tbuckley/cabot-search huggingface dataset:
Abstract 4141180: Opportunistic assessment of cardiovascular risk using deep learning of the heart and aorta on non-contrast chest computed tomography
Authors: Vineet Raghu, Audra Sturniolo, Douglas Kiel, Hugo Aerts, Pradeep Natarajan, Michael Lu
Journal: Circulation (2024)

Purpose: Primary prevention of cardiovascular (CV) disease relies on accurate risk estimation. The coronary artery calcium score (CAC) can be measured on routine chest computed tomography (CT); however, it is unclear whether the heart and thoracic aorta regions on CT can provide additional information about future risk beyond calcium and risk factors. Methods: We applied the open-source TotalSegmentator tool to extract heart and thoracic aorta volumes from 27,943 non-contrast non-ECG gated chest CTs from 17,241 National Lung Screening Trial participants. We used the segmented volumes from 10,356 participants as input to train a new 3D Densenet169 deep learning model to predict 12-year CV mortality. Independent testing was performed in 5,165 individuals not used for model training with no history of type 2 diabetes, myocardial infarction, or stroke (eligible for primary prevention). The deep learning score was compared to a regression model using demographics, smoking, BMI, comorbidities, and the radiologist’s findings from the CT. We stratified the CAC and deep learning scores into high vs. low-risk groups using a CAC&gt;100 and deep learning &gt;10% risk threshold, respectively. Results: In the independent testing dataset, (N=5165; median age 60.0±8.0 years; 62.6% male), 3.3% died of CV disease. The deep learning score had higher discrimination for CV mortality than risk factors and CT findings (deep learning AUC 0.72 [0.68,0.76] vs. baseline AUC 0.66 [0.61,0.69], p &lt; 0.001). Similar results were found for secondary outcomes of fatal myocardial infarction and fatal stroke. In a subset of 2,972 testing set individuals with measured CAC, those with high CAC and a high deep learning score had a 10.8% rate of 12-year CV mortality, higher than those with high CAC alone (4.1%, p&lt;0.001). Conclusion: Based on the heart and thoracic aorta regions from CT, a deep learning model predicted 12-year CV mortality beyond prevalent risk factors, CAC, and imaging findings. Clinical Relevance: Opportunistic screening of chest CT using deep learning may enhance risk assessment to guide decisions for preventing CV events. External validation in population-representative cohorts is needed before clinical use.
Abstract 4141312: Safe Initial Dosing of Innovative Enalapril Orodispersible Minitablets in Newly Treated Newborns, Infants and Young Children with Heart Failure – Results of a Population Pharmacokinetic Analysis of the LENA Trials
Authors: Melina Steichert, Stephanie Laeer, Willi Cawello
Journal: Circulation (2024)

Background: Safe dosing in children with heart failure requires consideration of clinically relevant covariates. In the European project Labeling of Enalapril from Neonates up to Adolescents (LENA), heart failure was treated with innovative enalapril orodispersible minitablets (ODMT) using an age- and weight-dependent dosing regimen. Research Question: Does the population pharmacokinetic analysis of the LENA data reveal relevant clinical covariates in dosing besides age and weight for newborns, infants and young children newly treated with enalapril ODMT? Methods: We analyzed data of ACE inhibitor naïve subjects with heart failure due to congenital heart disease (n=31) or dilated cardiomyopathy (n=3) from the prospective, open-label, multicenter phase II/III pharmacokinetic bridging studies using NONMEM ® . Allometric scaling was applied to the clearance (CL/F) and volume of distribution (V d /F) of enalapril and enalaprilat. The covariates age, sex, serum creatinine and Ross score were tested using stepwise covariate modeling. Simulations were conducted to assess the effects of the identified covariates. Results: In total, 173 enalapril and 268 enalaprilat serum concentrations from 34 subjects (25 days–2.1 years, median age=0.3 years) were included in the analysis. A combined model with a one compartment model of enalapril coupled with a one compartment model of enalaprilat with absorption lag was chosen as the structural model. The population estimates were 4.98 L (V d /F of enalapril), 34.1 L (V d /F of enalaprilat), 4.61 L/h (CL/F of enalapril) and 1.55 L/h (CL/F of enalaprilat). For enalaprilat, part of the variance in CL/F could be explained by age and serum creatinine, while part of the variance in V d /F could be explained by the Ross score. The simulations indicated that age, weight, and serum creatinine values above the normal reference range are clinically relevant covariates for the initial dose and the dose at steady state, while the Ross score is a relevant covariate for the initial dose. An increase in the Ross score by one point leads to an average increase in the initial maximum concentration of enalaprilat of 24% in the examined Ross score range from 0 to 11. Conclusion: The newly detected covariate Ross score provides the scientific basis for considering the severity of heart failure at the initial dose. The initial dose should be lowered depending on the level of the Ross score to avoid high peak concentrations and a potential drop in blood pressure.
Abstract 4140895: Pre-procedural Red Cell Distribution Width As A Prognostic Biomarker In Patients Undergoing Transcatheter Aortic Valve Implantation: A Systematic Review and Meta Analysis
Authors: Lakshmi Subramanian, Sashwath Srikanth, Nikitha Devaprasad, Jinye Liu, Zoofi Shan, Pavan Vihar Reddy Podduturi, Urmi Jindal, Divyank Patel, Rupak Desai
Journal: Circulation (2024)

