tbuckley/cabot-search huggingface dataset:
Abstract 4136234: Increased Reactive Oxygen Species using [18F]ROStrace PET and Dihydroethidium Staining in Myocardial Infarction Reperfusion injury
Authors: Marina Awad, Sophia Swago, Chiara Camillo, Elizabeth Thompson, Abhijit Bhattaru, Brianna Moon, Giovanni Ferrari, Estibaliz Castillero, Evan Gallagher, Meagan McManus, Victor Ferrari, Robert Gorman, Cory Tschabrunn, Robert Mach, JOEL KARP, Paco Bravo, Walter Witschey
Journal: Circulation (2024)

Introduction: Patients with reperfusion injury following myocardial infarction (MI) are at a higher risk of heart failure. Reactive oxygen species (ROS) activity can further damage cardiomyocytes and compromise heart function. Imaging methods are needed to assess ROS in vivo to investigate targeted adjunctive therapies. Our group developed a novel ROS-activated PET radiotracer [18F]ROStrace to fill this gap. In this study, we measured [18F]ROStrace fractional uptake rate (FUR) and for the first time compared it with histologic assessment of infarct and myocardium specimens. We hypothesized that [18F]ROStrace FUR was increased in the infarct and that [18F]ROStrace FUR was supported by [18F]ROStrace analogue dihydroethidium (DHE) staining. Methods: MI was induced in five swine, followed by reperfusion after 90 minutes. In vivo LGE CMR imaging and [18F]ROStrace and [82]Rb PET were performed at ~3-4 days after infarction. A terminal procedure was then performed. DHE and 4′,6-diamidino-2-phenylindole (DAPI) staining was done. Two swine received injections of DHE in the right and left coronary arteries to assess ROS. ROS activity was determined from [18F]ROStrace by computing the [82]Rb myocardial blood flow (MBF) corrected FUR. The linear relationship between infarct and MVO size, and MBF-corrected [18F]ROStrace FUR were calculated using the Pearson’s r. Results: There was a strong and positive correlation between infarct and MVO size (r=0.9, p=0.04). The MBF-corrected ROStrace FUR at baseline was 0.07±0.06 ml/g, infarct was 0.15 ± 0.05 ml/g, and remote was 0.09 ± 0.05 ml/g. We observed a significant difference between ROS in the infarct and remote region (p=0.01), which is also seen in the increased DHE staining in the infarct. We also observed increased DAPI staining in the infarct region compared to free wall due to the presence of inflammatory cells, thus increasing the number of nuclei. Conclusion: [18F]ROStrace is increased in the infarct during the subacute period post-MI compared to healthy and remote myocardium and supported by histological assessment. This work may lead to the use of in vivo [18F]ROStrace PET to support development of therapeutic strategies targeting ROS to reduce MI.
Abstract 4136169: Phenotypic clustering of right heart dilatation in pulmonary arterial hypertension
Authors: Lucas Celant, Jeroen Wessels, lilian meiboom, J. Tim Marcus, Harm Bogaard, Gustav Strijkers, M Handoko, Anton Vonk Noordegraaf, Frances De Man
Journal: Circulation (2024)

