tbuckley/cabot-search huggingface dataset:
Abstract 18816: Association Between Perceived Exertion Intensity of Physical Activity and Agiographic Score in Patients With Coronary Artery Disease: A Pilot Study
Authors: Brenda Acacio, Antônio Carlos Battaglia Filho, Guilherme Wesley Peixoto da Fonseca, Francis Ribeiro de Souza, Renata do Val, Carlos Eduardo Negrão, Roberto Kalil Filho, Maria Janieire de Nazaré Nunes Alves
Journal: Circulation (2023)

The protective role of physical activity on coronary artery disease (CAD) has been demonstrated by many studies. The influence of physical activity intensity on CAD progression is unknown. Purpose: To evaluate the association between physical activity intensity and angiography score. Methods: 94 patients evaluated, 63 patients with known CAD and 31 patients without CAD who had coronary computed tomography angiography. Muscle strength was measured by handgrip. A pedometer was used to quantify steps/day. Physical activity questionnaire was used to determine physical activity in months and intensity was determined by the modified BORG scale (BORG). Gensini score was used to calculate atherosclerotic load. Results: There was no difference between patients with and without CAD for age , systolic blood pressure, diastolic blood pressure, BORG, total steps, and handgrip, respectively. Gensini was higher for patients with CAD than those without CAD [14 (6-24) vs 0 (0-0); p=0.012, respectively. There was a negative correlation between Gensini and week total steps (r=-0.29; p=0.027). Univariate logistic regression model using Gensini&gt;13 as the dependent variable, age (OR, 1.082; 95% CI, 1.012-1.157; p=0.021), moderate-to-high intensity (OR, 0.359; 95% CI, 0.134-0.958; p=0.041), and very vigorous intensity (OR, 4.308; 95% CI, 0.899-20.632; p=0.047) were associated with Gensini, whereas light intensity was not significantly associated with Gensini (OR, 1.218 ; 95% CI, 0.472-3.138; p=0.68). In a multivariate logistic regression model, age (OR, 1.144; 95% CI, 1.039-1.260; p=0.006) and moderate-to-high intensity (OR, 0.316; 95% CI, 0.107-0.931; p=0.037) remained associated with median Gensini&gt;13 adjusted by presence of dyslipidemia, hypertension, diabetes independently, smoking, handgrip strength, week steps, and months of physical activity. Conclusion: our results show that only moderate-to-high intensity of physical activity is independently associated with Gensini score, suggesting a protective effect of intensity from moderate to high on progression of coronary alterations.
Abstract 14132: Thirty-Six Month Results in Patients With Resistant Hypertension After Endovascular Ultrasound Renal Denervation in the RADIANCE-HTN TRIO Trial
Authors: Michael J Bloch, Ajay J Kirtane, MICHEL AZIZI, Felix Mahfoud, Jan N Basile, Joost Daemen, Manish Saxena, Philippe Gosse, Kintur Sanghvi, Roland E Schmieder
Journal: Circulation (2023)

Background: Endovascular ultrasound renal denervation (uRDN) has been shown to reduce blood pressure (BP) and medication burden in patients with resistant hypertension in the multicenter, blinded, randomized, sham-controlled RADIANCE-HTN TRIO trial through 6 months. We report the 36-month safety and durability of treatment effect on office BP (OBP) in the patients treated with uRDN. Methods: Patients with hypertension resistant to a 3-drug single-pill confirmed by daytime ambulatory BP ≥135/85 mmHg were randomized to uRDN (n=69) or sham procedure (n=67). From 2-5 months, if monthly home BP was ≥135/85 mmHg, prespecified standardized stepped-care antihypertensive treatment including an aldosterone antagonist (AA) was started under blinding to treatment assignment. After 6 months, patients were unblinded and received antihypertensive medications (AHM) at treating physicians’ discretion. We assessed changes in OBP of the uRDN group at 36 months vs. baseline and screening. Results: Forty-nine of 69 (71%) patients (age: 53.0 ± 7.4 years; 18% female) originally randomized to uRDN completed their 36-month follow-up. OBP at screening in those patients was 159/103 ± 15/10 mmHg on a mean of 3.9 AHM with 33% of patients on AA. Baseline OBP after starting the single-pill combination was 153/99 mmHg. At 36 months OBP changed by -14.5/-9.0 mmHg from screening (p&lt;0.001 for both) and -8.0/-5.0 mmHg from baseline (p=0.007; p=0.02) on a mean of 3.7 AHM with 41% of patients on AA. At 36 months, OBP change from baseline was irrespective of whether or not patients were taking AA. Given ambulatory BP was used to qualify patients at baseline, some patients had OBP &lt;140/90 mmHg. For those with baseline OBP ≥140/90 (n=39), change in OBP at 36 months from baseline was -12.9/-7.4 mmHg (p&lt;0.001 for both) on mean 3.6 AHM. No new uRDN-related long-term safety concerns were identified. Conclusion: In patients with resistant hypertension, the effectiveness and safety of uRDN were durable to 36 months.
