tbuckley/cabot-search huggingface dataset:
Abstract 4147568: Sociodemographic Disparities Associated with Stress, Cardiovascular Disease, and Cancer Outcomes in the <i>All of Us</i> Research Program
Authors: Lakeshia Cousin, Ruina He, Keesha Roach, Mandy Hill, Arnethea Sutton
Journal: Circulation (2024)

Introduction: Cardiovascular disease (CVD) and cancer are among the leading causes of morbidity and mortality worldwide. Increasing evidence suggests that sociodemographic factors such as race, ethnicity, income, education, and stress levels significantly influence the prevalence and outcomes of these diseases. The All of Us Research Program provides a unique opportunity to explore these disparities across a diverse U.S. population. This study aims to examine how sociodemographic disparities are associated with stress, CVD, and cancer outcomes. We hypothesize that higher perceived stress levels, lower income, lower education levels, and minority race/ethnicity groups are associated with higher incidences of CVD and cancer. Methods: Data from 55,505 All of Us Research program participants were analyzed. Key variables included age, race, ethnicity, education, household income, perceived stress level, and history of CVD and cancer. Descriptive statistics were used to summarize participant demographics. Multivariate logistic regression models were employed to examine the associations between sociodemographic factors and the outcomes of interest (CVD and cancer). Results: Older participants had a higher prevalence of both CVD (mean age: 60.8 vs. 50.5, p &lt; 0.001) and cancer (mean age: 63.6 vs. 51.7, p &lt; 0.001). Black/African Americans had a higher incidence of CVD (21.3% vs. 78.7%, p &lt; 0.001), while Whites had a higher prevalence of cancer (5.3% vs. 94.7%, p &lt; 0.001). Lower income and higher stress levels were also associated with higher CVD incidence (&lt;$25k: 20.1% vs. 79.9%, p &lt; 0.001; high stress: 15.0% vs. 85.0%, p &lt; 0.001). Multivariate logistic regression showed significant predictors for CVD, including age (OR = 1.05), Black race (adjusted OR = 1.18), and high stress (adjusted OR = 1.27). For cancer, significant predictors were age (OR = 1.06), Hispanic ethnicity (OR = 0.53), and moderate stress (adjusted OR = 1.12). Conclusion: The study highlights significant sociodemographic disparities in the incidence of CVD and cancer. Older age, Black/African American race, lower income, and higher perceived stress levels were associated with higher odds of CVD. For cancer, older age, White race, and higher income were significant predictors. Perceived stress level plays a crucial role in mediating these associations, underscoring the need for targeted interventions to address these disparities in high-risk populations.
Abstract Or101: Evaluating the National Institutes of Health Pipeline for Resuscitation Science Investigators
Authors: Ryan Coute, Ryan Huebinger, Sarah Perman, Marina Del Rios, Michael Kurz
Journal: Circulation (2024)

Background: The pipeline of investigators studying resuscitation science and their contributions to the field after attaining research independence are largely unknown. Our objective was to identify and compare the number of National Institutes of Health (NIH) K awardees studying CA vs. stroke research and determine both cohorts’ success rates in transitioning to independent R01 funding. Methods: The NIH RePORTER database was queried from 2008 to 2018 to identify CA grants using published methodology. The CA grants were filtered by activity code to identify mentored individual K awards (defined as K01, K08, K23, or K99). A second query was then performed using principal investigators (PIs) for each K award, and the results were filtered to identify all R01 grants with the former K award recipients listed as the contact PI/PD or other PI/project lead. Stroke grants from the same epoch were exported from the NIH categorical spending reports, where stroke research is a distinct line item. Subsequent R01 funding for the stroke grants was identified using the above process. The outcome measures include: total K awards, R01 conversion within 5 or 7 years from K award receipt, and the proportion of awardees who remained focused on CA or stroke research at the R01 level. Data were presented as counts, proportions, and median/interquartile ranges. Proportions were compared using the Chi-Square test or Fisher’s exact test. P-values &lt; 0.05 were considered statistically significant. Results: A total of 857 CA grants were identified, including 272 individual awards, compared to 8,520 stroke grants with 2,788 individual awards. K awards comprised 11.4% of CA grants versus 6.6% for stroke grants (p=0.003). The R01 conversion rate was 51.6% for CA and 57.3% for stroke (p=0.555). The median transition time from K to R01 was 5.5 years (IQR 4-6) for CA and 5 years (IQR 4-7) for stroke. CA K awardees secured 27 funded R01s, while stroke counterparts received 163. A total of 48.1% of CA K awardees continued CA research at the R01 level, versus 63.8% for stroke (p=0.121). Conclusion: Although the volume of federally funded grants and K awards focused on CA research is significantly smaller than that of stroke research, the outputs for both fields appear similar. More than half of R01 awards from the CA cohort departed from their original content focus. These findings should help inform efforts to expand the resuscitation science young investigator pipeline.
Abstract 4147849: Extracellular Transcriptomics-driven Identification and Characterization of lncRNA LINC00989 in Heart Failure Progression
Authors: Priyanka Gokulnath, Michail Spanos, Quanhu Sheng, Aarush Singh, Emeli Chatterjee, Marta Garcia Contreras, Saumya Das
Journal: Circulation (2024)

