tbuckley/cabot-search huggingface dataset:
Abstract 16857: Acute Pericarditis With Concomitant Stemi Associated With Delayed Presentation in the Setting of SARS-COV-2 Pandemic
Authors: Jason Galo, Diego Celli, Mariam Khandaker, Murry Drescher, Carlos Alfonso
Journal: Circulation (2020)

Background: The classic ST-segment elevations seen in a STEMI can similarly be found during an episode of acute pericarditis, making the two entities difficult to distinguish. The incidence of post-myocardial infarction injury syndromes presenting with findings such as acute pericarditis is estimated to be around 3%. Prompt seek of medical care is pivotal in successful outcomes, which has been affected during the pandemic. Case: A 30-year-old female with a past medical history of uncontrolled type 1 diabetes, chronic kidney disease, obesity presented with a 24-hour long history of non-radiating chest pain. Upon interrogation she endorsed that initially she delayed her coming presentation to the hospital because of fears of contracting coronavirus. Physical examination showed tachycardia and tachypnea. EKG demonstrated diffuse ST elevations in the anterolateral leads concerning for a STEMI, PR-segment depressions on most leads and troponin elevation to 0.09 ng/ml. Point of care ultrasound (POCUS) echocardiogram showed significant anterolateral wall hypokinesis. Decision making: Given her high cardiovascular risk factors the patient was urgently taken to the catheterization laboratory which found a 100% ostial left anterior descending artery and a large left main coronary artery thrombus. The thrombus was initially treated with mechanical thrombectomy and the plaque with a percutaneous coronary intervention (PCI) with a drug-eluding stent to the proximal LAD. In the days following her PCI, the patient continued to endorse sporadic sharp chest pain with the same characteristics as on presentation. Post-PCI transthoracic echocardiogram demonstrated ejection fraction of 20-25% and a small pericardial effusion. She was started on colchicine for pericarditis. She was discharged home on dual antiplatelet therapy with close follow up. Conclusion: Given that our patient had clinical pericarditis before her presentation to the hospital with a STEMI, it is unlikely that her pericarditis was due to a post myocardial infarction syndrome. Delayed presentation to the hospital associated with fear of contracting or spreading COVID-19 is a silent collateral culprit that adds up to increased cardiovascular morbidity and mortality during this pandemic.
Abstract 16836: Quantitative Speckle Tracking Strain Analysis of Border and Remote Left Ventricular Regions After an Infero-Lateral Myocardial Infarction in a Chronic Swine Model
Authors: Daisuke Onohara, Takanori Kono, Kirthana Suresh, Alan Amedi, Muralidhar Padala
Journal: Circulation (2020)

Introduction: A myocardial infarction (MI) imposes a significant pathological load on the viable myocardium, leading to an acutely adaptive response and chronically maladaptive remodeling. In patients with an inferolateral MI, the mechanical load on the remote regions is significant, and thus the resulting ventricular remodeling is extensive and often leading to congestive heart failure. In this study, we used 3D echocardiography combined with speckle tracking strain to quantify the myocardial strains of the remote and border zone in an inferolateral MI swine. Hypothesis: An inferolateral MI imposes significant changes in myocardial strains is not only the border zone but also the remote regions. Methods: Six swine were induced with an inferolateral MI by ethanol injection. The animals were survived to 10 weeks post-infarction. Nine healthy swine were used as controls. Both animal groups underwent cardiac echocardiography with Siemens, by tunneling of a transesophageal probe into the thoracic cavity for direct placement onto the left atrium, such that the entire left heart was imaged. Strain analysis was performed with eSie LV analysis (Figure A). Results: EF was significantly lower than the control group (43.0±8.2% vs 52.2±5.2%, p=0.0190). EDV and ESV in the MI group were greater compared to the control group (127.8±32.0 ml vs 81.9±19.2 ml, p=0.0040, and 74.5±28.6 ml vs 38.5±6.8 ml, p=0.0027, respectively) indicative of remodeling. Circumferential end-systolic strains of basal- and mid-inferolateral wall in the MI group were significantly reduced compared to the control group (24.1±20.0% vs 48.0±18.6%, p=0.0339 and 10.5±11.4% vs 27.8±12.8%, p=0.0186, respectively). Similarly, longitudinal strain in mid-inferolateral wall in the MI group was significantly reduced (-7.8±5.8% vs -16.3±12.8%, p=0.0120) (Figure B, C). Conclusion: Reduction in both circumferential and longitudinal strains were observed in the border zone, but not in the remote zone.
