bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15356: Serial Evaluation of Chemotherapy-Induced Vascular Toxicity in a Rat Model Using
18
F-FDG PET/CT Imaging
Authors: Nabavinia Mahboubeh , Beall Maren , Rimmerman Eleanor T , Musini Kumudha , Deep Donny , Stacy Mitchel R
Published: June 2023

Introduction:
Cancer treatment with chemotherapeutics can lead to off-target effects on the vasculature. Fluorine-18 (
18
F)-fluorodeoxyglucose (FDG) PET/CT imaging is standard of care for staging and monitoring of numerous cancers and may offer a tool for assessing vascular toxicity. We hypothesized that PET/CT imaging could quantify changes in chemotherapy-induced arterial inflammation. Thus, we sought to validate PET/CT imaging as a tool for assessing vascular toxicity in a rat model using in vivo imaging and post-mortem analyses.

Methods:
Male Wistar rats (n = 11 total) were divided into a control group that received twice weekly IV saline (n=5; 1 ml/kg) or a group that received twice weekly IV doxorubicin (n=6; 1 mg/kg) for 2.5 weeks (i.e., 7 mg/kg cumulative dose). Rats underwent
18
F-FDG microPET/CT imaging of the abdominal aorta (AA) at 3 time points (baseline, after 4 mg/kg dosing, and after 7 mg/kg cumulative dose) to quantify serial changes in arterial inflammation, expressed as changes in the maximum standard uptake value (SUV
max
). Following terminal imaging, AA tissue was harvested and cut into 3 mm sections for gamma counting of
18
F-FDG uptake, hematoxylin and eosin morphological staining, and immunohistochemistry of macrophage expression.

Results:
In vivo image analyses demonstrated that
18
F-FDG uptake remained unchanged for the control group during the treatment period, but significantly increased from baseline levels in the doxorubicin-treated group after 4 mg/kg (p=0.0007) and 7 mg/kg (p=0.001) cumulative dosing. In vivo image analyses were confirmed by post-mortem gamma counting of
18
F-FDG uptake in anatomically-matched AA tissue samples. Histological analyses revealed increased levels of macrophage expression in sections with increased
18
F-FDG uptake identified by in vivo and ex vivo analyses.

Conclusions:
18
F-FDG PET/CT imaging non-invasively quantifies serial changes in chemotherapy-induced arterial toxicity that are at least partially mediated by increased macrophage activity. Routine assessment of
18
F-FDG uptake on PET/CT imaging studies during cancer treatment could provide a translatable approach for characterizing the time course of vascular toxicity associated with various chemotherapeutics.
Abstract 15361: Rurality and Characteristics of Participants With Heart Failure in the Reasons for Geographic and Racial Differences in Stroke (Regards) Study
Authors: Clarkson Stephen , Brown Todd , Heindl Brittain F , Cherrington Andrea , Levitan Emily B , Jackson Elizabeth A , Zhu Aowen
Published: June 2023

Introduction:
Individuals living with heart failure (HF) in rural settings have higher age-adjusted mortality than urban dwelling individuals. Thus, we sought to examine sociodemographic and clinical differences between rural and urban populations with HF to better understand this disparity.

Methods:
We examined participants from the REasons for Geographic and Racial Differences in Stroke (REGARDS) population-based cohort who completed a computer-assisted telephone interview (CATI) 10-years following initial recruitment, and who either self-reported a history of HF or had an adjudicated HF hospitalization prior to the CATI. Rural and urban designations utilized a dichotomized adaption of the Rural Urban Commuting Area. We compared sociodemographic and clinical characteristics between rural/urban participants. Logistic regression was used to examine the association between depression and health literacy with urban dwelling.

Results:
A total of 1002 participants had self reported HF or an adjudicated HF hospitalization during approximately 10 years of follow-up, of which 195 (19%) were classified as rural. Rural dwelling participants with HF were younger (73.5 vs 75.4 years; p=0.004) and more likely to live in the stroke belt (45% vs 33%; p<0.001), earn <$20,000/year (27% vs 20%; p=0.030), experience depressive symptoms (52% vs 45%; p=0.05), and have low health literacy (24% vs 16%; p=0.02). Rural dwelling was associated with higher odds of low health literacy (aOR 1.79, CI 1.07-3.01; p=0.017) and depressive symptoms (aOR 1.13, CI 0.78-1.63; p=0.52).

Conclusions:
Rural dwelling participants with HF have a lower income and education than urban dwellers. Living in a rural setting was associated with a higher odds of having low health literacy, and half of rural dwelling participants with HF experience depressive symptoms. Addressing these factors may reduce rural/urban disparities in HF outcomes.
Abstract 15362: Checkpoint Kinase 1-Associated Senp2 S344 Phosphorylation Under Laminar Flow Attenuates Endothelial-Mesenchymal Transition and Atherogenesis
Authors: Nguyen Minh T , Imanishi Masaki , Li Shengyu , Ko Kyung Ae , Banerjee Priyanka , Velatooru Loka reddy , McBeath Elena , Fujiwara Keigi , Kotla Sivareddy , Chau Khanh , Abe Rei , borchardt mae k , Yeh Edward T , Cooke John P , Wang Guangyu , Abe Junichi , Le Nhat Tu T
Published: June 2023

Aims:
To investigate the role of Checkpoint Kinase 1 (CHK1)-associated SENP2 S344 phosphorylation in laminar flow (LF)-regulated Endothelial-Mesenchymal Transition (EndMT) inhibition and the underlying mechanisms.

Methods:
We generated deSUMOylation enzyme sentrin-specific isopeptidase 2 (SENP2) S343A (equivalent to human SENP2 S344) knock-in (KI) and endothelial cell (EC)-specific SENP2 knock-out (SENP2 EKO) mice to detect EC activation, EndMT, and atherogenesis
in vitro
and
in vivo
. We also performed next-generation RNA sequencing (RNA-seq) analysis in ECs derived from these mice.

