bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12629: Intravascular Dual Targeted NIRF Molecular Imaging Integrated With OCT for Calcifying Inflammatory Activity in the Plaque
Authors: Kang Dong , Lim Yong Geun , Kim Yeon Hoon , Song Joon Woo , Park Ye Hee , Kim Ryeong Hyun , KIM JIN HYUK , Kim Hyun Jung , Nam Hyeong Soo , Oh Wang-Yuhl , Park Kyeongsoon , Yoo Hongki , Kim Jin Won
Published: April 2024

Background/Objectives:
Spotty calcification linked with macrophage activity is a major target for high-risk plaque but the biological interconncetion remains questionable. To address this issue, we newly developed intravascular multimodal imaging strategy by fully integration of OCT with dual-targeted near-infrared fluorescence (NIRF) molecular imaging using customized osteogenic activity and macrophage targetable probes.

Methods/Results:
We newly integrated intravascular OCT structural imaging with dual-targeted NIRF imaging. Scale-up novel NIRF emitting probe targeting osteogenic activity was fabricated by chemically coupling alendronate ligand and Cy5.5 to the ends of azide-PEG-NHS ester (Al-Cy5.5). Based on biodistribution, OCT/dual-NIRF in vivo imaging of rabbit aortoiliac atheroma was acquired 72 hrs after intravenous injection of Al-Cy5.5 (5.0 mg/kg) and macrophage mannose receptor targeted Cy7-emitting probe (7.5 mg/kg). NIRF signals of Cy5.5 and Cy7 were highly enhanced in spotty calcification and inflammatory sites of the plaque, respectively (Figure) (p<0.01). Fluorescence microscopy and immunostainings from the corresponding sections well corroborated the in vivo findings. Intriguingly, an interconnection of osteogenic activity (TRAP stain) with macrophages was more prominent in superficial spotty calcification rather than outer dense calcification (Figure) (p<0.01).

Conclusions:
Our intravascular OCT/dual-NIRF imaging was feasible to simultaneously image osteogenic activity and macrophages in the coronary-sized atheroma. This novel imaging strategy is expected to expand the understanding for the biological behavior of calcifying inflamed activity in the high-risk plaques existing on cap microcalcification.
Abstract 12636: ECG-Based Risk Stratification of Long-Term Mortality in Suspected Acute Coronary Syndrome
Authors: Bouzid Zeineb , Faramand Ziad , Frisch Stephanie , Gregg Richard , Sejdic Ervin , Al-Zaiti Salah S
Published: April 2024

Introduction:
Non-invasive risk stratification can play a significant role in the initial triage of patients with suspected acute coronary syndrome. Numerous ECG features have been previously linked with mortality in both the general and cardiac populations. We sought to build an ECG-based model that can predict time-to-death in high-risk chest pain patients transported by Emergency Medical Services.

Methods:
This was a prospective observational cohort study of patients evaluated for suspected acute coronary syndrome. The study recruited consecutive patients evaluated at the emergency department of three UPMC-affiliated tertiary care hospitals. We included consecutive patients in whom a prehospital echocardiogram was performed during indexed encounter. Baseline ECGs were preprocessed using manufacturer specific algorithms. We evaluated 554 temporal-spatial features of the 12-lead ECG in multivariate proportional hazards Cox regression model for predicting all-cause death during long term follow up. Death was ascertained using phenotyping UPMC electronic hospital records and through the CDC National Death Index database. Model fit was evaluated using C-statistic and AIC. We set alpha at 0.01 for two-tailed hypothesis testing.

Results:
Our sample included 2311 patients (aged 59 ± 16.6, 47% females, 41% Black). Over a median follow up period of 1868 days (IQR = 688; [Q1, Q3] = [1511, 2199]), there was 622 (26.9%) adjudicated deaths. During univariate analysis, 288 features were significantly associated with time-to-death. In the final multivariate model (c-statistic = 0.79, AIC = 9066.05), controlling for demographic and clinical data, 15 ECG features remained predictive of the study outcome, with Selvester score being the strongest predictor (Hazard Ratio = 1.09, 95% CI = 1.03 - 1.16). Other clinically important ECG features included horizontal-plane QRS axis, QRS-T angle, QTc interval, QTpeak, T peak-end, S wave morphology the inferior leads, QRS morphology in lead aVR, and T wave morphology in the anterior leads.

Conclusions:
The presenting 12-lead ECG can serve as a powerful risk stratification tool of long-term mortality in patients with chest pain. Selvester score can serve as a plausible and easy to use clinical decision tool.
Abstract 12657: Overexpression of Small-Cajal Body Associated RNA20 (scaRNA20) Reduces Inflammatory Response and Improve Cardiomyogenesis
Authors: SIGAMANI VINOTH , Gurusamy Narasimman , RAJASINGH SHEEJA , Johnson Rajasingh
Published: April 2024

Introduction:
The non-coding RNAs, particularly small cajal-body associated RNAs (scaRNAs) play a critical role in alternative splicing and maturation of mRNAs. Although scaRNAs have been implicated in autoimmune diseases, their roles in the immune responses are largely unknown. Recently, we have identified that scaRNA20 play a major role during the differentiation of cardiomyocytes. In this study, we elucidated the role of scaRNA20 and its immune response towards the ischemic myocardium, using
in vitro
induced pluripotent stem cell (iPSC)-derived normal cardiomyocytes (iCMC).

Hypothesis:
We hypothesize that overexpression of scaRNA20 reduces the inflammatory response in cardiomyocytes leading to enhanced cardiomyogenesis.

