tbuckley/cabot-search huggingface dataset:
Abstract 4142740: O <sub>2</sub> -independent photodynamic neuroimmune modulation for prevention and treatment of malignant arrhythmia post myocardial infarction
Authors: Hengyang Liu, Heng Lin, Lilei Yu
Journal: Circulation (2024)

Background: Hyperactivation of the left stellate ganglion (LSG) is a key link in the occurrence of ventricular arrhythmias after myocardial infarction (MI). It is reported that neuroimmune interaction based on the depleting of macrophages modulated the overactive neural activity. However, exogenous macrophage scavengers, which is the common depletion strategy in animal models, are hardly capable of depleting the target cells selectively in certain tissues and transient control performance. Consequently, a degradable nanocomposite (PPSM@CS/DSS) were fabricatedto deplete M1 macrophages selectively in LSG and further inhibit the overactive LSG neural activity after myocardial infarction. Hypothesis: In this study, we constructed a degradable nanocomposite with dual functions of targeting M1 macrophages and oxygen-independent PDT-mediated neuroimmune modulation, which isanticipated to deplete M1 macrophages selectively in LSG and further inhibit the overactive LSG neural activity after myocardial infarctionfor prevention and treatment of ventricular arrhythmias post MI. Methods: The prepared nanocomposite material, which is capable of targeting M1 macrophages and oxygen-independent PDT-mediated neuroimmune modulation, was slowly microinjected into LSG of Beagle dogs. The effectiveness and safety of this method based on apoptosisof M1 macrophagesby oxidizing active species was explored and the mechanism of prevention as well as treatment of malignant arrhythmias were discussed. M1 macrophages were selectively apoptotic in the LSG after myocardial infarction under the irradiation of near infrared light. Results: PPSM@CS/DSS is a core-shell structure with a particle size of about 50nm. The PPSM@CS/DSS nanocomposites exhibits band adsorption between 200-900 nm with a pronounced peaks at 650 nm.Cell experiments showed that PPSM@CS/DS was targeted and mainly induced apoptosis of M1 macrophages under 650nm near-red light, but did not significantly increase apoptosis of neuronal cells. PPSM@CS/DSS significantly reduced LSG activity and the incidence of malignant arrhythmias after MI in Beagle dogs under the action of 650nm light. Conclusion: An innovative nanomaterial for regulating LSG through depletion M1 macrophages selectively in LSG is developed to prevent and treat malignant arrhythmias after myocardial infarction.The implementation of this work will provide a novel neural modulation strategy for preventing ventricular arrhythmias.
Abstract 4142743: VEIN-SCORE: a new risk score for chronic venous insufficiency in patients who experienced leg swelling
Authors: Chi Young Shim, Kyu Kim, Hyun-Jung Lee, Iksung Cho, Geu-Ru Hong, Jong-Won Ha
Journal: Circulation (2024)

Backgrounds: Chronic venous insufficiency (CVI) is a condition of the venous wall and/or valves’ dysfunction in the leg veins prone to venous thrombosis and reducing quality of life. This study sought to find risk factors of CVI and develop a dedicated risk score model to predict the presence of chronic venous insufficiency in patients who experience leg edema Methods: In a total of 1,226 patients (age 65.2± 15.0, 662 women) with leg swelling, specialized protocols for venous function tests were applied for diagnosis of CVI in a single center vascular ultrasound laboratory from Mar 2015 to Dec 2020 after exclusion of the presence of deep vein thrombosis. Duplex ultrasound scan on the greater and lesser saphenous veins was performed with patients erect or as upright as possible. Using a tilt table, patients’ position was flexibly changed. For the distal augmentation to assess for venous incompetence, we used the Hokanson ® E20 Rapid Cuff Inflator. Pathologic reflux is defined by reversal of flow greater than 500 milliseconds in duration. The new CVI scoring system was calculated from logistic regression model. The VEIN-score were compared with cardiovascular risk scoring system established for other purposes. Results: 607 patients (49.5%) were diagnosed with CVI. The final risk score ranged from 0 to 6 points and included six parameters: age ≥ 65 years, male sex, obesity (body mass index ≥ 25 kg/m 2 ), hypertension, atrial fibrillation, and a history of myocardial infarction, which were derived from the results of logistic regression model ( Figure A ). The incidence of CVI gradually increased from 39% to 100%, as the score increased from 0 up to 6 points ( Figure B ). The new scoring system showed modest predictive value (C-index: 0.575, 95% CI: 0.544-0.606, cut-off value 3), higher than the CHA 2 DS 2 -VASc score and H 2 FPEF score. Conclusions: Old age, male sex, obesity, history of atrial fibrillation and myocardial infarction were significant risk factors for CVI. We propose VEIN-SCORE as a dedicated risk score model to predict chronic venous insufficiency in patients with leg swelling.
Abstract 4142663: Mechanism of empagliflozin improves aortic pathological remodeling in TAAD mice based on NLRP3 inflammasome
Authors: Shen Li, Danyan Xu, Huali Qin
Journal: Circulation (2024)

