tbuckley/cabot-search huggingface dataset:
Abstract 18522: Pyridoxamine (vitamin B6) Mitigation Of Structural Valve Degeneration Of Bioprosthetic Heart Valves
Authors: Andrey Zakharchenko, Tina Thomas, Emily Hall, Michael Chorny, Giovanni Ferrari, Robert Levy
Journal: Circulation (2023)

Introduction: Bioprosthetic heart valves (BHV) fabricated from glutaraldehyde treated bovine pericardium (BP) have limited durability due to structural valve degeneration (SVD) resulting from both calcification and advanced glycation end product (AGE) deposition. Hypothesis: We investigated the hypothesis that PYR modification of BHV leaflets mitigates AGE-serum protein uptake, oxidation, and calcification mechanisms in model studies, both in vitro and in vivo. Methods: To model AGE accumulation in BHV, we used well-established in vitro and in vivo models. AGE and serum albumin (SA) uptake in BP were quantitated per immunohistochemistry (IHC) staining intensity. PYR uptake was quantified using a novel fluorescent assay. BP collagen was examined by second-harmonic generation (SHG) microscopy. Calcification studies investigated the activity of BP alkaline phosphatase (ALP), and BP calcium levels were quantitated using a colorimetric assay. In vivo studies used a juvenile rat subdermal BP implantation model with PYR oral administration or BP-PYR modification. Endpoints were calcification, SA, and AGE accumulation per IHC and ALP activity per enzyme histochemistry. Results: PYR modification of BP resulted in high-affinity binding of PYR with 2.0±0.2 μg/mg of PYR binding to BP that was stable for 28 days in physiological conditions. Modification had an inhibitory effect on SA uptake in vitro with 60±5% (p&lt;0.001) reduction in IHC staining intensity; PYR modification of BP resulted in increased protection from oxidative damage in vitro with collagen structure preservation (by SHG) after ten days, while control tissues were degraded. After 28-day of in vivo subdermal BP implantation in rats, a significant 70±5% (p&lt;0.001) decrease and 80±5% (p&lt;0.001) decrease in SA IHC staining and AGE staining, respectively, as well as ALP activity was documented in BP-PYR. Quantitative analysis of calcium content demonstrated a reduction from 108±5 μg/mg in control to 77±5 μg/mg in BP-PYR explants (p&lt;0.001). Conclusions: Our study demonstrated that PYR mitigates SVD mechanisms in vitro and in vivo, limiting both AGE-serum protein accumulation and calcification with associated inhibition of ALP.
Abstract 11996: National Survey of Coronary Artery Bypass Grafting in Adult Patients With Coronary Artery Lesions Caused by Kawasaki Disease in Japan
Authors: Etsuko Tsuda, Tetsuya Kitagawa, Yoshihide Mitani, Hiraku Kumamaru, Noboru Motomura
Journal: Circulation (2023)

About 50 years have passed since the first report of Kawasaki disease (KD), and adult patients with coronary artery lesions caused by KD have increased. The national results of coronary artery bypass grafting (CABG) in adult KD patients who had undergone CABG between 2008 and 2019 in the National Clinical Database of Japan were investigated. A total of 343 patients were identified. Furthermore, the outcomes of the 167 patients (49%) after discharge were surveyed by questionnaires. There were 264 male (77%) and 79 female (23%) patients. The median age at operation was 39 (5 th -95 th percentile, 13-72 years). The numbers of emergent operations was 37 (10%). Previous CABG and previous percutaneous coronary intervention were performed in 16 (5%) and 50 (15%) patients, respectively. Acute myocardial infarction was found in 64 patients (19%), and cardiogenic shock was found in 10 patients (3%). The mean numbers of grafts and anastomosed vessels were 2 each. The grafts used were as follows. internal thoracic artery 316; saphenous vein grafts 118; gastroepiploic artery 52, and radial artery 56. The anastomosed vessels were as follows. left anterior descending artery 305, right coronary artery 209, left circumflex 145, and diagonal branch 73. Mitral valve surgery and aortic valve surgery were performed in 10 and 9 patients, respectively. The coronary risk factors were as follows: Previous smoking 124 (36%), dyslipidemia 126 (37%); hypertension 124 (36%); and diabetes mellitus 35 (10%). Antiplatelet agents after CABG were administered after CABG to all patients, and coumadin was given to 133 patients (39%). Statins and beta-blockers were given to 143 (42%) and 198 patients (58%), respectively. Three patients (0.8%) died in hospital, and 7 patients died in the late period. Survival rates after CABG at 1, 5 and 10 years were 98%, 94% and 93%, respectively (n= 343). Survival rates at 5 years depending on the values of the preoperative left ventricular ejection (LVEF) were as follows. bad (&lt;30%, n=24), 72%, medium (≧30% but &lt; 60%, n=140), 93% good (≧60%, n=189), 97%. There were significant differences among the 3 groups (p&lt;0.01). The preoperative LVEF affected on the outcome after CABG.
Abstract 17744: Intracranial Atherosclerosis Disease (ICAD) and Risk of Cognitive Impairment and Dementia: Systematic Review and Meta-Analysis
Authors: Behnam Sabayan, Roham Goudarzi, Afshin Borhani-Haghighi, Yuekai Ji, Barbara Olson-Bullis, Sanaz Sedaghat
Journal: Circulation (2023)