Background: Red cell distribution width (RDW) is a measurement of variability in erythrocyte size and volume, routinely reported as part of a complete blood count. Recently, it has gained popularity as a novel prognostic biomarker for cardiovascular disease outcomes. Our study investigates the predictive value of pre-procedural RDW for all-cause mortality (ACM) within one year for patients undergoing transcatheter aortic valve implantation (TAVI). Methods: We comprehensively reviewed databases like PubMed, Google Scholar, Embase, and Scopus until May 2024, looking for studies reporting an association between pre-procedural RDW and outcomes in TAVI. A binary random effects model was used to calculate the pooled adjusted odds ratio (aOR), and subgroup analysis was performed. I2 statistics were used to determine the heterogeneity of studies, further enhancing the robustness of our research. Results: Our systematic review and meta-analysis included five studies (three retrospective, two prospective) encompassing 2,565 patients with a mean age of 81.32 years. Our study showed a slight female predominance (52%). The mean follow-up period was one year. Comorbidities like coronary artery disease, diabetes melitus, atrial fibrillation, prior myocardial infarction were commonly reported among the study population. Higher pre-procedural RDW was associated with increased odds of ACM at the end of one year with an unadjusted pooled OR 1.86 (95% CI: 1.30-2.67, p&lt;0.01) and adjusted pooled aOR 2.21 (95% CI: 1.81-2.69, p&lt; 0.01) (Figure 1). Leave one out sensitivity analysis confirmed the robustness of the meta-analysis, as no single study disproportionately affected the overall results. Conclusion: Our study demonstrates the potential of pre-procedural RDW as a prognostic biomarker for predicting 1-year ACM in post-TAVI patients. However, further research is warranted to fully elucidate the role and mechanism of RDW in this context.
Abstract 4141622: Pathway between race, historic and contemporary measures of structural racism, and life expectancy in the US
Authors: Leonard Egede, Rebekah Walker, Jennifer Campbell, Sebastian Linde
Journal: Circulation (2024)

Background: A growing body of evidence highlights the role of structural racism, or the ways in which societies foster racial discrimination through mutually reinforcing systems, on cardiovascular outcomes. This study aimed to better understand this relationship using historic structural racism (historic redlining) and a novel measure of contemporary structural racism (structural racism effect index) on life expectancy, accounting for distribution of race across counties in the US. Methods: After combining census tract level data, the final analytic sample consisted of 15,190 census tracts across 157 counties, within 50 states including DC. Historic structural racism was defined as historic redlining using the Home Owners’ Loan Corporation (HOLC) neighborhood grades (score between 1=best and 4=redlined). Contemporary structural racism was defined using the structural racism effect index (SREI), a summary score of nine domains (built environment, criminal justice, education, employment, housing, income/poverty, social cohesion, transportation, and wealth). Life expectancy was based on the National Center for Health Statistics’ US Small-area Life Expectancy Estimates Project using 2010-2015 data. Structural equation modeling in Stata v17 was used to investigate direct and indirect relationships between race, historic structural racism, contemporary structural racism, and life expectancy in the US. Results: Mean life expectancy was 77.3 years and 26.7% of the US population within each census tract was Black/African American. Historic redlining (-0.06, p&lt;0.001), contemporary structural racism (-0.61, p&lt;0.001), and proportion of the census tract reporting Black race (-0.21, p&lt;0.001) were directly associated with decreased life expectancy. Historic redlining was indirectly associated with decreased life expectancy via the pathway of contemporary structural racism (0.19, p&lt;0.001). Black race was indirectly associated with decreased life expectancy through both more exposure to historic redlining (0.18, p&lt;0.001) and higher levels of contemporary structural racism (0.56, p&lt;0.001). Conclusion: Structural racism, measured using historic or contemporary measures, is associated with decreased life expectancy. Contemporary structural racism is a stronger relationship for the pathway through which Black race is associated with lower life expectancy and is a pathway through which historic residential redlining influences life expectancy.
Abstract 4140858: Racial Disparities in Cardiovascular Outcomes Among Hospitalized Patients with Diabetes Mellitus
Authors: Chikodili Nebuwa, Olayiwola Bolaji, BLANCHE ECHARI, Hazique Mohammad, UFUOMA AGBEDIA-EJUGHEMRE, Vishnu Shenoy, Saeed Shoar, M Chadi Alraies
Journal: Circulation (2024)

