tbuckley/cabot-search huggingface dataset:
Abstract 11446: The Role of Heart Rate Recovery in Chronic Heart Failure - Results from the Myovasc Study
Authors: David Velmeden, Jakob Söhne, Alexander Schuch, Silav Zeid, Andreas Schulz, Sven-Oliver Troebs, Felix Müller, Marc Heidorn, Gregor Buch, Wilfried Dinh, Karl J Lackner, Tomaso Gori, Thomas Muenzel, Philipp S Wild, Juergen Prochaska
Journal: Circulation (2021)

Background: Reduced heart rate recovery (HRR) has been associated with cardiac autonomic dysfunction, particularly the parasympathetic nervous system, and all-cause mortality in patients with heart failure (HF). Methods: In the present study, data of the MyoVasc study (NCT04064450; N=3,289), a prospective cohort study on chronic HF, were analyzed. Participants received a comprehensive 5-hour examination in a dedicated study center including cardiopulmonary exercise testing (CPET) using modified WHO protocols. HRR 60 was defined as the decrease in heart rate in beats per minute one minute after cessation of CPET peak strain. Information on clinical outcome (i.e. all-cause mortality, worsening of HF (wHF)) was derived from structured follow-up with subsequent validation and independent adjudication of endpoints. Results: The analysis sample comprised N=1,179 individuals (mean age: 65.0±10.4 years; 28.2% females) with data on HRR 60 . In a multivariable linear regression analysis, age (β-estimate -0.171 ([95% confidence interval -0.226; -0.116]; P&lt;0.0001), sex (β -0.189 [-0.311;-0.0678]; P=0.0023), diabetes mellitus (β -0.300 [-0.424; -0.175]; P&lt;0.0001), smoking (β -0.236 [-0.361; -0.111]; P= 0.00021), obesity (β: -0.266 [-0.380; -0.151]; P &lt;0.0001), peripheral artery disease (β -0.432 [-0.640; -0.224]; P&lt;0.0001), chronic obstructive pulmonary disease (β -0.179 [-0.304;-0.0542]; P=0.0050) and chronic kidney disease (β -0.322 [-0.474; -0.170]; P&lt;0.0001) were identified as clinical determinants of HRR 60 . In Cox regression analysis, HRR 60 ≤15 bpm (1 st tertile vs. 2 nd /3 rd tertile of HRR 60 ) demonstrated an increased risk for all-cause death (hazard ratio (HR) 1.90 [1.29; 2.79]; P=0.0011). HRR 60 was also a strong predictor of w HF (HR T1vsT2-3 1.58 [1.17; 2.13]; P=0.0031) independent of clinical determinants and medication. The results remained robust for all-cause mortality (HR T1vsT2-3 1.61 [1.10; 2.38]; P =0.016) and wHF (HR T1vsT2-3 1.36 [1.01; 1.84]; P= 0.045) after additional adjustment for NT-proBNP. Conclusion: HRR 60 - a measure associated with cardiac autonomic function - was identified as a strong predictor of clinical outcome of HF patients independent of NT-proBNP, suggesting a potential to advance risk stratification in HF.
Abstract 13045: Metformin in Management of Diabetic Patients With Advanced Heart Failure (HFrEFf): A Propensity Score-Matched Analysis
Authors: Jan Benes, Martin Kotrc, Katerina Kroupova, Peter Wohlfahrt, Jan Kovar, Janka Franekova, Marketa Hegarova, Lenka Hoskova, Eva Hoskova, Terezie Pelikanova, Petr Jarolim, Josef Kautzner, Vojtech Melenovsky
Journal: Circulation (2021)

