tbuckley/cabot-search huggingface dataset:
Abstract 15432: Racial and Sex Disparities in Age-Adjusted Mortality in COVID-19 Patients With Atrial Fibrillation in the United States
Authors: Caleb Carver, Saurabh Deshpande, Kamleshun Ramphul, Hassan Khan, Raheel Ahmed, Mohammad Nour Salloum, Olayinka Agboola, Edmond Obeng-Gyimah, Brian Schuler, Mohammed Khanji, Hiroyuki Sawatari, Syed Emir Irfan Wafa, Virend K Somers, Deepak Padmanabhan, Rui Providencia, Anwar Chahal
Journal: Circulation (2023)

Introduction: While Coronavirus disease 2019 (COVID-19) primarily affects the respiratory system but can impact the cardiovascular system can triggering various complications. Hypothesis: To investigate the trend in age-adjusted mortality rates (AAMRs) in patients with atrial fibrillation(AF) among COVID-19-positive patients (CPP) by race and sex. Methods: Trends in AAMRs (per 100,000) from all-cause in patients with AF between April to December 2016-2020 were evaluated via the National Inpatient Sample and the US Census Bureau. The AAMRs among CPP with AF in 2020 was also evaluated between racial and sex cohorts. Results: A gradual rise in AAMR(all causes) in patients with AF was observed between 2016-2019, with a 49.4% overall rise between 2019(271 per 100,000) and 2020(405 per 100,000) ( Table 1a and Figure ). Around 250475 COVID-19-positive patients had AF, and 24.2% of cases did not survive their hospitalization (vs. 10.9% in those without AF, p&lt;0.01, aOR 1.457, 95% CI 1.438-1.477). Among CPP males and females with AF that died, White females and males were the oldest, while Black males and females reported the highest mean Charlson Comorbidity Index (CCI) score ( Table 1b ).Furthermore, among the CPP with AF in 2020, Hispanics reported a higher AAMR (119.6 per 100,000) than Whites(111.1 per 100,000) and Blacks(101.9 per 100,000). AAMRs in males were higher in Hispanic males (144.8 per 100,000), followed by White males (129.7 per 100,000), and Black males (110 per 100,000). However, the AAMRs in females were highest in Black females (91.3 per 100,000), followed by White females (88.3 per 100,000) and Hispanic females (87.0 per 100,000). ( Table 1c ) Conclusions: AAMRs in patients with AF are on the rise and a sharp growth was seen during the first year of the pandemic. AAMRs among CPP patients with AF were highest among Black females and Hispanic males, while White males and females were oldest and Black males and females reported the highest CCI scores.
Abstract 14080: Broadening Indications for Neonatal Balloon Atrial Septostomy in Dextro-Transposition of the Great Arteries Reduce Predictive Value of Fetal Echocardiography
Authors: Hamsika Chandrasekar, Shiraz A Maskatia, Meaghan J Beattie, Michelle A Kaplinski, Rajesh Punn, Charitha D Reddy, Theresa A Tacy
Journal: Circulation (2023)

Introduction: Neonates with dextro-transposition of the great arteries (d-TGA) require adequate mixing at the atrial level. If not present, these infants experience severe cyanosis, necessitating an urgent balloon atrial septostomy (BAS). Multiple studies have identified various fetal echocardiography (FE) findings as risk factors for postnatal BAS. Anecdotally, the predictive value of these findings remains poor in clinical use. Hypothesis: We aimed to determine the relationship between inter-rater reliability (IRR) of FE BAS predictors and need for postnatal BAS, hypothesizing that IRR would be poor and perhaps contributing to limited predictive value of FE findings. Methods: We identified d-TGA pregnancies followed at our institution between 2012 and 2022, excluding fetuses with large ventricular septal defects and pregnancies that were either terminated or lost to follow up. Three independent readers blinded to BAS outcome assessed 7 FE predictors: pulmonary vein Doppler velocity &gt; 41 cm/sec, reverse flow in patent ductus arteriosus (PDA), restrictive PDA, restrictive patent foramen ovale (PFO), bidirectional PFO flow, flat septum primum, and hypermobile septum primum. IRR was determined with the S metric. Clinical information immediately before BAS was collected to evaluate postnatal physiology. A multivariable logistic regression was used to determine significant associations between FE findings and postnatal BAS. Results: Fifty-six fetuses were included in this study, of whom 25 (45%) underwent BAS. IRR was lowest for PFO flow direction and highest for restrictive PDA, likely due to its rarity. The remainder of FE predictors had either a moderate or substantial level of IRR. The last pre-BAS range of PaO 2 (24-49 mmHg), O 2 saturation (56-86%) and pH (7.18-7.52) reflected variable physiology. Of the 5 FE characteristics that could be included in the regression analysis, none were found to be significantly associated with odds of a BAS. Conclusions: Our results demonstrate substantial but not excellent IRR for current FE BAS predictors, but no significant association between these predictors and postnatal BAS in d-TGA patients. Poor predictive value of FE for postnatal BAS could be impacted by broadening indications for BAS.
Abstract 100: Blood Pressure Targets and Hemodynamics According to Initial Blood Lactate Levels in Patients With Comatose Out-of-Hospital Cardiac Arrest - A Substudy of the BOX Trial
Authors: Rasmus Paulin Beske, Henrik Schmidt, Laust Obling, Henrik Hoejgaard, Johannes Grand, Jacob Moeller, Jesper Kjaergaard, Christian Hassager
Journal: Circulation (2023)

