tbuckley/cabot-search huggingface dataset:
Abstract 12727: Microvascular Coronary Dysfunction Affects Global Longitudinal Strain After Dipyridamole Stress Echocardiography
Authors: Ercole Tagliamonte, Caterina Montuori, Roberta Astarita, Lucia Riegler, Alberto Forni, Raffaella Scarafile, Simona Sperlongano, Alessandro Di Vilio, Francesco Gambardella, Juri Radmilovic, Gennaro Cice, Antonello D'Andrea
Journal: Circulation (2020)

Introduction: Coronary microvascular dysfunction (CMD) is a potential cause of myocardial ischemia and may affect myocardial function. CMD can be identified, in patients with non-obstructive coronary artery disease (CAD), by a reduced transthoracic Doppler-derived coronary flow reserve (CFR), which is an index of coronary arterial reactivity. Hypothesis: The aim of this study was to investigate the dipyridamole-induced changes of global longitudinal strain (GLS) in patients with CMD. Methods: fiftythree patients (35M, 18F; mean age 67±8 years) without obstructive CAD, assessed by invasive coronary angiogram, underwent dipyridamole stress echocardiography. CFR were determined as the ratio of hyperaemic to baseline diastolic coronary flow velocity. CMD was defined as CFR &lt; 2. GLS was visualized as a bull’s-eye map in a quick and feasible manner. In each patient, we used a frame rate of 70 frames/sec for adequate 2D strain analysis. We analyzed GLS at each step of stress test and compared peak-dose values with baseline. Results: Sixteen patients (30%) among the overall population showed CMD. There were no significant differences in baseline characteristics between patients with or without CMD. GLS, at baseline, was significantly lower in patients with CMD (-16.7±3.77 vs. -17.9±3.75 - p&lt;0.01). We observed a different response to dipyridamole stress echocardiography, between the two groups: GLS significantly increased up to peak dose in patients without CMD (from -17.9±3.75 to -19.5±4.12 - p&lt;0.01), whereas on the other hand, a significant decrease from rest to peak dose was observed in patients with CMD (from -16.7±3.77 to -15.4±4.21- p&lt;0.01). There was a significant inverse correlation between CFR and delta GLS measured at rest and after dipyridamole peak dose (r = -0.83 - p&lt;0.01). Conclusions: GLS analysis, performed by comparing dipyridamole peak-dose with baseline values, shows that in patients with CMD there is a different response of left ventricular myocardiim to stress test. It could be assumed that the inverse correlation between CFR and delta GLS reflects a progressive subclinical worsening of left ventricular myocardial function in these patients. Larger studies could confirm our data.
Strain-Guided Management of Potentially Cardiotoxic Cancer Therapy
Authors: Paaladinesh Thavendiranathan, Tomoko Negishi, Emily Somerset, Kazuaki Negishi, Martin Penicka, Julie Lemieux, Svend Aakhus, Sakiko Miyazaki, Mitra Shirazi, Maurizio Galderisi, Thomas H. Marwick, Kazuaki Negishi, Ben Costello, Leah Wright, Andre La Gerche, Phil Mottram, Liza Thomas, Mitra Shirazi, Martin Penicka, Tomas Ondrus, Stephanie Seldrum, Krassimira Hristova, Paaladinesh Thavendiranathan, Eitan Amir, Babitha Thampinathan, Julie Lemieux, Marc-Andre Cote, Jonathan Deblois, Manish Bansal, Maurizio Galderisi, Ciro Santoro, Koji Kurosawa, Nobuaki Fukuda, Hirotsugu Yamada, Yoshihito Saijo, Sakiko Miyazaki, Masaki Izumo, Tomomi Suzuki, Kazuko Tajiri, Goo Yeong Cho, Svend Aakhus, Klaus Murbræch, Richard Massey, Wojciech Kosmala, Maciej Sinski, Dragos Vinereanu, Diana Mihalcea, Bogdan Popescu, Andreea Calin, Evgeny Shkolnik, Jose Banchs, Shelby Kutty
Journal: Journal of the American College of Cardiology (2020)
Sixty seconds on . . . Marcus Rashford
Authors: Gareth Iacobucci
Journal: BMJ (2020)

True, but the Manchester United and England star has recently been making as many headlines for his positive contributions off the pitch as on it.

