tbuckley/cabot-search huggingface dataset:
Abstract 12958: Temporal Association of Systemic Inflammatory Biomarkers With Incidence of Postoperative Atrial Fibrillation After Botulinum Toxin Type A Administration in Epicardial Fat Pads
Authors: Hannah Huh, Mihai V Podgoreanu, William G Ferguson, Jie Shen, Louis P Perrault
Journal: Circulation (2023)

Background: A one-time injection of botulinum toxin type A (BoNT/A) in epicardial fat pads was evaluated for post-operative atrial fibrillation (POAF) in patients undergoing open-chest cardiac surgery in the Ph2 NOVA trial. Treatment with 125U BoNT/A numerically reduced the incidence of POAF in the mITT (36.5% vs 46.1%) and CABG populations (28.4% vs 40.0%), with statistical significance observed in the CABG + ≥65 years subgroup (27.5% vs 56.4%; P &lt;0.01). No significant reduction was observed in the 250U group vs placebo. Purpose: Explore systemic inflammatory biomarker changes after treatment with BoNT/A and the temporal relation to incidence of POAF. Methods: This analysis included 308 patients who received 125U BoNT/A (n=103), 250U BoNT/A (n=103), or placebo (n=102). Subgroup analysis was done for CABG (n=198), age ≥65 years (n=185), and CABG + ≥65 years (n=118). Serum samples were collected preoperatively prior to dosing on Day 1, then post-treatment on Days 2-4 to test for IL-6, IL-10, and hsCRP. A 2-sample t test was used for mean concentrations and a linear mixed model was used for fold change (FC) from baseline. Results: Baseline levels of IL-6, IL-10, and hsCRP were similar between treatment groups. Reduction of IL-6 (45.7 ± 4.4 vs 62.4 ± 5.8 pg/mL, P &lt;0.05; 10.8 vs 15.9 FC, P &lt;0.01) and IL-10 (1.49 ± 0.13 vs 2.04 ± 0.24 pg/mL, P &lt;0.05; 1.96 vs 2.66 FC, P &lt;0.01) was most significant on Day 2 in CABG patients treated with 125U vs placebo, which aligns with the highest rate and risk of POAF (Figure 1). Mean hsCRP was most significantly reduced on Day 4 in the 250U group among CABG patients (193 ± 8 vs 227 ± 10 mg/dL, P &lt;0.01) followed by 125U vs placebo (196 ± 10 vs 227 ± 10 mg/dL, P &lt;0.05); a similar dose-dependent reduction was observed by FC analysis. Conclusions: Treatment with 125U BoNT/A in cardiac surgery patients lowered the incidence of POAF vs placebo and reduced postoperative systemic IL-6 and IL-10 on Day 2, most significantly in the CABG population.
Abstract 14025: Health Status Profiles in Patients With New or Worsening Peripheral Artery Disease Symptoms and 12-month Hospitalization Risk From the Portrait Registry
Authors: Jacob Cleman, Gaelle Romain, Lindsey Scierka, Clementine Labrosciano, Mehdi H Shishehbor, David M Safley, Philip Jones, John Spertus, John F Beltrame, Carlos Mena-Hurtado, Kim G Smolderen
Journal: Circulation (2023)

Introduction: Risk stratification for healthcare utilization in PAD is critical given rising costs. The association between health status measures and hospitalization is unknown. We examined the association between a disease-specific patient-reported outcome measure and risk of hospitalization at 12 months. Methods: Patients with new or worsened lower extremity claudication enrolled at US sites in the PORTRAIT registry from 2011 to 2015 were included. The Peripheral Artery Questionnaire, a PAD-specific patient-reported outcome measure, was used to measure health status. PAQ summary scores range from 0 to 100 (better health status). Kaplan-Meier failure curves and adjusted Cox proportional hazards models assessed the association between baseline PAQ summary score and (1) the combined endpoint of all-cause hospital admission and ED visit (AD-ED) and (2) all-cause hospital admission (AD) at 12 months. Results: Of the 796 patients (mean age 69 ± 10 years, 42% female, 72% white, mean baseline PAQ summary score 46.8 ± 22.0) included, 349 (44%) had a hospital admission or ED visit at 12 months, with a total of 661 visits. Patients in the lowest PAQ quartile had higher rates of AD-ED at 30 days (16.1% vs. 4.3%), 90 days (29.8% vs. 12.8%), and 12 months (53.3% vs. 22.4%). In the fully adjusted model, lower PAQ score was associated with higher risk for AD-ED (HR per 10-point decrease, 1.12, 95% CI, 1.06-1.19, P&lt;0.001) and AD (HR per 10-point decrease, 1.14, 95% CI, 1.06-1.22, P&lt;0.001). Conclusion: Lower PAD-specific health status is associated with an increased risk in the combined endpoint of hospital admission or ED visits and all-cause hospital admission. These results support the use of baseline health status as a strong predictor for healthcare utilization in a high-risk population and may help to offset costs.
Abstract 14046: Cardiac Tamponade: A Handy Case of Early Detection
Authors: Khanhphi C Tranvu, Andrew Faturos, Jeffrey A Southard, Jason Rogers
Journal: Circulation (2023)