Results:
LF, but not disturbed flow (DF), triggered SENP2 S344 phosphorylation through CHK1. The decreased ERK5- and p53-SUMOylation by LF was abolished in ECs derived from SENP2 S343A KI mice. Both EC apoptosis and VCAM-1 expression were upregulated in SENP2 S344A KI mice. The increased atherogenesis in SENP2 S344A KI was regulated by vascular, but not hematopoietic, cells based on bone marrow transplantation (BMT) study. CHK1 expression was decreased by ionizing radiation (IR), leading to an enhanced ERK5- and p53-SUMOylation as well as EC inflammation. RNA-seq analysis revealed the involvement of SENP2 S344 phosphorylation in changes of fibrotic phenotypes and EndMT-related genes. Further, SENP2 S344A point mutation prevented LF-regulated TGFbR1 SUMOylation inhibition in vitro, as well as hypercholesterolemia-induced EndMT in vivo.

Discussions:
These data revealed the unique role of CHK1-associated SENP2 S344 phosphorylation in not only LF-regulated EndMT inhibition but also IR-associated EndMT activation and the subsequent atherogenesis. Maintaining CHK1-associated SENP2 S344 phosphorylation can be an ideal approach to mitigate EndMT, which is important in tumor radio-resistance as well as IR-associated cardiovascular disease.
Abstract 15397: Pericardial Delayed Hyperenhancement Predicts Outcomes in Idiopathic Recurrent Pericarditis
Authors: Syed Alveena B , Layoun Habib , Yesilyaprak Abdullah , Majid Muhammad , Agrawal Ankit , Furqan Muhammad M , Kumar Ashwin , Yaker Zachary S , Berglund Felix , Klein Allan L
Published: June 2023

Introduction:
Recurrent pericarditis (RP) is defined as recurrence of pericarditis after an initial documented episode of pericarditis and symptom free interval of four to six weeks. In this study, we aimed to investigate the prognostic value of the pericardial delayed hyperenhancement (DHE) in patients with idiopathic recurrent pericarditis (IRP).

Hypothesis:
We hypothesize that moderate to severe DHE is correlated with worse outcomes.

Methods:
Consecutive patients (n=223) with IRP from 2012-2019 were included. Out of 223 patients, 213 had DHE tracing. Patients were then followed for events of clinical improvement (CI), clinical remission (CR), and clinical recurrence.

Results:
The mean age of the 223 patients included was 45 ± 16 years, and 51% were females. DHE was divided into two groups none/mild (n=160) and moderate/severe (n=53). At baseline, median number of prior recurrences was 3 (Q1, Q3: 2,5). Furthermore, when adjusted for age, gender, prior number of recurrences, and anti-inflammatory therapy on multivariable cox-regression analysis, moderate to severe DHE was independently associated with less likelihood of having CI (HR 0.24, p<0.001) and CR (HR 0.31, p=0.011), and more likelihood of having clinical recurrence (HR 1.58, p=0.02). On Kaplan Meier analysis, moderate to severe DHE was associated with more time to clinical improvement (log rank p<0.0001), more time to clinical remission (log rank p<0.0001), and less time to clinical recurrence (log rank p=0.0047).

Conclusions:
Moderate to severe DHE is independently correlated with worse outcomes in patients with IRP. DHE should be considered an important part of evaluation in patients with recurrent pericarditis and should be included in new guidelines. Our study will help clinicians utilize DHE as a prognostic marker in patients with IRP.
Abstract 15399: Proteomic Landscape of Plasma Lipoprotein Responses to Regular Exercise
Authors: Barber Jacob L , Cai Guoshuai , Robbins Jeremy M , Rao Prashant , Mi Michael , Ghosh Sujoy , Clish Clary , Katz Daniel H , Bouchard Claude , Gerszten Robert E , Sarzynski Mark A
Published: June 2023

Introduction:
Lipoproteins are among the strongest predictors of CVD and are altered through regular exercise. However, the molecular changes underlying the potential benefits of exercise on plasma lipoproteins are unclear.

Methods:
Proteins (n=4979) were quantified from the plasma of 647 Black and White adults (56% women, mean age = 34.9 yrs) before and after 20-weeks of endurance exercise training using SomaScan. All subjects had complete data for 7 lipoprotein traits that improved with training: HDL-C, TG, large TG rich lipoprotein particles (LTRLP), small LDL particles (SLDLP), large HDL particles (LHDLP), TRLP size, and LDLP size. Fully adjusted linear mixed models were used to test the association of 1) baseline proteins with baseline lipoproteins and 2) delta proteins with delta lipoproteins (delta = post training - baseline value). Significance was determined as FDR<0.05.

Results:
We identified numerous proteins associated with baseline levels of at least one of the seven lipoprotein traits (range: 48-1099) and whose changes in response to regular exercise were associated with concomitant changes in lipoproteins (range: 4-95) (
Table 1
). Substantial overlap was found between proteins associated with lipoproteins across timepoints, with 16 proteins associated with 4 or more lipoprotein traits at both timepoints. Plasma abundance of 12/16 proteins significantly changed with training (FDR <0.05). Additionally, for these proteins plasma abundance changed in concordance with the beneficial direction of the associated lipoprotein trait (e.g., proteins associated with atheroprotective lipoprotein traits increased with training and proteins associated with atherogenic traits decreased).

Conclusions:
Beneficial alterations to plasma lipoproteins with regular exercise are reflected in changes to the plasma proteome. Proteins identified here may represent novel markers of the benefits of regular exercise and of systemic lipoprotein metabolism.
Abstract 15422: Trend of Stroke in Mechanical Circulatory Support Devices: Insight From the National Inpatient Sample Database
Authors: Sandhyavenu Harigopal , Taha Amro , Badu Irisha , Ananthaneni Sindhura , Faisaluddin Mohammed , Ullah Waqas
Published: June 2023

Background:
Mechanical circulatory support (MCS) is increasingly being used as a bridge or destination therapy in advanced heart failure. Data on the risk of complications including stroke are limited.

Methods:
The National Inpatient Database (NIS) from 2002-2019 was analyzed to identify patients with stroke and classified based on MCS use into MCS and no-MCS groups. Using a linear regression model, trends of stroke were obtained.