Introduction: Heart failure (HF) poses a significant clinical challenge, necessitating a deeper understanding of its molecular mechanisms for effective therapeutic interventions. Long non-coding RNAs (lncRNAs) have emerged as key regulators in cardiovascular diseases. However, their role in HF progression, particularly in human pericytes and association with cardiac remodeling, remains poorly understood. Hypothesis: We hypothesize that LINC00989, a novel lncRNA identified through plasma extracellular vesicle (EV) transcriptomics of ADHF patients, plays a significant role in human pericytes towards its profibrotic function and contributes to HF remodeling. Methods: We characterized LINC00989 expression in primary human pericytes and its response to stressors mimicking HF. Cellular and extracellular fractionation experiments were performed to examine LINC00989 localization and its association with EVs. Loss-of-function experiments were conducted using RNA anti-sense oligos, while gain-of-function experiments involved overexpression vectors. Further downstream interactors were characterized using RNA sequencing analysis. Profibrotic effects of LINC00989 were investigated using adoptive transfer model with induced pluripotent stem cell-derived cardiac fibroblasts. Results: Our findings demonstrate high expression of LINC00989 in primary human pericytes, with differential regulation under stress conditions. Loss-of-function experiments revealed alterations in epithelial-mesenchymal transition and angiogenesis markers, implicating LINC00989 in maintaining pericyte phenotype. Gain-of-function experiments supported its role in modulating pericyte morphology. Additionally, LINC00989 indicated a profibrotic role on cardiac fibroblasts. Conclusion: These findings underscore the significance of LINC00989 in human pericyte function and its potential as a therapeutic target in HF progression. Understanding its molecular mechanisms could lead to novel therapeutic interventions in heart failure. Further studies are needed to validate these findings and explore clinical implications.
Abstract 4147922: Quality of Life Patient Reported Outcomes for Survival Prediction after Cardiac Resynchronization Therapy
Authors: Joe Demian, Aritra Paul, Niraj Varma, J. Emanuel Finet, Arshneel Kochar, Feras Bader, Oussama Wazni, Wilson Tang, John Rickard
Journal: Circulation (2024)

Background: Patient-reported outcomes, such as quality of life (QoL) scores, provide a comprehensive measure of health status from the patient's perspective, which may be relevant for predicting survival after cardiac resynchronization therapy (CRT). Hypothesis: We hypothesize that a healthier QoL score at 6 months post-CRT is associated with better long-term survival. Aim: To evaluate the association between a validated QoL at 6 months post-CRT and two-year survival in CRT patients. Methods: A prospective cohort study recruited 524 patients who received CRT at the Cleveland Clinic between May 2016 and June 2022. The 5-level EuroQol-5 Dimension (EQ-5D-5L) was used to assess QoL at 6 months post-CRT (higher scores indicating worse QoL) and patients were divided into two strata (EQ-5D-5L ≤ or &gt; 10). Our primary endpoint was Event-Free Survival (EFS) – defined by the absence of both significant cardiac interventions (LVAD implantation or heart transplant) and mortality. Results: The population had a median (IQR) age of 71 years (IQR: 62-78), with 343 (65.5%) men and 419 (80%) received a defibrillator. Median EQ-5D-5L was 7 (IQR: 5-9). The response rate at 6 months post-CRT was 321 (68.2%), and the 2-year EFS rate was 397 (75.8%). Univariate analysis re revealed that EQ-5D-5L&gt;10 was significantly associated with increased EFS. The Cox proportional hazard model showed it to be an independent predictor of EFS (HR: 2.33, 95% CI [1.53-3.56], p&lt;0.001), after adjusting for potential confounders, including age, gender, diabetes mellitus, ischemic cardiomyopathy, AFib/flutter, history of TIA/CVA, NYHA Class, and COPD. The Kaplan-Meier survival curves demonstrated a significantly lower EFS probability for patients with EQ-5D-5L&gt;10 (log-rank test: p&lt;0.001). Conclusions: QoL assessed at 6 months post-CRT is a significant predictor of two-year survival in CRT patients. The EQ-5D-5L score can be a valuable tool to enhance patient risk stratification and management.
Abstract Su1004: Timing and Mode of Death after Pediatric In- and Out-of-Hospital Cardiac Arrest
Authors: Megan McSherry, Kathryn Graham, Jeremy Herrmann, Matthew Kirschen, Ryan Morgan, Robert Sutton, Alexis Topjian
Journal: Circulation (2024)

