tbuckley/cabot-search huggingface dataset:
Abstract 4142913: Characteristics and Prognosis of In-Hospital Onset Non-ST-Segment Elevation Acute Myocardial Infarction in Patients Hospitalized for Non-Cardiac Diseases: Comparison of Cardiology Referral vs. Non-Referral
Authors: Lei Zhu, Tian-Shu Gu, Ze Zhang, Su-Tao Hu, Chao Jiang, Yu-Kun Zhang, Jing-Kun Zhang, Xue Wu, Xing Liu, Tong Liu, Kang-Yin Chen
Journal: Circulation (2024)

Background: NSTEMI accounts for the majority of the in-hospital MI. However, whether differences exist between in-hospital NSTEMI patients referred to cardiology and those who are not remains unclear. Aims This study aims to compare the characteristics and prognosis of in-hospital NSTEMI patients referred to cardiology with those who are not. Methods: Data for this study were obtained from a retrospective cohort comprising patients from 72 hospitals between 2010 and 2023. Patients who developed NSTEMI during hospitalization were identified and classified into the referral and the non-referral group based on whether they were referred to cardiology. The primary endpoint was Major Adverse Cardiovascular and Cerebrovascular Events (MACCE), comprising cardiovascular death(CD), recurrent MI, stroke, and repeat revascularization at 1 year. The secondary endpoints were in-hospital all-cause mortality, 1-year all-cause mortality, CD, and Net Adverse Clinical Events (NACE), including CD, recurrent MI, BARC≥3 bleeding events, and repeat revascularization. Kaplan-Meier curves were used to depict survival between the two groups. A multivariable Cox regression model, adjusted for age, sex, Killip classification, and medical history, was utilized to analyze the association between referral and 1-year outcomes. Additionally, multivariate logistic regression analysis was employed to examine the factors related to in-hospital mortality. Results: The study included 6218 patients were in the non-referral group (mean age 73 years, 43.4% women) and 1260 in the cardiology referral group (mean age 70.8 years, 43.4% women). The non-referral group was less likely to take antiplatelet drugs, statins, or undergoing PCI (p&lt;0.001). Multivariate logistic regression showed that cardiology referral was a significant factor affecting in-hospital mortality (OR: 0.405, 95%CI: 0.310-0.528). All the 1-year endpoints-free survival rates were better in the referral group than in the non-referral group (Log-rank p&lt;0.001). Multivariate Cox regression analysis showed that referral were associated with a lower risk of 1-year MACCE (HR: 0.878, 95%CI: 0.801-0.964), NACE (HR: 0.882, 95%CI: 0.805-0.967), all-cause mortality (HR: 0.729, 95%CI: 0.658-0.808) and CD (HR: 0.743, 95%CI: 0.657-0.840). Conclusion: In-hospital NSTEMI patients referred to cardiology had better outcomes compared to those who were not, partly due to higher rates of revascularization and adherence to guideline-recommended medical therapy.
Abstract 4143062: Altered Pulmonary Arterial Hemodynamics in Repaired Tetralogy of Fallot Patients Referred for Pulmonary Valve Replacement: A Cross-Sectional 4D Flow Study
Authors: Takashi Fujiwara, Michael Kwong, Brian Fonseca, Matthew Stone, Lorna Browne, Alex Barker
Journal: Circulation (2024)

