squared, 0.360). The optimal combination of explanatory variables with linear regression was age, BNP level, TRPG level, and CTR (averaged R squared, 0.388). The R squared of the optimal multivariable linear regression model was higher than that of the univariable linear regression model with only TRPG. Conclusion: We constructed a more accurate prediction model for mPAP in patients with CTEPH than a model of TRPG only. The prediction performance of our model was improved by selecting the optimal machine learning method and combination of explanatory variables. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article published in PLoS ONE. The correction addresses concerns about Figure 2, specifically the duplication of images in Fig 2A. The authors explain that this duplication was due to a figure preparation error and provide an updated version of Fig 2 with corrected images. Additional concerns were raised about the cytological quantification of TERT, and the authors provide explanations and methodological details in response. The underlying image data and individual-level quantitative data supporting Fig 2 are also made available. A member of the PLOS ONE Editorial Board reviewed the updated figure and data and confirmed that the raw data support the published results. The authors apologize for the errors in the published article. [Extracted from the article]

Purpose: In chronic thromboembolic pulmonary hypertension (CTEPH), fibrosis of thrombi in the lumen of blood vessels and obstruction of blood vessels are important factors in the progression of the disease. Therefore, it is important to explore the key genes that lead to chronic thrombosis in order to understand the development of CTEPH, and at the same time, it is beneficial to provide new directions for early identification, disease prevention, clinical diagnosis and treatment, and development of novel therapeutic agents. Methods: The GSE130391 dataset was downloaded from the Gene Expression Omnibus (GEO) public database, which includes the full gene expression profiles of patients with CTEPH and Idiopathic Pulmonary Arterial Hypertension (IPAH). Differentially Expressed Genes (DEGs) of CTEPH and IPAH were screened, and then Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) functional enrichment analyses were performed on the DEGs; Weighted Gene Co-Expression Network Analysis (WGCNA) to screen the key gene modules and take the intersection genes of DEGs and the key module genes in WGCNA; STRING database was used to construct the protein-protein interaction (PPI) network; and cytoHubba analysis was performed to identify the hub genes. Results: A total of 924 DEGs were screened, and the MEturquoise module with the strongest correlation was selected to take the intersection with DEGs A total of 757 intersecting genes were screened. The top ten hub genes were analyzed by cytoHubba: IL-1B, CXCL8, CCL22, CCL5, CCL20, TNF, IL-12B, JUN, EP300, and CCL4. Conclusion: IL-1B, CXCL8, CCL22, CCL5, CCL20, TNF, IL-12B, JUN, EP300, and CCL4 have diagnostic and therapeutic value in CTEPH disease, especially playing a role in chronic thrombosis. The discovery of NF-κB, AP-1 transcription factors, and TNF signaling pathway through pivotal genes may be involved in the disease progression process. [ABSTRACT FROM AUTHOR]

Notch pathway has played a significant role in the pathophysiology of pulmonary hypertension (PH). However, the role of Jagged 2 (Jag2), one ligand of Notch, remains to be elucidated.Therefore, determining the contribution of Jag2 to PH and its impact on pulmonary artery smooth muscle cells (PASMCs) was the aim of this investigation. Adeno-associated virus-mediated Jag2 inhibition was used to explore the role of Jag2 in peripheral pulmonary vascular remodeling assessed in a rat model of chronic hypoxia (10% O2, 4 weeks) induced pulmonary hypertension. In vitro, the effect of Jag2 silencing on hypoxia (1% O2, 24h) induced rat PASMCs was determined. Group differences were assessed using a 2-sided unpaired Student's t-test for two groups and one-way ANOVA for multiple groups. Jag2 upregulation was first confirmed in rats with sustained hypoxia-induced PH using publicly available gene expression data, experimental PH rat models and hypoxia induced rat PASMCs. Jag2 deficiency decreased oxidative stress injury, peripheral pulmonary vascular remodeling (0.276±0.020 vs. 0.451±0.033 μm, P<0.001, <50μm), and right ventricular systolic pressure (36.8±3.033 vs. 51.8±4.245 mmHg, P<0.001) in the chronic hypoxia-induced rat model of PH. Moreover, Jag2 knockdown decreased proliferation (1.227±0.051 vs. 1.45±0.07, P = 0.012), increased apoptosis (16.733%±0.724% vs. 6.56%±0.668%, P<0.001), and suppressed mitochondrial injury in hypoxia–treated rat PASMCs. Jag2 inhibition restored the activity of the Nrf2/HO-1 pathway, which was abolished by Sirtuin 1 deficiency. These findings show that Jag2 is essential for modulating pulmonary vascular dysfunction and accelerating PH, and that inhibition of Jag2 expression suppresses the progression and development of PH. [ABSTRACT FROM AUTHOR]

In dogs with degenerative mitral valve disease (DMVD), pulmonary hypertension (PH) is a common complication characterized by abnormally elevated pulmonary arterial pressure (PAP). Pulmonary arterial remodeling is the histopathological changes of pulmonary artery that has been recognized in PH. The underlying mechanisms that cause this arterial remodeling are poorly understood. This study aimed to perform shotgun proteomics to investigate changes in protein expression in pulmonary arteries and lung tissues of DMVD dogs with PH compared to normal control dogs and DMVD dogs without PH. Tissue samples were collected from the carcasses of 22 small-sized breed dogs and divided into three groups: control (n = 7), DMVD (n = 7) and DMVD+PH groups (n = 8). Differentially expressed proteins were identified, and top three upregulated and downregulated proteins in the pulmonary arteries of DMVD dogs with PH including SIK family kinase 3 (SIK3), Collagen type I alpha 1 chain (COL1A1), Transforming growth factor alpha (TGF-α), Apoptosis associated tyrosine kinase (AATYK), Hepatocyte growth factor activator (HGFA) and Tyrosine-protein phosphatase non-receptor type 13 (PTPN13) were chosen. Results showed that some of the identified proteins may play a role in the pathogenesis of pulmonary arterial remodeling. This study concluded shotgun proteomics has potential as a tool for exploring candidate proteins associated with the pathogenesis of PH secondary to DMVD in dogs. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases related to the right side of the heart, such as Pulmonary Hypertension, are some of the leading causes of death among the Mexican (and worldwide) population. To avoid invasive techniques such as catheterizing the heart, improving the segmenting performance of medical echocardiographic systems can be an option to early detect diseases related to the right-side of the heart. While current medical imaging systems perform well segmenting automatically the left side of the heart, they typically struggle segmenting the right-side cavities. This paper presents a robust cardiac segmentation algorithm based on the popular U-NET architecture capable of accurately segmenting the four cavities with a reduced training dataset. Moreover, we propose two additional steps to improve the quality of the results in our machine learning model, 1) a segmentation algorithm capable of accurately detecting cone shapes (as it has been trained and refined with multiple data sources) and 2) a post-processing step which refines the shape and contours of the segmentation based on heuristics provided by the clinicians. Our results demonstrate that the proposed techniques achieve segmentation accuracy comparable to state-of-the-art methods in datasets commonly used for this practice, as well as in datasets compiled by our medical team. Furthermore, we tested the validity of the post-processing correction step within the same sequence of images and demonstrated its consistency with manual segmentations performed by clinicians. [ABSTRACT FROM AUTHOR]

Introduction: The classification and management of pulmonary hypertension (PH) is challenging due to clinical heterogeneity of patients. We sought to identify distinct multimorbid phenogroups of patients with PH that are at particularly high-risk for adverse events. Methods: A hospital-based cohort of patients referred for right heart catheterization between 2005–2016 with PH were included. Key exclusion criteria were shock, cardiac arrest, cardiac transplant, or valvular surgery. K-prototypes was used to cluster patients into phenogroups based on 12 clinical covariates. Results: Among 5208 patients with mean age 64±12 years, 39% women, we identified 5 distinct multimorbid PH phenogroups with similar hemodynamic measures yet differing clinical outcomes: (1) "young men with obesity", (2) "women with hypertension", (3) "men with overweight", (4) "men with cardiometabolic and cardiovascular disease", and (5) "men with structural heart disease and atrial fibrillation." Over a median follow-up of 6.3 years, we observed 2182 deaths and 2002 major cardiovascular events (MACE). In age- and sex-adjusted analyses, phenogroups 4 and 5 had higher risk of MACE (HR 1.68, 95% CI 1.41–2.00 and HR 1.52, 95% CI 1.24–1.87, respectively, compared to the lowest risk phenogroup 1). Phenogroup 4 had the highest risk of mortality (HR 1.26, 95% CI 1.04–1.52, relative to phenogroup 1). Conclusions: Cluster-based analyses identify patients with PH and specific comorbid cardiometabolic and cardiovascular disease burden that are at highest risk for adverse clinical outcomes. Interestingly, cardiopulmonary hemodynamics were similar across phenogroups, highlighting the importance of multimorbidity on clinical trajectory. Further studies are needed to better understand comorbid heterogeneity among patients with PH. [ABSTRACT FROM AUTHOR]

