tbuckley/cabot-search huggingface dataset:
Abstract 17152: Use and Outcomes of the Medical Hybrid Procedure for Stage 1 Palliation in Infants With Hypoplastic Left Heart Syndrome and Variants
Authors: Daniel N Beauchamp, Christopher J Statile, Huaiyu Zang, David A Parra, Justin A Godown, Natalie M Jayaram, Matthew L Moehlmann, Garick D Hill
Journal: Circulation (2023)

Background: Staged palliation of hypoplastic left heart syndrome (HLHS) and variants typically begins with the Norwood operation or the hybrid procedure. Hybrid palliation is used in 13% of patients nationally and is often reserved for high-risk patients. A stented hybrid (SH) consists of bilateral pulmonary artery bands (bPAB) and a ductal stent while a ‘medical hybrid’ (MH) consists of bPAB and prostaglandins. MH use and outcomes have not been well described. Hypothesis: MH is used in higher-risk patients and therefore has lower survival than other stage 1 strategies. Aims: Compare use and outcomes of MH, SH, and surgical stage 1 (SS1) using a multicenter database. Methods: Patients from the National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) database were categorized by initial intervention: MH, SH, or SS1. Other/unclear procedures were excluded. Results: The study included 2423 patients from 65 centers: 277 (11%) MH, 133 (5%) SH, 2013 (83%) SS1. MH had the lowest birth weight (BW) and gestational age (GA), most non-cardiac anomalies, and most preoperative risk factors (PRF). Most centers performed MH in a minority of cases, though use ranged from 0% to 82% at centers with ≥10 patients. Transplant-free survival at 1 year was 56% for MH, 66% for SH, and 81% for SS1 (p&lt;0.0001). Using multivariable logistic regression, predictors of MH vs SS1 were lower BW (p&lt;0.001), lower GA (p&lt;0.001), genetic syndrome (p=0.010), non-cardiac anomaly (p=0.031), and ≥4/12 PRF (p&lt;0.001). Predictors of MH vs SH were HLHS (p=0.044) and ≥4/12 PRF (p=0.045). Cox proportional hazards regression was used to compare risk-adjusted outcomes, excluding one center that performed &gt;50% SH: MH had higher risk of one-year mortality/transplant compared to SS1 (HR = 1.89, 95% CI 1.47-2.42) and no difference compared to SH (HR = 1.16, 95% CI 0.76-1.79). Conclusions: Survival after MH is similar to SH and worse than SS1. This may be due to patient risk factors not controlled for in this study.
Abstract 14829: Inflammatory Cells and Cytokines Are Increased in Mice With Pulmonary Arterial Hypertension Associated With Hematopoietic Dnmt3a Depletion
Authors: Isaac Emon, Ruaa Al-Qazazi, Patricia Lima, Ashley Martin, Michael Rauh, Stephen L Archer
Journal: Circulation (2023)

Background: Pulmonary Arterial Hypertension (PAH) is characterized by pulmonary vascular remodeling of the precapillary pulmonary arteries. Increasing evidence suggests that inflammation plays an essential role in PAH development. Understanding the involvement of immunity in this context can provide valuable insights into the pathogenesis of PAH. DNA Methyltransferase 3A ( DNMT3A ) mutations can lead to altered DNA methylation patterns in immune cells, potentially affecting the expression of immune-regulatory genes. Here, we investigate the role of inflammation in PAH driven by hematopoietic Dnmt3a depletion in mice. Methods: We used male and female conditional, Vav-Cre-driven hematopoietic Dnmt3a knockout mice ( Dnmt3a –/– ) and compared them to controls (n=3/group). Lung tissue and plasma were collected. Single-cell suspensions of digested lungs were stained to detect total leukocytes (CD45+), T cells (CD3+), B cells (CD19+), macrophages (Ly6G-, F4/80+), and neutrophils (Ly6G+, F4/80-) via flow cytometry. Plasma samples were screened for 32 distinct cytokines using a cytokine array. Results: Dnmt3a –/– mice spontaneously developed PAH at 4.5 months. PAH was associated with a 19% increase in total CD45+ leukocytes in the lungs compared to controls. T cells, and B cells were increased in Dnmt3a –/– mice compared to controls (7.9% and 3.1%, respectively). In contrast, there was no difference in lung neutrophil count. Two subsets of macrophages were observed based on granularity. Compared to controls, Dnmt3a –/– mice had a 29% increase in agranular macrophages and a 19.7% increase in granular macrophages. IL-13, known for its role in alternative monocyte/macrophage activation in PAH patients associated with systemic sclerosis (SSc-PAH), was significantly increased in the plasma of Dnmt3a –/– mice compared to controls (1.8 times higher, p=0.02). IL-12p40, a chemoattractant for macrophages, showed a trend towards being increased in Dnmt3a –/– mice compared to controls (5.7 times higher, p=0.14). Conclusion: Deletion of DNMT3A in the hemopoietic system triggers an inflammatory form of PAH in mice, associated with increased macrophages, B- and T-cells in the lung. IL-13 may be a potential diagnostic marker in PAH.
