bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12516: Vascular Calcification Does Not Affect Cardiovascular Structure and Function During the Reversal of Atherosclerosis
Authors: Kalta Daniel M , Lin Xin , Singh Mohnish , Savinova Olga V
Published: April 2022

Introduction:
Animal models are used to study the mechanisms of reversal of atherosclerosis. Due to the minimal extent of plaque calcification, commonly used mouse models do not provide good insight into the regression of calcified plaques. To address this question, we developed a mouse strain that is genetically predisposed to atherosclerotic calcification.

Hypothesis:
The purpose of this study was to compare the effects of the reversal of atherosclerosis on cardiovascular physiology between mice predisposed to calcification and control mice.

Methods:
All mice (n=35) had a mutation of a low-density lipoprotein receptor and developed atherosclerosis over a course of 15 weeks while on a Western diet. The experimental groups consisted of mice overexpressing TNAP (tissue-nonspecific alkaline phosphatase) in macrophages under the control of LysM-Cre recombinase, and the control littermates. After 23 weeks of age (baseline), mice were switched to a normal diet. Echocardiographic studies were performed to assess cardiac structure and function at baseline and at 52 weeks of age at the completion of the diet reversal protocol. MicroCT analysis of calcification was performed
ex vivo
. Data were analyzed via 2-way ANOVA to calculate the effect of diet (atherosclerotic baseline vs reversal) while adjusting for sex.

Results:
Cardiac parameters including left ventricular (LV) mass, LV internal diameter and wall thickness, ejection fraction, fractional shortening, and aortic valve flow velocity were within the normal range and not statistically different between the two genotypes. CT data confirmed an increase in calcium volume in TNAP overexpressor mice compared to controls.

Conclusions:
Our data suggest that under conditions of the reversal of atherosclerosis, plaque calcification at baseline is not associated with the deterioration of cardiac structure and function in a mouse model.
Abstract 12533: Progerin Causes a Disproportionate Senescence in Endothelial Cells
Authors: Xu Qiu , Mojiri Anahita , Morales Elisa , Walther Brandon K , Boulahouache Luay , Cooke John P
Published: April 2022

Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disorder caused by the mutation of LMNA gene leading to irreversibly farnesylated lamin A protein, i.e. progerin. The major causes of death in HGPS are coronary and arterial occlusive disease. In the murine model of HGPS, vascular smooth muscle cells (VSMCs) loss is the primary vascular manifestation, which is quite different from the human arterial occlusive disease. To identify the mechanisms of HGPS vascular disease in humans, we differentiated isogenomic endothelial cells (ECs) and VSMCs from the same lines of HGPS-iPSCs and control-iPSCs. Both HGPS-ECs and HGPS-VSMCs manifested cellular hallmarks of aging, including dysmorphic nuclei, impaired proliferation, increased β-galactosidase staining, shortened telomeres, upregulated secretion of inflammatory cytokines, increased DNA damage, loss of heterochromatin and altered shelterin complex expression. However, at similar passage number, HGPS-ECs are more severely affected compared to VSMCs, as indicated by a higher percentage of β-galactosidase positive cells, significantly shortened telomere length, and greater frequency of DNA damage signals. With increasing passage number, there is progressive senescence in HGPS-ECs that is greater than that observed in HGPS-VSMCs. Using immunoprecipitation and mass spectrometry, we compared the integrity of the Shelterin Protein Complex (SPC), which is composed of six different proteins and whose function is to protect the telomeres, on the ECs and VSMCs of HGPS and control cells. We observed increased γH2A.X binding to RAP1 (member of SPC) and to Lamin A (nuclear envelope) in HGPS cells. The expression of γH2A.X was greater in HGPS ECs than VSMCs, and is associated with loss of SPC integrity, telomere shortening and loss of heterochromatin formation. Whereas progerin expression has deleterious effect in both vascular ECs and VSMCs, the severity of dysfunction is more extensive in HGPS-ECs in comparison to HGPS-VSMCs. These studies indicate that an endothelial-targeted therapy may be useful in HGPS.
Abstract 12548: Temporal Strain Data Reconstruction From Echocardiographic Strain Graphs
Authors: Devathu Rahul A , Wehbe Ramsey M , Nelson Lauren , Shah Sanjiv J , Thomas James D
Published: April 2022

Introduction:
Myocardial strain imaging provides a complex dataset that is often reduced to a single parameter, global longitudinal peak strain (GLPS). Raw temporal strain data is largely unexplored and restricted as studies often only save images of graphs lacking numerical data. While certain strain imaging packages do allow for the prospective export of raw data, the task is slow, rarely done, and cannot be done retrospectively. The troves of retrospective strain studies saved as images can be unlocked by reconstructing the numerical values contained in strain graphs. Such a dataset would be critical to future artificial intelligence strain analysis and morphological detection of disease modalities. This study aims to investigate the methods of extracting and reconstructing strain curve graphs to raw numerical outputs.

Methods:
By using vendor-specific color recognition algorithms, individual curves can be isolated as scattergram type plots of pixels. These pixel locations are converted to temporal strain values by defining scale factors for the graph. Intelligence-guided filtering, interpolation, and curve overlap filling can convert the pixel scattergrams into clean and complete temporal strain data. Using a set of 21 studies each containing 3 views (2Ch, 4Ch, APLAx) with each view containing 6 regional curves, 378 unique curves were reconstructed and compared to prospectively exported temporal strain data.

Results:
Results demonstrate that this method reconstructs the numerical data with high accuracy and precision. The reconstructed data was compared with the exported numerical data, yielding an average R
2
of .996 with an average runtime per study of 7.32s. The minute deviation from fidelity can be attributed to the finite resolution of the pixels in the analyzed graph.

