tbuckley/cabot-search huggingface dataset:
Abstract 4127909: Smartphone-enabled, home-based exercise in patients with symptomatic peripheral arterial disease: the Smart Step Grady randomized trial
Authors: Aishat Mustapha, Yunyun Chen, Madeline Meer, Alaaedin Alrohaibani, Cate Parrish, Smah Abdelhamid, Keri Minton, Jaime Benarroch-Gampel, Christopher Ramos, Ravi Rajani, Nanette Wenger, Manuel Garcia-Toca, Amit Shah, Arash Harzand
Journal: Circulation (2024)

Introduction: About 10% of peripheral artery disease (PAD) patients develop claudication, with African Americans at higher risk and more severe symptoms. While supervised exercise therapy (SET) is a primary treatment, its uptake is low. We assessed the feasibility and effectiveness of smartphone-delivered home-based exercise therapy (HBET) in improving functional capacity and PAD symptoms in low-resource settings lacking SET. Methods: We conducted an interim analysis of Smart Step, a pilot randomized trial (1:1 ratio) comparing smartphone-enabled HBET to usual care (UC) in symptomatic PAD patients at Grady Memorial Hospital, a public safety net hospital in Atlanta, GA, from August 2018 to March 2024. The HBET group received virtual exercise coaching, app-based education, messaging, and reminders for 12 weeks. The primary outcome was the change in 6-minute walking distance (6MWD) at 12 weeks. Secondary outcomes included changes in the Walking Impairment Questionnaire (WIQ) and Short Form 36 (SF-36) scores. Data were analyzed using intention-to-treat, with mixed model repeated measures regression assessing the association between 6MWD and treatment. Results: We screened 102 patients and enrolled 46. To date, 26 (56%) participants have completed the study, 6 (13%) dropped out, and 14 (30%) are pending completion. The mean [SD] age was 63 [12] years, with 50% female and 90% African American. After 12 weeks, the mean 6MWD increased by 15.7 m from a baseline of 336.0 m in the HBET arm (n=13) and decreased by 6.6 from a baseline of 310.2 m in the UC arm (n=13). The between-group difference was 22.4 [95% CI -11.8 – 56.6] m; p=0.19). The WIQ stair climbing score changed by -10.9 in the UC arm vs. 7.1 in the HBET arm (between group difference 17.9 [95% CI 1.1-34.8]; p=0.04), while the other WIQ sub-scores were more similar between groups. The 12-week changes in SF-36 scores were not different by group. Conclusion: In this preliminary analysis, the HBET arm showed within-group improvements in 6MWD and symptoms after 12 weeks, but most changes were not significantly different when comparing them with the UC arm. Future analyses are pending and will provide the necessary statistical power for a more precise measure of the treatment effects.
Abstract 4132149: Elevated Levels of Plasma Mitochondrial DNA Damage-Associated Molecular Patterns (DAMPS) in Humans and Dogs with Heart Failure and Reduced Ejection Fraction
Authors: Hani Sabbah, Ramesh Gupta, Kristina Szekely, Sean Kalabat, David Lanfear
Journal: Circulation (2024)

Background: Heart failure (HF) with reduced ejection fraction (HFrEF) is associated with increased inflammatory response that contributes to progressive worsening of the HF state. Potential endogenous triggers of this process include damage-associated molecular patterns (DAMPs). DAMPs originate from within cells following tissue stress or injury and activate pattern recognition receptors of the immune system, triggering an inflammatory response. Mitochondria are the major cell organelles that release DAMPs into the circulation. Chronic HF is associated with multi-organ mitochondrial dysfunction and cell injury and death. Purpose: The present study sought to quantify differences in mitochondrial DNA (mtDNA) DAMPs in the setting of HFrEF in humans and dogs compared to normal humans and dogs. Methods: Plasma samples were obtained from 9 HFrEF patients with left ventricular ejection fraction (LVEF) ≤35% and 9 age-matched healthy subjects, and from 6 dogs with coronary microembolization-induced HF (LVEF ≤35%) and 6 normal dogs. DNA fragments were isolated from 1 ml of plasma using a commercially available kit. Quantitative PCR and specifically designed primers were used to measure the amount of DNA in plasma from COX1 (cytochrome c oxidase subunit 1), ND1 (NADH dehydrogenase subunit 1) and ND6 (NADH dehydrogenase subunit 6) using an Applied Biosystems 7500 Fast-PCR unit. The relative abundances of plasma mtDNA DAMPs were expressed as threshold cycles (C T ). Results: Compared to normal human subjects, mtDNA DAMPs levels of COX1 , ND1 and ND6 in plasma of HFrEF patients was 4-fold, 9-fold and 8-fold greater, respectively. Similarly, compared to normal dogs, mtDNA DAMPs levels of COX1 , ND1 and ND6 in plasma of HFrEF dogs was increased 48-fold, 12-fold and 4-fold, respectively. Conclusions: These findings indicate a marked increase of mtDNA DAMPs in plasma of humans and dogs with HFrEF. The increase of mtDNA DAMPs is consistent with the elevated systemic inflammatory state of HFrEF. The results underscore mitochondrial abnormalities as integral players in the progressive worsening of HFrEF.
Abstract 4130929: The Effect of Weight loss and Weight Maintenance on Branch Chain Amino Acid Levels
Authors: Damon Swift, Joshua McGee, Laura Matarese, Joseph Houmard, Robert Carels, Walter Pories
Journal: Circulation (2024)