Methods & Results:
scaRNA20 gene was cloned into mammalian expression vector CAG-GFP, and transfected into iPSCs for its overexpression and further differentiated into cardiomyocytes (scaRNA20-OE-iCMC). The results were compared with the iCMCs and transfected with empty vector (TC-iCMC). Our qRT-PCR results showed that the scaRNA20-OE-iCMCs led to a significant reduction in the fold change expression of pro-inflamatory genes such as TNFa and IL11 when compared to the TC-iCMCs and normal iCMCs normalized with normal skin fibroblast (SF) (Fig. A). In addition, the scaRNA20-OE iCMCs showed an increased expression of cardiac specific genes such as GATA4 and cardiac troponin T, compared with the TC-iCMCs and iCMCs. The functional cardiomyocytes can be assessed by the number of beating colonies. Our data showed a significantly increased number of beating colonies in scaRNA20-OE iCMCs when compared to the TC-iCMCs and iCMCs (Fig. B).

Conclusions:
Taken together, our results show for the first time that the overexpression of scaRNA20 reduced the inflammatory response, and at the same time improved the cardiomyogenesis. These results suggest that treatment with scaRNA20 can improve the regeneration of the ischemic myocardium.
Abstract 12666: Role of a Comprehensive ST-Elevation Myocardial Infarction Protocol in Improving Outcomes among Elderly Patients With ST-Elevation Myocardial Infarction
Authors: Kassis Nicholas , Nair Raunak , Kumar Anirudh , Huded Chetan , Johnson Michael , Kravitz Kathleen A , Reed Grant W , Krishnaswamy Amar , Menon Venu , Jaber Wael A , Lincoff A M , Kapadia Samir R , Khot Umesh N
Published: April 2024

Introduction:
Increasing age is a harbinger of poor outcomes from ST-elevation myocardial infarction (STEMI). It is uncertain whether measures can be implemented to improve care delivery and outcomes in this high-risk cohort. We assessed the impact of a comprehensive STEMI protocol (CSP) in elderly patients presenting with STEMI.

Methods:
A 4-step CSP was implemented, including: (1) Emergency Department catheterization lab activation; (2) STEMI Safe Handoff Checklist; (3) immediate catheterization lab transfer; and (4) radial-first percutaneous coronary intervention (PCI). Baseline characteristics, complications, procedural features, and outcomes were compared between consecutive STEMI patients >65 years of age who underwent PCI at the Cleveland Clinic pre- (01/01/2011-07/14/2014) and post-CSP (07/15/2014-07/15/2019) implementation.

Results:
Among 265 and 445 elderly patients in the pre- and post-CSP cohorts, respectively, overall the mean age was 74 years and 58% were males. More active smoking and obesity and less prior myocardial infarction and coronary artery bypass graft were observed in the post-CSP group. Relative to pre-CSP, post-CSP patients experienced significantly less cardiogenic shock (19% vs 9%, p<0.001) and cardiac arrest (16% vs 9%, p=0.009). Significant improvements were observed post-CSP implementation in median door-to-balloon time [111 (84-146) vs 89 (67-109) minutes, p<0.001] and trans-radial access (16% vs 72%, p<0.001), translating to significant reductions in major adverse cardiovascular events (14% vs 8%, p=0.02), major bleeding (16% vs 11%, p=0.05), and in-hospital mortality (12% vs 5%, p=0.001).

Conclusion:
The implementation of a CSP was associated with marked reductions in complications and improvements in in-hospital outcomes including mortality among elderly patients presenting with STEMI. Our findings highlight the opportunity to improve outcomes in high-risk elderly STEMI patients through a CSP.
Abstract 12668: Mutant Smooth Muscle α-Actin Predisposes to Atherosclerosis and Augments Cholesterol-Driven Phenotypic Modulation of Vascular Smooth Muscle Cells
Authors: Kaw Kaveeta , Chattopadhyay Abhijnan , Chen Jiyuan , Duan Xue Yan , Ma Shuangtao , Kwartler Callie , Milewicz Dianna M
Published: April 2024

Heterozygous variants in
ACTA2
(smooth muscle α-actin) predispose to thoracic aortic disease and early-onset coronary artery disease (CAD). Single cell RNA sequencing (scRNA-Seq) identified phenotypically modulated SMCs (mSMCs; de-differentiated SMCs with upregulation of macrophage and fibroblast markers) that appear with atherosclerotic plaque formation in the aortas of
Apoe
-/-
mice. Importantly, this transition is dependent on Kruppel-like factor 4 (Klf4). We previously demonstrated that SMCs exposed to free cholesterol complexed to methyl-β-cyclodextrin (MBD-Chol)
in vitro
activate unfolded protein response (UPR) pathways upstream of Klf4 and assume a mSMC phenotype. Blocking the UPR Perk pathway abolishes modulation. We sought to determine how
ACTA2
p.Arg149Cys causes early-onset CAD.

Acta2
R149C/+

mice were generated using CRISPR/Cas9.

Acta2
R149C/+

mice were crossed into
Apoe
-/-
mice and fed a high fat diet for 3 months. Oil Red O staining and
en face
aortic analysis showed that

Acta2
R149C/+
Apoe

-/-
aortas developed significantly more plaques than similarly treated
Apoe
-/-
mice (p<0.01) with no difference in plasma lipid levels (
Fig. 1A
). ScRNA-Seq of the root and ascending aorta showed no novel SMC cluster, however mSMC clusters demonstrated increased expression of UPR markers and Klf4 in the

Acta2
R149C/+
Apoe

-/-
aortas compared to
Apoe
-/-
aortas. Strikingly,

Acta2
R149C/+

SMCs upregulate modulation markers at much lower levels of cholesterol than WT SMCs due to activation of the UPR Perk-Klf4 by misfolded mutant SM α-actin (
Fig. 1B
). Importantly, blocking Perk abolishes the augmented phenotypic modulation in

Acta2
R149C/+

SMCs. These findings identify a novel pathway driving atherosclerosis independent of lipid metabolism and confirm a key role of SMCs in atherosclerotic plaque formation.
Abstract 12675: Intravenous Iron Decreases Rehospitalizations but Doesn’t Change Mortality in Patients Admitted With Acute Heart Failure and Iron Deficiency: A Systematic Review and Meta-Analysis
Authors: Baral Nischit , Karki Nabin R , Rauniyar Rohit , Savarapu Pramod , Abdelazeem Basel , KHAN ASHIYA , Christy Joshua , Kandah Emad , Adhikari Govinda , dhungana santosh , Paudel Anish C , Ranabhat Bandana , Rikabi Kamal , Pandit Trailokya , Kunadi Arvind
Published: April 2024

Introduction:
The role of intravenous (IV) iron in chronic heart failure has been well studied, however, its role in acute heart failure (AHF) is lesser well-known. Including the recent late breaking AFFIRM-HF trial, we performed a systematic review and meta-analysis to highlight the role of IV iron in AHF in iron deficiency.

