tbuckley/cabot-search huggingface dataset:
Abstract 17938: Identifying the Prevalence of Coronary Artery Disease Among Patients With Non-Alcoholic Fatty Liver Disease in the Adult US Population
Authors: Yelena Pleshkova, Alexia Sawyer, Chad Brands, Urvish Patel, Nishad Barve, Anusha Kavarthapu, Darshi Desai, Aditya Desai, Parth Shah, chandu siripuram, Deep Mehta, Mohammad Parvez
Journal: Circulation (2023)

Introduction/Background: In the twenty-first century, new findings have helped unravel the outstanding significance of contributory roles of the different pathologies in the proper regulation of physiologic and metabolic homeostasis. NAFLD is presently considered one of the emerging gastroenterological pathologies in the world. In our research study, we describe the contributory potential of NAFLD to cardiovascular disease. We also examined the patterns of NAFLD and identified specific emerging subgroups to improve our understanding of intertwined mechanisms between NAFLD and the pathogenesis of systemic atherosclerotic diseases. Aims and Objective: The primary outcome of the study was to identify the prevalence of NAFLD. The secondary outcome was to evaluate the prevalence of CAD in people with NAFLD and to describe the association between these two processes. Methods: We performed a retrospective cross-sectional study using the National Health and Nutrition Examination Survey (NHANES) database from 2015 to 2018. Adults with a secondary diagnosis of NAFLD were identified. Univariate analysis was performed using Mann Whitney U test and chi-square test. A multivariable logistic regression analysis was performed to describe the association between NAFLD and CAD. Results: Among a total of 275,968 people in this selected NHANES cohort, 0.26 were identified to have NAFLD. In the cohort, NAFLD was more prevalent in older (median: 62 years), males, Mexican Americans and Hispanics, and people with median household income &gt;$100,000. People with NAFLD had an early onset of CAD (47 vs 60 years) with higher prevalence of CAD in NAFLD compared to the group without NAFLD (15.90% vs 4.64%). People with NAFLD had a significantly higher association of having CAD (prevalence odds: 9.78 [95% CI: 9.76-9.80]). Conclusion: In a select NHANES cohort, positive correlations were identified between groups with NAFLD and the early onset of CAD. Additional findings include positive correlations for ethnicity, social economic status, and gender. Prospective studies and long-term clinical follow-up will be required to further characterize specific populations with NAFLD in an attempt to mitigate the burden of CAD within the population of NAFLD patients.
Abstract 13300: Recovery From Acute Cardiac Events in Lower-Socioeconomic Status Patients: Physical and Psychological Outcomes Over Time
Authors: Diann Gaalema, Sherrie Khadanga, Patrick Savage, Brian Katz, William Middleton, Stephen Higgins, Philip Ades
Journal: Circulation (2023)

Introduction: Participation in cardiac rehabilitation (CR) reduces morbidity, and mortality, while improving quality of life following major cardiovascular events. Patients with lower-socioeconomic status (SES), such as those enrolled in Medicaid, are much less likely to attend and complete CR, despite being at increased risk for recurrent cardiovascular events. Methods: A secondary analysis was performed on a randomized controlled trial in which 130 individuals enrolled in Medicaid, with a CR-qualifying cardiac event, were randomized 1:1 to receive financial incentives for completing CR sessions or to usual care. Participants were assessed on clinical and cognitive outcomes soon after discharge as well as at 4 months, and 1 year following entry. The current analyses focused on how outcomes changed over the three timepoints. Outcomes included changes in psychological measurements (depressive/anxious symptoms, quality of life), body composition (waist circumference, body mass index), and fitness (peak VO2/METS). Mixed model repeated measures analyses of variance were used to test for main effects while controlling for sex, smoking status, age, and qualifying diagnosis. Results: Lower-SES patients entering CR had remarkably low levels of fitness and high rates of psychological issues. Fitness improved between intake and 4-months, and gains were maintained through one year (p&lt;0.001) (Table 1) however gains were less in females and those who completed fewer sessions of CR. Body composition measurements significantly worsened between 4-months and 1-year (p&lt;0.03). Psychological measures did not improve in the year following the event. Conclusion: While fitness improved in lower-SES patients, especially among those who completed more sessions of CR, psychological symptoms were elevated and did not improve. Future research should seek to understand how we can better serve this population, especially in the area of psych symptoms.
Abstract 18110: Assessing the Impact of a Multidisciplinary Cardio-Kidney Care Team on the Overall Care Satisfaction in Patients With Heart Failure With Reduced Ejection Fraction And Chronic Kidney Disease
Authors: Shaitalya Vellanki, Priscilla Muhanji, Hina Patel, Elizabeth Evans, Sowmya Swamy, Maximillian Lee, Max Egers, Jeffery Turley, Ashley Govi, Jessica Huang, Eison De Guzman, Kevin Lo, Gurusher S Panjrath, Janani Rangaswami
Journal: Circulation (2023)

