tbuckley/cabot-search huggingface dataset:
Abstract 14976: Proteomic Measures Linking Social Determinants of Health to Heart Failure Risk: The Atherosclerosis Risk in Communities Study
Authors: Diego Ramonfaur, Rani Zierath, Victoria Lamberson, Yimin Yang, Brian Claggett, Anna Kucharska-Newton, Keenan A Walker, Nrupen A Bhavsar, Patricia Chang, Ana V Diez Roux, Ganga Bey, Kenneth R Butler, Chiadi E Ndumele, Josef Coresh, James S Floyd, Michelle C Odden, Amil M Shah
Journal: Circulation (2023)

Introduction: Adverse social determinants of health (SDOH) are risk factors for heart failure (HF), and both disproportionately burden Black adults. The mechanisms linking SDOH to incident HF are unclear. Methods: Among 9910 HF-free participants in the community-based ARIC study with proteomic data (Somascan v4) at Visit 3 (V3; 1993-95), we performed race-stratified (Black and non-Black race) analyses of the association of 4955 plasma proteins with SDOH and incident HF. We derived a SDOH factor based on income, education level, and neighborhood area deprivation index using exploratory factor analysis. We evaluated cross-sectional associations of the SDOH factor with proteins using age- and gender- adjusted linear regression at Bonferroni significance. The association of SDOH-associated proteins with incident HF during 10 years post-V3 was assessed using Cox PH regression further adjusting for cardiovascular co-morbidities, using an FDR &lt;0.05. Mendelian randomization analysis assessed for a possible causal effect on HF among candidate proteins common to both race groups. Results: Of 9910 participants, 1981 reported Black race (age 59±6 years; 60% female) and 7929 non-Black race (60±6; 52% female). The SDOH factor was associated with incident HF in both race strata (adjusted HR 1.29 [95% CI 1.07-1.54] and 1.38 [1.24-1.53] respectively). Among Black participants, 80 proteins associated with the SDOH factor, 52 of which associated with incident HF. Among non-Black participants, 866 proteins associated with the SDOH factor, 188 of which associated with incident HF. Twenty-two proteins were associated with SDOH and HF in both race groups (Figure). Mendelian randomization supported a possible causal effect of C1QTNF1, an inflammation-associated adiponectin paralog, on HF. Conclusions: Large scale proteomics identifies proteins potentially linking SDOH to HF risk. C1QTNF1 associates with SDOH burden, has a possible causal effect on HF, and warrants further study.
Abstract 18022: Multiplexed Generation and Functional Annotation of Hypertrophic Cardiomyopathy-Associated <i>MYH7</i> Missense Variants in Isogenic Gene-Edited Stem Cell-Derived Cardiomyocytes
Authors: Clayton E Friedman, Shawn Fayer, Sriram Pendyala, Wei-Ming Chien, Alexander Loiben, Linda Tran, Leslie S Chao, Ashley Mckinstry, Dania Ahmed, Elaheh Karbassi, Aidan M Fenix, Charles E Murry, Lea M Starita, Douglas M Fowler, Kai-chun Yang
Journal: Circulation (2023)

Hypertrophic cardiomyopathy (HCM) is an inheritable cardiac condition affecting 1:200-500 people and is characterized by left ventricular hypertrophy that can cause heart failure. Autosomal-dominant, missense mutations in MYH7 (encoding MHC-β) cause 33% of genotype + HCM cases. Despite this, 75% of MYH7 missense variants are of unknown clinical significance (VUS). Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) can elucidate the effect(s) of VUS, however, new variant identification by genetic testing outpaces methods to gene edit hiPSCs. Thus, we developed a method called CR ISPR a On- T arget E diting R etrieval (CRaTER) which increased successful gene-editing 25-fold over current methods. We leveraged CRaTER to enrich for edited hiPSCs, generating a library of 113 MYH7 missense variants. As mutations can reduce protein stability and abundance, we flow sorted MYH7 variant hiPSC-CMs into bins based on differing MHC-β protein abundance followed by next generation sequencing to calculate variant abundance scores. This multiplexed assay identified 31 residue substitutions as functionally abnormal, including all tested pathogenic variants and VUS. MHC-β depletion was validated in clonal hiPSC-CMs and by Western blotting of patient myocardium with a MYH7 mutation. Additionally, we found that severe MHC-β depletion is associated with increased cell size, a hallmark pathological phenotype of HCM. Finally, single-cell contractility analyses of hiPSC-CMs with a pathogenic MYH7 variant revealed hyperdynamic physiology relative to isogenic controls, suggesting an association between MHC-β loss and systolic dysfunction. Together, CRaTER enables the generation of isogenic hiPSC variant libraries at unprecedented scale for differentiation to disease-relevant cell types. Functional analyses of MYH7 variant hiPSC-CMs have revealed a novel correlation between MHC-β protein depletion and pathogenicity that accurately predicts MYH7 variant effect and has implications for future MYH7 variant effect interpretations.
Abstract 17927: Acipimox Does Not Improve Endothelial Function and Insulin-Stimulated Vasodilation in Patients With Metabolic Syndrome
Authors: Alexander Sullivan, Emily M Shardelow, Aaron W Aday, Quinn S Wells, Matthew S Freiberg, Joshua A Beckman
Journal: Circulation (2023)

