tbuckley/cabot-search huggingface dataset:
Abstract 4138380: Cardiac protection of hiPSC-CMs loaded chitosan cardiac patch in myocardial infarcted swine
Authors: Zilong Zheng, Yichen Li, Weijie Tang, Wangping Chen, Jinfu Yang, Chengming Fan
Journal: Circulation (2024)

Background: The low grafting rate of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) following direct injection into the myocardium limits the efficacy of cardiac repair after myocardial infarction (MI). Chitosan-based scaffolds have emerged as functional biomaterials for designing delivery systems in cardiac therapies. This study aimed to enhance the potency of cardiac repair using a hiPSC-CMs loaded chitosan cardiac muscle patch (hCCMP). Methods: The patches were fabricated using chitosan. Characterization of the chitosan patches involved assessing their swelling rate and porosity. The biocompatibility of the hCCMP was analyzed through scanning electron microscopy (SEM) and the CCK8 assay. 16 Yorkshire swine (15-20 kg, 45-50 days of age) were randomly divided into 4 groups (n=4 per group): Sham, MI without further intervention, MI with an empty patch (without hiPSC-CMs), and MI with hCCMP implantation. One and four weeks post-MI, heart function, Infarction size, myocardial perfusion and metabolism were evaluated via cardiac PET-MRI. Engraftment was assessed through human cardiac troponin T staining. Histological analysis including left ventricular anterior wall thickness, cardiac remodeling, angiogenesis, arterialization, and apoptosis in the infarct border area were analyzed using immunofluorescence. Results: SEM showed that the chitosan patch had regular pore size and good 3D structure; porosity was about (96.7±0.37)%. On day3, the patch swelling rate was about (715±64.55)%. SEM, CCK8 assay showed a normal cells growth in the chitosan patch. The hiPSC-CMs grafted well with chitosan patch delivery systems and was associated with significantly improvement in LV function, infarction size, angiogenesis and cardiomyocyte apoptosis in pigs 4 weeks after MI. Conclusions: The 3D chitosan cardiac patch with hiPSC-CMs loaded can enhance the potency of cardiac repair in pigs after MI and present a novel and promising therapic strategy.
Abstract 4138555: The ApoB/LDL-C Ratio Predicts Cardiovascular Events in Coronary Artery Disease Patients Independently of Type 2 Diabetes Status
Authors: Barbara Larcher, Thomas Plattner, Arthur Mader, Alexander Vonbank, Andreas Leiherer, Axel Muendlein, Heinz Drexel, Christoph H Saely
Journal: Circulation (2024)

A high ApoB/LDL-C ratio reflects small LDL particle size which like type 2 diabetes (T2DM) is associated with insulin resistance. Whether the ApoB/LDL-C ratio and the presence of T2DM are mutually independent predictors of cardiovascular events is unclear and is addressed in the present study. We enrolled a large high-risk cohort of 1200 patients with coronary artery disease. T2DM was diagnosed according to current ADA guidelines. Prospectively, cardiovascular events were recorded over a mean follow-up period of 10.5±4.9 years. At baseline, the ApoB/LDL-C ratio was significantly higher in patients with T2DM (n=422) than in subjects who did not have T2DM (0.81±0.18 vs. 0.74±0.15 p&lt;0.001). During follow-up, 662 patients suffered cardiovascular events. The Apo B/LDL-C ratio predicted cardiovascular events in univariate analysis (HR=1.11 [1.03-1.20] p= 0.006), and the event rate was higher in patients with than in those without T2DM (62.2% vs. 52.3%; p=0.001). In a multivariate adjusted Cox regression model both the ApoB/LDL-C ratio and T2DM significantly predicted cardiovascular events in a mutually independent manner, with standardized adjusted HRs of 1.11 [1.03-1.20]; p=0.008 and 1.39 [1.18- 1.64]; p&lt;0.001, respectively. We conclude that in subjects with coronary artery disease the ApoB/LDL-C and T2DM are mutually independent predictors of cardiovascular events.
Abstract 4138606: Toll-like Receptor 4 Signaling Establishes Trained Innate Immunity Through Interferon-Mediated Epigenetic Modifications Leading to Cardioprotection in a Stress-induced Cardiomyopathy Model
Authors: Kenji Rowel Lim, Junedh Amrute, Attila Kovacs, Abhinav Diwan, Douglas Mann
Journal: Circulation (2024)