Introduction: The role of metformin (MET) in the treatment of patients with advanced heart failure with reduced ejection fraction (HFrEF) and type 2 diabetes mellitus (DM) is not firmly established. Hypothesis: Meformin treatment will be associated with better outcome even in DM patients with advanced HFrEF. Methods: A total of 847 stable patients with advanced HFrEF (57.4± 11.3 years, 67.7% NYHA III/IV, LVEF 23.6± 5.8%) underwent clinical and laboratory evaluation and were prospectively followed for a median of 1126 (IQRs 410; 1781) days for occurrence of death, urgent heart transplantation or mechanical circulatory support implantation. A subgroup of 380 patients (44.9%) had DM, 87 of DM patients (22.9%) were treated with MET. Results: Compared with MET-free diabetic patients, MET-treated individuals had similar fasting glucose, but worse DM control (Hb1Ac 60 mmol/mol, IQRs 50-73 vs. 52 IQRs 48-62, p=0.002), higher insulin, glucagon, β-hydroxybutyrate levels and increased insulin resistance (all p&lt; 0.05), but better quality of life (MLHFQ-score: 36 vs. 48 points, p= 0.002). Compared to diabetics treated with any other glucose-lowering agent, MET-treated patients had better event-free survival (p=0.0005, Fig. 1), which remained significant (p= 0.035) even after adjustment for BNP, BMI and eGFR. Propensity score-matched analysis with 17 covariates yielded 81 pairs of patients and showed a significantly better survival for MET-treated subgroup (p= 0.01). Conclusions: MET treatment in patients with advanced HFrEF and DM is associated with better quality of life and improved outcome, by mechanisms beyond the improvement of blood glucose control. MET should stay among frontline drugs for treatment of HFrEF patients with DM. Supported by a grant no. NV19-02-00130 by Czech Health Research Council.
Abstract 12461: Identification of Differentially Expressed Long Non-Coding RNAs in Human-Induced Pluripotent Stem Cell-Derived Endothelial Cells Triggered by E-cigarette Exposure
Authors: Hoai Le, Chen-wei Liu, Philip Denaro, Ning-Yi Shao, Sang-Ging Ong, Won Hee Lee
Journal: Circulation (2021)

Introduction: Electronic-cigarette (e-cig) usage, particularly in the youth population, is a growing concern. It is known that e-cig causes endothelial dysfunction, which is a risk factor for the development of cardiovascular diseases; however, the mechanisms involved remain unclear. We hypothesized that long non-coding RNAs (lncRNAs), a novel class of non-coding RNA that has been shown to affect endothelial function, may play a role in e-cig-induced endothelial dysfunction. Methods and Results: We profiled lncRNAs that are dysregulated in human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) from healthy individuals following 24 hours of e-cig aerosol extract treatment. Using microarray analysis, we identified that 183 lncRNAs and 132 mRNAs were upregulated while 297 lncRNAs and 413 mRNAs were downregulated. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analyses of the mRNAs dysregulated by e-cig exposure followed by the functional characterization of the top 5 differentially expressed (DE) lncRNAs by co-expressed protein-coding genes analysis. Interestingly, the lncRNA-mRNA association analysis revealed several mRNAs associated with metabolic disorders. Subsequently, we found that e-cig caused dysregulation of endothelial metabolism resulting in increased fatty acid oxidation activity, higher mitochondrial membrane potential, and decreased glucose uptake and glycolysis. These results suggest that e-cig-induced altered EC metabolism and increased fatty acid oxidation compensate for energy deficiency in ECs. Conclusion: Collectively, the identification of potential regulators and pathways of the interaction between lncRNAs and mRNAs in ECs treated with e-cig provides novel insights into endothelial biology and could have a significant impact on our understanding of vascular complications upon e-cig exposure.
STEM-09. DEFINING THE ROLE OF CD97 IN GLIOBLASTOMA STEM CELL SELF-RENEWAL
Authors: Niklas Ravn-Boess, Nainita Bhowmick, Takamitsu Hattori, Alexis Corrado, Akiko Koide, Afreen Karimkhan, Shohei Koide, Christopher Park, Dimitris Placantonakis
Journal: Neuro-Oncology (2021)