Introduction: Insulin resistance increases circulating free fatty acid (FFA) concentrations, which causes the release of inflammatory cytokines and induces endothelial dysfunction. Acipimox reduces FFA efflux and may improve insulin sensitivity and endothelium-dependent microvascular vasodilation. Hypothesis: We hypothesize that acipimox treatment will improve insulin-stimulated forearm blood flow (FBF) compared to placebo in volunteers with metabolic syndrome. Methods: We conducted a randomized, double-blind, placebo-controlled crossover trial (NCT00759291) evaluating 1-week of acipimox 250 mg QID on insulin-stimulated FBF in patients with and without metabolic syndrome. Results: Sixteen patients received acipimox (6 metabolic syndrome and 10 healthy controls). Patients with metabolic syndrome were older (63.8 vs 49.9 years old, p&lt;0.001) with higher baseline insulin levels (15.9 vs 3.5 μU/mL, p=0.002), and trended towards higher BMIs (30.9 vs 24.6 kg/m 2 , p=0.083). Baseline insulin sensitivity by Homeostatic Model Assessment for Insulin Resistance (HOMA IR) differed between controls and those with metabolic syndrome (0.68 vs 3.28, p=0.001) but did not change with acipimox (p=0.540, Panel A). Insulin stimulation increased FBF in patients treated with placebo (p=0.01, Panel B) and acipimox (p=0.03, Panel C) but was not augmented by acipimox in participants with metabolic syndrome or healthy controls (Panel D and E). In multivariable-adjusted regression analysis, acipimox did not increase FBF, even after adjusting for baseline FBF and key baseline differences, including metabolic syndrome. Conclusion: Acipimox did not improve insulin sensitivity and had no effect on microvascular endothelial dysfunction assessed by insulin-stimulated FBF. This suggests that FFA modulation does not reverse microvascular dysfunction in patients with metabolic syndrome.
Abstract 13746: Mental Health and Implantable Cardioverter Defibrillator Implantation in Black Patients at Risk for Sudden Cardiac Death
Authors: Brian C Boursiquot, Lonnie T Sullivan, Andrew Maul, Apurva Khedagi, Rebecca Young, Brooke Alhanti, Samuel F Sears, Larry R Jackson, Kevin L Thomas
Journal: Circulation (2023)

Introduction: Black patients with guideline indications for implantable cardioverter defibrillators (ICD) have lower rates of implantation compared to White patients. The Educational Videos to Address Racial Disparities in ICD Therapy Via Innovative Designs (VIVID) trial enrolled self-identified Black individuals with chronic systolic heart failure and studied the impact of a video-based decision-support tool on decisional quality and ICD implantation. Hypothesis: We hypothesized that depressive symptoms are associated with greater decisional conflict and lower rates of ICD implantation among study participants. Methods: Participants were administered the Patient Health Questionnaire-2 (PHQ-2) depression screen; and the 12-Item Short-Form Health Survey, from which we derived the Mental Component Summary-12 (MCS-12). A decisional conflict scale (DCS) adapted from the Ottawa framework for shared decision-making was used to assess decisional conflict associated with the decision for ICD implantation. An analysis of covariance was used to assess differences in DCS scores. Multivariable logistic regression was used to examine the association between mental health scores and ICD implantation at 90 days. Results: Among 306 included participants, 60 (19.6%) reported depressed mood and 142 (46.4%) reported anhedonia. Participants with the lowest MCS-12 scores (poorer mental health) had greater decisional conflict regarding ICD assent compared to those with the highest MCS-12 scores (adjusted mean difference in DCS score = 3.05 [95% CI: 0.32, 5.78]). By 90-day follow-up, 204 participants (66.6%) underwent ICD implantation. There was no significant association between either PHQ-2 score or MCS-12 score and ICD implantation. Conclusions: Depressed mood and anhedonia were prevalent among Black patients considering primary prevention ICD. Poorer mental health did not impact the likelihood of ICD implantation in this population.
Abstract 18653: Long Term Outcomes in Patients With Systemic Lupus Erythematosus Undergoing Cardiac Surgery: A Propensity Analysis
Authors: heba wassif, Benjamin Kramer, Bianca Honnekeri, Ashley Lowry, Eugene H Blackstone, Mohamed M Gad, Emily Littlejohn, Venu Menon, Eric E Roselli, Lorenzo Braghieri
Journal: Circulation (2023)