Hypothesis:
We hypothesized that IV iron doesn’t change mortality or heart failure re-hospitalization rates in patients with AHF with iron deficiency.

Methods:
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and cohort studies published from inception till May 8, 2021. We searched PubMed, MEDLINE, EMBASE (embase.com), and Cochrane database including only RCTs and Cohort studies. We included one prospective and one retrospective Cohort studies and two RCT in our meta-analysis. Eligible studies included adults with AHF, LVEF less than 40%-50%, and able to receive iv iron therapy. Outcomes included re-hospitalization rates and overall mortality from 30 days to 52 weeks post randomization (in one RCT). We used random-effects model calculating Risk Ratio (RR) with 95% confidence interval (95%CI) using Review Manger 5.4 software. I
2
statistics was used to assess heterogeneity.

Results:
There were total 1561 participants in both groups (iv iron and placebo/control) of four studies. The controls were comparable in both cohort studies and both the RCTs were well matched. Our results showed re-hospitalization in 278 of 833 (33.37%) patients in the IV iron/exposure group and 337 of 728 (0.46%) patients in the placebo/control group. The pooled result showed that the risk of rehospitalization was comparable across both groups (RR 0.85, 95%CI 0.62-1.17; I
2
=45%, P=0.14). However, subgroup analysis, including RCTs only showed that iv iron decreases re-hospitalization rate by 28% compared to placebo (RR 0.72, 95% CI: 0.64, 0.82, I
2
=0%, P<0.00001) but didn’t improve mortality when compared to placebo (RR 0.97, 95% CI: 0.73, 1.30, I
2
=0%).

Conclusions:
IV iron showed significant improvement in re-hospitalization rate for AHF hospitalizations in iron deficient patients but didn’t improve overall mortality. We need larger RCTs to further validate its effect on mortality.
Abstract 12678: Marketplace Plan Designs for Cardiometabolic Therapies in Rural and Urban Counties in the US
Authors: Hermes Zachary , Bunn David A , AbdelHameid Duaa , Jaji Zainab , Machado Sara , Vaduganathan Muthiah
Published: April 2024

Introduction:
In the US, important variation exists in cardiovascular risk factor burden and rates of death across rural and urban counties. Affordability and non-financial mechanisms can present as barriers to treatment, yet little is known about if there may be systematic variation in plan design by rural and urban settings. We assessed whether rural or urban county type is associated with insurance plan design for sacubitril/valsartan, dapagliflozin, and empagliflozin.

Methods:
We evaluated the median premium silver-level plan from 26 selected states with federally-facilitated marketplaces based on the Bureau of Economic Analysis Regions. We then examined features such as coverage, tier, copay or coinsurance, expected out-of-pocket costs for 30 day supply, and coverage contingent non-financial elements including prior authorization, step therapy, and quantity limits. Logistic regression models, stratified by medication and state, assessed if rural/urban county type was a predictor of cost-sharing mechanism, coverage contingent elements, or out-of-pocket costs.

Results:
The mean population of urban and rural counties was 1.2M (±1.3M) and 19,364 (± 40,006), respectively. Urban counties had a higher proportion of Black/Hispanic individuals (31% vs. 16%) and higher median household incomes ($65,835 ± $17,452 vs. $47,212 ± $10,549); all P < 0.01. Over 90% of plans covered each of the three medications, irrespective of rural/urban county type. Across each of the three medications and states, plans in urban counties had higher odds of including prior authorization (OR: 10.59; 95% CI: 2.55-43.96; P = 0.001) and use of coinsurance (OR: 9.06; 95% CI: 2.55-32.20; P = 0.001) compared with plans in rural counties. For each drug, predicted out-of-pocket costs differed as much as $250 between rural and urban counties for a given state.

Conclusion:
Most plans cover these newer cardiometabolic therapies across sampled US counties, but there was substantial variation in plan architecture across counties with greater utilization of prior authorization and coinsurance as a cost-sharing mechanism in urban counties. Given a greater population density, these mechanisms may guard against moral hazard and overutilization in urban settings.
Abstract 12682: Markers of Microbial Translocation Biomarkers in People Living With HIV Infection and Their Relationship With Myocardial Function and Fibrosis: Myocardial and Coronary Abnormalities in HIV Infection (MACHIN) Study
Authors: Khan Farhaad , Banayan April , Reddy Pavan , Minasian Arazin , Javed Ahsan , Valencerina Samuel , Bahrami Hossein
Published: April 2024

Background:
Microbial translocation (MT) is suggested to play a role in increases risk of myocardial fibrosis (MF) and LV dysfunction in people living with HIV infection (PLWH). We investigated the association of biomarkers of MT with myocardial disease in MACHIN study.

Methods:
Biomarkers of MT (soluble CD14 (sCD14), FABP, SGP130, and BDG) were measured in serum samples of 92 participants (54 PLWH and 38 HIV- controls, mean age 47±14 years, 28% female). Myocardial structure and function were assessed using CMR. In addition, our protocol included detection of overt MF using delayed-enhancement images as well as diffuse MF using extracellular volume (ECV)-measured by T1 mapping.

