tbuckley/cabot-search huggingface dataset:
Abstract 11966: Translational Cardioinformatics: Neutrophil-Derived Translocator Protein as a Novel Regulator of Myocarditis and Coronary Artery Aneurysm in Kawasaki Disease and Multisystem Inflammatory Syndrome in Children
Authors: Jan Vincent B Beltran, Fang-Ping Lin, Chaw-Liang Chang, Taiming Ko
Journal: Circulation (2023)

Introduction: Cardiovascular disease (CVD) in Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) lead to increased mortality through myocardial infarction. Hypothesis: Since KD and MIS-C are shaped by the same immune continuum, the cardiac pathologies and lethal complications may be averted by targeting a key regulator controlling both diseases; however, the pathogenic drivers are largely undefined. Methods: Through integrated, multi-cohort, single-cell meta-analysis of KD and MIS-C PBMC scRNA-seq profiles, we investigated the immunological drivers associated with systemic damage and cardiac pathologies, compared with other pediatric diseases, and validated across independent cohorts of KD, MIS-C, and myocardial infarction. Via cheminformatics approaches, we identified FDA-approved drugs for repurposing. Results: We found the expansion and hyperactivation of CD177 + neutrophils in KD and MIS-C, but not in other pediatric diseases. CD177 + neutrophils overexpressed markers and causal mediators of CVD development, supported by activation of prognostic CVD gene signatures (acute CVD, major adverse cardiovascular and limb events, and myocardial infarction). CD177 + neutrophils’ overactivated effector repertoire may mediate systemic inflammation and molecular damage via a vascular homing mechanism. We identified a dysfunctional SPI1-dependent regulatory network shared by KD and MIS-C during neutrophil hyperactivation, as well as key regulators which may induce cardiac disorders. Importantly, we found that TSPO is associated with myocarditis and coronary artery aneurysm, disease severity, IVIG treatment, and patient recovery. Via independent cohorts analyses, we validated TSPO as a prime target against KD and MIS-C pathologies. Murine myocardial infarction model confirmed the cardiac hyper-infiltration of hyperactivated CD177 + neutrophils. Lastly, we identified FDA-approved drugs against KD and MIS-C neutrophil hyperactivation. Conclusions: Collectively, CD177 + neutrophils have a pivotal role in KD/MIS-C systemic pathologies, clinical severity, and prognosis. We suggest drugs that can be developed as a single therapeutic strategy against either KD or MIS-C for clinical translation.
Abstract 11687: Percutaneous Coronary Intervention for Chronic Total Occlusions is Associated With Higher Inpatient Mortality and Complications
Authors: Mohammad Reza Movahed, Allistair Nathan, Mehrtash Hashemzadeh
Journal: Circulation (2023)

Background: Percutaneous coronary intervention (PCI) in patients with chronic total occlusion (CTO) is commonly performed despite unclear long-term benefits. Hypothesis: The goal of this study was to evaluate the post-procedural outcome of patients with CTO intervention. Methods: The National Inpatient Sample (NIS) database, years 2016-2020, was studied using ICD 10 codes. Patients with CTO intervention were compared to patients without CTO. We evaluated post-procedural mortality and complications. Results: PCI in patients with CTO was associated with higher mortality and all post-procedural complications. A total of 2,011,854 patients underwent PCI with 259,574 having CTO. The CTO group had a 3.17% mortality rate vs 2.57% of non-CTO PCI. (OR, 1.24; CI:1.18-1.31; p&lt;0.001). Using multivariate analysis adjusting for age, sex, race, diabetes mellitus, and chronic kidney disease, CTO PCI remained significantly associated with higher mortality (OR, 1.37; 95% CI, 1.3 - 1.45; p&lt;0.001). Patients with CTO compared to non-CTO PCI patients had higher rates of myocardial infarction (OR, 2.85; 95% CI, 2.54 - 3.21; p&lt;0.001), coronary perforation (OR, 6.01; 95% CI, 5.25-6.89; p&lt;0.001), tamponade (OR, 3.36; 95% CI, 2.91-3.88, p&lt;0.001), contrast-induced nephropathy (OR, 2.05; 95% CI, 1.45-2.90), p&lt;0.001), procedural bleeding (OR, 3.57; 95% CI, 3.27-3.89, p&lt;0.001), and acute post-procedural respiratory failure (OR, 2.07; 95% CI, 1.81-2.36, p&lt;0.001). All post-procedural complications were more than 3 times the non-CTO patients (OR, 3.45; 95% CI, 3.24-3.67; p&lt;0.001). Conclusion: Using a large national inpatient database, PCI performed in patients with CTO was associated with significantly much higher mortality and post-procedural complications compared to PCI in non-CTO patients.