Background: Pulmonary hypertension (PH) is a common and morbid complication of left heart disease (LHD), comprising two subtypes: (1) isolated post-capillary pulmonary hypertension (Ipc-PH) and (2) combined post-capillary and pre-capillary pulmonary hypertension (Cpc-PH). Knowledge regarding the physiological characteristics that distinguish Cpc-PH, which has a worse prognosis, from Ipc-PH remains limited. Therefore, this study aimed to assess the utility of cardiopulmonary exercise testing (CPET) variables in detecting Cpc-PH. Methods and results: Among 105 consecutive patients with LHD (age: 55 ± 13 years; male/female = 79/26) who underwent right heart catheterization and CPET, 45 (43%) were classified as PH-LHD (mean pulmonary artery pressure >20 mmHg). Ipc-PH (n = 24) was defined as pulmonary vascular resistance (PVR) ≤ 3 WU and Cpc-PH (n = 21) as PVR > 3 WU. Patients with Cpc-PH had a significantly lower peak partial pressure of carbon dioxide (PETCO2) (Non-PH/Ipc-PH/Cpc-PH = 38.2 ± 6.6 vs. 38.3 ± 6.0 vs 33.0 ± 4.4 mmHg, p = 0.006), higher VE vs. VCO2 slope (Non-PH/Ipc-PH/Cpc-PH = 33.0 [28.3, 36.6] vs. 32.5 [28.1, 37.8] vs. 40.6 [33.6, 46.1], p = 0.007), and lower ΔVO2/ΔWR (Non-PH/Ipc-PH/Cpc-PH = 8.5 ± 1.4 vs. 8.0 ± 1.7 vs. 6.8 ± 2.0 mL/min/watt, p = 0.001) than those with Ipc-PH and non-PH. Using multivariable logistic regression analysis, CPET variables were found to be independent predictors of Cpc-PH (lower peak PETCO2: odds ratio, 0.728 [95% confidence interval {CI}: 0.616–0.840], p = 0.003 and lower ΔVO2/ΔWR: odds ratio, 0.747 [95% CI: 0.575–0.872], p = 0.003). Conclusion: From our exploratory analysis, CPET variables, especially in the lower peak PETCO2 and lower ΔVO2/ΔWR, were associated with Cpc-PH in patients with left heart disease. [ABSTRACT FROM AUTHOR]

Background: The one-minute sit-to-stand-test (1-min STST) is a quick, space saving test to evaluate functional capacity. Exercise testing plays an important role in the long-term follow-up of pulmonary hypertension (PH) patients and is currently evaluated using the six-minute-walk-test (6MWT). The aim of the study was to assess the convergent validity of the 1-min STST in patients with PH and its association with markers of PH severity. Methods: We evaluated 106 PH patients with the 1-min-STST and 6MWT and measured cardiorespiratory parameters (heart rate, blood pressure, oxygen saturation) before and after test conduction. N-terminal pro brain-type natriuretic peptide (NT-proBNP), WHO functional class (WHO-FC) and mean pulmonary artery pressure (mPAP) were defined as markers of PH severity. Results: Strong correlation was found between performances of 1-min STST and 6MWT (r =.711, p <.001), indicating convergent validity. Both tests were inversely associated with NT-proBNP (STST: r = -.405, p <.001; 6MWT: r = -.358, p <.001), WHO-FC (STST: r = -.591, p <.001; 6MWT: r = -.643, p <.001) and mPAP (STST: r = -.280, p <.001; 6MWT: r = -.250, p <.001). Significant changes in cardiorespiratory parameters were observed in both tests (all p < 0.001). Further the post-exercise cardiorespiratory parameters correlated strongly between the 1-min STST and 6MWT (all r ≥.651, all p <.001). Conclusion: The 1-min STST demonstrated good convergent validity with the 6MWT and was associated with markers of PH severity. Furthermore, both exercise tests caused similar cardiorespiratory responses. [ABSTRACT FROM AUTHOR]

Background: Balloon pulmonary angioplasty (BPA) is used for treatment of inoperable chronic thromboembolic pulmonary hypertension (CTEPH) and residual pulmonary hypertension after pulmonary endarterectomy (PEA) to improve hemodynamics, right ventricular function, and exercise capacity. However, the effectiveness and safety of guide extension catheters for BPA treatment in patients with CTEPH have not been demonstrated. Methods: We retrospectively analyzed 91 lesions in 55 sessions of 28 patients with CTEPH who underwent BPA using a guide extension catheter. The purpose (backup, coaxial, and extension), efficacy, and safety of the guide extension catheters were explored. The efficacy of the guide extension catheter was assessed based on the success of the procedures and safety was evaluated based on procedure-related complications. Results: Regarding the intended use, a guide extension catheter was used to strengthen the backup force of the guiding catheter in 52% of cases, extend the tip of the catheter in 38% of cases, and maintain the coaxiality of the guiding catheter in 10% of cases. Procedural success was achieved in 92.7% of 55 sessions and in 95.6% of 91 lesions. Complex lesions had a lower success rate than simple lesions (p = 0.04). Regarding safety concerns, complications were observed in 5 of 55 sessions (9.1%) and 6 of 91 lesions (6.6%). Only one case of pulmonary artery dissection using a guide extension catheter was reported. Except for this one case, extension catheter-related complications were not observed. Conclusions: A guide extension catheter can be used safely in BPA procedures with anatomically complex pulmonary artery branches and complex lesions by increasing backup support. [ABSTRACT FROM AUTHOR]

Objective: Physical activity (PA) is an established adjunct therapy for pulmonary hypertension (PH) patients to mitigate PH symptoms and improve quality of life. However, PA engagement within this population remains low. This study investigated PH patients' knowledge of PA, recalled advice, exercise preferences and PA support needs. Methods: Semi-structured interviews were conducted with 19 adults (mean age 50 years; SD ±12 years) diagnosed with PH, living in Ireland. Interview scripts were digitally recorded and transcribed verbatim. Thematic analysis was used to analyse the data. Results: Four key themes were identified: Lack of PA knowledge; exercise setting preference; accountability and monitoring; and clinician delivered PA information and guidance. Conclusion: This study found that PH clinicians provide suboptimal PA advice, yet patients desired clinician-delivered PA guidance. Home-based exercise was preferred with monitoring and external accountability deemed as important to facilitate sustained engagement. Practice implications: PH clinicians are well positioned to play a critical role in assisting and empowering PH patients to engage in PA. Providing training and education to PH clinicians regarding exercise prescription may be beneficial. Further research is needed to evaluate the feasibility and efficacy of home-based exercise interventions to improve quality of life and physical activity in PH. [ABSTRACT FROM AUTHOR]

Sickle cell disease (SCD) is a severe monogenic disease associated with high morbidity and mortality and a disproportionate burden on Black communities. Few population-based studies have examined the prevalence of comorbidities among persons with SCD. We estimated the prevalence of comorbidities experienced by individuals with SCD enrolled in employer-based health insurance plans in the US over their non-elderly lifetimes (0–64 years of age) with a retrospective cohort design using Truven Health MarketScan commercial claims data from 2007–2018. ICD-9/10 codes were used to identify individuals with SCD using a previously published algorithm. For this cohort, comorbidities associated with SCD were identified across 3 age categories (<18, 18–45, 46–64 years-old), based on the CMS Chronic Comorbidities Warehouse or SCD-specific diagnosis codes, when applicable. The total number of SCD patients available for analysis in each age category was 7,502 (<18 years), 10,183 (18–45 years) and 4,459 (46–64 years). Across all ages, vaso-occlusive pain, infections (non-specific), and fever were the most common comorbidities. Vaso-occlusive pain and infection were the most prevalent conditions for persons age <18- and 18–45-year-olds, while in the 46–54-year-old age group, infection and cardiovascular including pulmonary hypertension were most prevalent. Compared to persons <18 years old, the prevalence of vaso-occlusive pain, fever, and acute chest syndrome claims declined in older populations. The comorbidity burden of SCD is significant across all age groups. SCD patients experience comorbidities of age such as chronic pain, cardio-vascular conditions including pulmonary hypertension and renal disease at far higher rates than the general population. Novel disease modifying therapies in development have the potential to significantly reduce the comorbidity burden of SCD. [ABSTRACT FROM AUTHOR]

Background: Exercise and cardiopulmonary exercise testing are essential in the evaluation of physiological, biochemical, and molecular responses in the experimental studies on chronic diseases such as diabetes, heart failure and hypertension. The exercise tolerance and seem to be a valuable contribution to the experiments that are performed in animal models of pulmonary hypertension (PH), as well. The current survey uses detailed quantitative analyses to assess the advantages of exercise training programs performed in preclinical studies based on outcomes such as exercise capacity, cardiopulmonary hemodynamics, and mortality. Methods: Articles were identified through search engines in the online electronic databases Pubmed/Medline, Web of Science following the PRISMA Protocol. Studies conducted between 1991 and 2022 without language restrictions were included in this study. Heterogeneity was assessed using the Cochrane Q-test and I2 test statistics. Subgroup analysis was employed with evidence of heterogeneity. Quality assessment was carried out using SYRCLE's risk of bias tool for animal studies. Publication bias across studies was determined using the funnel plot and Egger's regression test statistic. Results: The available protocols typically included treadmill running, swimming, and voluntary wheel running with a different series of intensities, times and durations; these were also used in studies examining the efficacy of chronic training programs. In 66 interventions, PH induction reduced exercise endurance by half compared to healthy subjects, while exposure to tested medical agents normalized exercise capacity. The other 58 interventions demonstrated the advantages of various exercise training programs for PH. Induction of PH reduced exercise endurance by half compared to healthy subjects (R = 0.52; 0.48 − 0.55 95%CI; P<0.0001; I2 = 98.9%), while the exposure to tested medical agents normalized exercise capacity (R = 1.75; 1.61 − 1.91 95%CI; P<0.0001; I2 = 97.8%). Conclusion: Despite a wide spectrum of study protocols to measure exercise endurance in animals with PH, there is a significant correlation between worsening of exercise-related parameters and PH development, manifested by alterations in haemodynamic and remodeling parameters. Familiarization with exercise, training program schedule, method used for PH induction, or detailed training parameters such as slope, exercise intensity or individualization, can influence the final outcome. This in turn can impact on the diversity and reproducibility of results being obtained in particular experimental studies. [ABSTRACT FROM AUTHOR]