Evidence of Targetable Immune Dysfunction in the Bone Marrow of Patients with Intermediate/High-Risk Myelodysplastic Syndrome Refractory to Hypomethylating Agents
Authors: Cherie Green, Mark Yan, Stefani Nalle, Connie Ma, Alberto Robert, Judy Zhong, Kartik Krishnan, Patrick Phuong, John Byon, Paul Woodard, Michael J. Nemeth, Elizabeth A. Griffiths, Joanne I. Adamkewicz, Jeffrey M. Venstrom, Monique Dail
Journal: Blood (2017)
Abstract 051: Pre-pregnancy Cardiometabolic Risk Factors, Mediterranean Style Diet, And Risk Of Preeclampsia In The Boston Birth Cohort
Authors: Anum Minhas, Xiumei Hong, Xiaobin Wang, Noel T Mueller
Journal: Circulation (2021)

Background: Preeclampsia carries high acute and chronic maternal and fetal morbidity and mortality. It is still unclear how pre-pregnancy conditions affect preeclampsia risk, and whether diet reduces risk. We examined associations of pre-pregnancy hypertension, obesity, and diabetes with preeclampsia, and investigated if a Mediterranean-style diet associates with lower risk. Methods: We used data from the Boston Birth Cohort, which comprises racially/ethnically diverse, urban, low-income mothers. We obtained maternal demographic and dietary intake frequencies via interviewer-administered questionnaires within 24-72 hours after birth. We extracted additional pregnancy-related clinical information, including physician diagnosis of preexisting conditions and preeclampsia from medical records. We created tertiles of a Mediterranean-style diet score previously created by our group. We performed logistic regression to assess associations of pre-pregnancy conditions and Mediterranean style diet with odds of preeclampsia. Results: Of 8,507 women in the sample, 849 developed preeclampsia. 47% were black, 28% were Hispanic, and the remaining were white/other. After multivariable adjustment (see table), pre-pregnancy hypertension had the strongest association with preeclampsia (OR 7.81; 95% CI 6.25-9.76), followed by obesity (OR 1.67; 95% CI: 1.41-1.99). Pre-pregnancy diabetes was not associated with preeclampsia after adjustment for obesity and hypertension (table). A higher Mediterranean-style diet score associated with lower preeclampsia odds, but it did not attenuate associations of hypertension or obesity with preeclampsia (table). Conclusions: Pre-pregnancy hypertension and obesity are independently associated with higher preeclampsia odds. Self-report of adherence to Mediterranean-style diet was also associated with lower preeclampsia odds, but this did not mediate risk among obese and hypertensive women. Strategies to prevent preeclampsia among high-risk women are needed.