Pretty much, yes. Not content with forcing ministers into two separate U turns over offering free school meals to children from low income families outside term time, the striker’s latest goal is to improve child literacy …
Abstract 13807: Semaglutide Provides More Value for Money Than Dulaglutide or Liraglutide for Prevention of Major Adverse Cardiovascular Events in Patients With Type 2 Diabetes Mellitus and Established Cardiovascular Disease
Authors: Joseph Azuri, Enis Aboalhasan, Ariel Hammerman, Ronen Arbel
Journal: Circulation (2020)

Introduction: The Glucagon-Like Peptide-1 receptor agonists (GLP-1a) semaglutide, dulaglutide, and liraglutide reduce major adverse cardiovascular events (MACE) in patients with Type 2 diabetes mellitus ( T2DM) and established CVD. The American Diabetes Association currently recommends providing GLP-1a therapy to this patient population independently of glycaemic control. Despite proven clinical benefits, providing GLP-1a to all guideline eligible patients is a significant cost burden on healthcare systems. Therefore, it is imperative to compare the value for money of these agents. Hypothesis: The newly introduced GLP-1a Semaglutide may be cost-saving compared to dulaglutide and liraglutide for preventing MACE in patients with established CVD and T2DM. Methods: We calculated the cost needed to prevent one MACE, by multiplying the annualized number needed to treat to prevent one event, by the annual cost of the therapy. Efficacy estimates were extracted from published RCT data. We performed a sensitivity analysis to mitigate differences between trial populations and other uncertainties. Drug costs were based on published US prices. Results: The cost needed to prevent one MACE with semaglutide is $557,187 ($331,491-$2,194,483) compared to $1,179,360 ($732,888-$2,746,224) with liraglutide and $1,605,904 ($706,044-∞) for dulaglutide. Sensitivity analysis confirmed the advantage of semaglutide. Conclusions: Semaglutide prescribed for secondary prevention of MACE in patients with T2DM and established CVD seems to provide more value for money than dulaglutide and liraglutide for the same purpose.
Abstract 15428: Network Meta-analysis of Duration of Antiplatelet Therapy Following Transcatheter Aortic Valve Replacement
Authors: Yujiro Yokoyama, Toshiki Kuno, Alexandros BRIASOULIS, Makoto Mori, Masao Iwagami, Hisato Takagi, Sripal Bangalore
Journal: Circulation (2020)

Background: Although current guidelines recommend dual antiplatelet therapy (DAPT) for 3 to 6 months following transcatheter aortic valve replacement (TAVR), there are no studies directly comparing outcomes of different durations of DAPT following TAVR. Methods: Pubmed and EMBASE were searched through May, 2020 to identify clinical studies that investigated single antiplatelet therapy (SAPT) versus DAPT use following TAVR. Studies using oral anticoagulants and antiplatelet therapy concomitantly were excluded. The DAPT group was subdivided by the duration of DAPT. We extracted the risk ratios (RRs) of major or life-threatening bleeding, stroke, and all-cause mortality. Results: Three randomized controlled trials, two propensity-score matched studies, and one observational study were identified, yielding a total of 1,833 patients who underwent TAVR assigned to the SAPT group (n=918), 3-month DAPT group (n=151), or 6-month DAPT group (N=764). Pooled analyses demonstrated that the rates of major or life-threatening bleeding were significantly higher in the 6-month DAPT group compared with the SAPT group (RR [95% CI] =2.54 [1.49-4.33], P =0.007) while no such difference was observed between the SAPT vs. 3-month DAPT groups or the 3-month DAPT vs. 6-month DAPT groups (Figure). P-scores were 98.1% (SAPT), 32.3% (3-month DAPT), and 19.6% (6-month DAPT). The rates of stroke and all-cause mortality were similar among the groups. Conclusions: In our network meta-analysis, we observed that DAPT for 6 months following TAVR was associated with increased risk of bleeding without decreasing the risk of stroke compared with SAPT, while there was no difference between DAPT for 3 months and 6 months.
Diaphragm Pathology in Critically Ill Patients With COVID-19 and Postmortem Findings From 3 Medical Centers
Authors: Zhonghua Shi, Heder J. de Vries, Alexander P. J. Vlaar, Johannes van der Hoeven, Reinier A. Boon, Leo M. A. Heunks, Coen A. C. Ottenheijm
Journal: JAMA Internal Medicine (2020)