Introduction: Intracranial atherosclerosis disease (ICAD) alters cerebrovascular hemodynamics and is linked with brain structural changes and atrophy. Various studies evaluated the relationship between ICAD and risk of cognitive impairment with mixed results. This study aims to systematically review the current evidence and compile data on the association between ICAD and cognitive impairment and dementia. Methods: PubMed, EMBASE, PsycInfo and Web of Science were searched from January 1-2000, to March 1-2023, without language restriction. Cross-sectional and prospective cohort studies as well as post-mortem studies were included. Studies containing data on the link between ICAD and cognitive impairment and dementia were screened by two independent reviewers for inclusion in a systematic review and meta-analysis. From each study, data on the association between ICAD (at least 50% stenosis in one intracranial vessel) and cognitive impairment and dementia were extracted. Results: A total of 22 (17 observational and 5 post-mortem) unique studies comprising 11,184 individuals (average age range: 59.8 to 87.6 years, 45.7% female, 36.5% Asian) were included in the systematic review. Seven out of 10 cross-sectional studies and 5 out of 7 prospective studies showed a significantly higher risk of cognitive impairment and dementia in association with ICAD.Population-based studies and studies with patients with baseline cognitive impairment or dementia (consist of study participants from Asian, Europe and North America) consistently showed a significant association between ICAD and risk of cognitive decline. In the pooled analysis, ICAD was associated with 1.87-fold (95% confidence interval 1.49-2.35) increased risk of cognitive impairment. Meta-regression analysis did not show a significant impact of age, sex and ethnicity on the findings. All post mortem studies have shown that patients with Alzheimer’s disease and vascular dementia had a higher burden of ICAD as compared to cognitively normal controls. Conclusions: ICAD is associated with a higher risk of cognitive impairment and dementia in various age, sex and ethnic groups. Our findings underscore the importance of intracranial vascular health in brain health and prevention of dementia.
Abstract 17079: Relationship Between Neighborhood Level Deprivation and Cardiovascular Health Status Among 122,177 Adolescents, Analysis of PEDSnet Data
Authors: Carissa M Baker-Smith, Zugui Zhang, Daniel Eckrich, Carol Prospero, Varsha Zadokar, Bonita E Falkner, Robert E Akins
Journal: Circulation (2023)

Introduction: Preservation of cardiovascular health (CVH) across the lifespan is essential to reducing cardiovascular disease burden. Greater knowledge of the relationship between neighborhood level deprivation and CVH in youth is needed. Hypothesis: We hypothesized that worse socio/environmental deprivation is associated with poor/intermediate CVH status in adolescents. Methods: Data from 2009-2019 were extracted from PEDSnet (a PCORI-funded network of pediatric health data). We modeled the relationship between CVH and neighborhood deprivation. National Area Deprivation Index values (ADI; scaled 1-100) were coded into PEDSnet and divided into tertiles (ADI&lt;25=best, 25-52, &gt; 52=worst) for analysis. CVH status was scored from a subset of available AHA Life’s Essential 8 (LE8) scores including blood pressure, blood glucose, blood cholesterol, body mass index, smoking/tobacco exposure, and sleep. Overall CVH scores were derived as the average of the sum of the individual scores. Univariate and multivariate analyses were performed. SAS 9.4 was used ( p&lt;0.05) . Results: Data from 122,177 youth, 13-17 years old were analyzed. 51% were female, 24% lived in neighborhoods with ADI &lt;25; 35% lived in neighborhoods with ADI &gt; 52. 58% were non-Hispanic white and 22% non-Hispanic Black. According to a multivariate logistic model, ADI &gt; 52 was associated with a 48% greater odds of poor/intermediate CVH status compared to ADI &lt;25 (Figure). Female sex, ethnic-race categories of Non-Hispanic White and Other, as well private or other forms of non-public insurance coverage were associated with a lower odds of intermediate/poor CVH (Table). Interaction terms for age, ADI, race and ethnicity were not significant. Conclusions: Higher neighborhood deprivation is associated with poor/intermediate CVH status. We recommend greater attention to preserving CVH status within high deprivation communities to preserve and promote CVH status across the lifespan.
Abstract 17304: Assessing the Nonmedical Needs of Hospitalized Heart Failure Patients: A Qualitative Study
Authors: Sriram Palepu, Sarita Damaraju, Alexandra Rizaldi, Audrey Kellogg, Mehtaab Rakkar, Lauren A Eberly
Journal: Circulation (2023)