Introduction: Right ventricular (RV) and right atrial (RA) dilatation are important hallmarks of disease severity in patients with pulmonary arterial hypertension (PAH). To obtain more insights on the clinical significance of RA dilatation, we phenotypically characterized patients with right heart dilatation. Aim: Description of different RV/RA phenotypes in PAH Methods: 203 incident, treatment naïve PAH patients with cardiac magnetic resonance (CMR) imaging were included. Phenotypic clustering was based on RA and RV dilatation. Conform literature, RA dilatation was defined by a RA index maximal area &gt;15 cm 2 /m 2 . RV dilatation was defined by an RVEDV/LVEDV ratio &gt;1.3 and &gt;2.4 for extreme dilatation. Results: Four phenotypic patient clusters were identified: no dilatation (n=48), RV dilatation (n=78), RV+RA dilatation (n=53) and extreme RV dilatation + RA dilatation (n=23), Figure 1A. To unravel the additive clinical value of RA dilatation, we mainly compared patients with RV dilatation and patients with RV+RA dilatation. Intriguingly, patients with RV+RA dilatation demonstrated lower 3- and 5-year survival rates (58% and 43% vs. 75% and 55%) (Figure 1B) and were less likely to reverse RV dilatation after treatment initiation than patients with RV dilatation only. Despite the consequences of RA dilatation, we could not identify an explanation for the difference in RA dilatation between both groups. No difference in afterload was observed, shown by comparable pulmonary vascular resistance (9.9 [6.8-13] WU vs. 10 [7.5-12.3] WU, p&gt;0.05). RV function was similarly impaired (RV ejection fraction: 36±9% vs. 33±9%, p&gt;0.05). End-diastolic elastance (0.73 [0.39-1.11] mmHg/mL vs. 0.58 [0.40-0.94] mmHg/mL, p&gt;0.05) and severity of tricuspid regurgitation did not differ. Finally, diuretic use (40% vs. 40%, p&gt;0.05), age (54±16 vs. 57±19 yrs, p&gt;0.05), female gender (70% vs. 60%, p&gt;0.05) and iPAH diagnoses was similar (69% vs. 59%, p&gt;0.05). Conclusion: PAH-patients with both RA and RV dilatation have a worse clinical profile than patients with only RV dilatation. However, no clear trigger for RA dilatation was found and future mechanistic studies should unravel factors explaining these differences in right heart adaptation.
Abstract 4136289: Aortic Valve Calcium as a Predictor of Chronic Kidney Disease in a Multi-Ethnic Cohort: The MESA Study
Authors: Ashkan Abdollahi, Maryam Sani, Mahsima Shabani, Bruna Scarpa, Michael Blaha, Colin Wu, Bharath Ambale-Venkatesh, Matthew Budoff, Jordan Strom, Jerome Rotter, Wendy Post, Roger Blumenthal, David Bluemke, Joao AC Lima, Seamus Whelton
Journal: Circulation (2024)

Background: Aortic valve calcium (AVC) is associated with an increased risk of cardiovascular disease, non-cardiovascular disease such as dementia, and all-cause mortality. Traditional atherosclerotic cardiovascular disease risk factors are associated with both AVC and chronic kidney disease (CKD), but whether there is an association between AVC and CKD is unknown. Objectives: To ascertain whether AVC quantified by cardiac CT scanning is independently associated with the long-term risk of incident CKD among individuals without a previous history of cardiovascular disease. Methods: We examined 6,346 Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent cardiac CT scanning at Visit 1 (2000-02) and had an eGFR of ≥ 60 mL/min/1.73 m 2 . AVC was quantified using the Agatston method and categorized as 0, 1-99, and ≥100. Incident CKD was defined as an eGFR &lt; 60 mL/min/1.73 m 2 accompanied with an at least 40% decline in eGFR from baseline, and/or a diagnosis of CKD and indicators of end stage renal disease extracted from hospital records using the International Classification of Disease (ICD) codes. We performed Kaplan-Meier survival curve analyses along with multivariable Cox proportional hazard regression models, adjusted for age, gender, race/ethnicity, highest level of education and traditional cardiovascular risk factors along with coronary artery calcium (CAC), lipoprotein (a) (Lp[a]), and the APOE-ε4 genotype to examine the association between AVC (categorical and log-transformed) and incident CKD. Results: Participants had a mean age 62.2±10.1 years, 53% were women, and AVC &gt;0 was present in 795 (12%) participants. During a median follow-up time of 16.9 years, 982 (15%) participants developed incident CKD. AVC examined as a continuous variable was associated with a significantly increased risk of developing CKD (per log-unit [AVC+1] HR 1.06 [95% CI: 1.02-1.10]; p = 0.005). There was a stepwise increased risk for CKD with higher AVC levels ( Figure ). Similarly, in the multivariable adjusted Cox models, participants with AVC ≥100 had a higher risk of incident CKD, compared with the AVC=0 group (HR 1.48 [95% CI: 1.15-1.89]; p = 0.002). The observed associations remained after further adjusting for CAC score ( p = 0.024), Lp (a) ( p = 0.004), and the APOE-ε4 genotype ( p = 0.004). Conclusions: In a multi-ethnic cohort of participants free of CKD at baseline, AVC was independently associated with a higher risk of incident CKD.
Abstract 4136627: Development of a biomarker to predict refractory cases in Kawasaki disease patients -towards the development of diagnostic kit-
Authors: Yukako Yoshikane, Ryuji Fukazawa, WATANABE MAKOTO, Atsuhito Takeda, Shinichi Takatsuki, Keiichi Hirono, Taichi Kato, Kazuyuki Ikeda, Naho Kobayashi, Kenji Suda, Hazumu Nagata, Kyoko Imanaka-Yoshida
Journal: Circulation (2024)