Introduction: Pediatric cardiac arrest is associated with high mortality and morbidity. Timing and modes of death after pediatric out-of-hospital cardiac arrest (OHCA) varies across centers. Causes of death for children with in-hospital cardiac arrest (IHCA) have not been described. Aims: We sought to determine and compare timing and modes of death in children admitted to a PICU following return of circulation (ROC) after IHCA and OHCA. Hypothesis: Among children with ROC who did not survive to hospital discharge (SHD), we hypothesized that children with IHCA would more commonly die from withdrawal of life sustaining therapy (WLST) and children with OHCA would more commonly die from brain death (BD). Methods: Single center retrospective study of children &lt;18 years old who received &gt;1 minute of chest compressions, achieved ROC for &gt;20 minutes, and were admitted to the PICU from January 2017 - March 2023. We compared modes of death classified as: a) BD, b) WLST, c) circulatory death from recurrent arrest or d) recurrent arrest without attempted resuscitation (DNAR) between IHCA and OHCA using chi squared or Fisher’s exact test. Reason for WLST was categorized from physician notes. Time to death, defined as number of days between arrest and death, was compared between IHCA and OHCA by Wilcoxon rank-sum. Results: 857 children (median age 1.3 years [IQR 0.4, 8.8], 43% female, 553 (65%) IHCA and 304 (35%) OHCA) were included. In the IHCA cohort, 163/553 (29%) did not SHD (BD 7 [4%], WLST 92 [56%], recurrent arrest 28 [17%], DNAR 34 [21%]). The primary reasons for WLST were poor cardiovascular prognosis (42 [46%]) and poor neurologic prognosis (33 [36%]). In the OHCA cohort, 111/304 (37%) did not SHD (BD 55 [50%], WLST 42 [38%], recurrent arrest 7 [6%], DNAR 7 [6%]). The primary reason for WLST was poor neurologic prognosis (35 [83%]). The median time to death was longer for IHCA vs. OHCA (6 [0,30] vs 2 [1,5] days, p&lt;0.001). After IHCA, children were less likely to die from BD (p&lt;0.001) and more often underwent WLST due to poor cardiovascular prognosis (p&lt;0.01) than children with OHCA. Conclusions: Non-survivors after IHCA more frequently died due to WLST and circulatory death in the setting of care limitations, while non-survivors following OHCA died earlier and more frequently from BD. Understanding the timing and mode of death after OHCA and IHCA is critical for framing prognostic, goals-of-care conversations.
Abstract 4147845: Valsartan and Cardiac Remodeling in Early-Stage Hypertrophic Cardiomyopathy: The VANISH Trial Cardiac Magnetic Resonance Substudy
Authors: John Ostrominski, Brian Claggett, Michael Jerosch-Herold, Anna Axelsson, Sharlene Day, Mark Russell, Kenneth Zahka, Alexandre Pereira, Steven Colan, Anne Murphy, Charles Canter, Richard Bach, Matthew Wheeler, Joseph Rossano, Anjali Owens, Luisa Mestroni, Matthew Taylor, Amit Patel, Ivan Wilmot, Jonathan Soslow, Jason Becker, Neal Lakdawala, Henning Bundgaard, Jose Vargas, Carolyn Ho
Journal: Circulation (2024)