Abstract 18698: PCBP1 Regulates Alternative Splicing of Aars2 in Congenital Cardiomyopathy
Authors: Yao Wei Lu, Zhuomin Liang, Haipeng Guo, Tiago Fernandes, Ramon Espinoza-Lewis, Tingting Wang, Kathryn Li, Xue Li, Gurinder B Singh, Yi Wang, Douglas B Cowan, John D Mably, Caroline C Philpott, Hong Chen, Da-Zhi Wang
Journal: Circulation (2023)

Rationale: Alanyl-transfer RNA synthetase 2 (AARS2) is a nuclear encoded mitochondrial tRNA synthetase that is responsible for charging of tRNA-Ala with alanine during mitochondrial translation. Homozygous or compound heterozygous mutations in the Aars2 gene, including those affecting its alternative splicing, are linked to congenital cardiomyopathy in humans. However, the underlying molecular mechanism of how Aars2 regulates heart development remains unknown. Hypothesis: The alternative splicing of Aars2 and its function is essential for cardiac development. Methods and Results: We found that alternative splicing of the Aars2 transcript is mediated by poly(rC) binding protein 1 (PCBP1), an RNA binding protein, through direct interaction. Cardiomyocyte-specific deletion of Pcbp1 in mice resulted in defects in heart development that are reminiscent of human congenital cardiac defects, including noncompaction cardiomyopathy and a disruption of the cardiomyocyte maturation trajectory. Loss of Pcbp1 led to an aberrant alternative splicing and a premature termination of Aars2 in cardiomyocytes. Therefore, Pcbp1 is critical for the expression and function of Aars2. Additionally, Aars2 mutant mice with exon-16 skipping recapitulated heart developmental defects observed in Pcbp1 mutant mice. Mechanistically, we found dysregulated gene and protein expression of the oxidative phosphorylation pathway in both Pcbp1 and Aars2 mutant hearts; these data provide further evidence that the infantile hypertrophic cardiomyopathy associated with the disorder oxidative phosphorylation defect type 8 (COXPD8) is mediated by Aars2. Conclusion: Our study therefore identifies Pcbp1 and Aars2 as critical regulators of heart development and provides important molecular insights into the role of disruptions in metabolism on congenital heart defects.
