tbuckley/cabot-search huggingface dataset:
Abstract 12905: Epicardial and Intramyocardial Fat as Predictors of Ventricular Arrhythmia in Ischemic and Non-Ischemic Cardiomyopathy
Authors: Maryam Mojarrad Sani, Eric Sung, Marc Engels, Natalia Trayanova, Katherine C Wu, Jonathan Chrispin
Journal: Circulation (2023)

Background: Sudden cardiac death from ventricular arrhythmia (VA) is a global concern. While emerging evidence suggests a role for myocardial fat in the development of VA among ischemic (ICM) and non-ischemic cardiomyopathy (NICM) patients, the volume and distribution of epicardial adipose tissue (EAT) and intramyocardial fat (IMF) linked to VA remain underexplored. Objective: To evaluate the predictive value of LV tissue heterogeneity, EAT, and IMF volumes in assessing the risk of VA in ICM and NICM patients. Methods: Patients enrolled in the PROSE-ICD registry, who underwent contrast-enhanced computed tomography were included. The designated endpoint was ventricular arrhythmia, defined as appropriate ICD shock or sudden arrhythmic death. IMF volume (voxels between -180 and -5 HU), EAT volume (voxels between -200 to -50 HU), and myocardial fat tissue heterogeneity (defined as the magnitude of change between nearby voxels) were calculated. Logistic regression models were employed to assess the association between explanatory variables and outcome. Results: 98 patients (47 ICM, 51 NICM) were included with a mean follow up time of 5.6±3.4 years. Participants’ mean age was 56±13.2 years, and 66% were male. LV tissue heterogeneity (per HU/mm) was associated with VA incidence (OR = 1.11; P &lt; 0.01) in the ICM cohort, whereas EAT and IMF volume were associated with VA in the NICM subgroup [(OR = 1.12; P &lt; 0.01), and (OR = 1.21; P = 0.01), respectively]. Even after adjusting for various covariates, LV tissue heterogeneity in the ICM group and EAT in the NICM group maintained a significant association with VA. Conclusion: In ICM, increased fat distribution heterogeneity is associated with VA, while in NICM, increased IMF and EAT volume are linked to a higher risk for VA. These findings suggest that LV tissue heterogeneity and EAT volume offer valuable prognostic insights in cardiomyopathy patients, indicating that the contribution of fat to VA depends on the underlying substrate.
Abstract 11986: Erythropoietic Response After Intravenous Iron in Heart Failure With Reduced Ejection Fraction With or Without Background Treatment With Sodium-Glucose Co-Transporter 2 Inhibitors
Authors: Paula Matias, Pedro Marques, Joana T Vieira, Francisco Vasques-Novoa, Abhinav Sharma, Thomas A Mavrakanas, Fernando Frioes, Joao P Ferreira
Journal: Circulation (2023)

Introduction: Intravenous (IV) iron increases hemoglobin/hematocrit and improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF) and iron deficiency. Sodium glucose co-transporter 2 inhibitors (SGLT2i) also increase hemoglobin/hematocrit and improve outcomes in HF by mechanisms linked to nutrient deprivation signaling, and inflammation/oxidative stress reduction. The effect of IV iron among patients using SGLT2i has not yet been studied. Hypothesis: We hypothesize that HFrEF patients with iron deficiency treated with IV iron with a background treatment including a SGLT2i will have an increase erythropoietic response comparing to SGLT2i non users. Methods: Retrospective, single-center analysis of HFrEF patients with iron deficiency treated with IV iron using (n=60) and not using (n=60) SGLT2i, matched for age and sex. The primary outcome was the difference in absolute hemoglobin change (before vs after IV iron administration) between SGLT2i users and nonusers. The main secondary outcomes were the difference in hematocrit and iron biomarkers (total iron, ferritin and trasnferrin saturation) changes between SGLT2i users and nonusers. Results: Mean age was 73±12 years, 48% were men, with more than 65% of patients having chronic kidney disease and anemia. After adjustment for all baseline differences, SGLT2i users experienced a greater increase in hemoglobin and hematocrit compared to SGLT2i nonusers: hemoglobin +0.57 g/dL (95%CI 0.04-1.10, p=0.036) and hematocrit +1.64% (95%CI 0.18-3.11, p=0.029). No significant differences were noted for iron biomarkers or any of the secondary outcomes. Conclusion: Combined treatment with IV iron and background SGLT2i was associated with a greater increase in hemoglobin and hematocrit than IV iron without background SGLT2i. These results suggest that in HFrEF patients treated with IV iron, SGLT2i may increase the erythropoietic response.
Abstract 12001: To Bleed or Not to Bleed: The Challenging Management of Saddle Pulmonary Embolism in a Patient With Widely Metastatic Breast Cancer
Authors: Zeel K Patel, Keneil Shah, Afif Hossain, Arthi Palani, Pallavi Solanki
Journal: Circulation (2023)