Background: Repaired tetralogy of Fallot (rTOF) patients require pulmonary valve replacement (PVR). Indexed right ventricular systolic/diastolic volumes are currently used to determine PVR timing, but there are recognized limitations. Unique hemodynamic features in the pulmonary arteries of these patients have been found using 4D flow cardiovascular magnetic resonance (CMR), which we hypothesize may inform PVR timing. Hypothesis: Hemodynamic alterations in the pulmonary arteries of rTOF patients may inform timing of PVR. Aims: To compare pulmonary arterial hemodynamics for rTOF patients who were/were not indicated for PVR after the exams using 4D flow CMR. Methods: Clinical 4D flow CMR exams of rTOF patients were accessed retrospectively with IRB approval. Patients were classified into two groups depending on whether they underwent PVR after the CMR exam. Age-matched controls’ 4D flow data were also included. After pre-processing of 4D flow, the right ventricular outflow tract, main, left and right pulmonary arteries (RVOT, MPA, LPA and RPA) were manually segmented from phase-contrast magnetic resonance angiography. In addition to basic flow metrics such as regurgitant fraction, systolic and diastolic averages of helicity, vorticity, and viscous energy loss were computed for the four subdomains using an automated pipeline (Fig.1). Indexed end-systolic/diastolic right ventricular volumes were obtained from clinical CMR reports. P&lt;0.05 was considered statistically significant. Results: Eighteen controls (age, 14.9 [11.7-17.0] years) and 21 rTOF patients, consisting of 8 without PVR (noPVR; age, 14.7 [9.6-23.4] years) and 13 indicated for PVR after the exam (PVR; age, 16.1 [8.7 -20.3 years]; days between CMR and PVR, 134 [59.5 – 189.3] days), were included. The PVR group had significantly larger indexed right ventricular volume than the noPVR group (P=0.002; Table 1). Regurgitant fraction and diastolic vorticity at the LPA were significantly larger in the PVR group (P=0.007 for regurgitant fraction; P=0.02 for vorticity; Fig.2AB). Although not statistically significant, diastolic helicity at the MPA showed borderline significance (P=0.05; Fig.2C). Conclusion: In addition to right ventricular dilatation and larger regurgitant fraction, patients indicated for PVR had larger vorticity in the LPA. This preliminary result could be used for future longitudinal study to determine hemodynamic markers that inform PVR timing. A larger cohort is under evaluation.
Abstract 4142963: Effects of high-intensity inspiratory muscle training as a pre-cardiac rehabilitation intervention on cardiovascular function in patients with heart disease: A pilot study
Authors: RIDVAN AKTAN, Richard Severin, Cemal Ozemek
Journal: Circulation (2024)

Background: Endothelial function is closely associated with cardiovascular health among individuals being treated for heart disease. Inspiratory muscle training (IMT) consists of repeated inspirations against a resistance on a handheld device. The effects of high-intensity IMT on endothelial function and arterial stiffness is not well known in this population. Aim: The aim of this study was to investigate whether high-intensity IMT, beyond usual clinical care, improves endothelial function, arterial stiffness, inspiratory muscle strength, functional capacity, and dyspnea perception in patients with heart disease. Methods: In this randomized controlled trial participants qualifying for phase two, outpatient cardiac rehabilitation were included. After baseline assessments, participants were randomized to 4 weeks of either high-intensity inspiratory muscle training (IMT) with a resistance set to 60% of baseline maximum inspiratory pressure (MIP) or sham-IMT without resistance (control group). Endothelial function was assessed using flow-mediated dilatation (FMD%), arterial stiffness by pulse wave velocity (PWV), 6-min walk distance (6MWD) was used to quantify functional capacity, dyspnea perception by modified medical research council dyspnea (mMRC) scale, and inspiratory muscle strength by maximal inspiratory pressure (MIP) were assessed. An ANOVA was applied using the intention-to-treat analysis. Data are expressed in mean±SD. Effect sizes presented based on between groups ANOVA. Results: There were no differences between groups for baseline age, BMI, sex, FMD%, PWV, mMRC, 6MWD and inspiratory muscle strength. No significant changes in the respective measures of interest were observed in the control group (n=6). The intervention group (n=5) experienced significant improvements in FMD% (pre = 5.41 ± 1.93, post = 7.53 ± 1.62, p&lt; 0.05, η 2 effect size= 0.72), 6MWD (pre = 301.0 ± 39.8, post = 340.4 ± 36.6 meters, p&lt; 0.05, η 2 effect size= 0.94), mMRC score (pre = 2.8 ± 0.5, post = 1.6 ± 0.6 points, p&lt; 0.05, η 2 effect size= 0.76), and MIP (pre = 46.4 ± 13.4, post = 68.8 ± 13.6 cmH 2 O, p&lt; 0.05, η 2 effect size= 0.82).There were no significant difference between group in PWV (p&gt; 0.05). Conclusion: The findings of this study suggest that high-intensity IMT, as a pre-cardiac rehabilitation intervention, produced improvements in endothelial function, MIP, functional capacity, and dyspnea in patients with heart disease.
Abstract 4143006: Systemic Vascular Damage and Cardiac Dysfunction in a Mouse Severe Acute Pancreatitis Model
Authors: Aolin Du, Junmeng Zhang, Yu Huo, debiao zhao, Ahmed Fayyaz, Alessia Buglioni, Jeson Sangaralingham, Aurelia Lugea, Richard Waldron, Stephen Pandol, Margaret Redfield, Baoan Ji, Ying Wang
Journal: Circulation (2024)