Introduction: The mechanisms responsible for establishing preconditioning-induced cardioprotection remain unknown. We have shown that a high dose of isoproterenol (ISO) induces cardioprotection against a second ISO dose in mice. The durability of protection and the lack of an innate immune response suggests trained immunity as a novel cardioprotective mechanism. Hypothesis: We hypothesize that cardioprotection is conferred through trained immunity, by interferon signaling downstream of necrotic cardiac material-mediated Toll-like receptor 4 (TLR4) activation. Methods: Wild-type C57BL/6J mice were intraperitoneally injected with TLR agonists or diluent, and challenged with 300 mg/kg ISO 7 days later. Mice were assessed by 2-D echocardiography, serum cardiac troponin levels, flow cytometry immune cell counts, and Multiome (single nuclei RNA+ATAC) sequencing. Results: The TLR4 agonist lipopolysaccharide (LPS) induced cardioprotection against ISO injury, with mice having enhanced survival (P=0.049) and no changes in cardiac troponin levels (P&gt;0.99), cardiac neutrophil influx (P&gt;0.99) or left ventricular motion (P=0.057) relative to baseline values before injury. Treating LPS-injected mice with β-glucan reversed the effects of LPS on immune cells and abolished cardioprotection. Multiome analysis of genes linked to chromatin peaks with increased accessibility in LPS+vehicle (protected) compared to LPS+β-glucan and diluent control (non-protected) hearts revealed the interferon pathway to be up-regulated across all major cell types. Modulation of interferon signaling with monoclonal antibodies against type 1+2 interferon receptors abolished cardioprotection in LPS-treated mice, whereas pre-treatment with recombinant type 1+2 interferons induced cardioprotection. Importantly, interferon-treated hearts shared similar chromatin accessibility features and enriched transcription factor motifs, including interferon-specific motifs, with LPS-protected hearts across cell types, particularly among non-cardiomyocytes. Conclusions: TLR4-induced interferon signaling is sufficient and in part necessary for cardioprotection against ISO injury. Moreover, our findings show that epigenetic modifications downstream of interferon signaling lead to cardioprotection consistent with trained innate immunity.
Abstract 4138601: Comparison Between Mono VS Dual VS Triple Antiplatelet Therapy In Patients With Ischemic Heart Disease Undergoing PCI, A Network Meta-Analysis.
Authors: Ali Saad Al-Shammari, Ahmed Ibrahim, Laila Shalabi, Naiela Almansouri, Mohammed Tarek Hasan, Sai Gautham Kanagala, M Rafiqul Islam, Razan Alsawadi, Ahmed Al Sakini, Ibrahim Hassan, Sara A. Nada, Ameer Al-Wssawi
Journal: Circulation (2024)

Background: Antiplatelets are important in ischemic heart disease(IHD) patients. We aim to research the efficacy and safety of single(SAPT), dual(DAPT), and triple(TAPT) antiplatelet approaches in IHD patients undergoing PCI. Methods: A systematic review was conducted until April 1st, 2024, and a network meta-analysis using the Netmeta package in R studio 4.3.3 was performed. Primary outcomes were cardiac death, myocardial infarction(MI), stent thrombosis, stroke, and major bleeding(BARC 3-5). A sensitivity analysis was done to explain variables with high heterogeneity. Results: From 25 studies, a total of 65115 patients were included in the analysis. For cardiac death, 17 studies showed TAPT had a lower risk than DAPT compared to SAPT [RR = 0.74; 95%CI (0.40 to 1.35); p-value = 0.33], [RR = 1.01, 95%CI (0.84 to 1.19); p-value = 0.87] respectively. The heterogeneity was insignificant(I2=0%; p-value=0.58. For MI, 23 studies found TAPT had a lower risk than DAPT compared to SAPT [RR = 0.77; 95%CI (0.51 to 1.16); p-value = 0.2047], [RR = 0.81, 95%CI (0.64 to 1.03); p-value = 0.0850] respectively. The heterogeneity was significant (I2 = 53%). For stent thrombosis, 17 studies showed DAPT had a lower risk than TAPT compared to SAPT [RR = 0.74; 95%CI (0.45 to 1.21); p-value = 0.2284], [RR = 0.84, 95%CI (0.27 to 2.59); p-value = 0.7630] respectively. The heterogeneity in this comparison was significant. For stroke, 17 studies showed DAPT had a lower risk than TAPT for stroke in comparison to SAPT [RR = 0.91; 95%CI (0.75 to 1.10); p-value = 0.3209], and [RR = 0.87, 95%CI (0.43 to 1.76); p-value=0.6937], respectively. The heterogeneity was insignificant(I2=0%; p-value=0.8165). For Major bleeding(BARC 3-5), 15 studies showed DAPT had a lower risk than TAPT in comparison to SAPT[RR = 1.43; 95%CI (1.09 to 1.88); p-value = 0.0107], [RR = 2.78, 95%CI (0.90 to 4.78); p-value = 0.0852] respectively. The heterogeneity was significant(I2 = 49.5%). Conclusion: Personalized treatment approaches that consider the benefits and risks of different antiplatelet strategies are crucial for optimal patient management of IHD.
Abstract 4138604: Impact of GLP-1 Agonist on the Incidence of Atrial Fibrillation in Obese Patients Following Heart Failure Hospitalization
Authors: Thomas Fretz, Tanyanan Tanawuttiwat, Onyedika Ilonze, Mithilesh Das
Journal: Circulation (2024)

