tbuckley/cabot-search huggingface dataset:
Abstract 9846: Association Between Neutrophil Activity and Incident Heart Failure: The Atherosclerosis Risk in Communities Study
Authors: Leo F Buckley, Pranav Dorbala, Brian Claggett, Peter Libby, Weihong Tang, Josef Coresh, Christie M Ballantyne, Ron C Hoogeveen, Bing Yu, Amil M Shah
Journal: Circulation (2021)

Introduction: Inflammation-reduction with colchicine improves outcomes in coronary disease, possibly through effects on neutrophil activity. Inflammation also may contribute to incident heart failure (HF) and the association of neutrophil activity with HF is unclear. We assessed the association between 10 neutrophil-associated proteins that were altered by colchicine in two previous proteomic studies with incident HF. Methods: We studied 10,317 ARIC participants who were free of HF and had aptamer-based proteomic measurements (Somalogic, Colorado) at Visit 3 (1993-1995). Candidate proteins were included in a LASSO Cox regression model which were used to derive a neutrophil activity score. The association of the neutrophil activity score with incident HF was then assessed after adjustment for age, sex, race, study field center, hypertension, smoking history, diabetes, coronary disease, BMI, Visit 3 blood pressure, eGFR, and hsCRP and neutrophil-to-lymphocyte ratio. Results: The mean age was 60±6 years, 54% were women and 20% were black. Over a mean follow-up of 13 years, 1314 participants developed incident HF. Five of the 10 candidate proteins were associated with incident HF in multivariable uni-protein models (myeloperoxidase, suPAR, antichymotrypsin, BPIP, S100A12) at p &lt;0.05. LASSO model retained 4 proteins (suPAR, antichymotrypsin, BPIP, S100A12), from which a neutrophil activity score was developed. Higher neutrophil activity score was associated with older age, higher prevalence of cardiovascular comorbidities, and higher hsCRP. Higher neutrophil activity score was associated with greater risk of incident HF in multivariable models after adjustment for clinical risk factors, hsCRP and neutrophil-to-lymphocyte ratio ( Figure ). Conclusions: Increased neutrophil activity may contribute to incident heart failure in the community. These findings provide a putative mechanism by which treatment with colchicine may influence risk of HF.
Abstract 12489: Blood Type A1 Donor and Recipient Matching for Heart Transplant: Does It Matter?
Authors: Seong Kyu Kim, Jon A Kobashigawa, Jignesh Patel, Savannah Mersola, Tahli Singer-Englar, Nikhil Patel, Lawrence Czer, Michelle M Kittleson
Journal: Circulation (2021)

Introduction: ABO antibodies bind specific carbohydrate moieties defining the A and B antigens. With blood group A, inter-individual variation in transferase specificity and efficiency results in differential antigen expression and density. These subgroups of A are termed non-A1 and have fewer A antigen epitopes per red blood cell, which is less immunogenic. Our goal was to assess the impact of transplantation of an A1 organ to a non-A1 recipient. Methods: We assessed 138 blood-type A heart transplant recipients transplanted between 2013 and 2020. Comparison groups included a "match" group (A1 donor into A1 recipient, and non-A1 donor into non-A1 recipient, n=88) and a "mismatch" group (A1 donor into non-A1 recipient, and non-A1 donor into A1 recipient, n=50). Outcomes included 1-year survival, freedom from cardiac allograft vasculopathy (CAV: stenosis ≥30%), freedom from non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, heart failure, percutaneous coronary intervention, defibrillator/pacemaker implant, stroke), and 1-year freedom from any treated rejection (ATR), acute cellular rejection (ACR), and antibody-mediated rejection (AMR). Results: The mismatch group exhibited similar subsequent 1-year survival, freedom from CAV, and freedom from NF-MACE and subsequent 1-year freedom from ATR, ACR, and AMR compared to the match group. (Table) Conclusions: The mismatch of blood type in A1 and non-A1 between donors and recipients does not adversely affect outcomes after heart transplantation. Selective matching of specific A blood typing for heart transplantation is not necessary.
Abstract 10405: Associations Between Ivig Dose and Outcome of Kawasaki Disease Patients in Acute Phase
Authors: Takanori Suzuki, Nobuaki Michihata, Kazuyoshi Saito
Journal: Circulation (2021)

