tbuckley/cabot-search huggingface dataset:
Abstract 17854: Imaging Intravascular Macrophages Using Micro-Sized Superparamagnetic Decoys
Authors: Maxime Gauberti, Manuel Navarro-oviedo, Denis Vivien, Sara Martinez de Lizarrondo
Journal: Circulation (2023)

Introduction: During inflammatory processes, intravascular macrophages are capable of phagocytizing circulating debris in the circulation. Hypothesis: Intravenous injection of contrast-loaded decoys could be used to label intravascular macrophages and map their distribution by non-invasive imaging. Methods: We synthetized superparamagnetic decoys with hydrodynamic diameters from 20 nm to 4.5 μm. Experimental models of neuroinflammation (intrastriatal injection of LPS or TNF) and ischemic stroke (thrombin model and ferric chloride model) were performed in mice. High resolution 3D T2*-weighted MRI sequences were performed after intravenous injection of the superparamagnetic decoys. Results: In experimental models of neuroinflammation, intravenous injection of superparamagnetic decoys with a diameter of 1 μm (but neither smaller nor larger particles) reveals intravascular phagocytic cells in the cerebral circulation, in a dose dependent manner. In ischemic stroke, we found that intravenous injection of the decoys leads to numerous signal voids in the vessels in and around the infarct core at 48 hours (Figure 1a-b). Interestingly, the intravascular phagocytic activity appears much higher in permanent rather than transient models of ischemic stroke. Pre-treatment with anti-CD11a blocking antibodies significantly reduced the number of intravascular macrophages in stroke. Histological studies confirmed that injected decoys are phagocytized by intravascular cells which express typical markers of the monocyte/macrophage lineage including CX3CR1 dependent GFP expression and CD68 (Figure 1c). Conclusions: Intravenous injection of superparamagnetic decoys in the micrometer size range allows to image intravascular macrophages. This new method allows to study the pathophysiological roles of intravascular macrophages in experimental models and could be easily translated to humans.
Abstract 15477: Mitochondrial Drp1 Deficiency in Macrophage Limits Revascularization of Ischemic Muscle via Inflammatory Metabolic Reprograming and Macrophage Polarization
Authors: Shikha Yadav, Vijay C Ganta, Dipankar Ash, Sudhahar Varadarajan, Sheela Nagarkoti, Archita Das, Maggie McMenamin, Tohru Fukai, Masuko Ushio-Fukai
Journal: Circulation (2023)

Background: In preclinical peripheral artery disease (PAD) models, M2-like anti-inflammatory macrophage polarization, arteriogenesis and angiogenesis are crucial in restoring perfusion recovery and revascularization. Mitochondrial dynamics in macrophage regulates cell metabolism and inflammation. Mitochondrial fission protein, Drp1 GTPase is shown to be involved in pro- or anti-inflammatory macrophage phenotypes in a context-dependent manner. However, role of macrophage Drp1 in reparative neovascularization in experimental PAD model remains unknown. Method and Results: Macrophage-specific Drp1 knockout (MФ-Drp1-KO; LysCre x Drp1 fl/fl) or wild type (WT) mice were used for hindlimb ischemia (HLI), a preclinical PAD model. Drp1 expression was dramatically increased in F4/80 + macrophage in ischemic muscle at day 3 after HLI of WT mice. MФ-Drp1-KO mice showed decreased limb perfusion (78.3%), angiogenesis (53.0 %), arteriogenesis (46.3%), and muscle regeneration (41.9%) after HLI. This was associated with increased pro-inflammatory M1-like MФ (2.2 fold by FACS analysis), p-NFkB and TNFα expression and decreased anti-inflammatory M2-like MФ (2.3 fold by FACS analysis) and p-AMPK in ischemic muscle of MФ-Drp1-KO mice vs. WT mice. In vitro, bone marrow-derived MФ with hypoxia serum starvation (HSS) (in vitro PAD model) induced mitochondrial fission and activated Drp1. Drp1 KO MФ under HSS exhibited increased glycolysis (66.7%, ECAR) via reduced p-AMPK as well as excess mitochondrial (mito)ROS production (2 fold), which in turn increased M1-genes ( Nos2 and Ptgs2 ) and decreased M2-genes ( Arg1 and Retnla ). These responses in Drp1 KO MФ were rescued by AMPK activator AICAR and mitoROS scavenger mitoTEMPO. Finally, conditioned media from HSS-treated Drp1 KO MФ showed increased secretion of pro-inflammatory TNFα and GAPDH and suppressed angiogenic responses of cultured endothelial cells (50%). Conclusion: Drp1 dysfunction in macrophage promotes inflammatory macrophage polarization induced by hyperglycolysis via suppression of anti-inflammatory AMPK as well as excess mitoROS, which limits revascularization in experimental PAD.
Abstract 15475: Comparable Program Delivery Time: Home-Based versus Hospital-Based Cardiac Rehabilitation
Authors: Dana R Fletcher, Monica Martinez, josh durfee, amanda hajoglou, Marina Rice, Juan C Orendain, Prerna Gupta, R. Mark Gritz, Pamela Peterson
Journal: Circulation (2023)