Abstract 12124: GlycA is Associated With Both Coronary Artery Calcium Incidence and Progression: ELSA-Brasil Cohort Analysis
Authors: Ronaldo Correa Fabiano Filho, Giuliano Generoso, Rhanderson Cardoso, Steven R Jones, Raul D Santos, Peter P Toth, Isabela M Bensenor, Paulo A Lotufo, Marcio Bittencourt
Journal: Circulation (2023)

Introduction: GlycA is an emerging systemic inflammatory marker and quantifies N-acetyl glucosamine within the glycan region of acute phase proteins. Elevated levels of GlycA, are associated with a higher risk for coronary artery disease (CAD). There is conflicting evidence on whether GlycA levels can predict subclinical CAD progression in healthy adults. Hypothesis: High GlycA levels can predict subclinical CAD progression in healthy patients. Methods: We included 2,690 participants from the ELSA-Brasil cohort without cardiovascular/chronic inflammatory disease not receiving statin therapy who had GlycA level measured and two interval coronary artery calcium score (CAC) assessments between 2010 through 2018. Multivariable regression models adjusted for demographics, lifestyle, comorbidities, and laboratory parameters were used to assess the consistency of GlycA levels and CAC incidence and progression (Berry definition). CAC incidence required that the first CAC = 0. CAC progression required that the first CAC &gt; 0. Therefore, the presence of CAC incidence and progression were mutually exclusive. Results: The mean age of participants was 48.6 ± 7.7 years, 56.7% were female, 54.6% and 16.1% (429/2690) were White and Black, respectively. The mean CAC interscan period was 5.1 ± 0.9 years, the mean GlycA level was 414.7 ± 65 μmol/L, and the incidence of CAC was 13.1%. GlycA level odds ratio (OR) for CAC incidence was 1.002 (95% CI 1.0005-1.005, p = .016) adjusted for demographics, lifestyle, early (≤60 years) CAD family history, lipid panel, and comorbidities. The GlycA (≤p25 vs &gt;p75) OR for CAC progression (Berry definition) was 1.77 (95% CI 1.07-2.96, p = .03) in a similar multivariable adjustment model. Conclusions: Higher GlycA levels were associated with CAC incidence and progression even after adjusting for multivariable risk factors in a healthy Brazilian cohort. GlycA may have potential to further stratify CAD risk in healthy patients.