Abstract 15009: Extra-Low Energy Defibrillation With Epicardial Implantable Cardioverter Defibrillator Networks With Electrically Conductive Fibers in Disease Models
Authors: Toshiaki Akita, Toshiaki Hisada, Sho Akita
Journal: Circulation (2023)

Introduction: We previously reported that extra-low energy (&lt;0.6J) defibrillation is possible with the epicardial ICD net lead system (Ep-ICD) in normal canine hearts. Hypothesis: The aim of this study was to test whether the Ep-ICD can terminate ventricular fibrillation (Vf) with the same energy in two disease models (heart failure and long QT syndrome (LQT)). Methods: 1. Ep-ICD was constructed by fine tungsten fibers at the top and bottom of the cardiac mesh (Figure 1), connected to the RV and SVC coils of the DF-1 lead, respectively. 2. Heart failure was induced by rapid right ventricular pacing (170 bpm, 8 weeks). 3. Vf was induced by placing a 9V battery on the surface of the heart. DC shock was delivered with a minimum energy of 0.4J (Medtronic Viva XT). 4. Defibrillation threshold (DFT) was defined as 75% of defibrillation success. 5. LQT was simulated by reducing the conductance (Gk) of the IKS current by (x 1.0(CTL) or 0.8(LQT)) by computer simulation. Results: 1. DFT(J) of Ep-ICD in the canine HF model: 0.8, 1.2, 1.2. 3, Minimum DF energy(J): 0.6, 0.6, 0.8, 2. Maximum DF energy(J): 1.2, 1.6, 5, 52. Immediate return to sinus rhythm (SR) was achieved in most cases after DC delivery. In a small number of cases, brief periods of VT occurred, with rapid return to SR. No tachycardic arrhythmias occurred after return to SR. 3. The DFT was 0.39 for LQT and 0.52 for CTL. Conclusions: 1. DFT of Ep-ICD increased from 0.6 J in normal canine heart to 1.2 J in canine HF model, but still much lower energy used in current ICD system (36 J). 2. The Ep-ICD lead system is the least traumatic and still within the acceptable range while conscious. 3. DFT of LQT with Ep-ICD is 25% lower than normal heart. 4. Ultra-low energy DC can avoid conduction abnormalities or malignant arrhythmias after shock. Hearts return to SR immediately. 5. Ep-ICD can deliver the DC shock before loss of consciousness, improving quality of life and safety of ICD therapy.
