tbuckley/cabot-search huggingface dataset:
Abstract 18964: Long-Term Prognostication of Atherosclerotic Cardiovascular Disease Risk Based on the Discordance Between Coronary Artery Calcium Area and Density
Authors: Drumadala Gajbhiye, Syed Muhammad Hassan Bukhari, Shifa Younus, Azouba Gulraiz, Momna Wazir, Samina Raza, Maryam Munir, FNU Neelam, Saad Mehmood
Journal: Circulation (2023)

Introduction and Hypothesis: Coronary artery calcium scoring is used to quantify the burden of atherosclerotic plaque in coronary arteries in patients with coronary artery disease. It is measured as a product of two variables: plaque area and density. Our study sought to evaluate the long-term prognosis of atherosclerotic cardiovascular disease (CVD) based on the discordance between these two variables. Methods: 1750 patients with a CAC score greater than 0 were enrolled in this retrospective, multicenter study. Agatston CAC score was used to quantify a lesion as the product of plaque area and a 4-level categorical peak calcium density factor. COX proportional hazards were performed for atherosclerotic CVD mortality over a median period of 5.2 years while adjusting the Agatston CAC score and other classic risk factors. Results: The mean age was 61.2 years, and 19% were female. The prevalence of plaque discordance was 23% (12% high calcium area/low calcium density, 11% low calcium area/high calcium density). Compared to those with low calcium area/low calcium density, patients with low calcium area/high calcium density had a 65% lower risk of ASCVD death (HR: 0.27 [95% CI: 0.08-0.95]). Female sex ([95% CI: 1.25-1.76]) and body mass index ([95% CI: 1.16-1.32], per 5 kg/m2 higher) were significantly associated with high calcium density discordance. Conclusions: Our study concluded that high calcium density relative to plaque area confers lower long-term ASCVD risk, likely as an imaging marker for lesion severity. Additional studies are needed to define a robust definition of calcium area/density discordance for real-life clinical risk prediction.
Abstract 421: Automated External Defibrillator Implementation Gaps in Three Non-Urban U.S. Communities
Authors: Ryan A Coute, Jason Grady, Allison G Dupont, Megan A Ruby, James M Leaming, James Fountain, Michael A Revelle, Aarthi Kaviyarasu, Anahita Ghorbani, Julie Buckingham, Peter Z Hansen, Benjamin S Abella, Michael C Kurz
Journal: Circulation (2023)

Introduction: Automated external defibrillators (AEDs) represent a crucial component of bystander response to out-of-hospital cardiac arrest (OHCA), yet epidemiologic evidence suggests that AEDs are deployed by laypersons in less than 5% of OHCA events in the US. The reasons for low utilization remain poorly characterized, especially in rural/suburban environments. We hypothesized that in these non-urban environments, layperson AED use is mostly in commercial or public locations despite most arrests occuring in private residences. Methods: We conducted an analysis of EMS-treated atraumatic OHCA events from 3 non-urban US regions (Cumberland County, PA; Jackson, TN; Forsyth County, GA), abstracted from EMS patient care reports. Data included Utstein reporting elements, arrest location type, and response intervals as calculated by dispatch and EMS arrival times. We excluded events in skilled nursing facilities and prisons. CPR and AED delivery by laypersons was measured. Results: Between 12/8/17-12/31/21, we identified 1542 adult OHCA patients with median age 66.5 y (IQR 22.5), 37% female, 18% had initial shockable rhythms, and 75% occurred in private residences. Return of spontaneous circulation was obtained in 19% of cases. Bystander CPR was performed in 23% and AEDs were deployed by laypersons in 3%. Laypersons applied AEDs in 12% of OHCA in commercial locations, 6% of OHCA in public, and 3% of OHCA in private residences. EMS response times were 4% less than 4 min, 48% 4-9 min, and 48% &gt;9 min; prevalence of AED use was indistinguishable between time intervals of EMS response. 16% OHCA victims still had initial shockable rhythms even among the &gt;9 min EMS response cases; of these, 1% received AED use from laypersons. Conclusion: In three non-urban US regions, most arrests occurred in private residences while AED use was much more likely in public or commercial locales, suggesting an important gap in AED deployment. Even in cases with prolonged response times, many patients had shockable rhythms, suggesting an important opportunity for earlier AED deployment. Future work will test whether placement of AEDs in residential areas using trained volunteer responders in these same communities will improve OHCA response and survival outcomes.
Abstract 17634: CCN2 Deficiency in Vascular Smooth Muscle Cells Drives the Progression of Atherosclerosis
Authors: Qian Xu, Claire Holden, Hildebrando Ferreira Neto, Zhiyong Lin
Journal: Circulation (2023)