risk adults living with such workers.One limitation is that the study's prepandemic data do not reflect current employment levels, changes in ability to WAH, or local infection rates.Additionally, risk factors were reported by MEPS participants rather than measured by medical professionals, likely causing an underestimate of risk.Policy makers seeking to make efficient and equitable decisions about reopening the economy and about vaccine distribution should consider the health risks not only of workers, but also of those with whom they live.
Abstract 17202: Racial/Ethnic Minority Underreporting and Underrepresentation in Guideline-Driving Blood Cholesterol Clinical Trials
Authors: Ashish Sarraju, Areli Valencia, Joshua Knowles, David J Maron, Fatima Rodriguez
Journal: Circulation (2020)

Introduction: Cholesterol management is the cornerstone of atherosclerotic cardiovascular disease prevention. Diverse racial/ethnic participation in high-impact cholesterol trials is essential for the generalizability of trials and guidelines across the United States (US). Methods: We analyzed randomized clinical trials (RCTs) cited in the 2018 American Multi-society Guideline on the Management of Blood Cholesterol for reporting and representation of racial/ethnic minorities. We extracted participant level racial/ethnic data, including non-Hispanic White (NHW), Black, Hispanic, or Asian groups. For each race/ethnicity, we pooled trial data to assess overall representation compared to the general US population based on 2010 US Census and 2019 US Census American Community Survey estimates. Results: Among 71 cited RCTs from 1984 - 2017, 59.1% reported racial/ethnic data. NHW participation was reported in 58%, Black in 34%, Hispanic in 27%, and Asian in 17% (Figure). Four trials disaggregated Hispanic patients and none disaggregated Asians. Black trial representation was significantly lower than the US population per 2010 and 2019 Census data (trial: 5.5%, 2010: 12.6%, 2019: 13.4%, P &lt;0.001). Hispanic trial representation was significantly lower compared to the US population (trial: 10.6%, 2010: 16.3%, 2019: 18.3%, P &lt;0.001). NHW trial participation was lower compared to the US population (trial 69.2%; 2010: 72.4%; 2019: 76.5%, P &lt;0.001), but with smaller relative differences compared to Black and Hispanic representation. Asian participation was higher than US census representation. Conclusion: Among guideline-driving cholesterol RCTs, Black and Hispanic participants are significantly underrepresented compared to the general U.S. population. Few studies disaggregate major racial/ethnic subgroups. These findings represent a source of systemic bias that may limit the generalizability of trials and guidelines and potentiate health inequities.
Abstract 15381: Subjective and Objective Impact of Angiotensin Receptor-neprilysin Inhibitor on Systemic Right Ventricle Patients
Authors: Georges Ephrem, Jonathan C McCollum, Deborah Green-Hess, Stephen G Sawada, Maya Guglin, Roopa A Rao
Journal: Circulation (2020)