Background and Objective: Decline of cardiovascular (CV) function is commonly observed in patients with severe acute pancreatitis (AP), which is associated with high mortality and morbidity. While the pathological changes in the pancreas during severe AP have been extensively studied, the impact on the CV system has not been well characterized. Furthermore, obesity is a major risk factor for severe AP. Hereby we utilized an obesity-associated mouse AP model to assess potential alterations in vascular integrity and cardiac function, two major components of circulatory failure. Methods: Wild-type male C57BL6J mice were fed a normal or a high fat (to induce obesity) diet. Both groups received intraperitoneal injection of cerulein (100 mg/kg/h x12) to induce AP. H&amp;E and TUNEL staining of pancreas were performed to assess histology and cell death. To measure vascular integrity, we measured the leakiness of a fluorescein-conjugated dextran (70 kDa) in tissue parenchyma and serum levels of soluble vascular endothelial (VE)-cadherin, which has recently shown to be shed from endothelial cells with disrupted adherens junctions. Cardiac systolic and diastolic function were assessed by echocardiography at baseline and post-AP induction. Results: Compared to lean mice, obese mice developed more severe pancreatic edema, cell death and inflammatory cell infiltration, along with significantly increased accumulation of fluorescent dextran in multiple organs including pancreas, heart, lung, and kidney, suggesting systemic disruption of vascular integrity. Increased serum levels of soluble VE-cadherin in obese mice (vs. lean) after AP induction further supported compromised endothelial cell barrier function. At baseline, obese mice exhibited similar cardiac function to lean mice. However, obese mice, but not lean mice, developed impaired systolic and diastolic function post-AP induction, as supported by decreased ejection fraction and e’ velocity respectively. Conclusion: In this obesity-associated severe AP mouse model, systemic vascular permeability is increased, and cardiac function is substantially compromised. Systemic vascular hyperpermeability and cardiac dysfunction may represent therapeutic targets to enhance the outcomes in severe AP.
Abstract 4142901: Identification of ANGPTL4 and ITGAV as Therapeutic Targets for Calcific Aortic Valve Disease through Comprehensive Mendelian Randomization Using Human Plasma Proteome
Authors: Jin Lu, Dilin Xu, Haochang Hu, Ningjing Qian, Xianbao Liu, Jianan Wang
Journal: Circulation (2024)

Background: Calcific aortic valve disease (CAVD) is a degenerative disease characterized by aortic valve fibrosis and calcification with no medications available for treatment. Multi-omics research is highly beneficial for identifying disease targets. In this study, we aimed to identify potential therapeutic targets for CAVD through Mendelian randomization (MR) and summary data-based Mendelian randomization (SMR) combined with transcriptomic analysis. Methods: Protein quantitative trait locis (pQTLs) from two whole plasma protein databases deCODE and UK biobank pharma proteomics project (UKB-PPP) were utilized as the exposure. Three large CAVD cohorts from FinnGen (9,870 cases and 402,311 controls), the UK Biobank (3,552 cases and 425,855 controls) and France (3,123 cases and 6,531 controls) served as the outcome. MR and SMR was used to screen potential causal targets for CAVD. Colocalization analysis was performed to determine whether CAVD and target proteins shared common causal SNPs. Single-cell and bulk RNA sequencing was further used to detect the cell-type specific and differential expression of target proteins. Drug prediction and molecular docking was applied to discover potential medications. Results: 15 plasma proteins were identified via MR and SMR analysis with 6 strongly supported via colocalization analysis. Among them, angiopoietin-related protein 4 (ANGPTL4) and integrin alpha-V (ITGAV) were validated in the replication CAVD cohorts from the UK Biobank or France as well as the bulk RNA sequencing data. Both of ANGPTL4 (OR = 1.963, 95% CI: 1.460-2.641, P FDR = 7.30E-03) and ITGAV (OR = 1.579,95% CI: 1.257-1.985, P FDR = 3.48E-02) were risk factors of CAVD and the protein levels of ANGPTL4 and ITGAV was upregulated in valvular interstitial cells as proved by Western blot. Molecular docking suggested a stable binding between the target proteins and medications. Conclusions: In a combination of proteome-wide MR and RNA sequencing analysis, ANGPTL4 and ITGAV were identified as the pivotal protein targets associated with the progression of CAVD.
Abstract 4142856: Integrative Bulk And Single-Cell Meta-Analysis Defines SPP1+ Foamy Macrophage Contributing To Atherosclerosis Progression
Authors: Shengkang Huang, Ziang Yang, Chenglong Fang, Wei Feng
Journal: Circulation (2024)