Abstract 17029: Prospective Comparisons and Reference Ranges of Left Ventricular Global Longitudinal Strain by Contemporary Vendor-Neutral Echocardiography Software in Healthy Subjects
Authors: Aro Daniela Arockiam, Tiffany Dong, Ankit Agrawal, Joseph El Dahdah, Muhammad Majid, L L Rodriguez, Richard A Grimm, Zoran B Popovic, Brian P Griffin, Tom Kai Ming Wang
Journal: Circulation (2023)

Background: Left ventricular global longitudinal strain (LVGLS) by speckle-tracking is an established measure of left ventricular systolic function with many clinical applications. Most strain software traditionally can only analyze strain on scans of the same vendor, however recent advances have allowed them to analyze all scans, although external validation studies are lacking. We aimed to determine the normal ranges and compare two-dimensional LVGLS measurements by contemporary strain software in a healthy prospective cohort. Methods: One-hundred healthy subjects undergoing transthoracic echocardiography during January-April 2023 at our institution were prospectively recruited, 20 per age-group, 50% were female, and 50%GE and 50% Philips scans. TomTec version 51.02 (Autostrain LV), EchoPAC version 206 (AFI) and VVI software were utilized to quantify two-dimensional LVGLS in all patients for comparative and regression analyses. Results: Means (and lower limits of normal)±standard errors LVGLS were -17.1±0.2% (-13.2±0.3%) by TomTec, -17.8±0.3% (-12.7±0.4%) by EchoPAC and -16.3±0.3% (-11.0±0.5%) by VVI, with significant differences on all pairwise T-tests of means (P&lt;0.001-0.017). Means±standard errors LVGLS by strain software for each subgroup are listed in the Table. In multivariable linear regression analyses, factors significantly associated with LVGLS measurements with their beta-coefficients (95%CI) were heart rate (per 1 bpm) 0.05 (0.01-0.07) for TomTec; male sex 1.19 (0.13-2.26) and diastolic blood pressure (per mmHg) 0.06 (0.00-0.12) for EchoPAC; and body mass index (per kg/m 2 ) 0.12 (0.01-0.22) with VVI. Conclusion: All three contemporary strain software demonstrated vendor-neutral properties to measure LVGLS on both GE and Philips scans, with means and lower limits of normal determined, and notably, factors affecting LVGLS values differed by software vendor.
Abstract 11599: High-Density Lipoprotein Cholesterol and Statin Use for Primary Prevention Among US Adults With Intermediate 10-year Predicted ASCVD Risk
Authors: Alexander Zheutlin, Joshua Jacobs, Adam P Bress
Journal: Circulation (2023)

Introduction: Although there is no strong evidence of a causal relationship between high-density lipoprotein cholesterol (HDL-C) with atherosclerotic cardiovascular disease (ASCVD), HDL-C is considered “good cholesterol” by many which may impact decision making around statin use. We determined if statin use for primary prevention differed by HDL-C levels among adults without ASCVD, diabetes mellitus (DM), or low-density lipoprotein cholesterol (LDL-C) &gt;190 mg/dL but an intermediate 10-year predicted ASCVD risk. Methods: National Health and Nutrition Examination Surveys (NHANES) participants who were non-pregnant, 40-75 years with a 10-year ASCVD risk 7.5-&lt;20% and fasting lipids, and without ASCVD, DM, LDL-C &gt; 190 mg/dL, or triglycerides ≥500 mg/dL from 2013-2020 were included. Multivariable Poisson regression with robust error variance estimated adjusted prevalence and prevalence ratios (PRs) and 95% confidence intervals (CIs) for statin use associated with HDL-C levels (low [&lt;40 mg/dL], normal [40-60 mg/dL], high [ &gt; 60 mg/dL]). Models were adjusted for age, race, ethnicity, sex, education, healthcare access within 12 months, routine location for health care, health insurance, LDL-C, and body mass index. Results: Among 999 included US adults (representing 23.7 million adults) with a 10-year predicted ASCVD risk 7.5-&lt;20%, the multivariable adjusted prevalence of statin use was 32.5%, 28.6%, and 24.4% among adults with low HDL-C, normal HDL-C, and high HDL-C, respectively. After adjustment, the PR for statin use among adults with low HDL-C was 1.14 (95% CI 1.01,1.18) and high HDL-C was 0.85 (95% 0.83,0.88) vs. adults with normal HDL-C (Figure 1). Discussion In the current analysis, adults with high HDL-C were less likely to be taking a statin, while adults with low HDL-C were more likely. HDL-C may influence the decision to use statin medication among adults with intermediate 10-year ASCVD risk despite evidence that HDL-C level is not causally related to ASCVD.