Introduction: Adult Congenital Heart Disease (ACHD) patients have increased mortality and morbidity from heart failure. Angiotensin receptor-Neprilysin Inhibitors (ARNI) have emerged as a standard of therapy for adults with heart failure. These medicines have not been studied in ACHD patients. Hypothesis: ARNIs are associated with subjective and objective improvements in systemic right ventricle (SRV) patients. Methods: Eighteen SRV patients were prescribed ARNI at our institution in the last 3 years. Data including demographics, medical history, New York Heart Association functional class (NYHA FC), labs, 3D imaging, echocardiograms, cardiopulmonary stress test (CPET), and hospitalization were obtained by retrospective electronic chart review. Statistical analysis was performed using paired t and Wilcoxon rank sum tests. Results: Eighteen SRV patients (mean age 40 years, 72% male) were treated with ARNI (median 13 months) and conventional therapy (beta blocker (83%), loop diuretic (89%), antiarrhythmics (33%), and anticoagulation (50%)). Baseline data include: Mean blood pressure 118/75 mmHg, pulse 75 bpm, creatinine 0.86 mg/dL, potassium 4 meq/L, B-type natriuretic peptide (BNP) 322 pg/mL, and NT-Pro BNP 1091 pg/mL. Nine patients were NYHA FC 2, 7 FC 3, and 2 FC 4. High dose was achieved in 3 (17%) patients, and moderate in 3 (17%). CPET and imaging data were: VO2 18 mL/kg/min, VE/VCO2 38, RVEF 32%, FAC 21%, significant TR (12.5% moderate, and 12.5% severe) and TAPSE 9.4. There was no statistically significant difference pre vs post-ARNI in blood pressure, labs (creatinine, potassium, BNP and NT-ProBNP), or testing (VO2 18 vs 17, p=0.432; VEVCO2 38 vs 39, p=0.850; RVEF 32 vs 32%, p=0.648; FAC 18 vs 21%, p=0.489; TR p=0.317; and TAPSE 9.2 vs 9.1, p=0.906). There was a statistically significant improvement in median NYHA FC (2 vs 2.5, p=0.005), especially if baseline NYHA FC&gt;2 (2 vs 3, p=0.011). There was a noted decrease in cardiac hospitalization (4 vs 9) that did not reach statistical significance (p=0.313). Conclusions: ARNIs are associated with noticeable improvement in functional class without impact on objective measures in SRV patients. The study findings are promising and highlight the need for larger, prospective, multicenter studies.
Osteopontin Links Myeloid Activation and Disease Progression in Systemic Sclerosis
Authors: Xia Gao, Guiquan Jia, Anna Guttman, Daryle J. DePianto, Katrina B. Morshead, Kai-Hui Sun, Nandhini Ramamoorthi, Jason A. Vander Heiden, Zora Modrusan, Paul J. Wolters, Angelika Jahreis, Joseph R. Arron, Dinesh Khanna, Thirumalai R. Ramalingam
Journal: Cell Reports Medicine (2020)

Progressive lung fibrosis is a major cause of mortality in systemic sclerosis (SSc) patients, but the underlying mechanisms remain unclear. We demonstrate that immune complexes (ICs) activate human monocytes to promote lung fibroblast migration partly via osteopontin (OPN) secretion, which is amplified by autocrine monocyte colony stimulating factor (MCSF) and interleukin-6 (IL-6) activity. Bulk and single-cell RNA sequencing demonstrate that elevated OPN expression in SSc lung tissue is enriched in macrophages, partially overlapping with CCL18 expression. Serum OPN is elevated in SSc patients with interstitial lung disease (ILD) and prognosticates future lung function deterioration in SSc cohorts. Serum OPN levels decrease following tocilizumab (monoclonal anti-IL-6 receptor) treatment, confirming the connection between IL-6 and OPN in SSc patients. Collectively, these data suggest a plausible link between autoantibodies and lung fibrosis progression, where circulating OPN serves as a systemic proxy for IC-driven profibrotic macrophage activity, highlighting its potential as a promising biomarker in SSc ILD.
Abstract 341: A Simple Prognostic Tool for In-Hospital Death in Patients Presenting with Out-of-Hospital Cardiac Arrest and ST-Elevation Myocardial Infarction
Authors: Andy T Tran, Anthony J Hart, John Spertus, Philip Jones, Ali O Malik, Paul S Chan
Journal: Circulation (2020)