Introduction: Atrial fibrillation (AF) in patients with heart failure (HF) is associated with increased morbidity and mortality. Glucagon-like peptide-1 (GLP-1) agonists have been shown to reduce cardiovascular risk in patients with obesity and diabetes, respectively. Meta-analysis of prospective trials looking at GLP-1 agonist use on the incidence of AF suggest benefit in patients with diabetes but is of unclear benefit in this regard for patients with obesity. Hypothesis: GLP-1 agonists reduce atrial fibrillation incidence in patients with diabetes and obesity. Aims: The goal of the study is to assess the effects of GLP-1 agonist on incidence of new AF in patients with obesity and diabetes following heart failure hospitalization. Methods: The study included consecutive patients who were admitted to an academic tertiary care center over three years with a primary diagnosis of heart failure exacerbation and no prior diagnosis of AF. The primary outcome was incidence of AF within 12 months after hospitalization. Demographic, comorbidity, echocardiography, and medications were obtained. Cox-regression analysis was performed to identify the predictors of new-onset AF following HF hospitalization. Results: Of the patients included in our study, 1668 (42.9%) have a BMI greater than or equal to 30, 574 (14.5%) have BMI greater than or equal to 40, and 2300 (58.2%) have diabetes mellitus. GLP-1 use is associated with a significantly lower incidence of AF at one year in obese patients (p=0.042; RR 0.73; 95% CI: 0.54-.99) (Figure), while in non-obese individuals, GLP-1 receptor agonist was not associated with a decreased incidence of AF (p=0.674; RR 1.08; 95% CI: 0.76-1.53). In patients with diabetes, GLP-1 receptor agonist use did not reach statistical significance for reduced AF incidence following heart failure hospitalization ( p=0.091; RR 0.80; 95% CI 0.62-1.04 ). Conclusion: GLP-1 receptor agonist use is associated with a statistically significant reduction of incidence of new atrial fibrillation at one year following hospitalization for heart failure in obese patients.
Abstract 4138433: Prevalence, Clinical Characteristics, and Outcomes in Heart Failure with Improved Ejection Fraction by Chronological Age
Authors: Kishan Srikanth, Keane Lee, Rishi Parikh, Andrew Ambrosy, Thida Tan, Steven Hamilton, Orly Vardeny, Ashok Krishnaswami, Ivy Ku, Elena Vasti, Alexander Sandhu, Alan Go, Sirtaz Adatya, Ankeet Bhatt
Journal: Circulation (2024)