Background: Pulmonary hypertension (PH) is a complex syndrome characterized by increased pulmonary arterial pressure and classified into five groups, according to dyspnea on exertion and systemic muscle dysfunction. These symptoms can be identified using the sit-to-stand test (STS), which indirectly evaluates exercise tolerance and lower limb muscle strength. Previous studies used the STS in PH; however, psychometric properties to understand and validate this test were not described for patients with PH. Objective: To evaluate the psychometric properties (validity, reliability, and responsiveness) of different STS protocols in patients with PH. Methods and analyses: This is a systematic review protocol that will include studies using STS in patients with PH. Searches will be conducted on PubMed/MEDLINE, EMBASE, SciELO, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases following PICOT mnemonic strategy and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). Rayyan software will be used for study selection. The Risk of bias will be assessed using the Consensus‐Based Standards for the Selection of Health Measurement Instruments (COSMIN) tool, while the quality of evidence will be assessed using the modified Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Two researchers will independently conduct the study, and a third researcher will be consulted in case of disagreement. The psychometric properties will be evaluated according to the COSMIN. This protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO, no. CRD42021244271). Conclusion: This systematic review will attempt to identify and show the available evidence on STS for different groups of PH and report validity, reliability, and responsiveness of different protocols. [ABSTRACT FROM AUTHOR]

Introduction: Worldwide, congenital heart disease is the principal heart disease in children and constitutes one of the major causes of infant mortality, particularly in developing countries. Infants and children with congenital heart disease exhibit a range of delays in weight gain and growth. In some instances, the delay can be relatively mild, whereas in other cases, cause the failure to thrive. Objectives: To determine the nutritional status and associated factors of pediatric patients with congenital heart disease. Material and method: A cross sectional analytical study conducted over a period of 6 months (Feb to Jul 2020). A total of 228 subjects with congenital heart disease who visited the cardiac center during the study period where included until the calculated sample size attained. Data is collected from patient's card and their care giver. Data was then analyzed using Statistical Package for Social Sciences (SPSS) for windows version 25.0. Odds Ratio with 95% Confidence Interval (CI) was used to determine the effect of the independent variables on the outcome variable and P-value less than 0.05 was considered statistically significant. Results: A total of 228 children ranging from 3month to 17yrs of age with mean age of 4.7 years (SD = 3.8 years) were included in the study. Most of the subjects had acyanotic heart disease accounting for 87.7%. The overall prevalence of wasting, underweight and stunting were 41.3%, 49.1% and 43% respectively. Children with congenital heart disease and having pulmonary hypertension, were found more likely to develop wasting compared to those without pulmonary hypertension with an odds of 1.9 (95% CI: 1.0–3.4) and also have greater chance of stunting with an odds of 1.9 (95% CI: 1.0–3.4). Children 5 to 10 years of age were 2.3 times more likely to be underweight. Conclusion: Malnutrition is a major problem in pediatric patients with congenital heart disease. Pulmonary hypertension and older age are associated with increased risk of undernutrition. [ABSTRACT FROM AUTHOR]

Background: Risk stratification is central to the management of pulmonary arterial hypertension (PAH). For this purpose, multiparametric tools have been developed, including the ESC/ERS risk score and its simplified versions derived from large database analysis such as the COMPERA and the French Pulmonary Hypertension Network (FPHN) registries. However, the distinction between high and intermediate-risk profiles may be difficult as the latter lacks granularity. In addition, neither COMPERA or FPHN strategies included imaging-derived markers. We thus aimed at investigating whether surrogate echocardiographic markers of right ventricular (RV) to pulmonary artery (PA) coupling could improve risk stratification in patients at intermediate-risk. Material and methods: A single-center retrospective analysis including 102 patients with a diagnosis of PAH was performed. COMPERA and FPHN strategies were applied to stratify clinical risk. The univariate linear regression was used to test the influence of the echo-derived parameters qualifying the right heart (right ventricle basal diameter, right atrial area, and pressure, tricuspid regurgitation velocity, tricuspid annular plane systolic excursion -TAPSE-). Among these, the TAPSE and tricuspid regurgitation velocity ratio (TAPSE/TRV) as well as the TAPSE and systolic pulmonary artery pressure ratio (TAPSE/sPAP) were considered as surrogate of RV-PA coupling. Results: TAPSE/TRV and TAPSE/sPAP resulted the more powerful markers of prognosis. Once added to COMPERA, TAPSE/TRV or TAPSE/sPAP significantly dichotomized intermediate-risk group in intermediate-to-low-risk (TAPSE/TRV≥3.74 mm∙nm/s)-1 or TAPSE/sPAP≥0.24 mm/mmHg) and in intermediate-to-high-risk subgroups (TAPSE/TRV<3.74 mm∙(m/s)-1 or TAPSE/sPAP<0.24 mm/mmHg). In the same way, TAPSE/TRV or TAPSE/sPAP was able to select patients at lower risk among those with 2, 1, and 0 low-risk criteria of both invasive and non-invasive FPHN registries. Conclusions: Our results suggest that adopting functional-hemodynamic echo-derived parameters may provide a more accurate risk stratification in patients with PAH. In particular, TAPSE/TRV or TAPSE/sPAP improved risk stratification in patients at intermediate-risk, that otherwise would have remained less characterized. [ABSTRACT FROM AUTHOR]

Objective and design: We examined the role of eCIRP in the pathogenesis of bleomycin-induced pulmonary fibrosis (PF). Material and methods: Publicly available gene expression omnibus datasets were analyzed for the expression of CIRP in lung samples from patients with PF. Wild type (WT) or CIRP-/- mice received daily injections of 10 μg/g bleomycin for 10 days. A subset of bleomycin-injected WT mice was treated with the eCIRP antagonist C23 (8 μg/g/day) from day 10 to day 19. At three weeks, transthoracic echocardiography was performed to measure the degree of pulmonary hypertension, and lung tissues were collected and analyzed for markers of fibrosis. Results: Analysis of the mRNA data of human lung samples showed a significant positive correlation between CIRP and α-smooth muscle actin (α-SMA), an important marker of fibrosis. Moreover, the expression of CIRP was higher in patients with acute exacerbation of PF than in patients with stable PF. CIRP-/- mice showed attenuated induction of α-SMA and collagens (Col1a1, Col3a1), reduced hydroxyproline content, decreased histological fibrosis scores, and improved pulmonary hypertension as compared to WT mice. WT mice treated with C23 also had significant attenuation of the above endpoint measure. Conclusions: Our study demonstrates that eCIRP plays a key role in promoting the development of PF, and blocking eCIRP with C23 can significantly attenuate this process. [ABSTRACT FROM AUTHOR]

Background: Balloon pulmonary angioplasty (BPA) is an effective treatment for inoperable chronic thromboembolic pulmonary hypertension (CTEPH). The purpose of this study is to evaluate the therapeutic effect and safety of the non-slip element percutaneous transluminal angioplasty (NSE PTA) scoring balloons in BPA. Methods: 108 pulmonary artery branches in 14 CTEPH patients who underwent BPA using NSE PTA scoring balloon (the NSE PTA group) or plain balloon (the POBA group) and pressure gradient evaluation were analyzed. We compared the improvement of the pressure ratios after BPA (Δ Pressure ratio) of both groups. Results: There was no significant difference in the Δ Pressure ratios of the two groups (0.241 ± 0.196 POBA, 0.259 ± 0.177 NSE PTA, p = 0.63). No complications occurred in the NSE PTA group, while 3 episodes of hemoptysis were seen in the POBA group. This, however, was not found to be significant (p = 0.27). In the cases where balloon-to-vessel ratio exceeded 1.0 (n = 35), multivariate analysis showed that the use of NSE PTA scoring balloon and pressure ratio before BPA were significantly correlated with Δ Pressure ratio (β coefficient: 0.047, 95% CI: 0.0016 to 0.093, p = 0.043 and β coefficient: −0.60, 95% CI: −0.78 to −0.42, p < 0.01, respectively). Conclusions: Although NSE PTA scoring balloon was safe, there was no significant pressure gradient improvement with NSE PTA scoring balloon compared to conventional BPA. Nevertheless, the NSE PTA scoring balloon showed effective blood-flow improvement in the case of large balloon-to-vessel ratio. [ABSTRACT FROM AUTHOR]