Abstract 14459: Endothelial Cell Specific Expression of HIV-Nef Induces Endothelial Senescence and Reduced Cardiac Output
Authors: Moraima Noda, Sarvesh Chelvanambi, Matthias A Clauss
Journal: Circulation (2023)

Introduction: People living with HIV experience increased cardiovascular comorbidities despite immediate prescription of combined antiviral therapy (ART) upon HIV diagnosis. Previously, we reported that the virally encoded HIV-Nef protein persists in extracellular vesicles (EV) of aviremic HIV patients on ART and endothelial-specific transgenic expression of HIV-Nef in murine models causes increased endothelial surface expression of the pro-apoptotic protein EMAPII. Co-culture with HIV-Nef expressing T cells induced endothelial senescence which could be completely abrogated by using EMAPII-neutralizing antibodies. Hypothesis: Here we hypothesize that endothelial Nef expression in transgenic mice induces EMAPII-associated endothelial senescence after intermittent exposure to hypoxia. Methods: Female (n=5) transgenic mice with endothelium-specific Nef expression using VE-Cadherin promoter were challenged with 4 weeks of mild hypoxia (10% O 2 ) followed by 8 weeks of normoxia and then evaluated for cardiac function using non-invasive echocardiography with INVEVO2100. Results: We observed decreased cardiac output (Nef= 15.10 ul/min vs WT= 21.46 ul/min, p&lt;0.05). Subsequently, we observed a 3.5-fold increased frequency of senescent endothelial cells using the senescence-associated marker p16INK4α (Nef= 0.54% vs WT= 0.15%, p&lt;0.05) from the heart using flow cytometry. Furthermore, we also observed a 3.5-fold increase in the frequency of EMAPII+/P16INK4α+ cells (Nef= 0.50% vs WT= 0.14%, p&lt;0.05). Conclusions: Transgenic endothelial HIV-Nef expression leads to upregulation of endothelial cellular senescence and EMAPII expression. EMAPII-neutralizing antibodies and senolytic agents are likely tools to reduce HIV-Nef-induced senescence. Endothelial cell senescence could affect cardiac circulation to impair heart function. Future studies will evaluate sex differences in HIV-Nef induces cardiac output at various ages.
Abstract 15514: Ambulating Femoral Inserted Intra-Aortic Balloon Pump: Is It Safe?
Authors: Meshe Chonde, suzanne seidel, Billy Villao, Harriet Aronow, Sunny Hsu, Bernice L Coleman, Miguel Velazquez, Anthony Andreas, Alice T Chan
Journal: Circulation (2023)

Introduction: Patients undergoing heart transplant evaluation wait in the hospital for weeks. The intra-aortic balloon pump (IABP) is commonly used as a bridge to heart transplants. However, patients with a femoral-inserted IABP may face mobility limitations. Goal: To address this issue, the Cardiac Intensive Care Unit (CICU) implemented a modified Ramsey protocol aimed at ambulating patients with IABP. Goals: The goal was to improve patient health outcomes. The project aims to ambulate patients with f-IABP in Cardiac Intensive Care Unit (CICU) to prevent functional decline due to bed rest. Methods: The provider prescribed all IABP patients in the CICU ambulation. Before ambulation, patients who met the criteria were verticalized, utilizing the KREG Catalyst™ bed at 70 degrees for at least 45 minutes three times/day. After tolerating the verticalization at 70 degrees, nurses and physical therapists will assist the patient in stepping off the bed for at least 45 minutes 2 before ambulating around the unit. Results: A total of 14 patients were ambulated, of which twelve were male and two were female. The mean aged is 59 years, ranging from 30 to 72 years. The participants underwent an average of 15 ambulation sessions, with the minimum being one session and the maximum being 52 sessions. During these sessions, the participants covered an average total distance of 9619.29 feet, ranging from a minimum of 70 feet to a maximum of 36250 feet. The participants spent an average of 4061.86 seconds ambulating, with a minimum duration of one minute and a maximum of 30 minutes. The average catheter migration was 0.2229 centimeters upon implementation of the intervention. The findings show no significant adverse events with implementing this protocol. Conclusions: By implementing this protocol, healthcare professionals can enhance patient care and optimize post-heart transplant length of stay.