Abstract Glioblastoma (GBM) is the most common and aggressive primary brain malignancy. Despite multimodal therapy, resistant GBM stem-like cells (GSCs) inevitably mediate disease recurrence. To identify novel vulnerabilities of GSCs, we performed an arrayed CRISPR/Cas9 screen against select adhesion G protein-coupled receptors (aGPCRs), many of which we found to be de novo expressed in GBM. Knockout of CD97 (ADGRE5), previously implicated in GBM cell migration, produced the most striking proliferative disadvantage in patient-derived GBM cultures (PDGC) among aGPCRs tested. We found high CD97 surface expression in all our PDGCs, while levels remained nearly undetectable in non-neoplastic brain cells, confirming that CD97 is de novo expressed in GBM. Upon shRNA-mediated knockdown of CD97 in PDGCs from all three TCGA transcriptional subtypes, we observed significantly reduced proliferation, as measured by Ki67 and Hoechst cell cycle analysis, and significantly diminished surface expression of CD133, a GSC marker. Notably, CD97 knockdown also significantly reduced tumorsphere initiation capacity in six PDGCs, as measured by extreme limiting dilution assays. These findings suggest that CD97 regulates GSC self-renewal in vitro. RNA-sequencing and GSEA pathway analysis from PDGCs following CD97 knockdown indicate an enrichment of aerobic respiratory gene sets, suggesting one of the major regulatory roles of CD97 is metabolic regulation. Indeed, metabolic assays show that CD97 knockdown alters oxygen consumption and glycolysis rates in PDGCs. Lastly, we have developed human synthetic antibodies to target CD97 in order to investigate its therapeutic potential. We have observed internalization of some of these antibodies, thus identifying candidates for the development of antibody-drug conjugates. In addition, other clones reduced GBM cell proliferation and elicited expression of various differentiation markers. Overall; our studies identify novel roles of CD97 in regulating the cellular hierarchy in GBM and tumor cell metabolism, and provide a strong scientific rationale for developing biologics to target CD97 in GBM.
Group programmes for weight loss may be more effective than one-to-one sessions
Authors: Helen Saul, Deniz Gursul
Journal: BMJ (2021)

The studyAbbott S, Smith E, Tighe B, Lycett D. Group versus one-to-one multi-component lifestyle interventions for weight management: a systematic review and meta-analysis of randomised controlled trials. J Hum Nutr Diet 2021;34:485-93.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/group-weight-loss-programmes-more-effective-than-one-to-one-sessions/.
COVID-19<b>–</b>Associated Deaths After SARS-CoV-2 Infection During Pregnancy — Mississippi, March 1, 2020–October 6, 2021
Authors: Laurin Kasehagen, Paul Byers, Kathryn Taylor, Theresa Kittle, Christine Roberts, Charlene Collier, Britney Rust, Jessica N. Ricaldi, Jamilla Green, Lauren B. Zapata, Jennifer Beauregard, Thomas Dobbs
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Pregnant and recently pregnant women are at increased risk for severe illness and death from COVID-19 compared with women who are not pregnant or were not recently pregnant (1,2). CDC recommends COVID-19 vaccination for women who are pregnant, recently pregnant, trying to become pregnant, or might become pregnant in the future.*,† This report describes 15 COVID-19-associated deaths after infection with SARS-CoV-2 (the virus that causes COVID-19) during pregnancy in Mississippi during March 1, 2020-October 6, 2021.
Abstract 10828: Stem-Cell Therapy for Abdominal Aortic Aneurysms in Swine
Authors: Brian Zilberman, Gaby Ghobrial, Robert Emery, Nicholas De Leo, Clara Zhu, Rebecca Platoff, Ping Zhang, Olga Ostrovsky, Krystal Hunter, Vaishali Krishnadoss, Noshadi Iman, Spencer Brown, Jeffrey P Carpenter
Journal: Circulation (2021)