Case Presentation: A 63-year-old man with severe bicuspid aortic valve stenosis underwent surgical aortic valve replacement and the post operative echocardiogram was normal.In the month after discharge, the patient developed progressive episodes of lightheadedness, fatigue, and exertional weakness. He had no associated dyspnea on exertion, chest pain or fever. He was alerted of new sinus tachycardia on his Apple Watch, and the ECG morphology began changing with an overall decrease in QRS amplitude as well as alternating QRS amplitudes consistent with electrical alternans (Figure 1). These ECG strips were sent to the patient’s cardiologist who suspected a pericardial effusion due to these characteristic ECG findings.The patient underwent outpatient echocardiography which showed a normal functioning bioprosthetic valve with new large circumferential pericardial effusion and signs of cardiac tamponade physiology. The patient was admitted and underwent urgent pericardial drain placement with removal of 250cc of serosanguineous fluid. He recovered and was discharged with 3 months of colchicine. Discussion: Pericardial effusions are a known potential complication after cardiac surgery and often have an occult presentation making detection difficult. Smart watches with ECG capabilities provide valuable data because they can be used to detect the development of a new tachycardia and changes in QRS morphology. By observing the progressive changes in the QRS morphology from baseline, it is possible to monitor for the development of electrical alternans. This finding coupled with the patient’s clinical presentation prompted rapid evaluation and treatment. Conclusions: The Apple Watch can perform single-lead ECGs which are capable of diagnosing arrhythmias including atrial fibrillation. This case now opens the door to the early detection of postoperative pericardial effusions by monitoring the Apple watch for electrical alternans.
Abstract 12350: The Impact of an Electronic Best Practice Advisory on Patients’ Physical Activity and Cardiovascular Risk Profile
Authors: Margaret M McCarthy, Adam Szerencsy, Jason Fletcher, Gail D Melkus, Allison Vorderstrasse, Stuart Katz
Journal: Circulation (2023)

Background: Regular physical activity (PA) is one of eight components of cardiovascular health and it is associated with numerous benefits including a lower risk of CVD. Promoting PA to sedentary patients in primary care can result in significant improvements in PA. The aims of this study were to implement a PA counseling intervention using an electronic best practice advisory (BPA), in a preventive cardiology clinic, and to assess changes in PA and CVD risk factors in a sample of patients enrolled in 12 weeks of PA monitoring. Methods: Patients were assessed with the 3-question (days/minutes/intensity) physical activity vital sign (PAVS) via their electronic patient portal prior to an office visit. Those who self-reported less than 50% of current PA recommendations prompted a BPA to their cardiologist to counsel them on improving their PA. Patients were then offered participation in remote patient monitoring wearing a Fitbit for 12 weeks. Blood pressure, waist circumference, lipids, BMI, PA (using the PAVS and Fitbit step-counts) and the six-minute walk test (for cardiorespiratory fitness) were measured at baseline and 12 weeks. Paired t -tests assessed for changes in these CVD risk factors from baseline to 12 weeks. We calculated the percent of participants who achieved a clinically important difference of 25 meters in the six-minute walk test. Results: The enrolled sample (n=59) were primarily female (51%), White adults (76%) with a mean age of 61.13±11.6 years. There was significant improvement in moderate-to-vigorous PA as self-reported by the PAVS (43±86 vs. 114±157, p=.005). There was no significant difference between week 2 step counts (baseline) and week 12 (p=.07). There was significant improvement in the distance covered (in meters) during the six-minute walk test (469±108 vs. 494±132, p=.0034) and 23 participants (42%) improved at least 25 meters. There were also significant differences in total cholesterol (163±51 mg/dl at baseline vs. 148±45mg/dl at 12 weeks; p=.0.02). No other improvements in CVD risk factors were noted. Conclusion: Patients who reported low PA and triggered a BPA for PA counseling had improvements in some, but not all, CVD risk factors. Additional counseling may be needed to improve and maintain PA levels in patients at risk of CVD.
Abstract 12429: Potential Impact of Eliminating Physical Activity Activities Among the United States Adults
Authors: Kosuke Tamura, Marie F Martinez, Mohammad Moniruzzaman, Yangyang deng, Kevin L Chin, Colleen Weatherwax, Sarah Bartsch, Kavya Velmurugan, Jessie Heneghan, Sheryl Scannell, Bruce Lee
Journal: Circulation (2023)

