tbuckley/cabot-search huggingface dataset:
Abstract 16956: Historical Neighborhood Redlining and Bystander CPR Disparities in Out-of-Hospital Cardiac Arrest
Authors: Issam Motairek, Salil V Deo, Mohamed H.E. Makhlouf, Pedro R Salerno, Rabab Al-Araji, Jackson T Wright, Khurram Nasir, Sanjay Rajagopalan, Sadeer Al-Kindi
Journal: Circulation (2023)

Introduction: Out-of-hospital cardiac arrest (OHCA) is associated with low survival rates. Bystander cardiopulmonary resuscitation (CPR) is essential for improving outcomes, but its utilization remains limited, particularly among racial and ethnic minorities. Historical redlining, a practice that classified neighborhoods for mortgage risk in the 1930s, may have lasting implications for social and health outcomes. Hypothesis: This study sought to investigate the influence of redlining on the provision of bystander CPR during witnessed OHCA. Methods: We conducted an analysis using data from the comprehensive Cardiac Arrest Registry to Enhance Survival (CARES), encompassing 736,066 non-traumatic OHCA cases across the United States. The Home Owners' Loan Corporation (HOLC) map shapefiles were utilized to categorize census tracts of arrests into four grades (A signifying “best”, B “still desirable”, C “declining”, and D “hazardous”). Multivariable hierarchical logistic regression models were employed to predict the likelihood of CPR provision, adjusting for various factors including age, sex, race/ethnicity, arrest location, calendar year, and state of occurrence. Additionally, we accounted for the percentage of Black residents and residents below the poverty level. Results: Among the 43,186 witnessed cases of OHCA in graded HOLC census tracts, 37.2% received bystander CPR. The rates of bystander CPR exhibited a gradual decline across HOLC grades, ranging from 41.8% in HOLC grade A to 35.8% in HOLC grade D. In fully adjusted model, we observed significantly lower odds of receiving bystander CPR in HOLC grades C (OR 0.89, 95% CI 0.81-0.98, p=0.016) and D (OR 0.86, 95% CI 0.78-0.95, p=0.002) compared to HOLC grade A (Figure). Conclusions: Redlining, a historical segregation practice, is associated with reduced contemporary rates of bystander CPR during OHCA. Targeted CPR training in redlined neighborhoods may be imperative to enhance survival outcomes.
Abstract 16512: Significant Sociodemographic Disparities and the Burden of Major Adverse Cardiac and Cerebrovascular Events Among Cancer Survivors Hospitalized With COVID-19: A Nationwide Analysis
Authors: Priyatham Gurram, Adil S Mohammed, Sandeep Guntuku, Shanmukh sai pavan Lingamsetty, Ravi Venkata Sai Krishna Medarametla, Rishabh Baskara Salian, Vikas Yadav, Shariq Nawab, Zaki Ur Rahman Mohammed, ERUM SAEED, IRFAN SAEED, Rawnak Jahan, Akhil Jain, Rupak Desai
Journal: Circulation (2023)

Background: Cancer survivors are at an increased risk of cardiovascular disease due to various treatment modalities, and COVID-19 can further complicate their cardiovascular health. Therefore, we aimed to study the burden of major adverse cardiac and cerebrovascular events (MACCE) among cancer survivors hospitalized with COVID-19 and associated sociodemographic disparities. Methods: We analyzed the National Inpatient Sample Database (2020) to identify COVID-19 related adult (≥18 years old) hospitalizations among cancer survivors and associated MACCE (all-cause mortality, acute myocardial infarction, cardiac arrest, and stroke) using ICD-10 codes. A multivariable regression analysis of MACCE based on disparities like age, sex, race, and household income was done. Results: Of 112,270 COVID-19 related admissions in cancer survivors (51.8% males, 68% white, 14.7% black, and 9.8% Hispanic), 17.8% (n = 19935) patients experienced in-hospital MACCE. All MACCE events were higher among patients aged ≥ 65 years and 45-64 years compared with the 18-44 year age group, with ORs of 5.61 (95% CI: 3.43-9.19) and 2.30 (95% CI: 1.41-3.76) respectively. Males have higher odds of MACCE than females (OR 1.33, 95% CI: 1.23-1.43). The odds of MACCE were higher in Hispanics (OR 1.23, 95% CI: 1.08-1.39) and Native Americans (OR 1.71, 95% CI: 1.08-2.73) compared to Whites. Lowest income quartile patients had a higher MACCE than highest-income quartile patients (OR 1.13, 95% CI: 1.00-1.28). For all the above-mentioned ORs, the level of significance was p&lt;0.05. Conclusion: Among COVID-19 related admissions in cancer survivors, elderly patients, males, Hispanics, Native Americans, and those in the lowest income quartile are prone to have increased MACCE. Factors like age, sex, race, and socioeconomic status seem to play a role in MACCE incidence. Understanding these factors may help emphasize improving patient care, address health equity issues, and inform healthcare policymakers.
Abstract 16991: Rare Variants in BMP10 Confer Risk of Pulmonary Arterial Hypertension
Authors: XueJia Zhang, Rui Jiang, TianQi Li, TingTing Lv, MengTing Ye, MingJie Ma, WeiXian Yang, Xiaojian Wang
Journal: Circulation (2023)

