tbuckley/cabot-search huggingface dataset:
Abstract 9310: Aortic Arch Shape After Coarctation Repair Predicts Exercise Capacity: A Multicenter Analysis
Authors: Jason G Mandell, Jennifer Romanowicz, Yue-hin Loke, Nobuyuki Ikeda, Emily Pena, Umar Siddiqi, Narutoshi Hibino, Mark E Alexander, Andrew J Powell, Laura Olivieri
Journal: Circulation (2021)

Introduction: Patients with coarctation of the aorta (CoA) have decreased exercise capacity despite successful repair with no anatomic obstruction. Altered aortic arch shape after surgical repair may increase resistance to flow and affect flow distribution. This study correlates parameters of aorta size and flow with exercise capacity after successful CoA repair. Methods: We retrospectively reviewed patients with repaired CoA at 4 centers who had cardiac magnetic resonance imaging (CMR) and an exercise stress test with respiratory exchange ratio ≥ 1.09 within 1 year. Patients with significant valve disease, outflow tract obstruction, or need for cardiac bypass outside of their arch repair were excluded. Aorta size mismatch (D AAo /D DAo ), defined by the ratio of ascending (AAo) to proximal descending aorta (DAo) diameter, and DAo flow as a percentage of AAo flow, were measured from CMR. Each parameter was correlated with percent predicted peak oxygen consumption (VO2 max). Results: Forty-six patients (age 26 ± 8.4 years) with left ventricular ejection fraction (LVEF) &gt; 52%, met inclusion criteria. Larger D AAo /D DAo and lower %DAo flow correlated significantly with lower VO2 max (Fig). Compared to those with normal VO2 max (n=25), patients with VO2 max &lt;90% predicted (n=21) had a primary repair at an older age (p=0.03) and smaller DAo diameter/m 2 (p=0.04). There were no significant differences in prevalence of arch obstruction by echocardiogram, LVEF, hypertension, blood pressure gradient at rest or exercise, or AAo diameter/m 2 between groups. Conclusions: Aorta size mismatch, due to AAo dilation or small DAo, and associated decreased %DAo flow, correlate significantly with decreased exercise capacity after CoA repair in patients with normal left ventricular systolic function. CMR measurements of aorta geometry and flow can inform the definition of a successful repair and suggest that indications for re-intervention may not be limited to discrete re-coarctation.
NIMG-34. DELAYED PSEUDOPROGRESSION IN GLIOBLASTOMA PATIENTS TREATED WITH TTFIELDS: A REPORT OF TWO CASES
Authors: Norihiko Saito, Nozomi Hirai, Akinori Yagihashi, Shusaku Takahagi, Naoki Kushida, Sho Sato, Yu Hiramoto, Satoshi Fujita, Haruo Nakayama, Morito Haya, Takatoshi Sakurai, Satoshi Iwabuchi
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION: Tumor treating fields (TTFields) is an established treatment modality for glioblastoma (GBM) and is administered with the portable Optune system. Although the EF-14 phase 3 trial demonstrated the efficacy of TTFields for newly diagnosed GBM, uncertainty regarding the specific effects of this treatment has prevented its widespread clinical use. Pseudoprogression in response to chemoradiation is a known problem in GBM patients and most commonly occurs within 3 months after radiotherapy. We report 2 cases of TTFields delayed pseudoprogression. CASE REPORT: Two GBM patients being treated with TTFields showed signs of radiographic progression at 5 to 6 months after completing radiotherapy. Patient 1 was a 37-year-old woman with gliosarcoma in the right temporal lobe. Patient 2 was a 70-year-old man with wildtype-IDH GBM in the left temporal lobe. Both patients received TTFields in addition to maintenance temozolomide (TMZ) after radiotherapy (RT). Radiographic progression was noted at 5 and 6 months after RT in Patients 1 and 2, respectively. Second resections were performed, and pathology showed only the treatment effect, which ultimately led to diagnosis of pseudoprogression. DISCUSSION: Both patients had radiographic progression outside the typical pseudoprogression window. Recent studies reported that TTFields increased plasma cell membrane permeability, which could result in additional gadolinium leakage into the extracellular space. CONCLUSIONS: Better characterization of delayed pseudoprogression would improve treatment and could potentially reduce unnecessary surgeries and discontinuation of successful therapies.