Background: Thoracic aortic aneurism and dissection (TAAD) is a severe macrovascular disease that lead to aortic rupture and sudden death. To date, there are no effective clinical agents to prevent the formation or control the progression of TAAD. Objectives: Investigate the mechanism of empagliflozin improves aortic pathological remodeling in TAAD mice. Methods: Four-week-old male mice were given BAPN (β-aminopropionitrile monofumarate; 1 g/kg/d) in drinking water for 4 weeks for TAD modeling. RNA sequencing analysis was performed to recapitulate transcriptome profile changes.TRIM59 with USP7 and NLRP3 in VSMCs was tested by coimmunoprecipitation assay. Results: 1. Compared with BAPN group or MFS group, the degree of elastic fiber rupture and collagen fiber deposition in TAAD mice with two kinds of NLRP3 knockout were significantly improved (all P &lt;0.05). Transcriptional sequencing showed that the effect of NLRP3 knockout on the aorta of TAAD mice was mainly focused on extracellular matrix remodeling. 2. Empagliflozin was confirmed to significantly ameliorate pathological remodeling of aortic ECM in TAAD mice (all P &lt;0.05). GO/KEGG enrichment analysis revealed that empagliflozin primarily impacts ECM structure and function, as well as inflammation-related signaling pathways. Compared with the vehicle group, BAPN group displayed increased mRNA and protein levels of NLRP3, while empagliflozin decreased NLRP3 protein levels. These findings suggest that empagliflozin may regulate the post-transcriptional level of NLRP3. 3. In vitro studies have shown that empagliflozin promotes the degradation of NLRP3 protein in a dose- and time-dependent manner. MG132 offset the effect of empagliflozin on NLRP3 degradation; coimmunoprecipitation assay confirmed that empagliflozin promotes the degradation of NLRP3 through the ubiquitin-proteasome system (all P &lt;0.05). In addition, TRIM59 knockdown increased NLRP3 ubiquitination levels, whereas the presence of TRIM59 increased NLRP3 deubiquitination levels. Further through the Ubibrowser 2.0 website found that TRIM59 has a strong interaction with USP7. Finally, compared with DMSO group, the interaction between USP7 and NLPR3 was weakened and the ubiquitination level of NLRP3 was increased in the empagliflozin-treated group. Notably, overexpression of TRIM59 reversed this effects of empagliflozin. Conclusion: Empagliflozin reduces TRIM59 expression reduces the binding of USP7 to NLRP3 and promotes ubiquitination and degradation of NLRP3.
Abstract 4142588: Increased macrophage activity in non-culprit plaques in patients with acute coronary syndrome and familial hypercholesterolemia
Authors: Toshiyuki Iwaya, Yoshiyasu Minami, Kiyoshi Asakura, Takako Nagata, Masahiro Katamine, Takuya Hashimoto, Junya Ako
Journal: Circulation (2024)