Background: Genetic mutations in the genes of BMPR2 pathway are the most crucial cause of pulmonary arterial hypertension. BMP10 is the major ligand of BMPR2, but it remains elusive that whether BMP10 mutation are associated with pulmonary arterial hypertension (PAH). Methods: Whole exome sequencing was applied to screen the BMP10 mutations in 378 patients with congenital heart disease associated with pulmonary arterial hypertension (CHD-PAH). The pathogenicity of variants was assessed by ACMG guideline. Pedigree structures and familial transmission of variants were analyzed for the case who carried the BMP10 mutation. The deleterious function of BMP10 mutations were analyzed via in vitro experiments. Results: Five rare and pathogenic BMP10 variants were identified in five patients with CHD-PAH, including three missense mutations (p.Q74R, p.R96Q, p.I335S) and two nonsense mutations (p.Q116Ter, p.R313Ter). These five cases did not carry mutation in other known PAH risk genes. Five BMP10 mutations were classified as uncertain significance(UVS) or likely pathogenic(LP) variants according to ACMG guideline. It was notworthy that the high impact likely loss-of-function variants in BMP10 were found in 0.53% (2 out of 378) of cases, which was significiantly hihger than those of 0.002% (4 out 251106) in the general population from the GnomAD database (P&lt;10 -4 ). Familial analysis revealed that a case had inherited the heterozygous BMP10 p.I335S missense variant from her affected mother, strongly indicating the co-segregation of BMP10 mutaiton and PAH phenotype. Functional experiments implied that the missense mutation p.I335S and the nonsense mutation p.Q116Ter both resulted in reduced BMP10 protein expression in 293T cells. Conclusion: We identified strong association between rare damaging variants in BMP10 and PAH. The novel BMP10 mutations found in this study will provide new insights into the genetic mechanism of PAH.
Abstract 18589: Disparities in Low Cognitive Function Score and Mortality Risk Among Older Adults in the United States
Authors: Yuan Lu, Wenya Tian, Xumin Li, Yinfei Wu, Yuntian Liu, Kai Chen, Emma Zang, Jeph Herrin, Harlan M Krumholz
Journal: Circulation (2023)

Introduction: Low cognitive function predicts mortality in older adults. This study examined cognitive assessment disparities by age, sex, and race, and the association of low cognitive function with mortality. Methods: We analyzed data from the National Health and Nutrition Examination Survey (2011-2014) with linked mortality. Cognitive function was measured by the Digit Symbol Substitution Test (DSST), Consortium to Establish a Registry for Alzheimer's disease Word Test (CERAD), and Animal Fluency Test (AFT). Low cognitive function was defined as scoring below the 25th percentile. Cox regression models was used to assess the association with mortality. Results: The study included 3014 adults aged 60 or older (mean age: 69.7 years; 54.9% women; 9.2% Black, and 78.8% White). A total of 1192 participants had low cognitive function. Older age (70+), female sex, and Black race were associated with lower DSST scores by 11.7 (13.1-10.4) points, 3.4 (2.2-4.6) points, 14.7 (17.2- 12.1) points, respectively, compared with younger age (60-70), male, and White individuals. Low cognitive function was significantly associated with all-cause mortality (HR= 2.04, 95% CI: 1.47-2.81) and cardiovascular mortality (HR= 1.88, 95% CI: 1.41-2.50) after adjusting for age, sex, race/ethnicity, education, income, employment status, physical activity, and smoking. These associations were consistent across all measures of cognitive function. There were no significant interactions in HRs for mortality by age, sex, and race. Conclusions: In a community-based sample, cognitive dysfunction can double the risk of mortality. Whether this represents a marker or a mediator remains to be determined.
Abstract 12494: Role of Ceramide in Estrogen-Induced Oxidative Stress in Endothelial Cells From Individuals Assigned Male at Birth
Authors: Zachary Zirgibel, Gopika SenthilKumar, Brian J Lindemer, Henry Bordas-Murphy, Maria Jaramillo-Torres, Julie K Freed
Journal: Circulation (2023)