Discussion:
Highly accurate temporal data can be extracted from routine strain graphs in clinical studies, which may allow for more nuanced assessment and deep learning of strain.
Abstract 12555: Safety and Efficacy of Catheter Ablation for Atrial Fibrillation and Predictors of Arrhythmia Recurrence in Octogenarians
Authors: Akhtar Tauseef , Wallace Ryan , Daimee Usama A , Hart Erica , Marine Joseph E , Berger Ronald D , Calkins Hugh G , Spragg David D
Published: April 2022

Introduction:
Increasing numbers of elderly patients are undergoing catheter ablation (CA) of atrial fibrillation (AF). However, data regarding the experience with this procedure in the octogenarians are limited.

Objective:
To describe safety and efficacy of index CA of AF and predictors of arrhythmia recurrence in octogenarians.

Methods:
We conducted a retrospective analysis of patients
>
80 years old undergoing index AF ablation between 2012 and 2020 at a large academic medical center. Procedural complications and efficacy, defined as freedom from any atrial tachyarrhythmia (ATA) lasting ≥30 seconds, were assessed. All patients were followed for at least 1 year. Predictors of ATA recurrence were also evaluated.

Results:
A total of 69 patients were included in our analysis. The median age was 82 (81-85) years, 53.6% were men, and 36.2% had persistent AF (PsAF). The mean left atrial (LA) diameter was 4.3
+
0.8 cm, while the median CHA
2
DS
2
-VASc score was 4 (3-4.5). The majority (n=48, 69.6%) underwent radiofrequency ablation, and the remaining (n=21, 30.4%) patients underwent cryoballoon ablation. Pulmonary vein (PV) isolation was performed in all patients, and 31 (44.9%) patients underwent additional non-PV ablation. None of the patients developed any procedural complications. Acute procedural success with PV isolation was achieved in all the patients, and a total of 44 (63.8%) patients remained free of ATA at 1-year of follow-up. Among the patients with ATA recurrence, 24 (34.8%) were on antiarrhythmic drugs, and 12 (17.4%) patients underwent repeat ablation. Anticoagulation was continued in all the patients. In a multivariable model, only AF type (PsAF) was associated with ATA recurrence at 1-year follow-up (HR=3.42, CI: 1.17-9.94, p=0.02).

Conclusion:
CA of AF appears to be a safe and effective procedure in octogenarians. AF type (PsAF) is an independent predictor of ATA recurrence at 1-year follow-up.
Abstract 12818: The Role of Cellular Senescence in Aortic Dissection
Authors: Nakao Eichi , Aoki Hiroki , Majima Ryohei , Hashimoto Youhei , Shibata Ryo , HAYASHI Makiko , Ohno Satoko , Furusho Aya , Nishida Norifumi , HIRAKATA SAKI , Fukumoto Yoshihiro
Published: April 2022

Background:
Aortic dissection (AD) is a catastrophic disease that occurs suddenly. The acute mortality is high and those who survived frequently suffer from serious complications. Currently, pathogenesis of AD is largely unknown, which hampers the development of effective approaches to predict the prognosis and to alleviate the progression of AD. Previous studies revealed the importance of inflammation in AD pathogenesis. Recently we found that cell proliferation occurs during the development and the progression of AD. Because cell proliferation triggers cellular senescence, which is associated with secretion of proinflammatory cytokines, we hypothesized that cellular senescence might be involved in AD pathogenesis.

Objective:
We investigated if cellular senescence contributes to AD development and progression in a mouse AD model.

Methods and Results:
A mouse AD model was created by continuous infusion of beta-aminopropionitrile and angiotensin II (BAPN+AngII), where AD starts to develop in 3 days and occurs in most of the mice within 14 days. Infusion of BAPN+AngII resulted in the appearance of senescent cells that are positive for senescence-associated beta-galactosidase, and expression of senescence markers Arf and Ink4a in the aortic walls. Cellular senescence occurred in one day of BAPN+AngII infusion and was sustained throughout the observational period of 14 days. We examined the role of cellular senescence in AD pathogenesis by oral administration of ABT263 which is known as "senolytics" that eliminates senescent cells. ABT263 treatment reduced the expression of the senescence markers. In the vehicle-treated group, the mortality was 66.7% (12/18), whereas that of ABT263-treated group was 35% (14/20, P < 0.05 by log-rank test). The severity of AD, as assessed by the lesion length in vehicle group was 16.6±6.9mm, whereas that in ABT263 group was 12.2±4.2 mm (P < 0.05).

Conclusions:
These findings demonstrated that cellular senescence precedes AD development, and elimination of senescent cells effectively prevented AD progression and death, indicating the involvement of cellular senescence in AD pathogenesis. Therefore, cellular senescence represents a potential predictor and a therapeutic target for AD.
Abstract 12855: Left Atrial Reservoir Strain is an Early Marker of Atrial Fibrosis in Cardiovascular Surgery Patients
Authors: Nakajima Toshiaki , Haruyama Akiko , Hirose Suguru , Yazawa Hiroko , Fukuda Taira , Amano Hirohisa , Inami Shu , Obi Syotaro , Arikawa Takuo , Shibasaki Ikuko , Sakuma Masashi , Abe Shichiro , Fukuda Hirotsugu , Inoue Teruo , Toyoda Shigeru
Published: April 2022

Introduction:
Atrial fibrosis plays an important role in atrial remodeling and the development of atrial fibrillation (AF). Left atrium (LA) strain (LAS) measured by two-dimensional speckle tracking echocardiography (2DS) has been reported to be a useful method to predict the degree of atrial fibrosis.

Hypothesis:
To investigate whether LAS is an early marker of atrial fibrosis in cardiovascular surgery patients.

Methods:
Conventional echocardiography and 2DS method were performed in 131 patients (53 AF, 78 sinus rhythm (SR)) including cardiac valve disease (MR, AS, and CABG et al.). The mRNA and microRNA expression were analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR) in 59 cases in which LA tissues were removed from the appendage.

