tbuckley/cabot-search huggingface dataset:
Abstract 4143358: Epicardial Adipose Tissue is a Better Predictor of Structural Remodeling and Atrial Fibrillation Recurrence than Body Mass Index
Authors: Yaacoub Chahine, Nadia Chamoun, Ahmad Kassar, Nazem Akoum
Journal: Circulation (2024)

Background: Body mass index (BMI), a measure of overall obesity, is associated with various cardiovascular conditions including atrial fibrillation (AF). Epicardial adipose tissue (EAT), a visceral type of adipose tissue, distinct from the subcutaneous adipose tissue, promotes AF arrhythmogenesis through proinflammatory properties and proximity to the myocardium. We sought to compare left atrial (LA) EAT volume with BMI, in their relationship to LA structural remodeling (LA volume and fibrosis) and AF recurrence following catheter ablation. Methods: EAT was assessed via cardiac MRI using the 3D Dixon sequence, and fibrosis was assessed using Late Gadolinium Enhancement (LGE) sequence in 127 AF patients (Panel A). Of this cohort, 101 patients underwent radiofrequency or cryoballoon catheter ablation and were followed for AF recurrence. Results: The mean age of the cohort was 64±11 years (30.7% female). The mean BMI was 29.7±6.6 kg/m 2 . LA volume index was 57.45±20.58 mL/m 2 , LA EAT index was 18.1±8.5 mL/m 2 , and the LA fibrosis was 18.0±7.9%. Compared to BMI, LA EAT index correlated better with LA volume index (LA EAT: R=0.452, p&lt;0.001; BMI: R=−0.03, p=0.73). Similarly, LA EAT index, compared to BMI, correlated better with LA fibrosis (LA EAT: R=0.387, p&lt;0.001; BMI: R=0.104, p=0.251) (Panel B). The ROC curve for the logistic regression model of LA EAT index in the prediction of AF recurrence had an AUC of 0.77 (95% CI 0.68-0.86, p&lt;0.001) and showed an optimal cutoff value of 14.3 mL/m 2 to identify patients at risk of AF recurrence post-ablation. Whereas, the ROC curve for BMI in the prediction of AF recurrence post-ablation had an AUC of 0.56 (95% CI 0.44-0.68, p=0.33) (Panel C). Cox regression analysis showed LA EAT (HR = 1.089; 95% CI: [1.049–1.131], p &lt; 0.001) to be an independent predictor of post-ablation AF recurrence. Conclusion: EAT quantified using cardiac MRI, a reproducible and widely accessible imaging parameter, is a better predictor of LA volume, fibrosis and AF recurrence after catheter ablation than BMI.
Abstract 4143204: Participation in a Resilience Intervention for Caregivers of Recently Hospitalized Patients with Heart Failure and Stroke
Authors: Martha Abshire Saylor, Catherine Clair, Samantha Curriero, Natalie Wang, Amelia Tenberg, Mona Bahouth
Journal: Circulation (2024)

Introduction Family caregivers of persons with advanced heart failure (HF) and stroke bear increased responsibilities as care recipients recover from acute hospitalization. Few formalized supports are available. We conducted a feasibility pilot of a caregiver-targeted support program: Heart Failure and Stroke Resilience Intervention for Caregivers (HEROIC) using a randomized waitlist-control design. Here we sought to understand similarities and differences in participation between HF and stroke enrolled caregiver participants. Methods We recruited caregivers of HF and stroke patients via review of the electronic health record and/or provider referral after the first follow-up visit. Baseline surveys were collected electronically. Enrolled participants were randomized to the intervention or waitlist group. HEROIC consists of 5 nurse-led, remote sessions over a 10-week period. Components incorporate resilience resources including emphasis on caregiver life purpose and values, goal-setting for self-care, social support, community and palliative care resources. Characteristics of participants were analyzed using descriptive statistics and t-test or chi-square as appropriate. Results We identified 158 potential caregivers through electronic health records and provider referral. 65% (n=103) were reached by phone and 57/103 (55%) were eligible for participation. Fifty caregivers consented but only 31 completed baseline data collection and were randomized. Reasons for drop out included loss to follow-up, patient death and too many competing demands. Caregivers were on average 58.4 years old (SD: 11.4), 84% female and 45% Black. They supported patients with moderate to severe functional impairment and 5.5 ± 2.3 instrumental activities of daily living (IADL) on average. Over half of caregivers reported financial strain. Caregivers reported moderate caregiver strain using the Modified Caregiver Strain Index (Mean: 11.9, SD: 6.0). Most caregivers supported persons with HF (n=19). The only statistically significant difference noted between HF and stroke caregivers was gender; more caregivers of stroke patients were male. Conclusions Similarities in baseline characteristics of HF and stroke caregivers suggest similar caregiving experiences. HEROIC or other early post-hospital caregiver support interventions may appeal to caregivers to increase resilience to the stresses of transitions of care but recruitment strategies require additional consideration.
Abstract 4143433: Vascular Determinants of Functional Capacity in Peripheral Artery Disease
Authors: Alexander Sullivan, Adam Behroozian, Emily Shardelow, Emily Smith, Tara Holder, Quinn Wells, Aaron Aday, David Wasserman, Joey Barnett, Daniel Clair, Rachelle Crescenzi, Matthew Freiberg, John Curci, Clifford Garrard, Manus Donahue, Joshua Beckman
Journal: Circulation (2024)