Background: In the emergent setting of ST-Elevation Myocardial Infarction (STEMI) complicating out-of-hospital cardiac arrest (OHCA), decisions for immediate coronary angiography are made when the likelihood of hospital survival is unknown. Estimating the risk of mortality at the time of hospital arrival might inform decisions for primary percutaneous coronary intervention. Methods: From the Cardiac Arrest Registry to Enhance Survival (CARES), we included adult OHCA patients from 2013-2018 presenting to hospitals with a STEMI. We developed a predictive model for in-hospital mortality using multivariable logistic regression to derive a scoring tool that was internally validated with bootstrap methods. Results: Of 7120 patients with OHCA and STEMI admitted at a hospital (mean age 62±13.2 years, 27% female), 3159 (44.4%) died during hospitalization. Higher age, unwitnessed arrest, non-shockable cardiac arrest rhythm, no sustained return of spontaneous circulation (ROSC) at the time of hospital admission, and resuscitation time on scene were most predictive of mortality (C-index, 0.82). Using the model β coefficients, we developed an integer risk score ranging from 0 to 10 points, corresponding to observed mortality rates of 5% to 100% (Figure 1). The odds of in-hospital mortality doubled for each 1-unit score increase (odds ratio, 2.01; 95% CI, 1.94-2.09; p&lt;0.0001), and a score of ≥6, involving ~15% of patients, was associated with ≥85% in-hospital mortality risk. Conclusions: This risk score, based on simple prehospital characteristics, stratifies the range of in-hospital mortality from 5% to nearly 100% in OHCA patients with STEMI at the time of hospital presentation. The benefits of such a model in decision-making for immediate coronary angiography should be prospectively studied.
Abstract PO-019: The JAK/STAT3 pathway drives myeloid-mediated immunosuppression in pancreatic cancer
Authors: Ashley Velez-Delgado, Kristee Brown, Marina Pasca di Magliano
Journal: Cancer Research (2020)

Abstract Pancreatic Ductal Adenocarcinoma (PDAC) is a lethal malignancy with a 5-year survival rate of 10%. PDAC is characterized by a dense stroma with a heterogeneous population of fibroblasts and infiltrating immune cells. While the immune infiltration is abundant, it is mostly composed of immunosuppressive cells, such as tumor associated macrophages and myeloid derived suppressive cells (MDSCs). Hence, effective anti-tumor CD8+ T cell responses are not elicited in PDAC. My preliminary data shows that the JAK/STAT3 signaling pathway is active in the stroma, specifically in fibroblasts and myeloid cells. My main goal is to investigate the role of JAK/STAT3 signaling pathway in driving immunosuppression by myeloid cells. I hypothesize that targeting JAK/STAT3 pathway in myeloid cells will lead to reversion of the immunosuppressive phenotype aiding in the treatment of pancreatic cancer. To understand the role of JAK/STAT3 signaling in the polarization of myeloid cells and consequently in tumor growth, I used a genetically engineered mouse model (LysMCre;Stat3f/f) that depletes Stat3 specifically in myeloid cells. Using this mouse model, I implanted syngeneic tumor cells orthotopically in the pancreas. After two weeks, I weighed the tumor, and assessed the immune infiltration by Mass Cytometry (CyTOF). Deleting Stat3 from myeloid cells resulted in a significant decrease in tumor mass compared to controls. Analysis showed a decrease in macrophages and increase in memory CD8+ and CD4+ T cells, suggesting a decrease in the immunosuppressive capacity of the myeloid cells. Currently, I am investigating the mechanism by which JAK/STAT3 pathway disruption impairs tumor growth. Citation Format: Ashley Velez-Delgado, Kristee Brown, Marina Pasca di Magliano. The JAK/STAT3 pathway drives myeloid-mediated immunosuppression in pancreatic cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PO-019.
Abstract 17231: Adult Protein Energy Malnutrition is an Independent Risk Factor With Increased Odds of Cardiogenic Shock in Patients With Infective Endocarditis Who Had Valve Replacement
Authors: Pius Ojemolon, Hafeez Shaka, Ehizogie Edigin, Iriagbonse Asemota, Emmanuel Akuna
Journal: Circulation (2020)

