tbuckley/cabot-search huggingface dataset:
Abstract 17573: Reliability of Non-Invasive Arterial Pressure Monitoring via ClearSight System™ During Cardiac Ablation and Transvenous Pacemaker Lead Removal
Authors: Colton D Thompson, Dejan Vrtikapa, Jeffrey Olech, Jennifer Wright, John Dollerschell
Journal: Circulation (2023)

Background: Invasive arterial catheter (IAC) placement can lead to hematoma, vessel occlusion, pain and &amp; procedure delay. The ClearSight System™ (CSS) is a non-invasive blood pressure (NIBP) device that measures beat-to-beat arterial pressures (AP) via a finger cuff. The validity of CSS during cardiac ablation &amp; transvenous pacemaker lead removal has not been described. Therefore, we performed a single center observational study to validate AP monitoring by CSS compared to IAC in such patients (pts). Methods: Pts undergoing cardiac ablation or lead removal from June-November 2022 were included. AP was simultaneously measured via CSS &amp; IAC. Measurements were compared using Bland-Altman analysis. Acceptable bias &amp; precision (standard deviation) were defined as &lt;5 mm Hg &amp; &lt;8 mm Hg respectively based on Association for the Advancement of Medical Instrumentation standards. An exploratory analysis on impacts of BMI, sex, &amp; type of procedure on validity of CSS was also assessed. Results: Paired AP measurements were available for 61 pts (6967 paired measurements). Median age was 67 (IQR 60.5-73.5), BMI 29.2 (IQR 26.1-37.1) &amp; 31% of pts were female. Procedures included atrial fibrillation ablation (n=32), SVT ablation (n=13), lead extraction (n=9), &amp; VT ablation (n=7). Bland-Altman analysis comparing AP via CSS vs IAC showed that the CSS overestimated systolic arterial pressure (SAP) &amp; underestimated both diastolic arterial pressure (DAP) &amp; mean arterial pressure (MAP). Mean bias was 4.2 ± 12.9 (SAP), -4.99 ± 9.2 (DAP) &amp; -2.4 ± 11.78 (MAP) (Figure 1). Exploratory analysis showed that CSS was not interchangeable with IAC monitoring regardless of subgroup (MAP male sex -1.9 ± 11.1; BMI ≥30 -2.7 ± 9.7; ablation -1.8 ± 12.2). Conclusion: Continuous NIBP monitoring via CSS was not interchangeable with IAC monitoring in pts undergoing cardiac ablation &amp; lead extraction.
Abstract 17395: Effect of ION904, an Antisense Inhibitor of Angiotensinogen Production: Results of Phase 1 and Phase 2 Pilot Studies
Authors: Erin Morgan, Jason M Duran, Julia Weinland, Tao Lin, Adam E Mullick, Richard Geary, Sotirios Tsimikas
Journal: Circulation (2023)

Background: Drugs that inhibit the renin-angiotensin-aldosterone system (RAAS) act within the kidney and disturb tubuloglomerular feedback leading to renal dysfunction and hyperkalemia. We previously published that inhibiting angiotensinogen ( AGT ) mRNA in hepatocytes with GalNAc-modified antisense oligonucleotide (ASO)-IONIS-AGT-L Rx given subcutaneously (SC) weekly is effective in significantly reducing plasma angiotensinogen (AGT) with no on-target or off-target effects. Objective: We aimed to develop a more potent and durable ASO targeting AGT . ION904 is a GalNAc-conjugated ASO that specifically reduces hepatic AGT production with minimal activity in the kidneys. Methods: In a phase 1 study (PH1), healthy volunteers were treated with placebo saline (PBO) or ION904 SC with single ascending doses (PBO or 10-120 mg, n=56). A phase 2 (PH2) pilot study (n=48) in patients with uncontrolled hypertension (SBP &gt; 130 - ≤ 170 mmHg) on at least 1 antihypertensive medication were randomized to PBO or 30, 60, or 90 mg of ION904 SC every 4 weeks for 3 months (3:1 randomization). The primary endpoint was plasma AGT reduction at Week 15. The study was not powered for SBP reduction. Results: ION904 resulted in a significant mean percent reduction in plasma AGT levels compared to pooled PBO at Day 15 (-12% v. -76%, PBO v. 120 mg, p ≤ 0.001) in PH1. In PH2, the mean percent reduction in AGT levels were significantly greater in the ION904 group compared to PBO at the primary endpoint, Week 15, (-6% v. -79%, PBO v. 90 mg, p=0.001). Robust median AGT reductions were observed at the primary endpoint (-5% v. -86%, PBO v. 90 mg). A larger proportion of subjects (11/26, 42%) in the ION904 group achieved ≥ 10 mmHg reductions compared to PBO (3/10, 30%) at Week 15. No signals for hyperkalemia, renal dysfunction, hypotension (on target effect) or liver dysfunction or thrombocytopenia (off target effects) were noted. No drug-related serious adverse events occurred. Conclusions: Monthly administration of ION904 demonstrated significant plasma AGT reductions with a favorable safety and tolerability profile supporting development in heart failure and hypertension.