Background: The standard treatment of Kawasaki Disease (KD) is intravenous immunoglobulin (IVIG) 2g/kg and aspirin. However, the most effective dosage of IVIG to prevent coronary artery abnormalities (CAA) is not known. The purpose of this study was to identify the dose of IVIG for KD patients in acute phase using a national inpatient database in Japan. Method: We used the Diagnostic Procedure Combination database to identify KD patients treated with IVIG between 2010 and 2017. We used multiple logistic regression models to estimate the risk of proportion of CAA and IVIG resistance, and multiple regression models to estimate the difference of length of stay and medical cost. In all models, demographic characteristics and comorbidities were adjusted for as covariates. We generated restricted cubic splines models with the same covariate specification as the fully adjusted model with five knots to examine non-linear associations between IVIG dose and the different outcomes. Results: We extracted 42,331 eligible patients from the database. The age was 1.7 years (1.6 SD), male 24432 (58%), and body weight 11.1kg (4.9 SD). The mean dose of IVIG was 1.7g/kg (1.3 SD), proportion of CAA 1325(3.1%), and medical cost 6596 USD (5160- 8689). We found a reverse J-shaped association between the dose of IVIG and the proportion of CAA. IVIG dosage was also found to have U-shaped associations with length of stay and medical costs. Conclusion: When IVIG dose was less than 2g/kg, the proportion of CAA increased, and the length of stay and medical cost also increased; when IVIG dose was more than 2g/kg, the length of stay and medical cost could be increased, and 2g/kg IVIG was considered appropriate for the initial treatment of KD.
Abstract P497: Myocardial Infarct Outcome And Weight Gain In Menopause Mice Are Mitigated During Probiotic Oligofructose Treatment
Authors: Christina H Hoyer-Kimura, Alice E Solomon, Joshua P Fricks, Brij Kathuria, Christian Leber, Victoria Salcedo, Frank Duca, John P Konhilas
Journal: Circulation Research (2021)

The average woman spends over 40% of their life in menopause, during which estrogen’s protective roles are lost and women suffer an increased risk of developing inflammatory pathologies including obesity and worsened cardiovascular disease outcomes. Yet, safe, and effective menopause therapies are still unavailable. The gut microbiome impacts both metabolic and circulating estrogen homeostasis. A dysbiotic (unhealthy) gut can contribute to pathologies that are also observed during menopause including increased obesity and worsened myocardial infarct (MI) outcomes. We have previously demonstrated that gut manipulation through prebiotics (Oligofructose [OFS]), attenuates myocardial infarct injury, improved glucose tolerance, and reduced weight gain in mice. We hypothesize that loss of estrogen during menopause results in intestine morphological and microbial changes, worsens MI outcomes and increases weight gain, which can be mitigated with OFS treatment. Menopause was induced in female mice fed a high-fat-diet (HFD, 45% fat) via 4-vinylcycohexane diepoxide intraperitoneal injections (controls were injected with sesame oil), menopause (14+days diestrus) was determined by cytology. Following menopause, mice were treated for 6wks with 10% OFS supplemented into the diet (provided ad libitum; controls were fed HFD food only). Mice underwent 3day permanent ligation prior to sacrifice. We observed that menopause results in increased villi density in the duodenum and ileum, and that menopausal mice had a significant increase in both duodenum villi length and wall thickness. Menopause was associated with a shift in the gut microbiota composition. Relative abundance of Alistipes was reduced in menopausal mice, compared to premenopausal mice, and is restored with OFS treatment. Furthermore, menopausal mice had increased weight gain and infarct size compared to premenopausal mice, and OFS attenuated the differences between menopause and perimenopause weight gain over time and infarct size. Together these data demonstrate menopause is associated with intestinal morphological changes and shifts in the gut microbiome, and that in the presence of OFS infarct size and weight gain in menopausal mice are mitigated.
Abstract 401: Functional Impact Of Rbfox1c In Cardiac Pathological Remodeling Through Targeted Mrna Stability Regulation
Authors: Chen Gao, Zhaojun Xiong, Jianfang Liu, Nancy Cao, Tomohiro Yokota, Jijun Huang, Menglong Wang, Shuxun Ren, Christoph Rau, Katelyn Li, Xinshu Xiao, Thomas M Vondriska, Yibin Wang, Yi Xing
Journal: Circulation Research (2021)