Out-of-hospital cardiac arrest (OHCA) patients are often circulatory unstable and have high mortality in the first days following resuscitation. An increase in lactate will reflect the severity and duration of hypoperfusion in out-of-hospital cardiac arrest (OHCA). Further, the severity of hypoperfusion could modify the effect on survival and neurological injury of different mean arterial blood pressure (MAP) targets. In this sub-study of the BOX trial, adults successfully resuscitated comatose OHCA patients (n=789) with a presumed cardiac cause were randomized to a MAP 63 mmHg vs. 77 mmHg. Patients were arbitrarily grouped in low-lactate: &lt;25%, medium-lactate: 25%-75%, and high &gt;75 % according to blood lactate levels at hospital arrival as a surrogate of severity of hypoperfusion. Invasive evaluations were performed using an arterial line and pulmonary artery catheter (PAC). Logistic regression analysis evaluated whether lactate levels (as continuous and categorical) modify the effect of MAP targets on 1-year mortality. The three lactate groups were: low-lactate: &lt;2.9 mmol/L, medium-lactate: 2.9-7.9 mmol/L, and high-lactate &gt;7.9 mmol/L. The vasoactive inotropic score was higher with increasing initial lactate level with the largest difference at 6 hours (low-lactate: 7.8 (95%CI: 5.7 - 10.1) vs. high-lactate: 16.4 (95%CI: 13.4 - 19.6). No difference in the cardiac index or systemic vascular resistance was observed between lactate groups. The initial lactate level modified the effect of the two MAP targets (p=0.044), with a tendency to higher mortality for high-lactate patients if the MAP target were 77 mmHg (odds ratio: 1.7 (95%CI: 0.9-3.0, p=0.08). Comatose OHCA patients with high initial lactate levels required more vasoactive drugs on the first two days of ICU admission to meet the blood pressure target and have a poorer prognosis. The results do not support a higher MAP target benefit for patients with an initial high lactate level in the first 48 hours.
Abstract 14620: Association of Rural Residence With In-Hospital Mortality for Heart Failure Hospitalizations in Texas: A Population-Based Cohort Study
Authors: Rami Al-Ayyubi, Muhammad Qudrat Ullah, Andres Mata, Laura Gonzalez Reyes, Divya Parepalli, Muhammad Jehangir Malik, Raghavendra Sanivarapu, John Garza
Journal: Circulation (2023)

Background: Rural residents with heart failure may be at higher risk of mortality due to disparities in access to health care services. Patterns of urban-rural disparity in health care resources may vary across the United States and population level analyses of the impact of rural residence on hospitalized patients with heart failure in Texas are not conclusive. Hypothesis: Rural residence is associated with increased risk of in-hospital mortality in patients with heart failure. Methods: We used publicly available, statewide, and deidentified hospitalization records to study patients aged ≥18 years with heart failure as principal diagnosis in Texas for years 2016 through 2021. Three models estimated the association between rural residence and in-hospital mortality. Multilevel logistic regression with propensity adjustment was the primary analysis approach with propensity score matching and multivariable logistic regression without propensity score matching applied as alternative analyses. Additional analyses were completed for patient subgroups and for categories of heart failures. Results: Out of 460,798 heart failure hospitalizations (HFH), 61,480 (13.3%) were classified as rural residents. HFH with vs without rural residence were older (70.4% vs 64.8% aged ≥ 65years), more often white (63.5% vs 46.9%), less frequently had private insurance (26.2% vs 35.4%) and were less often admitted to teaching hospitals (19.5% vs 28.9%); p &lt; 0.0001 for each. Unadjusted in-hospital mortality among HFH with and without rural residence was 2.5% vs 2.1%. On adjusted analyses, rural residence remained associated with higher odds of in-hospital mortality (adjusted odds ratio 1.1685 (95% CI [1.0878 - 1.2554]). The results were similar for the alternative modeling approaches, subgroup analyses, and categories of heart failures. Conclusions: Rural residence in Texas was associated with higher risk of in-hospital mortality in patients with heart failure.
Abstract 14079: Inhibition of NOX2 Prevents Obesity-Mediated Atrial Fibrillation
Authors: Arvind Sridhar, Jaime DeSantiago, Mahmud Arif, Olivia T Ly, Hanna Chen, Miles Barney, Asia Owais, Jordan Jousma, Sarath Babu B Nukala, Xinge Wang, khaled Abdelhady, Malek G Massad, Lona Ernst Rizkallah, Sang-Ging Ong, Jalees Rehman, Dawood Darbar
Journal: Circulation (2023)