Introduction: Elevated branch chain amino acid levels (BCAA) have been associated with cardiovascular disease (CVD) and type-2 diabetes. While weight loss has been shown to improve BCAA levels, few studies have evaluated the impact of weight loss and weight maintenance with the OPTIFAST® weight loss program and supervised exercise training. Methods: The present study is a secondary analysis of the PREVAIL-P study. During the weight loss phase, overweight and obese adults (N=30) completed a 10-week OPTIFAST® program with supervised aerobic exercise training with the goal of achieving clinically significant weight loss (≥7%). Participants who met the weight loss goal were randomized to levels of aerobic training consistent with physical activity recommendations (PA-REC) (~550 MET minutes per week) or weight maintenance recommendations (WM-REC) (~970 MET minutes per week) for 18 additional weeks. Valine, leucine, isoleucine and total BCAA levels were measured using nuclear magnetic resonance (NMR) at baseline, after the weight loss phase (10 weeks) and at follow-up (28 Weeks) (LabCorp, Raleigh, NC). Results: Following the weight loss phase, participants had a significant mean reduction in weight (-8.8 kg, p&lt;0.001), total BCAA (-37.4 μmol/L, p&lt;0.001), valine (-15.2 μmol/L, p=0.012), leucine (-20.0 μmol/L, p&lt;0.001), but not isoleucine (-4.1 μmol/L, p=0.214) levels. Improvements in BCAA levels were associated with changes in HDL levels (r=-0.39, p=0.03) and approached significance for visceral fat (r=0.34, p=0.07). Furthermore, changes in BCAA metabolites were not associated with weight, glucose metabolism or other lipid variables for the weight loss phase (p&gt;0.05). In a subset of participants (N=14) who completed the weight maintenance phase (due to COVID pandemic), there were no group differences in the change in total BCAA, valine, leucine between the PA-REC and the WM-REC groups (all ps &gt;0.05). Changes in total BCAA levels (baseline to 28 weeks) were associated with higher mean aerobic exercise training intensity during the intervention (r=-0.64, p=0.013). Conclusion: Weight loss using the OPTIFAST® weight loss program diet combined with aerobic exercise improved BCAA levels, which is associated with decreased CVD risk. Lower BCAA levels during weight maintenance may be influenced by higher exercise intensity exercise. Future studies should evaluate the impact of lifestyle interventions on BCAA levels during long-term weight maintenance.
Abstract 4129223: Large Language Modeling-Enabled Analysis of Atrial Fibrillation Topics and Sentiments on Social Media
Authors: Shyon Parsa, Sulaiman Somani, Tina Hernandez-Boussard, Fatima Rodriguez
Journal: Circulation (2024)

