tbuckley/cabot-search huggingface dataset:
Abstract 15439: Association of Vigorous Physical Activity With Cardiovascular Disease and Mortality in 136,766 Adults From High-Income, Middle-Income and Low-Income Countries: The Prospective Urban Rural Epidemiological (PURE) Study
Authors: Scott Lear, SIDONG LI, Sumathy Rangarajan, Salim Yusuf
Journal: Circulation (2023)

Background: It’s recommended adults get 150-300 minutes of moderate physical activity (MPA) and/or 75-150 minutes of vigorous physical activity (VPA) per week. Some studies have found high VPA to be protective and others found it to be harmful. These studies have been conducted in high-income countries using recreational VPA as the exposure of interest. Purpose: To evaluate the effects of VPA with all-cause mortality, and cardiovascular disease (CVD) in countries at different economic levels. Methods: Participants aged 35-70 years were recruited from 21 countries at various stages of economic development. Physical activity (total, walking, MPA, VPA, as well as recreational vs. non-recreational PA) was assessed using the International Physical Activity Questionnaire. Primary clinical outcomes were the composite of mortality plus major CVD (CVD mortality, myocardial infarction, stroke, or heart failure) and mortality. A total of 136,766 participants without baseline CVD, cancer, and HIV were analyzed. Models were adjusted for age, sex, urban/rural residency, country income level, education, household wealth index, smoking, baseline chronic diseases, physical impairments, MPA, walking and centre as a random effect. Results: During the median follow-up of 11.5 (8.6-12.4) years, there were 9846 deaths and 7900 major CVD events. The median min/wk (IQR) for total PA, walking, MPA and VPA were 690 (250-1530), 40 (0-420), 330 (75-860), 0 (0-0). The mean VPA was 103±390 min/wk. Compared to no VPA, 150-299 minutes per week of VPA was associated with reduced risk for the composite outcome and mortality, HR = 0.82 (0.73,0.92) and 0.74 (0.64,0.86), respectively. When VPA was stratified into either recreational or non-recreational VPA, recreational VPA displayed a U-shape relationship, such that higher levels were associated with less benefit. Increasing non-recreational VPA continued to confer reduced risk even above 3000 min/wk. At any amount of moderate PA, higher VPA was associated with reduced risk for the composite outcome and mortality. Conclusion: Higher levels of VPA were associated with reduced risk for mortality and major CVD events up to more than 40 times the minimum recommended amount. At no point did VPA confer an increased risk.
Abstract 12069: Impact of Atrial Fibrillation on Outcomes in Patients With Heart Failure With Reduced, Mildly Reduced and Preserved Ejection Fraction. A Systematic Review and Meta-Analysis of Published Studies
Authors: Garen Kroshian, Jacob Joseph, SCOTT KINLAY, Adelqui Peralta, peter hoffmeister, Jagmeet Singh, Matthew Yuyun
Journal: Circulation (2023)

Background: Atrial fibrillation (AF) is highly prevalent in patients with heart failure (HF), however the difference in outcomes between the HF sub-types is not well known. Contemporary classification of HF categorizes it into HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF). With the new designation of HFmrEF, there have been studies researching the risk profile of AF in the three HF categories, however there is not yet a unifying statement on these data. Aim: Systematic review and meta-analysis aimed to determine if there are any significant differences in AF-associated all-cause mortality (primary endpoint), heart failure hospitalizations, cardiovascular mortality, and stroke (secondary endpoints) between HFrEF, HFmrEF, and HFpEF. Methods: A systematic search of PubMed, EMBASE, and Cochrane Library databases until February 28 th , 2023, identified studies reporting clinical outcomes linked to AF by HF category status. Data were combined using D+L random effects model. Results: The review included 21 studies comprising 238,107 patients. Pooled AF prevalence: 32% in HFrEF, 38% in HFmrEF, and 43% in HFpEF. AF was associated with a higher risk of all-cause mortality in HFmrEF and HFpEF only (Figure for pooled hazard ratio (HR) and 95% CI). AF associated with a higher risk of HF hospitalizations, in the total population (HR=1.29, 95% CI=1.14-1.46), HFmrEF (HR=1.64, 95% CI=1.20-2.24), and HFpEF (HR=1.46, 95% CI=1.17-1.83), but not HFrEF (HR=1.01, 95% CI=0.87-1.18). AF was only associated with cardiovascular mortality in the HFpEF subcategory but was associated with stroke in all three HF subtypes. Conclusion: AF was associated with a higher risk of all-cause mortality and heart failure hospitalization in HFmrEF and HFpEF only. As treatment guidelines for AF in HFmrEF are limited, the benefit of treatments to control AF in this subgroup should be further investigated.
Abstract 14841: Higher Than Daily RDA Recommended Vitamin D <sub>3</sub> Dosing and Multiple Titrations Are Required to Achieve &gt;40 ng/mL 25-hydroxy Vitamin D Levels in Acute Coronary Syndrome (ACS) Participants Enrolled and Randomized to Targeted Vitamin D Treatment: The Target D Trial
Authors: Viet T Le, Daniel Babcock, Libby Wayman, Heather Maestas, Jeffrey L Anderson, Kirk U Knowlton, Joseph B Muhlestein, Heidi T May
Journal: Circulation (2023)