Abstract 14222: Annual Vascular and Bleeding Outcomes in East Asian Poststenting Patients With Acute Coronary Syndrome: The BRIC-ACS II Trial
Authors: dandan li, Yundai Chen, Yani Yu, Xiaodan Tuo
Journal: Circulation (2023)

Objective: To determine the incidence of bleeding and thrombotic vascular events in the "real-world"acute coronary syndromes (ACS) Chinese patients over 1-year following stent implantation. Background: The balance between vascular and bleeding outcomes during dual antiplatelet therapy (DAPT) is a matter of considerable controversy, especially in Asian populations. In contrast to Europeans, Chinese patients experience more bleeding but less thrombotic events over aggressive DAPT with ticagrelor than after conventional clopidogrel. Methods and Results: From November 2017 till April 2020 we enrolled post-stenting ACS patients (n=5,515) from 30 tertiary hospitals with the strict 1-year follow-up (n=5.150). Only few 153(3.0%) patients developed MACE (a composite of all-cause death, myocardial infarction, ischemic stroke, or urgent coronary revascularization). The cumulative incidence of annual bleeding (BARC ≥2) was 5.8% (298/5150) among patients who completed 1year follow-up.The BARC ≥2 bleeding was almost twice higher 298 (5.8%) and was not associated with worsened MACE [CI:0.37 -1.67; P =0.52). Patients treated with ticagrelor (n=1620, 6.0%) had a significantly increased risk of bleeding than those treated with clopidogrel (n=2331; 4.1%) (HR=1.486; 95% CI:1.12-1.97; P=0.006), but similar risk of vascular MACE (2.7% vs 2.8%; HR= 0.94; 95% CI:0.64-1.38; P = 0.747).The factors independently associated with the comprehensive risk of BARC ≥2 bleeding and MACE , including female gender, renal insufficiency, peptic ulcer, atrial fibrillation, continuous use of ticagrelor and non-continuous DAPT. The discrimination of the nomogram model was further tested by the ROC curve (AUC value:0.610 (95% CI, 0.577-0.642 )). Conclusions: The annual incidence of BARC≥2 bleeding in ACS patients treated with PCI in China was almost twice higher (5.8%) than MACE (3.0%). DAPT with ticagrelor increased the bleeding rates with no trend towards MACE reduction. The trial was registered at the clinnicaltrials.org as NCT03402711.This study was sponsored by Sanofi.
Abstract 13308: Characteristics of Participants Enrolled in a Randomized Controlled Trial Evaluating Vitamin D Normalization on Major Adverse Cardiovascular-Related Events: The Target-D Trial
Authors: Heidi T May, Viet T Le, Daniel Babcock, Libby Wayman, Heather Maestas, Jeffrey L Anderson, Benjamin D Horne, Tami L Bair, Kirk U Knowlton, Stacey Knight, Joseph B Muhlestein
Journal: Circulation (2023)

Background: Many observational studies have reported associations between low 25-hydroxyvitamin D (25[OH] vit D) levels and adverse cardiovascular (CV) outcomes. Recent randomized clinical trials have not found vitamin (vit) D 3 supplementation to reduce CV risk. However, these trials gave “blanket” doses regardless of 25[OH] vit D level, with none having "treated to target". We are performing the first study where subjects are prescribed vit D 3 supplementation based on individual 25[OH] vit D levels. Methods: The purpose of Target-D (NCT: 02996721) is to determine if achieving 25[OH] vit D levels &gt;40 ng/mL among myocardial infarction (MI) patients will result in a reduction of adverse CV events. Subjects meeting study criteria from April 2017 to May 2023 were randomized to receive standard of care or clinical management of 25[OH] vit D levels. The treatment arm received targeted vit D 3 supplementation based on a dosing algorithm. Target-D is an event-driven trial that will conclude when 104 primary outcome events (composite of death, MI, heart failure hospitalization, and stroke) have occurred. Results: The study consort diagram is shown in Figure. Patient characteristics are shown in Table. Baseline 25[OH] vit D levels were 26.8±12.7 (median: 25) and were similar between arms (Table). Among those randomized to the treatment arm with a 25[OH] vit D levels &lt; 40, 58.5% of patients began vit D 3 dosing at 5000 IU. Conclusions: Average baseline 25[OH] vit D levels were deficient in Target-D participants. The discrepancy in findings between observational and randomized trials of vit D may be due to the inability of vit D 3 supplementation doses to achieve therapeutic 25[OH] vit D thresholds. Target-D will evaluate if it is the level of serum 25[OH] vit D achieved that provides CV benefit and not necessarily the vit D 3 supplementation dose that is received. It is anticipated that the number of events needed for this event-driven trial will be achieved by May 2024.