Introduction: Home-based cardiac rehabilitation (CR) adds flexibility for patients for whom hospital-based CR may not be accessible. The ERA-NUDGE study is a pragmatic randomized study, conducted at an urban safety-net hospital, which evaluated adherence and clinical outcomes of home- versus hospital-based CR, with mobile phone messaging. The resource requirements associated with home-based CR interactions are not yet well established. We aimed to compare program delivery time between home-based and hospital-based CR programming. Methods: For one random week in each of 22 months, program delivery times were recorded by a research team member who shadowed hospital CR sessions and reviewed chart notes for home-based CR interactions. Among the sub-set of participants who had interactions during these weeks, we compared time spent on four types of interactions and seven educational topics. Results: Among 326 patients that completed the parent study, 157 patients had 415 visits during the microcosting weeks (mean of 3.8 visits per patient). Demographics shown in Table 1. Home-based patients accounted for 134 encounters (32%) during microcosting collection weeks. Six- and twelve-week follow-up visits were split between hospital- and home-based groups (53% and 47%, respectively) (Table 2). Conclusions: Despite documented benefits for patients from CR, access remains low. Home-based CR may present an appealing alternative for patients with difficulties around CR access, but CR program directors may be wary of added staffing requirements to deliver these alternatives. Our analysis suggests that home-based CR can be delivered to patients without increases in personnel time.
Abstract 15187: Risk Factors for Type B Dissection in Marfan Syndrome: The Cornell Aortic Aneurysm Registry
Authors: Nupoor Narula, Richard B Devereux, Eloisa Arbustini, Xiaoyue Ma, Jonathan W Weinsaft, Leonard N Girardi, Grace P Malonga, Mary J Roman
Journal: Circulation (2023)

Introduction/Background: With improvements in the medical and surgical management of patients with Marfan syndrome (MFS), type A dissections are decreasing. As a corollary, most MFS dissections are now type B, for which risk factors remain largely uncertain. Research Questions/Hypothesis: In this prospective and retrospective observational study, we explore determinants of type B dissection risk in a large single-center MFS registry through analysis of systematic clinical and imaging data over four decades. Goals/Aim: Determinants of type B dissection risk in MFS will inform appropriate prognostication, management, and treatment of this patient population. Methods/Approach: Demographic and anthropometric features, cardiovascular disease, and surgical history were compared in MFS patients with and without type B dissection. Results/Data: Of 335 MFS patients, 56 (17%) experienced a type B dissection (versus type A in 9%). Patients with type B dissection were more likely to have undergone elective aortic root replacement (ARR; 75 vs. 46%, p&lt;0.001). 55% of patients had type B dissection a mean of 14.1 years after ARR, whereas 45% experienced type B dissection before ARR. Valve replacement was more common than valve-sparing repair in those with post-operative type B dissection (27% vs. 12%, p=0.02), although this difference was eliminated after adjusting for duration of post-operative follow up. 50 (89%) patients were aware of their MFS diagnosis prior to type B dissection. Among those with pre-dissection imaging, the descending aorta was normal or minimally dilated in 87%. In multivariable analyses, patients with type B dissection were more likely to have undergone ARR, mitral valve surgery, had a type II dissection, and to have lived longer. Conclusions: In our contemporary cohort, type B dissections are more common than type A. The associations of type B dissection with ARR, mitral surgery, and type II dissection suggest a more severe phenotype in the setting of prolonged life expectancy.
Abstract 15482: Trends in Cardiovascular Health Among Older Adults With and Without Cardiovascular Diseases: National Health and Nutrition Examination Survey (NHANES), 2013-2018
Authors: James Walker, Daniel Won, Ravi Patel, Hongyan Ning, Donald M Lloyd-Jones
Journal: Circulation (2023)

