bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4135629: Grades and trends from the 2024 United States Report Card on Physical Activity for Children and Youth
Authors: Webber-Ritchey Kashica , Staiano Amanda , Bai Yang , Dodson Elizabeth , Dooley Erin , Forseth Bethany , Greenberg Jayne , grimes amanda , Hasson Rebecca , Hibbing Paul , Pate Russell , Serrano Natalicio , Stanish Heidi , Jiang Qianxia , Spring Katherine , Fox Andrew , Moon Mallory , Steel Chelsea , Carlson Jordan
Published: November 2024

Background:
Regular physical activity provides numerous health benefits including improved cardiovascular health. Population-level physical activity surveillance is critical for informing research, practice, and policy efforts for supporting population health and health disparities. The United States Report Card on Physical Activity for Children and Youth addresses physical activity surveillance needs by integrating data from numerous sources capturing levels of physical activity and related behaviors (e.g., sedentary behavior, sleep), and facilitators and barriers for physical activity among United States youth. The 2024 Report Card is the 5
th
and decennial iteration in the series, released October 2024.

Methods:
A Report Card Working Group was assembled under the auspices of the Physical Activity Alliance and National Physical Activity Plan. Members reviewed the evidence for 11 indicators using data from nationally representative surveys and assigned grades. Data were examined for the overall population and, when possible, by age, sex, race/ethnicity, and disability subgroups. A standardized grading rubric was used to assign a letter grade to each indicator ranging from A to F. Trends in key benchmarks over time were examined since the first report card (2014) or earliest available data.

Results:
Sufficient data were available to assign grades for 8 of the 11 indicators. The assigned grades ranged from B- to F, with overall physical activity levels earning a D- (Table 1). No indicators improved since 2014. Five indicators - overall physical activity, organized sport participation, active transportation, sedentary behaviors, and school - worsened since 2014.

Conclusions:
The compiled surveillance report indicates generally poor grades and concerning trends over the recent decade. These findings highlight opportunities to improve physical activity levels and resources for supporting cardiovascular health among United States youth. Policy approaches are needed to combat societal factors that interfere with physical activity. Gaps in data availability, specificity, and quality point to needs for improved surveillance to track impacts. The 2024 Report Card can be a tool for supporting advocacy of regular physical activity at the national and local level.
Abstract 4135630: Improving Cardiac Rehab Referral and Enrollment Post-Percutaneous Coronary Intervention Through a Workflow Intervention at the Minneapolis VA: A Quality Improvement Study
Authors: Mohama Danny , SUBLETT LAURIE , Florea Viorel , Ferguson Jennifer , Lindquist Eric
Published: November 2024

Introduction:
Cardiac rehabilitation (CR) is a Class 1A recommendation post-percutaneous coronary intervention (PCI), yet it remains underutilized. At the Minneapolis VA, the referral and enrollment rates for CR post-PCI are significantly below the national goal of 70%, indicating a need for improved strategies to enhance veteran participation.

Research Questions:
This study investigates the impact of a workflow intervention on CR enrollment rates and seeks to understand how staffing changes may influence these rates. It also explores the potential for advanced practice providers to affect CR enrollment.

Aim:
We aim to increase CR enrollment to 40% and referrals to 50% post-PCI at the Minneapolis VA by August 2023, utilizing a nurse practitioner dedicated to interventional cardiology patients post-PCI.

Methods:
Utilizing the VA CART database, demographic data for patients undergoing PCI between October 2017 and August 2023 were analyzed, excluding those who died within 30 days of PCI. CR referrals within 90 days and enrollments within one year were tracked. Statistical process control charts were used to detect variations in referral and enrollment rates, with a t-test determining significance. The staffing change intervention occurred in May of 2020.

Results:
The intervention led to a significant increase in both referral and enrollment rates. The average monthly referral rate rose from 24% to 37%, and the enrollment rate from 14% to 28%. A statistical process control chart indicated special cause variation in the sample after the intervention, suggesting meaningful change. Statistical analysis confirmed these increases as significant (p<0.001).

Conclusion:
The staffing intervention at the Minneapolis VA significantly improved CR referral and enrollment rates post-PCI. This suggests that dedicated cardiac care providers can play a crucial role in enhancing CR utilization, potentially informing future quality improvement initiatives.
Abstract 4135636: Age- and Sex-Related Coronary Atherosclerosis by Artificial Intelligence Quantitative Coronary CT Angiography from the INVICTUS Registry
Authors: Matsuo Hitoshi , Sobue Yoshihiro , Kaneko Umihiko , Sato Hideyuki , Fujimoto Shinichiro , Nozaki Yui , Kajiya Takashi , Miyoshi Toru , Ichikawa Keishi , Abe Mitsunori , Kitagawa Toshiro , Ikenaga Hiroki , Osawa Kazuhiro , Saji Mike , Iguchi Nobuo , Nakazawa Gaku , Takahashi Kuniaki , Ijichi Takeshi , Mikamo Hiroshi , Kurata Akira , Moroi Masao , iijima raisuke , Crabtree Tami , Min James , Earls James , Nakanishi Rine
Published: November 2024

Background:
Coronary plaque analysis using artificial intelligence quantitative coronary CT (AI-QCT) is a promising tool to identify coronary atherosclerosis. However, there is insufficient data on coronary atherosclerosis volume and morphology using AI-QCT in patients who are at high risk of atherosclerosis. The purpose of this study is to clarify the differences in the volume and phenotypes of coronary atherosclerosis by age and gender using AI-QCT.