INTRODUCTION The burden of cardiovascular diseases, including coronary artery disease and valvular disease, is greater in patients with systemic lupus erythematosus (SLE) than in the general population. There is a paucity of robust data on short- and long-term outcomes after cardiac surgery in patients with SLE. AIM To evaluate early (&lt;30 days) and late post-operative morbidity and mortality in patients diagnosed with SLE who underwent valve repair or replacement with or without coronary artery bypass grafting (CABG) compared to non-SLE patients. METHODS This retrospective propensity matched comparative effectiveness study examined outcomes of patients who underwent valve repair or replacement with or without CABG, from 1/2000-1/2021. Outcomes in non-SLE and SLE surgical population were compared using 2:1 propensity score matching, accounting for baseline patient and procedural characteristics. Primary end points were 30-day and time-related mortality. Additional outcomes included occurrence of stroke, dialysis, blood transfusions, surgical re-exploration, and duration of intensive care unit (ICU) and hospital length of stay. RESULTS A total of 275,827 patient-years of follow-up information was available; median follow-up for death was 4.3 years. After matching, 265 patients with SLE were compared to 529 without SLE. Both cohorts demonstrated similar in-hospital mortality (2.8% SLE vs. 1.5% Non-SLE, P =.25), one-year survival (90% SLE vs. 89% Non-SLE) and 5-year survival (76% SLE vs. 71% Non-SLE). Length of post-operative ICU stay was shorter in the SLE cohort ( P =.007). CONCLUSION In patients with SLE selected to undergo cardiovascular surgery, in-hospital, 1 and 5-year morbidity and mortality were similar to the general operative population. A jeopardy for a diagnosis of SLE was not present.
Abstract 16139: Rising Cardiovascular Mortality in Prostate Cancer Patients: Results From Surveillance, Epidemiology and End Results (SEER) Database
Authors: Shailesh Niroula, Unnati Bhatia, Astha Prasai, Nischit Baral
Journal: Circulation (2023)

Introduction: Prostate cancer is the second most common cancer in men and the fifth leading cause of cancer related mortality. Advancement in therapy has led to improved survival among patients, however, there has been increased incidence of cardiovascular events among cancer survivors. Objective To observe the trend of cardiovascular specific death rate among patient with prostate cancer as compared to death due to cancer Methods: Patients with prostate cancer registered in SEER database from 2005 to 2020 were included. Prostate cancer specific mortality rate, cardiovascular (CV) specific mortality rate and all-cause mortality rate were analyzed using SEER*Stat version 8.4.1 software in the rate session. Joinpoint version 5.0.2 was used to create annual log-linear time trends. Results: The study included 857,410 patients diagnosed with prostate cancer from 2005 to 2020. The average annual percentage change (AAPC) of prostate cancer showed decreased incidence by 2.8 % (95% CI 1.8% to 4.1%, p&lt;0.05) from 2005 to 2020 with significant decrease in annual percent change (APC) from 2005 to 2014 by 4.9% (95% CI 2.9 % to 12.5, p&lt;0.05). AAPC of prostate cancer specific mortality rate increased by 1.8% ( 95% CI 1.3% to 2.9%, p&lt;0.05) from 2005 to 2020 with significant increase in APC by 2.4% (95% CI 1.3% to 9.2%, p&lt;0.05) from 2005 to 2018. AAPC of CV specific mortality rate increased by 4.4% (95% CI 4.1% to 4.9%, p&lt;0.05) from 2005 to 2020 with significant increase in APC by 7.1% (95% CI 6% to 9.2%, p&lt;0.05) from 2005 to 2011 and 2.6% (95% CI 2% to 3.1%, p&lt;0.05) from 2011 to 2020 (Figure 1). Conclusions: Around 2009, the cardiovascular specific mortality rate became higher than cancer specific mortality rate among prostate cancer patients and this trend has been consistent since then. It highlights advancement in treatment which has increased survival from prostate cancer, however it has increased cardiovascular mortality in patients due to advancing age as well as direct toxicity of treatment.
Abstract 15246: Myocardial Deformation for Prediction of Major Arrhythmic Events in Patients With Non-Ischemic Cardiomyopathy and Primary Prevention Implantable Cardioverter Defibrillators
Authors: Fahime Ghanbari, Julia Cirillo, Jennifer Rodriguez, Jennifer Yue, Daniel B Kramer, Manuel A Morales, Long Ngo, Warren J Manning, Reza Nezafat
Journal: Circulation (2023)