Introduction: Atherogenesis involves a complex interaction between immune cells and lipids, processes greatly influenced by the vascular smooth muscle cells (VSMCs) phenotype. Cellular communication network factor 2 (CCN2) is a matricellular protein with an established role in maintaining tissue and organ homeostasis. Various studies have demonstrated the importance of CCN2 in regulating cardiovascular diseases, however its role in atherosclerosis remains to be investigated. Hypothesis: SMC-restricted CCN2 deficiency exacerbates atherosclerosis development in murine models through the modulation of SMC phenotype switching. Aim: Determine the role of VSMC-derived CCN2 in regulating atherosclerosis progression. Methods: In this study, CCN2 was deleted in VSMCs using Cre-lox technology. To induce atherosclerosis, mice were rendered LDLR deficient via AAV8-PCSK9 injection, followed by administration of a high-fat diet for 20 weeks. Aortic atherosclerotic lesion development was then assessed along with single-cell RNA sequencing to map the molecular effects of CCN2 deficiency on the VSMCs phenotype. Gain and loss of function studies in VSMCs were performed to assess the impact of CCN2 alteration on VSMC phenotype switching. Results: SMC-specific CCN2 knockout (SMC-CCN2-KO) mice demonstrated exquisite susceptibility to atherosclerosis formation as evidenced by a significant increase of aortic lipid-rich plaques in aortic roots, arch, thoracic and abdominal aorta. Concomitant with this, a profound vascular inflammation was seen in SMC-CCN2-KO mice. Importantly, these phenotypic changes were associated with a dramatic shift in VSMC phenotype towards a proliferating, lipid-accumulating and macrophage-like cell phenotype. Mechanistic studies point to the requisite role of the KLF4 pathway in VSMC transdifferentiation in SMC-CCN2-KO mice, findings corroborated by cell culture experiments in which KLF4-dependent phenotypic changes were observed in CCN2-null human primary aortic VSMCs. Conclusions: Our findings show that CCN2 deficiency in VSMCs promotes atherosclerosis development through affecting the VSMC phenotypic transition into macrophage-like cells by activation of the KLF4 signaling pathway.
Abstract 19029: Cardio-Oncology Incidence, Cardiac Arrest, and Mortality for Adolescent versus Pediatric Patients: Machine Learning Propensity Score National Analysis
Authors: Jong Kun Park, Dominique Monlezun, Sofia Alexandrescu, Abdelrahman Ali, Bala Pushparaji, Efstratios Koutroumpakis, Mehmet Cilingiroglu, Gloria Iliescu, Konstantinos Marmagkiolis, Cezar Iliescu
Journal: Circulation (2023)

Introduction: The incidence of cardio-oncology disease, arrest, and inpatient mortality among adolescent and pediatric versus adult patients is largely unknown, which undermines optimal care of these high-risk patients. Methods: BAyesian Machine learning-augmented Propensity Score (BAM-PS) translational statistics with multivariable regression was performed on the National Inpatient Sample. Results: Of the 142,651,868 hospitalizations from 2017-2020, 13.69% were pediatric (0-13 years old), 1.13% were adolescent (14-17 years old), and 85.18% were adult patients (over 17 years old). Adults were significantly more likely than adolescent and pediatric patients to have cancer and cardiac disease (99.37% versus 0.15% versus 0.47%, p&lt;0.001). The most common primary malignancies among adolescent or pediatric patients with cardio-oncology disease were leukemia (39.66% versus 52.60%), bone/connective (27.00% versus 12.43%), brain/nervous (8.02% versus 13.80%), Hodgkin lymphoma (7.17% versus 1.09%), and renal (6.01% versus 1.27%). In active cardio-oncology disease by BAM-PS multivariable regression controlling for clinical confounders and severity, adolescent and pediatric patients had comparable mortality odds to adults. Outside of active cardio-oncology disease, pediatric patients (OR 4.95, 95%CI 4.70-5.20, p&lt;0.001) had significantly greater mortality odds than adults, as did adolescent patients but with less magnitude of increased odds (OR 2.03, 95%CI 1.78-2.31, p&lt;0.001). In active cardio-oncology disease, pediatric patients (OR 0.17, 95%CI 0.04-0.68, p=0.013) had significantly lower odds of arrest compared to adults, with adolescents having comparable arrest odds versus adults. Among adolescent and pediatric patients with active cardio-oncology disease, African American versus Caucasians (OR 4.67, 95%CI 1.18-18.42, p=0.028) had significantly greater mortality odds. Conclusions: This machine learning multi-year national study suggests the existence of increased mortality in African American adolescent and pediatric patients with concomitant cancer and cardiovascular disease. Overall, adolescent and pediatric patients with cardio-oncology have better outcomes with more effective long-term management.
Abstract 15654: Layered Plaques and Plaque Vulnerability in Patients With Stable Angina Pectoris
Authors: Takayuki Niida, Kinoshita Daisuke, Keishi Suzuki, Haruhito Yuki, Daichi Fujimoto, Damini Dey, Hang Lee, Iris McNulty, Maros Ferencik, Tsunekazu Kakuta, Ik-kyung Jang
Journal: Circulation (2023)