Result:
On trend analysis, there was a steep increase in the incidence of stroke from 2002-2013 (MCS: 21% to 41% and no-MCS: 20% to 36%) with a decline in the trend by 2019 in MCS group compared to no-MCS group (38% vs. 44%). Annual trends of stroke in impella, extracorporeal membrane oxygenation (ECMO), intra-aortic balloon pump (IABP) and left ventricular assist device (LVAD) had initial increasing trends from 2002-2013 (1% to 18%, 2.5% to 40%, 24% to 44% and 14% to 40% respectively). Patients on LVAD had a plateaued rate from 2014-2019 (40% to 46%) while the rate in impella and ECMO continued to increase exponentially from 2014-2019 (18% to 81% and 40% to 58% respectively). Conversely, there has been a decline in the trend in IABP by 2019 (32%).

Conclusion:
The risk of stroke in patients with the use of mechanical circulatory support devices increased exponentially until 2013 and has shown a declining trend thereafter.
Abstract 15438: Long-Term Outcomes of Bariatric Surgery in Patients With Atrial Fibrillation
Authors: Thakkar Samarthkumar J , Patel Harsh P , Patel Bhavin , Tan Bryan E-Xin , Sandhyavenu Harigopal , Thotamgari Sahith Reddy , Sheth Aakash , Boppana Hemanth Krishna , Pandya Krutarth K , Patel Kunal N , Rai Devesh , Faza Nadeen N , Rao Mohan , Desimone Christopher V , Deshmukh Abhishek
Published: June 2023

Introduction:
Obesity is associated with a higher burden of atrial fibrillation (AF) and related complications.

Hypothesis:
Bariatric surgery in patients with AF is associated with a reduction in mortality and long-term complications at 1 year.

Methods:
Patients with AF who underwent bariatric surgery were identified by analyzing the nationwide readmission database and incorporating the validated ICD-10 CM codes from October 2015 to December 2019. We performed the propensity score matching to adjust the confounders and cox proportional hazard regression to generate hazard ratios. Moreover, we generated Kaplan Meier curves for time-to-event analysis. The primary endpoint was all-cause mortality at 1 year, whereas secondary endpoints were ischemic stroke, major bleeding, and AF readmission at 1 year.

Results:
Out of 892488 obese patients with AF, 18766 underwent bariatric surgery. After propensity score matching, 18764 patients were identified in each group. At 1-year, patients undergoing bariatric surgery had a significant reduction in mortality (2.18% vs. 2.73%, HR: 0.91, 95% CI: 0.85-0.96, p=0.001). Additionally, risk of ischemic stroke was also reduced (1.98% vs. 2.29%, HR: 0.91, 95% CI: 0.86-0.97, p=0.01), whereas no difference was noted in AF readmissions (4.02% vs. 3.34%, HR: 0.97, 95% CI: 0.92-1.04, p=0.49) and risk of major bleeding was increased (5.74% vs. 3.42%, HR: 1.17, 95% CI: 1.10-1.25, p<0.0001) at 1 year in AF patients with bariatric surgery. (Figure 1)

Conclusions:
Bariatric surgery in patients with AF was associated with a reduction in 1-year mortality and ischemic stroke. However, the risk of major bleeding was noted to be increased and no difference was noted in AF readmission at 1 year.
Abstract 15471: Neonatal Mesenchymal Stem Cells Rejuvenate Cardiac Myocardium by Regulating Macrophage Polarization Revealed by Single Cell Sequencing After Ischemia-Reperfusion Injury in Rats
Authors: Mishra Rachana , Boyd Riley M , Sharma Sudhish , Kaushal Sunjay
Published: June 2023

Introduction:
Stem cells are an emerging therapy for cardiovascular disease. The immune system is modulated by stem cell administration, therefore we sought to characterize the immune environment following stem cell administration.

Hypothesis:
Neonatal cardiac mesenchymal stem cells (nMSC) improved heart function through an acute sterile immune response characterized by the temporal and regional of macrophages.

Methods:
nMSC were isolated from healthy neonatal myocardium. Brown Norway rats underwent ischemia-reperfusion injury (IRI) by temporary ligation of left anterior descending artery for 45 minutes. Following closure of the chest cavity, neonatal mesenchymal stem cells (nMSCs), dead nMSCs (dnMSCs), or placebo was administered by intra-coronary injection. At day five heart was collected for single cell suspensions. CD45 positive selection was performed and fed into the Chromium Single Cell Gene Expression workflow (Pleasanton, CA). Single cell sequencing analysis was completed using the Seurat package on RStudio v1.3.1093 (Boston, MA). Echocardiography was completed on post-operative days 7 and 28 for rats not sacrificed for single cell sequencing.

Results:
Our results demonstrate that nMSC treatment after IRI injury can significantly recover left ventricular ejection fraction. Single-cell sequencing analysis of CD45+ cells identified multiple unique CD68+ clusters. Notably, macrophage cluster 2 primarily consisted of cells from the nMSC treated group, whereas the macrophage cluster 1 was primarily cells from the dnMSC and placebo groups. Gene ontology analysis of macrophage cluster 2 demonstrated that this cluster primarily consisted of macrophages strongly associated with various aspects of the activated immune response, including lymphocyte activation and cytokine production. Conversely, macrophage cluster 1 gene ontology analysis revealed a weaker immune response signature.

Conclusions:
nMSCs are a promising therapeutic candidate for the treatment of myocardial infarction. The mechanism of this therapy is likely related to macrophage activation that further enhances the immune response in the impacted and at-risk myocardium following IRI injury.
Abstract 15472: Skeletal Muscle Sirt3 Deficiency Remotely Regulates Pulmonary Vascular Remodeling Via Loxl2-cnpy2-p53 Axis In Pulmonary Hypertension Associated With Heart Failure With Preserved Ejection Fraction
Authors: Jheng Jia-Rong , Noda Kentaro , Bai Yang , Joshua Huot , Halliday Gunner , Cook Todd , Simon Marc A , Forman Daniel E , Bonetto Andrea , Machado Roberto F , Gladwin Mark T , Lai Yen C
Published: June 2023

Background:
Pulmonary hypertension in the context of heart failure with preserved ejection fraction (PH-HFpEF) is the most common cause of PH worldwide. However, major pathways involved in the regulation of PH-HFpEF are still not well understood. We have previously reported a role of skeletal muscle sirtuin-3 (SIRT3) in PH-HFpEF. In the present study, we aimed to investigate how skeletal muscle SIRT3 defects remotely affect pulmonary vascular health in PH-HFpEF.