Results:
Left atrial reservoir strain (LASr) negatively correlated with left atrial volume index (LAVI), and E/e’ and positively correlated with LVEF, and left atrial conduit strain (LAScd). LASr was significantly lower, and LAVI was higher in AF group. The fibrosis-related (COL1A, COL3A1, TGFβ1) and peroxisome proliferator-activated receptor-α (PPARα)-related (PPARα, PGC1α, CPT1B) genes expression as a metabolic remodeling showed a positive association with atrial ANP mRNA expression level, reflecting atrial pressure and mechanical stretching. The expression level of COL1A and TGFβ1 mRNA was higher in AF group, compared with SR group. LASr, but not LAVI, negatively correlated with the expression of COL1A1, TGFβ1, and miR21. Multivariate regression analysis showed that LASr was an independent predictor of COL1A1, TGFβ1, or miR21 expression. The PPARα-related gene expression did not correlate with LASr, and LVEF in SR group, while they had a significant negative correlation with LVEF in AF patients. AF patients (LVEF<58%) had higher expression level of the PPARα-related genes, compared with those (LVEF≥58%).

Conclusions:
Low LASr exhibits increased atrial fibrosis, and LASr is extremely useful as an early marker for predicting atrial fibrosis and consequently AF in cardiovascular surgery patients. Furthermore, in progressed AF patients, overexpression of PPARα signaling may play a role in atrial degeneration eventually to leading to heart failure.
Abstract 12866: Ischemic Heart Disease Selectively Modifies The Right Atrial Appendage Transcriptome
Authors: Mulari Severi , Eskin Arda , Lampinen Milla , Nummi Annu , Nieminen Tuomo , Teittinen Kari , Ojala Teija , Kankainen Matti , Vento Antti , Laurikka Jari , Kupari Markku , Harjula Ari , Tunçbag Nurcan , Kankuri Esko
Published: April 2022

Introduction:
Although many pathological changes have been associated with ischemic heart disease (IHD), molecular-level alterations specific to the ischemic myocardium and their potential to reflect disease severity or therapeutic outcome remain unclear. Currently, diagnosis occurs relatively late and evaluating disease severity is largely based on clinical symptoms, various imaging modalities, or the determination of risk factors.

Objectives:
This study aims to identify IHD-associated signature RNAs from the atrial myocardium and evaluate their ability to reflect disease severity or cardiac surgery outcomes.

Methods:
We collected right atrial appendage (RAA) biopsies from 40 patients with invasive coronary angiography (ICA)-positive IHD undergoing coronary artery bypass surgery and from 8 patients ICA-negative for IHD (non-IHD) undergoing valvular surgery. Following RNA sequencing, RAA transcriptomes were analyzed against those 429 donors from the GTEx project without cardiac background.

Results:
The IHD transcriptome was characterized using repressed RNA expressions in pathways for cell-cell contacts and mitochondrial dysfunction. Specifically, we identified the increased expressions of the
CSRNP3
,
FUT10
,
SHD
,
NAV2-AS4
, and hsa-mir-181 genes to correlate with the complexity of coronary artery obstructions or with a functional cardiac benefit from bypass surgery.

Conclusions:
Our results provide an atrial myocardium-focused insight into IHD signature RNAs. The specific gene expression changes we characterized here pave the way for disease mechanism-based identification of biomarkers allowing for the early detection and treatment of IHD.
Abstract 12868: Normal Values and Reference Ranges for Left Atrial Strain by Speckle Tracking Echocardiography: The Copenhagen City Heart Study
Authors: Nielsen Anne B , Skaarup Kristoffer G , Hauser Raphael , Johansen Niklas D , Lassen Mats H , Jensen Gorm B , Schnohr Peter , Mogelvang Rasmus , Biering-Sørensen Tor
Published: April 2022

Background:
In current literature, left atrial (LA) function assessed by 2D speckle tracking echocardiography (2DSTE) has shown increasing clinical and prognostic significance. We sought to establish age- and sex-based normative values of LA strain measures in the general population and to assess the diagnostic and prognostic yield of the prediction intervals (PI) in relation to baseline and future atrial fibrillation (AF).

Methods:
We performed 2DSTE in members of the general population included in the 5
th
round of the Copenhagen City Heart Study. We determined normative values of peak atrial longitudinal strain (PALS), peak atrial contraction strain (PACS), and left atrial conduit strain (LACS) based on age and sex in 1,757 healthy participants. In a secondary analysis, 3,657 participants, regardless of health status, were included to assess the diagnostic and prognostic value of the established reference values.

Results:
In the healthy cohort, median age was 46 years (IQR: 33, 57), 62% were female. Median normative values of PALS, PACS, and LACS in the healthy participants were 39.1% (PI: 22.7-67.4%), 15.5% (PI: 6.3-28.0%), and 23.5% (PI: 8.6-44.8%), respectively. We observed higher values and reference limits of PALS and LACS in females compared to males, while no differences were observed for PACS. Across four different age categories, all three LA strain parameters differed significantly in both females and males. PALS and LACS decreased, while PACS increased with advancing age (Figure 1).

The lower reference limits of all three LA strain parameters showed high specificity (range 96-98%) in relation to baseline and future AF, implying a low risk of AF in participants with LA strain above the lower prediction interval in their respective sex and age group.