Introduction: The current treatment paradigm of abdominal aortic aneurysms (AAA) focuses on observing patients until their disease reaches certain thresholds for intervention, with no preceding treatment available. There is an opportunity to develop drug or cell-based therapies to prevent further aneurysmal growth and decrease the risk of a highly morbid rupture. A previously validated acute AAA swine model was treated directly with gelfoam containing human adipose-derived stem cells (h-ADSCs). Methods: Male Yorkshire swine (n=16) received periadventitial injections (type 1 collagenase and porcine pancreatic elastase) into a 4 cm segment of infrarenal aorta. Experimental group (n=7) received gel foam soaked with 10 million h-ADSCs and control group (n=9) media-soaked gel foam. Aortic diameters (AD) were monitored at post-operative day (POD) 7 and 14 using ultrasound with euthanasia on POD 21. Suprarenal (control) and infrarenal aortas (experimental) were harvested for PCR, mechanical tensiometry testing, histopathological analyses as well as immunohistochemistry (IHC). Each animal served as their own control. Groups were compared with paired t-tests and Mann Whitney U tests. Results: Twelve animals survived until POD 21. Stem cell treated AAAs, unlike controls, demonstrated no growth (-1.6 ± 8.8% vs. 34.8 ± 13.7%, p&lt;0.001), and had greater medial thickness (682.7 ± 149.1 um vs. 321.7 ± 194.0 um, p&lt;0.001), and greater areas of elastin (5.33 ± 1.49% vs. 2.57 ± 2.25%, p&lt;0.0001), smooth muscle (55.8 ±6.59% vs. 24.0 ± 6.84%, p&lt;0.001), collagen 1 (p=.014), and VEGF (p=.009) than untreated controls. MMP9 mRNA expression in stem cell AAA specimens was downregulated 0.501 (±0.464) fold compared to control segments from those same animals (p= 0.025). Though tensiometry data displayed greater strength within the stem cell AAA rings, this did not reach statistical significance (p=.15). Conclusion: Stem cell therapy prevents the development of aortic aneurysms in a swine model. Stem cell treated swine with induced AAAs show more normal gross features, histologic, and biochemical properties compared to untreated controls with induced AAAs. Further investigation is merited as a possible translatable therapy for aneurysmal disease.
Abstract 119: Donor Macrophages Modulate Cellular Rejection After Heart Transplantation
Authors: Benjamin Kopecky, Junedh Amrute, Hao Dun, C. Corbin Frye, DANIEL KREISEL, Kory J Lavine
Journal: Circulation Research (2021)

Heart transplant rejection is common and is associated with significant morbidity and mortality. Current immunosuppressive therapies primarily target recipient T-cells and have a multitude of untoward effects including infections, malignancies, and end-organ damage. Recent studies implicate the roles of antigen presenting cells towards pathogenesis of allograft rejection through recruitment and activation of T-cells. The importance of antigen presenting cell origin, identity, and functional importance remains unknown. Using complimentary imaging and single cell RNA sequencing techniques, we show that donor and recipient monocytes and macrophages co-exist after heart transplantation. These myeloid populations have diverse transcriptional signatures that evolve throughout ongoing rejection. Donor macrophages can be defined ontologically and based on their expression of C-C chemokine receptor 2 (CCR2) and expression of MHC-II. Donor CCR2+ and CCR2- populations can be further defined based on their gene expression profiles, highlighting the marked heterogeneity in the donor macrophage population. Selective depletion of CCR2+ macrophages result in prolonged allograft survival. We use longitudinal single cell RNA sequencing to show that donor CCR2+ and CCR2- macrophages have distinct activation mechanisms such that donor CCR2+ macrophages signal through MyD88/NF-kB. Conditional depletion of MyD88 in donor macrophages recapitulates the donor CCR2+ depletion phenotype. Further interrogation of MyD88 conditionally depleted allografts shows reduced T-cell alloreactivity, holding promise for a potential therapeutic target pathway. Together, we show the molecular identity, diversity, and evolution of donor and recipient monocytes and macrophages as well as the functional relevance and activation pathways of donor macrophages in cardiac allografts.
Abstract 11021: The Relationship Between TAPSE and HR During Exercise in Heart Failure of Any LVEF: A CPET Imaging Study
Authors: Marco Guazzi, Tadafumi Sugimoto, Greta Generati, Maurizio Losito, Francesco Bandera, eleonora alfonzetti
Journal: Circulation (2021)