Background: Low vitamin (vit) D serum levels in observational data are associated with increased cardiovascular (CV) events. Prevalence of vit D deficiency (≤20 ng/mL) in the USA is estimated at 40%. Meanwhile, doses for USA recommended dietary allowance (RDA) are 600-800 IU. Several randomized trials of vit D therapy did not use serum levels to target dosing, rather utilized doses from 2000 to 4000 IU daily. The Target-D trial utilizes an achieved vit D serum (&gt;40 ng/mL) strategy. We provide an initial overview of dosing and titration to achieve vit D serum levels &gt;40 ng/mL. Methods: Target-D (NCT: 02996721), a randomized event-driven trial, enrolled (April 2017-May 2023) a total of 632 (316/arm) acute coronary syndrome (ACS) patients to targeted vit D 3 treatment or standard of care. Vit D 3 supplementation was based on a dosing algorithm (Table 1). For baseline serum vit D &gt;40, no supplementation is given, and participants return at 12-months for reassessment. Those with a baseline serum vit D ≤40, the algorithm is applied, and participants return in 3-month intervals for assessment and dosing adjustment, until levels are &gt;40 ng/mL. Results: Of the 316 (62.8±11.3 yrs, 23.1% female, 90% white) treatment participants, 89.4% (n=279) required vit D 3 dosing. Mean serum vit D was 25.9±11.5 ng/mL (median: 24, range: 5-84). Table 2 shows the percent of participants achieving &gt;40 ng/mL at each interval by dose. Only 13.5% of participants were able to achieve &gt;40 ng/mL using &lt; 2000 IU, 20.8% needed 3000-4000 IU, 51% needed 5000-8000 IU, and 14.6% required &gt; 10,000 IU. Conclusions: At our center, ACS patients have low serum vit D levels. Participants randomized to vit D 3 required doses well above US daily RDA, with 86.5% requiring &gt;2,000 daily and 14.6% requiring &gt; 10,000 IU. Less than 65% achieved &gt;40 at 3 months, another 25% required 6 months. Contemporary vit D studies may have underdosed study participants, potentially achieving treatment serum levels less than “therapeutic”.
Abstract 13204: Single-Nucleus Multiomic Analyses Identifies Gene Regulatory Dynamics of Phenotypic Modulation in Human Aneurysmal Aortic Root
Authors: Qingyi Zeng, Xuanyu Liu, Zhou Zhou
Journal: Circulation (2023)

Introduction: Aortic root aneurysm is a potentially life-threatening condition because it may lead to aortic rupture. However, a single-nucleus transcriptomic and epigenomic landscape in the aortic root tissue of humans is lacking, and the regulatory mechanism of pathogenesis in aneurysmal aortic root remains elusive. We sought to identify molecular triggers for aortic root aneurysm in Marfan syndrome patients. Methods: Aneurysmal aortic root tissues from MFS patients (n=6) and normal aortic root tissues from age-matched, heart transplantation recipients (n=6) were collected. Samples from four subjects of each group were individually subjected to single-nucleus multiomic sequencing (gene expression and chromatin accessibility). Spatial transcriptomic assays were applied to aortic root tissue sections from two subjects of each group. Results: The single-nucleus dataset revealed three subclusters for the vascular smooth muscle cells (VSMCs) lineage including contractile VSMC1 (expressed a high level of RYR2 ), modulated VSMC2 and VSMC3(expressed a high level of CFH ). Statistically significant expansion of the modulated VSMCs was observed in MFS patients. In addition, the modulated VSMCs are not only associated with the diseased states but also associated with the spatial location. The modulated VSMCs are preferentially located in the inner layer of the tunica media close to the intima in both healthy and diseased conditions. Based on the evidence from comparative analyses, we obtained 11 candidate key regulators (such as FOXN3, TEAD1, and BACH1) that potentially drive the phenotypic modulation of VSMCs and the pathogenesis of aortic root aneurysms. The experimental evidence supporting that the forkhead transcription factor FOXN3 may function as a key regulator for maintaining the contractile phenotype of human aortic VSMCs, whose expression decreased during phenotypic modulation and was downregulated in MFS VSMCs. Conclusions: We present the first atlas of gene expression and chromatin accessibility in human aortic root tissue at single-nucleus and spatial resolution. FOXN3 was identified as a novel key regulator for maintaining the contractile phenotype of human aortic VSMCs, which may serve as a potential therapeutic target.
Abstract 18831: The Protective Effect of Duffy Antigen Receptor for Chemokines Gene Deletion on Abdominal Aortic Aneurysm Formation: Role of Lysyl Oxidase
Authors: Ghaith Aboud, Ragheb Harb, David Kim, Brandee Goo, Mourad OGBI, Praneet Veerapaneni, Ronnie Chouhaita, Philip Coffey, Richard Lee, Tyler W Benson, Phillip P Owens, Vladimir Bogdanov, Avirup Guha, Hong Shi, Ha Won Kim, Neal L Weintraub
Journal: Circulation (2023)