Abstract 12632: The Effect of Rhythm vs. Rate Control for Atrial Fibrillation in All-Cause Mortality in Patients With Heart Failure With Preserved Ejection Fraction: A Systematic Review and Meta-Analysis
Authors: Mohammed AlSadawi, Prabjot Grewal, Gregg Stevens, Robin Jacob, Kerry Cao, Faisal Aslam, ABHIJEET SINGH
Journal: Circulation (2021)

Introduction: This meta-analysis assessed the effect of rhythm control (ablation and/or antiarrhythmic medications) vs rate control for atrial fibrillation in patients with heart failure with preserved ejection fraction. Hypothesis: Rhythm control with ablation and/or antiarrhythmic medications for atrial fibrillation management may be associated with improved mortality in patients with heart failure with preserved ejection fraction. Methods: We searched the databases for studies reporting the effect of rhythm control vs rate control on mortality in patients with heart failure with preserved ejection fraction including Ovid MEDLINE, EMBASE, Scopus, Web of Science, Google Scholar, and EBSCO CINAHL. The search was not restricted to time or publication status. Outcomes included rates of long-term mortality (1 year or longer). Results: A total of 1210 studies have resulted from the literature search. A total of 9 studies and 18,011 patients were included; 56.2% men, with a mean age of 71.6 years were included in our systematic review and meta-analysis. Our analysis suggested rhythm control for atrial fibrillation was associated with lower risk all-cause mortality (1 year); (odds ratio 0.73, 95% confidence interval 0.541-0.984; P 0.03). The risk of bias is mild to moderate. Conclusions: Our results suggest that rhythm control for atrial fibrillation in patients with heart failure preserved ejection fraction was associated with lower risk all-cause long-term mortality &gt;1 year.
NCOG-11. ASSOCIATION OF HYPERGLYCEMIA AND TUMOR SUBCLASS ON SURVIVAL IN IDH-WILDTYPE GLIOBLASTOMA
Authors: Elisa Liu, Varshini Vasudevaraja, Vladislav Sviderskiy, Yang Feng, Ivy Tran, Jonathan Serrano, Christine Cordova, Sylvia Kurz, John Golfinos, Erik Sulman, Dimitris Placantonakis, Richard Possemato, Matija Snuderl
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND RNA expression and DNA methylation studies have identified different subclasses of isocitrate dehydrogenase (IDH)-wildtype (wt) glioblastoma (GBM). However, the prognostic significance of molecular subclasses is unclear. Although hyperglycemia has been previously associated with worse survival, attempts to lower glucose have yielded mixed responses. The role of hyperglycemia may be confounded by molecular heterogeneity and have different impact in molecularly distinct GBM subclasses. METHODS Clinical, laboratory, and molecular data on 89 IDH-wt GBMs profiled by clinical next-generation sequencing and treated with Stupp protocol were reviewed. IDH-wt GBMs were subclassified into RTKI (Proneural), RTKII (Classical) and Mesenchymal subtypes using DNA methylation. Average glucose was calculated by time-weighting plasma glucose measurements between diagnosis and last follow-up. RESULTS Patients were stratified into three groups using average glucose: tertile one (&amp;lt; 100mg/dL), tertile two (100-115mg/dL), and tertile three ( &amp;gt; 115mg/dL). Comparison across glucose tertiles revealed no significant differences in Karfnosky Performance Status (KPS), dexamethasone dose, MGMT methylation, or methylation subclass. Overall survival (OS) was not affected by methylation subclass (log-rank p=0.9) but decreased with higher glucose (log-rank p=0.015). Higher glucose tertiles were associated with poorer OS among RTK I (log-rank p=0.08) and mesenchymal tumors (log-rank p=0.05), but not RTK II (log-rank p=0.99). After controlling for age, KPS, dexamethasone dose, and MGMT status, glucose remained significantly associated with survival (adjusted hazard ratio=5.2, p=0.02). DNA methylation clustering did not identify a unique signature associated with high or low glucose levels. Metabolomic analysis of 23 tumors showed minimal variation across metabolites within the cohort with no differences across molecular subclasses. CONCLUSION Higher average glucose values were associated with poorer OS in RTKI and Mesenchymal IDH-wt GBM, but not RTKII. There were no discernible epigenetic or metabolomic differences between tumors in different glucose environments, suggesting a potential survival benefit with systemic glucose lowering in selected molecular subtype.