Introduction: Diabetes mellitus (DM), hypertension and pulmonary tuberculosis (PTB) are catastrophic illnesses that collectively lead to increased mortality and premature death. However, the size of the problem and the appropriate approach to deal with the burden is still unclear. We aimed to evaluate the yield, number needed to screen (NNS) to prevent one death or adverse event for screening DM and hypertension and assess the prevalence and contributors to DM and/or hypertension. Methods: Based on PTB contact tracing, a cross-sectional study was conducted among 801 PTB index cases and 972 household contacts from April 2019 to October 2020 in Guizhou, China. All the participants were screened for DM and hypertension. The yield was calculated as the proportion of newly detected cases among the study subjects, excluding known cases. The NNS was computed by dividing the number needed to treat for risk factors by the prevalence of the unrecognized diseases. The univariate and multivariate logistic regression analyses were applied to determine the independent predictors of DM and/or hypertension. Results: Of the 1,773 participants, the prevalence of DM and hypertension was 8.7% (70/801) and 15.2% (122/801) in the PTB patients, 3.2% (31/972) and 14.0% (136/972) in the contacts, respectively. The prevalence of DM and/or hypertension was 21.2% (170/801) among the PTB patients and 15.4% (150/972) among their contacts. The screening yields to detect new cases of DM and hypertension among PTB patients were 1.9% and 5.2%, and that in the contacts were 0.8% and 4.8%, respectively. The NNS for DM was 359 for the PTB cases and 977 for the contacts, 299 for PTB cases and 325 for hypertension, respectively. Older age, under or overweight and obesity, family history hypertension and earlier diagnosis of other chronic conditions were the independent predictors for DM and/or hypertension among both PTB cases and their contacts. Conclusion: Screening for DM and hypertension should be mandated in PTB patients and their household contacts to disclose undetected cases of these two conditions during TB contact tracing, which might reduce the potential cardiovascular disease deaths. [ABSTRACT FROM AUTHOR]

Background: Heart failure is a severe condition often involving pulmonary hypertension (PH). Soluble low-density lipoprotein receptor with 11 ligand-binding repeats (sLR11) has been associated with pulmonary artery hypertension. We examined whether sLR11 correlates with PH in left heart disease and can be used as a predictive marker. Method: We retrospectively analyzed patients with severe mitral regurgitation who underwent right heart catheterization before surgery for valve replacement or valvuloplasty from November 2005 to October 2012 at Juntendo University. We measured sLR11 levels before right heart catheterization and analyzed correlations with pulmonary hemodynamics. We compared prognoses between a group with normal sLR11 (≤9.4 ng/ml) and a group with high sLR11 (>9.4 ng/ml). Follow-up was continued for 5 years, with end points of hospitalization due to HF and death due to cardiovascular disease. Results: Among 34 patients who met the inclusion criteria, sLR11 correlated with mean pulmonary artery pressure (r = 0.54, p<0.001), transpulmonary pressure gradient (r = 0.42, p = 0.012), pulmonary vascular resistance (r = 0.36, p<0.05), and log brain natriuretic peptide (BNP). However, logBNP did not correlate with pulmonary vascular resistance (p = 0.6). Levels of sLR11 were significantly higher in the 10 patients with PH (14.4±4.3 ng/ml) than in patients without PH (9.9±3.9 ng/ml; p = 0.002). At 5 years, the event rate was higher in the high-sLR11 group than in the normal-sLR11 group. The high-sLR11 group showed 5 hospitalizations due to HF (25.0%) and 2 deaths (10.0%), whereas the normal-sLR11 group showed no hospitalizations or deaths. Analyses using receiver operating characteristic curves showed a higher area under the concentration-time curve (AUC) for sLR11 level (AUC = 0.85; 95% confidence interval (CI) = 0.72–0.98) than for BNP (AUC = 0.80, 95%CI = 0.62–0.99) in the diagnosis of PH in left heart disease. Conclusions: Concentration of sLR11 is associated with severity of PH and offers a strong predictor of severe mitral regurgitation in patients after surgery. [ABSTRACT FROM AUTHOR]

Introduction: Outcome predictions of patients with congenital diaphragmatic hernia (CDH) still have some limitations in the prenatal estimate of postnatal pulmonary hypertension (PH). We propose applying Machine Learning (ML), and Deep Learning (DL) approaches to fetuses and newborns with CDH to develop forecasting models in prenatal epoch, based on the integrated analysis of clinical data, to provide neonatal PH as the first outcome and, possibly: favorable response to fetal endoscopic tracheal occlusion (FETO), need for Extracorporeal Membrane Oxygenation (ECMO), survival to ECMO, and death. Moreover, we plan to produce a (semi)automatic fetus lung segmentation system in Magnetic Resonance Imaging (MRI), which will be useful during project implementation but will also be an important tool itself to standardize lung volume measures for CDH fetuses. Methods and analytics: Patients with isolated CDH from singleton pregnancies will be enrolled, whose prenatal checks were performed at the Fetal Surgery Unit of the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Milan, Italy) from the 30th week of gestation. A retrospective data collection of clinical and radiological variables from newborns' and mothers' clinical records will be performed for eligible patients born between 01/01/2012 and 31/12/2020. The native sequences from fetal magnetic resonance imaging (MRI) will be collected. Data from different sources will be integrated and analyzed using ML and DL, and forecasting algorithms will be developed for each outcome. Methods of data augmentation and dimensionality reduction (feature selection and extraction) will be employed to increase sample size and avoid overfitting. A software system for automatic fetal lung volume segmentation in MRI based on the DL 3D U-NET approach will also be developed. Ethics and dissemination: This retrospective study received approval from the local ethics committee (Milan Area 2, Italy). The development of predictive models in CDH outcomes will provide a key contribution in disease prediction, early targeted interventions, and personalized management, with an overall improvement in care quality, resource allocation, healthcare, and family savings. Our findings will be validated in a future prospective multicenter cohort study. Registration: The study was registered at ClinicalTrials.gov with the identifier NCT04609163. [ABSTRACT FROM AUTHOR]

Mitral valve disease (MVD) is an important and most frequently acquired heart disease found in dogs. MVD is classified into different stages according to its severity. There is a challenge in differentiation between asymptomatic and symptomatic stages of the MVD. Moreover, pulmonary hypertension (PH) is a common complication in dogs affected by MVD. In clinical practice, there are also some limitations to identify PH. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a technique that can characterize specific patterns of peptide mass called peptide barcodes from various samples. Besides, in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS), potential peptide sequences associated with specific conditions could be identified. The present study aimed to use MALDI-TOF coupled with LC-MS/MS to characterize specific peptide barcodes and potential peptide candidates in serum samples from healthy dogs, dogs with MVD stage B (MVD B, asymptomatic stage), MVD stage C (MVD C, symptomatic stage), MVD stage B with PH (MVD B PH), and MVD stage C with PH (MVD C PH). Discrete clusters of the 5 sample groups were identified by 3D plot analysis. Peptide barcodes also revealed differences in peptide patterns among the 5 groups. Six amino acid sequences of peptide candidates at 1,225.60, 1,363.85, 1,688.71, 1789.52, 2020.21, and 2156.42 Da were identified as part of the proteins CLCN1, CLUL1, EDNRA, PTEN, SLC39A7, and CLN6, respectively. The network interactions between these discovered proteins and common cardiovascular drugs were also investigated. These results demonstrate that MALDI-TOF MS has promise as an optional technique for diagnosing dogs affected by asymptomatic and symptomatic stages of MVD with and without PH. Further studies are required to identify peptide barcodes in dogs with other diseases to create peptide barcode databases in veterinary medicine before using this method as a novel diagnostic tool in the future. [ABSTRACT FROM AUTHOR]

The efficacy of extensive balloon pulmonary angioplasty (BPA) beyond hemodynamic improvement in chronic thromboembolic pulmonary hypertension (CTEPH) patients has been verified. However, the relationship between extensive BPA in CTEPH patients after partial hemodynamic improvement and exercise tolerance or quality of life (QOL) remains unclear. We prospectively enrolled 22 CTEPH patients (66±10 years, females: 59%) when their mean pulmonary artery pressure initially decreased to <30 mmHg during BPA sessions. Hemodynamic and echocardiographic data, cardiopulmonary exercise testing, and QOL scores using the 36-item short form questionnaire (SF-36) were evaluated at enrollment (entry), just after the final BPA session (finish), and at the 6-month follow-up (follow-up). We analyzed whether extensive BPA improves exercise capacity and QOL scores over time. Moreover, the clinical characteristics leading to improvement were elucidated. The peak oxygen uptake (VO2) showed significant improvement at entry, finish, and follow-up (17.3±5.5, 18.4±5.9, and 18.9±5.3 mL/kg/min, respectively; P<0.001). Regarding the QOL, the physical component summary (PCS) scores significantly improved (32±11, 38±13, and 43±13, respectively; P<0.001), but the mental component summary scores remained unchanged. Linear regression analysis revealed that age and a low peak VO2 at entry were predictors of improvement in peak VO2, while low PCS scores and low TAPSE at entry were predictors of improvement in PCS scores. In conclusion, extensive BPA led to improved exercise tolerance and physical QOL scores, even in CTEPH patients with partially improved hemodynamics. [ABSTRACT FROM AUTHOR]