Purpose: We utilized large language modeling (LLM) and automated topic modeling techniques to describe public perceptions regarding AF on Reddit, a social media platform. Methods: In this qualitative study, we curated all AF-related discussions on Reddit from 2006 to 2023 by searching for all posts and comments containing AF-related terms (“atrial fibrillation”, “afib”, and “atrial flutter”). Discussions were embedded using a state-of-the-art embedding model (BAAI/bge-base-en-v1.5). Embeddings are reduced in dimensionality using Uniform Manifold Approximation and Project and clustered using K-Means Clustering to find topics and groups. Topic and group labels are enhanced using large language models (Llama2 and GPT4, respectively). Results: We identified a total of 86,323 discussions related to AF from 38,183 unique users between April 14, 2006 and November 20, 2023. Discussions around wearables and ablations increased over time, while discussions around anticoagulation had periodic spikes. The topic modeling pipeline automatically identified 64 topics and 9 groups (Figure 1). Groups emphasized the following themes: lifestyle factors and triggers associated with AF (groups 1, 5, 7); patient experiences with management strategies including anticoagulation, rate control, pharmacological rhythm control, and ablation (groups 2, 4, 5); experiences with wearable devices (group 8); psychological burden of living with AF (group 6); and online advertisements for AF-related medications (groups 3, 9). Conclusions: Our AI-enabled topic modeling analysis revealed public perceptions about AF including triggers, experiences with different management strategies, impact of wearables, and psychological burden of the diagnosis, which may help guide potential strategies for improving shared decision making around the AF patient journey.
Abstract 4131486: Cardiovascular Mortality in Children and Young Adults: Trends and Demographic Differences in the United States, 1999 to 2021
Authors: Scheryar Saqib, Muhammad Talha Maniya, Aimen Shafiq, Ahmed Siddiqi, Kumail Mustafa Ali, Ali Salman, Adarsh Raja, Laibah Khan, Tariq Jamal Siddiqi, Michael Hall
Journal: Circulation (2024)

Background: Cardiovascular disease (CVD) mortality in the U.S. younger population is on the rise. However, limited data is available on CVD-related mortality trends in this population. Aim: This study aimed to assess the temporal trends and demographic differences in CVD-related mortality among the U.S. youth. Methods: The CDC WONDER dataset was analyzed from 1999-2021 for CVD-related mortality in children and young adults (age &lt;25 years). Socio-demographic data including gender, race/ethnicity, urbanization status and census region was acquired. Age adjusted mortality rates (AAMR) per 100,000 persons and annual percent changes (APCs) with 95% confidence interval (CIs) were calculated. Results: Between 1999-2021, a total 54,283 CVD-related deaths occurred among the youth in the U.S. The overall AAMR declined from 1999-2008 (APC, -1.15 [-3.4 to 0.53]), followed by sharp decrease from 2008-2012 (APC, -3.28 [-4.68 to 0.86]). The AAMR continued to decrease steadily from 2012 to 2019 (APC: -1.20, [-3.76 to -0.06]), followed by a sharp increase in from 2019 to 2021, (APC, 3.03 [-0.66 to 5.12]). Males consistently had higher AAMRs than females from 1999 (AAMR males: 2.99 vs females: 2.3) to 2021 (AAMR males: 2.39 vs females: 1.74). Non-Hispanic (NH) Black or African Americans had the highest AAMR in 2020 (3.68), followed by NH Whites (1.71), Hispanic or Latinos (1.59), and Asian and Pacific Islanders (1.2). AAMRs also showed significant variations across different regions (overall AAMR West 1.81; Northeast 1.93; Midwest 2.3; South 2.69). Metropolitan areas (2.23) consistently had lower mortality rates than nonmetropolitan areas (2.59). Conclusion: Our analysis revealed that CVD-related mortality in the youth declined from 1999-2019, followed by an increase in 2020 to 2021. Highest mortality rates were seen in males, Black or African Americans, Western region of the U.S, and nonmetropolitan areas. Tailored interventions are necessitated to decrease the burden of CVD-related mortality in these demographics among children and young adults in the United States.
Abstract 4129839: Successful Left Atrial Appendage Occlusion (LAAO) with WATCHMAN FLX via Transhepatic Approach
Authors: Gael Charbonne, Alex Card, Karley Fischer, Omar Mitiek, Damian Valencia, Brian Schwartz
Journal: Circulation (2024)

Left atrial appendage occlusion (LAAO) with the WATCHMAN FLX (Boston Scientific) has been proven to reduce stroke risk in patients with paroxysmal atrial fibrillation (PAF). Certain circumstances may preclude LAAO1. In this case, transhepatic vein access was used to successfully deploy a WATCHMAN FLX in a 72 year old male with PAF not on anticoagulation due to recent subdural hemorrhage and recurrent bilateral lower extremity deep venous thrombosis (DVT) post IVC filter placement. Recent attempt at LAAO was unsuccessful due to total occlusion of bilateral femoral veins (Figure 1 A-B) and inability to cross the IVC. Access to the inferior branch of the right hepatic vein was achieved by micropuncture technique at the right mid-axillary line at the level of the 12th rib, which was confirmed by venogram (Figure 2A). The 4F microsheath was upsized to 16F. Intraoperative TEE was used for device sizing and delivery (Figure 3A). The transseptal sheath and dilator were positioned in the right atrium at the level of the fossa ovalis (Figure 3B) before successfully crossing into the left atrium (Figure 2B). After confirming placement (Figure 3C), a pigtail catheter was positioned within the LAA (Figure 3D) and an angiogram was performed (Figure 2C). A 24 mm WATCHMAN FLX was partially unsheathed and positioned (Figure 3E). Repeat LAA angiogram was performed through the WATCHMAN delivery sheath (Figure 2D). A Tug test was performed. The device was released (Figure 3F). Repeat venogram was performed to confirm location (Figure 2E) of the access site, and coil embolization closure of the venotomy access site was performed (Figure 2F). The patient was discharged the following day on dual antiplatelet (aspirin, clopidogrel) without complication. Venous access via right hepatic vein is a viable option for LAAO using the WATCHMAN FLX device.
Abstract 4130072: Prognostic Impact of Renal Microcirculatory Dysfunction in Heart Failure Assessed by the Advanced Doppler technique, Superb Microvascular Imaging
Authors: Kiyomi Kayama, Shohei Kikuchi, Tadafumi Sugimoto, Yoshihiro Seo
Journal: Circulation (2024)