Introduction: Obesity is an independent risk factor for atrial fibrillation (AF). While oxidative stress plays an important role in obesity-mediated AF, the specific pathways that cause atrial remodeling remain unclear. NADPH oxidase 2 (NOX2), a major source of cytosolic reactive oxygen species (ROS) production in the heart, is increased in diet-induced obese (DIO) mice and can independently predispose to post-operative AF via atrial remodeling. Hypothesis: We used a Nox2 -knock-out (KO) mouse model and mature human iPSC-derived atrial cardiomyocytes (hiPSC-aCMs) to test the hypothesis that NOX2 increase modulates ion channel remodeling in obesity-mediated AF. Methods: DIO mice and palmitic acid (PA)-treated hiPSC-aCMs were given a NOX blocker (apocynin), and GSK2793059, a NOX2-specific small molecule inhibitor respectively. Trans-esophageal rapid (TE) pacing was used to examine changes to the AF phenotype. Whole-cell patch clamping, qPCR, Western blotting, and electrical mapping were performed to study ion channel remodeling in both models. Results: DIO, DIO-Apocynin, and DIO Nox2 -KO mice displayed increased weight compared to control and Nox2 -KO mice (Figure A). After TE pacing, DIO-Apocynin mice displayed 28.2 ± 25.4 s and DIO Nox2 -KO mice displayed 17.4 ± 31.8 s compared to 167.3 ± 168.9 s in DIO mice (Figure B). Electrophysiological studies show that Nox2 inhibition reverses ion channel remodeling in I Na , I Ks , and I Ca,L (Figure D-F), and atrial fibrosis (Figure H) and prolongs the atrial action potential (AP; Figure C) and increases conduction velocity (CV; Figure G-I) in both DIO mice (Figure C-I) and PA-hiPSC-aCMs (Figure J-L). Conclusions: Collectively, genetic and pharmacological inhibition of NOX2 in DIO mice and PA-treated hiPSC-aCMs abrogate ion channel and structural remodeling and prevents the development of obesity-mediated AF. These findings have important implications for targeted antioxidant therapy for obese patients with AF.
Abstract 13004: Blockade of Endothelial to Mesenchymal Transition (EndMT) by an AP-1 Inhibitor Attenuates Atherosclerosis in Diabetes
Authors: Waheed Khan, Misbah Aziz, Karin A Jandeleitdahm
Journal: Circulation (2023)

Background: Atherosclerotic cardiovascular disease is the leading cause of death in individuals with diabetes. Endothelial to mesenchymal transition (EndMT) is characterized by endothelial transformation to a mesenchymal like cellular state. EndMT-mediated endothelial cell dysfunction is known to be involved in cardiovascular complications of diabetes including atherosclerosis. Gene expression changes occur when endothelial cells transition to mesenchymal cells. These transcriptomic changes are regulated by multiple factors including transcription factors (TFs). Although, previous studies have implicated the role of EndMT in atherosclerosis, the role of AP-1 TF complex in EndMT in diabetes induced atherosclerosis is not known. Methods: Single cell transcriptomic (SCT) analysis of diabetic aorta in atheroprone Apoe -/- mice was performed using 10X Genomics platform. In vitro model mimicking diabetes-induced EndMT was established in human aortic endothelial cells (HAECs) using high glucose (25mM) and TNF- α ± a small molecular inhibitor of AP-1, T-5224. RNA and ChIP (chromatin Immunoprecipitation) sequencing was performed. Moreover, Apoe -/- mice made diabetic with streptozotocin, were treated with T-5224 (30 mg/kg daily for 5 weeks) in a 10-week intervention study. Results: SCT analysis of aorta identified increased expression of AP-1 members cFOS and Junb in diabetic endothelial cells in Apoe -/- mice. These genes were also upregulated in the HAECs-based in vitro EndMT model. Interestingly, AP-1 inhibition by T-5224 attenuated EndMT . RNA and ChIP sequencing identified several AP-1 target genes including Col1A2, Col4A1, TGFB, THBD, INSR, PIK3R3 (FDR &lt;0.05, Log2 fold change (2x)) that were common to many enriched pathways including “leukocyte trans-endothelial migration” and “AGE-RAGE signaling pathways in diabetic complications” directly relevant to EndMT in diabetes. Importantly, T-5224 treatment blocked EndMT resulting in reduced atherosclerosis in diabetic Apoe -/- mice. Conclusion: This study identified the AP-1 inhibition with T-5224 as a novel treatment for the first time for the diabetes induced EndMT and atherosclerosis.
Abstract 12991: Geographical Disparities in Cardiovascular Death in Sarcoidosis
Authors: Min Choon Tan, Noreen Mirza, Yong Hao Yeo, Boon Jian San, Jian Liang Tan, Justin Lee, Joanne Mazzarelli, Andrea M Russo
Journal: Circulation (2023)

