tbuckley/cabot-search huggingface dataset:
Abstract 11117: Metabolomic Signature of Ideal Cardiovascular Health in Black Adults: Results from the Morehouse-Emory Cardiovascular (MECA) Center for Health Equity
Authors: Shabatun Islam, Chang Liu, Appesh Mohandas, Kimberly Rooney, Aditi Nayak, Anurag Mehta, Yi-An Ko, Jeong Hwan Kim, Elizabeth I Olorundare, Tene Lewis, Herman A Taylor, karan uppal, Dean Jones, Arshed A Quyyumi, Charles D Searles
Journal: Circulation (2021)

Introduction: Black Americans suffer from disparate levels of CVD and CVD risk factors, but metabolic pathways that underlie cardiometabolic risk in Blacks remain largely unknown. Objective: We defined metabolomic profiles and associated metabolic pathways underlying CVH in a Black community that is richly diverse in ethnic origin and socioeconomic status. Methods: The MECA study cohort consisted of 375 Black adults (age 53 + 10, 39% male) without known CVD. CVH was determined by the AHA Life’s Simple 7 (LS7) score, calculated from measured blood pressure, body mass index (BMI), fasting blood glucose, total cholesterol, and self-reported physical activity, diet, and smoking. Plasma metabolites were assessed by high-resolution metabolomics. Metabolome wide association study (MWAS) was used to identify metabolites associated with LS7 after adjusting for age and sex. Metabolic pathways significantly enriched in metabolites associated with LS7 were identified using Mummichog software. Concentrations of metabolites representative of these pathways were compared across clinical domains of LS7 score (ANOVA) and then a multivariable model was developed into a metabolomics risk score for prediction of CVH. Results: MWAS and pathway analysis identified 301 metabolites significantly associated with LS7 score (FDR&lt;0.2) and enriched in pathways responsible for glutathione, alanine, tyrosine and glutamate metabolism. Plasma concentrations of six metabolites (glutamine, glutamate, serine, alanine, tyrosine and urate) were associated with blood pressure, fasting glucose, BMI, and physical activity (p&lt;0.05). Assessed in conjunction, these metabolites were independent predictors of CVH - 1 SD increase in metabolomics risk score was associated with 0.93 increase in LS7 or 12.1% decrease in incident CVD. Conclusions: We identified a novel metabolomic signature of ideal CVH in Blacks without known CVD. This includes five non-essential amino acids and urate, which are known to be central elements of key metabolic processes (i.e. TCA cycle, urea cycle, nucleotide synthesis, one carbon metabolism). These data provide insight into metabolic pathways underlying cardiometabolic risk in Blacks and potential avenues for addressing health disparities.
International variation in oesophageal and gastric cancer survival 2012–2014: differences by histological subtype and stage at diagnosis (an ICBP SURVMARK-2 population-based study)
Authors: Melina Arnold, Eileen Morgan, Aude Bardot, Mark J Rutherford, Jacques Ferlay, Alana Little, Bjorn Møller, Oliver Bucher, Prithwish De, Ryan R Woods, Nathalie Saint-Jacques, Anna T Gavin, Gerda Engholm, Michael P Achiam, Geoff Porter, Paul M Walsh, Sally Vernon, Serena Kozie, Agnihotram V Ramanakumar, Charlotte Lynch, Samantha Harrison, Neil Merrett, Dianne L O’Connell, Tom Mala, Mark Elwood, John Zalcberg, Dyfed W Huws, David Ransom, Freddie Bray, Isabelle Soerjomataram
Journal: Gut (2021)