Conclusion:
We report normal values for LA strain measures stratified by sex and age. The established lower reference limits showed high specificity regarding baseline and future AF diagnosis.
Abstract 12872: Adherence to Guidelines for Heart Rate in Stable Ischemic Heart Disease in the Primary Care Setting
Authors: Devera Justin , Lin Sonia , Marks Jennifer , Singhal Preeti
Published: April 2022

Per 2012 ACC/AHA Guidelines, patients with stable ischemic heart disease (IHD) should be treated with beta-blockers (BB) to target a resting heart rate (HR) of 55-60 bpm due to associations of higher HR with all-cause mortality. We sought to determine adherence to this in the resident primary care (PC) clinic at our institution. Two hundred twenty-nine patients with a medication list in the electronic medical record (EMR) that includes metoprolol succinate or tartrate or carvedilol who were seen in PC clinic in January 2020 were identified. Of these, 100 had a diagnosis of IHD, and their EMR were reviewed for vital signs; medication changes; and contraindications (CI) to BB titration such as hypotension, bradycardia, and max dosing; during their PC and cardiology visits. We found that 10% (10 of 100) had HR within goal during their PC visit, whereas 6 and 84 had HR below and above goal, respectively. Of the 90 whose HR was not at goal, 24 had some perceivable CI to BB titration. Of those without CI to titration, 9% (6 of 66) had their BB increased, 4.5% (3 of 66) had their BB switched to a different medication, and 85% (56 of 66) did not have their BB changed. Of those whose BB was unchanged, 79% (44 of 56) had no other antihypertensive changed. Moreover, 88% (74 of 84) of those with HR above goal had a HR also above goal at their last two PC visits. Sixty-eight of the 100 patients with IHD were also managed by cardiology, and in contrast, 18% (8 of 45) of those with HR not at goal and without CI to titration had their BB dose adjusted at their last cardiology visit. A chi-square test was performed to examine the relation between BB titration and clinic setting with no statistical significance, X
2
(1, N = 106) = 1.18,
p
= 0.28. In sum, adherence to guidelines for HR in stable IHD were poor and not significantly different in the PC and cardiology settings. Lack of provider initiative, perhaps due to trainee unfamiliarity with guidelines, may be one of many factors and warrants more investigation to improve quality of care.
Abstract 12877: National Trends of Atrial Fibrillation/Atrial Flutter Mortality in the United States From 1999 to 2019: Regional, Racial, and Gender Variations
Authors: Ghajar Alireza , Essa Mohammed , Parvez Arshi , DeLago Augustin , Aryan Zahra , Shalhoub Joseph , Hammond-Haley Matthew , Salciccioli Justin , Faridi Kamil , Philips Binu
Published: April 2022

Introduction:
There is an emerging need to evaluate Atrial Fibrillation/Atrial Flutter (AF/AFL) mortality trends in different races and genders in different regions across the US.

Methods:
In an observational study utilizing the CDC WONDER database, age-adjusted mortality rates (AAMR) per 100,000 people for AF/AFL between 1999 and 2019 were investigated. Trends in AAMR were determined by evaluating average annual percentage changes (AAPC)s with Joinpoint regression analysis.

Results:
In the total US population from 1999 to 2019, AAMR due to AF/AFL has increased from 3.1 to 6.5 per 100,000 population. AF/AFL-related mortality rates have nearly doubled in all racial groups, ranging from an 84% increase in Black males (2.5 to 4.6 per 100,000) to a 123% increase in White males (3.1 to 6.9 per 100,000). AF/AFL-related mortality relative increase was highest in the West (140%) followed by Midwest (124%) and South (103%) while North East (81%) came last. Comparing white race mortality rates in different census regions, West demonstrated the highest increase in AAMR in the white population [170% in males, 138% in females]. Meanwhile, Midwest had the highest increase in the Black/African American population with a 111% increase in Females and 130% increase in Males. The Northeast showed the least increase in AAMR in both blacks and whites. Joinpoint analysis demonstrated that AF/AFL-related mortality rate has plateaued for black females and white males since 2017; the same plateau occurrence can be seen for white females since 2015 (Figure 1).

Conclusion:
The greatest increases in mortality occurred among white men and women and in Western states. AAMR increase has plateaued recently in white males as well as black and white females. AAPCs demonstrate that the rates of increases in AF mortality are greatest in Caucasians, followed by Asian and Black Americans.
Abstract 12881: Abnormal Retinal Perfusion Indices by Optical Coherence Tomography Angiography (OCTA) Associate With Abnormal Coronary Flow Reserve
Authors: Weber Brittany N , AbuQamar Omar , Mendonça Luísa S , Barrett Leanne , Martell Laurel , Brown Jenifer M , Divakaran Sanjay , Bibbo Courtney , Wilson Evan , Werner Astrid , Huther Alexander , Liao Katherine P , Duker Jay , Deo Rahul C , Waheed Nadia , DI CARLI MARCELO
Published: April 2022

Background:
Retinal microvascular evaluation could serve as a marker for cardiovascular disease risk. OCTA is a noninvasive method to quantitatively assess the retinal microvasculature. Coronary flow reserve (CFR), an integrated measure of focal, diffuse, and small-vessel coronary artery disease, identifies patients at risk for cardiac death. We aimed to identify associations between OCTA findings and CFR in patients undergoing cardiac positron emission tomography (PET) testing.

Methods:
Subjects (n=60) underwent a stress myocardial perfusion PET scan to quantify CFR and OCTA of both eyes on same day. CFR is the ratio of myocardial blood flow at peak stress compared to rest and adjusted for baseline cardiac work. OCTA scans were analyzed using a custom-built software to quantify foveal avascular zone (FAZ) geometry and vessel density metrics in the retina, reflecting retinal microvasculature. We used Spearman to correlate markers of retinal microvasculature with CFR.

Results:
Demographics of enrolled subjects are shown in Table I. Baseline cardiac risk factors were common and 22 (37%) subjects had an abnormal stress test. Retinal perfusion as indicated by the vessel index (ρ=0.35, p=0.006) and vessel diameter index (ρ=0.27, p=0.039) in the superficial 6x6 mm slabs were positively correlated with CFR. There was a trend towards negative association between FAZ area in the retina slab and CFR (ρ= -0.17, p=0.1).