Methods and Results:
Using global mass spectrometry-based comparative analysis, we found increased secretion of lysyl oxidase homolog 2 (LOXL2) in SIRT3-deficeint skeletal muscle. Elevated circulation and protein expression levels of LOXL2 were also observed in plasma and skeletal muscle of
Sirt3
skm-/-
mice, rats with experimental PH-HFpEF (SU5416/Obese ZSF1, Ob-Su), and patients with PH-HFpEF. Additionally, expression levels of canopy fibroblast growth factor signaling regulator 2 (CNPY2), a known angiogenic and proliferative factor, were increased in PASMCs obtained from
Sirt3
skm-/-
mice and Ob-Su rats, suggesting a potential role of CNPY2 as a molecular target of skeletal muscle SIRT3-LOXL2 signaling in PASMCs. Treatment with LOXL2 recombinant protein resulted in increased levels of CNPY2, PCNA, and cellular proliferation
in vitro
in PASMCs. LOXL2 treatment, as well as CNPY2 overexpression, decreased the levels of tumor suppressor p53 in PASMCs. In addition, CNPY2 overexpression also decreased CNPY2 expression level in PASMCs. Media conditioned by SIRT3-deficient skeletal muscle cells increased CNPY2 expression in PASMCs, concomitant with decreased p53 and enhanced PCNA. Finally, knockdown of both SIRT3 and LOXL2 in skeletal muscle cells and/or suppression of LOXL2 with β-aminopropionitrile (BAPN) restored CNPY2, p53, and PCNA levels in PASMCs.

Conclusions:
These studies reveal a new endocrine signaling axis that links skeletal muscle SIRT3 deficiency to remote CNPY2 -p53 regulation in the pulmonary vasculature through myokine

LOXL2. Our data may also identify skeletal muscle SIRT3, myokine LOXL2, CNPY2, and p53 as potential targets for the treatment of PH-HFpEF.
Abstract 15477: Timely PCI Shows Beneficial Long-Term Outcomes in Late Presentation With STEMI: A Systematic Review and Meta-Analysis Between 2012 and 2022
Authors: Fatima Shumail , Chaudhary Rahul , Noor Rida , Nouraie Mehdi , Pacella John
Published: June 2023

Introduction:
Approximately 8-40% of ST-elevation Myocardial Infarction (STEMI) present later than 12 hours after symptom onset. Current ACC/AHA guidelines recommend primary percutaneous coronary intervention (PCI) for STEMI after 12 hours of symptom onset only in the setting of cardiogenic shock or severe acute heart failure, (Class Ia, LOE B) or persistent ischemic symptoms (Class IIa, LOE B). There are limited data comparing long-term outcomes among patients with a late STEMI presentation managed with PCI versus medical therapy (MT).

Objective:
To compare long-term outcomes among patients treated with PCI versus MT who have late presentation of STEMI

Methods:
We followed Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines to extract data from PubMed/Medline, Cochrane, Embase, and Clinicaltrials.gov databases by using the search terms “late” or “delayed” or “>12 hours” presentation with STEMI from 01/2012 through 12/2022. Included studies reported at least one of the following outcomes: all-cause mortality, reinfarction, heart failure, major adverse cardiac events (MACE), and stroke. Studies reporting delays in PCI due to COVID-19 positive status or COVID-19 enforced protocols were excluded to prevent the impact of pragmatic barriers on treatment. Relative risk (RR) was calculated using random effects model if heterogeneity was >50%, otherwise, fixed effects model was used

Results:
Seven studies (n=11,576, delayed PCI n=6,248, and medical therapy n=5,319) were included in our analysis. The median follow-up was 12 months (1-60 months). Overall, among patients with STEMI and PCI >12 hour after presentation had lower incidence of MACE (27% vs. 30%, RR 0.85, 95% CI 0.76-0.69, I2=30%, p=0.007) compared to MT alone, which was driven by a significantly reduced all-cause mortality with PCI (4.4% vs. 17%, RR 0.38, 95% CI 0.17-0.85, I2=95%, p=0.01). No significant differences were observed in the incidence of recurrent MI and heart failure hospitalizations.

Conclusion:
Our study suggests favorable outcomes of PCI in STEMI with presentation >12 hours compared with medical therapy. Further prospective studies are needed to validate our findings.
Abstract 15480: Liraglutide Inhibits Atherosclerotic Plaque Progression in Rabbits Through the Downregulation of Multiple Inflammatory and Metabolic Pathways
Authors: Kassab Mohamad B , Khraishah Haitham , Thrapp Andrew , Vijay Aatira , Song Du-Ri , Spicer Graham , Albaghdadi Mazen , Chowdhury Mohammed M , Hsieh Paishiun , Mauskapf Adam , Kawamura Yoichiro , Libby Peter , Libby Peter , Tearney Guillermo J , Jaffer Farouc A
Published: June 2023

Background:
Liraglutide, a GLP-1- receptor agonists approved for the treatment of type 2 diabetes and obesity confers a lower CVD mortality. However, mechanisms underlying this finding remain unknown, particularly in normoglycemic subjects. We investigated the effects of liraglutide on the progression and pathobiology of atherosclerosis using multimodal intravascular imaging in rabbits.