Introduction: Kawasaki disease (KD), which is the most common multisystem vasculitis with unknown causes in childhood, causes coronary artery lesions (CALs). Treatment with a high dose of intravenous immunoglobulin (IVIG) is the most effective therapy for the acute phase of KD. However, some very severe cases need several additional treatments and are at risk for CALs. Several scoring systems that have tried to predict IVIG-resistant patients failed in multiethnic populations. Aims: To develop the most effective biomarker for predicting refractory cases and determine the cut-off value for the development of the diagnostic kit. Methods: Multicenter, prospective, observational study was conducted at 49 hospitals in Japan between September 2017 and December 2023. The subjects consisted of 1310 KD patients, including Group 1 (n=50); treatment-resistant cases that required additional treatment of 3rd line or more (defined as refractory cases), and Group 2 (n=1260); cases that completed the treatment with 1st or 2nd line. Tenascin C (TN-C), Pentraxin 3 (PTX3), and Procalcitonin (PCT) values, which were selected by systematic review and a pilot study, were measured before initial treatment in each group. The cut-off value of the biomarker, which had the highest area under the curve (AUC), was determined. Results: All three biomarker values were significantly higher in Group 1 than Group 2 (p&lt;0.01). Median [Interquartile range] in Group 1 vs Group 2 and AUC were PTX3; 44.6 [32.3-67.9] vs 12.2 [6.9-26.9]ng/ml, AUC=0.83, PCT; 4.3 [1.9-7.8] vs 0.6 [0.2-1.9]ng/ml, AUC=0.81, TN-C; 182 [122-222] vs 123 [94-163]ng/ml, AUC=0.71. PTX3 showed the highest AUC with the cut-off value of 31.7ng/ml [95% confidence interval; 31.7-34.9]. Group 1 could be predicted by PTX3 with the sensitivity of 80%, the specificity of 82%, the positive predictive value of 13% and the negative predictive value of 99%. Conclusions: It may be possible to predict refractory KD cases with high sensitivity and specificity by PTX3 value before initial treatment, and possibly develop a diagnostic kit using PTX3 value for prediction of refractory cases.
Abstract 4136784: Diagnostic significance and prognosis prediction of electrocardiogram plane QRS-T angle in patients with non-ST segment elevation acute coronary syndrome
Authors: Yiming Chen, Junyi Zhang, Yafeng Zhou
Journal: Circulation (2024)

Objective: For patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS), the diagnostic efficacy of traditional ECG is not sensitive and specific. Plane QRS-T angle (PQRS-Ta) can be used as a supplement to the current diagnostic criteria of ECG. Methods: The patients with recurrent chest pain in our hospital were analyzed retrospectively, and the plane QRS-T angle of the patients was calculated. The main results were as follows: (1) the clinical indexes of the two groups were analyzed according to the angle of QRS-T. (2) all patients were divided into three groups according to the final diagnosis. The diagnostic efficacy of QRS-T angle combined with standard ECG diagnostic criteria was analyzed, and the incremental diagnostic value of the new standard relative to the original standard was calculated. (3) the patients were scored by Gensini, and the differences of plane QRS-T angle among patients with different scores were compared. (4) the frequency of MACE was recorded, and the prognostic effect of QRS-T angle on the study population was analyzed. Results: After analyzing the data, there was a difference in the value of plane QRS-T angle between NSTE-ACS population and non-ACS population (p &lt; 0.001). It was found that every 1 °increase of plane QRS-T angle increased the risk of NSTE-ACS by 2.5% (χ 2, 27.59, P &lt; 0.001). The diagnostic accuracy of AUC quantified plane QRS-T angle combined with standard ECG in the diagnosis of NSTE-ACS was 0.68 (CI [0.64 ~ 0.70]). Through the analysis of NRI and IDI index, the relative NRI of the new model to the original model is 6.67%, 95% CI is 3.91%, and the CI is 9.42% (P &lt; 0.001). The IDI is 6.30%, the CI is 4.65%, and the CI is 7.95% (P &lt; 0.001). The new model improves the prediction effect by 6%. When the QRS-T angle increased by 1 °, the Gensini score increased by 0.199 points (95% CIRV 0.149) (Fidel60.975 (P &lt; 0.001). Comparing prognosis of the three groups, there was a statistical difference in the overall survival time among the three groups (χ 2 = 19.090 P &lt; 0.001). Conclusion: Compared with the original standard, the new diagnostic standard can improve the diagnostic efficiency of ECG. QRS-T angle can predict the prognosis of patients with NSTE-ACS. The higher the value of QRS-T angle, the greater the probability of major adverse cardiovascular events (MACE) in patients with non-ST segment elevation acute coronary syndrome.
Abstract 4136462: Provider understanding of Coronary Artery Calcium Scoring (CAC) testing in Atherosclerotic CArdiovascular Disease risk stratification and Racial Disparities Study (CAC-CARD) to reduce healthcare disparities
Authors: Pawan Daga, Dakshinkumaar Devanand, Muhammad Umer, Usman Sagheer, Tushar Menon, Gurnoor Singh, Dinesh Kalra
Journal: Circulation (2024)