Methods:
The INVICTUS Registry is a multi-center registry enrolling patients who clinically underwent coronary CT angiography and invasive coronary angiography with invasive imaging modalities in Japan. Patients with a history of percutaneous coronary intervention or coronary artery bypass graft were excluded in this study. Using AI-QCT, the volume, and phenotypes (calcified, non-calcified, low-density non-calcified plaque [LD-NCP]) of coronary atherosclerosis were analyzed and assessed by age (<55, 55-64, 65-74, and 75 and older) and gender.

Results:
A total of 982 patients were enrolled in the study. The mean age was 70.3 ± 10.8 years, 71.9% were male. Approximately two-thirds of patients had hypertension (73.3%) and dyslipidemia (71.5%), and 36.7% had diabetes. Mean total plaque volume (PV), calcified PV, non-calcified PV, and low-density PV were 745.5±529.8 mm
3
, 248.3±302.0 mm
3
, 482.2±340.6 mm
3
, and 15.0±29.4 mm
3
, respectively. The results of plaque volume and phenotypes by age are shown in the figure. Compared to those under 55 years of age, total PV increased gradually and significantly by about 10% for every 10 years of age (p=0.022). Though no significant difference was observed in non-calcified PV between the age groups (p=0.379), calcified PV progressively and significantly increases approximately 70% for every 10 years of age (p<0.001). In contrast, the low-density plaque volume showed a trend toward a significant decrease with increasing age (p=0.073). These trends did not differ by gender.

Conclusion:
In a large cohort of patients at high risk for atherosclerosis analyzed by AI-QCT, total coronary PV increased with age, primarily calcified PV. While no change in non-calcified PV between the age groups, LD-NCPV was likely to decrease with increasing age. These findings may contribute to the guidance for the prevention of coronary artery diseases based on coronary atherosclerosis phenotype by age and gender.
Abstract 4135662: Dietary Inulin Improves Glucose Metabolism and Energy Balance in Obese Mice via Adipocyte Free Fatty Acid Receptor 2 (FFAR2)
Authors: May Karolline , Lee Angel , Wang Shari , Bryan Caeley , Blaser Martin , Layden Brian , Morton Gregory , Den Hartigh Laura
Published: November 2024

Background:
Inulin is a non-digestible prebiotic dietary fiber that can promote metabolic health including reduced body weight and improved glucose metabolism via effects on gut microbiota. We hypothesize that inulin prevents obesity-associated cardiometabolic alterations by augmenting the production of short-chain fatty acids (SCFA) from gut microbiota, which activate free fatty acid receptor 2 (FFAR2), a major SCFA receptor, in murine adipose tissue.

Methods:
8-week-old male C57BL/6J (wild-type, WT; n=34) and adipocyte FFAR2-knockout (Ad-FFAR2 KO; n=25) mice were fed a high-fat high-sucrose (HFHS) diet for 8 weeks, then randomized into experimental groups to receive either continued HFHS (n=8-13), or HFHS containing inulin (10% w/w chicory root inulin; n=17-21) for a further 5 weeks. Body weight was recorded weekly, food intake, body composition, and indirect calorimetry were assessed before and after the inulin intervention, and intraperitoneal glucose and insulin tolerance tests were performed. Subcutaneous and visceral white adipose tissue (WAT) samples were collected at the study termination.

Results:
HFHS-fed Ad-FFAR2 KO mice showed higher body weight (7.4%), fat mass, and WAT weight due to increased food intake, with worse glucose tolerance compared to WT mice. In WT mice, inulin significantly reduced body weight gain and body adiposity. These effects were associated with reduced locomotor activity and respiratory quotient (RQ) without effects on energy expenditure and were accompanied by improvements in glucose tolerance. Strikingly, inulin had no effect on body weight or body adiposity in Ad-FFAR2 KO mice but reduced RQ, locomotor activity, and improved glucose tolerance similar to WT mice.

Conclusions:
Our findings suggest that FFAR2 signaling in adipose tissue is crucial for improving cardiometabolic outcomes in obesity and that gut metabolites responsive to dietary interventions, such as inulin, are potential targets for obesity treatment strategies.
Abstract 4136901: Mechanosensitive channel protein Piezo1 synergizes with TLR4 to enhance osteogenic responses in human aortic valve interstitial cells
Authors: Lin Xiangjie , Su Shuwen , Duan Xiaolin , Li Wenyan , Hu Dongtu , Lin Ying-wen , Jiang Sijie , Wang Liusheng , Li Juncong , Xu Dingli , Qingchun Zeng
Published: November 2024

Background:
Calcific aortic valve disease (CAVD), a common heart valve disease in the elderly, has a complex pathogenesis. Abnormal blood flow shear can be regarded as an important factor in the development of CAVD, and a key molecule that responds to mechanical stress is the mechanosensitive ion channel protein Piezo1; however, the role of Piezo1 in CAVD has not been clarified.

Methods and results:
We collected CAVD patients and their age- and sex-matched controls, and compared the differences in the protein expression levels of Piezo1 and TLR4 between the two using Western blot and other techniques, and found that the expression of Piezo1 and TLR4 proteins was elevated in the CAVD group. We gave LPS or Piezo1 agonist Yoda1 to stimulate aortic valve mesenchymal stromal cells, respectively, and the Western blot results showed that ALP and Runx2 expression were elevated after LPS and Yoda1 stimulation, and immunofluorescence and alizarin red staining showed similar results. Inhibition of TLR4 or Piezo1 attenuated the osteogenic differentiation of AVICs. Cellular immunofluorescence results showed that TLR4 could be transported from the Golgi to the cell membrane under Yoda stimulation, and Golgi-cell membrane transport of TLR4 was attenuated after Rab3b knockdown by siRNA. After first pre-stimulation with Yoda1 and then stimulation with LPS, Western blot and immunofluorescence results showed that the protein levels of ALP and Runx2 as well as NF-κB phosphorylation were to be significantly increased.