Background: Atherosclerosis (AS) progression involves complex interactions and phenotypic plasticity among vascular and immune cell lineages. Single-cell RNA-seq (scRNA-seq) studies have highlighted lineage-specific transcriptomic signatures, but human cell phenotypes and crucial pathogenic cell subsets remain controversial. Methods: We performed an integrated meta-analysis of single-cell sequencing data from our center along with four other scRNA-seq libraries (GSE247238, GSE235436, GSE155512, GSE159677) to generate a comprehensive map of human atherosclerotic plaques, including both coronary arteries with no discernible atherosclerotic lesions and diseased carotid plaques. To validate our conclusions, three independent datasets were used, including two bulk transcriptomics datasets and one proteomics dataset (GSE28829, GSE16315 and PXD031052). Besides, the Biobank of Karolinska Endarterectomy (BiKE) dataset was used for Kaplan–Meier (KM) analysis. Comparative analyses were performed between the groups, including cellular compositional analysis, cell type–resolved transcriptomic changes, and functional analysis. Results: The final integrated single-cell dataset, comprising 134,710 cells, consisted of 8 major cell types. The annotated cell subpopulations were generally present across the various studies, but their proportions varied between different studies. Pathway analysis identified that the most significantly impacted pathways were those associated with immune cell functions and cellular metabolism. Notably, SPP1 is highly expressed in macrophages. Survival analysis showed significantly lower ischemic event-free survival in the high SPP1 expression group compared to the low expression group. Besides, compared to atherosclerotic plaques with early stage (EA), non-intraplaque hemorrhage (IPH), and non-calcified conditions, SPP1 expression was highly up-regulated in all stages of plaque progression, including advanced plaques (AA), hemorrhagic plaques, and calcified plaques. Meanwhile, the differences in cellular composition and transcriptomic profiles between the lesion and non-lesion groups further highlighted the significance of lipid metabolism-related SPP1 hi foamy macrophages. Conclusions: We created a unified atlas of human atherosclerosis informing cell state-specific mechanistic and translational studies of cardiovascular diseases. SPP1 hi foamy macrophages contributed importantly to AS progression.
Abstract 4142825: Anisotropic conductive hydrogel reduces the incidence of major adverse cardiac events in a beagle model of myocardial infarction
Authors: Xiaofei Wang, Zizhuo Zhang, Jiale Wang, Lilei Yu
Journal: Circulation (2024)

Background: The main adverse cardiac events after myocardial infarction (MI), including ventricular arrhythmia and heart failure, have an important impact on the survival rate and long-term prognosis of patients with MI. Hydrogel patch is a promising treatment method, but it has some disadvantages such as low bionic performance. Research Questions: The purpose of this proof-of-concept study was to investigate the cardiac protection potential of PPy-chitin hydrogels in beagle models of MI. Methods: In beagle MI models, body surface electrocardiogram and event-related potential were used to evaluate cardiac electrophysiology. Induced arrhythmias was assessed by programmed electrical stimulation. Transthoracic echocardiography was used to evaluate left ventricular function. Results: PPy-chitin hydrogel reduced the resistivity of infarct tissue (MI vs PPy, 3.36 vs. 1.67KΩ. cm, P&lt;0.01), improved electrical conduction(QT interval, 360.67 vs. 298.63ms, P&lt;0.01), and rebalanced the cardiac autonomic nervous system(low frequency /high frequency, 1.03 vs. 0.51, P&lt;0.01). PPy-chitin hydrogel improved left ventricular remodeling by improving myocardial fibrosis (11.42% vs. 7.56%, P&lt;0.01) and promoting neovascularization. Ultimately, PPy-chitin hydrogel improved cardiac function at 4 weeks post-MI (left ventricular ejection fraction, 42.88% vs. 56.72%, P&lt;0.01) and reduced post-MI arrhythmia susceptibility by 34.61%. Conclusions: Anisotropic conductive hydrogel significantly improved tissue remodeling, electrical remodeling and neural remodeling in the preclinical model of MI, further reducing the incidence of heart failure and ventricular arrhythmia after MI, which is expected to be translated into clinical practice.
Abstract 4142867: Dysregulated AP-1 Expression in Monocyte in Recurrent In-Stent Restenosis: Insights from Human Coronary Artery Blood Single-Cell Sequencing
Authors: miao yu, yu jiang, Fangshun Tan, Hai-Yan Qian, WeiXian Yang
Journal: Circulation (2024)