Abstract 14509: Life’s Simple 7 Predicts Mild Cognitive Impairment and Dementia in an Older Adult Population
Authors: Kyra E Lopez, Benjamin Katz, Brenda M Davy, Kevin P Davy
Journal: Circulation (2023)

Introduction: The American Heart Association’s Life’s Simple 7 (LS7) is a metric used widely in cardiovascular disease research. Lower scores on Life's Simple 7 predicts a lower performance on measures of cognitive functioning in young and middle-aged adults. Whether this is the case in older adults, however, is unclear. Hypothesis: Higher LS7 scores at baseline will be associated with a reduced risk of mild cognitive impairment (MCI) or dementia in older adults. Methods: Data from the Health and Retirement Study (HRS) between 2010 to 2018 was used in the analysis. The respondents were older than 50 years old and free from dementia and MCI at baseline. A survival-analysis was used and failures were defined as having MCI or dementia as determined by a 27-point Telephone Interview for Cognitive Status (TICS). LS7 scores were computed using smoking status (current and former), physical activity, diet, blood pressure, total cholesterol, blood glucose, and body mass index (BMI). A cox proportional hazard model was used to evaluate hazard ratio of developing mild cognitive impairment (MCI) and dementia in older adults. Results: There were 1,604 respondents with complete data included in this analysis. Of these respondents, 563 (35.1%) were male and 1,041 (64.9%) were female. 1,224 (76.3%) were white, 236 (14.7%) were black, and 143 (8.9%) were of another race. The average age of the respondents at baseline was 62.3±10.6 years. In 7,505 person-years, there were 1,197 events of MCI or dementia. After adjusting for age, gender, and educational attainment, a LS7 score less than 5 was associated with a 1.51 times higher risk of MCI or dementia than a LS7 score greater than 8 (p &lt; 0.005). However, LS7 scores between 7 or 8 was not significantly associated with increased risk of MCI or dementia compared to a LS7 score greater than 8 (HR: 1.12, p = 0.09). Conclusions: Lower LS7 score is associated with significantly lower performance on a measure of global cognitive functioning. As in young and middle-aged adults, maintaining a heart-healthy lifestyle may be important in preventing cognitive decline in older adults.