Background: Valsartan has previously been shown to attenuate cardiac remodeling among individuals with early-stage sarcomeric hypertrophic cardiomyopathy (HCM), a condition characterized, in part, by increased cardiomyocyte size. Cardiac magnetic resonance (CMR) imaging parameters, such as late gadolinium enhancement (LGE), are associated with disease progression and outcomes in HCM, but whether valsartan influences these parameters remains uncertain. Methods: In this prespecified CMR substudy of the international, multicenter, phase 2 VANISH (Valsartan for Attenuating Disease Evolution in Early Sarcomeric HCM) trial, we evaluated treatment effects of valsartan versus placebo on cardiac structure and function, including indexed extracellular volume (iECV), indexed intracellular volume (iICV; reflecting cell size or number), and LGE. Between-group differences in CMR parameters from baseline to 2 years were evaluated using multivariable mixed effects models. Results: Overall, 137 (77%) VANISH participants (mean age 23±10 years; 37% female; 97% White) had CMR imaging available at baseline and 2 years. Baseline characteristics and CMR parameters were well-balanced between the treatment arms. Baseline non-indexed ECV and ICV (available at baseline and year 2 in 52 participants) were 32±7% and 68±7%, respectively. Among those with detectable LGE (n=37; 27%), the median [IQR] global LGE mass was 10 [2-28] grams. Between baseline and 2 years, iICV was significantly reduced with valsartan vs. placebo (between-group difference, -5.0 mL/m 2 , 95% CI -9.7 to -0.4; P =0.032) ( Figure ). Valsartan was also associated with improved left ventricular end-diastolic volume index vs. placebo (between-group difference, +3.3 mL/m 2 , 95% CI 0.4 to 6.2; P =0.027); no significant between-group differences were observed for other CMR parameters, including iECV and global LGE mass. Conclusions: These findings provide important mechanistic insights into the effect of valsartan in early-stage HCM, showing potential benefits on myocardial intracellular volume. These findings support and extend those of the primary VANISH trial, stressing the need for further research efforts to identify cellular mechanisms of valsartan on HCM progression.
Abstract 4147824: Comparing Mobile Health Strategies to Improve Medication Adherence for Veterans with Coronary Heart Disease (Mobile4Meds): Results of a Randomized Clinical Trial
Authors: Linda Park, Abdelaziz Elnaggar, Thomas Hoffmann, Julia von Oppenfeld, Eileen Collins, Setareh Raygani, Celina Yong, Krishan Soni, DAVID WINCHESTER, Nicole Minniefield, Mary Whooley
Journal: Circulation (2024)

Background: Despite adherence to antiplatelet medications being critical to prevent stent thrombosis and subsequent life-threatening complications, rates of long-term non-adherence range from 21-57%. Text messaging (TM) and mobile applications (apps) are practical and inexpensive strategies to potentially promote medication adherence. Objective: The Mobile4Meds study sought to determine whether TM or a mobile app for medication adherence, compared to control, improved antiplatelet use among patients who experienced acute coronary syndrome or percutaneous coronary intervention (ACS/PCI). Methods: We recruited participants for the randomized clinical trial (RCT) from 4 national Veterans Affairs (VA) and 2 non-VA Northern California medical centers from 2018-2022. Participants were randomly assigned to: 1) customized TM on medication reminders, 2) a commercially available mobile app for self-management of medication use, or 3) control, and followed at 3, 6, and 12 months. The primary outcome was medication adherence, measured by Medication Event Monitoring System (MEMS) electronic caps. Self-reported endpoints were derived from the Adherence to Refills and Medications Scale (ARMS), and 7- and 30-day recall of all medications and antiplatelet therapy. We used linear mixed models with predictor variables of group (with control as reference), time (baseline, 3, 6 months), and group-by-time interactions to detect group differences. Results: The mean age of participants was 66.9 (SD 11), 49.5% female (N=99). Significant missingness from MEMS caps precluded conclusive analyses. No significant group differences were found with the ARMS. There were significant main effects of 7- and 30-day recall for all medications at 3 months for the app group (B=3.16, standard error [SE]=1.17, p&lt;.01; B=-1.99, SE=0.94, p&lt;.05, respectively) vs. the control group. Differences in 30-day recall for antiplatelet medication use were detected at 3 months; however, did not reach statistical significance (B=-2.08, SE=1.14, p&lt;.07). Conclusions: Our study signals the efficacy of using a mobile app for short-term medication adherence based on 7- and 30-day recall. The potential of mobile technology warrants additional research including measurement methodologies as medication nonadherence remains a major public health concern for individuals with CVD requiring strict medication adherence such as antiplatelet therapy after PCI.
Abstract 4147894: Epicardial vs endocardial ablation for ventricular tachycardia: Patient Characteristics, Procedural Factors, and Outcomes
Authors: Aastha Poddar, Pragyat Futela, Tiffany Woelber, Gurukripa Kowlgi, Kiyan Heybati, Narut Prasitlumkum, Hina Amin, Abhishek Deshmukh
Journal: Circulation (2024)