Introduction: Patients with diabetes mellitus (DM) experience diverse cardiovascular outcomes; this study aimed to evaluate the racial disparities in cardiovascular outcomes among patients with diabetes mellitus. Method: We conducted a retrospective cohort study using the National Inpatient Sample (NIS) database 2016-2021 and ICD 10 code and identified patients with DM, categorized them based on their race. Baseline characteristics were compared using Pearson's χ2 tests and univariable linear regression. The cardiovascular outcomes were examined using multivariable logistic regression. Group comparisons were carried out using Wilcoxson signed-rank test for continuous and Pearson's χ2 tests for categorical variables. Result: We analyzed data from 47,384,595 hospitalizations for DM across racial groups in the US between 2016 and 2021. Baseline characteristics of DM among racial groups over the study period is illustrated in Table 1. The mean age was oldest among Whites (67.7 years) and Asian/Pacific Islanders (68.1 years). Cardiovascular outcomes differed across groups (Table 2). In-hospital mortality was highest among Asian/Pacific Islanders (4.3%) and lowest among Blacks (2.9%, p&lt;0.001). Heart failure was most prevalent in Blacks (34.2%), while myocardial infarction rates were highest among Asian/Pacific Islanders (6.3%, p&lt;0.001). Blacks and Native Americans had higher rates of ESRD (15.6% and 15.2%) than other groups, especially compared to Whites (5.8%). Amputation rates were also higher among Native Americans (6.7%) and Blacks (4.8%) than Whites (3.3%). After adjusting for demographics, hospital characteristics and comorbidities, racial minorities remained at higher risk for adverse outcomes compared to Whites. Blacks (aOR 2.19, 95%CI 2.16-2.21), Hispanics (aOR 2.54, 95%CI 2.50-2.58), Asian/Pacific Islanders (aOR 2.56, 95%CI 2.51-2.61) and Native Americans (aOR 2.87, 95%CI 2.72-3.01) all had over double the odds of ESRD. Blacks, Hispanics and Native Americans also had significantly higher adjusted odds of amputation. However, Blacks (aOR 0.66, 95%CI 0.64-0.69) and Hispanics (aOR 0.89, 95%CI 0.86-0.93) had lower odds of in-hospital mortality than Whites. Conclusion: This study highlights racial disparities in cardiovascular outcomes among hospitalizations of patients with DM. Further research should be done to explore contributing factors to these disparities to improve and curb these outcomes.
Abstract 4140759: Clinical Outcomes Of SGLT2 Inhibitors In Patients Hospitalized With Acute Heart Failure: A Meta-analysis Of Randomized Control Trials
Authors: Soumya Gupta, Aditya Thakkar, Won-joon Koh, James Choi, Hannah Hart, Kiran Mahmood
Journal: Circulation (2024)