Introduction: Protein Energy Malnutrition (PEM) is common among adults with chronic medical conditions, especially in patients with chronic heart, lung disease and malignancies. These conditions are associated with worse in hospital outcomes. However, the complex relationship between chronic medical conditions and PEM make the true effect of PEM on outcomes difficult to ascertain. This is compounded by the relative underdiagnosis of PEM in adults. Our study aimed to determine if PEM is an independent risk factor for adverse outcomes among patients with infective endocarditis (IE) who had mitral valve (MV) and /or aortic valve (AV) replacement surgery. Methods: Data was obtained from the National Inpatient Sample for 2016 &amp; 2017. Studied cohort were patients with IE who underwent AV and /or MV replacement. This group was divided by presence or absence of PEM using ICD-10 codes. Primary outcome was inpatient mortality. Secondary outcomes were total hospital charges, length of stay (LOS), NSTEMI, post procedural cardiac complications, acute kidney failure (AKI) and need for intra aortic balloon pump (IABP). Multivariate logistic and linear regression models were used to compare outcomes. Results: A total of 4275 hospitalizations met the inclusion criteria, of which about a fifth (20.12%) had PEM.Patients with PEM had higher adjusted odds of post procedural cardiogenic shock (aOR: 3.65, 95% CI: 1.724 - 7.746), and need for IABP placement (aOR: 4.01, 95% CI: 1.958 - 8.199), as well as significantly higher mean difference in total hospital charges and length of stay, relative to patients without PEM. There was however no significant difference in mortality, composite post procedural cardiac complications, NSTEMI or AKI between the PEM and non-PEM subgroup. Conclusion: PEM is associated with post procedural cardiogenic shock and intra-aortic balloon pump placement in patients with infective endocarditis who underwent valve replacement surgery but this impact did not translate to higher mortality. More research is needed to elucidate the role of PEM as a major comorbidity.
Abstract 16335: Metabolic Reprogramming From Glycolysis to Amino Acid Utilization in Cardiac Hif1 Alpha Deficient Mice
Authors: Ivan Menendez-Montes, Beatriz Escobar, Manuel J Gómez, Teresa Albendea-Gomez, Beatriz Palacios, Elena Bonzon, Ana V Alonso, Alessia Ferrarini, Luis J Jimenez-Borreguero, Jesus Vazquez, Silvia Martin Puig
Journal: Circulation (2020)

Introduction: Hypoxia is an important environmental cue implicated in several physiopathological processes, including cardiac development. Several gain of function models described before indicate that HIF1 signaling needs to be tightly regulated to ensure proper heart formation. However, there is lack of consensus about the functional outcomes of cardiac HIF1 elimination. We have previously reported that HIF1alpha expression is spatiotemporally regulated along cardiogenesis, establishing metabolic territories in the embryonic myocardium and controlling a switch from glycolysis to fatty acid oxidation (FAO) essential for chamber formation and cardiomyocyte maturation. Objectives and Hypothesis: We aim to assess the consequences of cardiac deletion of HIF1alpha during heart development and identify the adaptations to HIF1 signaling loss. Based on the tight regulation of HIF1alpha expression during cardiogenesis, we anticipated significant alterations of cardiac metabolism as well as functional and structural defects in HIF1alpha mutants. Methods and Results: A new conditional Hif1alpha knock out was generated in NKX2.5 cardiac progenitors. By means of histology, electron microscopy and high-throughput genomics, proteomics and metabolomics, we found that deletion of Hif1alpha leads to impaired embryonic glycolysis without influencing cardiomyocyte size or proliferation and results in increased mitochondrial number, transient activation of amino acid response and upregulation of HIF2alpha and ATF4. HIF1alpha mutants display normal FAO metabolic profile and do not show cardiac dysfunction in the adulthood. Conclusions: We demonstrated that HIF1 signaling is dispensable for heart development and uncovered the metabolic flexibility of the mammalian embryonic myocardium, able to utilize alternative fuels to carbohydrates in contrast to other vertebrates like zebrafish. This data highlights the importance of HIF in cardiac metabolic programing and could explain the distinct proliferative and regenerative capacity of cardiomyocytes from different species in response to cardiac injury.