Background: Patients with peripheral artery disease (PAD) experience walking impairment that is incompletely explained by conduit artery atherosclerotic occlusive disease and ankle-brachial index (ABI). Microvascular dysfunction is associated with adverse outcomes including amputation but its effect on ambulation is unknown. We tested whether calf skeletal muscle microvascular function independently associates with walking distance and with ambulatory improvement following exercise therapy or revascularization. Hypothesis: Calf skeletal muscle microvascular function predicts walking distance after adjusting for conduit artery function and ABI. Methods: Sixty-eight participants, including 50 with PAD (ABI &lt; 0.85) and 18 controls underwent vascular function assessment after sphygmomanometer cuff-induced calf ischemia using magnetic resonance imaging (MRI) measures of blood-oxygenation-level-dependent (BOLD) perfusion-dependent reactivity and arterial-spin labeling-based perfusion reactivity. Functional status was assessed using 6-minute walk testing (6MWT). A subgroup of PAD patients underwent repeat testing after exercise therapy (n=14) or revascularization (n=14). Multivariable regression models were used to assess the association of microvascular function with 6MWT distance controlling for age, sex, diabetes, ABI, and macrovascular function. Results: Resting conduit artery pressure by ABI (R=0.74, p&lt;0.001), BOLD macrovascular reactive hyperemic blood flow (R=0.40, p&lt;0.001), and skeletal muscle microvascular BOLD maximal reactivity (R=0.66; p&lt;0.001) significantly correlated with 6MWT distance in univariable vascular testing (Figure 1A-C). In multivariable analysis of each vascular parameter, calf skeletal muscle microvascular reactivity most strongly associated with 6MWT (b=825.3, p=0.023). In those with repeat testing after intervention, the change in microvascular BOLD reactivity, but not ABI or macrovascular BOLD blood flow, significantly correlated with change in 6MWT distance (R=0.46, p=0.014, Figure 1D-F). Conclusions: Skeletal muscle microvascular function directly associates with walking distance independent of conduit artery blood flow and correlates with ambulatory improvement following PAD interventions.
Abstract 4143175: Real-world Long-term Effectiveness of Mavacamten in Patients with Symptomatic Obstructive Hypertrophic Cardiomyopathy: a Multicenter Observational Study (MARVEL-HCM)
Authors: Theodore Abraham, Said Alsidawi, Matthew Martinez, Matthew Wheeler, Kaitlin Roehl, Ruchi Patel, Marybeth Soutar, Morgane Herry, Manchen Annie Wang, Mi-Ok Kim, Patricia Schuler, Anand Dubey
Journal: Circulation (2024)