Background: Patients with heart failure with reduced ejection fraction (HFrEF) and chronic kidney disease (CKD) experience fragmented care in the usual referral-based model given poor care coordination between subspecialists and primary care clinicians (PCCs). Multidisciplinary specialty care teams can improve care coordination, increase use of guideline-directed medical therapies (GDMT), and potentially increase patient satisfaction. Methods: We conducted a randomized controlled trial in a single-center tertiary care institution, enrolling patients with both HFrEF (ejection fraction &lt;50%) and CKD (stages 2-5, not on hemodialysis) over 6 months. The patients’ PCCs were randomized to either the control arm in which usual care was continued, or to the treatment arm where PCCs were supported by a virtually organized cardio-kidney team with a heart failure specialist and nephrologist. Treatment arm PCCs received recommendations from the cardio-kidney team via electronic medical record secure messaging sharing guidance on GDMT use, necessary lab tests, etc. Patients’ quality of life and symptoms were assessed at both baseline and 3 months via the Kidney Disease Quality of Life (KDQoL) survey and Kansas City Cardiomyopathy Questionnaire (KCCQ), respectively. Results: 95 patients had 3 month follow-up data (treatment n=47, control=48). The mean patient age was 67.4±10.8, and 61% were male. The majority (76%) were African American with mean EF of 35.5 ±11.0. The treatment group had higher reported and clinically significant (&gt;at least a 5-point change) improvement of KCCQ scores from baseline to 3 months (52%) compared to the control group (38%), however, this was not statistically significantly different (p=0.15). Meanwhile, the proportion of deterioration was 39% and 40% in the treatment and control groups, respectively. There were no significant differences in KDQOL scores between or within both groups when comparing the baseline to 3 month data. Conclusion: Implementing a multidisciplinary care team to support PCCs is a feasible intervention and at 3 months, there was an increase (although statistically insignificant) in KCCQ scores. A longer duration of follow-up may be better able to assess the effects of multidisciplinary care team models.
Abstract 13694: Impact of an Interdisciplinary Heart Failure Clinic on Achieving Guideline-Directed Medical Therapy in the Community
Authors: Jessica Bregier, Jessica Cheuvront, Rowan Spence, Rebekah Krupski, Virginia Yoder, Mary Ellen Pisano, Maryann Choy-Ames, Gordon R Reeves
Journal: Circulation (2023)