Introduction: Acute heart failure (AHF) presents challenges due to its poor prognosis and limited therapeutic options compared to chronic heart failure (CHF). The potential benefits of SGLT2 inhibitors in AHF patients are being explored, yet systematic evaluation is lacking. Our meta-analysis aims to bridge this gap by comparing the efficacy and safety of SGLT2 inhibitors versus placebo in AHF patients. Research question: Clinical Outcomes Of SGLT2 Inhibitors In Patients Hospitalized With Acute Heart Failure Methods: We searched Medline, Embase, and Cochrane databases for randomized controlled trials involving adult patients hospitalized with AHF, who received SGLT2 inhibitors. Our primary outcomes were all-cause mortality, heart failure events, and readmissions. The secondary outcomes were change in KCCQ-TSS (Kansas City Cardiomyopathy Questionnaire), weight, length of stay and NT-proBNP levels. Safety outcomes included hypotension, hypoglycemia, UTI, DKA, and acute renal failure. We used Review Manager 5.4 for statistical analysis, employing standardized mean difference (SMD) and risk ratio (RR) with 95% confidence intervals (CI). Results: Seven RCTs were included, involving a total of 2321 patients, with 49.5% receiving SGLT2 inhibitors. Patients receiving SGLT2 inhibitors showed a significant reduction in the risk of readmissions by 32% (RR = 0.68, p &lt; 0.00001). They also showed a non-significant but reduced risk of all-cause mortality by 24% (RR = 0.76, p = 0.04), and heart failure events by 27% (RR = 0.63, p = 0.09). With respect to the secondary outcomes, there was a significant reduction in KCCQ-TSS (SMD= -0.17; 95% CI: -0.26 to -0.08; p=0.004) and weight (SMD= -0.34; 95% CI: -0.55 to -0.13; p=0.002) in the intervention group as compared to the placebo group. This group was also associated with a non-significant but reduced length of stay (SMD= -0.01; 95% CI: -0.20 to -0.18; p=0.90) and NT-proBNP levels (SMD= -0.06; 95% CI: -0.29 to -0.17; p=0.61). On analysis of the safety outcomes, there was a non significant difference in the risk of acute renal failure, UTI, and DKA. Conclusion: In patients with AHF, initiation of SGLT2 inhibitors showed a statistically significant reduction in heart failure rehospitalizations, improved weight-based diuretic efficiency, and KCCQ-TSS. These findings suggest that starting SGLT2 inhibitors in patients hospitalized for AHF is well tolerated and leads to clinical benefits.
Abstract 4141419: Predictors of Mortality and Hospitalization in Heart Failure with Preserved Ejection Fraction with Low NT-proBNP Levels
Authors: Masih Tajdini, Vivek Jani, Radu Tanacli, Mohammad Keykhaei, Virginia Hahn, Kavita Sharma
Journal: Circulation (2024)

Introduction: Many patients with heart failure with preserved ejection fraction (HFpEF) have relatively low natriuretic peptide (NP) levels, often related to obesity. The predictors of mortality and hospitalization (CV outcomes) within HFpEF patients with low NT-proBNP levels remain unclear. In this study, we examined these predictors, comparing HFpEF with low NT-proBNP (HFpEF-LoBNP) and high NT-proBNP (HFpEF-HiBNP) groups. Methods: Patients from the Johns Hopkins HFpEF Clinic (July 2014 - May 2024) were categorized into HFpEF-LoBNP (&lt;125 pg/mL) and HFpEF-HiBNP (≥125 pg/mL) groups. Diagnosis relied on clinical findings, standard echocardiography, and right heart catheterization when available. Group differences were analyzed using Chi-square or Mann-Whitney U tests. Cox models examined associations with CV outcomes, and Kaplan-Meier analysis assessed the combined factor impact on outcomes. Analyses compared within each BNP level category (HFpEF-LoBNP and HFpEF-HiBNP) those who experienced CV outcomes versus those who did not. Results: A total of 378 HFpEF patients were included, categorized as HFpEF-LoBNP (107 patients) and HFpEF-HiBNP (271 patients), with a median follow-up period of 36 months. Within the HFpEF-LoBNP group (mean age 59.5 years, 68% female), 26 (24.3%) experienced CV outcomes. HFpEF-LoBNP patients with CV outcomes had higher diabetes prevalence, HbA1c, RA pressure, PA systolic pressure, RV systolic pressure, PA diastolic pressure, PCWP, PVR, and lower albumin (Figure A) compared to HFpEF-LoBNP patients without CV outcomes. No significant differences were found in other characteristics. Within the HFpEF-HiBNP group (mean age 68.2 years, 59.4% female), 98 (36.2%) experienced CV outcomes. HFpEF-HiBNP patients with CV outcome were more likely to be on β-blocker therapy, had a higher E/e' ratio, NT-proBNP, cystatin C, uric acid, RV systolic pressure, PA systolic and diastolic pressures, PCWP, PVR, and lower albumin compared to those without CV outcomes (Figure B). There were no notable differences in other characteristics. Kaplan-Meier graphs showed poorer outcomes with an increasing number of factors in each subgroup (Figures C&amp;D). Conclusion: NT-proBNP is linked to HF prognosis but often low in HFpEF. HFpEF-LoBNP patients still face high CV outcomes. Predictors of CV outcomes in HFpEF-LoBNP, similar to HFpEF-HiBNP, include higher pulmonary pressures. Alternative prognosis markers, like hemodynamic testing, are needed for HFpEF-LoBNP patients.
Abstract 4141311: The Association Between Oxidative Balance Score and Hypertension: A Cross-Sectional Study
Authors: Kang Wang, Pengfei Chen, Bohao Tan, Cheng Wei, Jianjun Tang, Zhen-fei Fang, Qiming Liu, Zhangling Chen, Shenghua Zhou
Journal: Circulation (2024)