Introduction: Patients with familial hypercholesterolemia (FH) are at a very high risk of recurrent coronary events. However, the characteristics of non-culprit coronary plques in patients with FH remain unclear. Hypothesis: Patients with FH have a higher prevalence of vulnerable non-culprit coronary plaques compared to patients without FH. Methods: A total of 130 patients with acute coronary syndrome (ACS), who underwent optical coherence tomography (OCT) imaging of non-culprit plaques were included. The characteristics of non-culprit plaques were compared between patients with and without FH. Results: A total of 23 patients (8.9%) were clinically diagnosed with FH. The prevalence of macrophages (71.4 vs. 42.0%, p = 0.046) and layered plaques (78.6 vs. 37.8%, p = 0.008) was significantly higher in patients with FH than those without (Panel A) although the prevalence of non-culprit plaques (60.9 vs. 49.2%, p = 0.383) and the severity of stenosis was comparable between the groups (Panel B). The prevalence of plaques with a macrophage grade of 2 or higher (Semi-quantification of macrophages on OCT images: Panel C) was significantly higher in patients with FH than those without (42.9 vs. 16.0%, p = 0.021) (Panel D). Conclusions: Patients with FH had a higher prevalence of macrophages and layered plaque compared with those without FH in non-culprit plaques among patients with ACS. The present results further suggest the importance of FH diagnosis at the time of ACS event and the requirement of intense secondary prevention in patients concomitant with FH.
Abstract 4142452: LDL-C variability was affected by lipid-lowering strategies and associated with adverse cardiovascular outcomes
Authors: Dong-Eon Kim, Sung-jin Hong, Sripal Bangalore, Kyeong Ho Yun, Sang-Hyup Lee, Yong-Joon Lee, Seung-Jun Lee, Chul-Min Ahn, Jung-Sun Kim, Byeong-Keuk Kim, Young-Guk Ko, Donghoon Choi, Yangsoo Jang, Bum Hong, Myeong-Ki Hong
Journal: Circulation (2024)

Background: Prior studies have shown an independent association between visit-to-visit variability in low-density lipoprotein cholesterol (LDL-C) and adverse cardiovascular (CV) events and that this variability can be reduced by high-intensity statins (HIS). However, it is not known whether LDL-C variability can be reduced by moderate-intensity statin (MIS) plus ezetimibe combination or by a treat-to-target strategy (TTS). Hypothesis: We aimed to evaluate whether visit-to-visit variability in LDL-C is affected by lipid-lowering strategies and its association with CV outcomes in patients treated with HIS or MIS plus ezetimibe or statins with a target LDL-C levels of 50 to 70 mg/dL (TTS). Methods: Data from the RACING and LODESTAR trial in patients with atherosclerotic disease, LDL-C variability was evaluated from 3 months after randomization. In the RACING trial, MIS plus ezetimibe combination therapy was compared with HIS monotherapy. In the LODESTAR trial, TTS with a target LDL-C level of 50 to 70 mg/dL by titration of the statin intensity was compared with HIS strategy. LDL-C variability was compared according to these lipid-lowering strategies. The primary endpoint was a composite of death, myocardial infarction, stroke, or coronary revascularization. Results: Among the 6800 patients included, when compared with patients randomized to HIS, LDL-C variability was similar in the group randomized to MIS plus ezetimibe combination (SD 8.92±7.15 vs 9.17±7.34, P=0.325) but higher in those randomized to TTS (SD 8.9±7.2 vs 10.6±7.7, P=0.001). There was a linear association between LDL-C variability and primary endpoint (Figure 1). The variability in LDL-C (by SD) was a predictor of primary endpoint (HR 1.024; 95% CI 1.014 to 1.035; P&lt;0.001) even after adjustment for lipid-lowering strategy and mean LDL-C. Conclusions: Compared with HIS therapy, visit-to-visit variability in LDL-C was not increased in the MIS plus ezetimibe combination therapy, but was increased in the TTS. Even in those treated with MIS plus ezetimibe or HIS or statins with a target LDL-C levels of 50 to 70 mg/dL, increased LDL-C variability was significantly associated with higher risk of adverse CV outcome.
Abstract 4142628: Machine learning models based on hyperspectral images accurately diagnose coronary artery disease
Authors: Zeyan Li, Xiaomeng Yang, Xiaoyu Shi, Lilei Yu
Journal: Circulation (2024)