Post-transcriptional regulation plays a key role in transcriptome reprogramming during cardiac pathogenesis. In previous studies, we have identified that cardiac enriched RNA-binding protein, RBFox1 plays key role in cardiac hypertrophy through mRNA alternative splicing regulation in nuclei. However, RBFox1 gene also generates a cytosolic isoform (RBFox1c), suggesting additional functions of post-transcriptional regulation in heart. In adult heart, RBFox1c mRNA constituted ~ 40% of total RBFox1 level but was significantly repressed in pressure-overloaded failing mouse heart. Using CRISPR-Cas9 technology, we have established an isoform specific RBFox1c-cKO mouse. At baseline inactivation of RBFox1c led to decreased cardiac function along with induction of cardiac fibrosis. RBFox1c-cKO mice also showed macrophages infiltration into myocardium post 7days MI. In contrast, restoration of RBFox1c expression in adult intact hearts significantly reduced cardiac fibrosis post stress. RNA-seq analyses in RBFox1c expressing cardiomyocytes showed that RBFox1c specifically suppressed the expression of pro-inflammatory genes. Secondly, CLIP-Seq analysis and targeted RNA-IP showed that RBFox1c could directly interact with inflammatory pathway mRNAs. These results suggested the inflammatory mRNAs are direct downstream targets regulated by RBFox1c. Using both in vitro cultured cardiomyocytes and intact mouse hearts, we demonstrated that expression of RBFox1c reduces pro-inflammatory mRNA expression at baseline and upon hypertrophy stimulation. Lastly, we characterized the interactome of RBFox1c through proteomic analysis and found RBFox1c specifically interacted with a component of the RNA NMD machinery-Upf1. RBFox1c interaction with Upf1 in cardiomyocytes was diminished upon hypertrophic stress. Furthermore, by inactivation of Upf1 via siRNA, we demonstrated that RBFox1c mediated repression of proinflammatory genes was Upf1 dependent.RBFox1 regulates cardiac transcriptome reprogramming in two post-transcriptional processes via distinct isoforms. While the RBFox1n regulates RNA splicing, the RBFox1c functions through targeted mRNA repression of proinflammatory genes by recruitment of Upf1 mediated RNA degradation.
Abstract 12818: The Role of Cellular Senescence in Aortic Dissection
Authors: Eichi Nakao, Hiroki Aoki, Ryohei Majima, Youhei Hashimoto, Ryo Shibata, Makiko HAYASHI, Satoko Ohno, Aya Furusho, Norifumi Nishida, SAKI HIRAKATA, Yoshihiro Fukumoto
Journal: Circulation (2021)

Background: Aortic dissection (AD) is a catastrophic disease that occurs suddenly. The acute mortality is high and those who survived frequently suffer from serious complications. Currently, pathogenesis of AD is largely unknown, which hampers the development of effective approaches to predict the prognosis and to alleviate the progression of AD. Previous studies revealed the importance of inflammation in AD pathogenesis. Recently we found that cell proliferation occurs during the development and the progression of AD. Because cell proliferation triggers cellular senescence, which is associated with secretion of proinflammatory cytokines, we hypothesized that cellular senescence might be involved in AD pathogenesis. Objective: We investigated if cellular senescence contributes to AD development and progression in a mouse AD model. Methods and Results: A mouse AD model was created by continuous infusion of beta-aminopropionitrile and angiotensin II (BAPN+AngII), where AD starts to develop in 3 days and occurs in most of the mice within 14 days. Infusion of BAPN+AngII resulted in the appearance of senescent cells that are positive for senescence-associated beta-galactosidase, and expression of senescence markers Arf and Ink4a in the aortic walls. Cellular senescence occurred in one day of BAPN+AngII infusion and was sustained throughout the observational period of 14 days. We examined the role of cellular senescence in AD pathogenesis by oral administration of ABT263 which is known as "senolytics" that eliminates senescent cells. ABT263 treatment reduced the expression of the senescence markers. In the vehicle-treated group, the mortality was 66.7% (12/18), whereas that of ABT263-treated group was 35% (14/20, P &lt; 0.05 by log-rank test). The severity of AD, as assessed by the lesion length in vehicle group was 16.6±6.9mm, whereas that in ABT263 group was 12.2±4.2 mm (P &lt; 0.05). Conclusions: These findings demonstrated that cellular senescence precedes AD development, and elimination of senescent cells effectively prevented AD progression and death, indicating the involvement of cellular senescence in AD pathogenesis. Therefore, cellular senescence represents a potential predictor and a therapeutic target for AD.
A Minority of Women of Child Bearing Potential Are Tested for Pregnancy before Chemoimmunotherapy: An Australian Cancer Centre Experience
Authors: Verity L Chadwick, Georgia Mills, Pietro R Di Ciaccio, Catherine Tang, Rachel Dear, John Moore, Sam Milliken, Barbara Withers, Orly Lavee, Georgia J McCaughan, Jacinta Perram, Nada Hamad
Journal: Blood (2021)
Abstract 12313: Gender and Racial Differences in Outcomes of Patients With Non-Acute Myocardial Infarction Cardiogenic Shock Receiving Extracorporeal Membrane Oxygenation With or Without Left Ventricular Unloading Devices
Authors: Sumit Sohal, Krishna Prasad Kurpad, Harsh Mehta, Gautam K Visveswaran, Marc Cohen
Journal: Circulation (2021)