Results:
FABP levels were significantly higher in PLWH compared to controls (percentage of people in higher tertile 17% vs 47%, respectively, OR: 4.4, 95% CI: 1.4-13.5, p: 0.01) and this association was significant after adjustment for age and race. Higher values of FABP were significantly correlated with presence and extent of MF. Participants with higher tertile of FABP had a significantly higher odds of presence of MF (ECV above median) compared to controls (OR: 5.9, 95% CI: 1.3, 27.0, p: 0.02) after adjustment for HIV status, age, gender, and race. Furthermore, participants with high FABP also had higher extent of MF (calculated ECV values) compared to controls (adjusted regression coefficient 6.7%, p<0.01). Importantly, while HIV infection was significantly associated with presence and extent of MF, these associations were not significant when FABP was added to the models, suggesting that FABP may explain the relationship between HIV infection and MF. PLWH had significantly higher levels of sCD14 compared to controls (p <0.05), even after adjustment for age, gender, and race (p-value: 0.04). However, serum levels of sCD14 was not associated with LV and RV systolic function, LV mass, MF, or delayed-enhancement on cardiac MRI. SGP130 and BDG were not significantly associated with MF.

Conclusion:
Increased levels of biomarkers of microbial translocation is observed in virologically-suppressed PLWH and may explain the increased risk of MF in these patients.
Abstract 12751: Diallyl Trisulfide Augments Lymphangiogenesis via an Akt-Dependent Mechanism and Ameliorates Lymphedema
Authors: Suzuki Junya , Shimizu Yuuki , Pu Zhongyue , Hayashi Takumi , Che Yiyang , Calvert John W , Murohara Toyoaki
Published: April 2024

Background:
Secondary lymphedema is one of the serious clinical problems that can often occur after surgical resection of malignant tumors. However, no effective treatment options exist at present. Diallyl trisulfide (DATS) is an organic polysulfide found in garlic oil that liberates H2S under physiological conditions. We previously demonstrated that DATS augmented reparative angiogenesis and improved blood perfusion recovery in the HLI model. Here, we investigated the effects of DATS on lymphatic vessel growth and lymphedema in a mouse model and assessed its potential mechanism.

Methods and Results:
A mouse model of lymphedema was created by ablation of a tail surface lymphatic network, and the tail diameter was measured to estimate lymphedema at day 28 after induction of lymphedema. Lymphatic vessels were detected by immunohistochemical staining as LYVE-1 and podoplanin double-positive cells. The DATS group was intraperitoneally injected with DATS for up to 10 days following lymphedema induction. DATS treated mice (n=10) showed a smaller tail thickness compared with control wild-type (WT) mice (n=11) (p<0.001) which was accompanied by a greater number of lymphatic vessels in the injured tails (p<0.05). Interestingly, the distal lymphatic lumen area was dilated in the control group, whereas the DATS treatment group improve dilated lymphatic area at the distal site of the injured point (p<0.001). In vitro experiments revealed that treatment with DATS promoted the differentiation of human lymphatic endothelial cells (LECs) into tube-like structures (p<0.001) in a dose-dependent manner, when cultured on Matrigel matrix. DATS also stimulated the phosphorylation of Akt in LECs. Furthermore, blockade of Akt activation canceled the DATS-stimulated increase in LEC differentiation.

Conclusions:
Our data clearly demonstrate that DATS promotes reparative lymphatic vessel growth and ameliorates secondary lymphedema, at least in part, through activation of the Akt pathway within lymphatic endothelial cells.
Abstract 12756: Long-Term Efficacy and Safety of Evinacumab in Adult and Adolescent Patients With Homozygous Familial Hypercholesterolemia
Authors: Gaudet Daniel , saheb samir , Iannuzzo Gabriella , STEFANUTTI Claudia , Stroes Erik S , Rosenson Robert S , Turner Traci , ali shazia , Banerjee Poulabi , Drewery Tiera , pordy robert , Zhao Jian , Raal Frederick J
Published: April 2024

Introduction:
Homozygous familial hypercholesterolemia (HoFH) is an ultra-rare genetic lipid disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) and premature atherosclerotic cardiovascular disease, underscoring the need for early and aggressive treatment. Evinacumab, an angiopoietin-like 3 inhibitor, significantly reduced LDL-C in patients with HoFH in a pivotal Phase 3 trial (NCT03399786). The current study assesses long-term safety and efficacy of evinacumab in patients with HoFH.

Methods:
This is an interim analysis of an evinacumab open-label Phase 3 trial (NCT03409744) in adult and adolescent(12-<18 years) patients with HoFH. Patients who previously received evinacumab or who were evinacumab-naïve both received intravenous evinacumab 15 mg/kg every 4 weeks.

Results:
A total of 115 patients (50.4% male; mean [range] age 39 [12-75] years; 11.3% adolescent) were enrolled and treated for a mean (range) duration of 53 (4-132) weeks. At baseline, mean (standard deviation [SD]) LDL-C was 261.8 (160.5) mg/dL; 44 (38.3%) patients were receiving concomitant lipoprotein apheresis. At Week 24, data were available for 81 patients. From baseline to Week 24, evinacumab reduced mean LDL-C for all patients by 43.7% (mean [SD], 133.0 [125.9] mg/dL); mean LDL-C reduction for adult (n=72) and adolescent (n=9) subgroups was 42.6% (mean [SD], 126.7 [127.9] mg/dL) and 52.4% (mean [SD], 183.4 [101.6] mg/dL), respectively. Treatment-emergent adverse events (TEAEs) occurred in 76 (66.1%) patients; one patient reported pregnancy which led to discontinuation of study treatment per protocol. Serious TEAEs were reported by 16 (13.9%) patients; two (1.7%) patients experienced a TEAE resulting in death, none of which were considered related to study treatment.