Conclusion:
Stimulation of Piezo1 and TLR4 can enhance the osteogenic response of AVICs. Stimulation of Piezo1 enhances the transport of TLR4 from the Golgi to the cell membrane via Rab3b, and Piezo1 synergistically enhances the osteogenic response of AVICs with TLR4, thus promoting the development of CAVD.
Abstract 4136916: Indobufen: A Viable Alternative to Aspirin for Antiplatelet Therapy in patients with Aspirin Intolerance
Authors: Cavalcante Deivyd , Murali Krishna Mrinal , Joseph Meghna , Felix de Farias Santos Ana Clara , Ribeiro Asbeg Nicole , Kirabo Annet
Published: November 2024

Introduction:
Antiplatelet therapy with aspirin has been recommended for patients with stroke and myocardial infarction (MI). Clinicians face challenges when they come across aspirin hypersensitivity in their clinical practice. Therefore, potential alternative drugs can help avoid the omission of anti-thrombotic therapy. Indobufen is a cyclooxygenase-1 inhibitor studied as an alternative to aspirin.

Hypothesis:
Compared to aspirin, indobufen will be equally effective in preventing cardiovascular events in patients needing antiplatelet therapy but will cause fewer bleeding complications.

Methods:
We systematically searched PubMed, Scopus, and Cochrane Central databases for studies comparing antiplatelet therapy with indobufen vs. aspirin. The efficacy outcomes of interest were composite vascular events, MI, and ischemic stroke. The safety outcomes of interest were major bleeding and any bleeding. Heterogeneity was assessed using I
2
statistics. Analysis followed the PRISMA guideline and was registered in the PROSPERO database (CRD42024540911).

Results:
The systematic review identified 4 studies, including 11,495 patients (indobufen n=5,728, 49.83%), with two studies in patients post-MI and two post-stroke patients. Composite vascular events at 90 days (RR 1.03; 95%CI 0.58-1.86; p=0.911; I
2
=46%) and 1 year (RR 1.10; 95%CI 0.96-1.27; p=0.184; I
2
=0%) did not show any difference between the groups. MI (RR 0.67; 95%CI 0.36-1.23; p=0.197; I
2
=0%) and ischemic stroke (RR 1.17; 95%CI 0.99-1.38; p=0.064; I
2
=0%) at 1 year did not show any significant difference between the groups. Major (RR 0.68; 95%CI 0.36-1.27; p=0.225; I
2
=74%) and any bleeding (RR 0.62; 95%CI 0.36-1.06; p=0.079; I
2
=91%) at 1 year were also comparable between the groups.

Conclusion:
Antiplatelet therapy with indobufen was comparable with aspirin in efficacy and safety. Indobufen can be considered an alternative to aspirin in patients with intolerance or hypersensitivity. However, more trials with a larger population are needed to confirm the clinical applicability.
Abstract 4136969: Empagliflozin's Role in Post-Myocardial Infarction Management: Insights from a Meta-Analysis
Authors: Bilal Muhammad Ibraiz , Ashraf Danish Ali , Ahmed Usman , Naufil Syed Imam , Burki Atta Ul Haq , Kamran Farooq , Ahmed Shahzaib
Published: November 2024

Background:
Empagliflozin, a Sodium Glucose Cotransporter 2 (SGLT2) Inhibitor, is used to treat type 2 diabetes mellitus and heart failure. Its safety and efficacy in patients with Myocardial Infarction (MI) have been studied recently.

Research Questions/Hypothesis:
What is the role of Empagliflozin in post-myocardial infarction management by preventing cardiovascular deaths, reducing hospitalization due to heart failure, and minimizing adverse events?

Goals/Aims:
Role of Empagliflozin in post-myocardial infarction management by preventing cardiovascular deaths, reducing hospitalization due to heart failure, and minimizing adverse events

Methods:
A literature search was done on PubMed, Medline, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials from inception until May 2024. All Randomized Control Trials (RCT) reporting the safety and efficacy of Empagliflozin in MI management were selected. Outcomes were pooled as Mean Difference (MD) or Risk Ratio (RR) with 95% Confidence Intervals (CI) in this meta-analysis using Revman 5.4.

Results:
Data from ten RCTs, with a combined sample size of 10,560 patients was pooled, and showed that Empagliflozin is superior to placebo in terms of Cardiovascular death (RR=0.75, 95% CI [0.64, 0.88],p < 0.0004) and hospitalization due to heart failure (RR=0.70, 95% CI [0.59, 0.82], p < 0.0001). However, the results were non-significant for both groups in terms of adverse events (RR=1.00, 95% CI [0.96, 1.03], p < 0.78).

Conclusion:
Empagliflozin significantly lowers the risk of cardiovascular events in patients with MI who are at a high risk of death due to cardiovascular causes.
Abstract 4136975: Lipoprotein (a) Discovery Project: Assessing Patient and Professional Education Needs
Authors: Yuan Meg , Groom Allison , Collins Eliana , Pena David , Colson Kristin , Skinner Jeremy , Congdon Michelle , Pressley Alyssa
Published: November 2024

Introduction:
It is estimated that 1 in 5 Americans have high lipoprotein (a) [Lp(a)] levels. High levels of Lp(a) are an independent, predominantly inherited, and causal risk factor for atherosclerotic cardiovascular disease (ASCVD). More investigation is needed to better understand the gaps in both professional and patient education on Lp(a) and its associated risk with ASCVD.

Goals:
The American Heart Association (AHA) is implementing a national 3-year initiative called the Lp(a) Discovery Project to understand system-level practice patterns for patients screened for high Lp(a) and develop models for national education. We aim to gauge an understanding of healthcare professional (HCP) and patient awareness, perceptions, knowledge, and behaviors of Lp(a) to develop a comprehensive educational approach that ultimately encourages patient-provider shared decision-making.