Background: While cardiac involvement in sarcoidosis could be significant, data assessing geographical disparities in cardiovascular deaths (CVDs) among patients with sarcoidosis are limited. Objective: This study aims to determine the mortality attributed to CVDs with comorbid sarcoidosis in different geographic locations in the United States. Methods: We queried the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research database and performed serial cross-sectional analyses of national death certificate data for CVDs with comorbid sarcoidosis among patients aged 25 and above. Diseases of the circulatory system (ICD-10 I00-I99) were listed as the underlying cause of death, and sarcoidosis (ICD-10 D86) as contributing cause of death. We calculated age-adjusted mortality rates (AAMRs) per 1,000,000 individuals and compared the mortality among census regions and states. Results: In the 22-year study period, 5,630 CVDs with comorbid sarcoidosis in the United States were identified between 1999 and 2020. The South region had the highest AAMRs for CVDs with comorbid sarcoidosis (1.32 [95% CI, 1.26-1.37] per 1,000,000 individuals), followed by Northeast region (1.25 [95% CI, 1.18-1.32] per 1,000,000 individuals), Midwest region (1.24 [95% CI, 1.17-1.30] per 1,000,000 individuals), and West Region (0.92 [95% CI, 0.86-0.98] per 1,000,000 individuals). The AAMRs for CVDs with comorbid sarcoidosis were between 0.57 [95% CI, 0.43-0.75] per 1,000,000 individuals and 1.96 [95% CI, 1.73-2.19] per 1,000,000 individuals throughout the States, except Maryland and the District of Columbia, which recorded 2.79 [95% CI, 2.44-3.14] and 6.01 [95% CI, 4.44-7.94], respectively. Conclusion: The South region, particularly Maryland recorded the highest CVDs in sarcoidosis. Geographical disparities observed in CVDs with comorbid sarcoidosis highlight the need to improve public health measures at state-level.
Abstract 11419: Combination of Right Ventricular Global Longitudinal Strain and Conventional Echocardiographic Parameter Carries Improved Prognostic Value in Submassive Pulmonary Embolism
Authors: Shunsuke Eguchi, Yoshiyuki Orihara, Ayumi Eguchi, Michael Pfeiffer, Brandon Peterson, Mohammed Ruzieh, Zhaohui Gao, John Boehmer, John Gorcsan, Ryan Wilson
Journal: Circulation (2023)

Introduction and Hypothesis: Right ventricular (RV) dysfunction has been identified as a prognostic marker for adverse clinical events in patients with submassive pulmonary embolism (PE). We hypothesized that combination of right-sided strain analysis and conventional parameters can further risk stratify patients at high risk for mortality. Methods: Retrospective cohort study of patients with submassive PE between 2010 and 2018. The primary outcome was all-cause mortality at 30 days. Echocardiographic parameters including right to left ventricular end-diastolic diameter ratio (RV/LV ratio), RV global longitudinal strain (RVGLS), RV free wall strain and right atrium strain were compared between survivors and non-survivors. Multivariable analysis and receiver operator characteristic (ROC) curves analysis were used to demonstrate the predictive value of baseline measurements. Results: 251 patients were analyzed. Overall mortality rate at 30 days was 12.4 %. Multivariable analysis revealed RV/LV ratio was an independent predictor of 30-day mortality in conventional parameters, and RVGLS was also an independent predictor among the three strain parameters. ROC curves indicated that the best cutoff values for RVGLS and RV/LV ratio to predict mortality were 17.7 % and 1.03. When the 230 patients with measurable RVGLS and RV/LV ratio were divided into four groups using both cutoff values, patients with both high RVGLS and low RV/LV ratio had the lowest mortality (1.0 % at 30 days; n = 99) while patients with both low RVGLS and high RV/LV ratio had the highest mortality (46.2 % at 30 days; n = 39). Kaplan-Meier curves depicted the significantly different prognosis among the four groups (p &lt; 0.001. Figure). Conclusions: The combination of RVGLS and RV/LV ratio can help further risk stratify patients with submassive PE. This may identify patients at highest risk of mortality and ultimately alter treatment pathways.
Abstract 244: Geospatial Access to Extracorporeal Membrane Oxygenation in the United States
Authors: Hannah Van Wyk, Man Qi, Adam L Gottula, Bennett Lane, Christopher shaw, Kari Gorder, Amy Koshoffer, Justin Benoit, Cindy H Hsu
Journal: Circulation (2023)