Background: Patients undergoing epicardial access for ventricular tachycardia (VT) have a higher rate of complications and VT recurrence post-procedure. Data regarding electrophysiological factors driving the outcomes are scant. Objective: To compare the factors and outcomes associated with epicardial vs endocardial VT ablation. Methods: A single-center, retrospective study of patients undergoing catheter ablation for scar-related VT was conducted. Data collected included demographics, comorbidities, medications, relevant laboratory abnormalities, electrocardiograms, echocardiograms, detailed procedural characteristics, and outcomes. Results: Our cohort of 554 patients had 89 (16.1%) epicardial and 465 (83.9%) endocardial VT ablations. Patients undergoing epicardial ablation had a greater frequency of NICM, and more patients had undergone sympathetic modulation for VT (p &lt; 0.05) but had lesser frequency of valve surgery, and CABG. Epicardial ablation was associated with greater use of both short-term (&lt;3 months) and long-term (&gt;6 months) anti-arrhythmic drugs (AAD) (p&lt;0.01). Epicardial access was obtained by micropuncture or needle-in-needle technique for 22.5% (n=20) of patients. Except for more use of general anesthesia and the lesser usage of drugs for VT induction during epicardial procedures, there were no significant differences. Epicardial ablation had a higher risk of acute complications (&lt;30 days) after the procedure (driven by pericarditis) (25% vs 7.8%, p&lt;0.01). On survival analysis, epicardial access was associated with an increase in VT recurrence and repeat ablation (p&lt;0.01) during a mean follow-up of 1072 days. On multivariate analysis, after adjusting for age, sex and comorbidities, epicardial access was an independent predictor of VT recurrence or repeat ablation [aHR 1.61 (CI: 1.18- 2.2)] Conclusion: Patients undergoing epicardial ablations with fewer comorbidities demonstrated increased AAD usage prior to and after the procedure, and a higher risk of acute complications after the procedure. Epicardial access was an independent predictor of VT recurrence or repeat ablation.
Abstract 4148019: Shear Stress Affects Human Aortic Endothelial Heparan Sulfate Expression Response to Inflammatory Stimulus
Authors: Rick Mathews, Owen McCarty, Monica Hinds
Journal: Circulation (2024)

Background: Heparan sulfate (HS) proteoglycans act as mechanosensors on endothelial cells (ECs), regulating EC morphology and function. HS expression is affected by culture under static or dynamic conditions. HS response to inflammatory stimulus under both conditions is not well characterized. This study investigated HS expression on human aortic ECs (HAECs) under static and arterial flow conditions. Hypothesis: Inflammation modeled by TNFa significantly decreases HS epitope on HAECs under both static and arterial flow conditions. Aims: To establish the effect of TNFa on HS expression in HAECs. Methods: Passages 4 through 8 HAECs (ATCC) were cultured to confluence in endothelial growth medium (Vasculife) in Ibitreat µ-Slide 8 well high chambered coverslip slides or Ibitreat µ-Slide VI 0.4 flow channel slides. Cells were treated with TNFa at 100 ng/mL for 3 hours under static conditions or conditioned with 10 dyn/ cm2 of shear stress for 24 hours and then treated with TNFa at the same concentration added to the circulating media for 3 hours. HAECs were fixed in 2% paraformaldehyde/ 0.1% glutaraldehyde for 30 minutes followed by blocking with 2% goat serum for 30 minutes, both at room temperature. Primary antibody to the 10E4 HS epitope was incubated at 4°C overnight (1:100; 10E4 epitope, AMS Biotechnology, USA) followed by incubation in Alexa Fluor 488 goat anti-mouse secondary antibody (1:300, Molecular Probes, USA) for 1 hour at room temperature. HAECs nuclei were stained using 4′,6-diamidino-2-phenylindole and immersed in phosphate buffered saline for confocal imaging using a laser scanning microscope (Zeiss, LSM 880, 20X). Results: TNFa significantly (p &lt; 0.05) increased HS expression in HAEC monolayers treated under static conditions compared to untreated control and heparinase III treated HAECs (Figure 1A). HAEC monolayers conditioned under arterial shear stress expressed significantly (p &lt; 0.05, ANOVA with Tukey’s post-hoc) higher HS levels compared to baseline static controls; however, flow conditioned HAECs did not show any difference in HS expression under untreated compared to TNFa conditions (Figure 1B). Conclusion: These data indicate that fluid shear stress may program endothelial cells to significantly alter their HS expression and response to inflammatory stimuli.