Abstract 14190: Simultaneous Analysis of Myocardial Flow Reserve and Intra-Ventricular 4D Flow Using Hybrid <sup>13</sup> N-ammonia Positron Emission Tomography/Magnetic Resonance Imaging in Patients With Coronary Artery Disease
Authors: Keiichiro Endo, Masataka Katahira, Takatoyo Kiko, Ryo Yamakuni, Naoyuki Ukon, Takeshi Shimizu, Shiro Ishii, Takayoshi Yamaki, Kazuhiko Nakazato, Kenji Fukushima, Hiroshi Ito, Yasuchika Takeishi
Journal: Circulation (2023)

Introduction: Intra-left ventricular (LV) blood flow dynamics is closely related to wall kinetics and myocardial perfusion. 4D flow magnetic resonance imaging (MR) has been developed to simulate and quantify intra-LV blood flow. We aimed to evaluate the usefulness of simultaneous analysis of myocardial flow reserve (MFR) and intra-LV 4D flow measured by hybrid 13 N-ammonia positron emission tomography (PET)/MR in patients with coronary artery disease (CAD). Methods: Forty patients (mean 65±18 years, male 32) with CAD who underwent pharmacological stress PET/MR were enrolled. MFR was calculated from a series of dynamic rest-stress PET scans. Simultaneously, 4D flow MR acquisition was performed during the stress PET scan. The intra-LV 4D flow was visually assessed, where the smooth flow was defined as normal pattern, and random, or reverse flow was defined as abnormal (Figure A). The velocity of LV inflow and outflow were measured. Results: A normal flow pattern was found in 22 patients, while abnormal pattern was found in 18. MFR showed a significant correlation with the velocity of LV inflow and outflow (inflow: R = 0.552, P &lt; 0.001; outflow: R = 0.563, P &lt; 0.001). MFR was significantly lower in the abnormal flow compared to the normal flow (1.484 ± 0.559 vs. 1.931 ± 0.775, P = 0.041, Figure B). Additionally, when analyzing MFR in coronary artery territories, MFR in the left anterior descending artery was significantly lower in the abnormal flow compared to the normal flow (1.405 ± 0.526 vs. 1.881 ± 0.791, P = 0.029, Figure C). Conclusion: Simultaneous analysis of MFR and intra-LV 4D flow has a potential to serve as a novel indicator for assessing the severity of ischemia in patients with CAD.
Abstract 13094: Eliciting Home Health Aides Perspectives Towards Achieving Cardiovascular Health
Authors: Elizabeth Kuo, Melissa Yanez, Yefrenia Henriquez Taveras, Ann Lee, Rebecca Klahr, Jennifer D Lau, Monika M Safford, Erica Phillips, Faith Wiggins, Nicola Dell, Ariel Avgar, Nathalie Moise, Madeline R Sterling
Journal: Circulation (2023)

Introduction: Home Health Aides (HHAs) provide essential care to adults with cardiovascular (CV) disease in the home. Yet, HHAs themselves are a vulnerable workforce with a high burden of cardiovascular (CV) disease risk factors, which poses challenges to their own health, and potentially their patients’. We elicited the perspectives of HHAs towards achieving CV health within the context of their job. Methods: We conducted focus groups and interviews with HHAs from January to May 2023 in partnership with the 1199SEIU Training and Employment Fund, a benefit fund of the 1199SEIU United Healthcare Workers East, the largest US healthcare union. We included English and Spanish speaking HHAs with poor CV health, defined as having: 1) hypertension, 2) obesity, and 3) ≥1 other CV disease risk factor (self-reported hyperlipidemia, diabetes, smoking, and physical inactivity). Interviews were audio-recorded, professionally transcribed, and translated. Data were analyzed thematically using the Social-Ecological Model. Results: Nineteen HHAs from 12 home care agencies participated. They had a mean age of 57 years (SD 9.3), 18 (94.7 %) were female, 9 (47.4 %) were Black, and 7 (36.8 %) were of Hispanic ethnicity. In line with the Social-Ecological Model, 5 themes emerged. At the individual level, despite having several CV disease risk factors, HHAs’ perceptions of their health ranged from poor to excellent. Many were motivated to eat healthier and be more active but faced challenges including insufficient time and their own physical limitations. At the interpersonal level, the HHA-patient relationship influenced both aides’ and patients’ health (e.g., food in patients’ home). At the community level, HHAs wanted to connect with peers to improve their CV health together. At the organizational level, shift work, long commutes, and agency culture influenced their CV health. At the policy level, structural inequities (e.g., access to health insurance, citizenship) were barriers to CV health. Conclusion: HHAs’ ability to achieve CV health was influenced by personal, interpersonal, organizational, and societal-level factors. The findings can inform future, multi-level interventions, aiming to improve the CV health of HHAs and potentially their patients.