Aims: The significance of cardio-renal interactions in heart failure (HF) prognosis has become increasingly evident, yet there are no established methods to assess them. To address this issue, we propose a novel approach using Superb Microvascular Imaging (SMI), an ultrasound method that that enables detailed visualization of microvascular flow, to assess renal microcirculation. Methods: We retrospectively analyzed 78 patients who underwent renal ultrasonography using SMI from October 2020 to May 2023. We measured changes over time of Vascular Index (VI), which quantifies the blood flow signal area in the region of interest on the SMI image (Figure 1). Key measurements included Maximum VI (Max.VI), Minimum VI (Min.VI), and the cyclic variation of VI, calculated as the intrarenal perfusion index (IRPI) = (Max.VI - Min.VI) / Max.VI within one cardiac cycle. The primary endpoint of this study was a composite event (CE), defined as a composite of all-cause death and unplanned hospitalization for worsening HF. Results: During a mean follow-up period of 1.6±0.8 years, 13 of 78 patients (17%) experienced a CE. Compared with patients without CE, those with CE had significantly lower Max.VI (0.28±0.15 vs 0.46±0.18, p=0.002) and Min.VI (0.10±0.12 vs 0.22±0.14, p=0.007), and IRPI was significantly higher in the event group (0.68±0.19 vs 0.55±0.17, p=0.018). In univariable Cox regression analyses, Max.VI (HR 0.35, 95%CI 0.17-0.71, p=0.004), Min.VI (HR 0.28, 95%CI 0.10-0.75, p=0.012), IRPI (HR 1.97, 95%CI 1.11-3.51, p=0.021), creatinine (Cr) (HR 1.67, 95%CI 1.26-2.21, p&lt;0.001) and estimated right atrial pressure by echocardiography (eRAP) (HR 4.22, 95%CI 1.42-12.5, p&lt;0.001) were significantly associated with CE. In multivariable Cox regression analyses, Min.VI remained significantly associated with CE in the model adjusted for Cr (HR 0.35, 95%CI: 0.13-0.92, p=0.033), and in the model adjusted for eRAP (HR 0.11, 95%CI: 0.11-0.82, p=0.019). ROC curve analysis showed that, although not statistically significant, the predictive power of Min.VI was superior to that of Cr and eRAP (Figure 2). Stratifying patients by a Min.VI cut-off value of 0.08, determined through ROC analysis, showed that those with Min.VI &lt; 0.08 had a significantly poorer prognosis (log-rank p&lt;0.001) (Figure 3). Conclusion: The use of Superb Microvascular Imaging to assess renal circulation provides new insights into the prognosis of HF and allows risk stratification beyond conventional markers.
Abstract 4129733: Glucagon-like Peptide 1 Receptor Agonists Effect on Low-Density Lipoprotein Cholesterol and Total Cholesterol Levels Independent of Weight Reduction: A Meta-analysis and Meta-regression of Placebo-controlled Randomized Controlled Trials
Authors: Frederick Rivera, Marielle Nicole Chin, Jade Monica Marie Ruyeras, Wailea Faye Salva, Rajiv Hans Menghrajani, Drashti Desai, Sarang Choi, GERARD FRANCIS MANGUBAT
Journal: Circulation (2024)