Introduction: Cardiogenic shock (CS) is a state of end organ hypo-perfusion due to primary pump failure, 80% of which is due to acute myocardial infarction (AMI). Among patients with AMI-CS, women as well as black and Hispanic males have been found to have worse clinical outcomes with persistent sex disparities after receiving mechanical circulatory support (MCS). However similar differences in outcomes of CS in non-AMI patients with MCS are unknown. Methods: National Inpatient Sample database from years 2015 to 2018 was queried to identify patients admitted with non-AMI-CS. Gender and racial differences in baseline demographics and in-hospital outcomes were compared in patients who received VA-ECMO with or without LV unloading devices. Statistical significance was assigned at p&lt;0.05. Results: 178,605 patients met the criteria for non-AMI-CS out of which 2,190 (1.23%) patients received VA-ECMO alone, 965 (0.54%) received VA-ECMO plus Intra-aortic balloon pump (IABP) and 414 (0.23%) received VA-ECMO plus Impella. Gender and racial distribution of each cohort is shown in figure 1. On multivariate analysis, the in-hospital mortality rates in patients on VA-ECMO only or VA-ECMO plus Impella were non significantly higher for females as compared to males (OR: 1.29 (0.88-1.89), p=0.18), (OR: 1.97 (0.27-14.64), p=0.51) respectively, whereas in patients with VA-ECMO plus IABP they were non-significantly lower than males (OR: 0.74 (0.28-1.99), p=0.55). Furthermore, the in-hospital mortality was non significantly lower in African Americans when compared to Caucasians among patients on VA-ECMO with or without LV unloading devices. Conclusions: In patients admitted with non-AMI-CS requiring VA-ECMO with or without LV unloading devices no statistically significant gender or race-based differences occur in mortality outcomes.
Abstract P350: Myofibril Orientation In Cardiac Muscle And Its Implication For Heart Disease
Authors: Weikang Ma, Henry Gong, Vivek Jani, Maicon Landim-Vieira, Maria Papadaki, Jose R Pinto, Mohammed I Aslam, Anthony Cammarato, Thomas Irving
Journal: Circulation Research (2021)

Rationale: Myocyte disarray is a hallmark of cardiomyopathy. However, the orientation of individual myofibrils and myofilaments and how their alignment may be altered in disease progression have been largely underexplored. This oversight has been predominantly due to a paucity of methods for objective and quantitative analysis. Objective: To introduce a novel, less-biased approach to quantify myofibrillar and myofilament orientation in cardiac muscle under near physiological conditions and demonstrate its superiority versus traditional histological assessments. Methods and Results: Using small-angle X-ray diffraction, we first investigated changes in myofibrillar orientation at increasing sarcomere lengths in skinned, relaxed, wildtype mouse myocardium by assessing the angular spread of the 1,0 equatorial reflection (angle σ). At a sarcomere length (SL) of 1.9 μm, the angle σ was 0.23±0.01 rad, decreased to 0.19±0.01 rad at a SL of 2.1 μm, and further decreased to 0.15±0.01 rad at a SL of 2.3 μm (p&lt;0.0001). Angle σ was significantly larger in R403Q (a MYH7 HCM model) porcine myocardium (0.24±0.01 rad) compared to WT myocardium (0.14±0.005 rad, p&lt;0.0001) as well as in biopsied human heart failure tissue (0.19±0.006 rad) when compared to non-failing samples (0.17±0.007 rad, p=0.01). These data indicate that diseased myocardium suffers from myofibrillar disorientation compared to healthy controls. Finally, using control samples, we showed that traditional, histological-based analysis of disarray can be subject to user bias and/or sampling error and lead to false positives. Conclusions: Our method for assessing myofibrillar orientation limits the artifacts introduced by traditional histological processing and provides a precise and objective metric for phenotypically characterizing myocardium. The ability to obtain excellent X-ray diffraction patterns from frozen, biopsied human myocardium opens up new avenues of inquiry regarding the relation of myofibrillar structure to function in health and disease.
Abstract 12835: Transitions in Academic Cardiothoracic Surgery From 2018 to 2020
Authors: Simar S Bajaj, Hanjay Wang, Kiah M Williams, Oluwatomisin O Obafemi, Jack H Boyd
Journal: Circulation (2021)