Introduction: Heart failure (HF) patients experience unexpected hospitalizations, which can cause significant stress. The purpose of this qualitative study was to better characterize the nonmedical stressors during extended hospitalizations for HF patients. Objective: This aim of this survey study was to explore the unmet nonmedical needs of patients with HF admitted for an extended stay, focusing on identifying interventions that may enhance patient care and quality of life outside the hospital. Methods: A survey was conducted among n=25 HF patients admitted for &gt;5 days to the HF unit at a single institution. We assessed patients’ care gaps at home (e.g. caretakers, food, cleaning, pet care, mental health) and barriers to accessing those gaps. We determined the magnitude of potential impact (MPI) of a category by multiplying the number of people who rated it as stressful and the average level of stress it caused. Results: Of the 25 patients, 9 (36%) were female, 13 (52%) were white, and average age was 62.4 ± 13.3 years. Home accessibility (28%), housekeeping (24%), support groups (20%) and HF education (20%) were the most common unmet needs. Housekeeping had the highest MPI, with financial barriers and lack of information as the most frequently reported challenges. Housekeeping, home accessibility (e.g. stair lifts, ramps, rails), support groups, and finding a caretaker were issues identified as having the biggest impact on patient quality of life. Conclusion: This study is the first, to our knowledge, to characterize the unmet nonmedical needs of HF patients with extended hospitalizations and highlights possible interventions that may decrease stress and improve quality of life for these patients. The survey results indicate improving access to housekeeping, caretaking, home accessibility, and support groups may reduce patient stress during HF hospitalization. Further research is warranted to explore which interventions are feasible and cost effective.
Abstract 17326: Urine Exosomes Proteomics for Parenchymal Kidney Health in Heart Failure Patients With Mechanical Circulatory Support
Authors: Nandan K Mondal, Shiyi Li, Katherine V Nordick, Ivan Murrieta-Alvarez, Camila Hochman-Mendez, Alexis E Shafii, Kenneth K Liao, Carl P Walther
Journal: Circulation (2023)

Introduction: Kidney dysfunction frequently affects heart failure (HF) patients with left ventricular assist device (LVAD) support and is linked to unfavorable outcomes. However, the effects of LVAD support on parenchymal kidney health are uncertain. We performed a pilot study on urine exosome proteomics in LVAD recipients as they offer a non-invasive glimpse into kidney cellular states. Methods: We collected urine samples from 33 patients who underwent LVAD (HeartMate III) surgery between 01/2022-02/2023. Urine exosomes were isolated from the samples collected before the operation and on the 7th day after surgery. The exosome fraction underwent untargeted proteomics using LC-MS/MS and iBAQ quantification. Our investigation focused on identifying and studying kidney-enhanced proteins. Results: The exosomes isolated were verified by canonical exosome proteins (CD63, Hsp70) and TEM imaging (Fig.A,B), with 82.7% of exosomes between 51-120 nm (Fig.C). Over 7K strict genes were identified with an average of 1,150 proteins (Fig.D,E). In GO analysis, exosomes were the primary cellular compartment represented (Fig.F). A total of 176 kidney-enhanced proteins were present in &gt;50% of samples. Differential expression analysis revealed 8 proteins with increased expression on the 7 th day after surgery with FDR&lt;0.1(Fig.G). The 2 top proteins were glutathione peroxidase 3 (GPX3, log2 FC 3.4 [95%CI 2.1-4.8]), and fatty acid binding protein 3 (FABP3, log2 FC 2.9 [95%CI 1.7-4.2]). Enrichment analysis (Fig.H) demonstrated pathway changes consistent with inflammatory and ischemic kidney damage, metabolic dysfunction, and fibrotic transformation, consistent with kidney stress from advanced HF and cardiac surgery. Conclusions: We have demonstrated the feasibility of urine exosomes for non-invasive parenchymal kidney health assessment in LVAD patients. Further investigation in a larger cohort with additional sampling points may be warranted.
Abstract 17062: Disparities in Cardiovascular Mortality Among Disaggregated Asian Groups: Results From the 1999-2018 National Health Interview Survey
Authors: Adrian M Bacong, Frederick B Rivera, Lia Veronique Priela
Journal: Circulation (2023)