Balloon pulmonary angioplasty improves prognosis by alleviating pulmonary hypertension in patients with chronic thromboembolic pulmonary hypertension, even with incomplete revascularization. However, hypoxia or the requirement for pulmonary vasodilators often remain even after pulmonary hypertension relief. With this cohort study, we aimed to examine whether complete revascularization by additional balloon pulmonary angioplasty on residual lesions, even after pulmonary hypertension relief, could resolve hypoxia or the requirement for pulmonary vasodilators. During complete revascularization with balloon pulmonary angioplasty in 42 patients with chronic thromboembolic pulmonary hypertension, we investigated therapeutic effects at baseline (T1), pulmonary hypertension relief phase (T2), and at 6 months post-final balloon pulmonary angioplasty (T3). The pulmonary hypertension relief phase was defined as the first time that a mean pulmonary artery pressure ≤ 25 mmHg or pulmonary vascular resistance ≤ 240 dyn-s/cm5 was reached in right heart catheterization before balloon pulmonary angioplasty. The partial pressure of oxygen increased progressively over T1, T2, and T3 (59.2±8.5, 69.0±9.7, and 80.0±9.5 mmHg, respectively; P<0.001 T2 vs. T3). Minimum oxygen saturation levels during the 6-minute walk distance test were 87% (81‒89%), 88% (84‒92%), and 91% (89‒93.3%), respectively (P<0.001 T2 vs. T3), with gradual increase in the 6-minute walk distance (346±125 m, 404±90 m, 454±101 m, respectively; P<0.001 T2 vs. T3). The percentages of patients using pulmonary vasodilators (54.8%, 45.2%, 4.8%, respectively; P<0.001 T2 vs. T3) and requiring oxygen therapy (26%, 26%, 7%, respectively; P = 0.008 T2 vs. T3) decreased significantly without hemodynamic exacerbation or major complications. Despite the discontinuation of pulmonary vasodilators, mean pulmonary artery pressure improved (36.0 [31.0‒41.3], 21.4±4.2, 18.5±3.6 mmHg, respectively; P<0.001 T2 vs. T3). Complete revascularization with balloon pulmonary angioplasty beyond pulmonary hypertension relief benefits patients with chronic thromboembolic pulmonary hypertension; it may improve oxygenation and exercise capacity, and reduce the need for pulmonary vasodilators and oxygen therapy. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the agreement in detecting pulmonary perfusion defects in patients with chronic thromboembolic pulmonary hypertension using dual-energy CT and dynamic contrast-enhanced MRI. Second, to compare both imaging modalities in monitoring lung perfusion changes in these patients after undergoing pulmonary endarterectomy. Methods: 20 patients were examined with CT and MRI before and/or after pulmonary endarterectomy. Estimated perfusion defect percentage from both modalities was compared in a lobe-based analysis. Spatial agreement of perfusion defect maps was also assessed. Results: A significant correlation between CT and MRI based perfusion defect percentage was calculated in all lung lobes (r > 0.78; p < 0.001). In addition, a good spatial agreement between perfusion defect maps was found (mean spatial overlap for the whole lung was 68.2%; SD = 6.9). Both CT and MRI detected improvements in pulmonary perfusion after pulmonary endarterectomy: 8% and 7% decrease in whole lung perfusion defect percentage (p = 0.007 and 0.004), respectively. In a lobe-wise analysis, improvements were statistically significant only in lower lobes using both modalities (reduction in defect percentage ranged from 16–29%; p < 0.02). Conclusions: Dual-energy CT is an alternative to MRI in monitoring chronic thromboembolic pulmonary hypertension. Both imaging modalities provided comparable estimations of perfusion defects and could detect similar improvement in lung perfusion after pulmonary endarterectomy. [ABSTRACT FROM AUTHOR]

Beetroot (Beta vulgaris L.) has a high level of nitrate; therefore, its dietary intake could increase nitric oxide (NO) level in the body, possibly preventing the development of pulmonary hypertension (PH). In this study, we examined the effects of beetroot juice (BJ) supplementation on PH and the contribution of nitrate to such effects using a rat model of monocrotaline (MCT, 60 mg/kg s.c.)-induced PH. Rats were injected subcutaneously with saline or 60 mg/kg MCT and were sacrificed 28 days after the injection. In some rats injected with MCT, BJ was supplemented from the day of MCT injection to the day of sacrifice. First, MCT-induced right ventricular systolic pressure elevation, pulmonary arterial medial thickening and muscularization, and right ventricular hypertrophy were suppressed by supplementation with low-dose BJ (nitrate: 1.3 mmol/L) but not high-dose BJ (nitrate: 4.3 mmol/L). Of the plasma nitrite, nitrate, and their sum (NOx) levels, only the nitrate levels were found to be increased by the high-dose BJ supplementation. Second, in order to clarify the possible involvement of nitrate in the preventive effects of BJ on PH symptoms, the effects of nitrate-rich BJ (nitrate: 0.9 mmol/L) supplementation were compared with those of the nitrate-depleted BJ. While the former exerted preventive effects on PH symptoms, such effects were not observed in rats supplemented with nitrate-depleted BJ. Neither supplementation with nitrate-rich nor nitrate-depleted BJ affected plasma nitrite, nitrate, and NOx levels. These findings suggest that a suitable amount of BJ ingestion, which does not affect systemic NO levels, can prevent the development of PH in a nitrate-dependent manner. Therefore, BJ could be highly useful as a therapy in patients with PH. [ABSTRACT FROM AUTHOR]

The characterization of pulmonary arterial hypertension (PAH) relies mainly on right heart catheterization (RHC). Electrical impedance tomography (EIT) provides a non-invasive estimation of lung perfusion that could complement the hemodynamic information from RHC. To assess the association between impedance variation of lung perfusion (ΔZQ) and hemodynamic profile, severity, and prognosis, suspected of PAH or worsening PAH patients were submitted simultaneously to RHC and EIT. Measurements of ΔZQ were obtained. Based on the results of the RHC, 35 patients composed the PAH group, and eight patients, the normopressoric (NP) group. PAH patients showed a significantly reduced ΔZQ compared to the NP group. There was a significant correlation between ΔZQ and hemodynamic parameters, particularly with stroke volume (SV) (r = 0.76; P < 0.001). At 60 months, 15 patients died (43%) and 1 received lung transplantation; at baseline they had worse hemodynamics, and reduced ΔZQ when compared to survivors. Patients with low ΔZQ (≤154.6%.Kg) presented significantly worse survival (P = 0.033). ΔZQ is associated with hemodynamic status of PAH patients, with disease severity and survival, demonstrating EIT as a promising tool for monitoring patients with pulmonary vascular disease. [ABSTRACT FROM AUTHOR]

Background: Several forms of pulmonary hypertension (PH) disproportionately affect women. Animal and human studies suggest that estradiol exerts mixed effects on the pulmonary vasculature. Whether premature menopause represents a risk factor for PH is unknown. Methods and findings: In this cohort study, women in the UK Biobank aged 40–69 years who were postmenopausal and had complete data available on reproductive history were included. Premature menopause, defined as menopause occurring before age 40 years. Postmenopausal women without premature menopause served as the reference group. The primary outcome was incident PH, ascertained by appearance of a qualifying ICD code in the participant's UK Biobank study record. Of 136,715 postmenopausal women included, 5,201 (3.8%) had premature menopause. Participants were followed up for a median of 11.1 (interquartile range 10.5–11.8) years. The primary outcome occurred in 38 women (0.73%) with premature menopause and 409 (0.31%) without. After adjustment for age, race, ever-smoking, body-mass index, systolic blood pressure, antihypertensive medication use, non-high-density lipoprotein cholesterol, cholesterol-lowering medication use, C-reactive protein, prevalent type 2 diabetes, obstructive sleep apnea, heart failure, mitral regurgitation, aortic stenosis, venous thromboembolism, forced vital capacity (FVC), the forced expiratory volume in 1 second-to-FVC ratio, use of menopausal hormone therapy, and hysterectomy status, premature menopause was independently associated with PH (hazard ratio 2.13, 95% CI 1.31–3.23, P<0.001). In analyses of alternate menopausal age thresholds, risk of PH appeared to increase progressively with younger age at menopause (Ptrend <0.001), with 4.8-fold risk in women with menopause before age 30 years (95% CI 1.82–12.74, P = 0.002). Use of menopausal hormone therapy did not modify the association of premature menopause with PH. Conclusions: Premature menopause may represent an independent risk factor for PH in women. Further investigation of the role of sex hormones in PH is needed in animal and human studies to elucidate pathobiology and identify novel therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: The prognostic implications of combined pre- and post-capillary pulmonary hypertension (Cpc-PH) in patients with pulmonary hypertension due to left heart disease (PH-LHD) remain controversial. The aim of this retrospective study was to evaluate the new PH-LHD criteria, recommended by the 6th World Symposium on Pulmonary Hypertension and to determine the prognostic value of Cpc-PH. Methods: A total of 701 patients with symptomatic heart failure who had undergone right-heart catheterization were divided into the following four groups: (i) Isolated post-capillary PH (Ipc-PH) group; mean pulmonary artery pressure (mPAP) >20 mmHg, pulmonary artery wedge pressure (PAWP) >15 mmHg, and pulmonary vascular resistance (PVR) <3 Wood units (WU) (ii) Cpc-PH group; mPAP >20 mmHg, PAWP >15 mmHg, and PVR ≥3 WU (iii) borderline-PH group; mPAP >20 mmHg and PAWP ≤15 mmHg (iv) non-PH group; mPAP ≤20 mmHg. Multivariate Cox hazard analysis was used to investigate whether Cpc-PH was associated with cardiac outcomes. Results: The study subjects were allocated into the Ipc-PH (n = 268), Cpc-PH (n = 54), borderline-PH (n = 112), or non-PH (n = 267) groups. The Cpc-PH group was associated significantly with adverse cardiac events even after adjustment for clinically relevant confounding factors for heart failure prognosis (vs. non-PH group: HR 2.98 [95% CI 1.81–4.90], P <0.001; vs. Ipc-PH group: HR: 1.92 [95% CI 1.19–3.08], P = 0.007). Conclusions: The new definitions of PH-LHD stratified patients into 4 categories. Long-term clinical outcomes were significantly different between the four categories, with Cpc-PH having the worst cardiac outcomes. [ABSTRACT FROM AUTHOR]