Introduction: In patients with high-risk pulmonary embolism (PE), anticoagulation (AC) is the mainstay of treatment before and after systemic thrombolysis and/or catheter-directed therapy. Our case highlights a challenging clinical decision where AC had to be initiated due to hemodynamic instability despite its controversial role in patients with CNS metastases. Case Description: A 52 years old female with ER+/PR+/HER2- breast cancer with widespread brain &amp; vertebral metastases presented after a syncopal event. She had tachycardia and hypotension necessitating IV fluids and vasopressors. Echocardiogram showed RV dilation with reduced systolic function &amp; septal wall motion concerning for RV pressure overload. CTA of chest showed large saddle PE with extension into bilateral segmental arteries and enlarged RV. Significant labs: Troponin-I 1.64 ng/mL, BNP 186 pg/mL, hemoglobin 8 g/dL, and platelets 54,000/μl. She was initiated on IV heparin but given worsening hemodynamic instability, she underwent catheter-based thrombectomy with improvement in hemodynamics. Serial CT head showed no evidence of intracranial hemorrhage but she developed diffuse alveolar hemorrhage necessitating intubation. Her bleeding eventually resolved, and she was extubated and discharged on DOAC. Discussion: This patient had high-risk PE given her hemodynamic instability, elevation in cardiac biomarkers, and RV strain on imaging. Treatment includes AC followed by systemic thrombolysis or catheter-directed therapy followed by AC. This patient’s management was complicated due to widespread metastases, thrombocytopenia and anemia. AC was nonetheless initiated due to her hemodynamic instability and patient eventually required thrombectomy. Conclusion: Brain metastases are an absolute contraindication to systemic thrombolysis, but the role of systemic AC is controversial. Our case highlights the importance of personalized decision-making regarding AC.
Abstract 13741: Off-Label Dosing of Direct Oral Anticoagulants Among Inpatients With Atrial Fibrillation
Authors: Amneet Sandhu, Lisa Kaltenbach, Karen Chiswell, Vijay Shimoga, Carmel Ashur, Abby Pribish, Gregg C Fonarow, Jonathan P Piccini, Michael Ho, Paul D Varosy, Paul Hess
Journal: Circulation (2023)