Background: The impact of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on lipid components is unclear. The objective of this study was to measure the lipid-lowering effect of GLP-1RAs. Methods: A thorough database search was performed to identify placebo-controlled randomized controlled trials (RCTs) on GLP-1RA therapy through January 2023. From these trials, data was extracted and a robust statistical analysis was performed using a random effects model to determine outcomes with weighted mean difference (MD) in milligrams per deciliter (mg/dL) and 95% confidence intervals (CIs). The primary outcome was the mean difference in low-density lipoprotein cholesterol (LDL-C). Secondary outcomes were mean differences in total cholesterol (TC), triglycerides, high-density lipoprotein-C (HLD-C), and very low-density lipoprotein-C (VLDL-C). To account for covariates, subgroup analyses and meta-regression were performed. Results: A total of 33 studies were included in the final meta-analysis carried out between 2008 and 2023, which were conducted in 26 countries. Of the 5,918 participants, the study population comprised 2,603 (44%) males and 3,315 (56%) females, aged between 33.7 and 65.9 years. GLP-1RAs significantly reduced LDL-C compared to placebo (MD -2.93, 95% CI (-5.01, -0.85), P=0.01). Treatment effect was consistent regardless of duration of treatment;12 weeks or less MD: -5.39, 95% CI (-10.36, -0.42), P=0.03 vs &gt;12 weeks MD: -2.39, 95% CI (-4.70, -0.007), P=0.04, P interaction 0.28). In our analysis, GLP-1RA reduced TC by ~7 mg/dl. There was no significant reduction in triglycerides (MD = -7.19, 95% CI (- 15.01, 0.62], P=0.07) and VLDL-C ~4 mg/dl (MD = -3.99, 95%, CI (-8.73, 0.75), P=0.10). Furthermore, GLP-1RA did not increase HDL-C (MD = -0.12, 95% CI (-0.73, 0.49], P=0.69. Regression analysis determined that weight loss did not affect the treatment effect on LDL-C (tau2=28.38, I2=99.83, R2=0.0, p=0.67), and total cholesterol (tau2=93.6, I2=99.86, R2=0.0, p=0.92). Conclusion: Patients on GLP-1RA experienced modest LDL-C and TC lowering compared to placebo. GLP-1RA did not decrease triglycerides and VLDL-C. GLP-1RA did not increase HDL-C.
Abstract 4129974: Increased Expression of Histone Deacetylases-2 and -6 in Left Ventricular Myocardium of Dogs with Chronic Heart Failure
Authors: Ramesh Gupta, Kristina Szekely, Sean Kalabat, David Lanfear, Hani Sabbah
Journal: Circulation (2024)

Background: Histone deacetylases (HDACs) -2 and -6 are localized in the nucleus and cytoplasm of cells and have been implicated in the development of left ventricular (LV) hypertrophy, cardiac interstitial fibrosis, inflammation and worsening of LV systolic and diastolic function thus contributing to progressive worsening of heart failure (HF) with reduced ejection fraction (HFrEF) as well as HF with preserved ejection fraction (HFpEF). There is considerable interest in the application of small molecules that inhibit the activity of HDAC proteins in HF in the hope of fostering clinical benefit. Purpose: In the present study we examined the expression of HDAC-2 and -6 in LV tissue from normal (NL) dogs and dogs with chronic HF (LVEF &lt;35%) produced by multiple sequential intracoronary microembolizations. Methods: Studies were performed in LV tissue from 7 NL dogs and 7 HF dogs. HDAC-2 and -6 protein levels were determined by Western blotting in the lysate of homogenate and 9000g supernatant (cytosolic) fractions prepared from powder of approximately 200 mg frozen LV tissue. After determining the protein by Lowry method, approximately 30 μg homogenate and 15 μg supernatant for HDAC-2 and 8 μg protein for both homogenate and supernatant for HDAC-6 were separated on 4%-20% SDS-PAGE and transferred on PVDF membrane. Band intensities were quantified in densitometric units (du). All data were normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Results: HDAC-2 proteins levels normalized to GAPDH were higher in the cytosol (0.59 ± 0.10 vs. 0.17 ± 0.04, p&lt;0.05 vs. NL) and homogenate (0.75 ± 0.12 vs. 0.55 ± 0.10, not statistically significant) of LV tissue of dogs with HF compared to NL dogs. HDAC-6 protein levels were higher in the homogenate (2.54 ± 0.36 vs. 0.57 ± 0.19, p&lt;0.05 vs. NL) and the cytosol (0.96 ± 0.15 vs. 0.78 ± 0.13, not statistically significant) of LV tissue of dogs with HF compared to NL dogs. Conclusions: These findings indicate upregulation of protein levels of HDAC-2 and -6 isoforms in LV myocardium of dogs with chronic HF. These abnormalities are likely to contribute to worsening HF. Selective inhibition of HDAC-2 and -6 represents a potential therapeutic approach for the treatment of both HFrEF and HFpEF.