Abstract 11776: Sex Differences in Coronary Artery Disease Characteristics Among Patients With Type 2 Myocardial Infarction: Results From the Prospective DEFINE-Type 2 MI Study
Authors: Claire Lin, Cian P McCarthy, Reza Mohebi, Yuxi Liu, Ron Blankstein, Campbell Rogers, Sandeep Hedgire, Sean Murphy, Hannah Miksenas, Daniel Amponsah, Paula Rambarat, Avanthi Raghavan, Allison Levin, Jason H Wasfy, Brian Ghoshhajra, James L Januzzi
Journal: Circulation (2023)

Background: Type 2 Myocardial Infarction (T2MI) is a result of coronary supply and demand imbalance and is associated with a poor prognosis. It is crucial to identify potential sex-based differences in the prevalence and nature of coronary artery disease (CAD) within this specific population. Retrospective analyses are limited by selection bias, unequal proportions of male and female subjects, and lack of angiographic definition. Hypothesis: In patients with T2MI, women and men will have unique characteristics. Aim: To evaluate sex-based differences in presentation, prevalence/characteristics of CAD and clinical management of T2MI. Methods: In a single-center prospective study, patients with strictly adjudicated T2MI underwent coronary computed tomography angiography and Fractional Flow Reserve (FFR CT ) and quantitative plaque assessment was performed. Results: Of 50 study participants enrolled, 50% were women. Women with T2MI were older than men with T2MI (72.2 ± 10.1 vs. 64 ± 11.3 years; p = 0.009) but otherwise had similar baseline characteristics. A broad and similar mix of T2MI precipitants were present among both sexes. Ischemic ST depression was more common in women (64% vs. 32%; p = 0.05) while men were more likely to have T wave inversion (68% vs. 36%; p = 0.05). Women and men had comparable CAC scores (median [Q1, Q3] 152 [45, 762] vs. 234 [56, 422]; p = 0.07). Prevalence of any CAD (100% vs. 84%; p = 0.12), obstructive CAD (28% vs. 24%; p = 1.0), and hemodynamically significant focal stenosis with FFR CT &lt; 0.80 (64% vs. 56%; p = 0.08) were similar between men and women. While total plaque volumes were similar between men and women, women had significantly lower levels of low-attenuation plaque (median [Q1, Q3]: 3 [1,7] vs. 9 [3, 14]; p = 0.03). Men and women did not significantly differ in percentile of plaque burden. Both sexes showed comparable increases in the utilization of aspirin (OR = 0.67; p = 0.53), beta blockers (OR = 0.76; p = 0.71), and statins (OR = 0.22; p = 0.08) by discharge. Conclusions: This prospective study of using FFRCT in T2MI identifies similarities and differences in clinical presentation and CAD characteristics of T2MI in both men and women. These findings may be helpful in improving the identification and management of T2MI.
Abstract 11693: Comparison of In-Hospital Outcomes in Infective Endocarditis Patients With and Without Embolic Stroke
Authors: Ahmed Maraey, saleh alhalaseh, Nmair Alziadin, Apoorva T Raju, Zaid Alwarawrah, Sabrina A Mann, Omar Al Wahadneh
Journal: Circulation (2023)

Introduction: Infective endocarditis (IE) is a critical condition that can lead to complications such as embolic stroke. This study aimed to compare the in-hospital outcomes between IE patients with and without embolic stroke. Methods: We conducted a retrospective analysis using the National Inpatient Sample database from 2016 to 2020. We identified admissions with a principal diagnosis of IE, with embolic stroke as a secondary diagnosis. In-hospital outcomes, including mortality, length of stay, and total charge, were analyzed after adjusting for patients' demographics, hospital characteristics, and chronic comorbidities, including heart failure, hypertension, diabetes, chronic kidney disease, smoking, and hyperlipidemia. Results: A total of 62,200 admissions with IE were identified, of which 4,460 (7.2%) developed embolic stroke, with females accounting for 38% of the cohort. Patients who developed embolic stroke had a significantly higher risk of mortality (OR: 2.4, 95% CI: 1.8-3.1, P=0.000), longer length of stay (18 days, Coefficient: 5.8, 95% CI: 4.6-7.0, P=0.000), and higher total charge (285,285, Coefficient: 121,586, 95% CI: 98,119-145,054, P=0.000). Conclusion: Our study found that IE patients who experienced embolic stroke had significantly worse outcomes, including higher mortality rates, prolonged length of stay, and increased financial burden. These findings emphasize the need for targeted interventions and close monitoring for this high-risk subgroup to improve patient outcomes and resource utilization.