Conclusions:
In this large cohort of patients with HoFH, evinacumab markedly reduced LDL-C irrespective of age. Evinacumab was generally well tolerated, and the efficacy and safety of evinacumab was sustained over the long term.
Abstract 12766: Treatment of Patients With Atrial Fibrillation and Heart Failure in the AIM-AF (Antiarrhythmic Medication for Atrial Fibrillation) Study: A Physician Survey on the Prescription of Antiarrhythmic Drugs in the US and Europe
Authors: Piccini Jonathan P , Blomstrom-Lundqvist Carina , Boriani Giuseppe , Goette Andreas L , Kowey Peter R , Merino Jose , Reiffel James A , Saksena Sanjeev , Camm Alan J
Published: April 2024

Introduction:
ACC/AHA/HRS guidelines recommend dofetilide or amiodarone in patients with atrial fibrillation (AF) and symptomatic heart failure (HF). ESC 2020 guidelines added dronedarone (IA) and sotalol (IIbA) as antiarrhythmic drug (AAD) options for patients with AF and HF with preserved ejection fraction (HFpEF), retaining only amiodarone (IA) for AF and HF with reduced ejection fraction (HFrEF). Dronedarone was also added for patients with normal or mildly impaired (but stable) left ventricular function (IA). In both guidelines, catheter ablation (ABL) may be considered in AF and HFrEF to improve outcomes.

Methods:
An online survey to understand treatment practice in patients with AF and HF was conducted in the US, Germany, Italy, Sweden, and the UK. Respondents were cardiologists or cardiac electrophysiologists (N=629) actively treating ≥10 patients with AF who received AAD therapy and/or had received or were referred for ABL. The survey comprised 96 questions on physician demographics, AF types, and treatment practices.

Results:
After AF type and symptom status, presence of HF was the third most cited reason to select rhythm control over rate control (13% of respondents). Overall, 39% preferred first-line ABL over AADs in patients with AF and comorbidities such as HF; yet HFrEF was the top-ranked factor for favoring AADs over ABL by 20%. Amiodarone was the AAD selected most often in HFrEF (81%), and HFpEF (60%), and used less in the US than Europe (particularly in HFrEF: 71% vs 91%). Sotalol was selected by 18% as a typical choice for AF with HFrEF (US 25%, Europe 12%), not in accordance with guideline recommendations; class Ic drugs were also selected in HFrEF (US 8%, Europe 4%) contrary to recommendations. Use of dronedarone (18% vs 27%) and sotalol (26% vs 42%) was less common in the US than Europe in patients with HFpEF; use of class Ic agents, against recommendations, was the same in both regions (18%).

Conclusions:
Presence of HF is frequently considered by physicians in AF treatment decisions, but treatment patterns indicate divergence from guideline recommendations with several specific AADs. However, the guidelines do not clearly define HF and, in clinical practice, use of non-recommended agents appear acceptable to some in individual circumstances.
Abstract 12777: Bmi1 Mediates Chromatin Remodeling and Redox Homeostasis for Cardiac Repair After Myocardial Injury
Authors: Kraus Lindsay , Wagner Marcus J , Kino Tabito , Mohsin Sadia
Published: April 2024

Introduction:
Myocardial injury leads to oxidative stress that has a significant impact on the development and progression of disease. Increasing evidence suggests that oxidative stress globally influences chromatin landscape of the cells. Effects of oxidative stress on these chromatin alterations mediate a number of cellular changes, including DNA damage, cell death, and accelerated senescence which are all disease-driving mechanisms during the failing heart. Targeting oxidative stress-dependent pathways is thus a promising strategy for the prevention and treatment after myocardial injury. The Polycomb complex protein BMI-1 (Bmi1) an epigenetic regulator, is associated with numerous biological functions including, mediating DNA damage control, ROS signaling and senescence. However, there is currently a lack of understanding on how Bmi1 mediates epigenetic modifications affecting heart function during injury and is a focus of this study.

Hypothesis:
The epigenetic regulation by Bmi1 mediates reparative process after myocardial injury by regulating ROS production. Specifically, Bmi1 modulates the epigenetic landscape of cardiac cells that mediates various molecular processes during development and stress conditions.

Methods and Results:
Using a Bmi1 knockout (KO) model through the induction of a tamoxifen Cre recombinase system, cardiac function is determined through echocardiography using adult mice following myocardial infarction. The Bmi1 KO has a significant decrease in heart function after myocardial infarction, which has been associated with increased cellular ROS production, fibrosis, and apoptotic mechanisms which are measured by fluorescent ROS assays, TUNEL assays, western blotting, PCR, and immunohistochemistry. To date, we have found that cardiac cells, including adult cardiomyocytes and adult cardiac fibroblasts, isolated from the Bmi1 KO model have increased cellular ROS production, increased expression of fibrotic genes including Acta2, Vimentin, Collagen, and increased expression of apoptotic pathway regulators including Aldo1, Eno1, NFkB, Ap-1, and HIF1-a.

Conclusions:
Bmi-1 regulation mediates repair during pathological challenge by regulating ROS production after myocardial injury.
Abstract 12778: A High Physiological Stress Response is Dependent on Call Type in Firefighters
Authors: Rynne Paige J , Donahue Stephanie , Carty Megan A , Dickinson Rachel L , Lashley Meghan , Reeve Emily H , Gilpin Julia , McMorrow Carly , Almeida Andrew A , Sherman Will , Arsenault Myra , Feairheller Deborah L
Published: April 2024

Introduction:
CVD and impaired cardiovascular health is noticeably more prevalent in firefighters (FF) than the general population, with over 50% of line-of-duty deaths being cardiovascular related. Many FF have hypertension but less than 25% have their BP under control. The BP and HR response to different calls and job activity in FF is unknown. Thus, we aimed to evaluate and quantify the physiological stress resulting from different types of calls and job activity (fire, medical, riding apparatus) through ambulatory blood pressure (ABP) monitoring.