Methods:
To assess patient education needs, an online survey was conducted from October 11 to November 6, 2023, by Harris Insights&Analytics LLC with a nationally representative sample of 3,006 U.S. adults 18 years+. To assess professional education needs, the AHA engaged 10 champions from diverse health systems with established Lp(a) screening processes and workflows to participate in a Learning Healthcare System model to share best practices, inform on models for Lp(a) screening, and provide input on professional education topics.

Results:
The patient survey revealed that 34% of adults do not perceive high Lp(a) to pose an increased risk of heart attack, peripheral artery disease or stroke. If told that high Lp(a) does increase this risk, 63% are motivated to have their Lp(a) level checked and 88% would be motivated to reduce their risk for these conditions if they had high Lp(a). Ultimately, HCP recommendation was the most significant driver in getting screened among those who had their Lp(a) measured (61%). AHA-led champion interviews revealed that primary and specialty care HCPs need education on the importance of Lp(a) testing and cascade screening for family members as well as care considerations for patients with high Lp(a).

Conclusion:
Given that patients are most likely to be screened for Lp(a) if their HCP recommends it, we will focus on 1) educating patients and HCPs on the connection between Lp(a) and risk for cardiovascular disease and stroke and 2) providing HCPs with guidance on care considerations for those with high Lp(a) including cascade screening.
Abstract 4136995: Veterans Affairs (VA) Lipid Optimization Reimagined Quality Improvement Program (VALOR-QI) in Veterans with Atherosclerotic Cardiovascular Disease (ASCVD) at the San Juan VA
Authors: Alcocer Loriany , Rodriguez-Ospina Luis
Published: November 2024

ASCVD is the principal cause of morbidity and mortality for Veterans in the VA Healthcare System. San Juan VA is one of 50 VA sites participating in a national quality improvement initiative called the VALOR QI: VA Lipid Optimization Reimagined Quality Improvement Project. Is a collaborative project between the U.S. Department of Veterans Affairs (VA) and the American Heart Association (AHA) with the goal of positively impacting Veterans’ cardiovascular (CV) health. VA sites work with an AHA QI consultant to develop and deploy a local quality improvement plan to help overcome site specific barriers preventing Veterans from achieving optimal cholesterol levels. The program’s objectives include improving clinical pathways and processes to impact ASCVD management through a Learning Healthcare System model of quality improvement designed to improve the management of dyslipidemia among those with high-risk ASCVD.

The hypothesis is that patients who are part of the VALOR QI program will be more successful in reaching LDL-C target. This will help to reduce the risk of ASCVD and mortality for the patients, promoting better management of lipid levels through medications, diet and regular monitoring.

As part of the methodology, the patients are enrolled to the program using the criteria of Veterans > 18 years of age with diagnosis of ASCVD and LDL-C > 70 mg/dl or non-HDL > 100 mg/dl. The Healthcare Coach has a full track of their lipid medications, assists the patients with refills, provides educational materials, follows up with their clinical appointments, and emphasizes the importance of having a good compliance with therapy, appointments and diets to maintain the target of LDL-C. Once the patient starts with a new lipid medication, they are followed in 3 months with labs. After reaching the target the patient is followed up closely in 6 months with labs to prevent relapse.

The VALOR QI Program started at VA San Juan in June 2023 and, as of May 30, 2024, had directly engaged 282 Hispanic patients. 111 (39.4%) achieved target LDL-C; 268 (95%) have any statin use; 117 (41.5%) are on any non-statin lipid-lowering therapy (LLT); 116 (41%) are on statin plus LLT; 25 (8.9%) are on PCSK9, and 133 (47.2%) received educational materials. In conclusion, this initiative led to target LDL levels in 39% of patients which represents a significant population. As this program is further implemented in our institution, we expect improvement in patient outcomes and prognosis.
Abstract 4139162: Optical coherence tomography measures mechanical contractile properties of the beating murine heart
Authors: Zhou Yirong , Kim Junyoung , Tearney Guillermo , Aguirre Aaron
Published: November 2024

Introduction:
Optical imaging techniques can characterize properties of tissue at high temporal and spatial resolution, offering unique insights into electrically excitable tissues such as nerve and muscle. We hypothesized that the gated high-speed optical coherence tomography (OCT) could profile the contractile properties of mouse myocardial tissue and facilitate investigations of microscale mechanical function in the beating heart.

Methods:
C57BL/6 male mice (n=6) underwent a sternotomy while anesthetized and ventilated and were imaged at baseline with OCT. Another cohort of C57BL/6 male mice (n=6) were sacrificed and the hearts were ex vivo perfused with crystalloid using a Langendorff system. These hearts were imaged at baseline and after inhibition of contractile function with blebbistatin. OCT was performed using a custom tissue stabilizer and a Thorlabs TEL 321 OCT system, which was synchronized to physiologic signals using custom hardware and software and cardiac pacing protocols (Fig. 1A and 1B). OCT cross-sectional B-scan images (Fig. 1C) were obtained throughout multiple cardiac cycles in both in vivo and ex vivo preparations. Data were processed in MATLAB and ImageJ using the workflow in Fig. 1D.

Results:
Highly reproducible cross-sectional mean intensity changes were observed over the contractile cycle in vivo and ex vivo (Fig. 1E, left and middle). With mechanical contraction inhibited by blebbistatin, this cyclical intensity extinguished, linking the optical scattering change measured by OCT to myocardial contraction (Fig. 1E, right). B-scan curves averaged over multiple mice and temporally aligned with the ECG waveform (Fig. 1F) demonstrate a signal intensity waveform that reproducibly varies with the contractile cycle for both in vivo and ex vivo preparations. In vivo and ex vivo baseline waveforms both had peak intensity during systole and minimum in end-diastole (Fig. 1F). Reproducibility in ex vivo beating heart preparations without blood perfusion provides evidence that myocardial mechanical properties, not red blood cell flow, generate the intensity changes.