Methods:
Rabbits atherosclerosis (N=16) were induced by balloon injury of the abdominal aorta and cholesterol feeding for 6 weeks. Then, rabbits were imaged with intravascular ultrasound (IVUS) and near-infrared fluorescence optical coherence tomography (NIRF-OCT) for the analysis of plaque burden and plaque inflammation (ProSense VM110 NIRF agent, 4 mg/kg/iv) respectively. Next, rabbits were randomized into: Control (n=8) or liraglutide (n=8, 0.1 mg/kg/day) groups. Imaging was repeated after 4 weeks, followed by histopathology and RNA analysis. On per-slice basis (every 0.4 mm) of IVUS imaging, the percent atheroma volume (PAV) was measured across the 40 mm balloon injured area. Atheroma progression was quantified as the ΔPAV between 6 and 10 weeks.

Results:
IVUS analyses (3200 slices/16 rabbits) revealed that liraglutide significantly reduced plaque progression (ΔPAV, 1.5% [0.2-2.8] vs. 9.3% [6.7-13.0] control, p=0.05). In vivo distance-corrected VM110 cathepsin inflammatory plaque activity was similar (ΔNIRF average plaque 25.2 [-9.8- 62] vs. 22.6 [3.9- 52.5] nM control, p=0.72). Plaques from liraglutide-treated animals however exhibited fewer RAM11+ macrophages (21.3±11.4 vs. control 30.9±16.7 macrophages/section, p=0.01) stry. Both plaques showed similar αSMA (45.2±6.7% vs 52.4±1.2% αSMA+ area/section, p=0.327). Liraglutide decreased inflammatory RNA transcripts (IL-6 and TNF-α), and RNA-seq transcriptomic analysis revealed that liraglutide altered inflammatory and metabolic pathways (as CRP, CYP3A6, Apo-A4 and FMO3). Blood glucose was normal and similar between groups (p>0.05).

Conclusion:
Liraglutide suppresses in vivo atherosclerotic plaque progression and plaque macrophage expression in normoglycemic rabbits. Further investigation of its plaque stabilizing effects in subjects with and without diabetes is warranted.
Abstract 15485: Tectonic Infarct Analysis: A User-Friendly Standalone Software for Whole-Brain Infarct Volume Estimation From 2,3,5-Triphenyltetrazolium Chloride-Stained Tissues
Authors: Santo Briana , Ciecierska Shiau-Sing K , Koenigsknecht Carmon , Jenkins TaJania D , Pionessa Donald , Gutierrez Liza C , Baig Ammad A , Monteiro Andre , King Robert , Gounis Matthew J , Siddiqui Adnan H , Tutino Vincent M
Published: June 2023

Introduction:
Infarct volume measured from 2,3,5-Triphenyltetrazolium Chloride (TTC)-stained brain slices is critical for
in vivo
stroke models. However, current image tools are not automated and severely limited in their capability. Here, we developed an interactive, trainable software application that computes whole-brain infarct volume metrics from batches of serial TTC-stained brain sections.

Methods:
Male Wistar Rats (
n
=21) received middle cerebral artery occlusion and were euthanized after 24 h. Brains were serially sectioned (2 mm, coronal), stained with TTC, and optically scanned (anterior and posterior sides). Manual annotations of infarcted regions and calculation of infarct volume were used as ground truth. We performed computational image analysis to segment brain tissue and develop a custom semantic segmentation model for infarct detection (
n
=3 training cases) (Figure, top). Stroke parameters, including brain volume, infarct volume, infarct/non-infarct volume ratio (V), and % infarct were computed by measuring each feature per section, averaging over anterior and posterior faces, and summing across all slices. Results were compared against manual ground truth (
n
=18 testing cases) using accuracy, f1-score, and Spearman correlation. The pipeline was then packaged as a standalone, opensource software named Tectonic Infarct Analysis (Figure, bottom).

Results:
The software performed well for brain (accuracy=0.95, f1-score=0.90) and infarct (accuracy=0.96, f1-score=0.89) segmentation. Strong, significant correlation was observed between manual and computational calculation of infarct parameters: V
brain
(
ρ
=0.91,
p
<0.001), V
infarct
(0.97,
p
<0.001), V
non-infarct
(0.96,
p
<0.001), and % infarct (0.81,
p
=0.001). The software reduced analysis time by 25 min per case vs. manual effort.

Conclusions:
Tectonic Infarct Analysis software offers a robust and adaptable approach for rapid TTC-based stroke assessment.
Abstract 15552: Optimal Virtual Monoenergetic Settings in Spectral Ct With a Dual Layer Detector: Breakthrough in Achieving Best Contrast Between Non Calcified and Calcified Plaques and Lumen in Coronary Arteries
Authors: Funabashi Nobusada , Misumi Kazuo
Published: June 2023

Introduction:
Non calcified plaque (NCP) in coronary arteries on CT is correlated with occurrence of acute coronary syndromes and coronary artery calcification (CAC) may occasionally be co-existed. CAC induces a blooming artifact, which magnifies the calcification versus its actual size. The CT values of NCP and CAC are influenced by tube kilovoltage (kV). Recent spectral CT with a dual-layer detector can generate CT images at any kiloelectron voltage (keV) (range: 40-200) after ordinary acquisition using virtual monoenergetic settings (VMS).

Hypothesis:
Using a new spectral CT, we can determine the optimal VMS settings for achieving best contrast between NCP, CAC and the lumen in coronary arteries.

Methods:
We performed enhanced 128 slice Spectral CT 7500 scans using a dual-layer detector in 42 patients with NCP and CAC on CT (tube voltage: 120 kV). After scanning, VMS images at various keV values were created from the spectral-based images. We measured the mean CT values of NCP and CAC, lumen in left main artery (LMA), and fat tissue around coronary arteries within a 1.0 mm2 circle in the axial images at each keV in early phase with a contrast.

Results:
Lower keV values were linked to only slightly increased mean CT values of NCP, but markedly increased mean CT values of CAC. The CT values of the lumen in the LMA were markedly increased. Conversely, the CT values of fat tissue were slightly decreased. The greatest differences in mean CT values between NCP and the LMA were observed at 40 keV. However, considering blooming artifact of CAC at 40 keV, the optimal keV for achieving the best contrast between the CT values of NCP and the lumen in the LMA was influenced by age, male sex.