55P Molecular risk factors for distant metastases in premenopausal patients with HR+/HER2- EBC
Authors: H. Ni, J. Kumbrink, D. Mayr, A. Seiler, F. Hagemann, T. Degenhardt, S. Sagebiel, R. Wuerstlein, N. Harbeck, T.K. Eggersmann
Journal: Annals of Oncology (2021)
Abstract P023: Leukocyte Count, Adiposity And Incident Diabetes In A Biracial Cohort
Authors: Debora Kamin Mukaz, Insu Koh, April P Carson, Joshua J Joseph, Leann Long, Timothy B Plante, Mary Cushman
Journal: Circulation (2021)

Background: Diabetes is one the costliest diseases in the U.S, and excess inflammation associates with greater diabetes risk. Greater adiposity is associated with higher leukocyte count, but the interrelations of body size phenotype, leukocytes, and incident diabetes is unknown. Hypothesis: Body size phenotype and incident diabetes can be further understood using leukocyte count in Black and White people. Methods: The study included 8075 Black and White participants without diabetes at baseline (2003-2007) in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. Body size phenotypes included metabolically healthy non-obese, metabolically healthy obese, metabolically unhealthy non-obese, and metabolically unhealthy obese. The interaction of leukocyte count with body size phenotype was assessed. As an exploratory analysis, data were further stratified by race. Results: The interaction of leukocyte count with body size phenotype was significant (p=0.02). In metabolically healthy individuals with or without obesity, the risk of diabetes increased across leukocyte quartiles. In healthy non-obese individuals, the risk of diabetes was 3 times higher in the top compared to the bottom quartile of leukocyte count and 4.5 times higher in unhealthy obese individuals. In contrast, there was no association in metabolically unhealthy participants with or without obesity. Considering race differences, in metabolically healthy non-obese persons, the association was 4 times higher for Black individuals and 2 times higher among White individuals. In the healthy obese group, these associations was larger in White than Black people. Conclusions: Higher leukocyte count is associated with the risk of diabetes in metabolically healthy individuals with or without obesity, but not among metabolically unhealthy individuals. Inflammation, as assessed by leukocyte count, does not identify added risk among those who are already classified as metabolically unhealthy.
Abstract 16920: Transcatheter Aortic Valve Replacement in Aortic Regurgitation: The U.S. Experience
Authors: Chinmy T Jani, Shilpkumar Arora, Sopan Lahewala, ZACHARY ZUZEK, Rahul Jaswaney, Samarthkumar J Thakkar, Harsh P Patel, Anandita Singh, Raj Patel, Poonam Bhyan, Brian Hoit, Mohammed Najeeb Osman, Guilherme Attizzani, Anthony Main, Sidakpal S Panaich
Journal: Circulation (2020)

Background: Transcatheter aortic valve replacement (TAVR) may be an effective option for high-risk AR patients. Although international experiences of TAVR for AR are published, U.S. data is limited. The primary objective of this study was to investigate periprocedural and 30-days outcomes in terms of mortality and post-procedural complications in patients undergoing TAVR for AR using large national U.S. databases. Hypothesis: TAVR is a promising option in AR Methods: Study cohorts were derived from Nationwide Inpatient Sample (NIS) and Nationwide Readmissions Database (NRD) 2016-17. TAVR and AR were identified using ICD-10-CM-codes. The key outcomes were all-cause mortality, disabling stroke, valvular complications, complete heart block (CHB)/ permanent pacemaker placement (PPM), open heart surgery, acute kidney injury (AKI) requiring dialysis, and vascular complications. Multivariate logistic regression was used to adjust for confounders. Results: 915 patients from the NIS (male-71%, age 65-84.2%) and 822 patients from the NRD (male-69.3%, age 65-80.5%) underwent TAVR for AR. The median length of stay (LOS) was 4 days for both cohorts. In-hospital mortality was 2.7% in NIS and 30-day mortality was 3.3% in NRD. Disabling strokes were noted in 0.6% peri-procedurally and 1.8% at 30-days. Valve-related complications were 18-19% with paravalvular leak being the most common. Approximately 11% of patients developed CHB and/or needed PPM in both cohorts. In NRD, 2.2% of patients required dialysis for AKI, 1.5% developed vascular complications, and 0.6% required open-heart surgery within 30-days post-procedure. Anemia was predictive of increased overall complications and valvular complications, whereas, peripheral vascular disease was predictor of increased valvular complications and CHB/PPM. Conclusion: TAVR is a promising option in AR. Further studies are necessary for the expansion of TAVR as standard treatment in AR.