Background: Mavacamten was approved by the US Food and Drug Administration (FDA) in April 2022 for the treatment of adults with New York Heart Association (NYHA) class II-III symptomatic obstructive hypertrophic cardiomyopathy (HCM). Few studies have reported on the long-term real-world effectiveness and safety of mavacamten. We evaluated clinical outcomes in patients on mavacamten in multiple health centers across the United States. Research Questions: This study assessed the real-world effectiveness and safety of mavacamten in patients with symptomatic obstructive HCM. Methods: In this multi-center observational study, we evaluated patient characteristics at baseline, NYHA class, left ventricular outflow tract gradients (LVOTg) at rest and Valsalva, and left ventricular ejection fraction (LVEF) in patients with symptomatic obstructive HCM treated with mavacamten for up to 72 weeks. Results: Mavacamten was initiated in 172 patients across 4 US centers (UCSF, Mayo Arizona, Stanford, and Atlantic Health System/Morristown Medical Center). Baseline characteristics included: 56% female, mean age 64 (standard deviation ±13) years, 47% NYHA class III, mean resting LVOTg of 47 mmHg and mean Valsalva LVOTg of 89 mmHg, and 23% non-White. Comorbidities included hypertension (56%) and atrial fibrillation (25%) at baseline (Table). Patients experienced a notable early response to mavacamten in resting and Valsalva gradients by week 4, which was sustained through week 72 (Figure A). No patients were NYHA class III at week 72, compared to 47% at baseline (Figure B). Mean LVEF did not change substantially between baseline and week 72. No patients experienced an LVEF of &lt;40% and 2% experienced an LVEF of &lt;50%. Conclusions: This is the largest observational study to date demonstrating the effectiveness and safety of mavacamten with substantial sustained reductions in resting and Valsalva LVOTg, and progressive improvements in NYHA class without considerable changes in mean LVEF up to 72 weeks.
Abstract 4143378: Polygenic Risk Stratification for Risk of Venous Thromboembolism: Analysis of &gt;31K Individuals from the Women’s Genome Health Study and JUPITER trials
Authors: Michael Rosamilia, Nicholas Marston, Giorgio Melloni, Frederick Kamanu, Marc Sabatine, Christian Ruff, Paul Ridker, Daniel Chasman
Journal: Circulation (2024)

Introduction: Venous thromboembolism (VTE) carries high morbidity and mortality, highlighting the importance of early risk identification and prevention. Whether a recent polygenic risk score (PRS) could help identify those at highest risk in a longitudinal, primary prevention population is unclear. Hypothesis: PRS is an independent predictor of VTE risk in a primary prevention population. Methods: We applied the 2023 VTE PRS by Ghouse et al containing over 1 million VTE-associated SNPs to 2 primary prevention trials, JUPITER and Women’s Genome Health Study (WGHS). We calculated the adjusted hazard ratio (aHR) of VTE per 1 higher standard deviation (SD) of PRS and by risk categories: low (bottom 20%), intermediate (middle 60%), and high (top 20%) in a multivariable model adjusted for cardiovascular and demographic factors. Results: JUPITER included 8,749 participants (67.8% men, median age 66) with a median follow-up of 2.3 years and 77 VTE events (annualized event rate [ER] 0.38%). WGHS included 22,650 women (median age 53) with a median follow-up of 20.5 years and 618 VTE events (annualized ER 0.13%). Each SD increase in VTE PRS was associated with a 34% higher risk of VTE in JUPITER (aHR 1.34, 95% CI 1.08-1.67; p &lt; 0.01) and a 61% higher risk in WGHS (aHR 1.61 (1.5-1.73; p &lt; 0.01). Those in the high PRS category were 3.3-fold more likely to develop VTE compared to those with low PRS (JUPITER: aHR 3.30, 1.38-7.88; p &lt; 0.01 and WGHS: 3.27, 2.44-4.38; p &lt; 0.01) ( Fig A, B ). In comparison, Factor V and prothrombin gene mutations were associated with aHRs of 1.58 and 2.45 in JUPITER and 1.42 and 1.75 in WGHS, respectively. Additionally, the PRS predicted VTE to a similar or greater degree than established clinical risk factors. Finally, Kaplan-Meier curves demonstrated early and sustained separation in VTE events between each PRS risk group ( Fig C,D ). Conclusions: In two large primary prevention cohorts, PRS was a strong and independent predictor of VTE, with the top 20% imparting greater risk than that of established monogenic thrombophilia.
Abstract 4143291: Macrophage Drp1 Sulfenylation drives neovascularization and regeneration of ischemic muscle via promoting reparative polarization and metabolic reprograming
Authors: Shikha Yadav, Sheela Nagarkoti, Sudhahar Varadarajan, Archita Das, Malgorzata McMenamin, Stephanie Kelley, Tohru Fukai, Masuko Ushio-Fukai
Journal: Circulation (2024)