Introduction: Disparities in physical activity levels among adults have been a significant and growing concern in the United States (US) for the past few decades, disproportionately impacting minority populations. Yet, demonstrating and quantifying the potential benefits of eliminating these disparities is challenging as traditional statistics cannot simultaneously account for changes to physical activity levels, subsequent health-related factors, and socioeconomic measures. Aims: This study developed an agent-based model (ABM) to simulate the elimination of physical activity disparities among race/ethnic groups in the US. adults (ages 18-30), and determine the lifetime health and economic impact. Methods: We developed a computational simulation model representing US adults ages 18-30, their physical activity and subsequent weight changes over time, and the lifetime physical health outcomes and the associated costs. We simulated Black and Hispanic Americans getting the same physical activity levels as White Americans. Results: Eliminating disparities/achieving parity in physical activity among adults such that the same proportion of Black and Hispanic Americans are meeting the physical activity guidelines as White Americans could reduce overweight/obesity prevalence by 1.13% (95% confidence interval [CI]: 1.13%-1.14%) among Black and Hispanic Americans, resulting in approximately 203,000 fewer cases of overweight/obesity (95% CI: 202,000-204,000). Additionally, this could avert 65,000 (95% CI: 64,800-65,200) cases of weight-related diseases (i.e., coronary heart disease, cancer, and diabetes) and gain 249,000 (95% CI: 249,000-250,000) quality-adjusted life years (QALYs). This translates to savings of $3.94 billion (95% CI: $3.93-$3.95 billion) and $5.43 billion (95% CI: $5.41-$5.46 billion) from direct medical costs and productivity losses averted, respectively, due to improvements in physical health. Conclusions: These cost savings represent what could be invested to reduce physical activity disparities and still break even, which can give decision-makers a sense of how to prioritize achieving equity in physical activity levels in US adults.
Abstract 12440: Depression and Anxiety Accelerate the Rate of Gain of Cardiovascular Risk Factors: Mechanism Leading to Increased Risk of Cardiac Events
Authors: Giovanni Civieri, Michael Osborne, Shady Abohashem, Simran Grewal, Charbel Gharios, Wesam Aldosoky, Iqra Qamar, Karmel Choi, Jordan Smoller, Ahmed A Tawakol
Journal: Circulation (2023)

Introduction: Depression and anxiety are associated with a greater incidence of major adverse cardiovascular events (MACEs). Hypothesis: We hypothesized that: 1) depression and anxiety accelerate the development of cardiovascular risk factors (CVDRFs), which in turn significantly heightens MACE risk, and 2) a genetic marker of stress sensitivity (polygenic risk score for neuroticism; nPRS) also associates with accelerated gains of CVDRFs. Methods: Subjects enrolled in the Mass General Brigham Biobank were studied. Depression, anxiety, CVDRFs and MACE were defined using ICD codes. Subjects &lt;18 years old, with previous MACE or who developed depression/anxiety after study start date were excluded. CVDRFs were defined as hypertension, hyperlipidemia, and diabetes mellitus. The time between study start date and development of first new CVDRF was measured over 10 years of follow-up. Additionally, nPRS was assessed for subjects who provided genetic data; age of first CVDRF diagnosis was ascertained in this subgroup. Results: Data were obtained for 71,262 subjects (age 49.0 ± 15.6 yrs, 44.7% male). 27,048 (38.0%) subjects gained a new CVDRF (mean time 4.8 ± 2.6 yrs). Depression (β=-0.591; p&lt;0.001) and anxiety (β=-0.567; p&lt;0.001) associated with earlier development of a new CVDRF after adjusting for age, sex, and preexisting CVDRFs ( Fig. 1A). Further, in adjusted analyses, depression and/or anxiety increased the risk of MACE (adjusted odds ratio: 1.353; p&lt;0.001). Mediation analysis shows that 38.9% of the effect of depression and/or anxiety on MACE is explained by the accelerated gains in CVDRFs. Similarly, higher genetic sensitivity to stress (nPRS) associates with an earlier onset of first CVDRF (adjusted β=-0.317; p=0.005, Fig. 1B) . Conclusions: Depression and anxiety accelerate the acquisition of CVDRFs, which in turn significantly explains the heightened risk of MACE. Genetic risk associated with stress sensitivity also accelerates the development of CVDRFs.
Abstract 12477: ER Stress Chop Depletion in Endothelial Cells Protects From Renovascular Hypertension Pathogenesis
Authors: BALAJI SRINIVAS, Souad Belmadani, Khalid Matrougui
Journal: Circulation (2023)