Abstract 12129: Using a Polygenic Risk Score to Account for Genomic Risk Factors in a Model to Detect Individuals With Dilated Ascending Thoracic Aortas
Authors: John Depaolo, Gina Biagetti, Renae Judy, Grace Wang, Amit Iyengar, John J. Kelly, Nimesh D Desai, Wilson Y Szeto, Joseph E Bavaria, Michael Levin, Scott M Damrauer
Journal: Circulation (2023)

Background: Ascending thoracic aortic dilation is a complex trait that involves modifiable and non-modifiable risk factors and can lead to thoracic aortic aneurysm and dissection. Clinical risk factors have been shown to predict ascending thoracic aortic diameter. Polygenic risk scores (PRS) are increasingly used to assess clinical risk for multifactorial diseases. The degree to which a PRS improves aortic diameter risk prediction is not known. In this study we tested the extent to which the addition of PRS to clinical prediction algorithms improves the prediction of aortic diameter. Methods: Training and validation cohorts comprised 6,790 Penn Medicine Biobank (PMBB) participants with clinical data linked to whole exome sequencing. Linear regression models integrated PRS weights derived from a large genome wide association study of thoracic aortic diameter in the UK biobank and were compared to the performance of the standard and a reweighted variation of the recently published AORTA Score. Results: The training cohort of 5,092 participants (56% male) had a median age of 61 years (IQR 52-70) with a mean ascending aortic diameter of 3.4 cm (SD 0.5). Compared to the AORTA Score which explained 29.1% (95% CI 27.9%-30.8%) of the variance in aortic diameter, AORTA Score + PRS (explained 29.7%, 95% CI 28.5%-30.9%), the reweighted AORTA score (explained 30.7%, 95% CI 29.4%-32.3%), and the reweighted AORTA Score + PRS (explained 31.5%, 95% CI 30.0%-32.8%) had superior performance. For the predictive ability to identify thoracic aortic diameter of ≥ 4 cm, the addition of a PRS to both the AORTA Score and the reweighted AORTA Score improved sensitivity at a range of model threshold values. The respective areas under the receiver operator characteristic curve for the AORTA Score + PRS (0.762, 95% CI 0.731-0.794) and reweighted AORTA Score + PRS (0.779, 95% CI 0.749-0.809) were greater than the standard AORTA Score (0.758, 95% CI 0.727-0.789) and reweighted AORTA Score (0.775, 95% CI 0.745-0.805). Conclusions: We demonstrated that inclusion of a PRS to the AORTA Score results in a small performance enhancement. Further investigation is necessary to determine if incorporation of genetics into clinical risk prediction improve outcomes for thoracic aortic disease.
Abstract 12119: Work Environment, Burnout, and Intent to Leave Current Job Among Cardiology Team Members: Results From the National Coping With COVID Survey
Authors: Sanjoyita Mallick, Gautam R Shroff, Mark Linzer, Pamela S Douglas, Erin Sullivan, Roger Brown, Rehan Karim
Journal: Circulation (2023)

Introduction: Burnout amongst cardiologists has nearly doubled since the COVID pandemic, but few data describe burnout or its relationship to work environment factors among cardiology team members. Methods: The National Coping with Covid (CwC) Survey included over 1300 cardiology healthcare workers (HCWs). We determined likelihood of burnout among different roles (physicians, advanced practice providers [APPs], nurses [RNs] and other clinical staff [OCS]). Multilevel logistic regression examined independent work life variables in predicting and mitigating burnout, and relationships of burnout to intent to leave current job. Results: The CwC Survey was completed by 1,396 cardiology HCWs (306 MD/ 173 APP/452 RN/ 105 OCS). RNs were most likely to report burnout (59% RNs, 56% OCS, 46% APPs, 40% physicians, p&lt; 0.0001). Work overload was an independent correlate of burnout in all 4 groups, anxiety/depression due to COVID was meaningful in 3 groups, while childcare stress was not related in any group (adjusted Odds Ratios (aORs) 4-17, p’s &lt; 0.005, Table). Feeling valued (FV) was associated with lower burnout in all groups except OCS. A sense of purpose was not significantly associated with lower burnout in any group, although there was a borderline association in physicians (aOR 0.53, p = 0.07). Intent to leave was common, and associated with burnout in all groups, especially APPs (r=0.66) and OCS (r=0.73, p’s &lt; 0.01). Conclusions: Burnout, common among cardiology HCWs, is highest in nurses. While work life variables related to burnout differ between role types, burnout is consistently associated with intent to leave practice. Leaders should recognize that burnout is prevalent among team members, may have different contributors, and has consequences for retention. To prevent burnout in cardiology, strategies such as workload reduction, mental health services and explicitly and effectively valuing workers should be implemented.