Abstract 14176: Cardiac Structure and Function in Relation to Health-Related Quality of Life in Heart Failure Patients With Preserved Ejection Fraction: Results From the PARAGON-HF Study
Authors: Sahmin Lee, Brian Claggett, Amil M Shah, Alvin Chandra, Eldrin F Lewis, Riccardo M Inciardi, Ivo Planinc, Maja Cikes, Narayana Prasad, Felipe Martinez, Carolyn S Lam, John J McMurray, Scott Solomon, Hicham Skali, Sheila Hegde
Journal: Circulation (2023)

Background: Health-related quality of life (HRQL) is reduced in patients with heart failure with preserved ejection fraction (HFpEF). However, the extent to which HRQL outcomes are related to cardiac structure and function in patients with HFpEF is not well understood. Methods: We examined the association between baseline echocardiographic measures and longitudinal Kansas City Cardiomyopathy Questionnaire (KCCQ) measures in patients with HFpEF in the PARAGON-HF trial using longitudinal regression models adjusted for age, sex, baseline KCCQ score, randomization, and other important clinical confounders. Results: Among 1,094 patients with baseline KCCQ data at randomization and a baseline echocardiogram within 6 months of enrollment, the mean age was 74 years and 53% were women. Over 3 years, 78% completed KCCQ measures at baseline, 12, 24, and 36 months. Missing values for non-survivors (n=116) were imputed as zero to avoid survival bias. Posterior wall thickness, septal E/e’, and right ventricular (RV) end diastolic area were negatively associated with the KCCQ Overall Summary Score, and a similar pattern of associations was observed for the KCCQ Clinical Summary Score (Table). Pulmonary artery systolic pressure was additionally negatively associated with the KCCQ Total Symptom Score. Notably, left ventricular (LV) size, septal wall thickness, LV ejection fraction, LV strain, and left atrial size were not significantly associated with longitudinal changes in KCCQ. Conclusion: In patients with HFpEF, increased LV posterior wall thickness, elevated LV filling pressure, elevated pulmonary pressure, and RV enlargement - together suggestive of more advanced diastolic dysfunction - are associated with a decline in KCCQ scores and may influence future worsening of quality of life.
Abstract 17415: Oxygen Uptake Kinetics at the Onset of Incremental Ramp Exercise During Cardiopulmonary Exercise Testing in Patients Undergoing Evaluation of Dyspnea on Exertion
Authors: Catharine Griskowitz, Joseph Campain, Alexandra Minasian, Cheshta Prasad, Jennifer Rouvina, Casey White, Shaina McGinnis, Alyssa Kowal, Katherine Kelly, Rajeev Malhotra, Gregory Lewis
Journal: Circulation (2023)

Background: A high metabolic cost of initiating exercise, defined by workload equivalents of unloaded cycle ergometry exercise, has been described in obese patients with HFpEF. Implications of high BMI and exaggerated metabolic cost of exercise initiation on responses to incremental ramp exercise have not been defined. We hypothesized that exaggerated metabolic cost of exercise initiation would result in delayed metabolic response to incremental ramp exercise. Methods: Patients underwent invasive cardiopulmonary exercise testing (CPET) on a cycle ergometer, including rest, unloaded exercise, and maximum incremental ramp exercise. Mean response time (MRT) was defined as 67% of the time to reach steady state VO 2 during unloaded exercise. On-ramp VO 2 kinetics were defined by the amount of time that it took for VO 2 to permanently increase by 5% (t 5% ), 10% (t 10% ), and 15% (t 15% ) above steady state after initiation of incremental ramp exercise. These values were adjusted for ramp and related to demographic and CPET measures by multivariate linear regression. Results: 200 patients referred for evaluation of exertional dyspnea and suspected HFpEF (age 55 ± 16 years, 45% female, BMI of 30 ± 6 kg/m 2 , 52% HTN, 17% DM) demonstrated variability in their on-ramp VO 2 uptake kinetics after reaching steady state during unloaded exercise. Delayed VO 2 kinetic responsiveness to incremental ramp exercise, as measured by t 5% , t 10% , and t 15%, was not related to age but was directly related to BMI, internal work, and prolonged MRT for VO 2 upon exercise initiation. Conclusion: In this initial description of VO 2 uptake kinetic patterns during the transition from unloaded to incremental ramp exercise, increased BMI, slow exercise onset VO 2 kinetics, and heightened metabolic cost of exercise initiation are all related to delayed VO 2 on-ramp kinetics. Delayed on-ramp O 2 kinetics merit further evaluation in relation to functional limitations in dyspneic patients referred for suspicion of HFpEF.