Introduction: Extracorporeal Membrane Oxygenation (ECMO) is a form of complete cardiopulmonary support which has been associated with improved survival in both severe acute respiratory distress syndrome and refractory cardiac arrest. ECMO is a resource-intensive therapy limited to specialized centers in urban environments, restricting its availability in suburban and rural areas. We examined the proportion of the U.S. population within a 15-minute, 30-minute, and 45-minute drivetime area to an ECMO-capable center. Methods: Using geographic information systems (GIS), we created shapefiles with polygons representing 15, 30, and 45-minute drivetime areas to ECMO-capable centers. Census block group centroids were then overlaid to determine the proportion of the population with access to ECMO-capable centers. Results: We found that 22%, 52%, and 67% of the U.S. population live within 15, 30, and 45 minutes of ECMO-capable centers, respectively. One hundred and ten million people, more than one third of the U.S. population, live further than 45 minutes away from an ECMO-capable center. Puerto Rico, Wyoming, North Dakota, and Alaska have 0% population access. Texas, California, and Florida have the highest number of people with low access (9, 8, and 5 million, respectively). Conclusion: Population access to ECMO-capable centers in the U.S. is highly variable and limits time-dependent interventions, which are essential for successful deployment of extracorporeal cardiopulmonary resuscitation in refractory cardiac arrest. Our GIS model can be used for future planning of ECMO systems to optimize access for the U.S. population or to comparatively evaluate proposals to improve access.
Abstract 15500: Identifying Cardiomyocytes at Specific Cell-Cycle Stages by a New Cell-Cycle-Specific snRNAseq Analytic Method
Authors: Thanh Nguyen, Yuji Nakada, Jianyi J Zhang
Journal: Circulation (2023)

Background: Deciphering the cardiomyocyte cell cycle is a critical question in studying heart development and regeneration. We already collected the single-nuclei RNA sequencing (snRNAseq) data from fetal pig hearts and from pigs that underwent apical resection on postnatal day (P) 1 (AR P1 ) followed by myocardial infarction (MI) on P28 (MI P28 ); in these hearts, robust cardiomyocyte proliferation was confirmed. Research questions: Although our previous snRNAseq analyses found cardiomyocyte clusters that primed to proliferate, each of these clusters only appeared at one specific time point; furthermore, these clusters still contain a significant amount of non-cycling cell; and thus, we were unable to distinguish between cardiomyocytes in different phases of the cell cycle. Approach: In this report, we designed a new Autoencoder that only utilized 1646 cell-cycle-specific genes to cluster cardiomyocytes and applied the Autoencoder on pig heart GEO datasets number GSE185289. Results: Five cardiomyocyte clusters (pCM1+2, pCM3-pCM6) were identified. Five proliferation markers (AURKB, MKI67, INCENP, CDCA8, and BRCA5) highly co-expressed in pCM1+2; also, the top enriched gene ontologies of pCM1+2 were all related to cell-cycle. PCM1+2 percentages were ~6% in fetal hearts and ~2-3% in hearts from ARP1MIP28 pigs during the two weeks after MI induction but were nearly undetectable in all other experimental groups and at all other time points. We also identified four transcription factors (E2F8, FOXM1, GLI3, and RAD51) that explicitly coexpressed within pCM1. Also, a pseudo-time trajectory was constructed in Fetal cardiomyocyte, which began at pCM3 (G1/S phase, CCND2 localization), passed through pCM2 (S phase, CCNE2 localization), and ended at pCM1 (M phase, CCNB2 localization). Conclusions: Applying the more precise cell-cycle specific Autoencoder, we found three clusters that likely represented cardiomyocytes at three different cell-cycle stages.