Differences in Body Composition Convey a Similar Risk of Type 2 Diabetes Among Different Ethnic Groups With Disparate Cardiometabolic Risk—The HELIUS Study
Authors: Marleen Zethof, Charlotte M. Mosterd, Didier Collard, Henrike Galenkamp, Charles Agyemang, Max Nieuwdorp, Daniël H. van Raalte, Bert-Jan H. van den Born
Journal: Diabetes Care (2021)

Studies have shown a disparate association between body composition and the risk of type 2 diabetes. We assessed whether associations between differences in body composition and type 2 diabetes vary among ethnic groups with disparate cardiometabolic risk.We used data from the Healthy Life in an Urban Setting (HELIUS) study, including individuals aged 18-70 years of African Surinamese (n = 3,997), South Asian Surinamese (n = 2,956), Turkish (n = 3,546), Moroccan (n = 3,850), Ghanaian (n = 2,271), and Dutch (n = 4,452) origin living in Amsterdam. Type 2 diabetes was defined using the World Health Organization criteria. Logistic regression was used to assess the relation between body composition and type 2 diabetes. Waist-to-hip ratio (WHR), waist circumference, BMI, and body fat percentage by bioelectrical impedance were used to estimate body composition.Per unit change in BMI, only Ghanaian (odds ratio [OR] 0.94 [95% CI 0.89-0.99]) and Moroccan (0.94 [0.89-0.99]) women had a smaller increase in type 2 diabetes compared with the Dutch population, whereas the ORs for body fat percentage were 0.94 (0.89-1.00) for Ghanaian, 0.93 (0.88-0.99) for Moroccan, and 0.95 (0.90-1.00) for South Asian Surinamese women. There was no interaction between WHR and ethnicity on the risk of type 2 diabetes, and there were no differences in men. WHR had the highest precision in predicting type 2 diabetes in both men (C statistic = 0.78) and women (C statistic = 0.81).The association between differences in body composition and type 2 diabetes is roughly the same in all ethnic groups. WHR seems the most reliable and consistent predictor of type 2 diabetes regardless of ethnic background.
Liver Sinusoidal Endothelial Cells Suppress Bone Morphogenetic Protein 2 Production in Response to TGFβ Pathway Activation
Authors: Silvia Colucci, Sandro Altamura, Oriana Marques, Anne Dropmann, Natalie K. Horvat, Katja Müdder, Seddik Hammad, Steven Dooley, Martina U. Muckenthaler
Journal: Hepatology (2021)

Background and Aims TGFβ/bone morphogenetic protein (BMP) signaling in the liver plays a critical role in liver disease. Growth factors, such as BMP2, BMP6, and TGFβ1, are released from LSECs and signal in a paracrine manner to hepatocytes and hepatic stellate cells to control systemic iron homeostasis and fibrotic processes, respectively. The misregulation of the TGFβ/BMP pathway affects expression of the iron‐regulated hormone hepcidin, causing frequent iron overload and deficiency diseases. However, whether LSEC‐secreted factors can act in an autocrine manner to maintain liver homeostasis has not been addressed so far. Approach and Results We analyzed publicly available RNA‐sequencing data of mouse LSECs for ligand‐receptor interactions and identified members of the TGFβ family (BMP2, BMP6, and TGFβ1) as ligands with the highest expression levels in LSECs that may signal in an autocrine manner. We next tested the soluble factors identified through in silico analysis in optimized murine LSEC primary cultures and mice. Exposure of murine LSEC primary cultures to these ligands shows that autocrine responses to BMP2 and BMP6 are blocked despite high expression levels of the required receptor complexes partially involving the inhibitor FK‐506–binding protein 12. By contrast, LSECs respond efficiently to TGFβ1 treatment, which causes reduced expression of BMP2 through activation of activin receptor‐like kinase 5. Conclusions These findings reveal that TGFβ1 signaling is functionally interlinked with BMP signaling in LSECs, suggesting druggable targets for the treatment of iron overload diseases associated with deficiency of the BMP2‐regulated hormone hepcidin, such as hereditary hemochromatosis, β‐thalassemia, and chronic liver diseases.