Introduction: Among patients hospitalized for atrial fibrillation (AF), the frequency of off-label direct oral anticoagulant (DOAC) dosing, associated factors, hospital-level variation, and temporal trends in contemporary practice are unknown. Methods: Using the Get With The Guidelines® Atrial Fibrillation (GWTG-AF) registry, patients admitted from January 1 st , 2014 to March 31 st , 2020, and discharged on DOAC were stratified according to receipt of under, over, or recommended dose. Factors associated with off-label dosing were identified using logistic regression. Hospital-level variation and temporal trends were assessed. Results: Of 22,470 patients prescribed a DOAC at discharge from hospitalization (66% apixaban, 29% rivaroxaban, 5% dabigatran), underdosing occurred among 2006 (8.9%), overdosing among 511 (2.3%), and recommended dosing among 19953 (88.8%). Patient factors associated with off-label use included age (underdosing: OR 1.06 per 1-year increase [95% CI 1.06-1.07] and overdosing: OR 1.07 per 1-year increase [1.06-1.09]), dialysis dependence (underdosing: OR 5.50 [3.76-8.05] and overdosing: OR 5.47 [2.74-10.88]), female sex (overdosing: OR 0.79 [0.63-0.99]) and weight (overdosing: OR 0.96 per 1-Kg increase [0.95-1.00]). Across hospitals, the adjusted median odds ratio for off-label DOAC use was 1.45 [95% CI 1.34-1.65] (underdosing: 1.52 [1.39-1.76] and overdosing: 1.32 [1.20-1.84]), indicating significant hospital-level variation. Hospital characteristics associated with underdosing included West vs. Northeast location (OR: 1.55 [1.04-2.31]), rural vs. urban setting (OR: 0.48 [0.28-0.83]), and number of beds (&lt;200 vs. 500+, OR: 1.95 [1.29-2.95]). Recommended dosing significantly increased over time (81.9% in 2014 to 90.9% in 2020, p&lt;0.0001 for trend) with a corresponding decline in under (14.4% in 2014 to 6.6% in 2020, p&lt;0.0001 for trend) and overdosing (3.8% in 2014 to 2.5% in 2020, p=0.001 for trend). Conclusion: One of 10 patients hospitalized for atrial fibrillation is discharged on off-label dosing of DOAC with significant variation across hospitals. While the proportion of patients receiving recommended dosing has significantly improved over time, opportunities to improve DOAC dosing persist.
Abstract 11993: Integrative Analysis of Single-Cell Transcriptomics and Polygenic Risk Scores Uncovers Vascular Smooth Muscle Cell Heterogeneity in Human Aortic Aneurisms
Authors: Mark E Pepin, S.K. Vellari, D.S. Atri, Ankith Reddy, Oscar Sias-Garcia, Andrew R Hamel, Marie Billaud, Vivian Lee-Kim, Ayellet Segre, Rajat Gupta
Journal: Circulation (2023)

Background: Atherosclerosis is accompanied by distinct vascular phenotypes that underly its initiation and progression, though their contribution to its pathogenesis is currently unknown. By integrating polygenetic risk profiles from genome-wide association studies (GWAS) of vascular disease with single-cell transcriptional analyses, it is possible to implicate causal cellular subpopulations and functional states. Hypothesis: We sought to build a more precise understanding of the cellular mechanisms underlying vascular disease in humans by combining single-nuclear RNA-sequencing (snRNA-seq) data from vascular tissue with known polygenic risk loci associated with vascular disease. Methods: We performed snRNA-seq on five flash-frozen human aortas, implementing a novel dissociation method to isolate and sequence 14,228 quality-controlled nuclei from three thoracic aortic aneurysms and two samples without known aortopathy, obtained from patients aged 37-70 years. Cell types were defined using canonical gene markers, and non-linear dimensional reduction via tSNE was employed to identify transcriptional sub-phenotypes. The identified pathological programs were validated using polygenic risk and by integrating GWAS data from other vascular single-nuclear transcriptomic datasets. Results: Our analysis revealed ten distinct clusters representing all major vascular cell populations, with vascular smooth muscle cells (VSMCs) and myofibroblasts emerging as the most relevant cell types in relation to vascular disease based on polygenic risk. Within the VSMC population, two distinct subpopulations exhibited differential expression of genes related to the extracellular matrix, contractility, and proliferation. RNA-trajectory analysis further uncovered a continuum of gene expression linking VSMC1, VSMC2, and myofibroblast transcriptional clusters. Conclusions: This study validates novel methods for identifying pathologic VSMC states associated with vascular disease and implicates phenotypic switching as a pathogenic mechanism. We highlight genes and pathways associated with endothelial cell and VSMC state transitions that are enriched in GWAS of coronary artery disease (CAD).
Abstract 11999: COVID-19 Increases the Risk of New Myocardial Infarction in Patients With Prior Myocardial Infarction
Authors: Ayman El-Menyar, Ahmed Ramzee, Mohammad Asim, Hassan Al-thani, Sandro Rizoli
Journal: Circulation (2023)