Background: Guideline-directed medical therapy (GDMT) for patients with heart failure with reduced ejection fraction (HFrEF) is underutilized despite proven benefits. Strategies to implement GDMT are needed, especially in the era of sodium-glucose cotransporter-2 inhibitors (SGLT2is). Research Question: What is the impact of embedded interdisciplinary heart failure (HF) clinics on HFrEF GDMT prescribing within community cardiology practices? Goal: Compare GDMT prescribing for HFrEF patients followed in community cardiology practices with or without the added support of embedded interdisciplinary HF clinics. Methods: This retrospective chart review of four community-based cardiology practices in North Carolina identified 2,121 patients ≥ 18 years old with a diagnosis of HFrEF (EF ≤ 40%) who had encounters from January 1 to December 31, 2022. Patients were categorized based on whether their encounters included an HF clinic provider. Patients seen in HF clinic also had access to embedded clinical pharmacists and centralized social work support. Chi square test of independence was used to assess differences between groups. Results: Significantly more patients who attended HF clinic (n=1050) compared to those receiving usual care alone (n=1071) were female (36% vs 30%, p&lt;0.01), African American (39% vs 30%, p&lt;0.01), and had systolic BP &lt; 100 mmHg (12% vs 7%, p&lt;0.01). Mean age (67.8 ± 2.4 years), rates of potassium &gt; 5 mEq/L (10%), and rates of GFR &lt; 30 mL/min/1.73m 2 (12%) were similar between groups. HF clinic patients had significantly higher rates of angiotensin receptor/neprilysin inhibitors (ARNis) (72% vs 46%, p&lt;0.01), ACEi/ARB/ARNis combined (86% vs 77%, p&lt;0.01), SGLT2is (61% vs 20%, p&lt;0.01), and mineralocorticoid receptor antagonists (45% vs 32%, p&lt;0.01) prescribed compared to usual care alone. HF beta blocker prescribing was similar between groups (88% vs 89%, p=NS). Conclusion: Patients receiving care in interdisciplinary HF clinics within community cardiology practices had significantly higher rates of HFrEF GDMT prescribing for 3 of the 4 drug classes. Specialized HF clinics can provide patients additional support and resources to achieve GDMT.
Abstract 15827: Impact of Harvesting Techniques on Coronary Bypass Conduit Endothelial Cells and Collagen Exposure Using Ligand-Based Targeting
Authors: Nataliya Bahatyrevich, Lalithasri Ramasubramanian, Dake Hao, Emma Loll, Juan-Maria G Lopez, Mimmie Kwong, Curtis J Wozniak, Sabrina A Evans, JORGE CATRIP, Bob Kiaii, Aijun Wang
Journal: Circulation (2023)

Background: Coronary bypass is a mainstay therapy for coronary artery disease (CAD). Conduit options include the internal thoracic artery (ITA), radial artery (RA), and great saphenous vein (GSV). Long-term patency rates are &gt;95% (ITA), 75% (RA), and 50% (GSV) at 10 years. The impact of harvesting techniques on endothelial cells is not well understood. Hypothesis: We hypothesized that observed differences in patency rates could potentially be explained by differences in endothelial cell response to a harvesting technique. Aims: 1) Determine degree of endothelial cell damage between different conduits and various harvesting techniques. 2) Assess ability of a specific collagen binding peptide SILY to bind to exposed collagen in GSV. Methods: De-identified human graft samples of ITA, RA, and GSV were collected and analyzed from September 2021 through February 2023. The harvesting techniques were open for ITA and GSV, endoscopic for RA, and endoscopic for GSV. The samples were fixed and stained with anti-CD31 antibody to identify endothelial cells on the luminal surface with enface imaging. Binding of SILY peptide to GSV was tested at different concentrations and incubation times. Results: 51 specimens were obtained, 18 open ITA, 10 open GSV, 18 endoscopic GSV, and 5 endoscopic RA. Luminal surface covered by endothelial cells was 86.6±8.1% for ITA, 76.7±14.7% for RA, 58.3±14.0% for endoscopic GSV, and 59.0±5.5% for open GSV. Endothelial coverage area on ITA samples was significantly higher compared to endoscopic GSV, open GSV, and RA (p&lt;0.05). Endothelial coverage area on RA samples was significantly higher compared to endoscopic GSV and open GSV (p&lt;0.05). There was no statistically significant difference in endothelial coverage area between open and endoscopic GSV (p=0.43). Testing of SILY binding revealed colocalization with collagen fibers on luminal surface of GSV samples. Conclusions: Microscopic examination showed greatest preservation of endothelial cells on ITA followed by RA and GSV with no difference between open and endoscopic GSV. Targeting of exposed collagen with SILY in the areas of damaged endothelium might be a good approach for therapeutics in the future.
Abstract 15669: Proteomic Associations With Late-Life Cardiac Structure and Function: The Atherosclerosis Risk in Communities Study
Authors: Yimin Yang, Victoria Lamberson, Brian Claggett, Adrienne Tin, Ron C Hoogeveen, Kuni Matsushita, Christie M Ballantyne, Josef Coresh, Bing Yu, Amil M Shah
Journal: Circulation (2023)