Conclusions:
The NCP in coronary arteries, CAC, lumen of the LMA, and fat tissue exhibit unique characteristics. When conventional CT rather than spectral CT is used to evaluate the occurrence of NCP, it is necessary to determine the optimal tube voltage based on the age and male sex of the patient, CAC, and lumen of the LMA.
Abstract 15585: Myocardial Reserve After Milrinone to Predict Right Ventricular Failure After LVAD Implantation
Authors: Poonawalla Maria , Belkin Mark N , Han Jiho , Kalantari Sara , Houston Brian , Pinney Sean P , Tedford Ryan J , Grinstein Jonathan
Published: June 2023

Introduction:
Right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation is a common complication associated with increased morbidity and mortality. Identifying patients at risk for RVF remains challenging. We sought to assess pre-operative right ventricular myocardial reserve after milrinone loading as a risk predictor for post-LVAD RVF.

Methods:
Adult patients implanted with LVADs from 2013-2019 at a single center who had right heart catherization with milrinone drug study within 30-days preoperatively were included. In addition to standard hemodynamic variables, pulmonary artery pulsatility index (PAPI), right atrial to pulmonary capillary wedge pressure ratio (RA/PCWP), right ventricular stroke work index (RVSWI), pulmonary vascular resistance index (PVRi), and stroke volume index (SVI) were recorded before and after milrinone bolus (50 mcg/kg over ten minutes). Incidence of RVF defined by MCS-ARC criteria within one-year post LVAD were recorded. Student’s unpaired t-tests were used to compare mean of hemodynamic markers to RVF outcome.

Results:
A total 34 patients were included; 38% women, 50% African American, 68% had non-ischemic cardiomyopathy, 47% implanted with HeartMate 3 LVAD, 20.5% with HeartMate 2, and 32% with HeartWare HVAD. Final right atrial pressure (RAP) after milrinone was higher in those with post-LVAD RVF (15.5
+
7.8mmHg vs 9.2
+
3.9mmHg, p=0.005), as was final diastolic PA pressure (34.3
+
9.2mmHg vs 25.6
+
7.7mmHg, p=0.006). SVI post-milrinone was numerically higher in those without post-LVAD RVF (32.3
+
9.2 vs 26.0
+
7.9mL/m
2
, p=0.06). Percent change in PAPI (p=0.26), RA/PCWP (p=0.35), RVSWI (p=0.10), or PVRi (p=0.92) after milrinone were not associated with RVF.

Conclusions:
Persistently elevated RAP and diastolic PA pressure, despite milrinone infusion, are associated with RVF after LVAD implantation. Continued reduction in SVI post milrinone may also identify patients at risk for post-LVAD RVF.
Abstract 15605: Underrepresentation of Cardiologist Demographics in Review of Medicolegal Cardiology Cases
Authors: Patnam Mehul , Vidovich Mladen I
Published: June 2023

Introduction:
Cardiologists face an increased risk of medical professional liability (MPL) claims compared to physicians overall throughout their careers. Simultaneously, male physicians are over twice as likely to encounter medicolegal litigation than female physicians. Understanding the distribution of MPL claims across cardiologist demographics is vital to identify high risk areas and improve quality of patient care. Thus, we aimed to characterize current literature on the inclusion of demographic data in medicolegal cases against cardiologists.

Methods:
Searches were performed in the PubMed database. An initial search using a combination of the terms “cardiologist,” “cardiology,” “cardiac,” and “malpractice” yielded 802 results. Studies were screened by title and abstract for 1) relevance and 2) acquisition of data from a legal or insurance database. Data was manually extracted from eligible studies and categorized into 18 legal and demographic fields.

Results:
After applying eligibility criteria, 21 studies were analyzed. Comparison of key variables revealed an underrepresentation of cardiologist demographic data compared to patient data (Table 1). While two-thirds of medicolegal studies in cardiology described patient gender, no studies included gender of the defending cardiologist. Similarly, though two-thirds of studies mentioned patient age, none included cardiologist age. There was no mention of patient or cardiologist race in any of the 21 studies reviewed.

Conclusion:
In conclusion, knowledge of gender- and race-specific litigation patterns against cardiologists is absent from literature. Despite descriptions of patient characteristics, current studies on the medicolegal landscape of cardiology ignore key cardiologist variables. Incorporating demographics of prosecuted cardiologists could help elucidate the role of gender and race in medicolegal cases, minimize litigation risk, and enhance patient care outcomes.
Abstract 15615: The Association of Acute Kidney Injury With Angiotensin Converting Enzyme Inhibitor and Angiotensin Ii Receptor Blockers Use in Patients With Sars-cov-2
Authors: Douen Aaron , Sukhoo-Pertab Marc , Tan Samuel , Panetti Ryan , Siu Wenchy , Sadeghi Maryam , Kaldas Fady , Bowser Carly , Ramdass Prakash , Romney Wesley , Juang George , Toreli Aleksandre
Published: June 2023

Introduction:
Previous studies have suggested that SARS-CoV-2 causes microvascular inflammation and thrombosis, leading to microvascular angiopathy. A downstream sequela of microvascular angiopathy is AKI. Literature extensively describes the renoprotective effects of ACEI and ARB.

Hypothesis:
We hypothesize that using an ACEI/ARB in patients with SARS-CoV-2 is negatively associated with AKI.

Methods:
We conducted a retrospective chart review of patients 18 years and older who tested positive for SARS- CoV-2 using a polymerase chain reaction test between March 2020 and April 2021. Patients were divided into two groups, AKI, and non-AKI. The primary outcomes were all-cause mortality and hospitalization rate. The secondary outcomes were myocardial infarction, hypotension, intubation, use of vasopressors and ventricular tachycardia (VT). We used multivariate logistic regression to adjust for baseline characteristics.