Conclusion:
Gated high-speed OCT imaging can quantify the mechanical contraction wave in the myocardium. Combined with gated OCT angiography, OCT techniques will provide high resolution imaging of both blood flow and mechanical contractility of the beating heart in small animal models of heart disease.
Abstract 4139176: SUMOylation of TP53INP1 Is Involved in miR-30a-5p-Regulated Heart Senescence
Authors: hong yixiang
Published: November 2024

Introduction:
During natural aging, physiological remodeling of the heart is a critical for the cardiovascular disease and heart failure. miR-30a-5p is related to kidney injury, cancer, and autoimmune diseases. However, whether miR-30a-5p has an effect in cardiac aging has yet to be explored.

Hypothesis:
This study aimed to characterize the role and mechanism of action of miR-30a-5p in cardiac senescence.

Methods:
We established miR-30a-5p knockout/overexpressing mouse model. Natural heart aging (18-months-old) and D-galactose-induced aging mouse model were established. The mechanism was explored in D-galactose- or 10-days-cultured cardiomyocytes.

Results:
miR-30a-5p was downregulated in aged mouse hearts and neonatal rat cardiomyocytes (NRCMs). In vivo, using a combination of echocardiography and different molecular biological approaches, we investigated the role of miR-30a-5p knockout or overexpressed mice on natural- or D-galactose-induced heart aging. In vitro, using RNA-sequence and a series of molecular biology, the mechanism of miR-30a-5p-regulated cardiac senescence was explored in cardiomyocytes. miR-30a-5p knockout mice showed aggravated natural- or D-galactose-induced heart aging compared to wild-type littermate mice, with significantly decreased heart function, increased number of γH2AX-positive cells, reduced telomere length, and upregulated p21 and p53 expression. Cardiac-specific knockdown of miR-30a-5p using adeno-associated virus 9 in D-galactose-induced senescent wild-type mice showed effects similar to those observed in knockout mice. Notably, overexpression of miR-30a-5p in wild-type murine hearts alleviated D-galactose-induced heart senescence by improving heart function, increasing telomere length, decreasing the number of γH2AX-positive cells, and downregulating p53 and p21 expression. This was confirmed in D-galactose-treated or naturally aged NRCMs. Mechanistically, TP53INP1 was identified as a target of miR-30a-5p by mediating the SUMOylation of TP53INP1 and its translocation from the cytoplasm to the nucleus to interact with p53. Further evidence demonstrated that cardiac-specific TP53INP1 deficiency ameliorates miR-30a-5p knockout-aggravated cardiac dysfunction and heart senescence.

Conclusions:
This study identified miR-30a-5p as a crucial modulator of heart senescence and revealed that the miR-30a-5p–TP53INP1–p53 axis is essential for heart and cardiomyocyte aging.
Abstract 4140108: A CRISPR-Activation CROP-seq Screen Identifies HMGN1 as a Dosage-Sensitive Regulator of Heart Defects in Down Syndrome
Authors: Ranade Sanjeev , Li Feiya , Whalen Sean , Angelo Pelonero , Ye Lin , Huang Yu , Brand Abigail , Nishino Tomohiro , Costa Mauro , Mital Rahul , Boileau Ryan , Koback Frances , Padmanabhan Arun , Merriman Alexander , Wallace Langley , Nguyen Annie , Poulis Nikolaus , Gifford Casey , Pollard Katherine , Srivastava Deepak
Published: November 2024

Introduction/Background:
Congenital heart defects (CHD) are the most common form of developmental abnormalities, occurring in ~1% of live births, and can arise due to altered dosage of genes essential for cardiogenesis. Aneuploidy accounts for nearly 15% of CHD and the most frequent form involves trisomy of chromosome 21 (Ch21), resulting in Down Syndrome (DS). CHD is present in ~50% of DS cases, with a 1000-fold enrichment of atrioventricular canal (AVC) defects that disrupt the junction of the atria and ventricles.

Hypothesis:
We hypothesize that the presence of a third copy of one or more genes on Ch21 underlies AVC and other cardiac defects; however, the dosage-sensitive CHD gene(s) on Ch21 causing this are not fully defined.

Methods:
We used human pluripotent stem cells derived from an individual mosaic for DS, allowing us to compare Ch21 trisomy cells with isogenic control cells disomic for Ch21. We performed single cell RNA-sequencing (scRNA-seq) to define the transcriptional dysregulation associated with DS in atrioventricular canal myocardial cells (AVCM). We then introduced a CRISPR-activation transgene to disomic cells and delivered small guide RNAs (sgRNAs) against 66 candidate Ch21 CHD genes. We developed a new machine learning algorithm to assign a trisomic score to CRISPR perturbed (CROP-seq) cells. Finally, we reduced the copy number of our top candidate gene in a mouse model of Down Syndrome and used microCT to assess incidence of cardiac septal defects.

Results:
Using human pluripotent stem cell and mouse models of DS, we identify HMGN1, a nucleosome-binding epigenetic factor on Ch21, as a dosage-sensitive regulator of cardiac defects in DS. Single cell transcriptomics revealed that human AVC cardiomyocytes shifted to a more ventricular myocardial state in trisomy 21 hiPS-derived cells. CRISPR-activation in isogenic disomic cells of 66 candidate Ch21 genes expressed in heart development, followed by single cell RNA-sequencing (CROP-seq) combined with machine learning predictions indicated that increased expression levels of HMGN1 altered the transcriptional state of atrioventricular cardiomyocytes similar to trisomy 21. Finally, reduction of Hmgn1 from three to two alleles in a mouse model of DS attenuated the incidence of cardiac septal defects.