Introduction: Sudden cardiac death is a major cause of mortality in patients with non-ischemic cardiomyopathy (NICM). Implantable cardioverter-defibrillator (ICD) is an established prophylactic measure. But, optimal identification of patients with greatest likelihood of benefiting poses ongoing challenges. Objective: To assess the prognostic value of myocardial deformation for predicting ICD intervention while accounting for competing mortality risk. Methods: 180 NICM patients eligible for primary prevention ICD underwent cardiac magnetic resonance (CMR). Myocardial strains (left ventricular radial, circumferential, longitudinal; left atrial; and right ventricular free wall longitudinal strain (RV GLS)) were measured via CVI42 feature tracking. In a multivariable Fine-Gray competing risk model, incremental values of strains were assessed, adding to a baseline model based on clinical features and late gadolinium enhancement (LGE). The primary endpoint was ventricular tachycardia/fibrillation treated with ICD intervention, including shocks or anti-tachycardia pacing. Results: 159 patients with ICD (117 male; 54 ± 13 years) were included for final analysis (follow-up: 1176±960 days; median: 896). 26 patients met the primary endpoint. RV GLS showed a statistically significant difference between patients with and without events (-12.5% ± 5 vs -16.4% ± 5.5, p = 0.001). Univariate analyses revealed that LGE and RV GLS were significantly associated with outcome, even after accounting for competing risk (LGE: HR=3.69, 95% CI=1.28-10.62; RV GLS: HR=2.04, 95% CI=1.30-3.22). Adding RV GLS to the baseline model improved its prognostic value, with a c statistic improvement from 0.678 to 0.730. RV GLS hazard ratio remained significant in multivariate analysis after accounting for competing risk (HR=1.73, 95% CI=1.12-2.66) (Table 1). Conclusions: In NICM, RV GLS provides additional predictive value above LGE and clinical features for ICD intervention.
Abstract 12814: Impact of Obesity on Catheter Ablation of Ventricular Tachycardia in the United States: In-Hospital and 30-day Outcomes
Authors: Qi Xuan Ang, Min Choon Tan, Yong Hao Yeo, Bryan Tan, Pattara Rattanawong, Jian Liang Tan, Justin Lee
Journal: Circulation (2023)

Background: Catheter ablation for ventricular tachycardia (VT) has been increasingly performed. While it is estimated that 42% of adults in the United States are obese, the impact of obesity on VT ablation procedures remains unclear. Objective: This study aimed to evaluate the procedural outcomes and 30-day readmission among non-obese and obese patients who underwent catheter ablation of VT. Method: Using the Nationwide Readmissions Database, our study included patients aged 18 years or older who underwent catheter ablation for VT between 2017 and 2020. The study cohort was stratified into non-obese (BMI &lt; 30kg/m 2 ) and obese (BMI ≥ 30kg/m 2 ). The in-hospital procedural outcome and 30-day readmission were analyzed between these groups. Results: Our study included a total of 835 obese patients (19.7%) and 3393 non-obese patients (80.3%). Obese group had a higher rate of prolonged length of stay (&gt;7 days) (37.6% vs 31.2%, p&lt;0.01) and a higher cost of hospitalization ($39 983 vs $37 015, p&lt;0.01). Overall, there were no significant differences in early mortality (4.5% vs 3.8%, p=0.45). Apart from increased vascular complications in the obese group (1.8% vs 0.9%, p=0.03), there were no significant differences in other procedural complications between both groups. There were no significant differences in 30-day readmission rates between obese and non-obese groups (15.5% vs 14.1%, p=0.38). Additional analysis performed in the obese group revealed a non-significant decreasing trend in early mortality rate post-procedurally (5.4% to 4.8%, P trend = 0.66). On multivariable analysis, heart failure was associated with a higher risk of 30-day readmission in obese patients (OR: 2.00; 95% CI: 1.01-3.99; p=0.05). Conclusion: Our study suggests that catheter ablation for VT can be performed relatively safely in obese patients without significant differences in 30-day mortality and readmission outcomes. Patients should not be excluded from VT ablation on the basis of obesity.
Abstract 17268: Gender Distribution Within Medicine and Cardiology Journal Editorial Boards
Authors: Prisha Shivani, Anju Bhardwaj, Amanda Vest
Journal: Circulation (2023)