Introduction: The relationship between TAPSE vs heart rate (HR) during physical exercise may well represent the force-frequency relationship of the right ventricular (RV) whose impact on exercise performance and hemodynamics may translate in interesting insight. Aims: to phenotype heart failure (HF) patients based on the response in TAPSE vs HR. Methods: A total of 164 patients with HF and 32 healthy subjects with normal RV to pulmonary circulation (Pc) coupling, left atrium (LA) size and reservoir function (LA volume index &lt;34 ml/m 2 and LA-strain &gt;23%) underwent cardiopulmonary exercise testing combined with exercise Echo. TAPSE/HR slope was assessed using (peak TAPSE - rest TAPSE)/(peak HR - rest HR) ratio. According to the 95% confidence interval of TAPSE/HR slope (0.03 - 0.13, median 0.06) in healthy subjects, HF patients were divided into 2 groups: responders (TAPSE/HR ≥0.03, n=108) and non-responders (&lt;0.03, n=56) (figure). Results: There was no significant difference in age (65±12 vs 68±13 years), sex (70 vs 63% male), peak VO 2 (14±4 vs 13±4 ml/kg/min), and VE/VCO 2 slope (32±8 vs 33±10) between responder and non-responder group. However, responders exhibited a higher LA-strain at rest (21±12 vs 17±10%) and exercise (21±12 vs 17±10%), and a lower LA volume index (43±21 vs 52±27 ml/m 2 ) and mitral E/e’ (18±10 vs 22±11) than non-responders, respectively (P&lt;0.05). Non-responders exhibited a lower peak TPASE/pulmonary artery systolic pressure (PASP) ratio (0.34±0.18 vs 0.45±0.16, P&lt;0.001) than responders, although similar PASP (36±12 vs 34±15 mmHg) and TAPSE (19±5 vs 18±4 mm) were observed at rest in the 2 groups. Beta-blocker therapy was not a determinant of TAPSE/HR relationship. Conclusions: The RV force-frequency relationship may be impaired in HF. Especially in non-responders the lack of adaptive RV performance combines with worse RV to Pc coupling and atrial dysfunction. These data may offer additional insights in the concepts of exercise limitation in HF.
Abstract 11538: Impact of Family History of Premature Coronary Artery Disease on Non-Invasive Testing in Stable Chest Pain: A PROMISE Analysis
Authors: Viraj Raygor, Colby Ayers, Matthew W Segar, Kartik Agusala, Amit Khera, Ambarish Pandey, Parag H Joshi
Journal: Circulation (2021)

Introduction: Family history (FH) of premature CAD is a risk enhancer for adverse cardiovascular events. The preferred testing strategy to diagnose CAD in this high-risk population presenting with stable chest pain is unknown. Methods: This was a secondary analysis of the PROMISE trial, which randomized participants with stable chest pain to coronary computed tomographic angiography (CCTA) versus functional stress testing for the diagnosis of CAD and followed them for incident CV death or MI. Statistical analyses included logistic regression and Cox proportional hazard modeling. The effect of FH of premature CAD on the relationship between non-invasive testing modality and incident CV death or MI was assessed using interaction testing. Results: Patients with FH of premature CAD (n=3,098) were younger (58y vs 60y, p&lt;0.001) and more likely to be women (57% vs 51%, p&lt;0.001) than those without (n=6,584). They also had higher LDL-c levels (115 vs 112 mg/dL, p=0.01) and were more likely to be on aspirin (46% vs 44%, p=0.05) and a statin (48% vs 44%, p&lt;0.001) at baseline. Over a median follow-up of 2.1 years, 60 (1.9%) participants with and 148 (2.3%) participants without FH of premature CAD had a primary outcome event. FH of premature CAD was not associated with an increased risk of the primary composite outcome (HR 1.01; 95% CI 0.66, 1.57). There was no significant difference in CV death or MI whether patients underwent CCTA or functional stress testing, irrespective of FH of premature CAD (FIGURE; FH: 1.9% vs 2.0%, No FH: 2.2% vs 2.3%; interaction p-value=0.8). Conclusions: In patients with FH of premature CAD presenting with stable chest pain, an initial strategy of using CCTA to diagnose CAD is similar to functional testing for adverse cardiovascular outcomes.
Abstract 12022: Cardiac Rehabilitation for Patients With Idiopathic Hypertrophic Cardiomyopathy
Authors: Atsuko Nakayama, Hiroyuki Morita, Yuko Kato, Issei Komuro, Mitsuaki Isobe
Journal: Circulation (2021)