Introduction: Epidemiologic studies indicate that Blacks are protected against abdominal aortic aneurysm (AAA), despite similar risk factors as Caucasians. Approximately 70% of Blacks harbor a variant in the Duffy Antigen Receptor for Chemokines (DARC), a non-signaling receptor expressed primarily on erythrocytes which binds and regulates inflammatory chemokines. Since chemokines play a critical role in AAA, we tested the hypothesis that lack of DARC expression on erythrocytes protects against AAA, and we investigated the mechanisms. Methods: Mice lacking DARC on hematopoietic cells were created by mating DARC flox/flox mice with Vav1-Cre mice. At 10-14 weeks of age, both Vav1-Cre positive (DARC HKO ) and Vav1-Cre - mice [wild type (WT) littermate controls] received PCSK9 adeno-associated virus injection and were started on high fat diet. After 1 week, mice were infused with angiotensin II (AngII, 1,000 ng/kg/min) via osmotic minipump for 26 days to induce AAA. Results: Compared to WT, there was no difference in blood pressure or cholesterol levels in AngII-infused DARC HKO mice, which were confirmed to lack DARC on erythrocytes by flow cytometry. Aortic diameter and AAA incidence were significantly decreased in DARC HKO compared to WT mice (n=16-20, p=0.0257), in conjunction with reduced elastin degradation and macrophage infiltration. We did not find differences in levels of DARC-bound chemokines that could account for the protection against AAA. Interestingly, we found that the level and activity of lysyl oxidase (LOX), a cytokine-like enzyme that crosslinks extracellular matrix proteins and protects against AAA, were higher in DARC HKO mice compared to WT mice. Conclusions: Loss of DARC on hematopoietic cells protects against AAA formation, likely by upregulating aortic LOX. These findings provide novel insight into ethnic differences in susceptibility to AAA.
Abstract 18832: Early Leadless Pacemaker Implantation in a Case of Severe Cervical Spinal Cord Injury
Authors: Jude ElSaygh, Laura Bradel, Jeremy Berman
Journal: Circulation (2023)

Introduction: Bradycardia is a frequent cause of morbidity and mortality in spinal cord injury (SCI) patients and optimal timing of permanent pacemaker implant is unclear. Case Summary: A 67-year-old female with no cardiac history was admitted for fall of uncertain etiology complicated by severe cervical SCI and neurogenic shock. Despite emergent surgical decompression, the injury resulted in quadriplegia. Post-operatively, bradycardic arrest occurred requiring resuscitation and dependence on dopamine infusion. Rhythm strip from showed p-p slowing followed by high grade atrioventricular block with multiple blocked p waves. A decision was made for early intervention with implantation of a Micra leadless pacemaker (LPM) (Medtronic, Minneapolis, MN) for both hemodynamically significant bradycardia and backup to prevent bradycardic arrest. A LPM was successfully implanted without complication on hospital day 8. The pacemaker was set to VVI 60. Post operatively, the patient required intermittent pacing and tolerated dopamine weaning. Discussion: Bradycardia in SCI patients, especially those with high cervical and complete SCI, occurs due to unopposed parasympathetic activity, resulting in baseline sinus bradycardia. Even more concerning is the risk for sudden and unpredictable sinus arrest and/or AV block, which is a leading cause of mortality in the first year after SCI. While initial management of bradyarrhythmia in SCI patients may respond to pharmacologic intervention, temporary and/or permanent pacing may be indicated. Acute SCI patients may not be ideal candidates for traditional pacemakers since ICU and infectious complications are common in this cohort, but LPMs have extremely low risk of implant site and infectious complications and can be utilized earlier in the hospital course. Our case showcases this strategy of early leadless pacemaker implantation. Further study is needed to better evaluate the safety and efficacy of this strategy.
Abstract 16427: Despite Machine Learning Models, QRS Duration Remains the Superior ECG Criterion for Predicting Left Ventricular Dilation in Patients With Left Bundle Branch Block
Authors: Ashley DeBauge, Christopher Harvey, Tyan Fairbank, Sagar Ranka, Sania Jiwani, Seth Sheldon, Madhu Reddy, Amit Noheria
Journal: Circulation (2023)