Introduction: American Heart Association’s (AHA) Life’s Essential 8 (LE8) is a framework for quantifying cardiovascular health (CVH). Prior studies have focused on individuals without clinical cardiovascular disease (CVD). We sought to examine recent trends in LE8 scores among older adults with prevalent CVD. Methods: We included non-institutionalized older US adults (ages 65+) from NHANES (2013-18). Overall LE8 scores (range 0-100; higher = better CVH) were calculated for all participants with or without CVD, using methods recommended by the AHA. CVD diagnoses were self-reported, including coronary heart disease (CHD), stroke, heart failure (HF), hypertension (HTN), angina, and myocardial infarction (MI). Percent change in LE8 scores from 2013-18 was calculated for each diagnosis group, and a linear regression tested for significance of changes within groups. Results: The 3,050 participants represented 37,908,305 adults (54.7% women; mean age 72.6 y); 3.4% self-identified as Asian, 7.2% Black, 3.9% Mexican, 3.3% Other Hispanic, 2.4% Multi-racial, and 79.9% Non-Hispanic White. Overall LE8 scores tended to stay stable or decline between 2013-14 and 2017-18 for individuals with and without CVD (Figure 1). Significant decreases in mean LE8 scores occurred in those with HTN, with a 4.1% decline from 2013-18 (from 59.6 [95% CI: 58.4-60.8] to 57.1 [55.9-58.4]), stroke, with a 11.5% decline (from 60.6 [56.0-65.2] to 53.6 [50.7-56.5]), and HF, with a 15.2% decline (from 60.9 [57.2-64.6] to 51.6 [48.0-55.2]). Conclusions: Recent LE8 scores remained stable or declined for older US adults even before the pandemic. In particular, individuals with HTN, stroke, and HF had significant declines in LE8 scores. Since LE8 metrics include behavioral and physiologic metrics associated with CVD risk, these data indicate concerning trends and primary and secondary prevention opportunities in older US adults, who are at highest risk for incident and recurrent CVD events.
Abstract 17811: Biomarkers Are Superior to Left Atrial Strain Predicting Outcomes in a Multi-Ethnic HFpEF Population
Authors: Ibolya Csecs, Aaron Wengrofsky, Pamela Pina, Ushma Majmuda, Shaunak Mangeshkar, Carlos Gongora, Aldo L Schenone, Leandro Slipczuk, Mario J Garcia
Journal: Circulation (2023)

Introduction: In heart failure with preserved ejection fraction (HFpEF) atrial mechanics play an important role in diastolic dysfunction, and impaired atrial function is related to increased levels of atrial biomarkers such as NT-proBNP. We studied the predictive value of atrial function assessed by speckle-tracking strain and compared it to biomarkers in a multiethnic HFpEF population. Methods: We studied 237 consecutive patients who were admitted with acute decompensated heart failure and EF &gt; 50. The average age was 78±11, 69% of patients were female, and 36% (n=86) were non-Hispanic Black (NHB); 30% (n=71) Hispanic; 21% (n=50) non-Hispanic White (NHW) and 13% (n=30) Other. Left ventricular (LV), atrial (LA), and right atrial (RA) volumes, ejection fraction, and global longitudinal strain (GLS) were measured. During a two-year follow-up, heart failure readmissions and death were registered. Results: Most patients (n= 202) had an abnormal LA-EF of &lt; 45% and abnormal RA-EF &lt;46% (n=205). During a follow-up period of 2 years, 55 patients died, 28% Hispanic, 20% NHB, 20% NHW, and 17% Other. LA-GLS was impaired in all HFpEF patients (13.5+8.2) and was not associated with event-free survival (Figure) in the entire cohort or in any race/ethnicity subgroups. However, increased NT-proBNP (1,200 pg/mL) was associated with worst outcomes (p &lt; 0.01) (Figure). Conclusions: In a multiethnic HFpEF cohort, LA function was universally impaired but had no prognostic value. In contrast, elevated NT-proBNP at hospital discharge predicted recurrent hospitalization and death.
Abstract 15476: Advanced Assessment of Regional Differences in Myocardial Perfusion by Spectral CT in Patients With Acute Myocarditis
Authors: Cristian Herrera Flores, Antonio Sánchez-Puente, Claudia de Molina, Víctor Vicente-Palacios, Pablo Perez-Sánchez, Rosa Ana López-Jiménez, Ángel Hernández-Martos, Sara Rodriguez-Diego, Leticia Nieto García, Luis M Rincon, Javier Sánchez, Rafael Wiemker, Pedro L Sanchez, Candelas Pérez del Villar
Journal: Circulation (2023)