Introduction: Cardiac rehabilitation (CR) is strongly recommended for patients with cardiovascular diseases, but a few studies on exercise training for hypertrophic cardiomyopathy (HCM) are reported. Objective: The aim of this study is to clarify whether supervised CR could improve the long-term prognosis of patients with HCM. Methods: Our multicenter cohort study included 590 idiopathic HCM patients recruited into supervised CR with anaerobic threshold (AT) level from 2004 to 2018, who were divided into two groups according to CR duration; CR until discharge (non-CR group) and continuous outpatient CR after discharge (CR group). Mortality and major adverse cardiovascular events (MACE) were compared between the groups by Kaplan-Meier and Cox hazard analyses. Results: Follow-up period after registration was 3.4±2.6 years. Patients in CR group were older and their ejection fraction (EF) was lower than those in non-CR group (68±12 versus 62±19 years; p&lt;0.01 and 57±17 versus 63±15%; p&lt;0.001, respectively). The HCM patients in CR group had worse survival and relatively higher risk of MACE than those in non-CR group by Kaplan-Meier analysis (log rank, p=0.01 and p=0.08, respectively). However, the risk of death and MACE was similar between two groups by Cox hazard analysis adjusted by age, gender, hypertension, dyslipidemia, diabetes, smoking, EF, beta blockers, angiotensin-converting-enzyme inhibitors, angiotensin receptor blockers and statins (p=0.16 and p=0.64, respectively). Conclusions: Exercise with AT level for HCM patients did not significantly increase mortality, but continuous CR for patients with HCM should be carefully considered.
Abstract 13610: Obesity in Pediatric Hypertrophic Cardiomyopathy is Associated With Increased Inpatient Morbidity
Authors: Edward G Jones, Philip J Lupo, Joseph A Spinner, Hari P Tunuguntla, Jack F Price, Jeffrey J Kim
Journal: Circulation (2021)

Introduction: While obesity is associated with adverse outcomes among adults with hypertrophic cardiomyopathy (HCM), there has been little work to describe its impact on outcomes among children with HCM. Hypothesis: Obesity is associated with increased in-hospital morbidity in pediatric patients with HCM. Methods: In this cohort study, data from 52 children’s hospitals contained in the Pediatric Health Information System database from 2009 to 2019 were analyzed. Patients aged 2-18 years old with a primary diagnosis of HCM were included and assessed for obesity based on ICD-9/ICD-10 codes. Patients with a concomitant diagnosis of a congenital heart disease were excluded. Results: Out of a total of 2,667 children with HCM, the prevalence of obesity was 9.6%. Obese patients were more likely to be male, Black, Hispanic, older at age of initial hospitalization, and have a family history of sudden cardiac death (Table 1). After adjusting for age, sex, race, and ethnicity in multivariable analysis, obesity was independently associated with arrhythmia (OR 1.390 [1.029-1.879], P=0.032), heart failure (OR 1.809 [1.247-2.624, P=0.002), number of admissions (IRR 1.349 [1.158-1.573], P&lt;0.001), and cumulative length of stay (IRR 1.276 [1.093-1.491], P=0.002). Obesity was not associated with mortality. Conclusions: In pediatric patients hospitalized with a diagnosis of HCM, obesity was more common in underrepresented minorities and associated with increased morbidity after accounting for other risk factors. Reducing the burden of obesity in this population with effective counseling and lifestyle interventions may play a role in preventing obesity-related adverse outcomes.
Prophylaxis of Neutropenia with Mecapegfilgrastim in Patients with Hematologic Malignancies
Authors: Hui-qiang Huang, Zengjun Li, Gang Cheng, Gao Yan, Zhihua Yao, Guifang Zhang, Xiaoguang Wang, Zhengxiang Han, Yong Chen, Haijiao Yan, Weie Zheng, Jun Yan, Yulan Gu, Zhangxia Ren, Rusen Zhao, Ningling Zhang, Jun Ma
Journal: Blood (2021)