Abstract 076: Longitudinal Trajectories And Predictors Of County-level Cardiovascular Mortality In The United States (1980-2014)
Authors: Shreya Rao, Amy E Hughes, Colby Ayers, Sandeep R Das, Ethan A Halm, Ambarish Pandey
Journal: Circulation (2021)

Introduction: CV mortality has declined over 4 decades in the U.S. However, whether declines have been uniformly experienced across U.S. counties, and predictors of CV mortality trajectory are not known. Methods: County-level mortality data from 1980-2014 was obtained from the National Center for Health Statistics. We used a ClustMix approach to identify 3 distinct county phenogroups based on mortality trajectory. Adjusted multinomial logistic regression models were constructed to evaluate the associations between county-level characteristics (demographic, social, and health status) and CV mortality trajectory-based phenogroups. Results: Among 3,133 counties, there were parallel declines in CV mortality in all groups (Fig.1A). High-mortality counties were located in the South and parts of the Ohio and Mississippi River valleys (Fig. 1B). County phenogroups varied significantly in social characteristics such as non-white proportion (low vs. high mortality: 12% vs. 27%), high-school education (11% vs. 20%), and violent crime rates (.01 vs. 0.3/100 population). Disparities in health factors were also observed with higher rates of smoking, obesity, and diabetes in the high (vs. low) mortality groups. A substantial collinearity was observed between social and health factors. In adjusted analysis, social, environmental, and health characteristics explained 56% variance in the county-level CV mortality trajectory. Education status (OR [95% CI]=12.4 [9.4-16.3]), violent crime rates (OR [95% CI] =1.6 [1.3-1.9]), and smoking (OR [95% CI] = 3.9 [3.1- 4.9]) were the strongest predictors of high mortality trajectory phenogroup membership (ref: low mortality). Conclusions: Despite a decline in CV mortality, disparities at the county-level have persisted over the past 4 decades largely driven by differences in social characteristics and smoking prevalence. This highlights the need for multi-domain interventions focusing on safety, education and public health to improve county-level disparities in CV health.
Abstract 15780: The Utility of Exercise Stress Testing in the Evaluation of Ischemia Among Pediatric Patients With Exertional Chest Pain
Authors: Nicholas Robles, Shailendra Upadhyay
Journal: Circulation (2020)

Introduction: Exertional chest pain (CP) regularly prompts performing an exercise stress test (EST) out of concern for exercise-induced ischemia. We aimed to study the diagnostic utility of EST in the evaluation of ischemia among pediatric patients without previously diagnosed congenital heart disease (CHD) who present with exertional CP and to correlate EST results with available cardiac imaging findings. Methods: Retrospective chart review of all pediatric patients who underwent EST for exertional CP from Jan 2015 to Dec 2019 at our institution. Exercise stress test was performed on treadmill utilizing Bruce protocol. Analysis included demographic medical records and all available cardiac testing. Results: A total of 106 patients (56 males; 53%) were included. Cohort mean age, height, and weight were 15.1 ± 2.6 years (range: 7.3 - 19.6yr), 165 ± 12.7 cm, and 67.5 ± 26.2 kg. ST-T wave changes were noted in 8 patients (7.5%), 7 of which were non-specific and read as normal ESTs. One (0.94%) EST was suggestive of ischemic changes. His echocardiogram (echo) showed mild thickening of papillary muscles and ventricular septum. A follow-up exercise myocardial perfusion study showed no abnormality. Echo was performed on 86/106 (81%) patients. Of these, 23/86 (27%) had incidental abnormalities on echo; none contributed to the patients’ CP. Five patients (5/86; 5.8%) had notable coronary artery abnormalities on echo; all had normal ESTs. Two of these were confirmed by Cardiac CTA: 1) Left Main Coronary Artery (LMCA) arising from non-coronary cusp, and 2) dilated LMCA (Z-score 4.67) with slight dilation of Left Anterior Descending (Z-score 2.54). In the other 3 of 5 ( prominent LMCA, possible CA fistula, RCA with more leftward origin ) further coronary evaluations were not performed. Conclusions: Incidental non-specific echo abnormalities are common among pediatric patients who undergo EST for exertional CP. EST was negative in patients with coronary artery abnormalities. ESTs have a low yield in identifying cardiac abnormalities among pediatric patients without previously diagnosed CHD undergoing evaluation for exertional CP. Larger studies are needed to better evaluate the utility of EST in patients with coronary artery anomalies.