Background: People living with human immunodeficiency virus (PLWH) are at risk of developing pulmonary hypertension (PH) and right ventricular (RV) dysfunction, but understanding of the relationship of RV function to afterload (RV-PA coupling) is limited. We evaluated the clinical and hemodynamic characteristics of human immunodeficiency virus (HIV)-associated PH. Methods: We performed a retrospective review of patients with a diagnosis of HIV undergoing right heart catheterization (RHC) from 2000–2016 in a tertiary care center. Inclusion criteria were diagnosis of HIV, age ≥ 18 years and availability of RHC data. PH was classified as either pulmonary arterial hypertension (PAH; mean pulmonary arterial pressure [mPAP] ≥ 25mmHg with pulmonary artery wedge pressure [PAWP] ≤ 15mmHg) or pulmonary venous hypertension (PVH; mPAP ≥ 25mmHg with PAWP > 15). We collected demographics, CD4 cell count, HIV viral load, RHC and echocardiographic data. The single beat method was used to calculate RV-PA coupling from RHC. Results: Sixty-two PLWH with a clinical likelihood for PH underwent RHC. Thirty-two (52%) met PH criteria (15 with PAH, 17 with PVH). Average time from diagnosis of HIV to diagnosis of PH was 11 years. Eleven of 15 individuals with PAH were on antiretroviral therapy (ART) while all 17 patients with PVH were on ART. Compared to PLWH without PH, those with PH had an increased likelihood of having a detectable HIV viral load and lower CD4 cell counts. PLWH with PAH or PVH had increased RV afterload with normal RV contractility, and preserved RV-PA coupling. Conclusion: PLWH with PH (PAH or PVH) were more likely to have a detectable HIV viral load and lower CD4 count at the time of RHC. PLWH with PAH or PVH had increased RV afterload, normal RV contractility, with preserved RV-PA coupling suggestive of an early onset, mild, and compensated form of PH. These results should be confirmed in larger studies. [ABSTRACT FROM AUTHOR]

Diazoxide is the first-line drug for treating hyperinsulinism and the only pharmacological agent approved for hyperinsulinism by the Federal Drug Administration. This systemic review and meta-analysis aimed to investigate the efficacy and safety of diazoxide for treating hyperinsulinemic hypoglycemia (HH). The meta-analysis of the efficacy and safety of diazoxide in treating HH was performed by searching relevant studies in the PubMed, Embase, and Cochrane databases. The findings were summarized, and the pooled effect size and its 95% confidence interval (CI) were calculated. A total of 6 cohort studies, involving 1142 participants, met the inclusion criteria. Among the cohort studies, the pooled estimate of the response rate of diazoxide therapy was 71% (95% CI 50%–93%, Pheterogeneity< 0.001, I2 = 98.3%, Peffect< 0.001). The common side effects were hypertrichosis (45%), fluid retention (20%), gastrointestinal reaction (13%), edema (11%), and neutropenia (9%). Other adverse events included pulmonary hypertension (2%) and thrombocytopenia (2%). This meta-analysis suggested that diazoxide was potentially useful in HH management; however, it had some side effects, which needed careful monitoring. Furthermore, well-designed large-scale studies, such as randomized controlled trials, might be necessary in the future to obtain more evidence. [ABSTRACT FROM AUTHOR]

Purpose: Patients with pulmonary hypertension (PH) frequently suffer from supraventricular tachycardias (SVT). The main purpose of our study was to identify the cumulative incidence of SVT in patients with different etiologies of PH. The secondary objective was to analyse the clinical impact of SVT. Methods: We retrospectively studied the prevalence of SVT and the clinical outcome in 755 patients (41% males; 60 ± 15 years; mean follow-up 3.8 ± 2.8 years) with PH of different etiologies. The prevalence of SVT was analysed separately in isolated pre-capillary PH (Ipc-PH) and in patients with combined post- and pre-capillary PH (Cpc-PH). Results: The prevalence of SVT in the Ipc-PH group (n = 641) was 25% (n = 162). The most prevalent arrhythmias were atrial fibrillation followed by a typical atrial flutter (17% and 4.4% of all Icp-PH patients). An excessive prevalence of SVT was found in patients with pulmonary arterial hypertension associated with congenital heart disease (35%, p = 0.01). Out of the overall study population, Cpc-PH was present in 114 (15%) patients. Patients with Cpc-PH manifested a higher prevalence of SVT than subjects with Ipc-PH (58; 51% vs. 162; 25%; p <0.0001) and were more likely to have persistent or permanent atrial fibrillation (38; 29% vs. 61; 10%; p <0.0001). Parameters significantly associated with mortality in a multivariate analysis included age, male gender, functional exercise capacity and right atrial diameter (p < 0.05). Neither diagnosis of SVT nor type of arrhythmia predicted mortality. Conclusions: The study detected a significant prevalence of SVT in the population of PH of different origins. Different spectrum and prevalence of arrhythmia might be expected in different etiologies of PH. Patients with an elevated post-capillary pressure showed a higher arrhythmia prevalence, predominantly due to an excessive number of atrial fibrillations. The diagnosis of SVT was not associated with mortality. [ABSTRACT FROM AUTHOR]

Cardiopulmonary complications are among the most important complications of thalassemia major. Pulmonary hypertension is among these complications and studies addressing its frequency and associations in the latter disorder are sparse from Iraq. For this purpose a total 100 thalassemia major patients (≥ 8 years old) were enrolled from a main thalassemia center in Kurdistan, Northern Iraq. All patients had a full history and clinical examination. Full blood count, biochemical tests and viral screen including hepatitis B surface antigen and hepatitis C virus antibody, in addition to transthoracic Doppler echocardiography for tricuspid regurgitation jet velocity (TRV). The enrolled patients had a mean (SD) age of 17.6 (5.5) years, and included 52 males and 48 females. Pulmonary hypertension as defined by TRV> 2.8 m/s coupled with both exertional dyspnea and an absence of left sided heart failure, was identified in nine patients (9%). The latter subgroup of patients had significantly higher reticulocyte counts, S. LDH, S. ferritin, and hepatitis C sero-positivity compared to those without this complication by univariate analysis. While by multivariate logistic regression only reticulocytes and hepatitis C sero-positivity remained significant. Furthermore, TRV as a continuous variable was positively correlated with reticulocytes, S. bilirubin and LDH (p<0.001, p = 0.002 and p<0.001 respectively), but not with age or S. ferritin (p = 0.77, and p = 0.93 respectively). In conclusion, pulmonary hypertension is not uncommon in Iraqi patients with thalassemia major, and it appears to be linked to chronic hemolysis rather than iron overload. [ABSTRACT FROM AUTHOR]

Systemic sclerosis is a disease where microcirculation damage is critical in their beginning and vascular complications have similar pathogenic findings. Digital ulcers are a frequent complication in systemic sclerosis patients and pulmonary hypertension is one of the leading causes of death. The use of bosentan has been shown to be useful for the treatment of pulmonary arterial hypertension and to prevent new digital ulcers. However, is unknown if bosentan can prevent pulmonary hypertension. Our objective was to determine if bosentan is useful to prevent pulmonary hypertension in SSc patients. A retrospective study in 237 systemic sclerosis patients with digital ulcers history treated or not with bosentan to prevent it was made. We analyzed the occurrence of pulmonary hypertension defined by an echocardiogram pulmonary arterial pressure > 40 mmHg in the entire cohort. Demographic, clinical, and treatment variables were recorded for all patients. Statistical significance was denoted by p values < 0.05. Fifty-nine patients were treated with bosentan a median of 34 months. 13.8% of treated patients had pulmonary hypertension vs 23.7% of untreated patients (p 0.13) during the follow up. In multivariate analysis patients not treated with bosentan had 3.9fold-increased risk of pulmonary hypertension compared with patients under bosentan treatment (p < 0.02). Moreover the percentage carbon monoxide diffusing capacity (DLCO) in bosentan treated patients did not decrease from baseline to the end of follow-up (61.8±14% vs 57±20.1%, p = 0.89). We concluded that Systemic sclerosis patients with digital ulcers treated with bosentan seems to have less risk to develop pulmonary hypertension and to stabilize DLCO [ABSTRACT FROM AUTHOR]