Background: Reactive oxygen species (ROS) function as signaling molecules to regulate reparative macrophage polarization essential for ischemia-induced neovascularization and regeneration of skeletal muscle in peripheral arterial disease (PAD). Mitochondrial fission protein Drp1 GTPase is involved in pro- and anti-inflammatory macrophage phenotype and metabolism in a context-dependent manner. However, mechanistic link between macrophage Drp1 and ROS-dependent reparative angiogenesis and muscle regeneration during ischemia is entirely unknown. Methods and results: Using a mouse Hindlimb ischemia (HLI) model, a preclinical model of PAD, here we show that macrophage-specific Drp1 knockout (KO) mice exhibited significant reduction of blood flow recovery, angiogenesis (CD31+ capillary) and muscle regeneration following HLI. Flow cytometry analysis revealed that these responses were associated with an initial increase in Lys6G+ neutrophils (4-fold), followed by reduction in anti-inflammatory F4/80+CD206+ M2 macrophage (2-fold) in ischemic muscle of Drp1 KO mice at days 3 and 7 post HLI. Mechanistically, Drp1-CysOH formation (sulfenylation), but not Drp1 phosphorylation, was increased in bone marrow (BM) and ischemic muscles after HLI, which was markedly reduced in CRISPR/Cas9-generated “redox-dead” Drp1-C631A (C/A) knock-in mutant (Drp1-C/A) mice. Functionally, BM chimera mice in which BM in wild type (WT) mice is replaced with Drp1-C/A mutant showed impaired limb perfusion recovery (30%), angiogenesis (45%) and muscle regeneration after HLI. In vitro PAD model showed that macrophage exposed to hypoxia serum starvation (HSS) had increased ROS production and Drp1-CysOH formation without Drp1 phosphorylation at 1 h after HSS stimulation. Macrophage isolated from Drp1 KO or Drp1-C/A mice under HSS exhibited inhibition of Drp1-CysOH formation, while increased glycolysis (ECAR, 50%), pro-inflammatory M1-genes and decreased M2-genes (40%). Conclusion: Cysteine oxidation of Drp1 in macrophage promotes revascularization and regeneration of ischemic muscle by driving reparative metabolic reprogramming and macrophage polarization. This process represents a novel therapeutic target for treatment of PAD.
Abstract 4143309: Fluorescence-Labeled Very Low-Density Lipoproteins (VLDLs) Clearance Method for the Assessment of Dynamic VLDLs Function in Mice
Authors: Yujiao Zu, Mandana Pahlavani, Tatum Walker, Shane Scoggin, Naima Moustaid-Moussa
Journal: Circulation (2024)

Introduction: Very Low-Density Lipoproteins (VLDLs) serve as crucial transporters of triglycerides (TG) and cholesterol (C) from the liver to peripheral tissues, thereby contributing significantly to metabolic disorders such as atherosclerosis. Assessing the dynamic of VLDLs function involves evaluating its clearance from the bloodstream and distribution across various organs. Although VLDLs clearance has been extensively studied using dual radioactive isotopes 3 H and 14 C to label TG and C, this method requires large amounts of expensive tracers, compliance, and technical complexities. Our objective is to design and test a fluorescence-based approach to simultaneously assess and visualize VLDLs kinetics in a mouse model. Through this approach, we aim to unravel the intricate interplay between thermogenesis and VLDLs metabolism and provide insights into their collective influence on the progression of atherosclerosis in vivo. Method: Fluorescence-labeled VLDLs-like TG-rich nanoparticles (F-VLDLs) were prepared at various intensity by incorporating lissamine rhodamine-TG (Rhoda-TG, 1-5% of total TG) and TopFluor®-C (TopF-C, 20-80% of total C) to a mixture containing glycerol trioleate (7mg), egg yolk phosphatidylcholine (2.3mg), lysophosphatidylcholine (0.23mg), cholesteryl oleate (0.3mg), cholesterol (0.2mg) and kolliphor HS15 (2mg). B6 mice were fasted for 4 hours and injected via the tail vein with various intensities of F-VLDLs (2 mg TG/mouse). Blood samples were collected at 5-, 10- and 15-min post-injection to determine the plasma clearance of Rhoda-TG and TopF-C, after which mice were euthanized, and tissues harvested and imaged using an IVIS® spectrum in vivo imaging system. Results: The mean particle size of F-VLDLs was 80nm, with polydispersity index values of about 0.2. The Zeta potential of freshly made F-VLDLs was about −20 mV. In B6 mice, both Rhoda-TG and TopF-C signal intensities peaked at 5 minutes post-injection and subsequently declined in an intensity-dependent manner. In the collected tissues, Rhoda-TG and TopF-C intensity was as follows: liver&gt;brown fat&gt;subcutaneous white fat &gt;visceral white fat. Conclusion: We have designed novel fluorescence-labeled VLDVs-like particles as a viable approach for quantifying and visualizing dynamic VLDLs-TG and C flux in vivo. This approach will facilitate the assessment of how various metabolic interventions impact VLDLs metabolism and atherosclerosis.
Abstract 4143405: Clinical Features, Hemodynamics, and Outcomes of Pulmonary Hypertension in Adults with Coarctation of Aorta
Authors: Ahmed Abdelhalim, Ahmed Goda, Andrea Hsu, Alexander Egbe
Journal: Circulation (2024)