Introduction: In the United States, 50% of medical students and over 40% of internal medicine (IM) residents are women. Despite a visible increase in representation of women in academics, studies have noted underrepresentation in academic leadership. Hypothesis: We sought to evaluate if women have near equal representation in editorial boards in major journals reflective of the proportion of women in Medicine. Methods: We evaluated two leading IM and Cardiology journals each to assess whether there was equity in representation of women in editorial roles. The editorial boards of these journals were reviewed as of April 2023. The gender distribution of editorial board members was displayed graphically using pie charts. The combined proportions of women in the two IM and Cardiology journals, respectively, were compared using Fisher’s exact test (Prism v9.5.1). Results: For the IM journals, the editorial board of Journal of the American Medicine Association was comprised of 18 women and 34 men (34.6% women) and the New England Journal of Medicine had 32 women and 44 men (42.2% women, Figure 1). For the Cardiology journals, the editorial board of Circulation was comprised of 90 women and 306 men (22.7% women) and the Journal of the American College of Cardiology had 46 women and 215 men (17.6% women, Figure 1). When comparing the combined proportions of women, the IM journals had a greater representation of women (39.1%) than the Cardiology journals (20.7%), p&lt;0.0001. Conclusions: We observed that leading IM Journals have greater representation of women in editorial roles compared to Cardiology journals. This could be related to IM editorial boards drawing from a wider range of medical subspecialties, some of which may have greater representation of women. The ‘leaky pipeline’ in Cardiology may hinder gender-based parity at the highest academic ranks. Specific efforts to engage and mentor academic Cardiologists may help support diverse participation in editorial boards.
Abstract 13592: Addition of the Heart Score to a hsTnT Accelerated Diagnostic Protocol: Effect on Negative Predictive Value at Different hsTnT Thresholds
Authors: Muzna Hussain, Ria Garg, Kyle Marshall, Martin E Matsumura
Journal: Circulation (2023)

Background: The majority of pts with CP and low to modest elevations of high sensitivity troponin (hsTn) are safe for discharge from the ED; thus improvement of the negative predictive value (NPV) of the CP accelerated diagnostic protocol (ADP) can have significant impact on ED throughput. Prior studies have examined the role of adding bioclinical risk scores such as the HEART score (HS) to a hsTn ADP. In general these studies suggest the HS does not add to prediction of 30d MACE for pts with low peak troponin levels, i.e. less that the 99 th percentile. Little is known about the effect of the HS on hsTn ADP for higher values of troponin. Research question: How would the addition of the HS affect the NPV of a hsTnT ADP across a range of modest hsTnT elevations? Methods: Retrospective analysis of pts presenting with CP and assessed with a validated hsTnT ADP as well as an EHR-embedded HS decision tool from 5/2022-3/2023. The hsTnT ADP was derived from the ESC guidelines and pts were excluded if peak hsTnT was &gt; 52ng/l (the cutoff for “rule-in”). For calculation of NPV for MACE at 30 days post-discharge pts were grouped by peak hsTnT as &lt;6ng/l, &lt;12ng/l, and &lt;52ng/l. HS was grouped as &lt; 3 (low risk) or &gt;3 (intermediate-high risk). Comparison of NPV results was performed using chi square analysis. Results: Summarized in the Table. The addition of the HS did not significantly change the NPV for 30d MACE for CP pts with peak hsTnT &lt;6ng/l or &lt;12ng/l. In contrast, NPV in pts with peak hsTnT &lt;52ng/l was improved significantly by addition of the HS. Conclusion: The additive value of the HS to a hsTnT ADP for identifying pts safe for ED discharge depends on the range of troponin measurement- HS did not change NPV at very low levels (ie from &lt; limit of quantitation – approx. 99 th percentile) but did improve the NPV at modest elevations between the 99 th percentile and the cutoff for “rule-in” by our ADP. This findings should be considered when designing hsTn CP evaluation protocols that incorporate HS into the algorithm.