Compared to cis-males and females, risk for cardiovascular disease (CVD) is elevated in trans-females undergoing estrogen-containing gender affirming therapy. We have previously shown that continuous estrogen treatment of arterioles from healthy adults assigned male at birth promotes microvascular endothelial dysfunction, however the mechanism through which estrogen contributes to endothelial damage remains unknown. Estrogen increases expression of neutral sphingomyelinase (NSmase), an enzyme responsible for the production of ceramides. Ceramides are bioactive sphingolipids that can increase cellular levels of hydrogen peroxide (H 2 O 2 ). Together, we hypothesize that estrogen increases endothelial levels of oxidative stress through NSmase-mediated ceramide formation. Primary male human umbilical vein endothelial cells (HUVECs; pooled from n=3) were seeded in 8-well microscopy plates prior to treatments. Peroxy yellow 1 (PY1) was used to measure changes in endothelial H 2 O 2 . Wells were imaged at 20x and analyzed using ImageJ. Difference between %change in fluorescence ±standard error (SE) is reported, and significance is determined using One-Way ANOVA. Treatment with 17β-estradiol (E2; 100nM, 48hrs) increased endothelial H 2 O 2 production (control, n=6 vs E2, n=7; 13.9±6.3, p=0.038), an effect diminished in the presence of the NSmase inhibitor GW4869 (GW4869, 4μM, 48hrs; control, n=6 vs E2+GW4869, n=7; 1.7±6.3, p=0.78). Signal specificity for H 2 O 2 was confirmed with PEG-catalase treatment (500U/ml, 48hrs; control, n=6 vs E2+catalase, n=3; 2.3±7.9, p=0.77). Together, these results suggest that estrogen increases oxidative stress in endothelial cells isolated from individuals assigned male at birth which can be prevented through inhibition of the ceramide-forming enzyme NSmase. This work offers mechanistic insight into how estrogen containing gender affirming therapy may potentially contribute to endothelial damage and increase CVD risk in trans-females.
Abstract 16338: Outcomes in Patients With High-Risk Pulmonary Embolism Undergoing Extracorporeal Membrane Oxygenation and Adjunctive Treatment Strategy, Including Percutaneous and Surgical Management- A Retrospective Study at a Tertiary Care Center
Authors: Joseph H Park, James W Schurr, Steven Pugliese
Journal: Circulation (2023)

Introduction: The management of high-risk PE has remained challenging with high mortality rates. Several first-line treatments have been utilized, including percutaneous, surgical, and medical therapies. Extracorporeal membrane oxygenation (ECMO) has been utilized as a bridge toward definitive treatment in patients with persistent hemodynamic instability. Data on the use of combined ECMO and percutaneous management in high-risk PE are limited. Hypothesis: The goal of this study is to examine outcomes in patients with high-risk PE undergoing ECMO by their adjunctive treatment strategy (catheter-directed thrombolysis, percutaneous mechanical thrombectomy, surgical thrombectomy, systemic thrombolysis, or anticoagulation alone). Methods: Retrospective chart review at a tertiary care center of patients with high-risk PE undergoing ECMO between 2016-2023 was performed. Patients were classified into six groups by their adjunctive treatment strategy (see figure 1). Baseline clinical factors, predisposing factors for venous thromboembolism, cardiac arrest data, echocardiography, hospital course, and mortality were compared by ANOVA and chi-squared tests. Primary outcome of 30-day all-cause mortality was compared with Kaplan-Meier curve with log-rank test. Results: A total of 55 patients were included. Of these patients, 36/55 (67.3%) had a cardiac arrest. The overall all-cause 30-day mortality was 25/55 (45%). Patients receiving multiple therapies were younger compared to other groups (p value = 0.003). All-cause mortality was lower amongst patients who received interventional procedures compared with those who received medical management only (see figure). Conclusions: Our findings favor the use of combined ECMO and adjunctive procedural approaches rather than adjunctive medical therapies in patients with high-risk PE.
Abstract 18875: Using the Proteome to Detect Biomarkers of Cardiovascular Comorbidities
Authors: Yolanda Hagar, Jessica Chadwick
Journal: Circulation (2023)