Background: HF incidence increases with age. Modern treatments have led to more patients recovering LVEF, classified as HF with improved ejection fraction (HFimpEF). However, the age-related epidemiology and prognosis of HFimpEF remain unclear. Hypothesis: Compared to younger patients, older patients will have lower rates of HFimpEF after incident HFrEF and higher rates of HF-related morbidity and mortality. Aims: To describe the clinical characteristics and outcomes in HFimpEF across the age spectrum within a healthcare delivery system in the US. Methods: We identified adults ≥18 years with incident HFrEF (LVEF≤40%) between 2013-2018 within Kaiser Permanente Northern California (KPNC), a healthcare system serving 4.5 million members. HFimpEF was defined as baseline LVEF &lt;40% with subsequent &gt;10% improvement to &gt;40%. HFimpEF incidence was assessed by baseline age categories (&lt;50, 50-64, 65-79, ≥80 years [yrs]). Rates of worsening HF (WHF) events (i.e. HF-related hospitalization, ED, or outpatient visits) were compared between HFimpEF and persistent HFrEF patients across age using Cox proportional hazards models adjusted for sex and EF at the time of incident HFrEF, including potential interaction by age modeled continuously (cubic splines with 3 knots). Data: Among 12,639 adults with incident HFrEF, 33% experienced HFimpEF, with lower rates at older ages: 42% (&lt;50 yrs), 41% (50-64 yrs), 35% (65-79 yrs) and 18% (≥80 yrs). Among patients with HFimpEF alive at 1-year post-HFrEF (N=9954), WHF incidence (per 100 p-y) remained high (10.7) in younger (&lt;50 yrs) patients and increased by age: 14.5 (50-64 yrs), 21.6 (65-79 yrs), and 33.7 (≥80 yrs)(P &lt;0.001 for trend; Figure, Panel A). Patients with HFimpEF, compared to those with persistent HFrEF, had lower adjusted rates of WHF across the spectrum of age (pinteraction by age &lt; 0.001; Figure, Panel B). Conclusion: HFimpEF is common within a year of incident HFrEF, more prevalent in younger patients, and is associated with significant residual clinical risk. Compared to persistent HFrEF, improvements in LVEF are associated with a lower risk of WHF or death. Additional research is needed to understand HF symptom burden and medical therapy use in this population.
Abstract 4138427: Frailty Measured by The Risk Analysis Index as a Predictor of In-hospital Outcomes After PCI: A Retrospective Nationwide Analysis of 449,857 Patients
Authors: Michele Fouad, Ahmad Nawlo, Kerollos Abdelsayed, Hassan Alshaker, Kirellos Said Abbas, Abdul Rahman Akkawi, Yazan Almohtasib, Basel Abdelazeem, Mohammad Kawsara
Journal: Circulation (2024)

Background: Frailty emerges as an independent predictor of adverse outcomes post-cardiac procedures including percutaneous coronary intervention (PCI). Various indices have been developed to assess frailty, but no gold standard exists. The Risk Analysis Index (RAI) is a promising frailty index that enables better preoperative evaluation for personalized care. Objective: To assess RAI as a preoperative assessment tool for predicting post-PCI in-hospital outcomes. Methods: In this retrospective cohort analysis, The National Inpatient Sample was queried from 2016 to 2020 for patients who underwent PCI. Our cohort was stratified depending on RAI score into Robust, Prefrail, Frail, and Very Frail ( Figure 1.A ). Primary outcomes were non-home discharge (NHD), mortality, and extended length of stay (defined as length of stay exceeding 75% of the cohort) (eLOS). The statistical significance of difference in the primary outcomes was assessed amongst the four frailty groups using The Chi-square test ( x 2 ). In addition, RAI was tested for its ability to predict the primary outcomes using the area under the curve (AUC). Results: The study sample included 449,857 unweighted admissions, of which 67.09% were males, the median age was 50 (IQR: 46-54), 22.6% were Robust, 54.9% were Prefrail, 19% were Frail, and 3.5% were Very Frail ( Figure 1.A ). Increasing RAI frailty scores (robust versus very frail) correlated with significantly higher NHD (7.64% vs. 61.54%; p&lt;0.0001 ), eLOS (11.42% vs. 54.33%; p&lt;0.0001 ), and mortality (1.25% vs. 7.06%; p&lt;0.0001 ) ( Figure 1.B ). RAI effectively predicted NHD (C-statistic 0.73; 95% CI 0.72-0.73), eLOS (C-statistic 0.68; 95% CI 0.67-0.68), and mortality (C-statistic 0.66; 95% CI 0.65-0.66) ( Figure 1.C ). Conclusion: Frailty, measured by RAI, is a significant predictor of post-PCI in-hospital outcomes, including eLOS, NHD, and mortality. RAI facilitates better patient stratification and personalized care strategies in clinical practice.
Abstract 4138517: Role of Coronary Computed Tomographic Angiography in Patients with Discordant Findings on Exercise Stress Echocardiography
Authors: Nicholas Olivieri, Natalia Okon, Ivo Genev, Samantha Swamy, Mirza Baig, Menhel Kinno, Mushabbar Syed
Journal: Circulation (2024)