Background: Pulmonary hypertension (PH) and secondary right ventricle dysfunction is present in 20% of adults with coarctation of aorta (COA) based on echocardiographic studies. There are limited data about invasive hemodynamic characterization of PH in COA. The purpose of this study was to delineate the clinical features, hemodynamics, and outcomes of PH in COA. Method: Retrospective cohort study of adults with repaired COA that underwent right heart catheterization (RHC). PH was defined as pulmonary artery (PA) mean pressure &gt;20 mmHg, and PH was classified as isolated precapillary PH and combined pre/postcapillary PH. Results: Of 99 COA patients that underwent RHC, 57 (58%) had PH. Of the patients with PH, 14 (25%) had isolated precapillary PH while 43 (75%) had postcapillary PH with or without precapillary disease. The correlates of PH were PA compliance (adjusted OR 0.79, 95% CI 0.71-0.86 per 1 ml/mmHg), left atrial reservoir strain (adjusted OR 0.95, 95% CI 0921-0.98 per 1%), and atrial fibrillation (adjusted OR 2.18, 95% CI 1.20-13.5). Higher PA mean pressure was associated with risk of cardiovascular events (adjusted HR 1.04, 95% CI 1.02-1.06 per 1 mmHg) and all-cause mortality (adjusted HR 1.05, 95% CI 1.02-1.08 per 1 mmHg). Conclusions: PH was present in over half of adults with COA referred for RHC, and one-quarter of the patients with PH presented with isolated precapillary PH suggesting an underlying PA vascular dysfunction as a contributing mechanism. Further studies are required to determine optimal therapies and strategies for prevention and treatment of PH in this population.
Abstract 4143186: Prior Statin Therapy Reduces Inflammation and Improves Outcomes in Patients Hospitalized for Covid-19: A Prospective Multicenter Cohort Study
Authors: Anis Ismail, Husam Shadid, Yiyuan Huang, Christina Hutten, Alexi Vasbinder, Ian Pizzo, Tonimarie Catalan, Kristen Machado, Pennelope Blakely, Mousumi Banerjee, Melvyn Rubenfire, Geoffrey Williams, Rodica Busui, Salim Hayek
Journal: Circulation (2024)

Introduction: Statins are lipid-lowering agents with anti-inflammatory effects. Data surrounding the benefits of statins in patients with coronavirus disease 2019 (Covid-19) are conflicting. We sought to better understand the impact of statins in the context of Covid-19-related inflammation. Methods: We leveraged the International Study of Inflammation in Covid-19, a prospective multicenter cohort study of patients hospitalized specifically for Covid-19 between February 1, 2020 and October 30, 2022. Participants underwent systematic assessment of biomarkers of inflammation. We used logistic regression modeling and inverse probability-of-treatment weighting (IPTW) to examine the association between prior statin use and the composite outcome of in-hospital death, need for mechanical ventilation, and need for renal replacement therapy. Results: A total of 4,464 patients were included in the study, of whom 1,364 (27.5%) were taking a statin prior to admission. There were 1,061 primary outcome events, including 540 deaths, 854 mechanical ventilation and 313 renal replacement therapy. Amongst biomarkers of inflammation, statin use was associated solely with lower levels of soluble urokinase plasminogen activator receptor (suPAR) after adjusting for known confounders. In multivariable logistic regression analysis, statin use was associated with lower odds of the composite outcome (adjusted odds ratio (aOR) 0.63, 95%CI[0.53-0.76]) compared to patients not on statins. Findings were consistent with IPTW (aOR 0.92, 95%CI [0.89- 0.95]). The proportion of the effect of statin on the primary outcome mediated by suPAR was estimated at 31.5%. Conclusion: Prior statin use is associated with improved outcomes and lower inflammation as measured by suPAR levels in patients hospitalized for Covid-19.