Results:
We identified a total of 1,212 patients with AKI and 21,887 without AKI who tested positive for SARS-CoV-2. Incidence was 539 (44%) for all-cause mortality, 1144 (94.2%) for hospitalization, and 413 (34.6%) for patients taking ACEI/ARB. After logistic regression analysis, OR was 3.006 (95% Confidence Interval [CI]: 2.342-3.858; p<0.001) for hospitalization, 7.359 (95% CI:5.191-10.433, p <0.001) for all-cause mortality, and 1.034 (95% CI: 0.784-1.365; p< 0.810) for patients taking ACEI/ARB. The AKI group had significantly increased adjusted OR for hypotension (p< 0.001), calcium channel (p<0.001) and beta-blocker (p<0.038) use. Adjusted OR for all other secondary outcomes were not increased but not significant, including myocardial infarction (p<0.697), VT (p<0.184), vasopressor use (p<0.113), and intubation (p<0.096).

Conclusions:
This study suggests that ACEI/ARB use was not positively associated with AKI in patients with SARS-CoV-2, while calcium channel blocker and beta-blocker use were. A positive association between BB and CCB with AKI suggests that there should be a preference for ACEI/ARB in patients where all three medications are possible therapy options. Further studies are needed to confirm the association between ACE/ARB and AKI and rule out potential confounding variables.
Abstract 15617: Severe Heart Failure: Fistulous Connection Between Ectatic Left Anterior Descending Artery, Coronary Sinus, and Left Ventricular Cavity
Authors: Patel Aditya , Ali Ruhma , Fichadiya Hardik , Ahmad Asrar , Khan Ahsan , Suleiman Addi
Published: June 2023

Introduction:
Arteriovenous coronary fistula of LAD to the coronary sinus is a rare vascular anomaly present in 0.002% of the general population. We report a rare case of fistulous connection between exceptionally large LAD and coronary sinus into the LV cavity leading to severe systolic heart failure.

Case:
A 39-year-old male with no past medical history presented to the ED with complaints of dyspnea, chest pain and lower extremity edema for the past 3 months. The chest pain was substernal, squeezing, non-radiating, 2/10 in intensity, exacerbated by exertion and alleviated with rest. The patient did not have any cardiology work up in the past. Vitals were stable. The patient had irregular rhythm with prominent JVD and bilateral lower extremity edema on examination. Troponins were negative, BNP was elevated and thyroid function was normal. Chest x-ray showed cardiomegaly. EKG showed atrial fibrillation with no significant ST segment changes or Q waves. Echocardiogram showed severe systolic left ventricular dysfunction with an ejection fraction of 15-20% and moderate to severe secondary mitral regurgitation. Cardiac catheterization showed large ectatic LAD with mild stenosis in mid segment. An abnormal connection was noted between LAD and coronary sinus draining directly into the left ventricle. He was discharged on guideline directed medical therapy for heart failure.

Discussion:
Fistula between LAD, coronary sinus and LV cavity is a unique organic heart disease. Our patient presented with heart failure with no apparent identifiable cause. On angiography an ectatic LAD was connected to the coronary sinus and LV cavity which created a high output state on the LV. The management of this rare pathology is complex due to variable presentation and lack of specific treatment guidelines. Careful selection of certain cases for therapeutic intervention can result in better outcomes than medical therapy alone.
Abstract 15653: Impact of Atrial Fibrillation on Hospital Outcomes Among Covid-19 Patients - Insight From the 2020 California State Inpatient Database
Authors: Salami Joseph A , Rubens Muni , PATRICK BENJAMIN A , Saxena Anshul , Veledar Emir , Nasir Khurram
Published: June 2023

Introduction:
Recent estimates of COVID-19 in the US include over 84 million cases with over 1 million deaths. The association between new-onset atrial fibrillation (AF) and COVID-19 has been reported, but hospital outcomes has not been studied among COVID-19 patients with AF.

Hypothesis:
AF among COVID-19 hospitalizations is not associated with higher rates of adverse in-hospital outcomes.

Methods:
Using data from the 2020 California State Inpatient Database, we conducted a retrospective analysis of all hospitalized COVID-19 patients ≥18 years of age. Primary outcomes were: prolonged length of stay (LOS) [defined as LOS ≥75th percentile of the population], ICU admission, mechanical ventilation, vasopressor use, and in-hospital mortality. We examined the differences in adverse hospital outcomes among those with AF versus those without. Multivariate logistic regression analyses were used to estimate the association between AF and outcomes after adjusting for cofactors.

Results:
Our analysis had a total of 94,114 COVID-19 hospitalizations and 9,391 (10.0%) had AF. Adverse hospital outcomes such as prolonged LOS (40.0% versus 27.1%,
P
<0.001), ICU admission (18.4% versus 8.8%,
P
<0.001), mechanical ventilation (19.0% versus 9.1%,
P
<0.001), vasopressor use (4.4% versus 1.9%,
P
<0.001), and mortality (27.2% versus 9.6%,
P
<0.001) were significantly higher among COVID-19 hospitalizations with AF. The adjusted odds ratio (aOR) of adverse outcomes such as prolonged LOS (aOR, 1.37, 95% CI: 1.31-1.44), ICU admission (aOR, 2.01, 95% CI: 1.88-2.15), mechanical ventilation (aOR, 1.95, 95% CI: 1.72-2.20), vasopressor use (aOR, 1.98, 95% CI: 1.86-2.11), and mortality (aOR, 2.04, 95% CI: 1.92-2.16) were statistically significantly higher among COVID-19 hospitalizations with AF compared to those without AF.

Conclusions:
In 2020, AF occurred in about 10% of COVID-19 hospitalizations in California, USA, and was associated with significantly greater risk of adverse hospital outcomes and mortality. COVID-19 patients should be closely monitored for development of AF, and promptly managed like contemporary AF. More studies are however needed to understand the best approach to managing AF in COVID-19 patients.
Abstract 15664: In-Person Outpatient Care Delays, Virtual Clinic Visits and Associated Mortality Among Veterans With Heart Failure During the Covid-19 Pandemic
Authors: Vijayakumar Shilpa , Corneau Emily , ERQOU SEBHAT , Kokkirala Aravind , Wu Wen-Chih H
Published: June 2023

Background:
The impact of care delays and outcome among HF patients during the COVID-19 pandemic and role of virtual video or telephone visits has not been well studied. We studied changes in outpatient care patterns and associated mortality among HF patients during the pandemic.