Backgrounds: Layered plaque, a signature of previous plaque destabilization and healing, is one of the predictors for rapid plaque progression, the mechanism of which is unknown. Aims: To investigate the level of vascular inflammation and plaque vulnerability in layered plaques to elucidate possible mechanisms of rapid plaque progression. Methods: Patients who underwent both coronary computed tomography angiography (CTA) and optical coherence tomography (OCT) were selected. Plaques were defined as any tissue (noncalcified, calcified, or mixed) within or adjacent to the lumen. Pericoronary adipose tissue (PCAT) attenuation was measured at the plaque level on CTA. OCT features of plaque vulnerability were assessed at the corresponding site. Results: A total of 475 plaques from 195 patients presented with stable angina pectoris were included. Layered plaques (n=241), compared to non-layered plaques (n=234), had a higher level of vascular inflammation (-70.94 [-77.86, -64.66] HU vs. -73.52 [-80.83, -67.66] HU, P=0.014, Figure 1). Layered plaques also had a higher prevalence of the features of plaque vulnerability (Figure 2), including lipid-rich plaque (83.8% vs. 66.7%, P&lt;0.001), thin-cap fibroatheroma (TCFA) (26.1% vs. 17.5%, P=0.026), microchannel (61.8% vs. 34.6%, P&lt;0.001), and cholesterol crystal (38.6% vs. 25.6%, P=0.003). Conclusions: Layered plaque was associated with higher levels of vascular inflammation and plaque vulnerability, which might play an important role in plaque progression.
Abstract 17825: Heart Rate Fragmentation Analysis May Suggest Non-Autonomic Markers of Sudden Cardiac Death Risk in Adults With Williams-Beuren Syndrome
Authors: Brianna Cathey, mark D levin, Yi-Ping Fu, Kevin Smith, Sharon Osgood, Neelam Raja, Beth Kozel
Journal: Circulation (2023)

Background: Williams-Beuren syndrome (WBS) is a rare genetic disorder caused by a chromosomal microdeletion (7q11.23). It confers increased arrhythmia and sudden cardiac death (SCD) risk. Mechanisms underlying this risk remain obscure. We recently found HRV abnormalities in individuals with WBS that are known to correlate with sudden death risk in diabetes and following MI and stroke. Heart rate fragmentation (HRF) correlated with adverse CV events in some studies where HRV failed to identify high-risk subjects. Some argue that HRF quantifies non-autonomic CV modulators. We, therefore, sought to further explore non-autonomic modulators of cardiovascular disease by performing HRF analysis in a cohort of adults with WBS. Hypothesis: We hypothesize that those with WBS may exhibit increased sudden death risk from mechanisms not detected by conventional HRV measures. Aims: We aim to 1) Identify biomarkers that are predictive of SCD risk in WBS, and 2) Determine if HRF quantifies non-autonomic CV modulators. Methods: We performed HRF analyses on 24hr ECGs in subjects with WBS (n=18) and age- and sex-matched controls (n=18) enrolled in a prospective NIH study. HRF analyses include the percentage of inflection points (PIP), percentages of hard (PIP H ) and soft (PIP S ) inflection points, and the distribution of “words”, where W 0 ,W 1 ,W 2 , W 3 represent sequences of 4 beats with 0, 1, 2, or 3 inflection points. Inflection points were defined as a change in NN by more than 1/s, where ‘s’ is the sampling frequency. Mann-Whitney tests were used to compare HRF in subjects vs. controls. Spearman’s correlation was used to compare HRF to traditional HRV. Results: HRF markers (PIP, PIP S , and W 3 ) were significantly elevated in WBS subjects (P&lt;0.003)(Fig 1A-C). PIP S and W 3 were negatively correlated with parasympathetic markers HF power and SD1 among WBS subjects (Fig 1D). Conclusion: HRF may quantify some non-autonomic modulators of sudden death risk in those with WBS.
Abstract 17844: Association of Left Atrial Appendage Emptying Velocity With Type of Atrial Fibrillation
Authors: Matthew Bajaj, Ross Smith, Sarah Baghdadi, Carine Tabak, Riya Parikh, Robert Enders, Cody Uhlich, Ethan Morgan, Jacob Baer, Sania Jiwani, Christopher Harvey, Amit Noheria
Journal: Circulation (2023)