Abstract 13151: Shared Genetic Architecture Between Adiposity and Right Ventricular Structure
Authors: Vineet Agrawal, Minoo Bagheri, Nataraja Sarma Vaitinadin, Mingjian Shi, Jane F Ferguson, Evan Brittain, Anna R Hemnes, Quinn Wells, Deepak K Gupta, Jonathan Mosley
Journal: Circulation (2021)

Introduction: Right ventricular (RV) enlargement has been associated with increased mortality, regardless of the etiology. Pathophysiologic determinants of RV structure, however, are under characterized. Examining genetic architecture underlying variation in RV size may identify etiologic risk factors contributing to RV enlargement. Therefore, we interrogated a polygenic predictor for RV size to identify etiologic drivers of RV structure. Methods: We studied 10,522 adult subjects of European ancestry in Vanderbilt University Medical Center’s de-identified DNA biobank (BioVU) who had undergone an echocardiogram including measurement of RV diameter. Bayesian Sparse Linear Mixed Modeling (GEMMA v0.95) was used to create a polygenic predictor of RV diameter. A PheWAS using logistic regression was then conducted to determine clinical diagnoses significantly associated with genetically-determined RV diameter. Further associations between identified clinical factors and RV diameter were examined using 2-sample bivariate and multivariable Mendelian randomization (MR). Results: PheWAS identified obesity-related clinical diagnoses as the most significantly associated with RV diameter (Figure 1). Univariate MR for body mass index (BMI), waist circumference, fat mass, and body impedance all demonstrated a causal and positive association with RV diameter. Multivariable MR demonstrated the association between measures of adiposity and RV diameter persisted even after accounting for the effect of pulmonary pressure. Conclusions: Genetic architecture is shared between adiposity and RV structure. Measures of adiposity are causally associated with genetically predicted larger RV diameter. Common pathophysiologic mechanisms may regulate adiposity and right heart structure, suggesting adiposity may represent an intervenable therapeutic target for RV failure.
S1918: A Phase II/III Randomized Study of R-Minichop with or without Oral Azacitidine (CC-486) in Participants Age 75 Years or Older with Newly Diagnosed Diffuse Large B Cell Lymphoma, Grade IIIb Follicular Lymphoma, Transformed Lymphoma, and High-Grade B-Cell Lymphomas with MYC and BCL2 and/or BCL6 Rearrangements
Authors: Elizabeth A Brem, Hongli Li, Anne W. Beaven, Paolo F. Caimi, Leandro Cerchietti, Ash A. Alizadeh, Rebecca L. Olin, Norah Lynn Henry, Hildy Dilon, Richard F. Little, Cara Laubach, Michael L. Leblanc, Jonathan W. Friedberg, Sonali M. Smith
Journal: Blood (2021)
Abstract P332: Microfluidic Model Of Late-stage Calcific Aortic Valve Disease Develops Calcium Phosphate Mineralizations
Authors: Melissa Mendoza, Mei-Hsiu Chen, Bruce Murray, Peter Huang, Gretchen Mahler
Journal: Circulation Research (2021)

Introduction: Calcific aortic valve disease (CAVD) is an active pathological process leading to severe valve calcification. Late-stage CAVD is characterized by increased leaflet stiffness, disorganized collagen bundles and the deposition of glycosaminoglycans, such as chondroitin sulfate (CS), in the fibrosa layer. However, many details of the cellular pathological cascade remain unknown. Animal models such as mice, rabbits, and pigs are used in understanding human CAVD, but mice do not have similar anatomy, rabbits cannot spontaneously develop atherosclerotic lesions, and pigs require long, expensive and complex studies. Here we utilize microfluidic devices of the aortic valve fibrosa to model late-stage CAVD. Hypothesis: We assessed the hypothesis that microfluidic calcification will increase with increased shear rates and CS content. Methods: Valve-on-a-chip devices contained a hydrogel of 1.5 mg/mL collagen I-only healthy controls or 1.5 mg/mL collagen I with 1 mg/mL or 20 mg/mL CS. Porcine aortic valve interstitial cells (PAVIC) were embedded within and endothelial cells (PAVEC) were seeded onto the matrix. Steady shear stress at 1 dyne/cm 2 and 20 dyne/cm 2 were applied using a peristaltic pump for 14 days. Alizarin Red S (ARS), an assay to assess calcium deposition, was used to quantify calcific nodule formation. Scanning electron microscopy with energy dispersive x-ray (SEM/EDX) was used to further analyze sample mineralization. Results: Co-cultures in the presence of increasing shear stress and CS exhibit increased calcific nodule formation compared to static controls, both qualitatively and quantitatively (n≥3). SEM revealed the microstructure of calcified nodules and EDX confirmed calcium phosphate mineralization with physiologically-relevant calcium to phosphorous ratios (Ca/P= 0.88 - 1.4). Conclusions: These results show that in vitro calcification is driven by shear stress in the presence of PAVEC and CS. As seen in ex vivo studies of human calcification, these microfluidic-derived nodules are similarly composed of a range of naturally-occurring calcium phosphates. Given that CAVD has no targeted therapy, the creation of a physiologically relevant model of the aortic valve can provide a test bed for novel therapeutic interventions.
Abstract 12985: Genetic Susceptibility for Coronary Artery Disease Accentuates the Cardiovascular Disease Risk Associated With Air Pollution
Authors: Shady Abohashem, Taimur Abbasi, Samantha Atlas, Diana Atlas, Hadil Zureigat, Charbel Gharios, Kenechukwu Mezue, Alexander Cardeiro, Krishna Aragam, Sanjay Rajagopalan, Amit V Khera, Michael T Osborne, Ahmed A Tawakol
Journal: Circulation (2021)

Introduction: Air pollution (particulate matter of diameter &lt;2.5 μm, PM 2.5 ) and genetic risk for coronary artery disease (CAD) each associate with cardiovascular disease (CVD). It is unknown whether genetic risk for CAD enhances CVD risk associated with air pollution exposure. Hypothesis: We tested the hypothesis that high genetic risk for CAD accentuates the adverse impact of air pollution on CVD, (as coronary artery calcium [CAC]) and major adverse cardiovascular events [MACE]). Methods: Participants (N=9340, median age 66 yrs, 49% male) in the Mass General Brigham Biobank with genetic and air pollution data were studied. Genome wide polygenic risk score for CAD (PRS CAD ) and principal components of ancestry (PCI) were determined. Average PM 2.5 exposure one year before each person’s enrollment was derived using home addresses and Environmental Protection Agency data. CAC was assessed on those with available CT images (N=548). MACE and CVD risk factors were evaluated via International Classification of Diseases codes. Socioeconomic status (SES) was assessed as residential zip code level income using US Census data. The presence of an interaction between high PM 2.5 and PRS CAD vs. MACE was tested. Results: The Combination of high PRS CAD and PM 2.5 (both ≥ median vs. others) associated with greater CAC [standardized β (95% CI): 0.13 (0.06, 0.19), p=0.0002, Fig.1A ] after adjusting for age, sex, and PCI and with further adjustment for CVD risk factors (p=0.007). Over 5 years median follow up, 1139 subjects experienced first time MACE. Combined high PRS CAD and PM 2.5 also associated with higher MACE risk [OR (95% CI): 1.20 (1.15, 1.25), p&lt;0.001, p (interaction) &lt;0.001, Fig.1B ] after adjusting for age, sex, and PCI and with further adjustment for CVD risk factors (p&lt;0.001) and SES (p&lt;0.001). Conclusions: Among individuals exposed to air pollution, genetic risk for CAD accentuates CAC and MACE risk in a graded manner. Genetic context may impact the health effects of air pollution.