Background: Asian people generally have lower cardiovascular (CVD) morbidity and mortality relative to other race and ethnic groups. However, few studies have examined differences in CVD mortality among disaggregated Asian groups. Additionally, mortality data often lack comprehensive information on social and socioeconomic factors which could contribute to differences in mortality by race. Methods: Using the 1999-2018 National Health Interview Survey linked to the National Death Index, we examined cardiovascular (CVD) mortality among Asian Indian (N=4,660), Chinese (N=4,823), Filipino (N=4,835), and Other Asian (e.g., Korean, Japanese, Vietnamese, N=8,472) and Non-Hispanic White adults (N=312,850). We examined 5 nested multivariable Poisson regression models comparing CVD mortality of disaggregated Asian groups accounting for demographic, social, and socioeconomic factors, and body mass index (BMI). Results: There were vast differences in CVD mortality by 2018 follow up and participant characteristics by race and ethnicity. CVD mortality was lower among each disaggregated Asian ethnic group relative to Non-Hispanic White people (Table). Asian Indians were lowest (IRR = 0.19, 95% CI = 0.11, 0.30), followed by Chinese (IRR = 0.33, 95% CI = 0.24, 0.46), then Filipino (IRR = 0.46, 95% CI = 0.36, 0.60) and Other Asian (IRR = 0.54, 95% CI = 0.43, 0.69). This advantage remained when adjusting for age and sex, social factors, socioeconomic status, and BMI for all Asian groups except for Other Asians. Conclusions: Asian people have a CVD mortality advantage compared to Non-Hispanic White people. Demographic, social, and socioeconomic factors, and BMI accounted for some, but not all of the differences in CVD mortality among Asian groups compared to Non-Hispanic White people. Future epidemiological study should focus on the social and environmental factors that promote health among Asian groups.
Abstract 18995: Association Between Prediabetes and Higher Risk of Mortality Following Acute Ischemic Stroke: A Meta-Analysis
Authors: Bhavin A Patel, Kshitij Mahajan, Kanwar Bir Singh Dhaliwal, Vishrut Kaushik, sakshi Dixit, Samrath Singh Brar, Siddharth A Atwal, Jugraj Singh, Bakhtawar Nader, Rishika Trivedi, Avleen Dhingra, ARPIT ARORA, Ankit Vyas, Rupak Desai, Akhil Jain
Journal: Circulation (2023)

Introduction: Prediabetes is known to increase the risk of cardiovascular and cerebrovascular mortality. This study aims to examine the relationship between prediabetes and mortality in patients who have experienced a stroke. Methods: A systematic search was conducted in PubMed/Medline, SCOPUS, and Google Scholar databases until May 2023 to identify relevant articles reporting on the association of prediabetes with ischemic stroke mortality. A random-effects model was used to calculate odds ratios (OR), heterogeneity was assessed using I 2 statistics, and sensitivity analysis was performed using the leave-one-out method. Results: Our final analysis contained 11 studies which included 84,833 prediabetic patients with a mean follow-up time of 20.9 months. The prediabetes cohort comprised patients of an average age of 67 years from various countries, including Korea, Italy, Japan, China, Spain, and the Netherlands. Initially, the unadjusted analysis showed no significant association between prediabetes and post-stroke mortality (OR 1.06, 95% CI 0.51-2.19) with high heterogeneity (I2=94.7%, P&amp;lt;0.01). However, after adjusting for baseline characteristics and comorbidities, the prediabetes cohort exhibited a significantly higher risk of post-stroke mortality (adjusted OR 1.68, 95% CI 1.29-2.19) with moderate heterogeneity (I2=49.45%, P=0.03). Subgroup analysis by country revealed higher odds of mortality in Korea, Italy, Spain, Japan, and the Netherlands. However, statistical significance was not reached for each subgroup, indicating the need for larger studies. Conclusions: Our findings suggest that prediabetes is associated with a nearly 68% higher risk of mortality following a stroke. This warrants more prospective studies with prediabetes to validate these findings.
Abstract 16981: A Machine Learning Model Increases Genetic Confirmation of UKB Participants With Suspected Monogenic Cardiovascular Disease
Authors: Megan E Ramaker, Jawan W Abdulrahim, Kristin Corey, Sara Coles, Navid A Nafissi, Kaitlyn Amos, Lydia C Kwee, Svati H Shah
Journal: Circulation (2023)