Introduction: Left atrial appendage emptying velocity (LAAev) is a surrogate for propensity of LAA thrombus and cardioembolic stroke. While atrial fibrillation (AF) is a known cause of reduced LAAev, relationship between type of AF and LAAev is unclear. Hypothesis: Long-standing persistent/permanent (LSP) AF is associated with reduced LAAev compared to paroxysmal/persistent AF. Methods: We searched transesophageal echocardiogram (TEE) reports of unique individuals from 2016-2022 at the University of Kansas Medical Center. LAAev was obtained from Doppler TEE images. Type of AF and other variables were extracted from medical charts. Association of AF type with LAAev was assessed using univariate and multivariate linear regressions. The multivariate model including all significant univariate predictors comprised age, sex, hypertension, coronary artery disease, peripheral arterial disease, history of venous thromboembolism, left atrial size, mitral regurgitation, left ventricular ejection fraction, rhythm during TEE, general anesthesia, eGFR, and platelet count. Results: Our study comprised 995 patients (female 38.1%, age 71.3±12.7 yr, white 89.3%) of whom 817 (82.1%) had history of AF (43.6% paroxysmal, 21.7% persistent, 16.8% LSP. Among the 817 patients with AF, history of LSP AF was associated with reduced LAAev both in univariate (β=-8.65±1.70 cm/s, p&lt;0.0001) and multivariate (β=-3.77±1.98 cm/s; p=0.05) analyses. Conclusion: Even though CHA 2 DS 2 VASc score does not incorporate type of AF, we found LSP AF to be an independent marker for reduced LAAev. History of LSP AF should be considered in future AF-related stroke risk stratification models.
Abstract 16378: Adult Congenital Heart Disease Lesions Commonly Repaired at High-Quality Surgical Centers in Limited-Resource Settings Have Similar Outcomes as Pediatric Repairs
Authors: Rachel E Wittenberg, Kimberlee Gauvreau, Liang Qi, Luiz Caneo, sivakumar sivalingam, Kathy J Jenkins
Journal: Circulation (2023)

Introduction: Improved medical and surgical therapies have increased attention to congenital heart disease (CHD) across the lifespan. There are limited data on the global burden of adult CHD, which could guide treatment and program development in limited-resource settings. Methods: We analyzed all CHD surgeries from 2015-2020 at 33 programs in 16 countries, using audited data from the International Quality Improvement Collaborative for CHD. Demographic characteristics and outcomes (in-hospital mortality, major infection, and length of ICU stay) were compared for procedures with &gt;100 cases in patients ≥18 years. Adult and pediatric CHD outcomes were compared. Results: Five procedures each contributed &gt;100 cases, accounting for 56% of all adult CHD cases: atrial septal defect closure (ASD; 1061 cases), ventricular septal defect closure (VSD; 350 cases), tricuspid valvuloplasty (TV; 179 cases), tetralogy of Fallot repair (TOF; 141 cases), and pulmonary valve replacement (PVR; 118 cases). The distribution of adult CHD cases was relatively consistent from 2015-2020 (Figure 1A). Median age at surgery was 36 years (IQR 26-48) for ASD, 30 (23-41) for VSD, 39 (28-51) for TV, 26 (21-31) for TOF, and 23 (20-30) for PVR. Median BMI for TOF was 18.9 (IQR 16.7-21.4) compared to 21-22 for the other procedures. In-hospital mortality and major infection were higher for adult TOF (5.0% and 7.9%, respectively) and PVR (4.2%, 3.4%) compared to VSD (0.9%, 2.3%), TV (0.6%, 2.2%), and ASD (0.1%, 0.9%). Median duration of ICU stay was longer for TOF and PVR (77 and 72 hours, respectively) compared with the other procedures (41-48 hours). There was no significant difference in mortality or major infection between adult and pediatric patients for each procedure (Figure 1B). Conclusions: ASD, VSD, TOF, TV, and PVR are the most common adult CHD procedures at IQIC sites, accounting for over half of all adult cases. Adverse outcomes are low and similar among adult and pediatric patients.
Abstract 18360: Single-Cell Analysis Reveals Insights Into Visceral Adiposity in Mice With Diabetes-Associated Atherosclerosis
Authors: Anurag Jamaiyar, Jingshu Chen, Mark W Feinberg
Journal: Circulation (2023)