Background: The association between oxidative stress score (OBS) and hypertension remains unclear in the US population. Hypothesis: We hypothesized that higher OBS was associated with a lower risk of hypertension. Methods: A total of 22,938 adults (mean age: 47.2 years) were enrolled from 8 survey cycles of NHANES (2003-2004, 2005-2006, 2007-2008, 2009-2010, 2011-2012, 2013-2014, 2015-2016 and 2017-2018). The total OBS consisted of the dietary OBS and the lifestyle OBS, based on 16 dietary components (including dietary iron, zinc, total fat, copper, selenium, magnesium, calcium, vitamin C, E, B6 and B12, total folate, carotene, niacin, riboflavin, and fiber) and 4 lifestyle components (including body mass index, alcohol, smoking, and physical activity). Weighted multivariate logistic regression was used to investigate the association between OBS and hypertension, and restricted cubic spline (RCS) assessed the nonlinear relationship. Results: In the multivariate-adjusted model, a substantially inverse association was observed between total OBS and risk of hypertension. Comparing the extreme quartile groups, the OR and 95% CI were 0.62 (0.52-0.73). Furthermore, higher dietary OBS and lifestyle OBS were similarly associated with a lower risk of hypertension (OR (95%CI): 0.78(0.66,0.93); 0.38(0.33,0.44), respectively). The RCS exhibited a nonlinear dose-response association between total OBS and hypertension ( P non-linearity &lt; 0.001). Conclusion: These findings support the potential beneficial role of OBS for the prevention of hypertension in adults.
Abstract 4141629: Pulmonary Arterial Pruning is Associated with Increased Pulmonary Pressure and Worse Left Ventricular Systolic and Diastolic Function in Late Life
Authors: Aditya Dewanjee, Victoria Lamberson, Yimin Yang, Brian Claggett, Kunihiro Matsushita, Michael Blaha, George Washko, Raul San Jose Estepar, Amil Shah
Journal: Circulation (2024)

Background: Advanced age is associated with left ventricular (LV) remodeling and increased pulmonary pressure; both these alterations are associated with increased risk of heart failure. However, there is a lack of data regarding morphologic changes in the pulmonary vasculature underlying these associations. Aims: Determine the extent to which LV remodeling associates with pulmonary arterial (PA) pruning, and the relationship of PA pruning with pulmonary pressure. Methods: Among 2,275 participants in the community-based Atherosclerosis Risk in Communities (ARIC) study who underwent echocardiography and non-contrast chest CT at Visit 7 (2018-2019), we quantified the fraction of total pulmonary vascular area comprised of arterial vessels with diameter &lt;5 mm (BV5/TBV) using validated image processing (Panel A). We used multivariable linear regression to assess the association of BV5/TBV with echocardiographic measures of pulmonary artery systolic pressure (PASP) and LV structure, systolic function, and diastolic function. Models were adjusted for age, BMI, eGFR, gender, race, lung volume, SBP, prevalent CAD, diabetes, atrial fibrillation, and hypertension, cumulative pack years smoked at Visit 7, and low and high attenuation areas on CT. Results: Mean age was 80 ±4 years, 61% were women, 22% reported Black race, and mean LVEF was 64 ±7%. Mean BV5/TBV was 0.30 ±0.08. Lower BV5/TBV – reflecting greater PA pruning – was associated with older age, male sex, Black race, and greater BMI. There was no correlation between prevalent atrial fibrillation, hypertension, CAD, or stroke and PA pruning. Greater LV volume and mass, lower LVEF, and greater left atrial volume were each associated with lower BV5/TBV (Panel B). Lower BV5/TBV demonstrated a nonlinear association with greater PASP (Panel C), with increases in PASP noted at BV5/TBV values &lt;0.30. Conclusions: Worse LV systolic and diastolic function are associated with greater PA pruning, which is in turn associated with greater PASP once BV5/TBV falls below 0.30. Our findings clarify the pulmonary vascular remodeling that links cardiac dysfunction to elevated pulmonary pressure in late life and may help identify persons at particularly high risk for pulmonary hypertension.