Conclusions:
CFR was correlated with retinal perfusion indices based on OCTA, suggesting a relationship between coronary and retinal vascular health. These data provide potential insight into systemic vascular health and could provide an additional tool to assess cardiac risk.
Abstract 12907: Endovascular Mechanical Thrombectomy And Intravenous Alteplase In Patients Acute Stroke: A Network Meta-analysis Of Randomized Controlled Trials
Authors: Matsumoto Shingo , Mikami Takahisa , Ikeda Takanori , Takagi Hisato , Kuno Toshiki
Published: April 2022

Background:
The benefit and risk of administration of intravenous alteplase (IA) before endovascular mechanical thrombectomy (EMT) in acute stroke is actively debated.

Objectives:
We aimed to investigate the efficacy and safety of direct EMT compared to EMT with pre-administration of IA and IA alone with a network meta-analysis.

Methods:
PUBMED and EMBASE were searched through April 2021 for randomized control trials (RCTs) investigating the efficacy and safety of the treatment with direct EMT or EMT with IA or IA in patients with acute stroke caused by anterior large vessel occlusion. The primary outcome was functional independence evaluated by the modified Rankin Scale (mRS) score of 0 to 2 at 90 days from the onset of symptoms. The secondary outcomes were successful recanalization within 72 hours all-cause mortality at 90 days and symptomatic intracranial hemorrhage within 7 days.

Results:
We identified 11 RCTs with a total of 3,640 patients with acute stroke. Compared to EMT with IA, direct EMT had similar effects on achieving the primary outcome (relative risk (RR): 1.02; 95% confidence interval (CI): 0.88-1.19, P=0.12, I
2
=36.6%) (Figure 1A) and successful recanalization within 72 hours (RR: 0.95; 95% CI: 0.85-1.07, P=0.04, I
2
=61.2%) and had similar risk of all-cause mortality (RR: 1.05; 95% CI: 0.85-1.31, P=0.69, I
2
=0%) and symptomatic intracranial hemorrhage within 7 days (RR: 0.83; 95% CI: 0.57-1.20, P=0.96, I
2
=0%). In addition, direct MT had higher proportions in the primary outcome (RR: 1.41; 95% CI: 1.15-1.74) (Figure 1B) and successful revascularization (RR: 1.63; 95% CI: 1.32-2.01) than IA alone therapy.

Conclusions:
The current study suggested that direct EMT therapy provided acceptable outcomes even in comparison to EMT with IA. Further RCTs are warranted to identify the specific population requiring the administration of IA before EMT compared to direct EMT.
Abstract 12922: Electrocardiogram-Based Deep Learning and Clinical Risk Factors to Predict Incident Atrial Fibrillation
Authors: Khurshid Shaan , Friedman Samuel , Reeder Christopher , Di Achille Paolo , Diamant Nathaniel , Singh Pulkit , Harrington Lia , Wang Xin , Al-alusi Mostafa , Sarma Gopal , Ellinor Patrick T , Anderson Christopher D , Ho Jennifer E , Philippakis Anthony A , Batra Puneet , Lubitz Steven A
Published: April 2022

Introduction:
Deep learning-derived representations of 12-lead electrocardiograms (ECGs) may allow for atrial fibrillation (AF) risk prediction. However, it remains unclear whether ECG-based artificial intelligence improves prediction beyond established clinical risk factors for AF and whether predictions are generalizable.

Methods:
Within a dataset comprising over 500,000 individuals receiving regular primary care at a multi-institutional network, we trained a convolutional neural network to predict incident AF using 12-lead ECGs (“ECG-AI”). ECG-AI was trained in individuals with ≥1 ECG performed at Massachusetts General Hospital (MGH) within 3 years prior to start of follow-up. We then fit a Cox proportional hazards model with incident AF as the outcome and a) logit-transformed ECG-AI AF probability, and b) the Cohorts for Aging and Genomic Epidemiology AF (CHARGE-AF) score, as covariates (“CH-AI”). We compared the discrimination and calibration of CHARGE-AF versus CH-AI in three independent samples: MGH (n=4,166), Brigham and Women’s Hospital (BWH, n=37,963) and the UK Biobank (n=41,034). Based on available follow-up, AF was evaluated at 5 years in MGH and BWH, and 2 years in the UK Biobank.

Results:
ECG-AI was trained in 36,081 individuals with an ECG performed at MGH (mean age 55±17, 53% female). CH-AI had substantially better discrimination (area under the receiver operating characteristic curve [AUROC]: MGH 0.838, BWH 0.777, UK Biobank 0.746; average precision [AP] 0.30, 0.21, 0.06) versus CHARGE-AF (AUROC: 0.802, 0.752, 0.732; AP 0.21, 0.17, 0.02,
Figure
). CH-AI was well-calibrated in MGH (calibration error 0.012) and BWH (0.019), but overestimated AF risk in the UK Biobank (0.068). Calibration in the UK Biobank was excellent after recalibration to the sample-level 2-year AF hazard (error 7.1x10
-5
).

Conclusions:
A model combining clinical AF risk factors with deep learning-derived ECG-based AF risk is favorable for predicting 5-year risk of AF.
Abstract 12924: CCL18 Promotes Effector Functions of Pro-Inflammatory Macrophages by Inactivating GSK-3β
Authors: Zhao Tuantuan , Hu Zhaolan , Berry Gerald , Frye Robert , Bernstein Kenneth , Goronzy Jorg , Weyand Cornelia M
Published: April 2022

Background:
The risk for cardiovascular disease is multifold higher in patients with the autoimmune disease rheumatoid arthritis, but underlying mechanisms remain poorly defined. We have explored whether patients with rheumatoid arthritis (RA) and patients with coronary artery disease (CAD) share pro-inflammatory effector cells that sustain tissue inflammation, thus maintaining synovial inflammation and atherosclerotic plaque formation.