Introduction: Concomitant non-cardiovascular disorders in individuals with cardiovascular disease contribute to morbidity and mortality. However, commonly used statistical approaches for identifying biomarkers of disease typically only examine the relationship between the biomarker and one endpoint at a time, ignoring potential correlation across diseases. Use of more advanced statistical tools that model two endpoints simultaneously can provide additional insight beyond what is provided by commonly used methods. Hypothesis: Biomarker identification can be made more powerful through the use of Gaussian Process (GP) Bayesian analyses. This method quantifies how one or more biomarkers may predict two biological endpoints (which may or may not be correlated) simultaneously. It is hypothesized that this will allow for the detection of additional biomarkers of comorbidities that cannot be detected using standard univariate approaches. Methods: Plasma from 5,281 participants with cardiovascular disease and with or without at least one comorbidity (CKD and/or T2D) from the Atherosclerosis Risk in Communities study visit 5 were assayed for 5,284 proteins using the SomaScan® assay. The GP model was applied in a univariate context, quantifying the relationship between each individual protein and cardiovascular disease plus one either comorbidity (CKD or T2D), characterizing the relationship using t-tests and AUC. Results from the univariate Gaussian process models were compared to results from standard univariate logistic regression models. Results: The GP method identified an additional 283 proteins that were significant for both CVD and CKD simultaneously. These proteins were not identified using logistic regression. Similarly, in addition to the 969 found significant using logistic regression models, the GP method identified an additional 190 proteins that were significant for both CVD and T2D. Among all additional proteins identified, the average AUC increased 25-30%. Conclusions: Utilizing GP and the proteome, we can discover biomarkers and characterize their signal for comorbid endpoints associated with cardiovascular disease.
Abstract 14120: Characteristics, Outcomes and Treatment Response With Dapagliflozin Across the Range of Ejection Fraction in People With HF and a History of CABG Surgery: A Pooled Analysis From DAPA-HF and DELIVER
Authors: Subodh Verma, Jawad Butt, Rudolf A de Boer, Akshay S Desai, Kieran Docherty, Adrian F Hernandez, Pardeep S Jhund, Lars Kober, Mikhail N Kosiborod, Carolyn S Lam, Anna Maria Langkilde, Felipe Martinez, Piotr Ponikowski, Marc S Sabatine, Sanjiv J Shah, Muthiah Vaduganathan, Scott Solomon, John J McMurray
Journal: Circulation (2023)

Introduction: There is a paucity of data on contemporary outcomes of patients with a history of CABG who have heart failure (HF) with either reduced or preserved left ventricular ejection fraction (LVEF). We aimed to compare the baseline characteristics and outcomes by history of CABG, as well the efficacy and safety of the SGLT2 inhibitor, dapagliflozin, across the full range of LVEF in patients with heart failure. Methods: We conducted a patient-level pooled analysis of two trials testing dapagliflozin in 11,007 participants with HF and LVEF ≤40% (DAPA-HF trial) and &gt;40% (DELIVER trial). The primary outcome was the composite of a worsening HF event or death from CV causes; other outcomes examined included total hospital admissions for HF, MACE, all-cause mortality and Kansas City Cardiomyopathy Questionnaire (KCCQ) scores. Outcomes were compared by history of CABG. Results: Among 11,007 patients, 1576 had a prior history of CABG (~14%). Patients with CABG were characterised by a higher proportion of men, lower eGFR and LVEF, and higher rates of prior MI, PCTA, type 2 diabetes, antiplatelet and statin therapy. CABG patients were more likely to experience primary outcome (adjusted hazard ratio [aHR] 1.21, 95% CI 1.08-1.36), CV death (aHR 1.22, 95% CI 1.04-1.42), all-cause death (aHR 1.22, 95% CI 1.07-1.38), HF hospitalization (aHR 1.31, 95% CI 1.14-1.51), total HF events (adjusted rate ratio 1.38, 95% CI 1.20-1.59), and MACE (aHR 1.34 (1.17-1.52). Dapagliflozin consistently reduced the primary and key secondary endpoints in both people with and without a history of CABG across the entire spectrum of LVEF (P-interaction for all &gt; 0.48) (Table). Adverse events and tolerability were similar between groups. Conclusions: In patients with HF, a prior history of CABG is associated with higher rates of CV outcomes and mortality compared to those without a history of CABG. The efficacy and safety of dapagliflozin was similar in patients with and without a history of CABG.
Abstract 16208: Population Pharmacokinetics of Intravenously and Orally Administered Sotalol in Patients With Cardiac Arrhythmias
Authors: Venkata K Yellepeddi, Kevin Watt, Kimia Ghaffari, Thomas F Deering, Richard Holubkov, Robert Kennedy, Suneet Mittal, Parash Pokharel, Marco V Perez, Jonathan P Piccini, Salvatore Savona, T J Bunch, Benjamin A Steinberg
Journal: Circulation (2023)