Introduction: The pathology of coagulopathy in patients with COVID-19 infection is not fully understood and it is believed to differ from the other critical illness. Hypothesis: we aimed to investigate the incidence and type of thromboembolic events (TEE) and particularly myocardial infarction (MI) in patients who were hospitalized with Covid-19 infection with a prior MI. We hypothesized that Covid-19 infection increases the rate of new TEE in this population regardless of age and gender. Methods: A retrospective analysis was conducted for all adult patients (≥18 years of age) admitted for treatment in quarantine centers with COVID-19 infection and developed TEE during the hospital course between February and August 2020. Patients were categorized based on the history of prior MI, age (&lt;55 vs ≥55) and gender. The type of TEE was specified Results: Between February and August 2020, 16,903 patients with COVD-19 infection were admitted in the country and 210 (1.2%) developed TEE (89% were males, 55% were &lt;55 years old, 72% were south Asians, and 80.5% had prior MI). Out of patients with prior MI, 92.5% developed another MI (Figure 1). DVT and portal vein thrombosis were common than new MI in patients without prior MI (Figure 2). New MI was more evident in young male patients who had prior MI; however, it was also reported in young males with no prior MI. No new MI was noted in females with no prior MI. Conclusions: the rate of TEE, particularly MI, increases after Covid-19 infection in patients with prior MI. Age and gender had great impact on the occurrence of TEE as well.
Abstract 12257: The Relationship Between Histological Features of Epicardial Adipose Tissue and Aortic Valve Calcification Assessed on Computed Tomography
Authors: Toshiro Kitagawa, Kazuhiro Sentani, Yuki Ikegami, Shinya Takahashi, Yukiko Nakano
Journal: Circulation (2023)

Background: It has been hypothesized that epicardial adipose tissue (EAT) biologically contributes to the pathogenesis of cardiac diseases. However, it remains unclear how EAT correlates with the progression of aortic valve calcification (AVC). We evaluated if histological features of EAT are specifically related to AVC assessed on computed tomography (CT). Methods: We enrolled 35 patients undergoing cardiac CT examination before elective cardiac surgery (coronary artery bypass graft [CABG] and/or cardiac valve surgery), in which AVC was detected on CT. Each patient was evaluated with EAT volume, coronary calcium score (CCS), AVC score, and the presence of high-risk coronary plaque (HRP) on CT. During each cardiac surgery, histological samples for immunohistochemistry were obtained from EATs adjacent to the left anterior descending and right coronary arteries. Each patient was assessed with the numbers of CD-68 + and CD-11c + individual macrophages and osteocalcin + individual cells in a total of 6 random high-power fields (x400) of EAT samples. Results: In the histological findings of EAT, osteocalcin + cells showed a weak correlation with CD-68 + macrophages ( r = 0.40, p = 0.016) and a moderate correlation with CD-11c + macrophages ( r = 0.60, p = 0.0001). The AVC score on CT correlated with CD-11c + macrophages and osteocalcin + cells in EAT (Fig 1), whereas CCS had no correlation with such histological findings. On multivariate analysis adjusted for age, sex, CABG vs. non-CABG, EAT volume, CCS, and the presence of HRP, the AVC score independently correlated with increased CD-11c + macrophages (β = 0.58; p = 0.0036) and osteocalcin + cells (β = 0.59; p = 0.0021) in EAT. Fig 2 shows representative cases with different levels of AVC and EAT histology. Conclusions: The inflammatory and osteogenic activity in EAT significantly correlate with the progression of AVC, which may indicate a specific contribution of EAT to aortic valve degeneration through biological activities.
Abstract 12324: Current Trends in Anticoagulation, Referral and Utilization of Procedures for Rhythm Control for Atrial Fibrillation
Authors: Saima Karim, William R Lewis, Shari Bolen, Ashwini R Sehgal, Douglas Einstadter
Journal: Circulation (2023)