Methods:
Tissue cytokines expressed in RA synovial lesions were analyzed by cytokine array technology. Cytokine production in macrophages was verified with RT-PCR, immunohistochemistry and flow cytometry. Mitochondrial function was evaluated by Seahorse analyzer.

Results:
In highly inflamed synovial tissues, 21 of 60 cytokines tested were significantly elevated, with the small cytokine CCL18 being strongly associated with tissue inflammation. Immunohistochemical examination assigned CCL18 to CD68
+
tissue macrophages in both the atherosclerotic plaque and in rheumatoid synovitis. In monocyte-derived macrophages (MΦ), CCL18 enhanced production of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α and stimulated production of the tissue-injurious enzyme cathepsin K. Pro-inflammatory effector functions were linked to CCL18 induced activation of mitochondrial metabolism, quantified by oxygen consumption rates and generation of ATP. Macrophage stimulation with recombinant CCL18 resulted in the inactivating phosphorylation of the metabolic sensor GSK-3β. Immunoprecipitation experiments localized GSK-3β to the mitochondrial surface and imaging studies revealed excessive formation of mitochondria-endoplasmic reticulum connections in patient-derived CCL18
hi
macrophages.

Conclusions:
Pro-inflammatory MΦ in CAD and RA patients share a metabolic profile of increased mitochondrial oxygen consumption and ATP production. Mitochondrial activation depends on inactivation of the metabolic sensor GSK-3β and promote pro-inflammatory effector functions, such as production of cytokines and proteases. Inhibiting GSK-3β activation provides a novel therapeutic strategy to suppress pro-inflammatory macrophages in CAD and RA.
Abstract 12941: In-Hospital Outcomes Among Diabetics Undergoing Transcarotid Artery Revascularization for Carotid Artery Stenosis
Authors: Hasnie Ali , Hasnie Ammar , Adefisoye James , Magee Kelly , Allaqaband Suhail , Jan M. Fuad , Bajwa Tanvir , Haddadian Babak
Published: April 2022

Introduction:
Transcarotid artery revascularization (TCAR) is a novel procedure to intervene on clinically significant carotid artery stenosis. Periprocedural rates of stroke have remained exceedingly low in clinical trials (<1.5%). Diabetics are known to have elevated risk of periprocedural adverse events with both carotid endarterectomy and carotid artery stenting. TCAR may offer lower periprocedural rates of cerebrovascular accident given its novel flow reversal technique. However, outcomes among diabetics undergoing TCAR remain unknown. We sought to determine periprocedural cardiovascular and cerebrovascular events (MACCE) among diabetics undergoing the TCAR procedure in a large national database.

Methods:
The Vascular Quality Initiative database was queried for all TCAR procedures performed from January 2012 to March 2021. Baseline demographic information as well as periprocedural outcomes were obtained. In cases in which a patient had multiple procedures, only the most recent procedure was evaluated.

Results:
A total of 19,341 patients (median age 74 (IQR 67-80), 63.7% male and 90.3% white) underwent the TCAR procedure. Of this n=7,427 (38.4%) were diabetics. Compared to non-diabetics, the diabetic cohort had a higher risk of stroke (1.7% vs 1.3%, p=.02), transient ischemic attack (0.7% vs 0.4% p =.027), and myocardial infarction (0.7% vs 0.5% p=.064). Death remained a rare outcome, with diabetics having 0.5% periprocedural mortality vs 0.4% among non-diabetics (p=.096).

Conclusions:
TCAR is a safe revascularization method for significant carotid artery stenosis with an elevated risk of periprocedural MACCE in diabetics compared to non-diabetics. Further study is needed to define optimal patient selection for this novel and less-invasive management strategy for carotid artery disease.
Abstract 12949: Mitral Valve Geometry and Remodeling in a Three Month Swine Model of Post-Infarction Heart Failure
Authors: Silverman Michael , Onohara Daisuke , Corporan Daniella , Xu Dongyang , Sreerangathama Suresh Kirthana , Padala Muralidhar
Published: April 2022

Introduction:
Mitral regurgitation (MR) following myocardial infarction (MI) is a known risk factor for increased hospitalizations and mortality. The longitudinal mitral valve remodeling in chronic ischemic MR (IMR) is not fully understood and a reproducible, large animal model is therefore needed. In this study, we establish a swine model of chronic IMR and investigate the consequent changes in mitral valve geometry.

Methods:
Yorkshire swine (n=7) were induced with an MI via targeted angiographic ethanol injection of the left circumflex coronary artery, and were followed to 3 months. Mitral valve geometry and MR grade were investigated at baseline, immediately after MI, and 3 months post MI (
Fig. A
). Epicardial echocardiography was performed under mini left thoracotomy for direct placement onto the left atrium, such that the entire left heart was imaged.

Results:
3 months following MI, ejection fraction (EF) decreased compared to baseline (47.3 ± 8.4 vs 55.3 ± 6.5%, p=.03). Both effective regurgitant orifice area (EROA) and regurgitant volume (RV) increased compared to baseline (EROA: 12 ± .14 vs .01 ± .01cm
2
; p=.001; RV: 18.7 ± 21.3 vs .14 ± .38ml; p=.001). Both tenting height (TH) and tenting area (TA) also increased compared to baseline (TH: 11.7 ± 2.8 vs 6.8 ± 0.7mm; p=.01; TA: 190 ± 66 vs 95 ± 16mm
2
; p=.04), indicating tethering of the mitral valve. No differences were found in coaptation length (5.7 ± 1.4 vs 5.8 ± 0.8mm; p=.99) and anterior excursion angle (37.9 ± 10.5 vs 25.3 ± 11.9°; p=0.27). Posterior excursion angle decreased at 3 months following MI (25 ± 11.3 vs 39.6 ± 8.0°; p=.02), indicating restriction of the posterior leaflet (
Fig. B1-7
)