Hypothesis:
We hypothesize that fire calls will result in the largest BP surge in FF compared to other types of calls and work conditions.

Methods:
FF (n=41; 37M, 4F) wore an ABP monitor for at least 12-hours while working. BP was measured every 30 min during daytime and 60 min during nighttime, if worn overnight. Data was analyzed when > 70% of readings were captured. FF were instructed to force an ABP reading when the pager sounded and whenever they felt they entered a stressful situation. Activity and call type were documented on a log sheet for each measurement.

Results:
The FF were experienced (16.9 ± 11.9 yrs as FF), overweight (BMI: 30.3
+
4.6 kg/m
2
), middle aged (41.2 ± 13.1 yrs), and hypertensive with average ABP over the 12 hr shift at 131 ± 13.4 / 79.3 ± 8.8 mmHg and HR 75.7 ± 8.8 bpm. Systolic BP surged 19.2 ± 12.2 with fire calls and 18.7 ± 8.1 mmHg with medical calls. Diastolic BP surged 10.5 ± 9.9 with fire and 16.5 ± 10.5 mmHg with medical calls. There were no differences in BP, HR, or BP surge levels (
P
>0.05 for all) between the types of measurements (fire, medical, apparatus, alarms). Compared to average ABP values, the response was higher with fire calls (143.9/85.5 mmHg, 85.5 bpm) than medical calls (139.0/87.0 mmHg, 90.5 bpm). Physiological responses were also high when FF rode apparatus (139.8/83.7 mmHg, 81.9 bpm) and received false alarms (137.6/82.6 mmHg, 83.4 bpm).

Conclusion:
Fire and medical calls resulted in the greatest CV response. On average, fire calls resulted in a 9% increase in systolic BP and medical calls a 9% increase in diastolic BP and a 16% increase in HR. Further investigation in a larger population is warranted to substantiate these results as well as study other variables that may affect BP and HR responses in FF.
Abstract 12791: Facility Characteristics Associated With High-Performing Outpatient Diabetes and Cardiovascular Disease Risk Factor Program Awardees
Authors: Langabeer James R , Niu Ray , Sednew Renee , Pressley Alyssa , Overton Katherine , Heard Debbie , Scharnott Michelle
Published: April 2024

Background:
The American Heart Association (AHA) developed an outpatient recognition program centered around the care of patients with type 2 diabetes as part of the Know Diabetes by Heart initiative. The program offers two levels of recognition, Participant and Gold. With over 500 outpatient organizations in the program, specific facility characteristics and component protocols were analyzed to determine what variables increased a site’s likelihood of being a Gold awardee.

Methods:
The AHA Quality and Analytics team examined multiple data sets from 470 (203 Gold, 267 Participant) award winning facilities. 2020 recognition level was based on aggregate patient data from the 2019 calendar year and self-identified facility characteristics. Univariate regression modeling was carried out to determine facility characteristics that contributed to a site achieving Gold or Participant Target: Type 2 Diabetes award which are displayed in table 1.

Results:
Higher percentage of Gold-level recipients implemented more treatment plans and protocols for their patients compared to Participant-level recipients. This trend also exists in activities that elevated standard of care for all patients such as assessing for comorbidities, lifestyle modification, and motivation and depression.

Conclusion:
Facilities characterized as having multiple components in treatment protocols in T2D patients, diabetes self-management and education (DSME), and defined protocols for use of pharmacologic therapy had higher likelihood of achieving Gold award status. In contrast, smaller, non-academic, and high minority population organization were less likely to achieve Gold status, highlighting the care disparities that still need to be addressed. Resources focused on assisting facilities to adopt these evidence-based protocols could help organizations further elevate their T2D management practices, achieve improved patient outcomes and award levels for all organization types.
Abstract 13053: Cardiac Allograft Vasculopathy Following Donation After Circulatory-Determined Death Heart Transplantation
Authors: Cheshire Caitlin , Vokshi Ismail , Ali Jason , Messer Simon , Page Aravinda , Kydd Anna , Pettit Stephen , Lewis Clive , Tweed Katharine , Berman Marius , Kaul Pradeep , Tsui Steven , Jenkins David , Parameshwar Jayan , Bhagra Sai
Published: April 2024

Introduction:
Cardiac allograft vasculopathy (CAV) remains a major problem for heart transplant (HTx) recipients, limiting their long-term survival. Our centre has performed the world’s largest series of donation after circulatory-determined death (DCD) HTx. Five-year survival is equivalent to donation after brainstem-determined death (DBD) HTx. However, there is no information on CAV in DCD HTx recipients. We sought to evaluate the incidence of CAV in our cohort of DCD HTx recipients.

Methods:
All DCD HTx recipients at our centre between February 2015 and December 2019 who had undergone CAV screening were included. They were compared with all DBD recipients during the same period who had undergone CAV screening. Angiograms were retrospectively assigned an ISHLT CAV grade by two independent observers.

Results:
Thirty-six DCD and 70 DBD HTx recipients were included in the study. Median time to first imaging of coronary arteries was 621 days and 572 days for DCD and DBD cohorts respectively. There was a higher proportion of male donors in the DCD cohort (p= 0.03) but no other significant differences between donor baseline characteristics. DCD recipients had a lower median pre-transplant pulmonary vascular resistance (p=0.03) but there were no other significant differences in recipient baseline characteristics. The two cohorts had similar rates of pre-operative durable LVAD use, post-transplant mechanical circulatory support and post-transplant immunosuppression regimes. There was no significant difference in the rates of CAV between the DBD and DCD groups (p=0.41) (Figure 1). When adjusted for standard risk factors for development of CAV (including donor factors, CMV status and rejection) there remained no significant difference between rates of CAV between groups (OR 1.48, p=0.41, 95% CI 0.58-3.78).