Abstract 13334: Safety of Chest Compressions in Patients With a Durable Left Ventricular Assist Device
Authors: Balimkiz Senman, Jacob Pierce, VERAPRAPAS KITTIPIBUL, Stephanie Barnes, Bryner Benjamin, Meredith Whitacre, Jason N Katz
Journal: Circulation (2023)

Introduction: The safety of chest compressions (CC) during cardiopulmonary resuscitation (CPR) among pts with a durable left ventricular assist device (LVAD) is an area of controversy. Concerns regarding device malfunction or dislodgment with CC may result in significant delays or the withholding of life-sustaining intervention entirely. Current societal guidelines, based on small case reports, suggest that manual CC are probably not harmful, but offer no additional guidance. Furthermore, they acknowledge that there are no data regarding the use of machine-assisted CC. Methods: We retrospectively reviewed medical records of consecutive pts who underwent durable LVAD implantation at Duke University from 2013-2022. Charts were searched for “code”, “arrest”, “compressions”, and “rapid response team” to identify all instances of cardiac arrest (CA). Baseline pt characteristics, details of the arrest (including CC details), in-hospital care processes, and pt outcomes were abstracted. Results: Of 750 pts reviewed, 58 (mean age 64 years, 76% male, median LVAD support duration 19 months) had documented CA. Fifteen (26%) pts presented with an out-of-hospital CA. Twenty-four (41%) pts did not receive CC. The most commonly reported reason for avoiding CC was “LVAD in place - contraindicated.” The CPR duration was longer among those who received CC (median 30mins, range: 1-120 mins) than those who did not (median 20 mins, range: 2-79 mins). Two pts had support from a Lund University Cardiac Assist System (LUCAS) device. Among those who survived either manual and machine-assisted CC, 27% had a post-arrest TTE and none showed evidence of LVAD malfunction/dislodgment. Conclusions: Among pts with a durable LVAD who underwent CPR for CA we found no evidence of device dislodgment or safety concerns associated with either manual or LUCAS-assisted CPR. Future multicenter and prospective evaluation is necessary to both confirm these findings and to inform the guidelines.
Abstract 14278: 14 Days of Severe, Sustained Normobaric Hypoxic Enhances Left Ventricular Contractility in Patients After Myocardial Infarction
Authors: Jan Hoenemann, Fabian Hoffmann, Henning Weis, Darius Gerlach, Vlad G Zaha, Hesham A Sadek, Hannes Reuter, Stephan Baldus, Alexander Drzezga, Frank Splettstoesser, Stilla Frede, Benjamin D Levine, Jens Jordan, Ulrich Limper, Jens Tank
Journal: Circulation (2023)

Studies in mice with experimental myocardial infarction revealed, that sustained severe normobaric hypoxia (FiO2=0.07) reactivates cardiomyocyte proliferation and improves left ventricular ejection fraction. Our study aimed to test safety and feasibility in humans and to assess whether hypoxia improves left ventricular contractility in selected patients with myocardial scars following myocardial infarction.Three males, who suffered myocardial infarction 49-126 months prior to study entry, whose capability for hypoxia acclimatization was validated previously and one healthy male control participated in this proof-of-concept study. After preacclimatization we induced severe hypoxia by adding nitrogen