Conclusion:
In this paired analysis of mitral valve and ventricular remodeling after posterolateral MI, consistent increase in EROA and RV were observed. This model mimics a clinically relevant situation, providing a platform for studying the effects of IMR correction on ventricular remodeling.
Abstract 12952: Endothelial Cell Specific Deletion of mTOR Ameliorates Age-Related Arterial and Metabolic Dysfunction
Authors: Islam Torikul , Hall Shelby A , Bloom Samuel I , Bramwell R Colton C , Dutson Tavia , Tucker Jordan R , Kim John , Machin Daniel R , Donato Anthony J , Lesniewski Lisa A
Published: April 2022

Background:
Systemic inhibition of mammalian target of rapamycin (mTOR) improves age-related arterial and metabolic dysfunction. Although the mechanisms and tissues involved in this amelioration remain unknown, endothelial cells (ECs), key regulators of arterial and metabolic function, may be responsible for these effects.

Hypothesis:
The beneficial effects of systemic mTOR inhibition will be recapitulated after EC specific mTOR deletion in old mice.

Methods:
We studied 22-24 mo old wildtype (WT) and EC specific tamoxifen-inducible mTOR knockout (KO) mice. The arterial function was determined by assessing aortic stiffness by measuring pulse wave velocity (PWV) using Doppler ultrasound as well as endothelium-dependent dilation (EDD) and nitric oxide (NO) bioavailability using pressure myography. Carotid artery superoxide production was measured using electric paramagnetic resonance. Glucose (2g/kg, ip) and lipid (3mL/kg, oral) tolerance tests were performed to examine metabolic function.

Results:
Two weeks after tamoxifen administration (4mg/day, 4 days, oral), we found a ~ 60% reduction in EC mTOR protein (p=0.04). Aortic PWV was lower in KO compared to WT mice (Fig A), indicating lower aortic stiffness. EDD to acetylcholine (ACh) was higher in mesenteric arteries from KO compared to WT mice (Fig B) due to an increase in NO bioavailability (31.6 ± 8.6 vs 8.4 ± 2.3; p=0.01). Superoxide scavenger, TEMPOL, increased EDD in both WT and KO mice (Fig C), eliminating differences between groups. Superoxide was lower in carotid arteries of KO compared to WT (Fig D), suggesting that oxidative stress impairs EDD in WT mice and ablation of EC selective mTOR ameliorates this effect. Aged KO mice demonstrated greater glucose and lipid tolerance compared to WT (Fig E, F).

Conclusions:
Our findings demonstrate that EC specific deletion of mTOR provides beneficial effects on arterial function via reductions in oxidative stress and prevents metabolic dysfunction in old mice.
Abstract 12957: Determining Disease Co-Occurrence Architecture of Hypertensive Heart Disease in Penn Medicine Biobank Using Longitudinal EHR Data Linked With PMBB Participants
Authors: Singhal Pankhuri , Guerraty Marie A , Kim Dokyoon , Rader Daniel J , Ritchie Marylyn D , Verma Anurag
Published: April 2022

An estimated 1.2 billion individuals worldwide suffer from hypertension. Hypertensive heart disease (HHD) refers to structural alterations, such as left ventricular hypertrophy in the heart due to prolonged hypertension and can lead to ischemic heart disease, heart failure, and arrhythmias. HHD represents a transitory subclinical condition between the onset of hypertension and cardiovascular disease, typically remaining asymptomatic until the time of adverse cardiac event. The risk of HHD-related diseases is heightened due to hypertension-associated comorbidities such as dyslipidemia and renal failure. The complex etiology underlying HHD makes it challenging to predict outcomes in patients. The goal of this study is to leverage longitudinal electronic health record (EHR) data to identify the conditions and comorbidities that influence HHD outcomes for prognostication. We defined an HHD patient cohort (n = 4,268) in the Penn Medicine BioBank dataset using diagnosis code ICD-10: I11* for HHD. We constructed a disease-disease map of HHD comorbidities using the Ising model, a type of Markov Random Field undirected probabilistic graphical model. We estimated the co-occurrence of disease pairs by calculating pairwise similarities between diseases as relative risk and conducting network analyses. Our results reflect clusters of known disease-disease connections, including interactions between endocrine and nervous system diseases, as well as novel pairwise disease interactions between genitourinary and musculoskeletal diseases. Our findings shed light on the effect of comorbid conditions on the trajectory of HHD adverse outcomes. Using the probabilistic model of disease co-occurrence from these results, we can identify key comorbidities that predict adverse outcomes among HHD patients. This work lays the foundation to integrate rare and common genetic variants into the Ising model using a gene-based binning approach. Incorporating rare loss-of-function variants will enable us to evaluate shared genetic connections between HHD comorbidities. In conclusion, we used EHR data to identify the genetic and non-genetic connections between comorbidities of HHD to develop a predictive metric for the prevention and clinical monitoring of HHD.
Abstract 12965: Race-Specific Models to Predict In-Hospital Mortality in Patients With Heart Failure Using Machine Learning: The American Heart Association Get With the Guidelines Registry
Authors: Pandey Ambarish , Segar Matthew , Hall Jennifer , Navar Ann M , Powell-wiley Tiffany , Morris Alanna A , Kao David P , Fonarow Gregg C , Hernandez Rosalba , Ibrahim Nasrien E , Rutan Christine , Stevens Laura
Published: April 2022

Background:
Prior prognostic models for acute decompensated HF (ADHF) have incorporated race as a covariate may not have completely account for the social and biological factors that underlie the racial disparities in outcomes. We developed race-specific models to improve risk prediction and better identify race-specific predictors of mortality in patients with ADHF using machine learning (ML) methods.