Background: Exercise stress echocardiography is routinely used for risk stratification and diagnosis of myocardial ischemia in low-to-intermediate risk patients with suspected coronary artery disease (CAD). Discrepancies between exercise electrocardiography (EKG) and echocardiography (ECHO) are common in clinical practice. Prior literature suggests that patients with discordant stress test results generally have worse outcomes, though the extent of epicardial atherosclerotic disease remains unclear. Coronary computed tomographic angiography (CTA) has gained a class I recommendation for the assessment of atherosclerotic burden per ACC/AHA chest pain guidelines. Using non-invasive fractional flow reserve (CT-FFR), the functional significance of lesions can also be assessed. This study investigates the incidence and burden of CAD in patients with discordant exercise echocardiography findings. Methods: Patients aged 18 or older who had exercise echocardiography followed by CTA from January 1, 2013, to January 31, 2023, were retrospectively enrolled in this study and categorized into two discordant result groups: EKG+/ECHO- or EKG-/ECHO+. Those who failed to achieve the target heart rate or had a paced rhythm/left bundle branch block on baseline EKG were excluded. CTA findings were classified as no CAD, non-obstructive CAD (&lt;50% stenosis), obstructive CAD (≥50% stenosis), and obstructive CAD with FFR+ (&lt;0.75). Results: The study included 198 patients, the majority female (56.0%), with a mean age of 61 ±10 years. Among them, 159 (80.3%) were EKG+/ECHO- and 39 (19.7%) were EKG-/ECHO+ (Table 1). In the EKG+/ECHO- group, 55 (34.6%) had no CAD, 48 (30.2%) had non-obstructive CAD, and 56 (35.2%) had obstructive CAD, out of which 19 (33.9%) were FFR+. In the EKG-/ECHO+ group, 13 (33.3%) had no CAD, 17 (43.6%) had non-obstructive CAD, and 9 (23.2%) had obstructive CAD of which 3 (33.3%) was FFR+. There was no statistically significant difference in the degree of CAD between the two cohorts. Conclusions: The majority of patients with discordant results on exercise echocardiography were found to have CAD. There was no significant difference in the degree of disease between the EKG+/ECHO- or EKG-/ECHO+ groups. Overall, discordant results on exercise echocardiography should not be discounted and warrant further evaluation. CTA provides important information that can impact the diagnosis and further medical management of patients with chest pain and suspected CAD.
Abstract 4138473: Detailed Lipoprotein Profiling in Assessing Coronary Calcium Score Progression and Atherosclerotic Risk
Authors: Andrea Stephanus, Sergio Henrique Rodolpho Ramalho, Marcio Bittencourt, Isabela Bensenor, Michael J Blaha, Peter Toth, Steven Jones, Raul Santos, Paulo Lotufo, Luiz Sergio Carvalho, Alessandra Campos-Staffico
Journal: Circulation (2024)

Background: Coronary calcium scoring (CCS) evaluates atherosclerotic burden and cardiovascular risk, correlating with coronary artery disease (CAD) severity. Advances in Nuclear Magnetic Resonance ( 1 H-NMR) spectroscopy for lipoprotein fraction analysis highlight precise atherogenic lipid parameter estimation. Enhanced lipid testing, including sub-fractionation assays, improves risk assessment and identifies new biochemical markers for CAD burden. Hypothesis: Specific lipid fractions and subfractions are significantly associated with CCS progression, serving as biochemical markers of CAD progression. Aim: To evaluate the association between lipid fractions and subfractions with CCS progression, aiming to improve CAD risk stratification. Methods: This study used data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). CCS progression was any positive change in CCS values over 5 years. High-field 1 H-NMR spectroscopy assessed lipoprotein fractions and subfractions, including plasma concentration, particle size, cholesterol, and triglyceride content. Descriptive and inferential statistics compared baseline characteristics. Multivariable binary logistic regression models, both unadjusted and propensity score-adjusted, assessed associations between plasma levels of lipoprotein fractions and CCS progression. Statistical significance was set at p &lt;0.05. Results/Data: In this study of 2,986 participants, 1,008 (33.8%) experienced CCS progression over 5 years. Significant associations were found between plasma lipoprotein fractions and CCS progression. Large, medium, and very small TRLP (89-37 and 29-24 nm) were linked to increased CCS risk, while small TRLP (36-30 nm) had an inverse association. Small cLDLP (20.4-19 nm) were directly associated with CCS progression, while medium and large cLDLP (23-20.5 nm) were inversely associated. Small cHDLP (7.4-8.0 nm) increased CCS risk, whereas medium to large cHDLP (8.1-13.0 nm) had an inverse association. Specific HDL subspecies (H7P to H3P, 12.0-8.7 nm) were inversely associated with CCS progression, while H2P and H1P (7.8-7.4 nm) increased CCS risk. TRLZ (30-100 nm) levels were positively associated with CCS progression, whereas LDLZ (19-22.5 nm) and HDLZ (7.1-13 nm) were inversely associated. Conclusion(s): Plasma levels of specific lipoprotein fractions and subfractions are associated with CCS progression, providing insights into the complexity of lipoprotein characteristics in CAD.