The pathophysiological mechanisms underlying chronic thromboembolic pulmonary hypertension (CTEPH) are still unclear. Endothelial cell (EC) remodeling is believed to contribute to this pulmonary disease triggered by thrombus and hemodynamic forces disbalance. Recently, we showed that HSP70 levels decrease by proatherogenic shear stress. Molecular chaperones play a major role in proteostasis in neurological, cancer and inflammatory/ infectious diseases. To shed light on microvascular responses in CTEPH, we characterized the expression of molecular chaperones and annexin A2, a component of the fibrinolytic system. There is no animal model that reproduces microvascular changes in CTEPH, and this fact led us to isolated endothelial cells from patients with CTEPH undergoing pulmonary endarterectomy (PEA). We exposed CTEPH-EC and control human pulmonary endothelial cells (HPAEC) to high- (15 dynes/cm2) or low- (5 dynes/cm2) shear stress. After high-magnitude shear stress HPAEC upregulated heat shock protein 70kDa (HSP70) and the HSP ER paralogs 78 and 94kDa glucose-regulated protein (GRP78 and 94), whereas CTEPH-ECs failed to exhibit this response. At static conditions, both HSP70 and HSP90 families in CTEPH-EC are decreased. Importantly, immunohistochemistry analysis showed that HSP70 expression was downregulated in vivo, and annexin A2 was upregulated. Interestingly, wound healing and angiogenesis assays revealed that HSP70 inhibition with VER-155008 further impaired CTEPH-EC migratory responses. These results implicate HSP70 as a novel master regulator of endothelial dysfunction in type 4 PH. Overall, we first show that global failure of HSP upregulation is a hallmark of CTEPH pathogenesis and propose HSP70 as a potential biomarker of this condition. [ABSTRACT FROM AUTHOR]

Background: Accurate and regular risk assessment is important for evaluation and treatment of pulmonary arterial hypertension (PAH) patients, including those with functional class (FC) II symptoms, a population considered at low risk for disease progression. Risk assessment methods include subjective and objective evaluations. Multiparametric assessments include tools based on the European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines (COMPERA and FPHR methods, respectively) and the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL; REVEAL 2.0 tool). To better understand risk status determination in FC II patients, we compared physician-reported risk assessments with objective multiparameter assessment tools. Methods: This retrospective chart analysis included PAH patients with FC II symptoms receiving monotherapy or dual therapy. Physicians were surveyed (via telephone) to obtain an assessment of patient risk using their typical methodology, which might have been informed by objective risk assessment. Patient risk was then calculated independently using COMPERA, FPHR and REVEAL 2.0 tools. Factors associated with incongruent risk assessment were identified. Results: Of the 153 patients, 41%, 46%, and 13% were classified as low, intermediate, and high risk, respectively, by physicians. Concordance between physician gestalt and objective methods ranged from 43%–54%. Among patients considered as low risk by physician gestalt, 4%–28% were categorized as high risk using objective methods. The most common physician factor associated with incongruent risk assessment was less frequent echocardiography during follow-up (every 7–12 months vs. every 3 months; p = 0.01). Conclusions: More than half of FC II PAH patients were classified as intermediate/high risk using objective multiparameter assessments. Incorporating objective risk-assessment algorithms into clinical practice may better inform risk assessment and treatment strategies. [ABSTRACT FROM AUTHOR]

Introduction: Indigo naturalis (IN) is a blue pigment extracted from Assam indigo and other plants and has been confirmed to be highly effective for ulcerative colitis (UC) treatment in several clinical studies. Objective: We conducted a multicenter double-blind study to confirm the efficacy and safety of short-term IN administration. Methods: A multicenter, randomized controlled trial was conducted between December 2015 and October 2018 in our facilities. Forty-six patients with mild to moderate active UC (Lichtiger index: 5–10) were randomly assigned to the IN group or the placebo group and received 5 capsules (500 mg) twice a day for 2 weeks. We investigated the efficacy according to blood tests and the Lichtiger index before and after administration, and we also examined adverse events. Results: The analysis included 42 patients (20 males, 22 females) with an average age of 45 years. Nineteen patients were assigned to the placebo group, and 23 were assigned to the IN group. After treatment administration, in the placebo group, no change in the Lichtiger index was observed (7.47 to 6.95, p = 0.359), and hemoglobin was significantly reduced (12.7 to 12.4, p = 0.031), while in the IN group, the Lichtiger index (9.04 to 4.48, p = 0.001) and albumin (4.0 to 4.12, p = 0.022) improved significantly. Mild headaches were observed in 5 patients and 1 patient in the IN and placebo groups, respectively. Conclusions: Short-term administration of IN is highly effective without serious adverse events such as pulmonary hypertension or intussusception and may prevent the occurrence of serious adverse events. [ABSTRACT FROM AUTHOR]

Objective: Optimizing cardiac stroke volume during high-risk surgical anesthesia is of particular interest with regard to a therapeutic target to reduce the incidence of postoperative complications. However, intensive fluid management in critically ill small animals with pulmonary hypertension (PH) has been empirically performed, and thus it can be challenging. Stroke volume variation (SVV) has been used as a dynamic preload predictor of fluid responsiveness. We hypothesized that if SVV exhibited robust reliability in the setting of hemodynamically unstable condition, it would provide more precise information on fluid resuscitation to translate it into veterinary anesthesia. Thus the aim of this study was to investigate the utility of SVV measured by the electrical velocimetry (EV) method for predicting fluid responsiveness in dogs with PH. Methods: Sixteen dogs undergoing emergency abdominal surgery and diagnosed with PH secondary to myxomatous mitral valve disease (MMVD) on preoperative transthoracic echocardiogram were included. Dogs were randomly assigned to 2 groups with and without inotropic cardiac support with dobutamine. Hemodynamic measurements including stroke volume and SVV derived from the EV device were performed under general anesthesia before (baseline) and after surgery (fluid challenge with a colloid solution defined by a SV increase of ≥ 10%). Results: In both groups, SVV elevated significantly after abdominal surgery compared with baseline. In dobutamine infused group, the SVV values decreased significantly after fluid challenge (P < 0.05) with a greater number of responders than saline infused control group (P < 0.01). Receiver operating curve analysis of SVV confirmed high positive predictive value for dogs during dobutamine infusion (P < 0.05; cut-off value of 15%; specificity 90%, sensitivity 82%). Conclusions: Noninvasive EV monitoring may be useful for the prediction of fluid responsiveness in critically ill dogs with left-sided heart failure-related PH. This normalization of dynamic preload indices, which could be achieved more precisely under inotropic support, may prevent further detrimental consequence of fluid loading. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is a lethal disease characterized by a progressive increase in pulmonary artery pressure due to an increase in vessel tone and occlusion of vessels. The endogenous vasodilator prostacyclin and its analogs are used as therapeutic agents for PAH. However, their pharmacological effects on occlusive vascular remodeling have not been elucidated yet. Selexipag is a recently approved, orally available and selective prostacyclin receptor agonist with a non-prostanoid structure. In this study, we investigated the pharmacological effects of selexipag on the pathology of chronic severe PAH in Sprague-Dawley and Fischer rat models in which PAH was induced by a combination of injection with the vascular endothelial growth factor receptor antagonist Sugen 5416 and exposure to hypoxia (SuHx). Oral administration of selexipag for three weeks significantly improved right ventricular systolic pressure and right ventricular (RV) hypertrophy in Sprague-Dawley SuHx rats. Selexipag attenuated the proportion of lung vessels with occlusive lesions and the medial wall thickness of lung arteries, corresponding to decreased numbers of Ki-67-positive cells and a reduced expression of collagen type 1 in remodeled vessels. Administration of selexipag to Fischer rats with SuHx-induced PAH reduced RV hypertrophy and mortality caused by RV failure. These effects were probably based on the potent prostacyclin receptor agonistic effect of selexipag on pulmonary vessels. Selexipag has been approved and is used in the clinical treatment of PAH worldwide. It is thought that these beneficial effects of prostacyclin receptor agonists on multiple aspects of PAH pathology contribute to the clinical outcomes in patients with PAH. [ABSTRACT FROM AUTHOR]