Conclusions:
DCD HTx recipients have similar rates of CAV when compared to a contemporary population of DBD HTx recipients.
Abstract 13066: Circulating Cellular Clusters: A Proposed Mechanism and Novel Biomarker for Immunothrombosis and Clinical Outcomes in Patients With COVID-19
Authors: Dorken Gallastegi Ander , Li He , Naar Leon , Van Cott Elizabeth M , Rosovsky Rachel P , Gregory David J , Annamalai Damodaran , Kaafarani Haytham M , Velmahos George , Karniadakis George E , Lee Jarone , Frydman Galit H
Published: April 2024

Introduction:
Circulating Cellular Clusters (CCCs) have been studied in the context of cancer; however, CCCs in other inflammatory conditions, such as COVID-19, have not been explored.

Hypothesis:
CCC phenotypes play a role in immunothrombosis and in the development of adverse events.

Methods:
Blood samples were collected from patients with a positive SARS-CoV2 PCR treated at the Massachusetts General Hospital. Imaging flow cytometry was used to characterize CCCs, including: platelet-leukocyte aggregates (PLAs), leukocyte clusters (LCs) and platelet-erythrocyte aggregates (PEAs) (Fig1A). CCC phenotypes were compared with controls and were correlated with clinical outcomes. CCCs identified to be significant were used to guide a computational model investigating the mechanism of CCC formation and their behavior in circulation (Fig1C).

Results:
Forty-six COVID-19 and 12 control samples were analyzed. Statistically significant positive correlations were identified between CCCs and clinical outcomes in patients with COVID-19 (Fig1B). Using these data as inputs, computational simulations illustrated that CCCs may form in the circulation and be recruited by existing thrombi and sites of inflammation, or may detach from thrombogenic sites (Fig1D).

Conclusions:
CCCs are correlated with the development of significant clinical outcomes and cluster phenotypes appear to be associated with specific outcomes. CCCs may form de novo in the circulation or via the detachment from a thrombus. These CCCs may subsequently attach to a second thrombus downstream or serve as their own nidus for thrombus development, resulting in vessel lumen occlusion. Computational modeling serves as a powerful tool for the exploration of the pathophysiological mechanism by which CCCs contribute to thrombus formation. These findings may serve as novel biomarkers and aid in the identification of new drug targets for immunothrombotic complications in severe inflammatory conditions.
Abstract 13072: Association Between Baseline Lipoprotein(a) and Five-Year Outcomes in Patients Underwent Coronary Artery Bypass Grafting: A Post-Hoc Analysis of DACAB Trial
Authors: Yu Qixiang , Zhou Yanzai , Zhang Wei , Zhao Qiang , Zhu Yunpeng
Published: April 2024

Introduction:
Serum lipoprotein(a) [Lp(a)] is genetically determined and has been proposed to be associated with coronary artery lesion severity and clinical outcomes in coronary artery disease (CAD). But some researches suggested heterogeneous effects and marked variations of Lp(a) level between ethnic groups. The aim of this study was to investigate the impact of baseline Lp(a) on five-year clinical outcomes in Chinese population who underwent coronary artery bypass grafting (CABG).

Methods:
We performed a post-hoc analysis of the DACAB trial (NCT02201771), in which patients aged 18 to 80 years, male or female, underwent primary, isolated and elective CABG, were randomly assigned to receive different antiplatelet treatments. Serum Lp(a) was obtained and analyzed in 270/272 patients of one single center. The primary outcome was major adverse cardiovascular events (MACE). MACE-5 included all-cause death, myocardial infarction, stroke, repeated revascularization and rehospitalization for unstable angina, and MACE-3 included cardiovascular death, myocardial infarction, and stroke. The mean follow-up reached 59.4±9.4 months.

Results:
The baseline characteristics were generally comparable. High Lp(a) level was identified in 71 (26.3%) (cut-off ≥30mg/dL) and 33 (12.2%) (cut-off ≥50mg/dL) patients, respectively. During 5-year follow-up, MACE-5 reported in high and low Lp(a) group were 34.2% vs 28.8% when the cut-off value was 30mg/dL (hazard ratio [HR], 1.11; 95% CI, 0.69-1.78, p=0.66). While the cut-off value was 50mg/dL, MACE-5 reported in high and low Lp(a) group were 39.4% vs 28.9% (HR, 1.32; 95% CI, 0.73-2.38, p=0.36). Similar results were observed in MACE-3 (Cut-off value 30mg/dL: 24.2% vs 21.9%, HR 1.08, p=0.78; Cut-off value 50mg/dL: 27.3% vs 21.8%, HR 1.24, p=0.56). No statistical significant difference was achieved between the two groups.

Conclusions:
In this single center post-hoc analysis, baseline Lp(a) level ≥30mg/dL or ≥50mg/dL had no statistical significant association with 5-year MACE in post-CABG Chinese population. But higher baseline Lp(a) levels seem to be associated with more MACE in longer follow-up. Larger sample size from multicenter are needed to confirm our findings.
Abstract 13078: Cardiovascular Disease Risk Factors and Incident Myocardial Infarction in Patients on Buprenorphine
Authors: Munger Jordan , Wilkinson Katherine , Sparks Andrew , Koh Insu , Zakai Neil
Published: April 2024

Introduction:
People treated for opioid use disorder with buprenorphine may have increased cardiovascular disease (CVD) risk despite routinely seeing health care providers. We studied CVD risk factors and incident myocardial infarction (MI) in patients on buprenorphine to assess this population’s need for CVD prevention.

Hypothesis:
People on buprenorphine have a higher burden of CVD risk factors compared to age and sex matched controls.