Methods:
Retrospective analysis of HF patients using Veterans Affairs data, with exposure period 2/2020-9/2020 and outcome period 10/2020-4/2021. Veterans were diagnosed with HF prior to 2/2020 and had at least 1 cardiology/primary care visit in 2019. We compared volume/type of outpatient visit (in-person, virtual video, telephone, none) and yearly mortality rates 2 years before and 1 year after 2/2020. We related type of outpatient encounter to mortality during the outcome period. Hazard ratios and 95% confidence intervals were estimated using multivariable Cox-models adjusted for potential confounders.

Results:
290,789 Veterans with HF were included, with mean age 73 years, 96% male. Compared to the prior 2 years, in-person encounter days were lower (224.3/100 in 2018, 2019 vs 180.4/100 after 2/2020 P<0.01), while video encounter days increased (3.4/100 in 2018, 2019 vs 9.8/100 after 2/2020 P<0.01). Mortality rates were 12.7/1000 in 2018, 2019 and 12.9/1000 after 2/2020 P<0.01. Compared to those with no outpatient visits after 2/2020, mortality risk was lowest for Veterans with at least one in-person visit (HR 0.66, 95% CI 0.61-0.71), followed by video-only (HR 0.71, 95% CI 0.66-0.77) and lastly by telephone-only (HR 0.78, 95% CI 0.71-0.86) (Figure 1).

Conclusions:
During the COVID-19 pandemic, a decrease in outpatient visits and increase in mortality was seen among Veterans with HF compared to prior years. Veterans engaged in any outpatient care (evidenced by visits) had lower mortality compared to those with none. Patients with in-person visits had slightly lower mortality risk than those with virtual video only visits, whom had lower mortality risk than those with telephone-only visits.
Abstract 15671: Targeting Chromatin Structure: The Combined Inhibition of Histone Deacetylases and Bromodomain Proteins in Normalizing Persistently Activated Pulmonary Hypertensive Fibroblasts
Authors: Zhang Hui , Li Min , Hu Cheng-Jun , Stenmark Kurt R
Published: June 2023

Rationale:
The multifactorial nature of pulmonary hypertension (PH) suggests epigenetic changes as potential determinants of vascular remodeling through regulating gene expression (both up-regulated and down-regulated genes) in vascular cells. Changes in the chromatin state (especially histone acetylation) of specific genes can lead to their repression or activation. We and others have demonstrated histone deacetylases inhibitors (HDACi) and histone acetylation readers inhibitors (BRDi) can prevent and ameliorate PH changes by normalizing pathological gene expression. However, the non-histone protein targets and the narrow therapeutic window of currently available HDACi limits their clinical utility. In this study, we evaluated the effect of combination treatments using a new HDACi (OKI-005, US patent) with high potency and selectivity for HDACs (targeting decreased genes) together with BRDi (targeting increased genes), in low doses.

Methods and Results:
Cultured human pulmonary artery fibroblasts derived from patients with IPAH (PH-Fibs) or from control donors (CO-Fibs) were used as in vitro model system. PH-Fibs exhibit increased pro-inflammatory genes (e.g. CXCL12), proliferation markers (e.g. Mki67) and anti-apoptosis genes (e.g. BCL2) as well as decreased anti-inflammatory genes (e.g. HMOX1), anti-proliferation genes (e.g. P21) and pro-apoptotic genes (e.g. PERP). In PH-Fibs, the increased expressed CXCL2 gene exhibited more opened chromatin structure and BRD4 binding (ChIP-assay), and BRDi (JQ1) can decrease its expression in a dose dependent trend. At the low doses, JQ1 (100 nM) alone is sufficient to normalize most of increased genes, while the new HDACi (OKI-005) was more effective in normalizing decreased genes in PH- Fibs. The combination of low dose of JQ1 (100 nM) and OKI-005 (64 nM) was sufficient to normalize both increased genes and decreased genes thus inhibiting the persistently activated PH-phenotype without deleterious effects on CO-Fibs.

Conclusion:
Combination of HDACi and BRDi in low doses is effective in normalizing the persistent activation of PH-Fibs without deleterious effects on control cells, offering promise for epigenetic-targeted therapies in PH.
Abstract 15675: Mid-Ventricular Hypertrophic Cardiomyopathy Presenting With Minoca
Authors: Munoz Estrella Alba , Azhir Alaleh , Khachatoorian Yeraz , Konje Swiri , Talebi Soheila
Published: June 2023

Background:
Mid-ventricular hypertrophic obstructive cardiomyopathy (HOCM) is an uncommon form of cardiomyopathy that is linked to an apical aneurysm, increasing the risk of sudden death.

Cases:
We described four patients who presented with chest pain or SOB. Troponin elevation, acute myocardial infarction on cardiac MRI and absence of obstructive coronary disease confirmed the diagnosis of MINOCA. Echo revealed a pressure gradient between the apical and basal chambers of the left ventricle. Cardiac MRI showed mid-ventricular HOCM and mid-cavity obliteration with akinetic apical chamber LGE revealed areas of sub-endocardial or transmural myocardial infarction at the level of obstruction and at the apical segments distal to the obstruction. The presence of myocardial edema on tissue mapping in the same area suggested acute myocardial injury (Figure).

Discussion:
The pathogenesis of development of apical myocardial scarring and aneurysm formation in mid-ventricular HOCM remains unknown. Other variant of hypertrophic cardiomyopathy shows mid-myocardial foci of scar inside the hypertrophied segments, indicating fibrosis. Whereas in our patients, the LGE revealed a sub-endocardial or transmural infarct (myocardial infarction pattern) - an uncommon pattern in other hypertrophic cardiomyopathy variants. This pattern and elevation of troponin during the acute phase of illness supports the hypothesis that apical aneurysm is due to apical myocardial ischemia in mid-ventricular HOCM. Tissue characterization and pattern of scar by cardiac MRI in these patients could be useful in understanding the pathophysiology of this type of HOCM.