Introduction: The utility of ECG to diagnose left ventricular (LV) dilation in patients with left bundle branch block (LBBB) is not known. We sought to compare the diagnostic yield of ECG using (i) QRS duration, (ii) published LVH criteria, and (iii) machine learning (ML) models to detect increased left ventricular end diastolic volume indexed (LVEDVi) in the setting of LBBB. Hypothesis: ML is superior to QRS duration and LVH criteria to detect increased LVEDVi among LBBB. Methods: 12-lead ECGs were processed to reconstruct orthogonal X, Y, Z leads using Kors’s matrix and obtain root-mean-squared (3D) ECG. R wave, S wave and overall amplitudes, voltage-time-integrals (VTIs), and other ECG features were extracted from all ECG leads. ML algorithms [logistic regression (LR), support vector classifier (SVC), decision trees (DT), random forest (RF), gradient boosted machine (GBM) and boosted trees (BT)] were trained to predict increased LVEDVi (women &gt;61 mL/m 2 , men &gt;74 mL/m 2 ) from ECG features on a training set of 2668 ECGs with typical LBBB and echocardiogram within 45 days before or after ECG. LVEDV was measured using ASE biplane method of discs. We obtained ROC AUCs for prediction of increased LVEDVi by (i) QRS duration, (ii) published LVH criteria, and (iii) ML models in a separate validation set of adults with typical LBBB. Results: Among the validation set of 413 adults (53% women, age 73±12 yr) with LBBB, QRS duration alone had a higher AUC (women 0.668, men 0.699) for diagnosing increased LVMi compared to standard LVH criteria (Table). The best ML model (RF with overall AUC 0.694) did not substantially outperform QRS duration alone. Conclusions: In patients with LBBB, QRS duration ≥150 in women and ≥160 in men is a superior predictor of LV dilation than traditional ECG-based LVH criteria, with no additional value added by ML methods.
Abstract 15800: Evaluating the Correlation Between Right Ventricular Outflow Tract Dimensions and Arrhythmia Risk Following Self-Expanding Transcatheter Pulmonary Valve Replacement
Authors: Natalie Soszyn, Gabriel Yuen, Salvador A Rodriguez Franco, Gareth J Morgan, Jenny Zablah
Journal: Circulation (2023)

Introduction: The introduction of self-expanding valves has allowed for an expanded range of patients who can be treated with transcutaneous pulmonary valve replacement (TPVR). Though major complications are rare, ventricular tachycardia has been reported following self-expanding valve placement prompting investigation of potential risk factors. Hypothesis: Significant variation in valve dimensions within the right ventricular outflow tract (RVOT) throughout the cardiac cycle is postulated as a cause for increased arrhythmia risk. We hypothesized that greater dynamic variation of the valve in the RVOT correlates to higher ventricular arrythmia risk. Methods: A single center review was performed of patients who underwent TPVR with either Harmony TPV or Alterra Pre-stent with subsequent placement of 29mm Sapien valve between 2019 and 2023. Using post-procedural 3D rotational angiography, minimum (systole) and maximum (diastole) diameters (mm), perimeter (mm) and cross-sectional area (mm 2 ) of the valve frame were measured in two locations: closest to the branch pulmonary artery bifurcation and the RV cavity. Results: Twenty-eight patients were included (14 Harmony TPV, 14 Alterra). Higher frequency of ventricular arrythmia was seen in patients with congenital pulmonary stenosis ( p =0.004). Higher ventricular arrythmia rate was associated with larger diastolic diameter (34.1 vs 33.2mm, p =0.04), mean perimeter (118.3 vs 108.6mm, p =0.03) and area (1124.5 vs 926.2mm 2 , p =0.03) of the valve frame closest to the RV cavity. Conclusions: Increased movement of the valve frame close to the RV cavity may correlate with a higher ventricular arrythmia risk due to increased contact with the native RVOT throughout the cardiac cycle. Future studies should focus on more accurate, mathematical methodology to better understand whether the complex interaction between self-expanding valves and the native RVOT is a determinant for post-procedural ventricular arrythmia.
Abstract 17001: Enhancing Coronary Functional Angiography: Integrating Doppler-Based Left Circumflex Coronary Flow Reserve in Assessment
Authors: Namrita Ashokprabhu, Yulith Roca Alvarez, Christian Schmidt, Lauren Thompson, Michelle Hamstra, Timothy D Henry, Odayme Quesada
Journal: Circulation (2023)