until alveolar oxygen partial pressure reached about 35 mmHg. Hypoxia was maintained for 14 consecutive days (FiO2=0.095) and nights (FiO2=0.105). We assessed ventricular function by echocardiographic-derived global longitudinal strain (LVGLS), serum NTproBNP, high-sensitive Troponin I levels, and marker of myocardial repair. Cardiac 18F-FDG-PET-MRI was done at baseline, end of hypoxia exposure, and at 30 days follow-up. LVGLS increased in prior viable myocardium, but also in areas adjacent to the myocardial scar (baseline: -12.57±2.4 %, end of hypoxia: -14.37±2.62% recovery day 3: -14.33±2.72%, 30 days follow-up: -15.2±3.11%, p=0.0182). NTproBNP tended to decrease (baseline: 189±134 pg/ml, end of hypoxia: 127±28 pg/ml, recovery day 3: 114±18 pg/ml, 30 days follow-up: 108±65 pg/ml). These parameters were not affected in the control. MRI-derived left ventricular enddiastolic volume remained unchanged, but end-systolic left ventricular volume decreased in patients (baseline: 108±49 ml, recovery day 3: 92±50 ml, 30 days follow-up: 101±47 ml, p=0.0068). Troponin I remained in the reference range in all participants. The patient with the most pronounced increase in LVGLS revealed a relevant increase in FDG-uptake at the follow-up, which was also observed in areas adjacent to the myocardial scar.Given the small sample size and the selection of patients, our results have to be interpreted with caution. However, the data indicate potentially beneficial hypoxia-mediated effects in selected patients with ischemic heart disease.
Abstract 13093: Impact of Digital Health Coaching on Older Individuals With Cardiometabolic Conditions
Authors: Jasmine Moore, Sarah Rutland, Vanessia Tran, Jane Murphy
Journal: Circulation (2023)

Introduction: Cardiometabolic conditions are top contributors to low health-related quality of life and early mortality. The multi-faceted care needed to manage these conditions can become more challenging as patients age. This analysis aimed to identify if a digital health coaching (DHC) program can improve how older adults manage their cardiometabolic conditions. Methods: This retrospective analysis included adults 55 or older who participated in a DHC program for at least 3 months. Participants were referred by an employer/payor program or physician. Participants enrolled in 1 of 4 cardiometabolic condition-specific programs: Weight Management, Type 2 Diabetes, Hypertension, or Dyslipidemia. To assess outcomes and impact of participation in DHC, changes in psychosocial and cardiovascular-related quality of life measures collected at baseline and month 3 were evaluated. Results: Of 1,290 adults enrolled in a cardiometabolic DHC program, 639 remained engaged and completed outcome measure surveys. Most participants were female (80%), and the study population was racially diverse: 52% white, 48% nonwhite. At 3 months, self-reported diabetes distress scores (2.36 to 1.9, P&lt;0.05) and weight (206.5 to 201.765, P&lt;0.05) improved. Depression (2.36 to 1.9, P&lt;0.05), stress (3.97 to 3.27, P&lt;0.05), and anxiety (0.86 to 0.73, P&lt;0.05) scores also improved. Conclusions: DHC participants improved clinical and psychosocial outcomes in 3 months in this outcome analysis. Engaging in DHC may help patients manage their cardiometabolic conditions and help improve their health-related quality of life.