Background: Hyperspectral imaging (HSI) can be used for high-precision classification, offering high spectral resolution, wide spectral coverage, and high data dimensionality. Patients with coronary artery disease (CAD) possess distinctive body surface image characteristics. However, value of HSI for the diagnosis of CAD remains unclear Hypothesis CAD patients exhibit characteristic spectral signatures on surface, which can be used for diagnostic identification of CAD. Methods: This is a cross-sectional observational study. Clinical baseline characteristics, results of coronary artery angiography (CAG) and tongue dorsum hyperspectral images (spectral range:688-951nm) were collected from the subjects. In this study, 3650 hyperspectral images were included. These images are divided into training sets(N=2555) and validation sets(N=1095). Machine learning algorithms were used to selection of features in hyperspectral images and construction of CAD diagnosis models (including Gaussian process (GP), random forest (RF), support vector machine (SVM), gradient boosting (GB), TheilSen etc). Model fusion was achieved by forward selection strategies to improve model performance. The screened features are further used to generate new clinical markers through band math. Predictive performance of the models was assessed based on the results from CAG. Results: The model performance was evaluated through area under receiver operating characteristics (AUROC), decision curve analysis (DCA), calibration curve, accuracy, precision, sensitivity, specificity, and F1 score. (1) The top 5 performance models were selected from 29 models, including GP, RF, SVM, GB, and TheilSen. The corresponding AUROC for top 5 models were 0.879, 0.827, 0.844, 0.854 and 0.783.(2) Based on forward selection strategy, GP, GB and SVM models were selected to develop fusion model (GP-GB-SVM model). Model performance of GP-GB-SVM model was upgraded and AUROC of GP-GB-SVM was 0.92. (3) The top 10 features were recognized from top 5 models. Combination of 10 features through band math generated new clinical marker (Hyper-CAD), which can effectively predict risk of CAD. Conclusion: The present study suggests that patients with CAD exhibit characteristic HSI alterations on the surface. Patients with CAD can be effectively diagnosed and identified based on these alterations.
Abstract 4142631: Trends in Heart Failure-Associated Mortality in Individuals with Diabetes Mellitus Type II
Authors: Abdullah Nofal, Sara Rahman, Maheen Khurram, Sarah Ashraf Khaskheli
Journal: Circulation (2024)

Introduction: Diabetes mellitus type II is among the nine leading causes of mortality. All-cause mortality hikes by folds in those affected. Heart failure (HF) is a common cause; however, patient demographics and other factors impact the trends. Identifying these can help direct relevant healthcare agendas. Research Question: What are the trends in HF-associated mortality in individuals with diabetes mellitus type II in the USA? Goals: Identifying trends stratified by age, gender, race, and geographical location in HF-associated mortality in diabetic individuals. Methodology: Crude mortality rate (CMR) and age-adjusted mortality rate (AAMR) per 100,000 population were extracted from the National Vital Statistics System from 1999 to 2020 using the CDC Wonder database, with diabetes mellitus type II as the underlying cause and heart failure as a contributing cause. Changes over time, as annual percentage change (APC), were analyzed with Joinpoint regression analysis. Results: The overall AAMR increased from 1999-2004 (APC: 6.054), followed by a decrease during 2004-2014 (APC: -0.139) and a final incline till 2020 (APC: 11.52). Older adults (aged 85+) had the highest CMR of 97.08. Men had a higher AAMR than women (5.61 versus 3.87). Ethnicity-wise, the highest AAMR was observed in Non-Hispanic (NH) American Indians or Alaska Natives (7.13), followed by the Hispanic or Latino (5.26), NH Black or African American (4.90), NH White (4.57), and NH Asian or Pacific Islander (3.20) populations. Among states, the lowest AAMR was observed in the District of Columbia (1.63) while the highest was in Oregon (8.51). Stratified by census regions, the highest mortality rate was in the Western region (AAMR: 5.81), followed by the Midwestern, Southern, and Northeastern regions; 5.50, 4.17, and 2.97, respectively. Conclusions: Our study found substantially rising trends in HF-related mortality in type II diabetics. In different strata, the highest rates were observed in individuals over 85 years, males, NH American Indian or Alaska Natives, and those residing in the Western region, especially Oregon. Such results call for directive policy introduction in relevant areas of healthcare that can help limit fatal outcomes.
Abstract 4142622: Circulating biomarkers of collagen type-I degradation are associated with risk of mortality after ST-elevated myocardial infarction.
Authors: Emily Martin, Elisavet Angeli, Clara Laursen, Federica Genovese, Morten Karsdal, Martin Frydland, Jacob Moller, Christian Hassager
Journal: Circulation (2024)