Objective To provide the first international comparison of oesophageal and gastric cancer survival by stage at diagnosis and histological subtype across high-income countries with similar access to healthcare. Methods As part of the ICBP SURVMARK-2 project, data from 28 923 patients with oesophageal cancer and 25 946 patients with gastric cancer diagnosed during 2012–2014 from 14 cancer registries in seven countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the UK) were included. 1-year and 3-year age-standardised net survival were estimated by stage at diagnosis, histological subtype (oesophageal adenocarcinoma (OAC) and oesophageal squamous cell carcinoma (OSCC)) and country. Results Oesophageal cancer survival was highest in Ireland and lowest in Canada at 1 (50.3% vs 41.3%, respectively) and 3 years (27.0% vs 19.2%) postdiagnosis. Survival from gastric cancer was highest in Australia and lowest in the UK, for both 1-year (55.2% vs 44.8%, respectively) and 3-year survival (33.7% vs 22.3%). Most patients with oesophageal and gastric cancer had regional or distant disease, with proportions ranging between 56% and 90% across countries. Stage-specific analyses showed that variation between countries was greatest for localised disease, where survival ranged between 66.6% in Australia and 83.2% in the UK for oesophageal cancer and between 75.5% in Australia and 94.3% in New Zealand for gastric cancer at 1-year postdiagnosis. While survival for OAC was generally higher than that for OSCC, disparities across countries were similar for both histological subtypes. Conclusion Survival from oesophageal and gastric cancer varies across high-income countries including within stage groups, particularly for localised disease. Disparities can partly be explained by earlier diagnosis resulting in more favourable stage distributions, and distributions of histological subtypes of oesophageal cancer across countries. Yet, differences in treatment, and also in cancer registration practice and the use of different staging methods and systems, across countries may have impacted the comparisons. While primary prevention remains key, advancements in early detection research are promising and will likely allow for additional risk stratification and survival improvements in the future.
Abstract 10852: Cardiology and Telehealth in the Pandemic
Authors: Okechukwu Mgbemena, Kyeesha Becoats, Ian Tfirn, Gladys R Velarde
Journal: Circulation (2021)

Introduction: Historically, healthcare access has been an achilles heel of our healthcare system. Approximately 14.5% of US adults lack readily available access to healthcare and this has been worsened by the COVID-19 pandemic. There is limited data on use of telehealth in cardiology. We share our single-center experience on improving access to care via telehealth at the University of Florida cardiology fellows' clinic. Methods: Demographic and social variables were collected 6 months prior to and 6 months after initiation of telehealth. The effect of telehealth was determined via Chi-square and multiple logistic regression while controlling for demographic covariates. Results: We analyzed 3,316 cardiac clinic appointments over one year period. 1,569 and 1,747 scheduled clinic visits were prior to and after the start of telehealth, respectively. Patients that attended their scheduled follow-up had significantly greater odds of being in the post-telemedicine group while controlling for marital status and insurance type (OR 1.31, 95% CI 1.07 - 1.62). Patients who attended had higher odds of having city contract insurance (OR 3.51, 95% CI 1.79 - 6.87) compared to private insurance. City contract insurance is an indigenous care plan. There are also higher odds of being previously married (OR 1.34, 95% CI 1.05 - 1.70) or married/dating (OR 1.39, 95% CI 1.05 - 1.82) compared to being single for patients who attended their scheduled visits. Telehealth did not lead to increase in use of Mychart, the electronic patient portal (P-value 0.55). Conclusions: Telehealth improved patients’ access to care in a cardiology fellows' clinic during the COVID-19 pandemic. Telehealth as a resource adjunct to traditional care in cardiology fellows' clinic should be further explored.
Perioperative Outcomes Associated with Inhibitor Status in Patients with Hemophilia - a Retrospective Cohort Study
Authors: Omotola O. Olasupo, Charles Nakar, Alfonso Iorio, Craig Haddix, Thushara Mathew, Lynn M Malec, Davide Matino, Lawrence Mbuagbaw, Jean-Eric Tarride, Amy D. Shapiro
Journal: Blood (2021)
Abstract P358: Cardiac Innervation Remodeling And Impaired Brain Derived Neurotrophic Factor (bdnf) Levels In Physiological Aging Vivo Model
Authors: Andrea Elia, Alessandro Cannavo, Giuseppina Gambino, Maria Cimini, Nicola Ferrara, Raj Kishore, Nazareno Paolocci, Giuseppe RENGO
Journal: Circulation Research (2021)