Abstract 13076: Geriatric Nutritional Risk Index and Sarcopenia in Patients Undergoing Cardiac Transplantation
Authors: Alice Chung, Elissa Driggin, Erin Harris, Abraham Bordon, Salwa Rahman, Gabriel T Sayer, Koji Takeda, Nir Uriel, mathew S Maurer, Jay Leb, Kevin Clerkin
Journal: Circulation (2023)

Background: The Geriatric Nutrition Risk Index (GNRI) is a simple nutritional assessment tool used in elderly patients. Sarcopenia, defined as reduced muscle mass strength, is widely prevalent in patients with advanced heart failure, and has been associated with worse clinical outcomes including post-transplant infections and mortality but is not routinely assessed. The relationship between GNRI and sarcopenia in advanced heart failure patients undergoing cardiac transplantation has not been well-established. Aims/Hypotheses: The primary outcome was to determine if GNRI was associated with sarcopenia as diagnosed using pectoralis muscle area index. We hypothesize that patients with a higher nutritional risk (GNRI &lt; 92) will have higher rates of sarcopenia. Methods: Patients who underwent cardiac transplantation from January 2018 to June 2022 and who underwent preoperative chest CT scans were included. GNRI was calculated using albumin, height and weight on the day of transplant. Previous literature has defined malnutrition status as a GNRI &lt; 92. The primary outcome was sarcopenia which was diagnosed as pectoralis muscle area index in the lowest sex-specific tertile. Results: 172 patients were included in the primary analysis and were stratified into high (GNRI&lt;92) and low (GNRI&gt;92) nutritional risk. Patients with high nutritional risk had a lower BMI than those with low nutritional risk. Patients with high nutritional risk were more likely to meet criteria for sarcopenia than those with low risk (56.5% vs 28.9%, p=0.02). Additionally, patients with high nutritional risk had a longer hospital length of stay at their index hospitalization than patients with low nutritional risk (29 vs 22 days, p=0.03). There were no significant differences by nutritional risk in outcomes of rehospitalizations, days alive and out of the hospital, or death. Conclusions: Lower GNRI (higher nutritional risk) was associated with a greater prevalence of sarcopenia in patients undergoing cardiac transplantation. This index may represent a simple screening tool utilizing readily available data to ascertain sarcopenia in patients with advanced heart failure.
Abstract 17443: Wwox is a Critical Regulator of Pulmonary Artery Smooth Muscle Cell Homeostasis
Authors: Marta T Gomes, Jiwang Chen, Rafael Polidoro, Yang Bai, Clare Prohaska, Sunit Singla, C. Marcelo M Aldaz, Robert Stearman, Roberto F Machado
Journal: Circulation (2023)

Introduction: Pulmonary artery smooth muscle (PASMC) proliferation and apoptosis resistance are characteristic of pulmonary arterial hypertension (PAH). Expression loss of the tumor suppressor WW-domain containing oxidoreductase (WWOX) promotes cell survival and metabolic reprograming in cancer. We hypothesized that loss of WWOX expression in PASMC promotes pulmonary vascular remodeling by similar mechanisms. Methods and Results: mRNA and protein levels of WWOX are decreased in PASMC from patients with PAH, and in rat models of pulmonary hypertension (Sugen/ hypoxia and monocrotaline). PASMC-specific conditional Wwox knockout mice (WWOX-SMC KO) were treated with tamoxifen or vehicle for 5 days and exposed to 10% hypoxia for 4 weeks. WWOX-SMC KO animals developed worse hypoxia induced PH with increased right ventricular systolic pressure, right ventricular hypertrophy and pulmonary vascular remodeling, compared to control animals. WWOX loss via siRNA decreased