Background: Pulmonary arterial hypertension (PAH) is a progressive chronic disease with poor outcomes. One reason for poor prognosis is the lack of understanding regarding individual variability in response to treatment. Idiopathic PAH (IPAH) patients with bone morphogenetic protein receptor type 2 (BMPR2) mutations have distinct phenotypes that are crucial for individualized therapy but evidence regarding their prevalence and clinical features in the Korean population is lacking. Therefore, the present study aimed to screen Korean IPAH patients for BMPR2 mutations and analyze their clinical phenotypes. Methods: We enrolled 73 unrelated IPAH patients for BMPR2 mutation screening between March 2010 to November 2015 from 11 hospitals in Korea. Thirty-three lineal family members from 6 families of BMPR2 mutation carriers were also screened. Results: Among 73 patients, 16 (22%) had BMPR2 mutations. Mutation carriers were younger (27 vs. 47 years; p = 0.02) and had a higher mean pulmonary arterial pressure (mPAP) than non-carriers (64 vs. 51 mmHg; p<0.05). Of the 16 individuals with mutations, 5 deletion, 2 splice-site, 6 nonsense, and 3 missense mutations were found, among which, 9 were newly identified mutation types. Patients less than 30 years old had more BMPR2 mutations (44 vs. 14%; p = 0.04) and a higher mPAP (64 vs. 50 mmHg; p = 0.04) compared with those equaled to or over 30 years old. There were no differences in hemodynamic profiles or the proportion of BMPR2 mutation carriers between groups according to sex. Conclusion: The prevalence of BMPR2 mutations in Korean IPAH patients was 22%. Mutation carriers were younger and had a poorer hemodynamic profile compared with the non-carriers. Clinical trial registration: Clinicaltrials.gov NCT01054105 [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging (MRI) is an emerging tool for diagnosis and treatment monitoring of chronic thromboembolic pulmonary hypertension (CTEPH). The current study aims to identify central pulmonary arterial hemodynamic parameters that reflect clinical, cardiac and pulmonary changes after PEA. 31 CTEPH patients, who underwent PEA and received pre- and postoperative MRI, were analyzed retrospectively. Central pulmonary arterial blood flow, lung perfusion and right heart function data were derived from MRI. Mean pulmonary arterial pressure (mPAP) and 5-month follow-up six-minute walk-distance (6MWD) were assessed. After PEA, mPAP decreased significantly and patients achieved a higher 6MWD. Central pulmonary arterial blood flow velocities, pulmonary blood flow (PBF) and right ventricular function increased significantly. Two-dimensional (2D) phase-contrast (PC) MRI-derived average mean velocity, maximum mean velocity and deceleration volume changes after PEA correlated with changes of 6MWD and right heart ejection fraction (RVEF). Deceleration volume is a novel 2D PC MRI parameter showing further correlation with PBF changes. In conclusion, 2D PC MRI-derived main pulmonary hemodynamic changes reflect changes of RVEF, PBF and 5-month follow-up 6MWD and may be used for future CTEPH patient monitoring after PEA. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension due to left heart disease (PH-LHD) is a momentous pulmonary hypertension disease, and left heart disease is the most familiar cause. Mechanical stretching may be a crucial cause of vascular remodeling. While, the underlining mechanism of mechanical stretching-induced in remodeling of pulmonary vein in the early stage of PH-LHD has not been completely elucidated. In our study, the PH-LHD model rats were successfully constructed. After 25 days, doppler echocardiography and hemodynamic examination were performed. In addition, after treatment, the levels of matrix metalloproteinase-9 (MMP-9) and transforming growth factor-β1 (TGF-β1) were determined by ELISA, immunohistochemistry and western blot assays in the pulmonary veins. Moreover, the pathological change of pulmonary tissues was evaluated by H&E staining. Our results uncovered that left ventricular insufficiency and interventricular septal shift could be observed in PH-LHD model rats, and the right ventricular systolic pressure (RVSP) and mean left atrial pressure (mLAP) were also elevated in PH-LHD model rats. Meanwhile, we found that MMP-9 and TGF-β1 could be highly expressed in PH-LHD model rats. Besides, we revealed that stretch-activated channel (SAC)/mitogen-activated protein kinases (MAPKs) signaling pathway could be involved in the upregulations of MMP-9 and TGF-β1 mediated by mechanical stretching in pulmonary vein. Therefore, current research revealed that mechanical stretching induced the increasing expressions of MMP-9 and TGF-β1 in pulmonary vein, which could be mediated by activation of SAC/MAPKs signaling pathway in the early stage of PH-LHD. [ABSTRACT FROM AUTHOR]

Background: To date, the missed diagnosis rate of pulmonary hypertension (PH) was high, and there has been limited development of a rapid, simple, and effective way to screen the disease. The purpose of this study is to develop a deep learning approach to achieve rapid detection of possible abnormalities in chest radiographs suggesting PH for screening patients suspected of PH. Methods: We retrospectively collected frontal chest radiographs and the pulmonary artery systolic pressure (PASP) value measured by Doppler transthoracic echocardiography from 762 patients (357 healthy controls and 405 with PH) from three institutes in China from January 2013 to May 2019. The wohle sample comprised 762 images (641 for training, 80 for internal test, and 41 for external test). We firstly performed a 8-fold cross-validation on the 641 images selected for training (561 for pre-training, 80 for validation), then decided to tune learning rate to 0.0008 according to the best score on validation data. Finally, we used all the pre-training and validation data (561+80 = 641) to train our models (Resnet50, Xception, and Inception V3), evaluated them on internal and external test dataset to classify the images as having manifestations of PH or healthy according to the area under the receiver operating characteristic curve (AUC/ROC). After that, the three deep learning models were further used for prediction of PASP using regression algorithm. Moreover, we invited an experienced chest radiologist to classify the images in the test dataset as having PH or not, and compared the prediction accuracy performed by deep learing models with that of manual classification. Results: The AUC performed by the best model (Inception V3) achieved 0.970 in the internal test, and slightly declined in the external test (0.967) when using deep learning algorithms to classify PH from normal based on chest X-rays. The mean absolute error (MAE) of the best model for prediction of PASP value was smaller in the internal test (7.45) compared to 9.95 in the external test. Manual classification of PH based on chest X-rays showed much lower AUCs compared to that performed by deep learning models both in the internal and external test. Conclusions: The present study used deep learning algorithms to classify abnormalities suggesting PH in chest radiographs with high accuracy and good generalizability. Once tested prospectively in clinical settings, the technology could provide a non-invasive and easy-to-use method to screen patients suspected of having PH. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to assess prevalence of left ventricular (LV) systolic and diastolic function in stable cohort of COPD patients, where LV disease had been thoroughly excluded in advance. Methods: 100 COPD outpatients in GOLD II-IV and 34 controls were included. Patients were divided by invasive mean pulmonary artery pressure (mPAP) in COPD-PH (≥25 mmHg) and COPD-non-PH (<25 mmHg), which was subdivided in mPAP ≤20 mmHg and 21–24 mmHg. LV myocardial performance index (LV MPI) and strain by tissue Doppler imaging (TDI) were used for evaluation of LV global and systolic function, respectively. LV MPI ≥0.51 and strain ≤-15.8% were considered abnormal. LV diastolic function was assessed by the ratio between peak early (E) and late (A) velocity, early TDI E´, E/E´, isovolumic relaxation time, and left atrium volume. Results: LV MPI ≥0.51 was found in 64.9% and 88.5% and LV strain ≤-15.8% in 62.2.% and 76.9% in the COPD-non-PH and COPD-PH patients, respectively. Similarly, LV MPI and LV strain were impaired even in patients with mPAP <20 mmHg. In multiple regression analyses, residual volume and stroke volume were best associated to LV MPI and LV strain, respectively. Except for isovolumic relaxation time, standard diastolic echo indices as E/A, E´, E/E´ and left atrium volume did not change from normal individuals to COPD-non-PH. Conclusions: Subclinical LV systolic dysfunction was a frequent finding in this cohort of COPD patients, even in those with normal pulmonary artery pressure. Evidence of LV diastolic dysfunction was hardly present as measured by conventional echo indices. [ABSTRACT FROM AUTHOR]

Background: The pulmonary artery (PA) to ascending aorta diameter ratio (PA:A) has been evaluated in numerous studies analyzing cardiac magnetic resonance (CMR) and computed tomography (CT) data. Previously, no transthoracic echocardiography (TTE) cutoffs have been published. We sought to evaluate (1) the feasibility to image the pulmonary trunk in a prospective cohort, and (2) the ability of PA:A derived by TTE to predict pulmonary hypertension (PH). Methods: We performed a post-hoc analysis of a prospectively recruited consecutive cohort of patients referred to our tertiary center cardiology department due to suspicion for PH. Invasive hemodynamic assessment and quasi-simultaneous TTE was performed in all participants. Results: A total of 84 patients were included in the analysis, median age was 70.5 years (IQR 58–75), 46 (55%) were female. The PA was significantly wider in the PH group (28mm vs. 22.5mm, p<0.001) with a resulting median PA:A of 0.84 vs. 0.66 (p<0.001). Both PA diameter (r = 0.524 and r = 0.44, both p<0.001) and PA:A (r = 0.652 and 0.697, both p<0.001) significantly correlated with mPAP and with PVR, respectively. Area under the curve for the detection of PH was 0.853 (95%CI 0.739–0.967, p<0.001). Conclusion: The PA can be visualized in almost all echocardiographic exams, especially when it is dilated. A view showing the pulmonary trunk should be included in every routine TTE. An increased PA:A should raise suspicion for PH and prompt further evaluation and follow-up examinations of these patients. [ABSTRACT FROM AUTHOR]