Aging is a multifactorial process associated with gradual loss of function and decay involving several neurohormonal systems, such as the autonomic nervous system (ANS). Progressive remodeling of ANS, induces a circulating catecholamines spillover and cardiac autonomic fibers depletion with raising both morbidities and mortality risk. Neurotrophic factors (NF) play a pivotal role in modulating neuronal function and are impaired in cardiovascular disorders. Whether and how physiological aging impacts these neurobiomarkers and cardiac innervation remains still unclear. Therefore, we investigated the impact of aging on neurotrophins (such as BDNF and NGF) production and secretion and its consequences, on cardiac nervous system homeostasis. In vivo, we used young (age: 3 months; n=10) and old (age: 24 months; n=11) male Fisher rats. In vitro, human neuroblastoma cells (SH-SY5Y) were stimulated with serum withdrawn from both experimental groups. Old rats showed a significant reduction in overall ANS fiber density, sympathetic (marked by dopamine β-hydroxylase, dβh) and cholinergic compartment (evidenced by vesicular acetylcholine transporter, VaChT) compared to the young group, assessed by immunohistochemical staining. In addition, we observed a marked downregulation of GAP-43 and BDNF protein levels in left ventricle total lysates via immunoblot analysis, in aged hearts as opposed to young ones. Conversely, no changes were observed in NGF protein expression. To further investigate the autocrine effect of aging on autonomic nerve fibers, we treated SH-SY5Y cells in vitro, with blood serum obtained by young or old rats. Both stimuli induced a remarkable increase in neuronal sprouting, as evidenced via crystal violet assay. Nevertheless, we found a bulky drop in the neuronal function of cells stimulated with old rat serum. Interestingly, this effect was accompanied by a sizeable blunt in GAP-43 and BDNF protein levels, compared to cells treated with young rat serum. Taken together, our data suggest that neuronal function impairment aging-induced associated with significant BDNF impoverishment, might favor maladaptive remodeling of cardiac ANS.
Abstract P305: Patient-specific Ipsc-derived Cardiomyocytes Reveal Abnormal Regulation Of <i>Fgf16</i> In A Familial Atrial Septal Defect
Authors: Lingqun Ye, You Yu, Zhen-Ao Zhao, Dandan Zhao Zhao, Xuan Ni, Yong Wang, Xing Fang, Miao Yu, Yongming Wang, Junming Tang, Ying Chen, Zhenya Shen, Wei Lei, Shijun Hu
Journal: Circulation Research (2021)

Aims: Congenital heart disease (CHD) frequently occurs in newborns due to abnormal formation of the heart or major blood vessels. Mutations in the GATA4 gene, which encodes GATA binding protein 4, are responsible for atrial septal defect (ASD), a common CHD. This study aims to gain insights into the molecular mechanisms of CHD using human induced pluripotent stem cells (iPSCs) from a family cohort with ASD. Methods and Results: Patient-specific iPSCs possess the same genetic information as the donor and can differentiate into various cell types from all three germ layers in vitro , thus presenting a promising approach for disease modeling and molecular mechanism research. Here, we generated a patient-specific iPSC line (iPSC-G4 T280M ) from a family cohort carrying a hereditary ASD mutation in GATA4 gene (T280M), as well as a human embryonic stem cell line (ESC-G4 T280M ) carrying the isogenic T280M mutation using the CRISPR/Cas9 genome editing method. The GATA4-mutant iPSCs and ESCs were then differentiated into cardiomyocytes (CMs) to model GATA4 mutation-associated ASD. We observed an obvious defect in cell proliferation in cardiomyocytes derived from both GATA4 T280M -mutant iPSCs (iPSC-G4 T280M -CMs) and ESCs (ESC-G4 T280M -CMs), while the impaired proliferation ability of iPSC-G4 T280M -CMs could be restored by gene correction. Integrated analysis of RNA-Seq and ChIP-Seq data indicated that FGF16 is a direct target of wild-type GATA4. However, the T280M mutation obstructed GATA4 occupancy at the FGF16 promoter region, leading to impaired activation of FGF16 transcription. Overexpression of FGF16 in GATA4-mutant cardiomyocytes rescued the cell proliferation defect. The direct relationship between GATA4 T280M and ASD was demonstrated in a human iPSC model for the first time. Conclusions: In summary, our study revealed the molecular mechanism of the GATA4 T280M mutation in ASD. Understanding the roles of the GATA4-FGF16 axis in iPSC-CMs will shed light on heart development and provide novel insights for the treatment of ASD and other CHD disorders.
Abstract 11970: Left Atrial Hemodynamics and Invasive Functional Testing to Characterize Heart Failure With Preserved Ejection Fraction in Patients With Atrial Fibrillation
Authors: Jonathan P Ariyaratnam, Ricardo Mishima, Celine Gallagher, Mehrdad Emami, Christopher Wong, VARUN MALIK, John Fitzgerald, Olivia MacNamee, Dennis H Lau, Adrian Elliott, Prashanthan Sanders
Journal: Circulation (2021)