Introduction: Atrial fibrillation (AF) can reduce quality of life and cause thromboembolic events, heart failure and death. Prior studies have identified disparities in the treatment of AF based on sex, race, and ethnicity. Hypothesis: There will be disparities in procedures for rhythm control (RC) based on sex, race and ethnicity. Methods: Cohorts of patients with new AF from 2016 to 2021 were identified with 1 year follow up to identify referrals, anticoagulant prescription, and procedures for RC. We calculated the proportion of patients with each outcome overall stratified by sex and race/ethnicity. We used logistic regression to compare outcomes across sex and race/ethnicity after adjustment for confounding variables. Results: We identified 2,919 patients with a new onset AF. The mean age: 68 years, 53% were male, 66% had Medicare, 69% self-identified as White, 23% as Black, and 3% as Hispanic. There was no difference in referral rates between men and women. Compared to White patients, Black and Hispanic patients were more likely to be referred to Cardiology and more likely to complete a visit. Prescription of anticoagulants was high (83%) and did not differ between men and women (84% vs. 82%, p = 0.65). Compared to White patients, Black and Hispanic patients were more likely to receive a prescription for anticoagulation (86% and 88% vs. 81%, p = 0.006). Women were significantly less likely to receive cardioversion or ablation compared to men (17% vs. 25%, p &lt; 0.001). Similarly, Blacks and Hispanics were significantly less likely to receive procedures compared to Whites (17% vs. 23%, p = 0.01). Conclusions: Despite equal attendance at Cardiology visits, women and Black or Hispanic patients were significantly less likely to receive cardioversion or ablation compared to men and Whites respectively.
Abstract 11513: Impact of Pulmonary Hypertension on Patients With Heart Failure With Preserved Ejection Fraction: A 5-year Analysis
Authors: Qusai Alitter, Omar Al Wahadneh
Journal: Circulation (2023)

Introduction: The purpose of this retrospective study is to determine the impact of pulmonary hypertension on the outcome of patients with heart failure with preserved ejection fraction (HFpEF). The study investigated various outcomes associated with pulmonary hypertension in HFpEF patients. Methods: We analyzed data from the National Inpatient Sample between 2016 and 2020 to identify patients admitted to the hospital with an acute exacerbation of HFpEF and pulmonary hypertension as a secondary diagnosis. This retrospective study used multivariable logistic and linear regression analysis to identify factors associated with mortality, hospital length of stay, total charges, and other secondary outcomes. Outcomes were adjusted to multiple factors including age, race, gender, and other comorbidities. Results: 343,490 patients were admitted with an acute exacerbation of HFpEF from 2016 to 2020, of whom 127,655 also carried the diagnosis of pulmonary hypertension. Patients with pulmonary hypertension were at higher risk for mortality, longer hospital stay, and incurred greater healthcare costs. Additionally, patients with pulmonary hypertension were at increased risk of atrial fibrillation, ventricular tachycardia, and ventricular fibrillation. Despite no difference in the rate of developing acute respiratory failure between both groups, patients with pulmonary hypertension were more likely to need non-invasive ventilation or mechanical ventilation. Conclusions: The study concludes that the presence of pulmonary hypertension in HFpEF patients is linked to poorer outcomes, including increased mortality risk, longer hospital stay, higher healthcare costs, and greater risk for complications such as arrhythmias and ventilation requirements. Early identification and management of pulmonary hypertension are important to improve patient outcomes, Nevertheless, more research is needed to determine the most effective treatment approaches.
Anti‐Inflammatory Effect of <scp>High‐Density</scp> Lipoprotein Blunted by Delivery of Altered <scp>MicroRNA</scp> Cargo in Patients With Rheumatoid Arthritis
Authors: Qiong Wu, Quanhu Sheng, Danielle Michell, Marisol Ramirez‐Solano, Olivia Posey, Anastasiia Phothisane, Shahensha Shaik, Kasey C. Vickers, Michelle J. Ormseth
Journal: Arthritis & Rheumatology (2023)