Introduction: Spectral CT (SCT) is a valuable tool for assessing coronary anatomy and myocardial damage. Iodine distribution maps (IDM) obtained by SCT serve as surrogates for first-pass myocardial perfusion, exhibiting reduced iodine uptake in ischemic areas and increased uptake in hyperemic areas due to inflammatory injury. Hypothesis: We aimed to determine if SCT data analysis can detect regional differences in first-pass myocardial perfusion reflecting inflammatory injury in acute myocarditis (AM) patients. Methods: We retrospectively searched for acute myocarditis patients admitted to our center who also underwent SCT angiography to rule out CAD. Spectral images (40 keV monoenergetic images and IDM) from a dual-layer CT scanner (Philips Spectral CT 7500) were analyzed using a perfusion tool developed by Philips Research. LV myocardium was segmented following the AHA-17 model, and CT number (HU) and iodine density values (mg/ml) were quantified. Data were normalized using blood pool values. Healthy controls were included for comparison and differences were assessed with a one-way ANOVA. Results: Six patients with myocarditis (median age: 57 [IQR 30-65]; table 1) and 3 controls (median age: 50 [IQR: 47.5-59.5]) were analyzed. Myocarditis patients (figure 1) showed higher normalized median iodine density values (ratio 0.13 vs. 0.11, p&lt;0.001) and similar differences in 40 keV monoenergetic images (ratio 0.16 vs. 0.13, p=0.005). Conclusions: Spectral CT data analysis can detect first-pass myocardial perfusion differences in acute myocarditis patients, likely reflecting hyperemia. Further research is needed to evaluate the clinical benefits of SCT in this context.
Abstract 15341: A Prospective Study on the Safety and Effectiveness of Apixaban for the Prevention of Thromboembolism in Adults With Congenital Heart Disease and Atrial Arrhythmias: The PROTECT-AR Study
Authors: Anastasios Kartas, Andreas Papazoglou, Dimitrios Moysidis, Stefanos Despotopoulos, Diamantis Kosmidis, Amalia Baroutidou, Athanasios Koutsakis, Sotiria Liori, Sotiria Apostolopoulou, Alexandra Frogoudaki, Afrodite Tzifa, Apostolos Galatas, GEORGIOS ALEXANDRIDIS, Efstathios Spyridonidis, Ioannis Doundoulakis, EFSTRATIOS KARAGIANNIDIS, Charalampos I Karvounis, Antonios Ziakas, George Giannakoulas
Journal: Circulation (2023)

Introduction: In adults with congenital heart disease (ACHD), atrial arrhythmias (AA) confer an increased risk of thromboembolic events. Limited data exist on non-vitamin K oral anticoagulant (NOAC) treatment for ACHD. We aimed to assess the effectiveness and safety of apixaban in ACHD patients with AA. Methods: PROTECT-AR (NCT03854149) was a prospective, multicenter, observational study conducted from 2019 to 2023. ACHD patients with atrial fibrillation, atrial flutter, or intra-atrial re-entrant tachycardia, who were routinely treated with apixaban, were included. The primary efficacy endpoint was the composite of stroke or thromboembolism. The primary safety endpoint was major bleeding. Patients who were previously on vitamin K antagonists (VKAs) before transitioning to apixaban served as a historical control group. Results: In total, 218 patients with ACHD and AA on apixaban (previous VKA users 34.9%) were included (mean age 51±17 years; 45.9% male; predominantly moderate complexity). Over a mean follow-up of 2.4±1.3 years, the rate of stroke or thromboembolism was 0.57% [95% confidence interval (CI): 0.15-1.55] and the rate of major bleeding was 1.52% [95%CI: 0.71-2.88] per patient-year, respectively. In the subset of patients who were previously on VKA, the risk of the primary endpoints did not differ significantly between apixaban and VKA-treatment periods (Figure). Conclusion In ACHD patients with AA on routine apixaban treatment, the risk of major thromboembolic and bleeding events was low. Among prior VKA users, the risk of adverse events during the apixaban-treatment period was comparable to that during the VKA-treatment period. Prospective studies directly comparing NOAC and VKA-treated patients are needed.
Abstract 15364: The Association of Exhaled Carbon Monoxide With Atrial Fibrillation and Left Atrial Size in the Framingham Heart Study
Authors: Oseiwe 'Benjamin' Eromosele, Ayelet Shapira-Daniels, Amy Yuan, Abdulkareem Lukan, Olumuyiwa Akinrimisi, Marius Chukwurah, Matthew G Nayor, Emelia J Benjamin, Honghuang Lin
Journal: Circulation (2023)