Aims: Recurrent in-stent restenosis (RISR) refers to a second event of ISR after successful revascularization procedures of an initial ISR lesion. However, due to its unclear pathogenesis, effective treatment methods are lacking in clinical practice. Therefore, this study aims to investigate the potential mechanisms underlying RISR pathogenesis from an immunological perspective using single-cell RNA sequencing (scRNA-seq), to provide theoretical support for clinical interventions. Methods: Single-cell RNA sequencing was conducted to profile coronary blood mononuclear cells (CBMCs) obtained from 10 patients with recurrent in-stent restenosis (RISR) and 10 control individuals without ISR one year after stent implantation. The potential pathogenic pathway was identified through comprehensive bioinformatics analyses and further validated at the cellular level by isolating monocytes via flow cytometry from the coronary blood of patients in the RISR validation cohort (n=8). Results: RISR altered the proportion of monocyte subtypes, including an increasing trend in FCGR3A+ Monos and a decrease in MHC-II+ Monos. And a marked elevation of activator protein-1 (AP-1) complex within monocytes was identified as key contributor to the unique transcript profile observed in RISR. Evidence at both the RNA and protein levels demonstrated that in RISR patients, CCL5 secreted by T cells can specifically interact with CCR1 of monocytes, thereby upregulating the p38 MAPK/AP-1/inflammatory cytokine axis. Furthermore, co-culture experiments revealed that these monocytes with heightened expression of inflammatory cytokines can indeed promote the proliferation and migration of endothelial cells (EC) and smooth muscle cells (SMC), thus contributing to the occurrence and progression of RISR. Conclusion: Our study provides the first depiction of immunological landscape in the coronary blood of RISR patients. The upregulation of the CCR1/p38 MAPK/AP-1/cytokine axis in monocytes is a critical mechanism that facilitates RISR. Our study fills the gap in the understanding of RISR pathogenesis and holds significant implications for guiding clinical interventions.
Abstract 4142850: SGK1 inhibition attenuated left ventricular thickening and diastolic dysfunction in a mouse model of Heart Failure with Preserved Ejection Fraction
Authors: Aneesh Bapat, Sabindra Pradhananga, Dinesh Srinivasan, Philip Sager, Patrick Ellinor
Journal: Circulation (2024)

Background: Heart failure with preserved ejection fraction (HFpEF) is growing in prevalence and expected to become the dominant form of heart failure in the future. Given its significant burden, it is important that novel therapeutic options are explored to identify potential drug targets. Serum and glucocorticoid regulated kinase 1 (SGK1) is a PI3-kinase-dependent kinase and lies downstream of insulin signaling pathways. Hypothesis: Given the association between HFpEF and insulin resistance, we hypothesized that SGK1 activation is involved in HFpEF pathogenesis, and that SGK1 inhibition may have therapeutic potential. Methods: In this study, we utilized a mouse model of HFpEF, derived by combining obesity and increased afterload.C57BL6/J mice (age 10 weeks) were either fed with control chow and control water (CTL, N=5) or high fat diet (HFD) and Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME, 0.5g/L in drinking water) (HFpEF, N=8) or HFD chow with an incorporated SGK1 inhibitor as well as L-NAME in drinking water (SGK1I, N=6). After treatment for 15 weeks, the mice underwent tail-cuff blood pressure measurements as well as transthoracic echocardiography (TTE) to assess cardiac structural parameters, systolic function, and diastolic function. Results: After 15 weeks of treatment, the two groups of mice fed HFD had increased body weight and higher systolic and diastolic tail-cuff BPs than the control group. There were no differences in LV chamber size or systolic function as determined by LVEF or fractional shortening. The HFpEF group had significantly higher diastolic posterior wall thickness (HFpEF: 1.2±0.06, CTL: 1.08±0.04 mm p=0.001), but these differences were attenuated in the SGK1I group (1.09±0.05, p=NS compared to CTL). HFpEF mice, when compared to controls, had a significantly lower early diastolic mitral annular septal tissue velocity (e’) (CTL:37.5±3.2; HFpEF: 24.8±4.2; p=0.002), as well as a significantly higher ratio of E/e’ (CTL: 23±1.2; HFpEF 32.4±6.6; p=0.01). Treatment with SGK1I mitigated HFD+L-NAME induced diastolic dysfunction (e’: 31±8.1; E/e’ 28±4.6; p=NS compared to control for both). Conclusions: SGK1 inhibition attenuated left ventricular thickening and diastolic dysfunction in mice treated with HFD and L-NAME. Further investigation is warranted to determine the underlying mechanisms and assess for translational promise.