mRNA and protein levels of BMPRII, upregulated HIF 1alpha expression, increased hPASMC proliferation and migration. RNAseq revealed dysregulation in multiple pathways in WWOX-silenced hPASMCs, including cell-cycle regulation, TGF-β, mTOR and STAT3 signaling. Loss of WWOX showed decreased basal and maximal respiration, ATP production, reduced glycolytic capacity (40% in relation to control) and decreased mRNA expression of glycolytic enzymes (HK2, PFK1, PKM), generating 58% less lactate, and reduced mRNA expression of lactate dehydrogenase A. These cells exhibited increased mRNA and protein expression of glutaminase-1 and citrate lyase and had higher dependency on fatty acid oxidation and glutaminolysis compared to glucose, suggesting that these pathways are used when WWOX is suppressed. We also found mitochondrial hyperpolarization (JC-1 assay), decreased Sirtuin 3 expression, increased expression of acetylated manganese-superoxide dismutase, high production of reactive oxygen species and mitochondrial fission, indicating that loss of WWOX contributes to mitochondrial dysfunction. Conclusion: Loss of WWOX promotes cell cycle progression, proliferation, and metabolic reprogramming in PASMCs. Further studies are ongoing to better understand these effects.
Abstract 13109: Empagliflozin Reverses Oxidized LDL-Induced RECK Suppression, MMP Activation, and Human Aortic Smooth Muscle Cell Proliferation and Migration
Authors: Chandrasekar Bysani, Srinivas Mummidi, Vincent G. DeMarco, Patrice Delafontaine, Yusuke Higashi
Journal: Circulation (2023)

Empagliflozin, an FDA-approved anti-hyperglycemic agent, is a potent and highly selective inhibitor of sodium glucose co-transporter-2 (SGLT-2) in renal proximal tubule epithelial cells. It blocks glucose reabsorption and promotes glucose excretion via urine. Intriguingly, several clinical trials have reported the pleiotropic beneficial effects of SGLT-2 inhibitors in cardiovascular diseases, including antioxidant and anti-inflammatory effects. Here we investigated whether empagliflozin reverses oxidatively modified LDL (OxLDL)-induced matrix metalloproteinase activation and smooth muscle cell (SMC) migration and proliferation. Quiesced human aortic SMCs (Lonza) were treated with empagliflozin (1 uM) followed by human medium OxLDL (40 ug/mL; Kalen Biomedical). OxLDL stimulated SMC migration (1.8-fold, P&lt;0.05, n=4) and proliferation (1.5-fold, P&lt;0.05, n=4), and empagliflozin attenuated both by 67% (P&lt;0.05, n=4) and 61% (P&lt;0.05, n=4), respectively. Increased migration and proliferation by OxLDL were accompanied by elevated MMP-2 (3.2-fold, P&lt;0.05, n=5) and 9 (3.1-fold, P&lt;0.05, n=5) activities, which were also suppressed by empagliflozin by 65% and 67%, respectively (both P&lt;0.05, n=5). RECK (reversion inducing cysteine rich protein with Kazal motifs) is a membrane anchored MMP inhibitor, and we found that OxLDL dose-dependently downregulated RECK in SMCs (by 60%, P&lt;0.05, n=3) via NF-kB-dependent miR-30b induction. Intriguingly, empagliflozin restored the OxLDL downregulation of RECK to 88% of the control (n=3), as it inhibited miR-30b induction (by 49%, P&lt;0.05, n=5). Consistent with RECK-mediated effects of empagliflozin, adenoviral overexpression of RECK inhibited OxLDL-induced SMC migration (by 67%, P&lt;0.05, n=5) and proliferation (by 50%, P&lt;0.05, n=5). Together, these results suggest that the vasculoprotective effects of empagliflozin are at least in part mediated by restoring RECK, thereby attenuating SMC migration and proliferation under elevated oxidative stress condition. Our results also suggest therapeutic potential of empagliflozin or RECK overexpression in vascular proliferative diseases.