Background: Coronary Artery Calcium (CAC) scoring is critical in assessing Atherosclerotic Cardiovascular Disease (ASCVD) risk. Despite its utility, many primary care physicians lack confidence and familiarity with its application. Significant racial disparities in CAC scoring utilization have been observed, potentially affecting patient outcomes. Hypothesis: We hypothesized that a short targeted educational intervention would enhance physicians' confidence, knowledge, and utilization of CAC scoring and awareness of racial disparities. Methods: A pre- and post-intervention study (Image 1) was conducted among 39 physicians at the University of Louisville. The intervention included a 20-minute educational session on CAC scoring and racial disparities. A video summarizing the ACC2018 guidelines for prevention and cholesterol treatment was provided. A summary of key points for clinical practice was given. The ASCVD plus calculator app was provided. Data were collected using a structured questionnaire before and after the intervention. Viewing time and engagement were recorded. Descriptive and inferential statistics analyzed the data. Results: The average correct physician responses increased from a mean of 59.5% pre-intervention to 92.0% post-intervention. Post-intervention, the number of physicians who felt confident or very confident in CAC testing increased from 17.9% to 94.8%. Additionally, 33 out of 39 physicians (84.6%) reported likely to use CAC testing more frequently. Correct responses on racial disparities improved from 59% pre-intervention to 92.0% post-intervention. (Image 2). The average viewing time was 28 minutes. Time spent on the questionnaires was 14 min pre and 12 min post. Conclusion: Our targeted educational intervention significantly enhanced physicians' knowledge and confidence in CAC scoring for ASCVD risk assessment and raised awareness about racial disparities, promoting more equitable practices.
Abstract 4135534: Total and Regional Lung Volumes And Pulmonary Blood Flow In Repaired Tetralogy Of Fallot - Smaller Lungs And A Maldistribution of Flow
Authors: Mark Fogel, Kevin Whitehead, David Biko, Matthew Harris, Danish Vaiyani, Sara Partington, Laura Mercer-Rosa
Journal: Circulation (2024)

Introduction: Many pts with repaired tetralogy of Fallot (rTOF) are left with residual pulmonary regurgitation (PR) and poor exercise performance. Small studies in young children suggest that the total lung volume of rTOF pts are smaller than normal and may contribute to these sequelae. As exercise and cardiac performance are intimately related to lung function, it’s surprising that few rTOF studies have investigated cardiopulmonary interactions. Aims: To determine if regional and total lung volumes in rTOF pts are the same size as normals and if the larger amount of forward blood flow courses to the bigger lung. We hypothesized that this may not be the case. Methods: rTOF patients undergoing clinically indicated cardiac magnetic resonance (CMR) were evaluated for lung volumes using dark blood imaging (figure) and blood flow to the branch pulmonary arteries (bPA) using velocity mapping. Significance &lt; P=0.05. Results: Eleven rTOF patients and 25 normal controls were studied. Total control lung volume was significantly larger than those of rTOF. Regional rTOF right and left lung volumes were smaller than their respective control lung volumes, barely missed statistical significance (table). In 6 rTOF pts with CMR prior to and after pulmonary valve replacement (PVR), lung volumes did not differ between the 2 timepoints (1034 vs 998 cc/m 2 respectively). Only 3/11 (27%) rTOF pts had the higher bPA flow coursing to the higher regional lung. The ratio of right bPA forward flow/right lung volume to left bPA forward flow/left lung volume ranged from 0.72-1.51 (ideal balanced flow to each lung would be 1), implying a maldistribution of flow. Conclusion: rTOF patients have smaller total lung volumes than controls with no change after PVR in our study. In addition, only a small proportion of rTOF patients have the larger amount of flow coursing to the larger lung. The ratio of individual bPA flow to individual lung volume implies a maldistribution of pulmonary flow relative to the respective lung volume. Our findings may have implications for timing of PVR, partially explaining PR and poor exercise performance. Flow limiters placed by cath or surgery may be able to redistribute the appropriate flow to regional lung fields.
Abstract 4136285: Large-Scale Proteomics Identifies Novel Shared Biomarkers of Heart Failure and Cancer: the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Yimin Yang, Bonnie Ky, Victoria Lamberson, Ron Hoogeveen, Christie Ballantyne, Chiadi Ndumele, Corinne Joshu, Josef Coresh, Elizabeth Platz, Elizabeth Selvin, Bing Yu, Amil Shah
Journal: Circulation (2024)