Conclusion:
Our results identify HMGN1 as a dosage sensitive regulator of heart defects in DS and represent a generalizable approach for identifying candidate genes within areas of aneuploidy.
Abstract 4140122: Bioengineered Self-Adhering Electrospun Nanoscaffolds to Deliver Mitochondrial Antioxidant, JP4-039
Authors: Broadwin Mark , Oh Amy , Imarhia Frances , Ferbert Mason , Lyakhovych Zakhar , Teixeira Rayane , Wipf Peter , Bhowmick Sankha , Sellke Frank , Abid Ruhul
Published: November 2024

Introduction:
Treatment of pathologic remodeling and subsequent decline in cardiac function post-myocardial infarction (MI) remains limited. Our lab has previously demonstrated that the targeted mitochondrial antioxidant, JP4-039 (JP4), can abrogate post-MI remodeling and decline in cardiac function, and that JP4 released from electrospun nanoscaffolds improved proliferation and migration of coronary vascular endothelial cells
in vitro
. The aims of this study were to develop a suture-free, bioadhesive electrospun nanoscaffold that will adhere post-MI cardiac tissue and reliably release JP4 in a localized manner.

Hypothesis:
Plasma treatment of JP4-loaded biocompatible electrospun nanoscaffold will adhere to cardiac tissue and deliver active moiety of JP4.

Methods:
A 2% poly(l-lactide-co-glycolide) (PGLA) was electrospun with and without 1% JP4. Nanoscaffolds then underwent plasma treatment for one minute followed by a force adhesion assay. SEM imaging and
electron
paramagnetic resonance (
EPR
) assays before and after plasma treatment of both control and JP4-loaded patches were performed to examine patch consistency and ensure the release of the unaltered, active structure of JP4.

Results:
JP4 loading and plasma treatment did not affect fiber dimeter of the scaffolds (p > 0.5 for all; Fig. 1B). JP4-loaded patches demonstrated similar release pattern of the antioxidant’s nitroxide moiety by displaying a characteristic triple peak both before and after plasma treatment as determined by EPR (Fig. 1C). Plasma-treated patches demonstrated significant increase in force adhesion compared to non-treated patches in both the control and JP4-loaded scaffolds (p < 0.0001) (Fig. 1A.). No significant difference in force adhesion was observed between the plasma treated control and JP4 loaded patch (p > 0.05) as determined by ANOVA (Fig. 1A). There was no significant difference in force adhesion between one minute and two minutes of plasma treatment (p > 0.05; Fig. 1A lower panel).

Conclusion:
The findings demonstrate that plasma-treated biocompatible JP4-loaded patches may reliably adhere to cardiac tissue and release the bioactive component of the mitochondrial antioxidant, JP4.
Abstract 4140126: Comparison of Clinical Risk Calculators for Atherosclerotic Cardiovascular Diseases: PREVENT, Pooled Cohort Equations, and QRISK3
Authors: Naderian Mohammadreza , Kullo Iftikhar
Published: November 2024

Introduction:
The cardio-kidney-metabolic pathway has a crucial role in ASCVD, motivating development of the PREVENT equation. There is a need for external validation of the PREVENT equation and assessment of its performance in independent cohorts to assess generalizability across diverse populations.

Aim:
To compare predictive performance of the PREVENT equation with previously developed risk calculators; pooled cohort equations (PCE), and QRISK3.

Methods:
We used data from 500k participants of the United Kingdom Biobank (UKB). ASCVD was defined as the composite outcome of fatal and non-fatal myocardial infarction, coronary revascularization, and stroke. We ascertained demographic and clinical covariates required to calculate ASCVD risk, using the base model of PREVENT, PCE, and QRISK3, at the time of recruitment. Those with a diagnosis of ASCVD at the time of recruitment or missing data on age, sex, or ethnicity were excluded. We used the area under the ROC curve (AUC) and calibration plots for analysis.

Results:
Of 459,681 participants (mean age 56.3±8.1 years, 44.4% male, and 94.7% White), 24,514 (5.4%) participants had a new diagnosis of ASCVD during a 10-year follow-up. The median [interquartile range] of estimated 10-y ASCVD risk was 3.7% [1.9% - 6.1%] for PREVENT, 5.6% [2.4% - 11.3%] for PCE, and 8.0% [3.9% - 13.8%] for QRISK3 (Figure 1A). The calibration slope (95% CI) was 1.71 (1.66 – 1.76) for PREVENT, 0.64 (0.63 – 0.66) for PCE, and 0.66 (0.64 – 0.67) for QRISK3 (Figure 1B). The AUC for ASCVD prediction was 0.741 (0.738 - 0.744) for PREVENT, 0.744 (0.741 – 0.747) for PCE, and 0.751 (0.749 – 0.755) for QRISK3 (Figure 1C).

Conclusion:
In the UKB cohort, the PREVENT equation underpredicted while the PCE and QRISK3 overpredicted ASCVD risk, with a similar discrimination. Consequently, fewer individuals would be eligible for primary prevention with statins, based on the actionable thresholds of 7.5% or 10% when considering ASCVD risk based on PREVENT. Therefore, the external application of the PREVENT equation requires recalibration and context-specific interpretation.
Abstract 4140134: Impact of Cancer on Outcomes in Patients with Acute Myocardial Infarction; a Systematic Review and Meta-analysis.
Authors: Shrestha Abhigan , Afroze Tanzina , Jaiswal Vikash , Goyal Aman , Devkota Anirudra , Shrestha Sajina , Rajak Kripa
Published: November 2024

Background:
Cardiovascular diseases are the second leading cause of death among cancer patients, after cancer-related mortality. It has not been well established if a patient's malignancy status increases their risk of cardiovascular events following a myocardial infarction (MI).