Introduction: Renovascular hypertension poses a significant risk for cardiovascular diseases, with endoplasmic reticulum (ER) stress playing a critical role in their development. However, the specific impact of ER stress-induced C/EBP homologous protein (CHOP) expression in endothelial cells on renovascular hypertension-induced cardiovascular complications remains unexplored. This study investigates the effects of disrupting ER stress CHOP in endothelial cells on microvascular dysfunction associated with renovascular hypertension. Hypothesis: We hypothesize that deleting ER stress CHOP in endothelial cells (EC) can mitigate renovascular hypertension-induced vascular endothelial dysfunction. Methods: Eight-week-old male and female mice (CHOP flx/flx and EC CHOP-/- ) were divided into eight groups: control groups undergoing a sham operation for 4 weeks and renovascular hypertension groups subjected to 2-kidney-1-clip (2K1C) surgery for 4 weeks. Body weight, blood pressure, running performance, cardiac hypertrophy and fibrosis, lung edema, inflammation, vascular endothelial function, and signaling were assessed. Results: Male and female CHOP flx/flx mice subjected to 2K1C for four weeks exhibited hypertension, cardiac hypertrophy and fibrosis, lung edema, impaired running performance, and endothelium-dependent vascular relaxation dysfunction. In contrast, male and female EC CHOP-/- mice subjected to 2K1C for four weeks were protected against the pathogenesis of renovascular hypertension. Furthermore, mesenteric resistance arteries from CHOP flx/flx mice displayed reduced endothelial nitric oxide synthase (eNOS) phosphorylation, while EC HOP-/- mice showed no such effect. Conclusions: These findings emphasize the significance of targeting ER stress CHOP in endothelial cells of male and female mice to protect against the development and pathogenesis of renovascular hypertension.
Abstract 12425: Stim1 Deletion in Treg Cell Protects From HFpEF Pathogenesis
Authors: BALAJI SRINIVAS, Jiang Xu, Hongmei Peng, Hani N Sabbah, Souad Belmadani, Nour E Rhaleb, Khalid Matrougui
Journal: Circulation (2023)

Introduction: Heart failure with preserved ejection fraction (HFpEF) is a cardiovascular disease that remains untreatable in its pathogenesis. Therefore, there is a critical need to uncover the cellular and molecular mechanisms underlying HFpEF pathogenesis and identify potential targets for treatment that can enhance cardiac function and restrict disease progression. Previous studies have shown that Treg cells are crucial in hypertension-induced cardiovascular complications and metabolic dysregulation. Moreover, the function of Stromal interaction molecule 1 (STIM1) varies depending on the cell type. Hypothesis: We hypothesize that the deletion of STIM1 in Treg cells can protect against the development of HFpEF and its associated conditions. Methods: Male mice aged eight weeks (Stim1 flx/flx and Treg Stim1-/- ) were divided into four groups: control groups receiving a standard diet and water for five weeks, and HFpEF groups fed a high-fat diet (HFD) and N[w]-nitro-l-arginine methyl ester (L-NAME - 0.5g/L) in the drinking water for five weeks. Various measurements and assessments were conducted, including echocardiography, evaluations of metabolism and hypertension, analysis of heart and kidney injury markers, and assessment of vascular endothelial function. Results: After five weeks, Stim1 flx/flx mice subjected to HFD and L-NAME displayed evidence of HFpEF, including hypertension, metabolic disorders, cardiac hypertrophy with fibrosis, kidney injury with fibrosis, impaired exercise tolerance and vascular endothelial function, increased body weight and E/E' ratio, reduced cardiac index, and unchanged ejection fraction. Interestingly, Treg Stim1-/- mice were protected against HFD and L-NAME-induced HFpEF and its associated pathologies. Conclusions: These findings underscore the significance of targeting STIM1 in Treg cells to protect from the development and pathogenesis of HFpEF.
Abstract 12480: Characterization of Symptoms and Diagnostic Procedures Prior to Diagnosis Among Patients With Pulmonary Arterial Hypertension in the United States
Authors: Hilary M DuBrock, Hayley D Germack, Marjolaine Gauthier-Loiselle, Jörg Linder, Ambika Satija, Ameur M. Manceur, Martin Cloutier, Patrick Lefebvre, Sumeet Panjabi, Robert P Frantz
Journal: Circulation (2023)