Abstract 16488: Sestrin2 Protects Against Long-Term Cardiac Injury and Remodeling by Modulating mTORC1 Activation in Myocardial Ischemia/Reperfusion
Authors: Xuan Li, Zhen Wang, Jussara M Docarmo, Alexandre A Da, Alan J Mouton, Ana C Omoto, John E Hall
Journal: Circulation (2023)

Introduction: Myocardial ischemia/reperfusion (I/R) injury can lead to long-term cardiac dysfunction and heart failure with reduced ejection fraction (HFrEF) in aged hearts. However, young hearts may exhibit some resistance to this process and retain better cardiac function. Our previous studies have identified a novel protein called Sestrin2 (Sesn2), which is downregulated in aged hearts. Hypothesis: Sesn2 may protect hearts from progressing to HFrEF following myocardial I/R. Methods: We induced myocardial I/R injury by ligation/release of the left anterior descending coronary arteries (LAD) in both C57BL/6J mice and mice with cardiac-specific Sesn2 knockout (Sesn2 cKO ). Cardiac function was assessed, and samples were collected at baseline, one day post I/R, seven days post I/R, and 28 days post I/R. Results: In wild-type (WT) hearts (12-18 weeks), cardiac function showed a slight decrease 28 days post I/R (IR28D), but the ejection fraction (EF) remained above 50%. However, Sesn2 cKO mice exhibited a significant reduction in cardiac function at IR28D, with an about 27.5% decrease in EF compared to WT hearts. We also observed a significant increase in volume at diastole in Sesn2 cKO mice at IR28D compared to their baseline and corresponding WT. Furthermore, when comparing mitochondrial respiration in the area at risk (AAR) of the left ventricles between the two groups, we found a significant decrease in oxygen consumption rate (OCR) and a significant increase in H 2 O 2 production in Sesn2 cKO hearts. Additionally, the mammalian target of rapamycin complex 1 (mTORC1) was significantly upregulated in Sesn2 cKO mice compared to WT hearts. Conclusions: Sesn2 exerts a cardiac protective effect by downregulating mTORC1 activation, thereby reducing long-term cardiac injury following I/R, attenuating cardiac remodeling, and improving mitochondrial respiration in the AAR of the heart.