Hypothesis:
This study aims to assess the impact of cancer on cardiovascular outcomes following an acute myocardial infarction.

Methods:
We systematically searched electronic databases such as Pubmed, Embase and Cochrane Library from inception until March 2024 using the appropriate Mesh terms, “ cancer,” “myocardial infarction,” and “cardiovascular mortality”, “in-hospital mortality”. Pooled relative risk and their corresponding confidence interval were calculated using the random effect model. A p-value of <0.05 was considered statistically significant.

Results:
A meta-analysis was conducted with seven articles, with 32856 cancer patients and 520421 noncancer patients with MI. Pooled analysis showed that patients with cancer had to have a significantly higher risk of recurrent MI in (RR 1.49, 95% CI:1.03-1.96), major bleeding (RR 1.96, 95% CI: 1.28-2.64), cerebral infarction (RR 1.29, 95% CI: 1.21-1.38), the in-hospital mortality rate (RR 1.62, 95% CI: 1.04-2.20), cardiovascular mortality (RR 1.57, 95% CI: 1.00-2.13), and hospitalization due to heart failure (RR 1.51, 95% CI 1.46, 1.56) when compared with noncancer patients.

Conclusion:
This study shows that cancer is strongly associated with an increased risk of recurrent MI, major bleeding, cerebral infarction, hospital mortality, cardiovascular mortality, and hospitalisation due to heart failure in patients with acute MI. Proper monitoring of cardiac function and lab markers can be effective in reducing morbidity and mortality.
Abstract 4140136: Aortic Valve Calcification Density Performs Better Compared to Absolute Aortic Valve Calcification in Aortic Stenosis Risk Stratification
Authors: Ahmad Syed , Watson HangYu , Awad Maan , Patel Kunal , Nassar Sameh , Thyagaturu Harshith , Balla Sudarshan , Kawsara Mohammad , Daggubati Ramesh , Zeb Irfan
Published: November 2024

Aortic valve calcification (AVC) scores can be used to stratify aortic stenosis (AS) severity. Current practice guidelines recommend use of absolute AVC scores without considering body surface area or aortic annulus size. We investigated whether size variation in aortic annular area should be considered in identifying optimal AVC cutoffs for patients with severe AS.

This was a retrospective analysis of AS patients that underwent AVC assessment during 2018-2023. Outcomes were composite of valve intervention or all-cause mortality. AVC density was defined by dividing AVC by echo-derived left ventricular tract area. Receiver operator curve analysis determined optimal AVC density scores. Absolute AVC cutoffs of >1200AU for females and >2000AU for males were used to identify severe AS.

The study included 749 patients (mean age 78 years, 46% female). Median CT-annulus area was larger for males compared with females (532mm
2
[Q1, Q3: 479, 582] vs. 413mm
2
[370, 458], p<0.001). There was a strong association of absolute AVC with CT-annulus area for both males and females (Spearman coefficient: 0.87 and 0.83, p<0.01 each) respectively (Figure 1). The optimal AVC density cutoffs for males and females were 427 and 326, respectively (accuracy 76%, sensitivity 83%, specificity 51%). Composite outcomes were better differentiated with AVC density (males: HR 2.48, 95% CI: 1.82-3.37, p<0.001; females: HR 2.37 (1.71-3.28), p<0.001) compared with absolute AVC scores (males: HR 1.81 (1.43-2.30), p<0.001; females: HR 2.11 (1.62-2.74), p<0.001) (Figure 2).

AVC is strongly associated with CT-annulus area and risk stratification is improved with the use of AVC density compared with absolute AVC. This may be especially helpful in patients with extremes of annulus area sizes.
Abstract 4140139: Cardio-ankle vascular index (CAVI) in prediction of chronic coronary artery disease: risk, coronary artery lesions, and cardiovascular disease events
Authors: Dung Le Van , Nguyen Son Pham , Pho Dinh Cong , Son Pham Truong
Published: November 2024

Introduction:
The cardio-ankle vascular index (CAVI) is a significant metric for evaluating arterial function. The test measures the stiffness of the arteries from the beginning of the aorta to the ankle, and the algorithm used is not influenced by blood pressure. Recent statistics indicate that a high CAVI score has the potential to predict future cardiovascular disease (CVD) occurrences. However, no research has been conducted in Vietnam to investigate this matter.

Methods:
A prospective study was conducted on 222 patients. Out of these, 162 patients had chronic coronary artery disease (CAD), while the remaining 62 patients were free of CAD. The study took place between October 2019 and December 2022. Participants who fulfilled the criteria were evaluated using the CAVI baseline measurement and clinical and paraclinical parameters. A total of 162 patients with chronic coronary artery disease (CAD) were monitored for cardiovascular disease (CVD) events over a period of 2 years.

Results:
CAVI in chronic CAD patients (9.21±0.79) was significantly higher compared to those in free-CAD patients (8.48 ± 0.62) with p<0.001. CAVI with a cut-off point ≥ 8.83 was a significant predictor for chronic CAD (OR = 9.6; 95%CI: 4.0-18.8). The Area under the curve (AUC) of CAVI for chronic CAD was 0.796 (95% CI: 0.736-0.856 ; p<0.001). In addition, CAVI has a statistically significant increase in severe stenosis (≥75%) and multivessel coronary artery disease. CAVI in the CVD events group (9.77±1.06) was significantly higher than CAVI in the free–CVD events group (9.13±0.72) group (p=0.009). The patients with CAVI ≥9.63 have significantly higher CVD events (HR=6.4 ; 95% CI: 1.9-21.9, p=0.046).