Methods:
All patients with primary care visits in a large health network between 2010-2019 were included. Buprenorphine use was defined as receiving buprenorphine during the study period. Incident hospitalized myocardial infarction (MI) was an internally validated electronic health record derived computable phenotype. Patient characteristics and CVD risk factors were compared between buprenorphine use and non-use cohorts after age and sex matching. The risk of incident MI associated with buprenorphine was estimated with Cox-proportional hazards regression matching for age, sex, and a propensity score (PS).

Results:
In 61,495 people, 539 (0.88%) were on buprenorphine, of which 52.7% (284/539) were female and the average age was 34.6 ± 12 years. Relative to age and sex-matched controls (n=10,780), buprenorphine users had a higher burden of CVD comorbidities including diabetes (5.4% vs 3.6%), hypertension (15.6% vs 12.6%), chronic kidney disease (1.5% vs 0.5%), peripheral artery disease (0.9% vs 0.4%), and history of MI (1.7% vs 0.6%;
Table
). The age and sex-matched adjusted hazard of incident MI for buprenorphine was 1.23 (95% CI: 0.38 – 3.94), decreasing to 0.92 (95% CI: 0.23 – 3.70) after PS matching.

Conclusions:
People on buprenorphine had a higher burden of CVD risk factors than age and sex-matched controls, and a higher point estimate of incident MI that attenuated after accounting for CVD risk factors. There may be an opportunity to reduce the CVD risk of people on buprenorphine, a population already engaged with health care.
Abstract 13090: Racial and Ethnic Differences in Anthracycline Cardiotoxicity
Authors: Zhang Lili , Song Justin , Clark Rachel , Mangoni Arduino , Goldberg Ythan , Slipczuk Leandro , Garcia Mario J , Bansal Neha , Sadler Diego B , Neilan Tomas , Sica Roberto Alejandro , Sparano Joseph A , Rodriguez Carlos J
Published: April 2024

Background:
There are limited data on anthracycline cardiotoxicity in racially and ethnically diverse populations. Therefore, our study sought to examine incident heart failure (HF) in cancer survivors treated with anthracycline in a multiracial community.

Methods:
We included consecutive adult patients who underwent anthracycline-based chemotherapy in 2016 and 2019 for any types of cancer at a single academic health system that serves a large multiracial community. Patients with preexisting HF were excluded. The end point was new development of clinical HF (ascertained by ICD-9 or 10 codes). Multivariable Cox proportional hazards models, adjusting for demographics, cardiovascular risk factors and anthracycline dose, were performed.

Results:
Our cohort studied 1,084 patients, including 21% Non-Hispanic White (NHW), 24% Non-Hispanic Blacks (NHB), 32% Hispanics and 2% Asians (Figure 1A). Mean age of the cohort was 58 ± 15 years, with 66% women. Hypertension, diabetes and hyperlipidemia were more prevalent in NHB, Hispanics and Asians than in NHW. Socioeconomic status score of NHB (-2.8 ± 2.7), Hispanics (-3.8 ± 2.8) and Asians (-2.0 ± 2.5) was significantly lower than NHW (0.1 ± 2.1, p<0.001). Mean cumulative anthracycline dose was 321 ± 205mg/m
2
and it was similar across groups. During median follow-up of 15 months, 113 patients developed HF. The cumulative incidence of HF was 11% in the entire cohort, with 6% in NHW, 12% in NHB, 11% in Hispanics and 23% in Asians (Figure 1B, p=0.055). Asian race (HR 3.8, 95%CI 1.3-11.5, p=0.016) and increased age (HR 1.02, 95%CI 1.01- 1.04, p=0.023) were significantly associated with incident HF. NH Black (HR 1.5, 95%CI 0.8-3.1) and Hispanic (HR 1.3, 95%CI 0.7-2.7) groups did not reach significance in multivariable adjusted analysis.

Conclusions:
In a large cohort of multiracial cancer survivors treated anthracycline-based chemotherapy, a higher incidence of clinical HF was identified in NHB, Hispanics and Asians compared with NHW.
Abstract 13121: Isolation and Primary Culture of Murine Aortic Cells for Atherosclerosis Research
Authors: Chen Jingshu , Zhuang Rulin , Assa Carmel , Cheng Henry , Feinberg Mark W
Published: April 2024

Introduction:
Atherosclerosis is a chronic inflammatory disease of the vascular wall characterized by abnormal lipid deposition, immune cell infiltration, and plaque formation. Isolation of the cellular constituents of the mouse aorta is commonly used for expression or functional analyses in experimental atherosclerosis. Endothelial cell, smooth muscle cell, leukocyte, and fibroblast are four major contributors to the progression of atherosclerosis. However, the isolation and culture of the primary aortic cells is considered difficult, often resulting in low yields. Current procedures are either only focused on isolation of one cell type or required long time for isolation and culture.

Objective:
To address the gap in experimental atherosclerosis research, we provide a fast and efficient protocol to isolate and culture a diverse range of cell types from the mouse aorta using immunomagnetic cell sorting.

Methods and Results:
Aortic cells were obtained using an enzymatic solution and different cell types were isolated using magnetic beads conjugated to antibodies targeting endothelial cell (CD31+), leukocyte (CD45+), and fibroblast cell (CD90.2+). Aortic smooth muscle cells were isolated by negatively selection after positive removal of the other cell types. Our protocol allows the isolation of relatively large numbers of cells (approximately 10,000 cells per mouse aorta) in a predictable manner, and the purity of the magnetic beads-selected cells was over 90% which was verified by detection of cell-marker genes expression, immunofluorescence staining, and flow cytometry. We also provide a quick and simple method to collect aortic intima-enriched RNA utilizing an intima peeling approach with Trizol.

Conclusion:
This protocol provides an effective means for magnetic beads-based isolation of different cell types from the mouse aortic wall, and the isolated cells can be utilized for functional and mechanistic vascular studies including atherosclerosis.