Abstract 17416: Epigenetic Regulation of Fibroblast Fate Transition in Cardiac Wound Healing
Authors: Ngefor Asangwe, Lindsay Kraus, Thomas Knight, Hajime Kubo, Mohsin Khan, Sadia Mohsin
Journal: Circulation (2023)

Background: Fibroblast transitioning between physiological and pathological states can define cardiac wound healing ability of the heart in response to stress. Preventing fibroblast activation and differentiation into myofibroblast formation can attenuate cardiac fibrosis and adverse cardiac remodeling. Changes in chromatin structure and accessibility are one of the essential drivers of gene expression/repression involved in myocardial injury. One such driver of chromatin remodeling is the group of polycomb proteins that alter expression of genes involved in cardiac wound healing including B cell specific Moloney murine leukemia virus integration site 1 (Bmi1), a component of the polycomb repressive complex 1 (PRC1). Bmi1 have been linked to self-renewal, proliferation, quiescence, and lineage commitment in many organs however, how Bmi1 can mediate fibroblasts states and mediate wound healing after cardiac injury is not understood. Hypothesis: Bmi1 mediates myofibroblast activation and transition, scar maturation, stability, and fibrotic responses by regulating histone marks after injury. Methods and Results: To establish the role of Bmi1 in cardiac wound healing, we developed an inducible knock out mouse model for Bmi1, which showed decrease in cardiac structure and function with maladaptive remodeling following myocardial injury. Bmi1 knockout (KO) mice showed significant decrease in ejection fraction and fractional shortening measured by echocardiography after cardiac injury. Concurrently, this significant decrease in heart function was associated with increased fibrosis and DNA damage analyzed using immunohistochemistry. Additionally, we found that the adult cardiac fibroblasts, isolated from the Bmi1 KO mice have increased expression of fibrotic genes including TGFβ, Acta2, and collagen using RTPCR analysis. Using single cell sequencing RNA and ATAC sequencing and cellular staining assays, we found significant changes in fibrotic signaling pathways of TGFβ. We found SMAD3 chromatin accessibility was increased with the loss of Bmi1 with the decrease in H2AK119Ub. Conclusion: Bmi1 mediates wound healing ability by regulating cardiac fibroblast transition after cardiac injury.
Abstract 15321: Association Between Cardiovascular Risk Factors, Social Determinants of Health and Cardio-Ankle Vascular Index (CAVI) Scores Among African-American Adults: The FAITH! Heart Health+ (HH+) Study
Authors: Victoria E Thomas, Iftikhar J Kullo, Mathias Lalika, Carrie R McCoy, Matthew P Johnson, Sharonne N Hayes, Clarence Jones, Lisa A Cooper, Christi A Patten, LaPrincess C Brewer
Journal: Circulation (2023)

Background Cardio-ankle vascular index (CAVI) is a measure of arterial stiffness associated with cardiovascular (CV) events and mortality. African American (AA) adults have a higher prevalence of CV risk factors (RFs) and adverse social determinants of health (SDOH) leading to a higher CV mortality risk than White adults. These disparities may be associated with arterial stiffness, however limited research exists on the association of CV RFs, SDOH, and CAVI among AAs. Hypotheses We hypothesized that CV RFs (eg, diabetes) and SDOH (eg, income) would be associated with CAVI among AA adults. Our secondary hypothesis was that AA adults would have a higher prevalence of abnormal CAVI scores (≥8.0) than White adults. Methods In the FAITH! HH+ study, CAVI measurements, CV RFs, and SDOH surveys were obtained. We collected CAVI readings and CV RFs from a secondary cohort of White adults (n=600), referred for echocardiography and without structural cardiac disease. The association of CV RFs, SDOH and CAVI scores among AAs was assessed via ANOVA and univariable linear regression. We compared CV RFs among both cohorts using Chi-squared tests and ANOVA, followed by comparing CAVI scores between cohorts using a multivariable linear regression model. Results In total, 48 AAs were included from the FAITH! HH+ cohort (mean age [SD]: 54.2 [11.5] years, 67.4% women). There was no significant association between CV RFs or SDOH with CAVI scores. In the 600 White adults assessed, mean age was 59.5 [14.7] years and 45.7% were women. Compared to White adults, AA participants had a lower burden of hyperlipidemia (43.5% vs 61.4%; p=0.017), but a higher burden of hypertension (73.9% vs 57.7%; p=0.031), diabetes (28.3% vs 9.3%; p&lt;0.001), and obesity (71.7% obese vs 36.0%; p&lt;0.001). There was no significant difference in CAVI scores between groups when adjusted for age, sex, and CV RFs (AA cohort: mean: 8.0 [1.4] vs White cohort: 8.4 [1.5]; p=0.790). Conclusions In this pilot study, SDOH and CV RFs were not associated with CAVI scores among AAs. There was no significant difference in CAVI scores between AA and White adults, despite a significantly higher burden of CV RFs in the AA cohort. Further studies are warranted to identify factors linked with onset and progression of arterial stiffness among AAs.