Introduction: Extracellular matrix (ECM) remodelling is a critical consequence of ST-elevated myocardial infarction (STEMI). Type-I collagen (COL1) is the main constituent of the myocardium, and its’ degradation could result in destabilisation of the cardiac tissue and increase the risk of adverse events. Aim: We sought to quantify circulating peptides reflecting COL1 degradation in STEMI patients. Methods: COL1 degradation was measured using two enzyme-linked immunosorbent assays (ELISA) targeting MMP-generated fragments of COL1 (C1M and C1SIG) in plasma of 1,464 patients admitted with STEMI from the PREDICT-CS study (72.7% male, median age: 63.5) (Rigshospitalet, Denmark). Survival analysis and Cox proportional hazard analysis were used to determine the association the biomarker to mortality within 1-year of STEMI. Results: C1M and C1SIG were lowly correlated (R = 0.204, p &lt; 0.0001). Patients with circulating levels of C1M and C1SIG above the median at a higher mortality risk at 1-year post-admission, compared to those with biomarker levels below the median (C1M: p = 0.0006, C1SIG: p &lt; 0.0001, Log-rank test). Univariate Cox proportional regression analysis showed a 90% increase in risk of death per doubling of C1M and a 120% increased risk of death per doubling of C1SIG over 1-year (C1M: HR 1.9 [1.6-2.4], C1SIG: HR 2.2 [1.6-3.0], both: p &lt;0.001). In Model 1 (adjusment for age, sex, hypercholesterolemia, blood pressure, diabetes, and smoking), C1M and C1SIG retained the association with risk of mortality (C1M: HR 1.6 [1.2-2.0], C1SIG: HR 2.2 [1.5-3.1], both: p &lt;0.001). In Model 2, including Model 1 and the cardiac and inflammatory markers MR pro-adrenomedullin, Copeptin, proANP, ST2 and CRP, C1SIG, but not C1M, continued to remain an independent predictor of mortality over 1-year (HR 1.9 [1.2-3.0], p &lt;0.001 for C1SIG; HR 1.4 [0.9-1.9], p = 0.109 for C1M). Conclusion: Circulating levels of C1M and C1SIG showed a significant and independent association with risk of mortality in STEMI patients after 1 year, in a multivariate model based on the Framingham Score. The association was retained for C1SIG after adjustment for markers of cardiac injury and inflammation. Assessing acute ECM processing in STEMI patients using COL1 biomarkers could be beneficial for predicting mortality and identifying a patient-subset at increased risk of long-term outcome.
Abstract 4142259: The Increase Of High Sensitive Troponin Post Percutaneous Coronary Intervention Is Associated With An Increase Of The Index Of Microcirculatory Resistance
Authors: Danilo Maksud Maksud, Pedro Jallad, Bruno Alves, Jean Carlos Calderon, ROGER GODINHO, Brunna Pileggi, Neuza Lopes, Luis Henrique Gowdak, Alexandre Abizaid, CARLOS CAMPOS
Journal: Circulation (2024)

Background: A reduction or delay in myocardial flow and perfusion, despite recanalization of the epicardial coronary arteries, is a well-known phenomenon. However, the association between microvascular resistance and troponin levels following elective percutaneous coronary intervention (PCI) is not well established. Objective: The present study aimed to assess the angiographic-derived index of microcirculatory resistance (AMR) in patients undergoing elective PCI and its relationship with high-sensitivity troponin (hsT) values post-procedure. Methods: Between June 2021 and December 2023, patients who underwent elective PCI were considered for inclusion. Patients with successful PCI outcomes were selected for the IMR analysis using AngioPlus Core (Shanghai Pulse Medical Technology Inc); individuals with branch occlusion were excluded. All patients had hsT collected at least twice in the first 24 hours after PCI. Results: A total of 330 patients were included into the analysis. Compared with baseline, there was an increase in AMR in 89.6% of the patients, from 174.9 pre-PCI to 256.2 post-PCI (p&lt; 0.001, Figures 1A-C). The higher the hsT peak after PCI, the greater the delta IMR (p = 0.004, Figure 1D) and the post-PCI IMR (p &lt; 0.001, Figure 1E). There was a positive and significant correlation between the absolute values of hsT peak and delta IMR (p &lt; 0.001, Figure 1F). Conclusion: In patients who underwent elective successful PCI, the increase in hsT is closely related to increase in the index of microcirculatory resistance during the procedure.