Abstract 17089: In Hospital Cardiovascular Outcomes of Patients With End Stage Renal Disease and Septic Shock a Propensity Matched Analysis
Authors: Olubumi A Braimah, Abhiram Challa, Mohinder Reddy Vindhyal, Elizabeth Ablah
Journal: Circulation (2023)

Background: Sepsis affects approximately 1.7 million adults in the US every year, and progression to septic shock (SS) leads to an increase in cardiovascular disease (CVD) and a 26% increase in mortality. Patients with end stage renal disease (ESRD) on dialysis are at an increased risk of developing SS and CVD. The increase in mortality with SS is well established in the literature, however, there is limited data determining the impact of ESRD on SS. This study aims to identify the impact of ESRD on in-hospital mortality and CVD outcomes among patients with SS. Methods: The 2020 National Readmissions Database was analyzed. Patients with SS and ESRD were identified using relevant ICD-10 codes. Nearest propensity matching was conducted using a 1:1 ratio for several demographic, social and clinical variables. Subsequently, in-hospital outcomes were compared between patients with and without ESRD using t-test and chi-squared test as appropriate. Results: A total of 822,321 patients were included in this study, with a mean age of 65 years. Majority of patients in this study with and without ESRD respectively were male (54.39% and 50.83%, p &lt;0.001). In- hospital mortality for patients with SS, with and without ESRD, were 38.68% and 30.01%, respectively. Among patients with SS, mortality with and without ESRD was 38.36% and 30.01% (p &lt; 0.001) respectively. Other significant cardiovascular events among patients with and without ESRD, respectively were ischemic stroke (3.82% vs. 3.28%, p &lt;0.001), atrial fibrillation (11.85% vs. 10.2%, p &lt;0.001), Endocarditis (4.06% vs. 2.24%, p &lt;0.001), and acute diastolic heart failure (10.17% vs. 9.41%, p =0.001). Conclusions: SS in patients with ESRD is associated with an increased frequency of in-hospital mortality and worse cardiovascular outcomes when compared to patients without ESRD. Further research is needed to help establish and identify the causative factors in determining the association between SS and ESRD.
Abstract 17462: Angiotensin II-Mediated Suppression of Skeletal Muscle Autophagy via mTOR and FoxO3a Pathways
Authors: Fareed Sindi, Patrice Delafontaine, Tadashi Yoshida
Journal: Circulation (2023)

Background: Chronic skeletal muscle (SK.M) atrophy, cachexia, occurs in diseases such as congestive heart failure (CHF), which is associated with high levels of angiotensin II (Ang-II). We have shown that Ang-II infusion reproduces major aspects of CHF-induced SK.M atrophy and causes mitochondrial (MT) damage and dysfunction in SK.M. Ang-II also inhibits autophagy/mitophagy, and a combination of these effects likely causes accumulation of damaged MT, leading to SK.M atrophy. Hypothesis: Ang-II infusion suppresses autophagy in SK.M via activation of mTOR and inhibition of FoxO3a. Aim: To understand the molecular mechanisms whereby Ang-II inhibits autophagy/mitophagy in SK.M. Methods: 12 weeks old male FVB mice were infused with Ang-II (1.0 μg·kg -1 ·min -1 ) or saline via osmotic minipumps (ALZET 1007D) for 7 days (N=6). Expression of autophagic markers and FoxO3a target genes were analyzed in tibialis anterior muscles by western blotting (at d1 &amp; d7) and qPCR (at d4), respectively. Colchicine treatment was included in the analyses to assess autophagic flux in vivo . For statistical analysis Two-way ANOVA and t-test were used. Results: In the presence of colchicine, LC3 lipidation was decreased in Ang-II infused mice, indicating that Ang-II inhibits autophagy at the autophagosome formation step. Furthermore, Ang-II increased p62 and PINK1 and decreased BNIP3, suggesting that Ang-II-mediated reduction of autophagy causes disruption of damaged MT clearance via mitophagy. Mechanistically, Ang-II likely inhibits autophagosome formation via two pathways, mTOR and FoxO3a: Ang-II increased phosphorylation of mTOR at Ser2448 (p&lt;0.005) and its downstream target 4E-BP1 at Thr37/46 (p&lt;0.0005). Lastly, Ang-II increased phosphorylation of FoxO3a at Thr32 (p&lt;0.0005), associated with reduced mRNA expression of FoxO3a target genes, such as LC3B and BNIP3 (24% and 46% reductions, respectively). Conclusion: Ang-II inhibits autophagosome formation in SK.M via mTOR activation and FoxO3a inhibition. Suppression of autophagy via these pathways likely disrupts clearance of damaged MT, leading to SK.M atrophy. These results provide insights for future development of therapies for CHF-induced cachexia by targeting mTOR and FoxO3a pathways to restore autophagy.