Introduction: Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) commonly coexist. The contribution of abnormal left atrial (LA) hemodynamics to the development of HFpEF in symptomatic AF patients is unknown. Hypothesis: Hemodynamic testing of patients with symptomatic AF will reveal coexistent HFpEF associated with increased LA pressures and stiffness. Methods: Consecutive patients with AF and preserved ejection fraction (awaiting AF ablation) were prospectively recruited. Participants underwent exercise echocardiography and cardiopulmonary exercise testing (CPET), and were grouped according to low, intermediate or high probability of HFpEF based on the ‘HFA-PEFF’ score. At ablation, participants underwent invasive monitoring of LA and right atrial pressures during infusion of 15mL/kg of normal saline directly into the LA over 8 minutes. LA size was monitored during infusion with transesophageal echocardiography. LA stiffness was calculated as Δ LA pressure/Δ LA diameter. Statistical comparison across groups was performed using analysis of variance. Results: Amongst 64 participants, probability of HFpEF was low in nine (14%), intermediate in 39 (61%) and high in 16 (25%) participants. High probability HFpEF was associated with higher baseline mean LA pressure (Fig. 1A) and greater increases in peak (p=0.06) and nadir LA (p&lt;0.01) pressures with saline loading, without significant increases in RA pressure. LA stiffness was increased in patients with high probability of HFpEF (Fig. 1B). Non-invasive testing revealed reduced peak VO 2 (p=0.01), reduced LA emptying fraction at rest and with exercise (p&lt;0.01) and reduced LA reservoir strain (p&lt;0.01) in participants with higher probability for HFpEF. Conclusions: In AF patients undergoing ablation, 25% meet the criteria for HFpEF. Higher probability of HFpEF is characterized by increased LA pressures and LA stiffness, exercise intolerance and reduced LA function.
Abstract 10894: Socioeconomic Status and Differences in Trends of Atrial Fibrillation In-Hospital Mortality Among Black and Non-Black Adults in the United States
Authors: Chaitanya Rojulpote, Shivaraj Patil, Abhijit Bhattaru, Karthik Gonuguntla, Kashyap Kela, Sanskriti Shrivastava, Ajinkya Buradkar, Tapan Buch
Journal: Circulation (2021)

Introduction: Race and socioeconomic status (SES) is interconnected. There is scarce data analyzing trends of atrial fibrillation (AF) in-hospital mortality in black and non-black adults based on SES. Methods: We queried the National Inpatient Sample database from January 2004 to December 2018 to identify patients admitted with AF. We used ICD-9-CM and ICD-10-CM diagnosis codes to identify all patients who were 18 years of age or older and hospitalized with a primary discharge diagnosis of Atrial Fibrillation. Our cohort was further categorized by race, into black and non-black groups, and socioeconomic status (SES) using median household income (MHI) as a surrogate, into low SES (MHI 0-50) and high SES (MHI 51-100). We excluded all patients with incomplete data on age, gender, race, MHI and in-hospital mortality status. Also, in order to reduce the possibility of data duplication, the patients with an indicator for transfer to another acute-care facility were excluded. Cochran-Armitage Test was utilized to estimate temporal trends. Results: Black and non-black adults have had improvement of in-hospital mortality, although black adults still have higher trends as compared to non-black counterparts (p&lt;0.001). Conclusions: Trends of AF in-hospital mortality between black and non-black individuals are comparable despite a significantly smaller proportion of blacks in our study. There is a dynamic interplay among social and health risk factors associated with AF in black individuals and further studies are required to better understand this relation.
Evaluation of the impact of tiered restrictions introduced in England during October and December, 2020, on COVID-19 cases: a synthetic control study
Authors: Xingna Zhang, Gwilym Owen, Mark Green, Iain Buchan, Ben Barr
Journal: The Lancet (2021)