Introduction: Alterations in cardiac structure and function underlie heart failure (HF). Identification of novel markers of cardiac function may provide insights into HF pathophysiology. Methods: Among 4253 participants in ARIC who were free of HF and atrial fibrillation at study Visit 5 (2011-13) and had aptamer-based proteomics (SomaScan v4), we used exploratory factor analysis to reduce 21 echocardiographic measures (2D, spectral and tissue Doppler, strain) to 5 factors. We assessed the association of 4955 plasma proteins with each factor using multivariable linear regression. Hierarchical clustering grouped proteins associated with ≥1 factor by their pattern of association with the factors. Association of protein levels with incident HF post-Visit 5 was assessed using multivariable Cox models. Two-sample Mendelian randomization (MR) was performed to evaluate potential causal effects of proteins on HF and left/right ventricular (LV/RV) size &amp; function. Results: Mean age was 75±5 years, 41% were male, 17% reported Black race. We identified 5 factors representing: cardiac structure, LV myocardial motion, LV chamber level contractility, LV filling pressure, and RV myocardial motion. 409 proteins were significantly associated with ≥1 factor, 101 of which were significantly associated with HF. Hierarchical clustering grouped proteins into 6 clusters (Figure). The 54 proteins in Cluster 5 demonstrated consistent associations across all factors and were enriched for proteins associated with HF. MR identified 7 proteins, including CHST15 - a sulfotransferase involved in proinflammatory cytokine biosynthesis - which demonstrated potential causal effects on HF and on LV/RV volume. Conclusion: We uncovered a subset of plasma proteins associated with multiple dimensions of cardiac structure and function and with HF risk. A subset, including CHST15, had potential causal effects on cardiac structure/function and HF and warrant further investigation.
Abstract 11679: The Crucial Role of Estrogen-Related Receptor in Human Cardiomyocyte Maturation
Authors: Tomoya Sakamoto, Kirill Batmanov, Daniel P Kelly
Journal: Circulation (2023)

During the developmental transition from fetal to adult, the heart undergoes dramatic mitochondrial and sarcomeric maturation. This process is partially reversed during development of heart failure. We have identified the nuclear receptors, estrogen-related receptor (ERR) α and γ, as critical transcriptional regulators of energy metabolic and sarcomeric genes during postnatal maturation of mouse heart. Here, we aimed to define the transcriptional mechanisms involved in ERR-mediated maturation in human cardiomyocytes. Genomic interrogation with published datasets revealed that approximately 50% of super-enhancer regions (SEs) overlapped with ERRγ peaks in human-induced pluripotent stem cell-derived cardiac myocytes. Intersection of the ERRγ cistrome with a published H3K27ac Hi-ChIP dataset from human hearts identified over 3,000 ERR-containing enhancer-promoter loops, which are associated with genes related to cardiac contractile function. These results highlighted the essential role of ERR in cardiomyocyte enhancer function. Among the SEs defined by mediator complex deposition, we found that both ERRα and γ occupied the enhancer region flanking the MYH6/MYH7 cluster, a well-characterized locus for fetal to adult developmental switching. Targeting ERR recruitment on the enhancer using catalytically-dead Cas9-KRAB or proteolysis targeting chimeric (PROTAC) strategies resulted in the reversal of MYH6/7 switching. RNA-sequencing analysis following PROTAC treatment revealed that deactivation of ERRα resulted in downregulation of a wide array of genes encoding cardiac structural proteins, particularly adult-type ventricular sarcomeric proteins. Additional cistrome analyses demonstrated that PROTAC treatment resulted in decreased ERRα peak signals on cardiac structural genes, including enhancer regions directing MYH6/7 transcription consistent with the observed gene expression changes. In summary, ERR signaling is essential for the transcriptional program of structural maturation in human cardiomyocytes. This process likely involves establishing proper cardiac chromatin architecture. These results support a novel therapeutic strategy of utilizing ERR activators to reverse fetal shifts in failing hearts.
Abstract 15117: Estimating Ejection Fraction From the 12 Lead Electrocardiogram in Acute Heart Failure
Authors: sunita pokhrel bhattarai, Mary G Carey, Dillon J Dzikowicz, Sudhir Kumar K Mummidi, Mehmed Aktas
Journal: Circulation (2023)