Background: Studies from the Framingham Heart Study (FHS) have reported that exhaled carbon monoxide (eCO) is associated with cardiovascular disease (CVD) and stroke. To our knowledge, no study has assessed the association between eCO with atrial fibrillation (AF) and left atrial (LA) size. We related eCO to AF and LA size. Methods: eCO was measured using an Ecolyzer instrument among participants who attended Exam 6 and Omni 1 participants who attended Exam 1. AF was assessed on electrocardiography (ECG) and LA size on echocardiography. We used Cox and logistic regression models in assessing the relationship between eCO and incident AF (primary model), and prevalent AF and LA size (secondary models). Participants were also analyzed according to tertiles of eCO concentration, and we also adjusted for current smoking, and other covariates - age, race, sex, height, weight, systolic blood pressure (BP), diastolic BP, diabetes, hypertension treatment, prevalent myocardial infarction (MI), and prevalent heart failure (HF). Results: Our study sample included 3814 participants, with a median age of 58 ± 10 years; 54.4% were women, and 11.6% of the study population was non-White. eCO was associated with incident AF after adjusting for known AF risk factors (HR=1.31, 95% confidence interval [CI] 1.09-1.58). Higher eCO levels were associated with an increased cumulative risk of AF, with the risk rising with increasing tertiles of eCO. The association remained significant after additionally adjusted for CRP and BNP, and interim MI and HF. In the stratified analysis, eCO remained associated with incident AF in the men-only analysis and in never or previous smokers (men: HR: 1.30, CI: 1.02-1.65, p = 0.03; never or previous smokers: HR: 1.39, CI: 1.31-1.72, p = 0.002), but not in women, current smokers and age-stratified (≤60 years and &gt;60 years) analyses. eCO was not associated with LA size or prevalent AF in either age and sex adjusted models or multivariable adjusted models. Conclusion: We found an association between eCO and incident AF after adjusting for known AF-related risk factors. There is a need for more research to better understand how eCO mediates incident AF, how much it may contribute to the pathogenesis of AF, and potential therapeutic benefits it may offer.
Abstract 17952: Age-Dependent Disparities on Associations of Socioeconomic, Lifestyle, and Metabolic Risk Factors With Major Cardiovascular Diseases and Mortality
Authors: Yunan Liu, zilin xiao, Geng Zong
Journal: Circulation (2023)

Introduction: Existing studies that quantified and compared the relative risks (RRs) and population-attributable risks (PARs) of modifiable risk factors for cardiovascular diseases (CVDs) and mortality by age have been limited to conventional factors and moderate PARs. Methods: 335 540 participants from UK Biobank were stratified into &lt;55 years (n=138 058), 55-65 years (n=140 224), and ≥65 years (n=57 258). The outcomes included incident CVD, coronary heart disease, heart failure (HF), ischaemic stroke, CVD mortality, and all-cause mortality. Results: The PARs for CVD cases and deaths were 11-24% for socioeconomic factors, 14-27% for lifestyle factors, and 34-41% for metabolic factors, which collectively measured 58-82%. Younger participants had significantly higher RRs of CVDs associated with socioeconomic, lifestyle, and metabolic risk factors (P interaction &lt;0.05), and higher PARs from socioeconomic and lifestyle risk factors (Figure). For socioeconomic factors, area deprivation accounted for 10.5% of CVD deaths, while PARs of low education for CVDs and mortality ranged from 9.1% to 12.8%. Smoking accounted for 4.2-10.9% of PARs for CVDs and mortality, and other lifestyle factors such as unhealthy sleep (i.e. 5.6% for CVD mortality) and poor diet (i.e. 5.5% for IS) also contributed to moderate PARs. Metabolic risk factors accounted for 30.9% (28.6-33.2%) to 44.9% (39.0-50.7%) of CVD cases and deaths in all age groups, with hypertension being the predominant risk factor (22.4-32.5%). Conclusions: Socioeconomic and lifestyle risk factors showed stronger associations with CVDs and mortality among relatively younger people, while cases attributed to metabolic risk factors were consistently high in all age groups. This study further supports the role of an integrated CVD prevention strategy that combines social, behavioural, and medical approaches, especially among younger population.