BackgroundIn 2020, a second wave of COVID-19 cases unevenly affected places in England, and different levels of tiered restrictions were introduced in different parts of the country. Previous research has examined the impact of national lockdowns on transmission. We aimed to examine the differences in the effect of localised restrictions on COVID-19 cases and how these differences varied by deprivation.MethodsWe examined the transmission impact of tier 3 restrictions using data on weekly reported COVID-19 cases, adjusted for case-detection rates for 7201 neighbourhoods in England. We identified areas that entered tier 3 restrictions in October and December, 2020, constructed a synthetic control group of places under tier 2 restrictions, and compared changes in weekly infections over a 4-week period. Sufficiently granular data on deaths were not available to investigate excess mortality. We analysed whether this effect varied by level of deprivation and the prevalence of a new variant (B.1.1.7), by stratifying the synthetic control weighting by subgroups and then including an interaction term between subgroup and intervention in the regression model. We used the English Indices of Multiple Deprivation and its tertiles in the stratification to measure deprivation. We tested the spatial spillover effects excluding tier 2 areas within 20 km of tier 3 areas. Ethics approval was not needed.FindingsThe introduction of tier 3 restrictions was associated with a reduction in infections of 14% (95% CI 10–19) in October and of 20% (13–29) in December, or with a reduction in absolute number of total infections of 3536 (95% CI 2880–4192) in October and of 92 732 (49 776–135 688) in December, compared with what would have been expected under tier 2 restrictions. The effects were similar across levels of deprivation and by the prevalence of the new variant. We found smaller effects with high non-significant p values when excluding boundary areas.InterpretationCompared to tier 2 restrictions, restrictions on hospitality and meeting outdoors in tier 3 areas had a moderate effect on transmission and these restrictions did not appear to increase inequalities in COVID-19 cases. Limitations include a lack of specificity as to which of the main restrictions contributed to this effect, potentially biases from the crude measure of case-detection rates applied, and the lack of controls for individual or household characteristics in this ecological analysis.FundingNational Institute for Health Research (NIHR).
Abstract 11799: The Direction and Magnitude of Cardiac Contractile Motion: Considerations for Stereotactic Radio-Ablation of Ventricular Tachycardia
Authors: Bryan Wu, Sai Vanam, Todd Atwood, Andrew Bruggeman, Kevin Moore, Elliot McVeigh, Frederick Han, Jonathan C Hsu, Kurt S Hoffmayer, Farshad Raissi, Ulrika Birgersdotter-green, JENNIFER KARUNAMUNI, PAUL STARK, Gregory K Feld, Arno Mundt, David Krummen, Gordon Ho
Journal: Circulation (2021)

Introduction: Stereotactic ablative radiotherapy is an emerging therapy for ventricular tachycardia (VT), but it is unknown whether its precision may be limited by cardiac motion from the beating heart. Hypothesis: The magnitude of cardiac contractile motion may vary between patients and across different directions in 3D. Methods: Patients who underwent 4D cardiac computed tomography (4DCT) prior to a catheter ablation procedure for atrial or ventricular arrhythmias at 2 medical centers were studied retrospectively. 4DCT was acquired using cardiac-gated Siemens Force or GE Revolution scanners. The displacement of transvenous right atrial (RA) and right ventricle (RV) ICD lead tips across the cardiac cycle (divided into 10 time phases) were measured in orthogonal 3D views on a maximal-intensity projection CT reconstruction (Fig 1) using imaging analysis software (Horos Project). Displacement was compared using 1-way ANOVA. Results: In 14 patients (age 65±11.7 years), contractile motion along the left-right axis, craniocaudal axis, and anteroposterior axis were significantly different for both the RV (0.7±0.4, 0.4±0.2, 0.4±0.2cm, p=0.017) and RA (0.7±0.5, 0.4±0.2, 1.1±0.7cm, p=0.008). The greatest variability between patients in the displacement of the RV lead tip was along the left-right axis (range 0.16cm to 1.52cm) and of the RA lead tip was along the anteroposterior axis (0.2cm to 2.3cm). Clinical characteristics (i.e. ejection fraction) were not associated with the magnitude of motion. Conclusions: Contractile motion was greatest in the left-right direction in the ventricle (up to 1.52cm), but there was a large variation in motion between patients (ranging up to 1.4cm). The magnitude of contractile motion should be assessed on a patient-specific basis. Further studies are underway to develop optimal strategies to account for contractile motion, such as patient-tailored planned target volume expansions and cardiac-gated radiotherapy delivery.