Abstract 12677: Impaired Cardiomyocyte Contractility to Angiotensin-(1-12) in a Humanized Angiotensinogen Model of Hypertension
Authors: Yixi Liu, Heng Jie Cheng, Xiaoqiang Sun, Jing Cao, Zhe Chen, Jessica L VonCannon, Sarfaraz Ahmad, Carlos M Ferrario, Che Cheng
Journal: Circulation (2020)

Background: Angiotensin-(1-12) [Ang-(1-12)] is a chymase-dependent source for Angiotensin II (Ang II) inotropic activity that may be impaired in a model of sustained hypertension with high cardiac Ang II content due to insertion of the human angiotensinogen (AGT) gene in the rat genome. Accordingly, we evaluated the effects of Ang-(1-12) and Ang II on myocyte contractility and [Ca 2+ ] i regulation in 9 adult male transgenic rats expressing the human AGT gene [TGR(hAGT)L1623)] and 9 SD controls. Methods: We compared LV myocyte contraction, relaxation and [Ca 2+ ] i transient ([Ca 2+ ] iT ) responses to Ang-(1-12) (4x10 -6 M) and Ang II (10 -6 M) in freshly isolated LV myocytes. Results: Myocyte contraction (dL/dt max , 109.6 vs 127.9 μm/s), relaxation (dR/dt max , 95.3 vs 107.5 μm/s) and [Ca 2+ ] iT (0.15 vs 0.24) were depressed in TGR(hAGT)L1623 rats compared to SD controls. Moreover, cell contractile and [Ca 2+ ] iT responses following exposure to Ang-(1-12) or Ang II were markedly blunted. In SD myocytes, versus baseline, Ang II or Ang-(1-12) superfusion produced significant increases in dL/dt max [Ang II: 44% vs Ang-(1-12): 34%], dR/dt max (33% vs 26%) and [Ca 2+ ] iT (31% vs 25%). Importantly, the magnitude of the responses to the two agents in TGR(hAGT)L1623 myocytes was significantly reduced. Versus the changes in SD myocytes, Ang-(1-12) caused significantly less increases in dL/dt max (22%), dR/dt max (16%) and [Ca 2+ ] iT (15%) in TGR(hAGT)L1623 myocytes . Ang II also caused similar significantly attenuated increases in dL/dt max (27%), dR/dt max (25%) and [Ca 2+ ] iT (23%). The Ang-(1-12)-induced inotropic effects were completely prevented in the presence of the inhibitory cAMP analog, Rp-cAMPS (10 –4 M, 2 hours) in both SD and TGR(hAGT)L1623 myocytes, but were further augmented only intransgenic rats after incubation of myocytes with the G i inhibitor, pertussis toxin (PTX, 2 μg/ml, 36°C, 5 hours). Conclusions: Ang-(1-12) stimulates LV myocyte contractile function and [Ca 2+ ] iT in both SD and TGR(hAGT)L1623 rats. Furthermore, we now show that the blunted inotropic responses to Ang-(1-12) and Ang II in rats expressing the human AGT gene is mediated through a cAMP-dependent mechanism that is coupled to both stimulatory G and inhibitory PTX-sensitive G proteins.
Prediction of Severe Acute Graft-Versus-Host Disease (aGVHD) Based on Whole Transcriptome Sequencing of Donor CD4 T Cells
Authors: Silvy Lachance, Jonathan Séguin, Ann Brasey, Jean-Philippe Laverdure, Vincent T Ho, Jerome Ritz, Jan Storek, Denis-Claude Roy, Lambert Busque, Sébastien Lemieux, Claude Perreault
Journal: Blood (2017)