Background: Coronary microvascular dysfunction (CMD), predominantly affecting women is associated with poor outcomes and has limited diagnostic options. Coronary functional angiography (CFA) is used for diagnosing CMD in patients with refractory angina and no obstructive coronary artery disease (ANOCA). The assumption is that endothelial-independent CMD is a homogenous disease process, therefore current gold-standard for diagnosis is measure of coronary flow reserve (CFR) in the proximal left anterior descending artery (LAD). However, there is limited data on CFR in the left circumflex (LCx). Objective: Examine the benefits of measuring CFR using Doppler-tipped guide wire in LCx in addition to proximal LAD. Methods: Examined 191 ANOCA patients with Canadian Cardiovascular Society (CCS) class 3 or 4 angina despite optimal medical treatment who underwent CFA for assessment of CMD. CFR measurements were obtained using Doppler-tipped guidewire during the administration of 72 mcg of adenosine in both the proximal LAD and LCx and CFR of &lt;2.5 was used to define CMD. Results: 191 patients underwent CFA including 91% female with a median age of 59 years (IQR: 50, 67). The correlation in CFR measurements between the proximal LAD and LCx was 0.610 (p&lt;0.001). 149 (78%) patients had concordant results including 113 (59%) with abnormal CFRs and 36 (19%) with normal CFRs in both vessels. 12 (6%) had abnormal proximal LAD CFR and normal LCx CFR; and 30 (16%) had an abnormal LCx CFR and normal proximal LAD CFR and would have gone undiagnosed without measuring LCx CFR. Conclusion: The addition of LCx CFR measurement to the current standard CFA protocol using the Doppler guidewire improves diagnosis of CMD in patients. Further studies are needed to evaluate a comprehensive assessment of CMD including measurement of LCx CFR.
Abstract 14168: A Randomised Open-Label Controlled Trial of a Remote Cardiac Rehabilitation System With Wearable Medical Devices - An Interim Report of the TELE-REHA Trial
Authors: Atsuko Nakayama, NORIKO ISHII, Kentaro Hori, Azusa Yoshida, Mitsuaki Isobe
Journal: Circulation (2023)

Introduction: Outpatient cardiac rehabilitation (CR) prevents recurrence after cardiac surgery or cardiac catheterisation, but participation rate of outpatient CR is low. Although attempts at remote CR have been investigated with advances in equipment, they have not yet reached the stage of social implementation, and it is not clear whether remote CR can be an alternative to outpatient CR. Objective: The aim of this study was to confirm the safety and efficacy of remote CR management using wearable devices feasible in Japan, and to implement the device early in society. Primary outcome: All-cause death, cardiovascular events, EFs, e/e', BNPs, CRPs, PeakVO2, VE-VCO2 slop, muscle mass; secondary outcome: EQ5D. Subjects: Patients discharged home after hospitalization for cardiovascular diseases. Study design: A single-centre, randomised, open-label, parallel-group study was conducted to evaluate the efficacy and safety of wearable device (Apple Watch)-based Remote-CR versus Outpatient-CR. In Remote-CR group, ECG and SpO2 are measured by Apple Watch before and after exercise. Biweekly health information, weight, blood pressure, heart rate, electrocardiogram (ECG) and EQ5D are automatically transmitted by the app. Tele-nursing was provided by trained nurses on a bi-weekly basis, based on the health information provided by the app. For both groups, the intervention period was 90 days, and blood sampling, ECG, cardiopulmonary exercise testing (CPX), and body composition testing were performed at the end of the study. Results: A total of 110 cardiovascular patients were randomly divided into Remote-CR group and Outpatient-CR group. The background of the two groups was similar. Though the PeakVO2 and EQ5D scores after the CR program were not significantly improved in Outpatient-CR group, those were significantly improved in Remote-CR group (P=0.02). The dropout rate from CR program was lower in Remote-CR group than Outpatient-CR group. No significant incident occurred in both group. Conclusions: Remote-CR is expected to be as effective as Outpatient-CR and safe for patients after cardiac treatment, and can provide a relapse prevention programme for those who are difficult to attend.