Introduction: Pulmonary arterial hypertension (PAH) is a progressive, fatal disease associated with non-specific symptoms, which may lead to diagnosis delays and poor outcomes. Research Question: Which symptoms and diagnostic procedures occur prior to PAH diagnosis and do they vary based on diagnosis delay? Aim: To describe PAH symptoms and diagnostic procedures among patients newly diagnosed with PAH. Methods: Adults with PAH were identified from Optum’s de-identified Clinformatics ® Data Mart Database (2016-2021). Eligible patients had continuous health plan enrollment ≥12 months (mo) before the first recorded PAH-related symptoms (i.e., index date ) and from the index date until the first recorded PAH diagnosis on a medical claim (i.e., study period ). Patients also had ≥1 fill for a PAH treatment and ≥1 right heart catheterization at any time post-index. PAH symptoms and diagnostic procedures were described during the study period, overall, and stratified by time between the index date and first PAH diagnosis (i.e., diagnosis delay ; ≤12 mo, 12–24 mo, and &gt;24 mo). Results: The sample included 538 patients (≤12 mo: N=327; 12–24 mo: N=126; &gt;24 mo: N=85). Mean age was 66 years, 60.6% were female, and mean (range) diagnosis delay was 11.8 (0.0–50.2) mo. During the study period, most patients had ≥2 unique symptoms recorded, but those with longer delay had more fatigue (≤12 mo: 26.6%; 12–24 mo: 55.6%; &gt;24 mo: 54.1%), edema (29.1%; 42.9%; 51.8%), and dizziness (10.1%; 23.0%; 18.8%), among others. Mean delay was shorter when the first symptoms were ascites (4.2 mo) and syncope (6.4 mo) and longer for fatigue (14.2 mo) and dizziness (14.0 mo). On average, patients with longer delay had more diagnostic procedures pre-diagnosis (≤12 mo: 4.3; 12–24 mo: 8.2; &gt;24 mo: 8.7), driven by more electrocardiograms (ECG; 1.9; 4.2; 4.5). Overall, 85.5% of patients had an ECG and 83.5% had a transthoracic echocardiography pre-diagnosis. Conclusions: Symptoms such as fatigue, edema, and dizziness were more common in patients with longer time to diagnosis and these patients had more diagnostic procedures. Greater physician awareness and new screening tools (e.g., predictive algorithms using ECG data) could accelerate PAH diagnosis and treatment aiming at improving patient outcomes.
Abstract 12365: Liraglutide Improves Myocardial Stress Perfusion and Energetics in Patients With Type 2 Diabetes- A Randomised, Single Centre, Open Label, Cross-Over Drug Trial
Authors: Amrit Chowdhary, Sharmaine Thirunavukarasu, Nicholas Jex, Sevval Akkaya, Sindhoora Kotha, Marilena Giannoudi, Henry Procter, Peter Kellman, John GREENWOOD, Sven Plein, Eylem Levelt
Journal: Circulation (2023)

Background: Insulin secretion and insulin resistance in Type 2 diabetes (T2D) are amenable to pharmacological intervention. In a single center, open-label, randomized, cross-over drug trial we compared two glycaemic control strategies using Glucagon-like peptide-1 receptor agonists liraglutide and peroxisome proliferator activated receptor-gamma agonist-pioglitazone to see the effect on myocardial perfusion, energetics and function. Methods: Forty-one eligible patients with T2D and no known prior CV disease were randomized in a 1:1 ratio to the study drugs for a 16-week treatment period followed by an 8-week washout and a further 16-week treatment period for the second drug. Participants underwent rest and dobutamine stress 31 phosphorus magnetic resonance spectroscopy followed by CMR scans. The CMR protocol consisted of rest and dobutamine stress cine imaging, perfusion imaging and late gadolinium enhanced imaging immediately before and after each treatment arm. Results: Liraglutide therapy resulted in significant reductions in the body mass index. Pioglitazone led to a significant increment in LV mass. Liraglutide therapy resulted in increased rest and dobutamine stress energetics, global stress myocardial blood flow and myocardial perfusion reserve. With pioglitazone treatment, an isolated increase in the E/A was observed. Conclusions: In this study we showed for the first time that four months treatment with GLP-1RA (liraglutide) results in significant improvements in myocardial perfusion and energetics, while the insulin sensitiser pioglitazone shows no effect in modulation of these parameters.