Abstract 12036: Decreased Sympathetic Innervation Around the Left Atrium After Multiple Catheter Ablation Procedures for Atrial Fibrillation
Authors: Hiroshi Fukunaga, Nobuo Iguchi, Yuhei Kasai, Sou Asano, Takahiko Nagase, Yukio Sekiguchi, KOHEI TANIZAKI, Junichi Nitta, Mitsuaki Isobe
Journal: Circulation (2021)

Introduction: Cardiac sympathetic activity is involved in the initiation and maintenance of atrial fibrillation. A novel technique that evaluates the atrial accumulation of 123I-MIBG may be able to assess the atrial sympathetic innervation. The purpose of this study was to visually evaluate the modification of sympathetic innervation caused by multiple catheter ablations. Methods: The total study cohort comprised 32 patients with atrial fibrillation. 21 patients underwent only one ablation using a balloon catheter (cryoballoon in 10 patients; hot balloon in 11 patients) (group 1), while 11 patients underwent multiple radiofrequency catheter ablation procedures (three procedures in 6 patients; four procedures in 5 patients) (group 2). In all patients, the left atrial sympathetic activity was evaluated using MIBG images obtained using a novel solid-state whole-body scanner (VERITON). For local quantitative evaluation, the site with the strongest discrete MIBG accumulation was automatically recognized by the computer and compared in pre- and post-procedural images. Results: In all patients, the total left atrial MIBG accumulation value after ablation (6.64х10 4 ±1.65х10 4 PROPCNTS) was significantly lower than that before ablation (7.74х10 4 ±2.25х10 4 PROPCNTS, p=0.0289). At the site with the strongest discrete MIBG accumulation, the MIBG accumulation after ablation was decreased in 19 patients, unchanged in 9, increased in 3, and shifted in 1. The total left atrial MIBG accumulation value before ablation was significantly lower in group 2 (5.74х10 4 ±1.40х10 4 PROPCNTS) than group 1 (6.67х10 4 ±1.57х10 4 PROPCNTS, p=0.0485). Conclusions: The MIBG accumulation in the left atrium decreased after catheter ablation. Furthermore, preoperative evaluation revealed a significant decrease in MIBG accumulation after multiple ablation procedures. This suggests that multiple catheter ablation of the left atrium modifies the sympathetic innervation.