Introduction: Monogenic cardiovascular diseases (MCVDs) are collectively common yet highly underdiagnosed. Genetic testing for pathogenic variants can facilitate diagnosis and familial screening of MCVDs. Yet, most genetic variants within MCVD-associated genes currently annotated in ClinVar are variants of uncertain significance (VUS). VUS clinical utility is limited as VUS cannot be used for genetic confirmation of disease or for familial cascade screening. We previously developed a disease- and tissue-specific machine learning model for reclassification of VUS (Cardiovascular Disease-Pathogenicity Predictor [CVD-PP]). We sought to determine if use of CVD-PP on VUS identified through whole exome sequencing (WES) would increase genetic diagnosis of patients suspected of having a MCVD in the UK Biobank (UKB) cohort. Methods: We filtered for variants in 47 genes associated with 5 MCVDs (cardiomyopathies, channelopathies, aortopathies, cardiac amyloidosis, and familial hypercholesterolemia) in UKB participants with WES data. Participants harboring an American College of Medical Genetics confirmed ClinVar pathogenic or likely pathogenic (P/LP) variant in one of these genes were excluded. Phenotyping for presence of MCVDs was performed using EHR, clinical, cardiac imaging, and ECG data. CVD-PP was utilized to predict the pathogenicity of variants that were classified as VUS, had conflicting interpretations, or were absent from ClinVar. Results: Of participants with QC’ed WES data in UKB (n=452,933), 34.7% (n=157,030) had expression of a MCVD. Of these, 0.51% (n=799) carried a P/LP variant in a MCVD gene. Of the remaining P/LP variant-negative participants expressing disease (n=156,231), 4.1% (n=6,346) carried a VUS or non-ClinVar variant that was predicted pathogenic by CVD-PP. Conclusion: We demonstrate the potential utility of using a disease-and tissue-specific computational tool, CVD-PP, for deeper characterization of VUS in MCVD genes. Prioritization of CVD-PP-predicted pathogenic variants increases yield of genetic diagnosis in patients with evidence of clinical MCVDs from 0.51% using only ClinVar P/LP variants to 4.6% in UKB. This work provides a potential framework for increasing overall diagnostic yield of MCVDs.
Abstract 17382: Black Patients With Heart Failure Consume Diets That Are More Proinflammatory and Higher in Micronutrient Insufficiencies Than White Patients
Authors: JungHee Kang, Terry A Lennie, Martha J Biddle, Misook L Chung, Debra K Moser
Journal: Circulation (2023)

Background: Black patients experience disparities in heart failure (HF) outcomes compared to their White counterparts. Differences in diet quality, dietary inflammatory potential, and micronutrient deficiencies may contribute to these disparities. Aims: To compare the inflammatory potential of diet, dietary micronutrient insufficiencies, and diet quality between Black and White patients with HF. Methods: Patients with HF (n=361) who recorded food intake over 3-4 days were included (65% male, 62±12 years old). The inflammatory potential of diet (dietary inflammatory index [DII]), number of dietary micronutrient insufficiencies, and diet quality (Healthy Eating Index [HEI-2015]) were compared. Generalized linear regression models were used to evaluate the association between race and dietary indicators, controlling for age, sex, marital status, body mass index, financial status, and calories. For the regression model, the DII and number of dietary micronutrient deficiencies were dichotomized using median values due to the non-normal distribution. Results: Black patients with HF had more proinflammatory diets, a higher number of dietary micronutrient insufficiencies, and lower diet quality than White patients (1.39±2.15 vs 0.13± 2.40, P&lt;.001; 6.5±3.9 vs 4.8±3.4, P&lt;.001; and 49.8±14.4 vs 54.1±15.6, P=.021, respectively). Controlling for covariates, race was still associated with the proinflammatory potential of diet (P=.001) and number of dietary micronutrient deficiencies (P=.03) but not diet quality. Black patients were 2.7 times more likely to have more proinflammatory diet (95% CI: 1.50, 4.98) and 1.8 times more likely to have a higher number of dietary micronutrient insufficiency (95% CI: 1.06, 3.18).Conclusions: We found differences in dietary inflammatory potential and dietary micronutrient insufficiencies between Black and White patients with HF. Diet quality did not differ between Black and White patients after adjustment for covariates. Our findings suggest Black patients may be at higher risk for diets high in proinflammatory potential and micronutrient insufficiencies. In contrast, diet quality measured by HEI-2015 was less influenced by race than other factors controlled in the analysis.