Abstract 11949: Novel First-Trimester Serum Biomarkers for Early Prediction of Preeclampsia
Authors: Yan Li, Hong-Jin Zhao, Daimin Wei, Zi-Jiang Chen
Journal: Circulation (2023)

Background: Preeclampsia (PE) is a leading cause of maternal and perinatal mortality and morbidity worldwide, but effective early prediction remains a challenge due to the lack of reliable biomarkers. Research questions: Could potential imbalances in cytokines and autoimmune antibodies be detectable in the first trimester of pregnancy in women who later develop PE? Goals: Our study aims to discover novel biomarkers within the first trimester and construct an efficient predictive model to enhance early PE screening strategies. Methods: Based on the extensive human biobank of our large-scale assisted reproductive cohort platform, we measured the first-trimester serum levels of 48 cytokines, total immunoglobulins (Igs), anti-phosphatidylserine (aPS) antibodies, and several previously identified PE biomarkers—including placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and activin A—in 34 women diagnosed with PE and 34 matched normotensive controls. Results: Our analysis revealed that the PE group exhibited significantly elevated first-trimester serum levels of hepatocyte growth factor (HGF), interleukin (IL)-2Rα, IL-9, RANTES, tumor necrosis factor-β (TNF-β), total IgM, and total IgG, and aPS IgG optical density (OD) value, in addition to decreased first-trimester serum levels of PlGF and total IgA and aPS-IgG immune complexes (IC) OD value compared to the control group. The combination of the top five first-trimester serum biomarkers (total IgM, total IgG, PlGF, aPS IgG, and total IgA) achieved superior predictive value [area under the curve (AUC) and 95% confidence interval (CI): 0.983 (0.952-1.000)] for PE development compared to PlGF and PlGF/sFlt-1 independently [AUC and 95% CI: 0.825 (0.726-0.924) and 0.670 (0.539-0.800), respectively]. Conclusion: We identified novel first-trimester serum biomarkers and developed an effective prediction model integrating immune-related factors and PlGF for early PE detection, which could facilitate the development of early diagnostic strategies and provide immunological insight into the further mechanistic exploration of PE.
Abstract 106: Assessing Out-of-Hospital Cardiac Arrest Management With a New Automated External Defibrillator Algorithm: A Prospective Before-After Study on Ventricular Fibrillation Detection During Chest Compressions With a Shortened CPR Cycle
Authors: Daniel Jost, Clément Derkenne, Vivien Hong Tuan Ha, Benoit Frattini, Sarah MENETRE, Jean Philippe Didon, Frankie BEGANTON, Sabine Lemoine, Wulfran Bougouin, Frederic Lemoine, Eloi Marijon, Xavier Jouven, Stephane Travers
Journal: Circulation (2023)

Introduction: During out-of-hospital cardiac arrests (OHCA), AEDs analyze cardiac rhythm every 2 minutes with chest compressions (CC) having to be interrupted. Since 2021, the Paris Fire Brigade has used AEDs equipped with an "Analysis While Compressing" (AWC) module that enables an external electric shock (EES) to be delivered every minute if required. This new algorithm aligns AED analysis timing with potential VF recurrence but results in redistribution between CC time and analysis periods. We aimed to assess the CC fraction (CCF) in OHCA patients who received AWC and compared it with the CCF in 2017 patients who received a standard (STD) algorithm. Method: In this observational, prospective before-after study, we included adult non-traumatic OHCA patients with initial Ventricular Fibrillation (iVF) rescued by firefighters. Their AEDs provided STD