Conclusion:
CAVI is higher in chronic CAD and can predict chronic CAD with a cut-off point ≥ 8.83. In chronic CAD, CAVI is higher in severe stenosis and multivessel coronary artery disease. Increased CAVI was significantly associated with CVD events.
Abstract 4140142: Neighborhood Perceptions Associate with Lipid Biomarkers in African-American Women with Cardiovascular-Kidney-Metabolic Syndrome: Data from the Step It Up Digital Health-Enabled, Community-Engaged Physical Activity Intervention
Authors: Reynolds Sandy , Andrews Marcus , Baumer Yvonne , Sandler Dana , Sharda Sonal , Hicks Shelby , Aquino Peterson Elizabeth , Abhinav Saurabh Fnu , Cintron Manuel , Pita Mario , Tarfa Hannatu , Dave Ayushi , Osei Baah Foster , Ayers Colby , Mendelsohnl Laurel , Deguzman Sarah , Redai Azeb , Marah Marie , Wells Ayanna , Tolentino Katherine , Sampson Maureen , Remaley Alan , Powell-Wiley Tiffany
Published: November 2024

Background:
Cardiovascular-kidney metabolic (CKM) syndrome is exacerbated among individuals experiencing chronic exposure to both environmental and psychosocial stressors. Both neighborhood and individual-level stressors increase chronic inflammation resulting in worsened CKM factors, such as hypertension, diabetes, and dys/hyperlipidemia. However, associations between neighborhood perceptions (NP) and lipid profiles remain understudied. Therefore, we examined associations between NP domains and lipid profiles among African-American (AA) women with ≥Stage 1 CKM syndrome (overweight/obesity) residing in resource-limited neighborhoods within the Washington, DC area.

Methods:
Participants were enrolled in Step It Up, a technology-enabled, community-engaged physical activity (PA) intervention. Fasting blood samples were drawn at baseline to measure lipoproteins using Nuclear Magnetic Resonance (NMR) spectroscopy. Factor analysis of overall NP identified four perception sub-scores: disorder, social cohesion, violence, and safety (higher score=favorable perception). Associations between NP domains and lipoprotein particles were analyzed using multivariable regression adjusting for BMI, ASCVD 10-year risk score, and lipid-lowering therapy.

Results:
Participants (n=169) had mean age=57.16 ± 12.00 and BMI 35.99 ± 6.57. Perceptions of safety were positively associated with LDL concentrations (LDLc) and large LDL particles (L-LDLp) (β=4.70 [SD=2.41], p=0.05, β= 43.75 [17.70], p= 0.01), respectively). Perceptions about neighborhood violence were positively associated with L-LDLp (marginally) and very-low-density lipoprotein size (VLDLz) (β= 7.10 [3.96], p=0.08, β= 0.31 [0.14], p= 0.02, respectively). No associations were found between disorder and social cohesion with lipid biomarkers.

Conclusions:
After adjusting for BMI, ASCVD risk, and lipid-lowering therapy, there were significant associations between neighborhood perceptions of safety and violence with lipid profiles among AA women with CKM syndrome. Greater perceived safety was associated with higher LDLc and L-LDLp while more favorable perception about neighborhood violence was associated with higher L-LDLp. Future work should examine whether improving neighborhood resources and perceptions may improve CKM health among urban AA women.
Abstract 4140154: Highly Sensitized Heart Transplant Recipients Who Have Undergone Pre-Transplant Desensitization Therapies Demonstrate Acceptable Medium-Term Outcomes
Authors: Jain Rashmi , Nikolova Andriana , Kransdorf Evan , Kittleson Michelle , Chang David , Patel Jignesh , Kobashigawa Jon
Published: November 2024

Introduction/Research Question:
Allosensitization, the presence of circulating anti-HLA antibodies, is a barrier in heart transplantation (HT), restricting the donor pool size, and leading to increased waitlist mortality and rejection risk post-HT. Desensitization therapies can be used to broaden the donor pool in highly sensitized patients, defined as pre-HT calculated panel reactive antibodies (cPRA)≥50%, for antibodies with mean fluorescence intensity (MFI)>10,000. There is paucity of data on longer-term outcomes in such high-immunological risk patients.

Methods:
Sensitized patients with pre-HT cPRA>50%, who were treated with desensitization and then received HT between 2011-2022 at Cedars-Sinai Medical Center were included. Desensitization therapies included bortezomib, rituximab, tocilizumab, obinutuzumab, intravenous immunoglobulin (IVIG), and plasmapheresis. cPRA, donor-specific antibody (DSA) levels, and post-HT clinical outcomes were assessed up to 5-year follow-up, loss to follow-up, or death.

Results:
40 patients were analyzed. 77.5% of patients were female, and all had at least 1 risk factor for sensitization. cPRA decreased from 84.5±13.5% at baseline to 74.1±22.4% after completion of desensitization therapy, prior to transplant (p=0.005). Mean follow-up time post-HT was 4.3±2.9 years. 45.0% of patients had antibody-mediated rejection (AMR), 12.5% had CAV. Overall survival was 94.9%, 92.1%, and 87.5% at 1, 3, and 5 years respectively. All patients except 1 had normal left ventricular function at last follow-up. 72.5% of patients were transplanted in the presence of DSA, and 60.0% underwent post-HT induction with eculizumab in addition to antithymocyte globulin (ATG)/IVIG, while the remaining received ATG/IVIG alone. Among HT recipients with pre-formed DSA, 41.4% had high-level DSA (MFI > 10,000) at time of HT. At 6-12 months post-HT, only 17.2% had high-level DSA, and 41.4% had resolution of DSA.

Conclusion:
Highly sensitized HT candidates who underwent pre-HT desensitization had comparable survival and CAV rates as compared to the general HT population reported in the literature. However, sensitized patients experienced higher rates of AMR which were not associated with graft dysfunction or mortality.