Introduction: There is a bidirectional relationship between cancer and cardiovascular disease risk. Identifying proteins associated with both cancer and heart failure (HF) may provide insight into common biological pathways underlying both conditions. Methods: Among 10,136 participants in the community-based ARIC cohort study who were free of HF and cancer at study visit 2 (1990-92) and had aptamer-based proteomics (SomaScan v4), we assessed the association of 4,955 plasma proteins with incident HF and with incident site-specific cancer ascertained by cancer registry linkage supplemented with medical records (lung, post-menopausal breast, prostate, colorectal, and hematologic) using multivariable Cox models adjusted for demographics, clinical characteristics, and social determinants of health. Two-sample cis-Mendelian randomization ( cis- MR) was performed to evaluate potential causal effects of proteins on HF, left ventricular (LV) function, and site-specific cancer. Results: Mean age at baseline was 56±6; 54% were female; and 24% reported black race. Over a median follow-up of 10 [IQR 10, 10] years, there were 604 incident HF events and 1,207 incident cancers (169 lung, 85 hematologic, 105 colorectal, 206 breast, 288 prostate). Using a Bonferroni significance threshold (p &lt; 1.0x10 -5 ), 23 proteins were associated with both HF and lung cancer, 2 with HF and hematologic malignancy, 1 with HF and colorectal cancer, and none with HF and breast or prostate cancer. Six proteins remained significantly associated with both HF and lung cancer after further adjustment for pack-years of smoking (Figure). In cis- MR of these six proteins, ICAM5 and MMP12 showed potential causal effect on LV volume and lung adenocarcinoma, and PLAUR showed potential causal effect on HF and lung adenocarcinoma. Conclusion: Among various types of cancer, proteins associated with lung cancer showed the greatest overlap with proteins associated with HF, which was largely accounted for by smoking exposure. We uncovered a set of 6 plasma proteins associated with both incident HF and lung cancer after accounting for smoking. MR identified proteins with potential causal effects on both lung adenocarcinoma and LV size (ICAM5, MMP12) and HF (PLAUR).
Abstract 4136398: Gender Disparities Absent in Citation Metrics and Online Attention Across Thoracic Surgery Publications
Authors: Alyssa Sato, Ronald Karlsberg, Carlos Quesada
Journal: Circulation (2024)

Introduction: A recent study by Women As One highlighted the prevalence of “MANuscripts” (publications authored solely by men) and their potential impact on equity in academic promotions within cardiology. The study revealed notable differences in citation rates and online attention between publications in cardiology journals led by male and female authors. To further explore these disparities, we examined publications in prominent thoracic surgery journals. Hypothesis: Thoracic surgery publications where women hold key authorship roles (primary and senior) receive lower citations and online attention compared to those with men as leading authors. Methods: We analyzed data from peer-reviewed publications in 2019 from two high-impact thoracic surgery journals: The Annals of Thoracic Surgery and The Journal of Thoracic and Cardiovascular Surgery. Citation metrics and Altmetric Attention Scores (AAS) were sourced from Google Scholar paired with the Altmetric Google Chrome extension. Citation rates, AAS, and names of primary and senior authors were manually collected between September 22, 2023 and December 21, 2023. The genders of key authors were determined using Genderize, a gender-determination software, supplemented by manual searches for authors not detected by the software. A minimal number of publications were excluded if either their AAS or citation metrics were unavailable. Significant differences in the data were analyzed using one-sided Mann-Whitney U-tests. Results: Of the 1,482 authors included in the analysis, 18.4% were females in primary or senior roles. Our analysis found no significant differences in citation rates or AAS between male and female primary authors (p=0.09 and p=0.31, respectively), or between male and female senior authors (p=0.48 and p=0.38, respectively). Furthermore, after combining the data of male primary and senior authors and comparing it to the combined data of female primary and senior authors, no significant discrepancies were found for both citations (p=0.13) and AAS (p=0.28). Conclusion: Contrary to analyses of cardiology journals, our data from thoracic surgery articles does not indicate a gender disparity between male and female authors in terms of citations and online attention. While this does not definitively rule out the presence of inequity in thoracic surgery research, it suggests that male-authored manuscripts may not be a primary source of gender disparity in this field.