Objective High‐density lipoprotein (HDL) has well‐characterized anti‐atherogenic cholesterol efflux and antioxidant functions. Another function of HDL uncharacterized in rheumatoid arthritis (RA) is its ability to transport microRNAs (miRNAs) between cells and thus alter cellular function. The study's purpose was to determine if HDL‐miRNA cargo is altered and affects inflammation in RA. Methods HDL‐microRNAs were characterized in 30 RA and 30 control participants by next generation sequencing and quantitative polymerase chain reaction. The most abundant differentially expressed miRNA was evaluated further. The function of miR‐1246 was assessed by miRNA mimics, antagomiRs, small interfering RNA knockdown, and luciferase assays. Monocyte‐derived macrophages were treated with miR‐1246‐loaded HDL and unmodified HDL from RA and control participants to measure delivery of miR‐1246 and its effect on interleukin‐6 (IL‐6). Results The most abundant miRNA on HDL was miR‐1246; it was significantly enriched two‐fold on HDL from RA versus control participants. HDL‐mediated miR‐1246 delivery to macrophages significantly increased IL6 expression 43‐fold. miR‐1246 delivery significantly decreased DUSP3 1.5‐fold and DUSP3 small interfering RNA knockdown increased macrophage IL6 expression. Luciferase assay indicated DUSP3 is a direct target of miR‐1246. Unmodified HDL from RA delivered 1.6‐fold more miR‐1246 versus control participant HDL. Unmodified HDL from both RA and control participants attenuated activated macrophage IL6 expression, but this effect was significantly blunted in RA so that IL6 expression was 3.4‐fold higher after RA versus control HDL treatment. Conclusion HDL‐miR‐1246 was increased in RA versus control participants and delivery of miR‐1246 to macrophages increased IL‐6 expression by targeting DUSP3 . The altered HDL‐miRNA cargo in RA blunted HDL's anti‐inflammatory effect. image
Abstract 13937: Socioeconomic Status in Pediatric Patients With Anomalous Aortic Origins of Coronary Arteries: An Individual- and Zip Code-Level Analysis
Authors: Sameer A Sidiq, Thomas Przybycien, Kimberly Gray, Sandra Mihail, Tam Doan, Shagun Sachdeva, Dana Reaves-O'Neal, Ziyad Binsalamah, Silvana M Molossi
Journal: Circulation (2023)

Introduction: Anomalous aortic origin of a coronary artery (AAOCA) is the second leading cause of sudden cardiac death in the young. Limited data is available on potential disparities on access to care and whether socioeconomic status is associated with AAOCA. Hypothesis: AAOCA occurrence, severity, and treatment relate to socioeconomic status and may unfold inequities to care. Methods: Single-center retrospective study of 553 pediatric patients with AAOCA residing in Texas. Zip code socioeconomic characteristics were extracted from American Community Survey 2021 5-year estimates. All Texas zip codes were ordered into quartiles by characteristic. Age at diagnosis, signs of ischemia, and surgery status were compared by race and zip code parameters. Mann-Whitney U test was for non-parametric variables and χ 2 test, Fisher’s test, or one-way ANOVA for categorical variables. Results: Table 1 depicts patients’ demographics. AAOCA patients tended to reside in zip codes at the 4 th quartile of income (39%, p=&lt;0.001), education (29%, p=0.003), and employment (42%, p=&lt;0.001) (Table 2). There was no difference in age at diagnosis, signs of ischemia, or occurrence of coronary surgery by individual race or zip code socioeconomic parameters. Conclusions: AAOCA pediatric patients tend to live in zip codes with higher socioeconomic status (SES). These differences may reflect disparities in access to diagnosis and care. Further studies are needed to determine the burden of AAOCA in low SES populations.