Introduction: Recently, an intravenous (IV) formulation of sotalol was approved to provide a loading dose before initiating oral sotalol therapy to reduce hospitalization days. However, the population pharmacokinetics (PK) of sotalol after administration of an IV loading dose regimen in patients with atrial fibrillation were not characterized. Understanding the PK of IV sotalol loading dose in patients with atrial fibrillation is required to ensure safety and optimal therapeutic outcomes. Hypothesis: The population PK model of IV and orally administered sotalol can be developed using data from two clinical PK studies with reasonable empirical Bayes estimates (EBEs) of PK parameters absorption rate constant (Ka), clearance (CL), and volume of distribution (Vd). Methods: The PK dataset of sotalol was from: 1) Relative bioavailability study with IV and oral sotalol PK data by sponsor AltaThera Inc., 2) Prospective Evaluation Analysis and Kinetics of IV Sotalol (PEAKS) registry study. Population PK was evaluated using NONMEM® 7.5, Perl-speaks-NONMEM (PsN®) version 5.3.0. Results: 545 sotalol concentrations in 25 patients were analyzed. A one-compartment model with a first-order elimination rate best described the data (Figure 1). The data correlated QTc interval levels within the observed sotalol concentration range (1.2 to 1900 ng/mL) were below 500 ms. In the final model, the EBE’s of sotalol PK parameters were, Ka - 1.44 hr -1 , CL 0.46 - L/h/kg, and the Vd -5.6 L/kg. Further PK/PD studies are needed to establish the correlation between sotalol PK and safety in this population. Conclusions: The PK of sotalol after IV and oral doses were adequately described using a population PK modeling approach. The QTc levels correlated to the plasma concentrations in this study were within the safety limit of 500 ms. This population PK model could be used to correlate the PK with safety (QTc interval prolongation) further to optimize the sotalol IV and oral dosing regimen.
Abstract 18513: Causes and Predictors of 30-day Readmissions Following Covid-19 Hospitalizations and Co-Existing Acute Heart Failure: Insights From National Readmission Database 2020
Authors: Rohan Gajjar, Aniesh Bobba, Ufuk Vardar, Taha Teaima, Sadichhya Karki, Karthik Gangu, Siri Vummaneni, Neha Yadav
Journal: Circulation (2023)

Introduction: COVID-19 infection notably impacts the cardiovascular system, with evidence of higher in-hospital mortality in patients with acute heart failure (AHF) and COVID-19 infection. However, less is known about short-term outcomes following discharge. Therefore, we sought to analyze readmission data in COVID-19 hospitalizations with AHF from the National Readmission Database (NRD). Methods: NRD (2020) was queried to identify all COVID-19 hospitalizations and co-existing AHF using ICD-10 CM codes. The group was then stratified into heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). The outcomes were 30-day readmission rate, length of stay (LOS), total hospital charge (THC), and predictors of readmission. Multivariate/univariate logistic and linear regression analyses were used to analyze the outcomes and adjust for possible confounders. Results: A total of 53,337 COVID-19 admissions with co-existing AHF were identified, of which 38,401 were discharged alive. Within 30 days from discharge, 8,159 (21.26%) were readmitted. Upon stratification, 51% belonged to the HFrEF group and were found to have scarcely higher 30 days readmission rates than encounters with HFpEF (21.46% vs. 21.14%). Readmissions lead to an additional mean THC of $85,687 and a mean LOS of 7.8 days. The top five all-causes of readmissions were COVID-19 infection (24.8%), heart failure (16.2%), sepsis (15.4%), acute kidney injury (2.2%), and pneumonia (1.2%). Figure-1 shows a multivariate analysis of independent factors associated with readmissions. Conclusions: Our analysis showed a 21.26% 30-days readmission rate following acute heart failure during COVID-19 infection. Cirrhosis, anemia, diabetes mellitus, chronic lung diseases, and discharge against medical advice were significant readmission predictors. Optimizing these co-morbidities during index admission may reduce readmissions and overall financial burden.