Prenatal and Postnatal Household Air Pollution Exposure and Infant Growth Trajectories: Evidence from a Rural Ghanaian Pregnancy Cohort
Authors: Ellen Boamah-Kaali, Darby W. Jack, Kenneth A. Ae-Ngibise, Ashlinn Quinn, Seyram Kaali, Kathryn Dubowski, Felix B. Oppong, Blair J Wylie, Mohammed N. Mujtaba, Carlos F. Gould, Stephaney Gyaase, Steven Chillrud, Seth Owusu-Agyei, Patrick L. Kinney, Kwaku Poku Asante, Alison G. Lee
Journal: Environmental Health Perspectives (2021)

Background: The exposure–response association between prenatal and postnatal household air pollution (HAP) and infant growth trajectories is unknown. Objectives: To evaluate associations between prenatal and postnatal HAP exposure and stove interventions on growth trajectories over the first year of life. Methods: The Ghana Randomized Air Pollution and Health Study enrolled n=1,414 pregnant women at ≤24wk gestation from Kintampo, Ghana, and randomized them to liquefied petroleum gas (LPG), improved biomass, or open fire (control) stoves. We quantified HAP exposure by repeated, personal prenatal and postnatal carbon monoxide (CO) and, in a subset, fine particulate matter [PM with an aerodynamic diameter of ≤2.5μm (PM2.5)] assessments. Length, weight, mid-upper arm circumference (MUAC) and head circumference (HC) were measured at birth, 3, 6, 9, and 12 months; weight-for-age, length-for-age (LAZ), and weight-for-length z (WLZ)-scores were calculated. For each anthropometric measure, we employed latent class growth analysis to generate growth trajectories over the first year of life and assigned each child to a trajectory group. We then employed ordinal logistic regression to determine associations between HAP exposures and growth trajectory assignments. Associations with stove intervention arm were also considered. Results: Of the 1,306 live births, 1,144 had valid CO data and anthropometric variables measured at least once. Prenatal HAP exposure increased risk for lower length [CO odds ratio (OR)= 1.17, 95% CI: 1.01, 1.35 per 1-ppm increase; PM2.5 OR= 1.07, 95% CI: 1.02, 1.13 per 10-μg/m3 increase], lower LAZ z-score (CO OR= 1.15, 95% CI: 1.01, 1.32 per 1-ppm increase) and stunting (CO OR= 1.25, 95% CI: 1.08, 1.45) trajectories. Postnatal HAP exposure increased risk for smaller HC (CO OR= 1.09, 95% CI: 1.04, 1.13 per 1-ppm increase), smaller MUAC and lower WLZ-score (PM2.5 OR= 1.07, 95% CI: 1.00, 1.14 and OR= 1.09, 95% CI: 1.01, 1.19 per 10-μg/m3 increase, respectively) trajectories. Infants in the LPG arm had decreased odds of having smaller HC and MUAC trajectories as compared with those in the open fire stove arm (OR= 0.58, 95% CI: 0.37, 0.92 and OR= 0.45, 95% CI: 0.22, 0.90, respectively). Discussion: Higher early life HAP exposure (during pregnancy and through the first year of life) was associated with poorer infant growth trajectories among children in rural Ghana. A cleaner-burning stove intervention may have improved some growth trajectories. https://doi.org/10.1289/EHP8109
Abstract 10044: Efficacy of Sacubitril-Valsartan in Patients with Reduced Left Ventricular Ejection Fraction
Authors: Hiroki Ueyama, Toshiki Kuno, Alexandros Briasoulis
Journal: Circulation (2021)

Introduction: Angiotensin receptor-neprilysin inhibitor (ARNI) reduces death and heart failure (HF) hospitalization in patients with HF and reduced ejection fraction (HFrEF). In addition to the PARADIGM-HF, PARADISE-MI and LIFE trial has recently tested the safety and efficacy of ARNI in subgroups of patients with reduced left ventricular ejection fraction (LVEF) such as those patients at risk for HFrEF after myocardial infarction (without prior HF) and advanced HF patients. Methods: We performed a random-effects model meta-analysis of three randomized controlled trails investigating the effect of ARNI in patients with reduced LVEF. The main endpoints were the composite of cardiovascular death and HF hospitalization, and HF hospitalization. Results: A total of 14,395 patients were included in our analysis. The characteristics of the included studies are demonstrated on Table 1. The composite endpoint and HF hospitalization were non-significantly reduced with ARNI compared with angiotensin-converting enzyme inhibitor or angiotensin II receptor blockers (composite endpoint adjusted hazard ratio [HR] 0.9, 95% confidence intervals 0.75-1.08 and HF hospitalizations: HR 0.87, 0.72-1.04, Figure 1). The heterogeneity among trials was high (I 2 &gt;50%). Conclusions: In line with the recently reported trials, our findings support the use of ARNI in patients with HFrEF that meet the inclusion criteria of PARADIGM-HF trial. It is important to tailor medical therapy by matching individual patient profiles to inclusion criteria of the published randomized clinical trials.