algorithm in 2017 and AWC algorithm in 2022. All AED parameters were measured within 10 minutes of the initial shock. Primary outcome was the CCF, a criterion sensitive to algorithm modifications. Secondary outcomes were pre and post-shock pauses, and the percentage of time the cardiac rhythm was organized. We matched patients from both periods on four key covariates (sex, age, location, bystander status) using propensity score matching. The estimator for continuous variables was the median [interquartile range]. Results: We included 285 consecutive patients in each period. Most were men, 74% (212/285) in 2017 and 81% (231/285) in 2022; median ages were 58 [49-69] and 60 [51-72] years. After propensity score matching, CCF improved significantly with the AWC algorithm (77% [72%-80%]) vs. the STD algorithm (72% [67%-76%], p&lt;0.01). Pre and post-shock pauses decreased from 19 [17-23] and 4.5 [3-6] to 11[9-16] and 3.8 [2-5] sec. in 2017 and 2022, respectively (p &lt; 0.01). Delay from VF recurrence to the next shock decreased from 124 [92-135] sec. in 2017 to 60 [37-71] sec. in 2022 (p&lt; 0.01). The time spent in an organized rhythm during the first ten min. of AED connection increased from 7 % [0-46] in 2017 to 14% [0-58] in 2022 (p&lt; 0.01). Conclusion: AWC improved hands-on times, CCF, and time ratio spent in cardiac organized rhythm. Further analyses are underway to measure its impact on survival at hospital discharge.
Abstract 11964: The Effect of Endothelin-1 on Angiotensin II-Induced Renal Injury
Authors: Tomiharu Niida, Kikuo Isoda, Fumie Ohtomo, Koji Akita, Kenichi Kitamura, Tomoyasu Kadoguchi, Tohru Minamino
Journal: Circulation (2023)

Introduction: Hypertension (HT) and kidney disease is increasingly recognized as a global public health problem. Angiotensin II (AngII) induces endothelin-1 (ET-1), and ET-1 is a key mediator of kidney fibrosis. Hypothesis: Inhibition of ET-1 may contribute to modulation of HT and renal injury induced by angiotensin II. Methods: In addition to wild-type (WT) mice, we also used IL-1 receptor antagonist-deficient (IL-1Ra -/- ) mice that were prone to AngII-induced renal inflammation, because WT (C57BL) mice were genetically resistant to renal injury in response to AngII. Both mice were infused with AngII (1000ng/kg/min) using subcutaneous osmotic pumps for 14 days. Results: Systolic blood pressure in IL-1Ra -/- mice significantly increased compared with WT mice (197±5 vs 169±9 mmHg, p&lt;0.05). Furthermore, renal preproendothelin-1 mRNA expression and serum levels of ET-1 were also significantly higher in IL-1Ra -/- mice (p&lt;0.05). Immunostaining revealed that ET-1 was elevated in glomeruli and tubules in the cortex of IL-1Ra -/- mice compared with WT mice (Figure upper panels: ET-1 staining), indicating elevated ET-1 might contribute to glomerular injury (Figure middle panels: PAS staining) and intratubule fibrosis (Figure lower panels: Elastica Masson staining) detected in the histological analysis. Finally, we investigated whether pharmacological inhibition of ET receptors could prevent AngII-induced renal injury in IL-1Ra -/- mice. Bosentan significantly decreased AngII-induced HT, and protected renal injury in IL-1Ra -/- mice. On the other hand, treatment of hydralazine, an antihypertensive agent, did not suppress renal damage in AngII-infused IL-1Ra -/- mice in spite of improvement of HT. Conclusions: Our results indicate that inhibition of ET-1 might protect AngII-induced renal inflammation beyond an antihypertensive therapy, suggesting that we might be required to develop new strategies for blocking ET-1 to prevent hypertensive renal injury.