Introduction: - Visceral white adipose tissue (vWAT), once considered passive and uniform, is a dynamic and heterogeneous tissue involved in glucose and lipid metabolism and immune response. Changes in adipose tissue morphology, physiology, and cellular composition occur in response to dietary fat and carbohydrates, associated with insulin resistance, dyslipidemia, and type 2 diabetes. vWAT also has implications for vascular diseases such as atherosclerosis. However, the connection between vWAT metabolism and atherosclerosis in mouse models remains to be fully elucidated. Methods: - vWAT from male Ldlr -/- mice fed either a chow diet or high fat, high sucrose containing (HFSC) diet for 24 weeks were harvested. Single cell RNA sequencing, histology and immunofluorescence were used to analyze the cellular and transcriptomic profiles in the chow and HFSC groups. Results: - We identified distinct subpopulations of vascular endothelial cells (ECs), immune cells, and adipose stem and progenitor cells (ASPCs), revealing differences between healthy and diseased groups. Notably, we observed a significant increase in immune cell composition, accompanied by a decrease in ECs and progenitor cells in HFSC-fed mice. Within the macrophage population, we noted increased activated macrophages, B-cell derived macrophages, and collagen-expressing macrophage subclusters. In ECs, we observed increased lymphatic and vascular EC subgroups. Furthermore, inflammation and altered metabolism pathways were found in both macrophage and ECs. We identified novel markers, such as Lyz2 and Trem2, that were highly associated with diabetes associated atherosclerosis in male Ldlr -/- mice. Through cell-cell interaction analysis (CellChat), we discovered distinct interactions patterns associated with enriched pathways such as chemokine, Wnt, and BMP signaling in multiple cell types, including macrophages, mesothelial cells, ASPCs, pericytes, SMCs, and ECs. Conclusion: Our scRNAseq atlas reveals interactions amongst adipose cell types in lean and obese states, with the chemokine pathway emerging as a prominent player. This dataset serves as a valuable resource for studying genes and cell types involved in vWAT function in diabetes-associated atherosclerosis.
Abstract 17831: Magnetic Particle Imaging Using Microparticles of Iron Oxide Targeted to Endothelial Adhesion Molecules Reveals Leucocyte - Endothelium Interaction During Sepsis and Neuroinflammation
Authors: Sara Martinez de Lizarrondo, Swannie Pedron, Denis Vivien, Thomas Bonnard, Maxime Gauberti
Journal: Circulation (2023)

Introduction: The ability to track leucocyte - endothelium interactions using non-invasive imaging could allow early diagnosis and monitoring of disease activity in vascular disorders. To this aim, we can use magnetic particle imaging (MPI), a new imaging modality that can detect superparamagnetic material in the human body with high sensitivity. Hypothesis: Superparamagnetic microparticles of iron oxide (MPIO) targeted to endothelial adhesion molecules could be used as leucocyte-mimicking particle and reveal the sites of leucocyte - endothelium interactions by MPI. Methods: We synthesized MPIO targeted to vascular cell adhesion molecule 1 (VCAM-1). These MPIO@VCAM-1 were characterized in vitro by transmission electronic microscopy, flow cytometry and flow chamber experiments. Then, we performed in vivo imaging in models of vascular inflammation in mice, including sepsis and neurovascular inflammation. MPI was performed using a MPI/CT system (Momentum CT, Magnetic Insight). Results: MPIO@VCAM-1 bind specifically to activated endothelial cells in vitro. In control mice, intravenously injected MPIO@VCAM-1 are rapidly eliminated from the circulation by the reticulo-endothelial system and accumulate in the liver and spleen. In LPS-induced sepsis, MPIO@VCAM-1 bind in the lungs and kidneys in a dose dependent manner, revealing inflammation (Figure 1a-b). In conditions of neurovascular inflammation, MPIO@VCAM-1 accumulate on activated endothelial cells of inflamed brain regions (Figure 1c-f). In all these models, control MPIO@IgG do not give any signal beyond passive accumulation in the liver. Moreover, pre-treatment with blocking anti-VCAM-1 antibodies completely abrogates MPIO@VCAM-1 binding, demonstrating imaging specificity. Conclusions: MPI using MPIO@VCAM-1 reveals sites of leucocyte trafficking, allowing quantitative assessment of leucocyte - endothelium interactions in clinically relevant contexts.