Introduction: New training paradigms and increasing surgeon demands have shaped how individuals enter and exit academia. We examined the characteristics of surgeons who moved into and out of academic cardiothoracic (CT) surgery between 2018 and 2020. Methods: We created a database of academic CT surgeons in the U.S. at all 77 accredited CT surgery training institutions in 2018 (n=992) and all 79 such institutions in 2020 (n=1065). Surgeon-specific professional history data were obtained from institutional webpages and other publicly available sources. Categorical data are presented as counts with percentage. Results: Between 2018 and 2020, 119/992 (12.0%) surgeons exited centers with training programs. Of the 992 surgeons in 2018, 22 (2.2%) passed away or retired, 38 (3.8%) moved to a university center without a training program, and 53 (5.3%) moved to private or community practice. 56/992 (5.6%) surgeons also moved from one training center to another between 2018 and 2020, with 19 (33.9%) moving to an institution with greater National Institutes of Health (NIH) funding. At these 2020 institutions, 15 (26.8%) are now assistant professors, 17 (30.4%) associate professors, and 21 (37.5%) professors; 20 (35.7%) received a promotion in academic rank upon moving. Between 2018 and 2020, 164/1065 (15.4%) surgeons entered centers with training programs. Directly before entering, 9 (5.5%) completed I6 residencies, 45 (27.4%) completed traditional CT surgery fellowships, 39 (23.8%) completed advanced CT surgery fellowships, 34 (20.7%) were attendings at a university center without a training program, and 17 (10.4%) were attendings in private or community practice. Of the 77 institutions in both 2018 and 2020, there was a median increase of 1 surgeon per institution, with 20 (26.0%) programs shrinking in size, 13 (16.9%) staying stable, and 44 (57.1%) expanding. Conclusions: Between 2018 and 2020, there has been growth in academic CT surgery with a net increase of surgeon faculty by 4.5% and a majority of training centers expanding faculty size. Among those who switched institutions, more stayed in academia than shifted to private practice. This transition from one training program to another represents one of the many diverse pathways into academic CT surgery.
Abstract 10551: Management of Guideline-Directed Medical Therapy for Heart Failure in Office, Video and Telephone Outpatient Visits
Authors: Yasser Sammour, Michael L Main, Bethany A Austin, Anthony Magalski, Brett Sperry
Journal: Circulation (2021)

Background: There are limited data about management of guideline-directed medical therapy (GDMT) in heart failure with reduced ejection fraction (HFrEF) with telehealth visits versus office visits. We sought to compare differences in the use of GDMT and loop diuretics between office, video, and telephone visits. Methods: We included 13,481 outpatient visits performed for 5,439 unique patients with HFrEF between March 16, 2020 and March 15, 2021. Multivariable logistic regression analysis was used to test differences between visit modes. Results: Overall, at least one GDMT class was started in 11.7% of office visits, 9.6% of video visits and 7.2% of telephone visits. Meanwhile, loop diuretics were initiated in 4.4% of office visits, 2.5% of video visits and 2.6% of telephone visits. After adjustment to baseline use of GDMT and loop diuretics, the rates of starting at least 1 GDMT class were similar between video and office visits (adjOR 0.95; 95% CI 0.82-1.12; p=0.558). There were no differences between video and office visits in discontinuing at least 1 GDMT class (adjOR 0.86; 0.71-1.04; p=0.119). Telephone visits were associated with less frequent initiation of at least 1 GDMT class compared with office visits (adjOR 0.77; 0.71-0.83; p&lt;0.001), and video visits (adjOR 0.61; 0.51-0.74; p&lt;0.001). Discontinuing at least 1 GDMT class during telephone visits was also less frequent than office visits (adjOR 0.91; 0.84-0.99; p=0.041), albeit similar to video visits. Compared with office visits, adding loop diuretics was less frequent with both video visits (adjOR 0.62; 0.47-0.83; p=0.001), and telephone visits (adjOR 0.62; 0.48-0.79; p&lt;0.001) ( Figure ). Conclusion: The initiation of GDMT for HFrEF was similar between office and video visits, but lower with telephone visits, whereas the initiation of loop diuretics was lower with both video and telephone visits compared with office visits. These data can be useful when planning to augment GDMT in HFrEF using telehealth visits.