Methods:
Race-specific ML-models for in-hospital mortality were developed and validated in ADHF patients enrolled in the GWTG-HF registry between 2007 to 2020 (14,586 Black and 50,351 Non-Black adults) using over 40 candidate variables. External validation was performed among participants from the ARIC study with ADHF (n=1,115 Black and 2,028 Non-Black adults). The discrimination and calibration was compared with a previously validated risk score and cohort-specific logistic regression (LR) models. The changes in model reclassification performance with addition of zip-code level data of socioeconomic (SES) parameters was also assessed.

Results:
In the GWTG-HF cohort, the ML models had superior performance in both Black and Non-Black participants compared with the traditional GWTG-HF risk score (
Table
). The superior performance of the ML-model was also observed in the external validation cohort as compared with the other LR models (
Table
). Addition of measures of SES did not meaningfully change the performance but improved the reclassification metrics of the ML-models with net up-classification of risk in Black [NRI = 0.21 (0.07, 0.35)] and down-classification in Non-Black patients [NRI = -0.08 (-0.12, -0.04)]. SES was responsible for 21.7% of the total attributable mortality risk in Black adults compared to 0.4% in Non-Black adults.

Conclusion:
Race-specific, ML-based mortality models demonstrated superior performance when compared to traditional HF mortality risk models. Socioeconomic distress is an important contributor to risk in Black adults.
Abstract 12967: Deletion of G Protein-Coupled Receptor 39 Protects Angiogenesis in Hyperglycemia
Authors: Meda Venkata Sai , Li Hainan , Nguyen Huong , Koh Jia Yi , Wang Jie-mie
Published: April 2022

Introduction:
Endothelial cells (ECs) are essential to vascular homeostasis and angiogenesis. Endothelial dysfunction significantly contributes to critical limb ischemia in patients with diabetes. G protein-coupled receptor (GPR) 39 is an orphan receptor whose role in EC functions is unknown. We hypothesize that inhibition of GPR 39 protects angiogenesis under hyperglycemic conditions.

Methods and Results:
Healthy human aortic endothelial cells (H-HAECs) and diabetic human aortic endothelial cells (D-HAECs) were cultured
in vitro
. The migration (Modified Boyden Chamber assay) and tube formation capacity of H-HAECs were impaired by the transfection of adenovirus carrying human GPR39 or by a GPR39 agonist, TC-G-1008 (both n=5, p<0.05). Conversely, GPR39 siRNA improved D-HAEC migration (n=4 per group, p<0.05). In an angiogenesis protein profiler array, GPR39 overexpression has significantly reduced vascular endothelial growth factor (VEGF), Interleukin-8, monocyte Chemoattractant Protein-1 (MCP1), and Angiopoietin-2 in H-HAECs (n=5 per group, p<0.05). Adult male GPR39 global knockout (GPR39
KO
) mice and age- and sex-matched wild-type (GPR39
WT
) litters were rendered diet-induced obese (DIO) by a 10-week high-fat and an add-on 8-week hyperglycemia by low-dose streptozotocin (STZ) injections chow as they reflect the human condition where obesity is closely linked to type 2 diabetes development. Hind limb ischemia was created by left femoral artery ligation. Laser Doppler imaging showed that GPR39
KO
mice had a faster blood perfusion recovery from ischemia than GPR39
WT
mice (n=5 per group, p<0.05). In adult male C57BL/6 with DIO-STZ, intramuscular injection of EC-affinitive AAV-mediated shRNA against GPR39 significantly accelerated blood perfusion recovery and prevented tissue necrosis compared to empty AAV treatment (n=5 per group, p<0.05).

Conclusion:
Our data indicated that genetic inhibition of GPR39 improved EC functions and accelerated angiogenesis from ischemia. We believe that the investigations in endothelial GPR39 may help better identify the novel therapeutic potential of targeting GPR39 in treating vascular complications in hyperglycemia.
Abstract 12969: Community-Level Socioeconomic Distress, Race, and Risk of Adverse Outcomes Following Heart Failure Hospitalization Among Medicare Beneficiaries
Authors: Mentias Amgad , Vaughan Sarrazin Mary S , Rao Shreya , Desai Milind Y , Morris Alanna A , Hall Jennifer , Menon Venu , Yancy Clyde , Sims Mario , Lewis Alana A , Fonarow Gregg C , Girotra Saket , Pandey Ambarish
Published: April 2022

Background:
Socioeconomic (SE) disadvantage is a strong determinant of adverse outcomes in patients with HF. The contribution of SE disparities to adverse outcomes in HF may differ among Black vs. White patients and has not been well studied.

Methods:
Using the 100% CMS MedPAR data, Black and White patients hospitalized with HF between 2014 and 2017 were identified and stratified based on the distressed community index (DCI)—a measure of the SE disadvantage of residential ZIP codes on a continuous scale (range 0-100, see Fig. legend)—into two groups: SE distressed (Q5) vs. non-distressed (Q1-4). The rates of 30-day and 1-year mortality and readmission were compared across the distressed vs. non-distressed race groups. The adjusted association between DCI and risk of adverse outcomes was assessed separately across the race groups using adjusted hierarchical logistic regression models with restricted cubic splines.

Results:
The study included 1,238,537 White (14.8% distressed) and 190,721 Black (44.4% distressed) patients. White patients living in SE distressed communities had a significantly higher risk of adverse outcomes at 30-days and 1-year f/u (Fig. A). In contrast, among Black patients, the risk of adverse outcomes among those living in distressed vs. non-distressed communities were not meaningfully different at 30-days and became more prominent by 1-year f/u. Similar results were noted in the restricted cubic spline analysis with stronger and more graded association between DCI score and risk of adverse outcomes in White (vs. Black) patients (Fig. B).

Conclusion:
SE distress is strongly associated with risk of adverse outcomes in White patients with HF. Among Black patients, SE distress is more common, but its adverse effects are less evident during short-term f/u and are better highlighted in the long-term. Other societal factors such as structural racism and poor access to care may be important prognostic determinants in Black patients with HF.