Introduction: The 2022 AHA Guidelines for the Management of Heart Failure (HF) emphasized initiating guideline-directed medical therapy (GDMT) as early as possible during acute hospitalization. GDMT significantly differs between HF patients with reduced and preserved ejection fraction (EF). The electrocardiogram (ECG) is one of the first tests performed to assess cardiac function among HF patients. Purpose: To develop a linear model to estimate EF using the ECG and clinical covariates. Methods: Medical record data from 2020-21 of HF patients &gt; 18 years and positive Framingham Heart Failure Diagnostic Criteria excluding those with ventricular assist devices were extracted. Demographics, NYHA class, EF, and comorbidities, 12-lead ECG closest to the time of the echocardiogram were analyzed. We extracted 312 different features from the ECG using the Philips DXL Algorithm. Recursive LASSO regression was used to identify a subset of features in domain blocks. All analyses were completed in RStudio (4.3.0). Results: Among 126 patients (age 69.4 + 15.5 years; BMI 31.2 + 8.2 kg/m 2 ; EF 40 + 19%; the time between ECG-echocardiogram 13.30 + 40.67 hours: minutes), the predominant cardiac rhythm (70%, n=88) was sinus. Among the 312 ECG features, 39 (13%) were significant; the final linear model included 9 (3%) features: S Duration V1, QRS Duration III, Horizontal T Angle, Mean Heart Rate, Q Duration aVL, Maximum QRS Angle, R Duration V3, S Amplitude V3, and P amplitude V3. The final linear model achieved an R 2 =0.498 and adjusted R 2 =0.459. We adjusted the model for age, body mass index, and sex, and model performance improved by R 2 =0.107 adjusted R 2 =0.104. The addition of time between ECG-echocardiogram to the model did not significantly change performance. From the predicted values, 50% (n=63) were within the margin of error, and the correlation between predicted and true values was moderate (r=0.629 [95%CI, 0.510-0.724]). The mean difference between predicted and true EF values varied between + 12.06%. Conclusions: Our initial results demonstrate the ability to estimate EF using a 12-lead ECG. While the results are limited due to the small sample size and significant time between ECG and echocardiogram, these preliminary results support the feasibility of future research.
Abstract 16180: The Adherence and LDL-C Lowering Effect of Inclisiran Among Patients Who Received Treatment at Outpatient Clinics
Authors: Nihar R Desai, Nicholas Van Hise, Charlene Niu, Elizabeth Ghera, Sean McElligott
Journal: Circulation (2023)

Introduction: Inclisiran is a novel small interfering RNA (siRNA) indicated as an adjunct to diet and maximally tolerated statin to lower LDL-C among adults with clinical atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) in the US. It is administered subcutaneously initially, again at 3 months, and then every six months by an HCP. Subsequent doses may be administered within three months after the scheduled dose without restarting a new dose schedule. Metro Infusion Center (MIC) is one of the largest infusion centers across the US with over 200 centers in 38 states and has clinician oversight over each administration. Hypothesis: To describe the real-world adherence to inclisiran and changes in low-density lipoprotein cholesterol (LDL-C) levels associated with inclisiran use at MICs. Methods: Patient charts for those who initiated inclisiran from March 1, 2022 to November 31, 2022 were reviewed retrospectively. Demographics and clinical characteristics at initiation were collected and patients were followed until May 2023 for the current analysis. The study outcomes included the proportion of eligible patients who received the 2 nd or 3 rd dose and the percent change in LDL-C levels from baseline to the latest available data. Results: A total of 562 patients were included in the analysis from 107 different MICs in over 21 states. Mean (SD) age was 70.6 (9.6) years; 51% were female. The majority of patients (80%) were covered by Medicare. 492 (88%) had a history of ASCVD and 60 (11%) had HeFH. Mean (SD) baseline LDL-C was 147.6 (59.9) mg/dl. Of the 562 patients initiated inclisiran, 531 (95%) received their 2 nd dose, and 91% received the 2 nd dose within ±7 days of the schedule. There were 233 patients eligible to receive a 3 rd dose, 196 (84%) of them had received the 3 rd dose. Among 274 patients who had the LDL-C measured after inclisiran initiation, the average LDL-C reduction from baseline was 46.3%. On average, the first LDL-C measurement was taken at 3 months after receiving at least one dose of Inclisiran. Conclusions: These real-world data demonstrate high adherence to inclisiran with LDL-C reductions of 46.3% at 3 months. This finding was consistent with the ORION clinical development program.